Combined Prophylaxis Research Articles

Posttransplant cyclophosphamide versus anti-thymocyte globulin versus combination for graft-versus-host disease prevention in haploidentical transplantation for adult acute myeloid leukemia: A report from the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party.

The optimal choice for graft-versus-host disease (GVHD) prophylaxis in haploidentical stem cell transplantation (haplo-SCT) remains debatable. Posttransplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are two common strategies, but little is known about their combination. Using the European Society for Blood and Marrow Transplantation (EBMT) registry, the authors identified 3649 adult patients with acute myeloid leukemia (AML) who underwent haplo-SCT in complete remission between 2007 and 2021 at 260 EBMT-participating centers who received either PTCy (n=2999), ATG (n=358), or combination prophylaxis (n=292). Cord blood transplants, combined bone marrow and peripheral grafts, and transplants with ex vivo graft manipulation were excluded. Median follow-up was 31.8 months. On multivariate analysis, adjusting for patient age and performance status, disease status at transplant, cytogenetic risk, conditioning intensity, stem cell source, female-to-male graft, and donor and patient CMV status, we present the following. Compared to PTCy, ATG had a higher risk of nonrelapse mortality (hazard ratio [HR], 1.6; p=.003), worse leukemia-free survival (HR, 1.4; p=.002), overall survival (HR,1.49; p=.0009), and GVHD-free and relapse-free survival (HR,1.29; p=.012). The combination of PTCy and ATG, however, led to significantly reduced rates of grade 2-4 (HR, 0.51; p=.0003) and grade 3-4 (HR, 0.5; p=.018) acute GVHD and did not affect any transplant outcomes compared to PTCy without ATG. The authors conclude that ATG alone is a less effective prophylaxis strategy compared to PTCy, however, the combination of PTCy and ATG is superior to either monotherapy. They propose that this combination could be considered a potential new standard of care for GVHD prophylaxis in haplo-SCT for AML.

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.

THE ROLE OF PATIENT SCREENING AND RISK STRATIFICATION IN THE PREOPERATIVE PREPARATION OF PATIENTS WITH ANTERIOR ABDOMINAL WALL HERNIAS

Introduction. Lifestyle, poor physical condition, bad habits, malnutrition and adverse psychological factors reduce the body's resistance to overcome the physiological stress of surgery. Abdominal wall hernia repair is one of the most common surgical operations. A high body mass index, smoking, diabetes and immunosuppression are risk factors for the development of postoperative hernia, and in the case of its surgical correction, these factors significantly worsen the perioperative prognosis. Assessing the risk of serious complications and death during the perioperative period is crucial for the patient. Aim. To assess the role and necessity of patient screening and risk stratification in the complex of preoperative preparation of patients with anterior abdominal wall hernias. Materials and methods. In the research took part 91 patients who underwent surgical treatment of abdominal wall hernias. They were divided into 3 groups according to the type of anesthesia (general, neuraxial and fascial blocks of the abdominal wall). The analysis was carried out according to comorbidity, the presence of lifestyle risks, the risk of cardiovascular complications (LI index), the risk of anesthesia according to the ASA (American Society of Anesthesiologist's) scale and the risk of thromboembolic complications according to the Caprini scale, factors that affect the frequency postoperative nausea, vomiting and their prevention. Results and discussions. It was determined that the most common concomitant pathology in patients of 1, 2 and 3 study groups was arterial hypertension. Ischemic heart disease was most often observed in patients of group 3. Patients with a history of acute coronary syndrome dominated in the 3rd observation group. Patients were also noted to have diabetes mellitus, chronic obstructive pulmonary disease, and a history of impaired cerebral circulation. It was determined that many patients in the studied groups did not have additional risk factors, but all of them smoked and were overweight. Many patients had anesthetic risk according to ASA II or III. Patients received combined prophylaxis of postoperative nausea and vomiting. Conclusions. All groups were dominated by patients with an average and high risk of developing perioperative complications. Careful examination, identification of potential risk factors related to comorbidities and lifestyle are important to reduce the risk of complications in patients with abdominal wall hernias in the complex of preoperative preparation. Patients with a high risk of developing perioperative complications are recommended to choose neuraxial or regional anesthesia to prevent the development of postoperative complications.

Cost-Effectiveness Analysis of Maternal Respiratory Syncytial Virus Vaccine in Protecting Infants from RSV Infection in Japan.

