Prophylaxis Regimens Research Articles

Incidence of post-operative nausea and vomiting after endoscopic bariatric and metabolic therapy procedures and the role of neurokinin-1 receptor antagonists: a retrospective cohort study.

Both the transoral gastric reduction (TORe) and endoscopic sleeve gastroplasty (ESG) procedures are novel endoscopic bariatric and metabolic therapies (EBMT). Our practice has an aggressive approach to prophylaxis of postoperative nausea and vomiting (PONV) for EBMT cases, but there is divergence of practice regarding use of prophylactic neurokinin-1 receptor (NK-1) antagonists (aprepitant, fosaprepitant). Herein, we determined the incidence of PONV and its potential association with NK-1 antagonist administration following EBMT. We identified and reviewed medical records of patients who underwent EBMT between 2018 and 2023. Patients were divided into those administered or not administered an NK-1 antagonist. We analyzed rates of PONV, which was defined as rescue antiemetics during anesthesia recovery. A propensity score was calculated, and outcomes were assessed using generalized estimating equations with inverse probability of treatment weighting (IPTW). We identified 404 patients undergoing EBMT (256 [63%] TORe, 148 [37%] ESG), and of these 253 patients developed PONV, (62.6% [95% CI: 57.9% to 67.3%]). NK-1 antagonists were administered to 119 (29.5%) patients. PONV was experienced by 42 (35%) and 211 (74%) of patients who were or were not administered an NK-1 antagonist, respectively (IPTW OR = 0.18, [95%CI: 0.10 to 0.31], P < 0.001). EBMT has a high incidence of PONV during anesthesia recovery. Administration of a NK-1 antagonist as part of a multiagent PONV prophylaxis regimen dramatically reduces risk for this common adverse event.

Actual opportunistic ocular surface microflora and its sensitivity to antimicrobials and bacteriophages in patients with cataracts

Background: Species of opportunistic microflora often are the pathogenic agents that causes endophthalmitis in cataract surgery. Frequently microorganisms are characterized by resistance to several antimicrobial medicaments, which limits the ability to choose an effective agent. This problem requires a detailed study and monitoring of the sensitivity of ocular surface microflora. Aim: To study the species composition of the ocular surface microflora patients before phacoemulsification and to evaluate the antimicrobial activity of antimicrobial medicaments including antiseptics and bacteriophages. Materials and methods: A total of 60 patients were examined before phacoemulsification. The sensitivity to antimicrobial medicaments and bacteriophages was determined of microorganisms isolated from three loci (conjunctival cavity, eyelid margin, lacrimal ducts). Results: Among all microorganisms isolated, there was a significant prevalence of Staphylococcus epidermidis — 48,4 %. Almost all antiseptics showed high antimicrobial activity. All staphylococci cultures were sensitive to staphylococcal bacteriophage number 2. The smallest proportion of resistant microorganisms to antimicrobial medicaments used in ophthalmology was registered in the group of aminoglycosides. Conclusions: Antimicrobial activity of the investigated medicaments was different among different bacterial species. The sensitivity of microflora changes over time, therefore it is appropriate to carry out periodic monitoring and adjust antimicrobial prophylaxis regimens based on the results received.

Postoperative outcomes after receipt of ertapenem antimicrobial prophylaxis for colon surgery: a multicenter retrospective cohort study.

To evaluate postoperative outcomes among patients undergoing colon surgery who receive perioperative prophylaxis with ertapenem compared to other antibiotic regimens. Multicenter retrospective cohort study among adults undergoing colon surgery in seven hospitals across three health systems from 1/1/2010 to 9/1/2015. Generalized linear mixed logistic regression models were applied to assess differential odds of select outcomes among patients who received perioperative prophylaxis with ertapenem compared to other regimens. Postoperative outcomes of interest included surgical site infection (SSI), Clostridioides difficile infection (CDI) and clinical culture positivity for carbapenem-resistant Enterobacteraciae (CRE). Inverse probability weights were applied to account for differing covariate distributions across ertapenem and non-ertapenem groups. A total of 2,109 patients were included for analysis. The odds of postoperative SSI was 1.56 times higher among individuals who received ertapenem than among those receiving other perioperative antimicrobial prophylaxis regimens in our cohort (46 [3.5%] vs 20 [2.5%]; IPW-weighted OR 1.56, [95% CI, 1.08-2.26], P = .02). No statistically significant differences in odds of postoperative CDI (24 [1.8%] vs 16 [2.0%]; IPW-weighted OR 1.07 [95% CI, .68-1.68], P = .78) were observed between patients who received ertapenem prophylaxis compared to other regimens. Clinical CRE culture positivity was rare in both groups (.2%-.5%) and did not differ statistically. Ertapenem use for perioperative prophylaxis was associated with increased odds of SSI among patients undergoing colon surgery in our study population, though no differences in CDI or clinical CRE culture positivity were identified. Further study and replication of these findings are needed.

