Israel Medical Association Journal

Background: Male breast cancer (MBC) is a rare disease that is poorly understood. Treatment protocols are widely extrapolated from breast cancer in women.

Objectives: To review the experience with MBC of a single center in Israel over a period of 22 years.

Methods: This single center retrospective study evaluated all patients diagnosed with MBC over a period of 22 years (1993–2015). Data were extracted from patient medical charts and included demographics, clinical, surgical, and oncological outcomes.

Results: The study comprised 49 patients. Mean age at diagnosis was 64.1 ± 13.5 years. The majority were diagnosed at early stages (1A–2A) (54.4%), 30.6% were stage 3B mostly due to direct skin and nipple involvement, and 59.2% of the patients had node negative disease. All of the patients were diagnosed with invasive ductal carcinoma and 30.6% had concomitant ductal carcinoma in situ. Estrogen receptor (ER) status was predominantly positive and luminal B (HER2-) was the most common subtype. Of the patients, 18.4% were BRCA carriers. The majority of patients underwent mastectomy. Radiotherapy was delivered to 46.9% and hormonal therapy to 89.8%. Chemotherapy was administered to 42.9%. Overall survival was 79.6% with a median survival of 60.1 (2–178) months; 5- and 10-year survival was 93.9% and 79.6%, respectively. Progesterone receptor (PR)-negative patients had a significantly improved overall survival.

Conclusions: MBC has increasing incidence. PR-negative status was associated with better overall survival and disease-free interval. Indications to radiotherapy and hormonal therapy need standardization and will benefit from prospective randomized control trials.

Background: The number of investigative esophagogastroduodenoscopies (EGD) in children has increased over several decades, despite their unclear diagnostic yields.

Objectives: To evaluate the indications for performing EGD, their diagnostic yields, and consequences on pediatric patient management.

Methods: A retrospective chart review was performed of consecutive pediatric patients aged 0–18 years, who underwent EGD between January and August 2014.

Results: During the study period, 547 EGD were performed on 478 children. The most frequent indications were suspected celiac disease, chronic non-specific abdominal pain, persistent Helicobacter pylori infection, and gastrointestinal hemorrhage. The yield of the diagnostic EGD was 59.2%, and the most common new diagnoses were celiac disease (28%), Helicobacter pylori-positive gastritis (16.5%), and Crohn’s disease (5.4%). Of the patients with documented follow-up, 74.1% reported improved symptoms. Procedures performed for chronic unexplained abdominal pain had significantly lower yields (26.2%) and only 39.3% improved at follow-up.

Conclusions: Our findings suggest a general high diagnostic yield for EGD in pediatric patients, stemming mainly from patients in whom a specific condition was suspected a priori. However, the role of the procedure in the diagnosis and management of non-specific gastrointestinal complaints was minor suggesting that EGD may be superfluous for some of these patients.

Background: The impact of revascularization of coronary chronic total occlusion (CTO) on survival is unknown. Several studies, which included subjects with varied coronary anatomy, suggested that CTO revascularization improved survival. However, the contribution of CTO revascularization to improved outcome is unclear since it was more commonly achieved in subjects with fewer co-morbidities and less extensive coronary disease.

Objectives: To study the association between CTO revascularization and survival in patients with uniform coronary anatomy consisting of isolated CTO of the right coronary artery (RCA).

Methods: A registry of 16,832 coronary angiograms was analyzed. We identified 278 patients (1.7%) with isolated CTO of the RCA who did not have lesions within the left coronary artery for which revascularization was indicated. Survival of 52 patients (19%) who underwent successful percutaneous coronary intervention was compared to those who did not receive revascularization.

Results: Revascularized patients were younger (60.2 vs. 66.3 years, P = 0.001), had higher creatinine clearance (106 vs. 83 ml/min, P < 0.0001), and had fewer co-morbidities than those who did not receive revascularization. Lack of CTO revascularization was a univariable predictor of mortality (hazard ratio [HR] = 2.65, 95% confidence interval [95%CI] 1.06–6.4) over 4.3 ± 2.5 years of follow-up. On multivariable analysis, the only predictors of mortality were increased age (HR 1.04, 95%CI 1.01–1.07), reduced creatinine clearance (HR 1.02, 95%CI 1.01–1.03), and ejection fraction below 55% (HR 2.24, 95%CI 1.22–4.11).