Respiratory syncytial virus (RSV) is one of the major causes of respiratory tract infections among children. Until recently, the monoclonal antibody palivizumab was the only RSV prophylaxis available in Japan. In 2024, the bivalent RSV prefusion F protein-based (RSVpreF) vaccine was approved for the prevention of RSV infection in infants by active immunization of pregnant women. In this study, we assessed the cost-effectiveness of a combined strategy of RSVpreF vaccine and palivizumab in Japanese setting. Using a Markov model, we evaluated prevented cases and deaths of medically attended RSV infections from birth to age 11months for each of the three healthcare settings: inpatient (hospitalization), emergency department visits, and outpatient visits. Incremental cost-effectiveness ratios (ICERs) were calculated from economic outcomes (intervention costs, medication costs, and productivity losses) and quality-adjusted life years (QALYs). Further, we calculated the maximum price of RSVpreF vaccine within which the program would be cost-effective. In comparison with the current prophylaxis (palivizumab alone), a combined prophylaxis of year-round RSVpreF vaccination of pregnant women and palivizumab prescription for premature infants born in < 32weeks gestational age (wGA) and all infants with high risk prevented 14,382 medically attended cases of RSV (hospitalization, 7490 cases; emergency department, 2239 cases; outpatient, 4653 cases) and 7 deaths, respectively. From a healthcare payer perspective, when the price of RSVpreF vaccine was equal to or less than ¥23,948 (US$182), a combination prophylaxis was cost-effective under the ICER threshold of ¥5million per QALY. The other combination prophylaxis of year-round RSVpreF vaccination and palivizumab prescription of premature born in < 32wGA regardless of risk in infants was a dominant strategy (more effective and less costly). A combined prophylaxis of year-round RSVpreF vaccine and palivizumab could be a cost-effective strategy to protect neonates throughout the infant stage (< 1years old) in Japan.

Risk Factor Analysis for Anti-epidermal Growth Factor Receptor Monoclonal Antibody-induced Problematic Skin Toxicities in Patients With Liver Metastatic Colorectal Cancer.

We previously reported that patients with metastatic colorectal cancer (mCRC) and baseline liver metastasis are at a higher risk of developing grade ≥2 overall skin toxicities when treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibody. This study aimed to identify additional factors associated with skin toxicities induced by anti-EGFR treatment in patients with liver metastatic CRC. Patients with liver metastatic CRC who initially received anti-EGFR monoclonal antibody-containing treatment (n=77) were retrospectively assessed. The primary endpoint was to identify the factor(s) responsible for the development of grade ≥2 overall skin toxicities. Additionally, factors for grade ≥2 rash and paronychia were evaluated. The incidence of grade ≥2 overall skin symptoms, rash, and paronychia was 62.3%, 31.2%, and 28.6%, respectively. Multivariate Cox proportional hazard regression analyses revealed that age <65 years and anemia were independent baseline risk factors for grade ≥2 overall skin toxicities (adjusted hazard ratio 2.09, 95% confidence interval=1.10-3.97, p=0.02 for age; 2.36, 1.20-4.61, p=0.01 for anemia). In contrast, combination prophylaxis using systemic minocycline and corticosteroid ointment was a preventive factor (0.47, 0.25-0.88, p=0.02). Males and age <65 years were baseline risk factors for grade ≥2 rash, and combination prophylaxis was identified as a preventive factor. No factors were identified for paronychia. Age <65 years and anemia were identified as independent baseline risk factors. Additionally, combination prophylaxis was found to be a preventive factor against anti-EGFR monoclonal antibody-induced grade ≥2 overall skin toxicities in patients with liver metastatic CRC.

Antifungal Therapies for Aspergillus spp.: Present and Future.

Currently available and recommended options for the treatment of pulmonary aspergillosis include the triazoles, echinocandins, and amphotericin B products. These therapies have significant limitations. Only the azoles are available orally, but their use is often limited by toxicities, drug-drug interactions, pharmacokinetic variability, and emerging resistance. While the echinocandins are safe agents and may have a role in combination therapy, they are unproven as monotherapy. Amphotericin B preparations are toxic and require intensive monitoring. Finally, aspergillosis continues to be a disease conferring substantial morbidity and mortality, and clinical trials have not identified a therapeutic approach clearly associated with improved outcomes. As a result, there is a great need for new options in the treatment of invasive aspergillosis. Ideally, such options would be safe, have high oral bioavailability, have favorable pharmacokinetics to sequestered sites and retain activity against azole-resistant isolates. Reassuringly, there is a robust pipeline of novel therapies in development. Rezafungin (a once-weekly dosed echinocandin) and ibrexafungerp (oral agent with same mechanism of action as echinocandins) will likely be reserved for combination therapy or refractory/intolerance scenarios with no other options. Inhaled opelconazole is an attractive option for combination therapy and prophylaxis of pulmonary aspergillosis. Development of an oral form of amphotericin B that avoids nephrotoxicity and electrolyte disturbances is an exciting development. Finally, olorofim and fosmanogepix, two agents with novel mechanisms of action and oral formulations, hold significant potential to challenge the triazole antifungals place as preferred therapies. However, many questions remain regarding these novel agents, and at the time of this writing, none of these agents have been robustly studied in Phase III studies of aspergillosis, and so their promise remains investigational.

Evaluation of the additional prophylactic effect of topical steroid ointment to systemic minocycline against anti-epidermal growth factor antibody-induced skin toxicities in metastatic colorectal cancer treatment.

