Israel Medical Association Journal

Background: Perivascular cuffing as the sole imaging manifestation of pancreatic ductal adenocarcinoma (PDAC) is an under-recognized entity.

Objectives: To present this rare finding and differentiate it from retroperitoneal fibrosis and vasculitis.

Methods: Patients with abdominal vasculature cuffing were retrospectively collected (January 2011 to September 2017). We evaluated vessels involved, wall thickness, length of involvement and extra-vascular manifestations.

Results: Fourteen patients with perivascular cuffing were retrieved: three with celiac and superior mesenteric artery (SMA) perivascular cuffing as the only manifestation of surgically proven PDAC, seven with abdominal vasculitis, and four with retroperitoneal fibrosis. PDAC patients exhibited perivascular cuffing of either or both celiac and SMA (3/3). Vasculitis patients showed aortitis with or without iliac or SMA cuffing (3/7) or cuffing of either or both celiac and SMA (4/7). Retroperitoneal fibrosis involved the aorta (4/4), common iliac (4/4), and renal arteries (2/4). Hydronephrosis was present in 3/4 of retroperitoneal fibrosis patients. PDAC and vasculitis demonstrated reduced wall thickness in comparison to retroperitoneal fibrosis (PDAC: 1.0 ± 0.2 cm, vasculitis: 1.2 ± 0.5 cm, retroperitoneal fibrosis: 2.4 ± 0.4 cm; P = 0.002). There was no significant difference in length of vascular involvement (PDAC: 6.3 ± 2.1 cm, vasculitis: 7.1 ± 2.6 cm, retroperitoneal fibrosis: 8.7 ± 0.5 cm).

Conclusions: Celiac and SMA perivascular cuffing can be the sole finding in PDAC and may be indistinguishable from vasculitis. This entity may differ from retroperitoneal fibrosis as it spares the aorta, iliac, and renal arteries and demonstrates thinner walls and no hydronephrosis.

Background: Depression has been shown to be associated with cervical tumors (CTs), an association mostly demonstrated in studies in which temporality could not have been ascertained.

Objectives: To study the association between depression and CTs and the influence of co-morbidities of this association in a large cohort study.

Methods: A retrospective computer-based cohort study was conducted. The cohort included 357,450 female members of Maccabi Healthcare Services. The cohort was classified as depressed or non-depressed using the International Classification of Diseases 9/10 codes. For each subgroup, demographic characteristics, behavioral characteristics, co-morbidities, and CTs diagnosis were obtained. The burden of co-morbidities was defined as the sum of major co-morbidities. We used zero-inflated negative binomial regression analysis due to over-dispersion to estimate the relative risk (RR) for CTs with 95% confidence interval (95%CI).

Results: Depression was diagnosed in 15,789 women. Among this group, CTs were diagnosed in 1585 (10.0%). Among the 341,661 non-depressed, CTs were diagnosed in 4185 (1.2%). After adjustment to age and socioeconomic status, the association between depression and CTs was RR=9.2 (95%CI 8.7–9.9, P-value < 0.0001). The association between depression and CTs increased as the burden of clinical conditions increased (P-value < 0.0001).

Conclusions: Women with depression are at a higher risk for CTs, especially among those who have several co-morbidities. Tighter gynecology surveillance is crucial among these women.

Background: In Israel, breast cancer prevalence is lower among Arab than Jewish women, but incidence is increasing among Arab women at a younger age.

Objectives: To explore differences between Arab and Jewish women with breast cancer with respect to age at diagnosis, associated risk factors, and use of hormonal medications.

Methods: We conducted a retrospective database study comparing Arab and Jewish women with breast cancer focusing on age at diagnosis, smoking history, obesity, and previous hormonal medication usage, including oral combined contraceptive pills (OCCP), progestogens, hormonal medications for treatment of infertility, and hormone replacement therapy (HRT).

