Post-treatment Infection Research Articles

Long-term immune changes in patients with relapsed/refractory chronic lymphocytic leukemia following treatment with venetoclax plus rituximab.

Immune dysregulation is a hallmark of chronic lymphocytic leukemia (CLL). Anti-CD20 antibodies (e.g., rituximab [R]) can be combined with venetoclax (Ven) to treat CLL. However, anti-CD20 antibodies can increase hypogammaglobulinemia risk, while the effects of Ven on immune dysregulation are still uncertain. We report long-term immune changes in VenR- and bendamustine-R (BR)-treated patients with relapsed/refractory CLL in the MURANO trial (NCT02005471). Patients were randomized to fixed-duration VenR (2 years Ven; VenR for the first 6 months) or BR (6 months). Immune cell levels were evaluated at the end of combination treatment (EOCT), end of treatment (EOT; VenR arm only), and 12 and 24 months post-EOCT. Overall, 130/194 VenR- and 134/195 BR-treated patients completed treatment without progressive disease. In patients who completed VenR combination therapy, median immunoglobulin (Ig)G and IgM levels decreased from baseline to EOT (p ≤ 0.01 and p ≤ 0.0001, respectively); by 24 months, post-EOT IgG had returned to baseline level and IgM had increased from baseline (p ≤ 0.001). Median IgA levels increased from baseline to 12 (p ≤ 0.0001) and 24 months post-EOT (p ≤ 0.0001). In BR-treated patients, changes in IgG, IgA, and IgM levels across the assessed time points were not significant, and by 24 months, post-EOCT IgG, IgA, and IgM were above baseline levels. Grade ≥3 infection rates on treatment were low. Overall, immune recovery was observed with VenR and BR, with stabilization of Ig levels after treatment. Post-treatment infection rates were generally low, making these very tolerable therapies for CLL.

Putative mRNA Biomarkers for the Eradication of Infection in an Equine Experimental Model of Septic Arthritis.

Septic arthritis (SA) in horses has long-term health implications. The success of its resolution hinges on the implementation of early, aggressive treatment, which is often sustained over a prolonged period. Common diagnostic methods do not allow for the reliable detection of the eradication of joint infection. A potential alternative is the discovery and characterization of mRNA biomarkers. The purpose of this study was to identify potential mRNA biomarkers for the eradication of joint infection in equine SA and to compare their expression with our previously published proteomics data. In addition, the transcriptomics data were compared to the mRNA biomarker panel, SeptiCyte Lab, used to distinguish sepsis from non-septic shock in humans. A comparative transcriptomics analysis of synovial fluid from the SA joints of five horses with active infection and subsequent post-treatment eradicated infection in the same joints and five horses with non-septic synovitis was performed. Eight novel mRNA transcripts were identified that were significantly upregulated (>3-fold) in horses with active SA compared to horses post-eradication of infection after treatment and horses with non-septic synovitis. Two proteins in our proteomics data corresponded to these mRNA transcripts, but were not statistically different. The transcripts used in the SeptiCyte test were not differentially expressed in our study. Our results suggest that mRNA may be a useful source of biomarkers for the eradication of joint infection in horses and warrants further investigation.

Efficacy of Single-Dose Azithromycin for Ocular Chlamydial Infection: A Longitudinal Study.

Millions of doses of azithromycin are distributed each year for trachoma, yet the treatment efficacy of a single dose of azithromycin for ocular Chlamydia infection has not been well characterized. In this study, four villages in Niger received a mass azithromycin distribution for trachoma. All 426 children aged 0-5 years residing in the study villages were offered conjunctival swabbing every 6 months to test for ocular Chlamydia trachomatis. Among the children infected with ocular Chlamydia before treatment, 6% (95% CI: 2-15%) tested positive for ocular Chlamydia infection 6 months later, and 15% (95% CI: 7-28%) tested positive 12 months later. The most important predictor of post-treatment ocular Chlamydia infection was pretreatment ocular Chlamydia infection (relative risk: 3.5, 95% CI: 1.3-9.4). Although the 6-monthly monitoring schedule was suboptimal for testing the treatment efficacy of an antibiotic, these findings are nonetheless consistent with high treatment efficacy of a single dose of azithromycin and suggest that additional interventions might be most effective if targeted to those children infected prior to treatment.

