Israel Medical Association Journal

Background: The association between use of renin-angiotensin-aldosterone (RAAS) inhibitors and both SARS-CoV-2 infection and the development of severe COVID-19 has been presented in the recent medical literature with inconsistent results.

Objectives: To assess the association between RAAS inhibitor use and two outcomes: infection with SARS-CoV-2 (Model 1) and severe COVID-19 among those infected (Model 2).

Methods: We accessed used electronic health records of individuals from Israel who were receiving anti-hypertensive medications for this retrospective study. For Model 1 we used a case-control design. For Model 2 we used a cohort design. In both models, inverse probability weighting adjusted for identified confounders as part of doubly robust outcome regression.

Results: We tested 38,554 individuals for SARS-CoV-2 who had hypertension and were being treated with medication; 691 had a positive test result. Among those with a positive test, 119 developed severe illness. There was no association between RAAS inhibitor use and a positive test. Use of RAAS inhibitors was associated with a decreased risk for severe COVID-19 (adjusted odds ratio [OR] 0.47, 95% confidence interval [95%CI] 0.29–0.77) compared with users of non-RAAS anti-hypertensive medication. The association remained significant when use of angiotensin-converting-enzyme inhibitors (adjusted OR 0.46, 95%CI 0.27–0.77) and angiotensin II receptor blockers (adjusted OR 0.39, 95%CI 0.16–0.95) were analyzed separately.

Conclusions: Among individuals with hypertension using RAAS inhibitors, we found a lower risk of severe disease compared to those using non-RAAS anti-hypertensive medications. This finding suggests that RAAS inhibitors may have a protective effect on COVID-19 severity among individuals with medically treated hypertension.

Background: The reduced immune response of maintenance hemodialysis patients to coronavirus disease 2019 (COVID-19) vaccines is a major concern.

Objectives: To analyze the late (6 months after full vaccination) antibody response and compare it to early post-vaccination titer.

Methods: We conducted a multicenter prospective study of 13 hemodialysis units in Israel.

Results: We demonstrated that the low titers observed among ESRD patients 2–3 months after vaccination with the Comirnaty vaccine (median 63.8 AU/ml) declined to critically lower values 6 months after full vaccination. (Mediananti S antibodies, 31 AU/ml). Seropositivity significantly declined among hemodialysis patients from 89% to 74% (P < 0.0001), although it did not significantly change among controls.

Conclusions: We recommend all patients on hemodialysis receive a booster COVID-19 vaccine 6 months after the second dose.

Background: Patients with juvenile myoclonic epilepsy (JME) are especially prone to having antiseizure medications (ASMs) withdrawal seizures (WS).

Objectives: To clarify whether WS in JME patients are caused by a high tendency of non-adherence from seizure-free patients or by a constitutive increased sensitivity to drug withdrawal.

Methods: Epilepsy patients followed in a tertiary epilepsy clinic between 2010 and 2013 were included in the study. WS prevalence was compared between drug-responsive and drug-resistant JME patients and patients with other types of epilepsy.

Results: The study included 23 JME patients (16 drug-responsive and 7 drug-resistant) and 138 patients with other epilepsies (74 drug-responsive and 64 drug-resistant). JME patients were younger and included more women than non-JME patients. Significantly more WS were seen in JME than in non-JME patients (P = 0.01) and in the drug-resistant fraction of JME patients in comparison to drug-resistant non-JME patients (P = 0.02). On logistic regression, the type of epilepsy, but not the patient’s sex, was found to significantly predict WS. No significant difference was found in the prevalence of WS between drug-responsive and drug-resistant JME patients. The main ASM discontinued in JME was valproic acid (VPA), especially in women.

Conclusion: Our findings suggest a higher sensitivity of JME patients to withdrawal of medications. It is important to educate JME patients about treatment adherence and to explain to their physicians how to carefully reduce or replace ASMs to mitigate the morbidity and mortality related to ASM withdrawal

Cardiac tumors are rare and the majority are from a primary source outside of the heart. Most are found, incidentally, with echocardiography but often additional cardiac imaging is needed to refine the differential diagnosis. For this purpose, cardiac magnetic resonance imaging (MRI) and to a lesser extent cardiac computed tomography (CT) or ¹⁸F-fluorodeoxyglucose positron-emission tomography/computed tomography (¹⁸F-FDG PET/CT) are useful imaging modalities to better characterize a cardiac tumor and determine the likelihood of a neoplastic versus non-neoplastic origin. Cardiac CT may be useful to evaluate the effect of treatment while using ¹⁸F-FDG PET/CT to evaluate cardiac masses is under-studied but may be useful in patients who are already having a scan performed for oncologic reasons. It is through understanding the clinical context of a newly discovered cardiac mass, knowledge of the typical locations of various cardiac tumor types, combined with imaging techniques that avoid ionizing radiation that yield the greatest confidence in the noninvasive diagnosis of a cardiac mass

Background: Pilonidal sinus is a chronic, inflammatory condition. Controversy exists regarding the best surgical  management for pilonidal sinus, including the extent of excision and type of closure of the surgical wound.

Objectives: To assess the short- and long-term outcomes and success rate of the trephine procedure for the treatment of pilonidal sinus.

