Prophylaxis Therapy Research Articles

The Use of External Beam Radiation Therapy for Heterotopic Ossification Prophylaxis After Surgical Fixation of Acetabular Fractures: A Randomized Controlled Trial.

To determine the effect of external beam radiation (XRT) on preventing severe heterotopic ossification (HO) after acetabular surgery. Randomized controlled trial. Two level I academic trauma centers. Patients with an acetabular fracture (OTA/AO type 62) surgically treated through a posterior or combined anterior and posterior approach. Radiographic HO was determined using Brooker Classification at the last follow-up. The primary outcome was severe HO (Brooker classes III-IV). The secondary outcome was any HO (Brooker classes I-IV). The incidence of radiographic HO was compared between patients who did and did not undergo postoperative XRT. The results were analyzed in both an intention-to-treat (randomized to XRT) and as-treated (received XRT) basis. Severe HO occurred in 3 of 54 (6%) patients randomized to XRT and 9 of 50 (18%) patients randomized to no XRT (odds ratio 0.24, 95% confidence interval, 0.05 to 0.94; P = 0.05). Any HO occurred in 10 (19%) patients assigned to XRT and 17 (34%) patients in the no XRT control group (odds ratio 0.39; 95% confidence interval, 0.13 to 1.05; P = 0.07). The findings of this dual-center randomized controlled trial suggest that XRT after acetabular surgery significantly reduced the odds of severe HO compared with patients who did not receive XRT. These results can help guide shared decision making between surgeons and patients regarding the use of XRT for HO prophylaxis. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Effectiveness of a Pharmacist-Led Intervention to Reduce Acid Suppression Therapy for Stress Ulcer Prophylaxis in ICUs in China: A Multicenter, Stepped-Wedge, Cluster-Randomized Controlled Trial.

This study aimed to evaluate the effectiveness of a pharmacist-led intervention in decreasing the overuse of stress ulcer prophylaxis (SUP) compared with the usual care for adult patients in Chinese ICUs. Pragmatic, multicenter, stepped-wedge, cluster-randomized controlled trial. Twenty-six ICUs in China from October 2022 to March 2023. We enrolled 2199 patients 18 years old or older who were newly admitted to the participating ICUs. Using the Medical Research Council framework for developing and evaluating complex intervention measures, a multidisciplinary team (Scenarios, Improving and Refining Interventions, Constructing, Refining and Testing Research Theories, Incorporating Stakeholders, Identifying Important Uncertainties, and Economics Considerations) designed a multifaceted intervention. The primary outcomes were the proportion of patients receiving SUP and that with overt gastrointestinal bleeding. We conducted intention-to-treat analyses using generalized linear mixed models to adjust for potential confounders (age, sex, and acute physiology and chronic health evaluation II score) with random effects for the site. The proportion of patients receiving SUP in the intervention group was lower than that in the control group (45.5% vs. 49.5%; odds ratio [OR], 0.81; 95% CI, 0.68-0.96; p = 0.017). The proportion of patients with overt gastrointestinal bleeding was similar (3.7% vs. 4.0%; OR, 1.05; 95% CI, 0.65-2.85; p = 0.81). The pharmacist-led intervention reduced the proportion of patients receiving SUP in the ICUs, without significantly affecting the proportion of patients with overt gastrointestinal bleeding. These findings will help guide ICU medical decision-making.

P-1921. Risk Factors for Hospitalization due to COVID-19 in the Current Era of the Pandemic

Abstract Background Certain risk factors place SARS-COV-2 infected individuals at a higher risk of hospitalization and death. While increased vaccination rates and herd immunity have decreased the overall risk of hospitalization and death from COVID-19, some groups of patients may still be at significant risk of morbidity and mortality from COVID-19. However, this population has not been well-described. This study sought to understand the current landscape of patients hospitalized due to COVID-19 to gauge who would most benefit from pre-exposure prophylaxis and other therapies for COVID-19.Table 1:Demographics.Demographics of patients admitted to hospital due to COVID-19.*Immunosuppression defined as having at least one of the following: hematologic malignancy, solid organ transplant, bone marrow transplant, metastatic cancer, asplenia, HIV with CD4 count < 200, other immunosuppressive disease with impaired humoral or cell-mediated immunity, or immunosuppressive medication including corticosteroids (prednisone ≥ 2mg/kg/day or ≥ 20 mg/day or equivalent dose of other corticosteroid) for > 14 days, chemotherapy within past 3 months, calcineurin inhibitor, anti-proliferative agent, mTOR inhibitor, B-cell or T-cell depleting medication, or TNF-alpha inhibitor. Methods This was a retrospective study of adults admitted to a single center for a COVID-19-related reason from August 4, 2023, through February 5, 2024. All admitted patients with a positive SARS-CoV-2 test were identified; patients who were admitted for a non-COVID-19 related reason were excluded from manual chart review. Patient demographic information, vaccination status, risk factors, symptoms, hospital course, and treatment interventions were collected. These data were then analyzed and descriptively characterized.Table 2:OutcomesClinical outcomes of patients admitted to hospital due to COVID-19. Results Of the 408 patients identified who were hospitalized for a COVID-19-related reason during the study period, the median age was 70 years (IQR 60 – 81) with a median length of stay of 5 days (IQR 3-8). Only 13% of patients were up to date on their COVID-19 vaccination at their time of admission (Table 1). Admitted patients had a median of 3 (IQR 2 – 4) risk factors for severe infection, and 26.5% of patients were noted to be immunosuppressed (Table 1). Nearly half of all patients did not require supplemental oxygen during their stay (47%); 38% required only low flow nasal cannula (Table 2). There was a 7.8% 90-day mortality rate. Conclusion These data suggest that most admitted patients in the current COVID-19 era have multiple risk factors and are under-vaccinated. This high-risk population may benefit from updated vaccination, pre-exposure prophylaxis, and/or other therapies to reduce the morbidity from COVID-19. Disclosures Kathleen Degnan, MD, Gilead: Grant/Research Support Amanda Binkley, PharmD, BCIDP, AAHIVP, Viiv: Advisor/Consultant

