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BACKGROUND: Venous thromboembolism (VTE) is a preventable medical condition which has substantial impact on patient morbidity, mortality, and disability. Unfortunately, adherence to the published best practices for VTE prevention, based on patient centered outcomes research (PCOR), is highly variable across U.S. hospitals, which represents a gap between current evidence and clinical practice leading to adverse patient outcomes. This gap is especially large in the case of traumatic brain injury (TBI), where reluctance to initiate VTE prevention due to concerns for potentially increasing the rates of intracranial bleeding drives poor rates of VTE prophylaxis. This is despite research which has shown early initiation of VTE prophylaxis to be safe in TBI without increased risk of delayed neurosurgical intervention or death. Clinical decision support (CDS) is an indispensable solution to close this practice gap; however, design and implementation barriers hinder CDS adoption and successful scaling across health systems. Clinical practice guidelines (CPGs) informed by PCOR evidence can be deployed using CDS systems to improve the evidence to practice gap. In the Scaling AcceptabLE cDs (SCALED) study, we will implement a VTE prevention CPG within an interoperable CDS system and evaluate both CPG effectiveness (improved clinical outcomes) and CDS implementation. METHODS: The SCALED trial is a hybrid type 2 randomized stepped wedge effectiveness-implementation trial to scale the CDS across 4 heterogeneous healthcare systems. Trial outcomes will be assessed using the RE2-AIM planning and evaluation framework. Efforts will be made to ensure implementation consistency. Nonetheless, it is expected that CDS adoption will vary across each site. To assess these differences, we will evaluate implementation processes across trial sites using the Exploration, Preparation, Implementation, and Sustainment (EPIS) implementation framework (a determinant framework) using mixed-methods. Finally, it is critical that PCOR CPGs are maintained as evidence evolves. To date, an accepted process for evidence maintenance does not exist. We will pilot a Living Guideline process model for the VTE prevention CDS system. DISCUSSION: The stepped wedge hybrid type 2 trial will provide evidence regarding the effectiveness of CDS based on the Berne-Norwood criteria for VTE prevention in patients with TBI. Additionally, it will provide evidence regarding a successful strategy to scale interoperable CDS systems across U.S. healthcare systems, advancing both the fields of implementation science and health informatics. TRIAL REGISTRATION: Clinicaltrials.gov - NCT05628207. Prospectively registered 11/28/2022, https://classic. CLINICALTRIALS: gov/ct2/show/NCT05628207 .

There is significant variability in postoperative chemoprophylaxis protocols amongst spine providers due to perceived risks and benefits, but limited data on the topic. At our institution, both orthopaedic spine and neurosurgery departments utilize unfractionated subcutaneous heparin in identical dosages and frequency, with the only difference being time to initiation postoperatively. To evaluate the rate of symptomatic venous thromboembolism (VTEs) and unplanned reoperation for hematoma based on timing of chemoprophylaxis initiation. Single institution retrospective cohort study. Patients undergoing elective spine surgery, excluding patients undergoing surgery in the setting of trauma, malignancy, or infection. Outcome measures included the diagnosis of a venous thromboembolism within 90 days of surgery and unplanned reoperation for a hematoma. Patients undergoing elective spine surgery from 2017 to 2021 were grouped based on chemoprophylaxis protocol. In the "immediate" group, patients received subcutaneous heparin 5000 units every 8 hours starting immediately after surgery, and in the "delayed" group, patients received chemoprophylaxis starting postoperative day (POD)-2 for any decompressions and/or fusions involving a spinal cord level (ie, L2 and above) and POD-1 for those involving only levels below the spinal cord (ie, L3 to pelvis). A cox proportional hazards model was created to assess independent predictors of venous thromboembolic events, while a logistic regression was utilized for unplanned reoperations for hematoma. Of 8,704 patients, a total of 98 (1.13%) VTE events occurred, of which 43 (0.49%) were pulmonary embolism. Fifty-four patients (0.62%) had unplanned reoperations for postoperative hematomas. On cox proportional hazards model analysis, immediate chemoprophylaxis was not protective of a venous thromboembolism (Hazard Ratio: 1.18, p=.436), but, it was a significant independent predictor for unplanned reoperation for hematoma on multivariable logistic regression modeling (Odds Ratio: 3.29, p<.001). Both chemoprophylaxis protocols in our study resulted in low rates of VTE and postoperative hematoma. However, our findings suggest that the delayed chemoprophylaxis protocol may mitigate postoperative hematoma formation without increasing the risk for a thrombotic event. [ABSTRACT FROM AUTHOR]

