Tel Aviv Medical Center Research Articles

West Nile virus encephalitis: Clinical characteristics and a comparison to other infectious encephalitides

PurposeTo compare functional outcomes and help differentiate between important causative agents of acute infectious encephalitis in adults, focusing on West Nile virus encephalitis (WNVE). MethodsThe electronic database of the Tel Aviv Medical Center was screened for patients admitted during 2010–2020 with acute encephalitis. Additionally, patient laboratory results during the same period were screened for CSF samples positive for common pathogens causing encephalitis. The main patient groups were compared in terms of clinical characteristics and functional outcomes. ResultsOne hundred and five infectious encephalitis patients were identified. WNVE patients (n = 31) and VZV encephalitis (VZVE) patients (n = 31) were older than HSV1 encephalitis (HSV1E) patients (n = 15) (median ages 73, 76, 51, respectively). WNVE patients had a more prominent inflammatory profile. CSF characteristics significantly differed between groups, with an extreme mononuclear white blood cell predominance in VZVE patients (median 98 %).Functional outcomes at discharge were significantly worse in WNVE patients (median modified Rankin Scale score 4 at hospital discharge, 2.5 at last follow-up) when compared with HSV1E patients (2.5, 1, respectively) and VZVE patients (1.5, 1, respectively). ConclusionIn odds with previous reports, WNVE and VZVE in this study were far more prevalent than HSV1E. Differences in clinical characteristics could prove clinically useful early in encephalitis, including an association of WNVE with a relatively prominent inflammatory profile (somewhat resembling a bacterial infection) and an extreme mononuclear white blood cell predominance in VZVE. The detrimental outcome of WNVE emphasizes the need to advance research on WNV infection.

Comparison between OCT B-scan and En Face Imaging for the Diagnosis of Early Macular Atrophy in Age-Related Macular Degeneration

The gradings of complete retinal pigment epithelium and outer retinal atrophy (cRORA) and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) on spectral domain optical coherence tomography (SD-OCT) B-scans were compared with the grading of persistent choroidal hypertransmission defects (hyperTDs) on swept-source OCT angiography (SS-OCTA) en face images. Comparative diagnostic analysis of prospective study data METHODS: Patients with late nonexudative AMD underwent same day 6 × 6 mm macular scans using both SD-OCT (Spectralis® Heidelberg, 512 × 97, ART:9) and SS-OCTA (PLEX® Elite 9000, Carl Zeiss Meditec, 500 × 500 angio pattern) instruments. SS-OCTA and SD-OCT en face images were generated from a sub-retinal pigment epithelium slab positioned 64-400 μm below Bruch's membrane. SD-OCT B-scan gradings, which included an inspection of neighboring B-scans for the diagnosis of cRORA and iRORA, were performed at the Moran Eye Center, while gradings of en face images to identify persistent choroidal hyperTDs were performed at the Bascom Palmer Eye Institute and Tel Aviv Medical Center. There was a high degree of agreement (99.6%) between the gradings of cRORA lesions and persistent hyperTDs. However, 27.4% of iRORA lesions were found to be contained within persistent hyperTDs. This discrepancy was due to the finding that 27.5% of iRORA lesions were diagnosed as having a greatest linear horizontal dimension of < 250 µm on B-scans, but on en face images, these B-scan defined iRORA lesions were found to have a greatest linear dimensions in the non-horizontal dimension that were ≥ 250 µm. This report demonstrates the benefits of using en face OCT imaging to identify cRORA lesions and highlights the need to acquire dense raster B-scans with the grading neighboring B-scans when identifying iRORA lesions to assess the full extent of the iRORA lesions in the non-horizontal dimension. Even though neighboring B-scans were inspected, 27.5% of iRORA lesions were actually part of larger cRORA lesions when graded using an en face strategy.

Predictive Hypoxemic Threshold for Tolerating the Apnea Test While Assessing Death by Neurological Criteria

