Israel Medical Association Journal

There are numerous experimental studies on the effect of immune modulation on the skeleton but few clinical ones.

In this letter, we supplement the previous information on enhanced bone healing. A new branch of medicine, osteoimmunology, describes fracture healing as an active immune system process evolving in a cascade of repairs.

A 52-year-old man with a history of gout presented to the emergency department with painful purulent ulcers on the left index finger. Serum C-reactive protein was elevated to 112 mg/L. Hand radiographs [Figure 1A] demonstrated almost complete osteolysis of the two distal phalanges of the involved finger (asterisk), with multiple typical gouty erosions with sclerotic margins and overhanging edges in a marginal and juxta-articular distribution (white arrows), and soft tissue tophi (black arrows). Osteomyelitis of the index finger was suspected, and the finger was amputated.

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.

Recognizing myocarditis is a diagnostic and therapeutic challenge due to the heterogeneity of its clinical presentation and the wide range of etiologies. There is a lack of uniformity among position papers and guidelines from various professional societies regarding the definition and diagnostic workout, including recommendations for performing endomyocardial biopsy (EMB) and medical management, especially the use of immunosuppressive regimens [1-3]. Moreover, there is significant variability among medical centers in Israel in the diagnostic and therapeutic approaches to acute myocarditis. The purpose of this position paper is to present ways to standardize the management of acute myocarditis in Israel [4] by providing up-to-date definitions of the clinical categories of myocarditis, diagnostic criteria, and therapeutic approaches that correspond to the realities of our healthcare system.

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: 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: 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: 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.

In September 2020, a 37-year-old man without significant medical history or medication use presented to the emergency department with shortness of breath. The patient denied any history of shortness of breath, travel history, recent sick contacts, or history of lung disease. On arrival, the patient was afebrile with a respiratory rate of 26 breaths per minute (b/m), oxygen saturation 82% on ambient air, blood pressure 130\80 mmHg, and heart rate 130 beats per minute (bpm). He was started on three liters per minute oxygen therapy, which improved his saturation to 90%. Physical examination was remarkable for tachypnea and diffuse bilateral inspiratory lung crackles. Electrocardiogram revealed sinus tachycardia.

Romidepsin is an intravenously administered antineoplastic agent, which acts by inhibiting histone deacetylases, thus preventing removal of acetyl groups from histones. The accrual of acetyl groups on histones causes cell cycle arrest and apoptotic cell death. It was approved for use in the United States in 2009 for treatment of refractory or relapsed cutaneous and peripheral T cell lymphomas [1-3].

The most common side effects are mild to moderate in severity and include nausea, vomiting, fatigue, fever, myelosuppression (e.g., anemia, neutropenia, thrombocytopenia), elevated liver enzymes, constipation, and rash. More severe adverse events can include marked neutropenia, thrombocytopenia, serious infections such as line sepsis, acute renal failure, tumor lysis syndrome, and cardiac arrhythmias [1].

Background: Acute kidney injury (AKI) is a risk factor for morbidity and mortality during critical illness especially in very old patients admitted to intensive care units.

Objectives: To identify prognostic markers for AKI patients.

Methods: This single-center retrospective study was based on a patient registry of a medical intensive care unit. Hospital records of patients aged 80 years or older admitted between 2005 and 2015 were examined. Patients who developed AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines within 4 days of admission were included in this study.

Results: The study comprised 96 patients with AKI and 81 age- and sex-matched controls without AKI. Mean acute physiology and chronic health evaluation (APACHE) II score was 30 with an ICU mortality of 27% in very old patients with AKI. The odds ratio of hospital mortality for these patients was 5.02 compared to controls (49% vs. 16%). APACHE II score and fluid balance in the first 2 days of ICU admission were the strongest predictors of ICU mortality with an area under the receiver operating characteristic of 0.76. Of the 47 patients with AKI who survived hospital admission, 30 were discharged home.

Conclusions: Mortality was increased in very old ICU patients with AKI. Among survivors, two-thirds returned home.

Background: In developed countries, amblyopia has an estimated prevalence rate of 1–4%, depending on the socioeconomic gradient. Previous studies performed on pediatric populations in Ethiopia demonstrated amblyopia rates up to 16.7.

Objectives: To assess rates of amblyopia, refractive errors, strabismus, and other eye pathologies among Ethiopian-born children and adolescents who immigrated to Israel compared to Israeli-born children.

