Israel Medical Association Journal

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: 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: When a breast lesion is suspected based on a physical exam, mammography, or ultrasound, a stereotactic core needle biopsy (CNB) is usually performed to help establish a definitive diagnosis. CNBs are far less invasive than excisional biopsies, with no need for general anesthetics or hospitalization, and no recovery period. However, since only samples of the mass are removed in a CNB and not the whole mass, sampling errors can occur.

Objectives: To compare the degree of agreement between the pathological data from CNBs and excisional biopsies from a single tertiary referral hospital.

Methods: The concordance of pathological data was compared in patients who underwent CNBs and had their surgical procedures at the same medical center.

Results: From the 894 patients who underwent CNBs, 254 (28.4%) underwent subsequent excisional biopsies at our medical center. From the total of 894 patients, 227 (25.3%) who underwent a CNB were diagnosed with a malignancy, with the rest of the CNBs being diagnosed as benign pathologies. The pathological findings in the CNBs and in the excisional biopsies concurred in 232/254 (91.3%) of the cases.

Conclusions: A CNB to confirm mammographic or clinical findings of breast lesions is an accurate method to establish a pathological diagnosis of breast lesions. The accuracy is higher for invasive carcinomas than for non-invasive cancers. Excisional biopsies are necessary for lesions with anticipated sampling errors or when the core needle biopsy findings are discordant with clinical or mammographic findings.

Background: A dental appliance for obstructive sleep apnea (OSA) is recommended for patients who cannot adjust to continuous positive airway pressure (CPAP) treatments.



Objectives: To describe patients with extremely severe OSA who were successfully treated with a dental appliance and to compare their characteristics with the relevant literature to identify clinical features associated with a good outcome.



Methods: The clinical, management, and outcome data of three patients with an apnea-hypopnea index (AHI) of > 80 who showed clinical improvement following treatment with a dental appliance were collected retrospectively from sleep laboratory reports in Israel over a period of 3 years. 



Results: The patients included one man and two women, aged 33, 56, and 61 years, respectively. The diagnosis of OSA was based on clinical examination and polysomnography. AHI values at presentation were 83, 81, and 84, respectively. Treatment with a dental appliance (Herbst® or MDSA®) was proposed due to patient noncompliance with CPAP. Follow-up polysomnography with the dental appliance revealed a reduction in the AHI to 1.7, 10.7, and 11, respectively. All patients had supine OSA and a retrognathic mandible, both of which have been found to be associated with a good prognosis for treatment with a dental appliance.



Conclusions: Dental appliances may be considered an appropriate second-choice option to treat severe OSA in patients who are noncompliant with CPAP. This study helps physicians identify patients with extremely severe OSA who are suitable for dental appliance treatment. Well-designed large-scale studies are needed to reach definitive conclusions. 

Background: Skin colonization of microorganisms in blood cultures (BCs) are generally considered clinically non-significant and can be the source of a true infection, particularly in immunosuppressed patients.

Objectives: To study the epidemiology and risk factors for bacteremia caused by contaminants.

Methods: This retrospective, descriptive study is based on adult BCs collected (2004–2013) and categorized as positive (True bacteremia [TrueB] or contamination) or negative. Clinical, demographic, and laboratory characteristics of BCs positive for the six most common potential contaminant pathogens (PCPs) that can cause TrueB and contamination (Coagulase-negative Staphylococcus [CoNS], Streptococcus viridans, Propionibacterium acnes, Corynebacterium spp., Bacillus spp., Clostridium spp.) were assessed. Ninety-two TrueB were identified vs. 196 contaminations (1:2 ratio).

Results: From 74,014 BCs, PCPs were found in 3735 samples, of which 3643 (97.5%) were contaminations and 92 (2.5%) were TrueB. The overall rate of BC contamination decreased during the study period from 6.7% to 3.8%. CoNS was the most common PCP. Bacillus spp. were only contaminants. Clostridium spp. and Streptococcus viridans were more often TrueB. In a multivariate model, predictors of TrueB included high creatinine levels, Streptococcus viridans in BC, and multiple positive BCs. A single culture of CoNS was strongly predictive of contamination.

Conclusions: Ten years of data on BCs, focusing on six PCPs, demonstrates a significant, yet insufficient reduction in the rate of contamination. High creatinine level, isolation of Streptococcus viridans, and multiple positive BCs were predictors of TrueB, while growth of CoNS was strongly predictive of contamination. This model could assist in diagnostic and therapeutic decision making.

Background: Supracondylar humerus fractures are the most common elbow fractures in the pediatric population.

Objectives: To evaluate the outcomes of French's corrective osteotomy for correction of post-traumatic cubitus varus deformity in children.

Method: We conducted a retrospective review of medical charts of all patients who had undergone French's corrective osteotomy in our institution from 1998 to 2012. We recorded range of motion, cosmetic deformity, carrying angle, lateral cortex prominence index, hyperextension, and lateral cortex step before and after the surgery.

Results: Seven patients were enrolled the study. Average follow-up time was 4.6 years (range 2–9 years). An average of 18.3º of limited flexion (range 5º–35º) compared to the healthy elbow was recorded in three patients. Lateral condylar prominence was recorded in one patient. The average preoperative carrying angle was -20.5º (range -15º–30º) and postoperative angle was 9.6º (range 7º–13º). In comparison, the average carrying angle in the healthy elbow was 8.5º (range 4º–13º). No lateral cortex prominence was recorded. An average of 27.5º (range 15º–35º) of hyperextension of the distal fragment was recorded immediately postoperatively in four patients; however, during postoperative follow-up, the hyperextension was corrected spontaneously in all patients.

Conclusions: As described by French, osteotomy has the ability to correct the varus deformity only in the coronal plane. However, our research supports the assumption that hyperextension in the sagittal plane might be corrected spontaneously.