Since its discovery in 1957, respiratory syncytial virus (RSV) has been widely recognized as a common and deadly pathogen. Although early studies focused on the impact of RSV on the health of children, more recent data show that RSV imposes a significant burden on individuals aged ≥ 70 years. RSV also substantially harms the health of individuals with cardiopulmonary diseases. Early efforts to develop an RSV vaccine were hampered by toxicity due to antibody-enhanced viral pneumonia and a lack of efficacy in vaccines that targeted the postfusion configuration of the F fusion protein, which is crucial to the pathogenesis of RSV-mediated injury. A newer wave of vaccines has targeted a stabilized prefusion F protein, generating effective neutralizing antibodies and reducing the burden of mild and severe RSV lower respiratory tract injury. This review focuses on the burden of RSV in patients with pulmonary diseases, highlights the tumultuous path from the early days of RSV vaccine development to the modern era, and offers insights into key gaps in knowledge that must be addressed to adequately protect the vulnerable population of patients with severe pulmonary diseases. RSV vaccination with bivalent RSVPreF or RSVPreF3OA, which target the stabilized prefusion F protein, can be broadly recommended to adults aged ≥ 60 years with pulmonary diseases. However, more data are needed to understand how these vaccinations affect key clinical outcomes in individuals with pulmonary disease. [ABSTRACT FROM AUTHOR]

Introduction: Over the past decade, several randomized controlled trials have compared single-day dexamethasone (dexamethasone-sparing) regimens to the current standard multi-day dexamethasone antiemetic regimen for chemotherapy-induced nausea and vomiting (CINV). The aim of this systematic review and meta-analysis is to compare the efficacy and safety of dexamethasone-sparing regimens to standard multi-day dexamethasone, used for the prophylaxis of CINV. Methods: Ovid Medline and Embase were searched from database inception to March 2024. Studies were included if they reported on randomized controlled trials of adult cancer patients receiving different scheduling of dexamethasone, for the endpoints of complete response, complete control, no nausea, no vomiting, and no use of rescue medication. Safety was also assessed. Meta-analysis, leave-one-out meta-analysis, and cumulative meta-analysis were conducted to generate summary effect estimates and assess the influence of single trials on the summary effect estimate. Results: Ten trials reporting on 2234 patients were included. Dexamethasone-sparing regimens were found to be no different to control arm in the acute (Risk Ratio [RR] 1.01; 95% CI, 0.94–1.08), delayed (RR 0.97; 95% CI, 0.89–1.05) and overall phases (RR 0.98; 95% CI, 0.90–1.06) for complete response. There was likewise no difference for complete control, no nausea, no vomiting, and no use of rescue medication. Safety profile was similar. There was no concern for bias in the published literature. No difference was found between studies reporting on anthracycline/cyclophosphamide-based highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). Conclusion: In this comprehensive systematic review and meta-analysis, dexamethasone-sparing regimens were found to be no different to current multi-day regimens with respect to efficacy and safety for MEC and anthracycline/cyclophosphamide-based regimens. Clinicians and future guidelines should strongly consider greater adoption and endorsement of dexamethasone-sparing regimens. [ABSTRACT FROM AUTHOR]

Background Prior vaccination is often studied for its impact on individuals' post-infection prognosis. Ayurveda, Yoga, Unani, Siddha and Homeopathy (AYUSH) medicines, advised by the Government of India as prophylaxis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic, were consumed by the masses in 2020. A study was therefore undertaken to observe any association between the prior usage of AYUSH prophylactic medicines and post-infection severity as reported by recovered COVID-19 individuals. Methods This was a retrospective, multi-centre, cohort study conducted in 21 cities of India from 5th August to 30th November 2020. Data from recovered COVID-19 patients, of either sex or any age, captured information about AYUSH prophylactic medicines intake prior to infection, disease severity, symptomatology, duration of complaints, etc. The study participants were grouped into AYUSH intake and non-intake. Primary composite outcome was the disease clinical course. Secondary clinical outcomes were the rate of and time to clinical recovery. Results Data of 5,023 persons were analysed. Ayurveda or homeopathic prophylactic medicines were consumed by more than half of the study participants: that is, 56.85% (n = 1,556) and 56.81% (n = 1,555) respectively. The overall adjusted protective effect (PE) of AYUSH prophylactic intake against moderate/severe forms of COVID-19 disease was 56.7% (95% confidence interval [CI], 48.7 to 63.50; p < 0.001). Adjusted PE for homeopathy and Siddha was 52.9% (95% CI, 42.30 to 61.50; p < 0.001) and 59.8% (95% CI, 37.80 to 74.10; p < 0.001), respectively. A statistically significant association was found between AYUSH prophylactic medicine intake and clinical recovery more frequently by the 3rd day of illness (χ 2 = 9.01; p = 0.002). Time to resolution of symptoms in the AYUSH intake group was on average 0.3 days earlier than in the non-intake group (p = 0.002). Conclusion AYUSH prophylactics were associated with statistically significant levels of protection against COVID-19 disease severity. Amongst these, previous intake of homeopathy or Siddha medicines was associated with some protection against moderate/severe illness and with a somewhat quicker clinical recovery. Prospective studies with experimental research design are needed to validate the findings of this study. Study registration Clinical Trials Registry—India (CTRI/2020/08/027000). [ABSTRACT FROM AUTHOR]

