Abstract Introduction: Solid organ transplant recipients are at risk for coccidioidomycosis due to primary inoculation, reactivation, or donor derived mycosis. We present a case of disseminated coccidioidomycosis in a renal transplant recipient in the immediate post-transplant period, despite negative pre-transplant serology and guideline-based post-transplant prophylaxis. Case Presentation: A 36-year-old woman with remote history of treated latent tuberculosis and end-stage renal disease from IgA nephropathy underwent an en bloc deceased donor kidney transplantation. Nine days post-discharge and 17 days post-transplant, she presented with fever, malaise, cough productive of clear sputum, and right-sided pleuritic pain. She reported strict adherence to the prescribed immunosuppressant regimen (mycophenolate, tacrolimus, prednisone) and post-transplant infectious prophylaxis (atovaquone, fluconazole, and valganciclovir). On admission, her temperature was 102.7°F; otherwise, her vital signs were stable, and her lungs were clear to auscultation. Initial workup revealed elevated liver function tests, a normal white blood cell count, and a chest x-ray showing a 2cm right upper lobe (RUL) nodule. Computed tomography (CT) of the chest confirmed a nodular, necrotic 2x2cm RUL opacity with peribronchial wall thickening and right hilar lymphadenopathy. She was empirically treated with piperacillin-tazobactam and remained on prophylactic atovaquone and valganciclovir while awaiting serologic and sputum studies, including expectorated MTB-PCR. Her exposure history included travel to the Philippines, Idaho, California, and Colorado within the last 5 years. On day four, a positive 1,3-beta-D-glucan prompted the initiation of posaconazole. Repeat chest CT showed rapid enlargement of the RUL opacity with small cavitation, new subcentimeter opacities, increased lymphadenopathy, and enlarging right hilar soft tissue nodule (Figure 1). Pulmonology was consulted after the patient developed small volume hemoptysis and worsening pleuritic chest pain. Subsequent bronchoscopy confirmed Coccidioides on bronchoalveolar lavage culture. She was started on IV liposomal amphotericin B after blood and right hallux vesicle cultures confirmed fungemia and cutaneous involvement. Cerebrospinal fluid cultures were negative. She was discharged home on a prolonged course of voriconazole for disseminated coccidioidomycosis, with ongoing symptomatic and radiographic improvement. Discussion: Despite negative pre- and post-transplant serologies and fungal prophylaxis, this patient developed disseminated coccidioidomycosis less than three weeks post-transplant. Coccidioidomycosis develops in 1.4 – 6.9% of solid organ transplant recipients. Donor-derived Coccidioides typically presents within one month of transplant with severe infection and carries a mortality rate nearing 30%. Although routine fungal prophylaxis has reduced the incidence of disseminated disease, maintaining a high index of suspicion remains necessary for early identification and treatment.

Liver cirrhosis is the end stage of chronic liver disease, characterized by progressive fibrosis, architectural distortion, and impaired hepatic function. It arises from diverse etiologies including viral hepatitis, alcohol-associated liver disease, non-alcoholic fatty liver disease, autoimmune hepatitis, and cholestatic disorders. Complications such as portal hypertension, hepatic encephalopathy, ascites, and hepatocellular carcinoma significantly impact morbidity and mortality, particularly in decompensated stages. Early identification and etiology-specific treatment, including antiviral therapy, alcohol cessation, and metabolic management, are essential to slow progression. Multidisciplinary care, nutritional optimization, infection prophylaxis, and regular surveillance for hepatocellular carcinoma are key components of effective management. Liver transplantation remains the definitive therapy for selected patients with advanced disease. As global prevalence increases, there is an urgent need for integrated care models, improved access to treatment, and innovations in antifibrotic therapies. This review highlights current strategies and future directions in the comprehensive management of liver cirrhosis.

