Search

Objective Studies have demonstrated a potential correlation between low vitamin D status and both an increased risk of infection with SARS-CoV-2 and poorer clinical outcomes. This retrospective study examines if, and to what degree, a relationship exists between pre-infection serum 25-hydroxyvitamin D (25(OH)D) level and disease severity and mortality due to SARS-CoV-2. Participants The records of individuals admitted between April 7th, 2020 and February 4th, 2021 to the Galilee Medical Center (GMC) in Nahariya, Israel, with positive polymerase chain reaction (PCR) tests for SARS-CoV-2 (COVID-19) were searched for historical 25(OH)D levels measured 14 to 730 days prior to the positive PCR test. Design Patients admitted to GMC with COVID-19 were categorized according to disease severity and level of 25(OH)D. An association between pre-infection 25(OH)D levels, divided between four categories (deficient, insufficient, adequate, and high-normal), and COVID-19 severity was ascertained utilizing a multivariable regression analysis. To isolate the possible influence of the sinusoidal pattern of seasonal 25(OH)D changes throughout the year, a cosinor model was used. Results Of 1176 patients admitted, 253 had records of a 25(OH)D level prior to COVID-19 infection. A lower vitamin D status was more common in patients with the severe or critical disease (p < 0.001). Patients with vitamin D deficiency (p < 0.001). Conclusions Among hospitalized COVID-19 patients, pre-infection deficiency of vitamin D was associated with increased disease severity and mortality.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in the western world. One of the treatments offered for CLL is immunotherapy. These treatments activate various cellular and biochemical mechanisms, using the complement system. Recently it was shown that the complement system in CLL patients is persistently activated at a low level through the classical pathway (CP). The mechanism of chronic CP activation involves the formation of IgG-hexamers (IgG-aggregates). According to recent studies, formation of ordered IgG-hexamers occurs on cell surfaces via specific interactions between Fc regions of the IgG monomers, which occur after antigen binding. The present study investigated the formation of IgG-hexamers in CLL patients and normal (non-malignant) controls (NC), their ability to activate complement, their incidence as cell-free and cell-bound forms and the identity of the antigen causing their formation. Sera from 30 patients and 12 NC were used for separation of IgG- aggregates. The obtained IgG- aggregates were measured and used for assessment of CP activation. For evaluation of the presence of IgG- aggregates on blood cells, whole blood samples were stained and assessed by flow cytometry. Serum levels of IgG- aggregates were higher in CLL and they activated the complement system to a higher extent than in NC. Alpha 2 macroglobulin (A2M) was identified as the antigen causing the hexamerization/aggregation of IgG, and was found to be part of the hexamer structure by mass spectrometry, Western blot and flow cytometry analysis. The presence of A2M-IgG-hexamers on B-cells suggests that it may be formed on B cells surface and then be detached to become cell-free. Alternatively, it may form in the plasma and then attach to the cell surface. The exact time course of A2M-IgG-hexamers formation in CLL should be further studied. The results in this study may be useful for improvement of current immunotherapy regimens.

To assess the usefulness of proton MR-spectroscopy (1H-MRS) and diffusion-weighted MRI (DW-MRI) sequences in the follow-up of CLL-patients with chemotherapy treatment.

Background: Northern Israel is characterized by a multi-ethnic population. We looked for differences in the risk factors for hyperglycemia in Jews, Muslims and Druze without diabetes. Methods: Adult visitors to our Medical Center without known diabetes were included in the study. A point-of-care (POC) capillary blood glucose level with institutional glucometer and a seated blood pressure were measured and additional data were collected from an interview. We excluded people with hypoglycemic drug usage, acute disease, glucocorticoid usage, pregnancy and capillary blood glucose in the diabetes range. The blood glucose levels were divided according to last caloric intake to postprandial (4 hours or less) or pre-prandial (more than 4 hours). Hyperglycemia was defined as pre-prandial blood glucose level ≥100 mg/dl or postprandial glucose level ≥140 mg/dl. High systolic blood pressure was defined as ≥140 mm Hg. Backward stepwise logistic regression was used to identify the factors independently associated with hyperglycemia. Results: A total of 1062 Jews, 419 Muslims and 341 Druze were included in the analysis. 57% of Muslims, 44% of Jews and 34% of Druze reported that they are religious. Compare to Jews, Muslims had increased risk for hyperglycemia (OR 1.73, 95% CI 1.22-2.43, p=0.002) and Druze had no significant difference. After adjusting for sex, high systolic blood pressure and fewer than 12 years of education, age was a significant risk factor for hyperglycemia in all three religions and obesity was an independent risk factor for Druze (OR 2.45, 95% CI 1.28-4.69, p=0.07) and Muslims (OR 2.25, 95% CI 1.31-3.86). Only religious Muslims had an independently lower risk for hyperglycemia than non-religious Muslims (OR 0.5, 95% CI 0.29-0.86, p=0.012). Conclusion: Religion and religiosity are independently associated with hyperglycemia in people without diabetes. Muslims in north Israel have increased risk for hyperglycemia compared to Jews but this risk is lower in religious people. Disclosure A. Bashkin: None. M. Shehadeh: None. R. Yaacovy: None. M. Nodelman: None. A. Zur: None. M. Barhoum: None.