Results: The study included 2494 women who were diagnosed with breast cancer during 2004–2015. Age at diagnosis was lower among Arab women (50.7 ± 13.1 years vs. 55.4 ± 12.6 years, P < 0.0001). The rate of smoking was higher among Jewish women (16.0% vs. 4.3%, P < 0.0001). The rate of obesity was higher in Arab women older than 50 years at diagnosis (59.0% vs. 42.4%, P < 0.0001). Arab women demonstrated a lower overall chance of previous use of all types of hormonal medications (odds ratio [OR] 0.6, 95% confidence interval [95%CI] 0.6–0.8) compared to Jewish women. Arab women were more likely to have used progestogens (OR 1.7, 95%CI 1.4–2.2) and medications for treatment of infertility (OR 2.3, 95%CI 1.5–3.4) and less likely OCCP (OR 0.4, 95%CI 0.3–0.6) and HRT (OR 0.4, 95%CI 0.3–0.5).

Conclusions: Previous use of hormonal medications may contribute to incidence of breast cancer in Arab women.

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.

Carpal tunnel syndrome (CTS) is a collection of symptoms and signs caused by compression of the median nerve as it travels through the carpal tunnel. Symptoms include paresthesia and/or numbness in the median nerve distribution, aching in the thenar eminence, and weakness at later stages. CTS is the most common entrapment neuropathy with a prevalence of 1–5%, and even higher among females, manual workers, and the elderly. Therefore, many patients with signs and symptoms of CTS refer to their primary care physician who should recognize, diagnose, and provide initial treatment.

Background: Infants younger than 6 months of age are not eligible for coronavirus disease 2019 (COVID-19) vaccinations. Maternal variables during pregnancy and the postnatal period may affect the clinical and laboratory course of COVID-19 positive infants.

Objective: To assess the clinical manifestation and laboratory differences in infants with three maternal variables: breastfeeding, vaccinated, and co-illness.

Methods: We conducted a single-center retrospective cohort study of positive COVID-19 infants with three subgroups of maternal variables. The population included infants under 6 months of age hospitalized due to COVID-19. Data about clinical features, laboratory tests, and maternal information including vaccination status, breastfeeding status and maternal positive COVID-19 infection was gathered. All variables were compared among the three subgroups.

Results: Breastfed infants had shorter hospitalization period (mean 2.61 ± 1.378 days) compared to non-breastfed infants (mean 3.8 ± 1.549) (P = 0.051). COVID-19 infants of positive COVID-19 mothers had a higher absolute neutrophil count (mean 4.4 ± 3.8) compared to infants of COVID-19 negative mothers (mean 2.7 ± 2.4) (P = 0.042).

Conclusion: Breastfeeding was associated with shorter periods of hospitalization in COVID-19 positive infants. In addition, positive COVID-19 infants of mothers who were positive for COVID-19 are likely to have a higher absolute neutrophils count.

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: Factor VII (FVII) deficiency is characterized by normal activated partial thromboplastin time (aPTT) and prolonged prothrombin time (PT) values. It is diagnosed by determining protein level and coagulation activity (FVII:C). FVII:C measurements are expensive and time consuming.

Objectives: To analyze correlations between PT, international normalized ratio (INR), and FVII:C in pediatric patients before otolaryngology surgery and to establish alternative methods for identifying FVII deficiency.

Methods: FVII:C data were collected from 96 patients with normal aPTT and prolonged PT values during preoperative otolaryngology surgery coagulation workup between 2016 and 2020. We compared demographic and clinical parameters using Spearman correlation coefficient and receiver operating characteristic (ROC) curve analysis to determine the accuracy of PT and INR values to predict FVII deficiency.

Results: The median values of PT, INR and FVII:C were 13.5 seconds, 1.14, and 67.5%, respectively. In total, 65 participants (67.7%) displayed normal FVII:C compared to 31 (32.3%) with decreased FVII:C. A statistically significant negative correlation was observed between FVII:C and PT values and between FVII:C and INR. Despite statistically significant ROC of 0.653 for PT (P-value = 0.017, 95% confidence interval [95%CI] 0.529–0.776) and 0.669 for INR (P-value = 0.08, 95%CI 0.551–0.788), we were unable to determine an optimal cutoff point to predict FVII:C deficiency with high sensitivity and high specificity.

