Israel Medical Association Journal

Background: Coronavirus disease 2019 (COVID-19) causes severe complications in 15% of patients, many of whom are pregnant. Most infected women continue their pregnancies until term even though severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates in the decidua.

Objectives: To assess the impact of SARS-CoV-2 infection remote from delivery on obstetric outcomes.

Methods: Women diagnosed with SARS-CoV-2 infection confirmed by polymerase chain reaction at least 14 days prior to delivery were enrolled prospectively and followed monthly until delivery. Their obstetric outcomes were compared to those of women who gave birth at our center during the year preceding the pandemic. The primary endpoint was a composite of hypertensive disorders of pregnancy, oligohydramnios, and fetal distress or meconium-stained amniotic fluid during labor. Other demographic and obstetric variables were also recorded.

Results: The obstetric outcomes of 143 patients were compared to those of 3565 patients who gave birth during the year preceding the pandemic. The composite rate of placental complications was significantly higher in the study group (58 [41%] vs. 593 [17%], respectively), with an odds ratio of 3.4 (95% confidence interval 2.4–4.7). There was also an increased rate of labor induction or advancing the elective cesarean date in the study group (37 [26%] vs. 601 [17%]). No significant differences were found in the Apgar score, cord pH or gestational age at infection.

Conclusions: The risk of placental complications remains greater in pregnant women infected with SARS-CoV-2 after acute illness resolution. Those patients should be monitored closely until delivery.

Background: Co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) affects approximately 2.2 million people globally and is associated with accelerated liver disease progression, increased morbidity, and reduced quality of life (QoL). While direct-acting antivirals (DAAs) have revolutionized HCV treatment with high cure rates, evidence of their long-term impact on liver-related QoL and associated metabolic or immunologic shifts in HIV/HCV co-infected populations remains limited.

Objectives: To evaluate the effect of achieving sustained virologic response (SVR) with DAAs on long-term QoL in HIV/HCV co-infected patients and to examine associated changes in CD4 count, kidney function, and glucose levels.

Methods: This retrospective observational study was conducted at the Rambam Health Care Campus, between 2015 and 2019. We collected demographic, clinical, and laboratory data from all patients with HIV/HCV co-infection. QoL was evaluated for at least 6 months after the end of treatment. Metabolic variables were collected before and after treatment to test the effects of treatment.

Results: All 70 patients in the cohort achieved SVR. Successful treatment with DAAs resulted in a significant decrease in liver enzymes and globulin levels, and a substantial increase in CD4. A significant improvement in QoL after treatment was noticed in both sexes, regardless of liver fibrosis stage. FIB-4 calculations 6 months and 1 year after the end of therapy showed improved fibrosis levels after SVR.

Conclusions: The use of DAAs in HCV/HIV co-infected patients has improved the long-term QoL, metabolic factors, and fibrosis stage.

Background: Tunneled hemodialysis catheters are frequently used and are a major source of catheter-related bloodstream infections (CRBSI), which result in significant morbidity.

Objectives: To examine the adverse outcomes associated with CRBSIs, including hospitalization, recurrence, 1-year mortality, and catheter outcomes in a hemodialysis setting that uses modern preventive catheter-care practices.

Methods: We conducted a retrospective cohort study of adults with jugular tunneled hemodialysis catheters who met criteria for CRBSI from 1 January 2015 to 31 December 2020 at a tertiary referral center.

Results: Of 380 hemodialysis patients, 75 experienced CRBSI events. The average rate was 1.55 CRBSIs per 100 patient months. The median time from catheter insertion to CRBSI was 179 days; and 68% required inpatient management. Gram-positive bacteria accounted for 53% of isolates, with Gram-negative organisms also being common. Recurrence occurred in 16% of cases and was independently associated with ferritin levels over 500 ng/ml (P = 0.02), albumin levels below 3.5 g/dl (P = 0.011), and uric acid levels under 2.5 mg/dl (P = 0.04). Catheters were removed in 61.3%, exchanged over a guidewire in 24%, and salvaged in 18.6%. The 1-year mortality rate was 28% and was associated with lower weight, catheter salvage, neutrophilia, hypoalbuminemia, and hypokalemia. Using chlorhexidine exit-site dressings was associated with fewer hospital admissions.

