Israel Medical Association Journal

Background: Mycosis fungoides (MF) combined with photosensitive/autoimmune diseases has been reported, yet there are limited data regarding the therapeutic considerations in these patients, specifically phototherapy, a mainstay skin-directed treatment (SDT), being a relative or complete contra-indication.

Objectives: To outline therapeutic considerations for patients with MF who had also been diagnosed with photosensitive/autoimmune diseases.

Methods: We conducted a retrospective analysis of patients with MF who were treated at our center between January 2008 and December 2024with photosensitive/autoimmune diseases, especially collagen vascular diseases (CVD) or autoimmune bullous diseases (AIBD),

Results: Eight patients were diagnosed with MF at a median age of 39 years. Seven had early-stage (4-IA, 3-IB) and one had Sézary syndrome. Six early-stage MF patients were diagnosed with lupus erythematosus (LE, 4) or AIBD (2) and were treated with SDT (topical corticosteroids/chlormethine gel), systemic retinoid or methotrexate. A patient with resistant early-stage MF and discoid LE was treated with electron beam and interferon. One patient who presented with variegate porphyria and localized MF was treated with electron beam. The patient with Sézary syndrome had inclusion body myositis. He was treated with low-dose total skin electron beam, methotrexate, extracorporeal photopheresis, and subsequently with romidepsin. After a median of 8 years, no stage progression of MF was observed. The Sézary syndrome patient achieved down-staging and was at stage IB. There was no aggravation of the co-morbidity in any of the patients.

Conclusions: Effective management of MF and associated photosensitive or autoimmune co-morbidities underscore the need for individualized treatment strategies in patients with these unique dual diagnoses.

Psoriasis is a chronic, immune-mediated skin disease characterized by inflammatory lesions and systemic co-morbidities. Emerging evidence highlights the significant role of the microbiome in psoriasis pathogenesis. Dysbiosis of the skin and gut microbiota has been linked to increased disease severity and co-morbidities such as psoriatic arthritis and cardiovascular disease. In this review, we explored the microbiome's influence on immune responses in psoriasis and its potential as a therapeutic target. Microbial therapies, such as probiotics and fecal microbiota transplantation, hold promise for restoring microbial balance and improving outcomes. We also discuss how the microbiome modulates drug efficacy and toxicity, offering insights for personalized treatment approaches. While challenges remain in establishing causality and translating findings into clinical practice, leveraging the gut-skin axis may optimize psoriasis management and improve patient outcomes.

Background: Botulinum toxin (BT) can alleviate limb dystonia, but limited insurance coverage hinders its utilization.

Objectives: To compare the therapeutic efficacy of BT injections for spasticity and dystonia of the limbs.

Methods: BT injections of hypertonic limbs were administered under ultrasound guidance between 2019 and 2024 for either limb dystonia or limb spasticity.

Results: Of 74 patients included, 57 were diagnosed with spasticity and 17 with dystonia. In total, 276 therapeutic cycles were administered. The dropout rates were 45.6% in the spasticity group and 41.2% in the dystonia group (P = 0.48). There was no significant difference in subjective motor improvement between dystonia and spasticity (P = 0.16). Dystonia patients reported significantly better pain relief (98.5 ± 4.9% vs. 72.4 ± 35.6% respectively, P < 0.001). Notably, 74.3% of dystonia treatments reported moderate or marked improvement, whereas only 54.0% of spasticity treatments did (P > 0.05), based on patient the global impression of change (PGI-C) scale. Side effects were infrequent.

Conclusions: BT injections for limb spasticity and dystonia are partially effective. Nonetheless, the dropout rate is high. While BT injections are more effective in relieving pain for dystonia compared to spasticity, disease severity gradually improves over time in treated patients with spasticity but not with dystonia.