Methods This observational cross-sectional study included children and adolescents 5–19 years of age who immigrated to Israel up to 2 years before data collection and lived in an immigration center. Demographic data and general health status of the children were obtained from the parents, and a comprehensive ophthalmologic examination was performed. Results were compared to Israeli-born children.

Results: The study included 223 children and adolescents: 87 Ethiopian-born and 136 Israeli-born. The rate of amblyopia in the Ethiopian-born group vs. Israeli-born was 3.4% and 4.4%, respectively. Even after controlling for age, there was still no significant difference between the two groups (P > 0.99).

Conclusions: Despite originating from a country with limited resources and fewer medical facilities, the amblyopia rate in Jewish Ethiopian immigrants was not higher, and even mildly lower, compared to Israeli-born children.

Background: The global refugee crises have raised concerns among medical communities worldwide; nonetheless, access to healthcare has rarely been studied even though refugees are a medically high-risk group.

Objectives: To compare pediatric department admission rates from the pediatric emergency department (PED) of refugees and Israelis.

Methods: We compared data from refugee and Israeli children admitted to the pediatric department at Wolfson Medical Center in Israel between 2013–2017.

Results: A total of 104,244 patients (aged 0–18 years) came to the PED. Admission rate to the pediatric department for refugees was 695/2541 (27%) compared to 11,858/101,703 (11.7%) Israeli patients (P < 0.001). Hospital stay for patients 0–2-years of age was 3.22 ± 4.80 days for refugees vs. 2.78 ± 3.17 for Israelis (P < 0.03). Re-admission rate within 7 days was 1.3% for refugees and 2.6% for Israelis (P < 0.05). Dermatological diseases (e.g., impetigo and cellulitis) were more frequent in refugees (23.30% vs. 13.15%, P < 0.01); however, acute gastroenteritis and respiratory diagnoses were more common in Israelis (18.52% vs. 11.72%, P < 0.05 and 14.84% vs. 6.26%, P < 0.01, respectively). Neurological diseases (e.g., febrile convulsions) were also more frequent in Israelis (7.7% vs. 3%, P < 0.05). Very significantly, 23% of refugees had no healthcare coverage, while only 0.2% of the Israelis had none (P < 0.001).

Conclusions: We found significant morbidity in refugees compared to the local Israeli pediatric population, highlighting the need for different approaches for each population.

Stevens-Johnson Syndrome (SJS), or toxic epidermal necrolysis, is a rare syndrome that develops after an allergic reaction to a medication [1,2]. It affects the skin and the mucocutaneous tissue. Individuals diagnosed with SJS are rarely referred to a rehabilitation medicine (RM) facility.

The annual prevalence of SJS is about one in one million. The skin is covered with blisters. Usually, it affects about 10 % of body surface area. The patients are treated usually by ophthalmologists, dermatologists, allergologists, and immunologists. When severe complications occur, plastic surgeons and intensive care physicians may also be involved. Few publications were found that linked SJS with comprehensive rehabilitation treatment [3-5].

Background: Anal squamous cell carcinoma (ASqCC) is a rare malignancy, traditionally treated with combined chemoradiation, with a continuous infusion of 5-fluorouracil (5-FU) and mitomycin C (MMC). Replacing intravenous (IV) 5-FU with oral capecitabine (oral fluoropyrimidine) has been reported as a non-inferior treatment option. However, these data are scarce, with variable results.

Objectives: To examine the outcome of patients with ASqCC treated with either IV 5-FU or capecitabine concomitantly with radiation therapy. To compare treatment side effects, local recurrence, and general outcome.

Methods: We reviewed charts of patients who were diagnosed with stage I–III ASqCC. All participating patients received chemoradiation at the Assuta Medical Center between 2011 and 2019.

Results: In this study, 43 patients with ASqCC were eligible; 14 received 5-FU and 29 were treated with capecitabine. Basic characteristics were similar between the two groups, with longer follow-up for the 5-FU group. Six months following treatment, 100% (13/13 with adequate follow-up) of the 5-FU group had complete clinical response, compared to 84% in the capecitabine group (21/24), P = 0.143. The local recurrence incidence was higher in the 5-FU group at 23% (7, 10, 26 months following therapy, and none in the capecitabine group (P = 0.088). Although local and hematological toxicities were similar between groups, one patient receiving capecitabine died during chemoradiotherapy.

Conclusions: Oral capecitabine demonstrated non-inferior disease control in ASqCC treated with chemoradiotherapy. We recommend oral capecitabine over continuous IV 5-FU in locally and locally advanced ASqCC. Close monitoring of side effects is required to reduce major toxicity.