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1. Glucose-dependent Insulinotropic Polypeptide (GIP) Resistance and β-cell Dysfunction Contribute to Hyperglycaemia in Acromegaly.

Author

Shekhawat, Vikram, Bhansali, Shobhit, Dutta, Pinaki, Mukherjee, Kanchan, Vaiphei, Kim, Kochhar, Rakesh, Sinha, Saroj, Sachdeva, Naresh, Kurpad, Anura, Bhat, Kishor, Mudaliar, Sunder, and Bhansali, Anil

Subjects
Acromegaly, Adult, Blood Glucose, Case-Control Studies, Diabetes Mellitus, Type 2, Female, Gastric Inhibitory Polypeptide, Glucagon, Glucagon-Like Peptide 1, Glucose Clamp Technique, Humans, Hyperglycemia, Incretins, Insulin, Insulin Resistance, Insulin-Secreting Cells, Male, Prospective Studies, Receptors, Gastrointestinal Hormone
Abstract

Impaired insulin sensitivity (IS) and β-cell dysfunction result in hyperglycaemia in patients of acromegaly. However, alterations in incretins and their impact on glucose-insulin homeostasis in these patients still remain elusive. Twenty patients of active acromegaly (10 each, with and without diabetes) underwent hyperinsulinemic euglycaemic clamp and mixed meal test, before and after surgery, to measure indices of IS, β-cell function, GIP, GLP-1 and glucagon response. Immunohistochemistry (IHC) for GIP and GLP-1 was also done on intestinal biopsies of all acromegalics and healthy controls. Patients of acromegaly, irrespective of presence or absence of hyperglycaemia, had similar degree of insulin resistance, however patients with diabetes exhibited hyperglucagonemia, and compromised β-cell function despite significantly higher GIP levels. After surgery, indices of IS improved, GIP and glucagon levels decreased significantly in both the groups, while there was no significant change in indices of β-cell function in those with hyperglycaemia. IHC positivity for GIP, but not GLP-1, staining cells in duodenum and colon was significantly lower in acromegalics with diabetes as compared to healthy controls possibly because of high K-cell turnover. Chronic GH excess induces an equipoise insulin resistance in patients of acromegaly irrespective of their glycaemic status. Dysglycaemia in these patients is an outcome of β-cell dysfunction consequent to GIP resistance and hyperglucagonemia.

Published
2019

2. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Author

Collaborators, GBD 2016 Risk Factors, Gakidou, Emmanuela, Afshin, Ashkan, Abajobir, Amanuel Alemu, Abate, Kalkidan Hassen, Abbafati, Cristiana, Abbas, Kaja M, Abd-Allah, Foad, Abdulle, Abdishakur M, Abera, Semaw Ferede, Aboyans, Victor, Abu-Raddad, Laith J, Abu-Rmeileh, Niveen ME, Abyu, Gebre Yitayih, Adedeji, Isaac Akinkunmi, Adetokunboh, Olatunji, Afarideh, Mohsen, Agrawal, Anurag, Agrawal, Sutapa, Ahmadieh, Hamid, Ahmed, Muktar Beshir, Aichour, Miloud Taki Eddine, Aichour, Amani Nidhal, Aichour, Ibtihel, Akinyemi, Rufus Olusola, Akseer, Nadia, Alahdab, Fares, Al-Aly, Ziyad, Alam, Khurshid, Alam, Noore, Alam, Tahiya, Alasfoor, Deena, Alene, Kefyalew Addis, Ali, Komal, Alizadeh-Navaei, Reza, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Al-Raddadi, Rajaa, Alsharif, Ubai, Altirkawi, Khalid A, Alvis-Guzman, Nelson, Amare, Azmeraw T, Amini, Erfan, Ammar, Walid, Amoako, Yaw Ampem, Ansari, Hossein, Antó, Josep M, Antonio, Carl Abelardo T, Anwari, Palwasha, Arian, Nicholas, Ärnlöv, Johan, Artaman, Al, Aryal, Krishna Kumar, Asayesh, Hamid, Asgedom, Solomon Weldegebreal, Atey, Tesfay Mehari, Avila-Burgos, Leticia, Avokpaho, Euripide Frinel G Arthur, Awasthi, Ashish, Azzopardi, Peter, Bacha, Umar, Badawi, Alaa, Balakrishnan, Kalpana, Ballew, Shoshana H, Barac, Aleksandra, Barber, Ryan M, Barker-Collo, Suzanne L, Bärnighausen, Till, Barquera, Simon, Barregard, Lars, Barrero, Lope H, Batis, Carolina, Battle, Katherine E, Baumgarner, Blair R, Baune, Bernhard T, Beardsley, Justin, Bedi, Neeraj, Beghi, Ettore, Bell, Michelle L, Bennett, Derrick A, Bennett, James R, Bensenor, Isabela M, Berhane, Adugnaw, Berhe, Derbew Fikadu, Bernabé, Eduardo, Betsu, Balem Demtsu, Beuran, Mircea, Beyene, Addisu Shunu, Bhansali, Anil, Bhutta, Zulfiqar A, Bicer, Burcu Kucuk, Bikbov, Boris, Birungi, Charles, Biryukov, Stan, Blosser, Christopher D, Boneya, Dube Jara, Bou-Orm, Ibrahim R, Brauer, Michael, and Breitborde, Nicholas JK

Subjects
Epidemiology, Health Sciences, Prevention, Aetiology, 2.2 Factors relating to the physical environment, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Air Pollution, Body Mass Index, Cause of Death, Child, Child, Preschool, Communicable Diseases, Disabled Persons, Environmental Health, Female, Global Burden of Disease, Humans, Infant, Infant, Newborn, Life Expectancy, Male, Metabolic Diseases, Middle Aged, Noncommunicable Diseases, Occupational Diseases, Quality-Adjusted Life Years, Risk Assessment, Sex Distribution, Smoking, Water Supply, Young Adult, GBD 2016 Risk Factors Collaborators, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundThe Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context.MethodsWe used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2016. This study included 481 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk (RR) and exposure estimates from 22 717 randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources, according to the GBD 2016 source counting methods. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. Finally, we explored four drivers of trends in attributable burden: population growth, population ageing, trends in risk exposure, and all other factors combined.FindingsSince 1990, exposure increased significantly for 30 risks, did not change significantly for four risks, and decreased significantly for 31 risks. Among risks that are leading causes of burden of disease, child growth failure and household air pollution showed the most significant declines, while metabolic risks, such as body-mass index and high fasting plasma glucose, showed significant increases. In 2016, at Level 3 of the hierarchy, the three leading risk factors in terms of attributable DALYs at the global level for men were smoking (124·1 million DALYs [95% UI 111·2 million to 137·0 million]), high systolic blood pressure (122·2 million DALYs [110·3 million to 133·3 million], and low birthweight and short gestation (83·0 million DALYs [78·3 million to 87·7 million]), and for women, were high systolic blood pressure (89·9 million DALYs [80·9 million to 98·2 million]), high body-mass index (64·8 million DALYs [44·4 million to 87·6 million]), and high fasting plasma glucose (63·8 million DALYs [53·2 million to 76·3 million]). In 2016 in 113 countries, the leading risk factor in terms of attributable DALYs was a metabolic risk factor. Smoking remained among the leading five risk factors for DALYs for 109 countries, while low birthweight and short gestation was the leading risk factor for DALYs in 38 countries, particularly in sub-Saharan Africa and South Asia. In terms of important drivers of change in trends of burden attributable to risk factors, between 2006 and 2016 exposure to risks explains an 9·3% (6·9-11·6) decline in deaths and a 10·8% (8·3-13·1) decrease in DALYs at the global level, while population ageing accounts for 14·9% (12·7-17·5) of deaths and 6·2% (3·9-8·7) of DALYs, and population growth for 12·4% (10·1-14·9) of deaths and 12·4% (10·1-14·9) of DALYs. The largest contribution of trends in risk exposure to disease burden is seen between ages 1 year and 4 years, where a decline of 27·3% (24·9-29·7) of the change in DALYs between 2006 and 2016 can be attributed to declines in exposure to risks.InterpretationIncreasingly detailed understanding of the trends in risk exposure and the RRs for each risk-outcome pair provide insights into both the magnitude of health loss attributable to risks and how modification of risk exposure has contributed to health trends. Metabolic risks warrant particular policy attention, due to their large contribution to global disease burden, increasing trends, and variable patterns across countries at the same level of development. GBD 2016 findings show that, while it has huge potential to improve health, risk modification has played a relatively small part in the past decade.FundingThe Bill & Melinda Gates Foundation, Bloomberg Philanthropies.

Published
2017

3. Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016

Author

Collaborators, GBD 2016 SDG, Fullman, Nancy, Barber, Ryan M, Abajobir, Amanuel Alemu, Abate, Kalkidan Hassen, Abbafati, Cristiana, Abbas, Kaja M, Abd-Allah, Foad, Abdulkader, Rizwan Suliankatchi, Abdulle, Abdishakur M, Abera, Semaw Ferede, Aboyans, Victor, Abu-Raddad, Laith J, Abu-Rmeileh, Niveen ME, Adedeji, Isaac Akinkunmi, Adetokunboh, Olatunji, Afshin, Ashkan, Agrawal, Anurag, Agrawal, Sutapa, Kiadaliri, Aliasghar Ahmad, Ahmadieh, Hamid, Ahmed, Muktar Beshir, Aichour, Miloud Taki Eddine, Aichour, Amani Nidhal, Aichour, Ibtihel, Aiyar, Sneha, Akinyemi, Rufus Olusola, Akseer, Nadia, Al-Aly, Ziyad, Alam, Khurshid, Alam, Noore, Alasfoor, Deena, Alene, Kefyalew Addis, Alizadeh-Navaei, Reza, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Allen, Christine, Al-Raddadi, Rajaa, Alsharif, Ubai, Altirkawi, Khalid A, Alvis-Guzman, Nelson, Amare, Azmeraw T, Amini, Erfan, Ammar, Walid, Ansari, Hossein, Antonio, Carl Abelardo T, Anwari, Palwasha, Arora, Megha, Artaman, Al, Aryal, Krishna Kumar, Asayesh, Hamid, Asgedom, Solomon Weldegebreal, Assadi, Reza, Atey, Tesfay Mehari, Atre, Sachin R, Avila-Burgos, Leticia, Avokpaho, Euripide Frinel G Arthur, Awasthi, Ashish, Azzopardi, Peter, Bacha, Umar, Badawi, Alaa, Balakrishnan, Kalpana, Bannick, Marlena S, Barac, Aleksandra, Barker-Collo, Suzanne L, Bärnighausen, Till, Barrero, Lope H, Basu, Sanjay, Battle, Katherine E, Baune, Bernhard T, Beardsley, Justin, Bedi, Neeraj, Beghi, Ettore, Béjot, Yannick, Bell, Michelle L, Bennett, Derrick A, Bennett, James R, Bensenor, Isabela M, Berhane, Adugnaw, Berhe, Derbew Fikadu, Bernabé, Eduardo, Betsu, Balem Demtsu, Beuran, Mircea, Beyene, Addisu Shunu, Bhala, Neeraj, Bhansali, Anil, Bhatt, Samir, Bhutta, Zulfiqar A, Bicer, Burcu Kucuk, Bidgoli, Hassan Haghparast, Bikbov, Boris, Bilal, Arebu I, Birungi, Charles, Biryukov, Stan, Bizuayehu, Habtamu Mellie, Blosser, Christopher D, Boneya, Dube Jara, Bose, Dipan, and Bou-Orm, Ibrahim R

Subjects
Infectious Diseases, Pediatric, Prevention, Rare Diseases, Good Health and Well Being, Adolescent, Adult, Child, Child Abuse, Sexual, Child, Preschool, Conservation of Natural Resources, Female, Global Burden of Disease, Global Health, Health Status, Health Status Indicators, Humans, Infant, Infant Mortality, Infant, Newborn, Male, Middle Aged, Noncommunicable Diseases, Quality-Adjusted Life Years, Sex Offenses, Young Adult, GBD 2016 SDG Collaborators, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundThe UN's Sustainable Development Goals (SDGs) are grounded in the global ambition of "leaving no one behind". Understanding today's gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990-2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030.MethodsWe used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0-100, with 0 as the 2·5th percentile estimated between 1990 and 2030, and 100 as the 97·5th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment.FindingsGlobally, the median health-related SDG index was 56·7 (IQR 31·9-66·8) in 2016 and country-level performance markedly varied, with Singapore (86·8, 95% uncertainty interval 84·6-88·9), Iceland (86·0, 84·1-87·6), and Sweden (85·6, 81·8-87·8) having the highest levels in 2016 and Afghanistan (10·9, 9·6-11·9), the Central African Republic (11·0, 8·8-13·8), and Somalia (11·3, 9·5-13·1) recording the lowest. Between 2000 and 2016, notable improvements in the UHC index were achieved by several countries, including Cambodia, Rwanda, Equatorial Guinea, Laos, Turkey, and China; however, a number of countries, such as Lesotho and the Central African Republic, but also high-income countries, such as the USA, showed minimal gains. Based on projections of past trends, the median number of SDG targets attained in 2030 was five (IQR 2-8) of the 24 defined targets currently measured. Globally, projected target attainment considerably varied by SDG indicator, ranging from more than 60% of countries projected to reach targets for under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria, to less than 5% of countries projected to achieve targets linked to 11 indicator targets, including those for childhood overweight, tuberculosis, and road injury mortality. For several of the health-related SDGs, meeting defined targets hinges upon substantially faster progress than what most countries have achieved in the past.InterpretationGBD 2016 provides an updated and expanded evidence base on where the world currently stands in terms of the health-related SDGs. Our improved measure of UHC offers a basis to monitor the expansion of health services necessary to meet the SDGs. Based on past rates of progress, many places are facing challenges in meeting defined health-related SDG targets, particularly among countries that are the worst off. In view of the early stages of SDG implementation, however, opportunity remains to take actions to accelerate progress, as shown by the catalytic effects of adopting the Millennium Development Goals after 2000. With the SDGs' broader, bolder development agenda, multisectoral commitments and investments are vital to make the health-related SDGs within reach of all populations.FundingBill & Melinda Gates Foundation.

Published
2017

4. Rounds Today: A Qualitative Study of Internal Medicine and Pediatrics Resident Perceptions

Author

Rabinowitz, Raphael, Farnan, Jeanne, Hulland, Oliver, Kearns, Lisa, Long, Michele, Monash, Bradley, Bhansali, Priti, and Fromme, H Barrett

Subjects
Curriculum and Pedagogy, Education, Health Services, Clinical Research, Behavioral and Social Science, Patient Safety, Quality Education, Good Health and Well Being, Adult, Attitude of Health Personnel, Family, Female, Focus Groups, Hospitals, Teaching, Humans, Internal Medicine, Internship and Residency, Male, Patient Care, Patient Participation, Pediatrics, Perception, Teaching Rounds, Curriculum and pedagogy
Abstract

BackgroundAttending rounds is a key component of patient care and education at teaching hospitals, yet there is an absence of studies addressing trainees' perceptions of rounds.ObjectiveTo determine perceptions of pediatrics and internal medicine residents about the current and ideal purposes of inpatient rounds on hospitalist services.MethodsIn this multi-institutional qualitative study, the authors conducted focus groups with a purposive sample of internal medicine and pediatrics residents at 4 teaching hospitals. The constant comparative method was used to identify themes and codes.ResultsThe study identified 4 themes: patient care, clinical education, patient/family involvement, and evaluation. Patient care included references to activities on rounds that forwarded care of the patient. Clinical education pertained to teaching/learning on rounds. Patient/family involvement encompassed comments about incorporating patients and families on rounds. Evaluation described residents demonstrating skill for attendings.ConclusionsResident perceptions of the purposes of rounds aligned with rounding activities described by prior observational studies of rounds. The influence of time pressures and the divergent needs of participants on today's rounds placed these identified purposes in tension, and led to resident dissatisfaction in the achievement of all of them. Suboptimal congruency exists between perceived resident clinical education and specialty-specific milestones. These findings suggest a need for education of multiple stakeholders by (1) enhancing faculty teaching strategies to maximize clinical education while minimizing inefficiencies; (2) informing residents about the value of patient interactions and family-centered rounds; and (3) educating program directors in proper alignment of inpatient rotational objectives to the milestones.

Published
2016

5. Differentiating Benign From Malignant Bone Marrow B-Cell Lymphoid Aggregates: A Statistical Analysis of Distinguishing Features

Author

Johnston, Abbey, Brynes, Russell K, Naemi, Kaveh, Reisian, Niloufar, Bhansali, Deepty, Zhao, Xiaohui, and Rezk, Sherif A

Subjects
Rare Diseases, Lymphoma, Clinical Research, Hematology, Cancer, Adolescent, Adult, Aged, Aged, 80 and over, B-Lymphocytes, Biomarkers, Tumor, Biopsy, Bone Marrow, Bone Marrow Cells, Child, Diagnosis, Differential, Female, Humans, Immunophenotyping, Lymphoid Tissue, Lymphoma, B-Cell, Male, Middle Aged, Predictive Value of Tests, T-Lymphocytes, Young Adult, Clinical Sciences, Pathology
Abstract

ContextLymphoid aggregates are seen in a minority of bone marrow biopsy specimens, and when present, their neoplastic nature is often apparent by morphologic evaluation. However, the distinction between benign and malignant aggregates can be a diagnostic challenge when there are multiple aggregates with no documented history of lymphoma.ObjectiveTo aid in the distinction between benign and malignant B-cell lymphoid aggregates.DesignPreviously, we described specific distribution patterns for B and T lymphocytes within bone marrow aggregates. To statistically analyze the significance of these patterns as well as previously reported criteria, we examined 128 bone marrow specimens with benign aggregates and 78 specimens with documented malignant B-cell aggregates and calculated specific odds ratios (ORs) and 95% confidence intervals (CIs) to aid in differentiating between benign and malignant B-cell aggregates.ResultsAggregates with infiltrative edges (OR, 80.54; 95% CI, 31.76-204.21), a B-cell pattern (OR, 30.08; 95% CI, 13.28-68.10), paratrabecular location (OR, 10.17; 95% CI, 3.96-26.12), size greater than 600 μm (OR, 6.83: 95% CI, 3.61-12.93), or cytologic atypia correlated with malignancy.ConclusionsWhen taken collectively, the presence of more than 2 of these characteristic features was strongly predictive of malignancy.

Published
2015

6. Cholesterol lipoproteins and prevalence of dyslipidemias in urban Asian Indians: A cross sectional study

Author

Guptha, Soneil, Gupta, Rajeev, Deedwania, Prakash, Bhansali, Anil, Maheshwari, Anuj, Gupta, Arvind, Gupta, Balkishan, Saboo, Banshi, Singh, Jitendra, Achari, Vijay, and Sharma, Krishna Kumar

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Nutrition, Clinical Research, Cardiovascular, Atherosclerosis, Biomarkers, Cholesterol, Cross-Sectional Studies, Dyslipidemias, Female, Humans, India, Lipoproteins, Male, Prevalence, Risk Factors, Urban Population, Atherogenic dyslipidemia, Coronary heart disease, Epidemiology, Lipids, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

ObjectiveTo determine levels of cholesterol lipoproteins and prevalence of dyslipidemias in urban Asian Indians.MethodsPopulation based 6123 subjects (men 3388) were evaluated. Mean±1SD of various cholesterol lipoproteins (total, HDL, LDL and non-HDL cholesterol) and triglycerides were reported. Subjects were classified according to US National Cholesterol Education Program.ResultsAge-adjusted levels in men and women were cholesterol total 178.4 ± 39 and 184.6 ± 39, HDL 44.9 ± 11 and 51.1 ± 11, LDL 102.5 ± 33 and 106.2 ± 33, total:HDL 4.15 ± 1.2 and 3.79 ± 1.0 and triglycerides 162.5 ± 83 and 143.7 ± 83 mg/dl. Age-adjusted prevalence (%) in men and women, respectively were, total cholesterol ≥200 mg/dl 25.1 and 24.9, LDL cholesterol ≥130 mg/dl 16.3 and 15.1 and ≥100 mg/dl 49.5 and 49.7, HDL cholesterol

Published
2014

7. Achievement of guideline recommended diabetes treatment targets and health habits in people with self-reported diabetes in India (ICMR-INDIAB-13): a national cross-sectional study

Author

Ranjit Mohan Anjana, Ranjit Unnikrishnan, Mohan Deepa, Ulagamathesan Venkatesan, Rajendra Pradeepa, Shashank Joshi, Banshi Saboo, Ashok Kumar Das, Sarita Bajaj, Anil Bhansali, Sri Venkata Madhu, Vinay Kumar Dhandhania, Puthiyaveettil Kottayam Jabbar, Sunil M Jain, Arvind Gupta, Subhankar Chowdhury, Mohammed K Ali, Elangovan Nirmal, Radhakrishnan Subashini, Tanvir Kaur, Rupinder Singh Dhaliwal, Nikhil Tandon, Viswanathan Mohan, and Shashank R Joshi

Subjects
Adult, Blood Glucose, Male, Biomedical Research, Urban Population, Endocrinology, Diabetes and Metabolism, India, Cholesterol, LDL, Middle Aged, Habits, Cross-Sectional Studies, Endocrinology, Diabetes Mellitus, Prevalence, Internal Medicine, Humans, Self Report
Abstract

There is little information on comprehensive diabetes care comprising glycaemic, lipid, and blood pressure control in India; therefore, we aimed to assess the achievement of treatment targets among adults with self-reported diabetes.The Indian Council of Medical Research (ICMR)-India Diabetes (INDIAB) study is a cross-sectional, population-based survey of adults aged 20 years or older in all 30 states and union territories of India. We used a stratified multistage sampling design, sampling states in a phased manner, and selected villages in rural areas and census enumeration blocks in urban areas. We used a three-level stratification method on the basis of geography, population size, and socioeconomic status for each state. For the outcome assessment, good glycaemic control was defined as HbABetween Oct 18, 2008, and Dec 17, 2020, 113 043 individuals (33 537 from urban areas and 79 506 from rural areas) participated in the ICMR-INDIAB study. For this analysis, 5789 adults (2633 in urban areas and 3156 in rural areas) with self-reported diabetes were included in the study population. The median age was 56·1 years (IQR 55·7-56·5). Overall, 1748 (weighted proportion 36·3%, 95% CI 34·7-37·9) of 4834 people with diabetes achieved good glycaemic control, 2819 (weighted proportion 48·8%, 47·2-50·3) of 5698 achieved blood pressure control, and 2043 (weighted proportion 41·5%, 39·9-43·1) of 4886 achieved good LDL cholesterol control. Only 419 (weighted proportion 7·7%) of 5297 individuals with self-reported diabetes achieved all three ABC targets, with significant heterogeneity between regions and states. Higher education, male sex, rural residence, and shorter duration of diabetes (10 years) were associated with better achievement of combined ABC targets. Only 951 (weighted proportion 16·7%) of the study population and 227 (weighted proportion 36·9%) of those on insulin reported using self-monitoring of blood glucose.Achievement of treatment targets and adoption of healthy behaviours remains suboptimal in India. Our results can help governments to adopt policies that prioritise improvement of diabetes care delivery and surveillance in India.Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare.