Conclusions: Among hemodialysis patients with CRBSI, recurrence and mortality might be linked to a patient's nutritional and inflammatory status. Current preventive measures might reduce hospitalization rates, but in this cohort, they were not associated with lower recurrence or mortality rate.

Phlycten syndrome was described as a traumatic surgical syndrome of the lower limbs, beginning as streptococcal cellulitis and progressing to necrotizing edema in individuals with starvation-induced hypoalbuminemia and electrolyte imbalance. Independently documented by three physicians during their imprisonment in Nazi concentration camps in World War II, the syndrome also developed when edematous, emaciated prisoners were flogged, causing rapid progression to gangrene and sepsis.

Background: The incidence of non-tuberculous mycobacterium (NTM) infections has been rising in patients with chronic lung diseases. These infections cause significant morbidity, mortality, and elevated healthcare costs due to challenges in recognition, delayed diagnosis, and treatment. While NTM infections in natural stone silicosis are documented, the incidence in artificial stone silicosis remains unexplored despite increasing exposure to silica dust.

Objectives: To describe the clinical, radiological, and pathological features of NTM infections in patients with artificial stone silicosis and emphasize the importance of early diagnosis.

Methods: We reviewed the database of a tertiary medical center in Israel from 2010 to 2024 and identified patients with occupational artificial stone silicosis diagnosed with NTM infection.

Results: We found eight patients with occupational artificial stone silicosis, all male, aged 42–74 years. Key symptoms included dyspnea, cough, weight loss, and fever. Computed tomography revealed mediastinal lymphadenopathy, progressive massive fibrosis, calcifications, pulmonary cavitations, pleural thickening, traction bronchiectasis, pulmonary nodules, and honeycombing. Biopsies showed silicotic nodules, birefringent crystals, pulmonary alveolar silico-proteinosis, fibrosis, and honeycombing. Four patients received NTM-targeted antibiotics, and six underwent lung transplantation. Four patients died.

Conclusions: Artificial stone silicosis may be associated with NTM infections. Early diagnosis requires a high degree of clinical suspicion. New or worsening respiratory or systemic symptoms in patients with silicosis should prompt further microbiological evaluation, including sputum culture or bronchoalveolar lavage. Further studies are needed to assess the incidence of NTM infections in this population.

Background: Pediatric urinary tract infections (UTIs) are a significant health concern, with rising antibiotic resistance complicating treatment decisions. We investigated pathogen distribution, antibiotic susceptibility patterns, and the cost-effectiveness of treatment options among hospitalized children at a tertiary medical center in Israel.

Objectives: To assess antibiotic susceptibility patterns of UTI pathogens in hospitalized children and evaluate cost-effective alternatives to gentamicin.

Methods: A retrospective analysis of 1649 pediatric UTI cases (January 2010–May 2022) at Galilee Medical Center examined patient demographics, urine culture results, and antibiotic susceptibility. A cost-effectiveness analysis was performed using incremental cost-effectiveness ratios (ICERs), based on susceptibility rates from the study and antibiotic costs from the Israel Ministry of Health, with gentamicin as the comparator.

Results: Escherichia coli was the most common pathogen (63.7%). High susceptibility rates were observed for carbapenems and amikacin (> 99%), with lower rates for gentamicin (91.7%) and ceftriaxone (87.6%). Treatment costs ranged from US$2.54 (trimethoprim/sulfamethoxazole) to US$307.80 (ertapenem). Fosfomycin demonstrated higher susceptibility than gentamicin (94.2% vs 91.7%) and lower cost (US$3.77 vs US$8.05), dominating gentamicin in cost-effectiveness analysis. Piperacillin/tazobactam and ceftriaxone were dominated by gentamicin in terms of cost-effectiveness.

