Israel Medical Association Journal

Background: Granulomatosis with polyangiitis (GPA) is a rare small vessel vasculitis. It usually involves the respiratory tract and kidney. Rarely, tumor-resembling inflammatory changes ensue.

Objectives: To report three unique cases of GPA presenting with tumor-like lesions in various organs.

Methods: We presented three cases of GPA. Case 1 presented with typical upper respiratory symptoms of GPA and a mediastinal mass. Case 2 presented with low back pain, a large retroperitoneal mass, and nodular skin lesions. Case 3 presented with epigastric pain and a paravertebral inflammatory mass.

Results: The patients were treated successfully with rituximab.

Conclusions: Clinicians should be aware of this presentation of granulomatosis with polyangiitis, which is known as Tumefaction Wegener’s granulomatosis

Background: Real-world information regarding the use of direct oral anticoagulants therapy and the outcome in patients with renal dysfunction is limited.

Objectives: To evaluate the clinical characteristics and outcomes of patients with atrial fibrillation (AF) and severe renal dysfunction who are treated with apixaban.

Methods: A sub-analysis was conducted within a multicenter prospective cohort study. The study included consecutive eligible apixaban- or warfarin-treated patients with non-valvular AF and renal impairment (estimated glomerular filtration rate [eGFR] modification of diet in renal disease [MDRD] < 60 ml/min/BSA) were registered. All patients were prospectively followed for clinical events and over a mean period of 1 year. Our sub-analysis included the patients with 15 < eGFR MDRD < 30 ml/min/BSA. The primary outcomes at 1 year were recorded. They included mortality, stroke or systemic embolism, major bleeding, and myocardial infarction as well as their composite occurrence.

Results: The sub-analysis included 155 warfarin-treated patients and 97 apixaban-treated ones. All had 15 < eGFR MDRD < 30 ml/min/BSA. When comparing outcomes for propensity matched groups (n=76 per group) of patients treated by reduced dose apixaban or warfarin, the rates of the 1-year composite endpoint as well as mortality alone were higher among the warfarin group (30 [39.5%] vs. 14 [18.4%], P = 0.007 and 28 [36.8%] vs.12 [15.8%], P = 0.006), respectively. There was no significant difference in the rates of stroke, systemic embolism, or major bleeding.

Conclusions: Apixaban might be a reasonable alternative to warfarin in patients with severe renal impairment.

Surgical interventions in patients with systemic sclerosis (SSc), in particular plastic procedures, might cause undesired consequences. Notably, liposuction seems to possess greater risk as adipose tissue has been shown to play an important role in treating wounds and ulcers in patients with SSc. While anticentromere antibodies were found to be correlated with vasculopathy in SSc, patients with SSc and anticentromere antibodies might be more vulnerable to surgical wound complications following liposuction. A 46-year-old female patient, who had been diagnosed with SSc at the age of 31 years, had antinuclear as well as anticentromere antibodies. She underwent abdominoplasty with liposuction and developed severe skin necrosis of the abdomen following the procedure and at the site of liposuction. The correlation with anticentromere and the role of liposuction in skin necrosis in SSc are presented.

Background: The collapse of the Syrian healthcare system during the civil war led numerous citizens to cross the Syrian–Israeli border to seek medical care.

Objectives: To describe the epidemiology of peripheral nerve injuries (PNIs) sustained in war, their management, and short-term outcomes.

Methods: A retrospective case series study was conducted on 45 consecutive patients aged 25.7 ± 9.3 years. These patients were referred to the hand surgery unit of the department of orthopedic surgery and traumatology at Galilee Medical Center between December 2014 and June 2018. Median time between injury and presentation was 60 days. Injury pattern, additional injuries, surgical findings and management, complications, and length of hospital stay were extracted from medical records.

Results: Most injuries were blast (55.6%) followed by gunshot injuries (37.8%). There were 9 brachial plexus injuries, 9 sciatic nerve injuries, and 38 PNIs distal to the plexus: specifically 20 ulnar, 11 median, and 7 radial nerve injuries. In the latter group, neurotmesis or axonotmesis was found in 29 nerves. Coaptation was possible in 21 nerves necessitating cable grafting in 19. A tendon transfer was performed for 13 peripheral nerves, occasionally supplementing the nerve repair. The patients returned to their country after discharge, average follow-up was 53.6 ± 49.6 days.

Conclusions: For nerve injuries sustained in war, early surgical treatment and providing adequate soft tissue conditions is recommended. Tendon transfers are useful to regain early function.