Theoretical considerations for root canal re-treatment

When considering performing root canal re-treatment, we must first consider why the original treatment failed. Failure of root canal treatments can occur when ideal technical standards for control of the root canal infection are not achieved. Sometimes, extra-radicular infection may prevent a successful treatment outcome. Teeth with post-treatment peri-apical infection can be managed by either non-surgical or surgical root canal re-treatment, both of which aim to restore health to the peri-apical tissues and prolong the survival of the tooth in the oral cavity. CPD/Clinical Relevance: Examples of different clinical circumstances that were considered for root canal re-treatment are presented.

Epidemiology of soil-transmitted helminth infections and the differential effect of treatment on the distribution of helminth species in rural areas of Gabon

BackgroundSoil-transmitted helminth (STH) infections are a public health concern in endemic areas. For efficient control, the epidemiology of the disease needs to be monitored. This report assesses the prevalence, incidence, post-treatment infection (PTI) rate, and risk factors for STH infections in two rural areas of Gabon.MethodIn this longitudinal and prospective study, participants aged six to 30 years from the vicinity of Lambaréné and selected households using a simple randomization process were included and followed in two consecutive periods of six and nine months. Stool samples were obtained at the beginning and the end of each follow-up phase (FUP). The Kato-Katz technique was used for the detection of STH eggs, while the Harada-Mori technique and coproculture were used for the detection of larvae in stool processed within a maximum of four hours of collection. Prevalence was determined at the three main time points of the study, incidence was assessed during the two study phases, and PTI was defined as an infection detected nine months post-treatment.ResultsA total of 262 participants were included. The overall prevalence of STH infections was 42% (95%CI: 34–50) and 44% (95%CI: 37–51) at baseline for the six and nine month FUPs, respectively. Trichuris trichiura was the most prevalent species at each time point of assessment. The cumulative incidence of STH at the 6- and 9-month follow-ups was 18% (95%CI: 12–27) and 35% (95%CI: 27–43), respectively, while the incidence rates were 41 (95%CI: 28–55) and 56 (95%CI: 46–67) per 100 person-years, respectively. The PTI rates at the 9-month follow-up for T. trichiura, hookworm, and Ascaris lumbricoides were 58% (95%CI: 41–74), 31% (95%CI: 11–59) and 18% (95%CI: 5–40), respectively. The STH infection intensity was generally light.ConclusionThe prevalence level of STH infection is moderate in the vicinity of Lambaréné, with T. trichiura being the most prevalent species. Our results reveal a rapid spread of the disease in the population mainly following intervention, particularly for trichuriasis, and therefore call for the full implementation of the World Health Organization’s recommendations in the area.Trial registration clinicaltrials.gov Identifier NCT02769013. Registered 21 April 2016, https://clinicaltrials.gov/study/NCT02769013

Factors Influencing the Clinical Outcomes of Two-Stage Re-Implantation in Patients With Periprosthetic Joint Infection After Total Knee Arthroplasty.

Introduction Infection is one of the most distressing complications of total knee arthroplasty (TKA), requiring a long treatment process and may negatively affect patient satisfaction. All surgeons aim to achieve infection-free survival, painless, functional, and stable knee after treatment of periprosthetic joint infection (PJI) with two-stage revision treatment. Many factors play a role in determining clinical outcomes. We aimed to evaluate the factors influencing the clinical outcomes of patients undergoing two-stage revision knee arthroplasty for PJI. Methods Forty-nine patients were retrospectively evaluated. Forty-four patients met the inclusion criteria. Spacer types, growth rates in culture, types and amount of antibiotics added to the cement, and intervals between stages were evaluated. Pre- and post-treatment infection parameters, changes in the range of motion (ROM), clinical and functional (C&F) Knee Society Score (KSS) results, and complications were also studied. Results After a mean follow-up of 48.8 ± 16.5 months, re-infection was detected in five out of 44 patients (10.4%). No significant difference was noted regarding C&F KSS when comparing time intervals between the two stages, whether they were shorter or longer than 10 weeks. However, better ROM results were obtained in patients with less than 10 weeks between stages. The relationship between spacer type, ROM, and C&F KSS was not found to be significant. Particularly, the addition of 4g of teicoplanin to the cement shortened the time between the two stages. Conclusion C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels can be considered safe parameters for diagnosis, reimplantation timing, and follow-up. The use of dynamic spacers or reimplantation performed within 10 weeks after the first stage is associated with better ROM outcomes. Additionally, the addition of teicoplanin to the cement shortened the duration of antibiotic therapy.

