Israel Medical Association Journal

The potential influence of seasonal variations on vasculitis is unclear. Emerging evidence has suggested that seasonal factors may play a role in the onset of vasculitis. We extracted data from the electronic medical records at Clalit Health Services (CHS), Israel's largest health maintenance organization. We identified patients older than 18 years of age with new onset of giant cell arteritis (GCA), ANCA-associated vasculitis, immunoglobulin A (IgA) vasculitis, and Behçet's disease from 2007 to 2021. We constructed a time series of new vasculitis cases per month and explored the potential impact of seasonality on the disease onset. Our cohort included 4847 patients, including 2445 with GCA, 749 with ANCA-associated vasculitis (AAV), 547 with IgA vasculitis, and 1106 with Behçet's disease. We observed a decreased risk of GCA in September (relative risk [RR] 0.84, [95% confidence interval] 95%CI 0.72–0.98) and a significant reduction in AAV incidence in August (RR 0.68, 95%CI 0.48–0.96). For IgA vasculitis, an elevated risk was noted in February (RR 1.58, 95%CI 1.02–2.45), while Behçet's disease showed an increased risk in January (RR 1.25, 95%CI 1.02–1.55). No association was found between any specific season and the onset of vasculitis for any of the studied conditions. Our study results indicate that the onset of vasculitis conditions may be influenced by environmental factors associated with seasonality.

Background: Diabetic ketoacidosis (DKA) is an acute metabolic, life-threatening complication of diabetes mellitus with a mortality rate that now stand at less than 1%. Although mortality is coupled with the etiology of DKA, literature on the influence of DKA etiology on patient outcome is scarce.

Objectives: To study different triggers for DKA and their effect on outcomes.

Methods: We conducted a retrospective study that include 385 DKA patients from 2004 to 2017. The study compared demographics, clinical presentation, and mortality rates by different precipitating factors.

Results: Patients with DKA due to infections had a higher risk to develop in-hospital mortality after controlling for age and sex (odds ratio 4.40, 95% confidence interval 1.35–14.30), had a higher Charlson Comorbidity Index score, a higher risk of being mechanical ventilated (14% vs. 3%, P < 0.01), and a longer duration of hospitalization (5 days vs. 3 days, P < 0.001).

Conclusions: It is crucial to find the triggers that precipitate DKA and start the treatment as early as possible in addition to the metabolic aspect of the treatment especially when the trigger is an infectious disease.

Celiac disease (CD) is an immune-based reaction to dietary gluten. CD can present with a diverse array of symptoms. Many CD patients have no symptoms at all. Thus, a great number of atypical cases of CD remain undiagnosed, leading to a risk of long-term complications. Some atypical symptoms of CD such as pregnancy complications, infertility, recurrent abortions, intrauterine growth restriction, preterm delivery, and severe preeclampsia have been investigated in undiagnosed and diagnosed pregnant women with CD. Nutrient deficiency and autoimmune pathogenic mechanisms have been hypothesized to be the explanation of these adverse pregnancy outcomes. Recently, an association between obstetric complications and anti-tissue transglutaminase antibodies titers in women with CD has been reported. While the adverse effects of CD on the reproductive system are well investigated, there are only a few reports in the literature on the effect of pregnancy and puerperium on CD. We reviewed the published literature on the adverse effects and pathophysiology of CD in reproductive disorders and the effect of pregnancy and puerperium on the manifestation of CD.

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.

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.

Late, preterm premature rupture of the membranes (PPROM) presents a major obstetrical challenge balancing between iatrogenic prematurity and risk of prolonged rupture of membranes. In recent years, the pendulum has been shifting toward expectant management until gestation week 37 + 0. We examined the latest guidelines and major trials and summarized optimal management. We addressed the major dilemmas of women with PPROM during gestation weeks 34 + 0 to 36 + 6.

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.

Background: Male breast cancer (MBC) is a rare disease representing less than 1% of breast cancers. In the absence of a screening program, such as for females, the diagnostic workup is critical for early detection of MBC.

Objectives: To summarize our institutional experience in the workup of male patients referred for breast imaging, emphasizing the clinical, imaging, and histopathological characteristics of the MBC cohort.

Methods: All male patients who underwent breast imaging between 2011 and 2016 in our institution were retrospectively reviewed. Clinical, radiological, and histopathological data were collected and statistically evaluated. All images were reviewed using the American College of Radiology Breast Imaging Reporting and Data System.

