Israel Medical Association Journal

Recent studies using propensity score matching have clearly indicated that contrast nephropathy following computed tomography occurs in hospitalized patients with advanced chronic kidney disease (eGFR < 30 ml/min/1.73 m²) and that this iatrogenic complication is likely underestimated because of concomitant renal functional recovery, unrelated to the imaging procedure. These findings should be considered regarding contrast-enhanced studies in such patients.

Background: Age-related changes in multiparametric magnetic resonance imaging (mpMRI) of the prostate have been reported in the general population but not in screening cohorts.

Objectives: To evaluate age-related changes on prostatic mpMRI in a screening cohort of BRCA1/2 mutation carriers.

Methods: Asymptomatic BRCA1/2 mutation carriers underwent mpMRI as part of a screening program. All included patients were followed for 3 years with no evidence of prostate cancer. mpMRIs were retrospectively evaluated by two abdominal radiologists for peripheral zone (PZ) patterns on T2 (homogenous hyperintensity, wedge-shaped hypointensities, patchy hypointensities, or diffuse hypointensity), and transition zone (TZ) pattern on T2 (homogenous, heterogeneous, nodular). Apparent diffusion coefficient (ADC) values of PZ and TZ were measured. Statistical analysis was performed using a predefined age cutoff of 50 years old.

Results: Overall, 92 patients were included: 38 in the younger age group (40–49 years) and 54 in the older age group (50–69 years). PZ homogenous hyperintensity and wedge-shaped hypointensities were more common in the older patients, whereas diffuse hypointensity was more common in younger patients (P < 0.001 for both readers) with substantial inter-reader agreement between the readers (kappa=0.643). ADC values were lower in young patients in the PZ (P < 0.001) and TZ (P = 0.003).

Conclusions: Age-related differences in mpMRI were validated in BRCA mutation carriers. As some features overlap with prostatic carcinoma, awareness is crucial, specifically to diffuse T2 hypointensities of the PZ and lower ADC values in the PZ and TZ, which are more common in younger patients.

In the position statement on the definition and diagnosis of acute myocarditis on page XXX of this issue of the Israel Medical Association Journal (IMAJ), we discussed contemporary criteria for definition of acute myocarditis and inflammatory cardiomyopathy [1-6]. We also addressed current diagnostic methods including indications for endomyocardial biopsy (EMB) [7-21]. In this position statement, we discuss the management approaches during hospitalization and following hospital discharge, including specific forms of myocarditis and recommendations for returning to physical activity after myocarditis [21-36].

Background: Morbidly adherent placentation (MAP) increases the risk for obstetric hemorrhage. Cesarean hysterectomy is the prevalent perioperative approach. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive and relatively simple endovascular procedure to temporarily occlude the aorta and control below diaphragm bleeding in trauma. It has been effectively used to reduce obstetric hemorrhage.

Objectives: To evaluate whether REBOA during cesarean delivery (CD) in women with morbidly adherent placentation is a safe and effective treatment modality.

Methods: We introduced REBOA for CD with antepartum diagnosis of MAP in 2019 and compared these patients (RG) to a standard approach group (SAG) treated in our center over the preceding year, as a control. All relevant data were collected from patient electronic files.

Results: Estimated blood loss and transfusion rates were significantly higher in SAG; 54.5% of SAG patients received four RBC units or more vs. one administered in RG. No fresh frozen plasma, cryoprecipitate, or platelets were administered in RG vs. mean 3.63, 6, and 3.62 units, respectively in SAG. Ten SAG patients (90.9%) underwent hysterectomy vs. 3 RG patients (30%). Five SAG patients (45%) required post-surgical intensive care unit (ICU) admission vs. no RG patients. Bladder injury occurred in five SAG cases (45%) vs. 2 RG (20%). One RG patient had a thromboembolic event. Perioperative lactate levels were significantly higher in SAG patients.

Conclusions: Use of REBOA during CD in women with MAP is safe and effective in preventing massive bleeding, reducing the rate of hysterectomy, and improving patient outcome.