Twice-yearly lenacapavir: A milestone for HIV prevention in young African women

The PURPOSE 1 trial1 demonstrated that after 52weeks, no cisgender women acquired HIV infection after receiving subcutaneous twice-yearly lenacapavir. HIV incidence with lenacapavir was significantly lower than HIV incidence with daily oral emtricitabine/tenofovir alafenamide (F/TAF) or daily oral emtricitabine/tenofovir disoproxil fumarate (F/TDF). It is the first pre-exposure prophylaxis regimen with 100% efficacy in young women.

Risk profile and thromboprophylaxis practices among patients undergoing laparotomy at Moi teaching and referral hospital

Background: Venous thromboembolism (VTE) significantly causes hospital mortality worldwide, with abdominal surgery a risk factor. Venous thromboprophylaxis can reduce VTE risk, but has adverse effects. Local research on risk profile and practice helps individualize thromboprophylaxis and develop local protocols. Methods: A prospective study was conducted at Moi teaching and referral hospital (MTRH) on adult laparotomy patients. The minimal sample size was 325 patients, using consecutive sampling. DVT was assessed using Well's score perioperatively, 2 weeks and 4 weeks postoperatively. A lower limb Doppler ultrasonography was performed on patients with a score of 2 or greater to rule out DVT. Results: The mean age of study participants was 38 years, with a 1.5:1 male-to-female ratio. Infection in the abdomen was the main reason for laparotomy. All procedures were open, and 75.4% of individuals had high or moderate VTE risk. Within 72 hours, 82.7% of patients were mobilized. Chemoprophylaxis was limited to enoxaparin post-op. Enoxaparin duration was unstandardized, and MTRH VTE risk categorization chart use was not reported. 3% of individuals received chemoprophylaxis against ACCP guidelines and 12% received enoxaparin despite contraindications. Only 13% and 24% of intermediate and high-risk patients got chemoprophylaxis. No mechanical prophylaxis was used. Symptomatic DVT was 6.8%. Advanced age, Caprini score, and enoxaparin prescription increased symptomatic DVT risk. Conclusions: Despite increased laparotomies for intra-abdominal infection and middle-aged patients, VTE is common in MTRH patients. Poor VTE risk stratification and MTRH protocol failure led to improper thromboprophylaxis. Prescribers should employ MTRH VTE regimen for proper prophylaxis. Providing prescribers with thromboprophylaxis choices to customize prescriptions.

Antibiotic prophylaxis for the prevention of surgical site infections following colorectal surgery: protocol for network meta-analysis of randomized trials

BackgroundSurgical site infections continue to be a significant challenge following colorectal surgery. These can result in extended hospital stays, hospital readmissions, increased treatment costs, and negative effects on patients’ quality of life. Antibiotic prophylaxis plays a crucial role in preventing infection during surgery, specifically in preventing surgical site infections after colorectal surgery in adult patients. However, the optimal antibiotic regimen is still unclear based on current evidence. Considering the limitations of existing reviews, our goal is to conduct a comprehensive systematic review and network meta-analysis of randomized controlled trials to evaluate the comparative benefits and harms of available antibiotic prophylaxis regimens for preventing surgical site infections following colorectal surgery in adult patients.MethodsWe will search the Medline, EMBASE, CINAHL, Scopus, and Cochrane Central Register of Controlled Trials databases to identify relevant randomized controlled trials. We will include trials that (1) enrolled adults who underwent colorectal surgeries and (2) randomized them to any systemic administration of antibiotic (single or combined) prophylaxis before surgery compared to an alternative systemic antibiotic (single or combined antibiotic), placebo, control, or no prophylactic treatment. Pairs of reviewers will independently assess the risk of bias among eligible trials using a modified Cochrane risk of bias instrument for randomized trials. Our outcomes of interest include the rate of surgical site infection within 30 days of surgery, hospital length of stay, 30-day mortality, and treatment-related adverse effects. We will perform a contrast-based network meta-analysis using a frequentist random-effects model assuming a common heterogeneity parameter. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will be utilized to assess the certainty of evidence for treatment effects.DiscussionBy synthesizing evidence from available RCTs, this study will provide valuable insight for clinicians, patients, and health policymakers on the most effective antibiotics for preventing surgical site infection.Systematic review registrationPROSPERO CRD42023434544.

