Israel Medical Association Journal

Background: The human papillomavirus (HPV) test has proven to be efficient in triaging women with abnormal Pap findings in women with low cytological atypia, but there is no data about the accuracy for large loop excision of transformation zone in cases of recurrent atypia.

Objectives: To assess the clinical correlation between results of HPV typing and conization histology in women who had recurrent abnormal Pap test results with no colposcopy findings.

Methods: Our retrospective cohort study included 138 women enrolled in the Maccabi Healthcare Services who had consecutive atypical Pap test results for 2 years in which no abnormal colposcopic findings were detected. These women had an HPV typing and then conization.

Results: Among the total study population (n=138), 71.7% had negative histology, 19.6% had ≤ cervical intraepithelial neoplasia grade 1 (≤ CIN1), and 8.7% had CIN2+. With regard to HPV typing, 34.8% were negative and 65.2% were positive. Of those testing positive, 34.4% were positive for HPV 16 or 18. Sensitivity, specificity, positive predictive value, and negative predictive values of HPV typing for women were 89.7%, 44.4%, 38.9%, and 91.7%, respectively, and for HPV 16 or 18: 71.4%, 67.7%, 32.3%, and 100.0%, respectively. After stratification by cytological grades, for women with high-grade cervical cytology, the sensitivity and negative predictive values of the HPV typing were higher than among low-grade cervical cytology, while specificity and positive predictive values were lower.

Conclusions: HPV typing is a useful tool for the management of patients with persistently abnormal Pap test results.

Background: Children and adolescents are commonly referred to an orthopedic surgeon to assess knee malalignment.

Objectives: To assess the prevalence of genu varum and valgum among adolescents, and to identify correlates of these conditions.

Methods: A medical database of 47,588 candidates for military service presenting to the northern recruitment center during an 11 year period was analyzed to identify clinical knee alignment. Based on the standing skin surface intercondylar distance (ICD) or intermalleolar distance (IMD), the prevalence rates of genu varum (ICD ≥ 3 cm) and genu valgum (IMD ≥ 4 cm) were calculated. The association of gender, body mass index (BMI), and place of residence to knee alignment was studied.

Results: The rates of genu varum and valgum were 11.4% (5427) and 5.6% (2639), respectively. Genu varum was significantly more prevalent among males than females (16.2% vs. 4.4%, P < 0.001). It was also more prevalent among underweight subjects and less prevalent among overweight and obese subjects (P < 0.001). Genu valgum was significantly more prevalent among females than males (9.4% vs. 2.9%) and in overweight and obese subjects compared to those with normal BMI, while less prevalent in underweight subjects (P < 0.001). Multivariate analysis revealed that genu varum was independently positively associated with male gender, underweight, and living in a rural area. Genu valgum was independently positively associated with female gender, overweight, and obesity.

Conclusions: This study establishes a modern benchmark for the cutoff and prevalence of genu varum and valgum as well as associations with gender and BMI.

Background: Biological agents for anti-tumor necrosis factor-α therapy have revolutionized treatments for autoimmune diseases; however, approximately 20% of rheumatology and 40% of gastroenterology patients do not respond to the therapy, or they show reduced drug efficacy because of anti-drug antibody (ADA) formation.

Objectives: To evaluate laboratory tools for individual monitoring of infliximab therapy and the relationship between ADA and infliximab serum levels, ADA and clinical response, and ADA and autoantibodies.

Methods: Our study comprised patients treated with infliximab and affected by selected rheumatology and gastroenterology diseases. Sera were analyzed for infliximab, total-anti-drug antibodies (Total-ADA), and free-anti-drug antibodies (Free-ADA) serum levels and for the detection of specific autoantibodies.

Results: We analyzed 73 patients. Total-ADA were detected in 26 rheumatology and 21 gastroenterology patients. Serum infliximab levels were significantly lower in Total-ADA positive patients (P = 0.01 for rheumatology group, P = 0.02 for gastroenterology group). A lack of response was observed in 7 rheumatology and 15 gastroenterology samples. Total-ADA serum levels were statistically significantly higher in patients with treatment failure in both groups (P = 0.01 and P = 0.001, respectively). There was no significant association between the presence of Total-ADA and other autoantibodies. Free-ADA were detected in only 27 rheumatology patients. Results showed a significant correlation with clinical outcome (P = 0.006).

Conclusions: The correlation with clinical response suggests that the presence of ADA could interfere with efficacy of therapy. The tests for monitoring therapy may be an important tool to assist clinicians in early detection and prevention of therapy failure.

Background: The distribution of pathology and clinical characteristics of lacrimal gland diseases are different in different areas of the world.