Conclusions: We could not identify a PT or INR threshold to best predict clinically relevant FVII:C levels. When PT is abnormal, determining FVII:C protein levels is needed for diagnosing FVII deficiency and considering surgical prophylactic treatment.

Background: The annual incidence of epilepsy increases with age, from nearly 28 per 100,000 by the age of 50 years to 139 per 100,000 by the age of 75 years. Late-onset epilepsy differs from epilepsy at a young age in the prevalence of structural-related epilepsy, types of seizures, duration of seizures, and presentation with status epilepticus.

Objectives: To check the response to treatment in patients with epilepsy with age of onset of 50 years and older.

Methods: We conducted a retrospective study. The cohort included all patients referred to the Rambam epilepsy clinic between 1 November 2016 and 31 January 2018 with epilepsy onset at age 50 years or older and at least one year of follow-up at the recruitment time point and epilepsy not caused by a rapidly progressive disease.

Results: At recruitment, most patients were being treated with a single antiseizure medication (ASM); 9 of 57 patients (15.7%) met the criteria for drug-resistant epilepsy (DRE). The mean duration of follow-up was 2.8 ± 1.3 years. In an intention-to-treat analysis, 7 of 57 patients (12.2%) had DRE at the last follow-up.

Conclusions: Late-onset epilepsy, which is defined as a first diagnosis in patients older than 50 years of age, is easy to control with monotherapy. The percentage of DRE in this group of patients is relatively low and stable over time.

Background: Implantable loop recorders (ILRs) are a central tool in the evaluation of unexplained syncope. These devices record and store electrocardiograms, both automatically and on patient-dependent activation. Therefore, obtaining optimal diagnostic results relies on a patient's comprehension and collaboration.

Objectives: To evaluate the effect of ethnic background and mother-tongue language on the diagnostic yield (DY) of ILRs.

Methods: Patients at two medical centers in Israel, who had ILRs as part of syncope workup were included. Inclusion criteria were age over 18 years and an ILR for at least one year (or less if the cause of syncope was detected). Patient demographics, ethnic background, and previous medical history were recorded. All findings from ILR recordings, activation mode (manual vs. automatic), and treatment decisions (none, ablation, device implantation) were collected.

Results: The study comprised 94 patients, 62 Jews (i.e., ethnic majority) and 32 non-Jews (i.e., ethnic minority). While baseline demographic characteristics, medical history, and drug therapy were similar in both groups, Jewish patients were significantly older at the time of device implantation: 64.3 ± 16.0 years of age vs. 50.6 ± 16.9, respectively; (P < 0.001). Arrhythmias recorded in both groups as well as treatment decisions and device activation mode were similar. Total follow-up time from device implantation was longer in the non-Jewish vs. the Jewish group (17.5 ± 12.2 vs. 24.0 ± 12.4 months, respectively; P < 0.017).

Conclusions: The DY of ILR implanted for unexplained syncope did not seem to be influenced by patient's mother-tongue language or ethnicity.

Background: Direct oral anticoagulants (DOACs) are the treatment of choice for patients with non-valvular atrial fibrillation; however, bleeding risk remains significant. We reported a single-center experience with 11 patients who presented with hemorrhagic cardiac tamponade while treated with DOACs.

Objectives: To evaluate the characteristics and clinical outcomes of patients under DOACs with cardiac tamponade.

Methods: We retrospectively identified 11 patients treated with DOACs admitted with pericardial tamponade in our cardiology unit during 2018–2021.

