Israel Medical Association Journal

Phosphoglucomutase 1 (PGM1) deficiency is a rare genetic disorder that affects glycogen metabolism and manifests as a multisystem disease. Most patients present with oropharyngeal malformations, cardiomyopathies, elevated liver enzymes, and hypoglycemia. Treatment with D-galactose has been shown to improve symptoms. Our patient presented with PGM1 deficiency. She conceived spontaneously. Throughout her pregnancies, our patient was monitored by a multidisciplinary team of cardiologists, endocrinologists, and physicians with experience in high-risk pregnancy. She delivered twice by cesarean section. Our case highlights the importance of a multidisciplinary approach and individualized management of prenatal and postpartum care of a patient with a PGM1 deficiency. To the best of our knowledge, there have been no reports about a PGM1-deficient patient who conceived and delivered.

Background: The evaluation of syncope in emergency departments (EDs) and during hospitalization can be ineffective. The European Society of Cardiology (ESC) guidelines were established to perform the evaluation based on risk stratification.

Objectives: To investigate whether the initial screening of syncope adheres to the recent ESC guidelines.

Methods: Patients with syncope who were evaluated in our ED were included in the study and retrospectively classified based on whether they were treated according to ESC guidelines. Patients were divided into two groups according to the ESC guideline risk profile: high risk or low risk.

Results: The study included 114 patients (age 50.6 ± 21.9 years, 43% females); 74 (64.9%) had neurally mediated syncope, 11 (9.65%) had cardiac syncope, and 29 (25.45%) had an unknown cause. The low-risk group included 70 patients (61.4%), and the high-risk group included 44 (38.6%). Only 48 patients (42.1%) were evaluated according to the ESC guidelines. In fact, 22 (36.7%) of 60 hospitalizations and 41 (53.2%) of 77 head computed tomography (CT) scans were not mandatory according to guidelines. The rate of unnecessary CT scans (67.3% vs. 28.6%, respectively, P = 0.001) and unnecessary hospitalization (66.7% vs. 6.7%, respectively, P < 0.02) were higher among low-risk patients than high-risk patients. Overall, a higher percentage of high-risk patients were treated according to guidelines compared to low-risk patients (68.2% vs. 25.7% respectively, P < 0.0001).

Conclusions: Most syncope patients, particularly those with a low-risk profile, were not evaluated in accordance with the ESC guidelines.

Background: Acute coronary syndrome (ACS) represents a spectrum of ischemic myocardial disease including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). Various prognostic scores were developed for patients presenting with NSTEMI-ACS. Among these scores, the GRACE risk score offers the best discriminative performance for prediction of in-hospital and 6-month mortality. However, the GRACE score is limited and cannot be used in several ethnic populations. Moreover, it is not predictive of clinical outcomes other than mortality.

Objective: To assess the prognostic value of traditional cardiovascular risk factors and laboratory biomarkers in predicting 6-month major adverse cardiac and cerebrovascular events (MACCE), including hospitalization, recurrent percutaneous coronary intervention (PCI), stroke, and cardiovascular mortality in patients with NSTEMI treated with PCI.

Methods: This retrospective study included consecutive patients admitted with an initial diagnosis of NSTEMI to the cardiac intensive care unit (CICU) at the Tzafon Medical Center, Israel, between April 2015 and August 2018 and treated by PCI within 48 hours of admission.

Results: A total of 223 consecutive patients with NSTEMI treated by PCI were included in the study. Logarithm_ebrain natriuretic peptide (LogₑBNP), prior MI, and Hb levels were found to be significant predictors of any first MACCE. Only logₑBNP was found to be an independent predictor of a first MACCE event by multivariate logistic regression analysis.

Conclusions: LogₑBNP is an independent predictor of worse prognosis in patients with NSTEMI. Routine evaluation of BNP levels should be considered in patients admitted with NSTEMI.

