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עמוד בית
Sat, 20.07.24

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February 2023
Dana Yelin MD MPH, Ran Levi BPT, Chinanit Babu BPT, Roi Moshe MSc, Dorit Shitenberg MD, Alaa Atamna MD, Ori Tishler MD, Tanya Babich MSc, Irit Shapira-Lichter PhD, Donna Abecasis PhD, Nira Cohen Zubary MSc, Leonard Leibovici MD, Dafna Yahav MD, Ili Margalit MD, MPH

Background: Clinical investigations of long-term effects of coronavirus disease 2019 (COVID-19) are rarely translated to objective findings.

Objectives: To assess the functional capacity of individuals reported on deconditioning that hampered their return to their pre-COVID routine.

Methods: Assessment included the 6-minute walk test (6MWT) and the 30-second sit-to-stand test (30-STST). We compared the expected and observed scores using the Wilcoxon signed-rank test. Predictors of test scores were identified using linear regression models.

Results: We included 49 individuals, of whom 38 (77.6%) were recovering from mild COVID-19. Twenty-seven (55.1%) individuals had a 6MWT score lower than 80% of expected. The average 6MWT scores were 129.5 ± 121.2 meters and 12.2 ± 5.0 repeats lower than expected scores, respectively (P < 0.001 for both). The 6MWT score was 107.3 meters lower for individuals with severe COVID-19 (P = 0.013) and rose by 2.7 meters per each 1% increase in the diffusing capacity of carbon monoxide (P = 0.007). The 30-STST score was 3.0 repeats lower for individuals who reported moderate to severe myalgia (P = 0.038).

Conclusions: Individuals with long COVID who report on deconditioning exhibit significantly decreased physical capacity, even following mild acute illness. Risk factors include severe COVID-19 and impaired diffusing capacity or myalgia during recovery.

December 2021
Yuval Avda MD, Jonathan Modai MD, Igal Shpunt MD, Michael Dinerman MD, Yaniv Shilo MD, Roy Croock MD, Morad Jaber MD, Uri Lindner MD, and Dan Leibovici MD

Background: Patients with high-risk prostate cancer are at higher risk of treatment failure, development of metastatic disease, and mortality. There is no consensus on the treatment of choice for these patients, and either radical prostatectomy (RP) or external beam radiation therapy (EBRT) is recommended. Surgery is less common as the initial treatment for high-risk patients, possibly reflecting the concerns regarding morbidity as well as oncological and functional outcomes. Another high-risk group includes patients with failure of previous EBRT or focal treatment. For these patients, salvage radical prostatectomy (SRP) can be offered.

Objectives: To describe our experience with surgery of high-risk patients and SRP.

Methods: This cohort included all high-risk patients undergoing RP or SRP at our institution between January 2012 and December 2019. We reviewed the electronic medical charts and collected pathological, functional, and oncological outcomes.

Results: Our cohort included 39 patients; average age was 67.8 years, and average follow-up duration was 40.9 months. The most common postoperative morbidity was transfusion of packed cells. There were no life-threatening events or postoperative mortality. Continence was preserved (zero to one pad) in 76% of the patients. Twenty-three patients (59%) had undetectable prostate specific antigen levels following the surgery, 11 (30%) were treated with either adjuvant or salvage EBRT, and 12 patients (31%) were found with no evidence of disease and no additional treatment was needed.

Conclusions: Radical prostatectomy and SRP are safe options for patients presenting with high-risk prostate cancer, with good functional and oncological outcomes.

September 2021
Roy Croock MD, Jonathan Modai MD, Yuval Avda MD, Igal Shpunt MD, Yaniv Shilo MD, Yamit Peretz MD, Uri Lindner MD, Avraham Bercovich MD, and Dan Leibovici MD

Background: Radical cystectomy is a complicated surgery with significant risks. Complications of Clavien–Dindo grade 3–4 range from 25% to 40% while risk of mortality is 2%. Pelvic surgery or radiotherapy prior to radical cystectomy increases the challenges of this surgery.

Objectives: To assess whether radical cystectomy performed in patients with prior history of pelvic surgery or radiation was associated with increased frequency of Clavien–Dindo grade 3 or higher complications compared to patients without prior pelvic intervention.