Copyright of Journal of Orofacial Orthopedics/Fortschritte der Kieferorthopadie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary This study retrospectively compared outcomes of various allogeneic haematopoietic cell transplantation (allo‐HCT) platforms in patients with adult T‐cell leukaemia/lymphoma. Platforms included human leukocyte antigen (HLA)‐haploidentical‐related donors using post‐transplant cyclophosphamide (PTCY), HLA‐matched related donors (MRD), HLA‐matched unrelated donors (MUD) and cord blood transplantation (CBT). Patients who underwent their first allo‐HCT between 2016 and 2021 were included. Outcomes analysed were overall survival (OS), relapse and non‐relapse mortality (NRM). Seven hundred patients were included (PTCY, n = 121; MRD, n = 91; MUD, n = 160; CBT, n = 328). With a median follow‐up of 794 days for survivors, 2‐year OS was 48.1% (PTCY), 48.8% (MRD), 48.4% (MUD) and 34.6% (CBT); the respective 2‐year cumulative incidence of relapse was 37.1%, 47.5%, 33.9% and 45.1% and that of NRM was 24.2%, 19.8%, 24.7% and 27.3%. PTCY was associated with delayed platelet engraftment relative to MRD and MUD. There was no increase in the incidence of severe acute or chronic graft‐versus‐host disease. In the PTCY group, poor performance status was a significant predictor of inferior OS, and infused CD34+ cell numbers of less than 5 × 106/kg were associated with delayed neutrophil and platelet engraftment. These results suggest that allo‐HCT with PTCY is a safe and effective platform for patients with adult T‐cell leukaemia/lymphoma. [ABSTRACT FROM AUTHOR]

Letermovir (LTV) prophylaxis is effective in reducing the incidence of clinically significant cytomegalovirus (CMV) infection (cs CMVi) after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Since our centre began administering LTV prophylaxis in June 2022, we have observed a certain increase in the incidence of Epstein–Barr virus (EBV) reactivation after haploidentical HSCT. We retrospectively analysed 230 consecutive patients who underwent haploidentical HSCT with rabbit anti-thymocyte globulin (ATG) from October 2022 to June 2023. The LTV group included 133 patients who received LTV prophylaxis, and the control group included 97 patients who did not receive LTV prophylaxis. At 1 year after HSCT, EBV reactivation was observed in 36 patients (27%) in the LTV group and 13 patients (13%) in the control group (p = 0.012). All patients with EBV reactivation had EBV-DNAemia, and one patient in each group developed EBV-associated posttransplantation lymphoproliferative disorder (PTLD). The proportion of patients with low EBV-DNA loads (> 5 × 102 to < 1 × 104 copies/mL) was greater in the LTV group than in the control group (23% vs. 10%, p = 0.01). The proportion of patients with CMV reactivation was lower in the LTV group than in the control group (35% vs. 56%, p = 0.002). There was no significant difference between the groups in terms of neutrophil and platelet count recovery, the cumulative incidence of acute/chronic graft-versus-host disease, overall survival, cumulative relapse rate or nonrelapse mortality. Our results show that the increased incidence of EBV reactivation may be associated with LTV prophylaxis for CMV after haploidentical HSCT. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Highlights In Thailand, an upper‐middle‐income country, managing haemophilia A (HA) with inhibitors poses significant challenges, often necessitating bypassing agents (BPAs) for bleeding control. This study evaluates the cost‐effectiveness and budget impact of emicizumab, a novel prophylactic agent, as an alternative to both episodic and prophylactic BPA treatments from a societal perspective.A Markov model was employed to estimate the lifetime societal costs and outcomes of emicizumab prophylaxis for HA patients with inhibitors. Treatment efficacy, cost, and epidemiological data were obtained through a comprehensive literature review and incorporated into the model. A 5‐year budget impact analysis complemented the cost‐utility analysis, with a 3% annual discount rate applied to future costs and outcomes.In the base‐case scenario, emicizumab prophylaxis in HA patients aged 2 years and above demonstrated superior cost‐effectiveness, yielding 18.1 quality‐adjusted life years (QALYs) per patient over a lifetime and resulting in cost savings of 138 million Thai Baht (THB) compared to BPA prophylaxis. Compared to episodic BPA treatment, emicizumab yielded 30.5 QALYs and saved 25 million THB per patient. The 5‐year budget impact was projected at 1775 million THB.Emicizumab offers a cost‐saving approach for HA treatment with inhibitors in Thailand, promising significant health benefits and budgetary savings. This supports its potential inclusion in Thailand's National List of Essential Medicines to enhance haemophilia care access. Managing haemophilia A (HA) with inhibitors in Thailand, an upper‐middle‐income country, faces challenges due to limited access to effective treatments or newer drugs for bleeding management. Emicizumab prophylaxis found to as a cost‐effective and viable alternative to traditional treatments, effectively preventing bleeding in Thai HA patients over 2 years old with inhibitors. Demonstrating improved clinical outcomes and reduced costs, emicizumab prophylaxis outperforms episodic BPA treatments, positioning it as a superior treatment option for HA patients with inhibitors in Thailand. [ABSTRACT FROM AUTHOR]