Conclusions: E. coli was the predominant pathogen in pediatric UTIs among hospitalized children. Carbapenems and amikacin showed high susceptibility but were costly. Fosfomycin demonstrated high susceptibility, favorable cost-effectiveness, and the advantage of oral administration, making it a promising option for empiric treatment. Empiric antibiotic selection should integrate susceptibility patterns, clinical context, and economic considerations.

Ventriculoperitoneal shunt (VPS) placement is a standard treatment for pediatric hydrocephalus. However, infection remains a significant complication, occurring in 5–27% of cases, with coagulase-negative staphylococci (CONS) and Staphylococcus aureus being the most common pathogens [1]. Current guidelines recommend empirical antibiotic treatment and surgical removal of the infected shunt [2]. While shunt removal and replacement are recommended for managing shunt infections, these procedures subject the child to the risks associated with multiple surgeries. However, recent approaches have suggested that in certain cases antibiotics alone may suffice, thus avoiding the risks of surgery [3].

We describe two children with VPS infections caused by CONS who were successfully treated with vancomycin and rifampicin alone, without the need for shunt removal.

Background: Inflammatory and thrombotic markers play crucial roles in risk stratification for various diseases.

Objectives: To investigate the relative importance of inflammation, measured by C-reactive protein (CRP), and platelet turnover, indicated by immature platelet fraction (IPF), in predicting outcomes for patients with cardiovascular disease, coronavirus disease 2019 (COVID-19), and bacterial infections.

Methods: In this retrospective observational study, we analyzed data from 1473 individuals admitted to the Samson Assuta Ashdod University Hospital between 2018 and 2022. Patients were categorized based on CRP and IPF levels, with a focus on 280 patients in the high CRP/low IPF or high IPF/low CRP tertiles.

Results: The high CRP low IPF group demonstrated significantly higher mortality rates compared to the low CRP high IPF group (13.5% vs. 0.8%, P < 0.001). Logistic regression analysis revealed that the high CRP and low IPF combination was the strongest predictor of mortality (odds ratio 12.951, 95% confidence interval 1.409–119.020, P = 0.024).

Conclusions: The combination of inflammatory (CRP) and thrombotic (IPF) markers provides superior prognostic information compared to individual disease diagnoses in patients with cardiovascular disease, COVID-19, and bacterial infections.

Background: Solid organ transplant (SOT) recipients represent a particularly vulnerable group due to their reliance on immunosuppressive therapies. Previous studies indicated a mortality rate of 20%-30% among SOT recipients with coronavirus disease 2019 (COVID-19). With the advent of the Omicron variant in November 2021, characterized by milder symptoms and lower mortality rates in the general population, safety measures relaxed, potentially impacting vulnerable populations like SOT recipients.

Objectives: To investigate mortality and morbidity among hospitalized SOT recipients with COVID-19 infection during the Omicron wave.

Methods: A retrospective, propensity-matched cohort study conducted at the Rabin Medical Center, Israel, spanned from November 2021 to June 2023. Adult SOT recipients hospitalized with COVID-19 were compared to matched controls.

Results: Among 139 hospitalized SOT recipients and 209 controls, SOT recipients hospitalized with COVID-19 displayed higher in-hospital mortality (19% vs. 11%) and 90-day all-cause mortality (30% vs. 17%). In addition, the 90-day readmission rate was significantly higher among SOT recipients (43% vs. 31%). Multivariable analysis confirmed these trends, with SOT recipients exhibiting increased risk for mortality, readmission, invasive ventilation, and intensive care unit admission.

Conclusions: The heightened vulnerability of hospitalized SOT recipients during the Omicron wave was characterized by higher mortality and readmission rates compared to matched controls. Despite the perceived milder nature of the Omicron variant, SOT recipients remain disproportionately affected. Continued vigilance and targeted interventions are necessary for this population including vaccinations and adherence to preventive measures. Investigating this population’s outcomes through the changing COVID-19 variants is still warranted.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease pathway is heavily influenced by different inflammatory cytokines. There is ample evidence of cannabidiol (CBD) immunomodulation effects.