Despite the application of recommended guideline-driven therapies and optimal medical interventions, individuals with established cardiovascular disease remain susceptible to additional cardiovascular incidents, a phenomenon referred to as residual risk. Analyses of clinical trial data reveal significant residual cardiovascular risk in all treated patients, even in the setting of optimal LDL-C reduction, thus enforcing the need to revise the algorithms beyond focusing on LDL-C levels. We present a case that highlights the problem of residual risk upon well controlled LDL-C levels and provide insights for additional measures for residual risk reduction.

Background: Patients with mechanical prosthetic heart valves must be treated with vitamin K antagonists (VKA) due to an increased risk of valve thrombosis and systemic embolism.

Objectives: To assess the effects of the COVID-19 pandemic on VKA treatment control in patients with mechanical prosthetic heart valves.

Methods: We conducted a retrospective nationwide cohort study using the Clalit Health Services database. The cohort included patients who underwent either aortic or mitral valve replacement using a prosthetic mechanical valve. The primary outcomes included the overall time in therapeutic range (TTR) and the percent of patients with a TTR < 50% during the first year of the COVID-19 pandemic compared to preceding year.

Results: The cohort included 2381 patients. The percentage of patients who had at least two international normalized ratio (INR) tests during the first year of the COVID-19 pandemic was significantly lower compared to the year preceding the pandemic (81% and 87%, respectively, P < 0.001). In both years, the percentage of patients without any documented INR test was high (31.5% in the first COVID-19 pandemic year and 28.9% in the preceding year, P < 0.001). TTR was significantly lower during the 1st year of the COVID-19 pandemic compared to the preceding year (68.1% ± 26 and 69.4% ± 24, P = 0.03). A TTR > 50% was demonstrated in 78% and 81% during the pandemic and the preceding year, P = 0.009.

Conclusions: We noted overall poor VKA control in patients with mechanical heart valves. During the COVID-19 pandemic, VKA control became even worse as reflected by significantly lower TTR and INR tests rates.

Background: Gram-negative bloodstream infections (GN-BSI) are life threatening. Appropriate antimicrobial therapy and source control when indicated improve survival. Dementia is an independent risk factor for death and is associated with increased risk for infections, especially in advanced stages. Data about the best diagnostic and therapeutic approaches for patients with dementia and GN-BSI are lacking.

Objectives: To evaluate patients with dementia and GN-BSI and determine whether diagnostic imaging improves clinical outcomes.

Methods: We performed a retrospective cohort study of adult patients with GN-BSI, during 2019–2022. Patients with or without a diagnosis of dementia were compared. Outcomes were in-hospital mortality and recurrent bacteremia. Demographic, clinical, diagnostic, and therapeutic data were collected and analyzed.

Results: A total of 87 patients with dementia and 130 without were included. Patients with dementia received appropriate empirical antimicrobial therapy in 38% of cases compared to 62% of patients without dementia, P < 0.001. Imaging studies were performed in half of patients in both groups. In the dementia group, 17% had abnormal findings that required source control versus 30% in the control group (P = 0.049). Source control was performed in 15% of patients with dementia versus 28% of patients without dementia (P = 0.032). Mortality was 27.6% in the dementia group versus 22.3% in the control group (P = 0.42).

Conclusions: In patients with dementia and GN-BSI, imaging studies have lower effect on clinical outcomes. Imaging studies should be performed in selected cases only and not conducted routinely.

Background: Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma. There are limited data on the management of PCNSL outside of clinical trials.

Objectives: To report experience with three main high-dose methotrexate (HDMTX)-based protocols for PCNSL treatment at one medical center.

Methods: We conducted a retrospective review of the medical records of patients diagnosed with PCNSL who were treated at Soroka Medical Center between 2007 and 2019.

Results: The study included 36 patients, median age 64.9 years; 33 patients received a HDMTX backbone induction therapy, 21 (58.3%) received consolidation treatment in addition. In the entire cohort, 25 patients (75.7%) achieved complete remission (CR, CRu-unconfirmed), with mean progression-free survival (PFS) 32 ± 6.9 months and median overall survival (OS) 59.6 ± 12.4 months. More aggressive regiment such as combination of rituximab, HDMTX, cytarabine and thiotepa had better responses 5 (100%) CR, but also a higher incidence of side effects such as neutropenic fever 5 (100%). In subgroup analysis by age (younger vs. older than 60 years), the PFS was 24.2 vs. 9.3 months, and OS was 64.1 vs. 19.4 months, respectively.