Objectives: To evaluate the incidence rate, patient characteristics, and indications for surgical intervention of lacrimal gland lesions in a tertiary care center in Israel.

Methods: All biopsied or surgically removed lacrimal gland lesions at the Goldschleger Eye Institute from 2009 to 2015 were identified. The following data were collected: age, gender, indications for surgical intervention, diagnosis, treatment, and prognosis.

Results: We evaluated 28 lacrimal gland biopsies from 26 patients (11 men, 15 women). Mean age at biopsy was 47.5 years old. The most common presenting symptoms were: eyelid swollenness (57.14%), ptosis (32.14%), and proptosis (10.71%). All patients underwent computed tomography and magnetic resonance imaging. In 28 cases, infiltrations of the lacrimal gland were found. In nine cases infiltration of muscles or orbital extension were found. The most common pathologies were non-specified inflammation (44.82%), lymphoma (20.68%), and immunoglobulin G4-related disease (10.34%). The treatment was diverse according to the patient diagnosis. Prognosis of lacrimal gland disease was good; however, in five patients the systemic disease progressed.

Conclusions: Lesions of the lacrimal gland comprise a wide variety of pathological findings that require different treatment strategies. Lacrimal gland biopsies enable physicians to precisely recognize the pathology; therefore, it is important to consider this surgical method in any patient with lesions in the lacrimal gland.

Electrocardiography abnormalities are a common finding in athletes. To facilitate the differentiation of physiological adaptation versus pathological remodeling, a series of guidelines has emerged in the past decade that attempt to improve specificity while maintaining a high sensitivity. Recently, T wave inversion in the athletic population gained more attention, resulting in accelerated research leading to novel findings not yet integrated into clinical practice. We aim to simplify the knowledge to date and integrate it into one easy to use practical flowchart.

Background: Ureaplasma species (Usp) are the most prevalent genital Mycoplasma isolated from the urogenital tract of both men and women. Usp may be commensals in the genital tract but may also be contributors to a number of pathological conditions of the genital tract. Because they can also just colonize the genital tract of healthy people, their pathogenic role can be difficult to prove.

Objectives: The aim of the study was to evaluate the efficacy of a quantitative polymerase chain reaction (qPCR) method for the discrimination between infection and colonization by measuring prevalence of Usp in asymptomatic versus symptomatic patients.

Methods: Urine samples were tested for U. parvum and U. urealyticum using a semi-quantitative multiplex PCR technique for sexually transmitted diseases (Anyplex™ STI-7 Detection Kit, Seegene, South Korea). A total of 250 symptomatic and 250 asymptomatic controls were included.

Results: A strong positive result for U. parvum was significantly more prevalent in symptomatic compared to asymptomatic patients. This finding was observed especially in women and in the young group (15–35 years of age). No significant differences were observed between the prevalence in symptomatic and asymptomatic patients of U. parvum with low strength of positivity and for U. urealyticum in all groups by age, gender, and strength of positivity.

Conclusions: The significant difference between the symptomatic and asymptomatic group in the highest positivity group for U. parvum using the Anyplex™ STI-7 detection kit in urine may indicate a high probability of infection rather than colonization, especially in women and young patients.

A 47 year old man presented with a combination of dry mouth and lightheadedness while standing. His medical background was unremarkable except for cigarette smoking and hyperlipidemia. Sjögren’s syndrome was ruled out, and he was referred for evaluation of orthostatic hypotension, which by then included syncopal episodes and injuries. Additional symptoms included dry eyes, constipation, reduced sweating, and erectile dysfunction. After excluding medications and structural cardiac abnormalities as causes of orthostatic hypotension, a clinical autonomic evaluation was performed. The pattern of beat-to-beat blood pressure associated with performance of the Valsalva maneuver, and a low plasma norepinephrine level that did not increase in response to standing, established that the orthostatic hypotension was neurogenic. Treatment with an alpha-adrenoceptor agonist and fludrocortisone yielded partial improvement. After systemic diseases involving autonomic failure were excluded, cardiac sympathetic neuroimaging was performed by ¹²³I-metaliodobenzylguanidine (MIBG) scanning. The normal uptake seen in the heart indicated intact post ganglionic sympathetic innervation. There were no signs of central neurodegeneration or peripheral neuropathy. Because of symptoms and signs of both parasympathetic and sympathetic failure without denervation, an autonomic ganglionopathy was considered. A high titer of antibody to the neuronal nicotinic receptor, which mediates ganglionic neurotransmission, was obtained. The diagnosis of autoimmune autonomic ganglionopathy (AAG) was made, and the management strategy shifted to first lowering the antibody burden by plasma exchanges and then instituting chronic anti-autoimmune treatment with rituximab and a low dose of cortiosteroid. The patient showed remarkable improvement.

