Israel Medical Association Journal

Background: One of the main causes of iron deficiency anemia (IDA) is chronic gastrointestinal blood loss. The use of video capsule endoscopy (VCE) after negative bidirectional endoscopy in patients with IDA is controversial.

Objectives: To evaluate the effect of VCE in the management and long-term outcomes of IDA patients.

Methods: A retrospective case-control study was performed on all patients with IDA undergoing VCE over a 5-year period. We compared those with positive findings on VCE to those with normal findings. All participants previously underwent a negative bidirectional endoscopy

Results: We performed 199 VCE examinations; median follow-up time was 4 years (IQR 2–5). Positive findings were identified in 66 patients (diagnostic yield 33.2%). Double balloon enteroscopy or push enteroscopy was performed in eight patients (18.6%); only one was therapeutic. The main therapy in both groups was iron supplementation. There were no significant differences in iron treatment before and after VCE in each group and between groups. Anemia improved in both groups. There was no difference in the level of hemoglobin change between the groups during each year of follow-up compared to the baseline level prior to VCE. Anemia resolved in 15 patients (35%) in the positive VCE group and in 19 (45%) in the negative VCE group (P = 0.33).

Conclusions: Positive findings on VCE led to subsequent endoscopic interventions only in a small percentage of patients with IDA. Anemia improved and resolved equally whether or not there were VCE findings. The main intervention that appears to help IDA is iron supplementation.

Background: Upper eyelid blepharoplasty surgery is one of the most common plastic surgeries. Khat is used topically to reduce tissue edema.

Objectives: To evaluate the effect of topical khat administration after eyelid surgery on postoperative healing.

Methods: Our prospective comparative study included 24 patients who underwent upper eyelid blepharoplasty or ptosis surgery between 2019 and 2020. Patients were randomly assigned to 48 hours of cold dressing with frozen khat leaves and frozen peas dressing (common practice). Postoperative photographs of the eyes were evaluated for the degree of ecchymosis and edema on postoperative days (PODs) 1, 3, and 7 by three blinded observers. Measures included tissue swelling and hemorrhage on PODs 1, 3, and 7.

Results: The mean age of the cohort was 67 ± 7 years; 17 females (71%). Khat application was associated with lower postoperative ecchymosis at each time point. Females had lower levels of postoperative ecchymosis on POD 7 (P = 0.07). Eyelid edema was more pronounced in the khat group on PODs 1 and 3, but this was reversed on POD 7. There was good agreement among all three observers in grading ecchymosis and edema (P < 0.001).

Conclusions: The use of khat was associated with less tissue ecchymosis after oculoplastic surgery, although this was not statistically significant even following sub-population analysis. The outcome can be attributed to the active ingredients of cathinone and cathine, which cause vasoconstriction and lipolysis, and to the anti-inflammatory and anti-oxidative flavonoids and phenolic compounds. These encouraging preliminary findings warrant additional studies on a biochemical/cellular level.

Cannabis and cannabinoids have been known for thousands of years for their promising potential as analgesics. Chronic pain is a common complaint among many patients with rheumatic conditions. These disorders have revisited the medical approach toward cannabis and its potential role in pain relief. In addition, in recent years, information has mounted about the immunomodulatory effects of cannabis. In this review we discuss findings on the benefits cannabis may have in rheumatic and autoimmune disorders.

Background: Neutrophil-to-lymphocyte ratio (NLR) is a simple and cost-effective marker of inflammation. This marker has been shown to predict cardiac arrhythmias, progression of valvular heart disease, congestive heart failure decompensation, acute kidney injury, and mortality in cardiovascular patients. The pathologic process of aortic stenosis includes chronic inflammation of the valve and therefore biomarkers of inflammation might offer additive prognostic value.

Objectives: To evaluate NLR and its association with long term mortality in transcatheter aortic valve implantation (TAVI) patients.

Methods: We evaluated data of 1152 consecutive patient from the Tel Aviv Medical Center TAVI registry who underwent TAVI. Data included baseline clinical, demographic, and echocardiographic findings; procedural complications; and post-procedure mortality. Patients were compared by using the median NLR value (4.1) and evaluated for long-term mortality.

Results: Patients with NLR above the median had higher mortality rates (26.4% vs. 16.3%, P < 0.001) at 3 years post-procedure. A multivariable analysis found NLR to be an independent risk factor for mortality (hazard ratio = 1.47, 95% confidence interval 1.09–1.99, P = 0.013). In addition, high NLR was linked to complicationsduring and after the procedure.

