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Sepsis is extremely common amongst critically ill patients and requires early diagnosis. Hence, identifying a biomarker that could acknowledge sepsis at its prior stage is of vital significance. Immature platelets are a percentage of circulating platelets that contain RNA and is a newer parameter that is measured using automated hematology analyzers in diagnosing sepsis. This review article discusses 10 articles that reveal the role of immature platelet fraction in predicting the onset of sepsis and its relationship with mortality in sepsis. Literature search was done using PubMed, Scopus and Google Scholar and words like platelet indices and immature platelet fraction were typed in the search bar. The aim of this review article is to present a precise form of data that talk about immature platelet fraction (IPF) and its association with the severity and mortality of sepsis. Five out of 10 articles suggest that immature platelet fraction can predict the onset of sepsis and eight out of 10 articles suggest that increased IPF values are associated with high mortality.

During pregnancy the maternal heart undergoes significant physiological change. Technological advancements in echocardiography (echo) have improved our ability to assess the right heart in detail and yet there is little research into adaptation during pregnancy. In this pilot study, we considered how three measures of right heart function changed in normal women from the 1st trimester through to the post-partum period. We observed a significant increase in tricuspid annulus planar systolic excursion (TAPSE) and right ventricular systolic velocity (RV S’) from the 1st to the 2nd trimester; both measures of longitudinal right ventricular function. There was no significant difference in right ventricular systolic area change, which is more difficult to accurately measure, and reflects radial function. TAPSE and RV S’ are easy to accurately measure with modern echo technology. This pilot study suggests that any reduction in these values from the 1st to the 2nd trimester should prompt more detailed assessment, and correlation with clinical symptoms. It would be valuable to undertake a comprehensive study to define normal ranges for common measures of right ventricular function, using echo, during pregnancy. The ability to assess the right heart, with an understanding of expected normal values, has the potential to significantly improve our understanding and management of maternal cardiovascular disease.

Fungal infections have been drastically increasing in incidence in recent years, preferentially affecting immunocompromised hosts and causing potentially fatal outcomes. One of the emerging fatal fungal pathogens is Trichosporon asahii, a non-Candida yeast that has been increasingly reported in recent years. Previous literature has described T. asahii as primarily affecting immunocompromised hosts, specifically those who are neutropenic, and causing fatal disseminated infections. Herein, we describe a case of an isolated subcutaneous abscess with T. asahii in an immunocompetent host without overlying skin manifestations or predisposing factors that resulted in complete mycotic cure when treated with voriconazole and terbinafine.

Contains fulltext : 245701.pdf (Publisher’s version ) (Open Access) The role of inflammation in cardiovascular pathophysiology has gained a lot of research interest in recent years. Cardiovascular Magnetic Resonance has been a powerful tool in the non-invasive assessment of inflammation in several conditions. More recently, Ultrasmall superparamagnetic particles of iron oxide have been successfully used to evaluate macrophage activity and subsequently inflammation on a cellular level. Current evidence from research studies provides encouraging data and confirms that this evolving method can potentially have a huge impact on clinical practice as it can be used in the diagnosis and management of very common conditions such as coronary artery disease, ischaemic and non-ischaemic cardiomyopathy, myocarditis and atherosclerosis. Another important emerging concept is that of myocardial energetics. With the use of phosphorus magnetic resonance spectroscopy, myocardial energetic compromise has been proved to be an important feature in the pathophysiological process of several conditions including diabetic cardiomyopathy, inherited cardiomyopathies, valvular heart disease and cardiac transplant rejection. This unique tool is therefore being utilized to assess metabolic alterations in a wide range of cardiovascular diseases. This review systematically examines these state-of-the-art methods in detail and provides an insight into the mechanisms of action and the clinical implications of their use.

Pericardial inflammation is a recognised feature of coronavirus disease (COVID-19). The authors herein present the case of a female with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection who developed a large and life-threatening pericardial effusion over a few days following the onset of pericarditis, despite prompt commencement of treatment. This was successfully drained, and she was discharged in stable condition on oral nonsteroidal anti-inflammatory drugs and colchicine.At 6-week follow-up she had made a full recovery, and repeat echocardiography demonstrated no recurrence of effusion or evidence of constrictive physiology.

Radiation cystitis can present as gross hematuria and occurs secondary to irritation of the bladder urothelium. Continuous bladder irrigation (CBI) is commonly used for the treatment of hemorrhagic cystitis for evacuation of blood clots and to maintain catheter drainage. Most commonly, CBI is performed using 0.9% sodium chloride. We report a 77-year-old female who developed hyperchloremic non-anion gap metabolic acidosis (H-NAGMA) and pulmonary edema secondary to absorption of 0.9% normal saline (NS) from CBI. In such cases, ringer lactate with low concentration (109 mEq) of chloride as compared to NS (154 mEq) can prove to be a suitable alternative.

