Israel Medical Association Journal

In the absence of definitive anti-viral therapy, there is considerable interest in mitigating against severe inflammatory reactions in coronavirus disease-2019 (COVID-19) pneumonia to improve survival. These reactions are sometimes termed cytokine storm. PDE4 inhibitors (PDE4i) have anti-inflammatory properties with approved indications in inflammatory skin and joint diseases as well as chronic obstructive pulmonary disease (COPD). Furthermore, multiple animal models demonstrate strong anti-inflammatory effects of PDE4i in respiratory models of viral and bacterial infection and also after chemically mediated lung injury. The rationale for PDE4i use in COVID-19 patients comes from the multimodal mechanism of action with cytokine, chemokine, and other key pathway inhibition all achieved with an excellent safety profile. We highlight how PDE4i could be an overlooked treatment from the rheumatologic and respiratory armamentarium, which has potential beneficial immune-modulation for treating severe COVID-19 pneumonia associated with cytokine storms. The proposed use of PDE4i is also supported by age-related immune changes in inflammation severity in PDE4i modifiable pathways in primate coronavirus disease. In conclusion, over-exuberant anti-viral immune responses in older patients with COVID-19 may pose a substantial risk to patient survival and mitigation against such hyper-inflammation with PDE4i, especially with anti-viral agents, is a strategy that need to be pursed, especially in older patients

Background: Cyclophosphamide treatment has been associated with ovarian function impairment. Co-treatment with gonadotropin-releasing hormone-analogue (GnRH-a) seems to be able to prevent this complication. However, even though data are available on neoplastic patients, limited data have been published on systemic lupus erythematosus (SLE) women cohorts

Objectives: To evaluate GnRH-a efficacy on ovarian function preservation in SLE women receiving cyclophosphamide treatment

Methods: The authors performed a retrospective study including SLE women requiring cyclophosphamide treatment and compared those treated with and without GnRH-a (case and controls, respectively). All patients were evaluated before cyclophosphamide treatment and every 3 months in the following years. Ovarian function was evaluated using hormonal profiles

Results: The study comprised 33 SLE cyclophosphamide-treated women: 18 co-treated with triptorelin and 15 controls. The mean follow-up was 8.1 ± 5.1 years (range 4–11). Premature ovarian failure (POF) prevalence was significantly lower in SLE women treated by cyclophosphamide plus triptorelin compared to controls (11.1% vs. 33.3%, P = 0.0002). The occurrence of POF was significantly associated with higher age at the time of cyclophosphamide treatment (P = 0.008). Only patients in the GnRH-a treated group had successful pregnancies

Conclusions: The study provides information about the efficacy of co-treatment with GnRH-a in SLE women receiving cyclophosphamide, as demonstrated by the lower POF incidence compared to untreated subjects, based on long-term follow-up. These results reinforce the use of GnRH-a for fertility preservation in premenopausal SLE patients treated by cyclophosphamide

Background: Cardiovascular disease (CVD) is more frequent in patients with systemic lupus erythematosus (SLE) compared with age- and sex-matched healthy subjects. SLE is an autoimmune disease that is more prevalent in women (9:1). Women tend to develop CVD in post-menopausal years; however, women with SLE may develop endothelial dysfunction and CVD at a younger age in the pre-menopausal years.

Objectives: To study the endothelial function of adult-onset SLE patients from the north of Israel (the Galilee region) and to determine whether modern management (including biological treatments) changes the risk of developing CVD.

Methods: Thirteen females with adult-onset SLE without renal involvement were recruited to this prospective study. Clinical parameters (age, height, body mass index [BMI]), laboratory parameters (C-reactive protein [CRP] and hemoglobin level), and vascular responsiveness (flow mediated diameter percent change [FMD%]) were evaluated and compared to 11 age-matched healthy females. Student's t-test was used to find differences between the two groups.

Results: No difference was observed in adult-onset SLE female patients and their age- and sex-matched controls with regard to age (42.1 ± 11.8 years vs. 36.6 ± 10.8 years, P = NS), BMI (25 ± 1.8 kg/m² vs. 25 ± 2.5 kg/m², P = NS), and hemoglobin level (11.9 ± 0.9 gr% vs. 12.7 ± 1.2 gr%, P = NS). However, a significant difference was found in CRP (2.57 ± 2.2 mg vs. 0.60 ± 0.37 mg, P = 0.001), vascular responsiveness (0.94 ± 6.6 FMD% vs. 9.2 ± 8.1 FMD%, P = 0.012), and height (165.7 ± 4.5 cm vs. 171.6 ± 5.8 cm, P = 0.009).

Conclusions: Adult-onset SLE females had impaired endothelial function even though they were treated by modern protocols.

Background: Coronary artery bypass grafting (CABG) for primary reperfusion in patients with ST elevation myocardial infarction (STEMI) has largely been superseded byf primary percutaneous coronary intervention (PCI) and is estimated to be performed in ≤ 5% of STEMI cases.