Published
2022

8. Cost-effectiveness of population-based screening for diabetes and hypertension in India: an economic modelling study

Author

Ankur Gupta, Akashdeep Singh Chauhan, Jerard M Selvam, Anil Bhansali, Ashu Rastogi, Yot Teerawattananon, Pvm Lakshmi, Gaurav Jyani, Shankar Prinja, Sanjay Jain, Gunjeet Kaur, M Muniyandi, and Karikalan Nagarajan

Subjects
Adult, Male, Marginal cost, Cost effectiveness, Cost-Benefit Analysis, Population, MEDLINE, India, Comorbidity, Isoindoles, Quality of life (healthcare), Diabetes mellitus, Environmental health, Diabetes Mellitus, Humans, Mass Screening, Medicine, education, Aged, Cost database, education.field_of_study, business.industry, Decision Trees, Age Factors, Public Health, Environmental and Occupational Health, Middle Aged, Patient Acceptance of Health Care, medicine.disease, Markov Chains, Annual Screening, Thiazoles, Models, Economic, Hypertension, Quality of Life, Female, Quality-Adjusted Life Years, business
Abstract

Summary Background India faces a high burden of diabetes and hypertension. Currently, there is a dearth of economic evidence about screening programmes, affected age groups, and frequency of screening for these diseases in Indian settings. We assessed the cost effectiveness of population-based screening for diabetes and hypertension compared with current practice in India for different scenarios, according to type of screening test, population age group, and pattern of health-care use. Methods We used a hybrid decision model (decision tree and Markov model) to estimate the lifetime costs and consequences from a societal perspective. A meta-analysis was done to assess the effectiveness of population-based screening. Primary data were collected from two Indian states (Haryana and Tamil Nadu) to assess the cost of screening. The data from the National Health System Cost Database and the Costing of Health Services in India study were used to determine the health system cost of diagnostic tests and cost of treating diabetes or hypertension and their complications. A total of 962 patients were recruited to assess out-of-pocket expenditure and quality of life. Parameter uncertainty was evaluated using univariate and multivariable probabilistic sensitivity analyses. Finally, we estimated the incremental cost per quality-adjusted life-year (QALY) gained with alternative scenarios of scaling up primary health care through a health and wellness centre programme for the treatment of diabetes and hypertension. Findings The incremental cost per QALY gained across various strategies for population-based screening for diabetes and hypertension ranged from US$0·02 million to $0·03 million. At the current pattern of health services use, none of the screening strategies of annual screening, screening every 3 years, and screening every 5 years was cost-effective at a threshold of 1-time per capita gross domestic product in India. In the scenario in which health and wellness centres provided primary care to 20% of patients who were newly diagnosed with uncomplicated diabetes or hypertension, screening the group aged between 30 and 65 years every 5 years or 3 years for either diabetes, hypertension, or a comorbid state (both diabetes and hypertension) became cost-effective. If the share of treatment for patients with newly diagnosed uncomplicated diabetes or hypertension at health and wellness centres increases to 70%, from the existing 4% at subcentres and primary health centres, annual population-based screening becomes a cost saving strategy. Interpretation Population-based screening for diabetes and hypertension in India could potentially reduce time to diagnosis and treatment and be cost-effective if it is linked to comprehensive primary health care through health and wellness centres for provision of treatment to patients who screen positive. Funding Department of Health Research, Government of India.

Published
2022

9. Etiology-, Sex-, and Tumor Size-Based Differences in Adrenocorticotropin-Dependent Cushing Syndrome

Author

Naresh Sachdeva, Rosario Pivonello, Sivashanmugam Dhandapani, Abhishek Hajela, Sanjay Kumar Bhadada, Aditya Dutta, Uma Nahar Saikia, Chiara Simeoli, Nidhi Gupta, Rama Walia, Anil Bhansali, Chirag Kamal Ahuja, Pinaki Dutta, Walia, Rama, Dutta, Aditya, Gupta, Nidhi, Bhansali, Anil, Pivonello, Rosario, Ahuja, Chirag Kamal, Dhandapani, Sivashanmugam, Dutta, Pinaki, Bhadada, Sanjay Kumar, Simeoli, Chiara, Hajela, Abhishek, Sachdeva, Naresh, and Saikia, Uma Nahar

Subjects
Adult, Male, medicine.medical_specialty, Hydrocortisone, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Population, 030209 endocrinology & metabolism, Adrenocorticotropic hormone, Gastroenterology, 03 medical and health sciences, Cushing syndrome, 0302 clinical medicine, Endocrinology, Adrenocorticotropic Hormone, Retrospective Studie, Internal medicine, medicine, Humans, sex, 030212 general & internal medicine, Pituitary ACTH Hypersecretion, education, Cushing Syndrome, Retrospective Studies, Transsphenoidal surgery, education.field_of_study, business.industry, Cushing disease, tumor size, General Medicine, medicine.disease, Hypokalemia, Cushing Disease, Inferior petrosal sinus sampling, ACTH Syndrome, Ectopic, Etiology, Female, ACTH-dependent Cushing syndrome, medicine.symptom, business, Human
Abstract

Objective To examine demographic, clinical, and biochemical differences in patients with adrenocorticotropin (ACTH)-dependent Cushing syndrome (CS) based on etiology, sex, and tumor size. Methods This was a single-center study of 211 patients with ACTH-dependent CS followed for 35 years. Patients were stratified into 3 groups based on etiology: Cushing disease (CD)/transsphenoidal surgery, Cushing disease/total bilateral adrenalectomy (CD/TBA), and ectopic ACTH secretion (EAS). Patients were also stratified based on sex and tumor size (nonvisualized, microadenoma, and macroadenoma). Results CD was the commonest cause of ACTH-dependent CS (190; 90%). Most patients presented in the third decade (median age, 29 years). Clinical features, cortisol, and ACTH were significantly greater in the EAS group. The CD/TBA group had more nonvisualized tumors (22% vs 8%; P = .000) and smaller tumor size (4 vs 6 mm; P = .001) compared with the CD/transsphenoidal surgery group. There was female predominance in CD (2.06:1) and male predominance in EAS (2:1). Men had shorter duration of symptoms (2 years; P = .014), were younger (23 years; P = .001), had lower body mass index (25.1 kg/m2; P = .000), and had more severe disease (low bone mineral density, hypokalemia). Macroadenomas were frequent (46; 24.2%), and ACTH correlated with tumor size in CD (r = 0.226; P = .005). Conclusion Our cohort presented at an earlier age than the Western population with a distinct, but slightly lower, female predilection. Patients with CD undergoing TBA had frequent negative imaging. Men had a clinical profile suggesting aggressive disease. Microadenoma and macroadenoma were difficult to distinguish on a clinicobiochemical basis.

Published
2021

10. ACTH increment post total bilateral adrenalectomy for Cushing’s disease: a consistent biosignature for predicting Nelson’s syndrome

Author

Rama Walia, Chirag Kamal Ahuja, Pinaki Dutta, Ravimohan S. Mavuduru, Sanjay Kumar Bhadada, Liza Das, Sivashanmugam Dhandapani, Anil Bhansali, Santosh Kumar, Uma Nahar Saikia, Arunanshu Behera, Rosario Pivonello, Das, L., Bhansali, A., Pivonello, R., Dutta, P., Bhadada, S. K., Ahuja, C. K., Mavuduru, R., Kumar, S., Behera, A., Saikia, U. N., Dhandapani, S., and Walia, R.

Subjects
Male, endocrine system, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Discriminatory feature, 030209 endocrinology & metabolism, Gastroenterology, Nelson Syndrome, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Adrenocorticotropic Hormone, Pituitary adenoma, Proximal myopathy, Internal medicine, medicine, Humans, Cushing Syndrome, Proportional Hazards Models, Nelson’s syndrome, Proportional hazards model, business.industry, Nelson's syndrome, Adrenalectomy, Cushing's disease, Cushing’s disease, medicine.disease, ACTH, Protein catabolism, Female, Bilateral adrenalectomy, business, Complication, 030217 neurology & neurosurgery
Abstract

Purpose: Nelson’s syndrome (NS) is regarded as an aggressive complication of total bilateral adrenalectomy (TBA) for Cushing’s disease (CD). This challenge may be addressed by using clinical criteria to guide frequency of neuroimaging to enable timely management of NS and also avoid unnecessary frequent imaging. Methods: All patients (n = 43) with CD subjected to TBA over 35 years at a tertiary care centre were included. NS was defined as a newly appearing or expanding (> 2 mm) pituitary adenoma with or without ACTH levels exceeding 500 pg/ml. Pre-and post-TBA parameters like clinical symptomatology, cortisol, ACTH and radiology were analysed for the prediction of NS. Results: NS developed in 39.5% (n = 17) patients with a median follow-up of 7 years. Half of them had new appearance, while rest had an expansion of pre-existing pituitary tumour. Majority (90%) had ACTH above 500 pg/ml. On Cox proportional hazards analysis, frequent discriminatory features of protein catabolism (≥ 4) (HR 1.15, CI 0.18, 7.06), proximal myopathy (HR 8.82, CI 1.12, 69.58) and annual ACTH increment of 113 pg/ml (HR 12.56, CI 1.88, 88.76) predicted NS. First post-operative year ACTH indices predicting NS included ACTH rise of 116 pg/ml and absolute ACTH of 142 pg/ml (sensitivity, specificity exceeding 90%). Annual ACTH increment exceeding 113 pg/ml, ≥ 4 discriminatory features and uncontrolled hypertension had the best overall prediction. Conclusion: Patients who developed NS had higher rebound rise of ACTH following TBA and a more severe disease phenotype at baseline. Consistent ACTH increment can be used as a marker for predicting the development of NS.

Published
2020

11. Metformin upregulates mitophagy in patients with T2DM: A randomized placebo‐controlled study

Author

Veena Dhawan, Anil Bhansali, Shipra Bhansali, Pinaki Dutta, and Rama Walia

Subjects
0301 basic medicine, Adult, Male, endocrine system diseases, type 2 diabetes mellitus, medicine.medical_treatment, MFN2, PINK1, Pharmacology, medicine.disease_cause, Models, Biological, Parkin, Placebos, 03 medical and health sciences, 0302 clinical medicine, Voglibose, Mitophagy, medicine, Humans, RNA, Messenger, Membrane Potential, Mitochondrial, business.industry, Insulin, nutritional and metabolic diseases, Cell Biology, Original Articles, Middle Aged, Metformin, Mitochondria, Up-Regulation, 030104 developmental biology, Diabetes Mellitus, Type 2, 030220 oncology & carcinogenesis, randomized controlled trial, Linear Models, Molecular Medicine, Original Article, Drug Therapy, Combination, Female, nucleotide‐binding oligomerization domain‐like receptor family pyrin domain‐containing 3 (NLRP3), business, Reactive Oxygen Species, Oxidative stress, Biomarkers, Inositol, medicine.drug
Abstract

Impaired mitochondrial autophagy (mitophagy) and NLRP3 inflammasome activation have been incriminated in the pathogenesis of T2DM. Metformin besides being an insulin sensitizer also induces autophagy; however, its effect on mitophagy and NLRP3 activation in patients with T2DM still remains elusive. Forty‐five drug‐naïve T2DM patients with HbA1C 7%‐9% (53‐75 mmol/mol) were randomly assigned to receive either metformin, voglibose, or placebo for 3 months, and were also recommended for lifestyle intervention programme (n = 15 each). Mitochondrial oxidative stress (MOS) parameters, qPCR and immunoblotting of mitophagy‐related markers (PINK1, PARKIN, MFN2, NIX, LC3‐II, LAMP2), p‐AMPKα (T172), and NLRP3 proteins, as well as transmission electron microscopy (TEM) for assessing mitochondrial morphology were performed in the mononuclear cells of study patients. Both metformin and voglibose showed a similar efficacy towards the reduction in HbA1c and MOS indices. However, multivariate ANCOVA divulged that mRNA and protein expression of mitophagy markers, NLRP3 and p‐AMPKα (T172), were significantly increased only with metformin therapy. Moreover, PINK1 expression displayed a significant positive association with HOMA‐β indices, and TEM studies further confirmed reduced distortions in mitochondrial morphology in the metformin group only. Our observations underscore that metformin upregulates mitophagy and subsequently ameliorates the altered mitochondrial morphology and function, independent of its glucose‐lowering effect. Further, restoration of normal mitochondrial phenotype may improve cellular function, including β‐cells, which may prevent further worsening of hyperglycaemia in patients with T2DM.

Published
2020

12. Effect of a Dual PPAR α/γ agonist on Insulin Sensitivity in Patients of Type 2 Diabetes with Hypertriglyceridemia- Randomized double-blind placebo-controlled trial

Author

Nimisha Jain, Akhilesh Sharma, Anil Bhansali, Ashu Rastogi, Shobhit Bhansali, Sandeep Kaur, Anura V Kurpad, and Meredith Hawkins

Subjects
0301 basic medicine, Agonist, Adult, Male, medicine.medical_specialty, medicine.drug_class, Endpoint Determination, Placebo-controlled study, lcsh:Medicine, Type 2 diabetes, 030204 cardiovascular system & hematology, Placebo, Article, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Double-Blind Method, Internal medicine, medicine, Humans, In patient, PPAR alpha, Pyrroles, lcsh:Science, Glycated Hemoglobin, Hypertriglyceridemia, Multidisciplinary, Phenylpropionates, business.industry, Saroglitazar, lcsh:R, Insulin sensitivity, Endocrine system and metabolic diseases, nutritional and metabolic diseases, medicine.disease, Lipids, PPAR gamma, 030104 developmental biology, Diabetes Mellitus, Type 2, Female, lcsh:Q, Insulin Resistance, business, medicine.drug
Abstract

Saroglitazar is a dual PPAR-α/γ agonist approved for the treatment of diabetic dyslipidemia. In addition to reduction in atherogenic lipids, it may also contribute to improvement in insulin sensitivity through PPAR-α/γ agonism, which remains unexplored. We conducted a randomized, double-blind, placebo-controlled trial in treatment-naive T2DM individuals with serum triglyceride >150 mg/dL. Participants were randomized to receive either saroglitazar 4 mg or placebo (1:1) daily for 4 months (n = 30). Insulin sensitivity (SIclamp) was studied using hyperinsulinemic-euglycemic clamp at baseline and at 4 months. We observed a significant reduction in TG (p = 0.001), HbA1c (p = 0.019) and fasting plasma glucose (p = 0.019) and significant increase in HDL-C levels (p clamp (p = 0.026) with the effect persisting despite adjusting for baseline weight, TG, HDL-C and HbA1c (p = 0.002). This was accompanied with significant increase in HOMA-β (p = 0.01) in the saroglitazar group and change in HOMA-β showed a trend towards significance with SIclamp (r = 0.503, p = 0.056). However, change in SIclamp did not significantly correlate with reduction in HbA1c and TG. We conclude that saroglitazar effectively reduces hypertriglyceridemia and improves insulin sensitivity along with β-cell function by reduction in gluco-lipotoxicity and possibly directly through PPAR-γ agonism in patients ofT2DM with hypertriglyceridemia.

Published
2019

13. Efficacy and safety of low‐dose naltrexone in painful diabetic neuropathy: A randomized, double‐blind, active‐control, crossover clinical trial

Author

Amitava Chakrabarti, Anand Srinivasan, Pinaki Dutta, Dipika Bansal, Debasish Hota, and Anil Bhansali

Subjects
Male, Visual analogue scale, Amitriptyline, Endocrinology, Diabetes and Metabolism, Pain, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Naltrexone, 03 medical and health sciences, 0302 clinical medicine, Diabetic Neuropathies, Double-Blind Method, Diabetes mellitus, medicine, Humans, Adverse effect, Pain Measurement, Cross-Over Studies, business.industry, Analgesics, Non-Narcotic, Middle Aged, medicine.disease, Clinical trial, Diabetes Mellitus, Type 2, Anesthesia, Female, Low-dose naltrexone, medicine.symptom, business, Somnolence, medicine.drug
Abstract

There is a need for newer therapies for chronic painful diabetic neuropathy as the existing drugs have their own limitations. Clinical trials on low-dose naltrexone (1-5 mg/d) showed efficacy and safety in certain chronic painful conditions, but not in painful diabetic neuropathy. Hence the present study was planned.Sixty-seven participants with painful diabetic neuropathy were randomized to receive either 2 mg naltrexone or 10 mg amitriptyline daily following a 2-week run-in period. The participants were followed up every 2 weeks for a total of 6 weeks. Up-titration was done (to 4 mg naltrexone or 25/50 mg amitriptyline) if the pain reduction was less than 20% on the visual analog scale (VAS) during the next follow-up visit. Efficacy was assessed using the change in VAS score at the end of 6 weeks from baseline. Safety was evaluated at each follow-up visit. After 2 weeks of washout period, the participants were crossed over to receive the comparator drug for another 6 weeks with similar evaluations.The difference (confidence interval) in the change in VAS score between groups from baseline was 1.64 (-0.92 to 4.20) in per-protocol analysis and 1.5 (-1.11 to 4.13) in intention-to-treat analysis. Eight and fifty-two adverse events were reported in the naltrexone and amitriptyline groups, respectively (P .001). The most common adverse events were mild diarrhea with naltrexone and somnolence with amitriptyline.Low-dose naltrexone exhibited similar efficacy and a superior safety profile compared with amitriptyline in painful diabetic neuropathy.背景: 由于现有药物有其自身的局限性，因此需要新的治疗方法来治疗慢性痛性糖尿病神经病变。低剂量纳曲酮(1-5 mg/d)的临床试验显示，在某些慢性疼痛情况下，纳曲酮是有效和安全的，但对痛性糖尿病神经病变无效，因此我们计划了本研究。 方法: 67名患有痛性糖尿病神经病变的患者被随机分为两组，每天服用2毫克纳曲酮或10毫克阿米替林。参与者每2周随访一次，共6周。在下一次随访中，如果疼痛减轻在视觉模拟评分(VAS)上小于20%，则进行向上滴定(纳曲酮4 mg或阿米替林25/50 mg)。根据基线后6周末VAS评分的变化来评估疗效。在每次随访时对安全性进行评估。经过2周的洗涤期后，参与者被交叉接受另一组6周的对照药物，进行相似的评估。 结果: 两组间VAS评分相对基线变化的置信区间分别为1.64(-0.92~4.20)(完成治疗分析) 和1.5(-1.11~4.13)(治疗意向分析)，纳曲酮组和阿米替林组分别报告了8和52个不良事件(P0.001)。最常见的不良反应是纳曲酮引起的轻度腹泻和阿米替林引起的嗜睡。 结论: 与阿米替林相比，低剂量纳曲酮治疗痛性糖尿病神经病变具有相似的疗效和更好的安全性。.

Published
2021

14. Impaired anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with diabetes mellitus: A preliminary report

Author

Shiv Lal Soni, Soham Mukherjee, Ashish Bhalla, Deepy Zohmangaihi, Naresh Sachdeva, Anil Bhansali, Sanjay Kumar Bhadada, Goverdhan Dutt Puri, Navin Pandey, Sant Ram, Rimesh Pal, and Vikas Suri

Subjects
Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Endocrinology, Diabetes and Metabolism, T2DM, 030209 endocrinology & metabolism, Antibodies, Viral, Gastroenterology, Article, Antibodies, Young Adult, 03 medical and health sciences, COVID-19 Testing, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Internal Medicine, Humans, Medicine, 030212 general & internal medicine, Seroconversion, Aged, Retrospective Studies, biology, SARS-CoV-2, business.industry, COVID-19, Type 2 Diabetes Mellitus, General Medicine, Middle Aged, Hepatitis B, medicine.disease, Humoral immunity, Antibody response, Diabetes Mellitus, Type 2, Antibody Formation, biology.protein, Female, Antibody, business
Abstract

Background and aims Patients with diabetes mellitus (DM) often demonstrate impaired antibody response to influenza/hepatitis B vaccines. Hence, we compared anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with and without type 2 diabetes mellitus (T2DM). Methods Records of non-severe COVID-19 patients admitted at our institution between April 10, 2020 and May 20, 2020 were retrieved. Qualitative detection of total (IgG + IgM) anti-SARS-CoV-2 antibody was performed using electrochemiluminescence immunoassay in plasma samples collected at least 14 days post-polymerase chain reaction (PCR) confirmation of diagnosis. Results Thirty-one non-severe COVID-19 patients were included. Nine patients (29%) had T2DM with mean HbA1c at admission of 8.3 ± 1.0%. Anti-SARS-CoV-2 antibody was estimated at a median of 16 (14–17) days post-PCR confirmation of COVID-19 diagnosis. Only three patients (10%) were seronegative, and all had T2DM. Patients with T2DM were more likely to have non-detectable anti-SARS-CoV-2 antibodies than those without DM (p = 0.019). Conclusions COVID-19 patients with T2DM may not undergo seroconversion even after two weeks of diagnosis. Impaired seroconversion could theoretically increase the risk of reinfections in patients with DM. However, the finding requires validation in large-scale studies involving serial estimations of anti-SARS-CoV-2 antibodies in patients with and without DM., Highlights • Non-severe COVID-19 patients with T2DM were more likely to be seronegative for anti-SARS-CoV-2 antibodies. • Seronegative patients had higher HbA1c and longer duration of T2DM than seropositive patients. • Absence of anti-SARS-CoV-2 antibodies might increase the risk of reinfections in patients with T2DM.

Published
2021

15. Primary Hyperparathyroidism Presenting as Posterior Reversible Encephalopathy Syndrome: A Report of Two Cases

Author

Sanjay Kumar Bhadada, Kanhaiya Agrawal, Arunanshu Behera, Nimisha Jain, Aditya Dutta, Pinaki Dutta, Anil Bhansali, and Rimesh Pal

Subjects
Male, medicine.medical_specialty, posterior reversible encephalopathy syndrome, Adolescent, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Case Report, Malignancy, Gastroenterology, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Diagnosis, Differential, Endocrinology, Risk Factors, Internal medicine, medicine, Vitamin D and neurology, Humans, primary hyperparathyroidism, Child, Parathyroid adenoma, Eclampsia, lcsh:RC648-665, business.industry, lcsh:RJ1-570, hypercalcemia, Posterior reversible encephalopathy syndrome, lcsh:Pediatrics, Hyperparathyroidism, Primary, Prognosis, medicine.disease, Hyperintensity, Pediatrics, Perinatology and Child Health, Posterior Leukoencephalopathy Syndrome, Differential diagnosis, business, Primary hyperparathyroidism
Abstract

Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological entity characterized by subcortical vasogenic edema presenting with acute neurological symptoms. Common precipitating causes include renal failure, pre-eclampsia/eclampsia, post-organ transplant, and cytotoxic drugs. Hypercalcemia is a rare cause of PRES; most cases occur in the setting of severe hypercalcemia secondary to malignancy or iatrogenic vitamin D/calcium overdose. Primary hyperparathyroidism (PHPT), as a cause of PRES, is an oddity. We report two cases of adolescent PHPT presenting with generalized tonic-clonic seizures and altered sensorium. On evaluation, both had hypertension, severe hypercalcemia (serum calcium 14.1 mg/dL and 14.5 mg/dL, respectively) and elevated parathyroid hormone levels. Magnetic resonance imaging (MRI) revealed T2/fluid-attenuated inversion recovery hyperintensities located predominantly in the parieto-occipital regions, suggestive of PRES. Identification and excision of parathyroid adenoma led to the restoration of normocalcemia. Neurological symptoms and MRI changes improved subsequently. An extensive literature search revealed only four cases of PHPTassociated PRES; none of them being in the pediatric/adolescent age group. The predominant clinical manifestations were seizures and altered sensorium. All had severe hypercalcemia; three had hypertension at presentation, while one was normotensive. Parathyroid adenomectomy led to normalization of serum calcium and resolution of neurological symptoms and radiological changes. Thus, severe hypercalcemia, although rare in PHPT, can lead to hypercalcemic crisis precipitating acute hypertension that can result in cerebral endothelial dysfunction with the breakdown of the blood-brain barrier, culminating in PRES. We therefore recommend that serum calcium levels should be checked in all patients with PRES and that PHPT be regarded as a differential diagnosis in those with underlying hypercalcemia.

Published
2020

16. Anthropometric and Pubertal Outcomes in Girls With Classical Congenital Adrenal Hyperplasia

Author

Japleen Kaur, Mandeep Singla, Anil Bhansali, Sanjay Bhadada, and Rama Walia

Subjects
Adult, Male, Young Adult, Adolescent, Adrenal Hyperplasia, Congenital, Anthropometry, Hydrocortisone, Pediatrics, Perinatology and Child Health, Humans, Female, Body Height, Retrospective Studies
Abstract

To evaluate the anthropometric and pubertal outcomes, over a spectrum of treatment regimens and compliance.We reviewed records of the patients with classical CAH seen at the endocrinology clinic of a tertiary care center between 1995 and 2016.25 females were included in the study, the majority (80%) with simple virilizing variant. All patients had genital ambiguity since birth, yet 40% (10/25) presented much later with menstrual complaints. All patients received hydrocortisone, but some switched to dexa-methasone (n=7) or prednisolone (n=4). 7/9 (77.9%) girls who achieved target height, were on hydrocortisone. Menarche occurred with corticosteroid treatment in 60% (15/25) patients at a median (IQR) age of 16 (12-22) years.Hydrocortisone seems to have a beneficial effect on linear growth. Once target height is achieved, dexamethasone may be considered as an alternative.

