Israel Medical Association Journal

Background: Cardiac damage caused by oncological therapy may manifest early or many years after the exposure.

Objectives: To determine the differences between sub-acute and late-onset cardiotoxicity in left ventricular ejection fraction (LVEF) recovery as well as long-term prognosis.

Methods: We studied 91 patients diagnosed with impaired systolic function and previous exposure to oncological therapy. The study population was divided according to sub-acute (from 2 weeks to ≤ 1 year) and late-onset (> 1 year) presentation cardiotoxicity. Recovery of LVEF of at least 50% was defined as the primary end point and total mortality was the secondary end point.

Results: Fifty-three (58%) patients were classified as sub-acute, while 38 (42%) were defined as late-onset cardiotoxicity. Baseline clinical characteristics were similar in the two groups. The mean LVEF at presentation was significantly lower among patients in the late-onset vs. sub-acute group (28% vs. 37%, respectively, P < 0.001). Independent predictors of LVEF recovery were trastuzumab therapy and a higher baseline LVEF. Although long-term mortality rates were similar in the groups with sub-acute and late-onset cardiotoxicity, improvement of LVEF was independently associated with reduced mortality.

Conclusions: Our findings suggest that early detection and treatment of oncological cardiotoxicity play an important role in LVEF recovery and long-term prognosis.

Background: Nail-patella syndrome (NPS) is characterized by changes in the nails, knees, and elbows, as well as the presence of iliac horns detected by X-ray of the pelvis. A higher occurrence of psychiatric disorders has also been suggested in NPS. Heterozygous mutations in the gene encoding the LIM-homeodomain transcription factor (LMX1B) are identified in most patients with typical clinical findings of NPS.

Objective: To report on the association between NPS and schizophrenia.

Methods: Genomic DNA were isolated from a patient's venous blood and collected on ethylenediaminetetraacetic 5% with the Gentra Puregene Blood Kit. All exons and flanking regions of the LMX1B gene (LMX1B: NM_001174146.1) were amplified by standard polymerase chain reaction and analyzed by direct DNA sequencing with BigDye Terminators on an ABI 3100 sequencer. Sequence chromatograms were analyzed using SeqScape software version 1.1. Mutation analysis and characterization of variants was performed with the Alamut Software Version 2.1.

Results: We report a patient presenting to the psychiatry department with schizophrenia. Clinical examination revealed characteristic findings consistent with NPS. Since NPS was suspected, based on clinical findings, sequencing of all coding exons of LMX1B gene was completed. Results revealed a novel heterozygous mutation in the proband: c.546_547insACCG(het); p.Glu183Thrfs*11.

Conclusions: Based on LMX1B expression in brain regions that are implicated in neuropsychiatric illness, and especially in the development of dopaminergic neurons, we hypothesize that schizophrenia may be part of the clinical spectrum of NPS.

Background: Risk factors for bleeding complications after percutaneous kidney biopsy (PKB) and the role of primary hemostasis screening are not well established.

Objectives: To determine the role of primary hemostasis screening and complication outcomes among individuals who underwent PKB.

Methods: We reviewed data of 456 patients who underwent PKB from 2010 to 2016 in a large university hospital. In 2015, bleeding time (BT) testing was replaced by light transmission aggregometry (LTA) as a pre-PKB screening test.

Results: Of the 370 patients who underwent pre-PKB hemostasis screening by BT testing, prolonged BT was observed in 42 (11.3%). Of the 86 who underwent LTA, an abnormal response was observed in 14 (16.3%). Overall, 155 (34.0%) patients experienced bleeding: 145 (31.8%) had minor events (hemoglobin fall of 1–2 g/dl, macroscopic hematuria, perinephric hematoma without the need for transfusion or intervention) and 17 (3.7%) had major events (hemoglobin fall > 2 g/dl, blood transfusion or further intervention). Abnormal LTA response did not correlate with bleeding (P = 0.80). In multivariate analysis, only prolonged BT (P = 0.0001) and larger needle size (P = 0.005) were identified as independent predictors of bleeding.