Objectives: To compare early CABG (within 30 days following admission) and primary PCI outcomes following STEMI.

Methods: We analyzed a retrospective cohort of patients hospitalized with acute STEMI for early reperfusion therapy between January 2008 and June 2016. Short- and long-term outcomes were assessed for patients with STEMI undergoing primary PCI vs. early CABG as reperfusion therapy.

Results: The study comprised 1660 STEMI patients, 38 of whom (2.3%) underwent CABG within 30 days of presentation. Unadjusted 30-day mortality was more than twice as high in the CABG group (7.5%) than in the PCI group (3.3%); however, it did not reach statistical significance. Similar results were demonstrated for mortality rates beyond 30 days (22% vs. 14%, P = 0.463). All patients undergoing CABG beyond 72 hours following admission survived past 2 years. Multivariate analysis found no differences between the two groups in long-term mortality risk. propensity score matched long-term mortality comparison (30 days–2 years) yielded a 22% mortality rate in the CABG groups compared with 14% in the PCI group (P < 0.293).

Conclusion: Early CABG was performed in only a minority of STEMI patients. This high-risk patient population demonstrated worse outcomes compared to patients undergoing PCI. Performing surgery beyond 72 hours following admission may be associated with lower risk.

Background: Cardiac rehabilitation (CR) is underutilized globally despite evidence of clinical benefit. Major obstacles for wider adoption include distance from the rehabilitation center, travel time, and interference with daily routine. Tele-cardiac rehabilitation (tele-CR) can potentially address some of these limitations, enabling patients to exercise in their home environment or community.

Objectives: To evaluate the clinical and physiological outcomes as well as adherence to tele-CR in patients with low cardiovascular risk and to assess exercise capacity, determined by an exercise stress test, using a treadmill before and following the 6-month intervention.

Methods: A total of 22 patients with established coronary artery disease participated in a 6-month tele-CR program. Datos Health (Ramat Gan, Israel), a digital health application and care-team dashboard, was used for remote monitoring, communication, and management of the patients.

Results: Following the 6-month tele-CR intervention, there was significant improvement in exercise capacity, assessed by estimated metabolic equivalents with an increase from 10.6 ± 0.5 to 12.3 ± 0.5 (P = 0.002). High-density lipoproteins levels significantly improved, whereas low-density lipoproteins, triglyceride, glycosylated hemoglobin, and systolic and diastolic blood pressure levels were not significantly changed. Exercise adherence was consistent among patients, with more than 63% of patients participating in a moderate intensity exercise program for 150 minutes per week.

Conclusions: Patients who participated in tele-CR adhered to the exercise program and attained clinically significant functional improvement. Tele-CR is a viable option for populations that cannot, or elect not to, participate in center-based CR programs.

Background: Abdominal tumors invading the inferior vena cava (IVC) present significant challenges to surgeons and oncologists.

Objectives: To describe a surgical approach and patient outcomes.

Methods: The authors conducted a retrospective analysis of surgically resected tumors with IVC involvement by direct tumor encasement or intravascular tumor growth. Patients were classified according to level of IVC involvement, presence of intravascular tumor thrombus, and presence of hepatic parenchymal involvement.

Results: Study patients presented with leiomyosarcomas (n=5), renal cell carcinoma (n=7), hepatocellular carcinoma (n=1), cholangiocarcinoma (n=2), Wilms tumor (n=1), neuroblastoma (n=1), endometrial leiomyomatosis (n=1), adrenocortical carcinoma (n=1), and paraganglioma (n=1). The surgeries were conducted between 2010 and 2019. Extension of tumor thrombus above the hepatic veins required a venovenous bypass (n=3) or a full cardiac bypass (n=1). Hepatic parenchymal involvement required total hepatic vascular isolation with in situ hepatic perfusion and cooling (n=3). Circular resection of IVC was performed in five cases. Six patients had early postoperative complications, and the 90-day mortality rate was 10%. Twelve patients were alive, and six were disease-free after a mean follow-up of 1.6 years.

Conclusions: Surgical resection of abdominal tumors with IVC involvement can be performed in selected patients with acceptable morbidity and mortality. Careful patient selection, and multidisciplinary involvement in preoperative planning are key for optimal outcome.

Background: The effect of weight reduction following bariatric surgery is already well known.

Objectives: To investigate the effects of abdominoplasty on metabolic markers indicative of weight loss.

Methods: The authors prospectively enrolled consecutive obese patients after laparoscopic sleeve gastrectomy. They were candidates for post-bariatric surgery abdominoplasty. The authors measured metabolic markers one day prior to surgery, 24 hours after, and 3 months following surgery. They recorded medical and demographic parameters.