Conclusions: Among patients with isolated RCA CTO who underwent extended follow-up, revascularization was not an independent predictor of increased survival.

Background: The use of a high flow nasal cannula (HFNC) was examined for different clinical indications in the critically ill.

Objectives: To describe a single center experience with HFNC in post-extubation critical care patients by using clinical indices.

Methods: In this single center study, the authors retrospectively evaluated the outcome of patients who were connected to the HFNC after their extubation in the intensive care unit (ICU). At 48 hours after the extubation, the patients were divided into three groups: the group weaned from HFNC, the ongoing HFNC group, and the already intubated group.

Results: Of the 80 patients who were included, 42 patients were without HFNC support at 48 hours after extubation, 22 and 16 patients were with ongoing HFNC support and already intubated by this time frame, respectively. The mean ROX index (the ratio of SpO₂ divided by fraction of inspired oxygen to respiratory rate) at 6 hours of the weaned group was 12.3 versus 9.3 in the ongoing HFNC group, and 8.5 in the reintubated group (P = 0.02). The groups were significantly different by the ICU length of stay, tracheostomy rate, and mortality.

Conclusions: Among patients treated with HFNC post-extubation of those who had a higher ROX index were less likely to undergo reintubation.

The authors reviewed the two most common current uses of brain ¹⁸F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET) at a large academic medical center. For epilepsy patients considering surgical management, FDG-PET can help localize epileptogenic lesions, discriminate between multiple or discordant EEG or MRI findings, and predict prognosis for post-surgical seizure control. In elderly patients with cognitive impairment, FDG-PET often demonstrates lobar-specific patterns of hypometabolism that suggest particular underlying neurodegenerative pathologies, such as Alzheimer’s disease. FDG-PET of the brain can be a key diagnostic modality and contribute to improved patient care.

Background: The introduction of pneumococcal conjugate vaccine-13 (PCV-13) has reduced the burden of invasive pneumococcal disease.

Objective: To characterize true positive blood cultures of children who presented to our hospital following implementation of the PCV-13 vaccine.

Methods: A retrospective study was conducted on positive blood cultures of children presenting with fever from 2010–2017. Subjects were divided into two age groups: a younger group 3–36 months and an older group 3–18 years. Patients were classified as either having or not having a focus of infection at the time of their bacteremia. Pneumococcal isolates were typed at Israel's Streptococcal Reference Laboratory.

Results: The samples included 94 true positive blood cultures. Focal infection with concomitant bacteremia was more common than bacteremia without a focus both overall: 67/94 (71%) vs. 27/94 (28.7%), P <0.001 as well as in the two groups: 32/48 (66%) vs. 16/48 (33%), P = 0.02 in the younger group and 35/46 (76%) vs. 11/46 (24%), P = 0.001 in the older group. Streptococcus pneumoniae was the most common pathogen overall, 27/94 (29%), and in the younger group, 21/48 (44%), but rare in the older group, 6/46 (13%). In the latter, Brucella species predominated, 12/46 (26%), along with Staphylococcus aureus 12/46 (26%).

Conclusions: Our findings are consistent with other studies reporting decreased pneumococcal bacteremia, bacteremia primarily accompanying focal infection, and changing etiological agents among PCV-13-vaccinated children. Brucella species was prominent in older children with osteoarticular infections. Ongoing surveillance is warranted to better understand the implications of PCV-13.

Background: The treatment of elderly patients with advanced stage ovarian carcinoma is challenging due to a high morbidity.

Objective: To evaluate the clinical course and outcome of elderly patients with advanced stage ovarian carcinoma receiving neoadjuvant chemotherapy (NACT).

Methods: A retrospective study of all patients with stage IIIC and IV ovarian carcinoma receiving NACT in one medical center (between 2005 and 2017). The study group criteria age was above 70 years. The control group criteria was younger than 70 years old at diagnosis. Demographics and treatment outcomes were compared between groups. Primary outcomes were progression-free survival (PFS) and overall survival (OS).