Abstract Background The apnea test (AT) plays a vital role in diagnosing brain death by evaluating the absence of spontaneous respiratory activity. It entails disconnecting the patient from mechanical ventilation to raise the CO2 partial pressure and lower the pH. Occasionally, the AT is aborted because of safety concerns, such as hypoxemia and hemodynamic instability, to prevent worsening conditions. However, the exact oxygen partial pressure level needed before commencing AT, indicating an inability to tolerate the test, is still uncertain. This study seeks to determine pre-AT oxygen levels linked with a heightened risk of test failure. Methods We conducted a retrospective cohort study involving patients suspected of having brain death at the Tel Aviv Medical Center from 2010 to 2022. The primary outcome was defined as an arterial partial O2 pressure (PaO2) level of 60 mmHg or lower at the conclusion of the AT. This threshold is significant because it marks the point at which the saturation curve deflects, potentially leading to rapid deterioration in the patient’s oxygen saturation. Results Among the 70 patients who underwent AT, 7 patients met the primary diagnostic criteria. Patients with a PaO2 ≤ 60 mmHg at the conclusion of the AT exhibited a significantly lower initial median PaO2 of 243.7 mmHg compared with those with higher pre-AT PaO2 levels of 374.8 mmHg (interquartile range 104.65–307.00 and interquartile range 267.8–444.9 respectively, P value = 0.0041). Pre-AT PaO2 levels demonstrated good discriminatory ability for low PaO2 levels according to the receiver operating characteristic (ROC) curve, with an area under the curve of 0.76 (95% confidence interval 0.52–0.99). Conclusions PaO2 values at the conclusion of the AT are closely associated with PaO2 values at the beginning of the test. Establishing a cutoff value of approximately 300 mmHg PaO2 at the onset of AT may assist in avoiding saturation drops below 90%.

Effect of GBA1 Mutations and APOE Polymorphisms on Survival and Progression Among Ashkenazi Jews with Dementia with Lewy Bodies.

Glucocerebrosidase 1 (GBA1) mutations are associated with reduced survival in Parkinson's disease but their effect on survival in dementia with Lewy bodies (DLB) is unclear. To assess the impact of GBA1 mutations on survival among Ashkenazi Jews with DLB, while controlling for APOE status. One hundred and forty participants from Tel Aviv Medical Center, Israel were genotyped for GBA1 mutations and APOE polymorphisms. Survival rates and follow-up cognitive screening scores were analyzed. GBA1 mutation carriers had a two-fold increased risk of death (HR = 1.999), while APOE status did not independently affect survival. In a subset of patients with available clinical data (N = 63), carriers of the APOE ε4 allele showed faster cognitive deterioration, while GBA1 mutation carriers also declined more rapidly albeit not significantly. Understanding the genetic effects on survival and progression is crucial for patient counseling and inclusion in clinical trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cellular immune response to the anti-SARS-CoV-2 BNT162b2 mRNA vaccine in pediatric autoimmune inflammatory rheumatic disease patients and controls.

This paper aims to compare the cellular immune response to the SARS-CoV-2 BNT162b2 vaccine of pediatric patients with autoimmune inflammatory rheumatic disease (pAIIRD) and healthy controls. A prospective longitudinal study was conducted between April 2021 and December 2022 at the Tel Aviv Medical Center. Children <18 years, with pediatric-onset AIIRD and healthy controls, who have received at least two doses of the BNT162b2 vaccine, were included. Humoral response was evaluated by serum levels of anti-SARS-CoV-2 receptor-binding domain antibodies. Cellular response was evaluated by flow cytometry, measuring IFNγ and TNFα production by CD4+ T cells following stimulation with SARS-CoV-2 Spike peptide mix. The study included 20 pAIIRD patients and 11 controls. The mean age of participants was 12.6 ± 2.94 years, with 58.1% females. The cellular response to the BNT162b2 vaccine was statistically similar in both groups. However, the humoral response was statistically lower in pAIIRD compared with the healthy control group. There was no statistically significant correlation between the humoral response and cellular response. During the study period, 43.75% of AIIRD children and 72.7% of controls had a breakthrough COVID-19 infection (P = 0.48). Bivariate models examining the effect of the cellular response and presence of an AIIRD on breakthrough infections found no effect. Compared with healthy controls, pAIIRD demonstrated similar cellular responses. Patients showed reduced humoral response compared with healthy adolescents, but similar breakthrough infection rates. These findings may support the importance of the cellular response in protecting against COVID-19 infections.

Use of a Novel Beyeonics One Three-dimensional Head-mounted Digital Visualization Platform in Vitreoretinal surgeries.