Background: Pulmonary arterial hypertension (PAH) is a significant consequence of congenital heart disease (CHD). Its presence and severity is associated with increased morbidity and mortality. 

Objectives: To evaluate the clinical and demographic characteristics of adults with congenital heart diseases (ADCHD) and PAH at a single center. 

Methods: A prospective registry of all patients with PAH was conducted between 2009 and 2015. 

Results: Thirty-two patients were identified. The mean age at the last visit was 44 years (range 19–77 years). The prevalence of PAH among all ADCHD patients was 6% (95% confidence interval 4.3%–8.4%). A much higher prevalence (53%) was found in patients with Down syndrome. Most patients with PAH had moderate or severe disease. Fifteen patients (47%) were treated with pulmonary vasodilators and 6 (19%) with combination therapy. The average World Health Organization functional class was 2.6. Morbidity included cerebral vascular accident or transient ischemic attack in 22% (mostly in patients with right-to-left shunt) and arrhythmia in 37% of the patients. During a median follow-up of 3.5 years, 5 patients (15.6%) died. Of 13 women with no mental retardation, 11 were or had been married and all had children (between 1 and 13, mean 3.3). 

Conclusions: Patients with congenital heart disease and PAH have significant morbidity and mortality. PAH is more prevalent in patients with Down syndrome. While pulmonary pressure during the reproductive years was not always known, 27% of women with PAH at the time of the study were multiparous.

 

Background: Pulmonary infiltrates (PIs) detected in patients with non-Hodgkin lymphoma (NHL) may present a diagnostic challenge due to their wide differential diagnosis, including infection, pulmonary lymphoma and immunochemotherapy-associated pulmonary toxicity.

Objectives: To characterize therapy-associated PIs by positron emission tomography/computed tomography (PET/CT) imaging.

Methods: We conducted a historical analysis of fluorodeoxyglucose-PET/CT (¹⁸F-FDG-PET/CT) PIs in NHL patients treated with combined immunochemotherapy including rituximab. Incidence of PIs, radiological features, patients’ characteristics, underlying NHL type, rituximab/chemotherapy dosing schedules, and symptoms were recorded. Therapy-associated PIs were defined as new or worsening PIs appearing after treatment onset, without evidence of active pulmonary lymphoma or infection.

Results: Among 80 patients who met the pre-specified criteria, therapy-associated PIs were identified in 17 (21%), 6 of whom had accompanying symptoms. Increased FDG uptake was observed in nine, and PI resolution in six. The incidence of PIs was higher in females and in patients with aggressive lymphoma, at advanced stages, and in those who had received treatment consisting of a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 14 days (R-CHOP-14).

Conclusions: This characterization of therapy-associated PIs may support the clinician managing NHL patients. Further prospective studies are needed to establish the role of each therapeutic component and the natural history of this phenomenon.

Background: The optimal approach to the evaluation of asymptomatic bacteruria in stroke patients is uncertain. 

Objectives: To compare elderly patients after an acute stroke with and without asymptomatic bacteriuria for the development of symptomatic urinary tract infections (UTI).

Methods: We prospectively monitored patients over 65 years of age admitted to our rehabilitation hospital after an acute stroke, with and without asymptomatic bacteriuria, for the development of symptomatic UTIs. The prevalence of bacteriuria was determined by urine cultures obtained 2 and 4 weeks after admission. Patients with and without persistent bacteriuria were compared to identify variables associated with bacteriuria.

Results: Fifty-five patients were included in the study. The prevalence of asymptomatic bacteriuria at baseline was 20%. Of all 55 stroke patients, 13 (23.6%) developed a symptomatic UTI during the 30 day follow-up. Patients with stroke and asymptomatic bacteriuria at baseline had an increased risk of developing a symptomatic UTI (54.5% with asymptomatic bacteriuria vs. 15.9% without, P = 0.011). To exclude the effects of several confounders, we performed multivariate Cox regression analysis, which showed that bacteruria remained a significant covariate for symptomatic UTI (hazard ratio 2.86, 95% confidence interval 0.71–10.46, P = 0.051). When subjects who experienced symptomatic urinary infection were included, the prevalence of bacteriuria in the study cohort declined to about 45.5% by 30 days. 

Conclusion: Elderly patients with stroke and asymptomatic bacteriuria have an increased risk of developing a symptomatic UTI compared to those without asymptomatic bacteriuria during a 30 day post-stroke follow-up.