Israel Medical Association Journal

Background: Several studies have shown that patients with fibromyalgia present with neuroendocrine, inflammatory, and coagulation features linked to cardiovascular disease development. However, the exact profile of cardiovascular risk factors and events in fibromyalgia remains to be defined.

Objectives: To compare the profile of cardiovascular risk factors and events between fibromyalgia outpatients and the general population in Italy.

Methods: Cardiovascular risk factors and events in fibromyalgia females were collected using the criteria adopted in the CUORE Project.

Results: The study comprised 62 female fibromyalgia patients and 4093 female controls from 35 to 75 years of age. The prevalence of hypertension, diabetes, atrial fibrillation, transient ischemic attack, and cardiovascular total burden was significantly higher in fibromyalgia females than in the general Italian population. No difference was found in blood fasting glucose, triglycerides, total and fractionated cholesterol levels, body mass index, and metabolic syndrome (MetS). The MetS rate was underestimated for methodological aspects.

Conclusions: Fibromyalgia is associated with an increased cardiovascular burden, probably through a specific risk factor profile.

Congenital cardiac tumors are rare in neonates. A rhabdomyoma, the most common neonatal cardiac tumor, tends to regress in the first year of life. Indications for intervention include hemodynamic compromise and intractable arrhythmias. To the best of our knowledge, rhabdomyoma-induced ischemia has not yet been reported. We report a case of a neonate with multiple rhabdomyomas with myocardial infarction related to compression of a coronary artery.

Migraine is very common headache disorder, usually starting at a young age with a higher prevalence in females. In this narrative review, we summarize the prevalence, burden, and socio-demographic characteristics of migraineurs worldwide and specifically in Israel. We searched standard electronic bibliographic databases, including MEDLINE (via PubMed), Embase, Google Scholar, and Up to Date using combinations of search terms and reviewed the articles we found. The factors reviewed included prevalence and incidence, burden, sex differences, age distribution, cognitive function, socioeconomic status, religion, country of origin, and urban vs. rural dwelling.

Idiopathic inflammatory myopathies (IIM) are a group of rare, autoimmune, systemic diseases with a large spectrum of clinical phenotypes. The diagnosis and management of myositis demand an integrated evaluation of different clinical, laboratory, and pathological findings in various organs. Recent developments in IIM research, especially in the serological testing and pathology fields, has led to a new classification and better recognition of patients with early or extra-muscular disease, with improvement in clinical care and prognosis.

Background: Peripartum cardiomyopathy (PPCM) is a rare but potentially devastating complication of pregnancy. Although the pathophysiology of PPCM is not fully understood, there are known risk factors for developing PPCM, which are maternal and gestation related. In the first wave of the coronavirus disease 2019 (COVID-19) pandemic, we witnessed an elevated incidence of PPCM among COVID-19 survivors.

Objectives: To present a single-center case series of three patients diagnosed with peripartum cardiomyopathy after recovered from COVID-19 during the index pregnancy.

Methods: In this single center case study, all patients diagnosed with PPCM at our institute during the examined time frame were included. Electronic medical records were studied.

Results: Three patients previously diagnosed with asymptomatic or mildly symptomatic COVID-19 disease during pregnancy presented with PPCM before or shortly after delivery. Patients underwent testing to rule out residual COVID-19 myocarditis, were treated pharmacologically and with wearable defibrillators as needed, and were examined in follow-up 1–9 months after delivery.

Conclusions: Residual endothelial damage due to COVID-19 disease, even if originally mild in presentation, could predispose pregnant patients to PPCM and should be considered as a risk factor when assessing patients with new onset symptoms of heart failure. Further research is needed to confirm this hypothesis and fully determine the underlying pathophysiology. These preliminary findings warrant a high index of suspicion for PPCM in COVID-19 recoverers.

Background: Signet ring cell carcinoma (SRCC) is classified as an undifferentiated gastric carcinoma with poor prognosis. Early SRCCs are associated with improved prognosis.

Objectives: To describe the outcomes of incidental SRCC.

Methods: In this case series, 900 medical charts of patients with SRCC were screened to identify patients with incidental SRCC, defined as diagnosed in random, non-focal-lesion-targeted biopsies.

Results: Six patients were diagnosed with incidental SRCC and underwent gastrectomy. The final pathology of five patients revealed one or more small foci of early SRCC without lymphovascular invasion. Only one patient had no evidence of malignancy. The median follow-up after surgery was 4.2 years (50 months, range 37–90 months). No deaths or recurrences were recorded during the follow-up period. These results resemble the reported survival rate for early SRCC.

