Prophylaxis Strategies Research Articles

Outcomes of Coccidioides Seropositive Solid Organ Transplant Recipients After Self-discontinuation of Antifungal Prophylaxis: The EIA-IgM-only Conundrum.

Solid organ transplant recipients are at risk of severe coccidioidomycosis and are given prophylaxis to mitigate the risk. Patients with seropositive testing typically receive lifelong prophylaxis; currently, this prophylaxis strategy includes patients who are positive only for IgM by enzyme immunoassay (EIA-IgM-only), although this result may be falsely positive. We conducted a retrospective study at a large-volume transplant center in an endemic coccidioidomycosis region to compare outcomes of non-lung transplant recipients who were seropositive for Coccidioides but discontinued prophylaxis (case patients) to outcomes of patients who continued prophylaxis (controls). No case or control patients developed active coccidioidomycosis during the follow-up period. Before transplant, 62 of 77 case patients (80.5%) had a single positive serologic test, of whom 27 of 62 were EIA-IgM-only positive (43.5%). In contrast, 57 of 77 controls (74.0%) had a single seropositive result (16/57 [28.1%] were EIA-IgM-only). The single EIA-IgM-only result was classified as falsely positive by infectious disease consultants in 20 of 43 patients (46.5%) compared with all other Coccidioides serologic results (13/111 [11.7%], P < 0.001). Lifetime antifungal prophylaxis was felt to be unnecessary for 28 of 43 patients (65.1%) who were EIA-IgM-only versus 31 of 111 patients (27.9%) with other serologic results (P < 0.001). For patients repeatedly positive for EIA-IgM-only and no evidence of seroconversion, compatible clinical illness, or radiographic findings, discontinuing antifungal prophylaxis may be reasonable after the first posttransplant year.

Historical perspectives supporting the ambitious anesthetist aiming for zero nausea/vomiting: should one trust every consensus statement every time?

Within the domain of perioperative prophylaxis against postoperative nausea and/or vomiting (PONV), there seems to be (i) a consensus-guided “hard stop” recommendation after four prophylactic anti-emetic medications are utilized, and (ii) an assumption that each of the four “usual” PONV medications/categories produces 25% risk reduction from the “previous baseline”, representing a “law of diminishing returns.” Meanwhile, recently-described 5-medication PONV prophylaxis (palonosetron, perphenazine, aprepitant, dexamethasone, diphenhydramine) has been observed to achieve 90%–95% prophylaxis success, particularly in patients receiving intrathecal morphine (a known, potent emetogenic stimulus). This meaningful prevention thematically differs from the scholarly prevention benchmark that may be over-reliant on patient-specific preoperative risk factors, described in the 1990s and before, dictating prophylaxis strategies. Meaningful prevention with 5-medication PONV prophylaxis (which we recommend before entry into the operating theater) (i) may serve as a surprisingly effective antecedent to further avoid postoperative opioids, (ii) may be augmented throughout hospitalization and convalescence with daily “booster dosing”, and (iii) may (in combination with booster dosing) mitigate possible “rebound nausea” that has been reported by esteemed PONV thought leaders in the context of post-discharge nausea and/or vomiting. The described processes (pan-prophylaxis before emetic stimuli are incurred, antiemetic booster dosing, and potential downstream opioid reduction by enhancing adherence to postoperative oral/enteral non-opioid analgesic formulations) would seem to create a win-win scenario for patients and hospitals alike. The described antiemetic techniques remain compatible with available opioid-free anesthetic techniques [lidocaine, acetaminophen, N-methyl-D-aspartate (NMDA) antagonists, etc.]. Some perspectives shared herein may further inform as to how and why.

Addition of an NK1 receptor antagonist to standard antiemetic prophylaxis in patients with B-cell lymphoma receiving EPOCH.

Data on the optimal management of patients with hematologic malignancies and chemotherapy-induced nausea and vomiting (CINV) are lacking, particularly for multiday chemotherapy regimens. We report our institutional experience in patients with B-cell lymphoma receiving multiday dose-adjusted R-EPOCH chemotherapy utilizing two CINV prophylaxis strategies. We performed a retrospective, single-center, cohort study evaluating hospitalized patients with aggressive non-Hodgkin B-cell lymphoma receiving DA-R-EPOCH (April 2016 to October 2022). All patients received prophylactic corticosteroid and 5HT3-receptor antagonist, and were categorized by the addition of an NK1 receptor antagonist (NK1RA) or not. The primary outcome was complete response (CR, no vomiting, and no rescue medication use) over 120 h. Secondary outcomes included as-needed antiemetic use (acute, delayed, and overall phases), CR without escalating prophylactic antiemetics in cycle 2, and complete control. We performed a descriptive analysis and multivariate logistic regression for NK1RA use, adjusting for age and sex. Of 128 patients, 56 (43.8%) received an NK1RA as part of their antiemetic regimen, and 72 (56.3%) did not. No patients received prophylactic olanzapine. CR was achieved in 32 (57.1%) of those who received an NK1RA and 30 (41.7%) who did not (OR 0.45; 95% CI, 0.21-0.96; p = 0.039). We observed trends between groups in as-needed antiemetics use (29 [51.8%] vs. 49 [68.1%]; p = 0.061), with most use in the delayed phase (22 [39.3%] vs. 37 [51.4%], p = 0.173). We found no difference in healthcare utilization between the first and second cycle. CINV control in patients with non-Hodgkin B-cell lymphoma receiving DA-R-EPOCH in the hospital was suboptimal. These data support the need to optimize prophylactic antiemetic regimens for patients receiving DA-R-EPOCH.