Background: Perianal abscesses require immediate incision and drainage (I&D). However, prompt bedside drainage is controversial as it may compromise exposure and thorough anal examination.

Objectives: To examine outcomes of bedside I&D of perianal abscesses in the emergency department (ED) vs. the operating room (OR).

Methods: We conducted a retrospective review of all patients presented to the ED with a perianal abscesses between January 2018 and March 2020. Patients with Crohn’s disease, horseshoe or recurrent abscesses were excluded.

Results: The study comprised 248 patients; 151 (60.89%) underwent I&D in the OR and 97 (39.11%) in the ED. Patients elected to bedside I&D had smaller abscess sizes (P = 0.01), presented with no fever, and had lower rates of inflammatory markers. The interval time from diagnosis to intervention was significantly shorter among the bedside I&D group 2.13 ± 2.34 hours vs. 10.41 ± 8.48 hours (P < 0.001). Of patients who underwent I&D in the OR, 7.3% had synchronous fistulas, whereas none at bedside had (P = 0.007). At median follow-up of 24 months, recurrence rate of abscess and fistula formation in patients treated in the ED were 11.3% and 6.2%, respectively, vs. 19.9% and 15.23% (P = 0.023, 0.006). Fever (OR 5.71, P = 0.005) and abscess size (OR 1.7, P = 0.026) at initial presentation were risk factors for late fistula formation.

Conclusions: Bedside I&D significantly shortens waiting time and does not increase the rates of long-term complications in patients with small primary perianal abscesses.

Background: Group A Streptococcus (GAS), the predominant bacterial pathogen of pharyngitis, is sometimes difficult to distinguish clinically from viral pharyngitis. Despite the high prevalence of viral pharyngitis in children, antibiotic treatment is common.

Objective: To investigate the effectiveness of an antibiotic stewardship program (ASP) on antibiotic prescription in children with GAS pharyngitis (GAS-P) at a large pediatric community clinic.

Methods: Antibiotic prescription data were collected from October 2016 to March 2017 (pre-intervention period) and from October 2017 to March 2018 (post-intervention period). The intervention was a one-day seminar for primary care pediatricians on the diagnosis and treatment of GAS-P in children according to national guidelines.

Results: The overall prevalence of testing differed between the two time periods. There was a decrease in children who did not undergo any testing (from 68% to 63%), an increase in streptococcal rapid antigen detection testing (28% to 32%), and a slight increase in throat cultures (3% to 4%) (p = 0.02). There was no change in the types of antibiotics prescribed before and after the intervention (p = 0.152).

Conclusions: The ASP resulted in a slight reduction in the percentage of children who did not undergo laboratory testing for GAS-P and a slight reduction in the percentage of children who received antibiotic treatment. The ASP did not reduce the use of broad-spectrum antibiotics and macrolides.

Background: Treatment of gestational diabetes mellitus (GDM) has been shown to improve both maternal and neonatal outcomes. For women with GDM who require glucose-lowering medication, insulin is regarded as the drug of choice by most medical societies. Oral therapy, with metformin or glibenclamide, is a reasonable alternative in certain medical circumstances.

Objectives: To compare the efficacy and safety of insulin detemir (IDet) vs. glibenclamide for GDM when glycemic control cannot be achieved through lifestyle modification and diet.

Methods: We conducted a retrospective cohort analysis of 115 women with singleton pregnancy and GDM treated with IDet or glibenclamide. GDM was diagnosed via the two-step oral glucose tolerance test (OGTT) of 50 grams glucose, followed by 100 grams. Maternal characteristics and outcomes (preeclampsia and weight gain) and neonatal outcomes (birth weight and percentile, hypoglycemia, jaundice, and respiratory morbidity) were compared between groups.

Results: In total, 67 women received IDet and 48 glibenclamide. Maternal characteristics, weight gain, and the incidence of preeclampsia were similar in both groups. Neonatal outcomes were also similar. The proportion of large for gestational age (LGA) infants was 20.8% in the glibenclamide group compared to 14.9% in the IDet group (P = 0.04).

