Israel Medical Association Journal

Idiopathic eosinophilic vasculitis is a newly recognized form of hypereosinophilic syndrome. While little is understood about the condition, criteria for its definition have been proposed. We aimed to determine whether three patients with eosinophilia and vasculitis could be retrospectively diagnosed with this condition. We performed a retrospective descriptive analysis on three cases with hypereosinophilia and vasculitis who were treated in Sheba Medical Center, Sourasky Medical Center, and Meir Medical Center in Israel between 2009 and 2021. A thorough review of all three cases was conducted. The findings were compared to the suggested criteria for idiopathic eosinophilic vasculitis.

All patients shared the symptoms of progressive limb ischemia, eosinophilic rash, and peripheral neuropathy that are consistent with vasculitis. No lower or upper respiratory abnormalities or the presence of anti-neutrophil cytoplasmic antibodies (ANCA) autoantibodies associated with eosinophilic granulomatosis with polyangiitis were detected. Primary monoclonal abnormalities, drug interactions, infections, allergy, and other secondary causes of hypereosinophilia were excluded. After a thorough review, we suggest that our three patients with previously unexplained hypereosinophilia and vasculitis fit the diagnosis of idiopathic eosinophilic vasculitis. These results highlight the existence of this novel condition and the importance of its recognition and consideration as part of the differential diagnosis in patients with marked eosinophilia and vasculitis. Further research for elucidating the mechanisms and treatment approach for this potentially severe condition is urgently needed.

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.

Intravesicular administration of Bacillus Calmette–Guérin (BCG), a live attenuated strain of Mycobacterium bovis, has long been used as adjuvant therapy for treatment of non-muscle invasive bladder carcinoma. BCG is usually well tolerated; however, infectious complications can range from 1–5% of cases. Infectious complications of BCG [1] can be divided into localized disease, which is considered a late onset disease occurring 3 months following treatment such as cystitis, Epididymo-orchitis, and pyelonephritis. Another form is a systemic disease, which is an early onset manifestation including sepsis syndrome that usually occurs directly after treatment and is the most common form of disseminated BCG infection.

Cannabis and cannabinoids have been known for thousands of years for their promising potential as analgesics. Chronic pain is a common complaint among many patients with rheumatic conditions. These disorders have revisited the medical approach toward cannabis and its potential role in pain relief. In addition, in recent years, information has mounted about the immunomodulatory effects of cannabis. In this review we discuss findings on the benefits cannabis may have in rheumatic and autoimmune disorders.

Background: Neutrophil-to-lymphocyte ratio (NLR) is a simple and cost-effective marker of inflammation. This marker has been shown to predict cardiac arrhythmias, progression of valvular heart disease, congestive heart failure decompensation, acute kidney injury, and mortality in cardiovascular patients. The pathologic process of aortic stenosis includes chronic inflammation of the valve and therefore biomarkers of inflammation might offer additive prognostic value.

Objectives: To evaluate NLR and its association with long term mortality in transcatheter aortic valve implantation (TAVI) patients.

Methods: We evaluated data of 1152 consecutive patient from the Tel Aviv Medical Center TAVI registry who underwent TAVI. Data included baseline clinical, demographic, and echocardiographic findings; procedural complications; and post-procedure mortality. Patients were compared by using the median NLR value (4.1) and evaluated for long-term mortality.

Results: Patients with NLR above the median had higher mortality rates (26.4% vs. 16.3%, P < 0.001) at 3 years post-procedure. A multivariable analysis found NLR to be an independent risk factor for mortality (hazard ratio = 1.47, 95% confidence interval 1.09–1.99, P = 0.013). In addition, high NLR was linked to complicationsduring and after the procedure.

Conclusion: NLR is an independent prognostic marker among TAVI patients. This marker may represent an increased inflammatory response and should be added to previous known prognostic factors.

Background: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations, but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients.

Objectives: To investigate the possible implication of TR among STEMI patients.

Methods: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI) and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR, its relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded.

Results: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%; P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (hazard ratio 2.44; 95% confidence interval 1.06–5.62; P = 0.036) for patients with moderate-severe TR.

