Israel Medical Association Journal

Background: The single-breath diffusing capacity of the lungs (DLCO_SB) test measures the extent to which carbon monoxide (CO) passes from the lung air sacs into the blood. The accessible alveolar volume (VA_SB) is measured by inert gas during a 10-second period. The single-breath transfer coefficient of the lung for carbon monoxide (KCO_SB) is the DLCO_SB divided by VA_SB. Cystic fibrosis (CF) disease comprises progressive airway obstruction with bronchiectasis and parenchyma fibrosis. Yet, the KCO_SB appears insignificant in the assessment of pulmonary function in CF.

Objectives: To challenge the precision of normal KCO_SB in CF.

Methods: The authors collected pulmonary function tests (PFT) data from 74 confirmed CF patients (mean age 26 ± 10 years) with various levels of pulmonary disease severity. Tests included spirometry, DLCO_BP, and body plethysmography (_BP). Anatomical dead space was calculated by deducting anatomical dead space from total lung capacity TLC(_BP) to establish alveolar volume (VA_BP) and to determine KCO_BP. We also included individual data of arterial pCO₂ blood-gas level.  

Results: KCO_SB values were normal or higher in most patients, regardless of patient FEV1 value (R² = 0.2204; P < 0.02). In contrast, the measurements of KCO_BP were low corresponding with low FEV1 values, and negatively correlated with the elevation of trapped air and pCO₂ levels (R² = 0.1383; P = 0.0133, P > 0.05, respectively).

Conclusions: The 10- second perfusion time of the inert gas during DLCO_SB represent the communicative alveolar volume in CF patients with advanced pulmonary disease. The findings justify the use of DLCO_SB with the deterioration of FEV1 and elevation of pCO₂ levels.

Background: Acute pulmonary embolism (PE) is considered to be one of the most common cardiovascular diseases with considerable mortality. Conflicting data imply possible role for echocardiography in assessing this disease.

Objectives: To determine which of the echo parameters best predicts short-term and long-term mortality in patients with PE.

Methods: We prospectively enrolled 235 patients who underwent computed tomography of pulmonary arteries (CTPA) and transthoracic Echocardiography (TTE) within < 24 hours. TTE included a prospectively designed detailed evaluation of the right heart including right ventricular (RV) myocardial performance index (RIMP), RV end diastolic and end systolic area, RV fractional area change, acceleration time (AT) of pulmonary flow and visual estimation. Interpretation and performance of TTE were blinded to the CTPA results.

Results: Although multiple TTE parameters were associated with PE, all had low discriminative capacity (AUC < 0.7). Parameters associated with 30-day mortality in univariate analysis were acceleration time (AT) < 81 msec (P = 0.04), stroke volume < 44 cc (P = 0.005), and RIMP > 0.42 (P = 0.05). The only RV independent echo parameter associated with poor long-term prognosis (adjusted for significant clinical, and routine echo associates of mortality) was RIMP (hazard ratio 3.0, P = 0.04). The only independent RV echo parameters associated with mortality in PE patients were RIMP (P = 0.05) and AT (P = 0.05). Addition of RIMP to nested models eliminated the significance of all other parameters assessing RV function.

Conclusions: Doppler-based parameters like pulmonary flow AT, RIMP, and stroke volume, have additive value in addition to visual RV estimation to assess prognosis in patients with PE.

Background: Ferritin, the cellular protein storage for iron, has emerged as a key molecule in the immune system, orchestrating the cellular defense against inflammation. At the end of 2019, the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rapidly spread throughout China and other countries around the world, resulting in a viral pandemic.

Objectives: To evaluate the correlation between ferritin and disease severity in coronavirus disease-2019 (COVID-19).

Methods: In this cross-sectional study, we obtained clinical and laboratory data regarding 39 hospitalized patients with confirmed COVID-19 from two hospitals in Israel.

Results: A significant increase in ferritin levels was demonstrated in patients with moderate and severe disease, compared to patients with mild disease (P = 0.006 and 0.005, respectively). Severe patients had significantly higher levels of ferritin (2817.6 ng/ml) than non-severe patients (708.6 ng/ml) P = 0.02.

Conclusions: In this preliminary cross-sectional study, elevated ferritin levels were shown to correlate with disease severity in 39 patients from Israel with confirmed COVID-19 infection. Our results further strengthen the hypothesis that severe COVID-19 disease might be due to an underlying dysregulated hyperimmune response. In order to identify these patients early and prioritized resources, we believe that all patients with COVID-19 should be screened for hyperferritinemia.