Method: A retrospective observational cohort study was conducted at a single center. Patients who underwent trephine procedure between 2011 and 2015 were included. Data collection included medical records review and a telephone interview to establish long-term follow-up.

Results: A total of 169 patients underwent the trephine technique for the repair of pilonidal sinus. Follow-up included 113 patients, median age 20 years. Initial postoperative period, 35.6% recalled no pain and 58.6% reported a mild to moderate pain. Postoperative complications included local infection (7.5%) and mild bleeding (15.1%). On early postoperative follow-up, 47.1% recalled no impairment in quality of life, and 25%, 21.2 %, and 6.7% had mild, moderate and sever disturbance respectively. The median time to return to work or school was 10 days. At a median follow-up of 29 months (IQR 19–40), recurrence rate was 45.1% (51/113), and 38 (33.9%) of the patients underwent another surgical procedure. Overweight, smoking, and family history were associated with higher recurrence rate.

Conclusion: The trephines technique has a significant long-term recurrence rate. Short-term advantages include low morbidity, enhanced recovery, and minimal to mild postoperative impairment to quality of life. The trephine procedure may be justified as a first treatment of pilonidal disease

Background: A paraovarian cyst (POC) is located between the ovary and the fallopian tube. In many cases POCs are diagnosed and managed as ovarian cysts. But since POC are a distinct entity in their clinical presentation and surgical intervention, they should be better defined.

Objectives: To describe the clinical perioperative and operative characteristics of patients with POCs in order to improve pre-operative diagnosis and management.

Methods: A retrospective cohort study of patients with an operative diagnosis of POC between 2007 and 2019 in a single university-affiliated tertiary care medical center was included. Demographic characteristics as well as symptoms, sonographic appearance, surgery findings, and histology results were retrieved from electronic medical records.

Results: During the study period 114 patients were surgically diagnosed with POC, 57.9% were in their reproductive years and 24.6% were adolescents. Most presented with abdominal pain (77.2%). Preoperative sonographic exams accurately diagnosed POC in only 44.7% of cases, and 50.9% underwent surgery due to suspected torsion, which was surgically confirmed in 70.7% of cases. Among women with confirmed torsion, 28.9% involved the fallopian tube without involvement of the ipsilateral ovary. Histology results showed benign cysts in all cases, except two, with a pathological diagnosis of serous borderline tumor.

Conclusions: POC should always be part of the differential diagnosis of women presenting with lower abdominal pain and sonographic evidence of adnexal cysts. If POC is suspected there should be a high level of suspicion for adnexal torsion and low threshold for surgical intervention, especially in adolescent, population who are prone to torsion

Background: Ureteroscopy is becoming the primary treatment for ureteral stones. As a standard of care, ureteroscopy is performed under the supervision of fluoroscopy. Recent advances in endourological technology make the need for fluoroscopy questionable.

Objectives: To summarize our experience with a no-fluoroscopy technique for selected cases of ureteral stones.

Methods: Patients were considered suitable for fluoroless ureteroscopy if they had one or two non-impacted stones, in any location in the ureter, 5–10 mm size, with a normal contralateral renal unit and no urinary tract infection. Procedures were performed using rigid scopes, nitinol baskets/forceps for stone retrieval, and Holmium:YAG laser for lithotripsy. Stents were placed per surgeon's decision.

Results: During an 18-month period, 103 patients underwent fluoroless ureteroscopy. In 94 patients stones were removed successfully. In six, the stones were pushed to the kidney and treated successfully on a separate session by shock wave lithotripsy. In three patients no stone was found in the ureter. In five patients, miniature perforations in the ureter were noted and an indwelling double J stent was placed.

Conclusions: Fluoroless ureteroscopy resulted in a high rate of success. We believe that in selected cases it can be used with minimal adverse events

Background: Patients with high-risk prostate cancer are at higher risk of treatment failure, development of metastatic disease, and mortality. There is no consensus on the treatment of choice for these patients, and either radical prostatectomy (RP) or external beam radiation therapy (EBRT) is recommended. Surgery is less common as the initial treatment for high-risk patients, possibly reflecting the concerns regarding morbidity as well as oncological and functional outcomes. Another high-risk group includes patients with failure of previous EBRT or focal treatment. For these patients, salvage radical prostatectomy (SRP) can be offered.

Objectives: To describe our experience with surgery of high-risk patients and SRP.

Methods: This cohort included all high-risk patients undergoing RP or SRP at our institution between January 2012 and December 2019. We reviewed the electronic medical charts and collected pathological, functional, and oncological outcomes.

Results: Our cohort included 39 patients; average age was 67.8 years, and average follow-up duration was 40.9 months. The most common postoperative morbidity was transfusion of packed cells. There were no life-threatening events or postoperative mortality. Continence was preserved (zero to one pad) in 76% of the patients. Twenty-three patients (59%) had undetectable prostate specific antigen levels following the surgery, 11 (30%) were treated with either adjuvant or salvage EBRT, and 12 patients (31%) were found with no evidence of disease and no additional treatment was needed.