A multicenter, double-blind, placebo-controlled, randomized, comparative study of the efficacy and safety of Meglumine acridone acetate (enteric-coated tablets, 150 mg) for post-exposure prophylaxis of influenza and other acute respiratory viral infections (ARVI) in adults was conducted. The study was performed in 6 centers in Russia according to the permission of the Ministry of Health of Russia to conduct clinical study No. 418 dated August 8, 2023. A total of 578 male and female subjects aged 18—65 years were randomized to group I (taking Meglumine acridone acetate 4 tablets (600 mg) daily) or group II (taking placebo 4 tablets daily) according to the scheme on days 1, 2, 4, 6, 8. The results showed statistically significant superiority of Meglumine acridone acetate over placebo. The odds ratio of not getting sick after close contact with a first-order patient was 3.651 (95% CI 1.753; 7.602). In the context of the cost-effectiveness analysis, it was found that in group I (Meglumine acridone acetate), the average costs per patient, taking into account patient’s expenditures, were 8.5% lower, taking into account the government’s expenditures, were 19.8% lower, and taking into account all costs (society perspective), they were 15.9% lower compared to group II (placebo). Thus, the clinical and pharmacoeconomic efficacy of Meglumine acridone acetate (enteric-coated tablets, 150 mg) compared with placebo was shown, and a favorable safety profile of the study drug was established when used for post-exposure prophylaxis of influenza and other ARVI in adults.

Vancomycin is less effective than cefazolin at preventing periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). The purpose of this study was to quantify and compare the costs associated with vancomycin and cefazolin TKA prophylaxis. We used previously published PJI rates associated with vancomycin and cefazolin prophylaxis to create a model that captured the costs associated with these two options for antibiotic prophylaxis prior to TKA. The model included the cost of the antibiotic used, the cost of staff salaries in both preoperative holding and operating rooms, and the cost of a 2-stage septic TKA revision. National projections were used to account for future TKA volume. The average per-patient cost associated with cefazolin TKA PJI prophylaxis was $469.79, accounting for a PJI rate of 0.50%. The average per-patient cost associated with vancomycin TKA PJI prophylaxis was $ $1,640.22, accounting for a 1.00% PJI rate. This cost discrepancy could amount to nearly $4.0billion by 2040 given projections of TKA incidence. The per-patient cost associated with vancomycin TKA prophylaxis is 250% higher than cefazolin. This difference is due to the increased cost of primary treatment, labor costs associated with prolonged infusion time, and differential PJI rates. In an era of value-based care, cefazolin has been consistently demonstrated as the gold standard for TKA PJI prophylaxis and is associated with significant cost advantages.

Background. Infection caused by M. genitalium (MG) is classified as sexually transmitted infections (STIs). At the same time, MG infection is not currently registered at the state level, in this connection data on its prevalence in countries around the world can only be obtained from scientific publications. Objective. To analyze the publications on the epidemiology of MG infection in countries around the world between 2017 and 2024. Material and methods. The search for publications of the PubMed database according to «Mycoplasma genitalium prevalence» keywords during the period from 1988 to 2024 (date of search — 14.08.2024) was performed. A total of 961 publications were found for this date; we analyzed a number of relevant publications (86 in total) on the prevalence of MG infection in the world from 2017 to 2024. Results. MG causes urethritis in men and reproductive tract damage in women. The prevalence of MG in countries around the world in general is not very high and amounts to 1—3.3% men and women in the total population. The indicator of MG infection prevalence among persons from «risk groups» (commercial sex workers, MSM), patients of STIs clinics with symptoms of urethritis, cervicitis, PID is significantly higher, reaching 20—45%. Risk factors for MG infection are young age, early sexual activity, «risky» sexual behavior (sexual promiscuity, neglect of barrier contraception, receptive anal sex), alcohol addiction, smoking, presence and pre-exposure prophylaxis of HIV infection, co-infection by other causative agents of STIs (e.g., C. trachomatis, N. gonorrhoeae), past history of STIs, abnormal vaginal microecology.