Introduction: The COVID-19 surge at our institution required deployment of large numbers of non-intensive care unit (ICU) physicians and advanced practice providers to assist in the management of the critically ill. A 3-hour “uptraining” simulation session was offered to these providers that focused on various aspects of ICU care. Hypothesis: We hypothesized that following a 3-hour simulation session, providers would feel more comfortable in managing critically-ill patients with COVID-19. Methods: One hundred and seventy-five providers underwent a 3-hour simulation-based session focused on management of shock, acute respiratory distress syndrome, and critical care ultrasound. All participants were sent surveys to assess their comfort with various aspects of ICU care following return to their usual work environments. Results: One hundred and eight providers of 175 (62%) completed the surveys. Cardiology fellows and faculty accounted for 36% of the responders, acute care nurse practitioners (NPs) accounted for 16%, while other NPs, residents, and fellows accounted for the remainder. Prior to simulation training, 31% regularly managed patients in the ICU and 28% occasionally managed ICU patients. Following training, 71% of participants were deployed to a COVID-19 ICU as part of their workflow. Overall, 104/108 responders (96%) felt training either significantly or somewhat improved their knowledge in the management of ICU patients. Ninety-four participants (91%) felt training impacted their care of critically ill patients with COVID-19. Table 1 is a display of specific ICU skillsets taught in the session and if the participants felt better equipped to utilize what was covered post deployment. Conclusions: Simulation-based training improved provider comfort in the management of critically ill patients with COVID-19. Table 1: Participants response to “if they felt better equipped to utilize ICU skills following simulation training”

We describe a patient who had chronic lymphocytic leukaemia (CLL) Binet stage A at presentation with further evidence of disease at multiple sites but who initially required no treatment. However, several years later, her peripheral blood lymphocyte count started to increase, and soon after that she suffered an acute myocardial infarct (in the absence of coronary atheroma) together with proteinuric renal failure due to membranoproliferative glomerulonephritis. Her renal function improved markedly following anti-CLL chemotherapy. We postulate that her cardiac and renal disease were both complications of her CLL. In patients with CLL who develop new clinical signs or symptoms (even if apparently unrelated), consideration should be given as to whether these may be disease complications as this may serve as an indication to commence anti-CLL therapy; close liaison between different specialties is vital.

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a multisystem inflammatory disorder sharing the clinical features of Kawasaki disease (KD) and toxic shock syndrome. CASE PRESENTATION: A 19-year-old male with no known past medical history presented to the emergency room with myalgia, headache, fever, photophobia, and rash on bilateral upper and lower extremities for more than one week. He tested positive for SARS-CoV-2 by RT-PCR 6 weeks prior to the presentation. Symptoms worsened with the development of a maculopapular skin rash, high-grade fevers, diarrhea, and vomiting. On admission he was afebrile (97.6 °F), had tachycardia (133/min) and tachypnea (48/min) along with hypotension (78/33 mmHg), and saturating 85% on 4L/min. Lab abnormalities included WBC of 28.2 k/uL with 55% bands, procalcitonin 42.91 ng/mL, lactic acid 4 mmol/L, BUN 65 mg/dl, serum creatinine 7 mg/dl and elevated D-dimer of 3.1 mg/L. Cardiac labs were remarkable for proBNP 76,275 pg/mL, and peak troponin 31.10ng/mL in 12 hours. EKG consistent with myopericarditis. CT scan of the abdomen/pelvis found edema of the cecum and ascending colon with pericolonic fat stranding of ascending colon possible mesenteric adenitis. He initially required 3 vasopressors to maintain his MAP>65mmHg. Echocardiography revealed a left ventricle ejection fraction (LVEF) of 20% with moderate global hypokinesis of the left ventricle. Cardiac catheterization revealed elevated wedge pressure and had clean coronaries with no aneurysms. MIS-C was suspected and was started on 1g/kg IVIG, high dose aspirin, methylprednisolone, and anakinra. Rash dissipated in days after starting steroids. His LVEF recovered to 55-60% prior to discharge from the hospital. He was kept on Anakinra, continued for 4 weeks till normalization of ferritin. DISCUSSION: MIS-C is a rare sequela of COVID-19 manifesting 2-8 weeks after the initial SARS-CoV-2 infection. In severe cases, cardiac involvement leads to cardiogenic shock. The echocardiographic findings of myocarditis and pericarditis have been frequently reported[1]. Inflammatory markers including ESR, C-reactive protein, ferritin, and IL-6 are reported to be elevated in all the cases [2]. Though its pathogenesis is not well defined, proposed hypotheses include hyper-immune response, macrophage activation, and T cell stimulation with a delayed cytokine storm. Various case have reported clinical outcomes with the use of intravenous immunoglobulin, corticosteroids, IL-1 inhibitor (anakinra), or IL-6 receptor inhibitor (tocilizumab) [3]. However, further research is needed to define clinical predictors and treatment modalities to manage MIS-C. CONCLUSIONS: Our case emphasizes the complexity of MIS-C with multisystem involvement, and it highlights a timely use of IVIG, high dose aspirin, anakinra, and methylprednisolone as potential therapeutics for this hyperinflammatory condition. REFERENCE #1: Alsaied T, Tremoulet AH, Burns JC, et al. Review of Cardiac Involvement in Multisystem Inflammatory Syndrome in Children. Circulation. 2021;143(1):78-88. doi:10.1161/CIRCULATIONAHA.120.049836 REFERENCE #2: Abrams JY, Godfred-Cato SE, Oster ME, et al. Multisystem Inflammatory Syndrome in Children Associated with Severe Acute Respiratory Syndrome Coronavirus 2: A Systematic Review [published online ahead of print, 2020 Aug 5]. J Pediatr. 2020;226:45-54.e1. doi:10.1016/j.jpeds.2020.08.003 REFERENCE #3: Tanner T, Wahezi DM. Hyperinflammation and the utility of immunomodulatory medications in children with COVID-19. Paediatr Respir Rev. 2020;35:81-87. doi:10.1016/j.prrv.2020.07.003 DISCLOSURES: No relevant relationships by Faran Ahmad, source=Web Response No relevant relationships by Sunil Nair, source=Web Response No relevant relationships by Sanu Rajendraprasad, source=Web Response

