Early rituximab treatment is associated with increased and sustained remission in pemphigus patients: A retrospective cohort of 99 patients.

Rituximab is the front-line therapy for pemphigus disease. Although very effective, relapse rates are high. We assessed factors associated with disease remission and early relapse following the first rituximab cycle. A single center, retrospective cohort study of patients with pemphigus treated with rituximab (1000 mg 0, 14 days) at the Autoimmune Bullous Disease Clinic of the Division of Dermatology in Rabin Medical Center, Israel, between January 1, 1995 and March 31, 2020. The cohort included 99 patients with a median follow-up of 37 months (range 12-155). After a single rituximab cycle, 74 patients (75%) achieved remission. Increased time to rituximab was associated with decreased remission rates (OR, 0.98 per month; 95% CI, 0.97-0.998). Of patients in remission with sufficient follow-up, 15/69 (22%) experienced an early relapse (≤12 months from remission). Prolonged time to rituximab and increased baseline disease severity, were associated with early relapse (OR, 1.02 per month; 95% CI, 1.001-1.04; OR, 1.04 per point; 95% CI, 1.01-1.08, accordingly). Initiating rituximab early following diagnosis is recommended. Maintenance rituximab infusions, especially for patients with severe baseline disease, should be further investigated.

The diagnostic accuracy of dermoscopy for basal cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: Dermoscopy is a noninvasive technique for the diagnosis of skin lesions. Its accuracy for basal cell carcinoma (BCC) has not been systematically studied. OBJECTIVE: We sought to systematically investigate the accuracy of dermoscopy for the diagnosis of BCC compared with examination with the naked eye. METHODS: A systematic review of studies reporting the accuracy of naked eye examination and dermoscopy for the diagnosis of BCC was conducted. A meta-analysis for sensitivity and specificity was performed using a bivariate mixed-effects logistic regression modeling framework. RESULTS: Seventeen studies were identified. The pooled sensitivity and specificity of dermoscopy for the diagnosis of BCC were 91.2% and 95%, respectively. In studies comparing test performance, adding dermoscopy to naked eye examination improved sensitivity from 66.9% to 85% (P = .0001) and specificity from 97.2% to 98.2% (P = .006). The sensitivity and specificity of dermoscopy were higher for pigmented than nonpigmented BCC. Sensitivity increased when dermoscopy was performed by experts and when the diagnosis was based on in-person dermoscopy as opposed to dermoscopic photographs. LIMITATIONS: Significant heterogeneity among studies with a medium-to-high risk of bias. CONCLUSION: Dermoscopy is a sensitive and specific add-on tool for the diagnosis of BCC. It is especially valuable for pigmented BCC.

Early isolated optic neuropathy caused by cyclosporine.

PURPOSE: To examine, for the first time, whether cyclosporine intake has an early isolated effect on the optic nerve. MATERIALS AND METHODS: This observational case series consisted of 192 eyes of 98 patients treated with cyclosporine. Patient age and duration and dosage of cyclosporine were recorded, and visual acuity, optic nerve function, visual fields, and visual evoked potential (VEP) were tested. Fundus examination was also performed. Patients with glaucoma, vascular retinopathies, and deep amblyopia were excluded. RESULTS: Mean patient age was 46 years, average duration of treatment was 6 years, and median dosage of cyclosporine was 200 mg daily. VEP was tested in 73 patients (142 eyes) and yielded a delayed P100 wave in 9 (12.32%) (14 eyes). Among these 9 patients, abnormal findings were also noted on the Ishihara colour test in 42.86% of the eyes, and on the visual field test in 64.3% of the eyes. Abnormal VEP showed a significant correlation (p < 0.05) with older age (> 46 years) and a non-significant correlation with longer duration of treatment. Higher abnormal VEP potential was not correlated with higher cyclosporine dose, and there was no correlation between abnormal VEP and blood level of cyclosporine. CONCLUSION: Optic neuropathy was significantly associated with older age in cyclosporine-treated patients. A correlation between optic neuropathy with longer duration of cyclosporine treatment was noted but was not statistically significant. We suggest that tests of optic nerve function, including VEP, be a part of the follow-up of patients receiving cyclosporine.

Association of bullous pemphigoid with malignancy: A systematic review and meta-analysis.

