This post-hoc exploratory analysis of data from the STEP 2 trial assessed the effect of a higher dose of the glucagon-like peptide-1 analog semaglutide (up to 2.4 mg) vs placebo on albuminuria in adults with overweight or obesity (body mass index ≥27 kg/m2) and type 2 diabetes.

Despite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.

This systematic review examined the impact of exercise training interventions on energy intake (EI) and appetite control in adults with overweight/obesity (≥18 years including older adults). Articles were searched up to October 2019. Changes in EI, fasting appetite sensations, and eating behavior traits were examined with random effects meta-analysis, and other outcomes were synthesized qualitatively. Forty-eight articles were included (median [range] BMI = 30.6 [27.0–38.4] kg/m 2 ). Study quality was rated as poor, fair, and good in 39, seven, and two studies, respectively. Daily EI was assessed objectively ( N  = 4), by self-report ( N  = 22), with a combination of the two ( N  = 4) or calculated from doubly labeled water ( N  = 1). In studies rated fair/good, no significant changes in pre-post daily EI were found and a small but negligible (SMD < 0.20) postintervention difference when compared with no-exercise control groups was observed (five study arms; MD = 102 [1, 203] kcal). There were negligible-to-small pre-post increases in fasting hunger and dietary restraint, decrease in disinhibition, and some positive changes in satiety and food reward/preferences. Within the limitations imposed by the quality of the included studies, exercise training (median duration of 12 weeks) leads to a small increase in fasting hunger and a small change in average EI only in studies rated fair/good. Exercise training may also reduce the susceptibility to overconsumption (PROSPERO: CRD42019157823).

OBJECTIVE Most individuals with type 2 diabetes also have obesity, and treatment with some diabetes medications, including insulin, can cause further weight gain. No approved chronic weight management medications have been prospectively investigated in individuals with overweight or obesity and insulin-treated type 2 diabetes. The primary objective of this study was to assess the effect of liraglutide 3.0 mg versus placebo on weight loss in this population. RESEARCH DESIGN AND METHODS Satiety and Clinical Adiposity—Liraglutide Evidence (SCALE) Insulin was a 56-week, randomized, double-blind, placebo-controlled, multinational, multicenter trial in individuals with overweight or obesity and type 2 diabetes treated with basal insulin and ≤2 oral antidiabetic drugs. RESULTS Individuals were randomized to liraglutide 3.0 mg (n = 198) or placebo (n = 198), combined with intensive behavioral therapy (IBT). At 56 weeks, mean weight change was −5.8% for liraglutide 3.0 mg versus −1.5% with placebo (estimated treatment difference −4.3% [95% CI −5.5; −3.2]; P < 0.0001). With liraglutide 3.0 mg, 51.8% of individuals achieved ≥5% weight loss versus 24.0% with placebo (odds ratio 3.41 [95% CI 2.19; 5.31]; P < 0.0001). Liraglutide 3.0 mg was associated with significantly greater reductions in mean HbA1c and mean daytime glucose values and less need for insulin versus placebo, despite a treat-to-glycemic-target protocol. More hypoglycemic events were observed with placebo than liraglutide 3.0 mg. No new safety or tolerability issues were observed. CONCLUSIONS In individuals with overweight or obesity and insulin-treated type 2 diabetes, liraglutide 3.0 mg as an adjunct to IBT was superior to placebo regarding weight loss and improved glycemic control despite lower doses of basal insulin and without increases in hypoglycemic events.

AbstractDespite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. We report the development of a rapid, highly specific and sensitive electrochemiluminescent assay for detecting IgM, IgA, and IgG antibodies toward two distinct SARS-CoV-2 antigens namely, the receptor binding domain (RBD) and the nuclear protein (NP). Whereas IgM antibodies toward RBD were detected at early stages of the disease, IgM antibodies against NP did not develop. Analysis of the antibody response in mild versus moderate/severe patients revealed a rapid onset of IgG and IgA antibodies, specifically in moderate/severe patients. Finally, we observed a marked reduction in IgM/IgA antibodies and to lesser extent, IgG, over time. We provide a comprehensive analysis of the human antibody response, and has major implications on our understanding and monitoring of SARS-CoV-2 infections, as well as finding effective vaccines.One Sentence SummaryUsing a newly developed assay to detect anti-SARS-Cov-2 IgM, IgG and IgA antibodies we reveal a rapid onset of IgG and IgA antibodies towards distinct viral antigens, specifically in moderate/severe COVID-19 patients,