STATEMENT: The dramatic outbreak of COVID-19 placed unprecedented strain on the critical care workforce of New York City. The enhanced precautions required to safely care for COVID-19 patients impacted the performance of even routine critical care procedures. Meanwhile, staff were stretched to care for exponentially rising case volume as COVID intensive care units (ICUs) expanded. Simulation was used to bridge these gaps-first to familiarize personnel within the Division of Pulmonary and Critical Care with revised COVID-19 care procedures, then to orient noncritical care clinicians volunteering from other specialties for COVID ICU deployment to general critical care and COVID-19 care principles. Using mannequin-based simulation scenarios followed by comprehensive debriefing sessions, simulation participants received high-intensity, high-fidelity training in respiratory failure, circulatory failure, bedside ultrasound, bedside ICU procedures, and elements of COVID-19-specific care. More than 200 physicians and advanced practice practitioners completed simulation training in preparation for deployment, supplementing and enhancing the ICU workforce at a decisive time during the outbreak.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden. The ERIC-PPCI trial was funded by a British Heart Foundation clinical study grant (grant number CS/14/3/31002) and a University College London Hospitals/University College London Biomedical Research Centre clinical research grant. The CONDI-2 trial was funded by Danish Innovation Foundation grants (grant numbers 11-108354 and 11-115818), Novo Nordisk Foundation (grant number NNF13OC0007447), and TrygFonden (grant number 109624). DJH was supported by the British Heart Foundation (grant number FS/10/039/28270), the National Institute for Health Research (NIHR) Biomedical Research Centre at University College London Hospitals, the Duke-National University Singapore Medical School, the Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist-Senior Investigator scheme (grant number NMRC/CSA-SI/0011/2017) and its Collaborative Centre Grant scheme (grant number NMRC/CGAug16C006), and the Singapore Ministry of Education Academic Research Fund Tier 2 (grant number MOE2016-T2-2-021). HEB was supported by the Novo Nordisk Foundation (grant numbers NNF14OC0013337, NNF15OC0016674). RKK is supported by the Oxford NIHR Biomedical Centre. The research was also supported by the NIHR infrastructure at Leeds. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health. This article is based on the work of COST Action EU-CARDIOPROTECTION (CA16225) and supported by COST (European Cooperation in Science and Technology). We thank all study personnel for their invaluable assistance. Sí

Aggressive fluid resuscitation has become standard of care for hypotensive patients with sepsis. However, sepsis is a syndrome that occurs in patients with diverse underlying physiology and a one-size-fits-all approach to fluid administration seems misguided. To individualize fluid management, several methods to assess fluid responsiveness have been validated, but even in fluid responsive patients, fluid administration may still be harmful and lead to pulmonary edema. Hence, to individualize fluid management, in addition to fluid responsiveness, fluid tolerance needs to be assessed. This article examines whether lung ultrasound can be useful to detect excess extravascular lung water (EVLW) and thus assess fluid tolerance. The physiology of EVLW and the principles of lung ultrasound are briefly described. Articles examining the correlation between EVLW and lung ultrasound findings in various clinical settings are carefully reviewed. Overall, lung ultrasound has been found to be an excellent tool to detect EVLW, but large outcome studies investigating lung ultrasound-guided fluid management are still lacking.

Objectives To determine the necessary screening interval for retinopathy in diabetic patients with no retinopathy based on time to laser therapy and to assess long-term visual outcome following screening. Methods In a population-based community screening programme in North Wales, 2917 patients were followed until death or for approximately 12 years. At screening, 2493 had no retinopathy; 424 had mostly minor degrees of non-proliferative retinopathy. Data on timing of first laser therapy and visual outcome following screening were obtained from local hospitals and ophthalmology units. Results Survival analysis showed that very few of the no retinopathy at screening group required laser therapy in the early years compared with the non-proliferative retinopathy group ( p Conclusions Optimum screening intervals should be determined from time to active treatment. Based on requirement for laser therapy, the screening interval for diabetic patients with no retinopathy can be extended to two to three years. Patients who attend for retinal screening and treatment who have no or non-proliferative retinopathy now have a very low risk of eventual blindness from diabetes.