BACKGROUND: Studies evaluating whether malignancy rate is increased in patients with bullous pemphigoid (BP) have reached conflicting results. OBJECTIVE: We sought to determine whether BP is associated with malignancy. METHOD: Medline, EMBASE, the Cochrane library, and reference lists of included studies were searched for comparative studies that evaluated the relationship between BP and malignancy. Data were analyzed on the basis of study design: cross-sectional, case control, and cohort. A meta-analysis was performed by using a random effects model to estimate pooled odds ratio. RESULTS: The review included 8 studies. No association between BP and overall cancer was found for any of the study designs. Although a single cohort study reported an association with lymphoid leukemia and kidney and larynx cancer, a pooled analysis of case-control studies did not. A pooled analysis of cross-sectional studies found a significant association between BP and hematologic malignancies. LIMITATIONS: The paucity of well-designed studies hindered the possibility of proving or disproving the BP-cancer association. CONCLUSION: We did not find an association of BP with overall malignancy, but a possible association with hematologic malignancy was observed.

Are Ultrasonographic Findings Suggestive of Ovarian Stromal Edema Associated with Ischemic Adnexal Torsion?

OBJECTIVE: To study whether sonographic findings suggestive of ovarian stromal edema are associated with tissue ischemia in patients with adnexal torsion. METHODS: A study of 79 patients with adnexal torsion was performed. Patients were divided into an ischemic group, in which the twisted adnexa were seen as blue or black, and a non-ischemic group, in which the adnexa retained normal color and appeared viable. Clinical and ultrasonographic findings, specifically the presence of ultrasonographic signs suggestive of ovarian stromal edema, were compared between the two groups. RESULTS: Of the 79 patients with torsion, in 44 (55.7%) the adnexa appeared ischemic at surgery. The presence of ischemia was not associated with age, pregnancy, duration of pain, vomiting or findings at physical examination. There was no significant difference between the ischemic and the non-ischemic group in the proportion of patients with signs of ovarian stromal edema (59 vs. 40%, p = 0.11), in the proportion of patients with absent/diminished stromal Doppler flow (36 vs. 28%, p = 0.12%) or in the proportion of patients with both signs of stroma edema and absent/diminished stromal Doppler flow (20 vs. 12%, p = 0.36). CONCLUSION: Ultrasonographic signs of ovarian stromal edema do not assist in differentiating between ischemic and non-ischemic adnexal torsion.

The role of adjuvant therapy in pemphigus: A systematic review and meta-analysis.

BACKGROUND: The assumption that adjuvant modalities have added value to oral glucocorticoids in the treatment of pemphigus is intuitively sound but has not been conclusively proven. OBJECTIVE: We sought to compare the efficacy and safety of oral glucocorticoid treatment with or without adjuvants for pemphigus vulgaris and pemphigus foliaceus. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials. The primary outcome was remission. Secondary outcomes were disease control, time to disease control, relapse, time to relapse, cumulative glucocorticoid dose, withdrawal because of adverse events, and all-cause death. Trials were pooled irrespective of adjuvant type evaluated. RESULTS: Ten trials (559 participants) were included. Adjuvants evaluated were azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine, intravenous immunoglobulin, plasma exchange, and infliximab; not all were included in every analysis. Although adjuvants were not beneficial for achieving remission, they were found to collectively decrease the risk of relapse by 29% (relative risk 0.71, 95% confidence interval 0.53-0.95). LIMITATIONS: Different adjuvants were pooled together. CONCLUSION: Adjuvants have a role in pemphigus treatment, at least in reducing the risk of relapse. Further randomized controlled trials of other promising modalities are warranted.

Laboratory challenges in response to silent introduction and sustained transmission of wild poliovirus type 1 in Israel during 2013.

Wild poliovirus type 1 (WPV1) introduction into southern Israel in early 2013 was detected by routine environmental surveillance. The virus was identified genetically as related to the South Asian (SOAS) R3A lineage endemic to Pakistan in 2012. Intensified, high-throughput environmental surveillance using advanced molecular methods played a critical role in documenting and locating sustained transmission throughout 2013 and early 2014 in the absence of any acute flaccid paralysis. It guided the public health responses, including stool-based surveillance and serosurveys, to determine the point prevalence in silent excretors and measured the effect of vaccination campaigns with inactivated polio vaccine and bivalent oral polio vaccine on stopping transmission.

Opportunistic infections in patients with pemphigus.