Anti-epidermal growth factor receptor (EGFR) antibodies often cause skin toxicities. Preemptive skin treatments using systemic antibiotics with or without topical steroid are reportedly effective although the most suitable method remains unclear. This study aimed to determine whether combination prophylaxis using systemic minocycline and topical steroid is superior to minocycline alone in a real-world metastatic colorectal cancer (mCRC) treatment. Patients with mCRC (n = 87) who received anti-EGFR monoclonal antibodies were retrospectively assessed. The primary objective was to compare the incidence of grade ≥ 2 overall skin toxicities during all treatment periods between the control group receiving prophylactic minocycline 100 mg/day, and the combination prophylaxis group receiving minocycline 100 mg/day + topical steroid. The incidence of each skin symptom was also evaluated. The incidence of grade ≥ 2 overall skin toxicities was 63.6% in the control and 56.9% in the combination groups, with no significant difference (P = 0.63). Similarly, the incidence of grade ≥ 2 dry skin, fissures, paronychia, and pruritus did not significantly differ. In addition, incidence of all-grade skin toxicities was not different. However, the incidence of grade ≥ 2 papulopustular rashes was significantly lower in the combination group (23.1% vs. 50.0%, P = 0.03). Propensity score-matched analysis supported these results. Multivariate logistic regression analysis showed no significant association between combination prophylaxis and grade ≥ 2 overall skin toxicities, but it did show a reduction in grade ≥ 2 papulopustular rashes. Adding topical steroids to systemic minocycline did not mitigate grade ≥ 2 overall skin toxicities induced by anti-EGFR antibodies; however, it significantly improved papulopustular rashes.

Non-T-Depleted Haploidentical Transplantation with Post-Transplant Cyclophosphamide in Patients with Relapsed/Refractory Secondary Versus De Novo AML: A Study from the ALWP/EBMT

Background: Secondary acute myeloid leukemia (sAML) is a distinct type of AML. Transplantation, a potentially curative therapy, outcomes are inferior compared to de novo AML. We recently demonstrated (J Hematol Oncol 2023) that results of non-T-cell depleted haploidentical stem cell transplantation (HaploSCT) with post-transplant cyclophosphamide (PTCy) in sAML in complete remission are not significantly different from those in denovo AML. However, the challenge in relapse (Rel)/primary refractory (PR) AML is much higher. Methods:The study aim was to compare the outcomes of HaploSCT with PTCy, performed between 2010 and 2022, in first Rel(Rel1)/PR sAML versus those in Rel1/PR de novo AML. Statistical tests included a multivariate analysis (MVA) adjusting for potential confounding factors using a Cox proportional-hazards regression model for main outcomes. Results: A total of 719 patients (pts) met the inclusion criteria, 129 with sAML and 590 with de novo AML. Median follow-up was 45.6 (IQR] 39.1-57.9) and 43.5 (IQR, 37.5-48.0) months for pts with sAML and de novo AML, respectively (p=0.20). Pts with de novo AML were younger, with a median age of 55.4 (range 18-77.8) versus 61.3 (21-78.8) years, (p&amp;lt;0.0001). The median year of the transplant was 2018 (2010-2011) in pts with sAML and 2017 (2010-2022) in those with de novo AML (p=0.62) and 65.1% and 57.6%, were male (p=0.11). In 81.4% of sAML pts, the antecedent hematological disorder was myelodysplastic syndrome. The cytogenetic risk was categorized as intermediate (58.6% vs 59.4%), adverse (37.4% vs 34.7%), and favorable (4% vs 5.9%) for pts with sAML and de novo AML, respectively (p=0.75) (data missing for 145 pts). A higher percentage of pts with sAML vs de novo AML had PR disease (73.6% vs 58.6%) (p=0.002). HCT-CI was higher in the sAML vs the de novo AML group, with HCT-CI &amp;gt;3 in 40.3% vs 21.9%, respectively (p&amp;lt;0.0001), while the Karnofsky performance status (KPS) did not differ. There was no difference in the frequency of cytomegalovirus (CMV) seropositivity and female donor to male pt combination between the two pt groups. Reduced intensity conditioning was received by 60.2% and 52.2% of the sAML and de novo AML pts, respectively (p=0.1), with thiotepa/busulfan/fludarabine being the most frequent regimen for both groups (38.8% vs 42%, respectively). Graft source was mainly peripheral blood stem cells (PB) in both sAML (69.8.5%) and de novo (66.8%) groups. All pts received PTCy as graft- versus-host disease (GVHD) prophylaxis in combination with immunosuppression, which was cyclosporine A (CSA)/ mycophenolate mofetil in 41.1% vs 52.9% and CSA/tacrolimus in 41.1% vs 33.6% respectively. Cumulative incidence of absolute neutrophil count (ANC) &amp;gt;0.5 x 10 9/L at day 60 was 83.5% vs 88.4% (p=0.13), respectively. Day 180 incidence of acute (a) GVHD II-IV and III-IV was 20% vs 26.9% (p=0.12) and 8.9% vs 10.4%, (p=0.21), respectively. The 2-year (y) total and extensive chronic (c) GVHD were 25.3% vs 20.7% (p=0.27) and 12.5 % vs 10.3% (p=0.46), respectively. In MVA HaploSCT outcomes did not differ significantly between the Rel1 /PR sAML and de novo groups; 2-y non-relapse mortality (NRM) hazard ratio (HR)=1.38 (95% CI 0.96-1.98, p=0.083). Infections and GVHD were the cause of death in 20.8% and 9.3% of pts who died. The HR for 2-y relapse incidence (RI) was 0.68 (95% CI 0.4.7.-1.00, p=0.051) and RI was the main cause of death in 40.9% and 59.3% of pts who died, respectively. The 2-y leukemia-free survival (LFS), overall survival (OS), and GVHD-free, relapse-free survival (GRFS) did not differ between the two groups with HR=0.99 (95% CI 0.76-1.28, p&amp;lt;0.94), HR=0.99 (95% CI 0.77-1.29, p=0.973) and HR=0.99 (95% CI 0.77-1.27, p=0.94), respectively. Adverse-risk cytogenetics was a poor prognostic factor for RI and both higher age (per 10y) and lower KPS were poor prognostic factors for NRM. Adverse-risk cytogenetics and lower KPS were poor prognostic factors for LFS, OS, and GRFS. In addition, pt CMV seropositivity was a poor prognostic factor for OS. Finally, PB grafts were associated with increased risk of all grades and severe aGVHD. Conclusions: In this registry-based retrospective analysis, we observed similar outcomes, of HaploSCT with PTCy for Rel1/PR sAML compared to Rel1/PR de novo AML, with HaploSCT being able to rescue about one-third of the pts. However, relapse is still 43%. The recently approved novel agents for sAML will hopefully further improve sAML outcomes.

