Israel Medical Association Journal

Background: Preeclampsia is a unique vascular disease during pregnancy that generally appears after 20 of weeks gestation or until 6 weeks after delivery. Left undiagnosed, preeclampsia can lead rapidly to death of both mother and fetus.

Objectives: To verify the efficacy of peripheral blood inflammatory markers (BIMs)in diagnosing preeclampsia and compare them with results from other studies.

Methods: Our retrospective case-control study comprised two patient groups. Pregnant women with preeclampsia and pregnant women without preeclampsia were compared for BIMs: neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and mean platelet volume (MPV). The primary endpoint of our research was to assess the predictive power of BIMs for preeclampsia diagnosis.

Results: The sample size was calculated based on expected differences of BIMs between the control and study groups. Comparison of quantitative variables was conducted with independent sample t-test or alternatively by Wilcoxon rank sum test. The MPV values were slightly higher in the preeclampsia group, but not statistically significant. NLR and PLR did differentiate between study and control groups.

Conclusions: The diagnostic accuracy of BIMs is unsatisfactory for preeclampsia diagnosis. Discrepancies concerning these values need to be clarified. Further large prospective studies are necessary to validate the potential factor accuracy in preeclampsia diagnosis.

Idiopathic eosinophilic vasculitis is a newly recognized form of hypereosinophilic syndrome. While little is understood about the condition, criteria for its definition have been proposed. We aimed to determine whether three patients with eosinophilia and vasculitis could be retrospectively diagnosed with this condition. We performed a retrospective descriptive analysis on three cases with hypereosinophilia and vasculitis who were treated in Sheba Medical Center, Sourasky Medical Center, and Meir Medical Center in Israel between 2009 and 2021. A thorough review of all three cases was conducted. The findings were compared to the suggested criteria for idiopathic eosinophilic vasculitis.

All patients shared the symptoms of progressive limb ischemia, eosinophilic rash, and peripheral neuropathy that are consistent with vasculitis. No lower or upper respiratory abnormalities or the presence of anti-neutrophil cytoplasmic antibodies (ANCA) autoantibodies associated with eosinophilic granulomatosis with polyangiitis were detected. Primary monoclonal abnormalities, drug interactions, infections, allergy, and other secondary causes of hypereosinophilia were excluded. After a thorough review, we suggest that our three patients with previously unexplained hypereosinophilia and vasculitis fit the diagnosis of idiopathic eosinophilic vasculitis. These results highlight the existence of this novel condition and the importance of its recognition and consideration as part of the differential diagnosis in patients with marked eosinophilia and vasculitis. Further research for elucidating the mechanisms and treatment approach for this potentially severe condition is urgently needed.

Background: The neutrophil to lymphocyte ratio (NLR) has demonstrated prognostic value in various malignant conditions, including gastric adenocarcinoma. However, chemotherapy may affect NLR.

Objectives: To evaluate the prognostic value of NLR as an accessory decision-making tool in terms of operating patients after neoadjuvant chemotherapy in patients with resectable gastric cancer.

Methods: We collected oncologic, perioperative, and survival data of patients with gastric adenocarcinoma who underwent curative intent gastrectomy and D2 lymphadenectomy between 2009 and 2016. The NLR was calculated from preoperative laboratory tests and classified as high (> 4) and low (≤ 4). The t-test, chi-square, Kaplan-Meier analysis, and Cox multivariate regression models were used to assess associations of clinical, histologic, and hematological variables with survival.

Results: For 124 patients the median follow-up was 23 months (range 1–88). High NLR was associated with greater rate of local complication (r=0.268, P < 0.01). The rate of major complications (Clavien-Dindo ≥ 3) was higher in the high NLR group (28% vs. 9%, P = 0.022). Among the 53 patients who received neoadjuvant chemotherapy, those with low NLR had significantly improved disease-free survival (DFS) (49.7 vs. 27.7 months, P = 0.025). Low NLR was not significantly associated with overall survival (mean survival, 51.2 vs. 42.3 months, P = 0.19). Multivariate regression identified NLR group (P = 0.013), male gender (P = 0.04), and body mass index (P = 0.026) as independently associated with DFS.

Conclusions: Among gastric cancer patients planned for curative intent surgery who underwent neoadjuvant chemotherapy, NLR may have prognostic value, particularly regarding DFS and postoperative complications.

Background: Among chronic kidney disease (CKD) patients, baseline neutrophil gelatinase-associated lipocalin (NGAL) may reflect the severity of renal impairment. No data exists on serial changes in serum NGAL levels in CKD patients before and after percutaneous coronary intervention (PCI).

Objectives: To evaluate serial serum NGAL levels relation to contrast induced acute kidney injury (CI-AKI) following PCI.

Methods: The study included 58 patients with CKD who underwent elective PCI. Plasma NGAL measurements were performed before (pre-NGAL) and 24 hours following (post-NGAL) PCI. Patients were followed for CI-AKI and changes in NGAL levels. Receiver operator characteristic identified the optimal sensitivity and specificity for pre-NGAL levels compared with post-NGAL for patients with CI-AKI.