Conclusions: A difference in CR and PFS favored a more aggressive protocol, but the toxicity of the multiagent combinations was significantly higher. The prognosis in younger was better than in older patients, with higher rates of CR, PFS, and OS, although not statistically significant. Overall treatment outcomes are encouraging; however, there is a real need for an adaptive approach for older patients and balancing among the effectiveness and side effects.

Background: One of the main causes of iron deficiency anemia (IDA) is chronic gastrointestinal blood loss. The use of video capsule endoscopy (VCE) after negative bidirectional endoscopy in patients with IDA is controversial.

Objectives: To evaluate the effect of VCE in the management and long-term outcomes of IDA patients.

Methods: A retrospective case-control study was performed on all patients with IDA undergoing VCE over a 5-year period. We compared those with positive findings on VCE to those with normal findings. All participants previously underwent a negative bidirectional endoscopy

Results: We performed 199 VCE examinations; median follow-up time was 4 years (IQR 2–5). Positive findings were identified in 66 patients (diagnostic yield 33.2%). Double balloon enteroscopy or push enteroscopy was performed in eight patients (18.6%); only one was therapeutic. The main therapy in both groups was iron supplementation. There were no significant differences in iron treatment before and after VCE in each group and between groups. Anemia improved in both groups. There was no difference in the level of hemoglobin change between the groups during each year of follow-up compared to the baseline level prior to VCE. Anemia resolved in 15 patients (35%) in the positive VCE group and in 19 (45%) in the negative VCE group (P = 0.33).

Conclusions: Positive findings on VCE led to subsequent endoscopic interventions only in a small percentage of patients with IDA. Anemia improved and resolved equally whether or not there were VCE findings. The main intervention that appears to help IDA is iron supplementation.

Background: Patients admitted to the hospital after successful resuscitation from sudden cardiac death (SCD) are treated with therapeutic hypothermia (TH) to facilitate brain preservation. The prognostic significance of J (Osborn) waves (JOW) in the 12 leads electrocardiogram in this setting has not been elucidated as yet.

Objectives: To ascertain retrospectively the prognostic significance of JOW recorded during TH in SCD survivors.

Methods: The study comprised 55 consecutive patients who underwent TH. All patients achieved a core temperature of 33°C at the time of electrocardiogram analysis. We compared 33 patients with JOW to 22 patients without JOW. The endpoints were in-hospital, long-term all-cause mortality, and irreversible anoxic brain injury (IABI).

Results: Patients with JOW compared to patients without JOW were younger (55.1 ± 11.6 vs. 64.5 ± 11.7 years, respectively, P < 0.006), with a lower incidence of hypertension (52% vs. 86%, P < 0.007), diabetes mellitus (15% vs. 50%, P < 0.005), and congestive heart failure (15% vs. 45%, P < 0.013). In-hospital and long-term mortality were significantly higher in patients without JOW (86% vs. 21%, 91% vs. 24%, respectively, P < 0.000001). Among patients without JOW who survived hospitalization, 66.7% presented with IABI versus 7.7% of the patients with JOW (P < 0.0001). In multivariate analysis, the absence of JOW was a significant predictor for poor prognosis.

Conclusions: The absence of J (Osborn) waves on electrocardiograms obtained during TH is associated with poor prognosis among SCD survivors

Background: Progress in the treatment of breast cancer has led to substantial improvement in survival, but at the cost of increased side effects, with cardiotoxicity being the most significant one. The commonly used definition is cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction reduction of > 10%, to a value below 53%. Recent studies have implied that the incidence of CTRCD among patients with breast cancer is decreasing due to lower doses of anthracyclines and low association to trastuzumab and pertuzumab treatment.

Objectives: To evaluate the prevalence of CTRCD among patients with active breast cancer and to identify significant associates for its development.

