Clinicoepidemiologic characteristics of scrub typhus and murine typhus: A multi-center study in southern Taiwan

BackgroundThis study aimed to offer key features to differentiate scrub typhus (ST) and murine typhus (MT) at the early stage of the diseases and provide clinicoepidemiologic characteristics of ST and MT in southern Taiwan, a region where both diseases are endemic. Comparison of doxycycline treatment efficacy between the two diseases by matching disease severity and delayed treatment had never been investigated.MethodsWe reviewed the medical records of cases of ST and MT in four hospitals in southern Taiwan. Propensity-score matching was used to analyze the defervescence curves between patients with doxycycline-treated ST and MT by log-rank test.ResultsBetween 2004 and 2016, 265 ST and 63 MT cases were diagnosed. The number of cases of ST was significantly related to temperature (Rs = 0.77) and rainfall (Rs = 0.63). Island area exposure, arthropod bite, eschar, and lymphadenopathy were only recorded in ST patients. Multivariate analysis revealed that mountainous area exposure (odds ratio [OR], 11.0; 95% confidence interval [CI], 4.4–27.2) was an independent predictor for ST, while contact with rats (OR, 8.4; 95% CI, 3.3–21.3) was that for MT. After propensity-score matching, there was no difference in defervescence curves between these two rickettsioses treated with doxycycline (p = 0.24).ConclusionIn the present study, island area exposure, arthropod bite, eschar, and lymphadenopathy were unique manifestations of ST. Mountainous area exposure is a predictive factor for ST, while contact with rats predicted MT. There was no difference in defervescence time between these two rickettsioses after doxycycline treatment.     

Distribution of virulence genes in bacteremic methicillin-resistant Staphylococcus aureus isolates from various sources

Background/purposeMethicillin-resistant Staphylococcus aureus (MRSA) can encode proteins which directly bind bacteria to many tissues and medical devices or catheters to trigger pathogenesis. However, the relationship between genetic backgrounds and virulent factors in MRSA isolates remained incompletely understood yet.MethodsMRSA isolates were collected from blood cultures of patients with infective endocarditis, bone/joint infection, skin/soft tissue infection, or catheter-related bacteremia in hemodialysis at a tertiary medical center between 2005 and 2011. MRSA isolates were characterized by the methods of spa, multilocus sequence, and staphylococcal cassette chromosome mec (SCCmec) typing. Identification of virulence gene expression was measured by Power SYBR Green PCR Master Mix.ResultsOverall collected were 136 MRSA bacteremic isolates, including those from the cases of infective endocarditis (n = 23), bone/joint infection (n = 49), skin/soft tissue infection (n = 20), or catheter-related bacteremia in patients with acute kidney injury or end-stage renal stage receiving hemodialysis (n = 54). CC8-ST239-MRSA-SCCmec type III-spa type t037 was the most prevalent type observed in all of 136 MRSA bacteremic isolates. The prevalent genes in the group of infective endocarditis were clfA, clfB, fnbA, ebpS, eap, emp, sae, and eno; bone/joint infections clfA, emp, sae, and eno; skin/soft tissue infection eno; hemodialysis catheter-related bacteremia clfA and sae. The distribution of each gene was not statically different among four groups.ConclusionsA major MRSA lineage, CC8-ST239-MRSA-SCCmec type III-spa type t037, is noted among bacteremic MRSA isolates. No disease-specific virulent genes can be identified.     

G-CSF-Mobilized Blood and Bone Marrow Grafts as the Source of Stem Cells for HLA-Identical Sibling Transplantation in Patients with Thalassemia Major

As an inherited anemia, thalassemia major (TM) is currently only curable with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here we report an allo-HSCT protocol for patients with TM who received a combination of granulocyte colony-stimulating factor-primed bone marrow and peripheral blood stem cells (G-BM & PBSCs) from a matched sibling donor (MSD). The conditioning regimen consisted of i.v. busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin. Chimerism analysis was performed for all patients. Immunosuppressive treatment was terminated if rejection was suspected, and donor lymphocyte infusion was administered once no response was observed. A total of 184 patients with TM were enrolled in the study between July 2007 and July 2018. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 13.1%, and that of moderate or severe chronic GVHD was 5.7%. The cumulative incidence of graft rejection was .6%. In the total cohort, the 3-year overall survival, thalassemia-free survival, and GVHD-free, relapse-free survival were 97.8%, 97.3%, and 89.5%, respectively. Collectively, our results indicate that G-BM & PBSCs from an MSD is be a good stem cell source for patients with TM undergoing allo-HSCT.     