Prevention and Management of Infectious Complications in Pediatric Patients With Cancer: A Survey Assessment of Current Practices Across Children's Oncology Group Institutions.

While clinical practice guidelines (CPGs) for pediatric oncology infection prophylaxis and management exist, few data describe actual management occurring at pediatric oncology centers. An electronic survey querying infection management practices in nontransplant pediatric oncology patients was iteratively created by the Children's Oncology Group (COG) Cancer Control and Supportive Care Infectious Diseases Subcommittee and sent to leaders at all COG institutions, limiting each site to one response to represent their institution. The response rate was 57% (129/227 institutions). Many sites reported utilizing COG-endorsed CPGs for antibacterial (76%) and antifungal prophylaxis (74%), and fever and neutropenia (FN, 64%). Most institutions reported using antimicrobial prophylaxis for patients with acute myeloid leukemia (88% antibacterial, 100% antifungal) and relapsed acute lymphoblastic leukemia (82% antibacterial, 95% antifungal). Definitions of fever, phagocyte recovery, and antibiotic duration in febrile patients varied. Most institutions administer empiric broad-spectrum antibiotics for nonneutropenic fever, although 14% reported withholding antibiotics based on initial clinical status or risk stratification tools. Most respondents reported (70%) admitting FN patients for at least 48 h, however 15% have low-risk FN protocols allowing outpatient management. FN patients remain admitted on antibiotics through count recovery in 50% of institutions, whereas the others employed various early discharge/early antibiotic discontinuation strategies. There is often consistency but also substantial variability in reported antimicrobial prophylaxis strategies and management of patients with fever and represents an opportunity for implementation studies to standardize application of CPG recommendations and randomized trials to advance evidence where knowledge gaps exist.

Event-driven PrEP beyond cisgender men who have sex with men.

Despite advancements in existing antiretroviral-based prevention strategies, including daily oral, locally acting, and injectable options, there is a pressing need for more inclusive and flexible event-driven pre-exposure prophylaxis (PrEP) strategies for all. Event-driven or intermittent dosing of PrEP in populations beyond cisgender men who have sex with men would offer a promising alternative by fitting prevention into the diverse lifestyles of affected populations and thereby advancing health equity. Evidence from PrEP clinical trials, pharmacokinetic studies, modelling studies, and real-world observational research suggests that event-driven PrEP could be a flexible and inclusive option, yet optimal dosing has not been established across sex and gender spectrums. To advance PrEP equity through inclusivity, studies on event-driven PrEP should include people across the gender spectrum. Real-world demonstration studies and simulation studies of optimal dosing strategies are needed. While awaiting further evidence, clinical providers can offer shared decision making and counselling on available data to include event-driven dosing as an option, especially when daily oral, locally acting, or injectable PrEP are not acceptable or preferred methods. Wider access to diverse PrEP options for all populations fosters a more inclusive and effective global HIV prevention strategy.

The long‐term risk of immune‐related conditions in survivors of diffuse large B‐cell lymphoma: A Danish nationwide registry study

AbstractBackgroundThere is limited knowledge of the long‐term effects on the immune system after treatment for diffuse large B‐cell lymphoma (DLBCL).MethodsThis study included DLBCL patients from the Danish Lymphoma Registry who obtained complete remission (CR) after (R)‐CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)‐like immunochemotherapy. Each R+ CHOP‐like treated patient was matched to five comparators from the Danish background population and furthermore compared to R− CHOP‐like treated patients. Incidence rate ratios (IRRs) and risk differences (RDs) were calculated for a wide range of infections, autoimmune conditions, and immune deficiencies (AC‐IDs) combined and by subtypes.ResultsR+ CHOP‐like treated patients had a higher risk of infections overall (IRR 1.5, 95% confidence interval [CI] 1.4–1.7: 10‐year RD 5.0%, 95% CI 2.2%–7.8%) and for a majority of the subtypes than matched comparators. Likewise, they had a higher risk of AC‐IDs overall (IRR 1.4, 95% CI 1.1–1.7; RD 0.8%, 95% CI 0.7%–2.2%) than matched comparators, however only of clinical relevance for three subtypes; autoimmune diseases of the endocrine system, sarcoidosis and immune deficiencies. The addition of rituximab to CHOP‐like therapy did not alter the incidence rates (IR) of infections overall (IRR 1.1, 95% CI 0.9–1.3) or AC‐IDs overall (IRR 0.8, 95% CI 0.5–1.3) compared to CHOP‐like therapy alone, although the IR for respiratory infections was significantly elevated (IRR 1.5, 95% CI 1.1–2.1). However, an increased use of IVIG treatment was observed among R+ CHOP survivors.ConclusionR‐CHOP‐like treated patients face an increased risk of infections and AC‐IDs overall compared with the background population. The risk of infections and AC‐IDs did not change overall after the addition of rituximab to CHOP, however, an increased risk of respiratory infections is notable. These findings could highlight the need for expanded vigilance and prophylaxis strategies.