Secondary immunodeficiencies are clinically challenging and emphasize the need for a multidisciplinary approach. Our case underscores the importance of understanding the potential impact of B cell–targeting therapies, such as Bruton tyrosine kinase (BTK) inhibitors, on immune function, opportunistic infection prophylaxis, and clinical management. A 55-year-old male with a history of systemic lupus erythematosus (SLE) on hydroxychloroquine, antiphospholipid antibody syndrome on warfarin, anal cancer s/p resection, long-standing splenomegaly, and lymphadenopathy with unremarkable core needle biopsy in 2018 was diagnosed with marginal zone lymphoma via excisional lymph node biopsy in 2023. His clinical course was complicated by a hospitalization for septic shock secondary to Streptococcus agalactiae bacteremia and during this admission he was found to have significant immunodeficiency characterized by low T-lymphocyte counts (in cells/μL): CD3+ 141, CD4+ 65, and CD8+ 65, as well as low IgG levels 510 mg/dL (CD19 counts not obtained). Of note, he had persistent lymphopenia (0.06 to 0.49 cells/μL) and intermittent neutropenia (1.26-1.72 cells/μL) since 2009. After starting rituximab for lymphoma, he developed severe neutropenia (0.47 cells/μL), Candida esophagitis (requiring transient PEG tube placement), and a left ethmoid and sphenoid sinus abscess and orbital cellulitis due to Aspergillus fumigatus. Given the severe side effects and disease progression after rituximab, he was transitioned to a selective BTK inhibitor, zanubrutinib. For Pneumocystis jiroveci (PCP), antiviral and antifungal prophylaxis, he receives dapsone, acyclovir, and voriconazole, respectively. He has remained infection free since initiating zanubrutinib despite persistent lymphopenia (in cells/μL: CD3+ 147-183, CD4+ 74-108, CD8+ 48-62, CD19+ 8). His IgG levels improved to 700-800 mg/dL. His most recent PET scan showed stable disease. Notably, genetic testing was nondiagnostic. Our patient’s secondary immunodeficiency is multifactorial from SLE, lymphoma, and rituximab. The impact of selective BTK inhibitors on immune function is not well studied. Ibrutinib, a first-generation BTK inhibitor, improves T cell exhaustion with treatment of B cell lymphomas; similar findings were not observed for zanubrutinib, although studies are limited. Furthermore, recommendations on opportunistic infection prophylaxis often rely on data from HIV patients, yet it is unclear if the immune dysfunction is similar in individuals with non-HIV immunodeficiencies.

Background X-linked chronic granulomatous disease (XLCGD) is a rare inborn error of immunity (IEI) associated with infections, inflammation, and autoimmunity. Female carriers of XLCGD experience similar symptoms due to skewed X-chromosome inactivation (lyonization). National registries for IEI currently do not capture XLCGD carriers, creating deficiencies in understanding prevalence, clinical manifestations, complications, management, and long-term outcomes. We developed a patient survey to collect clinical and laboratory data to address these current gaps. Methods Thirteen XLCGD carriers were recruited to complete a REDCap® survey. Data collected included demographics, clinical symptoms, infections, autoimmune conditions, laboratory details, family history, and treatment, including antimicrobial and immunomodulatory medications. Dihydrorhodamine (DHR), used to assess neutrophil function, was collected when available. Results Symptoms were reported in 11 of 13 (84%) participants. The median age was 54.0 (range: 22-78) years. In those symptomatic, the age of symptom onset was median 13.8 years (range: 0.4-52) and duration of symptoms averaged 39 (range: 24.9-52.3) years. The most common symptoms were infection in 11 of 13 (84%), including pneumonia (n = 5), skin abscess (n = 7), cellulitis (n = 3), organ abscess (n = 1), lymphadenitis (n = 2), and urinary tract infections (n = 7). Serratia marcescens (n = 1), Staphylococcus aureus (n = 1), and Prevotella species (n = 1) were isolated from skin abscesses. Five (41%) participants received infection prophylaxis, including trimethoprim-sulfamethoxazole (n = 5), itraconazole (n = 3), and interferon gamma-1b (n = 1). One subject declined interferon gamma-1b due to insurance concerns. Autoimmunity was noted in 9 of 13 (69%) participants, including inflammatory bowel disease and photosensitive rash (both present in 25% of patients), and less commonly oral ulcers, rheumatoid and psoriatic arthritis, uveitis, celiac disease, pyoderma gangrenosum, lupus, Raynaud phenomenon, and autoimmune thyroid disease. The median DHR, available in 4 patients, was 9% (range: 6-33.5%) in those with infections (n = 3) and 52% in the asymptomatic participant. Conclusion To our knowledge, this is the first national patient registry for XLCGD carriers. The majority of XLCGD carriers were symptomatic, had a long duration of symptoms, and had a high symptom burden including infections and autoimmunity. A lower DHR percentile was associated with increased infections. Management often included antimicrobial prophylaxis. Recruitment is ongoing, and a larger cohort size is needed to expand these findings.