Conclusions: Bleeding complications following PKB were common and mostly minor, and the risk of major bleeding was low. Larger needle size and prolonged BT were associated with a higher bleeding risk. Due to the relatively low risk of major bleeding and lack of benefit of prophylactic intervention, the use of pre-PKB hemostasis screening remains unestablished.

Background: Evidence has been emerging that Helicobacter pylori may also impact colorectal cancer (CRC). Positron emission tomography/computed tomography (PET/CT) imaging can predict overall survival in CRC patients.

Objectives: To determine a possible association between H. pylori seropositivity and all-cause mortality among CRC patients evaluated by PET/CT scans.

Methods: This prospective cohort study was comprised of 110 consecutive CRC patients who had undergone a PET/CT evaluation in a tertiary academic medical center. Data included demographics, body mass index (BMI), tumor node metastasis stage at diagnosis, treatment, time from diagnosis to PET/CT, and PET/CT findings. All patients were tested for anti-H. pylori immunoglobulin G (IgG) antibodies and followed for 36 months from the day of the PET/CT scan. Mortality was documented. Univariate and multivariate Cox regression was used to estimate the hazard ratio (HR) of H. pylori serological status.

Results: During the follow-up period, of the 110 CRC patients 41 (37.3%) died and 69 (62.7%) survived. Of the 41 patients, 26 (63.4%) were H. pylori seropositive and 15 (36.6%) were seronegative. Multivariate analysis showed that H. pylori seropositivity was associated with increased mortality (HR 3.46, 95% confidence interval 1.63–7.32), stage IV at diagnosis, metastatic disease found on PET/CT, longer time from diagnosis to PET/CT, lower BMI, and older age.

Conclusions: Our findings suggest that H. pylori infection may be a risk factor for all-cause mortality among CRC patients who are evaluated by PET/CT. Multicenter studies with larger patient groups are needed to confirm our findings.

Background: Laparoscopic salpingectomy is strongly related to successful in vitro fertilization (IVF) treatments.

Objectives: To compare the ovarian reserve, including anti-mullerian hormone (AMH) levels, in patients who underwent salpingectomy before IVF to IVF patients who had not been salpingectomized.

Methods: In this retrospective study, medical records of women who were treated by the IVF unit at our institute were reviewed. We retrieved demographic data, surgical details, and data regarding the ovarian reserve. Details of 35 patients who were treated by IVF after salpingectomy were compared to 70 IVF patients with no history of salpingectomy treatment. Nine women underwent IVF treatment before and after having salpingectomy, and their details were included in both groups.

Results: The levels of AMH, follicular stimulating hormone (FSH), estradiol, and progesterone were not significantly different in the groups. The antral follicular count (AFC), number of oocytes retrieved, amount of gonadotropin administered for ovarian stimulation, and number of embryos transferred (ET) were also not significantly different.

Conclusions: Salpingectomy does not seem to affect ovarian reserve in IVF patients.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) (such as canagliflozin, empagliflozin, and dapagliflozin) are widely used to treat patients with type 2 diabetes mellitus (T2DM) to improve glycemic, cardiovascular and renal outcomes. However, based on post-marketing data, a warning label was added regarding possible occurrence of acute kidney injury (AKI).

Objectives: To describe the clinical presentation of T2DM patients treated with SGLT2i who were evaluated for AKI at our institution and to discuss the potential pathophysiologic mechanisms.

Methods: A retrospective study of a computerized database was conducted of patients with T2DM who were hospitalized or evaluated for AKI while receiving SGLT2i, including descriptions of clinical and laboratory characteristics, at our institution.

