A Case of Transient Hypercalcemia Following Fistulization of a Calcified Mitral Annulus.

We report a case of severe symptomatic hypercalcemia that resolved after a short course of therapy of exclusively fluids and furosemide. An extensive workup for metabolic, neoplastic, and drug-induced causes did not provide a possible etiology of the hypercalcemia. After calcium level returned to baseline, the patient was discharged, only to return a week later with multiple embolic strokes of unknown source. The comparison of cardiac imaging obtained during the hospitalization periods established a possible mechanism for both phenomena; the interior caseous cavity of a calcified mitral annulus (CMAC), which was demonstrated on echocardiography during the first hospitalization, disappeared in a subsequent study in the second hospitalization, probably reflecting a fistulization of the structure into the left ventricle. The spill of contents into the bloodstream, over several days presumably, explains the transient increase in calcium, and the embolic events that followed. We hereby demonstrate a clear relationship between the fistulization of a CMAC and hypercalcemia, emphasizing the risks of this valvular pathology, and introducing a rare mechanism for transient and potentially severe hypercalcemia.

Severe and fatal COVID-19 is characterised by increased circulating glucagon like peptide 1 and procalcitonin modulated by type 2 diabetes.

AIMS: Endotoxemia commonly occurs in severe and fatal COVID-19, suggesting that concomitant bacterial stimuli may amplify the innate immune response induced by SARS-CoV-2. We previously demonstrated that the endogenous glucagon like peptide 1 (GLP-1) system in conjunction with increased procalcitonin (PCT) is hyperactivated in patients with severe Gram-negative sepsis and modulated by type 2 diabetes (T2D). We aimed to determine the association of COVID-19 severity with endogenous GLP-1 activation upregulated by increased specific pro-inflammatory innate immune response in patients with and without T2D. MATERIALS AND METHODS: Plasma levels of total GLP-1, IL-6, and PCT were estimated on admission and during hospitalisation in 61 patients (17 with T2D) with non-severe and severe COVID-19. RESULTS: COVID-19 patients demonstrated ten-fold increase of IL-6 levels regardless of disease severity. Increased admission GLP-1 levels (p = 0.03) accompanied by two-fold increased PCT were found in severe as compared with non-severe patients. Moreover, GLP-1 and PCT levels were significantly increased in non-survived as compared with survived patients at admission (p = 0.01 and p = 0.001, respectively) and at 5 to 6 days of hospitalisation (p = 0.05). Both non-diabetic and T2D patients demonstrated a positive correlation between GLP-1 and PCT response (r = 0.33, p = 0.03, and r = 0.54, p = 0.03, respectively), but the intensity of this joint pro-inflammatory/GLP-1 response was modulated by T2D. In addition, hypoxaemia down-regulated GLP-1 response only in T2D patients with bilateral lung damage. CONCLUSIONS: The persistent joint increase of endogenous GLP-1 and PCT in severe and fatal COVID-19 suggests a role of concomitant bacterial infection in disease exacerbation. Early elevation of endogenous GLP-1 may serve as a new biomarker of COVID-19 severity and fatal outcome.

Endocrinology specialty service for inpatients: an unmet growing need.

BACKGROUND: There is recent concern regarding the documented mismatch between demand and supply, vis-à-vis the growing need for trained endocrinologists unmet by parallel rise in the world workforce of endocrinologist. Due to the increasing complexity of disease in inpatients, in recent years we have experienced a growing demand for inpatient endocrine consults. Surprisingly, the need for the endocrinology subspecialty in the overall care of inpatients in the current setting of general hospitals has received little attention. METHODS: A retrospective analysis of endocrine consult service based on solicited consults carried out during 3 consecutive months. RESULTS: During 3 months, there were 767 consults, comprised of 156 diabetes referrals and 611 endocrine/metabolic consult requests. The 611 "non-glucocentric" consult requests were related to 295 inpatients (2.1 ± 2.7 consults/patient). Mean patient age was 58.9 ± .18 years (range 21-92), with some F/M preponderance (58/42%). Requests for endocrine consults were evenly distributed (49.8%, 50.2%) between internal medicine and surgery wards. Case distribution was as follows: thyroid 45.4%, calcium & bone 11.5%, pituitary 12%, adrenal 10% and all others 8.1-0.7%. The mean response time was 4.4 ± 2.7 h. The consults had a discernible effect on the patients' disease management in 60% of the patients. Of these, the consults modified the hospital treatment in 74%, the discharge treatment recommendations in 19% and the diagnosis in 7%. CONCLUSION: At a large medical center, endocrine consults were requested for ~ 3.3% of all admitted inpatients. The endocrine consults modified pre-consult diagnosis or treatment in ~ 60% of the cases. Contrary to its common image as an exclusively outpatient-based subspecialty, endocrinology practiced by specialists and endocrine trainees has a notable role in the daily care of inpatients admitted to a referral general hospital.