Conclusion: NLR is an independent prognostic marker among TAVI patients. This marker may represent an increased inflammatory response and should be added to previous known prognostic factors.

Background: Risk factors for severe coronavirus disease-2019 (COVID-19) infection include old age, chronic illness, and neurological conditions. In contrast, high vitamin D levels are known to augment immune activity and to reduce the severity of viral infections. Recently, a possible association between the likelihood of COVID-19 infection, COVID-19 severity, and vitamin D blood levels was reported.

Objective: To assess the possible association between vitamin D long-term supplementation and COVID-19 symptomatic severity and complications of COVID-19 infection in elderly psychiatric inpatients, a high at-risk group.

Methods: We conducted a retrospective case series study. Data of 14 elderly COVID-19 positive inpatients, presenting with dementia or schizophrenia and other medical conditions were extracted from medical records. All patients maintained a 800 IU daily dose of vitamin D prior to the infection.

Results: Most of the inpatients were asymptomatic or presented very few symptoms. No need for intensive care unit intervention or deaths were reported. Cognitive functioning of the patients remained unchanged.

Conclusions: Pre-existing vitamin D supplementation may reinforce immunity and reduce COVID-19 severity in elderly psychiatric inpatients.

Background: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations, but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients.

Objectives: To investigate the possible implication of TR among STEMI patients.

Methods: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI) and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR, its relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded.

Results: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%; P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (hazard ratio 2.44; 95% confidence interval 1.06–5.62; P = 0.036) for patients with moderate-severe TR.

Conclusions: Among STEMI patients after primary PCI, the presence of moderate-severe TR was independently associated with adverse outcomes and significantly lower survival rate

Background: Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread musculoskeletal pain accompanied by various additional symptoms. The prevalence of FMS ranges between 2–8% of the population. The exact pathophysiology of the disease remains unknown, and under certain circumstances it is difficult for the physician to diagnose. Previous studies have shown a correlation between inflammatory biomarkers such as C-reactive protein (CRP) and FMS activity, suggesting that an inflammatory component may play a role in this disease pathogenesis.

Objectives: To investigate the role of certain new inflammatory biomarkers in the diagnosis of patients with FMS.

Methods: In this study data were collected from FMS patients who were admitted to Ziv Medical Center during the period 2013 to 2019 in an attempt to find a connection between inflammatory markers detectable by a traditional complete blood count (CBC) tests such as neutrophil-lymphocytes ratio (NLR), platelet-lymphocyte ratio (PLR), mean platelet value (MPV), red cell distribution width (RDW), and C-reactive protein (CRP) and FMS.

Results: We found significantly higher CRP levels, MPV, and PLR and lower lymphocyte count in the FMS group compared to the control group.

Conclusions: FMS has certain inflammatory components that may be useful in disease diagnosis

Background: Systemic sclerosis (SSc) is a connective tissue disease that may affect the heart and the autonomic nervous system (ANS). There is little knowledge regarding the degree of ANS involvement in SSc patients with unknown cardiac disease.

Objectives: To evaluate cardiac and pupillary autonomic functions in patients before cardiac involvement has emerged.

Methods: The study comprised 19 patients with SSc and 29 healthy controls. Heart rate variability (HRV) analysis for time and frequency domains, as well as deep breathing test and Ewing maneuvers, were performed in all patients. Automated pupillometry for the evaluation of pupillary diameter and pupillary light reflex was completed in 8 SSc patients and 21 controls.

Results: Both groups had similar characteristics, except for medications that were more commonly or solely prescribed for SSc patients. Compared with control subjects, the SSc patients had significantly lower HRV parameters of NN50 (15.8 ± 24.4 vs. 33.9 ± 33.1, P = 0.03), pNN50 (4.9 ± 7.4% vs.10.8 ± 10.8%, P = 0.03), and triangular index (11.7 ± 3.4 vs. 15.7 ± 5.8, P = 0.02). Abnormal adaptive responses in heart rate changes were recorded during deep breathing tests and Ewing maneuvers. There was no significant difference in any of the pupillometric indices or other HRV parameters within groups.

