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OBJECTIVE: To evaluate whether pathologic complete response (pCR) exclusively defines major pathologic response to treatment with improved survival. SUMMARY BACKGROUND DATA: pCR following trimodality therapy for esophagogastric adenocarcinoma is infrequent but associated with improved prognosis. Yet most clinical trials and correlative studies designate pCR as the primary endpoint. METHODS: We analyzed our prospectively maintained database for patients who underwent trimodality therapy for locally advanced esophageal adenocarcinoma between 1995 and 2017. Overall survival (OS) was examined by percentage treatment response (TR) in the primary tumor bed and pathologic nodal stage (ypN0) using Kaplan-Meier plots. Optimal thresholds of TR for differentiating patients in terms of OS were investigated with descriptive plots using restricted cubic spline functions; associations were quantified using Cox multivariable analysis. RESULTS: Among 788 patients, median follow-up was 37.5 months (range, 0.4–210.6); median OS was 48.3 months (95% CI, 42.2–58.8). Absence of residual nodal disease was independently associated with improved survival (P

Background and objectives Several anthropometric measurements have been suggested to identify a potentially difficult airway. We studied thyromental height (TMH) as a predictor of difficult laryngoscopy and difficult intubation. We also compared TMH, ratio of height to thyromental distance (RHTMD), and thyromental distance (TMD) as predictors of difficult airway. Methods This cross-sectional observational study was conducted in 300 adult surgical patients requiring tracheal intubation. Preoperatively airway characteristics were assessed. Standard anesthesia was administered. Degree of difficulty with mask ventilation, laryngoscopic view, duration of laryngoscopy, and difficulty in tracheal intubation (intubation difficulty scale score) were noted. Multivariate logistics regression analysis was performed to identify independent predictors for difficult laryngoscopy. Results Laryngoscopy was difficult in 46 of 300 (15.3%) patients; all 46 patients had Cormack-Lehane grade 3 view. Duration of laryngoscopy was 27 ± 11 s in patients with difficult laryngoscopy and 12.7 ± 3.9 s in easy laryngoscopy; p = 0.001. Multivariate analysis identified that TMH, presence of short neck, and history of snoring were independently associated with difficult laryngoscopy. Incidence of difficult intubation was 17.0%. A shorter TMH was associated with higher IDS scores; r = -0.16, p = 0.001. TMH and duration of laryngoscopy were found to be negatively correlated; a shorter TMH was associated with a longer duration of laryngoscopy; r = -0.13, p = 0.03. The cut-off threshold value for TMH in our study is 4.4 cm with a sensitivity of 66% and a specificity of 54%. Conclusion Thyromental height predicts difficult laryngoscopy and difficult intubation. TMD and RHTMD did not prove to be useful as predictors of difficult airway.

The proliferation of smartphones equipped with various sensors created a large user base, which includes robots (smartphone controlled) as well. The high processor enabled smartphones are used as software robots to track hour-to-hour activities of users using on-board motion sensors. The magnetometer, accelerometer, and gyroscope are non-permission based motion sensors. The logs of these sensors create discriminative patterns to identify users’ movements. This leverages an adversary to cause privacy threats using these non-permission based sensors without user consent. Recent research works also highlighted the privacy threats due to these motion sensors in smartphones. Therefore, in this paper, we present a potential misuse of technology where smartphones can be hacked by PIN Inference attack endangering the physical and software robots’ controlled user activities. We perform experiments to collect motion sensors’ data and infer 4-digit PIN of a smartphone. Our strategy is to detect every key pressed one by one constituting a 4-digit PIN. Our inference results are promising and prove that an adversary can make use of sensors’ data to infiltrate user’s sensitive information from smartphones. Our proposed model infers 84% of the PINs correctly within 40 attempts when tested on 50 PINs. Given real Android devices with different users, we can identify the PIN of smartphones by training our machine learning based model. We also compare our approach with existing state-of-the-art approaches to show the efficacy of our attack model.

A 30-year-old woman presented with right-sided abdominal pain associated with fever. Her ultrasound showed right renal calculus with no hydronephrosis along with collection in peritoneal cavity and pouch of Douglas. CT showed ruptured right kidney with multiple renal and ureteric calculi as well as displaced renal calculi in perinephric space and pararenal space. Exploratory laparotomy and right nephroureterectomy were done. Nephrolithiasis with secondary infection makes the kidney fragile due to pathological changes, which may cause rupture of the renal calyces with trivial trauma or may be spontaneous. Distal obstruction by the stone and increased back pressure in the calyces may have added to the spontaneous rupture of the calyx and subsequently renal parenchyma. Management includes early exploration with nephrectomy and it is often life saving.

The index finger plays a major role in hand function. Subjects who sustain traumatic amputation of the single index finger also suffer both psychological and functional loss. Most of previous studies primarily focused on psychological benefits with finger prosthesis; however, it is essential to identify the functional benefit of the silicone finger in respective activity spectrum. To determine the improvement in function and activities with silicone finger prosthesis in proximal phalanx index finger amputation. Sixteen subjects were evaluated for the grip strength, pinch strength, and activities with dynamometer position II, pinchometer, and DASH questionnaire, respectively. Significant improvement of grip strength revealed in dynamometer position II ( p = 0.041) when tested without and with silicone finger prosthesis. The overall abilities in activities of daily living were improved significantly ( p = 0.005) as assessed by disability of arm, shoulder and hand questionnaire. Large effect sizes were noted in some activities like writing, jar opening, and carrying heavy object. Silicone finger prosthesis provides a functional benefit to the subjects in multiple activities. Partial loss of a finger has a relationship in limitation of hand function. Generally, clinicians prescribe silicone prosthesis for rehabilitation of finger amputee to restore the cosmetic purpose; however, functionality of the finger is also required to be restored. This study describes the role of silicone finger prosthesis on function and different activities for the subjects suffering from the index finger proximal phalanx amputation. Nayak S, Lenka PK, Equebal A, et al. Impact of Silicone Finger Prosthesis in Activities of Daily Living and Passive Function in Proximal Phalanx Index Finger Amputation. Indian J Phys Med Rehab 2019;30(3):59–65.

Objectives : To estimate the prevalence of nephrolithiasis in people with disabilities (PWD), while accounting for known kidney stone disease risk factors. Methods : We used answers to the disability and kidney disease questionnaires from the 2013-2016 cycles of the National Health and Nutrition Examination Survey (NHANES), a nationally representative cross-sectional survey by the Centers for Disease Control, to calculate nephrolithiasis prevalence by functional disability type. We additionally estimated the total US population of stone formers with disabilities and compared disability prevalence between stone formers and non-stone formers. Multivariate logistic regression models were built using known correlates of nephrolithiasis. Results : 34.7% (CI: 30.5-39.1%) of United States stone-formers are PWD. The prevalence of nephrolithiasis in PWD is 16.1% (CI: 14.4-18.0) in comparison to 9.2% (CI: 8.3-10.3) in people without disabilities. PWD have significantly elevated odds of nephrolithiasis (un-adjusted OR: 1.91 CI: 1.55-2.36). Adjusting for age, gender, race, diabetes, hypertension, and obesity, odds of nephrolithiasis remains elevated in PWD overall (adjusted OR: 1.46 95% CI: 1.17-1.83) and in all disability domains. Conclusions : One in 3 people with nephrolithiasis are PWD. Odds of nephrolithiasis are increased in PWD even after adjustment for multiple known risk factors in all disability domains. PWD are known to be a unique population that can face significant health disparities, but there is a dearth of studies that estimate urologic disease prevalence within this group. Future urologic research should incorporate disability status to explore potential disparities.