Mediastinal Thoracic Duct Cyst Infection after Endoscopic Submucosal Dissection for Early Esophageal Cancer: A Case Report.

A mediastinal thoracic duct cyst that originates from the thoracic duct is a very rare disease in the mediastinum. There have been no reports of mediastinal thoracic duct cyst infection caused by endoscopic treatment. This is the first case of mediastinal thoracic duct cyst infection after endoscopic submucosal dissection for early esophageal cancer. We herein report a 75-year-old man with mediastinal thoracic duct cyst infection caused by esophageal endoscopic submucosal dissection. In cases where a mediastinal thoracic duct cyst is found before performing endoscopic esophageal treatment, we should carefully consider the potential risk of post-treatment cyst infection.

Post-Treatment Infection in Severe Burn Patients: A Comparative Review on Dermal Matrices

Artificial dermal regeneration templates have been widely used in burn reconstruction surgery, and this allows subsequent skin graft to be taken more successfully. However, many clinical studies have noted instances of infection when testing the effectiveness of a specific template. This review aims to compare two common dermal regeneration templates that are very different in nature -- NovosorbÒ Biodegradable Temporising Matrix (BTM) and IntegraÒ Dermal Regeneration Template. Extensive literature search was conducted, and infection rates associated with each template were recorded. Based on the articles included, Integra has shown to be a more effective method and has resulted in lower infection rates. While current studies have begun to examine the use of dermal regeneration templates in additional settings, more long-term evaluations should be included in the future since wound contracture is a continuous process.

Novel Antigens LMA and Kma Are Expressed on Malignant Bone Marrow Plasma Cells from Patients with Relapsed Refractory Multiple Myeloma and Plasma Cell Dyscrasias

Introduction Previous studies have identified the lambda myeloma antigen (LMA) and kappa myeloma antigen (KMA) on the surface of malignant plasma cells in myeloma patient bone marrow samples, human myeloma cell lines and other plasma cell dyscrasias1-3. LMA and KMA are not present on normal B cells and are found on occasional mononuclear cells in tonsillar tissue and secondary mucosal lymphoid tissue. Targeting KMA and LMA through cellular and other immunological therapies has the potential advantage of leaving a population of normal plasma cells untouched and minimising the risk of serious post-treatment infection. Characteristics of the antibodies called KappaMab and LambdaMabs (10B3 and 7F11) that bind to specific conformational epitopes in the constant regions of these surface-bound light chains have been described in clinical trials and in vitro experiments1, 2, 4-6. Here, we present data on a larger series of patients with plasma cell dyscrasias, demonstrating the expression of LMA on plasma cells from patients in whom myeloma evolves from monoclonal gammopathy of unknown significance (MGUS). We also describe the difference in phenotype between LMA and KMA expressing malignant plasma cells and the frequent expression of KMA in relapsed refractory myeloma patient (RRMM) samples. Methods Patient BM samples (κ=49 and λ=31) were analysed using multiparametric FCM immunophenotyping with APC labelled LambdaMab (10B3) and KappaMab Fab'2 fragments, CD38, CD138, CD269 (BCMA), CD319 (SLAM F7), CD56 and CD45 monoclonal antibodies. Plasma cells were identified as previously described by initial gating using CD38 and CD138. LMA and KMA expression was determined and compared with the other cell markers. Results Nine of 12 (75%) newly diagnosed λ-type patients with MGUS or SMM expressed LMA on the surface of BM plasma cells. Longitudinal data from two patients was available. One patient showed LMA expression and antigen density increasing on the surface of bone marrow plasma cells during progression from MGUS (2020) to smoldering myeloma (SMM) (2022) (% of plasma cells positive for LMA rose from 61% to 92%, antigen density increased from 532 to 5164 molecules of PE/cell). In a second individual, LMA expression and antigen density increased on bone marrow plasma cells during progression from SMM (2020) to myeloma (2022) (% of plasma cells positive for LMA rose from 94% to 100%, antigen density increased from 3981 to 8941 molecules of PE/cell). KMA expression continued to be observed on plasma cells in 4 of 6 patients after autologous stem cell transplant. KMA was expressed in 86% of patients with ĸRRMM (n=14). LMA expression was observed in 2 of 4 patients with λRRMM. Both KMA and LMA antigen densities were higher than BCMA in the RRMM population (KMA mean 1802, range 468-7943 vs BCMA mean 1306, range 350-2630 molecules of PE/cell), (LMA mean 2439, range 263-6664 vs BCMA mean 817, range 537-1065 molecules of PE/cell). Conclusions In an enlarged cohort of patients with myeloma, we have confirmed that KMA and LMA are expressed at all stages of disease. Our data examining longitudinal expression in individual patients suggests that expression of LMA on BM plasma cells increases from MGUS to MM. The majority of patients with relapsed refractory kappa myeloma expressed KMA. Further data is required to confirm LMA expression in this population. The antigen density of both LMA and KMA is higher than BCMA on RRMM BM plasma cells. KMA and LMA expression is independent of serum Ig and FLC levels and % marrow plasma cells. These data show that KappaMab and LambdaMab have therapeutic potential in the treatment of myeloma patients, especially in the setting of relapsed refractory disease where the combination of high antigen density and restriction of the target antigen to the malignant subpopulation of plasma cells will confer valuable clinical benefit.