Results: We identified seven patients in whom AKI occurred 7–365 days after initiation of SGLT2i. In all cases, renin-angiotensin-aldosterone system blockers had also been prescribed. In five patients, another concomitant nephrotoxic agent (injection of contrast-product, use of nonsteroidal anti-inflammatory drugs or cox-2 inhibitors) or occurrence of an acute medical event potentially associated with AKI (diarrhea, sepsis) was identified. In two patients, only the initiation of SGLT2i was evident. The mechanisms by which AKI occurs under SGLT2i are discussed with regard to the associated potential triggers: altered trans-glomerular filtration or, alternatively, kidney medullary hypoxia.

Conclusions: SGLT2i are usually safe and provide multiple benefits for patients with T2DM. However, during particular medical circumstances, and in association with usual co-medications, particularly if baseline glomerular filtration rate is decreased, patients treated with SGLT2i may be at risk of AKI, thus warranting caution when prescribed.

Background: Behçet’s disease (BD) is an inflammatory disorder potentially leading to life- and sight-threatening complications. No laboratory marker correlating with disease activity or predicting the occurrence of disease manifestations is currently available.

Objectives: To determine an association between serum amyloid-A (SAA) levels and disease activity via the BD Current Activity Form (BDCAF), to evaluate disease activity in relation to different SAA thresholds, to examine the association between single organ involvement and the overall major organ involvement with different SAA thresholds, and to assess the influence of biologic therapy on SAA levels.

Methods: We collected 95 serum samples from 64 BD patients. Related demographic, clinical, and therapeutic data were retrospectively gathered.

Results: No association was identified between SAA levels and BD disease activity (Spearman's rho = 0.085, P = 0.411). A significant difference was found in the mean BDCAF score between patients presenting with SAA levels < 200 mg/L and those with SAA levels > 200 mg/L (P = 0.027). SAA levels > 200 mg/L were associated with major organ involvement (P = 0.008). A significant association was found between SAA levels > 150 mg/dl and ocular (P = 0.008), skin (P = 0.002), and mucosal (P = 0.012) manifestations. Patients undergoing biologic therapies displayed more frequently SAA levels < 200 mg/L vs. patients who were not undergoing biologic therapies (P = 0.012).

Conclusions: Although SAA level does not represent a biomarker for disease activity, it might be a predictor of major organ involvement and ocular disease relapse at certain thresholds in patients with BD.

Background: Anemia management strategies among chronic hemodialysis patients with high ferritin levels remains challenging for nephrologists.

Objectives: To compare anemia management in stable hemodialysis patients with high (≥ 500 ng/ml) vs. low (< 500 ng/ml) ferritin levels

Methods: In a single center, record review, cohort study of stable hemodialysis patients who were followed for 24 months, an anemia management policy was amended to discontinue intravenous (IV) iron therapy for stable hemodialysis patients with hemoglobin > 10 g/dl and ferritin ≥ 500 ng/ml. Erythropoiesis-stimulating-agents (ESA), IV iron doses, and laboratory parameters were compared among patients with high vs. low baseline ferritin levels before and after IV iron cessation.

Results: Among 87 patients, 73.6% had baseline ferritin ≥ 500 ng/ml. Weekly ESA dose was greater among patients with high vs. low ferritin (6788.8 ± 4727.8 IU/week vs. 3305.0 ± 2953.9 IU/week, P = 0.001); whereas, cumulative and monthly IV iron doses were significantly lower (1628.2 ± 1491.1 mg vs. 2557.4 ± 1398.9 mg, P = 0.011, and 82.9 ± 85 vs. 140.7 ± 63.9 mg, P = 0.004). Among patients with high ferritin, IV iron was discontinued for more than 3 months in 41 patients (64%) and completely avoided in 6 (9.5%).ESA dose and hemoglobin levels did not change significantly during this period.

Conclusions: Iron cessation in chronic hemodialysis patients with high ferritin levels did not affect hemoglobin level or ESA dose and can be considered as a safe policy for attenuating the risk of chronic iron overload.

Background: Family physicians and internal medicine specialists play an essential role in treating cancer patients. Modern technological advances in radiotherapy are not widely appreciated by primary care physicians. Bone metastases are a frequent complication of cancer. Palliative radiation therapy, as a component of modern advances in radiation treatments, should not subject normal bodily structures to excessive doses of irradiation. The sacrum is a common destination site for bone metastases, yet its concave shape along with its proximity to the rectum, intestines, and femoral heads creates treatment-planning challenges.