Conclusions: SSc patients may manifest cardiac autonomic dysfunction, while their autonomic pupillary function is seemingly spared. The role of certain medications, the significance of differential organ involvement, as well as the prognostic value of our findings should be evaluated in future studies

Background: Early referral to palliative care services in patients with advanced cancer is widely accepted. In addition, the use of futile intervention at the end of life is a pivotal aspect of assessing quality of care at that time.

Objectives: To evaluate the use of palliative care and aggressive treatments during the last month of life in women with gynecological malignancies.

Methods: The study was designed in two steps. The first step included a retrospective analysis of a gynecologic oncology cohort that underwent end-of-life (EOL) care. In the second part, a questionnaire regarding EOL care was completed by family members. Since our palliative care service became more active after 2014, we compared data from the years 2013–2014 to the years 2015–2019.

Results: We identified 89 patients who died from gynecological malignancy during study period; 21% received chemotherapy and 40% underwent invasive procedures during their last month of life. A palliative care consultation was documented for 49% of patients more than one week before their death. No statistical difference was achieved between the two time periods regarding the use of chemotherapy or invasive procedures in the last month of life. Nonetheless, after the incorporation of palliative medicine more women had palliative care consultations and had EOL discussions. Most of the patients’ relatives were satisfied with EOL care.

Conclusions: Many aggressive interventions were given during the last month of life. EOL discussions were documented in the medical charts of most patients and the rates increased with time.

Background: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients.

Objectives: To investigate the possible implication of TR among STEMI patients.

Methods: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI), and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR as well as the relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded.

Results: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%, P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (2.44, 95% confidence interval 1.06–5.6, P = .036) for patients with moderate to severe TR.

Conclusions: Among STEMI patients after primary PCI, the presence of moderate to severe TR was independently associated with adverse outcomes and significantly lower survival rate

Background: Adnexal torsion in pregnancy is often associated with functional adnexal cysts, especially in pregnancies conceived by ovulation induction (OI) or in-vitro fertilization (IVF). During laparoscopy for adnexal de-torsion, drainage of the functional cysts can be attempted, although this procedure may cause bleeding.

Objectives: To investigate the characteristics of ovarian torsion in pregnancy associated with functional cysts and to compare the rate of torsion recurrence following de-torsion alone versus cyst drainage.

Methods: All cases of surgically diagnosed adnexal torsion occurring during pregnancy between January 2007 and April 2019 in our department were retrospectively analyzed. The cases of torsion associated with presumed functional ovarian cysts were selected. The rate of recurrent torsion during the same pregnancy was compared for de-torsion alone versus de-torsion and cyst aspiration.

Results: Of the 113 women who experienced adnexal torsion during pregnancy, 71 (67.0%) of torsion cases were caused by presumed functional ovarian cysts. Among women with torsion of functional ovarian cysts, the rate of torsion recurrence was significantly higher in patients who underwent de-torsion alone (n=28) compared to women who underwent aspiration and drainage of the ovarian cysts (n=43) (14.3% vs. 0, P = 0.021). There were no cases of intra- or post-operative bleeding in the study cohort.

Conclusions: Functional ovarian cysts are the most common adnexal pathology encountered in pregnant women with torsion. Intra-operative cyst aspiration and drainage may reduce the risk of recurrent torsion. Further multi-center studies are required to validate our data prospectively.

Background: Chronic lung diseases, especially emphysema and pulmonary fibrosis, are the third leading cause of mortality worldwide. Their treatment includes symptom alleviation, slowing of the disease progression, and ultimately organ transplant. Regenerative medicine represents an attractive alternative.

Objectives: To develop a dual approach to lung therapy by engineering a platform dedicated to both remodeling pulmonary architecture (bronchoscopic lung volume reduction) and regeneration of lost respiratory tissue (scaffold).

Methods: The authors developed a hydrogel scaffold based on the natural polymers gelatin and alginate. The unique physical properties allow its injection through long catheters that pass through the working channel of a bronchoscope. The scaffold might reach the diseased area; thus, serving a dual purpose: remodeling the lung architecture as a lung volume reduction material and developing a platform for tissue regeneration to allow for cell or organoid implant.

Results: The authors’ novel hydrogel scaffold can be injected through long catheters, exhibiting the physical and mechanical properties necessary for the dual treatment objectives. Its biocompatibility was analyzed on human fibroblasts and mouse mesenchymal cells. Cells injected with the scaffold through long narrow catheters exhibited at least 70% viability up to 7 days.