Published
2022

17. Bladder cancer with pioglitazone: A case-control study

Author

Bhanu Malhotra, Priya Hiteshi, Persis Khalkho, Ritu Malik, Sanjay Kumar Bhadada, Anil Bhansali, Nusrat Shafiq, Sameer Malhotra, Narendra Kumar, Rajesh Rajput, and Ashu Rastogi

Subjects
Male, Pioglitazone, Endocrinology, Diabetes and Metabolism, Urinary Bladder, General Medicine, Middle Aged, Diabetes Mellitus, Type 2, Urinary Bladder Neoplasms, Risk Factors, Case-Control Studies, Internal Medicine, Humans, Hypoglycemic Agents, Female, Thiazolidinediones, Hematuria
Abstract

Varied reports suggest a contentious relationship of bladder malignancy with pioglitazone in patients with type 2 diabetes.To study an association (prevalence and predictors) of bladder malignancy with pioglitazone therapy in Asian-Indian type 2 diabetes patients.In this observational multicenter study, type 2 diabetic patients attending out-patient diabetes-clinic were evaluated. A detailed history of anti-diabetic medication, dose, duration, pioglitazone usage, time since initiation of pioglitazone, physical examination, biochemical tests and details pertaining to prevalent neuropathy, retinopathy and nephropathy were recorded. Details of bladder cancer or any malignancy (if present), time since diagnosis, risk factors for bladder cancer and histopathology records were noted. The study cohort was divided into two groups-pioglitazone ever users (Group A) and never users (Group B).A total of 8000 patients were screened out of which 1560 were excluded. Among 6440 included patients, 1056 (16.3%) patients were in group A and 5384 (83.6%) group B. Patients on pioglitazone were older (59.1 vs 57.7 years, p 0.001), had longer duration of diabetes (12.7 vs 10.6 years, p 0.001) with poor glycemic control (HbA1c 8.5 vs 8.3%, p 0.01). A total of 74 patients had prevalent bladder cancer [16 (1.5%) in Group A and 58 in Group B (1.0%)]. Prevalent bladder cancer was not significantly greater in ever-users (odds ratio OR = 1.29, 95% confidence interval CI, 0.83-2.00) compared to never-users (odds ratio OR = 0.94, 95% confidence interval CI, 0.834-1.061) of pioglitazone (p = 0.207). However, history of hematuria in pioglitazone-users; while older age (58 year), history of smoking and hematuria in the whole cohort were significant associated with bladder cancer. In the entire study cohort, 254 patients; 3.5% of males (128 out of 3575) and 4.6% of females (126 out of 2713) developed any malignancy. Age was significantly associated with prevalent malignancy in people with diabetes (odds ratio OR 1.036, 95% confidence interval CI: 1.022-1.051, p = 0.00) on multivariate forward regression.Pioglitazone use in Asian-Indians is not associated with an increased bladder cancer risk. However, pioglitazone should be restricted in individuals with history of hematuria. Age more than 58 years is a significant risk factor for development of any malignancy, particularly bladder cancer.

Published
2022

18. Impact of concurrent diabetes on periodontal health in patients with acromegaly

Author

Rose Kanwaljeet Kaur, Mili Gupta, Ashish Jain, Shipra Gupta, Akanksha Jain, Anil Bhansali, and Nandini Bhaskar

Subjects
Adult, Male, medicine.medical_specialty, Dental diseases, lcsh:Medicine, 030209 endocrinology & metabolism, Oral Health, Gastroenterology, Article, Transforming Growth Factor beta1, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Periodontal disease, Internal medicine, Diabetes mellitus, Acromegaly, medicine, Humans, In patient, Insulin-Like Growth Factor I, Adverse effect, lcsh:Science, Glycated Hemoglobin, Platelet-Derived Growth Factor, Multidisciplinary, business.industry, Human Growth Hormone, Interleukin-6, Significant difference, lcsh:R, 030206 dentistry, Luteinizing Hormone, Middle Aged, medicine.disease, Comorbidity, Magnetic Resonance Imaging, Prolactin, Diabetes Mellitus, Type 2, Pituitary Gland, Pituitary hormones, Female, lcsh:Q, Follicle Stimulating Hormone, business
Abstract

Previous studies have suggested excess GH/IGF1 secretion in patients with acromegaly is protective for periodontal health. Diabetes is prevalent comorbidity in patients of acromegaly and is associated with worsening of periodontal disease. The present study evaluates the periodontal health and cytokines status in treatment-naive active acromegaly patients with and without diabetes. Eleven patients, each of acromegaly with and without diabetes and 20 healthy controls were enrolled. Periodontal parameters were assessed. GCF and blood samples for IL-6, TGF-β1, and PDGF were obtained. Serum GH, IGF1, HbA1c, pituitary hormones and MRI sella were performed in patients with acromegaly. There was no significant difference in periodontal status of patients with acromegaly and healthy controls. However, a significant increase in serum IL-6 (p = 0.019) and TGF-β1 (p = 0.025) levels in patients with acromegaly was observed and all patients had concurrent hypogonadism. Nevertheless, the patients with acromegaly having diabetes had modestly higher CAL and PD and serum IL-6 levels (p = 0.051), but it could not exert adverse effects on periodontal health in presence of GH/IGF1 excess. GH/IGF1 excess did not exert a protective effect on periodontal status in acromegaly, possibly due to concurrent hypogonadism and opposing cytokines; however, it could mask the ill-effects of diabetes on periodontal health.

Published
2020

19. Cross‐cultural adaptation and psychometric evaluation of Hindi version of Diabetes <scp>Self‐Management</scp> Profile‐Self Report in Indian type 1 diabetes patients

Author

Anjana Barola, Devi Dayal, Sandeep Grover, Anil Bhansali, and Pramil Tiwari

Subjects
Cross-Cultural Comparison, Male, medicine.medical_specialty, Adolescent, Psychometrics, Endocrinology, Diabetes and Metabolism, India, 030209 endocrinology & metabolism, Odds, 03 medical and health sciences, 0302 clinical medicine, Cronbach's alpha, Diabetes mellitus, Adaptation, Psychological, Internal Medicine, Humans, Medicine, Cross-cultural, 030212 general & internal medicine, Child, Hindi, Type 1 diabetes, business.industry, Self-Management, Reproducibility of Results, medicine.disease, Exploratory factor analysis, language.human_language, Regimen, Diabetes Mellitus, Type 1, Pediatrics, Perinatology and Child Health, Physical therapy, language, Female, Self Report, business
Abstract

Background No validated measures exist for evaluating diabetes self-management in Indian type 1 diabetes (T1D) patients. Objective To cross culturally adapt and evaluate the psychometric properties of Hindi version of Diabetes Self-Management Profile-Self Report (DSMP-SR-Hindi) in Indian T1D patients. Methods Total 160 T1D patients and their parents participated in the study. The mean age of patients was 13.5 ± 2.5 years and HbA1c was 8.6 ± 2.2%. Results Exploratory factor analysis employing principle axis factoring with promax rotation was conducted. Monte Carlo parallel analysis identified three sub-scales instead of five sub-scales proposed in original version. Because of underlying ceiling and floor effects and insufficient loadings, five items were eliminated. Consequently, final Hindi version of DSMP-SR contained 19 items from DSMP-SR-24. Internal consistencies were adequate for overall scale (Cronbach's α = 0.835), identified sub-scales (Cronbach's α = 0.702-0.802) and comparable between genders. DSMP-19 total scores (r = -0.74) and three subscales correlated significantly with HbA1c (SMBG and Corrective Adjustments [r = -0.58], Exercise [r = -0.48], and Conformity to Diet and Insulin Routine [r = -0.64]). For every one SD improvement (11.2 marks) in DSMP-SR-Hindi score, odds of falling into poor glycaemic group (HbA1c > 7.5%) dropped to 0.242 times (95% CI 0.144-0.405; P Conclusions DSMP-SR-Hindi is a reliable and valid self-report measure of diabetes self-management behavior in Indian T1D patients. The revealed three subscales are reliable to use in isolation and across the genders. It will help in monitoring patient's progress in stepwise manner, ranging from their basic understanding of prescribed regimen to taking advance corrective actions in face of altered needs.

Published
2020

20. Wolfram syndrome: clinical and genetic profiling of a cohort from a tertiary care centre with characterization of the primary gonadal failure

Author

Ashutosh Rai, Pinaki Dutta, Ravimohan S. Mavuduru, Sanjay Kumar Bhadada, Akhilesh Sharma, Liza Das, Naresh K. Panda, Kim Vaiphei, Anil Bhansali, Vishali Gupta, Paramjeet Singh, and Sailesh Lodha

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Diabetic ketoacidosis, Wolfram syndrome, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Tertiary Care Centers, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Atrophy, Hypergonadotropic hypogonadism, Diabetes mellitus, Biopsy, medicine, Humans, medicine.diagnostic_test, business.industry, Hypogonadism, Wolfram Syndrome, Diabetic retinopathy, Genetic Profile, medicine.disease, Optic Atrophy, 030220 oncology & carcinogenesis, Diabetes insipidus, Female, business
Abstract

Wolfram syndrome (WFS) is a rare, monogenic neurodegenerative syndrome characterised by insulin requiring non-autoimmune diabetes mellitus (DM) and optic atrophy which are usually the earliest and commonest manifestations. However, there are other features which are under-recognized, adding to morbidity and premature mortality in these patients. Five patients (three males, two females) with genetically confirmed WFS at a single tertiary care centre were prospectively followed up. Their symptomatology, clinical profile, genetic analysis and radiology were analyzed. Multidisciplinary approach was used for comprehensive clinical care of this cohort. Patients with primary gonadal failure were subjected to biopsy and immunohistochemistry (IHC) for wolframin was performed. DM was the earliest presenting manifestation at 6.2 ± 1.3 years followed by optic atrophy at 10.4 ± 2.3 years, diabetes insipidus at 12 ± 2.1 years and deafness at 12.8 ± 2.1 years. All patients were autoantibody negative with low C-peptide(

Published
2020

21. Determinants of Tobacco Use among Children of a Rural Village in India: An Exploratory Qualitative Study

Author

Chaya Chhabra, Akanksha Goyal, Sunita Agarwal, Suman Bhansali, Ashish Sharma, and Kumar Gaurav Chhabra

Subjects
0301 basic medicine, Adult, Male, Parents, Rural Population, Health Knowledge, Attitudes, Practice, Adolescent, India, Context (language use), Social issues, Social Environment, tobacco, 03 medical and health sciences, Habits, Tobacco Use, Young Adult, 0302 clinical medicine, Role model, Environmental health, Humans, Family, Peer pressure, Child, Social Behavior, Functional illiteracy, Determinants, Qualitative Research, Smoking, General Medicine, Focus group, 030104 developmental biology, Cross-Sectional Studies, 030220 oncology & carcinogenesis, Female, Thematic analysis, Psychology, Qualitative research, Research Article
Abstract

Background Tobacco is one of the leading causes of preventable deaths. It is both a major social and health problem. According to National Sample Survey Organization of Government of India about 20 million children of ages 10-14 are estimated to be tobacco-addicted. There are grave consequences of tobacco both socially and also on health thus it is of utmost importance to understand the factors leading to its use and to plan strategies to reduce its intake. However, the health implications of this social issue in a rural context have not been explored. Aims and objective this study makes an attempt to explore the health and social implications of tobacco usage by the children below the age of 14 years in hamlet. Materials and methods The present study employed a qualitative study design. Data was collected using focus group discussion and in-depth interview of key informants. Thematic analysis for exploring the explicit and implicit meanings within the data was done. The themes which emerged were knowledge about tobacco and the various products available, children and parents' tobacco use and habits, the health and social implication of tobacco use, reasons for tobacco use by the children. Results It was found tobacco use by the children was very common in the community. Parent, peer pressure, sibling pressure were found to be playing important role in the initiation of tobacco habit by the child. Further illiteracy and lack of awareness was also lead to tobacco use among children. Conclusion The study identifies education and awareness of parents about the ill-effects of tobacco play an important role as parents act as role model for their children, thus equal stress should be laid in improving the parental habits. Even raising the prices of tobacco products can help in controlling this habit. .

Published
2020

22. Unravelling a novel, promising and convenient tool for differential diagnosis of delayed puberty: GnRHa-stimulated inhibin B (GnRH-iB)

Author

S, Chaudhary, R, Walia, A, Bhansali, D, Dayal, N, Sachdeva, T, Singh, and S K, Bhadada

Subjects
Male, Gonadotropin-Releasing Hormone, Puberty, Delayed, Diagnosis, Differential, Hypogonadism, Humans, Female, Prospective Studies, Luteinizing Hormone, Follicle Stimulating Hormone, Child
Abstract

Etiological diagnosis of delayed puberty is difficult. Despite availability of various basal and stimulation tests differentiation between constitutional delay in puberty and hypogonadotropic hypogonadism is still challenging.To elucidate the role of GnRH agonist-stimulated inhibin B (GnRH-iB) for the differential diagnosis of delayed puberty.Participants were recruited into "exploratory cohort" (n = 39) and "validation cohort" (n = 16). "Exploratory cohort" included children with spontaneous puberty and patients with hypogonadotropic hypogonadism. "Validation cohort" constituted children who presented with delayed puberty.GnRHa (Triptorelin) stimulation test along with measurement of inhibin B level at 24 h after GnRHa injection was performed in all the study participants. Cut-offs for GnRH-iB were derived from the "exploratory cohort". These cut-offs were applied to the "validation cohort". Basal LH, basal inhibin B(INH-B), GnRHa-stimulated LH at 4 h (GnRH-LH) and GnRH-iB were evaluated for the prediction of onset of puberty on prospective follow-up.GnRH-iB at a cut-off value of 113.5 pg/ml in boys and 72.6 pg/ml in girls had 100% sensitivity and specificity for the documentation of puberty. In the "validation cohort" basal LH, basal INH-B, GnRH-LH, and GnRH-iB had a diagnostic accuracy of 68.75%, 81.25%, 68.75% and 93.75% respectively, for the prediction of onset of puberty. Basal LH, basal INH-B and GnRH-LH used alone or in combination were inferior to GnRH-iB used alone.GnRHa-stimulated inhibin B (GnRH-iB) is a convenient and easily employable test for the differentiation of constitutional delay in puberty from hypogonadotropic hypogonadism.CTRI/2019/10/021570.

Published
2022

23. Early Initiation of Temozolomide Therapy May Improve Response in Aggressive Pituitary Adenomas

Author

Liza Das, Nidhi Gupta, Pinaki Dutta, Rama Walia, Kim Vaiphei, Ashutosh Rai, Bishan Dass Radotra, Kirti Gupta, Sreejesh Sreedharanunni, Chirag Kamal Ahuja, Anil Bhansali, Manjul Tripathi, Ridhi Sood, and Sivashanmugam Dhandapani

Subjects
Adenoma, Adult, Male, Endocrinology, Diabetes and Metabolism, India, temozolomide, Diseases of the endocrine glands. Clinical endocrinology, Cohort Studies, Endocrinology, controlled disease, Early Medical Intervention, Humans, Neoplasm Invasiveness, Pituitary Neoplasms, aggressive pituitary adenomas, Retrospective Studies, Original Research, early therapy, Middle Aged, Prognosis, RC648-665, Neoadjuvant Therapy, digestive system diseases, Treatment Outcome, Female, MGMT
Abstract

IntroductionAggressive pituitary adenomas (APAs) are, by definition, resistant to optimal multimodality therapy. The challenge lies in their early recognition and timely management. Temozolomide is increasingly being used in patients with APAs, but evidence supporting a favorable response with early initiation is lacking.MethodsThis was a single-center study of all patients with APAs who received at least 3 cycles of temozolomide (150–200 mg/m2). Their baseline clinico-biochemical and radiological profiles were recorded. Immunohistochemical evaluation for cell-cycle markers O6-methylguanine-DNA methyltransferase (MGMT), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), MutL homolog 1 (MLH1), and postmeiotic segregation increased 2 (PMS2) was performed, and h-scores (product of the number of positive cells and staining intensity) were calculated. Response was assessed in terms of radiological response using the RECIST criteria. Patients with controlled disease (≥30% reduction in tumor volume) were classified as responders.ResultsThe study comprised 35 patients (48.6% acromegaly, 37.1% prolactinomas, and 14.3% non-functioning pituitary adenomas). The median number of temozolomide (TMZ) cycles was 9 (IQR 6–14). Responders constituted 68.6% of the cohort and were more likely to have functional tumors, a lower percentage of MGMT-positive staining cells, and lower MGMT h-scores. There was a significantly longer lag period in the initiation of TMZ therapy in non-responders as compared with responders (median 36 vs. 15 months, p = 0.01). ROC-derived cutoffs of 31 months for the duration between diagnosis and TMZ initiation, low-to-intermediate MGMT positivity (40% tumor cells), and MGMT h-score of 80 all had a sensitivity exceeding 80% and a specificity exceeding 70% to predict response.ConclusionEarly initiation of TMZ therapy, functional tumors, and low MGMT h-score predict a favorable response to TMZ in APAs.

Published
2021

24. Remission in Cushing's disease is predicted by cortisol burden and its withdrawal following pituitary surgery

Author

Anil Bhansali, Rama Walia, Sanjay Kumar Bhadada, Aditya Dutta, Pinaki Dutta, Rosario Pivonello, Naresh Sachdeva, Abhishek Hajela, Chiara Simeoli, Chirag Kamal Ahuja, Nishkarsh Gupta, Uma Nahar Saikia, Sivashanmugam Dhandapani, Dutta, A., Gupta, N., Walia, R., Bhansali, A., Dutta, P., Bhadada, S. K., Pivonello, R., Ahuja, C. K., Dhandapani, S., Hajela, A., Simeoli, C., Sachdeva, N., and Saikia, U. N.

Subjects
Male, Hydrocortisone, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Pituitary-Adrenal System, Disease, Logistic regression, Tertiary care, Gastroenterology, 0302 clinical medicine, Endocrinology, Glucocorticoid, Retrospective Studie, Recurrence, Relapse, Cushing’s disease, Magnetic Resonance Imaging, Treatment Outcome, 030220 oncology & carcinogenesis, Pituitary Gland, Female, medicine.drug, Human, Adult, medicine.medical_specialty, Hypothalamo-Hypophyseal System, Remission, Hormone Replacement Therapy, 030209 endocrinology & metabolism, Follow-Up Studie, 03 medical and health sciences, Young Adult, Diabetes mellitus, Internal medicine, Sphenoid Bone, medicine, Humans, Pituitary ACTH Hypersecretion, Glucocorticoids, Retrospective Studies, Transsphenoidal surgery, business.industry, Cushing's disease, Recovery of Function, medicine.disease, Pituitary surgery, business, Predictor, Follow-Up Studies
Abstract

Aim: To ascertain the predictors of remission and relapse in patients of Cushing’s disease (CD) undergoing pituitary transsphenoidal surgery (TSS). Methods: Patients with CD subjected to TSS over 35 years at a tertiary care center were included. Patients were grouped into remission and persistent disease at 1 year after surgery, and were further followed up for relapse. Demographic, clinical, biochemical, histological, radiological and post-operative follow-up parameters were analyzed. Results: Of the 152 patients of CD, 145 underwent TSS. Remission was achieved in 95 (65.5%) patients at 1 year. Patients in remission had shorter duration of symptoms prior to presentation (p = 0.009), more frequent presence of proximal myopathy (p = 0.038) and a tumor size of < 2.05 cm (p = 0.016) in comparison to those with persistent disease. Post-TSS, immediate post-operative 0800-h cortisol (< 159.85 nmol/L; p = 0.001), histological confirmation of tumor (p = 0.045), duration of glucocorticoid replacement (median 90 days; p = 0.001), non-visualization of tumor on MRI (p = 0.003), new-onset hypogonadism (p = 0.001), 3-month 0800-h cortisol (< 384.9 nmol/L; p = 0.001), resolution of diabetes (p = 0.001) and hypertension (p = 0.001), and recovery of hypothalamic–pituitary–adrenal axis (p = 0.018) favored remission. In logistic regression model, requirement of glucocorticoid replacement (p = 0.033), and resolution of hypertension post-TSS (p = 0.003) predicted remission. None of the parameters could predict relapse. Conclusion: The study could ascertain the predictors of remission in CD. Apart from the tumor characteristics, surgical aspects and low post-operative 0800-h cortisol, the results suggest that baseline clinical parameters, longer glucocorticoid replacement, and resolution of metabolic complications post-TSS predict remission in CD. Long-term follow-up is essential to look for relapse.

Published
2020

25. Molecular Imaging Targeting Corticotropin-releasing Hormone Receptor for Corticotropinoma: A Changing Paradigm

Author

Harmandeep Singh, Rajender Kumar, Apinderpreet Singh, Anil Bhansali, Bhagwant Rai Mittal, Rosario Pivonello, Chirag Kamal Ahuja, Rajesh Chhabra, Rakhee Vatsa, Naresh Sachdeva, Jaya Shukla, Sivashanmugam Dhandapani, Sanjay Kumar Bhadada, Nivedita Rana, Rama Walia, Uma Nahar, Sushant Sahoo, Rahul Gupta, Pinaki Dutta, Walia, Rama, Gupta, Rahul, Bhansali, Anil, Pivonello, Rosario, Kumar, Rajender, Singh, Harmandeep, Ahuja, Chirag, Chhabra, Rajesh, Singh, Apinderpreet, Dhandapani, Sivashanmugam, Sahoo, Sushant, Rana, Nivedita, Vatsa, Rakhee, Dutta, Pinaki, Bhadada, Sanjay Kumar, Sachdeva, Naresh, Mittal, B R, Nahar, Uma, and Shukla, Jaya

Subjects
Diagnostic Imaging, Adenoma, Adult, Male, endocrine system, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Corticotropin-releasing hormone receptor, India, Gallium Radioisotopes, Petrosal Sinus Sampling, Biochemistry, Receptors, Corticotropin-Releasing Hormone, Diagnosis, Differential, Young Adult, Endocrinology, BIPSS, Anterior pituitary, Adrenocorticotropic Hormone, In vivo, Pituitary adenoma, Internal medicine, Medicine, Humans, Receptor, Cushing Syndrome, medicine.diagnostic_test, business.industry, Biochemistry (medical), Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Molecular Imaging, 68Ga CRH PET-CT, ACTH Syndrome, Ectopic, medicine.anatomical_structure, ACTH-Secreting Pituitary Adenoma, Cushing', Female, business, hormones, hormone substitutes, and hormone antagonists, Hormone, MRI
Abstract

Background Corticotrophin-releasing hormone (CRH) is the major regulator of adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary and acts via CRH-1 receptors (CRH-1R). Corticotropinoma though autonomous, still retain their responsiveness to CRH and hence, we hypothesize that in vivo detection of CRH-1 receptors on pituitary adenoma using Gallium-68 (68Ga)-tagged CRH can indicate the functionality of adenoma, and combining it with positron emission tomography-computed tomography (PET-CT) can provide requisite anatomical information. Methods Subjects with ACTH-dependent Cushing’s syndrome (CS) (n = 27, 24 with Cushing’s disease [CD], 3 with ectopic CS [ECS]) underwent 68Ga CRH PET-CT. Two nuclear medicine physicians read these images for adenoma delineation and superimposed them on magnetic resonance imaging (MRI) sella. The information provided was used for intraoperative navigation and compared with operative and histopathological findings. Findings 68Ga CRH PET-CT correctly delineated corticotropinoma in all the 24 cases of CD, including the 10 cases with adenoma size < 6mm (4 cases were negative on MRI). Corticotropinoma location on 68Ga CRH PET fusion images with MRI were concordant with operative findings and were further confirmed on histopathology. There was no tracer uptake in the pituitary in 2 patients with ECS, while, in another, the diffuse uptake in pituitary suggested ectopic CRH production. Conclusion 68Ga CRH PET-CT represents a novel, noninvasive molecular imaging, targeting CRH receptors that not only delineate corticotropinoma and provides the surgeon with valuable information for intraoperative tumor navigation, but also helps in differentiating a pituitary from an extra-pituitary source of ACTH-dependent CS. Funding None.

