Antimicrobial Resistance in Bacterial Species Causing Orthopaedic Surgical Site Infections at a National Trauma Center, Kathmandu, Nepal.

Hospital-acquired infections, including surgical site infections (SSIs), pose a concerning challenge because of the growing resistance to multiple drugs, largely influenced by extensive prophylactic antimicrobial therapy. Although SSIs are well documented in advanced hospitals in developed nations, their prevalence and bacterial profiles are inadequately reported in low- and middle-income nations such as Nepal. This retrospective cohort study explored the prevalence of orthopaedic SSIs in relation to bacterial etiology and antimicrobial resistance. We examined the surgical and bacteriological records of patients suffering SSIs (clean or clean-contaminated wounds) within a month of their surgical procedures between January 2020 and June 2022 at the National Trauma Center, Kathmandu, Nepal. The prevalence of orthopaedic SSIs among hospital-visiting patients was 31.2% (448/1,438; 95% CI: 28.8-33.5). There were 341 (76.1%) males and 361 (80.6%) adults with SSIs. Knee/joint infections (n = 141, 31.5%) were predominant. An SSI typically occurs 7 days after surgery. Enterobacterales were dominated by Escherichia coli (n = 54, 40.9%), whereas nonfermenters gram-positive cocci (GPC) were dominated by Pseudomonas aeruginosa (n = 69, 81.2%) and Staphylococcus aureus (n = 216, 93.5%), respectively. Enterobacterales, nonfermenters, and GPC exhibited penicillin resistance at 74.5%, 29.8%, and 65.1%, respectively, whereas cephalosporin resistance was exhibited at 48.3%, 57.1%, and 49.6%; fluoroquinolone resistance at 25.9%, 40.5%, and 25.7%; and aminoglycoside resistance at 21.5%, 43.2%, and 17.3%. One-third of orthopaedic surgeries resulted in SSIs, mainly caused by S. aureus. Fluoroquinolones and aminoglycosides were moderately effective in treating bacterial SSIs, whereas penicillins and cephalosporins were the least effective. Nonfermenters exhibited higher antimicrobial resistance compared with Enterobacterales and GPC.

Anterior Cruciate Ligament Reconstruction with Semitendinosus Tendon Autograft among Paramilitary Patients Undergoing Arthroscopic Surgery in a Tertiary Care Centre.

Introduction: In orthopaedic practice, injuries to the anterior cruciate ligaments occur almost on an epidemic scale, yet it continues to be of interest in orthopaedic surgery whether semitendinosus or gracilis hamstring autografts can be used for better anterior cruciate ligament reconstruction. This study aimed to determine the prevalence of anterior cruciate ligament reconstruction using semitendinosus tendon autografts among paramilitary patients undergoing arthroscopic surgery in a tertiary care centre. Methods: This descriptive cross-sectional study was conducted among paramilitary individuals who had knee injuries and were admitted between 6 february 2020 and 26 January 2022 for arthroscopic surgery after obtaining ethical approval from the Institutional Review Committee. Demographic details and the mode of injury were obtained from the patients. The treating orthopaedic surgeons evaluated the pre- and post-analysis Lysholm Knee Score and Lysholm Knee Scale based on the patient's response. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 166 patients, anterior cruciate ligament reconstruction using a semitendinosus tendon autograft was done in 58 (34.94%) (27.69-42.19, 95% Confidence Interval). Most of the patients in the pre-analysis had mild/periodic limp issues 52 (89.66%), followed by instability during athletics or other severe exertion 43 (74.14%). Conclusions: The prevalence of anterior cruciate ligament injuries in our study is higher than other studies done in similar settings. Keywords: anterior cruciate ligament; grafts; semitendinosus tendon.

Targeting activation-induced cytidine deaminase overcomes tumor evasion of immunotherapy by CTLs.

Activation-induced cytidine deaminase (AID) is an enzyme essential for the generation of Ab diversity in B cells and is considered to be a general gene mutator. In addition, AID expression was also implicated in the pathogenesis of human B cell malignancies and associated with poor prognosis. In this study, we report that small interfering RNA silencing of AID in plasmacytoma dramatically increased its susceptibility to immunotherapy by CTLs. AID silencing did not decrease the mutation frequencies of tumor Ag gene P1A. Gene-array analysis showed dramatically altered expression of a number of genes in AID-silenced plasmacytoma cells, and upregulation of CD200 was shown to be in favor of tumor eradication by CTLs. Taken together, we demonstrate a novel function of AID in tumor evasion of CTL therapy and that targeting AID should be beneficial in the immunotherapy of AID-positive tumors.

Cytokine-induced killer T cells kill immature dendritic cells by TCR-independent and perforin-dependent mechanisms.

Cytokine-induced killer (CIK) cells are ex vivo, expanded T cells with proven anticancer activity in vitro and in vivo. However, their functional properties with the exception of their cancer cell-killing activity are largely unclear. Here, we show that CIK T cells recognize dendritic cells (DC), and although mature DC (mDC) induce CIK T cells to produce IFN-gamma, immature DC (iDC) are killed selectively by them. Moreover, CIK T cell activation by mDC and their destruction of iDC are independent of the TCR. The cytotoxicity of CIK T cells to iDC is perforin-dependent. Our data have revealed an important regulatory role of CIK cells.

Different lineages of P1A-expressing cancer cells use divergent modes of immune evasion for T-cell adoptive therapy.

Tumor evasion of T-cell immunity remains a significant obstacle to adoptive T-cell therapy. It is unknown whether the mode of immune evasion is dictated by the cancer cells or by the tumor antigens. Taking advantage of the fact that multiple lineages of tumor cells share the tumor antigen P1A, we adoptively transferred transgenic T cells specific for P1A (P1CTL) into mice with established P1A-expressing tumors, including mastocytoma P815, plasmocytoma J558, and fibrosarcoma Meth A. Although P1CTL conferred partial protection, tumors recurred in almost all mice. Analysis of the status of the tumor antigen revealed that all J558 tumors underwent antigenic drift whereas all P815 tumors experienced antigenic loss. Interestingly, although Meth A cells are capable of both antigenic loss and antigenic drift, the majority of recurrent Meth A tumors retained P1A antigen. The ability of Meth A to induce apoptosis of P1CTL in vivo alleviated the need for antigenic drift and antigenic loss. Our data showed that, in spite of their shared tumor antigen, different lineages of cancer cells use different mechanisms to evade T-cell therapy.

CD24 controls expansion and persistence of autoreactive T cells in the central nervous system during experimental autoimmune encephalomyelitis.

In the development of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS), autoreactive T cells must be activated and clonally expand in the lymphoid organs, and then migrate into the central nervous system (CNS) where they undergo further activation. It is unclear whether the autoreactive T cells further expand in the CNS and if so, what interactions are required for this process. We have demonstrated previously that expression by the host cells of the heat-stable antigen (CD24), which was recently identified as a genetic modifier for MS, is essential for their susceptibility to EAE. Here we show that CD24 is essential for local clonal expansion and persistence of T cells after their migration into the CNS, and that expression of CD24 on either hematopoietic cells or nonhematopoietic antigen-presenting cells in the recipient is sufficient to confer susceptibility to EAE.