Interpreting Immune Reconstitution and Clinical Outcome By Single-Cell Transcriptomic Analysis in T-ALL Patients Undergoing Donor-Derived CD7 CAR-T Immunotherapy

Background Twenty-five percent of T-ALL patients experience relapse after allo-HSCT, which indicates a dismal prognosis and represents a significant unmet clinical need. CD7 is continuously expressed on T-ALL cell surface at higher levels than that on normal T cells and is therefore considered as a viable CAR T therapeutic target. However, the impact of CD7-positive normal T and NK cell clearance on the development, function, and homeostasis of immune system remains to be addressed. Methods We designed an open label, phase I clinical trial enrolled patients with a pathologically confirmed CD7-positive T-ALL/LBL (ChiCTR2200058969). After a 6-day manufacturing, the patients received donor-derived CD7 CAR T cells at the target dose of 1×105/kg. To minimize CD7 CAR T-cell mediated fratricide, we used IntraBlock technology to prevent CD7 expression on CAR T cells surface. Single cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) were adopted to profile immune statues changes before and after CD7 CAR T-cell treatment. Results Seven eligible patients were enrolled between November 2020 and December 2021, and all were followed up until May 1, 2022. Three patients were diagnosed with R/R T-ALL and 4 with R/R T-LBL at relapse. All patients had a history of allo-HSCT prior to enrollment. Patients were heavily pretreated with a median of 4 (3-8) lines of therapies before enrollment. The rate of CRS and ICANS was 85.7% and 14.3%, respectively. Only one patient had a grade 3 CRS and a serious grade 4 ICANS, resolved by dexamethasone and tocilizumab. Only two patients (28.6%) developed GVHD. Hematologic CAR T cells related adverse events (AE) included leukopenia, thrombocytopenia and neutropenia were observed in 6 patients (85.7%). Infections occurred in 5 patients (71.4%). On day 28, the patients who had bone marrow involvement achieved minimal residual disease (MRD) negative complete remission (CR, n=1) or CR with incomplete hematologic recovery (CRi, n=2); The patients who had CNS leukemia achieved CR on day 28. Five patients with their EMD encountered CR at day 90. The optimal ORR and CR were 100% and 100%, respectively. The CR/CRi rate was 85.7% on month 3. The median followed-up time was 4 months (range 3-16 months). Two patients died of serious infection and one patient died of brain hemorrhage. Four patients were alive until the cut-off time. Additionally, CD7-positive T-cells in the peripheral blood (including normal and abnormal T cells) were eliminated in seven patients on day 11 after CD7 CAR T infusion. However, CD7-negative T cells dramatically increased in all patients. In addition, the CD4/CD8 ratio decreased, driven by the increase in the proportion of CD8-positive T cells. The absolute numbers of T/B/NK cells (excluding CAR+ and leukemia T cells) showed a transient decline, and recovered by a low cells number at day 21. PBMC samples from four patients (two alive and two died of infection) were tested by scRNA-seq. The profiling of immune cells demonstrated that the severe infection after treatment is mainly caused by the loss of monocytes. This kind of monocytes loss is related to the decline of high developmental potential subset of monocytes before treatment. Moreover, the reconstructed T cell populations may have normal or even enhanced immune functions than pre-treatment T cells in all samples, which is supported by the higher expression levels of TCRs, T cell activation pathway, and T cell function pathway in post-treatment samples. The main character of the reconstructed T cell populations is its similarity with T cells in autoimmune diseases. This includes the expansion of GZMH+ T cells, decline of CD4+ naïve T cells, and activation of autoimmune disease related pathways. We also observed consistently upregulation of S100A8 and S100A9 in leukocyte lineage as a signature of the patients with relapse lymphoma. Conclusion Among 7 patients with r/r T-ALL enrolled in this trial, donor-derived CD7 CAR T cells exhibited efficient expansion and achieved a high complete remission rate with manageable safety profile. Data from scRNA-seq of PBMCs indicated a fulfilled T lymphocytes immune function by CD7-negativeT cells. The major challenge on prevent post-treatment infection may be the protection from loss of monocytes. Key words CD7 CAR-T immunotherapy; Immune Reconstitution; Single-cell Transcriptomic Analysis; T-ALL