Humanized anti-CD25 monoclonal antibody replaces methotrexate as acute graft-versus-host disease prophylaxis in haploidentical allogeneic haematopoietic stem cell transplantation.

Acute graft-versus-host disease (aGVHD) significantly affects quality of life and outcomes in patients post-haploidentical haematopoietic stem cell transplantation (haplo-HSCT). Methotrexate (MTX) is commonly used to prevent aGVHD but can lead to complications like delayed haematological recovery and oral mucositis (OM). This study investigates the efficacy of anti-CD25 monoclonal antibody (mAb) as a potential MTX alternative. Participants were divided into two cohorts: a single-dose group (25 mg/day anti-CD25 mAb with MTX) and a double-dose group (50 mg/day anti-CD25 mAb without MTX). The primary end-point was the cumulative incidence (CI) of severe aGVHD by day 100. The double-dose cohort demonstrated a significantly lower CI of total aGVHD (23.53% vs. 42.11%, p = 0.009) and grade 3-4 aGVHD (7.35% vs. 18.42%, p = 0.047). After inverse probability of treatment weighting adjustment, the adjusted HR of double-dose compared with single-dose cohort for total aGVHD was 0.47 (95% CI 0.26-0.86; p = 0.015), 0.42(95% CI 0.15-1.22; p = 0.110) for grade III-IV aGVHD, 0.45 (95% CI 0.26-0.77; p = 0.004) for total cGVHD and 0.36 (95% CI 0.18-0.72; p = 0.004) for the moderate to severe cGVHD. Additionally, this double-dose regimen significantly reduced the incidence of oral mucositis and demonstrated lower rates of infections and haemorrhagic cystitis. These findings suggest that a double-dose anti-CD25 mAb regimen without MTX is a promising strategy for aGVHD prophylaxis in haplo-HSCT (ChiCTR2200060184).

Management of Acute Myocardial Infarction with ST Segment Elevation. Narrative Review

Thromboembolic disease is a pathological condition that encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE). Obese individuals have a 2 to 3 times greater risk of developing venous thromboembolism (VTE); several pathophysiological mechanisms contribute to this correlation. The incidence of VTE in patients who have undergone bariatric surgery ranges from 0.1 to 3% and represents 20% of related mortality. The previous history of VTE, long surgical time (&gt;3 hours) and the need for transfusion were the risk factors with the greatest impact on bariatric surgery. Thromboembolic risk stratification is essential to guide thromboprophylaxis. There are three tools specifically designed for bariatric surgery: The Cleveland Clinic calculator, BariClot and MBSC. Prophylaxis strategies include mechanical and pharmacological interventions. Various methods have been compared with the intention of identifying the most appropriate regimen for this patient population, however, evidence remains limited and results vary widely, so there is no consensus on the best treatment. This paper aims to carryout a narrative review of the most recent literature on thromboprophylaxis in patients undergoing bariatric surgery.

A Pharmacoeconomic Study of Post-Exposure Prophylaxis Strategies for Influenza Virus Infections in Japan.

Vaccines can prevent influenza (flu) infections and are cost-effective for society and healthcare. However, the cost-effectiveness of post-exposure prophylaxis as a follow-up strategy is unclear. This study aims to evaluate the cost utility of post-exposure prophylaxis and treatment strategies with neuraminidase inhibitors and a cap-dependent endonuclease inhibitor for flu infections from the perspective of healthcare costs in Japan. A base-case analysis was used to compare oseltamivir, zanamivir, and laninamivir for neuraminidase inhibitors and baloxavir marboxil for the endonuclease inhibitor. The costs of the first visit to a physician and pharmacy were excluded because of the policy on out-of-pocket expenses for post-exposure prophylaxis in Japan. Direct medical costs include the second physician visit, pharmacy and hospital admission expenses, and drug prices, based on the 2020 Japanese Medical Fee Index. The EuroQol-5Dimention-5Level was utilized to measure healthy participants' quality of life scores, with a time horizon of 14days. Deterministic and probabilistic sensitivity analyses were conducted. We have found baloxavir marboxil as the post-exposure prophylaxis agent and laninamivir as the treatment agent to be the most cost-effective strategy in Japan, followed by oseltamivir as the post-exposure prophylaxis agent and zanamivir as the treatment agent. Baloxavir marboxil and oseltamivir are cost-effective prophylactic agents for flu from the perspective of healthcare costs in Japan. This strategy to select baloxavir marboxil or oseltamivir would be helpful to manage a formulary for post-exposure prophylaxis in Japan.