Background: During the coronavirus disease-2019 (COVID-19) pandemic outbreak our blood bank developed protocols to guarantee accurate blood components to COVID-19 patients.

Objectives: To provide convalescent whole blood donor screening strategies for patients recovering from COVID-19.

Methods: We recruited COVID-19 recovering patients who met our defined inclusion criteria for whole blood donation. All blood units were screened for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA by real time reverse transcription polymerase chain reaction (RT-PCR) and SARS-COV-2 immunoglobulin G (IgG) antibodies against the S1 domain.

Results: We screened 180 blood units from patients recovering from COVID-19. All results were negative for SARS-CoV-2 RNA and 87.2% were positive for SARS-COV-2 IgG antibodies in the plasma.

Conclusions: Blood component units from recovering COVID-19 patients are safe. Plasma units with positive IgG antibodies could serve as an efficient passive immunization for COVID-19 patients. Moreover, in the face of increased transfusion demand for treatment of anemia and coagulation dysfunction in critical ill COVID-19 patients, red blood cells units and random platelets units from convalescent donors can be safely transfused.

Background: Benign tracheal stenosis has emerged as a therapeutic challenge for physicians involved in the care of survivors of critical care units. Although the traditional mainstay of open surgical reconstructive treatment is still considered the gold standard, endoscopic therapies such as laser re-canalization, balloon dilation, or stenting are commonly practiced in invasive bronchology. Recurrent obstructing granulomas pose a challenge for bronchoscopists. Mitomycin C (MyC) is a cytotoxic agent that is isolated from Streptomyces caespitosus and acts by inhibiting DNA and RNA synthesis through alkylation and cross-linkages. Topical MyC is commonly used in indirect laryngoscopies for the treatment of granulation tissue in the trachea by using saturated pledgets.

Objectives: To describe fiberoptic bronchoscopic submucosal injection of MyC as a treatment for recurrent bening tracheal stenosis.

Methods: The authors report their successful experience with submucosal intralesional injection of MyC in the management of recurrent obstructing granulomas/stenosis using the flexible fiberoptic bronchoscope in a series of 10 patients between 2005 and 2019.

Results: The results suggest that intralesional injection of MyC using the flexible bronchoscope after the endoscopic treatment of the stenotic lesion may reduce the rate of subsequent formation of granulation tissue and scarring without side effects.

Conclusions: The efficacy of MyC injection should be studied prospectively.

Background: The reported mortality rates of patients with polymyositis and dermatomyositis are highly variable worldwide. The excess mortality of patients with polymyositis/dermatomyositis has not been evaluated in an Israeli population.

Objectives: To investigate the overall mortality in a large and well-established cohort of patients with polymyositis/dermatomyositis as compared to the mortality expected in the matched general population in a tertiary medical center.

Methods: In this retrospective cohort study, the mortality of 166 patients with polymyositis/dermatomyositis was compared to age- and sex-matched control subjects in the general population. All-cause standardized mortality ratios (SMRs) were estimated.

Results: Overall, 47 (28.3%) deaths were observed among patients with polymyositis/dermatomyositis during a mean follow-up period of 5.8 ± 4.8 years, which was 7 times higher than in the control group (SMR 7.4, 95% confidence interval [95%CI] 5.5–9.8). The SMRs were comparable in patents with polymyositis (7.7, 95%CI 4.8–12.3) and dermatomyositis (7.2, 95%CI 5.0–10.3). The 1-, 5-, 10-, and 15-year overall survival rates were 90.0%, 82.8%, 51.5%, and 26.1%, respectively, in patients with polymyositis, and 80.3%, 59.6%, 40.0%, and 17.1%, respectively, in patients with dermatomyositis.

Conclusions: The overall mortality among Israeli patients with polymyositis/dermatomyositis is 7.4 times greater than for the general population. Although long-term mortality was comparable between patients with dermatomyositis and polymyositis, patients in the former group died at a notably earlier stage.

Background: In Israel, critically ill patients are ventilated and managed in intensive care units or general wards.

Objectives: To compare the mortality rates and long-term cognitive and functional outcomes of ventilated patients who underwent tracheostomy insertion in the Medical ICU (MICU) versus those cared for in the in-patient wards.

Methods: The study comprised 170 patients who underwent percutaneous dilatational tracheostomy (PDT) over an 18-month period in the MICU (n=102) and in in-patient wards (internal medicine and neurology) (n=68). Telephone interviews were conducted with living patients and/or their relatives at least 6 months after discharge from the hospital.

