Israel Medical Association Journal

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: Coronavirus disease-2019 (COVID-19) chest computed tomography (CT) involves ground-glass opacity (GGO) and denser consolidations, which are crucial for diagnosis.

Objectives: To determine optimal window settings for characterization and detection of GGO and dense consolidation on CT imaging in COVID-19 patients using a Simplex-based approach.

Methods: The study included 54 conventional CTs of COVID patients in two phases. First, CT images of 14 patients with GGO and 4 with dense consolidation were included. Seven radiologists evaluated representative images in different windows of varied width and center. They were graded for adequacy of characterization and detection. A Simplex algorithm was used to iteratively determine the optimal window settings. Surface response maps expressing the relationship between window settings and overall reader grades were constructed. Next, the reviewers compared manufacturer recommendations to the new optimal windows found on CT images of 40 patients.

Results: Overall, 12 different window settings were evaluated over a total of 1176 reads. Optimal characterization and detection of pure GGO was seen with a center of 630 HU and width 1460 HU, producing higher grades for both detection and characterization than the manufacturer window settings (P = 0.005). Optimal windowing for dense consolidation was like manufacturer measures (-585 HU and 1800 HU). In phase 2, an overwhelming preference of 78% favoring the optimal window compared to conventional settings was found.

Conclusions: GGO lung opacities characteristic for COVID-19 can be best seen using a lower CT windowing width than the manufacturer's recommendations, unlike denser consolidations, possibly due to differences in underlying pathophysiology.

Background: Uninterrupted antithrombotic treatment (ATT) during cardiac implantable electronic device (CIED) implantation increases bleeding and device-related infections (DRI) risk. The wide-awake-local-anesthesia-no-tourniquet (WALANT) technique, using large-volume local anesthesia and adrenaline, is successful in hand surgeries but its potential to mitigate bleeding risk in CIED implantations remains unknown.

Objectives: To investigate whether WALANT protocol for CIED implantations reduces clinically significant pocket hematoma in patients with a high bleeding risk or is a contraindication for interrupting ATT.

Methods: We conducted a prospective, double-blind, randomized controlled trial with CIED surgery patients on uninterrupted ATT. They received WALANT protocol (lidocaine 1% with adrenaline 1:100,000) or standard protocol (lidocaine 1%). Following implantation, patients were blindly monitored in the ward and pacemaker clinic. Patients were monitored for bleeding outcomes post-implantation.

Results: Forty-six consecutive patients (73.6 ± 9 years, 72% male) were enrolled. In the WALANT group (n=24) no intra-pocket pro-hemostatic agents were needed, compared to 45% in the control group (P = 0.0002). Postoperative pressure dressings were used in 12.5% vs. 68% (P = 0.0002). WALANT patients had smaller hematoma areas (median 3.7 cm² IQR [1–39] vs. 46 cm² [IQR 24–76], P = 0.0004) 1-day postoperative. ATT interruption occurred in 12.5% vs. 18% (P = 0.7). Superficial skin infection rates were 4% vs. 9% (P = 0.6). No DRI occurred. No WALANT-related side effects were observed.

Conclusions: WALANT protocol in CIED implantation with uninterrupted ATT reduced pro-hemostatic agents, pressure-dressing need, and hematoma size. Larger studies are needed to assess its impact on infection rates.

Background: The Agatston coronary artery calcium (CAC) score is a decision-guiding aid for risk assessment and personalized management in the primary prevention of atherosclerotic cardiovascular disease.

Objectives: To explore the real-life clinical experience of CAC testing by characterizing its indications, significance of scores, and corresponding lipid-lowering treatments.

Methods: A retrospective descriptive study of patients treated at the lipids clinic at Rabin Medical Center (Beilinson Campus), who underwent CAC score evaluation between 2017 and 2022 was conducted. The data collected from electronic medical files included demographics, co-morbidities, indications for the test, CAC score levels, and the recommended therapeutic regimen.

Results: The study cohort included 88 patients. The main indication was assessment of the existence of atherosclerosis in cases where there was no clear indication for lipid lowering treatment (65, 74%). In most patients, there was no evidence of atherosclerosis (CAC = 0 AU, n=30) or only mild disease (CAC=1–99 AU, n=35). As the CAC score increased, more patients were prescribed lipid lowering treatments, from very few prescriptions in those with a CAC score of 0 AU and almost 100% among those with score of ≥ 400 AU. The factors that predicted CAC > 0 AU were male sex and older age.

Conclusions: CAC scores should be used more often to determine risk assessment. Further analysis of the implications of scores between 0–400 AU is needed.