The breadth of the humoral immune response following SARS-CoV-2 infection was indicated to be important for recovery from COVID-19. Recent studies have provided valuable insights regarding the dynamics of the antibody response in symptomatic COVID-19 patients. However, the information regarding the dynamics of the serological and cellular memory in COVID-19 recovered patients in scarce. It is imperative to determine the persistence of humoral memory in COVID-19 recovered patients as it will help to evaluate the susceptibility of recovered patients to re-infection. Here, we describe the dynamics of both the SARS-CoV-2 specific serological and B cell response in COVID-19 recovered patients. We found that symptomatic SARS-CoV-2 patients mount a robust antibody response following infection however, the serological memory decays in recovered patients over the period of 6 months. On the other hand, the B cell response as observed in the SARS-CoV-2 specific memory B cell compartment, was found to be stable over time. Moreover, the frequency of SARS-CoV-2 specific B cell plasmablasts was found to be associated with the SARS-CoV-2 specific antibody levels. These data, suggests that the differentiation of short-lived plasmablasts to become long-lived plasma cells is impaired and the main contributor of antibody production are the short-lived plasmablasts. Overall, our data provides insights regarding the humoral memory persistence in recovered COVID-19 patients. Notwithstanding the insights from this study, it is still to be determined if the persistence of SARS-CoV-2 memory B cells can be considered as a correlate of protection in the absence of serological memory.

Silicone has been considered biologically inert; thus it has been employed in many medical devices and nowadays is commonly used in plastic surgery for mammary prosthesis. It is well tolerated in most cases. However, autoimmune disorders and siliconomas with granulomatous reactions after silicone implant rupture have been described. We report cases of four women who developed systemic disorders following rupture of silicone breast implants resulting in lymph node and thoracic silicone infiltration. The symptoms in these cases, including arthralgia, myalgia, generalized weakness, severe fatigue, sleeping disturbances, cognitive impairment, memory loss, irritable bowel syndrome, and weight loss, clearly match the criteria of the recently defined autoimmune/inflammatory syndrome induced by adjuvants (ASIA).

Background: Hyperglycemia in hospitalized patients is found to be associated with increased risk of complications, systemic infections and mortality. Thus, managing and controlling glucose blood levels in these patients are essential. The aim of the present retrospective study was to evaluate the efficacy of standardized electronic insulin orders, using a computerized physician order entry (CPOE), in controlling blood glucose levels, preventing hypoglycemic events and reducing the variability of daily blood glucose levels during hospitalization of patients with diabetes mellitus in internal medicine departments. Methods: Data were obtained from an internal medicine unit that used the standardized electronic insulin orders (Department 7) and compared to data from 6 other internal medicine departments in which the standardized electronic insulin orders was not used (Departments 1-6). The variability of daily changes in blood glucose levels was determined by the standard deviation of the daily changes and respective coefficient of variation. Results: 130,078 point-of-care bedside glucose tests were recorded from 13,577 hyperglycemic patients. The average daily mean blood glucose levels were significantly lower in patients from Department 7 than from Departments 1-6. The rate of patients achieving average daily mean blood glucose levels ≤ 180 mg/dL was higher in Department 7 than Departments 1-6. The percent of patient days with hypoglycemia and the variability of daily changes in blood glucose levels were significantly lower in Department 7 than Departments 1-6. Conclusions: A standardized electronic insulin orders of basal/bolus regimen improves glucose control in hospitalized patients.

Patient centred care is now considered the gold standard and there should be ‘no decision about me, without me’. Internists who treat patients with complex multi-morbidities should consider patients' preferred outcomes, following a ‘goal-oriented’ principle. Perhaps the most important barrier to goal-oriented care is that medicine is deeply rooted in a disease-outcome-based paradigm. Rather than asking what patients want, the culture of modern medicine has prioritised optimal disease management according to guidelines and population goals. Doing what is right for the patient should be based on trust. Patients and internists must therefore meet as equals: ‘I’ and ‘you’ should be replaced by ‘we’.

It is well known that patients with type 2 diabetes mellitus (T2DM) are at increased risk of cardiovascular (CV) disease. Elevated plasma glucose levels that independently lead to increased cardiovascular risk, combined with associated co-morbidities such as obesity, hypertension, and dyslipidemia, further contribute to the development of CV complications. Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors) are a relatively new class of drugs used for the treatment of diabetes and recently have been widely used in clinical practice. They exert their actions through degradation inhibition of endogenous glucagon-like peptides (GLP-1) and glucose-dependent insulinotropic peptides (GIP), with a resulting increase in glucose mediated insulin secretion and a suppression of glucagon secretion. Since GLP-1 is known to have an impact not only on plasma glucose levels but also to have cardiovascular protective effects there is increased speculation of whether DPP-4 inhibitors will have similar effects. Though many short-term studies have been encouraging, ongoing long-term clinical trials on humans are needed to provide further clarity to the complete safety profiles of these agents in terms of cardiovascular risk, and whether they may exert potential cardiovascular benefit. This review includes available data on the cardiovascular effects of DPP-4 inhibitors as well as their overall safety profile.