Efficacy and Safety of Three Doses of Ceftriaxone and Metronidazole as Prophylactic Uses during Acute Non-Perforated Appendicitis Surgical Operation: A Randomized Control Trial

Background: This study compared the efficacy of prophylactic antibiotics with seven days of conventional antibiotics. Objective: This present study was carried out to evaluate the effectiveness of three doses of prophylaxis with ceftriaxone and metronidazole. Methodology: This parallel arm, randomized control trial was conducted among fifty patients, consisting of 25 cases and 25 controls, with acute appendicitis admitted at Dhaka Medical College Hospital, Popular Medical College Hospital, Dhaka, and Ad-din Barrister Rafique Ul-Haq Hospital, Dhaka, during the period of November 2021 to April 2022. This study was done to evaluate the efficacy of three doses of combined prophylactic antibiotics, ceftriaxone and metronidazole, in acute non-perforated appendicitis cases. The patients in the control group were treated with seven days of conventional antibiotic therapy to compare the efficacy with three doses of prophylactic antibiotics. Results: Among 9 wound infections (15%), 4 patients were in the control group (36.5%), and 5 (40.5%) were in the case group in the study group with combined surgical prophylaxis of ceftriaxone and metronidazole (P=0.001). One patient develops both a wound infection and an intra-abdominal abscess. The study also found that amount to patient (3.3%) with intra-abdominal abscess formation 01 (50%) in control group and 01(50.0%) in combined prophylaxis group (ceftriaxone and metronidazole) (P&gt;0.3). Conclusion: In conclusion no significant difference could be found between the patients who received combined three doses of ceftriaxone and metronidazole and the control groups with regard to age, sex, distribution of symptoms before admission, preoperative temperature, duration of surgery, hospital stay, and concomitant diseases both overall and within each of the three groups of appendiceal examination. Bangladesh Journal of Infectious Diseases, June 2023;10(1):11-15

A phase 2 trial of CD24Fc for prevention of graft-versus-host disease

AbstractPatients who undergo human leukocyte antigen–matched unrelated donor (MUD) allogeneic hematopoietic stem cell transplantation (HSCT) with myeloablative conditioning for hematologic malignancies often develop acute graft-versus-host disease (GVHD) despite standard calcineurin inhibitor–based prophylaxis in combination with methotrexate. This trial evaluated a novel human CD24 fusion protein (CD24Fc/MK-7110) that selectively targets and mitigates inflammation due to damage-associated molecular patterns underlying acute GVHD while preserving protective immunity after myeloablative conditioning. This phase 2a, multicenter study evaluated the pharmacokinetics, safety, and efficacy of CD24Fc in combination with tacrolimus and methotrexate in preventing acute GVHD in adults undergoing MUD HSCT for hematologic malignancies. A double-blind, placebo-controlled, dose-escalation phase to identify a recommended dose was followed by an open-label expansion phase with matched controls to further evaluate the efficacy and safety of CD24Fc in preventing acute GVHD. A multidose regimen of CD24Fc produced sustained drug exposure with similar safety outcomes when compared with single-dose regimens. Grade 3 to 4 acute GVHD–free survival at day 180 was 96.2% (95% confidence interval [CI], 75.7-99.4) in the CD24Fc expansion cohort (CD24Fc multidose), compared with 73.6% (95% CI, 63.2-81.4) in matched controls (hazard ratio, 0.1 [95% CI, 0.0-0.6]; log-rank test, P = .03). No participants in the CD24Fc escalation or expansion phases experienced dose-limiting toxicities (DLTs). The multidose regimen of CD24Fc was well tolerated with no DLTs and was associated with high rates of severe acute GVHD–free survival after myeloablative MUD HSCT. This trial was registered at ClinicalTrials.gov as #NCT02663622.