Methods: Data were collected as part of the Israel Cardio-Oncology Registry, which enrolls all patients who are evaluated at the cardio-oncology clinic at our institution. Patients were divided to two groups: CTRCD and no-CTRCD.

Results: Among 103 consecutive patients, five (5%) developed CTRCD. There were no significant differences in the baseline cardiac risk factors between the groups. Significant correlations of CTRCD included treatment with trastuzumab (P = 0.001) or pertuzumab (P < 0.001), lower baseline global longitudinal strain (GLS) (P = 0.016), increased left ventricular end systolic diameter (P < 0.001), and lower e’ septal (P < 0.001).

Conclusions: CTRCD is an important concern among patients with active breast cancer, regardless of baseline risk factors, and is associated with trastuzumab and pertuzumab treatment. Early GLS evaluation may contribute to risk stratification and allow deployment of cardioprotective treatment

A virally-induced cytokine storm syndrome, associated with a massive and overwhelming systemic inflammation, burdens a subgroup of patients with severe coronavirus disease-2019 (COVID-19), which leads to pulmonary inflammation and extensive lung damage. These severe COVID-19 patients are characterized by high ferritin levels. These findings mirror what was previously reported about the prognostic role of this iron storage protein in other inflammatory diseases included in the hyperferritinemic syndrome. The latter suggests that ferritin could be a further pathogenic mediator in enhancing the inflammatory process, stimulating inflammatory pathways, and thus perpetuating a vicious pathogenic loop. Considering its activity as an immune activator, a therapeutic approach targeting ferritin may be also postulated in these diseases. Considering these observations, high ferritin levels characterize severe COVID-19 and other diseases included in the hyperferritinemic syndrome. Because ferritin could enhance the inflammatory process, it could be tested as a possible new therapeutic target to improve the outcome of these patients.

Falling from a height accounts for 14.1% of all hospital admissions for traumatic injury. In 5% of cases, the injury is severe or critical, and in 1.5%, it is fatal. The dangers of falling have been recognized since time immemorial. Indeed, the Bible instructs us to build a parapet around the roof of our home so that, “…you may not bring the guilt of bloodshed on your house if someone falls from it” (Deuteronomy 22:8). This commandment highlights the relatively simple and practical means by which we can prevent falls. It is also one of a series of ethical laws that are presented to help us understand and obey the larger Biblical precepts of loving one’s neighbor and guarding the sanctity of life. The concept teaches us that it is the responsibility of all individuals to be cognizant of others and to avoid harming people through negligence or carelessness. The aim of this article is to explain the commandment to build a parapet in the context of the risk of falling from a height and to expand on its wider implications. The present work was prompted in part by the alarming increase in fatal and near-fatal accidents in Israel in two particular populations.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive death of motor neurons leading to fatal paralysis. The causes of ALS remain unknown; however, evidence supports the presence of autoimmune mechanisms contributing to pathogenesis. Although several environmental factors have been proposed, the only established risk factors are older age, male gender, and a family history of ALS. To date, there are no diagnostic test for ALS, and clinicians rely on the combination of upper motor neuron and lower motor neuron signs in the same body region. The aim of this paper was to provide a comprehensive review of current clinical literature with special focus on the role of autoimmunity in ALS, differential diagnosis, and available therapeutic approaches. Current evidence suggests a contribution of the innate immune system in ALS, with a role of microglial cell activation at the sites of neurodegeneration. The median time from symptom onset to diagnosis of ALS is 14 months, and this time estimate is mainly based on specific clinical signs and exclusion of ALS-like conditions. Several therapeutic approaches have been proposed, including immunosuppressive drugs, to reduce disease progression. Riluzole has been established as the only, although modestly effective, disease modifying therapy, extending mean patient survival by 3to 6 months. Recent advances in understanding the pathophysiology mechanisms of ALS encourage realistic hope for new treatment approaches. To date, the cornerstones of the management of patients with ALS are focused on symptom control, maintaining quality of life and improving survival.