Published
2020

26. Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

Author

Gregory G. Schwartz, Michael Szarek, Vera A. Bittner, Rafael Diaz, Shaun G. Goodman, J. Wouter Jukema, Ulf Landmesser, Patricio López-Jaramillo, Garen Manvelian, Robert Pordy, Michel Scemama, Peter R. Sinnaeve, Harvey D. White, Ph Gabriel Steg, P.h. Gabriel Steg, Deepak L. Bhatt, Robert A. Harrington, Andreas M. Zeiher, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Corinne Hanotin, Guillaume Lecorps, Angèle Moryusef, William J. Sasiela, Jean-François Tamby, Philip E. Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N. Gotcheva, Juan-Carlos Prieto, Huo Yong, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Steen Hvitfeldt Poulsen, Margus Viigimaa, Markku S. Nieminen, Nicolas Danchin, Vakhtang Chumburidze, Nikolaus Marx, Evangelos Liberopoulos, Pablo Carlos Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M. Correa Flores, Rody G. Sy, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Jan Murin, Zlatko Fras, Anthony J. Dalby, José Tuñón, H. Asita de Silva, Emil Hagström, Christian Müller, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean F.P. van Diepen, Matthew D. Wilson, Andrew Tze-Kay Yan, Lilia B. Schiavi, Marcelo Garrido, Andrés F. Alvarisqueta, Sonia A. Sassone, Anselmo P. Bordonava, Alberto E. Alves De Lima, Jorge M. Schmidberg, Ernesto A. Duronto, Orlando C. Caruso, Leonardo P. Novaretto, Miguel Angel Hominal, Oscar R. Montaña, Alberto Caccavo, Oscar A. Gomez Vilamajo, Alberto J. Lorenzatti, Luis R. Cartasegna, Gustavo A. Paterlini, Ignacio J. Mackinnon, Guillermo D. Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R. Codutti, Horacio O. Jure, Julio O.E. Bono, Adrian D. Hrabar, Julio A. Vallejos, Rodolfo A. Ahuad Guerrero, Federico Novoa, Cristian A. Patocchi, Cesar J. Zaidman, Maria E. Giuliano, Ricardo D. Dran, Marisa L. Vico, Gabriela S. Carnero, Pablo N. Guzman, Juan C. Medrano Allende, Daniela F. Garcia Brasca, Miguel H. Bustamante Labarta, Sebastian Nani, Eduardo D.S. Blumberg, Hugo R. Colombo, Alberto Liberman, Victorino Fuentealba, Hector L. Luciardi, Gabriel D. Waisman, Mario A. Berli, Ruben O. Garcia Duran, Horacio G. Cestari, Hugo A. Luquez, Jorge A. Giordano, Silvia S. Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon H. Waites, Nicholas Collins, Allan Soward, Chris L.S. Hii, James Shaw, Margaret A. Arstall, John Horowitz, Daniel Ninio, James F. Rogers, David Colquhoun, Romulo E. Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam J. Lehman, Constantine Aroney, Steven G.M. Coverdale, Paul J. Garrahy, Gregory Starmer, Mark Sader, Patrick A. Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Mathias C.M. Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Azra Durak-Nalbantic, Mehmed Kulić, Dusko Vulic, Adis Muslibegovic, Boris Goronja, Gilmar Reis, Luciano Sousa, Jose C. Nicolau, Flavio E. Giorgeto, Ricardo P. Silva, Lilia Nigro Maia, Rafael Rech, Paulo R.F. Rossi, Maria José A.G. Cerqueira, Norberto Duda, Renato Kalil, Adrian Kormann, José Antonio M. Abrantes, Pedro Pimentel Filho, Ana Priscila Soggia, Mayler O.N. de Santos, Fernando Neuenschwander, Luiz C. Bodanese, Yorghos L. Michalaros, Freddy G. Eliaschewitz, Maria H. Vidotti, Paulo E. Leaes, Roberto V. Botelho, Sergio Kaiser, Euler Roberto F. Fernandes Manenti, Dalton B. Precoma, Jose C. Moura Jorge, Pedro Silva, Jose A. Silveira, Wladmir Saporito, Jose A. Marin Neto, Gilson S. Feitosa, Luiz Eduardo F. Ritt, Juliana A. de Souza, Fernando Costa, Weimar K.S.B. Souza, Helder J.L. Reis, Leandro Machado, José Carlos Aidar Ayoub, Georgi V. Todorov, Fedya P. Nikolov, Elena S. Velcheva, Maria L. Tzekova, Haralambi O. Benov, Stanislav L. Petranov, Haralin S. Tumbev, Nina S. Shehova-Yankova, Dimitar T. Markov, Dimitar H. Raev, Mihail N. Mollov, Kostadin N. Kichukov, Katya A. Ilieva-Pandeva, Raya Ivanova, Maryana Gospodinov, Valentina M. Mincheva, Petar V. Lazov, Bojidar I. Dimov, Manohara Senaratne, James Stone, Jan Kornder, Stephen Pearce, Danielle Dion, Daniel Savard, Yves Pesant, Amritanshu Pandey, Simon Robinson, Gilbert Gosselin, Saul Vizel, Gordon Hoag, Ronald Bourgeois, Anne Morisset, Eric Sabbah, Bruce Sussex, Simon Kouz, Paul MacDonald, Ariel Diaz, Nicolas Michaud, David Fell, Raymond Leung, Tycho Vuurmans, Christopher Lai, Frank Nigro, Richard Davies, Gustavo Nogareda, Ram Vijayaraghavan, John Ducas, Serge Lepage, Shamir Mehta, James Cha, Robert Dupuis, Peter Fong, Sohrab Lutchmedial, Josep Rodes-Cabau, Hussein Fadlallah, David Cleveland, Thao Huynh, Iqbal Bata, Adnan Hameed, Cristian Pincetti, Sergio Potthoff, Juan C. Prieto, Monica Acevedo, Arnoldo Aguirre, Margarita Vejar, Mario Yañez, Guillermo Araneda, Mauricio Fernandez, Luis Perez, Paola Varleta, Fernando Florenzano, Laura Huidobro, Carlos A. Raffo, Claudia Olivares, Leonardo Nahuelpan, Humberto Montecinos, Jiyan Chen, Yugang Dong, Weijian Huang, Jianzhong Wang, Shi'An Huang, Zhuhua Yao, Xiang Li, Lan Cui, Wenhua Lin, Yuemin Sun, Jingfeng Wang, Jianping Li, Xuelian Zhang, Hong Zhu, Dandan Chen, Lan Huang, Shaohong Dong, Guohai Su, Biao Xu, Xi Su, Xiaoshu Cheng, Jinxiu Lin, Wenxia Zong, Huanming Li, Yi Feng, Dingli Xu, Xinchun Yang, Yuannan Ke, Xuefeng Lin, Zheng Zhang, Zeqi Zheng, Zhurong Luo, Yundai Chen, Chunhua Ding, Yi Zhong, Yang Zheng, Xiaodong Li, Daoquan Peng, Shuiping Zhao, Ying Li, Xuebo Liu, Meng Wei, Shaowen Liu, Yihua Yu, Baiming Qu, Weihong Jiang, Yujie Zhou, Xingsheng Zhao, Zuyi Yuan, Ying Guo, Xiping Xu, Xubo Shi, Junbo Ge, Guosheng Fu, Feng Bai, Weiyi Fang, Xiling Shou, Xiangjun Yang, Jian'An Wang, Meixiang Xiang, Yingxian Sun, Qinghua Lu, Ruiyan Zhang, Jianhua Zhu, Yizhou Xu, Zhongcai Fan, Tianchang Li, Chun Wu, Nicolas Jaramillo, Gregorio Sanchez Vallejo, Diana C. Luna Botia, Rodrigo Botero Lopez, Dora I. Molina De Salazar, Alberto J. Cadena Bonfanti, Carlos Cotes Aroca, Juan Diego Higuera, Marco Blanquicett, Sandra I. Barrera Silva, Henry J. Garcia Lozada, Julian A. Coronel Arroyo, Jose L. Accini Mendoza, Ricardo L. Fernandez Ruiz, Alvaro M. Quintero Ossa, Fernando G. Manzur Jatin, Aristides Sotomayor Herazo, Jeffrey Castellanos Parada, Rafael Suarez Arambula, Miguel A. Urina Triana, Angela M. Fernandez Trujillo, Maja Strozzi, Siniša Car, Melita Jerić, Davor Miličić, Martina Lovrić Benčić, Hrvoje Pintarić, Đeiti Prvulović, Jozica Šikić, Viktor Peršić, Dean Mileta, Kresimir Štambuk, Zdravko Babić, Vjekoslav Tomulic, Josip Lukenda, Stanka Mejic-Krstulovic, Boris Starcevic, Jindrich Spinar, David Horak, Zdenek Velicka, Josef Stasek, David Alan, Vilma Machova, Ales Linhart, Vojtech Novotny, Vladimir Kaucak, Richard Rokyta, Robert Naplava, Zdenek Coufal, Vera Adamkova, Ivo Podpera, Jiri Zizka, Zuzana Motovska, Ivana Marusincova, Premysl Svab, Petr Heinc, Jiri Kuchar, Petr Povolny, Jiri Matuska, Steen H. Poulsen, Bent Raungaard, Peter Clemmensen, Lia E. Bang, Ole May, Morten Bøttcher, Jens D. Hove, Lars Frost, Gunnar Gislason, John Larsen, Peter Betton Johansen, Flemming Hald, Peter Johansen, Jørgen Jeppesen, Tonny Nielsen, Kjeld S. Kristensen, Piotr Maria Walichiewicz, Jens D. Lomholdt, Ib C. Klausen, Peter Kaiser Nielsen, Flemming Davidsen, Lars Videbaek, Mai Soots, Veiko Vahula, Anu Hedman, Üllar Soopõld, Kaja Märtsin, Tiina Jurgenson, Arved Kristjan, Heikki Huikuri, Juhani Airaksinen Pierre Coste, Emile Ferrari, Olivier Morel, Gilles Montalescot, Jacques Machecourt, Gilles Barone-Rochette, Jacques Mansourati, Yves Cottin, Florence Leclercq, Abdelkader Belhassane, Nicolas Delarche, Franck Boccara, Franck Paganelli, Jérôme Clerc, Francois Schiele, Victor Aboyans, Vincent Probst, Jacques Berland, Thierry Lefèvre, Bernard Citron, Irakli Khintibidze, Tamaz Shaburishvili, Zurab Pagava, Ramaz Ghlonti, Zaza Lominadze, George Khabeishvili, Rayyan Hemetsberger, Kemala Edward, Ursula Rauch-Kröhnert, Matthias Stratmann, Karl-Friedrich Appel, Ekkehard Schmidt, Heyder Omran, Christoph Stellbrink, Thomas Dorsel, Emmanouil Lianopoulos, Hans Friedrich Vöhringer, Roger Marx, Andreas Zirlik, Detlev Schellenberg, Thomas Heitzer, Ulrich Laufs, Christian Werner, Stephan Gielen, Sebastian Nuding, Bernhard Winkelmann, Steffen Behrens, Karsten Sydow, Mahir Karakas, Gregor Simonis, Thomas Muenzel, Nikos Werner, Stefan Leggewie, Dirk Böcker, Rüdiger Braun-Dullaeus, Nicole Toursarkissian, Michael Jeserich, Matthias Weißbrodt, Tim Schaeufele, Joachim Weil, Heinz Völler, Johannes Waltenberger, Mohammed Natour, Susanne Schmitt, Dirk Müller-Wieland, Stephan Steiner, Lothar Heidenreich, Elmar Offers, Uwe Gremmler, Holger Killat, Werner Rieker, Sotiris Patsilinakos, Athanasios Kartalis, Athanassios Manolis, Dimitrios Sionis, Geargios Chachalis, Ioannis Skoumas, Vasilios Athyros, Panagiotis Vardas, Frangkiskos Parthenakis, John Lekakis, Apostolos Hatzitolios, Sergio R. Fausto Ovando, Juan L. Arango Benecke, Edgar R. Rodriguez De Leon, Bryan P.Y. Yan, David C.W. Siu, Tibor Turi, Bela Merkely, Imre Ungi, Geza Lupkovics, Lajos Nagy, András Katona, István Édes, Gábor Müller, Iván Horvath, Tibor Kapin, Zsolt Szigeti, József Faluközy, Mukund Kumbla, Manjinder Sandhu, Sharath Annam, Naveen Reddy Proddutur, Reddy Regella, Rajendra K. Premchand, Ajaykumar Mahajan, Sudhir Pawar, Atul D. Abhyanakar, Prafulla Kerkar, Ravishankar A. Govinda, Abraham Oomman, Dhurjati Sinha, Sachin N. Patil, Dhiman Kahali, Jitendra Sawhney, Abhijeet B. Joshi, Sanjeev Chaudhary, Pankaj Harkut, Santanu Guha, Sanjay Porwal, Srimannarayana Jujjuru, Ramesh B. Pothineni, Minguel R. Monteiro, Aziz Khan, Shamanna S. Iyengar, Jasprakash Singh Grewal, Manoj Chopda, Mahesh C. Fulwani, Aparna Patange, Patil Sachin, Vijay K. Chopra, Naresh K. Goyal, Rituparna Shinde, Gajendra V. Manakshe, Nitin Patki, Sumeet Sethi, Vengatesh Munusamy, Sunil Karnaand Sunil Thanvi, Srilakshmi Adhyapak, Chandrakant Patil, Ulhas Pandurangi, Rishabh Mathur, Jugal Gupta, Suhas Kalashetti, Ajit Bhagwat, Bagirath Raghuraman, Shiv Kumar Yerra, Prasant Bhansali, Rohidas Borse, Patil Rahul, Srihari Das, Vinay Kumar, Jabir Abdullakutty, Shireesh Saathe, Priya Palimkar, Jabir Abdullkutty, Shireesh Sathe, Shaul Atar, Michael Shechter, Morris Mosseri, Yaron Arbel, Chorin Ehud, Havakuk Ofer, Chaim Lotan, Uri Rosenschein, Amos Katz, Yaakov Henkin, Adi Francis, Marc Klutstein, Eugenia Nikolsky, Robert Zukermann, Yoav Turgeman, Majdi Halabi, Alon Marmor, Ran Kornowski, Michael Jonas, Offer Amir, Yonathan Hasin, Yoseph Rozenman, Shmuel Fuchs, Vered Zvi, Osamah Hussein, Dov Gavish, Zvi Vered, Yoseph Caraco, Mazen Elias, Naveh Tov, Efrat Wolfovitz, Michael Lishner, Nizar Elias, Giancarlo Piovaccari, Annamaria De Pellegrin, Raffaella Garbelotto, Gabriele Guardigli, Valgimigli Marco, Giovanni Licciardello, Carla Auguadro, Filippo Scalise, Claudio Cuccia, Alessandro Salvioni, Giuseppe Musumeci, Michelle Senni, Paolo Calabrò, Salvatore Novo, Pompilio Faggiano, Marco Metra, Nicoletta B. De Cesare, Sergio Berti, Claudio Cavallini, Enrico Puccioni, Marcello Galvani, Maurizio Tespili, Piermarco Piatti, Michela Palvarini, Giuseppe De Luca, Roberto Violini, Alessandro De Leo, Zoran Olivari, Pasquale Perrone Filardi, Maurizio Ferratini, Vittorio Racca, Kazuoki Dai, Yuji Shimatani, Haruo Kamiya, Kenji Ando, Yoshihiro Takeda, Yoshihiro Morino, Yoshiki Hata, Kazuo Kimura, Koichi Kishi, Ichiro Michishita, Hiroki Uehara, Toshinori Higashikata, Atsushi Hirayama, Keiji Hirooka, Yasuji Doi, Satoru Sakagami, Shuichi Taguchi, Akihiro Koike, Hiroyuki Fujinaga, Shinji Koba, Ken Kozuma, Tomohiro Kawasaki, Yujiro Ono, Masatoshi Shimizu, Yousuke Katsuda, Atsuyuki Wada, Toshiro Shinke, Junya Ako, Kenshi Fujii, Toshiyuki Takahashi, Tomohiro Sakamoto, Koichi Nakao, Yutaka Furukawa, Hiroshi Sugino, Ritsu Tamura, Toshiaki Mano, Masaaki Uematsu, Noriaki Utsu, Kashima Ito, Takuya Haraguchi, Katsuhiko Sato, Yasunori Ueda, Akira Nishibe, Kazuteru Fujimoto, Motomaru Masutani, Jung Han Yoon, Hack-Lyoung Kim, Hun Sik Park, In-Ho Chae, Moo Hyun Kim, Myung Ho Jeong, Seungwoon Rha, Chongjin Kim, Hae Young Kim, Taekjong Hong, Seung-Jea Tahk, Youngkwon Kim, Arija Busmane, Natalija Pontaga, Aldis Strelnieks, Iveta Mintale, Iveta Sime, Zaneta Petrulioniene, Roma Kavaliauskiene, Ruta Jurgaitiene, Gintare Sakalyte, Rimvydas Slapikas, Sigute Norkiene, Nerijus Misonis, Aleksandras Kibarskis, Raimondas Kubilius, Stojko Bojovski, Nensi Lozance, Aleksandar Kjovkaroski, Snezana Doncovska, Tiong Kiam Ong, Sazzli Kasim, Oteh Maskon, Balachandran Kandasamy, Houng B. Liew, Wan Mohd Izani Wan Mohamed, Armando García Castillo, Jorge Carrillo Calvillo, Pedro Fajardo Campos, Juan Carlos Núñez Fragoso, Edmundo Alfredo Bayram Llamas, Marco Antonio Alcocer Gamba, Jaime Carranza Madrigal, Luis Gerardo González Salas, Enrique López Rosas, Belinda González Díaz, Eduardo Salcido Vázquez, Alfredo Nacoud Ackar, Guillermo Antonio Llamas Esperón, Carlos Rodolfo Martínez Sánchez, María Guerrero De Leon, Rodrigo Suarez Otero, Guillermo Fanghänel Salmón, Jesús Antonio Pérez Ríos, José Angel Garza Ruíz, Robert W. Breedveld, Margriet Feenema-Aardema, Alida Borger-Van Der Burg, Pieter A.M. Hoogslag, Harry Suryapranata, Antonius Oomen, Paulus Van Haelst, Margriet Feenema-Aradema, Jacobijne J. Wiersma, Dirk Basart, Ruud M.A. Van Der Wal, Peter Zwart, Pascalle Monraats, Henricus Van Kesteren, Ioannis Karalis, Johan Jukema, Gerardus J.E. Verdel, Bart R.G. Brueren, Roland PTh Troquay, Eric P. Viergever, Nadea Y.Y. Al-Windy, Gerard L. Bartels, Jan H. Cornel, Walter R.M. 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Bravo Mannucci, Javier Heredia Landeo, Nassip C. Llerena Navarro, Yudy M. Roldan Concha, Víctor E. Rodriguez Chavez, Henry A. Anchante Hernandez, Carlos A. Zea Nunez, Walter Mogrovejo Ramos, Arthur Ferrolino, Rosa Allyn G. Sy, Louie Tirador, Generoso Matiga, Raul Martin Coching, Alisa Bernan, Gregorio Rogelio, Dante D. Morales, Edgar Tan, Dennis Jose Sulit, Adrian Wlodarczak, Krystyna Jaworska, Grzegorz Skonieczny, Lidia Pawlowicz, Pawel Wojewoda, Benita Busz-Papiez, Janusz Bednarski, Aleksander Goch, Pawel Staneta, Elzbieta Dulak, Krzysztof Saminski, Wlodzimierz Krasowski, Wanda Sudnik, Aleksander Zurakowski, Marcin Skorski, Roman Lysek, Beata Miklaszewicz, Jacek Kubica, Jan Andrzej Lipko, Edyta Kostarska-Srokosz, Marek Piepiorka, Anna Drzewiecka, Ryszard Sciborski, Arkadiusz Stasiewski, Tomasz Blicharski, Leszek Bystryk, Michal Szpajer, Marek Korol, Tomasz Czerski, Ewa Mirek-Bryniarska, Jacek Gniot, Andrzej Lubinski, Jerzy Gorny, Edward Franek, Grzegorz Raczak, Hanna Szwed, Pedro Monteiro, Jose Mesquita Bastos, Helder H. Pereira, Dinis Martins, Filipe Seixo, Carlos Mendonça, Ana Botelho, Francisca Caetano, Bogdan Minescu, Octavian Istratoaie, Dan N. Tesloianu, Gabriel Cristian, Silviu Dumitrescu, Cristian G.C. Podoleanu, Mircea C.A. Constantinescu, Cristina M. Bengus, Constantin Militaru, Doina Rosu, Irinel R. Parepa, Adrian V. Matei, Tom M. Alexandru, Mihaela Malis, Ioan Coman, Rodica Stanescu-Cioranu, Doina Dimulescu, Yury Shvarts, Olga Orlikova, Zhanna Kobalava, Olga L. Barbarash, Valentin Markov, Nadezhda Lyamina, Alexander Gordienko, Konstantin Zrazhevsky, Alexander Y. Vishnevsky, Victor Gurevich, Raisa Stryuk, Nikita V. Lomakin, Igor Bokarev, Tatiana Khlevchuk, Sergey Shalaev, Larisa Khaisheva, Petr Chizhov, Inna Viktorova, Natalya Osokina, Vladimir Shchekotov, Evgenia Akatova, Galina Chumakova, Igor Libov, Mikhail I. Voevoda, Tatyana V. Tretyakova, Evgeny Baranov, Sergey Shustov, Sergey Yakushin, Ivan Gordeev, Niiaz Khasanov, Olga Reshetko, Tatiana Sotnikova, Olga Molchanova, Konstantin Nikolaev, Liudmila Gapon, Elena Baranova, Zaur Shogenov, Elena Kosmachova, Yuriy Karpov, Anton Povzun, Liudmila Egorova, Vadim V. Tyrenko, Igor G. Ivanov, Masterov Ilya, Sergey Kanorsky, Dragan Simic, Nikola Ivanovic, Goran Davidovic, Nebojsa Tasic, Milika R. Asanin, Stevo Stojic, Svetlana R. Apostolovic, Stevan Ilic, Biljana Putnikovic Tosic, Aleksandar Stankovic, Aleksandra Arandjelovic, Slavica Radovanovic, Branislava Todic, Jovan Balinovac, Dragan V. Dincic, Petar Seferovic, Ana Karadzic, Slobodan Dodic, Sinisa Dimkovic, Tamara Jakimov, Kian-Keong Poh, Hean Yee Ong, Justin Tang I-Shing, Karol Micko, Jan Nociar, Daniel Pella, Peter Fulop, Marian Hranai, Juraj Palka, Juraj Mazur, Ivan Majercák, Andrej Dzupina, František Fazekas, Jozef Gonsorcik, Viliam Bugan, Juraj Selecky, Gabriel Kamensky, Jaroslava Strbova, Rudolf Smik, Andrej Dukat, Peter Olexa, Ivan Žuran, Janez Poklukar, Nataša Černič Šuligoj, Matija Cevc, Henry P. Cyster, Naresh Ranjith, Clive Corbett, Junaid Bayat, Ellen Makoali Makotoko, Hendrik du Toit Theron, Ilse E. Kapp, Matthys M. de V Basson, Hanlie Lottering, Dina Van Aswegen, Louis J. Van Zyl, Peter J. Sebastian, Thayabran Pillay, Jan A. Saaiman, Patrick J. Commerford, Soraya Cassimjee, Garda Riaz, Iftikhar O. Ebrahim, Mahomed Sarvan, Joseph H. Mynhardt, Helmuth Reuter, Rajendran Moodley, Manuel Vida, Angel R. Cequier Fillat, Vicente Bodí Peris, Francisco Fuentes Jimenez, Francisco Marín, Jose M. Cruz Fernández, Rafael Jesus Hidalgo Urbano, Blas Gil-Extremera, Pablo Toledo, Fernando Worner Diz, David Garcia-Dorado, Andres Iñiguez, José Tuñón Fernández, Jose R. Gonzalez-Juanatey, Javier Fernandez Portales, Fernando Civeira Murillo, Laia Matas Pericas, Jose Luis Zamorano, Manuel De Mora Martin, Jordi Bruguera Cortada, Joaquin J. Alonso Martin, Jose Maria Serrano Antolin, José R. De Berrazueta Fernández, José Antonio Vázquez de Prada, Jose Francisco Díaz Fernández, José Alberto García Lledó, Juan Cosín Sales, Javier Botas Rodriguez, Gabriel Gusi Tragant, Amparo Benedicto, Carlos Gonzalez-Juanatey, Mercedes Camprubí Potau, Ignacio Plaza Perez, César Morís De La Tassa, Pablo Loma-Osorio Rincon, Javier Balaguer Recena, Juan M. Escudier, Antonio Coca Payeras, Norberto Alonso Orcajo, Pedro Valdivielso, Godwin Constantine, Ruvaiz Haniffa, Nirmali Tissera, Stanley Amarasekera, Chandrike Ponnamperuma, Nimali Fernando, Kaputella Fernando, Jayanthimala Jayawardena, Santharaj Wijeyasingam, Gotabhaya Ranasinghe, Ruvan Ekanayaka, Sepalika Mendis, Vajira Senaratne, Gnanamoorthy Mayurathan, Ajantha Rajapaksha, Thilak Sirisena, Jagath I. Herath, Naomali Amarasena, Stefan Berglund, Gundars Rasmanis, Ola Vedin, Nils Witt, Georgios Mourtzinis, Peter Nicol, Ole Hansen, Stefano Romeo, Steen Agergaard Jensen, Ingemar Torstensson, Ulf Ahremark, Torbjörn Sundelin, Tiziano Moccetti, Francois Mach, Ronald Binde, Oliver Gämperli, Wei-Chuan Tsai, Kwo-Chang Ueng, Wen-Ter Lai, Ming-En Liu, Juey-Jen Hwang, Wei-Hsian Yin, I-Chang Hsieh, Ming-Jer Hsieh, Wei Hsiang Lin, Jen-Yuan Kuo, Tsuei-Yuan Huang, Chih-Yuan Fang, Pinij Kaewsuwanna, Wasant Soonfuang, Woravut Jintapakorn, Apichard Sukonthasarn, Nattawut Wongpraparut, Krisada Sastravaha, Nakarin Sansanayudh, Wirash Kehasukcharoen, Dilok Piyayotai, Paiboon Chotnoparatpat, Ahmet Camsari, Hakan Kultursay, Bulent Mutlu, Murat Ersanli, Mustafa Demirtas, Cevat Kirma, Ertan Ural, Lale Koldas, Oleksandr Karpenko, Alexander Prokhorov, Ihor Vakaluyk, Halyna Myshanych, Dmytro Reshotko, Valeriy Batushkin, Leonid Rudenko, Ihor Kovalskyi, Mykola Kushnir, Vira Tseluyko, Yuriy Mostovoy, Mykola Stanislavchuk, Yulian Kyiak, Yuriy Karpenko, Yaroslav Malynovsky, Andriy Klantsa, Oles Kutniy, Ekaterina Amosova, Viktor Tashchuk, Oleh Leshchuk, Mykola Rishko, Mykola Kopytsya, Andriy Yagensky, Mykola Vatutin, Andriy Bagriy, Olga M. Barna, Olexiy Ushakov, Georgiy Dzyak, Borys Goloborodko, Anatolii Rudenko, Volodymyr Zheleznyy, Jasper Trevelyan, Azfar Zaman, Kaeng Lee, Andrew Moriarty, Rajesh K. Aggarwal, Piers Clifford, Yuk-Ki Wong, Syed M.R. Iqbal, Eduardas Subkovas, Denise Braganza, David Sarkar, Robert Storey, Huw Griffiths, Sam Mcclure, Rangasamy Muthusamy, Simon Smith, John Kurian, Terry Levy, Craig Barr, Honer Kadr, Robert Gerber, Audrius Simaitis, Handrean Soran, Anthony Mathur, Adrian Brodison, Mohammad Ayaz, Muhammad Cheema, Richard Oliver, Simon Thackray, Telal Mudawi, Gohar Rahman, Ayyaz Sultan, Timothy Reynolds, David Sharman, null david Sprigings, Rob Butler, Peter Wilkinson, Gregory Y.H. Lip, Julian Halcox, Sean Gallagher, Nicholas Ossei-Gerning, Gil Vardi, Duccio Baldari, David Brabham, Charles Treasure, Charles Dahl, Bruce Palmer, Alan Wiseman, Abul Khan, Sanjeev Puri, Ann Elizabeth Mohart, Carlos Ince, Enrique Flores, Scott Wright, Shi-Chi Cheng, Michael Rosenberg, William Rogers, Edward Kosinski, Les Forgosh, Jonathan Waltman, Misal Khan, Mohammad Shoukfeh, Georges Dagher, Patrick Cambier, Ira Lieber, Priya Kumar, Cara East, Perry Krichmar, Mian Hasan, Lindsey White, Thomas Knickelbine, Thomas Haldis, Eve Gillespie, Thomas Amidon, David Suh, Imran Arif, Mouhamad Abdallah, Faiq Akhter, Eric Carlson, Michael D'Urso, Fadi El-Ahdab, William Nelson, Katie Moriarty, Barry Harris, Steven Cohen, Luther Carter, Daniel Doty, Kenneth Sabatino, Tariq Haddad, Amir Malik, Sunder Rao, Angel Mulkay, Ion Jovin, Kim Klancke, Vinay Malhotra, Sai K. Devarapalli, Michael Koren, Harish Chandna, George Dodds, Tauqir Goraya, James Bengston, Matthew Janik, Joseph Moran, Andrew Sumner, John Kobayashi, William Davis, Shahram Yazdani, John Pasquini, Maitreya Thakkar, Amarnath Vedere, Wayne Leimbach, James Rider, Sarah fenton, Narendra Singh, Anil V. Shah, Denise Janosik, Carl Pepine, Brett Berman, Joseph Gelormini, Christopher Daniels, Kerensky Richard, Friederike Keating, Nicholas I. Kondo, Sanjay Shetty, Howard Levite, Winfried Waider, Theodore Takata, Mazen Abu-Fadel, Vipul Shah, Rahul Aggarwal, Mark Izzo, Anil Kumar, Brack Hattler, Rose Do, Chad Link, Anna Bortnick, George Kinzfogl, Arnold Ghitis, John Larry, Edward Teufel, Peter Kuhlman, Brent Mclaurin, Wenwu Zhang, Stephen Thew, Jalal Abbas, Matthew White, Othman Islam, Sumeet Subherwal, Nandkishore Ranadive, Babak Vakili, Christian Gring, David Henderson, Timothy Schuchard, Naim Farhat, Geoffrey Kline, Sharan Mahal, Jack Whitaker, Shawn Speirs, Rolf Andersen, Nizar Daboul, Phillip Horwitz, Firas Zahr, George Ponce, Zubair Jafar, Joseph Mcgarvey, Vipul Panchal, Stephen Voyce, Thomas Blok, William Sheldon, Masoud M. Azizad, Carsten Schmalfuss, Mark Picone, Robert Pederson, William Herzog, Keith Friedman, Jason Lindsey, Rosemary Nowins, Eichenlaub Timothy, Parilak Leonard, Norman Lepor, Mahfouz El Shahawy, Howard Weintraub, Anand Irimpen, Alvaro Alonso, Wade May, Daniels Christopher, Thomas Galski, Alan Chu, Freny Mody, Ebrahimi Ramin, Zachary Hodes, Joseph Rossi, Gregory Rose, James Fairlamb, Charles Lambert, Ajit Raisinghani, Antonio Abbate, George Vetrovec, Marilyn King, Charles Carey, Jaime Gerber, Liwa Younis, Hyeun Park, Mladen Vidovich, Thomas Knutson, Dennis Friedman, Fred Chaleff, Arthur Loussararian, Phillip Rozeman, Carey Kimmelstiel, Jeffrey Kuvin, Kevin Silver, Malcolm Foster, Glen Tonnessen, Andrey Espinoza, Mohamadali Amlani, Andreas Wali, Christopher Malozzi, Geert T. Jong, Clara Massey, Keattiyoat Wattanakit, Philip J. O'Donnell, Dinesh Singal, Naseem Jaffrani, Sridhar Banuru, Daniel Fisher, Mark Xenakis, Neal Perlmutter, Ravi Bhagwat, James Strader, Ronald Blonder, Ayim Akyea-Djamson, Ajay Labroo, Kwan Lee, H. John Marais, Edmund Claxton, Robert Weiss, Rohr Kathryn, Martin Berk, Peter Rossi, Parag Joshi, Amit Khera, Ajit S. Khaira, Greg Kumkumian, Steven Lupovitch, Joshua Purow, Stephen Welka, David Hoffman, Stuart Fischer, Eugene Soroka, Donald Eagerton, Samir Pancholy, Michael Ray, Norman Erenrich, Michael Farrar, Stewart Pollock, William J. French, Steve Diamantis, Douglas Guy, Lawrence Gimple, Mark Neustel, Steven Schwartz, Edward Pereira, Seals Albert, Douglas Spriggs, Janet Strain, Suneet Mittal, Anthony Vo, Majed Chane, Jason Hall, Nampalli Vijay, Kapildeo Lotun, F. Martin Lester, Ahed Nahhas, Theodore Pope, Paul Nager, Rakesh Vohra, Mukesh Sharma, Riyaz Bashir, Hinan Ahmed, Michael Berlowitz, Robert Fishberg, Robert Barrucco, Eric Yang, Michael Radin, Daniel Sporn, Dwight Stapleton, Steven Eisenberg, Joel Landzberg, Martin Mcgough, Samir Turk, Michael Schwartz, P. Sandy Sundram, Diwakar Jain, Mark Zainea, Carlos Bayron, Ronald Karlsberg, Suhail Dohad, Henry Lui, William Keen, Donald Westerhausen, Sandeep Khurana, Himanshu Agarwal, Jessica Birchem, William Penny, Mark Chang, Sherrill Murphy, John Henry, Branislav Schifferdecker, John M Gilbert, Gopal Chalavarya, Charles Eaton, John F. Schmedtje, Stuart Christenson, Imran Dotani, Douglas Denham, Alexander Macdonell, Paul Gibson, Aref Rahman, Tammam Al Joundi, Nizar Assi, Gary Conrad, Purushotham Kotha, Michael Love, Gregory Giesler, Howard Rubenstein, Dawood Gamil, Laura Akright, Justine Krawczyk, Joanne Cobler, Terry Wells, James Welker, Robert Foster, Richard Gilmore, Jay Anderson, Douglas Jacoby, Bill Harris, Geraldine Gardner, Ramprasad Dandillaya, Kishor Vora, John Kostis, John Hunter, David Laxson, Eric Ball, Flavia Egydio, Anelise Kawakami, Janaina Oliveira, Julianna Wozniak, Alexander Matthews, Caroline Ratky, Janine Valiris, Lisa Berdan, Anita Hepditch, Kirby Quintero, Tyrus Rorick, Melissa Westbrook, Andrea Pascual, Carla Rovito, Madeleine Bezault, Elodie Drouet, Tabassome Simon, Caroline Alsweiler, Anne Luyten, Julie Butters, Liddy Griffith, Michelle Shaw, Lena Grunberg, Shahidul Islam, Marie-France Brégeault, Nathalie Bougon, Douglas Faustino, Sylvie Fontecave, Judith Murphy, Melanie Verrier, null Veronique Agnetti, Dorthe Andersen, Emmy Badreddine, Mhamed Bekkouche, Cecile Bouancheau, Imane Brigui, Maddy Brocklehurst, Joseph Cianciarulo, Dawn Devaul, Szilvia Domokos, Cecile Gache, Caroline Gobillot, Severine Guillou, Jan Healy, Megan Heath, Gayatri Jaiwal, Carine Javierre, Julien Labeirie, Myriam Monier, Ulises Morales, Asmaa Mrabti, Bicky Mthombeni, Betim Okan, Lucile Smith, Jennifer Sheller, Sebastien Sopena, Valerie Pellan, Fadela Benbernou, Nafissa Bengrait, Maud Lamoureux, Katarina Kralova, Raphael Bejuit, Anthony Coulange, Christelle Berthou, Jérôme Repincay, Christelle Lorenzato, Alexis Etienne, Valerie Gouet, Virginie Loizeau, Mickael Normand, Anne Ourliac, Christelle Rondel, Antony Adamo, Pascale Beltran, Pauline Barraud, Helene Dubois-Gache, Benjamin Halle, Lamia Metwally, Maxime Mourgues, Marc Sotty, Marion Vincendet, Raluca Cotruta, Zhu Chengyue, Dominique Fournie-Lloret, Christine Morrello, Aurelie Perthuis, Patrick Picault, Isabelle Zobouyan, Helen M. Colhoun, Michael A. Dempsey, Mark A. McClanahan, Masira, and Laucevičius, Aleksandras