Proteomic Analysis Identifies Multiple Mechanisms of 5-Fluorouracil-Induced Gut Mucositis in Mice.

Background/Objectives. Damage of the gastrointestinal mucosa is a major side effect of the anticancer drug 5-fluorouracil (5-FU). Insight into the molecular pathogenesis of 5-FU-induced gut mucositis is expected to justify the strategies of prophylaxis. Methods. We analyzed intestinal specimens obtained from Balb/c mice treated with 70 mg/kg 5-FU daily for up to 6 days. Results. Manifestations of mucositis in the ileum and the colon included diarrhea, weight loss, and morphological lesions. The proteomic analysis revealed dozens of differentially expressed proteins governed by a set of master regulator proteins that regulated downstream pathways culminating in the complexes of specific transcription factors. Among the most important mechanisms of 5-FU-induced gut damage predicted by bioinformatics tools was stimulation of insulin-like growth factor 1 concomitant with inhibition of insulin receptor substrate 1, suggesting an involvement of the insulin pathway. Furthermore, the levels of 14-3-3γ protein and epinephrin B2 tyrosine kinase were interpreted as key inhibitory effects of 5-FU. These changes were detectable in the ileum as well as in the colon, pointing to the commonality of 5-FU responses across the gut. Conclusion. These results demonstrated a hierarchical network of gut injury mechanisms differentially regulated in the course of the emergence of 5-FU-induced mucositis.

Methotrexate Versus Mycophenolate Mofetil Prophylaxis inAllogeneic Hematopoietic Cell Transplantation for Chronic Myeloid Malignancies: A Retrospective Analysis on Behalf of the Chronic Malignancies Working Party of the EBMT.

Prophylaxis strategies for Graft versus host disease (GVHD) in allogeneic hematopoietic cell transplantation (allo-HCT) frequently encompass a combination of a calcineurin inhibitor (CNI) with either methotrexate (MTX) or mycophenolate mofetil (MMF). The aim of this retrospective, EBMT registry-based study was to determine outcome differences for chronic myeloid malignancies and secondary acute myeloid leukemia (sAML) between MTX- and MMF-based prophylaxis regimens while taking potential heterogeneity between subgroups into consideration. Eligible were patients transplanted between 2007 and 2017 who received either MTX- or MMF prophylaxis in combination with a CNI. Endpoints after allo-HCT were overall survival, relapse-free survival (RFS), relapse incidence, non-relapse mortality (NRM), and Grades 2-4 acute GVHD (aGvHD). Overall, 13 699 patients from 321 centers were included. Median follow-up was 42.8 months (IQR 19.8-74.5 months). MTX prophylaxis was associated with reduced overall mortality (HR 0.87, 95% CI 0.81-0.95, p = 0.001) and NRM (HR 0.86, 95% CI 0.78-0.96, p = 0.006) compared with MMF in multivariable Cox regression models in the whole cohort without significant interaction between prophylaxis and subgroups. In contrast, there was no significant association of prophylaxis with risk of relapse (HR 1.03 MTX vs. MMF, 95% CI 0.94-1.14, p = 0.53) or RFS (HR 0.95, 95% CI 0.88-1.01, p = 0.12). There was a reduced risk of Grades 2-4 acute GVHD and reduced mortality after acute GVHD with MTX prophylaxis but no association with outcome in a landmark analysis in patients without aGvHD at 3 months after allo-HCT. In conclusion, MTX-complemented CNI prophylaxis was associated with favorable survival, and with favorable survival after aGVHD compared with MMF.

To give or not give antibiotic prophylaxis for planned caesarean section: An assessment of risk of postpartum prescription of antibiotics depending on prophylaxis regimen

IntroductionNo national recommendation for antibiotic prophylaxis for planned caesarean section in Sweden exists. Swedish delivery units have chosen different strategies. Some units routinely administer antibiotic prophylaxis to all women for whom a caesarean section is planned, while other units give prophylactic antibiotics to risk groups only. We took advantage of this “natural experiment” to compare the risk of antibiotic prescription postpartum after planned caesarean section, by antibiotic prophylaxis strategy. Materials and methodsAn observational study based on data from Swedish registers. The population is based on women giving birth by planned caesarean section from 37 + 0 weeks of gestation, 2014–2020 (n = 7308).The risk of antibiotic prescription postpartum was compared between women who delivered in hospitals with a general routine of administrating antibiotics (n = 5637) for planned CS and women who delivered in hospitals administrating prophylaxis in conjunction with planned caesarean section to risk groups only (n = 1671). Adjusted incidence rate ratios (AIRR) were obtained using modified Poisson-regression models, adjusting for maternal age, parity, and body mass index. Main outcome measuresAntibiotic postpartum was defined as a prescription of antibiotics postpartum 2–42 days after planned caesarean section. ResultsNo difference in antibiotic prescription postpartum among women in hospitals with a general routine of prophylaxis, compared to women in hospitals with a risk-based strategy was found, RR: 1.18 (95 % CI 0.99–1.40). Women with identified risk factors (diabetes/gestational diabetes and/or BMI > 30), were more likely 1.52 (95 % CI 1.03–2.25) to receive a prescription postpartum in hospitals with a general routine of antibiotic prophylaxis than women delivered at hospitals with risk-based strategy. ConclusionsWe found no evidence that routinely administrated prophylactic antibiotics for women with planned caesarean section reduced the risk of a prescription of postpartum antibiotics in a setting with high hygiene standards. Instead, the incidence of prophylactic antibiotics was positively associated with postpartum antibiotic prescriptions and speculate that this reflects local practice routines rather than complication rates.

