Israel Medical Association Journal

The innovation that has taken place in medicine, combined with state-of-the-art technological developments, provides therapeutic options for patients in conditions that were previously considered incurable. This promotion at the same time presents us with new ethical challenges. In this article, we review the journey through life of an advanced heart failure patient, covering a variety of potential clinical and ethics subjects in the field of heart failure treatment. We review the ethical principles of the Hippocratic Oath against the background of the realities of practicing medicine and of the enormous advances in therapeutics.  

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: 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: Heart failure centers with specialized nurse-supervised management programs have been proposed to improve prognosis. The Heart Failure Center in Beit Shemesh, Israel, is located within a large primary care facility. The specialist team supervised the managememt of patients both within the frame of the center and while they were hospitalized.

Objectives: To evaluate the health services utilization by heart failure patients treated at a heart failure center and their clinical outcome.

Methods: In this retrospective study, we compared the clinical outcome of patients treated at a heart failure center to patients who received the standard care in 2013–2014. The clinical outcome included primary care visits, emergency room visits, hospitalizations, and death.

Results: The study comprised 430 heart failure patients; 82 were treated at the heart failure center and 348 under standard care. At baseline, no significant differences were seen in clinical parameters between the groups. Healthcare utilization was higher among the study group. No significant changes in healthcare utilization were found. During follow-up, patients treated in a heart failure center were more likely to get recommended heart failure medications. Mortality was significantly lower in patients treated in the heart failure center compared with those receiving standard care 3.6% vs. 24%, respectively (P = 0.001), hazard ratio 0.19, 95% confidence interval 0.06–0.62, P = 0.005.

Conclusions: Joint management of heart failure by primary clinics and a specialized community heart failure center reduced mortality. There was no decrease in healthcare utilizations among heart failure center patients, despite the reduction in mortality.

Background: During Transvaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) the surgeon operates exclusively through a single vaginal entry point, leaving no external scarring.

Objectives: To evaluate the learning curve of vNOTES hysterectomy by experienced gynecologists based on surgical times and short-term outcomes.

Methods: A retrospective study was conducted of the first 25 vNOTES hysterectomy surgeries performed from July to December 2018 at Rambam Health Care Campus by a single surgeon. The primary outcome was hysterectomy time. Secondary outcomes included intra-operative bleeding, length of hospitalization, postoperative pain, and need for analgesia. Socio-demographic and clinical data were retrieved from patient electronic medical charts.

Results: Median age was 64.5 years (range 40–79). Median hysterectomy time was 38 minutes (range 30–49) from the first cut until completion. Comparisons between median hysterectomy time in the first 10 hysterectomies and in the 15 subsequent procedures demonstrated a significant decrease in median total time: 45 minutes (range 41–49) vs. 32 minutes (range 30–38), respectively (P = 0.024). The median estimated intraoperative blood loss decreased from 100 ml (range 70–200) in the first 10 hysterectomies to 40 ml (range 20–100) in the subsequent procedures (P = 0.011)

Conclusions: vNOTES hysterectomy is feasible by an experienced gynecologist, with an exponential improvement in surgical performance in a short period as expressed by the improvement in hysterectomy time, low complication rates, negligible blood loss, minimal post-surgical pain, fast recovery, and short hospitalization. vNOTES allows easier and safer access to adnexal removal compared to conventional vaginal surgery.

Background: Congenital heart defects (CHD) may be associated with neurodevelopmental abnormalities mainly due to brain hypoperfusion. This defect is attributed to the major cardiac operations these children underwent, but also to hemodynamic instability during fetal life. Advances in imaging techniques have identified changes in brain magnetic resonance imaging (MRI)in children with CHD.

Objectives: To examine the correlation between CHD and brain injury using fetal brain MRI.

Methods: We evaluated 46 fetuses diagnosed with CHD who underwent brain MRI. CHD was classified according to in situs anomalies, 4 chamber view (4CV), outflow tracts, arches, and veins as well as cyanotic or complex CHD. We compared MRI results of different classes of CHD and CHD fetuses to a control group of 113 healthy brain MRI examinations.

Results: No significant differences were found in brain pathologies among different classifications of CHD. The anteroposterior percentile of the vermis was significantly smaller in fetuses with abnormal 4CV. A significantly higher biparietal diameter was found in fetuses with abnormal arches. A significantly smaller transcerebellar diameter was found in fetuses with abnormal veins. Compared to the control group, significant differences were found in overall brain pathology in cortex abnormalities and in extra axial findings in the study group. Significantly higher rates of overall brain pathologies, ventricle pathologies, cortex pathologies, and biometrical parameters were found in the cyanotic group compared to the complex group and to the control group.

Conclusions: Fetuses with CHD demonstrate findings in brain MRI that suggest an in utero pathogenesis of the neurological and cognitive anomalies found during child development.

Background: Temporary abdominal closure (TAC) surgical technique relates to a procedure in which the post-surgical abdominal wall remains open in certain indications. The Bogota bag (BB) technique is a tension-free TAC method that covers the abdominal contents with a sterilized fluid bag. There are very few reports of pediatric patients treated with this technique.

Objectives: To describe our institution’s 15 years of experience using the BB technique on pediatric patients.

Methods: A retrospective cohort study describing our experience treating patients with BB was conducted. The medical files of 17 pediatric patients aged 0–18 years were reviewed.

