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Objectives The mRNA coronavirus disease 2019 (COVID-19) vaccines have shown high effectiveness in the prevention of symptomatic COVID-19, hospitalization, severe disease and death. Nevertheless, a minority of vaccinated individuals might become infected and experience significant morbidity. Characteristics of vaccine breakthrough infections have not been studied. We sought to portray the population of Israeli patients, who were hospitalized with COVID-19 despite full vaccination. Methods A retrospective multicentre cohort study of 17 hospitals included patients fully vaccinated with Pfizer/BioNTech's BNT162b2 vaccine who developed COVID-19 more than 7 days after the second vaccine dose and required hospitalization. The risk for poor outcome, defined as a composite of mechanical ventilation or death, was assessed. Results A total of 152 patients were included, accounting for half of hospitalized fully vaccinated patients in Israel. Poor outcome was noted in 38 patients and mortality rate reached 22% (34/152). Notably, the cohort was characterized by a high rate of co-morbidities predisposing to severe COVID-19, including hypertension (108; 71%), diabetes (73; 48%), congestive heart failure (41; 27%), chronic kidney and lung diseases (37; 24% each), dementia (29; 19%) and cancer (36; 24%), and only six (4%) had no co-morbidities. Sixty (40%) of the patients were immunocompromised. Higher viral load was associated with a significant risk for poor outcome. Risk also appeared higher in patients receiving anti-CD20 treatment and in patients with low titres of anti-Spike IgG, but these differences did not reach statistical significance. Conclusions We found that severe COVID-19 infection, associated with a high mortality rate, might develop in a minority of fully vaccinated individuals with multiple co-morbidities. Our patients had a higher rate of co-morbidities and immunosuppression compared with previously reported non-vaccinated hospitalized individuals with COVID-19. Further characterization of this vulnerable population may help to develop guidance to augment their protection, either by continued social distancing, or by additional active or passive vaccinations.

Background Changing patterns of vaccine breakthrough can clarify vaccine effectiveness. Aim To compare breakthrough infections during a SARS-CoV-2 Delta wave vs unvaccinated inpatients, and an earlier Alpha wave. Methods In an observational multicentre cohort study in Israel, hospitalised COVID-19 patients were divided into three cohorts: breakthrough infections in Comirnaty-vaccinated patients (VD; Jun–Aug 2021) and unvaccinated cases during the Delta wave (ND) and breakthrough infections during an earlier Alpha wave (VA; Jan–Apr 2021). Primary outcome was death or ventilation. Results We included 343 VD, 162 ND and 172 VA patients. VD were more likely older (OR: 1.06; 95% CI: 1.05–1.08), men (OR: 1.6; 95% CI: 1.0–2.5) and immunosuppressed (OR: 2.5; 95% CI: 1.1–5.5) vs ND. Median time between second vaccine dose and admission was 179 days (IQR: 166–187) in VD vs 41 days (IQR: 28–57.5) in VA. VD patients were less likely to be men (OR: 0.6; 95% CI: 0.4–0.9), immunosuppressed (OR: 0.3; 95% CI: 0.2–0.5) or have congestive heart failure (OR: 0.6; 95% CI: 0.3–0.9) vs VA. The outcome was similar between all cohorts and affected by age and immunosuppression and not by vaccination, variant or time from vaccination. Conclusions Vaccination was protective during the Delta variant wave, as suggested by older age and greater immunosuppression in vaccinated breakthrough vs unvaccinated inpatients. Nevertheless, compared with an earlier post-vaccination period, breakthrough infections 6 months post-vaccination occurred in healthier patients. Thus, waning immunity increased vulnerability during the Delta wave, which suggests boosters as a countermeasure.