Results: 178 male patients (average age 61 years, median age 64), underwent breast imaging in our institution. The most common indication for referral was palpable mass (49%) followed by gynecomastia (16%). Imaging included mostly mammography or ultrasound. Biopsies were performed on 56 patients, 38 (68%) were benign and 18 (32%) were malignant. In all, 13 patients had primary breast cancer and 5 had metastatic disease to the breast. Palpable mass at presentation was strongly associated with malignancy (P = 0.007).

Conclusion: Mammography and ultrasound remain the leading modalities in breast imaging among males for diagnostic workup of palpable mass, with gynecomastia being the predominant diagnosis. However, presentation with palpable mass was also associated with malignancy. Despite a notable MBC rate in our cohort, the likelihood of cancer is low in young patients and in cases of gynecomastia.

The use of ultrasound endovaginal probes is common practice in the fields of gynecology and obstetrics. The vagina serves as a host environment for many microorganisms, contributing greatly to its defensive mechanisms. It is not known whether the introduction of other microorganisms into the vaginal region are detrimental or require intensive preventative measures. Several national ultrasonography societies, as well as the Israel Ministry of Health, have addressed the proper and adequate handling of sonographic endovaginal probes, including the use of high-level disinfecting agents following cleansing and prior to using probe covers between patients. However, many obstetrics and gynecology ultrasound units in Israel find it difficult to adhere to these strict disinfecting requirements. While most of the guidelines are based on the theoretical risk of contaminations when ultrasound endovaginal probes are used, the rate of nosocomial infections linked to the use of these probes has yet to be verified. Based on the information available, there is an urgent need to find a solution that enables gynecological ultrasound users to properly disinfect endovaginal probes between patients. Currently, it is almost impossible to pragmatically adhere to the Israel Ministry of Health guidelines. 

Background: Adjuvant radiotherapy for breast cancer reduces local recurrence and improves survival. In patients with left sided breast cancer, anterior heart position or medial tumor location may cause inadequate breast coverage due to heart shielding. Respiration gating using the Real-time Position Management (RPM) system enables pushing the heart away from the tangential fields during inspiration, thus optimizing the treatment plan.

Objectives: To compare breathing inspiration gating (IG) techniques with free breathing (FB), focusing on breast coverage.

Methods: The study comprised 49 consecutive patients with left sided breast cancer who underwent lumpectomy and adjuvant radiation. RPM was chosen due to insufficient breast coverage caused by an anterior heart position or medial lumpectomy cavity. FB and IG computed tomography simulations were generated for each patient. Breast (PTVbreast) and lumpectomy cavity (CTVlump) were defined as the target areas. Optimized treatment plans were created for each scan. A dosimetric comparison was made for breast coverage and heart and lungs doses.

Results: PTVbreast V95% and mean dose (Dmean) were higher with IG vs. FB (82.36% vs. 78.88%, P = 0.002; 95.73% vs. 93.63%, P < 0.001, respectively). CTVlump V95% and Dmean were higher with IG (98.87% vs. 88.92%, P = 0.001; 99.14% vs. 96.73%, P = 0.003, respectively). The cardiac dose was lower with IG. The IG left lung Dmean was higher. No statistical difference was found for left lung V20.

Conclusions: In patients with suboptimal treatment plans due to anterior heart position or medial lumpectomy cavity, RPM IG enabled better breast/tumor bed coverage and reduced cardiac doses.

Background: Radiation-induced dermatitis is commonly seen during radiotherapy for breast cancer. Melatonin-based creams have shown a protective effect against ultraviolet-induced erythema and a radioprotective effect in rats.

Objectives: To evaluate the efficacy of melatonin-containing cream in minimizing acute radiation dermatitis. 

Methods: In this phase II, prospective, randomized, placebo-controlled double-blind study, patients who underwent breast-conserving surgery for stage 0-2 breast cancer were randomly allocated to melatonin emulsion (26 women) or placebo (21 women) for twice daily use during radiation treatment and 2 weeks following the end of radiotherapy. All women received 50 Gy whole breast radiation therapy with 2 Gy/fx using computed tomography-based 3D planning. Patients were examined and completed a detailed questionnaire weekly and 2 weeks following the end of treatment.

Results: The occurrence of grade 1/2 acute radiation dermatitis was significantly lower (59% vs. 90%, P = 0.038) in the melatonin group. Women older than 50 had significantly less dermatitis than younger patients (56% vs. 100%, P = 0.021). The maximal radiation dermatitis in the study group was grade 2 in 15% of the treated patients.

Conclusions: Patients treated with melatonin-containing emulsion experienced significantly reduced radiation dermatitis compared to patients receiving placebo.