Outcomes of Corneal Transplantation for Herpetic Keratitis: A Narrative Review.

Herpes simplex virus (HSV) is one of the most common etiologic agents of corneal disease and a significant cause of corneal blindness worldwide. Although most cases can be successfully managed with medical therapy, HSV keratitis associated with visually significant stromal scarring often requires corneal transplantation for visual rehabilitation. While penetrating keratoplasty (PK) represented the traditional keratoplasty technique, the past few decades have seen a shift towards lamellar keratoplasty procedures, including deep anterior lamellar keratoplasty and mushroom keratoplasty. This paper describes the current surgical techniques and perioperative antiviral prophylaxis regimen for herpetic keratitis and reviews their postoperative clinical outcomes.

Intermittent Versus Daily Trimethoprim/Sulfamethoxazole Regimens for Pneumocystis Pneumonia Prophylaxis: A Systematic Review and Meta-analysis.

In immunocompromised individuals, trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis pneumonia (PCP) prophylaxis has adverse events, and the optimal dosage is unclear. The objective of this study was to assess efficacy and safety of intermittent versus daily TMP/SMX for PCP prophylaxis. This systematic review included randomized controlled trials (RCTs) indexed in the Cochrane Central Register of Controlled Trials, PubMed, Ichushi, or Embase databases, published from database inception to September 2023. The inclusion criteria were adults taking intermittent or daily TMP/SMX for PCP prophylaxis. Risk of bias was assessed using the Cochrane risk-of-bias tool. The primary outcomes were PCP incidence, PCP-related mortality, and adverse events requiring temporary or permanent TMP/SMX discontinuation. Four RCTs (N = 2808 patients) were included. PCP incidence did not differ significantly between the intermittent and daily regimen groups (risk ratio [RR], 1.17 [95% confidence interval {CI}, .89-1.53]; certainty: very low). There was no PCP-related mortality in the 3 RCTs reporting its outcome. Compared with the daily regimen group, the intermittent regimen group experienced significantly fewer adverse events requiring temporary or permanent TMP/SMX discontinuation (RR, 0.51 [95% CI, .42-.61]; certainty: low). This systematic review and meta-analysis suggests that intermittent TMP/SMX regimens for PCP prophylaxis may be more tolerable than daily regimens and may have similar efficacy. Further RCTs are needed to apply this to current practice. Clinical Trials Registration. PROSPERO (CRD42022359102).

Evaluation of FVIII pharmacokinetic profiles in Korean hemophilia A patients assessed with myPKFiT: a retrospective chart review

PurposeThis study aimed to investigate the pharmacokinetics (PK) of factor VIII (FVIII) in Korean patients, as limited information is available on the PK of FVIII in this population.MethodsWe collected the FVIII PK results from patients with moderate-to-severe hemophilia A using myPKFiT. PK variations were assessed according to age, blood type, inhibitor history, von Willebrand factor antigen (vWF:Ag) level, and body mass index. Additionally, the correlation between the PK profile and prophylaxis regimen was specifically analyzed for each product in severe cases.ResultsThe PK data of 48 and 81 patients treated with octocog alfa and rurioctocog alfa pegol, respectively, were obtained. The median half-lives of octocog alfa and rurioctocog alfa pegol were 9.9 (range: 6.3–15.2) h and 15.3 (range: 10.4–23.9) h, respectively. The PK profiles for each product did not differ according to age group; however, blood type-O patients had shorter half-lives and time to 1% compared to non-blood type-O patients. In regression analysis, the PK of octocog alfa showed a statistically significant difference according to age, whereas the PK of rurioctocog alfa pegol correlated with vWF:Ag. Only the frequency of rurioctocog alfa pegol use showed a statistically significant difference in relation to time to 1%, although the coefficient of determination was small.ConclusionThis study confirmed significant interpatient variation in the PK of FVIII among Korean patients with hemophilia A. To achieve optimized prophylaxis, personalizing the regimen based on the PK profile of each individual patient is essential.