The First Fatal Post-COVID-19 Adult Patient with Multi-System Inflammatory Syndrome in Israel.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is recognized as a respiratory illness, which includes pulmonary consolidations, hypoxemic states, and hypercoagulopathic tendencies with a broad clinical severity. Recently, more reports have described post-infection manifestations. These include multi-system inflammatory syndrome in children (MIS-C) with more than 400 cases published since the start of the coronavirus disease pandemic. In October 2020, the U.S. Centers for Disease Control and Prevention (CDC) published 27 cases [1] describing the new multi-system inflammatory syndrome in adults (MIS-A). Nine of the cases were reported directly to the CDC, 7 from published case reports and another 11 patients found in three distinct case series.

Years of potential life lost in pre-diabetes and diabetes mellitus: data from a 40-year follow-up of the Israel study on Glucose intolerance, Obesity and Hypertension.

INTRODUCTION: We examined years of potential life lost (YPLL) associated with pre-diabetes as compared with either normoglycemia or diabetes, using data of the Israel cohort of Glucose intolerance, Obesity and Hypertension 40-year follow-up. RESEARCH DESIGN AND METHODS: Men and women (N=2844, mean age 52.0±8.2 years) who underwent oral glucose tolerance test and anthropometric measurements, during 1976-1982, were followed for mortality until May 2019. Multiple imputation procedures for missing mortality dates and multivariable regression mixed models were applied. RESULTS: At baseline, 35.8%, 48.8% and 15.4% individuals were found with normoglycemia, pre-diabetes, and diabetes, respectively. The average difference in YPLL associated with pre-diabetes as compared with normoglycemia was 4.3 years (95% CI 3.3 to 5.2; p<0.001). YPLL were 1 year higher in women with pre-diabetes than in men with pre-diabetes. These differences persisted mainly in individuals younger than 60 years, and those with body mass index (BMI) <25 kg/m2, at baseline. Adjusting for age, sex, country of origin, smoking status, BMI, and blood pressure, the average difference in YPLL associated with pre-diabetes as compared with normoglycemia was 2.0 years (95% CI 1.2 to 2.8; p<0.001). Significant reductions of 5.9 years (95% CI 4.8 to 7.0) on average were observed for diabetes as compared with pre-diabetes and 7.9 years (95% CI 6.7 to 9.1) as compared with individuals with normoglycemia. CONCLUSIONS: This study reveals that life expectancy of middle-aged individuals with pre-diabetes is shorter than of normoglycemic ones. These findings are especially relevant in view of the rising worldwide prevalence of pre-diabetes within younger age groups and underscore the crucial importance of interventions by either lifestyle modification or drug therapy capable of delaying progression from pre-diabetes to diabetes to reduce the YPLL in this high-risk group.

Coronary atherosclerosis severity is closely associated with decreased GLP-1R positivity among CD16+ pro-inflammatory and patrolling monocyte subsets.

Background and aims: Glucagon Like Peptide-1 Receptor (GLP-1R) activation reduces pro-inflammatory responses of human monocytes, their accumulation in the vascular wall and foam cell formation inhibiting atherosclerogenesis. This suggests that reduction of circulating GLP-1-1R positive monocytes may have pro-atherogenic effects. It is unknown whether different CD14/CD16 monocytes subsets display GLP-1R and whether their relative proportions correlate with atherosclerosis severity. We evaluated the association between GLP-1R positivity in different CD14/CD16 monocyte subsets and coronary atherosclerosis severity. Methods: Relative amounts of classical (CD14+/CD16-), intermediate pro-inflammatory (CD14+/CD16+) and non-classical patrolling (CD14-/CD16+) subsets of total circulating monocytes and the proportions of GLP-1R positive monocytes in these subsets were determined in 13 control subjects and 10 dyslipidemic ischemic heart disease (IHD) patients with severe angiographic proven coronary atherosclerosis using flow cytometry analysis. Atherosclerosis severity was calculated by SYNTAX score. Results: In univariable analysis, severe atherosclerosis was associated with decreased proportion of classical monocytes and two fold increased CD16+ pro-inflammatory and patrolling subsets as compared with controls (p = 0.01, p = 0.02 and p = 0.01, respectively). Frequency of GLP-1R positive monocytes was decreased in both CD16+ subsets (p = 0.02 and p = 0.05, respectively) and negatively correlated with atherosclerosis severity (r = -0.65, p = 0.005 and r = -0.44, p = 0.05, respectively). Conclusions: Increased skewing of the classical monocyte population toward CD16+ pro-inflammatory and patrolling subsets accompanied by decreased in GLP-1R positivity are associated with coronary atherosclerosis severity in IHD patients with dyslipidemia. Although the effect of potential confounders cannot be ruled out, our data suggest that failure of GLP-1R-dependent anti-inflammatory/anti-atherogenic control results in innate immune system dysfunction and can promote atherosclerogenesis.

