Israel Medical Association Journal

Anti-tumor necrosis factor-alpha (anti-TNFα) medications are the most frequently used biologicals to treat inflammatory bowel disease (IBD). Little is known about the ocular side effects of this drug category. We present a case series of six young patients with Crohn disease (CD) and no previous ophthalmologic manifestations who developed blepharitis after commencing treatment with anti-TNFα therapy. Six otherwise healthy patients with CD, with no history of allergies or prior ocular complaints, developed blepharitis at a median of 7.5 months after the initiation of anti-TNFα therapy. All ophthalmic findings were treated topically. The ocular symptoms of two of the patients resolved shortly after discontinuation of the anti-TNFα treatment. The other four presented with relapsing-remitting symptoms. Blepharitis is a common ocular disease in the general population and an extra-intestinal manifestation in patients with IBD. It may be an adverse effect of anti-TNFα therapy in this patient population.

Background: Implantable loop recorders (ILRs) are a central tool in the evaluation of unexplained syncope. These devices record and store electrocardiograms, both automatically and on patient-dependent activation. Therefore, obtaining optimal diagnostic results relies on a patient's comprehension and collaboration.

Objectives: To evaluate the effect of ethnic background and mother-tongue language on the diagnostic yield (DY) of ILRs.

Methods: Patients at two medical centers in Israel, who had ILRs as part of syncope workup were included. Inclusion criteria were age over 18 years and an ILR for at least one year (or less if the cause of syncope was detected). Patient demographics, ethnic background, and previous medical history were recorded. All findings from ILR recordings, activation mode (manual vs. automatic), and treatment decisions (none, ablation, device implantation) were collected.

Results: The study comprised 94 patients, 62 Jews (i.e., ethnic majority) and 32 non-Jews (i.e., ethnic minority). While baseline demographic characteristics, medical history, and drug therapy were similar in both groups, Jewish patients were significantly older at the time of device implantation: 64.3 ± 16.0 years of age vs. 50.6 ± 16.9, respectively; (P < 0.001). Arrhythmias recorded in both groups as well as treatment decisions and device activation mode were similar. Total follow-up time from device implantation was longer in the non-Jewish vs. the Jewish group (17.5 ± 12.2 vs. 24.0 ± 12.4 months, respectively; P < 0.017).

Conclusions: The DY of ILR implanted for unexplained syncope did not seem to be influenced by patient's mother-tongue language or ethnicity.

Carbamoyl phosphate synthetase 1 (CPS1; MIM *608307; E.C. 6.3.4.16) is the first rate-limiting enzyme of the urea cycle, an essential metabolic pathway for ammonia detoxification. CPS1 deficiency (CPS1-D) is characterized by severe hyperammonemia during disease exacerbations. During a metabolic crisis, children with CPS1-D are admitted with vomiting, altered mental status, and high serum levels of ammonia. Rapid normalization of ammonia level ameliorates neurological outcome [1,2]. The first-line treatment for hyperammonemia in these patients is ammonia scavengers in combination with citrulline or arginine and high-calorie supplementation while controlling protein intake [1].

Background: Late-onset pulmonary complications can occur following hematological stem cell transplantation (HSCT). In allogeneic HSCT these complications are often associated with chronic graft-versus-host disease (GVHD). Lung transplantation (LTx) often remains the only viable therapeutic option in these patients.

Objectives: To describe our experience with LTx due to GVHD after HSCT and to compare the long-term survival of this group of patients to the overall survival of our cohort of LTx recipients for other indications.

Methods: We retrospectively retrieved all data on patients who had undergone LTx for end-stage lung disease as a sequela of allogeneic HSCT, between 1997 and 2021, at Rabin Medical Center in Israel.

Results: A total of 15 of 850 patients (1.7%) from our cohort of LTx recipients fulfilled the criteria of LTx as a sequela of late pulmonary complication after allogeneic HSCT. The median age at the time of HSCT was 33 years (median 15–53, range 3–60). The median time between HSCT and first signs of chronic pulmonary GVHD was 24 months (interquartile range [IQR] 12–80). The median time from HSCT to LTx was 96 months (IQR 63–120). Multivariate analysis showed that patients transplanted due to GVHD had similar survival compared to patients who were transplanted for other indications.

Conclusions: LTx for GVHD after allogeneic HSCT constitutes an important treatment strategy. The overall survival appears to be comparable to patients after LTx for other indications.

Background: Blood pressure (BP) is routinely measured while triaging children presenting to the pediatric emergency department (PED).

Objectives: To determine whether a medical clown shortens the time to acquire a BP measurement among children undergoing triage in the PED.

Methods: The study comprised 133 children. Patients were assigned to one of two groups: with a medical clown or without a medical clown.