Objectives: To investigate the effect of CBD on patients with SARS-CoV-2 and to measure the impact on inflammatory cytokines.

Methods: A double blind, placebo-controlled study to compare the clinical outcomes and selected serum cytokine levels in patients with SARS-CoV-2 that received sublingual CBD extraction. Seven patients were randomized to the treatment arm and three to the placebo group.

Results: Clinical outcomes were better in the patient group that received sublingual CBD vs. patients receiving placebo treatment. Serum cytokine mean concentration levels showed differences between the two groups but of mixed trends.

Conclusions: Patients presenting with SARS-CoV-2 and receiving CBD sublingually had better outcomes than those receiving a placebo, although these results did not reflect in selected serum cytokines. Further study is needed.

Background: Acute skin infections, like cellulitis or erysipelas, are common and respond well to antibiotic treatment. However, complete resolution of the inflammatory process is often slow and associated with prolonged pain and reduced mobility. Several studies have indicated that acupuncture may effectively treat inflammatory skin diseases.

Objectives: To evaluate the efficacy of acupuncture for treating cellulitis in patients hospitalized in internal medicine departments.

Methods: In this pilot randomized sham-controlled trial, patients hospitalized with cellulitis in internal medicine departments were randomized to acupuncture or sham acupuncture, in addition to standard care. The primary outcome was the degree of improvement in the cellulitis score at day 4 of hospitalization. Secondary endpoints included patient pain self-assessment and local and systemic inflammatory signs.

Results: The study comprised 29 patients; 15 treated with acupuncture, 14 by a sham procedure. At day 4, patients in the acupuncture arm had an improved cellulitis score (4.1 ± 2.8) compared with the sham-control group (7.9 ± 3.3, P = 0.003). Pain intensity based on the Visual Assessment Scale was lower in the acupuncture group 3.8 ± 2.7 vs. 6.3 ± 2.8; P = 0.023. There was no difference in the rate of leukocyte change. However, C-reactive protein significantly decreased to 27.0 ± 22.1 mg/L at day 4 following acupuncture compared to 63.9 ± 51.9 mg/L (P = 0.025).

Conclusions: In our pilot study, we found acupuncture to be efficacious as an adjunctive therapy in the treatment of leg cellulitis. A large-scale trial on the effectiveness of acupuncture for skin infections is needed.

Background: Gram-negative bloodstream infections (GN-BSI) are life threatening. Appropriate antimicrobial therapy and source control when indicated improve survival. Dementia is an independent risk factor for death and is associated with increased risk for infections, especially in advanced stages. Data about the best diagnostic and therapeutic approaches for patients with dementia and GN-BSI are lacking.

Objectives: To evaluate patients with dementia and GN-BSI and determine whether diagnostic imaging improves clinical outcomes.

Methods: We performed a retrospective cohort study of adult patients with GN-BSI, during 2019–2022. Patients with or without a diagnosis of dementia were compared. Outcomes were in-hospital mortality and recurrent bacteremia. Demographic, clinical, diagnostic, and therapeutic data were collected and analyzed.

Results: A total of 87 patients with dementia and 130 without were included. Patients with dementia received appropriate empirical antimicrobial therapy in 38% of cases compared to 62% of patients without dementia, P < 0.001. Imaging studies were performed in half of patients in both groups. In the dementia group, 17% had abnormal findings that required source control versus 30% in the control group (P = 0.049). Source control was performed in 15% of patients with dementia versus 28% of patients without dementia (P = 0.032). Mortality was 27.6% in the dementia group versus 22.3% in the control group (P = 0.42).

Conclusions: In patients with dementia and GN-BSI, imaging studies have lower effect on clinical outcomes. Imaging studies should be performed in selected cases only and not conducted routinely.

Background: Pyogenic flexor tenosynovitis (PFT) is a common and severe hand infection. Patients who present early can be treated with intravenous antibiotics.

Objectives: To determine whether PFT caused by animal bites and treated with antibiotics leads to a different outcome than other disease etiologies due to the extensive soft tissue insult and different bacterial flora.