Objectives: To investigated whether the volumetric modulated arc therapy (VMAT) technique is preferable to more conventional radiation strategies.

Methods: The study comprised 22 patients with sacral metastases who were consecutively treated between 2013 and 2014. Two plans were generated for the comparison: three-dimensional (3D) and VMAT.

Results: The planning target volume (PTV) coverage of the sacrum was identical in VMAT and 3D planning. The median values for the rectal dose for 3D and VMAT were 11.34 ± 5.14 Gy and 7.7 ± 2.76 Gy, respectively. Distal sacral involvement (S4 and S5) was observed in only 2 of 22 cases, while the upper pole of the rectum ended at the level above S3 in just 3 cases.

Conclusions: Radiation therapy continues to be an integral component of the palliative armamentarium against painful metastases. Radiation oncologist, in conjunction with referral physicians, can tailor treatment plans to reflect the needs of a given patient.

Background: A patient`s individual chance of being diagnosed with cardiovascular disease can be determined by risk scores.

Objectives: To determine the risk score profiles of patients presenting with a first acute coronary event according to pre-admission risk factors and to evaluate its association with long-term mortality.

Methods: The research was based on a retrospective study of a cohort from the 2010 and 2013 Acute Coronary Syndrome Israeli Surveys (ACSIS). Inclusion criteria included first event and no history of coronary heart disease or cardiovascular disease risk equivalent. The Framingham Risk Score, the European Systematic COronary Risk Evaluation (SCORE), and the American College of Cardiology/American Heart Association/ (ACC/AHA) risk calculator were computed for each patient. The risk profile of each patients was determined by the three scores. The prognostic value of each score for 5 year survival was evaluated.

Results: The study population comprised 1338 patients enrolled in the prospective ACSIS survey. The ACC/AHA score was the most accurate in identifying patients as high risk based on pre-admission risk factors (73% of the subjects). The Framingham algorithm identified 53%, whereas SCORE recognized only 4%. After multivariate adjustment for clinical factors at presentation, we found that no scores were independently associated with 5 year mortality following the first acute coronary event.

Conclusions: Patients with first acute coronary event had a higher pre-admission risk scores according to the ACC/AHA risk algorithm. No risk scores were independently associated with 5 year survival after an event.

Background: Unicuspid and bicuspid aortic valve (BAV) are congenital cardiac anomalies associated with valvular dysfunction and aortopathies occurring at a young age.

Objectives: To evaluate our experience with aortic valve repair (AVr) in patients with bicuspid or unicuspid aortic valves.

Methods: Eighty patients with BAV or unicuspid aortic valve (UAV) underwent AVr. Mean patient age was 42 ± 14 years and 94% were male. Surgical technique included: aortic root replacement with or without cusp repair in 43 patients (53%), replacement of the ascending aorta at the height of the sino-tubular junction with or without cusp repair in 15 patients (19%), and isolated cusp repair in 22 patients (28%).

Results: The anatomical structure of the aortic valve was bicuspid in 68 (85%) and unicuspid in 12 patients (15%). Survival rate was 100% at 5 years of follow-up. Eleven patients (13.7%) underwent reoperation, 8 of whom presented with recurrent symptomatic aortic insufficiency (AI). Late echocardiography in the remaining 69 patients revealed mild AI in 63 patients, moderate recurrent AI in 4, and severe recurrent AI in 2. Relief from recurrent severe AI or reoperations was significantly lower in patients who underwent cusp repair compared with those who did not (P = 0.05). Furthermore, the use of pericardial patch augmentation for the repair was a predictor for recurrence (P = 0.05).

Conclusions: AVr in patients with BAV or UAV is a safe procedure with low morbidity and mortality rates. The use of a pericardial patch augmentation was associated with higher repair failure.