Background: Patients with high-risk prostate cancer are at higher risk of treatment failure, development of metastatic disease, and mortality. There is no consensus on the treatment of choice for these patients, and either radical prostatectomy (RP) or external beam radiation therapy (EBRT) is recommended. Surgery is less common as the initial treatment for high-risk patients, possibly reflecting the concerns regarding morbidity as well as oncological and functional outcomes. Another high-risk group includes patients with failure of previous EBRT or focal treatment. For these patients, salvage radical prostatectomy (SRP) can be offered.

Objectives: To describe our experience with surgery of high-risk patients and SRP.

Methods: This cohort included all high-risk patients undergoing RP or SRP at our institution between January 2012 and December 2019. We reviewed the electronic medical charts and collected pathological, functional, and oncological outcomes.

Results: Our cohort included 39 patients; average age was 67.8 years, and average follow-up duration was 40.9 months. The most common postoperative morbidity was transfusion of packed cells. There were no life-threatening events or postoperative mortality. Continence was preserved (zero to one pad) in 76% of the patients. Twenty-three patients (59%) had undetectable prostate specific antigen levels following the surgery, 11 (30%) were treated with either adjuvant or salvage EBRT, and 12 patients (31%) were found with no evidence of disease and no additional treatment was needed.

Conclusions: Radical prostatectomy and SRP are safe options for patients presenting with high-risk prostate cancer, with good functional and oncological outcomes.

Background: Ga-prostate-specific membrane antigen positron emission tomography/computerized tomography (Ga-PSMA PET/CT) is part of the initial workup of patients with intermediate and high-risk prostate cancer provided by the Israeli national health services.

Objectives: To assess the incidence of metastatic spread in consecutive patients with newly diagnosed cancer, and the potential added value of Ga-PSMA PET/CT to the staging imaging algorithm.

Methods: Patients with newly diagnosed intermediate- and high-risk prostate cancer were referred for initial staging by Ga-PSMA PET/CT between May 2016 and April 2017. Blood prostate-specific antigen (PSA) levels, clinical history, imaging reports and histopathological reports (including Gleason scores) were obtained. Maximal standardized uptake values (SUVmax) were determined for the primary lesions detected within the prostate.

Results: The study included 137 consecutive patients with intermediate- and high-risk disease who underwent Ga-PSMA PET/CT staging. Of these, 75 had Ga-PSMA uptake in both prostate lobes, 57 had unilateral uptake, and 5 patients had no uptake. SUVmax in the primary tumor correlated significantly with PSA levels. Thirty-five patients had increased uptake compatible with metastatic disease involving lymph nodes, bone, and viscera. Twenty-seven patients had available bone scintigraphy results: 18 (69%) of their 26 bone metastases detected by Ga-PSMA PET/CT were missed on bone scintigraphy.

Conclusions: Ga-PSMA PET/CT shows promise as a sole whole-body imaging modality for assessing the presence of soft tissue and bone metastases in the setting of prostate cancer.

Background: Fetal alcohol spectrum disorder (FASD) may be under-recognized and under-diagnosed in Israel. Fewer than 10 FASD diagnoses were reported between 1998 and 2007; however, several hundred diagnoses have been made since. Furthermore, less than 10% of surveyed Israeli pediatricians reported adequate knowledge of FASD.

Objectives: To determine the prevalence of suspected FASD, to establish a database as a starting point for epidemiological studies, and to develop FASD awareness for health, social, and educational services.

Methods: A chart review was conducted at an educational facility for children and adolescents with behavioral and learning challenges. The following information was extracted: adoption status, history of alcohol/drug abuse in the biological mother, medical diagnoses, medication use, and information regarding impairment in 14 published neurobehavioral categories. Subjects were classified as: category 1 (highly likely FASD) – impairment in three or more neurobehavioral categories and evidence of maternal alcohol abuse was available; category 2 (possible FASD) – impairment in three or more neurobehavioral categories and evidence to support maternal substance abuse (type/time unspecified); and category 3 (unconfirmed likelihood of FASD) – impairment in three or more neurobehavioral categories and no information regarding the biological family.