Post-traumatic headache (PTH) is a common and debilitating consequence of traumatic brain injury (TBI), often resembling migraine and tension-type headaches. Despite its prevalence, the optimal treatment for PTH remains unclear, with current strategies largely extrapolated from other headache disorders. This review evaluates the use of onabotulinumtoxin A (ONA) and anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) in the treatment of PTH. A comprehensive literature search was conducted on PubMed, including studies published up to September 2024, focusing on the efficacy, safety, and mechanisms of onabotulinumtoxin A and anti-CGRP mAbs in PTH. Both clinical trials and observational studies were reviewed. ONA, widely recognized for its efficacy in chronic migraine, has shown limited benefits in PTH with only one trial involving abobotulinumtoxin A in a cohort of 40 subjects. A phase 2 trial with fremanezumab, an anti-CGRP monoclonal antibody, failed to demonstrate significant efficacy in PTH, raising questions about the utility of targeting CGRP in this condition. ONA may offer advantages over anti-CGRP mAbs, not only in terms of its broader mechanism of action but also in cost-effectiveness and higher patient adherence. Both ONA and anti-CGRP mAbs are potential options for the management of PTH, but the current evidence is insufficient to establish clear guidelines. The negative results from the fremanezumab trial suggest that CGRP inhibition may not be sufficient for treating PTH, whereas onabotulinumtoxin A's ability to target multiple pain pathways may make it a more promising candidate. [ABSTRACT FROM AUTHOR]

Background: Chagas disease (ChD) is endemic in many parts of the world and can be transmitted through organ transplantation or reactivated by immunosuppression. Organs from infected donors are occasionally used for transplantation, and the best way of managing the recipients remains a subject of debate. Methods: We present a single‐center cohort study describing a 10‐year experience of kidney transplantation in patients at risk of donor‐derived ChD and or reactivation. Patients received prophylactic treatment with Benznidazole and were monitored for transmission or reactivation. Monitoring included assessing direct parasitemia, serology, and polymerase chain reaction (PCR). Results: Fifty‐seven kidney transplant recipients (KTRs) were enrolled in the study. Forty‐four patients (77.2%) were at risk of primary ChD infection, nine patients (15.8%) were at risk of disease reactivation, and four patients (7.0%) were at risk of both. All patients received Benznidazole prophylaxis, starting on the first day after transplantation. Parasitemia was assessed in 51 patients (89.5%), serology also in 51 patients (89.5%), and PCR in 40 patients (70.2%). None of the patients exhibited clinically or laboratory‐detectable signs of disease. A single patient experienced a significant side effect, a cutaneous rash with intense pruritus. At 1‐year post‐transplantation, the patient and graft survival rates were 96.5% and 93%, respectively. Conclusion: In this study, no donor‐derived or reactivation of Trypanosoma cruzi infection occurred in KTRs receiving Benznidazole prophylaxis. [ABSTRACT FROM AUTHOR]