Conclusions: In pregnant women with GDM, glucose control on IDet yielded comparable results as on glibenclamide, except for a significantly lower rate of LGA neonates.

Background: A limited program for kidney donation from uncontrolled donation after cardiocirculatory determination of death (uDCDD) was implemented at four hospitals in Israel in close cooperation with Magen David Adom (MDA), the national emergency medical service.

Objectives: To assess the outcome of transplantations performed between January 2017 and June 2022.

Methods: Donor data included age, sex, and cause of death. Recipient data included age, sex, and yearly serum creatinine levels. A retrospective study of out-of-hospital cardiac arrest cases treated by MDA during 2021 were analyzed to assess their compatibility as potential uDCDD donors.

Results: In total, 49 potential donors were referred to hospitals by MDA. Consent was obtained in 40 cases (83%), organ retrieval was performed in 28 cases, and 40 kidneys were transplanted from 21 donors (75% retrieval rate). At 1-year follow-up, 36 recipients had a functioning graft (4 returned to dialysis) and mean serum creatinine 1.59 ± 0.92 mg% (90% graft survival). Outcome after transplantation showed serum creatinine levels (mg%) at 2 years 1.41 ± 0.83, n=26; 3 years 1.48 ± 0.99, n=16; 4 years 1.07 ± 1.06, n=7; and 5 years 1.12 ± 0.31, n=5. One patient died of multiple myeloma at 3 years. The MDA audit revealed an unutilized pool of 125 potential cases, 90 of whom were transported to hospitals and 35 were declared dead at the scene.

Conclusions: Transplant outcomes were encouraging, suggesting that more intensive implementation of the program may increase the number of kidneys transplanted, thus shortening recipient waiting lists.

Background: Cancellation of transesophageal echocardiography (TEE) tests leads to inefficient use of echocardiography laboratory (echo lab) time and wastes resources.

Objectives: To identify the causes of same-day TEE cancellations in hospitalized patients, to formulate a TEE order screening protocol, and to evaluate its efficacy at implementation.

Methods: We performed a prospective analysis of inpatients referred to a single tertiary hospital echo lab for TEE study by inpatient wards. A comprehensive screening protocol emphasizing active participation of all links directly involved in the chain of inpatient TEE referral was developed and implemented. Comparison of pre- and post-implementation of the new screening protocol on two consecutive periods of 6 months on TEE cancellation rates out of total ordered TEEs stratified by cause categories was performed.

Results: In total, 304 inpatient TEE procedures were ordered during the initial observation period; 54(17.8%) were canceled on the same day. The most common cancellation reasons were equally respiratory distress and patient not in fasted state (20.4% of total cancellations and 3.6% of all scheduled TEEs for each cause). Following implementation of the new screening process, total TEEs ordered (192) and cancelled (16) dropped significantly. A decrease in the rate of each cancellation category was observed, with statistical significance achieved for the overall cancellation rate (8.3% vs. 17.8%, P = 0.003), but not for the individual cancellation categories in split analysis.

Conclusions: A concerted effort to implement a comprehensive screening questionnaire significantly reduced same-day cancellations of scheduled TEEs.

Background: Esophageal cancer is comprised of adenocarcinoma and squamous cell carcinoma and is the sixth leading cause of cancer-related mortality worldwide. Upper endoscopy may reveal a partially or completely lumen-occluding mass at diagnosis, yet the prognostic significance of such a presentation is not clear.

Objectives: To investigate whether endoscopic obstructing lesions have a meaning regarding patient prognosis.

Methods: We reviewed upper gastrointestinal endoscopic studies performed over a 20-year period (2000–2020). We compared overall survival, disease stage, histologic criteria, and anatomic location of the lesions in esophagus lumen-obstructing and non-obstructing tumors. Differences between the two groups were statistically evaluated.