Supplemental Digital Content is available in the text., Objectives: To explore demographics, comorbidities, transfers, and mortality in critically ill patients with confirmed severe acute respiratory syndrome coronavirus 2. Design: Retrospective cohort study. Setting: Data were collected from a large tertiary care public hospital ICU that is part of the largest public healthcare network in the United States. Patients: One-hundred thirty-seven adult (≥ 18 yr old) ICU patients admitted between March 10, 2020, and April 7, 2020, with follow-up collected through May 18, 2020. Interventions: None. Measurements: Demographic, clinical, laboratory, treatment, and outcome data extracted from electronic medical records. Main Results: The majority of patients were male (99/137; 72.3%) and older than 50 years old (108/137; 78.9%). The most reported ethnicity and race were Hispanic (61/137; 44.5%) and Black (23/137; 16.7%). One-hundred six of 137 patients had at least one comorbidity (77.4%). One-hundred twenty-one of 137 (78.1%) required mechanical ventilation of whom 30 (24.8%) moved to tracheostomy and 46 of 137 (33.6%) required new onset renal replacement therapy. Eighty-two of 137 patients (59.9%) died after a median of 8 days (interquartile range 5–15 d) in the ICU. Male sex had a trend toward a higher hazard of death (hazard ratio, 2.1 [1.1–4.0]) in the multivariable Cox model. Conclusions: We report a mortality rate of 59.9% in a predominantly Hispanic and Black patient population. A significant association between comorbidities and mortality was not found in multivariable regression, and further research is needed to study factors that impact mortality in critical coronavirus disease 2019 patients. We also describe how a public hospital developed innovative approaches to safely manage a large volume of interhospital transfers and admitted patients.

The role of testosterone in the pathophysiology of inflammation is of critical clinical importance; however, no universal mechanism(s) has been advanced to explain the complex and interwoven pathways of androgens in the attenuation of the inflammatory processes. PubMed and EMBASE searches were performed, including the following key words: “testosterone„, “androgens„, “inflammatory cytokines„, “inflammatory biomarkers„ with focus on clinical studies as well as basic scientific studies in human and animal models. Significant benefits of testosterone therapy in ameliorating or attenuating the symptoms of several chronic inflammatory diseases were reported. Because anti⁻tumor necrosis factor therapy is the mainstay for the treatment of moderate-to-severe inflammatory bowel disease; including Crohn’s disease and ulcerative colitis, and because testosterone therapy in hypogonadal men with chronic inflammatory conditions reduce tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6, we suggest that testosterone therapy attenuates the inflammatory process and reduces the burden of disease by mechanisms inhibiting inflammatory cytokine expression and function. Mechanistically, androgens regulate the expression and function of inflammatory cytokines, including TNF-α, IL-1β, IL-6, and CRP (C-reactive protein). Here, we suggest that testosterone regulates multiple and overlapping cellular and molecular pathways involving a host of immune cells and biochemical factors that converge to contribute to attenuation of the inflammatory process.

Introduction: Prolactin circulates predominantly as a 23 kDa monomer, and a high molecular weight form largely consisting of a complex of prolactin and anti-prolactin IgG autoantibody called macroprolactin. The latter cross-reacts with conventional laboratory assays for prolactin. We here describe the use of serial macroprolactin measurement to assist in the management of a pregnant lady with pre-conception hyperprolactinaemia in whom a magnetic resonance imaging scan had not been performed. Case Report: A 24-year old lady was found to have a raised prolactin level of 2 332 mu/L (reference range: 40–530 mu/L). Prolactin was checked because of primary infertility. Macroprolactin screening was positive, accounting for 54% of measured prolactin (estimated monomeric prolactin=1 073 mu/L). As expected, measured prolactin levels rose through pregnancy to 6 975 mu/L at 20 weeks and to 8 374 mu/L at 36 weeks gestation. Adjustment for macroprolactin and big prolactin gave estimated monomeric prolactin levels of 2 370 mu/L at 16 weeks (macroprolactin/big prolactin=66%), 2 441 mu/L at 20 weeks (macroprolactin/big prolactin=65%) and 2 596 mu/L at 36 weeks (macroprolactin/big prolactin=69%). Thus, adjusted prolactin fell within the reference range for pregnancy at these points. Gel filtration chromatography was performed on the 20-week (second trimester) sample and compared with the pre-pregnancy sample. The pattern remained similar but all components were increased in the second trimester sample (including the monomeric, big prolactin and macroprolactin forms). Conclusion: In this case report, serial measurement of macroprolactin with estimation of monomeric prolactin enhanced clinical management throughout pregnancy, saving unnecessary further investigations and avoiding unnecessary distress for the patient.