The Risk of Bone Fractures in Post-Poliomyelitis Patients Transitioning to Middle Adulthood.

ObjectiveWhile osteoporotic fractures are reported in up to 40% of adults with post-poliomyelitis syndrome (PPS), clinical guidelines regarding bone mineral density (BMD) and indications for treatment are scarce. We investigated the characteristics of PPS patients, focusing on fractures and osteoporosis as the primary outcomes. METHODS: A cross-sectional retrospective data analysis from medical records of 204 PPS patients regarding their clinical characteristics and long-term outcome, with emphasis on bone metabolism status. RESULTS: Our cohort included 53% women; mean age was 65 years at study entry and 1.7 years at the diagnosis of acute poliomyelitis. The lower limb was involved in 97.5% of patients, and the BMD in the affected limb tended to be lower than the unaffected, with a mean T-score of -1.64 vs. -1.19, respectively (P = .06). Recurrent falls were documented in 39.2% of patients, and osteoporosis in 20.6%, being more frequent in women (P = .003) and patients with fractures (P = .002). At least one fracture occurred in 52.2% of patients, and more than one in 40.3%. The median age for the first fracture was 57.5 years (range, 30 to 83 years), and most fractures occurred in the affected limb (73.2%). CONCLUSIONS: Underdiagnosis and delayed treatment of osteoporosis in late-adulthood post-poliomyelitis patients underlie the need for comprehensive clinical guidelines to manage these patients, including recommendations on bone health assessment, medical treatment, and their inclusion as a high-risk group for bone fractures.

A 2017 SURVEY OF THE CLINICAL PRACTICE PATTERNS IN THE MANAGEMENT OF RELAPSING GRAVES DISEASE.

OBJECTIVE: Previous surveys from different world regions have demonstrated variations in the clinical management of Graves disease (GD). We aimed to investigate the clinical approach to GD relapse among endocrinologists. METHODS: Electronic questionnaires were e-mailed to all members of the Israeli Endocrine Society. Questionnaires included demographic data and different scenarios regarding treatment and follow-up of patients with GD relapse. RESULTS: The response rate was 49.4% (98/198). For a young male with GD relapse, 68% would restart antithyroid drug (ATD) (98% methimazole), while 32% would refer to radioactive iodine (RAI) treatment. Endocrinologists who treat >10 thyroid patients a week tended to choose ATDs over RAI ( P = .04). In the case of GD relapse with ophthalmopathy, 50% would continue ATDs, whereas 22.4% would recommend RAI treatment and 27.6% surgery. Most endocrinologists (56%) would continue ATDs for 12 to 24 months. Seventy-five percent would monitor complete blood count and liver function (39% for the first month and 36% for 6 months), and 44% would recommend a routine neck ultrasound. In a case of thyrotoxicosis due to a 3-cm hot nodule, most endocrinologists (70%) would refer to RAI ablation, 46.4% without and 23.7% with a previous fine-needle aspiration. No significant differences were found regarding gender, year of board certification, or work environment. CONCLUSION: Our survey demonstrates diverging patterns in the diagnosis and management of GD relapse that correlate well with previous surveys from other countries on GD-naïve patients and a less than optimal adherence to recently published clinical guidelines. ABBREVIATIONS: ATA = American Thyroid Association; ATD = antithyroid drug; CBC = complete blood count; GD = Graves disease; GO = Graves ophthalmopathy; LFT = liver function test; MMI = methimazole; PTU = propylthiouracil; RAI = radioactive iodine; TSI = thyroid-stimulating immunoglobulin.

Short-term Adherence with Discharge Recommendation for Insulin Treatment among Patients with Type 2 Diabetes.