Ophthalmic microscopes have been crucial in visualizing surgical fields, but their limitations in enhancing the surgical view through digital image processing have prompted the development of digital surgical microscopes. The Beyeonics One microscope, a novel digital microscope, offers ophthalmic surgeons a 3D visualization platform and an augmented reality (AR) surgical headset, potentially improving surgical decision-making and outcomes. While its initial use has been described in cataract and corneal surgeries, its application in vitreoretinal surgery remains relatively unexplored. In this interventional case series, we collected data from the medical records of patients who underwent vitreoretinal surgery using the Beyeonics One 3D visualization platform at the Tel Aviv Medical Center. A total of 36 eyes from 36 subjects were included. Surgical techniques included retinal detachment surgeries and macular surgeries, performed by experienced surgeons. The surgical visualization was facilitated by the Beyeonics One 3D head-mounted display (HMD) platform. The procedures were uneventful, and none intra- or postoperative complications were reported, and surgeons did not experience any signal delay in the real-time video. The Beyeonics One microscope offers several potential advantages in vitreoretinal surgery, including digital image processing, enhanced depth perception through the 3D HMD platform, and hands-free image control using head gestures. While this study demonstrates the feasibility and safety of the Beyeonics One microscope, addressing limitations related to hazy views and optimizing image quality are crucial for consistent visualization.

P682 A Retrospective Comparison of Different Treatment Modalities in Patients with Chronic Pouchitis

Abstract Background Chronic pouchitis affects ~30% of patients post total colectomy with ileal pouch anal anastomosis (IPAA) surgery. Treatment with anti-TNF, anti-integrin α4β7, anti-IL-12/23, or Crohn's disease exclusion diet (CDED), have shown promise in different studies. We aimed to compare the efficacy of these treatments in a real-world context and to detect factors that can aid in treatment choices. Methods A retrospective cohort study encompassing demographic, clinic, endoscopic, histologic and lab values of adult ulcerative colitis (UC) patients post-IPAA surgery with chronic pouchitis, treated with biologics or CDED at the Tel Aviv Medical Center. Data were collected at baseline, 12, 26, and 52 weeks of treatment. Primary outcomes were assessed using the modified Pouchitis Disease Activity Index (mPDAI). mPDAI response was defined as a reduction from baseline of ≥2 points, while mPDAI remission was defined as mPDAI response in addition to mPDAI score ≤4. Results Therapeutic interventions among 51 patients included CDED (n=10), vedolizumab (n=21), ustekinumab (n=7) and adalimumab (n=13) [Table 1]. At 12 and 26 weeks, overall mPDAI response rates were 52% and 48%, respectively, with no significant difference between groups. At 52 weeks, mPDAI response rates were significantly higher for ustekinumab and vedolizumab (60% and 55%, respectively) compared with adalimumab and CDED (27.3% and 0%, respectively), p=0.043. Fecal calprotectin reduction at week-26 was greatest for ustekinumab (93%), followed by vedolizumab (73%), adalimumab (55%), and CDED (-13%), p=0.003. Treatment persistence over 150 weeks was significantly higher for ustekinumab (100%) compared with adalimumab (46%), vedolizumab (33%), and CDED (20%), p&amp;lt;0.001 [Figure 1]. The predominant cause for treatment discontinuation was secondary loss of response (50%), followed by primary non-response and surgical complications (14.7% each), poor compliance (11.8%), side-effects (5.9%), and development of antibodies (2.9%). Patients without prior biologic or immunomodulator treatment for pouchitis had significantly higher mPDAI response rates at 12 weeks (90%, p=0.016 and 73.3%, p=0.03, respectively). Patients with surgical pouch complications showed a trend towards lower mPDAI-defined response rates at 12 weeks (25% vs. 64.7%; p = 0.064). Conclusion Ustekinumab and vedolizumab demonstrate higher likelihood of maintaining long-term clinical and endoscopic response, along with greater reduction in fecal calprotectin compared with adalimumab and CDED. Biologic and immunomodulator therapy-naïve patients achieved higher induction response rates.

P891 Comparative Effectiveness and Safety of Infliximab and Tacrolimus in the Treatment of Acute Severe Ulcerative Colitis