The aims of this study were to explore women's perceptions and experiences of being pregnant and having pre-existing type 1 diabetes mellitus, and to assess their physical, social, psychological, emotional and educational needs during their transition to motherhood. The qualitative design incorporated a purposive sample of seven women in their first pregnancy, who participated in one-to-one interviews with a researcher at 15-20 and 32-36 weeks gestation, and at 6-8 weeks post-partum. Qualitative analysis identified seven key themes from the data including: knowledge; physical and psychological impact; control and trust; catalyst to action; organisation of care and communication; attendance and intervention; expectations and systems. This study has shown that most women with diabetes who become pregnant are resigned to the fact that their pregnancy is considered high risk, and are willing to play their part to achieve a positive pregnancy outcome. However, they would also like to 'do the normal pregnant bit as well', 'normalise it and make it a nice experience' and make it feel 'less fragmented'. This woman-centred experience of pregnancy care, in women with type 1 diabetes mellitus, may motivate health professionals to revise their approach to care, prompt them to utilise the skills of each individual member of the multidisciplinary team to its full strength and potential, and assist in the provision of a positive, balanced and more holistic approach to care, specific to this client group.

Immunotherapy using short immunogenic peptides of disease-related autoantigens restores immune tolerance in preclinical disease models. We studied safety and mechanistic effects of injecting human leukocyte antigen-DR4(DRB1*0401)-restricted immunodominant proinsulin peptide intradermally every 2 or 4 weeks for 6 months in newly diagnosed type 1 diabetes patients. Treatment was well tolerated with no systemic or local hypersensitivity. Placebo subjects showed a significant decline in stimulated C-peptide (measuring insulin reserve) at 3, 6, 9, and 12 months versus baseline, whereas no significant change was seen in the 4-weekly peptide group at these time points or the 2-weekly group at 3, 6, and 9 months. The placebo group's daily insulin use increased by 50% over 12 months but remained unchanged in the intervention groups. C-peptide retention in treated subjects was associated with proinsulin-stimulated interleukin-10 production, increased FoxP3 expression by regulatory T cells, low baseline levels of activated β cell-specific CD8 T cells, and favorable β cell stress markers (proinsulin/C-peptide ratio). Thus, proinsulin peptide immunotherapy is safe, does not accelerate decline in β cell function, and is associated with antigen-specific and nonspecific immune modulation.

Vitamin D deficiency is associated with low circulating levels of calcium and phosphate. A 56-year-old asymptomatic gentleman was referred with laboratory findings of undetectable serum phosphate ( On questioning, it was revealed that he worked indoors between 06.00 h and 15.00 h for approximately 24 days per month, and on rest days he went out mainly in the evenings. Achievement of adequate sunlight exposure resulted in normalisation of 25-OHD status and serum phosphate levels. In relation to normalisation of vitamin D status, there was a reduction in urinary calcium excretion, which when elevated may have contributed to the renal calculi. The authors propose that investigation of low phosphate or calcium levels should always include an assessment of time spent outdoors in the daytime and vitamin D status.

Purpose: Lactate reduction, a common method of risk stratification, has been variably defined. Among patients with an initial lactate >= 4 mmol/L, we compared mortality prediction between a subsequent lactate > 4 mmol/L to a Materials and methods: We performed a single-center retrospective study of patients presenting to the emergency department with an initial lactate >= 4 mmol/L and suspected infection. Patients were stratified by lactate reduction using 3 previously identified definitions (subsequent lactate >= 4 mmol/L, and Results: A subsequent lactate >= 4 mmol/L and a lactate reduction Conclusions: A subsequent lactate = 4 mmol/L and lactate reduction

Diet and exercise reduce the incidence of diabetes in high-risk individuals as does metformin, although less dramatically. Here we evaluated if lifestyle and pharmacological intervention, for people at risk of diabetes, resulted in an improvement in their cardiometabolic risk profile.In a primary care based study, 92 individuals screened opportunistically and identified to have impaired glucose handling were offered detailed lifestyle advice, at 6 monthly intervals, with targeting of cardiovascular risk factors. Duration of follow-up was 4 years. The relation between fasting and 2h glucose with different cardio-metabolic risk factors over time was assessed using multi-level modeling.There was no significant weight reduction. At 24 months, mean fasting glucose level (6.4 mmol/L (95% CI 6.0-6.8)) was slightly lower than at baseline (6.6 mM (95% CI: 6.4-6.9), F=3.67; p0.001). For men and women combined, systolic blood pressure (mean difference=-6 mmHg, p=0.013), total cholesterol (-0.66 mmol/L, p0.0001) and triglycerides (-0.13 mmol/L, p=0.133) fell, whilst HDL-cholesterol (0.12 mmol/L, p=0.047) rose. Diabetes developed in 18/92 participants during follow-up (up to 4 years). Five per cent of participants were started on metformin, 88.5% on lipid lowering agents and 85.4% on anti-hypertensive agents. After adjusting for age, sex and BMI, 2 h glucose was independently and negatively associated with HDL-cholesterol (β=-2.17, p=0.041), and positively with systolic BP (β=0.24, p=0.004, per 5 mmHg).Targeted intervention had an effective role in improving lipid and BP profile in individuals with impaired glucose handling, with limited impact on glycaemia and no impact on weight. More work needs be done to evaluate the potential benefit of insulin sensitizing agents in this setting.