Venous Thromboembolism (VTE) in Post-Prostatectomy Patients: Systematic Review and Meta-Analysis.

Radical prostatectomy (RP) is one of the recommended treatments to achieve oncological outcomes in localized prostate cancer. However, a radical prostatectomy is a major abdominopelvic surgery. Venous thromboembolism (VTE) is a well-known complication associated with surgical procedures, including RP. There is a lack of consensus regarding VTE prophylaxis in urological procedures. The aim of this systematic review and meta-analysis was to investigate different aspects of VTE in post-radical prostatectomy patients. A comprehensive literature search was performed, and relevant data were extracted. The primary aim was to perform a systematic review and meta-analysis (wherever possible) of VTE occurrence in post-RP patients in relation to surgical approach, pelvic lymph node dissection, and type of prophylaxis (mechanical or combined prophylaxis). The secondary aim was to investigate the incidence and other risk factors of VTE in post-RP patients. A total of 16 studies were included for quantitative analysis. Statistical methods for analysis included the DerSimonian-Laird random effects. We were able to conclude that the overall incidence of VTE in post-radical prostatectomy is 1% (95% CI) and minimally invasive procedures (MIS), including laparoscopic, as well as robotic procedures for radical prostatectomy and RP without pelvic lymph node dissection (PLND), are associated with less risk of developing VTE. Additional pharmacological prophylaxis to mechanical methods may not be necessary in all cases and should be considered in high-risk patients only.

Is It Lupus? Is It Neuromyelitis Optica Spectrum Disorder (NMOSD)?—Why Not Both?

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are among the commonly considered differential diagnoses in patients with inflammatory central nervous system (CNS)-diseases. Formerly diagnosed competing autoimmune diseases might impair diagnostics and treatment. Here, we report on a 41-year-old woman admitted to our hospital with primary manifestation of NMOSD (paresthesia, paralysis of the lower extremities, and urinary incontinence) while undergoing treatment for a diagnosed systemic lupus erythematosus (SLE) with hydroxychloroquine. CNS manifestation of the disease was considered. Magnetic resonance imaging (MRI) of the cranium and spinal cord showed multiple supratentorial lesions of the white matter and massive intramedullary lesions with contrast enhancement. Cerebrospinal fluid (CSF) showed pleocytosis (20/µL), positive antinuclear antibodies (ANA), antiphospholipid antibodies, and SSA/Ro antibodies, while formerly positive dsDNA antibodies were negative. Further diagnostics revealed a 1:10,240 serum titer of Aquaporine-4 antibodies. The patient received intravenous methylprednisolone for three days (2 g per day), which led to an escalation to plasmapheresis and to an improved EDSS from 8.0 to 4.0. Because of the comorbidity, a combined relapse prophylaxis with satralizumab and mycophenolate mofetil was established. Rehabilitation and continued treatment improved EDSS to 1.0 with no impairment of mobilization. Although formerly diagnosed SLE could have explained the symptoms, it is important to reconsider competitive diseases in order to establish adequate immunotherapy.

Husbandry and breeding features of Fulani sheep in the Chari-Baguirmi and Mandoul provinces of Chad

&#x0D; &#x0D; &#x0D; &#x0D; A cross-sectional and retrospective survey was conducted from September 2021 to January 2022 in the provinces of Chari-Baguirmi and Mandoul (Chad) aiming at analyzing the husbandry and breeding features of Fulani sheep. A total of 144 sheep keepers owning the Fulani sheep breed were surveyed on the basis of their willingness to freely participate. Results show that the respondents belong in majority to Arab and Fulani ethnic groups. Youths and adults were the major groups of keepers (74.98%) followed by the group of above 50 years old (25%). The majority of respondents were married (98.1%). Monogamous families were more represented (63.19%) followed by polygamous families (34.72%). Large majority did not attend formal instruction level (61.80%), followed by 38.20% (either in Arabic or in French). Small family to medium family sizes were more represented (73.91%) compared to larger family size (27.07%). The main activity was livestock husbandry (91.66%), followed by crop production (69.44%) as a secondary activity. Inheritance and purchase constituted the mode of acquisition of Fulani sheep. Mobility was largely based on transhumance (95.48%) for pastoral lands (61.80%) and water sources (40.97%). About 93.75% of sampled herders were homeless and about 6.24% of them stock their flocks in paddocks made up of thorns. Natural carbonate soda source known as “Lime” was used as a mineral supplement in the rainy season by 45.76% of respondents (August-September). Groundnut cake (23.3%), cereal bran (18.21%) and cottonseed cake (11.86%) were used during the lean season (March-May) as supplementary feeds. Combined prophylaxis (vaccination and deworming) and deworming was practiced respectively by 55.54% and 15.6% as opposed to 26.48% who were reported to be without prophylaxis. Keeping the Fulani sheep was provided by family labor 54.5% followed by permanent employees who were mostly Fulani shepherds (29.72%). In terms of exploitation, reproduction (85.02%) was the main source to maintain flocks, where sales (40%), mortalities (29.4%) and slaughtering (19.5%) were the main factors affecting decrease in flock size. This study provides a better perception on the farming and breeding practices of the Fulani sheep of Chad. Thus, the sustainable use and enhancement of this sheep genetic resource require a better understanding of both phenotypic and molecular characteristics.&#x0D; &#x0D; &#x0D; &#x0D;