BACKGROUND: Opportunistic infections (OIs) can be defined as infections in immunosuppressed patients that are more frequent or severe because of immunosuppression. The literature on OIs in pemphigus is sparse. OBJECTIVE: We assessed the incidence, risk factors, and characteristics of OIs in patients with pemphigus. METHODS: This was a historical prospective study following a cohort of 172 patients with newly diagnosed pemphigus for the development of OIs. RESULTS: Fourteen patients developed OIs at a mean of 4 months from the time of diagnosis while taking a mean dose of 0.8 mg/kg/day of prednisone, 5 in conjunction with azathioprine. The risk of developing an OI in the first year after the diagnosis of pemphigus was 9.3%, subsequently dropping to 0. Advanced age and possibly diabetes were found to be risk factors for OI development. Infectious agents included Nocardia, cytomegalovirus, Legionella, and Listeria. Two patients died within 2 months of OI diagnosis, and 2 more had neurologic impairment. LIMITATIONS: Limitations include the extraction of historical data and the cohort originating from a single geographic region. CONCLUSION: OIs present in a significant number of patients with pemphigus during the first year after the diagnosis of pemphigus, with potential deleterious effects. Older and possibly diabetic patients are at increased risk. Physician vigilance and patient education on limiting pathogen exposure is recommended.

Integration of PET/CT into the preoperative evaluation of patients with early cervical cancer does not decrease the proportion of patients with positive lymph nodes found after surgery.

PURPOSE: The aim of this study was to evaluate whether preoperative positron emission tomography/computed tomography (PET/CT) in patients with early-stage cervical carcinoma reduced the proportion of patients with metastatic lymph nodes identified after surgery. PATIENTS AND METHODS: This is a multicenter case-control study of 599 patients with early cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy at 1 of 10 gynecological oncology units in Israel. The patients were divided into 2 groups according to whether or not they underwent a preoperative PET/CT. The primary outcome was the proportion of patients with nodal involvement. The 2 groups were compared with regard to the clinical and histological variables. RESULTS: Of the 599 patients who underwent surgery, 180 (36%) had preoperative PET/CT study. There were no significant differences between the PET/CT and control groups with regard to clinical and histological risk factors. The proportion of patients with involved nodes was similar in the control and PET/CT groups (20.8% vs 19%; P = 0.73) as well as the proportion of patients receiving adjuvant radiotherapy/chemoradiation (58.3% vs 55.1%; P = 0.55). CONCLUSIONS: Preoperative PET/CT in patients with early cervical cancer does not reduce proportion of patients with metastatic nodal involvement and the employment of multimodality treatment. Prospective clinical trials comparing management based on PET/CT findings are warranted.

Misoprostol treatment for early pregnancy failure does not impair future fertility.

AIMS: To examine whether misoprostol treatment for first trimester missed abortion affects future fertility. PATIENTS AND METHODS: In a historical prospective approach, we analyzed our database for patients treated with misoprostol. All eligible patients underwent an interview according to a questionnaire, which includes their demographic characteristics, obstetric, gynecologic and infertility history. They were asked about the side effects, intention and subsequent ability to conceive. Their future pregnancy rates were calculated and compared to the acceptable figures in the literature. RESULTS: The infertility rates among our patients were similar to those reported in the general population. Pregnancy rates 2 years after treatment were similar to the previously published reports, except for lower rates during the first three months post-treatment. Although no between-group differences were observed in the subsequent pregnancy rates, 2 years following misoprostol treatment in ≤35 versus >35 years old patients, primi- versus multigravida and nulli- versus parous women, higher pregnancy rates were observed in patients ≤35 versus >35 years old, primi- versus multigravida and nulli- versus, parous, during the first 3 months following misoprostol treatment. CONCLUSION: Misoprostol treatment, for women with first trimester missed abortion and favorable reproductive history, is an acceptable treatment with no detrimental effect on future fertility.

The influence of early diagnosis of endometrioid endometrial cancer on disease stage and survival.

OBJECTIVE: To evaluate whether the presence or duration of uterine bleeding is associated with disease stage, and survival of patients with endometrioid endometrial carcinoma (EEC). METHODS: The records of 220 patients with EEC who underwent surgery were reviewed. The patients were divided into three groups according to the presence and duration of vaginal bleeding at the time of surgery. Group 1, without vaginal bleeding; group 2, vaginal bleeding up to 3 months; group 3, vaginal bleeding exceeding 3 months prior to surgery. Disease stage and survival were between the three groups. RESULTS: Of the 220 patients, 42 (19%) were asymptomatic; 95 (43%) had symptom duration of up to 3 months and 83 (38%) experienced bleeding for >3 months. There were no significant differences between groups 1, 2 and 3 regarding the proportion of patients with deep invasion in stage I (21, 24, 26%, p = 0.84; respectively), with grade 3 tumors (10, 13, 14%, p = 0.42; respectively) or with advanced stage disease (12, 14, 15%, p = 0.92; respectively). Survival analysis demonstrated a non-significant trend toward better survival in asymptomatic patients and in patients with a shorter duration of symptoms (p = 0.172). CONCLUSIONS: Diagnosis of EEC in asymptomatic patients or in patients with a short duration of bleeding is associated with comparable stage and survival.