ImportanceWaning immunity against COVID-19 in parallel with an increased incidence during the Omicron outbreak led the Israeli Ministry of Health to recommend a second booster dose of BNT162b2 (Pfizer) to high-risk individuals. Israel was the first country to recommend this, allowing evaluation of the added protection of a fourth vaccine dose to hospitalized patients with severe diseases.ObjectiveTo assess the effect of a fourth dose for hospitalized patients with severe/critical breakthrough COVID-19.DesignA cohort study of hospitalized adults from 01/15/2022–01/31/2022.SettingsA multi-center study of 14 medical centers in Israel.ParticipantsHospitalized adult patients with PCR-confirmed severe/critical COVID-19. Excluded were patients lacking data on vaccination status.ExposureCases were divided according to the total number of vaccine doses received up to 7 days before diagnosis. Unvaccinated adults and single-dose recipients were grouped into an unvaccinated group.Main OutcomeA composite of mechanical-ventilation or in-hospital death was defined as poor outcome. Outcomes were compared between 3- and 4-dose vaccinees.ResultsIncluded were 1,049 patients with severe/critical COVID-19, median age 80 (IQR 69-87), 51% males. Among them, 360 unvaccinated, 34, 172, 386 and 88 were after 1, 2, 3 or 4 doses, respectively. Patients after 3 doses were older, had more males and immunosuppression, but with similar outcomes, 49% vs. 51% compared to unvaccinated patients (p=0.72). Patients after 4 doses were similarly older and immunosuppressed, but had improved outcomes compared to unvaccinated patients, 34% vs. 51% (pConclusion and RelevanceWithin a population of hospitalized patients with severe/critical breakthrough COVID-19, a recent fourth dose was associated with significant protection against mechanical ventilation or death, compared to fully vaccinated single-boosted individuals.Key pointsQuestionWhat is the benefit of a fourth vaccine dose (second booster) for hospitalized patients with severe COVID-19?FindingsIn this multicenter cohort study in Israel during the Omicron wave, hospitalized severe COVID-19 patients that received a recent fourth dose had a 49% lower odds for a poor outcome (mechanical ventilation or death) compared with those who received 3 doses approximately 5 months before diagnosis, a significant difference.MeaningA vaccine booster given at the onset of a COVID-19 wave can benefit vulnerable individuals.

Monkeypox virus, a zoonotic Orthopox DNA virus was rarely reported outside of African regions until April 2022. Since then, thousands of cases have been reported worldwide. In order to cope with the increasing need for laboratory diagnosis, the availability of reliable commercial PCR assays is of paramount importance. In this study we compared the diagnostic performance of two commercial real-time (RT)-PCR assays, the Novaplex™ MPXV Assay and the Bio-Speedy® Monkeypox Virus qPCR Kit, for the detection of Monkeypox virus (MPXV) DNA from 154 human samples. These assays were compared to a recently published in-house assay that included a general MPXV target (G2T) and a West African specific target (genericWA). All assays demonstrated 100% specificity. While sensitivity of the Novpalex assay was 100% the sensitivity of the other assays was lower; 94% for the Bio-speedy assay and G2R assay and 88% for the genericWA assay. The sensitivity differences between the methods manifested almost entirely in those pharyngeal samples in which the Ct values were high (≥35). The Novaplex™ MPXV Assay showed higher Ct values compared with the other methods with a median of 27.1 compared with the Bio-Speedy assay (median 15.8, p 0.001), the G2R assay (median 23.5, p 0.001) and the genericWA assay (median 23.6, p 0.001). For all 4 methods, the Ct values were higher in samples taken from oropharynx compared with samples from rectal and pustule swabs.

The urinary tract is considered an uncommon source of

Background “Palpitations” are one of the most common complaints prompting medical attention. Textbooks of medicine and cardiology as well as guideline documents and position papers describe palpitations as a common symptom of ventricular tachycardia (VT). However, data to support this description are lacking. The aim of our study was to evaluate the symptomatology of sustained monomorphic VT with emphasis on the prevalence of palpitations. Methods and Results Consecutive patients presenting to our center with a first event of a regular sustained monomorphic VT (n=59) or a regular supraventricular tachycardia (SVT; n=109) between January 2012 and September 2019 were interviewed regarding their symptoms during the arrhythmic event. We included only patients with a first arrhythmic event to avoid the influence of previous medical encounters on our patients’ terminology. As expected, patients with VT were older (age 68.8±13.6 versus 52.6±16.8 years; P P P P P =0.16), symptomatology differed significantly; specifically, palpitations were reported in only 8.8% of VT patients, compared with 90.7% of SVT patients ( P Conclusions Despite similar heart rate, patients with VT rarely report having palpitations, whereas patients with SVT do so commonly. This finding may assist with decision making in patients reporting palpitations in whom an ECG tracing is not available.