P-1878. Intravenous Ganciclovir Administration Outcomes via an Outpatient Parenteral Antimicrobial Therapy (OPAT) Program

Abstract Background Intravenous (IV) ganciclovir is used in the management of herpesvirus infections including cytomegalovirus (CMV). Ganciclovir is usually administered in the inpatient setting given the need for close monitoring of hematologic and renal parameters. This study describes our experience with IV ganciclovir administration in immunocompromised hosts, via an OPAT program at a tertiary academic medical center. Ganciclovir was chosen as choice of therapy either due to concern for GI absorption, or provider preference. Methods This is a retrospective, single-center review of patients discharged on IV ganciclovir via OPAT from August 2019 to December 2023. Patient demographics, underlying diagnoses, indication for ganciclovir, duration of therapy, treatment outcomes and adverse events were collected. Results We included 18 patients whose mean age was 58.6 (SD±12.4) years, with ten (55.6%) being male. The most common underlying immunocompromising condition was receipt of a transplanted organ in 15 (83.3%) patients, including five and ten recipients of hearts and kidneys, respectively. The mean duration of therapy was 25 (SD±11) days. In our cohort, 13 were treated for CMV disease as follows; 11 patients with gastrointestinal involvement and two patients with encephalitis/retinitis. Four patients had isolated viremia and one patient was treated for Epstein Barr Virus encephalitis. A majority (13 patients, 72.2%) transitioned to valganciclovir on completion of parenteral therapy for secondary prophylaxis or to continue induction therapy. The most common adverse event was worsening cytopenia in four (22.2%) patients, one of whom had baseline leukopenia. Neutropenia was documented in three patients, and one patient had thrombocytopenia. One (5.6%) patient developed acute kidney injury (AKI) through their treatment, requiring dose modification. Conclusion Ganciclovir is a viable option for outpatient parenteral therapy in the treatment of CMV disease where an extended duration of IV therapy is required. In our cohort of 18 immunocompromised patients, only one had early discontinuation of therapy due to ganciclovir-related AKI. Close monitoring of labs through an established OPAT protocol is needed for successful completion of therapy. Disclosures All Authors: No reported disclosures

633. Incidence and Outcomes of Pediatric Allogeneic Hematopoietic Cell Transplant (allo-HCT) Recipients Under Surveillance and Not Under Surveillance for Human Adenovirus (HAdV) in the Post-HCT Period