Anti-tumor necrosis factor-alpha (anti-TNFα) medications are the most frequently used biologicals to treat inflammatory bowel disease (IBD). Little is known about the ocular side effects of this drug category. We present a case series of six young patients with Crohn disease (CD) and no previous ophthalmologic manifestations who developed blepharitis after commencing treatment with anti-TNFα therapy. Six otherwise healthy patients with CD, with no history of allergies or prior ocular complaints, developed blepharitis at a median of 7.5 months after the initiation of anti-TNFα therapy. All ophthalmic findings were treated topically. The ocular symptoms of two of the patients resolved shortly after discontinuation of the anti-TNFα treatment. The other four presented with relapsing-remitting symptoms. Blepharitis is a common ocular disease in the general population and an extra-intestinal manifestation in patients with IBD. It may be an adverse effect of anti-TNFα therapy in this patient population.

Children affected with Poland syndrome are born with missing or underdeveloped muscles (typically pectoralis major) on one side of the body. Breast abnormalities such as unilateral hypoplasia or agenesis of the breast and nipple may also occur. Other muscles on the affected side, including other muscles in the chest wall, shoulder, arm, and hand, may be missing or underdeveloped [1]. Ribs may be noticeable due to the loss of subcutaneous fat. Sparse or absent axillary and pectoral hairs are a common manifestation of this syndrome.

Background: Abdominal pathology in pregnant patients is a frequent challenge for emergency department physicians. Ultrasound is the imaging modality of choice but is inconclusive in approximately one-third of cases. Magnetic resonance imaging (MRI) is becoming increasingly available, even in acute settings. Multiple studies have defined the sensitivity and specificity of MRI in this population.

Objectives: To evaluate the use of MRI findings in pregnant patients presenting with acute abdominal complaints to the emergency department.

Methods: This retrospective cohort study was conducted at a single institution. Data were collected on pregnant patients who underwent an MRI for acute abdominal complaints between 2010 and 2019 at a university center. Patient demographics, diagnosis at admission, ultrasound and MRI findings, and discharge diagnosis were recorded and evaluated.

Results: In total, 203 pregnant patients underwent an MRI for acute abdominal complaints during the study period. MRI was found without pathology in 138 cases (68%). In 65 cases (32%), the MRI showed findings that could explain the patient's clinical presentation. Patients presenting with long-standing abdominal pain (> 24 hours), fever, leukocytosis, or elevated C-reactive protein values were at a significantly increased risk of having an acute pathology. In 46 patients (22.6%), MRI findings changed the primary diagnosis and management while in 45 patients (22.1%) MRI findings improved characterization of the suspected pathology.

Conclusions: MRI is helpful when clinical and sonographic findings are inconclusive, leading to changes in patient management in more than one-fifth of patients.

Background: Chronic suppurative otitis media is a long-standing middle ear infection with a perforated tympanic membrane. Tympanoplasty is the mainstay of treatment. Most surgeons prefer to operate on dry ears; however, this may be difficult to achieve.

Objectives: To investigate the effect of otorrhea and positive cultures on the outcome of tympanoplasty.

Methods: This retrospective analysis reviewed patients with chronic suppurative otitis media who underwent tympanoplasty 2008–2015. Patients were divided into three groups: active discharge and bacterial growth, active discharge without bacterial growth, and no ear discharge. Surgical outcomes were compared among the groups.

Results: Among 101 patients included, 43 ears (42.6%) had discharge preoperatively, 58 (57.4%) were dry. Overall closure rate was 81.2% (82/101). Preoperative active discharge closure rate was 88.3% (38/43) and without discharge 75.9% (44/58). There were 38 positive cultures preoperatively and five negative cultures. Cultures were not obtained in 58 cases. Success rates were 89.5%, 80%, and 75.9%, respectively. No significant difference was found between patients who had positive or negative cultures before the procedure (P > 0.48) or among the three groups (P = 0.25). The most common bacteria were Pseudomonas aeruginosa (n=17), followed by Staphylococcus species (n=10). None was significantly associated with operative failure (P = 0.557). The postoperative air threshold difference was not affected by culture results (P = 0.3).

Conclusions: Tympanoplasty success rates and postoperative air threshold differences were not affected by the presence of preoperative otorrhea or positive ear cultures. Surgery can be performed even when the ear is not dry.

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: Mean platelet volume (MPV), an essential component of the complete blood count (CBC) indices, is underutilized in common practice. In recent years, MPV has drawn strong interest, especially in clinical research. During inflammation, the MPV has a higher value because of platelet activation.

Objectives: To verify whether high MPV values discovered incidentally in healthy naïve patients indicates the development or the presence of cardiovascular risk factors, particularly metabolic syndrome and pre-diabetes.

Methods: A cohort study was used to assess the diagnostic value of high MPV discovered incidentally, in naïve patients (without any known cause of an abnormal high MPV, greater than  upper limit of the normal range, such as active cardiovascular diseases and metabolic syndrome).

Results: The mean MPV value in the patient group was 12.3 femtoliter. There was a higher incidence of metabolic syndrome in our research group than in the general population and a non-significant tendency of pre-diabetes. Family doctors more frequently meet naïve patients with high MPV than a hospital doctor. The results of our study are more relevant for him, who should know the relevance of such a finding and search for a hidden pre-diabetes or metabolic syndrome.