MicroRNAs play functional roles in the etiology of type 2 diabetes mellitus (T2DM) and complications, and extracellular microRNAs have attracted interest as potential biomarkers of these conditions. We aimed to identify a set of plasma microRNAs, which could serve as biomarkers of T2DM and complications in a mixed Israeli Arab/Jewish patient sample. Subjects included 30 healthy volunteers, 29 early-stage T2DM patients, and 29 late-stage T2DM patients with renal and/or vascular complications. RNA was isolated from plasma, and the levels of 12 candidate microRNAs were measured by quantitative reverse transcription and polymerase chain reaction (qRT-PCR). MicroRNA levels were compared between the groups and correlated to clinical measurements, followed by stepwise regression analysis and discriminant analysis. Plasma miR-486-3p and miR-423 were respectively up- and down-regulated in T2DM patients compared to healthy controls. MiR-28-3p and miR-423 were up-regulated in patients with complicated T2DM compared to early T2DM, while miR-486-3p was down-regulated. Combined, four microRNAs (miR-146a-5p, miR-16-2-3p, miR-126-5p, and miR-30d) could distinguish early from complicated T2DM with 77% accuracy and 79% sensitivity. In male patients only, the same microRNAs, with the addition of miR-423, could distinguish early from complicated T2DM with 83.3% accuracy. Furthermore, plasma microRNA levels showed significant correlations with clinical measurements, and these differed between men and women. Additionally, miR-183-5p levels differed significantly between the ethnic groups. Our study identified a panel of specific plasma microRNAs which can serve as biomarkers of T2DM and its complications and emphasizes the importance of sex differences in their clinical application.

The immunotherapy treatments offered for Chronic lymphocytic leukemia (CLL) activate various cellular and biochemical mechanisms, including the complement system. Recently it was shown that the classical complement pathway (CP) in CLL patients is persistently activated at a low level through (Michelis et al. PlosOne, 2019), and that the mechanism of chronic CP activation involves the formation of IgG-hexamers (Michelis et al. PlosOne, 2020). According to recent studies, formation of ordered IgG-hexamers occurs on cell surfaces via specific interactions between Fc regions of the IgG monomers, which occur only after antigen binding. The study investigated the formation of IgG-hexamers in CLL patients and normal controls (NC), their ability to activate complement, their incidence as cell-free and cell-bound forms and the identity of the antigen causing their formation. Sera from 30 patients and NC were used for separation of IgG-hexamers. The obtained IgG-hexamers were measure and used for assessment of CP activity. For evaluation of the presence of IgG-hexamers on blood cells, whole blood samples were stained and assessed by flow cytometry. Serum levels of IgG-hexamers were higher in patients compared to NC. Also, they activated the complement system to a higher extent in patients than in NC. Alpha 2 macroglobulin (A2M) was recognized as the antigen causing the hexamerization of IgG, and was found to be part of the hexamer structure by mass spectrometry, Western blot and flow cytometry analysis. The presence of A2M-IgG-hexamers on B-cells suggests that it may be formed on B cells surface and then be detached to become cell-free. Alternatively, it may form in the plasma and then attach to the surface of the cells. The exact course of A2M-IgG-hexamers formation in CLL should be further studied. The results in this study may be useful for improvement of current immunotherapy regimens. Disclosures Tadmor: Neopharm: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Medison: Consultancy, Speakers Bureau; 6. Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Consultancy, Speakers Bureau. Aviv:Abbvie: Honoraria.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western world. The therapeutic approach to CLL includes chemotherapeutic regimens and immunotherapy. Complement-mediated cytotoxicity, which is one of the mechanisms activated by the therapeutic monoclonal antibodies, depends on the availability and activity of the complement (C) system. The aim was to study the structure of circulating C components and evaluate the importance of C5 structural integrity for C activity in CLL patients. Blood samples were collected from 40 naïve CLL patients and 15 normal controls (NC). The Western blot analysis showed abnormal C5 pattern in some CLL patients, while patterns of C3 and C4 were similar in all subjects. Levels of the C activation markers sC5b-9 and C5a were quantified before and after activation via the classical (CP) and alternative (AP) pathways. In patients with abnormal C5, basal levels of sC5b-9 and C5a were increased while activities of the CP and of the CP C5-convertase, the immediate C5-upstream complex, were decreased compared to NC and to patients with normal C5. The data indicate a link between CP activation and apparent C5 alterations in CLL. This provides a potential prognostic tool that may personalize therapy by identifying a sub-group of CLL patients who display an abnormal C5 pattern, high basal levels of sC5b-9 and C5a, and impaired CP activity, and are likely to be less responsive to immunotherapy due to compromised CP activity.