Abstract Background Human Adenovirus (HAdV) can cause life-threatening illness in pediatric allo-HCT recipients, but studies to define incidence and outcomes of HAdV in allo-HCT patients are limited. Use of PCR-based HAdV surveillance varies by HCT center, in part because there are no approved HAdV-directed therapies. This study describes the epidemiology of HAdV infection and disease in pediatric allo-HCT patients who did and did not undergo HAdV surveillance. Methods An allo-HCT cohort was assembled from July 2018 to June 2021 at ten US pediatric HCT centers. Patients were followed for 180 days from HCT to document presence of HAdV infection and disease and were considered under surveillance if ≥ 2 HAdV blood tests were run in the first 14 days post-HCT. Published HAdV disease and attributable death definitions were applied to patients with positive HAdV PCR tests from any site and adjudicated by a central review committee. HAdV events were designated asymptomatic infection or possible, probable, or proven disease. HAdV DNAemia and disease incidence, time to event, and mortality and attributable case fatality rates were described. Results The cohort included 831 allo-HCT recipients: 645 under surveillance & 186 not (Table 1). 15.5% of patients under surveillance had DNAemia; median time to DNAemia was 31.0 days from HCT (Table 2). Probable/proven disease was documented in 11.9% and 3.8% of patients under and not under surveillance, with median time to disease 37.0 days and 66.0 days from HCT, respectively (Table 3). Overall mortality rates were 7.6% and 8.6% in patients under and not under surveillance (Table 4). Attributable case fatality rates for those with probable or proven disease were 13.0% and 14.3% in those under and not under surveillance, respectively. Conclusion HAdV infection and disease events were frequent; however, incidence was higher in patients under surveillance, suggesting detection bias. HAdV disease was identified as a frequent cause of death. Attributable case fatality rates were similar regardless of surveillance, suggesting early detection did not improve outcomes. Future analyses of these data will determine patient factors that identify allo-HCT patients at high risk for HAdV infection and disease to target for novel prophylaxis or pre-emptive therapy studies. Disclosures Michael D. Green, MD, MPH, ADMA: Advisor/Consultant|Bristol Myers Squibb: Advisor/Consultant|ITB-MED: Advisor/Consultant|kamada: Honoraria Monica I. Ardura, DO, MSCS, Karius: Advisor/Consultant|Miravista: Grant/Research Support Jeffrey Auletta, MD, Ascella Health: Advisor/Consultant Diego R. Hijano, MD, MSc, FDA: Grant/Research Support|Merck: Grant/Research Support|National Institute of Health: Grant/Research Support William J. Muller, MD, Ansun Biopharma: Grant/Research Support|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|DiaSorin: Advisor/Consultant|DiaSorin: Honoraria|Eli Lilly and Company: Grant/Research Support|Enanta Pharmaceuticals: Advisor/Consultant|Enanta Pharmaceuticals: Grant/Research Support|F. Hoffmann-LaRoche Ltd (Roche): Grant/Research Support|Finley Law Firm, P.C.: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Melinta Therapeutics, Inc.: Grant/Research Support|Merck Sharpe & Dohme: Grant/Research Support|Moderna: Grant/Research Support|Nabriva Therapeutics, plc: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Pfizer: Grant/Research Support|ProventionBio: Advisor/Consultant|Sanofi: Advisor/Consultant|Sanofi: Honoraria|Tetraphase Pharmaceuticals, Inc.: Grant/Research Support Michael Grimley, MD, SymBio Pharmaceuticals Limited: Advisor/Consultant Lara A. Danziger-Isakov, MD, MPH, Aicuris: clinical research contract, paid to institutio|Ansun BioPharma: clinical research contract, paid to institution|Astellas: Advisor/Consultant|Astellas: clinical research contract, paid to institutio|Merck: clinical research contract, paid to institutio|Pfizer: Grant/Research Support|Takeda: clinical research contract, paid to institutio Brian T. Fisher, DO, MPH/MSCE, Allovir: Grant/Research Support|Astellas: Data Safety Monitoring Board|Merck: Grant/Research Support|Pfizer: Grant/Research Support

P-2310. Gammaproteobacteria Load Responses in the Intestinal Microbiota of Patients Undergoing Hematopoietic Cell Transplantation Predicts Resistant Gram-Negative Rod Colonization

Abstract Background Hematopoietic cell transplant (HCT) patients are at high risk of Gram-negative rod (GNR) blood stream infections (BSIs) particularly before pre-engraftment. Globally, breakthrough infections with resistant GNRs (rGNRs) are increasing in HCT while rGNR epidemiology has become increasingly complex to predict. It’s recognized that individualized antimicrobial HCT therapy is needed but it is unclear what screening strategies are optimal to detect rGNR colonization. Single taxon dominance of certain Gammaproteobacteria (ɣ-bacteria) species in HCT intestinal microbiomes is a BSI risk factor where colonizing strains present prior to transplant are predominant aetiologies of GNR BSIs. In this study we sought to understand how ɣ-bacteria loads respond to HCT antimicrobial therapy. Methods We performed a prospective study of 60 adult patients undergoing HCT at The Ottawa Hospital from 2021-2022. A baseline fecal sample collected < 1 week before conditioning was screened by culture for colonization with rGNR to fluoroquinolones (FQ), 3rd generation cephalosporins (3GC) and carbapenems. Total- and ɣ-bacteria loads were measured by qPCR in baseline and serial specimens until engraftment, expressed as the Log10 (ɣ-bacteria 16S copies / total 16S copies) per ng fecal DNA. Ceftriaxone (CTX) and piperacillin-tazobactam (TZP) are used for prophylaxis and empiric FN therapy, respectively at our institution. Results High ɣ-bacteria loads were associated with baseline rGNR colonization compared to no rGNR colonization (Log10 (-1.85) vs Log10 (-2.39), p < 0.0095) (Fig. 1). Highest loads occurred when resistant Escherichia coli or Klebsiella pneumoniae colonized the intestinal microbiota (Log10 (-1.34), p < 0.001). ɣ-bacteria loads were refractory to CTX and TZP therapy when colonizing E. coli or K. pneumoniae carried 3GC resistance (Fig. 2a). In contrast, ɣ-bacteria loads decreased > 2 Log10 in response to CTX and TZP if at baseline rGNRs were FQ resistant, expressed chromosomal AmpC, or if no rGNRs were detected (Fig. 2b, c, d). Conclusion ɣ-bacteria load measurement during HCT may be useful for predicting colonization with rGNR strains and identifying patients at risk of GNR BSI. Disclosures All Authors: No reported disclosures

P-1570. D-mannose for Prevention of Recurrent Urinary Tract Infection in Adult Women: An Updated Systematic Review and Meta-analysis