Results: Overall, 105 patients met the inclusion criteria, 71 patients (67.6%) were younger than 70 years and 34 patients (32.4%) older. Rates of interval cytoreduction were significantly higher in younger patients (76.1% vs. 50.0%, P = 0.01). Of those who underwent interval cytoreduction, no difference was found in rates of optimal debulking between groups (83.35% vs. 100%, P = 0.10). Using a Kaplan-Meier survival analysis, no significant differences were observed between groups in PFS or OS, P > 0.05. Among the elderly group alone, patients who underwent interval cytoreduction had significantly longer PFS than those without surgical intervention (0.4 ± 1.7 vs. 19.3 ± 19.4 months, P = 0.001).

Conclusions: Elderly patients with ovarian carcinoma who received NACT undergo less interval cytoreduction than younger patients, with no difference in PFS and OS. However, among the elderly, interval cytoreduction is associated with significantly higher PFS.

Background: Post-pericardiotomy syndrome (PPS) is a major cause of pericarditis, yet data on the risk of recurrence are limited, and the impact of steroids and colchicine in this context is unknown.

Objectives: To examine the effect of prednisone and colchicine on the rate of recurrence of PPS.

Methods: Medical files of patients diagnosed with PPS were reviewed to extract demographic, echocardiographic, X-ray imaging, and follow-up data.

Results: The study comprised 132 patients (57% men), aged 27–86 years. Medical treatment included prednisone in 80 patients, non-steroidal anti-inflammatory agents in 41 patients, colchicine monotherapy in 2 patients, and no anti-inflammatory therapy in 9 patients. Fifty-nine patients were given colchicine for prevention of recurrence. The patients were followed for 5–110 months (median 64 months). Recurrent episodes occurred in 15 patients (11.4%), 10 patients had a single episode, 4 patients had two episodes, and one patient had three episodes. The rate of recurrence was lower in patients receiving colchicine compared to patients who did not (8.5% vs. 13.7%), and in patients not receiving vs. receiving prednisone (7.7% vs. 13.8%) but the differences were non-significant. Twenty-three patients died and there were no recurrence-related deaths.

Conclusions: The rate of recurrence after PPS is low and multiple recurrences are rare. The survival of patients with recurrent PPS is excellent. Prednisone pre-treatment was associated with a numerically higher rate of recurrence and colchicine treatment with a numerically lower rate, but the differences were non-significant.

Background: Rapid and selective bromelain-based enzymatic debridement provides a non-surgical alternative for the eschar removal in deep burns, which allows for early debridement of large surface areas, accurate evaluation of burn and wound depth, and the need for skin grafting.

Objective: To evaluate the efficacy of application of a bromelain-based selective enzymatic debridement (Nexobrid®) beyond the manufacturer’s guidelines for use in burns > 48 hours as well as chemical, electrical, and pediatric burns, and chronic wounds

Methods: This retrospective review included records collected between January 2017 and April 2019, from male and female patients aged 8 months to 99 years with deep burns or wounds treated with bromelain-based selective enzymatic debridement.

Results: Of the 33 patients who received the bromelain-based selective enzymatic debridement agent beyond the manufacturer’s guidelines, 25 (76%) were observed to have successful debridement of the eschar, 8 (24%) were observed to have little effect on the burn eschar. Sixteen required further surgery after debridement. Clinical data on the use of bromelain-based selective enzymatic debridement agents are limited, but these results suggest the capacity to effectively debride burns > 48 hours (late presentation burns), use for pediatrics and for chemical and electrical burns, and apply to hard to heal full thickness chronic wounds.

Conclusions: Bromelain-based selective enzymatic debridement was found to be an effective treatment modality beyond the recommended guidelines including late presentation burns and chronic wounds. This debridement method warrants further consideration when making clinical decisions concerning burn and wound care.

Background: Autoimmune hepatitis (AIH) may be associated with other autoimmune diseases. Autoantibodies are common in AIH suggesting their potential role in the pathogenesis of the disease. Among these autoantibodies, thyroid autoantibodies have been reported in patients with chronic hepatitis, with greater prevalence in patients with chronic hepatitis C infection.

Objectives: To assess the prevalence of thyroid dysfunction among patients with AIH.

