Israel Medical Association Journal

Cardiac amyloidosis is a form of restrictive cardiomyopathy resulting from the accumulation of misfolded protein aggregates in the myocardial extracellular space. Cardiac amyloidosis stems primarily from the misfolding of monoclonal immunoglobulin light chains (AL) originating from abnormal clonal plasma cell proliferation or transthyretin amyloidosis (ATTR).

Diagnosis of amyloidosis demands a high index of suspicion and requires histological confirmation of pathognomonic green birefringence under polarized light when an infiltrated tissue specimen is stained with Congo-red staining [1,2].

Pleural involvement of systemic amyloidosis has rarely been reported and is considered a serious complication [3]. Pleural amyloidosis is diagnosed with the identification of amyloid deposits in pleural biopsy specimens. However, pleural biopsies are rarely performed for this indication.

We describe the case of a patient with AL cardiac amyloidosis presenting as intractable pleural effusion and diagnosed via pleural biopsy.

Background: In 2019, 1 mg subcutaneous semaglutide was registered for the treatment of diabetes in Israel. Recognition of its effect on weight has led to its use as a treatment for obesity.

Objectives: To explore physicians’ pre-therapy considerations, therapy practices, and attitudes regarding subcutaneous semaglutide for weight loss.

Methods: A 22-item questionnaire was disseminated to physicians who prescribed semaglutide 1-mg for weight loss using an authorized off-label path.

Results: In total, 127 physicians completed the questionnaire. As for pretreatment requirements, in the absence of diabetes, 30% requested a minimal body mass index of 30 kg/m². Additional requirements were documented lifestyle-change effort (67%) and prior weight loss medication use (13%). Half of the physicians regarded calorie restriction, and 23% considered physical activity as necessary for weight loss while on therapy. As for dose, most physicians (78%) started with a 0.25-mg weekly injection, 57% doubled the dose monthly, and all others recommended doubling when side effects subsided. Regarding weight loss goal, 43% of the physicians set a personal goal with each patient while 26% limited the goal to 10% of initial weight. Fewer than 50% of physicians discussed treatment duration with their patients, and 52% of patients discontinued therapy in the first 3 months. The main reasons for discontinuation were price, lack of effect, and fear of long-term side effects.

Conclusions: The diverse approaches regarding off-label use of semaglutide for weight reduction highlight the necessity to guide physicians and standardize treatment regimen.

Background: Fetal facial clefts are among the most common congenital anomalies detected prenatally. This finding may lead to termination of pregnancy in some cases.

Objectives: To compare a cohort of fetuses with facial clefts in which the pregnancy was terminated to the cohort of cases that were born with facial clefts. To investigate risk factors for facial clefts.

Methods: We conducted a retrospective chart review of all women with prenatal and postnatal diagnosis of facial cleft that were managed in our institute. A telephone questionnaire was conducted regarding a positive family history and/or genetic predisposition for facial clefts abnormalities.

Results: The final cohort consisted of two group. One group included 54 cases of termination of pregnancy (TOP) that were performed due to cleft lip (CL) or cleft palate (CLP); 27 women answered the telephone questionnaire. The second group comprised 99 women who delivered children with facial cleft during the same period; 60 answered the questionnaire. Only seven cases were diagnosed prenatal. Among the two groups, no correlation to family history was discovered. Of note, there was one case of three consecutive fetuses with CL in one woman, without any significant genetic findings.

Conclusions: To the best of our knowledge, this is the first study to describe an anatomical malformation posing an ethical dilemma before TOP. Primary prevention with folic acid and early sonographic detection of CL/CLP with multidisciplinary consultation should be considered.

Background: Acute kidney injury (AKI) is a risk factor for morbidity and mortality during critical illness especially in very old patients admitted to intensive care units.

Objectives: To identify prognostic markers for AKI patients.

Methods: This single-center retrospective study was based on a patient registry of a medical intensive care unit. Hospital records of patients aged 80 years or older admitted between 2005 and 2015 were examined. Patients who developed AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines within 4 days of admission were included in this study.

Results: The study comprised 96 patients with AKI and 81 age- and sex-matched controls without AKI. Mean acute physiology and chronic health evaluation (APACHE) II score was 30 with an ICU mortality of 27% in very old patients with AKI. The odds ratio of hospital mortality for these patients was 5.02 compared to controls (49% vs. 16%). APACHE II score and fluid balance in the first 2 days of ICU admission were the strongest predictors of ICU mortality with an area under the receiver operating characteristic of 0.76. Of the 47 patients with AKI who survived hospital admission, 30 were discharged home.

Conclusions: Mortality was increased in very old ICU patients with AKI. Among survivors, two-thirds returned home.

