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עמוד בית
Tue, 11.08.20

June 2020

Coronavirus (COVID-19)
Charlie Bridgewood PhD, Giovanni Damiani MD, Kassem Sharif MD, Abdulla Watad MD, Nicola Luigi Bragazzi MD PhD MPH, Luca Quartuccio MD, Sinisa Savic and Dennis McGonagle FRCPI PhD

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


Oren Biham BMedSc, Aviya Kedmi BMedSc, Mohamad Abo Sbet MD and Lior Zeller MD
Nisim Asayag BA, Anat Skliar BSc, Lior Rozental MD, Rotem Moshe MA and Yona Kitay-Cohen MD
Original Articles
Valeria Orefice MD, Fulvia Ceccarelli MD PhD, Giuseppina Perrone MD, Carlo Perricone MD PhD, Paola Galoppi MD, Viviana Antonella Pacucci MD, Francesca Romana Spinelli MD PhD, Cristiano Alessandri, Roberto Brunelli MD and Fabrizio Conti MD

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

Mohammad Adawi MD, Tair Abu-Gabel MD, Firas Sabbah MD, Itamar Yehuda PhD, Snait Tamir PhD and Arnon Blum MD

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.

Ilan Merdler MD MHA, Mustafa Gabarin MD, Itamar Loewenstein MD, Sivan Letourneau MD, David Zahler MD, Aviram Hochstadt MD, Yishay Szekely MD, Shmuel Banai MD and Yacov Shacham MD

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.

Irene Nabutovsky PhD, Saar Ashri BSc, Amira Nachshon RNMA, Riki Tesler PhD, Yair Shapiro MD MBA, Evan Wright MD, Brian Vadasz MD, Amir Offer MD FACC, Liza Grosman-Rimon PhD and Robert Klempfner MD

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.

Lior Orbach MD, Ido Nachmany MD, Yaacov Goykhman MD, Guy Lahat MD, Ofer Yossepowitch MD, Avi Beri MD, Yanai Ben-Gal MD, Joseph M. Klausner MD and Nir Lubezky MD

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.

Veacheslav Zilbermints MD, Oren Israeli MD, Binyamin Ben Abraham MD, Tuvia Ben-Gal MD, Victor Rubchevsky MD, Dan Aravot MD, Hanoch Kashtan MD, Nikolai Menasherov MD and David Aranovich MD

Background: Left ventricular assist devices (LVADs) are used more commonly in patients with advanced-stage heart failure. Some of these patients may require elective or urgent abdominal surgical procedures.

Objectives: To determine the outcomes of the management of LVAD-supported patients who underwent elective and urgent abdominal surgical procedures in our institution.

Methods: A retrospective review was conducted on 93 patients who underwent LVAD implantation between August 2008 and January 2017. All abdominal surgeries in these patients were studied, and their impact on postoperative morbidity and mortality was evaluated.

Results: Ten patients underwent abdominal surgical procedures. Of these procedures, five were emergent and five were elective. The elective cases included one bariatric surgery for morbid obesity, one hiatal hernia repair, two cholecystectomies, and one small bowel resection for a carcinoid tumor. The emergency cases included suspected ischemic colitis, right colectomy for bleeding adenocarcinoma, laparotomy due to intraabdominal bleeding, open cholecystectomy for gangrenous cholecystitis, and laparotomy for sternal and abdominal wall infection. All patients undergoing elective procedures survived. Of the five patients who underwent emergency surgery, three died (60%, P = 0.16) and one presented with major morbidity. One of the two survivors required reintervention. In total, 12 interventions were performed on this group of patients.

Conclusions: It is safe to perform elective abdominal procedures for LVAD-supported patients. The prognosis of these patients undergoing emergency surgery is poor and has high mortality and morbidity rates.

Lior Leibou MD, Tomer Perlok MD, Rivi Haiat Factor MD, Eyal Leibovitz MD, Jacob Frand MD, Stav Leibou, Dror Sadan MD and Mordechai Shimonov MD

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.

Yonit Wiener-Well MD, Mustafa Hadeedi MD, Yuval Schwartz MD, Amos M. Yinnon MD and Gabriel Munter MD

Background: Antibiotic stewardship programs are necessary to test the appropriateness of local guidelines for empirical antibiotic treatment by audits.

Objectives: To assess whether compliance to local guidelines achieved a higher rate of appropriate antibiotic treatment and reduced morbidity and mortality, and whether infectious disease counseling improved the rate of appropriate treatment.

Methods: Our cohort comprised 294 patients with proven bacteremia. Data were retrieved from medical records including diagnosis, empiric antibiotic treatment, and outcomes.

Results: The empirical treatment was consistent with bacterial susceptibility in 227 patients (77%), and matched in 64% of the time to the first line, and another 24% to the second line of institutional guidelines. A strong correlation was found between appropriate empiric treatment according to bacterial susceptibility and reduced mortality (odds ratio [OR] 0.403, P = 0.007). A similar correlation was found with the choice of appropriate antibiotics according to local guidelines (OR 0.392, P = 0.005). Infectious disease consultation was related to an increase in the rate of appropriateness of treatment according to guidelines (85% vs.76%, P = 0.005). A tendency to increased appropriateness was related to microbial susceptibility (87% vs. 74%, P = 0.07).

Conclusions: In this study, initiation of appropriate empiric antibiotic therapy, according to the hospital's guidelines, was found associated with reduced mortality in patients with bacteremia.

Lisa D. Amir MD MPH

Background: Rapid response teams (RRT) reduce in-hospital mortality and cardiac arrests. There are only a few articles describing RRT activations outside of North America and Australia.

Objectives: To describe demographic and clinical variables of RRT activations using 13 years of data.

Methods: Schneider Children's Medical Center of Israel is a pediatric hospital with the busiest pediatric emergency department in the country. We analyzed demographic and clinical data of RRT activation from 1 January 2008 to 31 December 2018.

Results: During the study period there were 614 RRT activations with an average of 55.8 activations per year (range 43–76). RRT activations occurred most commonly for children aged 0–12 months (43%) as compared to children 1–5 years of age (25%), 6–10 years of age (12%), 11–18 years of age (18%), and adults (2%). The most common reason for activation was respiratory deterioration (45.8%) followed by neurologic alteration (21%), and cardiac arrest (18%). Following resuscitation, 47% of the patients were admitted to the pediatric intensive care unit and 12% were pronounced dead. Intubation was performed in 48.9% of activations, chest compressions in 20.5%, intraosseous line insertion in 9.4%, and defibrillation in 3.4%. Procedures were usually performed in the emergency department (ED).

Conclusions: We describe RRT including RRT activations in the ED. The high frequency of interventions should be utilized to direct staff training for the RRT and the ED. The lack of standardization of reporting data for RRT activations makes comparisons among hospitals difficult.

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