Israel Medical Association Journal

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: 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.

Inappropriate shocks are a serious and still unresolved problem associated with implantable cardioverter defibrillators (ICDs) that have been associated with increased mortality and impairment of quality of life [1] despite advances in device safety. We report a case of electromagnetic interference (EMI) while showering that resulted in an inappropriate ICD discharge.

Background: Uterine tachysystole during labor can lead to a decrease in fetal oxygen saturation and intracerebral oxygen saturation. Acute tocolysis using atosiban can inhibit uterine smooth muscle activity, potentially improving fetal status and facilitating vaginal delivery or allowing time to prepare for operative delivery.

Objectives: To compare maternal and neonatal outcomes in cesarean and vaginal deliveries following atosiban administration during fetal prolonged deceleration and tachysystole at gestational age 37 0/7 to 43 0/7 weeks.

Methods: We conducted a single-center, descriptive retrospective cohort study at a large tertiary referral center.

Results: Of the 275 patients treated with atosiban, 186 (68%) delivered vaginally (either spontaneous delivery or instrumental delivery) and 89 (32%) underwent a cesarean delivery. In a univariate analysis, cesarean delivery was associated with higher body mass index (27.9 ± 4.3 vs. 30.2 ± 4.8, P = 0.003). Second stage atosiban administration was associated with vaginal delivery (89.3% vs. 10.7%, P = 0.01). Cesarean delivery was associated with lower Apgar at 1 and 5 minutes and a higher rate of neonatal intensive care unit admissions. The incidence of PPH among women treated with atosiban in our study (2.3–4.3%) was higher than the incidence reported in the literature (1–3%)  

Conclusions: Atosiban may be an effective acute intervention for non-reassuring fetal heart rate during tachysystole, increasing the rate of vaginal delivery and potentially reducing the need for cesarean delivery. However, the potential risk of postpartum hemorrhage should be taken into consideration.

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: 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.

Thyroid storm-related heart failure is a rare, life threatening complication of hyperthyroidism. In refractory cases, urgent thyroidectomy is required for definitive control of thyrotoxicosis. venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a supportive measure for cardiorespiratory failure requiring continuous anticoagulation to prevent clotting. We presented two cases of thyrotoxic cardiac failure that necessitated VA-ECMO. One of the patients was successfully treated with thyroidectomy while on VA-ECMO. To the best of our knowledge, only two such cases have previously been reported.

Sulfonylureas have been used to treat patients with diabetes for the last 80 years. The main side effect of this drug class is hypoglycemia, which might be severe and protracted. With the emergence of new medications with improved safety and better efficacy in preventing diabetes complications and cardiovascular morbidity and mortality, the use of these agents is waning.

Sulfonylureas are historically classified into two generations. The generation first includes drugs such as tolbutamide and chlorpropamide, which are no longer used. The second generation includes glibenclamide and glimepiride, which have different pharmacokinetic properties and active metabolites.

In this case report, we present a patient with diabetes and end-stage renal disease (ESRD) who developed prolonged hypoglycemia following the unauthorized use of a food supplement containing the first-generation sulfonylurea - tolbutamide.

A 26-year-old female at 28 weeks of gestation with her fourth pregnancy presented with a 24-hour history of diffuse abdominal pain and distension. In addition, she had nausea, vomiting, and constipation. The pain did not respond to analgesics. She had poor prenatal care during her pregnancy. She had previously had three cesarean deliveries. The first cesarean delivery was due to non-progressive second stage of labor, the second was preterm due to abdominal pain and suspected uterine rupture, and the last was due to the previous cesarean deliveries. In her last previous pregnancy, she presented with recurrent milder abdominal pain, which resolved spontaneously.

On examination, she was afebrile, with normal blood pressure and heart rate. Her abdomen was distended, tympanic, and mildly tender to palpation with no tenderness on the cesarean scar and no peritoneal signs. Her laboratory testing was normal except for mild hypokalemia.

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.

Global developmental delay (GDD), defined as a significant delay in two or more developmental domains (e.g., gross/fine motor, cognitive, speech/language, personal/social, activities of daily living), affects 1–3% of children. According to the Israeli Ministry of Health, thyroid function studies are not indicated in children with GDD unless there are systemic features suggestive of thyroid dysfunction (https://www.health.gov.il/hozer/mr36_2012.pdf). This approach also exists in other countries with newborn screening programs for congenital hypothyroidism.

We present the case of an infant with GDD, who despite normal newborn screening tests, underwent a repeated extended thyroid function analysis (including T₃ levels) leading to a diagnosis of Allan-Herndon-Dudley syndrome, a rare genetic neurodevelopmental syndrome.

Familial spastic paraparesis is a non-progressive disorder. However, clinical experience shows that after trauma, disease, surgery, or limb fracture that force a patient's long immobilization, a significant functional deterioration is observed. I describe two patients with Silver syndrome who experienced such functional deterioration after sustaining a simple fracture. A description of Silver syndrome and a biographical sketch of Dr. Silver, who explained the disorder in 1966, are given.