Conclusions: High MPV values discovered incidentally in healthy naïve subjects suggest the development or the presence of cardiovascular risk factors, particularly metabolic syndrome and pre-diabetes. No statistically significant association was found between MPV and the presence of cardiovascular disease

Background: The 2015 American Thyroid Association (ATA2015) and the American College of Radiology Thyroid Imaging and Reporting Data System (ACR TI-RADS) are two widely used thyroid sonographic systems.

Objectives: To compare the two systems for accuracy of cancer risk prediction.

Methods: Preoperative ultrasound images from 265 patients who underwent thyroidectomy at our hospital from January 2012 to March 2019 were retrospectively categorized by the ACR TI-RADS and ATA2015 systems. Diagnostic performances were compared.

Results: Of 238 nodules assessed, 115 were malignant. Malignancy risks for the five ACR TI-RADS categories were 0%, 7.5%, 11.4%, 59.6%, and 90.0%. Malignancy risks for the five ATA2015 categories were 0%, 6.8%, 17.0%, 55.5%, and 92.1%. The proportion of total nodules biopsied was higher with the ATA2015 system than the ACR TI-RADS system: 88.7% vs. 66.3%. Proportions of malignant nodules and benign nodules biopsied were higher with ATA2015 than with ACR TI-RADS: 93.3% vs. 87.8% and 84.4% vs. 46.3%, respectively. Specificity and sensitivity rates were 53.6% and 84.3%, respectively, for ACR TI-RADS, and 15.5% and 93.3%, respectively, for ATA2015. The two systems showed similarly accurate diagnostic performance (AUC > 0.88). False negative rates for ACR TI-RADS and ATA2015 were 15.6% and 6.6%, respectively. Rates of missed aggressive cancer were similar for the two systems: 3.4% and 3.7%, respectively.

Conclusion: ACR TI-RADS was superior to ATA2015 in specificity and avoiding unnecessary biopsies. ATA2015 yielded better sensitivity and a lower false negative rate. Identification of aggressive cancers was identical in the two systems

Background: Among dialysis patients, occlusive mesenteric vascular disease has rarely been reported.

Objectives: To report on the experience of one center with regard to diagnosing and treating this complication.

Methods: The retrospective case-series involved six patients (3 females, 3 males; age 52–88 years; 5/6 were smokers) on chronic hemodialysis at a single center. All patients with symptoms suggestive of occlusive mesenteric disease and a subsequent angiographic intervention were included. Demographic, clinical, and laboratory data were collected from patient charts for the period before and after angioplasty and stenting of the mesenteric vessels. A Wilcoxon signed-rank test was used to compare the relevant data before and after the intervention.

Results: All participants had variable co-morbidities and postprandial abdominal pain, food aversion, and weight loss. CT angiography was limited due to heavy vascular calcifications. All underwent angioplasty with stenting of the superior mesenteric artery (4 patients) or the celiac artery (2 patients). All procedures were successful in resolving abdominal pain, malnutrition, and inflammation. Weight loss before was 15 ± 2 kg and weight gain after was 6 ± 2 kg. C-reactive protein decreased from 13.4 ± 5.2 mg/dl to 2.2 ± 0.4 mg/dl (P < 0.05). Serum albumin increased from 3.0 ± 0.2 g/dl to 3.9 ± 0.1 g/dl (P < 0.05). Two patients underwent a repeat procedure (4 years, 5 months, respectively). Follow-up ranged from 0.5–7 years.

Conclusions: Occlusive mesenteric ischemia occurs among dialysis patients. The diagnosis requires a high degree of suspicion, and it is manageable by angiography and stenting of the most involved mesenteric artery.

Background: Heart failure with preserved ejection fraction (HFpEF) is a common clinical entity, with a mechanism that appears to involve endothelial dysfunction of the cardiac microcirculation. Endothelial progenitor cells (EPC) are bone marrow derived cells that are able to differentiate into functional endothelial cells and participate in endothelial surface repair.

Objectives: To compare the level and function of EPCs in patients with HFpEF compared with heart failure with reduced ejection fraction (HFrEF) and control subjects.

Methods: We enrolled 21 patients with HFpEF (LVEF ≥ 50%, age 74.5 ± 9.9 years, 43% men, 48% diabetes), 20 patients with HFrEF (LVEF < 40%, age 70 ± 11.5 years, 90% men, 60% diabetes), and 11 control subjects with cardiovascular risk factors (age 53.3 ± 6.1years, 90% men, 64% diabetes). Circulating EPC levels were evaluated by expression of vascular endothelial growth factor receptor-2 (VEGFR-2), CD34, and CD133 by flow-cytometry. EPCs colony forming units (CFUs) were quantified after 7 days in culture.

Results: The proportion of cells that co-expressed VEGFR-2 and CD34 or VEGFR-2 and CD133 was similar among the HFpEF and HFrEF groups, and significantly lower than in the control group. The number of EPC-CFUs was also similar among the two heart failure groups and significantly lower than the control group.

Conclusions: Patients with HFpEF, like HFrEF, have significant reduction in EPC level and function.