Therapy regimens for Chronic lymphocytic leukemia (CLL) commonly include chemotherapy and immunotherapy, which act through complement-mediated-cytotoxicity (CDC) and other mechanisms. CDC depends on several factors, including the availability and activity of the complement classical pathway (CP). Recently, a significant decrease in CP activity was shown to be associated with an immunoglobulin-C5a complex (Ig-C5a) and other markers of chronic CP activation in 40% of the patients. The study focused on the involvement of IgG-hexamers, an established CP activator, in the mechanism of chronic CP activation in CLL. Sera from 51 naïve CLL patients and 20 normal controls were collected. CP and alternative pathway (AP) activities were followed by the complement activity marker sC5b-9. Serum high molecular weight (HMW) proteins were collected by gel-filtration chromatography and their complement activation capacity was assessed. The levels of IgM, another established CP activator, were measured. Data were associated with the presence of Ig-C5a. Baseline levels of activation markers negatively correlated with CP and the AP activities, supporting chronic complement activation. In patients with Ig-C5a, HMW proteins that are not IgM, activated the complement. HMW proteins were identified as IgG-aggregates by affinity binding assays and Western blot analysis. The data indicate chronic CP activation, mediated by cell-free IgG-hexamers as a cause of decreased CP activity in part of the CLL population. This mechanism may affect immunotherapy outcomes due to compromised CP activity and CDC.

As an expected consequence of the civil war in Syria, emergent neurosurgical care for battlefield trauma has been provided for severely head-injured Syrians transferred to Northern Israel.Sixty-six patients suffering from brain injury were brought to the border and then referred to the institution after initial resuscitation. Both the time and type of injury were recorded based on paramedic testimony, forensic material or on details provided by patients. A retrospective analysis of all medical charts and imaging material was performed.Most injuries were combat-related, either caused by blast (13.6%), shrapnel (24.2%), assault (28.8%) or gunshot wound (15.2%). Only a minority of patients (18.2%) suffered from injuries that were not directly caused by weapon. A total of 55 surgical procedures were performed in 46 out of 66 patients, including craniotomies in 40 patients, burr hole alone for placement of intraparenchymal intracranial pressure (ICP) sensor in nine instances and ventricle peritoneal shunt in two patients. Decompressive craniectomy was used only for the treatment of gunshot wound and was performed in eight out of 10 patients. The most common complication consisted in cerebrospinal fluid fistulas (16.7%). Post-operative infections occurred in seven patients (10.6%). Short-term outcomes were favourable in 60.7%, with a mortality rate of 4.5%.The present findings suggest that aggressive surgery and neuro-intensive care measures may lead to good functional results, even in the presence of seemingly devastating injuries in some selected patients.

Introduction Hospitals worldwide are preparing for mass casualty incidents (MCIs). The Major Incident Hospital in the Netherlands was constructed 25 years ago as a dedicated hospital for situations wherein a sudden increase in medical surge capacity is mandated to handle an MCI. Over the years, more initiatives of dedicated MCIs have arisen. Herein, we compared the MCI facilities from three countries considering the reasons for construction and the functionality. Methods Three dedicated mass casualty hospitals and one hospital with a largely fortified structure were compared. The centres were located in the Netherlands, Italy, and Israel. Between August 2015 and January 2016, structured interviews were conducted with representatives of the hospitals’ medical operations. The interviews focussed on general information regarding the need for MCI preparedness and scenarios that require preparation, reasons for construction, hospital missions, and the experiences gained including training. Results All dedicated MCI hospitals had a common policy wherein they sought to create normal work circumstances for the medical staff by using similar equipment and resources as in normal hospitals. The MCI hospitals’ designs differed substantially, as determined by the threats faced by the country. In Europe, these hospitals are designed as a solution to surge capacity and function as buffer hospitals offering readily available, short term, additional medical capacity to the local health care system. Israel faces constant threat from long-term conflicts; during the 2006 war, several hospitals suffered direct missile impacts. Therefore, Israeli MCI hospitals are designed to be fortified structures offering shelter against both conventional and non-conventional warfare and intended as a long-term solution during siege situations. Conclusion Several dedicated MCI hospitals are presently being constructed. During construction, the local circumstances should be taken into account to determine the functionality for both short-term solutions for surge capacity and as fortified structures to withstand under-siege situations.