Conclusions: An aggressive surgical approach in incidental gastric SRCC patients is recommended, as they have a chance for long-term survival.

Background: Among the most frequent complications following transcatheter aortic valve replacement (TAVR) is hemostasis imbalance that presents either as thromboembolic or bleeding. Deviations in platelet count (PC) and mean platelet volume (MPV) are markers of hemostasis imbalance.

Objectives: To determine the predictive value of pre- and post-procedural PC and MPV fL 1-year all-cause mortality in patients who underwent TAVR.

Methods: In this population-based study, we included 236 TAVR patients treated at the Tzafon Medical Center between 1 June 2015 and 31 August 2018. Routine blood samples for serum PC levels and MPV fL were taken just before the TAVR and 24-hour post-TAVR. We used backward regression models to evaluate the predictive value of PC and MPV in all-cause mortality in TAVR patients.

Results: In this study cohort, MPV levels 24-hour post-TAVR that were greater than the cohort median of 9 fL (interquartile range 8.5–9.8) were the strongest predictor of 1-year mortality (hazard ratio 1.343, 95% confidence interval 1.059–1.703, P-value 0.015). A statistically significant relationship was seen in the unadjusted regression model as well as after the adjustment for clinical variables.

Conclusions: Serum MPV levels fL 24-hour post-procedure were found to be meaningful markers in predicting 1-year all-cause mortality in patients after TAVR.

Background: The parasympathetic system and its main neurotransmitter, acetylcholine, contributes to homeostasis of inflammation. Cholinergic dysregulation is thought to contribute to the pathogenesis of inflammatory rheumatic diseases. Cholinesterase activity in patients with psoriatic arthritis (PsA) has not been investigated.

Objectives: To compare the cholinesterase activity in patients with PsA and immunocompetent controls and to explore the correlation between cholinergic status (CS) and PsA disease activity.

Methods: Serum acetylcholinesterase (AChE) and total cholinesterase activity were measured in patients with PsA (n=88) and matched controls (n=84). Cholinergic activity before and 3–6 months after the initiation of a biologic treatment was evaluated in seven patients with PsA.

Results: The levels of AChE and CS were similar in both PsA patients and controls. PsA patients treated with biologics had significantly lower levels of AChE and CS compared to patients treated with non-biologics: 447.4 vs. 526 substrate hydrolyzed/min/ml, P = 0.005, and 1360.9 vs. 1536, P = 0.029, respectively. We found an association between C-reactive protein levels, AChE activity (r = 0.291, P = 0.008), and cholinergic status (r = 0.247, P = 0.026) in patients with PsA but not in controls. No correlation between AChE activity, cholinergic status, and the indices of PsA disease activity was found. After initiating or switching biologic treatment in 7 patients, AChE levels remained stable.

Conclusions: We demonstrated similar cholinesterase activity in patients with psoriatic arthritis and controls, highlighting a potential effect of biologic treatment on cholinergic activity in patients with PsA.

Background: Jejunal disease is associated with worse prognosis in Crohn's disease. The added value of diffusion weighted imaging for evaluating jejunal inflammation related to Crohn's Disease is scarce.

Objectives: To compare diffusion weighted imaging, video capsule endoscopy, and inflammatory biomarkers in the assessment of Crohn's disease involving the jejunum.

Methods: Crohn's disease patients in clinical remission were prospectively recruited and underwent magnetic resonance (MR)-enterography and video capsule endoscopy. C-reactive protein and fecal-calprotectin levels were obtained. MR-enterography images were evaluated for restricted diffusion, and apparent diffusion coefficient values were measured. The video capsule endoscopy-based Lewis score was calculated. Associations between diffusion weighted imaging, apparent diffusion coefficient, Lewis score, and inflammatory biomarkers were evaluated.

Results: The study included 51 patients, and 27/51 (52.9%) with video capsule endoscopies showed jejunal mucosal inflammation. Sensitivity and specificity of restricted diffusion for video capsule endoscopy mucosal inflammation were 59.3% and 37.5% for the first reader, and 66.7% and 37.5% for the second reader, respectively. Diffusion weighted imaging was not statistically associated with jejunal video capsule endoscopy inflammation (P = 0.813).

Conclusions: Diffusion weighted imaging was not an effective test for evaluation of jejunal inflammation as seen by video capsule endoscopy in patients with quiescent Crohn's disease.