Dear editor,Recently in this journal, the clinical expression and complications of coronavirus disease of 2019 (COVID-19) were described [1]. Cardiac complications were important and, moreover, sep...

Objectives To determine clinical outcomes associated with aminoglycosides versus other antimicrobial agents as empirical treatment of hospitalized patients with pyelonephritis. Patients and methods An institutional programme promoting aminoglycosides as empirical treatment of pyelonephritis was implemented in 2016. We reviewed the hospital records of patients with pyelonephritis from January 2017 to April 2019. The primary outcome was death within 30 days of index culture. Initial treatment with aminoglycoside-based regimens was compared with non-aminoglycoside antibiotics. Propensity score matching was performed to adjust for between-group differences in baseline covariates. Results The study cohort included 2026 patients, 715 treated with aminoglycosides and 1311 treated with non-aminoglycoside drugs (ceftriaxone, n = 774; piperacillin/tazobactam, n = 179; carbapenems, n = 161; and fluoroquinolones, n = 133); 589 patients (29%) had bloodstream infections. Treatment with aminoglycosides was associated with a higher likelihood of in vitro activity against clinical isolates (OR = 2.0; P Conclusions Within the context of an institutional programme, initial empirical treatment of pyelonephritis with aminoglycosides was associated with higher rates of in vitro activity and lower overall mortality compared with non-aminoglycoside drugs, without excess nephrotoxicity.

In this cohort of 42 patients with mild COVID19 we found a unique clinical feature of acute anosmia and dysgeusia in more than third of patients. Median onset of these features was 3.3 days after onset of illness (range 0-7) with rapid recovery in most patients.Article Summary LineAnosmia and dysgeusia appeared early in third of our patients with mild SARS-CoV-2 infection and were short-lived in most patients.

Administration of a BNT162b2 booster dose (Pfizer-BioNTech) to fully vaccinated individuals aged 60 years and older was significantly associated with lower risk of SARS-CoV-2 infection and severe illness. Data are lacking on the effectiveness of booster doses for younger individuals and health care workers.To estimate the association of a BNT162b2 booster dose with SARS-CoV-2 infections among health care workers who were previously vaccinated with a 2-dose series of BNT162b2.This was a prospective cohort study conducted at a tertiary medical center in Tel Aviv, Israel. The study cohort included 1928 immunocompetent health care workers who were previously vaccinated with a 2-dose series of BNT162b2, and had enrolled between August 8 and 19, 2021, with final follow-up reported through September 20, 2021. Screening for SARS-CoV-2 infection was performed every 14 days. Anti-spike protein receptor binding domain IgG titers were determined at baseline and 1 month after enrollment. Cox regression with time-dependent analysis was used to estimate hazard ratios of SARS-CoV-2 infection between booster-immunized status and 2-dose vaccinated (booster-nonimmunized) status.Vaccination with a booster dose of BNT162b2 vaccine.The primary outcome was SARS-CoV-2 infection, as confirmed by reverse transcriptase-polymerase chain reaction.Among 1928 participants, the median age was 44 years (IQR, 36-52 years) and 1381 were women (71.6%). Participants completed the 2-dose vaccination series a median of 210 days (IQR, 205-213 days) before study enrollment. A total of 1650 participants (85.6%) received the booster dose. During a median follow-up of 39 days (IQR, 35-41 days), SARS-CoV-2 infection occurred in 44 participants (incidence rate, 60.2 per 100 000 person-days); 31 (70.5%) were symptomatic. Five SARS-CoV-2 infections occurred in booster-immunized participants and 39 in booster-nonimmunized participants (incidence rate, 12.8 vs 116 per 100 000 person-days, respectively). In a time-dependent Cox regression analysis, the adjusted hazard ratio of SARS-CoV-2 infection for booster-immunized vs booster-nonimmunized participants was 0.07 (95% CI, 0.02-0.20).Among health care workers at a single center in Israel who were previously vaccinated with a 2-dose series of BNT162b2, administration of a booster dose compared with not receiving one was associated with a significantly lower rate of SARS-CoV-2 infection over a median of 39 days of follow-up. Ongoing surveillance is required to assess durability of the findings.