Effect of closure versus nonclosure of peritoneum at cesarean section on adhesions: a prospective randomized study.

OBJECTIVE: We sought to determine the effect of nonclosure of the visceral and parietal peritoneum during cesarean section on the formation of adhesions. STUDY DESIGN: This was a prospective randomized trial of 533 women undergoing primary cesarean section; in 256 the peritoneum was left open and in 277 it was closed. Fifty women in the nonclosure group and 47 women in the closure group were subsequently evaluated intraoperatively at a repeat cesarean. The presence of adhesions and their severity were evaluated at several sites. RESULTS: The nonclosure and closure groups were comparable with regard to the proportion of patients with adhesions at any site (60% vs 51%, respectively; P = .31). Time from incision to delivery was comparable in the nonclosure and closure groups (8.98 ± 4.7 vs 9.32 ± 5.2 minutes, respectively; P = .84). CONCLUSION: Closure or nonclosure of the peritoneum at cesarean section did not lead to large differences in the adhesion rate.

Genomic Epidemiology of Clinical Brucella melitensis Isolates from Southern Israel.

Brucellosis, a zoonosis mainly transmitted by consumption of unpasteurized dairy products, is endemic in Southern Israel, mainly among the Bedouin Arab population. However, the genomic epidemiology of B. melitensis in this region has not yet been elucidated. A cohort of brucellosis cases (n = 118) diagnosed between 2017-2019 was studied using whole-genome sequencing (WGS). Phylogenetic analyses utilized core genome MLST (cgMLST) for all local isolates and core genome SNPs for 347 human-associated B. melitensis genomes, including Israeli and publicly available sequences. Israeli isolates formed two main clusters, presenting a notable diversity, with no clear dominance of a specific strain. On a global scale, the Israeli genomes clustered according to their geographical location, in proximity to genomes originating from the Middle East, and formed the largest cluster in the tree, suggesting relatively high conservation. Our study unveils the genomic epidemiology of B. melitensis in Southern Israel, implicating that rather than a common source, the transmission pattern of brucellosis among Bedouin communities is complex, predominantly local, and household-based. Further, genomic surveillance of B. melitensis is expected to inform future public health and veterinary interventions and clinical care.

Short-term effects of closure versus non-closure of the visceral and parietal peritoneum at cesarean section: a prospective randomized study.

AIM: To determine the effect of non-closure of the visceral and parietal peritoneum during cesarean section on short-term postoperative morbidity. METHODS: A prospective randomized trial was conducted of 533 women undergoing primary cesarean section; 277 were randomized to closure and 256 to non-closure of the peritoneum. Perioperative outcome measures, such as analgesia dosage and morbidly measures were compared. RESULTS: There was no significant difference between the non-closure and closure groups in the mean number of narcotic analgesia doses (1.09 +/- 1.2 vs 1.05 +/- 1.0, P = 0.63; respectively), mean number of non-narcotic analgesia doses (4.69 +/- 2.7 vs 4.65 +/- 2.8, P = 0.89; respectively), number of women with postoperative fever >38 degrees C (18 vs 14, P = 0.37; respectively), number of women with wound infection (29 vs 35, P = 0.54; respectively) and mean number of hospitalization days (4.16 +/- 0.91 vs 4.14 +/- 0.71, P = 0.78; respectively). CONCLUSION: Closure or non-closure of the peritoneum at cesarean sections has no significant impact on postoperative analgesic usage and short-term morbidity.

Quantifying the effects of postcesarean adhesions on incision to delivery time.

OBJECTIVE: To quantify the effects of postcesarean section adhesions severity on the incision to delivery time. METHODS: Secondary analysis of data of a prospective randomized controlled trial of women undergoing first repeat cesarean section. The presence and severity of adhesions were reported by surgeons postoperatively and accrued into an adhesion severity score. The primary outcome measure was the correlation between adhesion severity score and incision to delivery time. RESULTS: Of the 97 women analyzed, 47 (48.5%) had an urgent cesarean delivery. Forty-four patients (45.4%) had adhesions. Adhesion score correlated with incision to delivery time (R = .38, p < .01). Patients with adhesions had a significantly longer incision to delivery time (10.3 + 5.9 versus 8.2 = 3.7 minutes, respectively; p = .04). In the Kaplan-Meier analysis, more patients with adhesions remained undelivered at any time point after incision (p = .036). The mean delivery time of patients with adhesion score three was significantly longer in comparison with women with no adhesions (13.0 versus 8.2 minutes, respectively; p = .002). CONCLUSIONS: Post cesarean adhesions delay delivery of the newborn. There is a linear correlation between adhesion severity and the incision to delivery interval.