Subjects
Male, Acute coronary syndrome, medicine.medical_specialty, Cardiac & Cardiovascular Systems, Randomization, PCSK9 inhibitor, LOW-DENSITY-LIPOPROTEIN, Antibodies, Monoclonal, Humanized, acute coronary syndrom, Placebo, Gastroenterology, lipoprotein(a), Internal medicine, medicine, Humans, Low-density lipoprotein cholesterol, Aged, Alirocumab, RISK, low-density lipoprotein cholesterol, Science & Technology, biology, business.industry, PCSK9, PCSK9 Inhibitors, Hazard ratio, ALIROCUMAB, acute coronary syndrome, Cholesterol, LDL, Lipoprotein(a), Middle Aged, EFFICACY, medicine.disease, Cardiovascular Diseases, CARDIOVASCULAR-DISEASE, SAFETY, Cardiovascular System & Cardiology, biology.protein, Female, lipids (amino acids, peptides, and proteins), STATIN, low-density lipoprotein, cholesterol PCSK9 inhibitor, CORONARY, Cardiology and Cardiovascular Medicine, business, Life Sciences & Biomedicine, Mace
Abstract

Digital, Background Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402), Ciencias Médicas y de la Salud

Published
2021

27. Spectrum of Endocrine Dysfunction and Association With Disease Severity in Patients With COVID-19: Insights From a Cross-Sectional, Observational Study

Author

Ashu Rastogi, Shakun Chaudhary, Kanhaiya Agrawal, Soham Mukherjee, Pankaj Malhotra, Sanjay Kumar Bhadada, Vikas Suri, Vijay Kumar, Sant Ram, Satyam Singh Jayant, Liza Das, Goverdhan Dutt Puri, Anil Bhansali, Naresh Sachdeva, Pinaki Dutta, Varun Mahajan, Rahul Gupta, and Rama Walia

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Cross-sectional study, Endocrinology, Diabetes and Metabolism, central hypoadrenalism, mixed thyroid dysfunction, 030209 endocrinology & metabolism, Endocrine System Diseases, Severity of Illness Index, Gastroenterology, Thyroiditis, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, endocrinology, 0302 clinical medicine, Internal medicine, Severity of illness, medicine, Humans, Endocrine system, hypogonadism, Original Research, hormones, business.industry, Thyroid, COVID-19, Low T3 Syndrome, Middle Aged, medicine.disease, RC648-665, Cross-Sectional Studies, 030104 developmental biology, medicine.anatomical_structure, Sick Euthyroid Syndrome, Female, business, Hormone
Abstract

IntroductionEvidence on new-onset endocrine dysfunction and identifying whether the degree of this dysfunction is associated with the severity of disease in patients with COVID-19 is scarce.Patients and MethodsConsecutive patients enrolled at PGIMER Chandigarh were stratified on the basis of disease severity as group I (moderate-to-severe disease including oxygen saturation 94% and without comorbidities) (n=49). Hypothalamo-pituitary-adrenal, thyroid, gonadal axes, and lactotroph function were evaluated. Inflammatory and cell-injury markers were also analysed.ResultsPatients in group I had higher prevalence of hypocortisolism (38.5 vs 6.8%, p=0.012), lower ACTH (16.3 vs 32.1pg/ml, p=0.234) and DHEAS (86.29 vs 117.8µg/dl, p= 0.086) as compared to group II. Low T3 syndrome was a universal finding, irrespective of disease severity. Sick euthyroid syndrome (apart from low T3 syndrome) (80.9 vs 73.1%, p= 0.046) and atypical thyroiditis (low T3, high T4, low or normal TSH) (14.3 vs 2.4%, p= 0.046) were more frequent in group I than group II. Male hypogonadism was also more prevalent in group I (75.6% vs 20.6%, p=0.006) than group II, with higher prevalence of both secondary (56.8 vs 15.3%, p=0.006) and primary (18.8 vs 5.3%, p=0.006) hypogonadism. Hyperprolactinemia was observed in 42.4% of patients without significant difference between both groups.ConclusionCOVID-19 can involve multiple endocrine organs and axes, with a greater prevalence and degree of endocrine dysfunction in those with more severe disease.

Published
2021

28. Acquired neuro-secretory defect in growth hormone secretion due to Imatinib mesylate and the efficacy of growth hormone therapy in children with chronic myeloid leukemia

Author

Anuradha Aggarwal, Anil Bhansali, Rama Walia, Anshita Aggarwal, Naresh Sachdeva, Deepak Bansal, Niranjan Khandelwal, and Neelam Varma

Subjects
Male, endocrine system, Antineoplastic Agents, Growth hormone, 03 medical and health sciences, 0302 clinical medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, Humans, Medicine, Insulin-Like Growth Factor I, Child, neoplasms, Growth Disorders, Growth retardation, Human Growth Hormone, business.industry, Myeloid leukemia, Imatinib, Hematology, Growth hormone secretion, Imatinib mesylate, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Pediatrics, Perinatology and Child Health, Imatinib Mesylate, Cancer research, Female, business, hormones, hormone substitutes, and hormone antagonists, 030215 immunology, medicine.drug
Abstract

Imatinib results in growth retardation in children with chronic myeloid leukemia (CML). The study was planned to assess the GHRH-GH-IGF1 axis in children with CML, receiving Imatinib and to evaluate the efficacy of human growth hormone (hGH) therapy. Twenty children with CML, receiving Imatinib for a period exceeding 6 months, with resultant growth retardation were included. The GHRH-GH-IGF1 axis was assessed using growth hormone stimulation tests. IGF-1 generation test was performed for the evaluation of GH insensitivity. The mean age at inclusion was 15.2 years. The mean duration of treatment with Imatinib was 5.7 years. The mean decrease in height

Published
2019

29. A distal enhancer that directsOtx2expression in the retinal pigment epithelium and neuroretina

Author

Ales Cvekl, Wei Liu, and Punita Bhansali

Subjects
Male, 0301 basic medicine, Genetically modified mouse, Mice, Transgenic, Retinal Pigment Epithelium, Biology, Retina, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Animals, Eye Proteins, Enhancer, Gene, Transcription factor, Otx Transcription Factors, Retinal pigment epithelium, Embryogenesis, Gene Expression Regulation, Developmental, Retinal, Immunohistochemistry, Cell biology, 030104 developmental biology, medicine.anatomical_structure, chemistry, Homeobox, Female, sense organs, 030217 neurology & neurosurgery, Protein Binding, Transcription Factors, Developmental Biology
Abstract

Background Homeodomain transcription factor Otx2 is essential for embryonic development of multiple head tissues, including retinal pigment epithelium (RPE) and neuroretina. Temporospatial regulation of Otx2 expression is critical for its functions. Molecular dissection of the cis-acting enhancers will help elucidate how Otx2 expression is regulated. Results We comprehensively characterized distal enhancer hs1150 that was previously identified in a high throughput study. We established multiple transgenic mouse lines in which human hs1150, corresponding mouse hs1150, and two highly conserved sub-fragments in the mouse hs1150 were individually fused to a minimal hsp68 promoter to drive reporter expression. We found that hs1150 enhancer directed reporter expression in the RPE, neuroretina, and brain in a developmentally regulated manner. Human hs1150-directed reporter expression largely recapitulated Otx2 expression in the RPE, in the early neuroretina, and to a lesser degree in the early brain. Mouse hs1150, although shorter than human hs1150, exhibited similar enhancer activity, indicating functional conservation of hs1150 enhancer across species. Both of the highly conserved subfragments in mouse hs1150 enhancer directed reporter expression in the early neuroretina, indicating that the hs1150 enhancer has two functional components. Conclusions Our findings provide insight into the molecular mechanisms underlying the regulation of Otx2 retinal expression.

Published
2019

30. The Patient Experience Debrief Interview

Author

Laura E. Hirshfield, Ian Chua, Rachael Holbreich, Mary C. Ottolini, Alyssa L. Bogetz, Matthew Lineberry, Terry Kind, Yoon Soo Park, Michele Long, and Priti Bhansali

Subjects
Adult, Male, medicine.medical_specialty, Students, Medical, Medical psychology, Formative Feedback, Patients, 020205 medical informatics, education, 02 engineering and technology, Pediatrics, Education, Interviews as Topic, Formative assessment, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Patient experience, 0202 electrical engineering, electronic engineering, information engineering, medicine, Humans, Family, 030212 general & internal medicine, Cluster randomised controlled trial, Debriefing, Clinical Clerkship, Reproducibility of Results, Rubric, General Medicine, Test (assessment), Hospitalization, Inter-rater reliability, Caregivers, Family medicine, District of Columbia, Female, Psychology, Education, Medical, Undergraduate
Abstract

PURPOSE To determine the effect of patient debrief interviews on pediatric clerkship student depth of reflection and learning. METHOD The authors conducted a multi-institutional, mixed-methods, cluster randomized trial among pediatric clerkship students from May 2016 to February 2017. Intervention students completed a debrief interview with a patient-caregiver, followed by a written reflection on the experience. Control students completed a written reflection on a memorable patient encounter. Three blinded authors scored written reflections according to the 4-level REFLECT rubric to determine depth of reflection. Interrater reliability was examined using kappa. REFLECT scores were analyzed using a chi-square test; essays were analyzed using content analysis. RESULTS Eighty percent of eligible students participated. One hundred eighty-nine essays (89 control, 100 intervention) were scored. Thirty-seven percent of the control group attained reflection and critical reflection, the 2 highest levels of reflection, compared with 71% of the intervention group; 2% of the control group attained critical reflection, the highest level, compared with 31% of the intervention group (χ(3, N = 189) = 33.9, P < .001). Seven themes were seen across both groups, 3 focused on physician practice and 4 focused on patients. Patient-centered themes were more common in the intervention group, whereas physician-focused themes were more common in the control group. CONCLUSIONS Patient debrief interviews offer a unique approach to deepen self-reflection through direct dialogue and exploration of patient-caregiver experiences during hospitalization.

Published
2019

31. Current Practices and Perspectives on Peer Observation and Feedback: A National Survey

Author

Amit Singh, Joanne Nazif, H. Barrett Fromme, Kamakshya P. Patra, Corrie E. McDaniel, Jennifer Maniscalco, Krista Birnie, Jacqueline M Walker, Marta King, Jimmy Beck, Priti Bhansali, Cherie F. Ginwalla, Elizabeth Seelbach, and Elena Griego

Subjects
Adult, Male, Formative Feedback, Attitude of Health Personnel, Pediatrics, Peer Group, Hospitals, University, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, 030225 pediatrics, Humans, 030212 general & internal medicine, Medical education, Professional development, Direct observation, Cognition, Middle Aged, United States, Improved performance, Cross-Sectional Studies, Teaching skills, Hospitalists, Pediatrics, Perinatology and Child Health, Female, Faculty development, Psychology
Abstract

Objective Peer observation and feedback (POF) is the direct observation of an activity performed by a colleague followed by feedback with the goal of improved performance and professional development. Although well described in the education literature, the use of POF as a tool for development beyond teaching skills has not been explored. We aimed to characterize the practice of POF among pediatric hospitalists to explore the perceived benefits and barriers and to identify preferences regarding POF. Methods We developed a 14-item cross-sectional survey regarding divisional expectations, personal practice, perceived benefits and barriers, and preferences related to POF. We refined the survey based on expert feedback, cognitive interviews, and pilot testing, distributing the final survey to pediatric hospitalists at 12 institutions across the United States. Results Of 357 eligible participants, 198 (56%) responded, with 115 (58%) practicing in a freestanding children's hospital. Although 61% had participated in POF, less than one half (42%) reported divisional POF expectation. The most common perceived benefits of POF were identifying areas for improvement (94%) and learning about colleagues’ teaching and clinical styles (94%). The greatest perceived barriers were time (51%) and discomfort with receiving feedback from peers (38%), although participation within a POF program reduced perceived barriers. Most (76%) desired formal POF programs focused on improving teaching skills (85%), clinical management (83%), and family-centered rounds (82%). Conclusions Although the majority of faculty desired POF, developing a supportive environment and feasible program is challenging. This study provides considerations for improving and designing POF programs.