Abstract Background Urinary tract infections (UTIs) are prevalent, especially among women as approximately 50% of all healthy women will encounter at least one episode of UTI during their lifetime. An estimated 25%-35% of them will experience a recurrence within the following year. Prolonged antibiotic therapy for prophylaxis of UTI poses the risk of antimicrobial resistance, alteration of normal flora, and high costs to the patient. D-mannose, a polysaccharide may reduce UTI by preventing the adherence of bacteria to uroepithelium by binding to the type1 pili and saturating the adhesin FimH. D-mannose is commonly marketed for urinary tract health and is touted to contribute to better antimicrobial management within primary care settings. We performed an updated meta-analysis comparing prophylaxis with D-mannose versus placebo or no treatment for prevention of recurrent UTI in adult women. Methods We systematically searched PubMed, Scopus, and Cochrane Central databases for trials comparing D-mannose versus placebo or no treatment for UTI prophylaxis in adult women. Outcomes of interest included one or more episodes of UTI within 6 months of randomization and adverse events. Statistical analysis was performed using R software. Heterogeneity was assessed using I2 statistics. The analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline (Figure 1). Risk estimation for recurrent UTI Results The systematic review identified three randomized controlled trials including 846 participants. Prophylaxis with D-mannose was given to 428 (50.59%) participants. The risk of recurrent UTI within 6 months of randomization (RR 0.75; 95%CI 0.46-1.23; p=0.259; I2=52%) showed no significant difference between the groups (Figure 2). Adverse events (RR 0.81; 95%CI 0.09-6.91; p=0.847; I2=94%) were also similar between the groups (Figure 3). Risk estimation for adverse events Conclusion In contrast to a previous meta-analysis, our study found that prophylaxis with D-mannose did not reduce the risk of recurrent UTIs in adult women. Adverse events were also comparable between the groups. Disclosures All Authors: No reported disclosures

Reported Postoperative Surgical Site Infections in Tertiary Care Hospitals, Systematic Review of Recent Literature.

The objective of this systematic review is to evaluate the patterns of postsurgical site infections, pre-surgical antibiotics prophylaxis, and related clinical outcomes in the recently published literature. This systematic review is registered with PROSPERO registration number CRD42023398963. Several databases and individual journal websites were used to collect data from PubMed/Medline, TRIP, SCOPUS, Elsevier, Springer, ProQuest, and EMBASE. The established criteria of inclusion were RCTs, retrospective, prospective, and cross-sectional studies with patients who had a recent surgical procedure. Excluded from the study designs were systematic reviews, prospective studies, data on pediatrics, and data on disabilities. Quality assessment analysis of the results for randomized controlled trials (RCT) used CONSORT guidelines and STROBE guidelines for cross-sectional and cohort studies. A total of 328 articles were identified from different databases. Among them, 15 studies were included for data extraction and qualitative analysis. A total of 33,193 patients with an average rate of 11.5% (surgical site infections- SSIs) were identified in these studies during 2008-2022. The mean rate of SSIs among the total number of immunocompromised patients/procedures was 10.2%. The SSI on patients undergoing major surgical procedures with visible incisions was 26.0%. The majority of the studies reported the use of pre-surgical antibiotic prophylaxis. Cefazolin was mostly prescribed antibiotics and administered in 90% of patients. Other antibiotics included ceftriaxone (4%), cloxacillin (3%), and vancomycin (4%). The mean reported rate of SSIs with combination antibiotic prophylaxis therapy was 22.8%. This systematic review concluded the limited reported data on surgical site infections (SSIs). The overuse of pre-surgical antibiotic prophylaxis has been reported in several studies. This study recommended developing standardized guidelines on the use of antibiotics related to surgical cases rather than co-morbidities.

P0317 Risk factors of Post Operative Recurrence in patients with Crohn’s Disease: a multicentre experience of 8 years of follow-up

Abstract Background Despite new medical therapy for Crohn’s disease (CD), bowel resection is still performed in 25% of patients within 10 years from the diagnosis of CD.1,2 The aim of our multicentres retrospective study was to evaluete the risk factors of endoscopic post operative recurrence (ePOR) of patients with CD. Methods We analyzed the relevance and impact of well-known risk factors for postoperative recurrence, such as clinical, laboratory, endoscopic, and ultrasound findings collected before and within 6 months after surgery, and surgical and histopathological features in a series of consecutive CD patients who underwent bowel resection between 2016 and 2023. All patients were followed up to 6 months, until November 2024. The ePOR of the disease was defined by a Rutgeerts’ score more than i2b. We compared prevalence of risk factors for recurrence in patients with and without ePOR during the follow-up. Logistic regression analysis was also performed to detect risk factors independently correlated with ePOR. Results We included 195 patients (male 48.7%, mean age at surgery 42.4±15.1) with a mean of follow-up 4.7±2.7 years (range). ePOR was observed in 83 (58.0%) and surgical recurrence in 19 (11.0%) patients. Pre-operative features (Table 1), correlated with ePOR were younger age at the diagnosis (29.5±14.4, p=0.290), colonic localization (55.4%,p=0.060), structuring behaviour (41.0%,p=0.562), older disease (12.3±10.0,p=0.273) and treatment with >1 biological therapy (44.6%,p=0.040). Patients with ePOR patients were more frequently operated with ileocolonic resection (74.7%,p=0.787) with laparoscopic approach (65.1%,p=0.204), end-to-end anastomosis (87.5%,p=0.255), and had a higher rate of postoperative complications (30.7%,p=0.075). Patients with ePOR showed higher postoperative levels of C-reaction protein (CRP, 6.9±10.0,p=0.050) and faecal calprotectin (FC, 174.2±189.2,p=0.099) such as higher rate of US recurrence at 6 or 12 months were observed (55.6%,p=0.158) and a less frequent prophylactic postoperative therapy (79.4%,p=0.018). In addition, patients who were treated with >2 different biological therapies before surgery (OR 6.12, 95%CI 1.25-29.9,p=0.025) and had post biological therapy (OR 2.85 95%CI 1.31-6.21,p=0.008), mainly because of lack of prophylactic therapy were significant predictors for ePOR. However, these risk factors were not confirmed at the multivariate analysis. Conclusion In our experience, patients with increase postoperative levels of CRP or FC have higher probability of having ePOR, and most of them did not start prophylaxis therapy after surgery, but were treated with biologics after surgery due to clinical relapse.