Results: Sixteen patients were recruited for participation in the study. Mean age was 47 years and 88% of the patients were female. Bariatric surgery achieved a mean decline in body mass index of 13.8 kg/m². All patients underwent abdominoplasty. Leptin and insulin levels were slightly increased at 3 months postoperative. No significant changes were observed in glucose, hemoglobin, or triglycerides throughout the study.

Conclusions: In a cohort of obese patients undergoing laparoscopic sleeve gastrectomy followed by abdominoplasty, no significant changes were noted in a patient’s metabolic profiles. The results suggest that abdominoplasty has no effect on the metabolic markers tested in contrast to other reports; however, the cosmetic, behavioral, and psychological advantages of abdominoplasty are well established.

Background: In February 2020, the World Health Organisation designated the name COVID-19 for a clinical condition caused by a virus identified as a cause for a cluster of pneumonia cases in Wuhan, China. The virus subsequently spread worldwide, causing havoc to medical systems and paralyzing global economies. The first COVID-19 patient in Israel was diagnosed on 27 February 2020.

Objectives: To present our findings and experiences as the first and largest center for COVID-19 patients in Israel.

Methods: The current analysis included all COVID-19 patients treated in Sheba Medical Center from February 2020 to April 2020. Clinical, laboratory, and epidemiological data gathered during their hospitalization are presented.

Results: Our 162 patient cohort included mostly adult (mean age of 52 ± 20 years) males (65%). Patients classified as severe COVID-19 were significantly older and had higher prevalence of arterial hypertension and diabetes. They also had significantly higher white blood cell counts, absolute neutrophil counts, and lactate dehydrogenase. Low folic acid blood levels were more common amongst severe patients (18.2 vs. 12.9 vs. 9.8, P = 0.014). The rate of immune compromised patients (12%) in our cohort was also higher than in the general population. The rate of deterioration from moderate to severe disease was high: 9% necessitated non-invasive oxygenation and 15% were intubated and mechanically ventilated. The mortality rate was 3.1%.

Conclusions: COVID-19 patients present a challenge for healthcare professionals and the whole medical system. We hope our findings will assist other providers and institutions in their care for these patients.

Background: Recent data regarding polymicrobial bacteremia (PMB) are lacking.

Objectives: To characterize risk factors as well as clinical, microbiological, and prognostic patterns of patients with PMB in a modern hospital setting.

Methods: A single center retrospective study including all patients diagnosed with PMB during 2013 was conducted. PMB was defined as two or more organisms cultured from the blood of the same patient within 72 hours. Patients with monomicrobial infections served as controls.

Results: There were 135 episodes (2% of all bacteremia episodes) of true PMB among 123 patients during the study period. Recent invasive procedures (odds ratio [OR] 3.59, 95% confidence interval [95%CI] 1.41–9.12, P = 0.006) and foreign bodies (OR 1.88, 95%CI 1.06–3.33, P = 0.04) were risk factors for PMB when compared with 79 patients with monomicrobial bacteremia. Central-line-associated infections were the most common infection source among patients with PMB (n=34, 28%). Enterobacteriaceae were the most commonly implicated pathogen (n=95, 77%). Non-fermenting Gram-negative bacilli were significantly more common than previously reported (n=55, 45%). Although crude 30-day mortality was higher (48% vs. 33%) in PMB patients, adjusted mortality was comparable in the two groups.

Conclusions: PMB rate in our cohort was considerably lower than in previous reports. Central-line-associated infections were more common than classic PMB sources. Mortality remained high. Strategies for early identification and better care for these patients should be pursued.

Background: Heart transplantation (HT) success rate is limited by a high incidence of cancer post-HT. Data on kidney cancer following solid organ transplantation, especially HT, are limited, and only a few cases have been reported.

Objectives: To report a unique case series of detected kidney cancer following HT.

Methods: Between 1997 and 2018, 265 patients who underwent HT were enrolled and prospectively followed in the HT registry of the Sheba Medical Center.

Results: The series included 5 patients, 4 men and a woman (age range 35–50 years at HT). The patients were diagnosed with kidney tumors 6–11 years after HT (age range at diagnosis 40–72 years). Two of the men were identical twin brothers. At HT four patients received induction therapy with anti-thymocyte globulin and all received an initial immunosuppressive regimen based on cyclosporine. All male HT recipients had a history of heavy smoking. Two male patients developed allograft vasculopathy, but all had preserved heart function. The 72-year-old woman developed a kidney tumor of the native kidney 5 years after re-HT and kidney transplantation. Two patients had features of multifocal papillary renal cell carcinoma (RCC) and eventually underwent bilateral nephrectomy, while another patient underwent left partial nephrectomy with preserved renal function.

Conclusions: To the best of our knowledge, this is the first case series study describing kidney tumors following HT. With the improving outcomes and life expectancy of HT patients, a better understanding of the factors that determine cancer risk is of the utmost importance and may have a major impact on the non-cardiac surveillance.