Abstract Background Acute severe ulcerative colitis (ASUC) affects approximately 20% of patients with ulcerative colitis (UC). Patients failing initial corticosteroid therapy receive salvage therapy with either infliximab (IFX) or calcineurin inhibitors, cyclosporine (CYS) or tacrolimus (TAC). We aimed to compare the effectiveness and safety of IFX and the oral calcineurin inhibitor, TAC, in this setting. Methods This retrospective cohort study included consecutive patients with ASUC, based on the Truelove and Witts criteria, admitted to Tel Aviv Medical Center between 2017 and 2022 and treated with salvage therapy. Demographic, clinical, and laboratory data were retrieved. The primary endpoint was successful salvage therapy defined as clinical response resulting in discharge without colectomy. Secondary endpoints included the colectomy rates at 90 days and the safety profile of the treatments. Results During the study period 96 patients with ASUC were admitted to our center. Of these, 40 patients received salvage therapy – 21 patients received IFX and 16 received TAC and were included in the analysis; 3 patients received CYS and were excluded from the study. Demographic data are detailed in Table 1. Disease duration was significantly longer in patients receiving TAC (mean (±SD) 9.7 years (±7.1) vs 4.5 (±5.9), p=0.04). In addition, patients receiving TAC had significantly greater prior exposure to advanced therapies (14 (87.5%) vs 6 (28.6%), p&amp;lt;0.001) and 12 (75%) patients had previous exposure to IFX. Baseline markers of disease severity including disease extent, hemoglobin, C-reactive protein (CRP), albumin and body mass index (BMI) were similar between the treatment groups (Table 1). Therapeutic success was similar between treatment groups (IFX: 18 (86%) vs TAC: 15 (94%), p=0.62). The 90-day colectomy rate (IFX: 4 (19%) vs TAC: 2 (12.5%), p=0.68), CRP upon discharge (median (IQR) IFX: 15 mg/L (3.3-27) vs TAC: 11 mg/L (5.4-25, p=0.64) and length of hospitalization (mean (±SD) IFX: 23.5 days (±19.46) vs TAC: 17.56 days (±5), p=0.19) were similar between the groups. Safety profiles were similar between the treatment groups with mild electrolyte disturbances treated conservatively in both groups and no observed infections, deaths or other adverse events. Conclusion This real world, retrospective study shows that IFX and TAC have similar effectiveness and safety in the setting of ASUC. In this study, patients receiving TAC had significantly longer disease duration and advanced therapy exposure than those receiving IFX and still maintained excellent effectiveness highlighting TAC’s value in this setting.

Suggested role for neutrophil extracellular trap formation in Ewing sarcoma immune microenvironment.

Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70%-80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescence. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared with those with local disease. High NET formation at diagnosis predicted poor response to neoadjuvant chemotherapy, relapse, and death from disease (p < 0.05). NET formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared with pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NET formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Electromechanical Window and Spontaneous Ventricular Tachyarrhythmias in Takotsubo Syndrome

QT interval prolongation is common in patients hospitalized with Takotsubo syndrome (TTS), however, only a minority experience ventricular tachyarrhythmias. Our aim was to characterize the electromechanical window (EMW) in patients with TTS and to evaluate its association with ventricular tachyarrhythmias. We preformed aretrospective analysis of 84 patients hospitalized with TTS in the Tel-Aviv Medical Center between 2013 and 2022. All patients underwent a comprehensive echocardiographic evaluation and the EMW was calculated by subtracting the QT interval from the QRS onset to the aortic valve closure obtained from a continuous-wave Doppler for the same beat. Of the 84 patients with TTS, 74 (88%) were female and the mean age was 70 ± 11 years. The mean left ventricular ejection fraction was 42 ± 8%. The EMW was negative in 81 patients (96%), and the mean EMW was -69 ± 50 ms. Ventricular tachyarrhythmias occurred in 7 patients (8%). The EMW of patients who experienced ventricular tachyarrhythmias was more negative than patients who did not (-133 ± 23 ms vs -63 ± 48 ms, p = 0.001). In the univariate analysis, EMW and QT were associated with ventricular tachyarrhythmias (univariate odds ratio [OR]EMW1.03, 95% confidence interval [CI] 1.01 to 1.05, p = 0.003 and univariate ORQTc1.02, 95% CI 1.01 to 1.03, p = 0.02); however, only EMW remained significant in the multivariate analysis (OREMW1.03 95% CI 1.03 to 1.05, p = 0.023). EMW was more effective than corrected QT interval in identifying patients who had ventricular tachyarrhythmias (AUCEMW: 0.89, 95% CI 0.82 to 0.97 vs AUCQTc0.77, 95% CI 0.61 to 0.93, p = 0.02), and a cut-off value of -108 ms was predictive of ventricular tachyarrhythmias with a sensitivity of 86% and a specificity of 79%. In conclusion, EMW is negative in patients with TTS and is associated with increased risk for ventricular tachyarrhythmias. The role of EMW in the risk stratification of patients with TTS warrants further investigation.

Enabling Expedited Disposition of Emergencies Using Telepsychiatry in Israel: Protocol for a Hybrid Implementation Study.

