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.

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.

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.

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.

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.

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.

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.

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.

Treatments for Cutaneous Lichen Planus: A Systematic Review and Meta-Analysis.

BACKGROUND: Cutaneous lichen planus (CLP) is an inflammatory dermatosis. Its chronic relapsing course and frequently spontaneous regression hamper the assessment of treatment effectiveness. OBJECTIVE: To evaluate the efficacy of available treatment modalities for CLP. DATA SOURCES: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov registry. METHODS: We performed a systematic review of the current literature. All randomized controlled trials, nonrandomized case-control studies, and cohort studies with more than one treatment arm were included. The primary outcomes were complete response and time to complete response. The secondary outcomes were partial response, relapse, time to relapse, reduction of itch, the adverse event rate, and withdrawal due to adverse events. DATA SYNTHESIS: Sixteen studies met the inclusion criteria, of which 11 were randomized controlled trials. Most trials had a small sample size. In the rare studies in which variants other than generalized or classic lichen planus were included, they could not be analyzed separately. Body-of-evidence quality ranged from very low to moderate. Acitretin, sulfasalazine, and griseofulvin were associated with increased overall response rates in comparison with placebo. Narrow-band ultraviolet B radiation (NBUVB) was more effective than 6 weeks' low-dose prednisolone in achieving a complete response, and prednisolone was more effective than enoxaparin. Hydroxychloroquine was more effective than griseofulvin in achieving an overall response. Betamethasone valerate 0.1% ointment had comparable efficacy to calcipotriol ointment. Methotrexate was effective, with a nonsignificant difference in the complete response rate in comparison with oral betamethasone. In nonrandomized controlled trials, oral psoralen plus ultraviolet A photochemotherapy (PUVA) had comparable efficacy to a PUVA bath and NBUVB. Psoralen plus sunlight exposure (PUVASOL) and betamethasone dipropionate 0.05% cream were effective relative to a short course of oral metronidazole. CONCLUSIONS: Several effective treatment options are available for CLP. Further well-designed studies are warranted to investigate the efficacy of topical glucocorticoids-the current first-line therapy-as well as other treatment modalities, and the treatment of different variants of CLP.

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.

Evaluation of Clinical and Pathologic Risk Factors May Reduce the Rate of Multimodality Treatment of Early Cervical Cancer.

OBJECTIVE: To assess the rate of postoperative adjuvant treatment in patients who underwent radical hysterectomy for early cervical cancer and to suggest criteria for the triage of patients who have a high probability of multimodality treatment. METHODS: This was a multicenter retrospective study of 514 patients with FIGO stages IA2-IIA cervical cancer who underwent radical hysterectomy between 1999 and 2010. The patients were divided into 2 groups according to whether or not postoperative radiation was administered. The 2 groups were compared with regard to clinical and histopathologic variables divided into major and minor criteria (intermediate risk factors) based on lymph nodes status, parametrial involvement, tumor size, deep stromal invasion, and lymph-vascular space invasion. RESULTS: We identified 294 (57.2%) patients who received adjuvant postoperative radiotherapy (RT) or chemoradiation. Fifty-three percent of these patients who were treated by adjuvant radiation had only intermediate risk factors. Combining the various combinations of 2 out of 3 of the following criteria, we found that 89% of patients with tumors ≥2 cm and lymph-vascular space invasion received RT, 76% of patients with tumors ≥2 cm and depth of invasion >10 mm received RT, and 87% of patients with tumors depth of invasion >10 mm and lymph-vascular space invasion received RT. CONCLUSIONS: This study suggests that in patients with early cervical cancer, clinicopathologic evaluation of tumor size and lymph-vascular space invasion should be undertaken before performing radical hysterectomy. This approach can serve to tailor treatment, reducing the rate of employing both radical hysterectomy and chemoradiation.

The Israeli public health response to wild poliovirus importation.

