Heart valve disease in primary antiphospholipid syndrome.

OBJECTIVES: Antiphospholipid syndrome (APS)-associated heart valve disease (HVD) is well described. Nonetheless, limited data exist on clinical parameters associated with the course of primary APS (pAPS) patients with HVD. The goal of this study was to assess clinical features and related outcomes in patients with APS associated HVD. METHODS: In this multicentre retrospective study, we identified 33 pAPS patients with HVD (pAPS-HVD group) and compared their clinical course with 128 pAPS patients with normal heart valves on echocardiography (pAPS-control group). RESULTS: pAPS-HVD patients had more cerebrovascular events 56.3% vs 25% (p= 0.005) and livedo reticularis 24.2% vs 7.8% (p= 0.013) than pAPS-controls. Furthermore, catastrophic-APS (CAPS) (12.1% vs 2.4%, p= 0.034), recurrent thrombosis (33.3% vs 4.7%, p< 0.001), and need for advanced therapy (i.e. IVIG, plasmapheresis or rituximab) were more frequent in pAPS-HVD patients. Anti-B2GPI-IgG. [84.8% vs 63.2% (p= 0.034)], anti-cardiolipin IgG [90.9% vs. 64.8% (p= 0.005)] and triple positive aPL [75.8% vs 56.5% (p= 0.047)] were commoner in pAPS-HVD patients vs pAPS-controls. Ten of the 33 patients with pAPS-HVD underwent valve surgery which was associated with male gender, smoking, arterial limb ischaemia and livedo reticularis. CONCLUSION: pAPS-HVD patients had a more severe APS clinical course including CAPS and thrombotic events as well as with specific serology namely IgG isotype aPL antibodies and triple positivity. Our data suggest that pAPS-HVD represents a high-risk subgroup of APS patients.

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.

Indwelling Urinary Catheter and Dementia Are Associated with Enterococcal Urinary Tract Infections in Hospitalized Patients.

BACKGROUND: The recent increase in enterococcal urinary tract infections (EUTI) and the potential morbidity and mortality associated with inappropriate antimicrobial treatment underscores the need for early risk assessment and institution of appropriate empirical antimicrobial therapy. OBJECTIVES: To identify high-risk features associated with hospitalized patients with EUTI. METHODS: Demographic, clinical, laboratory, and bacteriological data of 285 patients hospitalized with UTI during 2016 were retrieved from the computerized database of Shamir Medical Center. Patients were divided into two groups: EUTI and non-EUTI (NEUTI), according to the presence or absence of enterococcus in the urine culture. The features of the two groups were compared. RESULTS: We obtained 300 urine cultures from 285 patients. Of the total, 80 patients (26.6%) had EUTI and 220 patients (73.3%) had NEUTI. A higher prevalence of urinary multi-bacterial cultures was found in EUTI compared to NEUTI patients (P < 0.01). Higher prevalence of permanent indwelling urinary catheter and dementia were found in hospitalized patients with community-acquired EUTI and nosocomial EUTI respectively (P = 0.02, P = 0.016) compared to patients with NEUTI. CONCLUSIONS: Indwelling urinary catheter and dementia are risk factors for EUTI in patients with community and hospital acquired infection, respectively.

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.

Endogenous glucagon-like peptide-1 system response is impaired during ST-elevation myocardial infarction in type 2 diabetes patients.

We previously demonstrated increased glucagon-like peptide-1 (GLP-1) secretion during acute ST elevation myocardial infarction (STEMI) in non-diabetic (ND) patients. Whether the endogenous GLP-1 system response is different in patients with type 2 diabetes (T2D) during STEMI is unknown. Patients with STEMI (20 ND, 13 T2D) and 3 control groups (non-STEMI [14 ND, 13 T2D], stable angina pectoris [SAP] [8 ND, 10 T2D] patients and healthy subjects) (n = 25) were studied. Plasma levels of total and active GLP-1 and soluble dipeptidyl peptidase-4 (sDPP4) were estimated by enzyme-linked immunosorbent assay on admission and at 24 and 48 hours after percutaneous coronary intervention in all patients. Sharply elevated levels of total and active GLP-1 were found in ND STEMI patients at 24 h (P < 0.05 and P < 0.005, respectively), but not in T2D STEMI patients. All patients demonstrated decreased sDPP4 levels compared with healthy controls (P < 0.0005) accompanied by increased active/total GLP-1 ratio regardless of their ischemic state. These data demonstrate that T2D patients fail to further upregulate their endogenous GLP-1 system during STEMI. This may underlie their worse cardiovascular outcome.