Telepsychiatry is the use of virtual communication, such as a video link, to deliver mental health assessment, treatment, and follow-up. Previous studies have shown telepsychiatry to be feasible, accurate compared with in-person practice, and satisfying for psychiatrists and patients. Telepsychiatry has also been associated with reduced waiting times for evaluation and, in some studies, lower admission rates. However, most previous studies focused on using telepsychiatry in community settings and not on involuntary admission. The aim of this study is to examine the effectiveness and implementation process of patient assessment for involuntary admissions in the psychiatric emergency department (ED) using a video link. This type 1 hybrid implementation study will examine telepsychiatry effectiveness and the implementation process, by comparing telepsychiatry (n=240) with historical controls who had a face-to-face evaluation (n=240) during the previous, usual care period in 5 psychiatric EDs in Israel. A temporary waiver of the standing policy requiring in-person evaluations only, for the purpose of research, was obtained from the Israeli Ministry of Health. During the telepsychiatry phase, clinical staff and patients will join a video call from the ED, while the attending physician will log in elsewhere. The Promoting Action on Research Implementation in Health Services (PARIHS) framework will guide the evaluation of the telepsychiatry implementation process in the ED. PARIHS has the following 3 constructs: (1) evidence: staff's opinions regarding the innovation's viability and practicality, their satisfaction levels with its use, and patients' perceptions of the change; (2) context: level of approval of new strategies in the ED, decision-making processes, and the manner in which clinical teams converse and work together; (3) facilitation: adequacy of the facilitation efforts using champions reports. Primary clinical outcomes include ED length of stay and violent incidents obtained from medical records. This study received Helsinki approval from the Ethics Committee of Abarbanel Mental Health Center (174; March 13, 2023), Jerusalem Mental Health Center (22-21; November 6, 2022), Lev-Hasharon Mental Health Medical Center (LH12023; February 12, 2023), Tel-Aviv Medical Center (TLV-22-0656; January 3, 2023), and Sha'ar Menashe (1-4-23; April 18, 2023). Data collection began in July 2023 in 2 study sites and will begin soon at the others. Telepsychiatry could have significant benefits for patients in the psychiatric ED. Examining telepsychiatry effectiveness in the ED, in addition to identifying the facilitators and barriers of implementing it in different emergency settings, will facilitate better policy decisions regarding its implementation. ClinicalTrials.gov NCT05771545; https://clinicaltrials.gov/study/NCT05771545. DERR1-10.2196/49405.

Rate of Correction and All-Cause Mortality in Patients With Severe Hypernatremia

Hypernatremia is common among hospitalized patients and is associated with high mortality rates. Current guidelines suggest avoiding fast correction rates but are not supported by robust data. To investigate whether there is an association between hypernatremia correction rate and patient survival. This retrospective cohort study examined data from all patients admitted to the Tel Aviv Medical Center between 2007 and 2021 who were diagnosed with severe hypernatremia (serum sodium ≥155 mmol/L) at admission or during hospitalization. Statistical analysis was performed from April 2022 to August 2023. Patients were grouped as having fast correction rates (>0.5 mmol/L/h) and slow correction rates (≤0.5 mmol/L/h) in accordance with current guidelines. All-cause 30-day mortality. A total of 4265 patients were included in this cohort, of which 2621 (61.5%) were men and 343 (8.0%) had fast correction rates; the median (IQR) age at diagnosis was 78 (64-87) years. Slow correction was associated with higher 30-day mortality compared with fast correction (50.7% [1990 of 3922] vs 31.8% [109 of 343]; P < .001). These results remained significant after adjusting for demographics (age, gender), Charlson comorbidity index, initial sodium, potassium, and creatinine levels, hospitalization in an ICU, and severe hyperglycemia (adjusted odds ratio [aOR], 2.02 [95% CI, 1.55-2.62]), regardless of whether hypernatremia was hospital acquired (aOR, 2.19 [95% CI, 1.57-3.05]) or documented on admission (aOR, 1.64 [95% CI, 1.06-2.55]). There was a strong negative correlation between absolute sodium correction during the first 24 hours following the initial documentation of severe hypernatremia and 30-day mortality (Pearson correlation coefficient, -0.80 [95% CI, -0.93 to -0.50]; P < .001). Median (IQR) hospitalization length was shorter for fast correction vs slow correction rates (5.0 [2.1-14.9] days vs 7.2 [3.5-16.1] days; P < .001). Prevalence of neurological complications was comparable for both groups, and none were attributed to fast correction rates of hypernatremia. This cohort study of patients with severe hypernatremia found that rapid correction of hypernatremia was associated with shorter hospitalizations and significantly lower patient mortality without any signs of neurologic complications. These results suggest that physicians should consider the totality of evidence when considering the optimal rates of correction for patients with severe hypernatremia.