Chemical versus Mechanical and Chemical Venous Thromboembolism Prophylaxis in Neurocritically Ill Patients: A Cohort Study.

Patients admitted with neurocritical illness are presumed to be at high risk for venous thromboembolism (VTE). The administration of chemical and/or mechanical VTE prophylaxis is a common practice in critically ill patients. Recent data did not show a significant difference in the incidence of VTE between chemical compared to a combined chemical and mechanical VTE prophylaxis in critically ill patients with limited data in neurocritically ill population. The objective of this study is to investigate the incidence of VTE between chemical alone compared to chemical and mechanical VTE prophylaxis in neurocritically ill patients. This was a retrospective cohort study at a tertiary teaching hospital. Data were obtained from electronic medical records for all patients admitted with neurocritical illness from January 1, 2016, to December 31, 2020. Patients were excluded if they did not receive VTE prophylaxis during admission or were younger than 18 YO. Major outcomes were symptomatic VTE based on clinical and radiological findings, intensive care unit (ICU) length of stay (LOS), and hospital LOS. Minor outcomes included severe or life-threatening bleeding based on GUSTO criteria, and mortality at 28-days. Two hundred and twelve patients were included in this study. Patients did not have any significant differences in their baseline characteristics. The incidence of VTE was similar in the chemical only group compared to the combined VTE prophylaxis group (19/166 (11.3%) vs 7/46 (15.2%)); P = 0.49. No difference between groups in their ICU LOS 6 [3-16.2] vs 6.5 [3-19]; P = 0.52, nor their mortality (18/166 (10.7%) vs 3/46 (6.5%)); P = 0.38, respectively. Less bleeding events were seen in the chemical prophylaxis group compared to the combined VTE prophylaxis group (19/166 (11.3%) vs 12/46 (26.1%); P = 0.01). Our findings observed no difference between the administration of chemical VTE prophylaxis alone compared to the combined VTE prophylaxis strategy. More data are needed to confirm this finding with more robust methodology.

Tixagevimab/Cilgavimab in SARS-CoV-2 Prophylaxis and Therapy: A Comprehensive Review of Clinical Experience.

Effective treatments and vaccines against COVID-19 used in clinical practice have made a positive impact on controlling the spread of the pandemic, where they are available. Nevertheless, even if fully vaccinated, immunocompromised patients still remain at high risk of adverse outcomes. This has driven the largely expanding field of monoclonal antibodies, with variable results. Tixagevimab/Cilgavimab (AZD7442), a long-acting antibody combination that inhibits the attachment of the SARS-CoV-2 spike protein to the surface of cells, has proved promising in reducing the incidence of symptomatic COVID-19 or death in high-risk individuals without major adverse events when given as prophylaxis, as well as early treatment. Real-world data confirm the antibody combination's prophylaxis efficacy in lowering the incidence, hospitalization, and mortality associated with COVID-19 in solid organ transplant recipients, patients with immune-mediated inflammatory diseases and hematological malignancies, and patients in B-cell-depleting therapies. Data suggest a difference in neutralization efficiency between the SARS-CoV-2 subtypes in favor of the BA.2 over the BA.1. In treating COVID-19, AZD7442 showed a significant reduction in severe COVID-19 cases and mortality when given early in the course of disease, and within 5 days of symptom onset, without being associated with severe adverse events, even when it is used in addition to standard care. The possibility of the development of spike-protein mutations that resist monoclonal antibodies has been reported; therefore, increased vigilance is required in view of the evolving variants. AZD7442 may be a powerful ally in preventing COVID-19 and the mortality associated with it in high-risk individuals. Further research is required to include more high-risk groups and assess the concerns limiting its use, along the SARS-CoV-2 evolutionary trajectory.

Evaluation of Two Different CMV-Immunoglobulin Regimens for Combined CMV Prophylaxis in High-Risk Patients following Lung Transplant.