Background: Recently, studies have found that non-alcholic fatty liver disease (NAFLD) is associated with bacterial infections. Attempts to identify risk factors for recurrent urinary tract infections (rUTIs) are still underway.

Objectives: To examine a possible association between NAFLD and rUTIs among premenopausal women.

Methods: In a case-control study, 1009 hospitalized premenopausal women with a UTI during a period of 3 years were retrospectively studied. A total of 186 subjects with rUTIs and 186 controls without a history of rUTIs were included in this study. Each participant had an abdominal ultrasonogram as part of the inclusion criteria. The two groups were compared in terms of risk factors for rUTIs, such as maternal history of rUTIs, use of contraceptives, frequency of sexual intercourse, metabolic syndrome, obesity, use of probiotics, serum levels of vitamin D, and NAFLD. An rUTI was defined as three or more episodes of UTI over a period of 1 year. NAFLD was diagnosed based on abdominal ultrasonography examination.

Results: Mean age of the 372 participants was 39.7 ± 5 years. NAFLD was diagnosed in 81/186 subjects (43.5%) with rUTIs vs. 40/186 controls (21.5%), P = 0.05. Women with rUTIs were more often obese and presented with lower serum levels of vitamin D than controls. Multivariate analysis showed that NAFLD (odds ratio = 1.6, 95% confidence interval 1.3–2.0, P = 0.04) were associated with rUTIs in premenopausal women.

Conclusions: NAFLD was associated with rUTI in premenopausal women, independent of metabolic syndrome. Further studies are needed to confirm this association.

Background: Erythema nodosum (EN) is the most common type of panniculitis, commonly secondary to infectious diseases.

Objectives: To elucidate the causative factors and the clinical presentation of patients with EN (2004–2014) and to compare their data to those reported in a previous study.

Methods: A retrospective study was conducted of all patients diagnosed with EN who were hospitalized at Soroka University Medical Center (2004–2014). The clinical, demographic, and laboratory characteristics of the patients were compared to those in a cohort of patients diagnosed with EN from 1973–1982.

Results: The study comprised 45 patients with a diagnosis of EN. The most common symptoms of patients hospitalized with EN were arthritis or arthralgia (27% of patients). Patients with EN, compared to those reported in 1987, has significantly lower rates of fever (18% vs. 62% P < 0.001), streptococcal infection (16% vs. 44%, P = 0.003), and joint involvement (27% vs. 66%, P < 0.001). In addition, fewer patients had idiopathic causes of EN (9% vs. 32%, P = 0.006).

Conclusions: In the past decades, clinical, epidemiological, and etiological changes have occurred in EN patients. The lowering in rate of fever, streptococcal infection, and joint involvement in patients with EN are probably explained by improvements in socioeconomic conditions. The significantly decreasing rate of idiopathic causes of EN is possibly due to the greater diagnostic accuracy of modern medicine. The results of the present study demonstrate the impact of improvements in socioeconomic conditions and access to healthcare on disease presentation.

Background: Extended-spectrum beta-lactamase (ESBL) production is the most common antimicrobial resistance mechanism in the neonatal intensive care unit (NICU), with colonization and blood stream infections being a major threat to this population. Since 2013, all NICU admissions at our facility were screened twice weekly for ESBL colonization.

Objectives: To determine independent risk factors for colonization of infants with ESBL-producing bacteria in the NICU.

Methods: A retrospective case study of ESBL-colonized infants vs. controls (matched by date of birth and gestational age) was conducted in the NICU of Soroka University Medical Center, Israel, between 2013 and 2014. Epidemiological, laboratory, and clinical data were extracted from medical files. Univariable and multivariable analyses were used to assess associations between ESBL colonization and possible clinical risk factors.

Results: Of 639 admissions during the study period, 87 were found to be ESBL-colonized (case infants) and were matched to 87 controls. Five case infants became infected (5.7%) with ESBL strains. Klebsiella pneumoniae was the most common isolated bacteria. The mean time from admission to colonization was 15 days. Univariable analysis showed an association of male gender and highest Apgar score at 1 and 5 minutes with ESBL colonization (P < 0.05). Multivariable analysis yielded only a possible association of higher Apgar score at 1 and 5 minutes (hazard ratio [HR] 1.515, 95% confidence interval [95%CI] 0.993-2.314; HR 1.603, 95%CI 0.958–2.682, respectively) with ESBL colonization.

Conclusions: Future studies should focus on maternal colonization and possible strategies for preventing vertical transmission of ESBL strains to high-risk neonates.

Background: Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients.

Objectives: To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. 

Methods: In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. 

Results: The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data.

Conclusions: Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported.