Israel Medical Association Journal

Background: Unilateral intratonsillar abscess (ITA) is an underreported, well-known complication of acute tonsillitis. The prevalence of unilateral ITA compared to peritonsillar abscess (PTA) is 1:14. However, bilateral ITA is an extremely rare entity, with only four cases reported thus far.

Objectives: To describe past cases and our experience, elaborating the diagnostic challenge and the surgical treatment for bilateral ITA.

Methods: We conducted a literature search in the PubMed database using the key words intra-tonsillar abscess, tonsillar abscess, bilateral tonsillar abscess, bilateral intra-tonsillar abscess and bilateral peritonsillar abscess. Our search was limited to the years 1980 to 2020.

Results: We found that only four cases of bilateral ITA were previously published. All were characterized by a delay in diagnosis with a median of 10 days (4–14 days), symmetrical oral cavity appearance, enlarged bilateral kissing tonsils, and subsequent treatment by surgical drainage/paracentesis. Respiratory compromise was a concern in most cases. Our patient was treated with bilateral quinsy tonsillectomy and had a prompt recovery.

Conclusions: Bilateral ITA is a rare, deceiving entity, with a diagnosis delay attributed to the symmetrical oral bulging. We present the fifth case reported and the first ever reported in a pediatric patient. We describe the assumed pathogenesis and the main characteristics among all five patients, emphasizing the important role of a high index of suspicion and appropriate imaging, guiding to proper diagnosis and treatment.

Background: Chronic suppurative otitis media is a long-standing middle ear infection with a perforated tympanic membrane. Tympanoplasty is the mainstay of treatment. Most surgeons prefer to operate on dry ears; however, this may be difficult to achieve.

Objectives: To investigate the effect of otorrhea and positive cultures on the outcome of tympanoplasty.

Methods: This retrospective analysis reviewed patients with chronic suppurative otitis media who underwent tympanoplasty 2008–2015. Patients were divided into three groups: active discharge and bacterial growth, active discharge without bacterial growth, and no ear discharge. Surgical outcomes were compared among the groups.

Results: Among 101 patients included, 43 ears (42.6%) had discharge preoperatively, 58 (57.4%) were dry. Overall closure rate was 81.2% (82/101). Preoperative active discharge closure rate was 88.3% (38/43) and without discharge 75.9% (44/58). There were 38 positive cultures preoperatively and five negative cultures. Cultures were not obtained in 58 cases. Success rates were 89.5%, 80%, and 75.9%, respectively. No significant difference was found between patients who had positive or negative cultures before the procedure (P > 0.48) or among the three groups (P = 0.25). The most common bacteria were Pseudomonas aeruginosa (n=17), followed by Staphylococcus species (n=10). None was significantly associated with operative failure (P = 0.557). The postoperative air threshold difference was not affected by culture results (P = 0.3).

Conclusions: Tympanoplasty success rates and postoperative air threshold differences were not affected by the presence of preoperative otorrhea or positive ear cultures. Surgery can be performed even when the ear is not dry.

Background: The prognosis of long-term clinical outcomes for each patient is of utmost importance.

Objectives: To evaluate the association between rates of family attendance during rounds and long-term outcomes.

Methods: We conducted a historic cohort study.

Results: We followed 200 consecutive patients for a median of 19 months. Within the group of patients that had family members present in > 75% of rounds, the 30-day re-hospitalization rate was tenfold higher (P = 0.017). The overall prognosis (including median survival length) of patients who had the highest rates of family attendance (> 75%) was significantly worse compared to patients who had lower rates (P = 0.028). High rates of family attendance were found to correlate with other established risk factors for long-term mortality, including advanced age (r = 0.231, P = 0.001) and in-hospital delirium.

Conclusions: High family attendance during physician rounds in an internal medicine department is associated with worse patient prognosis.

Background: Serasis® (Serag-Wiessner KG, Naila, Germany) is a light-weight mid-urethral sling for treating stress urinary incontinence (SUI). Its insertion is considered less traumatic than other mid-urethral slings.

Objectives: To define postoperative outcomes following Serasis implantation. To compare the efficacy and complication rates of the implant to those of other common techniques.

Methods: Our retrospective study evaluated patients who underwent Serasis mid-urethral sling surgery for SUI. Data were collected from medical records prior to and at the time of surgery and by telephonic interview for postoperative pain and complications. Follow-up of patients was performed for up to one year postoperatively. Patients rated pain or discomfort according to the Visual Analogue Scale (VAS). The primary outcome was the development of early postoperative pain during the first month after surgery. Secondary outcomes were relief of SUI symptoms, groin pain or discomfort, and other postoperative complications up to 12 months after surgery.

Results: The study cohort included 50 consecutive patients aged 31 to 68 years. All patients underwent Serasis implantation procedures by a single surgeon and completed interviews. In total, 35 patients underwent concomitant anterior colporrhaphy. In the immediate postoperative period and at one month after the procedure, complaints were mild. No complaints were recorded during the 12-month follow-up period. Overall, 90% and 92% of the patients were free of SUI symptoms at one month and 12 months after surgery, respectively.

Conclusions: Serasis mid-urethral sling is safe, effective, and associated with mild postoperative pain and a low incidence of complications.

We clarified the diagnostic and therapeutic challenges associated with pseudohypertension in very elderly patients. Pseudohypertension is diagnosed when cuff blood pressure measurements for both systolic and diastolic blood pressure are significantly higher than direct intra-arterial blood pressure recordings. Pseudohypertension is considered a manifestation of combined intimal and medial arterial calcifications. Non-invasive diagnosis is extremely difficult, but pseudohypertension should be considered in certain groups of very elderly hypertensive patients. Importantly, most of the very elderly patients diagnosed with pseudohypertension present with hypertension, especially isolated systolic hypertension, and this condition should be treated. Treatment must be undertaken cautiously (start low, go slow), with a recommended target blood pressure ≤ 150/80 mmHg. Orthostatism should be measured routinely, both by the patient and the attending physician.

Serum sickness is an immune-complex-mediated hypersensitivity reaction that classically presents with fever, rash, polyarthritis, or poly arthralgias. Damage is caused by formation or deposition of antigen-antibody complexes in vessels or tissues. Deposition of immune complexes causes complement activation and/or recruitment of neutrophils by interaction of immune complexes with Fc immunoglobulin G receptors. The condition was first recognized as an entity in the early 1900s in patients who had received heterologous antisera, which was historically used to treat infectious diseases. The symptoms typically occur one to two weeks after exposure to an offending agent and resolve within several weeks of discontinuation [1].

Docetaxel (Taxotere®), obtained from the European yew Taxus baccata, is a widely used chemotherapeutic agent active against a variety of solid tumors including breast, lung, ovarian, gastric, head and neck, and prostate cancers. The drug is administered intravenously on a weekly or three-weekly schedule. Its main side effects include myelosuppression, fatigue, myalgias, arthralgias, fluid retention, peripheral neuropathy, paronychia, and lacrimation [1]. Myositis, however, has rarely been reported.

We describe a breast cancer patient who developed severe acute myositis while on treatment with docetaxel.

A 64-year-old male, with antineutrophil cytoplasmic antibody-associated vasculitis was being treated with methotrexate and low dose prednisone. He arrived at the clinic with bluish discoloration of the toes. Inflammatory markers and urine were normal. No history of chilblains or Raynoud's phenomena was noted. He recovered recently from mild coronavirus disease 2019 (COVID-19). A diagnosis of COVID toes (COVID digits) was made [Figure 1].

Background: The chloride intracellular channel (CLIC) protein family consists of six members in humans. CLICs are unique due to their metamorphic property, displaying both soluble and integral membrane forms. The transmembrane conformation was shown to give rise to ion-channel activity in vitro. In recent years, CLICs were implicated in a growing number of physiological processes in various organ systems and associated with distinct disease states. Indeed, the founding member of the family, CLIC5, was shown to be involved in hereditary deafness and various types of cancer. Nevertheless, the natural interactants and endogenous ligands of CLIC5 have not been discovered yet.

Objectives: To find ligands that affect the biochemical properties and activity of CLIC5. We hypothesized that such ligands could serve as important tools for resolving the long-sought cellular roles of CLICs and may offer novel therapeutic avenues for CLIC-associated conditions.

Methods: Using molecular biology and biochemical methods, CLIC5 was overexpressed in Escherichia coli and purified. Next, a high-throughput differential scanning fluorimetry thermal shift assay (TSA) was established and the interaction of approximately 500 natural compounds was examined.

Results: The TSA-based screening approach developed here allows to evaluate the effect of approximately 100 compounds in parallel within approximately 1 hour. Our proof-of-concept screening yielded 11 potential hits, significantly affecting the thermal stability of CLIC5. By examining the dose-dependence of this effect, we identified a specific interaction of CLIC5 with curcumin.

Conclusions: Using the approach we developed, large libraries of small molecules can be screened efficiently to identify novel CLIC5 interactants. Considering the participation of CLIC5 in various physiological and pathological processes, uncovering ligands that inhibit or activate CLIC5 may provide tools to modulate its activity and possibly to ameliorate CLIC5-related pathologies in the future.

Background: The exposure to ambient particulate matter (PM) is associated with increased morbidity and mortality from respiratory, cardiovascular, and other causes. A major contribution to this adverse effect is attributed to particles at the nanoscale range (ultrafine particles [UFP] particles < 100 nm). Most of the information about human exposure to PM has been collected by environmental monitoring of inhaled particles.

Objectives: To evaluate the use of direct measuring of UFP in the sputum as a biomarker for lung inflammation and functional impairment.

Methods: The study population included 121 patients who underwent an induced sputum (IS) test as a part of a clinical evaluation for respiratory symptoms. Cell differential count was performed, and the UFP content was measured in each IS sample. The UFP content in the sputum was compared among patients with different inflammatory phenotypes based on IS granulocytes levels: eosinophilic inflammation (EI) IS eosinophils > 2.7%, neutrophilic inflammation (NI) IS neutrophils > 65%, and mixed granulocytic inflammation (MGI) including both IS eosinophils > 2.7% and IS neutrophils > 65%. The association between the IS-UFP content and pulmonary function test (PFT) parameters was also tested.

Results: Patients with MGI had a distinct profile of particles in IS, which was characterized by the highest percentage of UFP (relative to larger particles) compared to patients with EI, NI, or normal IS cell count. Furthermore, EI and NI were found to have an interaction effect regarding the IS–UFP profile, as demonstrated by the significantly different IS–UFP profile of patients with MGI compared to the profile associated with EI and NI independently. Last, the profile of UFP in the IS samples was also correlated with patient PFT. Reduced forced mid-expiratory flow (FEF) 25–75 or FEV1 were correlated with a higher IS–UFP mean size. Reduced FEF25–75 was correlated with a lower IS–UFP concentration and percentage relative to larger particles.

Conclusions: To the best of my knowledge, this study is the first to report a distinct IS–UFP profile in patients with MGI, which suggest an interaction effect of EI and NI on the IS–UFP content. This finding may further support the consideration of MGI as a distinct inflammatory phenotype, beyond the simple combination of EI and NI independently. In addition, reduced PFT parameters were associated with a specific change in the IS–UFP profile. The results of this study may shed light on the use of IS–UFP content as a biomarker for lungs inflammation and functional impairment. Further prospective studies are needed to establish a cause and effect relationship between lungs inflammation and functional impairment to the IS–UFP content.

Endovascularly retrieved clots may be a potential resource for diagnosing stroke etiology. This method may influence secondary prevention treatment. We measure thrombin activity eluted by serially washing clots. We concluded that an assay measuring the change in thrombin in clots retrieved during acute stroke endovascular thrombectomy procedures may serve as a diagnostic marker of the origin of the clot. The suggested mechanism for these differences may be the clot location before its retrieval, with high blood flow causing thrombin washout in atherosclerotic clots, in contrast to atrium appendage low blood flow retaining high thrombin levels.

Background: APOE genotype strongly affects plasma lipid levels and risk for cardiovascular disease and cognitive decline. Studies of apo-e allelic and APOE genotype frequencies among several populations have revealed interesting ethnic variations that might affect cardiovascular morbidity and cognition deterioration.

Objectives: To evaluate apo-e allelic frequency among Israeli newborns based on known variances in apo-e allelic frequencies in different countries.

Methods: We examined 498 consecutive neonates born at Tel Aviv Sourasky Medical Center. Umbilical cord blood was sampled for genotyping and lipids. Birth weights were recorded. Demographics and parental risk factors for atherosclerosis were obtained from the mothers.

Results: Most parents were native-born Israelis. Other countries of origin of grandparents were Morocco, Russia, and Iraq. The prevalence of APOE genotypes in Israel is APOE 2/2: 1.4%, APOE 2/3: 8.2%, APOE 3/3: 77.7%, and APOE 4/4: 11.8%. There were no associations of APOE genotype with parental country of origin. However, there was a tendency for APOE 3/4 to be more frequent in newborns of parents of Asian and African origin. Genotype 3/3 was more frequent in newborns whose parents came from Europe and America (78%) compared to those from Asia or Africa (69%).

Conclusions: It is important to determine risk factors such as APOE genotype for evaluation of premature atherosclerosis. Determining genetic and environmental risk factors may facilitate earlier treatment and prevent heart and brain atherosclerosis. APOE genotypes did not appear to affect total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride levels in newborns.