Results: Between January 2000 and December 2014, 17 patients were treated with BB at our medical center (6 females, median age 12 years). Indications for BB were a need for a surgical site re-exploration, mechanical inability for primary abdominal closure, and high risk for ACS development. Median BB duration was 5 days and median bag replacement was 2 days. Median ICU length of stay (LOS) was 10 days and hospital LOS was 27 days. The ICU admission and BB procedure was tolerated well by 6 patients who were discharged home without complications. Of the remaining 11 patients, 6 patients died during the admission (35%) and the others presented with major complications not related to the BB but to the patient's primary disease.

Conclusions: This report represents the largest series of children treated with BB. The technique is simple to perform, inexpensive, and has very few complications.

Background: Pneumatic sleeves (PS) are often used during laparoscopic surgery and for prevention of deep vein thrombosis in patients who cannot receive anticoagulation treatment. There is very little information on the hemodynamic changes induced by PS and their effect on brain natriuretic peptide (BNP) in patients with severely reduced left ventricular ejection function (LVEF).

Objectives: To determine the safety and hemodynamic changes induced by PS and their effects on brain natriuretic peptide (BNP).

Methods: This study comprised 14 patients classified as New York Heart Association (NYHA) II–III with severely reduced LVEF (< 40%). We activated the PS using two inflation pressures (50 or 80 mmHg, 7 patients in each group) at two cycles per minute for one hour. We measured echocardiography, hemodynamic parameters, and BNP levels in each patient prior to, during, and after the PS operation.

Results: The baseline LVEF did not change throughout the activation of PS (31 ± 10% vs. 33 ± 9%, P = 0.673). Following PS activation there was no significant difference in systolic or diastolic blood pressure, the pulse measurements, or central venous pressure. BNP levels did not change after PS activation (P = 0.074).

Conclusions: The use of PS, with either low or high inflation pressures, is safe and has no detrimental effects on hemodynamic parameters or BNP levels in patients with severely reduced LVEF following clinical stabilization and optimal medical therapy.

Background: Adenovirus is responsible for 2–7% of childhood viral respiratory infections, 5–11% of viral pneumonia and bronchiolitis. Most are self-limited but may cause severe respiratory infection.

Objectives: To describe adenovirus respiratory infection in immunocompetent children in a pediatric intensive care unit (PICU).

Methods: Children with adenovirus respiratory infection in our PICU from 2007 to 2016 were included. Data were retrospectively retrieved, including background, clinical manifestation, and treatment. Adenovirus was diagnosed by polymerase chain reaction, immune fluorescence, or both.

Results: Of 9397 samples, 956 were positive for adenovirus in children hospitalized during the study period. In total, 49 patients (aged 2 months–11.5 years) were admitted to our PICU, five were immunocompromised and excluded from the study, 19/44 (43%) were referred from other hospitals. Twenty-eight (64%) had underlying conditions, 66% had fever and cough, 11% had conjunctivitis, and 34% received antibiotics before admission. White blood cell counts ranged from 790 to 34,300 (mean 14,600) and 36% had counts above 15,000. Chest X-ray was consistent with viral infection in 77% of patients and normal in three (13.6%). Viral co-infection was found in 9 patients, 7 had presumed bacterial super-infection, and 27 (61.4%) needed mechanical ventilation. Two patients received cidofovir, 33 (75%) steroids, and 37 (84 %) antibiotics. Four patients died.

Conclusions: Adenovirus respiratory infection may cause severe disease necessitating PICU admission and mechanical ventilation, mostly in patients with underlying conditions. Many patients received steroids and antibiotics, which may be unnecessary. Mortality was 9%, mainly among young infants and those with underlying conditions.

Background: Ophthalmic pathologies may further complicate the sensory input of patients with congenital hearing loss; however, data on children with coexisting impairment of vision and hearing is outdated, from before universal implementation of hearing screening programs.

Objectives: To examine the different ophthalmic pathologies among children with congenital sensorineural hearing loss (SNHL) before or after the introduction of a universal newborn hearing screening program (UNHSP).

Methods: Retrospective cohort study was conducted of 91 children diagnosed with congenital SNHL between 2005 and 2016 in a tertiary pediatric hospital. All patients completed an ophthalmologic examination, including assessment of visual acuity, refraction, ocular motility, slit lamp examination, and indirect funduscopy. Radiological assessment and genetic analysis were offered to all caregivers.

Results: Average age at diagnosis was 4.1 years. Nineteen children (21%) were diagnosed with an ophthalmic condition, of which the most common were refractive pathologies. Diagnosis of an ophthalmic pathology was twice as likely in the pre-UNHSP era (14 children, 27%) compared to the post-UNHSP era (5 children, 13%). Out of 91 children, 57 (63%) underwent a computed tomography scan and/or magnetic resonance imaging. Imaging was positive for structural abnormalities in 23 children (40%). There was no correlation between imaging and ophthalmic conditions. Genetic analysis was performed in 67 patients (74%).

Conclusions: The ophthalmic assessment of babies and children with congenital SNHL may yield in significant numbers of children with concomitant ophthalmic pathologies. Implementation of a UNHSP allows early diagnosis and treatment of coexisting ophthalmic and hearing conditions.