297. Infectious Complications Associated with Tocilizumab Use in Patients Infected with SARS-CoV-2 at a Mid-Atlantic Hospital Consortium

BackgroundThe IL-6 inhibitor Tocilizumab (TOCI) has been associated with infections in 5-8% of patients with Rheumatoid Arthritis. TOCI has now been recommended as a treatment option for select patients with COVID-19; however, the risk of infection in this patient population is yet to be determined. MethodsWe performed a retrospective chart review of patients diagnosed with COVID-19 and admitted to MedStar hospitals within the D.C./Baltimore corridor from 03/01/2020 to 12/31/2020. We identified patients who had positive culture data within 30 days of administration of TOCI-based regimens and analyzed clinical characteristics and outcomes. Univariate analyses (Wilcoxon, T-test, Chi-Square, Fisher’s Exact) were used to compare these outcome variables between patients who had post-treatment infections and those who did not. ResultsA total of 220 patients received TOCI-based regimens; 16% (N=36) of patients developed positive cultures within 30 days of treatment. Of the 99 cultures, 50% were gram positive (N=49), 38% were gram negative (N=38), 10% were Candida spp. (N=10), and 2% were anaerobic organisms (N=2). Only 9% (8/87) of the gram positive and gram negative organisms were MDROs. Bloodstream infections were the most common and accounted for 58.4% of all infections. Length of stay (LOS) was approximately twice as long in those with post-treatment infections (26 days) compared to those without infections (14 days, p< 0.001). Although the mortality rate was higher in patients with infections after TOCI-based treatment compared to patients with no post-treatment infection (47% vs 31% respectively), this did not reach statistical significance (p=0.09). Moreover, there was no significant difference in the infection rate of patients treated with TOCI alone compared to TOCI and Dexamethasone (16.6% vs. 13.3%, p=0.99). No cases of invasive Aspergillosis were observed. ConclusionTocilizumab treatment in patients with COVID-19 may predispose patients to an increased risk of infection which is associated with a prolonged LOS and possibly higher mortality. We observed a two-fold increase in infections in COVID-19 patients compared to other patient groups receiving this treatment. Disclosures Princy N. Kumar, MD, AMGEN (Other Financial or Material Support, Honoraria)Eli Lilly (Grant/Research Support)Gilead (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)GSK (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)Merck & Co., Inc. (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)

A Comparison of Single-Dose Versus Multidose Metronidazole by Select Clinical Factors for the Treatment of Trichomonas vaginalis in Women.

In a randomized controlled trial of 2 g (single-dose) metronidazole (MTZ) versus 500 mg twice daily for 7 days (multidose) for Trichomonas vaginalis treatment, multidose was superior. We examined if the effect was similar by select clinical factors to determine if treatment recommendations could be targeted. The primary outcome was T. vaginalis repeat infection at test-of-cure (TOC) 4 weeks after completion of therapy. Analyses were stratified by T. vaginalis history, baseline genital symptoms, and concurrent diagnosis of bacterial vaginosis (BV) per Nugent score at baseline. Women who returned for TOC (n = 540) were included. At baseline, 52.9% had a self-reported history of T. vaginalis; 79.3%, genital symptoms; 5.8%, a gonorrhea diagnosis; and 47.5%, BV. During follow-up, 97.4% took all MTZ as instructed and 34.5% had interval condomless sex with a baseline partner. At TOC, 14.8% tested positive for T. vaginalis. In stratified analysis, women randomized to single-dose MTZ had a higher rate of TOC T. vaginalis positivity than those randomized to multidose if they were symptomatic at baseline (21.4% vs. 10.8%, P = 0.003) or had a reported history of T. vaginalis (24.1% vs. 12.6%, P = 0.01). Test-of-cure T. vaginalis positivity was higher for women receiving a single dose (18.9%) versus multidose (10.8%), irrespective of baseline BV status (P > 0.06). In multivariable analysis, only a history of T. vaginalis and single-dose MTZ were independently associated with a positive TOC for T. vaginalis. Although multidose MTZ is recommended for all women with T. vaginalis, it is especially important for women with a T. vaginalis history and, given high posttreatment infection rates, a TOC should be performed.