Improving Patient Recall Following Operative Orthopaedic Trauma.

Orthopaedic trauma patients may experience poor recall regarding their injury and treatment, impairing postoperative outcomes. We sought to evaluate the impact of a standardized postoperative educational protocol on patient recall, adherence to the treatment plan, and satisfaction. Two hundred and twenty adult, English-speaking patients with surgically treated lower-extremity fractures were prospectively included. One hundred and ten patients in the educational intervention cohort met with a non-physician study member after surgery but before hospital discharge. They were given a written questionnaire evaluating knowledge of key aspects of their injury and treatment plan. For incorrectly answered questions, the study team member told the patient the correct answer (e.g., "No, you broke your tibia."). Immediately after, the patient was verbally asked the question again (e.g., "Which bone did you break?"), repeating the process until the answer was correct. The 110 patients in the control cohort did not receive this "teach-back" protocol. During their first postoperative appointment, all 220 patients completed a follow-up questionnaire assessing recall, adherence to the treatment plan, and satisfaction. The control cohort correctly answered 64% of recall-oriented questions versus 89% in the intervention cohort (p < 0.001). Eighty-two percent of control patients versus 89% patients in the intervention cohort adhered to postoperative weight-bearing restrictions (p = 0.09). Eighty-four percent of controls adhered to their deep venous thrombosis prophylaxis regimen versus 99% of the intervention cohort (p < 0.001). On a 5-point Likert scale, controls were less satisfied with their overall orthopaedic care compared with patients in the intervention cohort (mean of 4.38 ± 0.84 versus 4.54 ± 0.63 points; p = 0.02), although this difference was less than the minimal clinically relevant difference of 10% that was defined at study onset. On propensity score-weighted multivariable analysis, receipt of the postoperative educational intervention was the only modifiable factor associated with improvement in patient recall (26% improvement [95% confidence interval, 20% to 31%]; p < 0.001). Some orthopaedic trauma patients' nonadherence to surgeon recommendations and dissatisfaction with care may be mitigated by postoperative education. This standardized postoperative educational protocol improves orthopaedic trauma patients' recall, adherence to their treatment plan, and satisfaction in a manner requiring minimal time. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Knowledge, attitude and practices of surgeons regarding venous thromboembolism prophylaxis in tertiary healthcare hospitals of the Rawalpindi Districts.

To assess doctors' knowledge, attitudes and practices regarding venous thromboembolism prophylaxis. The cross-sectional study was conducted from April to September 2021 in three public-sector hospitals affiliated with the Rawalpindi Medical University: Holy Family Hospital, Benazir Bhutto Hospital and Rawalpindi District Headquarters Hospital, Rawalpindi, Pakistan, and comprised physicians of either gender who were actively involved in patient care. Data was collected using a predesigned questionnaire regarding venous thromboembolism. Data was analysed using SPSS 25. All the 220(100%) subjects approached responded positively to the study questionnaire. There were 144(65.45%) general surgeons, 50(22.72%) gynaecologists and 26(11.81%) orthopaedic surgeons. Overall, there were 26(11.81%) senior consultants, 65(29.54%) postgraduate residents and 129(58.63%) house officers. There were 150(68.2%) doctors who reported having witnessed deep-vein thrombosis in their patients, and 113(51.4%) had witnessed deaths related to pulmonary embolism. Among the methods employed for DVT diagnosis, the use of clinical criteria was the most common 136(36.1%), while venography was the least common technique used by 8(2.2%). While 210(95.5%) subjects expressed the desire for adopting an institute-wide regimen for venous thromboembolism prophylaxis, only 66(30%) were currently following such a regimen.