In 2013, a silent wild poliovirus type 1 importation and sustained transmission event occurred in southern Israel. With the aim of preventing clinical poliomyelitis and ensuring virus re-elimination, the public health response to the importation event included intensification of clinical and environmental surveillance activities, enhancement of vaccine coverage, and supplemental immunisation with a bivalent oral polio vaccine against wild poliovirus types 1 and 3. A national campaign launched in August, 2013, resulted in vaccination of 943,587 children younger than 10 years (79% of the eligible target population). Expanded environmental surveillance (roughly 80% population coverage) documented a gradual disappearance of wild poliovirus type 1 in the country from September, 2013, to April, 2014. No paralytic poliomyelitis case was detected. A prompt extensive and coordinated national public health response, implemented on the basis of evidence-based decision making, successfully contained this serious importation and sustained transmission event of wild poliovirus to Israel. On April 28, 2015, WHO officially declared Israel as a polio-free country.

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.

Field study of fecal excretion as a decision support tool in response to silent reintroduction of wild-type poliovirus 1 into Israel.

BACKGROUND: Israel has used an inactivated polio vaccine (IPV)-only schedule since 2005 (95% coverage). Silent reintroduction of wild type poliovirus 1 (WPV1) into Israel in early 2013 was detected in Southern Israel via routine environmental surveillance without clinical cases. OBJECTIVES: To estimate the rate of WPV1 excretion by age and residence and inform decision-making regarding supplemental immunization with OPV. STUDY DESIGN: A convenience sample of Bedouin and Jewish residential areas in the epicenter of the incident, focusing on under 8 year-olds who not previously given OPV. Fecal samples were directly tested for WPV1 RNA using a novel qRT-PCR assay. Positive samples were confirmed by gold standard cell culture and subject to genotyping. RESULTS: Overall, 2196 non-duplicate fecal samples were collected and analyzed. WPV1 was detected in 61 samples (2.8%), 55 of which (90.2%) were from Bedouins. WPV1 excretion rates were 5.4% among Bedouins and 0.6% among Jewish individuals. Respective age-specific rates among Bedouin and Jewish children were 4.9% and 0.2% for 0-2 years and 7.2% and 1.7% for 2-8 years. Molecular testing had 89.5% sensitivity (higher than culture) and 100% specificity. CONCLUSION: The rapid performance of a field study to evaluate WPV1 excretion unequivocally demonstrated substantial WPV1 infection rates among children under 8 years in Southern Israel, thus informing the decision to vaccinate this age group with bOPV and risk communication to both healthcare personnel and the public. Rapid development and implementation of molecular screening can thus underpin risk assessment and management in complex epidemiological situations.

Treatment of pemphigus vulgaris and pemphigus foliaceus: a systematic review and meta-analysis.

BACKGROUND: No optimal therapeutic approach has been established for pemphigus. OBJECTIVE: Our objective was to evaluate the efficacy, steroid-sparing effect, and safety of available treatment modalities. METHODS: PubMed, LILACS (up to July 2014), the Cochrane Central Register of Controlled Trials (CENTRAL, issue 5 of 12, May 2014), and the ClinicalTrials.gov registry and reference lists were searched for randomized controlled trials of any treatment modality for pemphigus vulgaris and pemphigus foliaceus. Data were extracted independently by two authors using predefined appraisal criteria and data fields. RESULTS: A total of 20 studies (826 participants) were included. Most were small and open-labeled; all but seven were not concealed for allocation. Owing to the variability in intervention arms, five meta-analyses were performed, each pooling the data of two to three trials. Studies excluded from the meta-analyses were described quantitatively. Azathioprine had a steroid-sparing effect but did not increase remission rate. Mycophenolate mofetil induced sustained remission more quickly than did placebo and delayed time to relapse but did not have a steroid-sparing effect or favorable remission rate. Cyclophosphamide had a steroid-sparing effect, though less than azathioprine, but did not affect the remission rate or time-to-disease control. Intravenous immunoglobulin had more favorable short-term efficacy than did placebo. Topical epidermal growth factor hastened lesion healing. CONCLUSIONS: Although some of the available therapeutic modalities for pemphigus are beneficial in terms of steroid-sparing, hastening response, or delaying relapse, none were found to increase the complete response rate compared with glucocorticoids alone, currently the mainstay of treatment. Multicenter randomized controlled trials and case control studies with uniform outcome measures 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.

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.

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.