Background: Dealing with the COVID-19 pandemic has been one of the most important objectives of many countries.Intently observing the growth dynamics of the cases is one way to accomplish the solution for the pandemic. Introduction: Infectious diseases are caused by a micro-organism/virus from another person or an animal. It causes difficulty at both the individual and collective levels. The ongoing episode of COVID-19 ailment, brought about by the new coronavirus first detected in Wuhan, China, and its quick spread far and wide revived the consideration of the world towards the impact of such plagues on an individual’s everyday existence. We suggested that a basic structure be developed to work with the progressive examination of the development rate (cases/day) and development speed (cases/day2) of COVID-19 cases. Methods: We attempt to exploit the effectiveness of advanced deep learning algorithms to predict the growth of infectious diseases based on time series data and classification based on symptoms text data and X-ray image data. The goal is to identify the nature of the phenomenon represented by the sequence of observations and forecasting. Results: We concluded that our good habits and healthy lifestyle prevent the risk of COVID-19. We observed that by simply using masks in our daily lives, we could flatten the curve of increasing cases.Limiting human mobility resulted in a significant decrease in the development speed within a few days, a deceleration within two weeks, and a close to fixed development within six weeks. Conclusion: These outcomes authenticate that mass social isolation is a profoundly viable measure against the spread of SARS-CoV-2, as recently recommended. Aside from the research of country- by-country predominance, the proposed structure is useful for city, state, district, and discretionary region information, serving as a resource for screening COVID-19 cases in the area.

To evaluate the technical quality of root canal obturations performed by undergraduate students.The records of 347 patients who underwent endodontic treatment by undergraduate students of Qassim University between 2018 and 2020 were assessed using standardised criteria based on obturation length, density and taper. All teeth that received primary endodontic treatment and had post-obturation periapical radiographs depicting the entire radicular length and the 2-3-mm periradicular area were included in the study.A total of 653 canals of 397 teeth were evaluated. The maxillary central incisor was the most commonly assessed tooth (15.1%). Overall, 80.2% of the evaluated canals were deemed acceptable based on all three assessment criteria. Maxillary teeth had significantly better obturation quality than the mandibular teeth. The mesio-lingual canal had the lowest quality in all three criteria.The technical quality of root canal obturations performed by undergraduate students in Qassim University was acceptable in the majority of the evaluated cases. Among the evaluated parameters of obturation quality, length control was the most frequently observed deficiency. Additional measures are therefore required to improve the quality of the obturation length.تقييم الجودة الفنية لسد قناة الجذر التي يقوم بها طلاب المرحلة الجامعية.تم تقييم سجلات 347 مريضًا خضعوا للعلاج اللبي من قبل الطلاب الجامعيين في جامعة القصيم بين عامي 2018 و 2020 باستخدام معايير موحدة على أساس طول التجويف والكثافة والاستدقاق. تم تضمين جميع الأسنان التي تلقت علاجا لبيا أساسيا والتي تم تصويرها بعد الانسداد صورا شعاعية محيطة بالذروة تصور الطول الجذري الكامل بالإضافة إلى 2-3 ملم من المنطقة المحيطة بالحوصلة في الدراسة.تم تقييم إجمالي 653 قناة من 397 سنا. كان القاطع المركزي العلوي هو السن الأكثر تقييما (15.1%). بشكل عام، تم اعتبار 80.2٪ من القنوات التي تم تقييمها مقبولة في معايير التقييم الثلاثة. تتميز الأسنان العلوية ذات الدلالة الإحصائية بجودة سد أفضل. كانت القناة الوسطى اللغوية هي الأقل جودة في المعايير الثلاثة.كانت الجودة الفنية لسد قناة الجذر التي أجراها طلاب المرحلة الجامعية في جامعة القصيم مقبولة في غالبية الحالات التي تم تقييمها. من بين العوامل التي تم تقييمها لجودة السد، لوحظ النقص الأكثر شيوعًا هو من حيث التحكم في الطول. التدابير مطلوبة لتحسين جودة طول السد.

Background Individuals with COPD have increased sensitivity to traffic-related air pollution (TRAP) such as diesel exhaust (DE), but little is known about the acute effects of TRAP on exercise responses in COPD. Research question Does pre-exercise exposure to TRAP (DE300, PM2.5=300 μg/m3) have greater adverse effects on exercise endurance, exertional dyspnea, and cardiorespiratory responses to exercise in participants with mild-to-moderate COPD compared to former smokers with normal spirometry and healthy controls? Study design and Methods In this double-blind, randomized, placebo-controlled, crossover study, 11 healthy never-smokers, 9 ex-smokers without COPD and 9 ex-smokers with COPD were separately exposed to filtered air (FA) and DE300 for 2 hours separated by a minimum of 4 weeks. Participants performed symptom limited constant load cycling tests within 2.5 hours of exposure with detailed cardiorespiratory and exertional symptom measurements. Results There was a significant negative effect of TRAP on exercise endurance time in healthy controls (DE300 vs. FA: 10.2±8.2 vs. 12.9±9.5 min, respectively; p=0.03), but not in ex-smokers without COPD (10.1±6.9 vs. 12.2±8.0 min; respectively, p=0.57) or ex-smokers with COPD (9.8±6.4 vs. 8.4±6.6 min, respectively, p=0.31). Furthermore, significant increases in inspiratory duty cycle and absolute end-expiratory and end-inspiratory lung volumes were observed, and dyspnea ratings were elevated at select submaximal measurement times only in healthy controls. Interpretation Contrary to our hypothesis, it was the healthy controls rather than the ex-smokers with and without COPD that were negatively impacted by TRAP during exercise.

Aroma and flavour represent the key components of food that improves the organoleptic characteristics of food and enhances the acceptability of food to consumers. Commercial manufacturing of aromatic and flavouring compounds is from the industry's microbial source, but since time immemorial, its concept has been behind human practices. The interest in microbial flavour compounds has developed in the past several decades because of its sustainable way to supply natural additives for the food processing sector. There are also numerous health benefits from microbial bioprocess products, ranging from antibiotics to fermented functional foods. This review discusses recent developments and advancements in many microbial aromatic and flavouring compounds, their biosynthesis and production by diverse types of microorganisms, their use in the food industry, and a brief overview of their health benefits for customers.