Conclusions: The catheter-injectable gelatin-alginate hydrogel represents a new concept, which combines tissue engineering with minimal invasive procedure. It is an inexpensive and convenient to use alternative to other types of suggested scaffolds for lung tissue engineering. This novel concept may be used for additional clinical applications in regenerative medicine.

Background: Recent data regarding polymicrobial bacteremia (PMB) are lacking.

Objectives: To characterize risk factors as well as clinical, microbiological, and prognostic patterns of patients with PMB in a modern hospital setting.

Methods: A single center retrospective study including all patients diagnosed with PMB during 2013 was conducted. PMB was defined as two or more organisms cultured from the blood of the same patient within 72 hours. Patients with monomicrobial infections served as controls.

Results: There were 135 episodes (2% of all bacteremia episodes) of true PMB among 123 patients during the study period. Recent invasive procedures (odds ratio [OR] 3.59, 95% confidence interval [95%CI] 1.41–9.12, P = 0.006) and foreign bodies (OR 1.88, 95%CI 1.06–3.33, P = 0.04) were risk factors for PMB when compared with 79 patients with monomicrobial bacteremia. Central-line-associated infections were the most common infection source among patients with PMB (n=34, 28%). Enterobacteriaceae were the most commonly implicated pathogen (n=95, 77%). Non-fermenting Gram-negative bacilli were significantly more common than previously reported (n=55, 45%). Although crude 30-day mortality was higher (48% vs. 33%) in PMB patients, adjusted mortality was comparable in the two groups.

Conclusions: PMB rate in our cohort was considerably lower than in previous reports. Central-line-associated infections were more common than classic PMB sources. Mortality remained high. Strategies for early identification and better care for these patients should be pursued.

Background: Solar urticaria (SU) is a rare and disabling photodermatosis. SU typically manifests as urticarial wheals and erythema appearing shortly after sun exposure. SU is often initially diagnosed clinically with subsequent confirmation through photoprovocation tests. Early diagnosis is important for correct management of patients.

Objective: To present the clinical features of three cases of atypical presentation of SU and to discuss possible underlying mechanisms.

Methods: We report a series of three patients who presented with transient pruritic erythema without wheals after sun exposure. All patients had photoprovocation tests conducted to confirm SU diagnosis and to determine their action spectra. Treatment outcomes were recorded.

Results: All three patients developed classical manifestations of SU during photoprovocation tests within the UVA1 spectrum. Two patients required high-dose irradiation to provoke urticaria.

Conclusions: Erythema without urticaria can be the primary manifestation of SU, especially in countries with sunny climates where natural skin hardening is common. Such cases require a high index of suspicion for SU and highlight the importance of photoprovocation testing to confirm the diagnosis.

Background: Urinary tract infection (UTI) is a common bacterial infection in children.

Early treatment may prevent renal damage in pyelonephritis. The choice of empiric antibiotic treatment is based on knowledge of the local susceptibility of urinary bacteria to antibiotics. In Israel the recommended empiric oral antibiotic treatment are First or second generation cephalosporin, trimethoprim-sulfamethoxazole or amoxicillin-clavulanic acid.

Objectives: To describe resistance rates of urine bacteria isolated from children with UTI in the community settings. Identify risk factors for resistance.

Methods: A retrospective cross-sectional study of UTI in children aged 3 months to 18 years diagnosed with UTI and treated as outpatients in a large community clinic between 7/2015 and 7/2017 with a diagnosis of UTI.

Results: A total of 989 urinary samples were isolated, 232 were included in the study. Resistance rates to cephalexin, cefuroxime, ampicillin/clavulanate and Trimethoprim-Sulfamethoxazole were 9.9%, 9.1%, 20.7%, and 16.5%, respectively. Urinary tract abnormalities and recurrent UTI were associated with an increase in antibiotic resistance rates. Other factors such as age, fever, and previous antibiotic treatment were not associated with resistance differences.

Conclusions: Resistance rates to common oral antibiotics were low compared to previous studies performed in Israel in hospital settings. First generation cephalosporins are the preferred empiric antibiotics for febrile UTI for outpatient children. Amoxicillin/clavulanate is not favorable due to resistance of over 20% and the broad spectrum of this antibiotic. Care should be taken in children with renal abnormalities as there is a worrying degree of resistance rates to the oral first line antibiotic therapy.