24880 A combination of 89% Vichy volcanic mineralizing water and hyaluronic acid after aggressive laser procedure for skin rejuvenating

Introduction: Procedures are popular in skin rejuvenation. Posttreatment erythema, pigment changes, prolonged healing, infection, and scarring can be observed, especially with ablative lasers (AL). M89 containing 89% of Vichy volcanic mineral water and hyaluronic acid, was developed to reinforce the skin barrier.

Termination of pregnancy services in Irish general practice from January 2019 to June 2019

ObjectiveTo describe how a general-practitioner-delivered community medical abortion service is provided in Ireland, including a description of the unique model of care delivered within the framework of new legislation. To investigate the characteristics and contraceptive choices of women attending in the first six months of the service. Study DesignTwenty-seven general practitioners conducted a retrospective chart review. We described the service and analyzed demographic characteristics, treatment outcomes, adverse events, and contraception use. We defined treatment success as complete abortion without surgical intervention. ResultsTwenty-seven general practitioners from the Southern Task Group on Abortion and Reproductive Topics (START) group collected data from 475 women who had attended requesting medical abortion from January 1st 2019 to June 30th 2019. Out of these, 315 (66%) were more than 25 years old, and 261 (55%) had at least one child. The mean gestational age at initial presentation was 49 days. Five (1%) had a gestational age which exceeded 84 days. Four hundred and twenty (89%) proceeded with community medical abortion following an initial consultation. The process was completed without the need for surgical intervention in 412 (98%) cases. Six (1.4%) women had a mild post-treatment infection, and received community treatment with oral antibiotics. Thirty-three (7.9%) patients were referred to hospital for additional evaluation following treatment. Two hundred ninety (69%) adopted contraception post abortion; only 160 (34%) were using contraception prior to pregnancy. ConclusionThe general-practitioner-delivered community medical abortion service described in the study is safe, effective, and accessible for the majority of, but not all women seeking abortion. The model of care used in Ireland provides an ideal opportunity to discuss contraceptive choice. Implications StatementThis review provides demographic, efficacy, and safety data for the general-practitioner-provided community medical abortion service in Ireland. An effective and largely accessible model of care is demonstrated. These findings can help inform legislative review, clinical guidelines, and generate hypotheses for future research.

Supplemented nutrition decreases helminth burden and increases drug efficacy in a natural host–helminth system

Gastrointestinal (GI) helminths are common parasites of humans, wildlife, and livestock, causing chronic infections. In humans and wildlife, poor nutrition or limited resources can compromise an individual's immune response, predisposing them to higher helminth burdens. This relationship has been tested in laboratory models by investigating infection outcomes following reductions of specific nutrients. However, much less is known about how diet supplementation can impact susceptibility to infection, acquisition of immunity, and drug efficacy in natural host–helminth systems. We experimentally supplemented the diet of wood mice (Apodemus sylvaticus) with high-quality nutrition and measured resistance to the common GI nematode Heligmosomoides polygyrus. To test whether diet can enhance immunity to reinfection, we also administered anthelmintic treatment in both natural and captive populations. Supplemented wood mice were more resistant to H. polygyrus infection, cleared worms more efficiently after treatment, avoided a post-treatment infection rebound, produced stronger general and parasite-specific antibody responses, and maintained better body condition. In addition, when applied in conjunction with anthelmintic treatment, supplemented nutrition significantly reduced H. polygyrus transmission potential. These results show the rapid and extensive benefits of a well-balanced diet and have important implications for both disease control and wildlife health under changing environmental conditions.

Management of first-trimester miscarriage: a systematic review and network meta-analysis.