Our patient is a 21-month-old male, born in Texas to consanguineous parents from Afghanistan. He presented as a newborn with petechiae, severe thrombocytopenia, and hepatitis. Family history was notable for two female siblings who had died in infancy and early childhood, one with neonatal thrombocytopenia and hemorrhage, the other with pulmonary hemorrhage and renal failure due to large vessel vasculitis. Our patient had an extensive workup which ruled out neonatal alloimmune/autoimmune thrombocytopenia, infection, and hemophagocytic lymphohistiocytosis. Bone marrow biopsy was unrevealing. Liver biopsy showed diffuse, spotty hepatocyte necrosis, rare foci of lobular neutrophilic, and periportal lymphocytic infiltration. He met clinical and histologic criteria for autoimmune hepatitis. He was given IVIG and started on dexamethasone. The thrombocytopenia responded partially and the hepatitis worsened. Whole-exome sequencing identified a homozygous mutation in ACP5 (p.H205Y) which was predicted to be deleterious and was not found in population databases. ACP5 deficiency causes spondyloenchodrodysplasia with immune dysregulation (SPENCD-I), a type 1 interferonopathy. This has been associated with neonatal thrombocytopenia and other autoimmune manifestations. The serum interferon alpha level and type 1 interferon response signature were found to be elevated. We therefore initiated baricitinib at 1 mg every 12 hours and continued steroids. Thrombocytopenia normalized. The hepatitis responded only partially, and we were unable to wean steroid (Figure 1). Furthermore, the type 1 interferon signature continued to be very elevated. Figure 1. We then initiated anifrolumab at 5.5 mg/kg/month intravenously and overlapped with baricitinib and systemic steroid. Two months after initiation of anifrolumab, the patient’s interferon signature normalized, liver function normalized, platelet count has remained normal, and we have been able to wean systemic glucocorticoid by over 10-fold. We are in the process of weaning baricitinib. The patient has thus far had no adverse effects from this medication regimen. He is on acyclovir and pentamidine for infectious prophylaxis, along with regular PCR monitoring for EBV, CMV, and BK virus. There is a paucity of published experience with baricitinib and anifrolumab in this age-range. This case demonstrates the safe and effective use of these medications in this young child with SPENCD-I, a severe type 1 interferonopathy.

BackgroundThe advanced disease management (ADM) package, which aims to reduce morbidity and mortality in people with Advanced HIV disease (AHD, WHO stage III/IV and/or CD4 count < 200 cells/mm3 or age < 5 years), is not fully implemented in India. We assessed the feasibility of implementing the full WHO ADM package as part of routine HIV care under the programmatic setting in antiretroviral therapy centers of Mumbai.MethodsWe implemented the ADM package (screening, treatment, and prophylaxis for major opportunistic infections, rapid ART initiation, and ART adherence support) in 17 ART centers from October 2020 to December 2021. Treatment naïve and experienced persons with AHD, including children, were enrolled. We assessed the feasibility through coverage of ADM package components and reported the proportion of rapid ART initiation (≤ 7 days), cotrimoxazole prophylaxis, TB preventive treatment (TPT) for those eligible [(excluded active TB disease (n = 280) and those completed TPT prior to enrolment (n = 1,186)], TB-LAM screening (excluded current TB disease), and cryptococcal antigen (CrAg) assay (excluded children < 10 years of age). We used a point of care test for TB (LAM) and cryptococcus (CrAg) screening. We followed the prospective cohort for one year (through 31 July 2022) to document outcomes for survival and lost to follow- up (LTFU).ResultsWe identified 4,334 PLHIV with AHD and provided the full ADM package to 64% (2,779/4,334); 297 did not receive ADM (146 died, 151 LTFU), and 1,258 received routine standard of care (587 had TB, 366 were at decentralized sites, and 305 LAM/CrAg kits were not available) with existing ART center staff. Nearly 78% (385/494) of treatment naïve were rapidly initiated on ART. Nearly 82% (1,129/1,383) and 99% (2,751/2,779) received TPT and cotrimoxazole prophylaxis, respectively. Of the eligible, 99% (2,508/2,524) and 98% (2,715/2,758) were screened for TB and cryptococcal infection, respectively. At the end of 12 months, 88% (2,458/2,779) were alive, 8% (210/2,779) died, and 4% (111/2,779) were LTFU. Mean survival time was significantly (p < 0.001) higher among treatment experienced people; 11.6 months (95% CI: 11.5,11.7) compared to treatment naïve people 10.8 months (95% CI: 10.5,11.0).ConclusionWith careful anticipatory planning, stakeholder engagement, and training, implementing the full ADM package is feasible in a routine program setting with existing human resources. Additional intensive case management may be necessary for the reduction of mortality among treatment naïve PLHIV.