BACKGROUND: Basal-bolus (BB) insulin treatment is increasingly used in poorly controlled diabetes patients during hospitalization and is commonly recommended at discharge; however, the extent of adherence with this recommendation is unknown. OBJECTIVES: To determine short-term adherence of type 2 diabetes mellitus (T2DM) patients discharged from internal medicine wards with recommendation for BB insulin treatment. METHODS: Prescription (primary physician adherence) and purchase (patient adherence) of long-acting and short-acting insulins during the first month following discharge from internal medicine wards was determined in 153 T2DM patients. Adherence was defined as full if prescription/purchase of both basal (long-acting) and bolus (short-acting) insulin was completed, and as partial if only one kind of insulin (basal or bolus) was prescribed/purchased. Association between demographic and clinical parameters and adherence was determined. RESULTS: Full adherence with discharge instructions was higher for primary physicians than for patients )79.1% vs. 69.3%, respectively, P = 0.0182). Pre-hospitalization hemoglobin A1C was significantly associated with adherence by both patients and primary physicians (full-adherence group 9.04% ± 2.04%; no-adherence group 7.51% ± 1.35%, P = 0.002). Age was negatively associated with adherence of both primary physicians and patients; however, this association did not reach statistical significance. Patients with certain background diseases such as atrial fibrillation, coronary heart disease, and chronic heart failure had significantly worse adherence (P < 0.05). When the sole cause of admission was diabetes, full adherence (100%) of both primary physicians and patients was found. CONCLUSIONS: Short-term adherence with discharge recommendation for BB insulin treatment is associated with pre-hospitalization patient characteristics.

Adherence to ATA 2015 guidelines in the management of unifocal non-invasive papillary thyroid cancer: a clinical survey among endocrinologists and surgeons.

BACKGROUND: Despite updated guidelines, management of thyroid nodules remains controversial. We aim to check implementation of new guidelines by ear-nose-throat (ENT) surgeons and endocrinologists. METHODS: A questionnaire was e-mailed including demographic data and an index case: a healthy 26-year-old women with a 3-cm Bethesda III (B3) atypia of undetermined significance solitary nodule and eventually papillary thyroid cancer (PTC). RESULTS: Respondent rate was 50.5%, 93 endocrinologists, 55 surgeons. For this case, 77.4% would repeat fine-needle aspiration (FNA), 25.3% order molecular analysis and 22.6% do surgery. If repeated FNA remained B3, 51% would choose surgery, 17.3% molecular analysis and 31.6% follow-up only. If repeated FNA was B6, 58.5% would recommend total (TTx) and 41.5% hemithyroidectomy (HTx). In pathologically confirmed PTC after HTx, 42.4% would recommend completion, 26.8% radioactive iodine (RAI) treatment. For a > = 4-cm tumor, 49.2% would recommend TTx. For a tumor 2-4 cm, 41% would recommend TTx. Variables favoring TTx were family history and radiation exposure. Only 17.4% would prefer TTx when small benign contralateral tumor is present. Reassessment at 1 year with undetectable thyroglobulin (Tg) included stimulated Tg (stTg) (72.5%), neck US only (27.5%) and combined US-stTg (59.4%); only 10.3% would order a diagnostic scan. For recurrence in two (13-9 mm) lymph nodes, 59.3% recommend reoperation, 16.3% RAI and 24.4% active surveillance. There were no major differences between endocrinologists and ENT surgeons. CONCLUSIONS: We report a considerable lack of adherence to new guidelines, with only 50% recommending HTx for a 4-cm unifocal low-risk PTC tumor.

Reassessment of Differentiated Thyroid Cancer Patients Using the Eighth TNM/AJCC Classification System: A Comparative Study.

BACKGROUND: Facing the prevailing concept that increased diagnosis with no change in mortality drives the increased incidence of differentiated thyroid cancer (DTC), considerable modifications have been introduced in the new edition of the tumor node metastasis (TNM)/American Joint Committee on Cancer (AJCC) staging system. The aim of this study was to compare a group of DTC patients before and after restaging, by mortality, disease severity, and disease outcomes. METHODS: DTC patients (N = 433) were restaged according to the eighth TNM/AJCC edition, and the results were compared to the seventh edition for clinicopathologic data, treatment modalities, and disease outcomes. RESULTS: When switched to the eighth edition, 97.5% of patients fell into stage I-II compared to 76.4% before, and only 11/102 patients remained in stages III-IV. Disease-specific mortality was recorded in 11/433 patients, six of whom were in stages I-II upon restaging, compared to none before (p > 0.05). In addition, more recurrences were seen in stages II (p = 0.05) and III (p = 0.03) using the eighth edition compared to the seventh edition. Stage II was affected the most, with recurrence risk increasing from 29% to 76% (p = 0.001) and persistence at last visit from 19% to 43% when switching to the eighth edition (p = 0.01). Considering stages I and II together, the recurrence risk increased from 16.7% to 28.2% (p = 0.01), lymph node metastases from 1.9% to 26.5% (p = 0.01), and persistence at last visit from 10% to 15% (p > 0.05). Of the 129 patients in the 45- to 54-year-old age group, 53 shifted to stage I (20 from stage II, 29 from stage III, and 4 from stage IV) and five shifted to stage II (all from stage IV). When comparing this age group in stage II only, the eighth edition showed more lymph node metastases (p = 0.001), more distant metastases (p = 0.003), higher recurrence risk (p = 0.002), and more persistence at the last visit (p > 0.05). CONCLUSION: The eighth TNM/AJCC edition provides a more accurate system to discriminate mortality and persistence in DTC patients. Yet, the severity of disease, especially in the 45- to 55-year-old age group and in stage II patients, should not be underestimated following the downstaging of these patients.

