Israel Medical Association Journal

Angiogenesis is the outgrowth of new blood vessels from existing ones and is an early occurrence in inflamed joint tissue. It is governed by a tightly controlled balance of pro- and anti-angiogenic stimuli, which promote or inhibit generation and proliferation of new endothelial cells, vascular morphogenesis, and vessel remodeling. At the beginning, capillary formation is crucial in maintaining the supply of various nutrients as well as oxygen to the inflamed tissue. Local and systemic expression of angiogenic factors may indicate a constant remodeling of synovial vasculature. Redox signaling is closely related to angiogenesis and can alter angiogenic responses of synovial cells. In this review we discuss key issues about the endothelial pathology in inflammatory arthritis followed by a review of angiogenic processes and main angiogenic mediators. We discuss the hypoxia-vascular endothelial growth factor (VEGF)-Ang/Tie2 system and its related therapeutic implications in detail with further review of various mediator protein targets and intracellular regulatory pathway targets with their current and potential future role in preclinical or clinical setting whilst ameliorating inflammation.

Throughout history, studies on episodes of famine have led to the discovery of metabolic abnormalities and hormonal aberrations as well as an increased incidence of cancer and mental health conditions. Starvation during early life is thought to nfluence the programming of childhood and adult bone metabolism, which may result in poor bone health in later life. This observational case series includes a small group (with no control group) of famine-exposed Holocaust survivors and their descendants. We proposed an investigational mechanism to determine any association between starvation and osteoporosis, both in the individual survivors and in their descendants.

Background: Reports of longevity in Holocaust survivors (HS) conflict with excess prevalence of chronic diseases described among them. However, data on their long-term risk of cardiovascular diseases (CVD) are limited. Clinical data on large representative groups of HS who were exposed to severe persecution are also limited.

Objectives: To determine the prevalence of CVD and the risk factors in a large cohort of elderly HS compared to elderly individuals who were not exposed to the Holocaust (NHS).

Methods: CVD prevalence rates and risk factors data from the computerized system of the central district of Clalit Health Services, the largest Israeli health maintenance organization (HMO) in Israel were evaluated in a retrospective observational study. The study was comprised of 4004 elderly HS who underwent direct severe persecution. They were randomly matched by identification numbers to 4004 elderly NHS.

Results: HS were older than NHS and 51% of them were older than 85 years. The prevalence rate of ischemic heart disease (IHD) was significantly higher among HS. HS underwent significantly more cardiac interventions (20% vs. 15.7%, P < 0.05). HS status was an independent risk factor for increased IHD and for more coronary interventions.

Conclusions: Despite having a higher prevalence of CVD, a substantial number of HS live long lives. This finding may imply both unique resilience and ability to cope with chronic illness of the survivors as well as adjusted medical services for this population. These findings may help in planning the treatment of other mass trauma survivors.

Background: When a woman with an endometrioma presents with acute abdominal pain, it is unclear whether ovarian torsion should be suspected.

Objectives: To compare patient characteristics, imaging results, and surgical management of endometriomas in elective versus emergent surgeries.

Methods: This retrospective cohort study included women treated at our institution during the period 1990–2015 who presented with histologically verified endometrioma and who underwent either planned surgery or emergent surgery due to suspected adnexal torsion.

Results: Of 225 surgeries performed, 174 were elective and 51 emergent. Patients in the emergent group were significantly younger (33.9 ± 11.1 vs. 39.01 ± 10.9 years, P = 0.004). Abdominal pain was the main complaint of all the emergent surgery patients and the leading complaint in 21% of the elective surgery patients (P < 0.001), with right-sided predominance in both groups. Sonographic parameters were similar in both groups. Bilateral ovarian cysts were noted in 11.7% and 11.0% of emergent and elective patients, respectively (P = 0.87). Laboratory evaluation was notable for a higher white blood cell count and CA125 levels among emergent patients. All patients in the emergent group and 93% of patients in the elective group were managed laparoscopically. No cases of torsion were noted. The rate of intra-pelvic adhesions was similar in both groups (56.8% vs. 66.6%, P = 0.19).

Conclusions: Endometrioma may present with acute abdominal pain. However, adnexal torsion in these patients is rare. These cases can be managed using a minimally invasive approach, assuming an optimal surgical setting.