Conclusions: Among STEMI patients after primary PCI, the presence of moderate-severe TR was independently associated with adverse outcomes and significantly lower survival rate

Background: Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread musculoskeletal pain accompanied by various additional symptoms. The prevalence of FMS ranges between 2–8% of the population. The exact pathophysiology of the disease remains unknown, and under certain circumstances it is difficult for the physician to diagnose. Previous studies have shown a correlation between inflammatory biomarkers such as C-reactive protein (CRP) and FMS activity, suggesting that an inflammatory component may play a role in this disease pathogenesis.

Objectives: To investigate the role of certain new inflammatory biomarkers in the diagnosis of patients with FMS.

Methods: In this study data were collected from FMS patients who were admitted to Ziv Medical Center during the period 2013 to 2019 in an attempt to find a connection between inflammatory markers detectable by a traditional complete blood count (CBC) tests such as neutrophil-lymphocytes ratio (NLR), platelet-lymphocyte ratio (PLR), mean platelet value (MPV), red cell distribution width (RDW), and C-reactive protein (CRP) and FMS.

Results: We found significantly higher CRP levels, MPV, and PLR and lower lymphocyte count in the FMS group compared to the control group.

Conclusions: FMS has certain inflammatory components that may be useful in disease diagnosis

Background: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients.

Objectives: To investigate the possible implication of TR among STEMI patients.

Methods: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI), and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR as well as the relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded.

Results: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%, P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (2.44, 95% confidence interval 1.06–5.6, P = .036) for patients with moderate to severe TR.

Conclusions: Among STEMI patients after primary PCI, the presence of moderate to severe TR was independently associated with adverse outcomes and significantly lower survival rate

Background: Chronic lung diseases, especially emphysema and pulmonary fibrosis, are the third leading cause of mortality worldwide. Their treatment includes symptom alleviation, slowing of the disease progression, and ultimately organ transplant. Regenerative medicine represents an attractive alternative.

Objectives: To develop a dual approach to lung therapy by engineering a platform dedicated to both remodeling pulmonary architecture (bronchoscopic lung volume reduction) and regeneration of lost respiratory tissue (scaffold).

Methods: The authors developed a hydrogel scaffold based on the natural polymers gelatin and alginate. The unique physical properties allow its injection through long catheters that pass through the working channel of a bronchoscope. The scaffold might reach the diseased area; thus, serving a dual purpose: remodeling the lung architecture as a lung volume reduction material and developing a platform for tissue regeneration to allow for cell or organoid implant.

Results: The authors’ novel hydrogel scaffold can be injected through long catheters, exhibiting the physical and mechanical properties necessary for the dual treatment objectives. Its biocompatibility was analyzed on human fibroblasts and mouse mesenchymal cells. Cells injected with the scaffold through long narrow catheters exhibited at least 70% viability up to 7 days.

Conclusions: The catheter-injectable gelatin-alginate hydrogel represents a new concept, which combines tissue engineering with minimal invasive procedure. It is an inexpensive and convenient to use alternative to other types of suggested scaffolds for lung tissue engineering. This novel concept may be used for additional clinical applications in regenerative medicine.

Background: Solar urticaria (SU) is a rare and disabling photodermatosis. SU typically manifests as urticarial wheals and erythema appearing shortly after sun exposure. SU is often initially diagnosed clinically with subsequent confirmation through photoprovocation tests. Early diagnosis is important for correct management of patients.

Objective: To present the clinical features of three cases of atypical presentation of SU and to discuss possible underlying mechanisms.

Methods: We report a series of three patients who presented with transient pruritic erythema without wheals after sun exposure. All patients had photoprovocation tests conducted to confirm SU diagnosis and to determine their action spectra. Treatment outcomes were recorded.

Results: All three patients developed classical manifestations of SU during photoprovocation tests within the UVA1 spectrum. Two patients required high-dose irradiation to provoke urticaria.

Conclusions: Erythema without urticaria can be the primary manifestation of SU, especially in countries with sunny climates where natural skin hardening is common. Such cases require a high index of suspicion for SU and highlight the importance of photoprovocation testing to confirm the diagnosis.