Single Admission C-reactive protein Levels as a Sole Predictor of Patient Flow and Clinical Course in a General Internal Medicine Department.

BACKGROUND: C-reactive protein (CRP) blood level is associated with clinical outcomes of several diseases. However, the independent predictive role of CRP in the heterogeneous population of patients admitted to internal medicine wards is not known. OBJECTIVES: To determine whether single CRP levels at admission independently predicts clinical outcome and flow of patients in general medicine wards. METHODS: This study comprised 275 patients (50.5% female) with a mean age of 68.25 ± 17.0 years, hospitalized with acute disease in a general internal medicine ward. The association between admission CRP levels and clinical outcomes including mortality, the need for mechanical ventilation, duration of hospitalization, and re-admission within 6 months was determined. RESULTS: A significant association was found between CRP increments of 80 mg/L and risk for the major clinical outcomes measured. The mortality odds ratio (OR) was 1.89 (95% confidence interval (95%CI, 1.37-2.61, P < 0.001), mechanical ventilation OR 1.67 (95%CI, 1.10-2.34, P = 0.006), re-admission within 6 months OR 2.29 (95%CI, 1.66-3.15 P < 0.001), and prolonged hospitalization >7 days OR 2.09 (95%CI, 1.59-2.74, P < 0.001). Lower increments of10 mg/L in CRP levels were associated with these outcomes although with lower ORs. Using a stepwise regression model for admission CRP levels resulted in area under the receiver operating characteristics curves between 0.70 and 0.76 for these outcomes. CONCLUSIONS: A single admission CRP blood level is independently associated with major parameters of clinical outcomes in acute care patients hospitalized in internal medicine wards.

Sepsis-induced activation of endogenous GLP-1 system is enhanced in type 2 diabetes.

BACKGROUND: High levels of circulating GLP-1 are associated with severity of sepsis in critically ill nondiabetic patients. Whether patients with type 2 diabetes (T2D) display different activation of the endogenous GLP-1 system during sepsis and whether it is affected by diabetes-related metabolic parameters are not known. METHODS: Serum levels of GLP-1 (total and active forms) and its inhibitor enzyme sDPP-4 were determined by ELISA on admission and after 2 to 4 days in 37 sepsis patients with (n = 13) and without T2D (n = 24) and compared to normal healthy controls (n = 25). Correlations between GLP-1 system activation and clinical, inflammatory, and diabetes-related metabolic parameters were performed. RESULTS: A 5-fold (P < .001) and 2-fold (P < .05) increase in active and total GLP-1 levels, respectively, were found on admission as compared to controls. At 2 to 4 days from admission, the level of active GLP-1 forms in surviving patients were decreased significantly (P < .005), and positively correlated with inflammatory marker CRP (r = 0.33, P = .05). T2D survivors displayed a similar but more enhanced pattern of GLP-1 response than nondiabetic survivors. Nonsurvivors demonstrate an early extreme increase of both total and active GLP-1 forms, 9.5-fold and 5-fold, respectively (P < .05). The initial and late levels of circulating GLP-1 inhibitory enzyme sDPP-4 were twice lower in all studied groups (P < .001), compared with healthy controls. CONCLUSIONS: Taken together, these data indicate that endogenous GLP-1 system is activated during sepsis. Patients with T2D display an enhanced and prolonged activation as compared to nondiabetic patients. Extreme early increased GLP-1 levels during sepsis indicate poor prognosis.

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.

[NEW TREATMENTS IN DIABETES MELLITUS - AN UPDATE].

INTRODUCTION: Diabetes is one of the most common chronic diseases. Most patients with type 2 diabetes are obese, and the global epidemic of obesity largely explains the dramatic increase in the incidence and prevalence of type 2 diabetes over the past 20 years. In the last decade intensive research has brought about an enormous change in the clinical approach to diabetes treatment. In this review we briefly discuss the main changes in diabetes treatment, such as new medications, bariatric surgeries and technology innovations. We hope that this short review would urge the reader to expand his knowledge on the subject.