Methods: We retrospectively evaluated all patients who underwent radical cystectomy at our center over a 7-year period. All patients with pelvic radiation or surgery prior to radical cystectomy comprised group 1, while group 2 included the remaining patients.

Results: In our study, 65 patients required radical cystectomy at our institution during the study period. Group 1 was comprised of 17 patients and group 2 included 48 patients. Four patients from group 2 received orthotopic neobladder, while an ileal conduit procedure was performed in the remaining patients. Estimated blood loss and the amount of blood transfusions given was the only variable found to be statistically different between the two groups. One patient from group 1 had four pelvic interventions prior to surgery, and her cystectomy was aborted.

Conclusions: Radical cystectomy may be safely performed in patients with a history of pelvic radiotherapy or surgery, with complication rates similar to those of non-irradiated or operated pelvises.

December 2018
Anca Leibovici MD, Rivka Sharon Msc and David Azoulay PhD

Background: Brain-derived neurotrophic factor (BDNF) is a neuronal growth factor that is important for the development, maintenance, and repair of the peripheral nervous system. The BDNF gene commonly carries a single nucleotide polymorphism (Val66Met-SNP), which affects the cellular distribution and activity-dependent secretion of BDNF in neuronal cells.

Objectives: To check the association between BDNF Val66Met-SNP as a predisposition that enhances the development of chemotherapy-induced peripheral neuropathy in an Israeli cohort of patients with breast cancer who were treated with paclitaxel.

Methods: Peripheral neuropathy symptoms were assessed and graded at baseline, before beginning treatment, and during the treatment protocol in 35 patients, using the reduced version of the Total Neuropathy Score (TNSr). Allelic discrimination of BDNF polymorphism was determined in the patients' peripheral blood by established polymerase chain reaction and Sanger sequencing.

Results: We found Val/Val in 20 patients (57.14%), Val/Met in 15 patients (42.86%), and Met/Met in none of the patients (0%). Baseline TNSr scores were higher in Met-BDNF patients compared to Val-BDNF patients. The maximal TNSr scores that developed during the follow-up in Met-BDNF patients were higher than in Val-BDNF patients. However, exclusion of patients with pre-existing peripheral neuropathy from the analysis resulted in equivalent maximal TNSr scores in Met-BDNF and Val-BDNF patients.

Conclusions: These observations suggest that BDNF Val66met-SNP has no detectable effect on the peripheral neuropathy that is induced by paclitaxel. The significance of BDNF Val66Met-SNP in pre-existing peripheral neuropathy-related conditions, such as diabetes, should be further investigated.

October 2018
Igal Shpunt MD, Dan Leibovici MD, Sergey Ikher MD, Alexey Kovalyonok MD, Yuval Avda MD, Morad Jaber MD, Abraham Bercovich MD and Uri Lindner MD

Background: Almost 50% of patients with germ-cell tumors (GCT) are subfertile, and every step of the treatment may further impair fertility. As a result, sperm banking is often advised prior to radical orchiectomy. However, whether affected testes contribute to fertility is unclear.

Objectives: To determine whether maximal tumor diameter (MTD) is correlated with ipsilateral fertility (IF) in patients treated for GCT.

Methods: We reviewed medical charts for demographic and clinical data of patients with GCT who had undergone orchiectomy at our institution between 1999 and 2015. The extent of spermatogenesis was categorized into three groups: full spermatogenesis, hypospermatogenesis, and absence of spermatogenesis. The presence of mature spermatozoa in the epididymis tail was also assessed. We defined IF as the combination of full spermatogenesis in more than 100 tubules and the presence of mature spermatozoa in the epididymis tail. Mann–Whitney was applied to determine the correlation between MTD and IF.

Results: Of 57 patients, IF was present in 28 (49%). Mean patient age was 32.8 years in patients with positive IF and 33.4 years those with negative IF. Seminoma was diagnosed in 46.4% of patients with positive IF and in 65.5% of patients with negative IF. Full spermatogenesis was observed in 33 patients (57.8%). In 48 (82.7%), mature epididymal spermatozoa were found. No correlation was found between MTD and IF.