Background: Gender differences in adolescent idiopathic scoliosis (AIS) have been documented in curve progression, response to bracing, and outcomes of surgical treatment. However, limited information is available about the relation between gender and scoliosis curve patterns and radiographical characteristics.

Objectives: To evaluate the effect of gender on curve pattern and compare clinical and radiographical characteristics between male and female patients with AIS.

Methods: We conducted a retrospective review of prospectively collected data that compared clinical and radiographical characteristics between male and female surgical candidates. Demographic and clinical data including age at presentation, gender, family history of scoliosis, brace treatment history, clinical coronal balance, shoulder asymmetry, and hump size were recorded. All patients graded their pain with the use of a visual analogue scale (VAS) on a scale from 0 to 10. Radiographs of the spine were reviewed to determine the type of curve according to the Lenke classification, Cobb angle, thoracic kyphosis angle, and the Risser sign. Radiologic coronal balance was recorded. Curve flexibility was determined by measuring the thoracic and lumbar curves magnitude on side bending radiographs

Results: The study included 163 patients with AIS including 35 males and 128 females patients. Although a trend toward more flexible major thoracic curves in females was noticed, there was no statistically significant difference between the 2 groups.

Conclusions: In this study we were not able to demonstrate any clinical nor radiological statistical differences between male and female patients who are candidate for surgical treatment.

Background: A history of childhood sexual abuse (CSA) has been linked to a variety of physical and psychiatric illnesses, including ischemic heart disease and post-traumatic stress disorder (PTSD).

Objectives: To determine the prevalence of past CSA and re-traumatization among hospital psychiatric consultations and to determine whether a CSA group in a hospital setting shared characteristics with community samples described in the literature.

Methods: We divided 228 consecutive psychiatric consultations into two groups. One group comprised patients with a past history of CSA while the other group had no such history. Both groups were further divided into a subgroup that presented with features of re-traumatization.

Results: In the cohort, 38% described a history of CSA. Twenty patients were identified as presenting with features of re-traumatization. There were significant differences between the two groups. The patients with a history of CSA were more likely to have arrived at the emergency department (ED) during the preceding 12 months with a diagnosis of PTSD, personality disorder, and substance use disorder. There was a greater proportion of patients in the CSA group who had grown up in an ultra-Orthodox Jewish household and who currently identified as being secular.

Conclusions: The characteristics of the patients with past CSA in this study are similar to community-based samples, except for a significant gender difference. To the best of our knowledge, this study is the first to investigate CSA history during hospital ED psychiatric consultations. A history of CSA should be considered during psychiatric consultations in a general hospital ED admission.

Background: Hyperchloremia is frequent in adult surgical patients and is associated with renal dysfunction. Studies in surgical pediatric patients are lacking.

Objectives: To identify both the incidence of postoperative hyperchloremia in children undergoing surgery for idiopathic and non-idiopathic scoliosis, and the association of postoperative hyperchloremia with intraoperative fluid management and postoperative diuresis.

Methods: The records of 74 children and adolescents who underwent elective scoliosis surgery were retrospectively evaluated. The primary endpoint was the incidence of serum chloride level ≥ 110 mEq/L at the end of surgery and 12 hours postoperatively. Secondary endpoints were the type and volume of administered fluids, 12 hours postoperative diuresis, and the incidence of postoperative oliguria.

Results: Hyperchloremia occurred in 55% of the patients at the end of surgery and in 52% 12 hours postoperatively. Hyperchloremic patients received larger intraoperative volume of 0.9% NaCl diluted cell-saver blood and 10% HAES than did normochloremic patients [median (interquartile range) 6.8 (2.5–11.0) ml/kg vs. 0 (0–7.3), P = 0.003 and 10.0 (0–12.8) vs. 4.4 (0–9.8), P = 0.02, respectively]. Additionally, when compared with normochloremic patients, diuresis during the first 12 hours postoperatively was lower in hyperchloremic patients. Postoperative oliguria (urine output < 0.5 ml/kg/hr for 12 hours) was diagnosed in 7 children (9%), of whom 6 were hyperchloremic at the end of surgery.

Conclusions: Early postoperative hyperchloremia is common in children undergoing scoliosis repair surgery and may be attributed to the administration of 0.9% NaCl diluted cell-saver blood and 10% HAES. Postoperative hyperchloremia might be associated with postoperative oliguria.