Risk Factors and Outcomes of Mucorales Infection in a Modern Cohort of Solid Organ Transplant, Hematopoietic Cell Transplant, and Chimeric Antigen Receptor T-cell Therapy Recipients

Mucorales infections continue to cause significant morbidity and mortality in immunocompromised hosts despite the advent of new approaches for diagnosis and treatment of fungal infections. We aimed to evaluate risk factors and outcomes of Mucorales infection in solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell therapy recipients. This single-center retrospective study included solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell patients with cultures positive for Mucorales. Forty-three patients were included for analysis; 34 solid organ transplant (79%) and 9 hematopoietic stem cell transplant or chimeric antigen receptor T-cell (21%). Infection with Mucorales occurred a median of 184 days after transplant. At the time of diagnosis, 36 patients were on antifungal prophylaxis with the majority receiving posaconazole (53%). Thirty-three had clinically significant disease; 30 received definitive anti-Mucorales therapy and 3 empiric antifungal therapy. Isavuconazole was the most common azole used for treatment in monotherapy recipients. All-cause mortality was 64% and, of these deaths, 18 (75%) were directly related to Mucormycosis. The highest mortality was seen in disseminated and intra-abdominal disease (100%), followed by pulmonary disease (50%). There was no significant association with mortality and transplant type or number of immunosuppressive agents. Mucormycosis is an important cause of morbidity and mortality in immunocompromised patients. Breakthrough infection was not uncommon in this study. Data regarding the incidence of infection at approximately 6 months after transplantation can inform prophylaxis and treatment regimens. The spectrum of antifungal regimens used reflects the lack of consensus on ideal regimens for these organisms and a need for more studies.

Risk Factors for Plate Infection, Exposure, and Removal in Mandibular Reconstruction.

Mandibular plate reconstruction (MPR) is often indicated after tumor ablation, osteoradionecrosis excision, and traumatic bone loss to restore oral functionality and facial cosmetics. There are limited analyses identifying risk factors that lead to plate infection (PIn), exposure, and removal ("plate complications"). Retrospective cohort study. Academic tertiary medical center. Patients who underwent MPR from 2013 to 2022 were identified. Risk factors for plate complications were analyzed based on demographic, clinical, intraoperative, and postoperative factors. Multivariable analysis was conducted with logistic regression. Survival analysis was conducted with a Cox model. Of the 188 patients analyzed, 48 (25.5%) had a plate complication [infection: 22 (11.7%); exposure: 23 (12.2%); removal: 35 (18.6%)]. Multivariate analysis revealed predictive associations between at least 1 plate complication and the following variables: smoking status, soft tissue defect size, number of plates, average screw length, and various postoperative complications. Other associations approached the threshold for significance. Prior and adjuvant radiation therapy, type of free flap, stock versus custom plates, and perioperative antibiotic prophylaxis regimens were not associated with plate complications. No plate complication was independently associated with lower overall survival. PIn (hazard ratio, HR: 7.99, confidence interval, CI [4.11, 15.54]) and exposure (HR: 3.56, CI [1.79, 7.08]) were independently associated with higher rates of plate removal. Plate complications are relatively common after MPR. Smoking history, specific disease characteristics, hardware used during surgery, and postoperative complications may help identify higher-risk patients, but additional larger-scale studies are needed to validate our findings and resolve discrepancies in the current literature.

P32 Bloodstream infection following transrectal ultrasound-guided prostate biopsy: antibiotic susceptibility of isolates relative to perioperative antibiotic prophylaxis regimen

P32 Bloodstream infection following transrectal ultrasound-guided prostate biopsy: antibiotic susceptibility of isolates relative to perioperative antibiotic prophylaxis regimen

Antiemetic prophylaxis regimens in haematologic malignancies patients undergoing a hematopoietic stem cell transplantation. Which is the best standard of care? A systematic review.

This systematic review, adhering to PRISMA guidelines, aimed to evaluate the efficacy and safety of antiemetic prophylaxis in haematological patients undergoing high-dose chemotherapy as part of their hematopoietic stem cell transplantation (HSCT) conditioning regimens. We performed a comprehensive search in PubMed, EMBASE, ClinicalTrials.gov and the Cochrane database to identify randomised controlled trials (RCTs) and systematic reviews of antiemetic prophylaxis. Studies in English, French, Italian or Spanish were included. This review is registered with PROSPERO, ID CRD42023406380. Eight RCTs were analysed. The antiemetic regimens evaluated ranged from monotherapy with 5-Hydroxytryptamine Receptor 3 antagonists (5-HT3RAs) to complex combinations including olanzapine, neurokinin-1 receptor antagonists, 5-HT3RAs and corticosteroids. Complete response rates for triplet or quadruple regimens varied between 23.5% and 81.9%. Although no significant adverse effects were observed, minor symptoms such as diarrhoea, constipation, sedation and headaches were reported. Existing evidence on HSCT antiemetic therapy highlights its benefits but fails to provide clear clinical directions. The choice between triplet and quadruplet therapies for different patient scenarios is still uncertain. Until more detailed research is available, healthcare providers must rely on the latest guidelines and their judgement to customise antiemetic care for each patient's specific needs and risks.