Conclusions: IF is present in almost half of the patients undergoing radical orchiectomy. Because IF cannot be predicted by MTD, routine pre-orchiectomy sperm banking is suggested.

 

July 2018
Kosta Y. Mumcuoglu PhD, Vera Leibovici MD, Inbal Reuveni MD and Omer Bonne MD

Delusional parasitosis (DP) is a somatic type of delusional disorder, usually mono-symptomatic, in which the patients are convinced they are being infested with animal parasites while no objective evidence exists to support this belief. The complaints are usually about skin infestation, but involvement of the gastrointestinal tract has also been described. Numerous samples are brought for examination from skin, clothes, and environmental sources, while a detailed description of the “parasite” is given. In primary DP, the delusion arises spontaneously as a mono-delusional disorder, while in secondary DP, the delusional disorder arises secondary to another major medical, neurological, or psychiatric disorder. Practically all patients refuse psychiatric help. Shared psychotic disorder – folie à deux – is a known mode of presentation in delusional parasitosis. More than one member within a family may experience the same delusional state. For diagnosis and treatment of DP, a close collaboration among dermatologists, psychiatrists, and parasitologists is essential. Patients whose delusion of parasitosis is not severe can sometimes be relieved of their symptoms by establishing a reliable and meaningful therapeutic relationship. Symptomatic medication may be prescribed for the relief of pruritus, pain, and other symptoms. In more severe cases, such patients should be treated with psychopharmacological agents.

July 2013
D. Leibovici, S. Shikanov, O.N. Gofrit, G.P. Zagaja, Y. Shilo and A.L. Shalhav
 Background: Recommendations for active surveillance versus immediate treatment for low risk prostate cancer are based on biopsy and clinical data, assuming that a low volume of well-differentiated carcinoma will be associated will a low progression risk. However, the accuracy of clinical prediction of minimal prostate cancer (MPC) is unclear.

Objectives: To define preoperative predictors for MPC in prostatectomy specimens and to examine the accuracy of such prediction.

Methods: Data collected on 1526 consecutive radical prostatectomy patients operated in a single center between 2003 and 2008 included: age, body mass index, preoperative prostate-specific antigen level, biopsy Gleason score, clinical stage, percentage of positive biopsy cores, and maximal core length (MCL) involvement. MPC was defined as < 5% of prostate volume involvement with organ-confined Gleason score ≤ 6. Univariate and multivariate logistic regression analyses were used to define independent predictors of minimal disease. Classification and Regression Tree (CART) analysis was used to define cutoff values for the predictors and measure the accuracy of prediction.

Results: MPC was found in 241 patients (15.8%). Clinical stage, biopsy Gleason`s score, percent of positive biopsy cores, and maximal involved core length were associated with minimal disease (OR 0.42, 0.1, 0.92, and 0.9, respectively). Independent predictors of MPC included: biopsy Gleason score, percent of positive cores and MCL (OR 0.21, 095 and 0.95, respectively). CART showed that when the MCL exceeded 11.5%, the likelihood of MPC was 3.8%. ;Conversely, when applying the most favorable preoperative conditions (Gleason ≤ 6, < 20% positive cores, MCL ≤ 11.5%) the chance of minimal disease was 41%.

Conclusions: Biopsy Gleason score, the percent of positive cores and MCL are independently associated with MPC. While preoperative prediction of significant prostate cancer was accurate, clinical prediction of MPC was incorrect 59% of the time. Caution is necessary when implementing clinical data as selection criteria for active surveillance. 

February 2013
Y. Shilo, S. Efrati, Z. Simon, A. Sella, E. Gez, E. Fenig, M. Wygoda, A. Lindner, G. Fishlev, K. Stav, A. Zisman, Y.I. Siegel and D. Leibovici

 Background: Hemorrhagic radiation cystitis (HRC) is a significant clinical problem that occurs after pelvic radiation therapy and is often refractory.

Objectives: To evaluate the efficacy and safety of hyperbaric oxygen therapy (HBO) for HRC.