Results: Of 237 files analyzed, 38 subjects (16%) had suspected FASD: 10 subjects (4%) in category 1, 5 (2%) in category 2, and 23 (10%) in category 3. Twenty-seven subjects with suspected FASD (69%) had been adopted.

Conclusions: This study is the most comprehensive review of FASD among Israeli children and adolescents in a population with learning and behavior challenges.

Background: Abnormal gestational weight gain (GWG) has been associated with adverse outcomes for mothers and their offspring.

Objectives: To compare the achievement of recommended GWG and lifestyle factors in women with high-risk versus normal-risk pregnancies.

Methods: Pregnant women hospitalized in a gynecological and obstetrics department and pregnant women who arrived at a community clinic for a routine checkup were interviewed and completed questionnaires relating to weight gain and lifestyle factors (e.g., smoking, diet, exercise). Recommended GWG was defined by the American Congress of Obstetricians and Gynecologists (ACOG).

Results: GWG higher than ACOG recommendations was reported by 52/92 women (57%) with normal pregnancies and by 43/86 (50%) with high-risk pregnancies. On univariate analysis, characteristics associated with greater GWG were: current or past smoking, age > 40 years, pre-gestational body mass index (BMI) > 25 kg/m², low fruit intake, and high snack intake. High-risk pregnancies were associated with pre-gestational BMI > 25 kg/m² (48% vs. 27%, P = 0.012), consumption of vitamins (84% vs. 63%, P = 0.001), avoidance of certain foods (54% vs. 21%, P = 0.015), receiving professional nutritionist consultation (65% vs. 11%, P = 0.001), and less physical activity (9% vs. 24%, P = 0.01).

Conclusions: A minority of pregnant women met the recommended GWG. No difference was noted between normal and high-risk pregnancies. High-risk population tended to have a less healthy lifestyle. Counseling to follow a healthy, balanced diet should be recommended, regardless of pregnancy risk, with particular attention to women at high risk of extra weight gain.

Background: Prolonged life expectancy has increased the number of elderly high risk patients referred for surgical aortic valve replacement (AVR). These referred high risk patients may benefit from sutureless bioprosthesis procedures which reduce mortality and morbidity.

Objectives: To present our initial experience with sutureless aortic bioprotheses, including clinical and echocardiographic results, in elderly high risk patients referred for AVR. 

Methods: Forty patients (15 males, mean age 78 ± 7 years) with symptomatic severe aortic stenosis underwent AVR with the 3F Enable™ or Perceval™ sutureless bioprosthesis during the period December 2012 to May 2014. Mean logistic EuroScore was 10 ± 3%. Echocardiography was performed preoperatively, intraoperatively, at discharge and at follow-up.

Results: There was no in-hospital mortality. Nine patients (22%) underwent minimally invasive AVR via a right anterior mini-thoracotomy and one patient via a J-incision. Four patients underwent concomitant coronary aortic bypass graft, two needed intraoperative repositioning of the valve, one underwent valve exchange due to inappropriate sizing, three (7.5%) had a perioperative stroke with complete resolution of neurologic symptoms, and one patient (2.5%) required permanent pacemaker implantation due to complete atrioventricular block. Mean preoperative and postoperative gradients were 44 ± 14 and 13 ± 5 mmHg, respectively. At follow-up, 82% of patients were in New York Heart Association functional class I and II.

Conclusions: Sutureless AVR can be used safely in elderly high risk patients with relatively low morbidity and mortality. The device can be safely implanted via a minimally invasive incision. Mid-term hemodynamic results are satisfactory, demonstrating significant clinical improvement.

 

Objectives: To present our initial experience with MitraClip implantation in 20 high risk patients at Sheba Medical Center.