Mass media effect on vaccines uptake during silent polio outbreak.

BACKGROUND: During 2013, isolation of a wild type 1 poliovirus from routine sewage sample in Israel, led to a national OPV campaign. During this period, there was a constant cover of the outbreak by the mass media. AIMS: To investigate the association of media exposure and OPV and non-OPV vaccines uptake during the 2013 silent polio outbreak in Israel. METHODS: We received data on daily immunization rates during the outbreak period from the Ministry of Health (MoH). We conducted a multivariable time trend analysis to assess the association between daily media exposure and vaccines uptake. Analysis was stratified by ethnicity and socio-economic status (SES). RESULTS: During the MoH supplemental immunization activity, 138,799 OPV vaccines were given. There was a significant association between media exposure and OPV uptake, most prominent in a lag of 3-5 days from the exposure among Jews (R.R 1.79C.I 95% 1.32-2.41) and high SES subgroups (R.R 1.71C.I 95% 1.27-2.30). These subgroups also showed increased non-OPV uptake in a lag of 3-5 days from the media exposure, in all vaccines except for MMR. Lower SES and non-Jewish subgroups did not demonstrate the same association. CONCLUSION: Our findings expand the understanding of public behaviour during outbreaks. The public response shows high variability within specific subgroups. These findings highlight the importance of tailored communication strategies for each subgroup.

Control of a Mycoplasma pneumoniae Outbreak in an Institutional Setting Using Azithromycin Prophylaxis.

BACKGROUND: Mycoplasma pneumoniae is a major cause of respiratory infection of varying severity. Outbreaks of M. pneumoniae infection commonly occur in closed or semi-closed communities and settings. The control of such outbreaks is challenging, owing to delayed detection, long incubation period, and paucity of infection control guidelines. METHODS: Between May and July 2015, a residential facility for adults with developmental disabilities in Southern Israel witnessed an outbreak of acute respiratory infection, subsequently diagnosed as associated with M. pneumoniae. All relevant data were collected as a part of a formal outbreak investigation. Strict infection control procedures were implemented, and azithromycin prophylaxis was provided to all residents. RESULTS: Out of 215 residents, there were 29 suspected cases, 23 of which were confirmed as M. pneumoniae infection by serology or nucleic acid testing, for an attack rate of 11%. There were no cases of severe or fatal illness. An infection control strategy, including implementation of strict case isolation, enforcement of hygiene measures, a high index of suspicion for case detection, and use of azithromycin prophylaxis for all residents, led to rapid cessation of the outbreak. DISCUSSION: The use of azithromycin prophylaxis may be worthwhile in closed institutional settings in which M. pneumoniae infections are documented. The dynamics of this outbreak suggest that if spread between wards is anticipated, expanding prophylaxis beyond immediate contacts of affected individuals should be considered.

Parental smoking and education as determinants of overweight in Israeli children.

INTRODUCTION: Obesity is a well-recognized risk factor for many chronic diseases. Pediatric overweight is an especially severe problem because its childhood onset increases the overall length of exposure to the detrimental effects of overweight, accelerates the onset of chronic disease, and affects children's physical, psychological, and social development. Several parental traits have been shown to be associated with an increased risk for childhood overweight. In our study, we quantified the mutual effects of parental education and smoking on the risk of filial overweight in a large population-based sample of Israeli schoolchildren, adjusting for the effects of age, sex, and immigration status. METHODS: Data were collected in 1997 and 2000 from 8623 Israeli schoolchildren aged 8 to 13 years in two cross-sectional samples. Overweight was defined as body mass index (BMI) of greater than the 85th percentile for age and sex, and severe overweight was defined as BMI greater than the 95th percentile for age and sex. RESULTS: Mean BMI was positively associated with number of parental smokers for a child. Parental smoking was an independent risk factor for both overweight and severe overweight, with a dose-response relationship between the number of parental smokers and the risk of filial overweight. Children whose parents did not attend college were at increased risk for overweight (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.03-1.42) and severe overweight (OR, 1.49; 95% CI, 1.09-2.05) compared with children whose parents both attended college. Children with one college-educated parent were at increased risk for severe overweight (OR, 1.31; 95% CI, 1.004-1.71) compared with children whose parents both attended college. CONCLUSION: Parental education and smoking are independent risk factors for filial overweight. Children of less-educated, smoking parents should be targeted for overweight prevention and intervention efforts. These findings should also be included as key messages in adult smoking prevention and cessation campaigns. Parents who smoke should be warned that not only is their own health at stake, but their children are also at increased risk for overweight and its associated diseases.