Background: Frozen section (FS) is often performed when histopathological evaluations are urgently required for implementation of therapeutic measures. In dermatology, this method is most commonly used to evaluate excision margins of tumors. FS are also routinely employed to differentiate toxic epidermal necrolysis from staphylococcal scalded skin syndrome. However, little is currently known about the performance of FS in the diagnosis of inflammatory dermatoses.

Objectives: To compare histopathological diagnoses in a series of patients with a clinical diagnosis of an inflammatory dermatosis for which FS and paraffin-section (PS) specimens were obtained on the same day.

Methods: We conducted a single-center retrospective analysis of 43 cases. All histological slides were reviewed by a single dermato-pathologist. Concordance was calculated between FS and PS.

Results: Patients were divided into three groups according to diagnosis: papulosquamous diseases (group I), drug eruptions (group II), and a heterogeneous group (group III) that included cases of bullous vasculitis and Sweet syndrome. Among the three groups, the results of FS and of PS were discordant only in five cases (5/43, 11.6%). Compared to PS, FS had a sensitivity of 92.9% [95% confidence interval (95%CI) 64.17–99.63%] and a specificity of 100% in group I, sensitivity of 90.9% (95%CI 57.12–99.52%) and specificity of 100% in group II, and sensitivity of 83.33% (95%CI 60.78–94.16%) and specificity of 100% in group III. The degree of agreement between the results of the FS and of the PS was almost perfect (kappa = 0.95, 0.93 and 0.85 respectively).

Conclusions: This study suggests that FS is a valid approach for the rapid diagnosis of inflammatory dermatoses. This method is as specific as PS, although it is less sensitive.

Background: Antibiotic treatment of Clostridium difficile infection (CDI) has a high failure rate. Fecal microbiota transplantation (FMT) has proven very effective in treating these recurrences. 

Objectives: To determine which method of fecal microbiota transplantation (upper or lower gastrointestinal) and which type of donor (a relative or unrelated) is superior.

Methods: This is a retrospective analysis of treatment protocols and outcomes in 22 patients with refractory or recurrent CDI who underwent FMT at two Israeli facilities. Each center used a different donor type, stool preparation and method of delivery. The Tel Aviv Sourasky Medical Center used unrelated fecal donors and frozen stool samples and delivered them primarily (92%) via the lower gastrointestinal (GI) tract. Shaare Zedek Medical Center used fresh donor stool of relatives and delivered them primarily (90%) via the upper GI tract.

Results: FMT had an overall 2 month cure rate of 89%. Patients treated with FMT that was executed through the lower GI tract recovered faster from the infection (1.6 ± 1.08 vs. 2.4 ± 1 days for the upper tract, P = 0.03). The results also showed that patients who received lower GI tract FMTs were more likely to be cured of CDI (100% vs. 75% for upper tract FMTs, P = 0.16). Five patients (22%) died of CDI/FMT-unrelated causes and two (10%) died of CDI/FMT-related causes during the study period.

Conclusions: Lower GI tract FMT is a safe and effective treatment for refractory and recurrent CDI, and yields quicker results than upper GI tract FMT. 

 

Background: Cardiac rupture is a rare but ominous complication of myocardial infarction.

Objectives: To study the clinical presentation, medical course, outcome and echocardiographic predictors of patients with myocardial rupture.

Methods: We evaluated 15 consecutive patients with cardiac rupture during a 4 year period in our department. The current report explores the presence of potential risk factors, timing, relation to the thrombolysis, coronary interventions and outcome.

Results: The index event in all patients was first ST elevation myocardial infarction. In seven patients rupture occurred in the first 24 hours. Pericardial effusion on admission with a clot was present in three patients. Five patients received thrombolytic therapy. Only three patients underwent coronary angioplasty, but in one case it was performed late and in two patients the culprit artery could not be opened. Six patients reached the operating room, of whom three survived.

Conclusions: The lack of early mechanical reperfusion in acute myocardial infarction and thrombolytic therapy are risk factors for cardiac rupture. Pericardial effusion on admission and evidence of a clot are echocardiographic indicators of cardiac rupture and should alert the medical team to further assess the possibility of cardiac rupture.