P0746 Impact of timing of prophylaxis therapy on post-operative endoscopic recurrence in a real-life cohort of patients whit Crohn’s disease

Abstract Background The optimal timing for initiating biologic therapy after resection surgery (SR) in Crohn's disease (CD) has not been established, and the impact of a delayed start remains unclear, particularly outside the context of clinical trials. Methods Our study aims to assess the impact of the timing of prophylactic biologic therapy initiation on endoscopic recurrence after resection surgery in CD, and to compare prophylactic treatment strategies used in patients already on biological therapy before SR. We conducted a retrospective study evaluating endoscopic outcomes of CD patients who underwent ileo-colonic resection. All patients underwent their first endoscopic evaluation within 6-12 months after surgery to assess POR, using the Rutgeerts score (POR defined as Rutgeerts ≥ 2). All patients received biological therapy for recurrence prevention within 16 weeks after surgery. Results We included 173 patients. Prophylactic biologic therapy was administered to all patients, with initiation within 8 weeks, 8-12 weeks, and 12-16 weeks in 45%, 19%, and 36% of patients, respectively. POR was observed in 50% of the entire cohort. Comparing the timing of prophylaxis therapy initiation in univariate analysis (<8, 8-12, >12 weeks), both initiation <8 and initiation between 8-12 weeks had a significantly lower recurrence rate than initiation >12 weeks (p= 0.004, OR 0.37, 0.18, 0.73, 95% CI and p=0.039, OR 0.40, 0.16, 0.95, 95% CI respectively. Furthermore, for patients already on biologic therapy prior to SR (103), therapy was either maintained unchanged, switched, or swapped in 54%, 18%, and 28% of patients, respectively. We noted that the therapeutic swap was significantly worse (p=0.0009, OR 3.65, 1.42, 10. 1 95%CI) compared with continuation of the same therapy. There was no difference between continuation of the same therapy and treatment switch. In the cohort of patients who were already on biologic therapy prior to SR, when considering treatment strategy, timing of therapy in the multivariate analysis, the swap showed significantly higher POR than maintaining the same therapy and the switch. (OR 3.42, 1.20, 10.5 95% CI, p=0.025) while therapy timing was not significant. All the groups were homogeneous in characteristics and post-operative complications. Conclusion Prophylaxis administered within 12 weeks after resection correlates with a reduced risk of post-operative recurrence. For patients already on biological therapy before the SR, the prophylaxis strategy had a significant impact on POR.

Letermovir treatment for refractory or resistant cytomegalovirus infection or disease or with concurrent organ dysfunction: a phase 2 open label study

Introduction: Refractory or resistant cytomegalovirus (CMV) infection and disease pose a significant challenge in immunocompromised patients, including solid organ transplant (SOT) and allogeneic hematopoietic cell transplant (allo-HCT) recipients. This study aimed to evaluate letermovir as a treatment for patients with CMV infection or disease. Methods: We performed an open-label, phase II non-randomized clinical trial. Adult and pediatric (≥12 years of age) patients who had undergone an SOT or allo-HCT and who required antiviral treatment for refractory or resistant CMV or who had CMV with concurrent organ dysfunction were eligible. Patients received letermovir treatment daily for up to 12 weeks with an optional additional 12 weeks of therapy for secondary prophylaxis if clinically indicated. The primary objectives were to evaluate the safety and efficacy of letermovir treatment based upon virological and clinical responses. Results: Ten patients were enrolled in the study and seven patients completed the study treatment and follow-up period. The overall virological response (defined as a complete virological response at the end of the study period) rate was 60% in the study population. The study drug was well tolerated as only two patients experienced study drug-related toxicity and only one grade 3 toxicity (elevated ALT) was observed. Letermovir was not associated with acute kidney injury, hepatotoxicity, cardiac arrhythmias, or bone marrow suppression. Conclusion: In this limited sample, letermovir for CMV treatment was safe and well tolerated. Further research is needed to determine if letermovir can be used for the treatment of refractory or resistant CMV infection or disease.