Prophylactic vs preemptive strategy for the prevention of CMV disease in solid organ transplant recipients: systematic review and meta-analysis of randomized controlled trials.

Cytomegalovirus (CMV) is associated with significant morbidity and mortality among solid organ transplant (SOT) recipients. Strategies for CMV prevention include universal prophylaxis or preemptive approach. We aimed to evaluate the optimal approach. We performed a systematic review and meta-analysis of randomized controlled trials comparing prophylaxis versus preemptive therapy for CMV in SOT. The primary outcome was CMV disease. Subgroup analysis of outcomes in D+ R- patients was performed. Nine trials have met inclusion criteria, five of them included kidney transplant recipients, all compared val/ganciclovir universal prophylaxis versus preemptive approach. Universal prophylaxis resulted in lower probability of CMV infection (relative risk [RR] 0.44, 95% confidence interval [CI] 0.33-0.58), yet the impact on CMV disease was insignificant (RR 0.54, 95% CI 0.24-1.23), in neither SOT recipients in general nor among D+R- subgroup (RR 0.93, 95% CI 0.37-2.32). Late-onset CMV disease rates were lower with preemptive approach. Sensitivity analysis according to allocation concealment and blinding showed similar results for CMV disease. No significant differences were demonstrated for the outcomes of mortality, bacterial or fungal infection or graft related outcomes. Acute kidney injury was significantly more common with prophylaxis (RR 1.79, 95% CI 1.12-2.89). Preemptive approach is a reasonable approach for CMV prevention in SOT recipients, if feasible. Strategies for combining the preemptive with prophylaxis strategies, as well as immune monitoring, should be investigated.

Hepatic Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease (SOS/VOD) Primary Prophylaxis in Patients Undergoing Hematopoietic Stem Cell Transplantation: A Network Meta-Analysis of Randomized Controlled Trials.

Introduction: Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a major complication following hematopoietic stem cell transplantation, resulting from immune and chemical toxicity in the sinusoidal endothelium and hepatocellular damage. In the most severe cases, multiorgan dysfunction occurs, so it is essential to promptly identify patients at greater risk of SOS/VOD and to adopt prophylactic strategies. Objectives: This study aims to systematize the impact of different approaches as primary prophylaxes against SOS/VOD in patients undergoing hematopoietic stem cell transplantation (HSCT). Methods: A systematic review and meta-analysis of randomized clinical trials evaluating different strategies for primary prophylaxis of SOS/VOD was carried out in pairwise fashion and with a consistent network structure. The odds ratio (OR) and corresponding confidence intervals were calculated using the random-effects model. Heterogeneity was assessed by the I2 method and the efficacy of each approach was estimated by SUCRA (surface under the cumulative ranking curve). Results: Considering all patients undergoing HSCT, ursodeoxycholic acid (UDCA) [OR = 0.38, 95%CI 0.14-1.06, SUCRA = 0.720] was associated with a lower incidence of VOD while defibrotide reached a modest reduction in its incidence [OR = 0.64, 95%CI 0.23-1.67; SUCRA = 0.486]. Considering the subgroup of patients undergoing hematopoietic progenitors allotransplantation, defibrotide scored higher [OR = 0.51, 95%CI 0.09-2.85, SUCRA = 0.650] by comparison with UDCA [OR = 0.53, 95%CI 0.14-1.96, SUCRA = 0.639]. Conclusions: This is the first meta-analysis comparing primary prophylaxes against SOS/VOD. UDCA yielded more promising results when considering all patients undergoing hematopoietic stem cell transplantation, yet, in a subgroup analysis of the ones exposed to allogeneic grafts, it becomes not significantly overrun by defibrotide.