The article discusses the impact of sulfonamide allergy labels on the risk of opportunistic infections after solid organ transplantation (SOT). SOT recipients with a sulfonamide allergy label were found to have an increased risk of Toxoplasma and Nocardia infections compared to those without the label. The study highlights the importance of reassessing sulfonamide allergy labels in SOT recipients to optimize prophylactic treatment and reduce the risk of opportunistic infections. Efforts should be made to identify safe delabeling strategies and promote the use of trimethoprim/sulfamethoxazole (TMP‐SMX) in eligible SOT recipients. [Extracted from the article]

Background: Cytomegalovirus (CMV) can cause tissue‐invasive disease and indirect effects after lung transplantation (LTx) such as acute rejection episodes and chronic lung allograft dysfunction. Monitoring CMV‐specific cell immune recovery (CMV‐CIR) after LTx can individualize CMV risks and establish better antiviral approach. This study evaluated the dynamics of CMV‐CIR, using QuantiFERON‐CMV assay (Qiagen Group), in the first year after LTx. Methods: Prospective observational cohort study included lung transplant recipients from December/2015 to December/2016. Universal antiviral prophylaxis with intravenous ganciclovir 5 mg/kg/day 3 days/week for 3 months was given for CMV‐seropositive recipients (R+) and only CMV‐seropositive donor and negative recipient (D+/R−) received a 6‐month‐prophylaxis with ganciclovir and valganciclovir, on alternate days, in the first 3 months and then, 3 more months of valganciclovir. QuantiFERON‐CMV was measured at the same time points of surveillance bronchoscopies. CMV infection was defined as any DNAemia detected and CMV disease with proven biopsy or antigenemia pp65 above 10 cells/300.000 neutrophils. Results: Thirty‐eight patients were included. On days 45, 90, and 365 days post‐LTx, 60%, 72%, and 81% QuantiFERON‐CMV were reactive, respectively. Eleven patients (28.9%) presented CMV‐disease and 27 DNAemia/CMV infections. Reactive tests were able to predict CMV disease only at 90 days after LTx (p =.027) but failed on DNAemia/CMV infection (p =.148). Daily prophylaxis, for D+/R− patients (13.2%), remained as an independently associated factor for not achieving reactive QuantiFERON‐CMV (adjusted OR.27, 95%CI.12–.60, p =.02). Conclusion: QuantiFERON‐CMV may be another diagnostic tool to help stratify CMV‐disease risk and individualized antiviral prophylaxis after LTx. [ABSTRACT FROM AUTHOR]

We aimed to characterize the population pharmacokinetics (PK) of vedolizumab for acute graft‐versus‐host disease prophylaxis in adults undergoing allogeneic hematopoietic stem cell transplantation (allo‐HSCT) and assess potential clinically relevant covariates. Dosing, patient characteristics, and PK from a phase 1b, open‐label, dose‐finding study of vedolizumab 75 mg initial dose escalated to 300 mg and a phase 3 study of vedolizumab 300 mg in patients receiving allo‐HSCT were analyzed using a two‐compartment population PK model with linear elimination. Covariates included age, race, weight, sex, albumin, lymphocyte count, GvHD type, and concomitant medications. Weight, albumin, and lymphocyte count were time‐varying covariates. Model selection was driven by goodness‐of‐fit criteria, precision of parameter estimates, and visual predictive checks. In 193 patients undergoing allo‐HSCT, vedolizumab PK were well described by a two‐compartment, linear PK model. Using reference covariate values, final parameter estimates (95% confidence intervals [CI]) were: clearance, 0.148 (0.136, 0.162) L/day; central volume of distribution, 3.12 (3.03, 3.21) L; intercompartmental clearance, 0.500 (0.408, 0.612) L/day; and peripheral volume of distribution, 3.95 (3.52, 4.44) L. Weight and albumin were the most important predictors of vedolizumab PK, with clearance decreasing by ≈20% for low body weight/high albumin and increasing by ≈30% for high body weight/low albumin. There was an inverse relationship between vedolizumab clearance and age, but no detectable effect for lymphocyte count or GvHD type. Post hoc analyses did not detect any relationship between vedolizumab PK and concomitant medications. In summary, the covariates studied did not have a clinically meaningful effect on the PK of vedolizumab. [ABSTRACT FROM AUTHOR]