Inhaled Exosomes Genetically Manipulated to Overexpress CD24 (EXO-CD24) as a Compassionate Use in Severe ARDS Patients.

Acute respiratory distress syndrome (ARDS) is a major global health concern with a significant unmet need. EXO-CD24 is delivered via inhalation-reduced cytokines and chemokine secretion and lung injury in ARDS and improved survival in mice models of ARDS, influenza, and sepsis. This clinical paper aims to evaluate the potential of EXO-CD24, a novel immunomodulatory treatment, in the compassionate care of critically ill, intubated patients with post-infection-induced acute respiratory distress syndrome (ARDS). Eleven critically ill patients diagnosed with post-infection ARDS (10 with COVID-19 and one with an adenovirus-associated infection) were administered EXO-CD24 in four medical centers across Israel. The patients had multiple co-morbidities, including cancer, hypertension, diabetes, and ischemic heart disease, and met the criteria for severe ARDS according to the Berlin classification. EXO-CD24 was administered via inhalation, and adverse events related to its use were carefully monitored. The administration of EXO-CD24 did not result in any recorded adverse events. The median hospitalization duration was 11.5 days, and the overall mortality rate was 36%. Notably, patients treated at the Tel Aviv Medical Center (TASMC) showed a lower mortality rate of 12.5%. The WBC and CRP levels decreased in comparison to baseline levels at hospitalization, and rapid responses occurred even in patients with kidney transplants who were off the ventilator within a few days and discharged shortly thereafter. The production of cytokines and chemokines was significantly suppressed in all patients, including those who died. Among the patients at TASMC, four had kidney transplants and were on immunosuppressive drugs, and all of them fully recovered and were discharged from the hospital. EXO-CD24 holds promise as a potential therapeutic agent for all stages of ARDS, even in severe intubated cases. Importantly, EXO-CD24 demonstrated a favorable safety profile without any apparent side effects with promising efficacy. Furthermore, the potential of EXO-CD24 as a platform for addressing hyper-inflammatory states warrants exploration. Further research and larger-scale clinical trials are warranted to validate these preliminary findings.

Crohn's Disease Exclusion Diet for the Treatment of Crohn's Disease: Real-World Experience from a Tertiary Center.

The Crohn's Disease (CD) exclusion diet (CDED) has been shown to induce remission in pediatric and adult patients with CD. In this retrospective cohort study, we describe our real-world experience with the CDED at the inflammatory bowel disease (IBD) unit of the Tel Aviv Medical Center between 2018-2021. CD patients with multiple clinical presentations and disease phenotypes who initiated the diet were included. Indications for treatment, medical and nutritional data were collected from dietician clinic visits and medical records. Clinical and biomarker responses were determined. The CDED was recommended to 220 CD patients. Seventy-two patients were included in the analysis for a clinically active disease (n = 48) or for remission maintenance (n = 24). Among patients with a clinically active disease, 62.5% of patients achieved clinical remission at week 6 and at week 12. A positive association between high adherence to the CDED and clinical remission at week 12 was observed (adjusted OR = 7.6, 95% CI 1.07-55.2, p = 0.043). Among patients treated for remission maintenance, remission at week 12 was maintained among 83.3% of patients. We conclude that the CDED may be a promising intervention for multiple CD presentations and indications. These findings should be further validated in larger, prospective, controlled studies.

Virtual reality and 3D printing in clinical anesthesia: a case series of two years' experience in a single tertiary medical centre.

Anatomically correct patient-specific models made from medical imaging can be printed on a three-dimensional (3D) printer or turned into a virtual reality (VR) program. Until recently, use in anesthesia has been limited. In 2019, the anesthesia department at Tel Aviv Medical Center launched a 3D program with the aim of using 3D modelling to assist in preoperative anesthesia planning. A retrospective review of all relevant patients between July 2019 and June 2021 referred for preoperative airway planning with 3D modelling. Patient files were reviewed for correlation between the model-based airway plan and the actual airway plan, the type of model used, and any anesthetic complications related to airway management. Twenty patients were referred for 3D modelling. Of these, 15 models were printed, including 12 children requiring one lung ventilation. Five patients had VR reconstructions, including three with mediastinal masses. One patient had both a 3D-printed model and a VR reconstruction. There were two cases (10%) where the model plan did not correlate with the final airway plan and one case where a model could not be created because of poor underlying imaging. For the remaining 17 cases, the plan devised on the model matched the final airway plan. There were no anesthetic complications. Three-dimensional modelling and subsequent printing or VR reconstruction are feasible in clinical anesthesia. Its routine use for patients with challenging airway anatomy correlated well with the final clinical outcome in most cases. High-quality imaging is essential.