Emergencies among adult travelers are numerous and clearly outsidethe scope of usual pre-travel consultations (vaccinations, infectious and/or tropical disease prophylaxis). No prospective studies have addressed this issue, and rare retrospective studies report trauma in 40 % of cases and non-transmissible medical emergencies in 60 % of cases. In-flight emergencies, traffic accidents, as well as environmental (altitude, carbon monoxide) and behavioral (selfies, alcohol consumption, medical tourism) injuries warrant attention. Finally, at-risk travelers should receive special counseling and be encouraged to purchase medical and evacuation insurance prior to travel.

In cases of complex proximal humeral fractures a fracture prosthesis is an established treatment option. In the geriatric patient population, the use of reverse total shoulder arthroplasty is gaining in relevance. This article focuses on the specific requirements and challenges associated with the application of reverse total shoulder arthroplasty. Decisive for the success are a structured perioperative management, meticulous preoperative planning, thorough patient education and standardized protocols for infection and bleeding prophylaxis. Intraoperatively, emphasis is placed on precise implantation techniques and stable tuberosity fixation, of which the latter is essential for postoperative function. Ahumeral inclination of 135° has been shown to be associated with better tuberosity healing. Complications, such as scapular notching or instability can be minimized through an accurate surgical technique and optimized implant management. Postoperative care is tailored to the individual, employing either ashoulder abduction brace or an early functional rehabilitation approach. Overall, reverse shoulder arthroplasty provides an effective fracture treatment for geriatric patients, ensuring long-term functional and clinical benefits.

Recurrent urinary tract infections (rUTIs) are typically treated using antibiotics. Given the growing issue of antimicrobial resistance, non-antibiotic management options for rUTIs have faced a recent resurgence in popularity. Methenamine hippurate is a urinary antiseptic used as a non-antibiotic prophylactic measure in those with rUTIs. The results of a recent randomised controlled trial showed methenamine hippurate to perform on par with antibiotic prophylaxis in adult women with rUTIs. However, little is known about the efficacy of methenamine hippurate in vulnerable patient populations, such as children, the elderly, patients with indwelling catheters and those with renal tract abnormalities. Moreover, an up-to-date, comprehensive evaluation of the entirety of the literature surrounding methenamine hippurate has yet to be carried out. As such, key trends within the literature, such as common side effects and specific avenues for future research, are difficult to determine. Therefore, we developed the methodology for a scoping review to map the entirety of the existing evidence base for methenamine hippurate. The protocol for this scoping review was developed in accordance with the framework set out by Arksey and O'Malley. We will search MEDLINE, Embase, Scopus, the Cochrane Central Register of Controlled Trials and ProQuest Dissertation and Theses from inception until August 2024, with no language restrictions applied. Studies including patients of any age and sex receiving methenamine hippurate treatment, either as a primary or adjunct treatment for rUTIs, will be eligible for inclusion. Interventional studies, such as randomised controlled trials and their protocols, non-randomised clinical trials, cohort studies, case-control studies and observational studies of any design, will be included. Grey literature, systematic reviews and qualitative studies will also be included. Two independent reviewers blinded to each other's decisions will assess the eligibility of articles at each stage using the Covidence review platform. After the relevant data from each study has been extracted, we will report the results of our scoping review using descriptive summary statistics and a narrative thematic analysis. Due to the nature of the present study, ethical approval was not required for this scoping review. The final manuscript of this scoping review will be published in an international, peer-reviewed journal and the findings of the review presented in relevant national and international conferences.