Past studies suggest that airway pressure release ventilation (APRV) is associated with reduced sedative requirements and increased recruitment of atelectatic lung, two factors that might reduce the risk for ventilator-associated pneumonia (VAP). We investigated whether APRV might be associated with a decreased risk for VAP in patients with pulmonary contusion.Retrospective cohort study.Of 286, 64 (22%) patients requiring mechanical ventilation for48 hours met criteria for pulmonary contusion and were the basis for this study. Subjects with pulmonary contusion had a significantly higher rate of VAP than other trauma patients, [VAP rate contusion patients: 18.3/1,000, non-contusion patients: 7.7/1,000, incidence rate ratio 2.37 (95% confidence interval [CI], 1.11-4.97), p=0.025]. Univariate analysis showed that APRV (hazard ratio, 0.15 [0.03-0.72; p=0.018]) was associated with a decreased incidence of VAP. Cox proportional hazards regression, using propensity scores for APRV to control for confounding, supported a protective effect of APRV from VAP (hazard ratio, 0.10 [95% CI, 0.02-0.58]; p=0.01). Pao2/FiO2 ratios were higher during APRV compared with conventional ventilation (p0.001). Subjects attained the goal Sedation Agitation Score for an increased percentage of time during APRV (median [interquartile range (IQR)] 72.7% [33-100] of the time) compared with conventional ventilation (47.2% [0-100], p=0.044), however, dose of sedatives was not different between these subjects. APRV was not associated with hospital mortality (odds ratio 0.57 [95% CI, 0.06-5.5]; p=0.63) or ventilator-free days (No APRV 15.4 vs. APRV 13.7 days, p=0.49).Use of APRV in patients with pulmonary contusion is associated with a reduced risk for VAP.

human kidney has a key role in the regulation of blood glucose predominantly by reabsorption of glucose from the glomerular filtrate via sodium glucose co-transporter 2 (SGLT-2) channels. These are expressed in the proximal renal tubules and are blocked by SGLT-2 inhibitors, which are novel pharmacological agents currently in development. Specific SGLT-2 inhibition results in significant increases in renal glucose excretion causing a net calorie loss and consequent weight loss, coupled with a lowering of blood glucose due to removal of glucose from the circulation. The main side effect of SGLT-2 inhibitors appears to be an increase in genital infections, although concerns remain about the potential adverse effects of dehydration and electrolyte imbalance. Dapagliflozin is the SGLT-2 inhibitor that is the furthest along in development, and is currently in phase III clinical trials. In this review article we consider the role of the kidney in glucose homeostasis in normal and diabetic subjects. We also review the history and concept of SGLT-2 inhibition, and discuss the future potential clinical utility of this promising new class of drugs. Copyright © 2010 John Wiley & Sons. Practical Diabetes Int 2010; 27(7): 311-316

An 80 year old man with a history of hypertension, stage 3 chronic kidney disease, and paroxysmal atrial fibrillation presented feeling generally unwell and lethargic. He was taking amiodarone 200 mg, bisoprolol 10 mg, amlodipine 10 mg, and lisinopril 20 mg a day. He did not have a fever and he was haemodynamically stable. His blood pressure was controlled (132/84 mm Hg). Physical examination was unremarkable. Blood tests showed hypokalaemia (1.9 mmol/L, reference range 3.5-5.0), hypomagnesaemia (0.58 mmol/L, 0.6-1.2), and metabolic alkalosis (35 mmol/L, 20-32). His symptoms resolved after electrolyte replacement and he was discharged home. When later reviewed in clinic, a focused history was taken and tests were organised to evaluate the causes of hypokalaemia and hypertension. He had no family history to explain this presentation, or a history of excess use of liquorice, carbenoxolone, or grapefruit juice. Cortisol after overnight dexamethasone (1 mg taken at midnight) suppression was 38 mmol/L (normal response

Background: Associations between human behaviour and psychiatric decompensation and weather variables have been inconsistent. Objectives: We studied the association of certain weather variables (specifically, humidity, wind speed, and barometric pressure) with emergent psychiatric presentations, psychiatric admissions, incidence of violent crimes, and suicides in a metropolitan area. Method: We performed a retrospective study for the year 1999 in a mid-sized city. We included all documented emergent psychiatric visits to the city's psychiatric emergency room. We obtained violence data from the city police department and suicide data from the county medical examiner. Results: The data suggest that total numbers of acts of violence and emergency psychiatry visits are significantly associated with low barometric pressure. Psychiatric inpatient admissions and suicides are not associated with any of the weather variables investigated. Conclusions: While alternate conclusions can be drawn, we propose that the data support the interpretation that low barometric pressure is associated with an increase in impulsive behaviours. Additional investigation is warranted.