Methods: In this case-control, retrospective study, we examined patients diagnosed with AIH according to both the original and revised international AIH group scoring systems. Patients with other hepatic pathologies were excluded AIH was evaluated as an independent risk factor for thyroid disease by a logistic regression model. Univariate and multivariate regression analyses were conducted using hypothyroidism and hyperthyroidism as the dependent variables.

Results: Our cohort comprised 163 patients diagnosed with AIH and 1104 healthy age- and gender-matched controls. Hypothyroidism was more prevalent among those with AIH compared to controls (17.7% vs. 5%, respectively, 95% confidence interval [95%CI] 1.68–2.48, P <  0.001). Hyperthyroidism was more prevalent in AIH patients compared to controls (odds ratio 3.2% and 1.2%, respectively, 95%CI 1.68–2.47, P <  0.001). Using a multivariate logistic analysis, we found an independent association between AIH and hypothyroidism but not with hyperthyroidism.

Conclusions: Thyroid dysfunction is more prevalent in patients with AIH. Whether thyroid dysfunction is the cause or a risk factor for AIH, or vice versa, is still unclear. Screening for thyroid dysfunction is warranted after AIH is diagnosed.

Background: Autologous hematological stem cell transplantation (HSCT) is a novel therapy for systemic sclerosis (SSc) that has been validated in three randomized controlled trials.

Objectives: To report the first Israeli experience with HSCT for progressive SSc and review the current literature.

Methods: Five SSc patients who were evaluated in our department and were treated by HSCT were included. Medical records were evaluated retrospectively. Demographic, clinical, and laboratory data were recorded. Continuous data are presented as the mean ± standard deviation. Categorical variables are presented as frequencies and percentages.

Results: Five SSc patients were treated with HSCT. Four patients were adults (mean age 53 ± 12 years) and one was a 12-year-old pediatric patient. All patients were female. HSCT was initiated 1.4 ± 0.8 years after diagnosis. Two patients were RNA POLIII positive, two were anti-topoisomerase 1 positive, and one only antinuclear antibodies positive. All patients had skin and lung involvement. The mean modified Rodnan Skin Score was 29 ± 4.7 before HSCT, which improved to 10.4 ± 9.6 after HSCT. The forced vital capacity improved from 68 ± 13% to 90 ± 28%. Diffusing capacity of the lungs for carbon monoxide increased by 6%. Among severe adverse events were cyclophosphamide-related congestive heart failure, antithymocyte globulin-related capillary leak syndrome, and scleroderma renal crisis. All symptoms completely resolved with treatment without sequela. No treatment related mortality was recorded.

Conclusions: HSCT is an important step in the treatment of progressive SSc in Israel. Careful patient selection reduces treatment related morbidity and mortality.

Despite advances in therapeutic modalities, especially with biologic treatments, the number of hospitalizations due to complications for Crohn's disease did not decrease. We examined the prevalence and possible predictive factors of hospitalizations in Crohn's disease. A systematic literature search was conducted until 31 October 2018. Relevant studies were screened according to established protocol. Retrospective cohort studies describing hospitalizations of Crohn's disease patients were included. Meta-analysis was performed by using comprehensive meta-analysis software. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated for the number of patients hospitalized. Twelve studies published before 31 March 2018 fulfilled the inclusion criteria and were comprised of 23 data-sets and included 4421 patients from six countries. A funnel plot demonstrates a moderate publication bias. We reported the event rates for the number of patients hospitalized, in a follow-up survey of 20,987 patient-years, and for the patients who underwent surgery in a follow-up of 5061 patient-years, with ORs of 0.233 with 95%CI 0.227–0.239, and 0.124 with 95%CI 0.114–0.135 (P < 0.001), respectively. Thus, when collecting the data from 12 cohort studies we found that hospitalization takes place in 23.3% of the patients, and operation in 12.4% along their disease duration. Patients with Crohn's disease may be hospitalized due to exacerbation of their inflammatory disease, because of non-inflammatory disease (such as fistula or stricture), or due to medical complications. The goal of therapy should be to keep the Crohn's disease patients in their natural environment and out of the hospital and to prevent surgery as much as possible.