Effectiveness of Prolonged Antibiotic Prophylaxis in Radical Cystectomy: Preliminary Analysis of the MACS Randomized Clinical Trial

BACKGROUND: Standard 24-hour antibiotic prophylaxis is widely employed to minimize the risk of infection complications within 30 days following radical cystectomy. However, a considerable variety of protocols and drug combinations don’t prevent a high complication rate, ranging from 37 to 67%. This paper presents the interim analysis of the MACS clinical trial, comparing antibiotic prophylaxis regimens by duration. OBJECTIVE: To evaluate the rate of infection complications within 30 days following radical cystectomy by comparing standard 24-hour antibiotic prophylaxis (Group A) with a prolonged 120-hour regimen (Group B). METHODS: Patients were randomized in a 1 : 1 ratio. The primary endpoint was the evaluation of the frequency of infection complications. The secondary endpoints were the rate of re-administrating antibiotics and the dynamics of the inflammation biomarker. RESULTS: A total of 78 patients (85.0% of the sample size) were enrolled (Group A: 40 and Group B: 38). The baseline and perioperative features were balanced between groups. The overall complication rate was higher in Group A (65.0% vs. 41.1%, p = 0.043). The infection complication rate was 2.7 times higher in the standard antibiotic prophylaxis group: 37.5% compared to 18.4% cases in Group B (p = 0.041), and upper urinary tract infection was more frequent in Group A (22.5% vs. 2.6%). The prolonged antibiotic prophylaxis reduced the overall frequency of infection complications compared with standard 24-hour prophylaxis (RR = 0.12; 95% CI 0.02–0.88; p = 0.037). CONCLUSIONS: In this interim analysis, the administration of prolonged antibiotic prophylaxis over 120 hours appears to be safe and feasible, demonstrating a reduction in the total number of complications, particularly infection complications.

Ciprofloxacin versus levofloxacin prophylaxis in hematopoietic stem cell transplantation: A randomized trial

ObjectivesWe aimed to assess whether there is a difference between ciprofloxacin and levofloxacin as prophylaxis in hematopoietic stem cell transplant (SCT) recipients. MethodsThis is a prospective, randomized trial in patients receiving SCT at Henry Ford Health in the United States of America. We randomly assigned patients (1:1) to receive ciprofloxacin or levofloxacin. The primary outcome was incidence of bloodstream bacterial infections (BSI) up to day 60 after SCT. ResultsBetween June 4, 2018, and May 23, 2022, we randomly assigned 308 consecutive patients to receive ciprofloxacin (154 patients) or levofloxacin (154 patients). BSI was similar in both the ciprofloxacin and levofloxacin groups (18 [11.7%] vs 18 [11.7%]). Pneumonia was more frequent in the ciprofloxacin group compared to the levofloxacin group (18 [18%] vs 7 [23%]; relative risk 2.57, 95% CI 1.11-5.98; p = 0.028). There were no differences in neutrophil engraftment, fever, Clostridium difficile infection, relapse incidence, overall survival, nonrelapse mortality, length of stay post-SCT, or intensive care unit admission. ConclusionAlthough both prophylaxis regimens demonstrated the same efficacy in SCT recipients, levofloxacin prophylaxis led to less pneumonia in the first 60 days post-SCT. Trial RegistrationThis study is registered on ClinicalTrials.gov, NCT03850379.

Low-dose anti-thymocyte globulin plus low-dose posttransplant cyclophosphamide-based regimen for prevention of graft-versus-host disease in haploidentical peripheral blood stem cell transplantation for pediatric patients with hematologic malignancies.