The aim of this pilot feasibility study was to investigate the efficacy and safety of hysteroscopy in the diagnosis and treatment of acute severe uterine bleeding. Forty-one women (mean age, 54 years) who underwent emergency hysteroscopy were assessed. In 40 women, a benign organic cause was found. In one postmenopausal patient, endometrial carcinoma was detected in endometrial chips and was managed with hysterectomy. None of the women with benign lesions required further surgery within the first postoperative year. One underwent hysterectomy at 18 months for new-onset fibromyomas. Hysteroscopy was found to be an effective tool for treating heavy uterine bleeding. It also prevented future episodes of severe bleeding in more than half the patients during 20 months of follow-up.

Wolfson Hospital (Leibovitz) (Gavish) Barzilai Medical Center (Yosefi) (Viskoper) Rabin Medical Center (Dicker)

Clostridium difficile is the main cause of nosocomial diarrhea mainly in elderly hospitalized patients and in nursing homes, but less common in the community. We report three elderly patients living in the community, one frail and two in reasonable good health who recently developed diarrhea due to C. difficile associated with Salmonella group C in two cases and Shigella flexneri in the other. The association with Shigella has not previously been reported and there have only been a few cases with Salmonella. These findings may be important due to the possibility that diarrhea caused by C. difficile associated with other enteric bacteria may be more prevalent than expected in the aging population, thus necessitating awareness and consequently appropriate treatment and follow-up.

1Medicine A, Wolfson Medical Center, Israel 2Medicine B, Barzilai Medical Center, Israel 3Medicine C, Golda Campus, Rabin Medical Center, Israel 4Sackler School of Medicine, Israel

Objective: To report a rare case of two normally karyotyped 46,XX siblings with severe ovarian dysgenesis and enlarged dysplastic kidneys.Design: Case report.Setting: Rabin Medical Center, a major tertiary university-affiliated care and referral facility.Patient(s): A healthy 30-31-year-old woman underwent termination of two pregnancies at 22 and 23 gestational weeks because of ultrasonographic observations of enlarged kidneys in both fetuses.Intervention(s): Prostaglandin-induced pregnancy terminations with feticide.Main Outcome Measure(s): Light microscopy observations.Result(s): Both siblings had a 46,XX karyotype, and the maternal a-fetoprotein level was within normal limits. In the first, no ovaries were identified, and in the second, bilateral streak ovaries devoid of ova were noted. In both cases, pathological examinations identified large dysplastic kidneys, with dysplastic changes in certain medullary areas. Apart from the kidneys and ovaries, all other organs were normal.Conclusion(s): To the best of our knowledge, this is the first report of two normally karyotyped 46,XX siblings with severe ovarian dysgenesis and renal abnormalities but without any other malformations.

Aims: Blood pressure (BP) reduction is crucial in reducing cardiovascular morbidity and mortality. The IBPC (Israeli Blood Pressure Control) program was initiated in order to enhance the control of modifiable risk factors among high-risk hypertensive patients under follow-up by general practitioners in Israel. The cost effectiveness of an intervention program is an important factor in the decision-making process of its implementation and therefore was evaluated here. The objective of this evaluation is to estimate the costs, monetary savings and benefits in terms of QALYs (quality-adjusted life years) that would be expected if the program were to be expanded to 100 clinics nationwide, enabling around 14 800 persons to be treated. Methods: Hypertensive patients were screened in 30 general practice clinics, supervised by specialists in family medicine, each seeing 1000-5000 patients; 50-250 hypertensive patients were diagnosed at each participating clinic. BP levels, body mass index (BMI), lipid and glucose levels, as well as target organ damage and medications were recorded for all patients. Results: A total of 4948 (2079, 42% males) were registered. Mean age was 64.8 +/- 12 years. After 1 year of follow-up versus baseline, the various parameters were as follows: BP control was achieved in 46.4% vs 29% of all hypertensive patients. LDL control (JNC VI criteria) was achieved in 41.7% vs 31.2% of all patients. Fasting plasma glucose control (glucose < 126 mg/dl) was achieved in 22% vs 19% of diabetic patients and 5.2% vs 3.1% of the diabetics had fasting plasma glucose levels > 200 mg/dl. Obesity (BMI > 30 kg/m(2)) was noted in 36.7% vs 43.8% at baseline. The cost utility analysis of the reduction in risk factors was calculated based on the international dicta applied to the reduction in risk factors as a result of treatment. For 100 clinics nationwide and 14800 persons to be treated the net saving to health services would be $977 993 and the increase in QALYs would be 602 years. Conclusions: Better risk factor control in hypertensive patients by general practitioners could reduce morbidity and mortality as well as be cost effective.