Results: Overall CI-AKI incidence was 33%. Both pre-NGAL (172 vs. 119 ng/ml, P < 0.001) and post-NGAL (181 vs. 121 ng/ml, P < 0.001) levels were significantly higher in patients with CI-AKI, but no significant changes were detected. Pre-NGAL levels were similar to post-NGAL levels in predicting CI-AKI (area under the curve 0.753 vs. 0.745). Optimal cutoff value for pre-NGAL was 129 ng/ml (sensitivity of 73% and specificity of 72%, P < 0.001). Post-NGAL levels > 141 ng/ml were independently associated with CI-AKI (hazard ratio [HR] 4.86, 95% confidence interval [95%CI] 1.34–17.64, P = 0.02) with a strong trend for post-NGAL levels > 129 ng/ml (HR 3.46, 95%CI 1.23–12.81, P = 0.06).

Conclusions: In high-risk patients, pre-NGAL levels may predict CI-AKI. Further studies on larger populations are needed to validate the use of NGAL measurements in CKD patients.

Background: Neutrophil-to-lymphocyte ratio (NLR) is a simple and cost-effective marker of inflammation. This marker has been shown to predict cardiac arrhythmias, progression of valvular heart disease, congestive heart failure decompensation, acute kidney injury, and mortality in cardiovascular patients. The pathologic process of aortic stenosis includes chronic inflammation of the valve and therefore biomarkers of inflammation might offer additive prognostic value.

Objectives: To evaluate NLR and its association with long term mortality in transcatheter aortic valve implantation (TAVI) patients.

Methods: We evaluated data of 1152 consecutive patient from the Tel Aviv Medical Center TAVI registry who underwent TAVI. Data included baseline clinical, demographic, and echocardiographic findings; procedural complications; and post-procedure mortality. Patients were compared by using the median NLR value (4.1) and evaluated for long-term mortality.

Results: Patients with NLR above the median had higher mortality rates (26.4% vs. 16.3%, P < 0.001) at 3 years post-procedure. A multivariable analysis found NLR to be an independent risk factor for mortality (hazard ratio = 1.47, 95% confidence interval 1.09–1.99, P = 0.013). In addition, high NLR was linked to complicationsduring and after the procedure.

Conclusion: NLR is an independent prognostic marker among TAVI patients. This marker may represent an increased inflammatory response and should be added to previous known prognostic factors.

Background: The CHA₂DS₂-VASc score has been shown to predict systemic thromboembolism and mortality in certain groups in sinus rhythm (SR), similar to its predictive value with atrial fibrillation (AF).

Objectives: To compare factors of inflammation, thrombosis, platelet reactivity, and turnover in patients with high versus low CHA₂DS₂-VASc score in SR.

Methods: We enrolled consecutive patients in SR and no history of AF. Blood samples were collected for neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), immature platelet fraction (IPF%) and count (IPC), CD40 ligand, soluble P-selectin (sP-selectin) and E-selectin. IPF was measured by autoanalyzer and the other factors by ELISA.

Results: The study comprised 108 patients (age 58 ± 18 years, 63 women (58%), 28 (26%) with diabetes), In addition, 52 had high CHA₂DS₂-VASc score (³ 2 for male and ³ 3 for female) and 56 had low score. Patients with low scores were younger, with fewer co-morbidities, and smaller left atrial size. sP-selectin was higher in the high CHA₂DS₂-VASc group (45, interquartile ratio [IQR] 36–49) vs. 37 (IQR 28–46) ng/ml, P = 0.041]. Inflammatory markers were also elevated, CRP 3.1 mg/L (IQR 1.7–9.3) vs. 1.6 (IQR 0.78–5.4), P < 0.001; NLR 2.7 (IQR 2.1–3.8) vs. 2.1 (IQR 1.6–2.5), P = 0.001, respectively. There was no difference in E-selectin, CD40 ligand, IPC, or IPF% between the groups.

Conclusions: Patients in SR with high CHA₂DS₂-VASc score have higher inflammatory markers and sP-selectin. These findings may explain the higher rate of adverse cardiovascular events associated with elevated CHA₂DS₂-VASc score.

Background: Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread musculoskeletal pain accompanied by various additional symptoms. The prevalence of FMS ranges between 2–8% of the population. The exact pathophysiology of the disease remains unknown, and under certain circumstances it is difficult for the physician to diagnose. Previous studies have shown a correlation between inflammatory biomarkers such as C-reactive protein (CRP) and FMS activity, suggesting that an inflammatory component may play a role in this disease pathogenesis.

Objectives: To investigate the role of certain new inflammatory biomarkers in the diagnosis of patients with FMS.