Background: Childhood cancer survivors are at risk for cardiovascular disease. We assessed the burden of potentially modifiable cardiometabolic risk factors (CRF) among survivors compared with population-matched controls. Methods: Survivors previously enrolled on Pediatric Oncology Group protocols 9404, 9425, 9426, 9754, and Dana-Farber Cancer Institute 95-01 from 1996 to 2001 with acute lymphoblastic leukemia/lymphoma, Hodgkin lymphoma, or osteosarcoma were prospectively assessed for the prevalence of CRFs and compared with an age, sex, and race/ethnicity-matched 2013 National Health and Nutrition Examination Survey (NHANES) population. We estimated future predicted cardiovascular risk based on general population (e.g., Framingham) and Childhood Cancer Survivor Study (CCSS) models. Results: Compared with NHANES (n = 584), survivors [n = 164; 44.5% female, median age 28 years (range, 16–38 years); median 17.4 years (range, 13–22 years) since cancer diagnosis; median doxorubicin dose 300 mg/m2; 30.5% chest radiation] had similar rates of obesity, diabetes, and dyslipidemia, but more prehypertension/hypertension (38.4% vs. 30.1%, P = 0.044). Survivors had fewer metabolic syndrome features compared with NHANES (≥2 features: 26.7% vs. 55.9%; P < 0.001). Survivors were more physically active and smoked tobacco less (both P < 0.0001). Therefore, general population cardiovascular risk scores were lower for survivors versus NHANES. However, with CCSS models, 30.5% of survivors were at moderate risk of ischemic heart disease, and >95% at moderate/high risk for heart failure, with a 9% to 12% predicted incidence of these conditions by age 50 years. Conclusions: Childhood cancer survivors exhibited similar or better cardiometabolic and lifestyle profiles compared with NHANES, but nonetheless are at risk for future clinically significant cardiovascular disease. Impact: Further strategies supporting optimal CRF control are warranted in survivors. See related commentary by Mulrooney, p. 515

The study examines the value addition provided by frontier markets vis-a-vis emerging markets in improving the diversification benefits of an international portfolio. The analysis is performed for Asia-Pacific and Europe. It also surveys international investors to corroborate the empirical findings. The results indicate that though frontier markets offer higher diversification opportunities than emerging markets, the frontier market investments are recommended for investors with good risk appetite. Asia-Pacific emerging markets perform better than frontier markets in improving the portfolio's performance. European frontier markets' performance was adversely affected by Covid 19 pandemic. Overall, Asia-Pacific equity markets provide greater potential for diversification than their European counterparts.

Background/Aims This study aimed to delineate the clinical profile of children diagnosed with progressive familial intrahepatic cholestasis (PFIC). Methods This study was a retrospective analysis of case records of children in the tertiary care hospital, with the diagnosis of PFIC from January 2017 to January 2020. The diagnosis was made using clinical and laboratory parameters and with genetic testing when available. Medical and surgical management was according to the departmental protocol. Liver transplant was offered to children with end-stage liver disease, intractable pruritus, or severe growth failure. Result There were 13 identified PFIC cases (familial intrahepatic cholestasis 1 [FIC1] deficiency-4, bile salt export pump (BSEP) deficiency-3, tight junction protein [TJP2] deficiency 3, multidrug-resistant protein 3 [MDR3] deficiency 2 and farnesoid X receptor deficiency-1). PFIC subtypes 1, 2, and 5 presented in infancy, whereas MDR3 presented in childhood. TJP2 deficiency had varied age of presentation from infancy to adolescence. Jaundice with or without pruritus was present in most cases. Genetic testing was carried out in 10 children, of which five had a homozygous mutation, three had a compound heterozygous mutation, and two had a heterozygous mutation. Three children (FIC1-2 and TJP2-1) underwent biliary diversion, of which clinical improvement was seen in two. Six children underwent liver transplantation, which was successful in four. Conclusion Byler's disease was the most common subtype. A clinicopathologic correlation with molecular diagnosis leads to early diagnosis and management. Liver transplantation provides good outcomes in children with end-stage liver disease.

Background and Aims Standard coagulation tests such as prothrombin time, activated partial thromboplastin time, and international normalized ratio are determined by liver-synthesized coagulation factors. Despite an increased international normalized ratio, patients with cirrhosis are in a “rebalanced” state of hemostasis as the concomitant effect of reduced protein C, protein S, and thrombomodulin is not evaluated in standard coagulation tests. The cell-based model of hemostasis indicates additional mechanisms such as systemic inflammation, sepsis, and organ failures tip the delicate coagulation balance to an anticoagulant type in acute-on-chronic liver failure. In acute liver failure, thrombin generation and platelet function remain intact despite a marked prolongation in prothrombin time. We aimed to explain the principles, application, and utility of viscoelastic tests such as thromboelastography, rotational thromboelastometry, and Sonoclot. Methods We reviewed the available literature from MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trial with the search terms 'coagulation', 'cirrhosis', 'acute-on-chronic liver failure', 'thromboelastography', 'thromboelastometry' and 'sonoclot' for cross sectional studies, cohort studies and randomized trials Results The point-of-care viscoelastic tests provide actionable targets for correcting the coagulation defect in a patient with bleeding and provide evidence-based algorithms for use in liver disease. A limitation of these tests is the inability to assess vessel injury and endothelial elements. Conclusion Global coagulation tests provide a comprehensive estimate of coagulation in vitro; however, their use has only been validated in the setting of liver transplantation. Newer guidelines for hemostatic resuscitation are now accepting these POC tests, but additional data are required to validate their use as standard of care.

Context: Yoga is increasingly popular, not only as a form of recreational exercise but also as a physician-recommended intervention for health conditions. While serious adverse effects accompanying yoga practice are rare, poses that involve upper-extremity weight-bearing have a high risk of discomfort. To better understand factors contributing to adverse effects, there is a critical need for robust instruments that objectively evaluate pose performance. The purpose of this study was to assess the interrater reliability of an observational scale developed to assess the alignment of 3 yoga poses. Design: Cross-sectional experimental study. Methods: Thirty-eight individuals were given standardized instructions and performed 3 poses (Downward Dog, Plank, and Side Plank). Lateral videos were rated by 2 raters. A rating scale evaluating the alignment of 7 regions was developed by the study team with input from yoga teachers. Descriptive statistics were used to summarize the percentage of subjects showing ideal alignment and deviations. Interrater reliability was quantified using Cohen kappa coefficient (κ). Results: In Downward Dog, the prevalence of ideal alignment was 20%, 28%, and 37%, at the neck, shoulder, and back, respectively; κ ranged from .44 to .69. In Plank, the prevalence of ideal alignment was 31%, 45%, and 54% at the neck, shoulder, and back, respectively; κ ranged from .47 to .95. In Side Plank, the prevalence of ideal alignment was 16, 41%, and 24%, at the neck, shoulder, and back, respectively; κ ranged from .20 to .84. Conclusion: The observational scale found a high prevalence of deviations, and demonstrated fair to substantial interrater agreement.

Background: Survivors of childhood cancer are at risk for therapy-related subsequent malignant neoplasms (SMN), including thyroid SMN. Telomere length (TL) is associated with cancer risk, but the relationship between TL and SMN risk among survivors is less clear. Methods: We conducted a nested, matched case–control study of radiation-exposed 15-year+ adult survivors of childhood cancer with thyroid SMN (cases) and without SMN (controls). Forty-six cases were matched to 46 controls by primary diagnosis, chemotherapy (yes/no), radiation field, and follow-up duration. Lymphocyte TL (LTL) was measured by telomere flow-FISH cytometry using blood samples banked at a mean of 38.9 years (cases), 39.2 years (controls). Genetic variation in telomere genes was assessed by whole genome sequencing. Point estimates for LTL Results: Cases had shorter median LTL than controls in three out of four leukocyte subsets. Cases were more likely to have NK cell LTL Conclusions: Long-term survivors have shorter than expected LTL, a finding that is more pronounced among survivors with thyroid SMN. Impact: The long-term impact of childhood cancer treatment on immune function is poorly understood. Our findings support immune function studies in larger survivor cohorts to assess long-term deficits in adaptive and innate immunity that may underlie SMN risk.

Background: Outcomes among Hodgkin lymphoma (HL) patients diagnosed between 22 and 39 years are worse than among those diagnosed Methods: We examined cancer-related expenditures among 22- to 39-year-old HL patients diagnosed between 2001 and 2016 using deidentified administrative claims data (OptumLabs Data Warehouse; CCC: n = 1,154; non-CCC: n = 643). Adjusting for sociodemographics, clinical characteristics, and months enrolled, multivariable general linear models modeled average monthly health-plan paid (HPP) expenditures, and incidence rate ratios compared CCC/non-CCC monthly visit rates. Results: In the year following diagnosis, CCC patients had higher HPP expenditures ($12,869 vs. $10,688, P = 0.001), driven by higher monthly rates of CCC nontreatment outpatient hospital visits (P = 0.001) and per-visit expenditures for outpatient hospital chemotherapy ($632 vs. $259); higher CCC inpatient expenditures ($1,813 vs. $1,091, P = 0.001) were driven by 3.1 times higher rates of chemotherapy admissions (P = 0.001). Out-of-pocket expenditures were comparable (P = 0.3). Conclusions: Young adults with HL at CCCs saw higher health-plan expenditures, but comparable out-of-pocket expenditures. Drivers of CCC expenditures included outpatient hospital utilization (monthly rates of non-therapy visits and per-visit expenditures for chemotherapy). Impact: Higher HPP expenditures at CCCs in the year following HL diagnosis likely reflect differences in facility structure and comprehensive care. For young adults, it is plausible to consider incentivizing CCC care to achieve superior outcomes while developing approaches to achieve long-term savings.

Summary Background Young survivors of cancer are at increased risk for cancers that are related to human papillomavirus (HPV), primarily caused by oncogenic HPV types 16 and 18. We aimed to examine the immunogenicity and safety of the three-dose series of HPV vaccine in young survivors of cancer. Methods We conducted an investigator-initiated, phase 2, single-arm, open-label, non-inferiority trial at five National Cancer Institute-designated comprehensive cancer centres in the USA. Eligible participants were survivors of cancer who were HPV vaccine-naive, were aged 9–26 years, in remission, and had completed cancer therapy between 1 and 5 years previously. Participants received three intramuscular doses of either quadrivalent HPV vaccine (HPV4; enrolments on or before March 1, 2016) or nonavalent HPV vaccine (HPV9; enrolments after March 1, 2016) over 6 months (on day 1, at month 2, and at month 6). We also obtained data from published clinical trials assessing safety and immunogenicity of HPV4 and HPV9 in 9–26-year-olds from the general population, as a comparator group. The primary endpoint was antibody response against HPV types 16 and 18 at month 7 in the per-protocol population. A response was deemed non-inferior if the lower bound of the multiplicity-adjusted 95% CI was greater than 0·5 for the ratio of anti-HPV-16 and anti-HPV-18 geometric mean titres (GMTs) in survivors of cancer versus the general population. Responses were examined separately in male and female participants by age group (ie, 9–15 years and 16–26 years). Safety was assessed in all participants who received at least one vaccine dose and for whom safety data were available. This study is registered with ClinicalTrials.gov, NCT01492582. This trial is now completed. Findings Between Feb 18, 2013, and June 22, 2018, we enrolled 453 survivors of cancer, of whom 436 received one or more vaccine doses: 203 (47%) participants had survived leukaemia, 185 (42%) were female, and 280 (64%) were non-Hispanic white. Mean age at first dose was 15·6 years (SD 4·6). 378 (83%) of 453 participants had evaluable immunogenicity data; main reasons for exclusion from per-protocol analysis were to loss to follow-up, patient reasons, and medical reasons. Data were also obtained from 26 486 general population controls. The ratio of mean GMT for anti-HPV types 16 and 18 in survivors of cancer versus the general population was more than 1 for all subgroups (ie, aged 9–15 years, aged 16–26 years, male, and female groups) in both vaccine cohorts (ranging from 1·64 [95% CI 1·12–2·18] for anti-HPV type 16 in female participants aged 9–15 years who received HPV9, to 4·77 [2·48–7·18] for anti-HPV type 18 in male participants aged 16–26 years who received HPV4). Non-inferiority criteria were met within each age and sex subgroup, except against HPV type 18 in female participants aged 16–26 years receiving HPV9 (4·30 [0·00–9·05]). Adverse events were reported by 237 (54%) of 435 participants; injection site pain was most common (174 [40%] participants). One serious adverse event (ie, erythema nodosum) was possibly related to vaccine (HPV9; 16–26 year female cohort). Interpretation Immunogenicity and safety of HPV vaccine three-dose series in survivors of cancer is similar to that in the general population, providing evidence for use in this clinically vulnerable population. Funding US National Cancer Institute, Merck, Sharp & Dohme, and American Lebanese Syrian Associated Charities.

A pyogenic hepatic abscess is an uncommon complication after laparoscopic sleeve gastrectomy (LSG) that can develop secondary to an infected hematoma or a staple line leak due to bacterial seeding. Appropriate screening for and management of a pyogenic hepatic abscess are essential in patients with clinical suspicion for complications after LSG. Early diagnosis is essential as pyogenic hepatic abscess can be fatal if not treated early. Only five cases have been reported in the literature so far. We present a case of pyogenic hepatic abscess that occurred two weeks after LSG in a 46-year-old female without immunosuppressive conditions or early postoperative leak. The abscess was diagnosed by computed tomography (CT) and was successfully treated with antibiotics and CT-guided drainage.

Purpose To define the burden of morbidity and mortality arising from COVID-19 in individuals with primary (PID) and secondary immunodeficiency (SID) in the United Kingdom. Methods In March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. Anonymised demographic data, pre-SARS-CoV-2 infection lymphocyte counts, co-morbidities, targeted treatments and outcomes were collected. Three groups were analysed in further detail: individuals with common variable immunodeficiency (CVID), individuals with any PID, including CVID, receiving immunoglobulin replacement therapy (IgRT) and individuals with secondary immunodeficiency. Results A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID, had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Conclusion Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count and the presence of co-morbidities are additional risk factors for poor outcome in this cohort.

Objectives: Head and neck cancer (HNC) constitutes a substantial portion of the cancer burden worldwide, with over 550,000 new cases and over 300,000 deaths annually, with disproportionately high mortality rates in the developing countries. The large majority of HNCs are caused by tobacco use, and synergistic effects of tobacco and alcohol use. Using the Common-Sense Model (CSM) as a framework, this qualitative study sought to understand South Asian HNC survivors' cognitive and emotional representations of their cancer; and to assess if these representations differ by smokeless tobacco (SLT) vs. smoked tobacco use. Design: In-depth semi-structured interviews, conducted with South Asian HNC survivors (N = 15, 80% participants were immigrants, while 20% came to the United States for treatment) to identify key themes and issues related to HNC experience and SLT vs. smoked tobacco use. Results: The results of the study provide a deeper understanding of South Asian HNC survivor experiences with receiving a HNC diagnosis, delays in seeking treatment and related medical care, disagreement regarding smoked tobacco/SLT history as potential causes of cancer, strategies to cure the cancer or prevent recurrence, enduring physical and psycho-social consequences of treatment, and emotional impact of the cancer experience. Three key implications emerged: (a) the utility of narratives as a method of eliciting HNC survivor experience to understand patient experiences and concerns; (b) the potential for public health practitioners to harness patients' voices and the power of storytelling for developing campaigns about public awareness of SLT use, providing information and support to SLT users, and encouraging SLT quitting resources; and (c) the importance of providing clear, personalized and culturally sensitive education regarding the risks of SLT use. Conclusions: This study underscores the significance of offering tailored tobacco cessation services to South Asian HNC survivors, and to help inform supportive models of care for others.

Tourism Social Entrepreneurship is a market-based strategy for sustainable tourism development. It solves complex social issues to benefit disadvantaged stakeholders, while seeking to achieve financial sustainability and boost the benefits of tourism. Currently, there is little insight into how social entrepreneurs create these innovative social solutions. This black box hinders the understanding and replication of tourism social entrepreneurial success in different contexts, thus preventing the social benefits of tourism from increasing. We suggest that the literature on TSE can be informed by design thinking - a human centered framework for social innovation. Taking a social enterprise in Vietnam as a case study of Community-Based Tourism Travel, this paper reveals that tourism social entrepreneurs have developed an intuitive ability to apply design thinking to social innovation, despite lacking training. The paper thus sheds light on the social entrepreneur's innovative abilities, and contributes to fostering successful social entrepreneurship in a tourism context.

PURPOSE The Pediatric Oncology COVID-19 Case Report registry supplies pediatric oncologists with data surrounding the clinical course and outcomes in children with cancer and SARS-CoV-2. METHODS This observational study captured clinical and sociodemographic characteristics for children (≤ 21 years) receiving cancer therapy and infected with SARS-CoV-2 from the pandemic onset through February 19, 2021. The demographic and clinical characteristics of the cohort were compared with population-level pediatric oncology data (SEER). Multivariable binomial regression models evaluated patient characteristics associated with hospitalization, intensive care unit (ICU) admission, and changes in cancer therapy. RESULTS Ninety-four institutions contributed details on 917 children with cancer and SARS-CoV-2. Median age at SARS-CoV-2 infection was 11 years (range, 0-21 years). Compared with SEER, there was an over-representation of Hispanics (43.6% v 29.7%, P < .01), publicly insured (59.3% v 33.5%, P < .01), and patients with hematologic malignancies (65.8% v 38.3%, P < .01) in our cohort. The majority (64.1%) were symptomatic; 31.2% were hospitalized, 10.9% required respiratory support, 9.2% were admitted to the ICU, and 1.6% died because of SARS-CoV-2. Cancer therapy was modified in 44.9%. Hispanic ethnicity was associated with changes in cancer-directed therapy (adjusted risk ratio [aRR] = 1.3; 95% CI, 1.1 to 1.6]). Presence of comorbidities was associated with hospitalization (aRR = 1.3; 95% CI, 1.1 to 1.6) and ICU admission (aRR = 2.3; 95% CI, 1.5 to 3.6). Hematologic malignancies were associated with hospitalization (aRR = 1.6; 95% CI, 1.3 to 2.1). CONCLUSION These findings provide critical information for decision making among pediatric oncologists, including inpatient versus outpatient management, cancer therapy modifications, consideration of monoclonal antibody therapy, and counseling families on infection risks in the setting of the SARS-CoV-2 pandemic. The over-representation of Hispanic and publicly insured patients in this national cohort suggests disparities that require attention.

Breast cancer (BC) is the most common malignancy in women. Particular subtypes with aggressive behavior are major contributors to poor outcomes. Triple-negative breast cancer (TNBC) is difficult to treat, pro-inflammatory, and highly metastatic. We demonstrate that TNBC cells express TLR9 and are responsive to TLR9 ligands, and treatment of TNBC cells with chemotherapy increases the release of nucleic-acid-containing damage-associated molecular patterns (NA DAMPs) in cell culture. Such culture-derived and breast cancer patient-derived NA DAMPs increase TLR9 activation and TNBC cell invasion in vitro. Notably, treatment with the polyamidoamine dendrimer generation 3.0 (PAMAM-G3) behaved as a nucleic acid scavenger (NAS) and significantly mitigates such effects. In mice that develop spontaneous BC induced by polyoma middle T oncoprotein (MMTV-PyMT), treatment with PAMAM-G3 significantly reduces lung metastasis. Thus, NAS treatment mitigates cancer-induced inflammation and metastasis and represents a novel therapeutic approach for combating breast cancer., Graphical abstract, Using a nucleic acid scavenger, Eteshola et al. present an innovative way to slow down metastasis following standard-of-care therapy in difficult-to-treat malignancies such as triple-negative breast cancer. By capturing tumor-derived nucleic acid-containing DAMPs in vitro and in a spontaneous transgenic murine model, this strategy lays the groundwork for improving the clinical management of cancer by adding an adjuvant that limits metastatic spread.

BACKGROUND: More than half of patients treated with esophagectomy for esophageal cancer experience recurrence. Oligometastasis, a proposed intermediate state of isolated local or solid-organ recurrence that occurs before widespread systemic disease, is a potential target for aggressive local intervention. We investigated presentation and prognosis between solid-organ recurrence sites. METHODS: Patients with isolated solid-organ recurrence at the liver, lung, or brain who underwent R0 esophagectomy from 1995 to 2016 were identified. Clinicopathologic characteristics and outcomes were compared between sites of recurrence. Overall survival was quantified using the Kaplan-Meier approach and Cox proportional hazards models. RESULTS: In total, 104 patients were included (site: brain, 37; lung, 27; liver, 40). Eighty percent of liver, 51% of brain, and 44% of lung oligometastases occurred in the first 12 months after esophagectomy. Despite the limited use of aggressive therapy, patients with lung oligometastasis had significantly longer median overall survival (2.41 years; 95% confidence interval [CI], 1.58–3.31) than patients with brain (0.95 years; 95% CI, 0.62–1.49) or liver (0.95 years; 95% CI, 0.82–1.41) oligometastasis (p

SARS-CoV-2 has infected a large number of pregnant women.To compare clinical, perinatal outcomes of women with COVID-19 from high-income countries (HICs) and low- to middle-income countries (LMICs).Online databases were searched.Original studies on pregnant women with COVID-19 were included.Information on clinical presentation, co-morbidities, pregnancy outcomes, neonatal outcomes, and SARS-CoV-2 infection in neonates was extracted.The pooled estimate of SARS-CoV-2 positive neonates is 3.7%. Symptomatic presentations are less common in LMICs compared to HICs (odds ratio [OR] 0.38). Diabetes (OR 0.5), hypertension (OR 0.5), and asthma (OR 0.14) are commonly reported from HICs; hypothyroidism (OR 2.2), anemia (OR 3.2), and co-infections (OR 6.0) are commonly reported in LMICs. The overall risk of adverse pregnancy outcomes is higher in LMICs compared to HICs (OR 2.4). Abortion (OR 6.2), stillbirths (OR 2.0), and maternal death (OR 7.8) are more common in LMICs. Preterm births and premature rupture of membranes are comparable in both groups. Neonatal deaths (OR 3.7), pneumonia (OR 7.5), and neonatal SARS-CoV-2 infection (OR 1.8) are commonly reported in LMICs.In LMICs, pregnant women and neonates are more vulnerable to adverse outcomes due to COVID-19. PROSPERO registration no: CRD42020198743.