Results: The presence of a medical clown led to a significantly shorter time to acquire a blood pressure measurement (60 ± 23 seconds vs. 81 ± 43.5 seconds, P < 0.001. Clowns had a significant effect on shortening total triage length among children of Jewish ethnicity compared to Arab ethnicity (113 ± 353.6 seconds vs. 154 ± 418 seconds, P = 0.012).

Conclusions: Using medical clowns while measuring BP during triage when used in a culturally appropriate manner shortens time.

Background: Granulomatosis with polyangiitis (GPA) otologic manifestations include conductive and sensorineural hearing loss (HL). Vasculitis is assumed to be the primary cause of otologic manifestations. Deaf patients and patients with HL who do not benefit from hearing aids can benefit from cochlear implants (CI). There are currently no specific guidelines for treatment of patients with GPA suited for CI.

Objectives: To assess whether patients who are deaf due to GPA are good candidates for CI and if prior surgical or medical treatment of the inflammation are needed.

Methods: A case report is presented.

Results: A 71-year-old female patient with GPA and bilateral profound HL underwent CI. Prior to CI, preparation consisted of audiological evaluations by an otolaryngologist and a rheumatologist, followed by a course of prednisone and methotrexate for middle ear and nasal inflammations. CI was performed with no complications. The speech reception threshold and the monosyllabic word discrimination score after surgery were 25 dBHL and 75%, respectively.

Conclusions: Inflammation due to GPA can be controlled medically with immunosuppressive medications without subtotal petrosectomy, as in chronic suppurative otitis media. Satisfactory audiological results can be expected.

Worldwide, students of healthcare professions attend clinical rotations at medical facilities. Much research, and consequently scientific publications, is produced during their studies, bearing the fruits of student–faculty collaboration. To the best of our knowledge, no previous contract has been proposed detailing the fine print to pre-determine mutual responsibilities and privileges of students and faculty. Our objective was to present such a contract to the relevant students and faculty. We conducted a literature review to study existing proposals and solutions for this dilemma. Appropriate guidelines were also scanned. We included a proposal for a standard contract as the basis for student–faculty agreement for conducting research and publishing collaborative work. Questions regarding the relative contribution of students and subsequent authorship often arise. Vague rules and absent regulations in this realm can, at times, can be disadvantageous to students. We foresee a future role for our proposed agreement.

Background: Contact dermatitis is an inflammatory skin disorder characterized by an erythematous pruritic rash. The disorder can be either irritant or allergic. Allergic contact dermatitis is diagnosed by patch testing along with patient history.

Objectives: To review the results of patch tests conducted thought 2 years and to present real-life data characterizing clinical features and comparing prevalent local allergens to the ones common worldwide.

Methods: The retrospective cohort included 517 participants (384 females and 133 males) who underwent patch testing during a 2-year period. For each patient, clinical and demographic data were collected, and statistical analysis was conducted.

Results: We found that 261 patients had a positive test for at least one allergen. More females tested positive than males (52.9% vs. 43.6%). Test indications other than dermatitis were associated with a negative result. Hands, head, and neck were the most prevalent body parts affected. Patients with a background of atopic dermatitis had a higher rate of contact sensitization (69 vs. 43). Patients with a specific suspected offending allergen had significantly higher contact sensitizations. The most common allergen was nickel.

Conclusions: Patch testing should be conducted in patients with relevant dermatological findings accompanied by taking a thorough medical history. Clinicians should be updated on emerging allergens and exposure trends.

Background: Accuracy of the number and location of pathological lymph nodes (LNs) in the pathology report of a neck dissection (ND) is of vital importance.

Objectives: To quantify the error rate in reporting the location and number of pathologic LNs in ND specimens.

Methods: All patients who had undergone a formal ND that included at least neck level 1 for a clinical N1 disease between January 2010 and December 2017 were included in the study. The error rate of the pathology reports was determined by various means: comparing preoperative imaging and pathological report, reporting a disproportionate LN distribution between the different neck levels, and determining an erroneous location of the submandibular gland (SMG) in the pathology report. Since the SMG must be anatomically located in neck level 1, any mistake in reporting it was considered a categorical error.

Results: A total of 227 NDs met the inclusion criteria and were included in the study. The study included 128 patients who had undergone a dissection at levels 1–3, 68 at levels 1–4, and 31 at levels 1–5. The best Kappa score for correlation between preoperative imaging and final pathology was 0.50. There were nine cases (3.9%) of a disproportionate LN distribution in the various levels. The SMG was inaccurately reported outside neck level 1 in 17 cases (7.5%).

Conclusions: At least 7.5% of ND reports were inaccurate in this investigation. The treating physician should be alert to red flags in the pathological report

Background: The current approach to performing sacral neuromodulation consists of a two-stage procedure, the first of which includes insertion of the sacral electrode under fluoroscopic visualization of the S3 foramen. Alternatively, in certain situations computed tomography (CT)-guided insertion can be used.