Trend, clinical characteristics, and pregnancy outcomes of pregnancy associated venous thromboembolism: a retrospective analysis of nearly 10 years

Background Pregnancy-associated venous thromboembolism (PA-VTE) seriously threatens maternal health. We aimed to investigate the clinical characteristics, risk factors, treatments, and pregnancy outcomes to better prevent and treat PA-VTE. Methods PA-VTE patients were selected from 171,898 women who were registered in the Department of Obstetrics of Fujian Maternity and Child Health Hospital from January 2014 to August 2023 and delivered to calculate the incidence. Clinical data were collected to retrospectively analyze the clinical characteristics, risk factors, treatments, and pregnancy outcomes of PA-VTE. Descriptive statistical analysis was used. Results There were 122 cases of PA-VTE with an incidence of 0.71 per 1000 pregnancies; the incidence showed an upward trend and peaked in 2022 (1.24‰). Pregnant women accounted for 28.69% (35/122), the onset were 5–39+6 weeks and incidence increased with the increase of trimester, reaching the highest level in puerperium with 87 cases (71.31%). VTE was mainly found in the lower extremities (112/122); a few were found in cranial venous sinus (4/122), pelvic vein (1/122), and pulmonary embolism (PE) in five cases. 78.68% (96/122) had clinical manifestations. By Royal College of Obstetricians and Gynaecologists (RCOG) risk assessment scale, 45.71% (16/35) of antepartum patients had risk score ≥3 with a maximum of 9, distributed in eight cases in the first trimester, four cases in the second trimester, and four cases in the third trimester. Patients with risk score <3 all occurred in the second and third trimester. Primary risk factors included advanced maternal age (AMA), thrombophilia. All patients received anticoagulant therapy, and seven patients were placed inferior vena cava (IVC) filter in antepartum period. Except one case of abortion in PPROM, the rest continued pregnancy to 29+1 to 40 weeks, only one case of postpartum hemorrhage and one case of severe neonatal asphyxia. The onset time in puerperium was three hours to 28 days after delivery; 62.07% (54/87) patients were scored ≥2. The main risk factors included elective cesarean section, AMA, and preterm birth. Anticoagulant therapy was given after diagnosis; two cases were placed with IVC filter, one case was placed with left iliac vein stent and thrombolysis. Conclusions The incidence of PA-VTE showed an increasing trend over the past decade, predominantly occurring postpartum. Main risk factors included AMA, thrombophilia, preterm birth, and elective cesarean section. Higher risk scores correlated with earlier onset. Early risk assessment, appropriate prophylaxis, and standardized anticoagulation therapy resulted in favorable maternal and fetal outcomes, with temporary IVC filter placement being beneficial in selected cases.

Tolerance to Factor VIII in the Era of Non-Factor Therapies: Immunological Perspectives and a Systematic Review of the Literature.

Persons with hemophilia A (PWHA) lack clotting factor VIII (FVIII) due to a genetic mutation in the F8 gene. The administration of FVIII concentrate leads to the development of neutralizing anti-FVIII antibodies (inhibitors) in about 30% of children with severe hemophilia A. The other 70% of children do not mount a detectable antibody response, suggesting that they may have developed tolerance towards FVIII. Our knowledge on the underlying immunological mechanisms that determine formation of inhibitors or apparent tolerance to FVIII is limited. Up to recently, FVIII concentrates were regularly used as prophylaxis. In the last years, Non-Factor Therapy (NFT) for prophylaxis is increasingly used, in which case FVIII concentrate administration is limited to treatment for bleeding or perioperative hemostasis. As NFT is very effective in the prevention of bleeds, patients may not be exposed to the deficient FVIII protein for periods up to a year or longer. Thus, while in the past persons with severe hemophilia were frequently exposed to the deficient antigen, exposure is now reduced to incidental treatment moments. It is currently not known how this will affect the tolerance for FVIII. In this review, we will discuss tolerance to FVIII from a clinical, immunological and epidemiological perspective. We aim to provide an outlook on the effect of reduced FVIII exposure on tolerance for FVIII in PWHA.

Persisting Gaps in Cytomegalovirus Prevention and Management After Solid Organ Transplantation in a Resource-Limited Setting.

Cytomegalovirus (CMV) infection remains among the leading complications after solid organ transplantation (SOT). Large international surveys mainly focused on high-income countries, detected considerable variability in the management of this infection after SOT. Limited data are available from resource-limited settings. A questionnaire-based cross-sectional study was performed. All transplant programs (TP) registered at the Brazilian Organ Transplantation Society (ABTO) were invited to participate. Sixty-one TP participated in the study. Of these, 59 (97%) reported using at least 1 preventive strategy (prophylaxis or preemptive therapy [PET]). Prophylaxis was reported by only 39 (64%). PET was used by 52 (85%), predominantly for R+ recipients (n=42/61; 70%). CMV monitoring was performed weekly in only 22 of 52 (42%) TP. This was significantly more common in TP reporting turnaround times ≤72h for quantitative nuclear acid amplification tests (p<0.001). Intravenous (IV) ganciclovir was the predominant drug chosen for prophylaxis (21/39 TP; 54%) and for PET (44/52 TP; 77%). Lack of regular access to valganciclovir was significantly associated with the choice of IV ganciclovir for prophylaxis and PET (p=0.002 for both comparisons). Only 8 (13%) TP had access to molecular diagnostic tests for ganciclovir resistance, and 14 (23%) had access to effective therapy for highly resistant infections. These results suggest that strategies to improve the management of CMV after SOT in such a resource-limited setting are needed and should include not only targeted educational programs but also initiatives to tackle economic and structural barriers.