Background Body composition is associated with chemotherapy toxicity (chemotoxicity) in adults with cancer; this association remains unexplored in children with cancer. Methods Using baseline computed tomography scans of 107 children with Hodgkin lymphoma (n = 45), non-Hodgkin lymphoma (n = 42), or rhabdomyosarcoma (n = 20), this study examined body composition (skeletal muscle index [SMI], skeletal muscle density [SMD], and height-adjusted total adipose tissue [hTAT]) to determine its association with chemotoxicity. Clinical characteristics and chemotoxicities were abstracted from medical records. Primary outcomes included grade 4 or higher hematologic toxicities and grade 3 or higher nonhematologic toxicities within 6 months of the diagnosis. Logistic regression models accounting for repeated measures were constructed to examine the association between body composition indices and chemotoxicities; adjustments were made for age at diagnosis, sex, race/ethnicity, cancer type, risk group, body mass index (measured as a percentile), or body surface area. Results The median SMI was 41.0 cm2 /m2 (range, 25.8-68.6 cm2 /m2 ), the median SMD was 54.1 HU (range, 35-69.4 HU), and the median hTAT was 19.5 cm2 /m2 (range, 0-226.7 cm2 /m2 ). Grade 4 or higher hematologic toxicities and grade 3 or higher nonhematologic toxicities were observed in 74.7% and 66.3% of the chemotherapy cycles, respectively. A higher SMD at diagnosis was associated with lower odds of grade 4 or higher hematologic toxicity (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.85-0.97; P = .004). SMI (OR, 0.99; 95% CI, 0.95-1.04; P = .7) and hTAT (OR, 1.00; 95% CI, 0.99-1.01; P = .9) were not associated with hematologic toxicities. Nonhematologic toxicities did not show any association with body composition. Conclusions The association between low SMD and hematologic toxicities in children with lymphoma or rhabdomyosarcoma could be due to body composition-based biodistribution of chemotherapeutic agents and needs further investigation. Lay summary Body composition at cancer diagnosis in children with lymphoma and rhabdomyosarcoma may provide information that could identify those at risk for serious side effects from chemotherapy. Routinely used measures such as body mass index and body surface area show poor correlations with body composition assessed via computed tomography scans.

Objectives: To analyse the spectrum of imaging findings of fungal infection as seen in MRI images of priorly treated for COVID. Materials and methods: The different patterns of findings of Neuro Rhino Sino Orbital Fungal Infections as seen in MRI images in 100 patients who received standard treatment for COVID in recent past and presented with suggestive signs and symptoms. Results: No positive MRI findings to suggest any neural tissue, orbital or Sino nasal involvement was seen in 35 % of cases. Only sino nasal involvement noted in 23 % cases. Sino-nasal as well as orbital involvement seen in 21 % cases. Neuro Sino Naso Orbital lesions were seen in 11% cases. Non fungal orbito-facial soft tissue inflammation was seen in 10 % cases. Conclusion: In patients who have received standard treatment for Covid and who later developed signs and symptoms of neural, orbital or Sino nasal involvement; positive imaging findings were noted in 65% cases. Fungal infections were seen more in middle aged population [40-60 years of age]. About 75 % of affected patients were known diabetics. Neural involvement was least common. This study proposes a new staging system [Stage 0, X, I, II, III, IV] for describing the affected region by fungal infection.

OBJECTIVE We sought to compare gastroesophageal junction (GEJ) cancer and gastric cancer (GC) and identify clinicopathological and oncological differences. SUMMARY BACKGROUND DATA GEJ cancer and GC are frequently studied together. Although the treatment approach for each often differs, clinicopathological and oncological differences between the 2 have not been fully evaluated. METHODS We retrospectively identified patients with GEJ cancer or GC who underwent R0 resection at our center between January 2000 and December 2016. Clinicopathological characteristics, disease-specific survival (DSS), and site of first recurrence were compared. RESULTS In total, 2194 patients were analyzed: 1060 (48.3%) with GEJ cancer and 1134 (51.7%) with GC. Patients with GEJ cancer were younger (64 vs 66 years; P < 0.001), more often received neoadjuvant treatment (70.9% vs 30.2%; P < 0.001), and had lower pathological T and N status. Five-year DSS was 62.2% in patients with GEJ cancer and 74.6% in patients with GC (P < 0.001). After adjustment for clinicopathological factors, DSS remained worse in patients with GEJ cancer (hazard ratio, 1.78; 95% confidence interval, 1.40-2.26; P < 0.001). The cumulative incidence of recurrence was approximately 10% higher in patients with GEJ cancer (P < 0.001). The site of first recurrence was more likely to be hematogenous in patients with GEJ cancer (60.1% vs 31.4%; P < 0.001) and peritoneal in patients with GC (52.9% vs 12.5%; P < 0.001). CONCLUSIONS GEJ adenocarcinoma is more aggressive, with a higher incidence of recurrence and worse DSS, compared with gastric adenocarcinoma. Distinct differences between GEJ cancer and GC, especially in patterns of recurrence, may affect evaluation of optimal treatment strategies.

ObjectiveThe understanding of acceptability of existing dosage forms is limited in most of the world and hinders the development of acceptable, age‐appropriate medicines. The attributes of paediatric medicine acceptability may differ from country to country based on culture, healthcare infrastructure and health policies. This study was designed to map the acceptability of oral medicines in paediatric patients treated in hospital in India.MethodsAn observational, cross-sectional study was conducted in patients aged below 18 years and taking any form of oral medication. Acceptability scores were obtained using CAST–ClinSearch Acceptability Score Test tool.Findings490 patients were recruited and 193 evaluations of different pharmaceutical products available in 20 dosage forms and 7 routes of administration were studied. Oral liquids (50%) and tablets (35%) were the most commonly prescribed and administered forms. Regardless of the therapeutic class and age, the oral liquids were ‘positively accepted’ in infants and toddlers. Acceptability of tablets improved with age and appeared to be generally good from the age of 6.ConclusionThis study indicates the limited progress towards adoption of age-appropriate dosage forms in India and thus impact on the acceptability of existing oral dosage forms. The key challenges posed by the adoption of age-appropriate formulations in India are (1) awareness of importance of appropriate administration and acceptability of medicines to children in India, (2) availability of age-appropriate dosage forms and (3) lack of child-appropriate medicine policies.

Nodular hyperplasia of parathyroid gland is an advanced state commonly seen in a secondary and tertiary hyperparathyroidism. It shares similarities on histology with parathyroid adenoma creating a diagnostic dilemma. Adequate history, biochemical investigations and radiological studies majorly supports the accurate diagnosis. Identifying correct state of hyperparathyroidism is essential in a view of therapeutic management and its outcome. Keywords: Chronic kidney disease, Nodular hyperplasia, Secondary hyperparathyroidism, Tertiary hyperparathyroidism.

BACKGROUND: The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.K. National Health Service. Other parts of this project focus on patients with cancer and infection.METHODS: We conducted a pilot study involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present. We collected data on clinical features with the use of Human Phenotype Ontology terms, undertook genome sequencing, applied automated variant prioritization on the basis of applied virtual gene panels and phenotypes, and identified novel pathogenic variants through research analysis.RESULTS: Diagnostic yields varied among family structures and were highest in family trios (both parents and a proband) and families with larger pedigrees. Diagnostic yields were much higher for disorders likely to have a monogenic cause (35%) than for disorders likely to have a complex cause (11%). Diagnostic yields for intellectual disability, hearing disorders, and vision disorders ranged from 40 to 55%. We made genetic diagnoses in 25% of the probands. A total of 14% of the diagnoses were made by means of the combination of research and automated approaches, which was critical for cases in which we found etiologic noncoding, structural, and mitochondrial genome variants and coding variants poorly covered by exome sequencing. Cohortwide burden testing across 57,000 genomes enabled the discovery of three new disease genes and 19 new associations. Of the genetic diagnoses that we made, 25% had immediate ramifications for clinical decision making for the patients or their relatives.CONCLUSIONS: Our pilot study of genome sequencing in a national health care system showed an increase in diagnostic yield across a range of rare diseases. (Funded by the National Institute for Health Research and others.).