To evaluate the outcome following internal fixation of olecranon fractures using the techniques of tension band wiring and plating. Design: retrospective evaluation. Setting: regional trauma center. 48 consecutive patients with fractures of the olecranon were treated over a 20- month period (May 1993 to December 1994). Analyses of the results were based on the medical records, preand postoperative radiographs of all 48 patients and clinical review of 39 patients at a mean follow-up of > 2 years (range 28–48 months). Intervention: 25 fractures were fixed using the AO tension band-wiring technique and 23 were fixed with a plate; the selection of method was based on agreed radiologic fracturepattern criteria. Main outcome measurements: radiographic evaluation of the quality of reduction was carried out using a grading system. Clinical outcome was assessed using the Broberg & Morrey functional rating index. Clinical evaluation of 39 patients was carried out. In the tension band-wiring group, 17 (85%) patients had an excellent or good outcome and eleven (55%) patients underwent a second procedure for symptomatic metalwork. In the plating group, 16 (84%) patients had an excellent or good outcome and two (11%) patients underwent a second procedure for symptomatic metalwork. The latter group had more complex and associated fractures and included the only poor result. Internal fixation of fractures of the olecranon results in good functional outcome. Patients who have tension band wiring more often require a second procedure for removal of symptomatic metalwork.

AIM The aim of the study was to investigate whether myocardial perfusion imaging at 15 min after injection (T15) is more accurate in detecting coronary artery disease than that at 45 min (T45). PATIENTS AND METHODS Two-day stress/rest 99mTc-tetrofosmin gated SPECT was performed at T15 and T45 in 50 patients. Coronary angiography was considered when poststress and resting images were discordant. Tracer washout rates were calculated for the myocardium, liver, and subdiaphragmatic region. Perfusion sum difference scores were derived using QPS software. RESULTS T15 and T45 were discordant in 18/50 (36%) patients. In 16/18 patients (89%) discordant deficits were more apparent at T15. A total of 13/16 patients underwent coronary angiography, of whom 12 had coronary artery disease. Poststress, but not resting, left ventricular ejection fraction was lower at T15 (P=0.02). Sum difference scores were higher at T15 [2.2 (1.9)] than at T45 [1.6 (1.7); P

Exenatide is a GLP-1 analogue used in the management of T2DM yet within a subset of patients fails due to adverse side effects or from failure to attain the end goal. This retrospective observational study aimed to determine whether we could predict response to exenatide in patients with T2DM. 112 patients on exenatide were included with patient age, gender, duration of T2DM, medications alongside exenatide and weight, BMI, and HbA1c at baseline and 3 and 6 months of exenatide use being recorded. 63 responded with 11 mmol/mol reduction from baseline HbA1c after six months and 49 did not respond to exenatide. HbA1c solely differed significantly between cohorts at baseline, 3 months, and 6 months (P< 0.05). Regression analyses identified a negative linear relationship with higher baseline HbA1c correlating to greater reductions in HbA1c by 6 months (P< 0.0001). HbA1c was the sole predictor of exenatide response with higher baseline HbA1c increasing the odds of response by 5% (P= 0.004). Patients with HbA1c reductions ≥15–20% by 3 months were more likely to be responders by 6 months (P= 0.033). Our study identified that baseline HbA1c acted as the sole predictor of exenatide response and that response may be determined after 3 months of exenatide administration.

A large number of stroke-surviving individuals exhibit deficits related to upper limb movement, thereby making post stroke rehabilitation a critical part of patients' health care system. The patients are typically treated with conventional occupational therapy at the hospital after stroke. However, due to economic pressures and limited health care resources often the patients receive less therapy than required causing them to be deprived of the potential therapeutic benefits. Thus implementing a cost-effective home based technology-assisted rehabilitation system which is capable of providing intensive, adaptive and individualized rehabilitation service is critical. Virtual reality (VR) based rehabilitation system seems to address this challenge effectively. VR technology for rehabilitation allows us to create an interactive environment with precise control over intensity of practice that influence one's motor control in an individualized manner. In this study we developed an interactive VR-based platform which challenges the coordination skill of individuals with upper limb impairment. Additionally, we used patient's physiological indices to understand their stress level while they interact with the VR-based rehabilitation environment. The system developed in this work is a first step to understand its potential to provide individualized home-based rehabilitative service with minimal dependency on physiotherapist. In our initial study designed as a proof-of-concept application, one stroke-surviving patient participated in the interactive VR-based task. The preliminary results obtained from this initial study indicate the potential of mapping one's stress level to his physiological indices. Thus these results indicate the potential applicability of such a system for various stroke-rehabilitation applications

OBJECTIVE Fasting is not routinely recommended for renal function tests, despite the known effects of cooked meat on creatinine. We therefore studied variation in creatinine and estimated glomerular filtration rate (eGFR) after a standardized cooked meat meal in 80 subjects: healthy volunteers and diabetic patients with chronic kidney disease (CKD) stages 1 and 2, 3a, 3b, and 4 (n = 16/group). RESEARCH DESIGN AND METHODS The interventions were a standardized cooked meat and a nonmeat meal, each providing ∼54 g protein, together with 250 mL water, on separate days. Fasting and postprandial blood samples at 1, 2, and 4 h were drawn for creatinine measurement using a kinetic alkaline picrate assay on an Olympus AU640 analyzer. The modified four-variable Modification of Diet in Renal Disease equation traceable to isotope dilution mass spectrometry creatinine was used to calculate eGFR. RESULTS Consumption of a standardized cooked meat meal significantly increased serum creatinine and resulted in significant fall in eGFR in all stages of CKD studied; 6 of 16 CKD 3a patients were misclassified as CKD 3b. This effect of cooked meat on serum creatinine disappears after 12 h of fasting in all study participants. CONCLUSIONS Creatine in meat is converted to creatinine on cooking, which is absorbed, causing significant increases in serum creatinine. This could impact management, as threshold for commencing and withdrawing certain medications and expensive investigations is defined by eGFR. eGFR calculated using fasting serum creatinine would be a better reflection of kidney function in these patients.