Background: The cornea is one of the most densely innervated in the body. Pterygium surgery includes removal of the pterygium tissue from the cornea and conjunctiva followed by autologous conjunctival grafting.

Objectives: To examine the change in corneal and conjunctival sensation post-pterygium surgery.

Methods: This prospective study included patients with primary pterygium. We collected and analyzed demographic data, visual acuity (VA), refraction, quantified sensation, and corneal tomography. Comparison in sensation in the cornea, conjunctiva, and conjunctival autograft was recorded the day of surgery and at least 6 months postoperatively.

Results: Nine patients participated in the study. Mean follow-up time was 9 months (9 ± 3.3, 6–12.4). No complications were documented during or following surgery and no recurrences were found. Statistically significant increases in corneal sensation in the nasal corneal and in the nasal conjunctival areas were noted by the end of follow-up compared to before surgery (P = 0.05, paired samples t-test). There was a significant correlation between the increase in nasal corneal and conjunctival sensation with improved Schirmer testing outcomes and tear break-up time after surgery (P = 0.05, P = 0.01, Pearson correlation). There was a positive correlation between the changes in nasal corneal sensation after surgery and improved changes in VA (P = 0.02, Pearson correlation).

Conclusions: We found improvement in sensation 9 months after pterygium surgery, which may be due to reinnervation of the cornea and conjunctival autograft from the neighboring non-injured nerve fibers. Larger studies with confocal microscopy should be conducted for further analysis.

Background: Higher body mass index (BMI) has been shown to be a protective factor from mortality in sepsis patients. Yet, whether this effect is different in the very elderly is currently unknown.

Objective: To investigate the relationship between BMI and sepsis outcomes in patients older and younger than 80 years of age.

Methods: A retrospective analysis of consecutive patients admitted with sepsis to Shamir Medical Center, Israel, was conducted. We compared patients older than and younger than 80 years of age with a BMI higher and lower than 25 kg/m² for hospitalization outcomes.

Results: Patients older than 80 years presented with multiple co-morbidities compared to younger patients, but with no difference between BMI groups. Similarly, hospitalization outcomes of functional deterioration, discharge to long-term care facilities, and readmission were not significantly different between BMI groups in the same age category. Mortality was significantly different between BMI groups in patients older than 80 years of age, with higher mortality in BMI < 25 kg/m²: in-hospital mortality (23.4% vs. 14.9%, P < 0.001), 30-day mortality (27.6% vs. 17.9%, P < 0.001), and 90-day mortality (43.4% vs. 28.9%, P < 0.001). This difference was not significant between the groups younger than 80 years old. On logistic regression, BMI over 25 kg/m² was protective in all mortality categories. Nevertheless, there was no significant interaction between age over 80 years to BMI over 25 kg/m² in all mortality outcomes.

Conclusions: Among patients hospitalized with sepsis, higher BMI is a protective factor against mortality in both elderly and younger patients.

The pathogenesis of atherosclerosis is multifactorial, mainly driven by complex inflammatory processes. Colchicine is an anti-inflammatory drug used in a variety of clinical settings. The purpose of this review is to evaluate the role of colchicine in atherosclerotic vascular disease and more specifically, its promising impact on the outcome of patients with stable and acute coronary syndrome and to review its effect in patients undergoing angioplasty. A literature review was performed using the search terms colchicine, coronary heart disease, or acute coronary syndrome, stable coronary disease. We accessed PubMed, Google scholar, and the Cochrane Library databases to search for studies. Patients with chronic coronary disease may benefit from treatment with low dose colchicine to reduce the occurrence of a cardiovascular event. Among patients with a recent myocardial infarction, colchicine treatment was associated with reduced ischemic cardiovascular events, although without a meaningful difference in mortality. Colchicine was found to be a promising agent that can be potentially integrated into the armamentarium of treatments for patients with atherosclerotic coronary disease pending careful patient selection

Background: Keratoconus is a non-inflammatory disease characterized by progressive corneal steepening, which leads to decreased visual acuity secondary to high irregular astigmatism.

Objectives: To compare the one-year outcomes of accelerated vs. standard collagen crosslinking (CXL) in the treatment of keratoconus.

Methods: A database search of patients who underwent CXL from 2009 to 2017 was conducted at the cornea clinic at Sheba Medical Center. Charts of 99 adult patients (124 eyes) were reviewed. All patients were diagnosed with keratoconus. Main outcome measures were change in keratometry, uncorrected visual acuity (UCVA), and best-corrected visual acuity (BCVA).