Maternal Immunization During the Second Trimester with BNT162b2 mRNA Vaccine Induces a Robust IgA Response in Human Milk: A Prospective Cohort Study

BackgroundThe human milk antibody response following maternal immunization with the BNT162b2 mRNA vaccine is important for the protection of the infant during infancy. The vaccine-specific antibody response is still unclear at different stages of human milk production, as are the effects of maternal immunization timing on the robustness of the antibody response. ObjectivesThe study aimed to assess the antibody response (IgG/IgA/IgM) during various lactation stages and identify the best vaccination timing during pregnancy. MethodsA prospective cohort study of 73 postpartum women who were administered the BNT162b2 COVID-19 mRNA vaccine during the second or third trimester of pregnancy were recruited. Statistical comparison was conducted using 16 human milk samples from a prepandemic control group. ResultsExcluding 11 women, the study included 62 lactating women who were administered the mRNA vaccine during the second or third trimester of pregnancy. A total of 149 samples of human milk were collected at different lactation stages. Our findings reveal that colostrum exhibits significantly higher levels of IgG (95% confidence interval [CI]: 1.3, 9.0; P = 0.023), IgA (95% CI: 55.98, 100.2; P = 0.0034), and IgM (95% CI: 0.03, 0.62; P < 0.0001) compared with mature milk IgG (95% CI: 0.25, 0.43), IgA (95% CI: 9.65, 13.74), IgM (95% CI: 0.03, 0.04). The timing of maternal immunization affected the antibody response. The level of IgA in mature milk was higher when immunization occurred in the second trimester (95% CI: 11.14, 19.66; P = 0.006) than in the third trimester (95% CI: 7.16, 11.49). Conversely, IgG levels in mature milk were higher when immunization occurred during the third trimester (95% CI: 0.36, 0.65; P < 0.0001) than in the second trimester (95% CI: 0.09, 0.38). ConclusionsOur study provides evidence that administering the mRNA vaccine to pregnant women during the second trimester increases vaccine-specific IgA levels during lactation. Considering the significance of human milk IgA in mucosal tissues and its prevalence throughout lactation, it is reasonable to recommend maternal immunization with the BNT162b2 mRNA vaccine during the second trimester.This trial was registered at the Helsinki Committee of the Tel Aviv Medical Center as clinical trial number 0172-TLV.

A single-center real-life study on the use of medical cannabis in patients with dystonia.

While cannabis-based medicine is being commonly used in patients with movement disorders, there is a scarcity of publications regarding the effect of cannabis on dystonia. We aimed to describe medical cannabis use in patients with dystonia and related pain. We employed a structured interview to obtain data on the cannabis treatment regimen, perception of effectiveness and side effect profile. Eligible participants were patients diagnosed with dystonia from the movement disorders unit at the Tel-Aviv Medical Center who had used licensed medical cannabis between January 2019 and January 2021. Twenty-three subjects were interviewed (11 women, mean age 52.7). The most common way of administration was smoking (n = 11). Following an average of 2.5 ± 2.9 years of use, those with widespread dystonia (generalized, hemi and multifocal, n = 11) self-reported on a numeric rating scale an average 63% (range 0%-100%) reduction in symptoms of dystonia, while those with more focal dystonia patterns reported a significantly lower treatment effect of 32%. Participants reported a positive impact in related pain and quality of life, with an average rating of 3.8 out of 5 (SD = 1.2, median = 4) and 3.6 out of 5 (SD = 1.15, median = 4), respectively. Most common side effects were dry mouth (65%), sedation (43%), dizziness (39%) and psychiatric disorders (26%). Three patients (13%) discontinued therapy. A subset of dystonia patients who use medical cannabis under clinical observation reported significant subjective improvement during 30 months of use in average. Further prospective randomized controlled trials are required to examine the effectiveness of cannabis in dystonia.