Methods: Daily 90 minute sessions of HBO at 2 ATM 100% oxygen were given to 32 HRC patients with American Society of Therapeutic Radiology and Oncology (ASTRO) grades 3-4 hematuria.

Results: The median age was 72.5 (48–88 years). The median time interval between radiation therapy and HBO was 4 years (1–26 years). The patients received a median of 30 HBO sessions (3–53). Hematuria resolved in 27 patients (84%) and persisted in 5. Cystectomy was required in two, and ileal-conduit and bilateral percutaneous nephrostomies were performed in one and two patients, respectively. With a median follow-up of 12 months (5–74 months), the hematuria cleared completely in 16 patients (59%) and mild hematuria requiring no further treatment recurred in 10 others. Another patient with ASTRO grade 4 hematuria needed bladder irrigation and blood transfusions. Complications included eardrum perforation in four patients and transient vertigo and mild hemoptysis in one case each. None of them required HBO discontinuation.

Conclusions: HBO controlled bleeding in 84% of the patients. A durable freedom from significant hematuria was achieved in 96% of the patients. HBO seems to be an effective and safe modality in patients with HRC.

March 2009
R. Ram, A. Gafter-Gvili, P. Raanani, M. Yeshurun, O. Shpilberg, J. Dreyer, A. Peck, L. Leibovici and M. Paul

Background: Monitoring the rate of infections in individual centers that treat patients with hematological malignancies is of major importance. However, there are no uniform guidelines for infection surveillance.

Objectives: To describe the epidemiology of bacterial and fungal infections in a single hematology ward and to compare methods for reporting surveillance and infection rates in other centers in Israel.

Methods: We conducted a prospective surveillance of all patients admitted to our hematology ward, applying standard definitions for invasive fungal infections and adapting definitions for non-fungal infections. Incidence rates were calculated using patients, admissions, hospital days and neutropenia days. We performed a search for other reported surveillance studies in Israel.

Results: We detected 79 infectious episodes among 159 patients admitted to the hematology ward during 1 year. Using neutropenia days as the denominator for calculation of incidence discriminated best between patients at high and low risk for infection. The incidence of invasive fungal infections was 7, 10 and 18 per 1000 neutropenia days, among all patients, those with acute leukemia and those with acute leukemia undergoing induction therapy, respectively. Only 10 reports from Israel were identified, 6 of which were prospective. Our data could not be compared to these reports because of the varying definitions and denominators used.

Conclusions: Hematology centers should monitor infection rates and report them in a uniform methodology.
 

January 2009
July 2007
O.Kalter-Leibovici, A.Atamna, F.Lubin, G.Alpert, M.Gillon Keren, H.Murad A.Chetrit, D.Goffer, S.Eilat-Adar, and U.Goldbourt

Background: Arabs in Israel have high morbidity and mortality from diabetes and cardiovascular disease. Obesity is a risk factor for both conditions.

Objectives: To investigate the prevalence of obesity (body mass index > 30 kg/m2), subjects' knowledge and behaviors, and their reports on practices of health-care professionals regarding body weight among Arabs and Jews.

Methods: The study participants (n=880) were randomly sampled from the urban population of the Hadera district in Israel. Data on demographic, socioeconomic and lifestyle characteristics; reports on height, current body weight and body weight at the age of 18 years; knowledge and behavior; and health-care professionals' practices with regard to body weight were obtained by interview. Anthropometric measurements were performed subsequently.

Results: Information on BMI[1] was available on 868 participants (49% Arabs, 49% women, median age 46 years). Although the median BMI did not differ significantly between Arabs and Jews at age 18, the prevalence of current obesity was 52% in Arab women compared to 31% in Jewish women (P < 0.001), and 25% in Arab men compared to 23% in Jewish men (P = 0.6). On multivariate analysis, obesity was significantly associated with age, BMI at the age of 18 years, leisure time physical activity and cigarette smoking, but not with ethnicity. Fewer Arabs reported measuring their body weight and Arab women were less frequently advised to maintain an active lifestyle.

Conclusions: The high prevalence of obesity among Arab women may be explained by lifestyle characteristics. Prevention of obesity in Arabs should be directed at women and should start preferably before adulthood.