OBJECTIVES High values of Red Blood Cell Distribution Width (RDW) have been associated with adverse outcome in various clinical settings. The mechanism behind this association is not clear. The Metabolic Syndrome (MetS) is a chronic inflammatory disorder that increases the risk for cardiovascular disease and death. The aim of our study was to evaluate the association between high RDW and the MetS in a relatively large cohort of patients. METHODS A cohort of 3,529 consecutive patients undergoing coronary angiography was used to evaluate the association between RDW and the MetS. The association was assessed by using a logistic regression. Cox's regression analysis was used to evaluate the impact of RDW on long term mortality. RESULTS The mean age was 65 years (range 24-97), with 27% women. Overall, 30% were diagnosed with metabolic syndrome. The prevalence of MetS was 29% in patients with RDW

AIM The varicella-zoster virus causes infections that are often mild but can cause substantial morbidity and mortality in otherwise healthy children. We examined trends in varicella-related hospitalisations before and after the implementation of a national two-dose varicella vaccination programme in Israel in September 2008. METHODS This retrospective chart review, performed at three tertiary care paediatric hospitals in greater Tel Aviv, compared data from 2004 to 2008 and 2009 to 2012, before and after the varicella programme was launched. It included all children to the age of 18 who were hospitalised for conditions associated with the varicella infection. RESULTS After the vaccination programme was introduced, the number of children hospitalised for varicella fell by 63% (p < 0.5), from 38.9 to 14.5 per 10 000, and there was a 75% reduction in children aged one to six. During the same period, the percentage of hospitalised children who were immunocompromised rose from 9.7% to 18.4% (p < 0.05). The most common complications were soft-tissue infections (60%), and the most prevalent pathogens were Group A β-haemolytic streptococcus (53%) and Staphylococcus aureus (32%). CONCLUSION The introduction of a two-dose immunisation programme dramatically decreased the varicella burden in Israel, leading to a major reduction in hospitalisation admissions linked to the infection.

Objectives: Previous studies investigating the prognostic value of HbA1c in patients undergoing coronary angiography reported a mixed pattern of results. Therefore, we aimed to better define the prognostic power of HbA1c among coronary catheterized patients. Methods: Patients undergoing coronary angiography (n = 3,749) were divided into four groups according to HbA1c levels (7%). Cox regression models assessed long-term mortality after adjusting for multiple covariates. Results: Baseline clinical profiles differed in HbA1c groups, with a higher prevalence of comorbidities in the groups with higher HbA1c levels. Median follow-up was 1,745 days (interquartile range 1,007-2,171). A J-shaped association curve was observed between HbA1c levels and all-cause mortality rates, with patients in the lowest and highest HbA1c groups suffering from significantly higher mortality rates compared to in-between groups (hazard ratio 1.9, 95% CI 1.32-2.74, p = 0.001, and hazard ratio 1.58, 95% CI 1.29-1.95, p < 0.001, for the lowest and highest HbA1c groups, respectively). This association persisted after adjustment for anemia, nutritional status, renal function, cardiovascular risk factors and inflammatory biomarkers. Conclusions: HbA1c levels 7% are predictors of all-cause mortality in patients undergoing coronary angiography.

Previous studies investigating the prognostic value of HbA1c in patients undergoing coronary angiography reported a mixed pattern of results. Therefore, we aimed to better define the prognostic power of HbA1c among coronary catheterized patients.Patients undergoing coronary angiography (n = 3,749) were divided into four groups according to HbA1c levels (5, 5-6, 6-7 and7%). Cox regression models assessed long-term mortality after adjusting for multiple covariates.Baseline clinical profiles differed in HbA1c groups, with a higher prevalence of comorbidities in the groups with higher HbA1c levels. Median follow-up was 1,745 days (interquartile range 1,007-2,171). A J-shaped association curve was observed between HbA1c levels and all-cause mortality rates, with patients in the lowest and highest HbA1c groups suffering from significantly higher mortality rates compared to in-between groups (hazard ratio 1.9, 95% CI 1.32-2.74, p = 0.001, and hazard ratio 1.58, 95% CI 1.29-1.95, p0.001, for the lowest and highest HbA1c groups, respectively). This association persisted after adjustment for anemia, nutritional status, renal function, cardiovascular risk factors and inflammatory biomarkers.HbA1c levels5 or7% are predictors of all-cause mortality in patients undergoing coronary angiography.