Methods: Twenty high surgical risk patients with symptomatic significant MR underwent MitraClip implantation. Clinical and echocardiographic parameters were recorded at baseline and at follow-up.

Results: The patients’ mean age was 76 years and 65% were male. Coronary artery disease was present in 85% and 45% had previous bypass surgery. Renal failure was present in 65%, atrial fibrillation in 60%, and 30% had an implantable cardioverter defibrillator/cardiac resynchronization therapy device. Mean left ventricular ejection fraction was 36%. Grade III-IV MR was present in all patients with the vast majority suffering from functional MR secondary to ventricular remodeling. New York Heart Association (NYHA) class was III-IV in 90%. Patients were followed for a mean of 231 days. Acute reduction of MR grade to ≤ 2 was accomplished in 19 of the 20 patients (95%) with a 30 day mortality of 5%. At follow-up MR was reduced to ≤ 2 in 64% of patients, and NYHA class improved in 70% of patients. An additional 2 patients (11%) died during follow-up.

Conclusions: MitraClip implantation is feasible and safe in high risk highly symptomatic patients with significant MR. Acute and mid-term results are comparable to similar high risk patient cohorts in the literature. Continued surveillance and longer follow-up are needed to elucidate which patients are most likely to benefit from the procedure.

Background: Transjugular kidney biopsy (TJKB) was first described in 1990. Indications for TJKB include uncorrectable bleeding disorders and conditions precluding the prone position. Objectives: To describe our initial experience with TJKB.

Methods: Between February 2008 and December 2009 all patients in whom percutaneous biopsy was contraindicated or unsuccessful underwent image-guided TJKB using a standard set with a 19 gauge core biopsy needle. Prospectively collected data included indication, number of needle passes, contrast dose, tissue yield, and complications.

Results: Twelve patients, age range 15–76 years (mean 55), underwent 14 TJKB procedures. Indications for the transjugular route included bleeding diathesis, dyspnea, ventral hernia, ascites, marked obesity, need for concomitant liver biopsy or concomitant insertion of tunneled dialysis catheter, discrepant kidney size, and failed percutaneous attempt. Thirteen biopsies were performed in 11 patients; in one patient TJKB was abandoned due to unfavorable renal vein anatomy. Four patients were premedicated with desmopressin and one with platelet transfusion, due to prolonged bleeding time. Three to six passes (mean 3.8) were made per biopsy, with an overall yield of 9.6 ± 8.2 glomeruli, providing a definite diagnosis in nine patients and a probable diagnosis in two. In two patients the first biopsy attempt yielded insufficient tissue, necessitating a repeat procedure. There were two minor bleeding episodes not requiring intervention. Serum creatinine was unchanged after the procedure and hemoglobin levels asymptomatically dropped by 0.3 ± 1.0 g/dl within 48 hours, requiring no treatment.

Conclusions: TJKB appears to safely allow adequate tissue diagnosis in patients at increased risk for complications from or contraindications to percutaneous renal biopsy.
 

There are major dilemmas regarding the optimal modalities for breast cancer screening. This is of particular relevance to Israel because of its high-risk population. It was suggested that an avenue for further research would be to incorporate advances in signal processing through the fast Padé transform (FPT) to magnetic resonance spectroscopy (MRS). We have now applied the FPT[1] to time signals that were generated according to in vitro MRS[2] data as encoded from extracted breast specimens from normal, non-infiltrated breast tissue, fibroadenoma and cancerous breast tissue. The FPT is shown to resolve and precisely quantify the physical resonances as encountered in normal versus benign versus malignant breast. The FPT unambiguously delineated and quantified diagnostically important metabolites such as lactate, as well as phosphocholine, which very closely overlaps with glycerophosphocholine and phosphoethanolamine, and may represent a magnetic resonance-visible molecular marker of breast cancer. These advantages of the FPT could clearly be of benefit for breast cancer diagnostics via MRS. This line of investigation should continue with encoded data from benign and malignant breast tissue, in vitro and in vivo. We anticipate that Padé-optimized MRS will reduce the false positive rates of MR-based modalities and further improve their sensitivity. Once this is achieved, and given that MR entails no exposure to ionizing radiation, new possibilities for screening and early detection emerge, especially for risk groups. For example, Padé-optimized MRS together with MR imaging could be used with greater surveillance frequency among younger women with high risk of breast cancer.