Hyperglycemia in Diabetic Patients in General Medicine Wards: No independent correlation with In- and Out-Of-Hospital Mortality.

BACKGROUND: Admission glucose levels correlate with clinical outcome in patients with type 2 diabetes mellitus (T2DM) hospitalized in general medicine wards. OBJECTIVE: To investigate whether in-hospital hyperglycemia alone, and after adjustment for age, gender and lipidemia, correlates with in- and out-of-hospital mortality. METHODS: Capillary glucose, serum lipids and diagnoses at discharge among patients with T2DM hospitalized in the general medical wards of our hospital were documented. Correlation with in- and out-of-hospital mortality was determined through uni- and multivariate analyses. RESULTS: Of the 4607 patients included in the study 22% died while hospitalized. From a median of five capillary glucose tests obtained per patient, average capillary glucose level was significantly lower in those who survived than in those who died (174 ± 64 vs. 180 ± 65 mg/dl, P = 0.005). Overall, blood cholesterol was higher in those who survived than in those who died (P < 0.001). Multivariate analysis, however, including age, gender, lipidemia and glycemia, showed that only age and male gender correlated with mortality. CONCLUSIONS: Hyperglycemia was associated with increased in- and out-of-hospital mortality on univariate analysis. However, it was not an independent risk factor when corrected for age, gender and hyperlipidemia.

Increased ERK and JNK activation and decreased ERK/JNK ratio are associated with long-term organ damage in patients with systemic lupus erythematosus.

OBJECTIVE: The activities of two mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), correlate with disease severity in SLE patients. Whether they are also associated with long-term organ damage is unknown. The aim of the present work was to determine whether impaired expression and activity of ERK and JNK correlate with long-term damage in SLE. METHODS: The expression of ERK and JNK and their phosphorylated active forms was determined by western blot analysis four times during the first year of follow-up in peripheral blood mononuclear cells from 36 SLE patients. A correlation analysis was performed between ERK and JNK expression and longterm organ damage estimated by the SLICC/ARC Damage Index (SDI) 4 years later. RESULTS: Mean levels of ERK and JNK activities during the first year correlated with long-term organ damage severity (r = 0.38 and r = 0.35, respectively; P = 0.05). Overall JNK expression increased with the severity of chronic damage (P = 0.01; P = 0.05 for SDI score 2 and 3, respectively). In contrast, overall ERK expression significantly decreased in patients with maximal organ damage (SDI score 3) compared with patients with an SDI score of 2 (P = 0.03). The ERK/JNK ratio decreased by approximately 40% and 30% in patients with an SDI score of 3 as compared with patients without organ damage and healthy controls, respectively. CONCLUSION: These results demonstrate that early activation of ERK and JNK along with decreased overall ERK expression and reduced ERK/JNK ratio may predict the severity of long-term organ damage in SLE patients.

Aiming for better glucose control: is HbA(1c) of 7% the 'holy grail'? The clinical approach or seven clinical questions about 7.

The diabetes epidemic imposes a substantial burden on health systems and economy all over the world. Over the last two decades, many health systems adopted health care quality and performance measures for diabetes mellitus, most notably haemoglobin A(1c). This article raises concerns regarding the significance of HbA(1c) as a performance measure and emphasizes the need for individualized therapy.

Interpreting the results of the Semmes-Weinstein monofilament test: accounting for false-positive answers in the international consensus on the diabetic foot protocol by a new model.

AIMS: The Semmes-Weinstein monofilament is the most widely used test to diagnose the loss of protective sensation. The commonly used protocol of the International Consensus on the Diabetic Foot includes a 'sham' application that allows for false-positive answers. We sought to study the heretofore unexamined significance of false-positive answers. METHODS: Forty-five patients with diabetes and a history of pedal ulceration (Group I) and 81 patients with diabetes but no history of ulceration (Group II) were studied. The three original sites of the International Consensus on the Diabetic Foot at the hallux, 1st metatarsal and 5th metatarsal areas were used. At each location, the test was performed three times: 2 actual and 1 "sham" applications. Scores were graded from 0 to 3 based upon correct responses. Determination of loss of protective sensation was performed with and without calculating a false-positive answer as a minus 1 score. RESULTS: False-positive responses were found in a significant percentage of patients with and without history of ulceration. Introducing false-positive results as minus 1 into the test outcome significantly increased the number of patients diagnosed with loss of protective sensation in both groups. CONCLUSIONS: False-positive answers can significantly affect Semmes-Weinstein monofilament test results and the diagnosis of LOPS. A model that accounts for false-positive answers is offered.

