Israel Medical Association Journal

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: 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.

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: 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.

Background: Early identification of patients with a likelihood of cardiac improvement has important implications for management strategies.

Objectives: To evaluate whether tissue Doppler imaging (TDI) and two-dimensional (2D) strain measures may predict left ventricular (LV) improvement in patients with recent onset dilated cardiomyopathy (ROCM).

Methods: Clinical and comprehensive echo were performed at baseline and at 6 months. Patients who achieved an increase of ≥ 10 LV ejection fraction (LVEF) units and LV reverse remodeling (LVRR) (group 1) and those who improved beyond the device threshold achieving LVEF of ≥ 0.40 (group 2) were compared to patients who did not improve to this level.

Results: Among 37 patients with ROCM (mean age 56.3 ± 12.9 years and LVEF 29.1 ± 7.0%), 48% achieved LVEF ≥ 0.40 and 37.8% demonstrated LVRR. Patients with LVEF improvement ≥ 40% presented at diagnosis with higher LVEF (P = 0.006), smaller LV end-diastolic diameter (LVEDd) (P = 0.04), higher E’ septal (P = 0.02), lower E/E’ ratio (P = 0.02), increased circumferential strain (P = 0.04), and apical rotation (P = 0.009). Apical rotation and LVEDd were found to be independent predictors of LVRR. End-systolic LV volume was a significant predictor of LVEF improvement (≥ 40%).

Conclusions: Nearly half of the patients with ROCM demonstrated cardiac function improvement beyond the device threshold by 6 months. Apical rotation was introduced in our study as 2D strain prognostic parameter and found to be an independent predictor of LVRR. LV size and volume were predictors of LV improvement.

Background: Concerns about metformin-associated lactic acidosis (MALA) prohibit the use of metformin in a large subset of diabetic patients, mostly in patients with chronic kidney disease. Increasing evidence suggests that the current safety regulations may be overly restrictive.

Objectives: To examine the association between chronic metformin treatment and lactate level in acute illness on the first day of admission to an internal medicine ward.

Methods: We compared diabetic and non-diabetic hospitalized patients treated or not treated with metformin in different sets of kidney function.

Results: A total of 140 patients participated in the study, 54 diabetic patients on chronic metformin treatment, 33 diabetic patients without metformin and 53 patients with no diabetes. Most participants were admitted for conditions that prohibit metformin use, such as heart failure, hypoxia and sepsis. Average lactate level was significantly higher in the diabetes + metformin group compared to the diabetes non-metformin group. Metformin treatment was not associated with higher than normal lactate level (hyperlactatemia) or low pH. No patient was hospitalized for lactic acidosis as the main diagnosis.

Conclusions: Chronic metformin treatment mildly increases lactate level, but does not induce hyperlactatemia or lactic acidosis in acute illness on the first day of admission to an internal medicine ward. These data support the expansion of metformin use.

Background: The prevalence and etiology of nephrolithiasis vary, depending on geography, gender and ethnicity. 

Objectives: To analyze the demographic data of return nephrolithiasis patients in a tertiary care center.

Methods: We retrospectively reviewed our prospective registry database of return patients seen at our outpatient clinic for nephrolithiasis. Data included gender, age at first visit, age at first stone event, body mass index (BMI), self-reported hypertension, diabetes mellitus (DM), and hyperlipidemia. All patients were seen at least twice and had undergone a metabolic workup. 

Results: A total of 260 return patients were seen during the period 2010–2015. The male:female ratio was 3.1:1. Mean age at the first stone event was 44.1 years. Median time elapsed since the first stone event to medical evaluation was 5 years (interquartile range 1–12 years). Hypertension was reported by 33.1% of the patients, DM by 23.5% and hyperlipidemia by 30.4%. All three diseases were reported by 11.5% of patients. The metabolic abnormalities detected were hypocitraturia (60%), low urine volume (LUV) (60%), hypercalciuria (40.8%), hyperoxaluria (24.2%), hyperuricosuria (16.5%) and hyperuricemia (13.5%). Stone compositions from most to least frequent were calcium-oxalate (81%), calcium-phosphate (11.9%) and uric acid (7.1%). We also found that 24.6% were obese (BMI ≥ 30 kg/m2) and showed higher rates of hypertension, DM, hyperlipidemia, hyperuricemia and hyperuricosuria compared with non-obese patients. Significantly higher rates of obesity and LUV were detected in females compared with males. Patients over age 45 had lower rates of hyperuricemia compared with patients ≥ 45 years old (P = 0.038).

Conclusions: Factors related to nephrolithiasis can potentially differ among populations and countries. Our findings emphasize the significance of individualized national health programs to address local issues.

 

Abstract

Background: Iatrogenic ureteral injury may be seen following abdominopelvic surgeries. While ureteral injuries identified during surgery should be immediately and surgically repaired, those that are postoperatively diagnosed may be treated non-surgically by draining the ipsilateral kidney. Data regarding the outcome of this approach are still missing.

Objectives: To evaluate the success rates of non-surgical management of ureteral injuries diagnosed following abdominopelvic surgeries.

Methods: We retrospectively reviewed the files of all patients treated for iatrogenic ureteral injuries diagnosed following abdominopelvic surgeries. Patients' ipsilateral kidney was percutaneously drained following diagnosis of injury by either nephrostomy tube (NT)/nephro-ureteral stent (NUS) or double-J stent (DJS) inserted retrogradely. The tube was left in place until a pyelogram confirmed healing or a conservative approach was abandoned due to failure.

Results: Twenty-nine patients were identified as having ureteral injury following abdominopelvic surgery. Median time from injury to renal drainage was 9 days, interquartile range (IQR) 4–17 days. Seven cases (24%) had surgical repair. Among the other 22 patients, in 2 oncology patients the conservative approach was maintained although renal drainage failed to resolve the injury. In the remaining 20, median drainage length was 60 days (IQR 43.5–85). Calculated overall success rates following renal drainage was 69% (18/29), and with NS approached 78.5%.

Conclusions: Ureteral injuries diagnosed following abdominopelvic surgeries can be treated conservatively. Ipsilateral renal drainage should be the first line of treatment before surgical repair, and NUS may be the preferred drainage to obtain spontaneous ureteral healing. 

Background: The pathophysiology of aortic stenosis (AS) involves inflammatory features including infiltration of the aortic valve (AV) by activated macrophages and T cells, deposition of lipids, and heterotopic calcification.

Objectives: To evaluate the correlation between white blood cell (WBC) differential count and the occurrence and progression of AS.

Methods: We identified in our institutional registry 150 patients with AS who underwent two repeated echo studies at least 6 months apart. We evaluated the association between the average of repeated WBC differential counts sampled during the previous 3 years and subsequent echocardiographic AS indices.

Results: There was no significant difference in total WBC, lymphocyte or eosinophil count among mild, moderate or severe AS groups. There was a progressive decrease in monocyte count with increasing AS severity (P = 0.046), more prominent when comparing the mild and severe groups. There was a negative correlation between AV peak velocity or peak or mean gradient and monocyte count in the entire group (r = -0.31, -0.24, and -0.25 respectively, all P ≤ 0.01). Similar partial correlations controlling for age, gender, hypertension, smoking, dyslipidemia and ejection fraction remained significant. The median changes over time in peak velocity and peak gradients in AS patients were 0.44 (0–1.3) m/sec/year and 12 (0–39) mmHg/year, respectively. There was no correlation between any of the WBC differential counts and the change in peak velocity or peak gradient per year.

Conclusions: Severe AS is associated with decreased total monocyte count. These findings may provide further clues to the mechanism underlying the pathogenesis of aortic stenosis.