Prevention of infectious complications after radical cystectomy: a systematic review and meta-analysis

The aim of this study was to conduct a systematic review and meta-analysis of the literature to evaluate the impact of different antibiotic prophylaxis (АР) strategies on the incidence of infectious complications within 30 days after radical cystectomy (RC).Material and Methods. The meta-analysis protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO): ID-CRD42023480525. A systematic search for studies published in the last 10 years (November 2013 – November 2023) was conducted in the PubMed and Cochrane Library databases by two independent researchers. A total of 7 full-text articles were included in the final statistical analysis (data from 90,935 patients). The analysis focused on three aspects: comparison of the effectiveness of different durations of antibiotic prophylaxis (24 hours or more), the impact of the type of antibacterial agent used, and the application of Enhanced Recovery after Surgery (ERAS) protocols on the overall incidence of infectious complications, the development of soft tissue infections, and upper urinary tract infections (UTIs). Meta-analysis was performed using R 4.3.2 (R Foundation for Statistical Computing, Vienna, Austria) and the metafor 4.2-0 package.Results. The median overall incidence of infectious complications was 31.78 % (23.8–58.8 %), surgical site infections – 16.46 % (6.25–35.41 %), and UTIs – 25.11 % (3.86–35.7 %), including cases leading to urosepsis. The meta-analysis did not reveal a statistically signifшcant effect of the duration of AP (24 hours or more) on the risk of infectious complications: for overall infectious complications, the risk was OR 1.11 (95 % CI 0.92–1.33; p=0.27), for surgical site infection OR 1.00 (95 % CI 0.87–1.15; p=0.97), and for UTIs OR 0.96 (95 % CI 0.84–1.10; p=0.59). However, the overall incidence of infectious complications was significantly higher in the standard perioperative management group, without ERAS protocols (OR=3.02 [95 % CI 2.07; 4.39], p&lt;0.001, I 2 =93.1 %). Conclusion. The results of this study indicate that existing AP strategies may be ineffective in reducing postoperative infectious complications in patients undergoing cystectomy with urinary diversion. Extending AP beyond 24 hours, as well as the standard regimen, did not demonstrate a reduction in infection risk, highlighting the need for a revision of clinical guidelines in this area. The principles of the ERAS program may play a crucial role in reducing infectious complications, showing promising results and requiring further research and implementation in clinical practice. Key words: radical cystectomy, antibiotic prophylaxis, complications, surgical site infection, upper urinary tract infections, ERAS&gt; ˂ 0.001, I2 =93.1 %).Conclusion. The results of this study indicate that existing AP strategies may be ineffective in reducing postoperative infectious complications in patients undergoing cystectomy with urinary diversion. Extending AP beyond 24 hours, as well as the standard regimen, did not demonstrate a reduction in infection risk, highlighting the need for a revision of clinical guidelines in this area. The principles of the ERAS program may play a crucial role in reducing infectious complications, showing promising results and requiring further research and implementation in clinical practice.

Impact of Systemic Antibiotics Use on Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Post-transplant complications lead to significant morbidity and mortality in the management of patients undergoing allogeneic hematopoietic stem cell transplant (allo-HCT). Broad-spectrum systemic antimicrobials and better prophylaxis strategies have reduced infection-related morbidity and mortality in allo-HCT patients. However, broad-spectrum antibiotic use disrupts the microbiome and immunome, which may result in poor post-transplant outcomes. We aimed to evaluate the impact of systemic antibiotics on allo-HCT outcomes. Methods: A retrospective multicenter analysis was conducted, including allo-HCT patients in the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry from 2013 to 2018 using P5646 data by Ramathan et al. Chi-square and t-tests were used to compare categorical and continuous baseline demographics. Multivariate Cox regression analyses were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), engraftment, and infection-related mortality between the two groups. Statistical analysis was conducted using R version 4.16, with statistical significance defined as p &amp;lt;0.05. Results: Among 7524 allo-HCT patients, 5779 were administered broad-spectrum systemic antibiotics (SA) while 1745 were not given systemic antibiotics (NSA). The median age was 58.58 years (range: 2.03-82.67) in the SA group and 56.18 years (range: 2.00 - 77.86) in the NSA group, and 58% were men in both groups. Ethnicities were Caucasian (76%), Hispanic (8%), African American (6%), and others (10%). The primary disorders included acute myeloid leukemia (47%), myelodysplastic syndrome (35%), and acute lymphoblastic leukemia (18%). Myeloablative conditioning was used in 53% of patients. Donor types were matched unrelated (49.5%), matched related (34%), and cord blood (16%). Graft sources were bone marrow (15%), peripheral blood stem cells (68%), and cord blood (16%). GVHD prophylaxis regimens included Tacrolimus and Cyclosporine-based (77%), post-transplant Cyclophosphamide-based (9%), Ex vivo T-cell depletion or CD34 selection (3%), and others (11%). In the multivariate regression analyses, systemic antibiotics independently predicted poor OS (55% SA vs 57% NSA; HR 1.13, 95% CI 1.01-1.22, p=0.026). Higher incidence of NRM (19% SA vs 15% NSA; HR 1.32, 95% CI 1.12-1.55, p=0.001), grade 2-4 aGVHD (41% SA vs 34% NSA; HR 1.24, 95% CI 1.12-1.38, p&amp;lt;0.001), and cGVHD (40% SA vs 39% NSA; HR 1.12, 95% CI 1.01-1.24, p=0.040) were observed with SA use. The two groups had no significant difference in DFS, relapse, infection-related mortality, and engraftment rates. The outcomes analyses were adjusted for the significant predictors identified in the univariate analyses. Conclusion: Systemic antibiotics use in allo-HCT patients is associated with higher morbidity and mortality. Judicious use and de-escalation of systemic antibiotics when safe may help to improve post-transplant outcomes. Future research exploring microbiome restoration could result in better post-transplant outcomes.