Objectives: To evaluate the use of CT in cases of reinsertion of the electrode due to infection, dislocation, or rupture.

Methods: Medical records of patients who underwent neuromodulation device reinsertion between 2005 and 2016 for fecal incontinence were reviewed. Study outcomes included procedure course, successful placement, and long-term treatment success.

Results: During the study period, we inserted a neuromodulation device in 67 patients. A CT-guided insertion of a sacral electrode was performed in 10 patients. In nine patients, the insertion and the final location of the electrode were successful. In one patient, the electrode migrated upward due to a malformation of the S3 foramen on both sides and had to be placed in S4. In a mean follow-up of 68.4 ± 30.0 months following the re-insertion, there was a significant reduction in the number of incontinence episodes per day (P < 0.001) and the number of pads used per day (P = 0.002).

Conclusions: CT-guided insertion of a sacral electrode is a safe and promising option, especially in recurrent and or selected cases

Background: Mean platelet volume (MPV), an essential component of the complete blood count (CBC) indices, is underutilized in common practice. In recent years, MPV has drawn strong interest, especially in clinical research. During inflammation, the MPV has a higher value because of platelet activation.

Objectives: To verify whether high MPV values discovered incidentally in healthy naïve patients indicates the development or the presence of cardiovascular risk factors, particularly metabolic syndrome and pre-diabetes.

Methods: A cohort study was used to assess the diagnostic value of high MPV discovered incidentally, in naïve patients (without any known cause of an abnormal high MPV, greater than  upper limit of the normal range, such as active cardiovascular diseases and metabolic syndrome).

Results: The mean MPV value in the patient group was 12.3 femtoliter. There was a higher incidence of metabolic syndrome in our research group than in the general population and a non-significant tendency of pre-diabetes. Family doctors more frequently meet naïve patients with high MPV than a hospital doctor. The results of our study are more relevant for him, who should know the relevance of such a finding and search for a hidden pre-diabetes or metabolic syndrome.

Conclusions: High MPV values discovered incidentally in healthy naïve subjects suggest the development or the presence of cardiovascular risk factors, particularly metabolic syndrome and pre-diabetes. No statistically significant association was found between MPV and the presence of cardiovascular disease

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: Idiopathic pulmonary fibrosis (IPF) has poor prognosis. Anti-fibrotic treatment has been shown to slow disease progression. Lung transplantation (LTx) offers a survival benefit. The 5-year survival after LTx in IPF is between 40 and 50%

Objectives: To evaluate which IPF patients have better prognosis following LTx.

Methods: A retrospective study was conducted with all IPF patients who had undergone LTx in the Rabin Medical Center between 2010 and 2018. We collected data on pre-evaluation of pulmonary function tests, echocardiographic and right heart catherization, and anti-fibrotic treatments. The Kaplan-Meier method was used for survival analysis.

Results: Among148 patients who underwent LTx, 58 were double LTx (DLT) and 90 single LTx (SLT). Mean age was 58.07 ± 9.78 years; 104 males and 44 females. DLT patients had significantly lower survival rates than SLT in the short and medium term after LTx. Patients with saturation above 80% after the 6-minute walk test (6MWT) had higher survival rates. Patients over 65 years of age had a lower survival rates. Those with pulmonary hypertension (PHT) above 30 mmHg had a poorer prognosis with lower survival rates.

Conclusions: IPF patients with higher mean PHT, older age (> 65 years), and desaturation following 6MWT had lower survival rates following LTx. DLT may decrease survival rate compared to SLT just for the short and medium period of time after LTx. These results may lead to better selection of IPF patient candidates for LTx. Additional studies are warranted for choosing which patients will have better prognosis after LTx.

Background: A thorough informed consent (IC) process is required before in vitro fertilization (IVF) treatments can begin because these treatments are by and large elective and they have expectable and preventable complications, such as ovarian hyper-stimulation syndrome and multi-fetal pregnancies.

Objectives: To empirically examine whether patient knowledge and understanding of potential hazards associated with IVF treatment are better after the IC process compared to before. The authors hypothesized that patients' better understanding of potential complications would be translated and expressed as rational choices of treatment alternatives.

Methods: Responses of 48 IVF patients after IC process (study group) from two IVF units in northern Israel were compared to those of 46 patients before IVF (control group).

Only women undergoing IVF for first time who were older than 18 years of age were eligible for the study.

Results: Socio-demographic parameters were found to be quite similar between the study group and the control group. Contrary to our expectations, in the study group 12 women (25.5%) considered delivery of a single baby as their optimal result, compared to 15 (32.6%) in the control group. Furthermore, preferences shifted toward triplets: eight patients (17%) after IC considered this option as their best result, compared to only five patients (11%) before IC.

Conclusions: IC process goals are not achieved under current practices, at least as far as IVF treatment are concerned. New tools and incentives should be implemented to meet the requirements dictated by the laws regarding patient rights.