Review protocol for a systematic review and meta-analysis on HIV inequities in transgender and non-binary populations

IntroductionGlobal disparities in HIV prevalence among transgender women are well documented. However, current epidemiological literature on HIV disparities demonstrates gaps in research that include the diversity within transgender populations—for example,...

AGA Clinical Practice Update on Management of Portal Vein Thrombosis in Patients With Cirrhosis: Expert Review.

Portal vein thromboses (PVTs) are common in patients with cirrhosis and are associated with advanced portal hypertension and mortality. The treatment of PVTs remains a clinical challenge due to limited evidence and competing risks of PVT-associated complications vs bleeding risk of anticoagulation. Significant heterogeneity in PVT phenotype based on anatomic, host, and disease characteristics, and an emerging spectrum of therapeutic options further complicate PVT management. This Clinical Practice Update (CPU) aims to provide best practice advice for the evaluation and management of PVT in cirrhosis, including the role of direct oral anticoagulants and endovascular interventions. This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute CPU Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPU Committee and external peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Asymptomatic patients with compensated cirrhosis do not require routine screening for PVT. BEST PRACTICE ADVICE 2: Patients with cirrhosis with PVTs identified on Doppler ultrasound should undergo cross-sectional imaging with computed tomography or magnetic resonance imaging to confirm the diagnosis, evaluate for malignancy, and document the degree of lumen occlusion, clot extent, and chronicity. BEST PRACTICE ADVICE 3: Patients with cirrhosis and PVT do not require a hypercoagulable workup in the absence of additional thromboemboli or laboratory abnormalities or family history suggestive of thrombophilia. BEST PRACTICE ADVICE 4: Patients with cirrhosis and PVT with evidence of intestinal ischemia require urgent anticoagulation to minimize ischemic injury. If available, these patients should be managed by a multidisciplinary team, including gastroenterology and hepatology, interventional radiology, hematology, and surgery. BEST PRACTICE ADVICE 5: Consider observation, with repeat imaging every 3 months until clot regression, in patients with cirrhosis without intestinal ischemia and recent (<6 months) thrombosis involving the intrahepatic portal vein branches or when there is <50% occlusion of the main portal vein, splenic vein, or mesenteric veins. BEST PRACTICE ADVICE 6: Anticoagulation should be considered in patients with cirrhosis without intestinal ischemia who develop recent (<6 months) PVT that is >50% occlusive or involves the main portal vein or mesenteric vessels. Patients who have increased benefit of recanalization include those with involvement of more than 1 vascular bed, those with thrombus progression, potential liver transplantation candidates, and those with inherited thrombophilia. BEST PRACTICE ADVICE 7: Anticoagulation is not advised for patients with cirrhosis with chronic (>6 months) PVT with complete occlusion with collateralization (cavernous transformation). BEST PRACTICE ADVICE 8: Patients with cirrhosis and PVT warrant endoscopic variceal screening if they are not already on nonselective beta-blocker therapy for bleeding prophylaxis. Avoid delays in the initiation of anticoagulation for PVT, as this decreases the odds of portal vein recanalization. BEST PRACTICE ADVICE 9: Vitamin K antagonists, low-molecular-weight heparin, and direct oral anticoagulants are all reasonable anticoagulant options for patients with cirrhosis and PVT. Decision making should be individualized and informed by patient preference and Child-Turcotte-Pugh class. Direct oral anticoagulants may be considered in patients with compensated Child-Turcotte-Pugh class A and Child-Turcotte-Pugh class B cirrhosis and offer convenience as their dosages are independent of international normalized ratio monitoring. BEST PRACTICE ADVICE 10: Patients with cirrhosis on anticoagulation for PVT should have cross-sectional imaging every 3 months to assess response to treatment. If clot regresses, anticoagulation should be continued until transplantation or at least clot resolution in nontransplantation patients. BEST PRACTICE ADVICE 11: Portal vein revascularization with transjugular intrahepatic portosystemic shunting may be considered for selected patients with cirrhosis and PVT who have additional indications for transjugular intrahepatic portosystemic shunting, such as those with refractory ascites or variceal bleeding. Portal vein revascularization with transjugular intrahepatic portosystemic shunting may also be considered for transplantation candidates if recanalization can facilitate the technical feasibility of transplantation.

A Second Look at Secondary Hypogammaglobulinemia.