Conclusions: Radical prostatectomy and SRP are safe options for patients presenting with high-risk prostate cancer, with good functional and oncological outcomes.

Background: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations, but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients.

Objectives: To investigate the possible implication of TR among STEMI patients.

Methods: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI) and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR, its relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded.

Results: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%; P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (hazard ratio 2.44; 95% confidence interval 1.06–5.62; P = 0.036) for patients with moderate-severe TR.

Conclusions: Among STEMI patients after primary PCI, the presence of moderate-severe TR was independently associated with adverse outcomes and significantly lower survival rate

Background: For locally advanced rectal cancer patients a watch-and-wait strategy is an acceptable treatment option in cases of complete tumor response. Clinicians need robust methods of patient selection after neoadjuvant chemoradiation.

Objectives: To predict pathologic complete response (pCR) using computer vision. To analyze radiomic wavelet transform to predict pCR.

Methods: Neoadjuvant chemoradiation for patients with locally advanced rectal adenocarcinoma who passed computed tomography (CT)-based simulation procedures were examined. Gross tumor volume was examind on the set of CT simulation images. The volume has been analyzed using radiomics software package with wavelets feature extraction module. Statistical analysis using descriptive statistics and logistic regression was performed was used. For prediction evaluation a multilayer perceptron algorithm and Random Forest model were used.

Results: In the study 140 patients with II–III stage cancer were included. After a long course of chemoradiation and further surgery the pathology examination showed pCR in 38 (27.1%) of the patients. CT-simulation images of tumor volume were extracted with 850 parameters (119,000 total features). Logistic regression showed high value of wavelet contribution to model. A multilayer perceptron model showed high predictive importance of wavelet. We applied random forest analysis for classifying the texture and predominant features of wavelet parameters. Importance was assigned to wavelets.

Conclusions: We evaluated the feasibility of using non-diagnostic CT images as a data source for texture analysis combined with wavelets feature analysis for predicting pCR in locally advanced rectal cancer patients. The model performance showed the importance of including wavelets features in radiomics analysis.

Background: Hip fracture is common in elderly patients and is associated with high morbidity and mortality. Acute kidney injury (AKI) following hip fracture may have additional impact on clinical outcomes.

Objectives: To investigate the incidence of AKI, the risk factors for its occurrence and impact on mortality, timing of surgery, and length of hospitalization (LOS) in patients undergoing hip fracture surgery.

Methods: We retrospectively examined the records of patients who underwent hip fracture surgery between 2013 and 2017. All patients had a baseline serum creatinine value and at least one later value. AKI was defined according to KDIGO guidelines.

Results: The study included 511 patients. Mean age was 72.6 years, 325 males (63.4%); 151 (29.5%) had baseline eGFR < 60 ml/min/1.73m². Of these, 87 (17%) developed AKI. Older age, diabetes mellitus, hypertension, and chronic heart condition were significantly more common in patients who developed AKI. Patients with AKI had increased 30-day mortality (hazard ratio [HR] 3.96, 95% confidence interval [95%CI] 1.62–9.7, P = 0.003) and mortality at one year (HR 2.72, 95%CI 1.5–4.9, P = 0.002). AKI was associated with surgery delay > 48 hours (HR 2.241, 95%CI 1.206–4.165, P = 0.011). Mean LOS was 10.9 days and 8 days for patients with AKI and without, respectively, P < 0.0001.

Conclusions: AKI is a common complication in patients with hip fracture and is associated with increased short- and long-term mortality, delayed surgery, and longer hospitalization. Interventions identifying and monitoring patients at risk may contribute to improve the outcomes

Background: Cystic periventricular leukomalacia (cPVL) is a strong indicator of subsequent motor and developmental impairments in premature infants. There is a paucity of publications on biomarkers of cPVL.

Objectives: To determine C-reactive protein (CRP) levels during the first week of life of preterm infants who later developed cPVL and to identify the association between CRP levels with perinatal factors.

Methods: We retrospectively included infants ≤ 32 weeks gestation and/or birth weights ≤ 1500 grams; 17 with a cranial ultrasound diagnosis of cPVL and 54 with normal ultrasounds. Serum CRP levels were measured during days 1-7 (CRP^1–7d) of life and subdivided into two timing groups: days 1–3 (CRP^1–3d) and days 4-7 (CRP^4–7d).

Results: The cPVL group had significantly higher mean CRP^4–7d levels compared to controls (12.75 ± 21.2 vs. 2.23 ± 3.1, respectively, P = 0.03), while CRP^1–3d levels were similar. CRP^1–7d levels were significantly correlated with maximal fraction of inspired oxygen during the first 12 hours of life (FiO₂-12h, r = 0.51, P < 0.001]. Additional risk factors were not associated with CRP levels.

Conclusions: Our finding of elevated CRP^4-7d levels and later development of cPVL supports earlier studies on the involvement of inflammation in the pathogenesis of cPVL. Whether CRP could serve as a biomarker of cPVL and its correlation with outcomes, awaits further trials. Furthermore, the correlation between FiO₂-12h and CRP^1–7d levels suggest that hypoxia and/or hyperoxia may serve as a trigger in the activation of inflammation during the first days of life of preterm infants