The low-dose anti-thymocyte globulin (ATG) plus low-dose post transplantation cyclophosphamide (PTCy) -based (low-dose ATG/PTCy-based) regimen had a promising activity in preventing of graft-versus-host disease (GVHD) in adult patients. However, its efficacy in pediatric patients remain to be defined. Here, we presented the findings from 35 pediatric patients undergoing haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with the new regimen for GVHD prophylaxis. The cumulative incidences (CIs) of grades II-III and III-IV acute GVHD (aGVHD) were 34% (95% CI, 17-48%) and 11% (95% CI, 0-21%) within 180 days post-transplantation, respectively. The CIs of chronic GVHD (cGVHD) and moderate-to-severe cGVHD within 2 years were 26% (95% CI, 7-41%) and 12% (95% CI, 0-25%), respectively. The 2-year probabilities of overall survival, relapse-free survival, and graft-versus-host disease and relapse-free survival were 89% (95% CI, 78-100%), 82% (95% CI, 68-98%) and 59% (95% CI, 43-80%), respectively. The CIs of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation by day 180 were 37% (95% CI, 19-51%) and 20% (95% CI, 6-32%) respectively. These results strongly advocate for the efficacy of the low-dose ATG/PTCy-based regimen as a robust strategy for GVHD prevention in haplo-PBSCT for pediatric patients.

Immunogenicity of 4-dose Essen intramuscular regimen for rabies post-exposure prophylaxis: A multi-center cross-sectional study in China

BackgroundThe 4-dose Essen intramuscular (IM) regimen for rabies post-exposure prophylaxis (PEP) has been recommended by Advisory Committee on Immunization Practices (ACIP) and World Health Organization (WHO), but the large-sample clinical evidence is still limited. MethodRabies virus neutralizing antibodies of 11,752 patients were detected from 409 rabies prevention clinics in 27 provinces in China. Patients with serum collected before or no later than 1 h after injection on the day of the fifth dose (day 28) of 5-dose Essen regimen were included in Group A to observe the immune efficacy of 4-dose Essen IM regimen, and patients with serum collected 14–28 days after injection of the fifth dose were included in Group B to observe the immune efficacy of 5-dose Essen IM regimen. ResultsFinally, 2351 cases met the inclusion and exclusion criteria, including 2244 cases in Group A and 107 cases in Group B. The antibody titer of Group A was higher than that of Group B [12.21 (4.15, 32.10) IU/ml vs. 9.41 (3.87, 27.38) IU/ml] (P = 0.002). In Group A, the median antibody titers were 4.01IU/ml, 11.63IU/ml and 29.46IU/ml in patients vaccinated with purified hamster kidney cell vaccine (PHKCV), purified Vero cell vaccine (PVRV), and human diploid cell rabies vaccine (HDCV), respectively, with statistical significance (P < 0.001). ConclusionsThe 4-dose Essen IM regimen could provide satisfactory immune effect, and HDCV induced higher antibody titer than PHKCV or PVRV.

Vascular biomarkers reveal a unique toxicity profile of posttransplant cyclophosphamide: secondary analysis of BMT CTN 0402 and 1202

AbstractPosttransplant cyclophosphamide (PTCy)–based graft-versus-host disease (GVHD) prophylaxis regimens are associated with very low rates of severe acute and chronic GVHD after hematopoietic cell transplant (HCT). However, concerns about cardiac and other organ toxicities persist. This study aimed to compare the vascular biomarker profile of PTCy with other GVHD regimens, including tacrolimus/sirolimus (Tac/Sir) and tacrolimus/methotrexate (Tac/MTX), to generate hypotheses for toxicity mitigation strategies. Plasma samples from day +28 after transplant were analyzed against pretransplant baseline measurements in patients receiving PTCy-based GVHD prophylaxis as part of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1202 (n = 112) vs Tac/MTX (n = 98) and Tac/Sir (n = 95) regimens from BMT CTN 0402. Compared with Tac/MTX, PTCy was associated with increasing angiopoietin-2 levels and decreasing epidermal growth factor levels at day +28. In contrast, Tac/Sir displayed increasing follistatin and endoglin levels and decreasing vascular endothelial growth factor receptor 2 (VEGFR2) plasma levels after HCT. Across all cohorts, increasing epidermal growth factor was protective from nonrelapse mortality, and decreasing VEGFR2 was associated with subsequent development of extensive chronic GVHD. These distinct biomarker profiles offer insights that could guide strategies to mitigate unique GVHD prophylaxis–associated toxicities.