Abstract Background/Aims Rituximab is associated with an increased risk of infection, highest in the weeks following infusion. We sought to establish UK clinicians’ approach to reducing this infection risk when prescribing rituximab in patients with systemic lupus erythematosus. Methods A standardised survey was devised by a rheumatologist and pharmacist working group using a web-based platform. Rheumatology and renal clinicians and pharmacists across the UK were asked to complete a survey in subject areas not covered by the current British Society of Rheumatology (BSR) SLE treatment guideline. It was deployed by email to 64 centres registered as contributors to British Isles Lupus Assessment Group Biologics Register (BILAG-BR) and posted on website forum of Rheumatology Pharmacists UK (RPUK) group. The information collected was assessed for common themes and differences in practice. Results 52 respondents (17%) of potential 304 (214 BILAG, 90 RPUK) responded. Most centres undertook pre-rituximab screening, with Hepatitis B/C serology (100%), immunoglobulin profile (96%), HIV (92%), tuberculosis (TB) (77%) and chest X-ray (89%) were most frequent tests. A small minority tested serology for COVID (2%), EBV (4%) and CMV (8%). Testing an immunoglobulin profile varied between ‘before every 1st dose of a 2-dose rituximab course’ (56%) to ‘regularly every 12 months’ (6%) regardless of when rituximab was administered. T/B cell subsets testing before/after rituximab courses varied, with a third of respondents never testing. Two-thirds (65%) only tested hepatitis B, C and HIV prior to 1st 2 doses of rituximab and did not repeat before subsequent courses. Pneumococcal (96%), influenza (94%) and COVID (94%) were most frequently recommended vaccinations given 2-4 weeks before commencing rituximab. However, there was no consensus when these vaccines should be given once rituximab treatment commenced, ranging from ‘after 3 months’ to ‘not at all’. Overall, 56% would prescribe infection prophylaxis alongside rituximab. Of these, co-trimoxazole (42%) was most frequently used agent. Only 19% of respondents would pause DMARDs during a course of rituximab. Mycophenolate (21%) was the most likely DMARD to be paused during rituximab treatment. A third of respondents (37%) told patients to omit oral steroids (if taking) on the day rituximab dose was administered to avoid excessive steroid exposure during dosing. Rituximab drug counselling was provided by all respondents, varying between consultant (73%), specialist nurse (81%), or pharmacists (35%). Conclusion This study demonstrates a wide variation of clinical practice in prevention of infection associated with the prescribing of rituximab for SLE in the UK, reflecting a lack of clear national guidance. Further research is needed to explore clinical practice gaps and areas highlighted to address with future updates of UK SLE national guidelines. Disclosure V. Reid: Grants/research support; Pharmacy Research UK PRUK-2019-TB-L3-4-VR. D. Steinke: None. B. Parker: None.

Antimicrobial wound lavages containing chlorhexidine gluconate (CHG) or povidone-iodine (PI) are commonly used for infection prophylaxis in arthroplasty surgery, including shoulder arthroplasty. However, the potential toxicity of these solutions to the surrounding native tissue, including rotator cuff tendons, is not well understood. The purpose of this study was to investigate the ex vivo effects of a 1-minute 0.05% CHG exposure and a 3-minute 0.35% PI exposure on the viability and biochemical content of rotator cuff tendon explants. Infraspinatus tendons (n = 6 per group) were isolated from the shoulders of Nubian goats. Tendons were submerged in 0.05% CHG in sterile water for 1 minute or 0.35% PI for 3 minutes per manufacturer guidelines, followed by phosphate-buffered saline (PBS) wash and culture in tissue medium. Control tendon specimens were bathed in PBS solution for 1 minute, followed by PBS wash and culture in tissue medium. Seven days after exposure, isolates from both the tendinous and enthesis portions were analyzed for tenocyte viability, biochemical content (collagen and glycosaminoglycan [GAG]), and matrix histology. Within the tendinous portion of the tendon, CHG and PI exposure led to reduced mean tenocyte viability compared to controls (4.35% ± 4.64% viability in the CHG group, P = .045; 14.4% ± 20.3% viability for the PI group, P = .097; vs. 35.4% ± 28.4% viability in the control group). Within the enthesis, CHG and PI exposure led to smaller and nonsignificant decreased mean tenocyte viability compared to controls (29.5% ± 22.9%, P = .336 for CHG; 37.5% ± 29.4%, P = .327 for PI). There were no significant differences in mean collagen content/wet weight or GAG/wet weight among groups within the tendinous and enthesis isolates, nor were there any appreciable differences on histology in collagen and GAG distribution among groups. Brief 0.05% CHG and 0.35% PI exposures to rotator cuff tendon may lead to reduced tenocyte viability, with the tendinous portion seemingly more susceptible than the enthesis. Additionally, at these concentrations tested, CHG appears to be more toxic than PI. These findings raise concern for the potential cytotoxic effects of low-dose CHG and PI on native tendon tissue, even after brief exposures commonly used for antimicrobial prophylaxis in shoulder arthroplasty.