First-trimester miscarriage affects up to a quarter of women worldwide. With many competing treatment options available, there is a need for a comprehensive evidence synthesis. We conducted a systematic review and network meta-analysis to assess the effectiveness and safety of treatment options for first-trimester miscarriage: expectant management (EXP), sharp dilation and curettage (D+C), electric vacuum aspiration (EVAC), manual vacuum aspiration (MVA), misoprostol alone (MISO), mifepristone+misoprostol (MIFE+MISO) and misoprostol plus electric vacuum aspiration (MISO+EVAC). We searched MEDLINE, Embase, CINAHL, AMED and Cochrane Library from inception till June 2018. We included randomized trials of women with first-trimester miscarriage (<14 weeks gestation) and conducted a network meta-analysis generating both direct and mixed evidence on the effectiveness and side effects of available treatment options. The primary outcome was complete evacuation of products of conception. We assessed the risk of bias and the global network inconsistency. We compared the surface under the cumulative ranking curve (SUCRA) for each treatment. A total of 46 trials (9250 women) were included. The quality of included studies was overall moderate with some studies demonstrating a high risk of bias. We detected unexplained inconsistency in evidence loops involving MIFE+MISO and adjusted for it. EXP had lower effectiveness compared to other treatment options. The effectiveness of medical treatments was similar compared to surgery. Mixed evidence of low confidence suggests increased effectiveness for MIFE+MISO compared to MISO alone (RR 1.49, 95% CI: 1.09-2.03). Side effects were similar among all options. Fewer women needed analgesia following EVAC compared to MISO (RR for MISO 0.43, 95% CI: 0.27-0.68) and in the EXP group compared to EVAC (RR 2.07, 95% CI: 1.25-3.41). MVA had higher ranking (low likelihood) for post-treatment infection and serious complications (SUCRA 87.6 and 79.2%, respectively) with the highest likelihood for post-treatment satisfaction (SUCRA 98%). Medical treatments for first-trimester miscarriage have similar effectiveness and side effects compared to surgery. The addition of MIFE could increase the effectiveness of MISO and reduce side effects, although evidence is limited due to inconsistency. EXP has lower effectiveness compared to other treatment options.Systematic review registration: Prospero CRD42016048920.

Residual lesions in uterine specimens after loop electrosurgical excision procedure in patients with CIN.

To identify the risk factors for residual lesion in hysterectomy specimens after loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN). We retrospectively analyzed the clinical data of 594 patients who underwent total hysterectomy after LEEP for CIN at the International Peace Maternity and Child Health Hospital affiliated to Shanghai Jiaotong University between July 2006 and June 2015. Among the 594 patients, there were no residual lesions in uterine specimens of 409 (68.9%) patients; residual CIN1 was found in 24 (4%) patients, CIN2 and CIN3 in 142 (23.9%) patients, and cervical cancer in 19 (3.2%) patients. On univariate analysis age, menopausal status, margin involvement, lesion grade, abnormal endocervical curettage (ECC) result, and persistent human papillomavirus (HPV) infection post operation were significantly associated with residual lesions after LEEP (P < 0.05). Multivariate regression analysis using the logistic regression model showed abnormal ECC result and persistent HPV positivity to be independent risk factors for residual lesions after LEEP. LEEP with positive margins and persistent HPV infection were also associated with high risk of invasive cervical cancer in CIN2+ patients. Abnormal ECC result and post-treatment HPV infection are predictors of residual lesion after LEEP. In combination, they could be useful for risk stratification and selection of the management approach. Postmenopausal CIN2+ patients with positive margins and persistent postoperative HPV infection may have high risk of cervical invasive cancer.

Presence of archaea and selected bacteria in infected root canal systems

Infections of the root canal have polymicrobial etiology. The main group of microflora in the infected pulp is bacteria. There is limited data that archaea may be present in infected pulp tissue. The aim of this study was to check the prevalence of archaea in necrotic root canal samples obtained from patients with primary or post-treatment infection. The prevalence of selected bacteria species (Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Synergistes sp.) in necrotic samples was evaluated as well. Sixty-four samples from root canal were collected for DNA and RNA extraction. A PCR assay based on the 16S rRNA gene was used to determine the presence of archaea and selected bacteria. Of the 64 samples, 6 were analyzed by semiquantitative reverse transcription PCR to estimate expression profiles of 16S rRNA, and another 9 were selected for direct sequencing. Archaea were detected in 48.4% samples. Statistical analysis indicated a negative association in coexistence between archaea and Treponema denticola (P < 0.05; Pearson's χ2 test). The main representative of the Archaea domain found in infected pulp tissue was Methanobrevibacter oralis. Archaea 16S rRNA gene expression was significantly lower than Synergistes sp., Porphyromonas gingivalis, and Tannerella forsythia (P < 0.05; Student's t test). Thus, it can be hypothesized that archaea may participate in the endodontic microbial community.