Results: The mean age was 84 ± 4 years; 7 males. Atrial fibrillation was the indication for anticoagulation in all cases. DOACs included apixaban (8 patients), dabigatran (2 patients), and rivaroxaban (1 patient). Urgent pericardiocentesis via a subxiphoid approach under echocardiography guidance was successfully performed in 10 patients. One patient was treated with urgent surgical drainage with a pericardial window. Reversal of anticoagulation using prothrombin complex concentrate and idarucizumab was given before the procedure to 6 patients treated with apixaban and one patient treated with dabigatran. One patient, initially treated with urgent pericardiocentesis, underwent pericardial window surgery due to re-accumulation of blood in the pericardium. The pericardial fluid analysis demonstrated hemopericardium. Cytology tests were negative for malignant cells in all cases. Discharge diagnoses regarding the cause of hemopericardium included pericarditis (3 patients) and idiopathic (8 patients). Medical therapy included non-steroidal anti-inflammatory drugs (1 patient), colchicine (3 patients), and steroids (3 patients). No patient died during hospitalization.

Conclusions: Hemorrhagic cardiac tamponade is a rare complication of DOACs. We found good short-term prognosis following pericardiocentesis.

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: Trabecular bone score (TBS) reflects vertebrae microarchitecture and assists in fracture risk assessment. The International Society of Clinical Densitometry postulates that the role of TBS in monitoring antiresorptive therapy is unclear. Whether changes in TBS correlate with bone resorption measured by bone turnover markers is not known.

Objectives: To determine whether longitudinal changes in TBS correlate with C-terminal telopeptide (CTX) of type I collagen.

Methods: Examinees with two bone mineral density (BMD) measurements were detected via the institutional database. Over 5.8% change in TBS was considered least significant and patients were grouped accordingly (increment, decrement, or unchanged). CTX, BMD, co-morbidities, incident fractures, and medication exposure were compared between the groups by Kruskal-Wallis. The correlation between TBS and BMD change and CTX in a continuous model was analyzed by Pearson's correlation coefficient.

Results: In total, 110 patients had detailed medical records. In 74.5%, TBS change was below least significant change. Two other TBS categories, fracture incidence or medication exposure, did not differ by CTX. In the continuous model, BMD and TBS change was positively correlated (r = 0.225, P = 0.018). A negative correlation was observed between BMD change and CTX. The decrease in BMD level was associated with higher CTX (r = -0.335, P = 0.004). No correlation was observed between CTX and TBS.

Conclusions: No correlation between TBS dynamics and bone resorption marker was found. Clinical interpretation and implication of longitudinal TBS changes should be further explored.

The prevalence of choroidal nevi associated with choroidal neovascular membrane (CNV) is estimated to range between 0.58% and 8.6% [1]. The pathogenesis of CNV is not completely understood. Researchers have suggested that damage caused to the choroid capillaries above the nevi affects the overlying retinal pigment epithelium and triggers production of angiogenic factors that, in turn, cause the development of CNV [2,3]. Hypoxia and inflammation may be involved in the process. Data have been inconsistent with both theories [4].

Germline pathogenic variants (PVs) in the RET proto-oncogene (OMIM 164761) are associated with a diverse phenotype based on the type of PV. Gain-of-function (GOF) PVs are associated with the highly penetrant multiple endocrine neoplasia type 2 (MEN2-OMIM 171400), which are hallmarked by an increased risk for developing medullary thyroid cancer (MTC), pheochromocytoma, and parathyroid adenomas. Loss-of-function (LOF) RET PVs are associated with incompletely penetrant Hirschsprung's disease (HSCR OMIM 142623), which are pathologically characterized by the absence of enteric ganglia affecting the distal colon and clinically manifest as neonatal intestinal obstruction. Despite anecdotal reports of familial clustering of neoplasms in HSCR families, mostly MEN2-associated tumors [1,2], HSCR is not considered to be associated with an increased risk for developing cancer [3]. We report on a family with an unusual multigenerational solid tumor phenotype and severe HSCR phenotype with a LOF RET PV.