The risk of regional analgesia catheter-related infections in immunocompromised patients remains uncertain. We therefore tested the hypotheses that catheter-related infections appear earlier and are more severe, and that antibiotic prophylaxis is more effective in immunocompromised than immunocompetent patients. Data were extracted from the Network for Safety in Regional Anesthesia and Acute Pain Therapy (net-ra) registry from 2007 to 2022. We used multivariable cox and ordinal regression to assess the effect of immune function and antibiotic prophylaxis indicated by surgery on infection onset and severity. We analyzed data from 196,711 catheters, including 1347 in immunocompromised patients. Infection severities in immunocompetent patients were none (190,220 (97.4%)), mild (4517 (2.3%)), and moderate/severe (627 (0.3%)). In immunocompromised patients, infection severities were none (1285 (95.4%)), mild (58 (4.3%)), and moderate/severe (4 (0.3%)). Immunocompromised patients who were not given antibiotics had a 29% greater infection hazard (HR 1.29 [95%CI: 0.95, 1.76], p=0.1) and 91% greater odds of higher infection severities (OR 1.91 [95%CI: 1.39, 2.63], p<0.001). Antibiotics were more effective in delaying infection onset (HR 0.65 [95%CI: 0.38, 1.12], p=0.12) and preventing infection (OR 0.54 [95%CI: 0.31, 0.94], p=0.029) in immunocompromised than immunocompetent patients. The number of patients needed-to-treat to prevent an infection with antibiotics was 55 in immunocompromised patients versus 83 in immunocompetent patients. Regional analgesia catheter-related infections occur slightly earlier and are more frequent in immunocompromised patients. Antibiotics are marginally effective for catheter infection prophylaxis and should be restricted to patients who are severely immunocompromised with and at special risks.

Invasive fungal infections (IFIs), particularly Candida infections, are a significant cause of morbidity and mortality in patients with acute leukemia. While fluconazole is widely used for prophylaxis, the optimal dosing regimen remains uncertain. This study aimed to evaluate the efficacy of low-dose fluconazole for primary prophylaxis against invasive Candida infections in patients with acute leukemia receiving intensive chemotherapy. A double-blind, randomized clinical trial was conducted with patients diagnosed with acute leukemia. Patients were assigned to receive either low-dose (150 mg/day) or standard high-dose (400 mg/day) fluconazole for primary prophylaxis against invasive Candida infections during intensive chemotherapy. The primary outcomes were the efficacy of antifungal prophylaxis and the safety profile. A total of 120 patients (60 per group) were enrolled. The overall incidence of Candida infections was similar between the groups (p = 0.615). Candida colonization was higher in the low-dose fluconazole group during the first week, particularly with non-albicans Candida at oral and subaxillary sites (p < 0.001). However, by the third week, both groups showed a significant decline in colonization, with the reduction in the oral cavity being statistically significant (p = 0.03). Aspergillosis occurred in 38.3% of patients, with no significant difference between groups (p > 0.99). Adverse events were similar in both groups (p > 0.05). Low-dose fluconazole is an effective alternative to high-dose regimens for preventing Candida infections in acute leukemia patients, with similar efficacy and safety. The rising threat of aspergillosis highlights the need for targeted prophylaxis. Further research is needed to refine strategies for high-risk patients. Iranian Registry of Clinical Trials (IRCT) number: IRCT20140818018842N37.

Valaciclovir is frequently prescribed for cytomegalovirus infection prophylaxis. Its major metabolite 9-carboxymethoxymethylguanine (9-CMMG), when accumulated in renally impaired patients, is neurotoxic. Its synthesis involves enzymes that could be impacted in liver transplant recipients. This retrospective study aimed to describe the pharmacokinetic (PK) and safety profile of aciclovir and 9-CMMG early after liver transplantation in patients receiving valaciclovir prophylaxis. Consecutive (ideally five) blood samples were drawn. Plasma concentrations of aciclovir/9-CMMG were quantified by UPLC-MS/MS. Medical data were collected from digital records. A joint population PK model for aciclovir/9-CMMG was developed (Monolix 2023R1). Monte Carlo simulations were used to estimate Cmin and AUC0-24. Fifty patients (21 women) in the postoperative phase of liver transplantation were enrolled, with median age of 56.0 years and median weight of 69.5 kg; 255 samples were collected 19.0 days after transplantation. No drug-drug interaction was reported. A one-compartment model with first-order absorption best described the pharmacokinetics (PK). Covariate analysis showed that aciclovir and 9-CMMG clearances correlated with estimated glomerular filtration rate (eGFR). In normorenal patients, receiving valaciclovir 2000 mg q8h, estimated AUC0-24 values were 44.8 and 13.3 mg·h/L for aciclovir and 9-CMMG, respectively. The median estimated metabolic ratio of AUC0-24 (9-CMMG/aciclovir) was 30.4% and 129.9% for patients with >90 and <30 mL/min/1.73 m2 eGFR, respectively. There were no valaciclovir-related adverse events during hospitalization. This model allowed the PK and basal metabolic ratio of aciclovir and 9-CMMG in early liver transplantation to be defined. The correlation with renal function suggests important implications for therapeutic drug monitoring of these compounds, which will need confirmation in different cohorts.