Objectives: Haemophilia B (HB), characterised by deficient factor IX (FIX), leads to spontaneous bleeds. Severe cases require prophylactic FIX replacement. This post hoc analysis assessed the first spontaneous bleeds among previously untreated patients (PUPs) with HB treated with recombinant FIX Fc fusion protein (rFIXFc) (NCT02234310) to identify factors influencing bleeds. Methods: Subjects included paediatric PUPs with HB (≤2 IU/dL endogenous FIX). Analyses described treatment patterns (on demand [OD] vs. prophylaxis) and prophylaxis type (started on vs. switched to prophylaxis). Kaplan–Meier analyses assessed the time to first spontaneous bleed, including median time to event and fitting models with predictors for treatment regimen and/or baseline age. Results: PUPs B‐LONG enrolled 33 subjects. Baseline age did not influence the time to first spontaneous bleed for any rFIXFc regimen. Those who started on prophylaxis with rFIXFc (n = 11), compared with those treated OD (n = 22), had an extended time to first spontaneous bleed. Starting prophylaxis afforded a 93% reduced risk of first spontaneous bleed versus starting OD (hazard ratio [95% confidence interval]: 0.071 [0.009–0.592]) (p =.015). Conclusion: rFIXFc prophylaxis, particularly starting early, reduced the risk of bleeding and delayed time to first spontaneous bleed compared with rFIXFc OD. Hence, initial treatment regimens impact bleed patterns in paediatric PUPs. [ABSTRACT FROM AUTHOR]

\nIntroduction: Hereditary angioedema (HAE) is a rare genetic disorder caused by deficiency or dysfunction of C1-esterase inhibitor that is characterized by recurrent episodes of bradykinin-mediated edema. Lanadelumab has been the only available first-line therapy for long-term prophylaxis (LTP) of HAE in China since its approval in 2020. The present study aimed to investigate the clinical efficacy and safety of lanadelumab for LTP in Chinese patients. Methods: A retrospective clinical data were collected for the 6 patients and used to examine the frequency of attack symptoms, disease-related loss of work days, and quality of life before and after LTP with lanadelumab. Health-related quality of life was assessed using the Dermatology Life Quality Index (DLQI) and the Angioedema Quality of Life Questionnaire (AE-QoL). Results: Lanadelumab led to reductions of 97.8% and 98.5% in the attack rate and treated attack rate, respectively. All patients exhibited significant improvements in AE-QoL and DLQI scores (100% reduction rates) during the early treatment period (4 weeks and 2 weeks, respectively) and in missed work days/year (98.9% reduction rate). The efficacy of lanadelumab remained stable during COVID-19 vaccination and infection. No serious/severe treatment-emergent adverse events occurred during lanadelumab treatment. Conclusion: This study is the first report that demonstrates the clinical efficacy of lanadelumab and safety of LTP in HAE patients from Chinese mainland. A reasonable dosage plan can ensure a quick and long-lasting protective role of lanadelumab against HAE attacks, during COVID-19 pandemic period. Hereditary angioedema (HAE) is a rare genetic disease characterized by recurring episodes of painful swelling of the subcutaneous and submucosal tissue, and its pathogenesis is due to the deficiency or dysfunction C1-esterase inhibitors. HAE attacks can affect many areas of the body, but most frequently involve the extremities, gastrointestinal tract, genitals, face, and upper airway. Swelling of the larynx can occur, with potentially fatal consequences owing to asphyxiation. Since 2020, China has had the only first-line treatment drug that can prevent HAE attacks – lanadelumab. Our study evaluated the efficacy and safety of lanadelumab by observing the 6 patients in China mainland who were the first to use it. Our research showed that lanadelumab can prevent the attack of HAE, greatly improve the quality of life of patients, and has good safety. A reasonable dosage plan can ensure stable therapeutic effects of lanadelumab. In addition, the efficacy of lanadelumab remained stable during COVID-19 vaccination and infection. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether oculoplastic surgeries can be performed without any topical and systemic antibiotics, in a "100% antibiotic free" fashion. Method: We conducted a multicenter retrospective study between November 2017 and December 2022. Patients who underwent an oculoplastic procedure were screened. Patients who received preoperative or postoperative systemic antibiotics were excluded. Intraoperative IV antibiotics were allowed. Patients were divided into two groups: those who were treated with local antibiotics ointments (LATB group) and those who were treated without local antibiotics ointments (LATB free group) postoperatively. The primary outcome was the incidence of surgical site infections (SSI). The relationship between the use of local antibiotics and the occurrence of SSI was assessed using Fisher's exact test. The alpha risk was set to 5% and two-tailed tests were used. Results: Among the 947 procedures included, 617 were included in the LATB group and 330 in the LATB free group. 853 and 80 procedures were classified Altemeier class 1 (clean) and class 2 (clean-contaminated) surgeries, respectively. Overall, 310 (32.73%) procedures were performed without any systemic nor topical antibiotics (100% antibiotic free fashion). SSI occured in four (4/617; 0.65%) and five (5/330; 1.52%) procedures in the LATB and LATB free group respectively, without any statistical difference between the groups (p = 0.290). A subgroup analysis was carried out by excluding the procedures performed under prophylactic intraoperative intravenous antibiotics and did not reveal any statistical difference between the two groups (p = 0.144). All SSI patients were treated with systemic antibiotics with favorable outcomes. Postoperative wound dehiscence was the only risk factor associated with postoperative SSI (p = 0.002). Conclusion: This study suggests that performing a "100% antibiotic free" oculoplastic surgery without systemic and topical antibiotics is reasonable in Altemeier class 1 and class 2 procedures. [ABSTRACT FROM AUTHOR]