Methods: In this study data were collected from FMS patients who were admitted to Ziv Medical Center during the period 2013 to 2019 in an attempt to find a connection between inflammatory markers detectable by a traditional complete blood count (CBC) tests such as neutrophil-lymphocytes ratio (NLR), platelet-lymphocyte ratio (PLR), mean platelet value (MPV), red cell distribution width (RDW), and C-reactive protein (CRP) and FMS.

Results: We found significantly higher CRP levels, MPV, and PLR and lower lymphocyte count in the FMS group compared to the control group.

Conclusions: FMS has certain inflammatory components that may be useful in disease diagnosis

Background: Immune cell counts in blood in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may be useful prognostic biomarkers of disease severity, mortality, and response to treatment.

Objectives: To analyze sub-populations of lymphocytes at hospital admission in survivors and deceased from severe pneumonia due to coronavirus disease-2019 (COVID-19).

Methods: We conducted a cross-sectional study of healthcare workers confirmed with SARS-CoV-2 in convalescents (control group) and healthy controls (HC) diagnosed with severe COVID-19. Serum samples were taken at hospital admission and after recovery. Serum samples ≥ 25 days after onset of symptoms were analyzed for lymphocyte subpopulations through flow cytometry. Descriptive statistics, Kruskall-Wallis test, receiver operating characteristic curve, calculation of sensitivity, specificity, predictive values, and Kaplan-Meier analysis were performed.

Results: We included 337 patients: 120 HC, 127 convalescents, and 90 severe COVID-19 disease patients (50 survivors, 40 deceased). For T cells, total lymphocytes ≥ 800/μL, CD3+ ≥ 400/μL, CD4+ ≥ 180/μL, CD8+ ≥ 150/μL, B cells CD19+ ≥ 80/μL, and NK ≥ 34/μL subsets were associated with survival in severe COVID-19 disease patients. All subtypes of lymphocytes had higher concentrations in survivors than deceased, but similar between HC and convalescents. Leukocytes ≥ 10.150/μL or neutrophils ≥ 10,000/μL were associated with increased mortality. The neutrophil-to-lymphocyte ratio (NLR) ≥ 8.5 increased the probability of death in severe COVID-19 (odds ratio 11.68).

Conclusions: Total lymphocytes; NLR; and levels of CD3+, CD4+, CD8+, and NK cells are useful as biomarkers of survival or mortality in severe COVID-19 disease and commonly reach normal levels in convalescents.

Background: Bariatric surgery has become the most common and effective therapeutic option for obesity. However, it is associated with morbidity and complications. Identification of predictors for surgical complications is an unmet need.

Objectives: To determine a simple non-invasive parameter that predicts early postoperative complications following bariatric surgery.

Methods: In this retrospective study of all patients who underwent elective bariatric surgery at Nazareth Hospital EMMS during a 4-year period (2015–2018). We collected clinical and laboratory parameters and determined predictors of complications.

Results: A total of 345 patients underwent bariatric surgery during the study period. Of the patients, 51 experienced early post-bariatric surgery complications as compared to 294 patients who had no complications. Univariate analysis revealed that neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR] 1.912, P < 0.0001) and platelet to lymphocyte ratio (OR 1.015, P < 0.0001) were associated with post-bariatric surgery complications. In a multivariate logistic regression analysis, only NLR remained a significant predictor (OR 1.751, 95% confidence interval 1.264–2.425, P = 0.0008) with a receiver operating characteristic curve for NLR of 0.8404.

Conclusions: We found that the NLR predicts post bariatric surgery early complications. Further prospective studies are needed to validate our findings.

Background: The incidence of Clostridium difficile-associated diarrhea (CDAD) is increasing and is associated with significant morbidity and mortality. Therefore, there is a need to find new tools to determine the severity of the disease.

Objectives: To investigate the prognostic values of inflammatory markers such as mean platelet volume (MPV), neutrophil-lymphocyte ratio (NLR), and C-reactive protein (CRP) in patients with CDAD.

Methods: The study comprised of 100 patients diagnosed with CDAD. The study included an additional control group of 69 patients with diarrhea who were negative for C. difficile toxin. The control group was age- and sex-matched and hospitalized at the same time period. NLR and MPV were obtained from complete blood count results. Serum CRP levels were measured by the latex particle enhanced immunoturbidimetric assay. Blood samples for all inflammatory markers were collected at time of diagnosis and prior to initiating the antibiotic therapy. Demographic, clinical, laboratory, and prognostic data were collected from medical records for a period of 90 days from the initial diagnosis of CDAD.

Results: The mean age of the CDAD group was 68.6 ± 21.5 years compared to 65.6 ± 24.5 in the control group (P = 0.29). Our findings show that patients with CDAD had significantly higher NLR, MPV and serum CRP levels compared to the control group (P < 0.001)). Moreover, significantly higher levels were observed when CDAD was fatal (P < 0.001).

Conclusions: Elevated NLR, MPV, and serum CRP levels may serve as biomarkers for prediction of recurrence and mortality in patients with CDAD.