Results: Sixty-nine patients were diagnosed with histologically confirmed esophageal cancer. As assessed through endoscopy, 32/69 (46%) patients had obstructive and 37/69 (54%) had non-obstructive cancers. Median survival was significantly shorter in the lumen-obstructing lesions compared with the non-obstructing lesions (3.5 months vs. 10 months, P = 0.001). Female median survival displayed a trend toward shorter survival compared to males (3.5 months vs. 10 months, P = 0.059). There was no statistically significant difference in the percentages of advanced, stage IV disease in the obstructive group and the non-obstructive group (11/32 [34.3%] and 14/37 [37.8%], respectively P = 0.80).

Conclusions: Obstructive esophageal cancers predict shorter median overall survival compared with non-obstructive cancers, without any correlation between obstruction of the lesion and tumor metastatic stage.

Background: Traditionally, transesophageal echocardiography (TEE) has been performed under moderate sedation and local pharyngeal anesthesia. Respiratory complications during the TEE can occur.

Objectives: To test the effectiveness of low-dose midazolam combined with verbal sedation during TEE.

Methods: The study comprised 157 consecutive patients who underwent TEE under mild conscious sedation. All patients received local pharyngeal anesthesia and low doses of midazolam combined with verbal sedation. The course of TEE and clinical characteristics of the patients were analyzed.

Results: The mean age was 64 ± 15.3 years, 96 males (61%). In 6% of the patients, low dose midazolam in combination with verbal sedation was insufficient and propofol was administrated. In women under 65 years of age with normal renal function, there was a 40% risk of low-dose midazolam being ineffective (P = 0.0018).

Conclusions: In most patients, TEE can be conducted easily using low-dose midazolam combined with verbal sedation. Some patients need deeper sedation with anesthetic agents like propofol. These patients tended to be younger, in good general health, and more often female.

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.

Contactin associated protein-like 2 (CASPR2) and leucine-rich glioma-inactivated protein 1 (LGI1) voltage gated potassium channel (VGKC) proteins are found in both the central and peripheral nervous systems [1]. Antibodies against these proteins are associated with encephalopathy, seizures, peripheral nerve hyper-excitability, autonomic dysfunction, hyponatremia, pain, and insomnia in varying severity and combination [1].

Morvan syndrome, first described in 1890, combines symptoms of peripheral nervous system (PNS), central nervous system (CNS), and autonomic nervous system dysfunction. It was later found to be associated with VGKC-complex antibodies, mainly against CASPR2 or LGI1 or both.

Our patient had a history of anti-LGI1 positive limbic encephalitis, which presented years later with anti-CASPR2 positive Morvan syndrome.

Fetal hydrops is a life-threatening condition defined as abnormal accumulation of fluid in two or more fetal compartments: ascites, pleural effusion, pericardial effusion, or generalized skin edema [1]. Fetal hydrops may also be associated with polyhydramnios and placental edema [2].

Based on pathophysiology results, fetal hydrops is classified as either immune or non-immune. The frequency of immune fetal hydrops has decreased dramatically since the development of Rh (D) immunization given to mothers at risk. Nonimmune hydrops fetalis (NIHF) accounts for almost 90% of cases [1]. The etiology of NIHF is further classified as cardiovascular (17–35%), chromosomal (7–16%), hematologic (4–12%), infectious (5–7%), and unknown (15–25%). Inborn errors of metabolism account for only 1–2% of NIHF cases [1]. NIHF is commonly progressive. Complete resolution of NIHF before birth is rare.

Metastatic pulmonary calcinosis (MPC) is characterized by deposits of calcium in normal pulmonary parenchyma. Diffuse pulmonary calcinosis commonly occurs in hypercalcemia and/or hyperphosphatemia and is more commonly related to renal failure than primary hyperparathyroidism, skeletal metastases, or multiple myeloma [1]. Calcium depositions favor alkaline tissue and are thus more common in the upper lobes of the lung, which have a higher ventilation to perfusion ratio and a low capillary pCO₂, resulting in an alkaline pH [2]. Therefore, the most common radiographic manifestation consists of poorly defined nodular opacities bilaterally in the upper lung zones [3].