We emulated a hypothetical target trial in which hematological subjects cared at the University Hospital of Pisa (Italy) received or not SARS-CoV-2 prophylaxis with tixagevimab/cilgavimab. Subjects who received prophylaxis (cases) were compared to those who did not (controls). The main outcome was SARS-CoV-2 infection in the subsequent 6 months. Inverse probability weighting (IPW) was used to adjust for confounders. A multivariable analysis was performed to identify variables associated with SARS-CoV-2 infection. We recruited 462 patients: 228 received prophylaxis, 234 were controls. COVID-19 was lower in cases compared to controls (16.7% vs 24.8%, p = 0.03, after IPW 14.3% vs 24.6%, p = 0.01). On multivariable analysis, B-cell depleting therapies (HR 2.09, 95%CI 1.05-4.18, p = 0.037) were associated with increased risk of COVID-19, while tixagevimab/cilgavimab prophylaxis (HR 0.45, 95%CI 0.27-0.73, p = 0.001) and previous SARS-CoV-2 infection (HR 0.27, 95%CI 0.14-0.51, p < 0.001) were protective. In conclusion, prophylaxis with monoclonal antibodies may reduce the risk of COVID-19 in hematological patients. [ABSTRACT FROM AUTHOR]

Objective: Antibiotics have been prescribed routinely in sialendoscopy procedures to reduce the risk of postoperative infection, despite the limited evidence supporting this practice. Being necessary to assess the need for antibiotics in Sialendoscopy, aiming to provide evidence-based guidance to clinicians regarding antibiotic administration in this procedure. Materials & method: A prospective, randomized, double-blind, controlled clinical trial to evaluate the of prophylactic antibiotics in Sialendoscopy was designed. Results: A total of 80 patients were included in this study, including 57 females (71.8%) and 23 males (28.8%). In terms of prophylaxis, 36 patients (45%) received prophylactic treatment, and 44 patients (55%) did not. The occurrence of infectious events was observed in 2 patients (5.6%) with prophylaxis and 4 patients (9.1%) without prophylaxis. However, this difference was not statistically significant (p = 0.556). Conclusion: In conclusion, our prospective, randomized clinical trial aimed to address the debate regarding the use of prophylactic antibiotics in sialendoscopy. Our study's findings suggest that the routine use antibiotics may not be necessary to prevent postoperative infections in sialendoscopy procedures. These results have important implications for clinical practice, potentially reducing the unnecessary use of antibiotics and addressing concerns related to antibiotic resistance and adverse drug reactions. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE), including both pulmonary embolism (PE) and deep vein thrombosis (DVT), is the leading cause of maternal death in developed countries. Pregnancy is associated with an increased risk of VTE due to physiologic changes during the obstetric period that promote a hypercoagulable state. Appropriate use of prophylactic anticoagulants can decrease the event rate of thrombus formation in at-risk patients. In the United States, there is not a validated risk-assessment tool for VTE in obstetric patients or a clear consensus on initiation and optimal dosing strategy for the prophylactic use of anticoagulants. This article reviews the mechanism of coagulation disturbance that leads to an increased risk of VTE in obstetric patients, as well as the available literature surrounding pharmacologic prophylaxis. [ABSTRACT FROM AUTHOR]

Venous thromboembolism prophylaxis with subcutaneous unfractionated heparin or low molecular weight heparin is a common practice in hospitalized patients. Typically, prophylactic doses of these medications have poor bioavailability and thus do not reach therapeutic serum concentrations. However, in certain circumstances, heparin binding proteins may become saturated. Here we report a case series of 5 patients who had elevated anti-Xa levels while receiving prophylactic dosing of subcutaneous unfractionated heparin. [ABSTRACT FROM AUTHOR]