Background: Severe asthma affects up to 20,000 citizens of Israel. Novel biological therapies, which individually have been proven to reduce asthma morbidity in clinical trials, have become available in recent years. Comparative data among different drugs are scarce.

Objectives: To describe and compare the clinical outcomes of biological therapies in severe asthma patients treated at Shamir Medical Center.

Methods: We conducted a cohort study based on a review of cases treated with monoclonal antibodies for severe asthma at our center. Data were extracted for demographics, eosinophil count, lung function (FEV1), exacerbation rate, and median dose of oral prednisone. Between-drug comparison was conducted by repeated measures ANOVA.

Results: The cohort included 62 patients receiving biological therapy. All biologic drugs were found to reduce exacerbation rate [F(1, 2) = 40.4, P < 0.0001] and prednisone use [F(1, 4) = 16, P < 0.001] significantly. ANOVA revealed no difference of efficacy endpoints between the different drugs. Eosinophil count was significantly reduced post-biologic treatment in the anti-interleukin-5 agents (P < 0.001) but not under treatment with omalizumab and dupilumab.

Conclusions: All of the biological therapies were effective for improving clinical outcomes. None of the agents was clearly superior to any other. These data emphasize the need for severe asthma patients to be seen by pulmonary medicine specialists and offered, where appropriate, biological therapies.

Background: The adherence to a narrowband ultraviolet B (NB-UVB) treatment plan is derived, in large part, from the patient’s skin tolerance to the phototherapy dose. At present, the initial and first-month incremental phototherapy doses are determined prior to treatment initiation based on the patient's Fitzpatrick skin phototyping.

Objectives: To identify variables that predict adherence to NB-UVB first-month treatment dosage plan.

Methods: Charts of 1000 consecutive patients receiving NB-UVB at a hospital-based phototherapy unit were retrospectively analyzed. We included patients receiving NB-UVB for atopic dermatitis, psoriasis, vitiligo, and mycosis fungoides. The first-month NB-UVB treatment plan was determined based on the patient's Fitzpatrick phototype. Adherence to treatment was defined as receiving at least 80% of the planned first-month cumulative dose. We compared adherent vs. non-adherent patient groups for age, sex, Fitzpatrick phototype, presence of freckles, nevus count category, and type of dermatological disease.

Results: The study included 817 eligible patients, mean age 40 (2–95) years; 54% men; 32% had Fitzpatrick phototype I-II. Distribution by diagnosis was atopic dermatitis (29%), psoriasis (27%), vitiligo (23%), and mycosis fungoides (21%). Adherence to NB-UVB treatment plan was observed in 71% of patients. Adherence decreased with age, with 7% decrease per year (P = 0.03) and was higher among mycosis fungoides patients (77.3%) compared to all other diagnoses (69.8%; P = 0.02).

Conclusions: Adherence to NB-UVB treatment may be related to age and diagnosis. Fitzpatrick phototype-based first-month treatment plans should be modified accordingly.

Background: Acute mesenteric ischemia (AMI) is a medical condition with high levels of morbidity and mortality. However, most patients suspected of AMI will eventually have a different diagnosis. Nevertheless, these patients have a high risk for co-morbidities.

Objectives: To analyze patients with suspected AMI with an alternative final diagnosis, and to evaluate a machine learning algorithm for prognosis prediction in this population.

Methods: In a retrospective search, we retrieved patient charts of those who underwent computed tomography angiography (CTA) for suspected AMI between January 2012 and December 2015. Non-AMI patients were defined as patients with negative CTA and a final clinical diagnosis other than AMI. Correlation of past medical history, laboratory values, and mortality rates were evaluated. We evaluated gradient boosting (XGBoost) model for mortality prediction.

Results: The non-AMI group comprised 325 patients. The two most common groups of diseases included gastrointestinal (33%) and biliary-pancreatic diseases (27%). Mortality rate was 24.6% for the entire cohort. Medical history of chronic kidney disease (CKD) had higher risk for mortality (odds ratio 2.2). Laboratory studies revealed that lactate dehydrogenase (LDH) had the highest diagnostic ability for predicting mortality in the entire cohort (AUC 0.70). The gradient boosting model showed an area under the curve of 0.82 for predicting mortality.

Conclusions: Patients with suspected AMI with an alternative final diagnosis showed a 25% mortality rate. A past medical history of CKD and elevated LDH were associated with increased mortality. Non-linear machine learning algorithms can augment single variable inputs for predicting mortality.