Israel Medical Association Journal

Takotsubo syndrome (TTS) or Takotsubo cardiomyopathy (TCM) is a cardiomyopathy that develops rapidly and is usually caused by mental or physical stress. It is usually a transient cardiomyopathy. The presumed cause of the onset of the syndrome is the increase and extreme secretion of adrenaline and norepinephrine due to extreme stress. An infectious disease such as sepsis can also be the cause [1].

One of the most widespread diagnostic tools is the revised version of Mayo Clinic Diagnostic Criteria for TTS (2008) [2], which incorporates transient wall-motion abnormalities, absence of a potential coronary culprit, myocarditis, and pheochromocytoma. The prognosis for TTS is usually favorable and resolves with complete recovery in 4–8 weeks in more than 90% of patients.

Paraneoplastic syndromes are reported in 8–15% of patients diagnosed with cancer [1]. They are defined as syndromes that occur due to an underlying malignancy, which has yet to be diagnosed, or at the time of the diagnosis and less frequently following the diagnosis of a malignancy. Several mechanisms are involved including autocrine and paracrine mediators, hormones, peptides, cytotoxic lymphocytes, and cytokines [1,2].

Klippel-Trenaunay syndrome (KTS) is a rare congenital complex vascular multisystem disorder characterized by bony and soft-tissue hypertrophy. It is famous for its hallmarks like port-wine stains and varicose veins. The syndrome is sporadic, although rare familial cases have been reported [1]. The most common ophthalmological alterations encountered in KTS are conjunctival telangiectasia, anterior chamber malformation, raised episcleral venous pressure with associated glaucoma, and choroidal hemangiomas [2].

The purpose of this report is to raise awareness of KTS and its diverse scale of expressions as well as complications. This study was conducted in accordance with the ethical standards set by the Declaration of Helsinki. The patient gave signed informed consent.

Common variable immunodeficiency (CVID) is a heterogeneous primary immune deficiency disorder characterized mainly by defective B lymphocyte differentiation, leading to hypogammaglobinemia and defective antibody production. It is often combined with cellular immune defects. A minority of patients present during childhood and adolescence. Infections are most often sinopulmonary but can affect any system. The noninfectious complications include progressive lung disease, autoimmunity, gastrointestinal inflammatory disease, liver disease, granulomatous disease, lymphoid hyperplasia and infiltrative disease, and the development of lymphoma and other cancers. In addition to recurrent infections and bronchiectasis, patients may develop chronic interstitial lung disease, granulomatous lung disease, lymphoma, and pulmonary hypertension.

Background: Data are scarce on the immunogenicity of coronavirus disease 2019 vaccines in patients with autoimmune rheumatic diseases (ARD).

Objectives: To measure the immunoglobulin G (IgG) response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization and to evaluate clinical characteristics associated with seropositivity.

Methods: Samples were collected after the second and third doses of the three different types of vaccines in ARD patients. Seroconversion rates and IgG antibody S1/S2 titers were measured.

Results: The type of ARD diagnosis and previous treatment had no significant impact on the serum IgG antibody levels measured after the second (P = 0.489 and P = 0.330, respectively) and boost dose (P = 0.441 and P = 0.446, respectively). What made a significant difference regarding serum IgG antibody levels after the second dose was the type of SARS-CoV-2 vaccine. The difference was highly statistically significant for all vaccine types (P = 0.001 with the highest odds ratio for the mRNA vaccine). After the boost with the mRNA vaccine, all patients achieved a high level of serum IgG antibody levels (t = 10.31, P = 0.001). No ARD patients experienced serious post-vaccinal reactions. Eight patients developed COVID-19 before the boost dose.

Conclusions: In ARDs patients, the highest level of serum IgG antibody against S1/S2 proteins was achieved with the mRNA vaccine, irrespective of the therapy applied or the type of the disease. We recommend a booster dose with mRNA vaccine in all ARDs for the highest SARS-CoV-2 protection without serious post-vaccinal reactions observed.

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.

Fibromyalgia syndrome is a chronic widespread musculoskeletal pain syndrome primarily characterized by fatigue, sleep disturbances, and cognitive impairment. Its etiology remains elusive despite ongoing research and has multifactorial elements. It has been shown that traumatic events and neuro-inflammation, autoimmunity, and genetic factors contribute to the pathogenesis of fibromyalgia syndrome.

Recent evidence has pointed to a bi-directional link between cardiovascular disease, traditional cardiovascular risk factors, and metabolic syndrome (MetS), together with the presence of fibromyalgia [1].

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: 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.

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: The DES-obstructive sleep apnea (DES-OSA) score uses morphological characteristics to predict the presence and severity of obstructive sleep apnea syndrome (OSAS).

Objectives: To validate DES-OSA scores on the Israeli population. To identify patients requiring treatment for OSAS. To evaluate whether additional parameters could improve the diagnostic value of DES-OSA scores.

Methods: We performed a prospective cohort study on patients attending a sleep clinic. Polysomnography results were examined independently by two physicians. DES-OSA scores were calculated. STOP and Epworth questionnaires were administered, and data on cardiovascular risk was extracted.

Results: We recruited 106 patients, median age 64 years, 58% male. DES-OSA scores were positively correlated with apnea-hypopnea index (AHI) (P < 0.001) and were significantly different between the OSAS severity groups. Interobserver agreement for calculating DES-OSA was very high between the two physicians (intraclass correlation coefficient 0.86). DES-OSA scores ≤ 5 were associated with high sensitivity and low specificity (0.90 and 0.27, respectively) for moderate to severe OSAS. In univariate analysis, only age was significantly correlated with the presence of OSAS (OR 1.26, P = 0.01). Age older than 66 years as a single point in the DES-OSA score slightly improved the sensitivity of the test.

Conclusions: DES-OSA is a valid score based solely on physical examination, which may be useful for excluding OSAS requiring therapy. DES-OSA score ≤ 5 effectively ruled out moderate to severe OSAS. Age older than 66 years as an extra point improved the sensitivity of the test.

The patient, a 32-year-old woman diagnosed with Sjögren's syndrome (SS), according to the 2016 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, presented with paresthesia of her face and limbs. Extra glandular manifestations of her primary disease included severe Raynaud's phenomenon and chronic interstitial nephritis. There was no family history of neurologic diseases. Neurological examination was notable for symmetrical decreased sensation in the upper limbs distally. The rest of the neurological examination was unremarkable.

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.

Ruxolitinib is an inhibitor of the cytosolic tyrosine kinase Janus kinase (JAK) family of proteins (JAK1/2), which is widely used to treat various myeloid neoplasms that are characterized by constant activation of the JAK-STAT signaling pathway.

Many side effects are associated with ruxolitinib, including anemia, thrombocytopenia, increased rate of infections (especially herpes zoster), and mild hypercalcemia noted in 15.4% of patients [1]. The possible mechanism causing hypercalcemia may involve altered bone and mineral metabolism with secondary hyperparathyroidism, as described for other kinase inhibitors [2].