Results: We evaluated outcomes in two groups: CXL with standard (3 mW/cm² for 30 minutes) vs. the accelerated (9 mW/cm² for 10 minutes) protocol. There were no significant differences between the groups with regard to BCVA, UCVA, and mean spherical equivalent (P =0.83, 0.0519, 0.181, respectively). The corneal thickness in the center and thinnest location were higher in the accelerated group than the in the standard group (P = 0.126). Complication rates did not differ between the two groups.

Conclusions: Accelerated and standard CXL are both safe and effective techniques. Accelerated CXL confers the added benefit of being a faster procedure to both patients and surgeons.

Background: Anti-endothelial cell antibodies (AECA) are a known biomarker of endothelial dysfunction and damage in clinical practice, especially in autoimmune disease.

Objectives: To determine the relation between natural AECA levels and prognosis related to coronary artery disease.

Methods: Candidates for coronary angiography were prospectively enrolled. AECA levels were determined by ELISA assay. Mortality was evaluated after more than 5 years follow-up.

Results: Of a total 857 patients, 445 had high AECA levels (group 1) and 412 had low levels (< 1 OD unit, group 2). Both groups did not differ in age, sex, or presence of diabetes. The median follow up was 2293 days (76 months). Patients with high AECA levels were more likely to have normal coronary arteries on angiography (21.6% vs. 16.9%, P = 0.047) and less likely to have calcified lesions (19.0% vs. 26.6%, P = 0.028) and lower prevalence of abnormal renal functions (71.1 mg/dl vs. 66.5 mg/dl, P = 0.033). Patients with higher AECA levels had lower mortality levels (20.1% vs. 27.6%, P = 0.006). A logistic regression model demonstrated independent association between lower AECA levels and the presence of coronary atherosclerosis based on angiogram.

Conclusions: After a median of more than 6 years, higher natural AECA levels were associated with less coronary artery disease and lower mortality rates in patients undergoing coronary angiography

Background: Little is known about oncologic outcomes following robot-assisted-radical-prostatectomy (RALP) for clinical T3 (cT3) prostate cancer.

Objectives: To investigate oncologic outcomes of patients with cT3 prostate cancer treated by RALP.

Methods: Medical records of patients who underwent RALP from 2010 to 2018 were retrieved. cT3 cases were reviewed. Demographic and pre/postoperative pathology data were analyzed. Patients were followed in 3–6 month intervals with repeat PSA analyses. Adjuvant/salvage treatments were monitored. Biochemical recurrence (BCR) meant PSA levels of ≥ 0.2 ng/ml.

Results: Seventy-nine patients met inclusion criteria. Median age at surgery was 64 years. Preoperative PSA level was 7.14 ng/dl, median prostate weight was 54 grams, and 23 cases (29.1%) were down-staged to pathological stage T2. Positive surgical margin rate was 42%. Five patients were lost to follow-up. Median follow-up time for the remaining 74 patients was 24 months. Postoperative relapse in PSA levels occurred in 31 patients (42%), and BCR in 28 (38%). Median time to BCR was 9 months. The overall 5-year BCR-free survival rate was 61%. Predicting factors for BCR were age (hazard-ratio [HR] 0.85, 95% confidence interval [95%CI] 0.74–0.97, P = 0.017) and prostate weight (HR 1.04, 95%CI 1.01–1.08, P = 0.021). Twenty-six patients (35%) received adjuvant/salvage treatments. Three patients died from metastatic prostate cancer 31, 52, and 78 months post-surgery. Another patient died 6 months post-surgery of unknown reasons. The 5-year cancer-specific survival rate was 92%.

Conclusions: RALP is an oncologic effective procedure for cT3 prostate cancer. Adjuvant/salvage treatment is needed to achieve optimal disease-control

Background: Dietary modifications and patient-tailored medical management are significant in controlling renal stone disease. Nevertheless, the literature regarding effectiveness is sparse.

Objectives: To explore the impact of dietary modifications and medical management on 24-hour urinary metabolic profiles (UMP) and renal stone status in recurrent kidney stone formers.

Methods: We reviewed our prospective registry database of patients treated for nephrolithiasis. Data included age, sex, 24-hour UMP, and stone burden before treatment. Under individual treatment, patients were followed at 6–8 month intervals with repeat 24-hour UMP and radiographic images. Nephrolithiasis-related events (e.g., surgery, renal colic) were also recorded. We included patients with established long-term follow-up prior to the initiation of designated treatment, comparing individual nephrolithiasis status before and after treatment initiation.