Results: Ward patients were 10 years older than ICU patients undergoing PDT (P = 0.003). The length of stay (LOS) in the wards was longer than in the ICU (P < 0.001), whereas the total LOS in the hospital was similar (P = 0.43). ICU mortality was lower than in the wards (P = 0.001) but hospital mortality was comparable between the two groups (P = 0.17). At 6 months follow-up more ICU patients were fully conscious, weaned from ventilation, and decannulated. More patients in the ICU group were at home and were independent or had mildly impaired activities of daily living. More patients in the ward group were residing in long-term care facilities with functional limitations.

Conclusions: MICU patients who undergo tracheostomy may have a good long-term functional and cognitive outcome. More studies are needed to further assess long-term outcomes in these patients.

Background: Neonatal hypothermia (< 36°C) has been associated with both neonatal morbidity and mortality.

Objectives: To develop a multifactorial approach to reduce the incidence of neonatal hypothermia at admission to the neonatal intensive care unit.

Methods: The approach involved a detailed quality improvement (QI) plan, which included the use of occlusive wrapping and exothermic mattresses as well as higher delivery and operating room environmental temperatures. The improvement plan was implemented over a 10-month period. Retrospective comparison to the same 10-month period during the previous year assessed the effectiveness of the approach in reducing the incidence of admission hypothermia.

Results: The QI project included 189 patients. These patients were compared to 180 patients during the control period. The characteristics of the patient groups were similar and included preterm infants, who were subsequently analyzed as a subgroup. We found a significant reduction in the incidence of hypothermia, which was most profound for the subgroup of premature infants born at < 32 weeks gestation. Neonatal hyperthermia was identified as an unintended consequence of the project, and subsequently improved after initiating simple preventive measures.

Conclusions: Occlusive wrapping, exothermic mattresses, and higher delivery and operating room environmental temperature may be successful in reducing admission neonatal hypothermia

Background: Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA.

Objectives: To evaluate SC tocilizumab in a real-life clinical setting.

Methods: Our study was a multi-center, open-label, single-arm study. Participants were adults with a diagnosis of active RA, previously treated with disease-modifying antirheumatic drugs (DMARDs), with or without biologic agents. Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or DMARDs for 24 weeks. Efficacy, safety, and immunogenicity were assessed.

Results: Treatment of 100 patients over 24 weeks resulted in improvement in all efficacy parameters assessed: Clinical Disease Activity Index, Disease Activity Score using 28 joint counts and erythrocyte sedimentation rate, American College of Rheumatology response scores, Simplified Disease Activity Index, tender and swollen joint counts, and patient-reported outcomes including fatigue, global assessment of disease activity, pain, and Health Assessment Quality of Life Disease Index. Improvement was achieved as early as the second week of treatment. There were 473 adverse events (AEs)/100 patient-years (PY) and 16.66 serious AEs/100 PY. The most common AEs were neutropenia (12%), leukopenia (11%), and increased hepatic enzymes (11%). Of a total of 42 PY, the rates of serious infections and AEs leading to discontinuation were 4.8, and 11.9 events/100 PY, respectively.

Conclusions: The safety, tolerability, and efficacy profile of tocilizumab SC were comparable to those reported in other studies evaluating the IV and SC routes of administration.

Background: Ferritin, the cellular protein storage for iron, has emerged as a key molecule in the immune system, orchestrating the cellular defense against inflammation. At the end of 2019, the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rapidly spread throughout China and other countries around the world, resulting in a viral pandemic.

Objectives: To evaluate the correlation between ferritin and disease severity in coronavirus disease-2019 (COVID-19).

Methods: In this cross-sectional study, we obtained clinical and laboratory data regarding 39 hospitalized patients with confirmed COVID-19 from two hospitals in Israel.

Results: A significant increase in ferritin levels was demonstrated in patients with moderate and severe disease, compared to patients with mild disease (P = 0.006 and 0.005, respectively). Severe patients had significantly higher levels of ferritin (2817.6 ng/ml) than non-severe patients (708.6 ng/ml) P = 0.02.

Conclusions: In this preliminary cross-sectional study, elevated ferritin levels were shown to correlate with disease severity in 39 patients from Israel with confirmed COVID-19 infection. Our results further strengthen the hypothesis that severe COVID-19 disease might be due to an underlying dysregulated hyperimmune response. In order to identify these patients early and prioritized resources, we believe that all patients with COVID-19 should be screened for hyperferritinemia.