The clinical benefits of the common off-label use of cytomegalovirus (CMV)-specific immunoglobulin (CMV-Ig) combined with antivirals in organ transplantation have not been previously assessed. The objective was to compare the risk of CMV infection and other post-transplantation outcomes between two CMV-Ig prophylaxis regimens in lung transplant recipients; Methods: Retrospective study of 124 donor CMV positive/recipient negative (D+/R-) patients receiving preventive ganciclovir/valganciclovir for 12 months, of whom 62 received adjunctive CMV-Ig as per label indication (short regimen [SR-Ig]; i.e., 7 doses over 2.5 months) and were compared to 62 who received an extended off-label regimen (ER-Ig) consisting of 17 doses over one year after transplantation. The incidence of CMV infection or disease, acute rejection, chronic lung allograft dysfunction, and survival did not differ between the two CMV-Ig schedules. Although the time to the first CMV infection after transplantation was shorter in the ER-Ig than in the SR-Ig adjunctive group (log-rank: p = 0.002), the risk was independently predicted by antiviral cessation (odds ratio = 3.74; 95% confidence interval = 1.04-13.51; p = 0.030), whereas the CMV-Ig schedule had no effect. Extending the adjunctive CMV-Ig prophylaxis beyond the manufacturer's recommendations up to one year does not confer additional clinical benefits regarding lung post-transplantation outcomes.

Combination prophylaxis in CMV high risk heart transplant recipients: A single center experience.

Cytomegalovirus (CMV) is the most clinically relevant infectious agent following heart transplantation (HTX). Data on the beneficial effects of prophylactic use of CMV immunoglobulins (CMVIG) are scarce. In this single-center, retrospective study, we reported patient outcomes following cardiac transplantation using prophylactic CMV treatment, including CMVIG. Distinct clinically relevant outcomes were compared across different CMV risk groups (CMV D-/R-, CMV D-/R+, CMV D+/R+, and CMV D+/R- or CMV high risk group). We included 272 heart transplant procedures, performed between 1/1/2009 and 1/11/2020. Sixty-one (22%) procedures belonged to the CMV high risk group, while 96 (35%), 50 (18%), and 65 (24%) were CMV D-/R-, CMV D-/R+, and CMV D+/R+, respectively. Baseline donor and recipient characteristics (sex, age, body mass index, cause of death, indication for HTX), ischemia times and baseline immunosuppressive regimens were similar across the different CMV risk groups, yet fewer patients were bridged with a mechanical circulatory support in the CMV D+/R- group. CMV disease following cardiac transplantation was more common in the CMV D+/R- risk group (n=40 or 66.7%; p<.001), yet mortality and re-transplantation rates, cardiac allograft vasculopathy (CAV) severity, rejection episodes, and development of donor-specific antibodies (DSA), post-transplant lymphoproliferative diseases (PTLD), and EBV infections were similar across all four CMV risk groups. High risk CMV D+/R- patients had a similar survival compared to low and intermediate CMV risk groups using a prophylactic strategy combining CMVIG and viral DNA polymerase inhibitors. This may be related to a number of factors unrelated to prophylaxis strategy as two out of three CMV D+/R- recipients developed CMV primary infection after prophylaxis was discontinued.

Gvhd Prophylaxis Incorporating Methotrexate in Allo-HCT for Chronic Myeloid Malignancies and sAML: A Retrospective Analysis from the Cmwp of the EBMT