[1] BMI = body mass index


June 2007
M. Paul, A. Gafter-Gvili, L. Leibovici, J. Bishara, I. Levy, I. Yaniv, I. Shalit Z, Samra, S. Pitlik, H. Konigsberger and M. Weinberger

Background: The epidemiology of bacteremic febrile neutropenia differs between locations and constitutes the basis for selection of empiric antibiotic therapy for febrile neutropenia.

Objectives: To describe the epidemiology of bacteremia among patients with neutropenia in a single center in Israel.

Methods: We conducted a prospective data collection on all patients with neutropenia (< 500/mm3) and clinically significant bacteremia or fungemia during the period 1988–2004.

Results: Among adults (462 episodes) the most common bloodstream isolate was Esherichia coli. Gram-negative bacteria predominated throughout the study period and the ratio between Gram-negative and Gram-positive bacteremia increased from 1.7 to 2.3 throughout the study period. Among children (752 episodes), the ratio between Gram-negative and Gram-positive bacteremia reversed from 1.2 to 0.7, due to increasing prevalence of coagulase-negative staphylcoccal bacteremia. Both among adults and children, the length of hospital stay prior to bacteremia had a major impact on the pathogens causing bacteremia and their antibiotic susceptibilities. The prevalence of E. coli decreased with time in hospital, while the rates of Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter spp., Acinetobacter spp., Enterococcus spp. and Candida spp. increased. Resistance to broad-spectrum empiric monotherapy in our center was observed in > 40% of Gram-negative bacteria when bacteremia was acquired after 14 days in hospital.
Conclusions: Improved infection-control measures for neutropenic cancer patients in our center are needed. Empiric antibiotic treatment should be tailored to patients’ risk for multidrug-resistant organisms. Individual hospitals should monitor infection epidemiology among cancer patients to guide empiric antibiotic treatment

A. Gafter-Gvili, M. Paul, A. Fraser, L. Leibovici.
August 2005
D. Leibovici, A. Cooper, A. Lindner, R. Ostrowsky, J. Kleinmann, S. Velikanov, H. Cipele, E. Goren and Y.I. Siegel
 Background: Stents offer a simple and effective drainage method for the upper urinary tract. However, ureteral stents are associated with frequent side effects, including irritative voiding symptoms and hematuria.

Objectives: To determine the side effects associated with ureteral stents and their impact on sexual function and quality of life.

Methods: Symptom questionnaires were administered to 135 consecutive patients with unilateral ureteral stents. The questionnaire addressed irritative voiding symptoms, flank pain, hematuria, fever, loss of labor days, anxiety, sleep impairment, decreased libido, erectile dysfunction, dyspareunia, painful ejaculation, and a subjective overall impact on quality of life. The items were graded from 1 (minimal or no symptoms) to 5 (maximal symptoms). The patients were seen and questionnaires filled at 2 weekly intervals following stent insertion until stent extraction. Following removal of the stent, stent patency, impaction and migration rates were determined. Admissions to hospital and ancillary procedures to retreive stents were noted.

Results: The findings presented refer to questionnaire items scoring 3 or more. Dysuria, urinary frequency and urgency were reported by 40%, 50% and 55% of the patients, respectively. Flank pain, gross hematuria or fever was reported by 32%, 42% and 15% respectively. Among working patients, 45% lost at least 2 labor days during the first 14 days, and 32% were still absent from work by day 30. A total of 435 labor days were lost in the first month. Anxiety and sleep disturbance were reported by 24% and 20% respectively, and 45% of patients reported impairment in their quality of life. Decreased libido was reported by 45%, and sexual dysfunction by 42% of men and 86% of women. Stent removal necessitated ureteroscpoy in 14 patients (10.5%), due to upward migration in 11 (8.2%) and incrustration and impaction in 3. Spontaneous stent expulsion occurred in one patient. Forty-six (34%) stents were obstructed at the time of removal. Obstructed stents were associated with a longer mean dwell time as compared to the whole population, 75 versus 62 days respectively (P = 0.04).

Conclusions: Ureteral stents are associated with frequent side effects and significantly impact on patient quality of life. Our findings should be considered when deciding on ureteral stent insertion and dwell time.

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