In today's world technology has advanced to such an extent that it is interchangeable with connection and convenience. ATM was one of the major breakthroughs, and over the time it has provided better convenience in fulfilling one’s banking needs. Although, there are certain predicaments that such ATM transactions are susceptible too. The conventional PIN based authentication that is presently accustomed in all ATM apparatus is liable to shoulder surfing, hassle in remembering the multiple PIN and the rest. The physical card brings along setbacks in particular, wearing out of the magnetic strip attributable to frequent usage, losing or getting it stolen. Aside from these there are other unlawful activities that are carried upon. The objective of this paper is to present a solution to the above stated problems. In contrast to standard architecture, the proposed solution incorporates NFC enabled smartphones as a substitute for physical card and iris based authentication for PIN.

Objective There are contradictory reports on the impact of COVID-19 on preterm births (PTBs). We aimed to compare the spontaneous preterm births (SPTBs), and iatrogenic preterm births (IPTBs) rates during both waves of the COVID-19 pandemic. Methods Retrospective analysis of the PregCovid registry of pregnant women with COVID-19 was done at a dedicated COVID-19 hospital in Mumbai, India. The data of 1,630 women was analyzed for this study. between April 4th, 2020 to July 4th, 2021. Prepandemic data were analyzed and compared with pandemic data. Main outcome measures was spontaneous preterm birth rate. Results Preterm deliveries were reported higher during second wave (14%, 46/329) compared to first wave (10.2%, 82/807) of the COVID-19 pandemic (p=0.065). Higher SPTBs were reported during second wave than first wave (12.5% vs 8.3%) [p=0.03] as well as the prepandemic period (12.5% vs 10.5%) (p=0.286). IPTBs were significantly lower in the pandemic period than in the prepandemic period (1.8 vs 3.3) (p=0.012). Conclusions In Mumbai, India, we found an unusual change in SPTBs during the 6 months of the second wave of COVID-19 compared with the previous 10 months of 1st wave of pandemic and one year of prepandemic.

Background A randomised trial designed to compare three and two doses of quadrivalent human papillomavirus (HPV) vaccine in adolescent girls in India was converted to a cohort study after suspension of HPV vaccination in trials by the Indian Government. In this Article, the revised aim of the cohort study was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years post vaccination. Methods In the randomised trial, unmarried girls aged 10-18 years were recruited from nine centres across India and randomly assigned to either two doses or three doses of the quadrivalent HPV vaccine (Gardasil [Merck Sharp & Dohme, Whitehouse Station, NJ, USA]; 0·5 mL administered intramuscularly). After suspension of recruitment and vaccination, the study became a longitudinal, prospective cohort study by default, and participants were allocated to four cohorts on the basis of the number vaccine doses received per protocol: the two-dose cohort (received vaccine on days 1 and 180 or later), three-dose cohort (days 1, 60, and 180 or later), two-dose default cohort (days 1 and 60 or later), and the single-dose default cohort. Participants were followed up yearly. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Married participants were screened for cervical cancer as they reached 25 years of age. Unvaccinated women age-matched to the married vaccinated participants were recruited to serve as controls. Vaccine efficacy against persistent HPV 16 and 18 infections (the primary endpoint) was analysed for single-dose recipients and compared with that in two-dose and three-dose recipients after adjusting for imbalance in the distribution of potential confounders between the unvaccinated and vaccinated cohorts. This trial is registered with ISRCTN, ISRCTN98283094, and ClinicalTrials.gov, NCT00923702. Findings Vaccinated participants were recruited between Sept 1, 2009, and April 8, 2010 (date of vaccination suspension), and followed up over a median duration of 9·0 years (IQR 8·2-9·6). 4348 participants had three doses, 4980 had two doses (0 and 6 months), and 4949 had a single dose. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95·4% (95% CI 85·0-99·9) in the single-dose default cohort (2135 women assessed), 93·1% (77·3-99·8) in the two-dose cohort (1452 women assessed), and 93·3% (77·5-99·7) in three-dose recipients (1460 women assessed). Interpretation A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and 18, the genotypes responsible for nearly 70% of cervical cancers, to that provided by two or three doses. Funding Bill & Melinda Gates Foundation.

Lay abstract ‘Precision oncology' has gained momentum as a term to describe cancer care that is optimized for an individual patient based on her/his unique characteristics. However, clinicians may encounter challenges with communication when delivering precision oncology care to patients and their families. We conducted three focus groups, or structured discussions, with breast, melanoma and thoracic oncology clinicians regarding their precision oncology communication experiences. Narrative transcripts of these discussions were analyzed by the research team to identify common themes. We identified four themes: varied definitions of precision oncology exist, clinicians and patients face unique challenges to precision oncology implementation, patient communication challenges engendered or heightened by precision oncology implementation, and clinician communication solutions and training needs. This study elucidated clinicians’ perspectives on delivering precision oncology and related communication challenges. Understanding these challenges and developing strategies to help clinicians navigate these discussions are critical for ensuring that patients reap the full benefits of precision oncology.

HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.5 cm clinical stage II/III HER2+ breast cancer, adaptively randomized to T-DM1/P, THP, or a common control arm of paclitaxel/trastuzumab (TH), followed by doxorubicin/cyclophosphamide, then surgery. Both T-DM1/P and THP arms ‘graduate’ in all subtypes: predicted pCR rates are 63%, 72% and 33% for T-DM1/P (n = 52), THP (n = 45) and TH (n = 31) respectively. Toxicity burden is similar between arms. Degree of HER2 pathway signaling and phosphorylation in pretreatment biopsy specimens are associated with response to both T-DM1/P and THP and can further identify highly responsive HER2+ tumors to HER2-directed therapy. This may help identify patients who can safely de-escalate cytotoxic chemotherapy without compromising excellent outcome., HER2-targeted therapy improves patient’s outcome in early breast cancer. Here, the authors present the efficacy and biomarker analysis of two HER2-targeted combinations (ado-trastuzumab emtansine plus pertuzumab and paclitaxel, trastuzumab and pertuzumab) in the context of the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence.