T follicular regulatory cells suppress Tfh-mediated B cell help and synergistically increase IL-10-producing B cells in breast carcinoma

T follicular regulatory (Tfr) cell is a recently discovered subset of T regulatory (Treg) cells. The main function of Tfr cells is thought to suppress germinal cancer reaction and inhibit B cell proliferation and Ig production. However, recent studies demonstrate that Tfr cells may be required for high-affinity Ig formation during acute virus infections. The role of Tfr cells in breast cancer is not thoroughly investigated. In this study, total circulating CD4 T cells were sorted into CD25⁺CXCR5⁻ Treg-like, CD25⁺CXCR5⁺ Tfr-like, and CD25⁻CXCR5⁺ Tfh-like subsets. Data showed that the Tfr-like subset presented intermediate levels of both Foxp3 and Bcl-6, while the Treg-like subset was high in Foxp3 and low in Bcl-6, and the Tfh-like was high in Bcl-6 and low in Foxp3. Of note, the frequencies of Tfr-like and Treg-like cells were significantly elevated in breast cancer (BC) patients than in non-cancer (NC) controls. Tfr-like cells in BC patients also expressed significantly higher levels of Foxp3 than those in NC controls. Neither Treg-like nor Tfr-like cells could support Ig production from naive B cells, while Tfh-like cells potently supported Ig production from naive B cells. Tfr-like cells increased the availability of IL-10, both by directly producing IL-10 and by increasing IL-10 production from B cells. Interestingly, Tfr-like cells increased IL-10 production from B cells synergistically with Tfh cells, but at the same time, significantly reduced Ig production in the Tfh-B cell coculture. These Tfr-mediated effects on Tfh cells were not found in canonical Treg cells. Overall, this study demonstrates several distinctive features in circulating Tfr cells and suggests that Tfr cells may promote the formation of IL-10-producing B cells in BC.

     

X-linked hyper-IgM syndrome complicated with interstitial pneumonia and liver injury: a new mutation locus in the CD40LG gene

Immunologic Research -     

Study on self-consciousness of children with learning disabilities and related factors

To study the self-consciousness of children with learning disabilities (LD) and to identify related factors. Methods Five hundred and sixty pupils graded from 1 to 6 in an elementary school were investigated. According to the pupil rating scale revised screening for learning disabilities (PRS), combined Raven‘s test (CRT) and achievement of main courses, 35 of 560 pupils were diagnosed as LD children. Thirty-five children were selected from the average children and 35 from advanced children in academic achievement equally matched in class, gender, and age with LD children as control groups. The three groups were tested by Piers-Harris children‘s self-concept scale. Basic information of each subject was collected by self-made questionnaire. Results Compared with the average and advanced children, LD children got significantly lower scores in self-concept scale. Based on logistic regression analysis, 3 factors were identified, including family income per month, single child and delivery model. Conclusion The results suggest that self-consciousness of children with LD is lower than that of normal children.     

Cost evolution of biological agents for the treatment of spondyloarthritis in a tertiary hospital: influential factors in price

Background Spending on biological agents has risen dramatically due to the high cost of the drugs and the increased prevalence of spondyloarthritis. Objective To evaluate the annual cost per patient and cost for each biological drug for treating patients with spondyloarthritis from 2009 to 2016, and to calculate factors that affect treatment cost, such as optimizing therapies by monitoring drug serum levels, the use of biosimilar-TNF inhibitors, and official discounts or negotiated rebates in biologicals acquired by the pharmacy department. Method Retrospective, observational study in a Spanish tertiary hospital. Main outcome Annual cost per patient and per drug. Factors that influenced the costs and socio-demographic parameters and disease activity. Results A total of 129, 215, and 224 patients were treated in 2009, 2013, and 2016, respectively. The annual cost per patient decreased: EUR11,604 in 2009, EUR8513 in 2013, and EUR7464 in 2016. The introduction of new drugs drives economic competition, leading to total savings per drug, with discounts reaching 5.8, 12.4, 16.7, 17.7, 13.7, and 24.8% for original infliximab, etanercept, adalimumab, ertolizumab, golimumab, and secukinumab, respectively, while rebates for biosimilar infliximab reached 31.90% in 2016. The number of patients with optimized therapies reached 47.5% in 2016, which led to cost savings of EUR798,614, in addition to savings from official discounts and rebates of EUR252,706 and savings from optimized therapies of EUR545,908 in 2016. Conclusion The cost of biological treatments declined after official discounts, negotiated rebates, and optimized therapies, leading to a significant decrease in the annual cost per patient. The greatest contribution to economic savings in biological therapy according to our study was biological therapy optimization.     

Evaluation of the effect of acetazolamide versus mannitol on cisplatin-induced nephrotoxicity,a pilot study

Background Cisplatin-induced nephrotoxicity still occurs despite the intensive hydration approach adapted to prevent its occurrence. Objective Evaluation of the effect of acetazolamide (ACTZ) on minimizing cisplatin-induced nephrotoxicity compared to mannitol when added to hydration regimen. Setting Nasser Institute Cancer Center (NICC), Cairo, Egypt. Method A total of 35 patients planned to receive cisplatin were divided into two groups: 20 patients received mannitol and 15 patients received ACTZ. Both groups received standard hydration measures as well for prevention of cisplatin-induced nephrotoxicity. Main outcome measure Patients’ kidney function was assessed using serum creatinine, creatinine clearance and blood urea nitrogen. Kidney injury was assessed using RIFLE criteria. Patients’ liver function tests and hematological parameters were also monitored. Results Patients in the mannitol group showed higher risk of developing kidney injury (30%) whereas those in the ACTZ group showed lower risk (8.9%), relative risk (RR) 0.269, 95% CI 0.108–0.815. No statistically significant difference occurred between the two groups concerning liver function tests or hematological parameters. Conclusion Use of ACTZ in addition to intensive hydration may have more beneficial effect on minimizing cisplatin-induced nephrotoxicity compared to mannitol plus intensive hydration approach. A large multicenter randomized clinical trials is recommended to confirm study results and to assess effect of ACTZ on tumor response.