Background Epidemiologic and experimental evidence suggests that individuals with diabetes are at increased risk of infection. We sought to examine the association of diabetes and insulin therapy with hospitalization for infection and 28-day mortality. Methods We performed a prospective cohort study using data from 30 239 community-dwelling participants aged ≥45 years enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. We defined diabetes as a fasting glucose level ≥126 mg/L (or ≥200 mg/L for those not fasting), the use of insulin or oral hypoglycemic agents, or self-reported history. We identified infection-related hospitalizations over the years 2003–2012. We fit Cox proportional hazards models to assess the association of diabetes with hazard rates of infection and logistic regression models for 28-day mortality. Results Among 29 683 patients from the REGARDS study with complete follow-up, 7375 had diabetes. Over a median follow-up period of 6.5 years, we identified 2593 first and 3411 total infection hospitalizations. In adjusted analyses, participants with diabetes had an increased hazard of infection (hazard ratio, 1.50; 95% confidence interval [CI], 1.37–1.64) compared with those without diabetes. Participants with diabetes hospitalized for infection did not have an increased odds of death within 28 days (odds ratio, 0.94; 95% CI, .67–1.32). Participants receiving insulin therapy had greater hazard of infection (hazard ratio, 2.18; 95% CI, 1.90–2.51) but no increased odds of mortality (odd ratio, 1.07; 95% CI, .67–1.71). Conclusions Diabetes is associated with increased risk of hospitalization for infection. However, we did not find an association with 28-day mortality. Insulin therapy conferred an even greater risk of hospitalization, without increased mortality.

INTRODUCTION: Prolactin circulates predominantly as a 23-kDa monomer, and a high-molecular-weight form largely consisting of a complex of prolactin and an anti-prolactin IgG autoantibody, called macroprolactin. This cross-reacts with conventional laboratory assays for prolactin. We here describe how quantitative adjustment for this may assist patient management.In a consecutive series of 218 patients with prolactin elevated to 400 mu/L or more in men (normal range ? 180) (n=79, 36.2% of sample) and 1 000 mu/L or more in women (normal range ? 500) (n=139, 63.8%) a macroprolactin screen was performed using PEG precipitation. RESULTS: Where present, median macroprolactin as a proportion of total prolactin was in women 13% (percentile 25-percentile 75: 7-25%) and in men 15% (7-30%).The distribution of macroprolactin as a proportion of total prolactin was markedly skewed to the left with 69.7% of women and 62.9% of men having macroprolactin proportion of 20% or less. There was no relation between %macroprolactin and total measured prolactin, age or gender.Of relevance to clinical management, in 24% of men and 20.5% of women, correction for estimated macroprolactin gave an adjusted monomeric prolactin level below the agreed threshold for further investigation, potentially avoiding unnecessarily referral.In our clinical series, quotation of an adjusted monomeric prolactin would have resulted in unnecessary further investigation being avoided in a number of cases. DISCUSSION: Screening for macroprolactin is a key element of laboratory assessment for hyperprolactinaemia.In cases where measured total prolactin is significantly raised, quantitative reporting of estimated monomeric prolactin instead of just 'macroprolactin' positive' can avoid unnecessary investigations.

We report a case of massive acute aortic valve regurgitation in a 54-year-old man secondary to a percutaneous extraction of infected permanent pacemaker leads. This case emphasizes how carefully patients should be monitored during and after the procedure, regardless of their hemodynamic status. The patient successfully underwent urgent surgical intervention.

Sodium-glucose cotransporter 2 (SGLT2) expressed in the proximal renal tubules accounts for about 90% of the reabsorption of glucose from tubular fluid. Genetic defects of SGLT2 result in a benign familial renal glucosuria. Pharmacological agents that block SGLT2 are being tested as potential treatment for type 2 diabetes mellitus.A Pubmed search was used to identify all relevant articles on the physiology of SGLTs as well as published preclinical and clinical experimental studies with SGLT2 inhibitors; a reference search of all retrieved articles was also undertaken.SGLT2 is almost exclusively expressed in the proximal renal tubules. Preclinical studies with selective SLGT2 inhibitors show dose-dependent glucosuria and lowering of blood glucose in models of type 2 diabetes. Preliminary clinical studies of up to 3-month duration show dose-dependent lowering of glycosylated hemoglobin up to 0.9% along with modest weight loss. Side effects include an increase in genital fungal infection compared to placebo, increased urine volume (300-400 ml/24 h), and evidence of volume depletion consistent with mild diuretic effect.SGLT2 inhibitors are showing promise as a useful addition to the current therapeutic options in type 2 diabetes mellitus. Results of ongoing phase III clinical trials are awaited and will determine whether the risk-benefit ratio will allow approval of this new class of drug for the management of type 2 diabetes mellitus.