Introduction: Methotrexate (MTX) given on days 1, 3, 6 (and 11) after allogeneic haematopoietic cell transplantation (allo-HCT) along with calcineurin inhibitors (CNI) was established as effective GVHD prophylaxis decades ago when myeloablative conditioning was standard. Mycophenolate mofetil (MMF) replaced MTX initially in minimal intensity conditioning protocols and then became increasingly popular due to its favorable toxicity profile. Although MMF was associated with more severe GVHD in some reports, similar survival outcomes were reported for both regimens in most randomized trials. However, two large retrospective studies from the CIBMTR reported inferior outcomes of MMF-based regimens in allo-HCT standard indications. Taking advantage of a very large sample size within the EBMT registry, the aim of this retrospective study was to determine outcome differences after allo-HCT between MTX- and MMF-based GVHD prophylaxis regimens considering subgroup heterogeneity. Patients and Methods: Eligible were patients from the EBMT registry with select chronic myeloid malignancies (CML, CMML, MDS, myelofibrosis, secondary AML) who were transplanted from matched related, matched unrelated and mismatched unrelated donors between 2007 and 2017 and received either MTX or MMF prophylaxis in combination with a CNI. Endpoints were overall (OS) and relapse-free survival (RFS), relapse incidence, non-relapse mortality (NRM), and cumulative incidence of grade 2-4 acute GVHD. Multivariable Cox regression analyses included age, conditioning intensity, TBI, diagnosis, disease stage, ATG, graft source, donor type, gender match, CMV (recipient), year of transplantation, and Karnofsky index. We tested whether the association between the type of prophylaxis and the outcome was different in patient subgroups by including interaction terms in multivariable analyses between prophylaxis type (MTX/MMF) and ATG, age, Tacrolimus, conditioning intensity, use of TBI, diagnosis, disease stage and recipient CMV status. Finally, we studied the association between the same set of variables and OS, relapse and NRM in patients after aGvHD and separately in a landmark analysis at 3 months in patients without aGvHD. Results: Overall, 13699 patients from 321 centers were included. Diagnoses were MDS (44%), Myelofibrosis (18%), CML (11%), CMML (6%), atypical CML (1%) and secondary AML (21%). The conditioning / prophylaxis combination was RIC/MMF in 34%, RIC/MTX in 22%, MAC/MMF in 12% and MAC/MTX in 32%. CNI prophylaxis was Tacrolimus (n=1248), ciclosporin (n=12286), both (n=165). Median follow up was 42.8 months (IQR 19.8-74.5 months). Unadjusted analyses demonstrated significantly better outcomes with MTX in all subgroups of patients (TBI/no TBI, RIC/MAC, diagnoses except myelofibrosis, ATG/no ATG, age at allo-HCT < or ≥60 years). Figure 1a shows OS curves for conditioning/prophylaxis combinations. The cumulative incidence of acute GVHD grade 2-4 was lower in in particular RIC patients (Figure 1b). MTX was associated with significantly reduced overall mortality (HR 0.88, 95%CI 0.81-0.95, p<0.001) and NRM (HR 0.87, 95% CI 0.78-0.96, p=0.008) in multivariable analyses in the whole cohort. In contrast, MTX prophylaxis was not significantly associated with relapse (HR 1.02, 95% CI 0.92-1.12, p=0.72) and relapse-free survival (RFS) (HR 0.94, 95% CI 0.88-1.01, p=0.11). Notably, there was no significant interaction effect between prophylaxis type and any of the eight variables (ATG, age, tacrolimus, conditioning intensity, use of TBI, diagnosis, disease stage and CMV status in recipients) tested for OS and NRM, except that the beneficial association of MTX on OS was weaker for patients with Myelofibrosis. OS after acute GVHD was significantly lower with MTX prophylaxis and this was similar in RIC and MAC. MTX did not significantly associate with improved outcome in a landmark analysis in patients without aGvHD at 3 months after allo-HCT. Conclusion: Compared to MMF, MTX-complemented calcineurin inhibitor prophylaxis was associated with favorable early OS and NRM, and in particular with favorable OS after aGVHD, in this large cohort of patients with chronic myeloid malignancies or sAML transplanted in a recent time period. This effect was observed across various subgroups. These results may have future impact on clinical practice and trial design. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Association between Iron and Folic Acid Supplementation and Malaria Prophylaxis and Linear Growth among Children and Neonatal Mortality in Sub-Saharan Africa-A Pooled Analysis.

The majority of research on linear growth among children is confined to South Asia and focuses on iron and folic acid (IFA) supplementation during pregnancy, without considering malaria prophylaxis. Similarly, there is limited evidence on the association of antenatal IFA supplementation and malaria prophylaxis with neonatal mortality in sub-Saharan Africa (SSA). This study aims to address these gaps. A pooled analysis of demographic and health survey (DHS) data from 19 countries in SSA was conducted to study the association between IFA supplementation and malaria prophylaxis and linear growth and neonatal mortality. Multivariate logistic and linear regression models were used. Malaria prophylaxis was significantly associated with stunting, height-for-age Z scores (HAZ scores), and neonatal mortality, but IFA supplementation was not associated with these outcomes. When women's height and body mass index (BMI) were introduced in the model, a significant association between combined malaria prophylaxis and IFA supplementation was found with HAZ scores only. For severe stunting, no significant association was found with either in the two models. In conclusion, this study underscores the importance of antenatal malaria prophylaxis as a potential intervention for nutrition outcomes (linear growth) and neonatal mortality, as well as the importance of coordinating efforts between malaria and the health and nutrition sectors to improve these outcomes in the countries of SSA.

Keep on tailoring CMV management in lung transplantation: 24 versus 12-month CMV hyperimmune globulins regimen effects in combined universal prophylaxis.

In lung transplantation (LTx), Cytomegalovirus (CMV) management is based on prophylaxis or pre-emptive therapy. CMV hyperimmune globulins (CMV IG) added to prophylactic antiviral agents reduce CMV manifestations and acute rejection. The length of prophylaxis regimens is variable among studies with different results. We conduced, after demonstrating efficacy of 12 months prophylaxis on acute rejections and CMV pneumonia, a single center retrospective study comparing, during the second year after LTx, clinical effects of a long (24 months) versus short (12 months) course of combined CMV prophylaxis scheme, based on antiviral agents and CMV IG. We included 120 patients, 70 received a long (24 months) and 50 a short (12 months) prophylaxis. The long prophylaxis group, at 18th month, had a lower rate of neutrophilic alveolitis in BAL (63.6% vs. 94.4%, P=0.029). No other statistically significant differences were observed among the two groups of patients although we observed a reduction in both CMV (56.4% vs. 76.0% P=n.s.) and bacterial infections (23.7% vs. 32.0%, P=n.s.) during the 18th month of follow-up. We did not observe differences among two groups in acute rejection rate on transbronchial lung biopsies. The combined long prophylaxis course based on antiviral agents and CMV IG provides a reduction trend in CMV or bacterial infections even if not statistically significant. The significant reduction in neutrophilia in BAL compared to the cohort undergoing prophylaxis for 12 months should be carefully interpreted. An 18-month prophylaxis could be a good suggestion to be tested by other larger prospective studies.