Background: The prevalence of aortic stenosis increases with advancing age. Once symptoms occur the prognosis in patients with severe aortic stenosis is poor. The current and recommended treatment of choice for these patients is surgical aortic valve replacement. However, many patients, mainly the very elderly and those with major comorbidities, are considered to be at high surgical risk and are therefore denied treatment. Recently, a transcatheter alternative to surgical AVR[1] has emerged.

Objectives: To describe the first year experience and 30 day outcome of transcatheter aortic self-expandable CoreValve implantation in Israel.

Methods: Transcatheter aortic valve implantation using the CoreValve system has been performed in Israel since September 2008. In the following year 55 patients underwent CoreValve TAVI[2] in four Israeli centers.

Results: Patients' mean age was 81.7 ± 7.1 years; there were 35 females and 20 males. The mean valve area by echocardiogram was 0.63 ± 0.16 cm². The calculated mean logistic Euroscore was 19.3 ± 8%. Following TAVI, mean transvalvular gradient decreased from baseline levels of 51 ± 13 to 9 ± 3 mmHg. The rate of procedural success was 98%. One patient died on the first day post-procedure (1.8%) and all-cause 30 day mortality was 5.5% (3 of 55 patients). One patient had a significant post-procedural aortic regurgitation of > grade 2. Symptomatic improvement was evident in most patients, with reduction in functional capacity grade from 3.2 ± 0.6 at baseline to 1.4 ± 0.7. The most common post-procedural complication was complete heart block, which necessitated permanent pacemaker implantation in 37% of patients.

Conclusions: The Israeli first year experience of transcatheter aortic valve implantation using the CoreValve self-expandable system demonstrates an effective and safe procedure for the treatment of severe aortic stenosis in patients at high surgical risk.

Background: Current treatment options for acute calculous cholecystitis include either early cholecystectomy, or conservative treatment consisting of intravenous antibiotics and an interval cholecystectomy several weeks later. Percutaneous drainage is reserved for patients in whom conservative therapy failed or as a salvage procedure for high risk patients.

Objective: To identify clinical and radiographic factors leading to failure of conservative treatment.

Methods: We prospectively collected data on consecutive patients admitted with the diagnosis of acute cholecystitis. Parameters were compared between patients who were successfully treated conservatively and those who required percutaneous cholecystostomy. Logistic regression analysis was performed to identify predictors for failure of conservative treatment. 

Results: The study population comprised 103 patients with a median age of 60 who were treated for acute cholecystitis. Twenty-seven patients (26.2%) required PC[1]. On univariate analysis, age above 70 years, diabetes, elevated white blood cell count, tachycardia (> 100 beats/min) at admission, and a distended gallbladder (> 5 cm transverse diameter) were found to be significantly more common in the PC group (P < 0.001). WBC[2] was higher in the PC group throughout the initial 48 hours. On multivariate analysis, age above 70 (odds ratio 3.6), diabetes (OR[3] 9.4), tachycardia at admission (OR 5.6), and a distended gallbladder (OR 8.5) were predictors for cholecystostomy (P < 0.001). Age above 70 (OR 5.2) and WBC > 15,000 (OR 13.7) were predictors for failure of conservative treatment after 24 and 48 hours (P < 0.001). 

Conclusions: Age above 70, diabetes, and a distended gallbladder are predictors for failure of conservative treatment and such patients should be considered for early cholecystostomy. Persistently elevated WBC (> 15,000) suggests refractory disease and should play a central role in the clinical follow-up and decision-making process for elderly patients with acute cholecystitis.