Published
2019

32. Intracranial Germinoma Masquerading as Secondary Granulomatous Hypophysitis: A Case Report and Review of Literature

Author

Anil Bhansali, Prathosh Gangadhar, Ashutosh Rai, Kim Vaiphei, Paramjeet Singh, Prakamya Gupta, Pinaki Dutta, Nirmalya Ray, Rimesh Pal, and Kanchan K Mukherjee

Subjects
Male, Pathology, medicine.medical_specialty, Adolescent, Hypophysitis, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Hypopituitarism, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Endocrinology, Polyuria, Internal medicine, Biopsy, medicine, Humans, Child, Pituitary stalk, Granuloma, Germinoma, medicine.diagnostic_test, Brain Neoplasms, Endocrine and Autonomic Systems, business.industry, medicine.disease, Diabetes insipidus, Female, medicine.symptom, business, Febrile neutropenia
Abstract

Germinomas are highly immunogenic tumors eliciting a strong peri-tumoral immune response that can spillover into the surrounding healthy tissues. This phenomenon can also occur in intracranial germinomas, manifesting as secondary hypophysitis. Herein, we report a case of 12-year-old-girl presenting with polyuria and polydispsia. She had central diabetes insipidus (CDI) and panhypopituitarism. Imaging revealed a sellar-suprasellar mass with infundibular stalk thickening. Transphenoidal biopsy revealed epithelioid granulomas with immunostaining negative for germinomatous cells. Other causes of hypophysitis were ruled out. Accordingly, she was diagnosed as primary granulomatous hypophysitis and treated with high-dose corticosteroids. Three years later she again presented with headache, vomiting and diminution of vision. Imaging showed a heterogeneous, solid-cystic peripheral rim-enhancing lesion at the same location with involvement of hypothalamus, ependyma and pineal gland. Cerebrospinal fluid beta-human chorionic gonadotropin was markedly elevated, confirming the diagnosis of an intracranial germ cell tumor. She was started on chemotherapy; however, she succumbed to febrile neutropenia. We performed a literature search and found 18 anecdotal cases of secondary hypophysitis associated with intracranial germinomas. There was a slight male preponderance (male:female 5:4). Two-thirds of the cases were below 18 years of age. Polyuria was the most common presenting manifestation (83%). CDI and panhypopituitarism were seen in 89 and 78% cases, respectively. Imaging evidence of pituitary stalk thickening was seen in 12 cases (67%), while pituitary enlargement and/or sellar mass were reported in 11 cases (61%). Pineal involvement was extremely rare, being reported in only 1 case, implying the predilection of suprasellar (rather than pineal) germinomas in causing secondary hypophysitis. Histologically, 82% had lymphocytic hypophysitis, while 18% had granulomatous hypophysitis. Initially, the diagnosis of germinoma was missed in 60% of the cases who were wrongly treated with corticosteroids. To conclude, physicians should make it a dictum that all children and adolescents presenting with CDI and pituitary stalk thickening should be rigorously screened for an underlying intracranial germinoma before labeling them as primary hypophysitis.

Published
2019

33. ‘Size does matter’: Prophylactic gonadectomy in a case of Swyer syndrome

Author

Gupta Parikshaa, Bhansali Anil, Rajwanshi Arvind, Parkhi Mayur, and Gainder Shalini

Subjects
Adult, Male, endocrine system, Gonad, Gonadal dysgenesis, Gonadoblastoma, Physiology, Dysgerminoma, Malignant transformation, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Castration, Gonadal Dysgenesis, 46,XY, Ovarian Neoplasms, 030219 obstetrics & reproductive medicine, Prophylactic Surgical Procedures, urogenital system, business.industry, Ovary, XY Genotype, Teratoma, Obstetrics and Gynecology, medicine.disease, medicine.anatomical_structure, Reproductive Medicine, 030220 oncology & carcinogenesis, Female, Immature teratoma, business
Abstract

Swyer syndrome also known as pure or complete gonadal dysgenesis is a very rare disorder of sex development wherein the individuals are phenotypically females with 46, XY genotype and preserved mullerian structures. These individuals characteristically have dysgenetic streak gonads which carry an increased risk of malignant transformation. Prophylactic gonadectomy is highly recommended as soon as a clinical diagnosis is established to diminish the chances of tumor development. We present a case of complete gonadal dysgenesis with bilateral small gonads with a dysgerminoma arising in a background of gonadoblastoma in one gonad and immature teratoma in the other. The present case, besides adding a rare case to the literature, highlights the importance of detailed pre-operative assessment of gonadal size and prompt prophylactic gonadectomy in cases with gonadal dysgenesis.

Published
2019

34. Efficacy and Safety of Low-Frequency, Noncontact Airborne Ultrasound Therapy (Glybetac) For Neuropathic Diabetic Foot Ulcers: A Randomized, Double-Blind, Sham-Control Study

Author

Shankar Ramachandran, Anil Bhansali, and Ashu Rastogi

Subjects
Adult, Male, Time Factors, Adolescent, Ultrasonic Therapy, India, 030209 endocrinology & metabolism, Risk Assessment, Severity of Illness Index, Statistics, Nonparametric, Double blind, Young Adult, 030207 dermatology & venereal diseases, 03 medical and health sciences, Wound care, 0302 clinical medicine, Diabetic Neuropathies, Double-Blind Method, medicine, Humans, Wound Healing, business.industry, Standard treatment, Ultrasound, General Medicine, Sham control, Middle Aged, medicine.disease, Diabetic foot, Diabetic Foot, Treatment Outcome, Diabetic foot ulcer, Anesthesia, Female, Surgery, Patient Safety, Wound healing, business, Follow-Up Studies
Abstract

The diabetic foot ulcer (DFU) healing rates remain dismally low. Therefore, many adjunctive therapies have been evaluated including ultrasound therapy. The prior studies with noncontact, low-frequency ultrasound were retrospective, single arm, unblinded, or with historical controls. The aim of the present study was to compare the efficacy of noncontact, low-frequency airborne ultrasound (Glybetac) therapy with sham therapy added to standard treatment in patients with neuropathic, clinically infected, or noninfected DFU (wound size >2 cm2), Wagner grades 2 and 3. Patients received ultrasound or sham therapy for 28 days dosed daily for first 6 days followed by twice a week for next 3 weeks along with standard of care. The primary outcome was percentage of patients with at least >50% decrease in wound area at 4 week of intervention. Fifty-eight patients completed the study protocol. The duration of wound was 15.8 ± 11.2 weeks and 12.1 ± 10.9 weeks and wound area of 11.3 ± 8.2 cm2 and 14.8 ± 13.8 cm2 ( P = .507) in the ultrasound and sham groups, respectively. A >50% reduction in wound area was observed in 97.1% and 73.1% subjects ( P = .042) in ultrasound and sham groups, respectively. Wound contraction was faster in the first 2 weeks with ultrasound therapy, 5.3 cm2, compared with 3.0 cm2 ( P = .025) with sham treatment. Overall, wound area reduction of 69.4 ± 23.2% and 59.6 ± 24.9% ( P = .126) was observed at 4 weeks in the ultrasound and sham groups, respectively. We conclude that the airborne low-frequency ultrasound therapy improves and hastens the healing of chronic neuropathic DFU when combined with standard wound care.

Published
2019

35. Teriparatide (recombinant human parathyroid hormone [1‐34]) increases foot bone remodeling in diabetic chronic Charcot neuroarthropathy: a randomized double‐blind placebo‐controlled study

Author

Anil Bhansali, Niranjan Khandelwal, Bhagwant Rai Mittal, David G. Armstrong, Anish Bhattacharya, Rajender Kumar, Mahesh Prakash, Ashu Rastogi, and Abhishek Hajela

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Urology, Placebo-controlled study, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Placebo, Bone remodeling, Fractures, Bone, 03 medical and health sciences, 0302 clinical medicine, Diabetic Neuropathies, Double-Blind Method, Teriparatide, Diabetes mellitus, Humans, Medicine, Bone mineral, Bone Density Conservation Agents, business.industry, Middle Aged, Prognosis, medicine.disease, Chronic Disease, Female, Bone Remodeling, Arthropathy, Neurogenic, business, Foot (unit), Follow-Up Studies, medicine.drug, Hormone
Abstract

BACKGROUND Currently, there is no consensus regarding the medical treatment of chronic Charcot neuroarthropathy (CN) of foot, except for effective off-loading. Because tarsal bones are predominantly trabecular, teriparatide may improve the macroarchitecture of foot bones in chronic CN. METHODS People with diabetes and chronic CN were randomized to receive either 20 μg teriparatide or placebo subcutaneous daily for 12 months. Thirty-eight patients were screened and data were analyzed for 20. The maximum standardized uptake (SUVmax ) value of 18 F-FDG PET/CT the region of interest, bone turnover markers and foot bone mineral density BMD were determined. The primary outcome measure was change in SUVmax g/ml. RESULTS Mid-foot was the most common region involved. After 12 months, SUVmax increased from 30.6 ± 14.7 to 37.7 ± 18.0 (P = 0.044) in the teriparatide group, but decreased from 27.6 ± 12.2 to 22.9 ± 10.4 with placebo (P = 0.148). The estimated treatment difference (ETD) was 11.9 ± 4.3 (95% CI 2.9, 20.8; P = 0.012). Similarly, P1NP increased with teriparatide (19.8 ± 5.5; P = 0.006) but decreased with placebo (-5.1 ± 3.8 ng/mL; P = 0.219); ETD was 24.8 ± 6.6 (95% CI 10.8, 38.8; P < 0.001) and CTX increased in both the teriparatide and placebo groups. Foot BMD increased by 0.06 ± 0.04 g/cm2 (P = 0.192) with teriparatide, but decreased by -0.06 ± 0.08 g/cm2 with placebo (P = 0.488; intergroup comparison, P = 0.096). CONCLUSION Teriparatide increases foot bone remodeling by an osteoanabolic action in people with CN.

Published
2019

36. Spectrum of hospitalized NeuroCOVID diagnoses from a tertiary care neurology centre in Eastern India

Author

Supriyo Choudhury, Vaishali Bagrodia, Mona Tiwari, Mohua Golder, Simin Rahman, Sakhi Bhansali, and Hrishikesh Kumar

Subjects
Male, Pediatrics, medicine.medical_specialty, Neurology, Encephalopathy, Population, India, Comorbidity, Physiology (medical), Diabetes mellitus, medicine, Humans, Medical diagnosis, education, Stroke, Retrospective Studies, education.field_of_study, business.industry, SARS-CoV-2, Tertiary Healthcare, COVID-19, General Medicine, Middle Aged, medicine.disease, Eastern india, Surgery, Neurology (clinical), business
Abstract

Purpose To describe the spectrum of hospitalized NeuroCOVID on admission in a tertiary neurology centre in Kolkata, the largest and most populated metropolitan city in Eastern India. Method We retrospectively studied confirmed COVID-19 patients admitted with a neurological condition from 1st May 2020 to 30th January 2021. Neurological diagnoses and their temporal relationship to respiratory features along with clinicodemographic profile for such patients was ascertained. Result 228 patients were diagnosed with NeuroCOVID at our centre. Of the 162 included population (median age was 59 (50–70) and 62.3% (1 0 1) were male) and 73.5% were diagnosed with NeuroCovid before any respiratory or febrile features. 46 patients (28.8%) had a pre/co-existing neurological illness, and 103 (63.6%) had systemic comorbidities. No significant difference was observed when comparing demographics and comorbidities of NeuroCOVID patients presenting with and without fever and respiratory features. Moreover, no individual NeuroCOVID diagnosis was more prone to present with respiratory or febrile features. Diabetes mellitus was the only comorbidity which was significantly higher in the ischemic stroke group, all other comorbidities and characteristics were evenly distributed between stroke and non-stroke NeuroCOVID patients and encephalopathy non encephalopathy NeuroCOVID patients. Conclusion Stroke and encephalopathy are the most prevalent parainfectious neurological conditions occurring with COVID-19 in the Indian population. This study demonstrates seemingly low-risk individuals (i.e. people without pre-existing systemic and neurological comorbidities) may develop neurological conditions. Moreover, NeuroCOVID may manifest independent of respiratory features and fever.

Published
2021

37. FSH-stimulated Inhibin B (FSH-iB): A Novel Marker for the Accurate Prediction of Pubertal Outcome in Delayed Puberty

Author

Tulika Singh, Shakun Chaudhary, Anil Bhansali, Sanjay Kumar Bhadada, Naresh Sachdeva, Rama Walia, and Devi Dayal

Subjects
Delayed puberty, Adult, Male, endocrine system, medicine.medical_specialty, Future studies, Adolescent, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, 030209 endocrinology & metabolism, Stimulation, Biochemistry, Sensitivity and Specificity, Cohort Studies, 03 medical and health sciences, Basal (phylogenetics), Young Adult, 0302 clinical medicine, Endocrinology, Hypogonadotropic hypogonadism, Predictive Value of Tests, Internal medicine, Medicine, Humans, Prospective Studies, Child, Inhibin b, Inhibin-beta Subunits, Puberty, Delayed, 030219 obstetrics & reproductive medicine, Triptorelin Pamoate, business.industry, Hypogonadism, Biochemistry (medical), Puberty, Reproducibility of Results, Luteinizing Hormone, medicine.disease, Cohort, Female, medicine.symptom, Follicle Stimulating Hormone, business, Puberty onset
Abstract

Background Clinicians have long been struggling to find an effective tool to predict onset of puberty. Objective To explore stimulability of inhibin B after exogenous FSH and its potential role for prediction of onset of puberty. Design and participants Study subjects were enrolled into “exploratory cohort” (n = 42) and “validation cohort” (n = 19). The exploratory cohort was further divided into group 1 (healthy children with spontaneous puberty [SP], n = 26) and group 2 (patients with hypogonadotropic hypogonadism [HH], n = 16). The validation cohort included children who presented with complaints of delayed puberty. Intervention and outcome Participants were subjected to FSH stimulation test and GnRH analogue stimulation test. Cutoffs derived from the exploratory cohort for basal and FSH stimulated inhibin B (FSH-iB) were applied on the validation cohort. Basal LH, GnRH analogue-stimulated LH, basal inhibin B, and FSH-iB were compared with clinical outcomes on a prospective follow-up for prediction of onset of puberty. Results There was statistically significant increment in inhibin B after exogenous FSH in group 1 (SP) in both male (188.8 pg/mL; P = 0.002) and female (1065 pg/mL; P = 0.023) subjects. The increment was not statistically significant in group 2 (HH) in both sexes. FSH-iB at a cutoff of 116.14 pg/mL in males and 116.50 pg/mL in females had 100% sensitivity and specificity for labelling entry into puberty. On application of these cutoffs on the validation cohort, FSH-iB had 100% positive predictive value, negative predictive value, and diagnostic accuracy for prediction of pubertal onset. Conclusion Inhibin B was stimulable in both male and female subjects. FSH-iB can be considered a novel and promising investigation for prediction of onset of puberty. Future studies are required for further validation.

Published
2021

38. Age- and sex-specific concentrations of bone remodeling markers in healthy Indian adults with and without vitamin D deficiency

Author

Sanjay Kumar Bhadada, Abhilasha Garg, Anshita Aggarwal, Anil Bhansali, Rimesh Pal, Naresh Sachdeva, and Sant Ram

Subjects
Adult, Male, 0301 basic medicine, Physiology, 030209 endocrinology & metabolism, Age and sex, Procollagen Type I, Collagen Type I, vitamin D deficiency, Bone remodeling, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Orthopedics and Sports Medicine, Child, Aged, business.industry, Significant difference, Healthy subjects, Middle Aged, Vitamin D Deficiency, medicine.disease, Peptide Fragments, Menopause, Female, Bone Remodeling, 030101 anatomy & morphology, Peptides, business, Biomarkers, Procollagen, Blood sampling
Abstract

Bone remodeling markers exhibit marked inter-ethnic variation; hence, population-specific data are required. Herein, we have established age- and sex-specific concentrations of serum PINP and CTX in healthy Indian adults with and without vitamin D deficiency that can be used in clinical practice for monitoring response to anti-osteoporotic therapy. The present study was undertaken to generate data on age- and sex-specific concentrations of serum procollagen type I N-propeptide (PINP) and type I collagen C-telopeptide (CTX) in healthy Indian adults with and without vitamin D deficiency. Apparently, healthy subjects aged ≥ 20 years with no prior co-morbidities were recruited from the community by door-to-door surveys. Provisionally eligible participants underwent blood sampling after overnight fast. Individuals with biochemical abnormalities that could potentially affect bone remodeling were excluded. However, subjects with vitamin D deficiency were not excluded. Serum total PINP and β-CrossLaps (CTX) were measured using electro-chemiluminescence immunoassay. After exclusion, 677 subjects were enrolled (M:F = 2.5:4.2, mean age = 45.0 years). Median serum PINP and CTX were 55.78 ng/ml (40.27–71.70) and 0.356 ng/ml (0.238–0.499), respectively. There was no difference in PINP/CTX between men and women or between premenopausal and postmenopausal women. Decade-wise distribution of PINP/CTX showed that maximum values were attained in 3rd decade; subsequently, in men, levels declined with age while in women, there was a peak in the 6th decade coinciding with the early years of menopause. Vitamin D deficiency and severe vitamin D deficiency were seen in 417 (61.5%) and 259 subjects (38.2%), respectively. There was no significant difference in PINP/CTX in subjects with and without vitamin D deficiency. The present study has allowed us to generate data on serum concentrations of PINP/CTX in a diverse group of healthy community-dwelling Indian adults with varying serum vitamin D levels. It might aid in monitoring response to anti-osteoporotic therapy amongst native Indians.

Published
2021

39. Baroreflex Failure After Anterior Cervical Discectomy and Fusion

Author

Arvind Gopalrao, Kulkarni, Sharvari, Gunjotikar, Thonangi, Yeshwanth, Shahrukh, Pathan, Praveen, Goparaju, Nagesh, Waghmare, and Gautam, Bhansali

Subjects
Male, Spinal Fusion, Treatment Outcome, Humans, Orthopedics and Sports Medicine, Surgery, Baroreflex, Middle Aged, Diskectomy, Retrospective Studies
Abstract

A 58-year-old man underwent anterior cervical discectomy and fusion (ACDF) for the treatment of cervical spondylotic myelopathy. Immediately after surgery, the patient experienced elevated blood pressure with a fall in oxygen saturation which prevented extubation. He required admission to the critical care unit and was diagnosed with baroreflex failure syndrome (BFS). He was managed with a 4-drug medical regimen and stabilized by the second postoperative day.BFS should be considered in the setting of sudden sharp elevation in blood pressure after ACDF. Early diagnosis and initiation of appropriate pharmacotherapy may reduce patient morbidity and mortality.

Published
2021

40. Influence of patient characteristics and immunosuppressant management on mortality in kidney transplant recipients hospitalized with coronavirus disease 2019 (COVID‐19)

Author

Alexey Zendel, Andrew D. Santeusanio, Arjun Bhansali, Graciela De Boccardo, Madhav C. Menon, Ron Shapiro, Samantha E. Jacobs, Samira S. Farouk, Yaniv Fenig, Meenakshi Rana, Fasika M Tedla, Veronica Delaney, Sarah Taimur, Dallas Dunn, Ahmad Mahamid, Caroline Liu, Fahima Mahir, Vinita Sehgal, Niralee Patel, Sander Florman, Timothy Sullivan, Emily Baneman, and Rafael Khaim

Subjects
Adult, Graft Rejection, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, Patient characteristics, kidney transplantation, HIV Infections, 030230 surgery, Kidney transplant, immunosuppressive agents, Tacrolimus, 03 medical and health sciences, 0302 clinical medicine, COVID‐19, Adrenal Cortex Hormones, Risk Factors, Internal medicine, White blood cell, medicine, Humans, Kidney transplantation, Aged, Retrospective Studies, Immunosuppression Therapy, Transplantation, transplant recipients, business.industry, COVID-19, Immunosuppression, Original Articles, Middle Aged, Mycophenolic Acid, medicine.disease, medicine.anatomical_structure, Concomitant, 030211 gastroenterology & hepatology, Original Article, Female, business
Abstract

The influence of patient characteristics and immunosuppression management on COVID‐19 outcomes in kidney transplant recipients (KTRs) remains uncertain. We performed a single‐center, retrospective review of all adult KTRs admitted to the hospital with confirmed COVID‐19 between 03/15/2020 and 05/15/2020. Patients were followed from the date of admission up to 1 month following hospital discharge or study conclusion (06/15/2020). Baseline characteristics, laboratory parameters, and immunosuppression were compared between survivors and patients who died to identify predictors of mortality. 38 KTRs with a mean baseline eGFR of 52.5 ml/min/1.73 m2 were hospitalized during the review period. Maintenance immunosuppression included tacrolimus (84.2%), mycophenolate (89.5%), and corticosteroids (81.6%) in the majority of patients. Eleven patients (28.9%) died during the hospitalization. Older age (OR = 2.05; 1.04‐4.04), peak D‐dimer (OR = 1.20; 1.04‐1.39), and peak white blood cell count (OR = 1.11; 1.02‐1.21) were all associated with mortality among KTRs hospitalized for COVID‐19. Increased mortality was also observed among KTRs with concomitant HIV infection (87.5% vs. 36.1%; p

Published
2021

41. Long-term foot outcomes following differential abatement of inflammation and osteoclastogenesis for active Charcot neuroarthropathy in diabetes mellitus

Author

Edward B. Jude, Ashu Rastogi, Mahesh Prakash, Liza Das, Anil Bhansali, and Pinaki Dutta

Subjects
Male, Critical Care and Emergency Medicine, Osteolysis, Physiology, Epidemiology, medicine.medical_treatment, Anti-Inflammatory Agents, Zoledronic Acid, Endocrinology, Medical Conditions, Diabetic Neuropathies, Bone Density, Osteogenesis, Immune Physiology, Medicine and Health Sciences, Traumatic Amputation, Immune Response, Trauma Medicine, Ulcers, Bone mineral, Innate Immune System, Multidisciplinary, Bone Density Conservation Agents, Feet, Middle Aged, Diabetic Foot, Treatment Outcome, Methylprednisolone, Bone Fracture, Cytokines, Legs, Medicine, Female, Anatomy, Arthropathy, Neurogenic, Traumatic Injury, Foot (unit), Research Article, medicine.drug, medicine.medical_specialty, Endocrine Disorders, Science, Immunology, Signs and Symptoms, Diabetes mellitus, Diabetes Mellitus, medicine, Humans, Inflammation, business.industry, Biology and Life Sciences, Bone fracture, Molecular Development, Bisphosphonate, medicine.disease, Surgery, Diabetes Mellitus, Type 2, Amputation, Immune System, Body Limbs, Metabolic Disorders, Clinical Medicine, business, Developmental Biology
Abstract

Aims Inflammatory osteolysis is sine-qua-non of active Charcot neuroarthropathy (CN) causing decreased foot bone mineral density (BMD) and fractures. We aimed to explore the effect of anti-inflammatory or anti-resorptive agents for effect on foot bone mineral content (BMC) and consequent long-term outcomes of foot deformities, fractures and amputation. Methods Forty-three patients with active CN (temperature difference >2°C from normal foot) were evaluated. Patients were off-loaded with total contact cast and randomized to receive either methylprednisolone (1gm) (group A), zoledronate (5mg) (group B) or placebo (100ml normal saline) (group C) once monthly infusion for three consecutive months. Change in foot BMC was assessed at 6 months or at remission and followed subsequently up to 4 years for the incidence of new-onset fracture, deformities, or CN recurrence. Results Thirty-six participants (24 male, 12 female) were randomized (11 in group A, 12 group B, 13 group C). The mean age was 57.7± 9.9 years, duration of diabetes 12.3± 5.8 years and symptom duration 6.5± 2.8 weeks. BMC increased by 36% with zoledronate (p = 0.02) but reduced by 13% with methylprednisolone (p = 0.03) and 9% (p = 0.09) with placebo at remission. There were no incident foot fractures, however, two patients sustained ulcers, and 3 had new-onset or worsening deformities and none required amputation during 3.36 ± 0.89 years of follow-up. Conclusion Bisphosphonate for active CN is associated with an increase in foot bone mineral content as compared to decrease with steroids or total contact cast but long-term outcomes of foot deformities, ulceration and amputation are similar. Trial registration ClinicalTrials.gov: NCT03289338.