Background: The currently accepted treatment for idiopathic sudden sensorineural hearing loss (ISSHL) is systemic steroids as first-line and intratympanic steroids as salvage therapy. Intratympanic (IT) treatment is applied worldwide in many different ways with no universally accepted protocol.

Objectives: To present the current disparity in ISSHL management and to discuss the necessity for establishing a common national protocol.

Methods: In 2014 we conducted a national survey by sending questionnaires on ISSHL management to otologists in every otolaryngology department in the country.

Results: The majority of otolaryngology departments (56%) admit patients with sudden sensorineural hearing. Almost two-thirds (61%) of departments recommend supplementary initial treatment in addition to systemic steroids. None of the medical centers offer intratympanic steroid treatment as primary therapy, but 94% offer this treatment as a salvage therapy. Fewer than half the medical centers (44%) consider the maximal period for intratympanic therapy to be 4 weeks since hearing loss appears. Almost half (48%) the departments use intratympanic steroids once every 5–7 days, usually in an ambulatory setting. Almost half (44%) the medical centers tend to use not more than four courses of IT steroids. In 44% of departments an audiogram is performed at the beginning and at the end of the intratympanic course.

Conclusions: Our results demonstrate a variability among Israeli medical centers in many aspects of intratympanic treatment. We believe this reinforces the need for a comparative international study in order to establish a standard protocol.

Background: Catheter ablation (CA) is a well-established therapeutic option for patients with recurrent symptomatic atrial fibrillation (AF). Data on gender-related differences are limited with regard to baseline characteristics and long-term success rates of catheter ablation for AF.

Methods: We analyzed a cohort of 251 consecutive patients who underwent a first catheter ablation for AF in our institute during the period 2008 through 2015. All patients were followed by regular annual clinic visits, electrocardiograms, periodic 24–48 hour Holter monitoring, and loop recorders. The primary endpoint was first recurrence of AF during 1 year of follow-up.

Results: The cohort comprised 26% women (n=65), who were older (62.1 ± 9.6 vs. 54.4 ± 11.3 years, P < 0.01) and had a higher proportion of diabetes mellitus (23.1 vs. 5.4%, P < 0.001) than male patients. No other significant differences were evident. At 1 year follow-up, the cumulative survival free of AF was significantly higher in women compared with men (83% vs. 66%, respectively, log rank P value = 0.021). Subgroup analysis showed an interaction between female and small indexed left atrial diameter (LADi < 23 mm/m²).

Conclusions: Our findings suggest that women experience a significantly lower rate of AF recurrence post-CA compared with men. This gender-related advantage appears to be restricted to women without significant left atrial enlargement. It further implies that left atrial enlargement has a stronger negative impact on post-CA AF recurrence in females than in males. Due to the relatively small sample number of females further research is warranted to validate our conclusions.

Background: Burn injury pathophysiology is characterized by severe catabolic state and poor glycemic control. A tight glycemic control protocol using insulin for burn victims has yielded inconsistent mortality and morbidity outcomes.

Objectives: To compare the effect of standard and tight glycemic control protocols on mortality and hypoglycemia events in critical care burn patients.

Methods: We conducted a case-control study of burn victims admitted to the burn intensive care unit between 2005 and 2011. Patients were assigned to either a standard or a tight glycemic control protocol.

Results: Of the 38 burn patients in the study, 28 were under a tight glycemic control protocol. No differences in glucose area-under-the-curve per day levels were observed between the groups (148.3 ± 16 vs. 157.8 ± 16 mg/dl in the standard and tight glycemic control protocol groups respectively, P < 0.12). The hypoglycemic event rate was higher in the tight glycemic control protocol group (46.4% vs. 0%, P < 0.008). No difference in mortality rate was noted (67.9% vs. 50%, P < 0.31). Mortality-independent risk factors found on multivariate analysis included total body surface area (adjusted hazard ratio [AHR] 1.039, 95% confidence interval  [95%CI] 1.02–1.06, P < 0.001), white blood cell count on admission (AHR 1.048, 95%CI 1.01–1.09, P < 0.02) and surgery during hospitalization (AHR 0.348, 95%CI 0.13–0.09, P < 0.03).

Conclusions: The tight glycemic control protocol in burn patients was associated with higher rates of hypoglycemic events, and no association was found with improved survival in the acute setting of burn trauma care.