Timeline and outcomes of viral and fungal infections after Chimeric Antigen Receptor (CAR) T-cell therapy: A large database analysis

ObjectivesThis large database analysis aims to describe the incidence, timeline, and risk factors for viral and fungal infections after chimeric antigen receptor (CAR) T-cell therapy. MethodsWe queried a global research network database, TriNetX, for patients who received CAR T-cell therapy, who were identified and followed for the development of viral and fungal infections. Baseline demographic, oncologic history, laboratory data and medication histories were collected. We evaluated risk factors for respiratory viral infections (RVI), herpesvirus, fungal infections and mortality using Cox regression. ResultsA total of 2,256 patients who received CAR T-cell therapy were included, 1,867 (82.7%) were CD19-targeted and 400 (17.7%) were BCMA-targeted. Following CAR T-cell infusion, RVI were the most prevalent (23.3%) with a median onset of 160 days (IQR 52-348 days), while herpesvirus and fungal infections were less frequent, occurring in 13.6% and 11.4% of cases with median onsets of 71 (IQR 18-252) and 73 days (IQR 14-236 days), respectively. On multivariable Cox regression, independent predictors of RVI included acute lymphoblastic leukemia (ALL, HR 1.61), prior hematopoietic cell transplant (HCT, HR 1.29), cytokine release syndrome (CRS, HR 1.41), hemophagocytic lymphohistiocytosis (HLH, HR 1.96), and glucocorticoids (HR 3.37). Prior HCT (HR 2.00), hypogammaglobulinemia (HR 1.51), immune-effector cell-associated neurotoxicity syndrome (ICANS, HR 1.52), and HLH (HR 1.99) were associated with a higher risk of herpesviruses. Independent predictors of fungal infections included prior HCT (HR 1.59), CRS (HR 1.58) and hypogammaglobulinemia (HR 1.40). Idecabtagene vicleucel was associated with a lower risk of herpesvirus and fungal infections (HR 0.39 and 0.44, respectively). ConclusionsIn a large cohort of CAR T-cell therapy recipients, respiratory viral infections were the most common but occurred later, while herpesvirus and fungal infections were less frequent but occurred earlier. Prospective studies investigating prophylaxis and pre-emptive monitoring strategies are needed in this population.

Effect of Antiseptic Irrigation with 0.05% Chlorhexidine Gluconate (Irrisept) on the Incidence of Cutibacterium acnes in Primary Shoulder Arthroplasty

Previous literature has demonstrated high rates of Cutibacterium acnes (C. acnes) colonization in patients undergoing primary shoulder arthroplasty. Residing primarily within the dermal layer, C. acnes poses a major threat to intraoperative wound contamination with subsequent risk of developing periprosthetic joint infection. Discovering an effective perioperative prophylaxis strategy is imperative. To date, no such regimen has shown the ability to reliably suppress C. acnes from the deeper tissues. This study was designed to investigate whether intraoperative Irrisept irrigation would result in a lower positive culture rate of C. acnes versus standard prophylaxis alone in primary total shoulder arthroplasty. Patients undergoing primary shoulder arthroplasty were randomized to the standard control group or the experimental Irrisept group. Intraoperative cultures were obtained from the incision site, dermis, inferior glenohumeral recess, and sterile kidney basin (control). All specimens were collected by one surgeon at one institution. Samples were shipped to ACM Global Laboratories. All cultures were observed for 14 days. Statistical analysis of the control and experimental quantitative values were compared via Fisher's exact test. Nominal variables were evaluated using the chi-square test. Multivariate analysis was performed to evaluate for differences in age, body mass index, smoking history, diabetic status, VAS, and ASES scores. Significance for all comparisons was p ≤ 0.05. Final analysis included 56 patients and 223 cultured specimens. Baseline demographics were similar between cohorts, indicating successful randomization. C. acnes positive culture rate of the control group did not significantly differ from the Irrisept group (5.77% versus 10.08%; P=0.49). No differences were noted in subgroup analysis. The total positive culture rate of all specimens was 8.07% (18/223). Incision site cultures had the highest rate of positivity (14.2%), followed by the dermis (7.14%), deep tissue (5.5%), and control (5.4%). No difference in culture rates were detected regarding age, BMI, smoking history, diabetic status, VAS, or ASES scores. There was 98.2% follow-up at two weeks, 91.1% at six weeks, 83.9% at three months, and 71.4% at six months. No additional complications or adverse events were noted in either cohort. The addition of intraoperative Irrisept irrigation did not significantly differ from standard perioperative prophylaxis for C. acnes positive culture rates in patients undergoing primary shoulder arthroplasty. While the findings should be cautiously interpreted due to the limited sample size, this pilot study provides a useful framework to inform a larger randomized controlled trial, emphasizing the importance of perioperative infection prophylaxis.