First Results of a Phase 2 Trial of Once-Weekly Hypofractionated Breast Irradiation (WHBI) for Early-Stage Breast Cancer

To report early outcome analysis of a prospective institutional phase 2 trial of weekly hypofractionated breast irradiation (WHBI) for patients undergoing breast-conserving surgery (BCS). Patients who underwent BCS for American Joint Committee on Cancer stage 0, I, or II breast cancer with negative surgical margins received whole-breast radiation therapy to 30 or 28.5Gy in 5 weekly fractions with or without an additional boost.The eligibility criteria were the same as for NSABP (National Surgical Adjuvant Breast and Bowel Project) B39/RTOG (Radiation Therapy Oncology Group) 0413, and there were no restrictions on age, breast size, tumor grade, receptor status, or the use of cytotoxic chemotherapy for otherwise eligible patients.The primary endpoint was ipsilateral breast tumor recurrence. Patients were also evaluated for acute toxicity (Common Terminology Criteria for Adverse Events version 3.0), cosmesis (Harvard Scale), development of distant metastatic disease, and overall survival. Between January 2011 and October 2015, 158 eligible patients underwent WHBI immediately following BCS. The median age was 60years (range, 30-84years), and the median follow-up period was 3years. Ipsilateral breast tumor recurrence developed in a total of 2 patients (1.3%), 1 in conjunction with widespread metastatic disease. Distant metastatic disease developed in 4 patients (2.5%), and the 3-year disease-free survival and overall survival rates were 97.5% and 96.2%, respectively.The most common grade 1 or 2 acute toxicities were breast pain, radiation dermatitis, and fatigue. There were 2 grade 3 events (1.3%): pain requiring narcotic analgesics (1) and posttreatment infection requiring hospitalization (1). The rate of excellent or good cosmesis versus fair or poor cosmesis was 82.3% versus 17.7%. The rate of significant cosmetic change from baseline to last follow-up (dropping from excellent or good to fair or poor) was 11.6%. Early outcomes after WHBI are favorable and parallel those seen with daily hypofractionated whole-breast irradiation. With broader entry criteria than all previous reports of WHBI, this study will facilitate comparison to the results of NSABP B39/RTOG 0413. With continued follow-up, future reports will assess cosmetic stability and disease-specific outcomes.

Effect of treatment failure on the CagA EPIYA motif inHelicobacter pyloristrains from Colombian subjects

AIMTo evaluate effect of treatment failure on cagA and vacA genotypes in Helicobacter pylori (H. pylori) isolates from Colombia.METHODSOne hundred and seventy-six participants infected with H. pylori from Colombia were treated during 14 d with the triple-standard therapy. Six weeks later, eradication was evaluated by 13C-Urea breath test. Patients with treatment failure were subjected to endoscopy control; biopsies obtained were used for histopathology and culture. DNA from H. pylori isolates was amplified using primers specific for cagA and vacA genes. The phylogenetic relationships among isolates obtained before and after treatment were established by conglomerate analysis based on random amplified polymorphic DNA (RAPD) fingerprinting.RESULTSTreatment effectiveness was at 74.6%. Of the participants with treatment failure, 25 accepted subjected to a second endoscopy. Prevalence of post-treatment infection was 64% (16/25) and 40% (10/25) by histology and culture, respectively. Upon comparing the cagA and vacA genotypes found before and after therapy, multiple cagA genotypes (cagA-positive and cagA-negative) were found before treatment; in contrast, cagA-negative genotypes decreased after treatment. vacA s1m1 genotype was highly prevalent in patients before and after therapy. The 3’cagA region was successfully amplified in 95.5% (21/22) of the isolates obtained before and in 81.8% (18/22) of the isolates obtained after treatment. In the isolates obtained from patients with treatment failure, it was found that 72.7% (16/22) presented alterations in the number of EPIYA motifs, compared to isolates found before treatment.CONCLUSIONUnsuccessful treatment limits colonization by low-virulence strains resulting in partial and selective eradication in mixed infections, and acts on the cagA-positive strains inducing genetic rearrangements in cagA variable region that produces a loss or gain of EPIYA repetitions.