Methods: We conducted a retrospective cohort study of 43 consecutive patients who presented with PFT between 2013 and 2020. The 10 patients who presented with PFT following an animal bite were compared to those who presented with PFT caused by any other etiology.

Results: Patients who were bitten pursued medical attention sooner: 1.9 ± 1.4 days compared with 5.3 ± 4.7 days (P = 0.001). Despite the quicker presentation, patients from the study group received similar antibiotic types and duration as controls. All patients were initially treated with intravenous antibiotics under surveillance of a hand surgeon. One patient (10%) from the study group and four controls (12%) were treated surgically (P = 1). Average follow-up was 17 ± 16 days. At the end of follow-up, one (10%) patient from the study group and three (9%) controls sustained mild range of motion limitation and one (3%) patient from the control group had moderate limitations (P = 0.855).

Conclusions: Intravenous antibiotic treatment, combined with an intensive hand surgeon follow-up, is a viable option for the treatment of PFT caused by animal bites.

Background: Group A Streptococcus (GAS) causes a wide spectrum of acute infections and immune-related diseases, most of which include a dermatological presentation. However, dermatological findings have a wide range of other possible etiologies. The diagnosis of GAS-related disease requires an indication of preceding GAS infection by direct culture or by measuring antistreptolysin O (ASLO) titer.

Objectives: To explore the correlation between ASLO positivity and dermatological diseases.

Methods: We analyzed clinical data from all cases of patients over 18 years of age who underwent ASLO testing between the years 2016 and 2020 in the Department of Dermatology at Rambam Health Care Campus.

Results: Of 152 adult patients with ASLO tests, 100 had diagnoses that were potentially related to streptococcal infection. Vasculitis and psoriasis were the most suspected diagnoses. Positive ASLO test was found in 44 (29%) patients. The diagnoses showing the highest ratio of positive ASLO were psoriasis (60%), erythema nodosum (46%), skin infections (43%), Sweet syndrome (33%), and vasculitis (15%). Psoriasis types included plaque psoriasis (8 patients), guttate psoriasis (3 patients), and palmoplantar pustulosis and erythroderma (2 patients each).

Conclusions: Although the applicability of ASLO for the spectrum of dermatological diseases remains unclear, our results enhance the practical relevance of the test. We showed a higher prevalence of positive ASLO tests in psoriasis and erythema nodosum cases and a lower prevalence in vasculitis. Notably, ASLO was positive in all psoriasis subtypes, suggesting high utility of the test for psoriasis.

Background: Hypothermia, as a sign of serious bacterial infection (SBI) in children and infants older than 90 days is poorly characterized, especially in the post-pneumococcal vaccine era.

Objectives: To assess the prevalence of SBI in children and infants presenting to the pediatric emergency department (PED) with reported or documented hypothermia.

Methods: Retrospective data analysis was conducted of all well-appearing children aged 0–16 years who presented with a diagnosis of hypothermia at two tertiary PEDs from 2010 to 2019.

Results: The study comprised 99 children, 15 (15.2%) age 0–3 months, 71 (71.7%) 3–36 months, and 13 (13.1%) > 36 months. The youngest age group had increased length of stay in the hospital (P < 0.001) and increased rates of pediatric intensive care unit admissions (P < 0.001). Empirical antibiotic coverage was initiated in 80% of the children in the 0–3 months group, 21.1% in the 3–36 months group, and 15.4% in > 36 months (P < 0.001). Only one case of SBI was recorded and no bacteremia or meningitis. Hypothermia of unknown origin was the most common diagnosis in all age groups (34%, 42%, 46%), respectively, followed by bronchiolitis (26%) and hypoglycemia (13.3%) for 0–3 month-old children, unspecified viral infection (20%) and otitis media (7%) for 3–36-month old, and unspecified viral infection (23%) and alcohol intoxication (15.2%) in > 36 months.

Conclusion: There is a low incidence of SBI in well-appearing children presenting to the PED with hypothermia and a benign course and outcome in those older than 3 months.