Background The evolution of cognitive impairment of vascular origin is increasingly becoming a prominent health threat particularly in this era where hypertension is the leading contributor of global disease burden and overall health loss. Hypertension is associated with the alteration of the cerebral microcirculation coupled by unfavorable vascular remodeling with consequential slowing of mental processing speed, reduced abstract reasoning, loss of linguistic abilities, and attention and memory deficits. Owing to the rapidly rising burden of hypertension in Tanzania, we sought to assess the prevalence and correlates of cognitive impairment among hypertensive patients attending a tertiary cardiovascular hospital in Tanzania. Methodology A hospital-based cross-sectional study was conducted at Jakaya Kikwete Cardiac Institute, a tertiary care public teaching hospital in Dar es Salaam, Tanzania between March 2020 and February 2021. A consecutive sampling method was utilized to recruit consented hypertensive outpatients during their scheduled clinic visit. General Practitioner Assessment of Cognition (GPCOG) Score was utilized in the assessment of cognitive functions. All statistical analyses utilized STATA v11.0 software. Pearson Chi square and Student’s T-test were used to compare categorical and continuous variables respectively. Logistic regression analyses were used to assess for factors associated with cognitive impairment. Odd ratios with 95% confidence intervals and p-values are reported. All tests were 2-sided and p Results A total of 1201 hypertensive patients were enrolled in this study. The mean age was 58.1 years and females constituted nearly two-thirds of the study population. About three quarters had excess body weight, 16.6% had diabetes, 7.7% had history of stroke, 5.7% had heart failure, 16.7% had renal dysfunction, 53.7% had anemia, 27.7% had hypertriglyceridemia, 38.5% had elevated LDL, and 2.4% were HIV-infected. Nearly two-thirds of participants had uncontrolled blood pressure and 8.7% had orthostatic hypotension. Overall, 524 (43.6%) of participants had cognitive impairment. During bivariate analysis in a logistic regression model of 16 characteristics, 14 parameters showed association with cognitive functions. However, after controlling for confounders, multivariate analysis revealed ≤primary education (OR 3.5, 95%CI 2.4–5.2, p p p = 0.01) and renal dysfunction (OR 1.7, 95%CI 1.0–2.7, p = 0.04) to have independent association with cognitive impairment. Conclusion This present study underscore that cognitive decline is considerably prevalent among individuals with systemic hypertension. In view of this, it is pivotal to incorporate cognitive assessment in routine evaluation of hypertensive patients.

Background: The Coronavirus Disease 2019 (COVID-19) pandemic is a significant challenge particularly for low and middle-income countries like Bangladesh. Interventions such as home isolation, frequent hand washing, wearing face mask, maintaining social distancing are difficult to implement in densely populated areas. The aim of the study was to delineate demographics, clinical manifestations, treatment modalities and outcomes of COVID-19 affected patients of our hospital. Methods: This prospective observational study was carried out at National Heart Foundation Hospital & Research Institute of Bangladesh between 08 March 2020 to 07 March 2021. During this period all admitted patients who subsequently were diagnosed as COVID positive and health care personnel of this hospital, who experienced fever or respiratory symptoms or came in close contact with COVID-19 patients at home or their workplace & become COVID positive were included. Results: During this one-year period a total of 769 COVID positive patients were detected in our hospital. Mean age of the patients was 48.16 ±15.63 years (range 1-92 years). Two third were male (64.9% vs 35.1%) and had multiple co-morbidities. One fifth of the patients were (19%) asymptomatic. The mean duration of onset of symptoms to test was 3.72±3.7 days. Most common symptoms were fever (65.3%), cough (37.1%), shortness of breath (33.6%) and fatigue (27.8%). Other symptoms were bodyache (18.6%), headache (16.6%), anosmia 16%), sore throat (12.1%), diarrhoea (6.8%), dizziness (5.3%), generalized itching (3.8%). Nearly two third of the COVID positive patients (63.2%) had a diagnosed cardiovascular disease at onset and remaining 36.8% patients presented with only COVID-19 disease. About 75% patients received ivermectin, 5.1% patients received favipiravir and 4.4% patients received remdesivir. Three fourth (74.38%) of patients were hospitalized and remaining one fourth (25.62%) patients were treated either in home isolation or in institutional isolation. Most of the patients recovered, with a case fatality rate of 3.5%. Diabetes, hypertension and age ≥50 years were the independent predictors of mortality. Conclusion: Although most of the patients had good outcome the study revealed 3.5% case fatality. Male with multiple co-morbidities were predominantly affected by COVID 19. Fever, cough, shortness of breath and fatigue were common presenting symptoms. Bangladesh Heart Journal 2021; 36(2): 89-97

Cervical cancer is the second most common cause of cancer deaths in women worldwide and remains the main reason of mortality among women of reproductive age in developing countries. Nitric oxide is involved in several physiological functions inclusive of inflammatory and immune responses. However, the function of NO in tumor biology is debatable. The inducible NOS (iNOS/NOS2) isoform is the one responsible to maintain the levels of NO, and it exhibits pleotropic effects in various cancers with concentration-dependent pro- and anti-tumor effects. iNOS triggers angiogenesis and endothelial cell migration in tumors by regulating the levels of vascular endothelial growth factor (VEGF). In drug discovery, drug repurposing involves investigations of approved drug candidates to treat various other diseases. In this study, we used anti-cancer drugs and small molecules to target iNOS and identify a potential selective iNOS inhibitor. The structures of ligands were geometrically optimized and energy minimized using Hyperchem software. Molecular docking was performed using Molegro virtual docker, and ligands were selected based on MolDock score, Rerank score, and H-bonding energy. In the study shown, venetoclax compound demonstrated excellent binding affinity to iNOS protein. This compound exhibited the lowest MolDock score and Rerank score with better H-bonding energy to iNOS. The binding efficacy of venetoclax was analyzed by performing molecular docking and molecular dynamic simulations. Multiple parameters were used to analyze the simulation trajectory, like root mean square deviation (RMSD), radius of gyration (Rg), and hydrogen bond interactions. Based on the results, venetoclax emerges to be a promising potential iNOS inhibitor to curtail cervical cancer progression.

The increase in use of collagen products in almost every sector of utility has stipulated the rising demand for collagen. It is an essential fibrous glycoprotein, which is abundantly present in the extracellular matrix and connective tissues in many living organisms. Owing to its unique characteristics such as biocompatibility, bioavailability and weak antigenicity it has gained major interest in the food, pharmaceutical, cosmetic, biomedical and leather industries. The collagen-based composites possess an enhanced capacity to dissipate mechanical energy, strength and stiffness making it the most promising biomolecule for its multifaceted applications. Recently, synthetic biology platforms are getting wide attention for the production of non-native collagen alternatives to meet the rising demand for collagen worldwide. In the initial part, this review aims to explain different sources, structures, biosynthesis of collagen and its types followed by the emerging applications of collagen as a next-generation biomaterial in the later part. The article emphasises the synthesis of non-native collagen using novel expression systems like plant and algae in addition to bacteria and yeast with industrial consideration. In the conclusion section, challenges and opportunities of using synthetic biology tools are described.

AIM To estimate the risk of blindness with primary angle-closure glaucoma (PACG) compared to primary open-angle glaucoma (POAG) in those population-based studies that reported blindness rates for both PACG and POAG. METHOD A systematic search was performed in PubMed for articles published in English between 2000 and 2020 reporting the prevalence of POAG as well as PACG among various ethnic populations. A study was included if it was (1) population-based (2) had published prevalence and blindness rates for both PACG and POAG in the same cohort. (3) Glaucoma was defined as per the International Society for Geographical and Epidemiological Ophthalmology (ISGEO) criteria. The proportion of blindness for both POAG and PACG for each study and the cumulative proportion taking all the studies were calculated. RESULTS We included 23 studies with 78,434 participants. POAG was diagnosed in 1702 persons with 151 (8.9%) blind. There were 724 cases of PACG with 196 (27.0%) blind. The risk ratio of blindness in PACG to POAG varied from 0.73 to 10.6 among the studies. The cumulative risk ratio was 2.39 (95% confidence interval (CI); 1.99, 2.87). Risk ratios for studies including visual field restriction while defining blindness were similar to studies that did not (1.92 vs 2.64, P = 0.11). Risk ratios were also similar for studies that used greater than 2 instead of 3 or more quadrants of iridotrabecular contact to define angle closure (2.79 vs 2.25). CONCLUSION Primary angle-closure disease is more likely to be associated with blindness.