Venous thromboembolism incidence and risk factors in patients undergoing hematopoietic stem cell transplantation

BackgroundMalignancy is a well-known risk factor for venous thromboembolism (VTE), and the Khorana risk score is effective for screening solid tumor patients. However, there is a lack of validated screening tools and established risk factors for patients undergoing hematopoietic stem cell transplant (HCT). Current literature reports VTE incidence in HCT patients ranging from 2.5% to 8.5%. Anticoagulation is difficult to manage post-transplant given prolonged thrombocytopenia and the likelihood of bleeding. By identifying risk factors, a predictive model may be developed to prospectively test prophylaxis strategies in patients at the highest thromboembolic event (TE) risk. ObjectivesThis study evaluated the cumulative incidence of TE at 6 months following allogeneic and autologous HCTs. This study also aimed to identify risk factors for developing TE, to evaluate time from HCT to TE, and to compare one-year survival following HCT between patients experiencing TE and those who did not. Study DesignThis is a retrospective single-center study evaluating the incidence of TE events in adult subjects undergoing HCT between March 2014 and December 2019. ICD-9 and ICD-10 codes were used to determine cancer diagnosis, TE events up 180 days after HCT, and comorbidities of interest. Each subject was reviewed for data accuracy by manual retrospective chart review. The study employed statistical tests such as the cumulative incidence method with competing risks, Gray's test, and univariate and multivariate Cox proportional hazards models to analyze the time to first thromboembolic (TE) event, evaluate risk factors, and assess 1-year survival post-HCT in relation to TE events within 180 days of HCT. Variables examined included age, sex, body mass index (BMI), transplant type, hospital length of stay, history of TE prior to transplant, active infections, graft-versus-host disease (GVHD), veno-occlusive disorder (VOD), cytomegaly virus (CMV) and other factors. ResultsThe study included 636 evaluable patients; the majority were male (57.9%), white (68.7%), and underwent an autologous HCT (68.4%). Twenty-nine patients (4.6%) experienced a TE event within 180 days post-transplant. TE events were more common in the allogeneic transplant group (n=13/201, 6.5%) than the autologous transplant group (n=16/435, 3.7%) (p=0.122). The cumulative incidence of TE was higher in patients who developed an active infection than those who did not (7.6% vs 3.1%, P=.011). Hospital LOS [HR 1.03, 95% CI 1.0-1.06, p=0.036] and active infection [HR 2.34, 95% CI 1.1-4.95, p=0.027] were significantly associated with TE in the univariate analysis but were not retained in the final multivariate model. There was no difference in one-year survival among all patients who experienced a TE event and those who did not; however, in the autologous HCT subgroup, one-year survival rate was significantly lower in those with TE compared to those without TE (Figure 3c, 80.4% vs 95.3%, P=.01). Examined variables, including history of TE event and GVHD, were not associated with TE event risk. ConclusionWhile the overall incidence of TE in our study was low, many patients received pharmacologic or mechanical prophylaxis, suggesting such strategies may be effective in mitigating TE risk. Factors such as infection and hospital LOS may further increase TE risk. Providers should continuously monitor for risk factors and signs and symptoms of TE post-transplant. It is also imperative to consider chemical prophylaxis if counts are recovered while hospitalized.

Pharmacological Thromboprophylaxis Effectiveness in Low-Risk Patients Undergoing Arthroscopic Anterior Cruciate Ligament Reconstruction: A Randomized Clinical Trial

Background: There is a paucity of evidence and controversies regarding prophylaxis strategies in low-risk patients undergoing knee arthroscopy. This study aims to evaluate the effectiveness and safety of aspirin and low-molecular-weight heparin (LMWH) in an arthroscopic anterior cruciate ligament (ACL) reconstruction for low-risk patients. Methods: We performed a preoperational evaluation a week before surgery for any sign of pulmonary embolism (PE) and deep vein thrombosis (DVT). For this purpose, we used single limited compression Doppler ultrasonography (CUS) of the lower extremities. Rehabilitation started before the time of the surgery to improve the range of motion (ROM) and quadriceps muscle function. A team of 3 orthopedists performed the procedures. The same surgical technique and graft were used with spinal anesthesia, and operation time was recorded. Results: The mean age of participants was 31.4 ± 5.6 years, with 93 individuals (67%) being men and 23% women. No cases of DVT or PE were observed. Three cases in the LMWH group and one case in the aspirin group experienced minor surgical site bleeding. One case of hemarthrosis with normal ultrasonography occurred in the LMWH group. Regarding safety and effectiveness, there was no statistically significant difference between the parallel arms. Conclusion: The use of LMWH or aspirin after simple arthroscopic ACL reconstruction in low-risk patients showed no difference in effectiveness. Hence, the routine use of thromboprophylaxis in this setting is questionable although adverse events are rare