Results: Inclusion criteria were met by 44 patients. Median age at treatment start was 60.5 (50.2–70.2) years. Male:Female ratio was 3.9:1. Median follow-up was 10 (6–25) years and 5 (3–6) years before and after initiation of medical and dietary treatment, respectively. Metabolic abnormalities detected included: hypocitraturia (95.5%), low urine volume (56.8%), hypercalciuria (45.5%), hyperoxaluria (40.9%), and hyperuricosuria (13.6%). Repeat 24-hour UMP under appropriate diet and medical treatment revealed a progressive increase in citrate levels compared to baseline and significantly decreased calcium levels (P = 0.001 and 0.03, respectively). A significant decrease was observed in stone burden (P = 0.001) and overall nephrolithiasis-related events.

Conclusions: Dietary modifications and medical management significantly aid in correcting urinary metabolic abnormalities. Consequently, reduced nehprolithiasis-related events and better stone burden control is expected.

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: Pancreatic injuries during nephrectomy are rare, despite the relatively close anatomic relation between the kidneys and the pancreas. The data regarding the incidence and outcome of pancreatic injuries are scarce.

Objectives: To assess the frequency and the clinical significance of pancreatic injuries during nephrectomy.

Methods: A retrospective analysis was conducted of all patients who underwent nephrectomy over a period of 30 years (1987–2016) in a large tertiary medical center. Demographic, clinical, and surgical data were collected and analyzed.

Results: A total of 1674 patients underwent nephrectomy during the study period. Of those, 553 (33%) and 294 patients (17.5%) underwent left nephrectomy and radical left nephrectomy, respectively. Among those, four patients (0.2% of the total group, 0.7% of the left nephrectomy group, and 1.36% of the radical left nephrectomy) experienced iatrogenic injuries to the pancreas. None of the injuries were recognized intraoperatively. All patients were treated with drains in an attempt to control the pancreatic leak and one patient required additional surgical interventions. Average length of stay was 65 days (range 15–190 days). Mean follow-up was 23.3 months (range 7.7–115 months).

Conclusions: Pancreatic injuries during nephrectomy are rare and carry a significant risk for postoperative morbidity.

Background: Anastomotic leakage (AL) is a major complication following colorectal surgery, with many risk factors established to date. The incidence of AL varies in the medical literature and is dependent on research inclusion criteria and diagnostic criteria.

Objectives: To determine the incidence of and the potential risk factors for AL following colorectal surgery at a single academic medical center.

Methods: We retrospectively reviewed all operative reports of colorectal procedures that included bowel resection and primary bowel anastomosis performed at Sheba Medical Center during 2012. AL was defined according to the 1991 United Kingdom Surgical Infection Study Group criteria. Data were assessed for leak incidence within 30 days. In addition, 17 possible risk factors for leakage were analyzed. A literature review was conducted.

Results: This cohort study comprised 260 patients, and included 261 procedures performed during the study period. The overall leak rate was 8.4%. In a univariate analysis, male sex (odds ratio [OR] 3.37, 95% confidence interval [95%CI] 1.21–9.43), pulmonary disease (OR 3.99, 95%CI 1.49–10.73), current or past smoking (OR 2.93, 95%CI 1.21–7.10), and American Society of Anesthesiologist score ≥ 3 (OR 3.08, 95%CI 1.16–8.13) were associated with an increased risk for anastomotic leakage. In a multivariate analysis, male gender (OR 3.62, 95%CI 1.27–10.33) and pulmonary disease (OR 4.37, 95%CI 1.58–12.10) were associated with a greater risk.

Conclusions: The incidence of AL in the present study is similar to that found in comparable series. Respiratory co-morbidity and male sex were found to be the most significant risk factors.

Background: Complete hydatidiform mole and a co-existing normal fetus (CHMCF) is associated with a high complication rate. A possible association with assisted conception might increase the prevalence of CHMCF.

Objectives: To study the potential association between assisted conception and the risks of CHMCF.

Methods: Case series at a single university hospital from 2008 to 2018 are presented and contrasted with data from a comprehensive literature review (1998–2018). Cases were identified from the institutional database that matched the sonographic criteria for CHMCF. A literature review showed comparable cases.

Results: None of the three pregnancies presented in this article resulted in a viable fetus, all were aborted. One of the three patients needed chemotherapy due to gestational trophoblastic neoplasia (GTN). A literature search identified 248 reported cases in which 22 fetuses (9%) reached term, 88/248 (35%) progressed to GTN, and 25/120 (21%) were conceived following assisted conception. From 2008 until 2018 at our medical facility, there were 3144 twin pregnancies of which 1667 (53%) were conceived using assisted conception. In our cohort, there was no statistical trend for assisted conception as an etiological factor for CHMCF.

Conclusions: No association between assisted conception and the risk for CHMCF was established at our hospital, although approximately one-quarter of all reported CHMCF pregnancies are attributed to assisted conception technology. However, these data are not always reported, making it difficult to draw definitive conclusions.