Published
2021

42. Efficacy of Autologous Bone Marrow-Derived Mesenchymal Stem Cell and Mononuclear Cell Transplantation in Type 2 Diabetes Mellitus: A Randomized, Placebo-Controlled Comparative Study

Author

Shobhit Bhansali, Anand Srinivasan, Ashish Jain, Neelam Marwaha, Niranjan Khandelwal, Anil Bhansali, Shipra Bhansali, Sunder Mudaliar, Vivekanand Jha, Naresh Sachdeva, Mukesh K Yadav, Meredith Hawkins, Pinaki Dutta, Ratti Ram Sharma, and Vinod Kumar

Subjects
Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, medicine.medical_treatment, Bone Marrow Cells, Biology, Mesenchymal Stem Cell Transplantation, Placebo, Transplantation, Autologous, Peripheral blood mononuclear cell, 03 medical and health sciences, Bone Marrow, Insulin-Secreting Cells, Internal medicine, medicine, Clinical endpoint, Humans, Hypoglycemic Agents, Insulin, Mesenchymal stem cell, Type 2 Diabetes Mellitus, Mesenchymal Stem Cells, Cell Biology, Hematology, Middle Aged, Transplantation, 030104 developmental biology, Diabetes Mellitus, Type 2, Immunology, Female, Stem cell, Developmental Biology
Abstract

Drugs targeting β-cells have provided new options in the management of T2DM; however, their role in β-cell regeneration remains elusive. The recent emergence of cell-based therapies such as autologous bone marrow-derived mesenchymal stem cells (ABM-MSCs) and mononuclear cells (ABM-MNCs) seems to offer a pragmatic approach to augment β-cell function/mass. This study aims to examine the efficacy and safety of ABM-MSC and ABM-MNC transplantation in T2DM and explores alterations in glucose-insulin homeostasis by metabolic studies. Thirty patients of T2DM with duration of disease ≥5 years, receiving triple oral antidiabetic drugs along with insulin (≥0.4 IU/Kg/day) with HbA1c ≤7.5%(≤58.0 mmol/mol), were randomized to receive ABM-MSCs or ABM-MNCs through targeted approach and a sham procedure (n = 10 each). The primary endpoint was a reduction in insulin requirement by ≥50% from baseline, while maintaining HbA1c7.0% (53.0 mmol/mol) during 1-year follow-up. Six of 10 (60%) patients in both the ABM-MSC and ABM-MNC groups, but none in the control group, achieved the primary endpoint. At 12 months, there was a significant reduction in insulin requirement in ABM-MSC (P 0.05) and ABM-MNC groups (P 0.05), but not in controls (P = 0.447). There was a significant increase in second-phase C-peptide response during hyperglycemic clamp in the ABM-MNC (P 0.05) group, whereas a significant improvement in insulin sensitivity index (P 0.05) accompanied with an increase in insulin receptor substrate-1 gene expression was observed in the ABM-MSC group. In conclusion, both ABM-MSCs and ABM-MNCs result in sustained reduction in insulin doses in T2DM. Improvement in insulin sensitivity with MSCs and increase in C-peptide response with MNCs provide newer insights in cell-based therapies.

Published
2017

43. Glucose-dependent Insulinotropic Polypeptide (GIP) Resistance and β-cell Dysfunction Contribute to Hyperglycaemia in Acromegaly

Author

Pinaki Dutta, Kim Vaiphei, Kanchan K Mukherjee, Sunder Mudaliar, Anil Bhansali, Anura V Kurpad, Vikram Singh Shekhawat, Saroj K. Sinha, Naresh Sachdeva, Shobhit Bhansali, Rakesh Kochhar, and Kishor Bhat

Subjects
Adult, Blood Glucose, Male, 0301 basic medicine, endocrine system, medicine.medical_specialty, lcsh:Medicine, Gastric Inhibitory Polypeptide, Incretins, Glucagon, Article, Receptors, Gastrointestinal Hormone, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Glucagon-Like Peptide 1, Insulin-Secreting Cells, Internal medicine, Diabetes mellitus, Acromegaly, medicine, Humans, Insulin, Prospective Studies, lcsh:Science, Multidisciplinary, business.industry, lcsh:R, digestive, oral, and skin physiology, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Diabetes Mellitus, Type 2, Case-Control Studies, Hyperglycemia, Glucose Clamp Technique, Duodenum, Immunohistochemistry, lcsh:Q, Female, Insulin Resistance, business, hormones, hormone substitutes, and hormone antagonists, 030217 neurology & neurosurgery, Homeostasis, Hyperglucagonemia
Abstract

Impaired insulin sensitivity (IS) and β-cell dysfunction result in hyperglycaemia in patients of acromegaly. However, alterations in incretins and their impact on glucose-insulin homeostasis in these patients still remain elusive. Twenty patients of active acromegaly (10 each, with and without diabetes) underwent hyperinsulinemic euglycaemic clamp and mixed meal test, before and after surgery, to measure indices of IS, β-cell function, GIP, GLP-1 and glucagon response. Immunohistochemistry (IHC) for GIP and GLP-1 was also done on intestinal biopsies of all acromegalics and healthy controls. Patients of acromegaly, irrespective of presence or absence of hyperglycaemia, had similar degree of insulin resistance, however patients with diabetes exhibited hyperglucagonemia, and compromised β-cell function despite significantly higher GIP levels. After surgery, indices of IS improved, GIP and glucagon levels decreased significantly in both the groups, while there was no significant change in indices of β-cell function in those with hyperglycaemia. IHC positivity for GIP, but not GLP-1, staining cells in duodenum and colon was significantly lower in acromegalics with diabetes as compared to healthy controls possibly because of high K-cell turnover. Chronic GH excess induces an equipoise insulin resistance in patients of acromegaly irrespective of their glycaemic status. Dysglycaemia in these patients is an outcome of β-cell dysfunction consequent to GIP resistance and hyperglucagonemia.

Published
2019

44. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Author

Kausik K Ray, Helen M Colhoun, Michael Szarek, Marie Baccara-Dinet, Deepak L Bhatt, Vera A Bittner, Andrzej J Budaj, Rafael Diaz, Shaun G Goodman, Corinne Hanotin, Robert A Harrington, J Wouter Jukema, Virginie Loizeau, Renato D Lopes, Angèle Moryusef, Jan Murin, Robert Pordy, Arsen D Ristic, Matthew T Roe, José Tuñón, Harvey D White, Andreas M Zeiher, Gregory G Schwartz, Philippe Gabriel Steg, Gregory G. Schwartz, Ph. Gabriel Steg, Deepak L. Bhatt, Vera A. Bittner, Shaun G. Goodman, Robert A. Harrington, J. Wouter Jukema, Harvey D. White, Andreas M. Zeiher, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Guillaume Lecorps, William J. Sasiela, Jean-François Tamby, Philip E. Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N. Gotcheva, Juan-Carlos Prieto, Huo Yong, Patricio López-Jaramillo, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Margus Viigimaa, Markku S. Nieminen, Vakhtang Chumburidze, Nikolaus Marx, Nicolas Danchin, Evangelos Liberopoulos, Pablo Carlos Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M. Correa Flores, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Zlatko Fras, Anthony J. Dalby, H. Asita de Silva, Emil Hagström, Ulf Landmesser, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez-Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean Van Diepen, Matthew D. Wilson, Andrew T. Yan, Lilia B. Schiavi, Marcelo Garrido, Andrés F. Alvarisqueta, Sonia A. Sassone, Anselmo P. Bordonava, Alberto E. Alves De Lima, Jorge M. Schmidberg, Ernesto A. Duronto, Orlando C. Caruso, Leonardo P. Novaretto, Miguel Angel Hominal, Oscar R. Montaña, Alberto Caccavo, Oscar A. Gomez Vilamajo, Alberto J. Lorenzatti, Luis R. Cartasegna, Gustavo A. Paterlini, Ignacio J. Mackinnon, Guillermo D. Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R. Codutti, Horacio O. Jure, Julio OE Bono, Adrian D. Hrabar, Julio A. Vallejos, Rodolfo A. Ahuad Guerrero, Federico Novoa, Cristian A. Patocchi, Cesar J. Zaidman, Maria E. Giuliano, Ricardo D. Dran, Marisa L. Vico, Gabriela S. Carnero, Pablo N. Guzman, Juan C. Medrano Allende, Daniela F. Garcia Brasca, Miguel H Bustamante Labarta, Sebastian Nani, Eduardo DS Blumberg, Hugo R Colombo, Alberto Liberman, Victorino Fuentealba, Hector L Luciardi, Gabriel D Waisman, Mario A Berli, Ruben O Garcia Duran, Horacio G Cestari, Hugo A Luquez, Jorge A Giordano, Silvia S Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon H Waites, Nicholas Collins, Allan Soward, Chris LS Hii, James Shaw, Margaret A Arstall, John Horowitz, Daniel Ninio, James F Rogers, David Colquhoun, Romulo E Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam J Lehman, Constantine Aroney, Steven GM Coverdale, Paul J Garrahy, Gregory Starmer, Mark Sader, Patrick A Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Franz Weidinger, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Mathias CM Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Mehmed Kulić, Azra Durak-Nalbantic, Dusko Vulic, Adis Muslibegovic, Boris Goronja, Gilmar Reis, Luciano Sousa, Jose C Nicolau, Flavio E Giorgeto, Ricardo P Silva, Lilia Nigro Maia, Rafael Rech, Paulo RF Rossi, Maria José AG Cerqueira, Norberto Duda, Renato Kalil, Adrian Kormann, José Antonio M Abrantes, Pedro Pimentel Filho, Ana Priscila Soggia, Mayler ON de Santos, Fernando Neuenschwander, Luiz C Bodanese, Yorghos L Michalaros, Freddy G Eliaschewitz, Maria H Vidotti, Paulo E Leaes, Roberto V Botelho, Sergio Kaiser, Euler Roberto Fernandes Manenti, Dalton B Precoma, Jose C Moura Jorge, Pedro G de B Silva, Jose A Silveira, Wladmir Saporito, Jose A Marin-Neto, Gilson S Feitosa, Luiz Eduardo F Ritt, Juliana A de Souza, Fernando Costa, Weimar KSB Souza, Helder JL Reis, Leandro Machado, José Carlos Aidar Ayoub, Georgi V Todorov, Fedya P Nikolov, Elena S Velcheva, Maria L Tzekova, Haralambi O Benov, Stanislav L Petranov, Haralin S Tumbev, Nina S Shehova-Yankova, Dimitar T Markov, Dimitar H Raev, Mihail N Mollov, Kostadin N Kichukov, Katya A Ilieva-Pandeva, Raya Ivanova, Maryana Gospodinov, Valentina M Mincheva, Petar V Lazov, Bojidar I Dimov, Manohara Senaratne, James Stone, Jan Kornder, Stephen Pearce, Danielle Dion, Daniel Savard, Yves Pesant, Amritanshu Pandey, Simon Robinson, Gilbert Gosselin, Saul Vizel, Gordon Hoag, Ronald Bourgeois, Anne Morisset, Eric Sabbah, Bruce Sussex, Simon Kouz, Paul MacDonald, Ariel Diaz, Nicolas Michaud, David Fell, Raymond Leung, Tycho Vuurmans, Christopher Lai, Frank Nigro, Richard Davies, Gustavo Nogareda, Ram Vijayaraghavan, John Ducas, Serge Lepage, Shamir Mehta, James Cha, Robert Dupuis, Peter Fong, Sohrab Lutchmedial, Josep Rodes-Cabau, Hussein Fadlallah, David Cleveland, Thao Huynh, Iqbal Bata, Adnan Hameed, Cristian Pincetti, Sergio Potthoff, Juan C Prieto, Monica Acevedo, Arnoldo Aguirre, Margarita Vejar, Mario Yañez, Guillermo Araneda, Mauricio Fernandez, Luis Perez, Paola Varleta, Fernando Florenzano, Laura Huidobro, Carlos A Raffo, Claudia Olivares, Leonardo Nahuelpan, Humberto Montecinos, Jiyan Chen, Yugang Dong, Weijian Huang, Jianzhong Wang, Shi'An Huang, Zhuhua Yao, Xiang Li, Lan Cui, Wenhua Lin, Yuemin Sun, Jingfeng Wang, Jianping Li, Xuelian Zhang, Hong Zhu, Dandan Chen, Lan Huang, Shaohong Dong, Guohai Su, Biao Xu, Xi Su, Xiaoshu Cheng, Jinxiu Lin, Wenxia Zong, Huanming Li, Yi Feng, Dingli Xu, Xinchun Yang, Yuannan Ke, Xuefeng Lin, Zheng Zhang, Zeqi Zheng, Zhurong Luo, Yundai Chen, Chunhua Ding, Yi Zhong, Yang Zheng, Xiaodong Li, Daoquan Peng, Shuiping Zhao, Ying Li, Xuebo Liu, Meng Wei, Shaowen Liu, Yihua Yu, Baiming Qu, Weihong Jiang, Yujie Zhou, Xingsheng Zhao, Zuyi Yuan, Ying Guo, Xiping Xu, Xubo Shi, Junbo Ge, Guosheng Fu, Feng Bai, Weiyi Fang, Xiling Shou, Xiangjun Yang, Jian'An Wang, Meixiang Xiang, Yingxian Sun, Qinghua Lu, Ruiyan Zhang, Jianhua Zhu, Yizhou Xu, Zhongcai Fan, Tianchang Li, Chun Wu, Nicolas Jaramillo, Gregorio Sanchez Vallejo, Diana C Luna Botia, Rodrigo Botero Lopez, Dora I Molina De Salazar, Alberto J Cadena Bonfanti, Carlos Cotes Aroca, Juan Diego Higuera, Marco Blanquicett, Sandra I Barrera Silva, Henry J Garcia Lozada, Julian A Coronel Arroyo, Jose L Accini Mendoza, Ricardo L Fernandez Ruiz, Alvaro M. Quintero Ossa, Fernando G Manzur Jatin, Aristides Sotomayor Herazo, Jeffrey Castellanos Parada, Rafael Suarez Arambula, Miguel A Urina Triana, Angela M Fernandez Trujillo, Maja Strozzi, Siniša Car, Melita Jerić, Davor Miličić, Martina Lovrić Benčić, Hrvoje Pintarić, Đeiti Prvulović, Jozica Šikić, Viktor Peršić, Dean Mileta, Kresimir Štambuk, Zdravko Babić, Vjekoslav Tomulic, Josip Lukenda, Stanka Mejic-Krstulovic, Boris Starcevic, Jindrich Spinar, David Horak, Zdenek Velicka, Josef Stasek, David Alan, Vilma Machova, Ales Linhart, Vojtech Novotny, Vladimir Kaucak, Richard Rokyta, Robert Naplava, Zdenek Coufal, Vera Adamkova, Ivo Podpera, Jiri Zizka, Zuzana Motovska, Ivana Marusincova, Premysl Svab, Petr Heinc, Jiri Kuchar, Petr Povolny, Jiri Matuska, Steen H Poulsen, Bent Raungaard, Peter Clemmensen, Lia E Bang, Ole May, Morten Bøttcher, Jens D Hove, Lars Frost, Gunnar Gislason, John Larsen, Peter Betton Johansen, Flemming Hald, Peter Johansen, Jørgen Jeppesen, Tonny Nielsen, Kjeld S Kristensen, Piotr Maria Walichiewicz, Jens D Lomholdt, Ib C Klausen, Peter Kaiser Nielsen, Flemming Davidsen, Lars Videbaek, Mai Soots, Veiko Vahula, Anu Hedman, Üllar Soopõld, Kaja Märtsin, Tiina Jurgenson, Arved Kristjan, Juhani K Helsinki, Saila Vikman, Heikki Huikuri, Juhani Airaksinen, Pierre Coste, Emile Ferrari, Olivier Morel, Gilles Montalescot, Jacques Machecourt, Gilles Barone-Rochette, Jacques Mansourati, Yves Cottin, Florence Leclercq, Abdelkader Belhassane, Nicolas Delarche, Franck Boccara, Franck Paganelli, Jérôme Clerc, Francois Schiele, Victor Aboyans, Vincent Probst, Jacques Berland, Thierry Lefèvre, Bernard Citron, Irakli Khintibidze, Tamaz Shaburishvili, Zurab Pagava, Ramaz Ghlonti, Zaza Lominadze, George Khabeishvili, Rayyan Hemetsberger, Kemala Edward, Ursula Rauch-Kröhnert, Matthias Stratmann, Karl-Friedrich Appel, Ekkehard Schmidt, Heyder Omran, Christoph Stellbrink, Thomas Dorsel, Emmanouil Lianopoulos, Hans Friedrich Vöhringer, Roger Marx, Andreas Zirlik, Detlev Schellenberg, Thomas Heitzer, Ulrich Laufs, Christian Werner, Stephan Gielen, Sebastian Nuding, Bernhard Winkelmann, Steffen Behrens, Karsten Sydow, Mahir Karakas, Gregor Simonis, Thomas Muenzel, Nikos Werner, Stefan Leggewie, Dirk Böcker, Rüdiger Braun-Dullaeus, Nicole Toursarkissian, Michael Jeserich, Matthias Weißbrodt, Tim Schaeufele, Joachim Weil, Heinz Völler, Johannes Waltenberger, Mohammed Natour, Susanne Schmitt, Dirk Müller-Wieland, Stephan Steiner, Lothar Heidenreich, Elmar Offers, Uwe Gremmler, Holger Killat, Werner Rieker, Sotiris Patsilinakos, Athanasios Kartalis, Athanassios Manolis, Dimitrios Sionis, Geargios Chachalis, Ioannis Skoumas, Vasilios Athyros, Panagiotis Vardas, Frangkiskos Parthenakis, Dimitrios Alexopoulos, Georgios Hahalis, John Lekakis, Apostolos Hatzitolios, Sergio R Fausto Ovando, Juan L Arango Benecke, Edgar R Rodriguez De Leon, Bryan PY Yan, David CW Siu, Tibor Turi, Bela Merkely, Imre Ungi, Geza Lupkovics, Lajos Nagy, András Katona, István Édes, Gábor Müller, Iván Horvath, Tibor Kapin, Zsolt Szigeti, József Faluközy, Mukund Kumbla, Manjinder Sandhu, Sharath Annam, Naveen Reddy Proddutur, Reddy Regella, Rajendra K Premchand, Ajaykumar Mahajan, Sudhir Pawar, Atul D Abhyanakar, Prafulla Kerkar, Ravishankar A Govinda, Abraham Oomman, Dhurjati Sinha, Sachin N Patil, Dhiman Kahali, Jitendra Sawhney, Abhijeet B Joshi, Sanjeev Chaudhary, Pankaj Harkut, Santanu Guha, Sanjay Porwal, Srimannarayana Jujjuru, Ramesh B Pothineni, Minguel R Monteiro, Aziz Khan, Shamanna S Iyengar, Jasprakash Singh Grewal, Manoj Chopda, Mahesh C Fulwani, Aparna Patange, Patil Sachin, Vijay K Chopra, Naresh K Goyal, Rituparna Shinde, Gajendra V Manakshe, Nitin Patki, Sumeet Sethi, Vengatesh Munusamy, Sunil Karna, Sunil Thanvi, Srilakshmi Adhyapak, Chandrakant Patil, Ulhas Pandurangi, Rishabh Mathur, Jugal Gupta, Suhas Kalashetti, Ajit Bhagwat, Bagirath Raghuraman, Shiv Kumar Yerra, Prasant Bhansali, Rohidas Borse, Patil Rahul, Srihari Das, Vinay Kumar, Jabir Abdullakutty, Shireesh Saathe, Priya Palimkar, Shireesh Sathe, Shaul Atar, Michael Shechter, Morris Mosseri, Yaron Arbel, Chorin Ehud, Havakuk Ofer, Chaim Lotan, Uri Rosenschein, Amos Katz, Yaakov Henkin, Adi Francis, Marc Klutstein, Eugenia Nikolsky, Robert Zukermann, Yoav Turgeman, Majdi Halabi, Alon Marmor, Ran Kornowski, Michael Jonas, Offer Amir, Yonathan Hasin, Yoseph Rozenman, Shmuel Fuchs, Vered Zvi, Osamah Hussein, Dov Gavish, Zvi Vered, Yoseph Caraco, Mazen Elias, Naveh Tov, Efrat Wolfovitz, Michael Lishner, Nizar Elias, Giancarlo Piovaccari, Annamaria De Pellegrin, Raffaella Garbelotto, Gabriele Guardigli, Valgimigli Marco, Giovanni Licciardello, Carla Auguadro, Filippo Scalise, Claudio Cuccia, Alessandro Salvioni, Giuseppe Musumeci, Michelle Senni, Paolo Calabrò, Salvatore Novo, Pompilio Faggiano, Marco Metra, Nicoletta B De Cesare, Sergio Berti, Claudio Cavallini, Enrico Puccioni, Marcello Galvani, Maurizio Tespili, Piermarco Piatti, Michela Palvarini, Giuseppe De Luca, Roberto Violini, Alessandro De Leo, Zoran Olivari, Pasquale Perrone Filardi, Maurizio Ferratini, Vittorio Racca, Kazuoki Dai, Yuji Shimatani, Haruo Kamiya, Kenji Ando, Yoshihiro Takeda, Yoshihiro Morino, Yoshiki Hata, Kazuo Kimura, Koichi Kishi, Ichiro Michishita, Hiroki Uehara, Toshinori Higashikata, Atsushi Hirayama, Keiji Hirooka, Yasuji Doi, Satoru Sakagami, Shuichi Taguchi, Akihiro Koike, Hiroyuki Fujinaga, Shinji Koba, Ken Kozuma, Tomohiro Kawasaki, Yujiro Ono, Masatoshi Shimizu, Yousuke Katsuda, Atsuyuki Wada, Toshiro Shinke, Junya Ako, Kenshi Fujii, Toshiyuki Takahashi, Tomohiro Sakamoto, Koichi Nakao, Yutaka Furukawa, Hiroshi Sugino, Ritsu Tamura, Toshiaki Mano, Masaaki Uematsu, Noriaki Utsu, Kashima Ito, Takuya Haraguchi, Katsuhiko Sato, Yasunori Ueda, Akira Nishibe, Kazuteru Fujimoto, Motomaru Masutani, Jung Han Yoon, Hack-Lyoung Kim, Hun Sik Park, In-Ho Chae, Moo Hyun Kim, Myung Ho Jeong, Seungwoon Rha, Chongjin Kim, Hyo-Soo Kim, Hae Young Kim, Taekjong Hong, Seung-Jea Tahk, Youngkwon Kim, Arija Busmane, Natalija Pontaga, Aldis Strelnieks, Iveta Mintale, Iveta Sime, Zaneta Petrulioniene, Roma Kavaliauskiene, Ruta Jurgaitiene, Gintare Sakalyte, Rimvydas Slapikas, Sigute Norkiene, Nerijus Misonis, Aleksandras Kibarskis, Raimondas Kubilius, Stojko Bojovski, Nensi Lozance, Aleksandar Kjovkaroski, Snezana Doncovska, Tiong Kiam Ong, Sazzli Kasim, Oteh Maskon, Balachandran Kandasamy, Houng B Liew, Wan Mohd Izani Wan Mohamed, Armando García Castillo, Jorge Carrillo Calvillo, Pedro Fajardo Campos, Juan Carlos Núñez Fragoso, Edmundo Alfredo Bayram Llamas, Marco Antonio Alcocer Gamba, Jaime Carranza Madrigal, Luis Gerardo González Salas, Enrique López Rosas, Belinda González Díaz, Eduardo Salcido Vázquez, Alfredo Nacoud Ackar, Guillermo Antonio Llamas Esperón, Carlos Rodolfo Martínez Sánchez, María Guerrero De Leon, Rodrigo Suarez Otero, Guillermo Fanghänel Salmón, Jesús Antonio Pérez Ríos, José Angel Garza Ruíz, Robert W Breedveld, Margriet Feenema-Aardema, Alida Borger-Van Der Burg, Pieter AM Hoogslag, Harry Suryapranata, Antonius Oomen, Paulus Van Haelst, Jacobijne J Wiersma, Dirk Basart, Ruud MA Van Der Wal, Peter Zwart, Pascalle Monraats, Henricus Van Kesteren, Ioannis Karalis, Johan Jukema, Gerardus JE Verdel, Bart RG Brueren, Roland PTh Troquay, Eric P Viergever, Nadea YY Al-Windy, Gerard L Bartels, Jan H Cornel, Walter RM Hermans, Johannes PR Herrman, Robert J Bos, Reginald GEJ Groutars, Coenraad C Van Der Zwaan, Refik Kaplan, Raymond Lionarons, Eelko Ronner, Bjorn E Groenemeijer, Patrick NA Bronzwaer, Anho AH Liem, Bernard JWM Rensing, Marcel JJA Bokern, Remco Nijmeijer, Ferry MRJ Hersbach, Frank F Willems, Antonius TM Gosselink, Saman Rasoul, John Elliott, Gerard Wilkins, Raewyn Fisher, Douglas Scott, Hamish Hart, Ralph Stewart, Scott Harding, Ian Ternouth, Nicholas Fisher, Samuel Wilson, Denise Aitken, Russell Anscombe, Laura Davidson, Tadeusz Tomala, Ottar Nygård, Jon Arne Sparby, Kjell Andersen, Lars Gullestad, Jarle Jortveit, Peter S Munk, Erlend gyllensten Singsaas, Ulf Hurtig, Jorge R Calderon Ticona, Julio R Durand Velasquez, Sandra A Negron Miguel, Enrique S Sanabria Perez, Jesus M Carrion Chambilla, Carlos A Chavez Ayala, Reynaldo P Castillo Leon, Rolando J Vargas Gonzales, Jose D Hernandez Zuniga, Luis A Camacho Cosavalente, Jorge E Bravo Mannucci, Javier Heredia Landeo, Nassip C Llerena Navarro, Yudy M Roldan Concha, Víctor E Rodriguez Chavez, Henry A Anchante Hernandez, Carlos A Zea Nunez, Walter Mogrovejo Ramos, Arthur Ferrolino, Rosa Allyn G Sy, Louie Tirador, Rody G Sy, Generoso Matiga, Raul Martin Coching, Alisa Bernan, Gregorio Rogelio, Dante D. 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Schmedtje, J, Christenson, S, Dotani, I, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Assi, N, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Gamil, D, Akright, L, Krawczyk, J, Cobler, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, Egydio, F, Kawakami, A, Oliveira, J, Wozniak, J, Matthews, A, Ratky, C, Valiris, J, Berdan, L, Hepditch, A, Quintero, K, Rorick, T, Westbrook, M, Pascual, A, Rovito, C, Bezault, M, Drouet, E, Simon, T, Alsweiler, C, Luyten, A, Butters, J, Griffith, L, Shaw, M, Grunberg, L, Islam, S, Bregeault, M, Bougon, N, Faustino, D, Fontecave, S, Murphy, J, Verrier, M, Agnetti, V, Andersen, D, Badreddine, E, Bekkouche, M, Bouancheau, C, Brigui, I, Brocklehurst, M, Cianciarulo, J, Devaul, D, Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Chengyue, Z, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, Dempsey, M, Mcclanahan, M, ODYSSEY OUTCOMES Comm Investigato, and Ege Üniversitesi