Pilot study on the significance of random intrasite placement of the Semmes-Weinstein monofilament.

BACKGROUND: The possible effect of random intrasite placement on the outcome of the Semmes-Weinstein monofilament (SWF) test is not known. We sought to determine the significance of this variable in the diagnosis of loss of protective sensation (LOPS) in patients with diabetes. METHODS: Forty-five patients with diabetes with history of pedal ulceration (group 1), 81 patients with diabetes without history of ulceration (group 2) and 21 non-diabetic controls (group 3) were studied. The three original sites of the International Consensus on the Diabetic Foot at the hallux, first and fifth sub-metatarsal areas were divided into peripheral and interior zones resulting in a total of six zones. RESULTS: Mean total scores of monofilament test were significantly lower in peripheral zones as compared with interior zones of both feet in all three groups and affected the resulting percentage of loss of protective sensation. CONCLUSIONS: Intrasite monofilament placement can significantly affect monofilament test results and the diagnosis of loss of protective sensation. A model that corrects the effect of random intrasite placement is needed.

Decreased nocturnal glucose variability in non-diabetic patients with sleep apnea: a pilot study.

BACKGROUND: Obstructive sleep apnea has been sho be associated with impaired glucose metabolism and overt diabetes mellitus. However, the effect of hypoxic episodes on nocturnal glucose regulation in non-diabetic patients is unknown. OBJECTIVES: To investigate the effect of hypoxemia and nocturnal glucose homeosatsis in non-diabetic patients with sleep apnea. METHODS: Seven non-diabetic patients with moderate to severe sleep apnea were connected to a continuous glucose-monitoring sensor while undergoing overnight polysomnography. Mean SpO2 and percentage of time spent at SpO2 90% were recorded. The correlation between mean glucose levels, the difference between consecutive mean glucose measurements (glucose variability) and the corresponding oxygen saturation variables were determined in each patient during REM and non-REM sleep. RESULTS: No consistent correlation was found forthe individual patient between oxygen saturation variables and glucose levels during sleep. However, a lower mean SpO2 correlated with decreased glucose variability during sleep (r = 0.79, P = 0.034). This effect was primarily evident during REM sleep in patients with significant, compared to those with mild, oxygen desaturations during sleep (> 30% vs. < 10% of sleeping tim spent with SpO2 < 90%) (P = 0.03). CONCLUSIONS: Severe nocturnal hypoxemia in non-diabetic patients with moderate to severe sleep apnea might affect glucose regulation primarily during REM sleep.

Normal and elevated HbA1C levels correlate with severity of hypoxemia in patients with obstructive sleep apnea and decrease following CPAP treatment.

PURPOSE: Sleep apnea is associated with higher HbA1C levels in patients with and without diabetes but whether its severity correlates with HbA1C levels ranging from normal to abnormal is less clear. Also, the effect of continuous positive airway pressure (CPAP) treatment on HbA1C levels in patients with sleep apnea is controversial. METHODS: Thirty consecutive patients with obstructive sleep apnea were studied. None of the patients was previously diagnosed with diabetes. All patients underwent overnight polysomnography and HbA1C levels were determined. Patients were subdivided into three groups according to their HbA1C levels: <6% (n = 10), 6-6.5% (n = 10), and ≥6.5% (n = 10). Polysomnography and determination of HbA1C level were repeated in patients with severe sleep apnea (n = 12) following 3-5 months of CPAP treatment. RESULTS: HbA1C levels across the spectrum from normal to abnormal correlated with severity of hypoxemia (average SpO(2), r = -0.43, p = 0.019 and percent time with SpO(2) < 90%, r = 0.48, p = 0.007). HbA1C levels decreased from a mean of 6.47 ± 0.67% to a mean of 6.28 ± 0.51%, p = 0.038 in 12 patients with severe sleep apnea following 3-5 months of CPAP treatment. CONCLUSIONS: The severity of hypoxemia in patients with sleep apnea correlates with HbA1C levels ranging from normal to pre-diabetes and diabetes. CPAP treatment for 3-5 months decreases HbA1C levels in patients with severe sleep apnea.