Neutrophil-to-lymphocyte ratio trend at admission predicts adverse outcome in hospitalized respiratory syncytial virus patients

Background and aimsSevere cases of respiratory syncytial virus (RSV) infection are relatively rare but may lead to serious clinical outcomes, including respiratory failure and death. These infections were shown to be accompanied by immune dysregulation. We aimed to test whether the admission neutrophil-to-leukocyte ratio, a marker of an aberrant immune response, can predict adverse outcome. MethodsWe retrospectively analyzed a cohort of RSV patients admitted to the Tel Aviv Medical Center from January 2010 to October 2020d. Laboratory, demographic and clinical parameters were collected. Two-way analysis of variance was used to test the association between neutrophil-lymphocyte ratio (NLR) values and poor outcomes. Receiver operating characteristic (ROC) curve analysis was applied to test the discrimination ability of NLR. ResultsIn total, 482 RSV patients (median age 79 years, 248 [51%] females) were enrolled. There was a significant interaction between a poor clinical outcome and a sequential rise in NLR levels (positive delta NLR). The ROC curve analysis revealed an area under curve (AUC) of poor outcomes for delta NLR of (0.58). Using a cut-off of delta = 0 (the second NLR is equal to the first NLR value), multivariate logistic regression identified a rise in NLR (delta NLR>0) as being a prognostic factor for poor clinical outcome, after adjusting for age, sex and Charlson comorbidity score, with an odds ratio of 1.914 (P = 0.014) and a total AUC of 0.63. ConclusionsA rise in NLR levels within the first 48 h of hospital admission can serve as a prognostic marker for adverse outcome.

The effect of body mass index reduction on intraocular pressure in a large prospective cohort of apparently healthy individuals in Israel.

To investigate the effect of change in body mass index (BMI) on intraocular pressure (IOP) in a large cohort of apparently healthy volunteers who underwent an annual comprehensive screening examinations. This study included individuals who were enrolled in the Tel Aviv Medical Center Inflammation Survey (TAMCIS) and had IOP and BMI measurements at their baseline and follow up visits. Relationships between BMI and IOP and the effect of change in BMI on IOP were investigated. A total of 7,782 individuals had at least one IOP measurement at their baseline visit, and 2,985 individuals had ≥2 visits recorded. The mean (SD) IOP (right eye) was 14.6 (2.5) mm Hg and mean (SD) BMI was 26.4 (4.1) kg/m2. IOP positively correlated with BMI levels (r = 0.16, p<0.0001). For individuals with morbid obesity (BMI≥35 kg/m2) and ≥2 visits, a change in BMI between the baseline and first follow-up visits correlated positively with a change in the IOP (r = 0.23, p = 0.029). Subgroup analysis of subjects who had a reduction of at least 2 BMI units showed a stronger positive correlation between change in BMI and change in IOP (r = 0.29, p<0.0001). For this subgroup, a reduction of 2.86 kg/m2 of BMI was associated with a reduction of 1 mm Hg in IOP. BMI loss correlated with reduction in IOP, and this correlation was more pronounced among morbidly obese individuals.

Licensed Medical Cannabis Use in Gilles de la Tourette Syndrome: A Retrospective Long-term Follow-Up.

Background: Medical cannabis (MC) is widely used in clinical practice to treat Gilles de la Tourette syndrome (GTS). However, legislation, multiple modes of administration, and inconsistent plant preparations have limited trials to assess its benefits and long-term safety. For the past decade, licensed MC has been authorized in Israel for use in resistant GTS. We aimed to describe subjects' satisfaction, consumption habits, and THC dose increment during long-term usage. Materials and Methods: A retrospective longitudinal data collection (up to 9 years) on cannabis use habits and structured questionnaires evaluating disease characteristics and MC influence from GTS subjects being treated in the Movement Disorders Unit of the Tel-Aviv Medical Center, Israel. Results: Twenty-five patients (84% male) participated in the study. The mean duration of MC use was 4.0±2.3 years (range 0.5-10). The majority of patients (96%) consumed MC primarily, but not exclusively, through inhalation methods such as smoking or vaporizing dried inflorescence. A linear increase was observed in mean monthly THC dose (p<0.0001) with an average increase of 0.6-0.7 g/year. MC led to a subjectively reported reduction in tics (75% average reduction) and symptoms associated with common comorbidities of GTS. MC was generally well tolerated, although most participants (88%) reported experiencing side effects. Conclusions: A subset of GTS subjects who use MC long term under clinical observation may subjectively improve control of symptoms. Subject-led dose increase can indicate emerging tolerance. Large randomized controlled and observational long-term trials are required to confirm these observations.