Subjects
Male, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, STATIN THERAPY, blood-glucose, Endocrinology, Diabetes and Metabolism, GUIDELINES, PCSK9, 0302 clinical medicine, Endocrinology, GENETIC-VARIANTS, Cardiovascular Disease, Diabetes Complication, Aged Antibodies, Monoclonal, Humanized / therapeutic use* Cardiovascular Diseases / blood Cardiovascular Diseases / prevention & control* Diabetes Complications / blood Diabetes Complications / prevention & control* Female Humans Male Middle Aged Substances, Clinical endpoint, Medicine, guidelines, 030212 general & internal medicine, Prediabetes, Myocardial infarction, myocardial-infarction, genetic-variants, statin therapy, risk, pcsk9, association, liraglutide, evolocumab, RISK, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, BLOOD-GLUCOSE, ASSOCIATION, Middle Aged, Cardiovascular Diseases, Female, Life Sciences & Biomedicine, Human, medicine.medical_specialty, Acute coronary syndrome, PCSK9 inhibitor, acute coronary syndrome, lipoprotein(a), low-density lipoprotein cholesterol, 030209 endocrinology & metabolism, Antibodies, Monoclonal, Humanized, Diabetes Complications, Endocrinology & Metabolism, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Internal Medicine, Humans, Aged, Alirocumab, diabetes, PCSK9, hyperlipidemia, Science & Technology, ODYSSEY OUTCOMES Committees and Investigators, business.industry, Unstable angina, EVOLOCUMAB, medicine.disease, MYOCARDIAL-INFARCTION, LIRAGLUTIDE, Human medicine, business
Abstract

Doi, Yasuji/0000-0002-8368-0827; galvani, marcello/0000-0001-5897-667X; Gislason, Gunnar H/0000-0002-0548-402X; Taskinen, Marja-Riitta/0000-0002-6229-3588; Sherwood, Matthew/0000-0002-4305-5883; Malynovsky, Yaroslav V/0000-0002-9118-1104; Viktorova, vic-inna@mail.ru I.A./0000-0001-8728-2722; bastos, jose/0000-0002-9526-3123; Yang, Eric H/0000-0003-4889-7454; Rudenko, Anatoliy Viktorovich/0000-0003-1099-1613; Novotny, Vojtech/0000-0003-3521-9945; Nikolaev, Konstantin/0000-0003-4601-6203; Reshetko, Olga/0000-0003-3107-7636; Leonardi, Sergio/0000-0002-4800-6132; Muenzel, Thomas/0000-0001-5503-4150; Ushakov, Alexei V/0000-0002-7020-4442; Tse, Hung Fat/0000-0002-9578-7808; Podoleanu, Cristian/0000-0001-9987-2519; Raffel, Owen C/0000-0001-5470-7050; Khasanov, Niiaz/0000-0002-7760-0763; Chumakova, Galina A/0000-0002-2810-6531; Ersanli, Murat/0000-0003-1847-3087; cornel, jan hein/0000-0002-1006-2112; Abbate, Antonio/0000-0002-1930-785X; Racca, Vittorio/0000-0002-4465-3789; Urina-Triana, Miguel A/0000-0001-6003-4622; Rasputina, Lesia/0000-0003-1230-4039; Racca, Vittorio/0000-0002-4465-3789; Reis, Gilmar/0000-0002-4847-1034; Sandhu, Manjinder/0000-0003-2538-2079; Keskin, Kudret/0000-0002-9049-1530; PAREPA, IRINEL/0000-0002-7571-9015; Manakshe, Gajendra/0000-0002-4983-4271; Nicolau, Jose C/0000-0002-9680-3689; Strelnieks, Aldis/0000-0003-3493-2562; Budaj, Andrzej/0000-0002-6395-2098; Marin, Francisco/0000-0001-7246-7708; Wongpraparut, Nattawut/0000-0002-1541-3313; Yuan, Zuyi/0000-0002-4141-0298; Jeong, Myung Ho/0000-0003-2424-810X; Mostovoy, Yuriy/0000-0002-7041-1230; Pepine, Carl/0000-0002-6011-681X; Lopez-Jaramillo, Patricio/0000-0002-9122-8742; Garcia-Lledo, Alberto/0000-0002-8986-2584; Tesloianu, Nicolae-Dan/0000-0002-1007-3022; Kosmacheva, Elena/0000-0001-8600-0199; Kunz Sebba Barroso Souza, Weimar/0000-0002-1265-1930; Katz, Amos/0000-0003-0422-934X; Tunon, Jose/0000-0002-1373-0999; Acevedo, Monica/0000-0002-7989-6633; Hove, Jens/0000-0002-5600-5623; Yakushin, Sergey/0000-0001-7202-742X; Gonzalez Juanatey, Jose Ramon/0000-0001-9681-3388; Lyamina, Nadezhda/0000-0001-6939-3234; Aylward, Philip/0000-0002-5358-8552; Apostolovic, Svetlana/0000-0001-9015-297X; Airaksinen, Juhani/0000-0002-0193-568X; Nahhas, Prof. Dr. Ahmed/0000-0002-2887-8187; Barbarash, Olga/0000-0002-4642-3610, WOS: 000475553300016, PubMed: 31272931, Background After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1.4-1.8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1-12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1: 1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0.65-1.30 mmol/L. in this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)-defined on the basis of patient history, review of medical records, or baseline HbA(1c) or fasting serum glucose-and risk of new-onset diabetes among those without diabetes at baseline. the primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials. gov, number NCT01663402. Findings At study baseline, 5444 patients (28.8%) had diabetes, 8246 (43.6%) had prediabetes, and 5234 (27.7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2.20-2.28 mmol/L), after 4 months' treatment with alirocumab (0.80 mmol/L), or after 4 months' treatment with placebo (2.25-2.28 mmol/L). in the placebo group, the incidence of the primary endpoint over a median of 2.8 years was greater in patients with diabetes (16.4%) than in those with prediabetes (9.2%) or normoglycaemia (8.5%); hazard ratio (HR) for diabetes versus normoglycaemia 2.09 (95% CI 1.78-2.46, p, Sanofi; Regeneron Pharmaceuticals, Sanofi and Regeneron Pharmaceuticals.

Published
2019

45. Caspase-1 inhibition ameliorates murine acute graft versus host disease by modulating the Th1/Th17/Treg balance

Author

Hai Cheng, Wei Chen, QingLing Kong, Gui-Zhen Su, Bin Pan, Lingyu Zeng, Kailin Xu, Shengyun Zhu, Jiang Cao, Kunming Qi, Qing-Yun Wu, Wentong Guo, Feng Zhu, Yan Xu, Zhenyu Li, Rahul Bhansali, and Miao Li

Subjects
0301 basic medicine, Male, Colon, medicine.medical_treatment, T cell, Immunology, Interleukin-1beta, Caspase 1, Graft vs Host Disease, Inflammation, Hematopoietic stem cell transplantation, HMGB1, T-Lymphocytes, Regulatory, Proinflammatory cytokine, Amino Acid Chloromethyl Ketones, 03 medical and health sciences, 0302 clinical medicine, Immunology and Allergy, Medicine, Animals, HMGB1 Protein, Pathological, Lung, Pharmacology, Mice, Inbred BALB C, biology, business.industry, Interleukin-18, Th1 Cells, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Liver, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Th17 Cells, medicine.symptom, business, Decoy
Abstract

Our previous studies have implicated Caspase-1 signaling in driving the proinflammatory state of acute graft versus host disease (aGVHD). Therefore, we aimed to elucidate the mechanism of Caspase-1 in in murine models of aGVHD through specific inhibition of its activity with the decoy peptide Ac-YVAD-CMK. We transplanted bone marrow from donor C57BL/6 (H-2b) mice into recipient BALB/c (H-2Kd) mice and randomized the recipients into the following treatment cohorts: (1) allogeneic hematopoietic stem cell transplantation and splenic cell infusion control (PBS group); (2) low dose Ac-YVAD-CMK (AC low group); (3) and high dose Ac-YVAD-CMK (AC high group). Indeed, we observed that Caspase-1 inhibition by Ac-YVAD-CMK ameliorated pathological damage and inflammation in the liver, lungs, and colon elicited by aGVHD. This was associated with reduced mortality secondary to aGVHD. Mechanistically, we found that Caspase-1 inhibition modulated donor T cell expansion, restored the balance of Th1/Th17/Treg subsets, and markedly decreased serum levels and aGVHD target organ mRNA expression of IL-1β, IL-18, and HMGB1. Thus, we demonstrate that inhibition of Caspase-1 by Ac-YVAD-CMK mitigates murine aGVHD by regulating Th1/Th17/Treg balance and attenuating its characteristic proinflammatory state.

Published
2020

46. Efficacy of medical treatment for Charcot neuroarthropathy: a systematic review and meta-analysis of randomized controlled trials

Author

Ashu Rastogi, Anil Bhansali, and Edward B. Jude

Subjects
Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Anti-Inflammatory Agents, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Cochrane Library, law.invention, Weight-Bearing, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Pharmacotherapy, Randomized controlled trial, law, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Aged, Randomized Controlled Trials as Topic, business.industry, General Medicine, Bisphosphonate, Middle Aged, medicine.disease, Combined Modality Therapy, Casts, Surgical, Denosumab, Treatment Outcome, Strictly standardized mean difference, Meta-analysis, Female, Arthropathy, Neurogenic, business, medicine.drug
Abstract

No pharmacotherapeutic agents are yet recommended for active CN though many anti-resorptive agents have been studied. We conducted a systematic review and meta-analysis of the randomized placebo-controlled trials (RCTs) evaluating the time to remission of active CN with anti-resorptive or antiinflammatory drugs. RCTs published in PubMed, EMBASE, SCOPUS and Cochrane Library from January 1994 to December 2019 were accessed. We reviewed studies and extracted information on study design, participants' characteristics, time to remission, bone turnover markers, bone mineral content (BMC) and temperature difference between feet. Five RCTs out of 588 total identified records were included. Standardized mean differences (SMD) between groups with 95% CI are summarized. Pharmacotherapy nonsignificantly increased time to remission [SMD 0.52 weeks (- 0.71, 1.75), p = 0.402; I2 = 88.6%] as compared to TCC alone. The pooled median time to remission with the intervention was 18.5 weeks (11.2, 28.1) compared to 16.8 weeks (8.7, 27.7) with TCC. A nonsignificant increase in BMC [SMD 3.39% (- 0.78, 7.56), p = 0.109; I2 = 96.7%], a decrease in foot temperature [SMD - 0.42 °C (- 0.78, - 0.07), p = 0.020; I2 = 0%] and alkaline phosphatase [SMD = -2.51% (- 3.24, - 1.77), p < 0.001; I2 = 0%] was observed with intervention. Limited evidence from available studies does not support the role of anti-resorptive or anti-inflammatory drugs for earlier remission when added to offloading with total contact cast for active CN of the foot.

Published
2020

47. Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study)

Author

G D Puri, Pankaj Malhotra, Vikas Suri, Narayana Yaddanapudi, Naresh Sachdeva, Anil Bhansali, Ashu Rastogi, and Niranjan Khare

Subjects
Vitamin, Adult, Male, medicine.medical_specialty, Placebo-controlled study, 030209 endocrinology & metabolism, Disease, Placebo, Fibrinogen, Gastroenterology, Asymptomatic, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Vitamin D and neurology, medicine, Humans, 030212 general & internal medicine, Vitamin D, Cholecalciferol, business.industry, SARS-CoV-2, COVID-19, General Medicine, Middle Aged, Vitamin D Deficiency, COVID-19 Drug Treatment, C-Reactive Protein, chemistry, Dietary Supplements, Ferritins, RNA, Viral, Female, medicine.symptom, business, Procalcitonin, Biomarkers, medicine.drug
Abstract

Background Vitamin D has an immunomodulatory role but the effect of therapeutic vitamin D supplementation in SARS-CoV-2 infection is not known. Aim Effect of high dose, oral cholecalciferol supplementation on SARS-CoV-2 viral clearance. Design Randomised, placebo-controlled. Participants Asymptomatic or mildly symptomatic SARS-CoV-2 RNA positive vitamin D deficient (25(OH)D Intervention Participants were randomised to receive daily 60 000 IU of cholecalciferol (oral nano-liquid droplets) for 7 days with therapeutic target 25(OH)D>50 ng/ml (intervention group) or placebo (control group). Patients requiring invasive ventilation or with significant comorbidities were excluded. 25(OH)D levels were assessed at day 7, and cholecalciferol supplementation was continued for those with 25(OH)D Outcome measure Proportion of patients with SARS-CoV-2 RNA negative before day-21 and change in inflammatory markers. Results Forty SARS-CoV-2 RNA positive individuals were randomised to intervention (n=16) or control (n=24) group. Baseline serum 25(OH)D was 8.6 (7.1 to 13.1) and 9.54 (8.1 to 12.5) ng/ml (p=0.730), in the intervention and control group, respectively. 10 out of 16 patients could achieve 25(OH)D>50 ng/ml by day-7 and another two by day-14 [day-14 25(OH)D levels 51.7 (48.9 to 59.5) ng/ml and 15.2 (12.7 to 19.5) ng/ml (p Conclusion Greater proportion of vitamin D-deficient individuals with SARS-CoV-2 infection turned SARS-CoV-2 RNA negative with a significant decrease in fibrinogen on high-dose cholecalciferol supplementation. Trial register number NCT04459247.

Published
2020

48. Persistence of 'non-dipping' pattern in blood pressure after curative parathyroidectomy in apparently normotensive patients with symptomatic primary hyperparathyroidism

Author

Rimesh Pal, Anil Bhansali, Jayaprakash Puravoor, Sanjay Kumar Bhadada, Arunanshu Behera, and Soham Mukherjee

Subjects
Adult, Male, Parathyroidectomy, medicine.medical_specialty, Mean arterial pressure, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Diastole, Blood Pressure, 030209 endocrinology & metabolism, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Internal medicine, Internal Medicine, medicine, Humans, Arterial Pressure, Prospective Studies, Prospective cohort study, Creatinine, business.industry, Blood Pressure Monitoring, Ambulatory, Middle Aged, Hyperparathyroidism, Primary, medicine.disease, Treatment Outcome, Blood pressure, chemistry, 030220 oncology & carcinogenesis, Ambulatory, Cardiology, Female, business, Primary hyperparathyroidism
Abstract

BACKGROUND The prevalence of hypertension in primary hyperparathyroidism (PHPT) varies from 20-80% with data being based on office-based blood pressure measurements. Little is known about ambulatory monitoring of blood pressure (AMBP) in PHPT and changes in blood pressure (BP) variables post-curative parathyroidectomy. Hence, we conducted a prospective study wherein we performed AMBP in apparently normotensive patients with PHPT and reevaluated them 3 months post-curative parathyroidectomy. METHODS Consecutive patients with symptomatic PHPT aged 20 years and above underwent 24 hours AMBP at enrollment and at 3 months after successful parathyroidectomy. Pre- and postoperative BP variables were compared and correlated with serum calcium, creatinine and intact parathyroid hormone (iPTH) levels. RESULTS After exclusion, 17 symptomatic PHPT patients were enrolled in the study. AMBP detected hypertension in 4 (23.5%) patients. There was a significant reduction in the average nighttime systolic (P=0.007) and diastolic BP (P=0.034) after parathyroidectomy. However, the average 24 hours systolic/diastolic BP, daytime systolic/diastolic BP and average 24 hours mean arterial pressure did not differ before and after surgery. Non-dipping blood pressure pattern was seen in 53% of patients at presentation and persisted in 50% of cases after successful surgery. None of the biochemical parameters significantly correlated with any BP variable. CONCLUSIONS AMBP can help detect hypertension in patients with PHPT that remains unrecognized with routine office-based blood pressure measurement. In addition, AMBP detects loss of normal dipping pattern in BP that persists in almost half of the patients even after successful parathyroidectomy, perhaps because of permanent vascular damage induced by PHPT.

Published
2020

49. Role of [68Ga]DOTANOC PET/computed tomography and [131I]MIBG scintigraphy in the management of patients with pheochromocytoma and paraganglioma: a prospective study

Author

Rakhee Vatsa, Harmandeep Singh, Bhagwant Rai Mittal, Anupriya Chhabra, Rajender Kumar, Deepa Singh, Uma Nahar, Rama Walia, Nandini Paul, Jaya Shukla, and Anil Bhansali

Subjects
Adult, Male, medicine.medical_specialty, SDHB, Adrenal Gland Neoplasms, Pheochromocytoma, Scintigraphy, 030218 nuclear medicine & medical imaging, Metastasis, Paraganglioma, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Germline mutation, Positron Emission Tomography Computed Tomography, medicine, Organometallic Compounds, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Prospective cohort study, medicine.diagnostic_test, business.industry, General Medicine, Middle Aged, medicine.disease, 3-Iodobenzylguanidine, 030220 oncology & carcinogenesis, Mutation, Histopathology, Female, Radiology, business
Abstract

Purpose The primary aim of study was to compare role of iodine-131 (I-131)-labeled metaiodobenzylguanidine ([I]MIBG) and gallium-68 (Ga-68)-labeled DOTA-l-Nal3-octreotide ([Ga]DOTANOC) PET/computed tomography (CT) in patients with pheochromocytoma (PCC) and paraganglioma (PGL), subsequent follow-up to see management. The secondary aim was to see association of germline mutation in histopathologically proven patients. Procedures We performed [Ga]DOTANOC PET/CT and [I]MIBG in 106 patients (61 men; age: 38.5 ± 16.2 years) of known or suspected PCC/PGL. Following scans, 16 histopathologically proven patients were screened for germline mutations. Results [I]MIBG detected 41 lesions in 34 patients and [Ga]DOTANOC PET/CT detected more than 79 lesions in 55 patients. The mean duration of follow-up was 20.6 ± 16.5 months. Management following scans: surgery in 35 patients (positive histopathology in 34 patients, negative in 1 patient); lutecium-177 (Lu-177)-labeled DOTA-0-Tyr-3 octreotate ([Lu]DOTATATE) therapy in 2 patients; chemotherapy in 1 patient; conservative therapy in 34 patients; no therapy in 17 patients; 2 patients have died and 3 were lost to follow-up. Among 12 previously operated, 2 patients showed metastatic disease and 1 showed residual disease. Out of 16 patients who underwent genotypic analysis (15 operated), 8 were positive for germline mutations. Mutations were seen in SDHB, RET, VHL, MDH2 and SDHA genes, including two germline mutations in two patients. Deletion was observed in one patient in SDHB gene and substitution in all other mutations. Four novel mutations in MDH2 (c.1005G>C, c.916G>A, c.580G>A) and SDHB (c.378_380delAAT) were observed (SRA accession: PRJNA551457). Conclusions [Ga]DOTANOC PET/CT should be considered as a first-line investigation in PCC/PGL especially at high risk of metastasis and screening of persons with familial syndrome.

Published
2020

50. A quality improvement initiative for COPD patients: A cost analysis

Author

F.W. Peyerl, Archita H. Bhansali, Dushon D. Riley, Teofilo L. Lee-Chiong, and David Trout

Subjects
Budgets, Male, Quality management, Palliative care, Pulmonology, Medical Doctors, Copd patients, Cost-Benefit Analysis, Health Care Providers, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Medicine and Health Sciences, 030212 general & internal medicine, Economic impact analysis, Medical Personnel, health care economics and organizations, Aged, 80 and over, COPD, Multidisciplinary, Palliative Care, Disease Management, Middle Aged, Quality Improvement, Hospitals, Professions, Models, Economic, Cohort, Acute Disease, Cost analysis, Alabama, Medicine, Engineering and Technology, Female, Research Article, Biotechnology, Adult, medicine.medical_specialty, Death Rates, Science, Chronic Obstructive Pulmonary Disease, Equipment, Bioengineering, Patient Readmission, 03 medical and health sciences, Population Metrics, Cost Savings, Physicians, medicine, Humans, Aged, Hospitalizations, Health economics, Noninvasive Ventilation, Population Biology, business.industry, Correction, Biology and Life Sciences, medicine.disease, Health Care, 030228 respiratory system, Health Care Facilities, Emergency medicine, People and Places, Medical Devices and Equipment, Population Groupings, business
Abstract

The objective of this analysis was to evaluate and report on the economic impact of implementing an integrated, quality, and operational improvement program on chronic obstructive pulmonary disease (COPD) care from acute through post-acute care settings. This initiative was established in a cohort of 12 hospitals in Alabama and sought to address COPD readmission through improved workflows pertaining to early diagnosis, efficient care transitions, and patient visibility across the entire care episode. Implementation of the initiative was influenced by lean principles, particularly cross-functional agreement of workflows to improve COPD care delivery and outcomes. A budget impact model was developed to calculate cost savings directly from objective data collected during this initiative. The model estimated payer annual savings over 5 years. Patients were classified for analysis based on whether or not they received noninvasive ventilation. Scenario analyses calculated savings for payers covering different COPD cohort sizes. The base case revealed annual per patient savings of $11,263 for patients treated through the quality improvement program versus traditional care. The model projected cumulative savings of $52 million over a 5-year period. Clinical incorporation of non-invasive ventilation (NIV) resulted in $20,535 annual savings per patient and projected $91 million over 5 years. We conclude that an integrated management program for COPD patients across the care continuum is associated with substantial cost savings and significantly reduced hospital readmissions.

Published
2020

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