Nutrient induced type 2 and chemical induced type 1 experimental diabetes differently modulate gastric GLP-1 receptor expression.

T2DM patients demonstrate reduced GLP-1 receptor (GLP-1R) expression in their gastric glands. Whether induced T2DM and T1DM differently affect the gastric GLP-1R expression is not known. This study assessed extrapancreatic GLP-1R system in glandular stomach of rodents with different types of experimental diabetes. T2DM and T1DM were induced in Psammomys obesus (PO) by high-energy (HE) diet and by streptozotocin (STZ) in Sprague Dawly (SD) rats, respectively. GLP-1R expression was determined in glandular stomach by RT PCR and immunohistomorphological analysis. The mRNA expression and cellular association of the GLP-1R in principal glands were similar in control PO and SD rats. However, nutrient and chemical induced diabetes resulted in opposite alterations of glandular GLP-1R expression. Diabetic PO demonstrated increased GLP-1R mRNA expression, intensity of cellular GLP-1R immunostaining, and frequency of GLP-1R positive cells in the neck area of principal glands compared with controls. In contrast, SD diabetic rats demonstrated decreased GLP-1 mRNA, cellular GLP-1R immunoreactivity, and frequency of GLP-1R immunoreactive cells in the neck area compared with controls. In conclusion, nutrient and chemical induced experimental diabetes result in distinct opposite alterations of GLP-1R expression in glandular stomach. These results suggest that induced T1DM and T2DM may differently modulate GLP-1R system in enteropancreatic axis.

GLP-1 receptor is expressed in human stomach mucosa: analysis of its cellular association and distribution within gastric glands.

The stomach is a target organ of the incretin hormone glucagon-like peptide-1 (GLP-1). However, the cellular expression and glandular distribution of its receptor (GLP-1R) in human gastric mucosa are not known. We determined the expression of GLP-1R in different regions of human stomach mucosa and its specific cellular association and distribution within gastric glands. Tissue samples from stomach body and antrum were obtained from 20 patients during routine esophagogastroduodenoscopy. mRNA encoding GLP-1R protein expression was evaluated by RT-PCR. Determination of cell types bearing GLP-1R, their localization, and their frequency in gastric glands in different gastric regions were estimated by immunohistochemical morphological analysis. Levels of GLP-1R mRNA were similar in body and antrum. GLP-1R immunoreactivity was found throughout the gastric mucosa in various types of glandular cells. The highest frequency of GLP-1R immunoreactive cells was found in the neck area of the principal glands in cells morphologically identified as parietal cells. GLP-1R immunostaining was also found on enteroendocrine-like cells in the pyloric glands. This study provides the first description of GLP-1R expression in human gastric glands and its specific cellular association. Our data suggest that GLP-1 may act directly on the gastric mucosa to modulate its complex functions.

Hand hygiene compliance by physicians: marked heterogeneity due to local culture?

BACKGROUND: Physician compliance with hand hygiene guidelines often has been reported as insufficient. METHODS: The study was conducted in 2 hospitals (Hadassah Ein Kerem [EK] and Mt Scopus [MS]) in Jerusalem, Israel. Covert observations were conducted during morning rounds by trained observers. The data were recorded as the percentage of times that hand hygiene was applied out of the total contacts with patients. After the observational step, an intervention-providing an alcohol gel and encouraging its use-was instituted in several wards. RESULTS: Physicians' compliance with hand hygiene averaged 77% at MS and 33% at EK (P < .001), and was characterized by a marked additional heterogeneity among wards. Rates of adherence ranged from as low as 4% in a gynecology ward to as high as 96% in a neonatal unit. Availability of a handwashing basin in the room and seniority status of the physician were associated with higher compliance rates but explained only a small part of the variation. Compliance improved significantly in 2 wards exposed to the intervention. CONCLUSION: The remarkable heterogeneity in physicians' hand hygiene compliance among sites within the same institution is consistent with an important role of the local ward culture.