An outbreak of mpox has triggered concerns regarding the adequacy of intervention strategies. Passive immunity conferred by neutralizing antibodies exhibits potential in the prophylaxis and treatment of orthopoxvirus infections. Despite this, the investigations of effective antibody therapeutics have been hindered by the varied nature of orthopoxvirus envelope proteins and the intricate mechanisms underpinning viral invasion. Our study involves the production of six mpox virus (MPXV) envelope proteins, which are relatively conservative and considered to play a role in the neutralization process. We employed a synthetic nanobody (Nb) library to derive a broad array of specific Nbs against these viral proteins. We identified a cross-reactive Nb, termed M1R-01, which targets the M1R protein and effectively neutralizes both vaccinia virus (VACV) and MPXV. Notably, the M1R-01-based antibody strategy provided optimal protection against a lethal VACV challenge in mice. Additionally, we determined the crystal structure of the M1R–Nb complex, uncovering novel binding attributes of M1R-01 and detailed conformational epitope information. This work provides a promising candidate for the therapy and prophylaxis of orthopoxvirus infections.

Background and purposePeriprosthetic joint infection (PJI) after elbow arthroplasty is a serious complication. Evidence of the best antibiotic prophylaxis for elbow arthroplasty is lacking. We aimed to investigate the regimens presently used in Sweden, incidence of PJI, and the bacteria most frequently found in elbow PJI.MethodsA questionnaire was sent out to all Swedish units performing elbow arthroplasty in 2019 asking about antibiotic prophylaxis routines. The Swedish Elbow Arthroplasty Register (SEAR) and national inpatient and outpatient registers (NPR) from the National Board of Health and Welfare were searched for procedures related to all primary total- or hemi-elbow arthroplasties performed during 2019–2021. Results of microbiological analyses of the suspected PJI cases were collected from the respective laboratory.ResultsMost centers used only cloxacillin (44%) or cloxacillin together with benzylpenicillin (44%), as prophylaxis. 250 primary procedures were performed between 2019 and 2021, and the most used antibiotic prophylaxes were cloxacillin (61%) and cloxacillin with benzylpenicillin (23%). In the NPR, 20 patients (8%) with a diagnosis that could indicate PJI were found and 9 (3.6%) had a confirmed PJI. The most common bacteria were Staphylococcus epidermidis, Cutibacterium acnes, and Staphylococcus aureus.ConclusionMost centers used cloxacillin antibiotic prophylaxis for elbow arthroplasty. The incidence of PJI was 3.6%. The most frequent diagnosed pathogen was Staphylococcus epidermidis.

Cytomegalovirus (CMV) infection is a common and life-threatening complication following allogeneic haematopoietic stem cell transplantation (allo-HSCT). Letermovir (LET) has been the standard prophylaxis for adult recipients, but studies in children remain limited. We retrospectively analyzed children with or without LET prophylaxis after haploidentical donor (HID) for the Beijing protocol or unrelated cord blood (UCB) transplantation. Of the 151 patients, 67 received LET, including 35 HID recipients and 32 UCB recipients. During the 180 days after transplantation, we found that the LET group had a lower incidence of clinically significant CMV infection (csCMVi) than the non-LET group (13.4% vs.56.0%, P＜0.001). In the LET group, later LET administration was identified as a risk factor for the occurrence of csCMVi (HR: 1.07, 95% CI: 1.01 - 1.14, P=0.029). Further, the HID subgroup had a lower incidence of csCMVi during follow-up than the UCB subgroup (2.9% vs.25.0%, P=0.009). In terms of safety, the incidence and severity of adverse events, overall survival, cumulative incidence of relapse, relapse free survival, nonrelapse mortality and graft versus host disease-free, relapse-free survival were similar between the two groups. LET is effective and safe in preventing csCMVi among Chinese children undergoing allo-HSCT. Compared to UCB recipients, children undergoing HID transplantation for the Beijing protocol develop less scCMVi up to 180 days post-HSCT.