Biological therapies with monoclonal antibodies have revolutionized the management of many inflammatory and autoimmune diseases. Combining biological treatments is very rarely indicated and may theoretically result in severe adverse effects, specifically, an increased tendency toward infectious diseases. We present the case of a woman in whom combination therapy with canakinumab for familial Mediterranean fever (FMF) and mepolizumab for chronic eosinophilic pneumonia was successfully employed.

Fever of unknown origin (FUO) is defined as the repeated occurrence of elevated body temperature above 38.3°C (101°F) lasting for at least 3 weeks with no clear diagnosis despite a thorough investigation of more than one-week duration. FUO cases could be categorized into three major etiologies: infectious, neoplastic, and systemic inflammatory. Despite novel diagnostic modalities, clinicians still encounter a significant number of unresolved FUO cases, accounting for as many as 50% of cases [1]. Prolonged futile FUO investigations may be a source of frustration for many clinicians [2]. We described a unique cause for FUO that shares the complexity of the diagnostic workup and emphasizes the importance of ¹⁸F-fluorodeoxyglucose positron-emission tomography/computed tomography (PET/CT) modality in the process of investigating FUO.

Acute or chronic aortic dissection is considered a rare emergency, with an estimated rate of 2.9 to 5 cases per 100,000 patients each year. This condition is most prevalent in males older than 65 years of age with a history of hypertension, atherosclerosis, and previous cardiac surgery [1,2]. To confirm the diagnosis, imaging is used, often by computed tomography angiography (CTA) of the chest. Although prompt treatment is required, patients often present with non-specific symptoms, such as abdominal pain or neurologic deficits, resulting in the early diagnosis of less than 20% and a high mortality rate [1].

Background: Up to half the patients diagnosed with acute coronavirus disease 2019 (COVID-19) presented with gastrointestinal symptoms. Gastric mucosal cells, enterocytes, and colonocytes express the viral entry receptor angiotensin-converting enzyme 2 (ACE2) and coreceptor transmembrane protease serine 2 (TMPRSS2) and are prone to infection. Direct infection of gastrointestinal epithelial cells has been demonstrated. COVID-19 disease was first diagnosed in Israel at the end of February 2020 with 842,536 confirmed cases and 6428 deaths by the end of June 2021. In our multicenter, retrospective cohort study, we looked for gastrointestinal signs and symptoms in two periods and correlated them with mortality. Period 1 included the first and second waves and the original virus. Period 2 represented the third wave and the alpha variant.

Objectives: To reveal gastrointestinal signs and symptoms in two periods and correlate them with mortality.

Methods: From 22,302 patients hospitalized in general medical centers, we randomly selected 3582 from Period 1 and 1106 from Period 2. The study was performed before vaccinations were available.

Results: Gastrointestinal signs and symptoms, diarrhea, vomiting, abdominal pain, and taste/smell loss were significantly more prevalent during Period 1. Thirty-day mortality and in-hospital mortality were significantly higher in Period 2 than in Period 1, 25.20% vs. 13.68%, and 21.17% vs. 12.87%, respectively (P < 0.001).

Conclusions: Thirty-day mortality and in-hospital mortality rates were 1.84 and 1.64 times higher from 6 November 2020 to 15 January 2021, the alpha variant, and in negative correlation with gastrointestinal symptoms.

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: Small left atria (LA) is associated with an increased risk of mortality.

Objectives: To determine whether the attributed risk of mortality is influenced by the underlying etiologies leading to decreased volumes.

Methods: We retrospectively evaluated patients with an available LA volume index (LAVI) as measured by echocardiography who came to our institution between 2011 and 2016. Individuals with small LA (LAVI < 16 ml/m²) were included and divided according to the etiology of the small LA (determined or indeterminate) and investigated according to the specific etiology.

Results: The cohort consisted of 288 patients with a mean age of 56 ± 18 years. An etiology for small LA was determined in 84% (n=242). The 1-year mortality rate of the entire cohort was 20.5%. Patients with indeterminate etiology (n=46) demonstrated a lower mortality rate compared with determined etiologies (8.7% vs. 22.7%, P = 0.031). However, following propensity score adjustments for baseline characteristics, there was no significant difference between the groups (P = 0.149). The only specific etiology independently associated with 1-year mortality was the presence of space occupying lesions (odds ratio 3.26, 95% confidence interval 1.02–10.39, P = 0.045).

Conclusions: Small LA serve as a marker for negative outcomes, and even in cases of undetected etiology, the prognosis remains poor. The presence of small LA should alert the physician to a high risk of mortality, regardless of the underlying disease.