Hypogammaglobulinemia is defined as a reduced immunoglobulin level, which can be either primary due to inborn errors of immunity or acquired in the setting of poor antibody production or increased antibody loss. Secondary hypogammaglobulinemia (SHG) should be considered in patients with a history of immunosuppressive therapy, transplant, protein loss syndromes, certain autoimmune conditions, and malignancies, as it can be associated with increased infectious risk. Appropriate history and lab-based screening in these populations can identify SHG allowing treatment and close monitoring as appropriate. Ideally, treatment focuses on control of underlying condition or removal of iatrogenic causes of SHG. However, in many cases, treatment of the underlying condition does not reverse SHG, or immunosuppressive therapy cannot be discontinued without significant risk to the patient. For these patients, strategies for risk mitigation against infectious complications include vaccination, antibiotic prophylaxis and immunoglobulin replacement therapy. This report aims to summarize the existing and emerging data in evaluation and management of SHG and highlight areas which require further investigation.

Sickle cell disease in India: the journey and hope for the future.

India, the most populous nation in the world, also has a high frequency of the sickle hemoglobin (HbS) allele globally. The Arab Indian HbS haplotype in India is characterized by a relatively high percentage of fetal Hb, with widely varying frequencies of α-thalassemia. Hence, sickle cell disease (SCD) in India was perceived to be mild. Advances in the past decade in screening and SCD management have revealed that the severity of SCD in India is comparable to many other parts of the world. Clinical features in India include vaso-occlusive crisis, acute chest syndrome, avascular necrosis, renal involvement, stroke, etc, at a relatively young age. Once a fatal disease of childhood, the majority of patients born with SCD are expected to survive into adulthood, largely because of improvements in comprehensive care programs including newborn screening, penicillin prophylaxis, transcranial Doppler, and hydroxyurea therapy. Several centers are performing hematopoietic stem cell transplants successfully for SCD. To address the urgent need to control and manage SCD in India's population, the Government of India launched the National Sickle Cell Anaemia Elimination Mission, with significant funding for large-scale measures to screen, treat, counsel, educate, and develop technologies and novel therapies and gene therapies.

Late complications and long-term care of adult CAR T-cell patients.

The success of chimeric antigen receptor (CAR) T-cell therapy in adult patients with hematologic malignancies has resulted in a large number of long-term survivors who may experience late complications distinct from those in the early CAR T-cell treatment period. These late complications, defined as occurring more than 90 days after CAR T-cell infusion, include cytopenias, infections, secondary malignancies, and delayed neurotoxicities. Late cytopenias may be from prolonged recovery after lymphodepleting (LD) chemotherapy or arise anew, raising concerns for recurrent primary disease or a secondary malignancy. Cytopenias are treated with supportive care, hematopoietic cytokines, and, occasionally, hematopoietic stem cell support. LD chemotherapy profoundly affects B, T, and natural killer cells. CD19 and B-cell maturation antigen are expressed on normal B cells and plasma cells, respectively, and the targeting of these structures by CAR T-cell products can result in prolonged lymphopenias and hypogammaglobulinemia, making infection an ongoing risk. Late infections are predominantly due to respiratory viruses, reactivation of herpes viruses, and Pneumocystis jirovecii. Patients may require ongoing prophylaxis and immunoglobulin replacement therapy. Although responses may be blunted, vaccinations are generally recommended for most adult CAR T-cell patients. Both hematologic and solid secondary malignancies are a known risk of CAR T-cell therapy; retroviruses used to produce CAR T-cell products have resulted in T-cell cancers secondary to insertional oncogenesis. It is essential to monitor for late complications in adult patients receiving CAR T-cells by using a multidisciplinary approach between referring hematologist oncologists and cell therapy centers to improve the outcomes and quality of life for these patients.

Physician Attitudes Towards Pharmacist-Prescribed HIV Post-Exposure Prophylaxis (PEP): A Survey of a State Medical Association.

Timely initiation of antiretroviral therapy (ART) for non-occupational post-exposure prophylaxis (nPEP) is crucial in preventing HIV infection and advancing efforts to end the HIV epidemic (EHE). nPEP must be administered within 72h of high-risk exposure, ideally within 24h. Pharmacies may play a role in increasing access to nPEP and facilitating referrals for additional care, such as PrEP. Recent legislation permits pharmacist-prescribed nPEP (PDP), though provider attitudes toward this change have not been studied. A survey querying physicians and medical trainees (students and residents) was conducted in 2024 during an annual state medical association conference. The survey included 24 questions on nPEP knowledge and attitudes towards pharmacist-prescribed nPEP (PDP). The survey was administered in person using electronic tablets, with voluntary participation incentivized by a monetary reward. Statistical analysis was conducted using SAS (9.4 version) software, with differences in responses between physicians and trainees evaluated. P values < 0.05 were considered statistically significant. Of 89 respondents (56% of attendees), 61 were physicians and 28 were trainees. Notably, 28% of licensed providers indicated that pharmacist-directed prescribing (PDP) should not be allowed in the State of Ohio, while no trainees expressed this same opposition (p = 0.001). Trainees were more likely to view pharmacist prescribing as safe and appropriate ((p = 0.0135, p = 0.013). Urban-based providers were more supportive of pharmacist prescribing than their rural counterparts (p = 0.0195). Trainees showed little opposition to PDP, whereas physicians expressed concerns about safety and appropriateness. Addressing these concerns is essential for integrating pharmacists into the EHE strategy.