Objective: This large database study assessed whether extended pharmacologic prophylaxis for venous thromboembolism after colon cancer resection was associated with improved oncologic survival. Background: Heparin derivatives may confer an antineoplastic effect via a variety of mechanisms (eg, inhibiting angiogenesis in the tumor microenvironment). Studies evaluating the oncologic benefit of heparin and its derivatives have been limited in postsurgical patients. Multiple society guidelines recommend consideration of 30-day treatment with low molecular weight heparin to reduce venous thromboembolism risk after abdominopelvic cancer surgery. However, utilization of extended prophylaxis remains low. Methods: Surveillance, Epidemiology, and End Results-Medicare data were used to identify patients (age 65+) undergoing resection for nonmetastatic colon cancer from 2016 to 2017. The primary outcomes were overall and cancer-specific survival. Log-rank testing and multivariable Cox regression compared survival in patients who received extended prophylaxis versus those who did not in an inverse propensity treatment weighted cohort. Results: A total of 20,102 patients were included in propensity-weighting and analyzed. Eight hundred (3.98%) received extended pharmacologic prophylaxis. Overall survival and cancer-specific survival were significantly higher in patients receiving prophylaxis on log-rank tests (P=0.0017 overall, P= 0.0200 cancer-specific). Multivariable Cox regression showed improved overall survival [adjusted hazard ratio 0.66 (0.56-0.78)] and cancer-specific survival [adjusted hazard ratio 0.56 (0.39-0.81)] with prophylaxis after controlling for patient, treatment, and hospital factors. Conclusions: Extended pharmacologic prophylaxis after colon cancer resection was independently associated with improved overall and cancer-specific survival. These results suggest a potential antineoplastic effect from heparin derivatives when used in the context of preventing postsurgical venous thromboembolism. [ABSTRACT FROM AUTHOR]

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Previable and periviable preterm prelabor rupture of membranes are challenging obstetrical complications to manage given the substantial risk of maternal morbidity and mortality, with no guarantee of fetal benefit. The following are the Society for Maternal-Fetal Medicine recommendations for the management of previable and periviable preterm prelabor rupture of membranes before the period when a trial of neonatal resuscitation and intensive care would be considered appropriate by the healthcare team and desired by the patient: (1) we recommend that pregnant patients with previable and periviable preterm prelabor rupture of membranes receive individualized counseling about the maternal and fetal risks and benefits of both abortion care and expectant management to guide an informed decision; all patients with previable and periviable preterm prelabor rupture of membranes should be offered abortion care, and expectant management can also be offered in the absence of contraindications (GRADE 1C); (2) we recommend antibiotics for pregnant individuals who choose expectant management after preterm prelabor rupture of membranes at ≥24 0/7 weeks of gestation (GRADE 1B); (3) antibiotics can be considered after preterm prelabor rupture of membranes at 20 0/7 to 23 6/7 weeks of gestation (GRADE 2C); (4) administration of antenatal corticosteroids and magnesium sulfate is not recommended until the time when a trial of neonatal resuscitation and intensive care would be considered appropriate by the healthcare team and desired by the patient (GRADE 1B); (5) serial amnioinfusions and amniopatch are considered investigational and should be used only in a clinical trial setting; they are not recommended for routine care of previable and periviable preterm prelabor rupture of membranes (GRADE 1B); (6) cerclage management after previable or periviable preterm prelabor rupture of membranes is similar to cerclage management after preterm prelabor rupture of membranes at later gestational ages; it is reasonable to either remove the cerclage or leave it in situ after discussing the risks and benefits and incorporating shared decision-making (GRADE 2C); and (7) in subsequent pregnancies after a history of previable or periviable preterm prelabor rupture of membranes, we recommend following guidelines for management of pregnant persons with a previous spontaneous preterm birth (GRADE 1C). [ABSTRACT FROM AUTHOR]

Background and Objectives: Migraine is a chronic neurological disorder affecting approximately 14% of the global population. Beyond physical pain, migraines significantly impact individuals' quality of life, influencing education, employment, and income levels. Topiramate, a second-generation antiepileptic medication, has demonstrated notable efficacy in reducing the occurrence of chronic migraine. Over the past three decades, extensive research has implicated the neuropeptide calcitonin gene-related peptide (CGRP) in migraine pathogenesis. Erenumab, the first FDA-approved CGRP inhibitor, received approval in 2018. This study aims to compare the clinical efficacy of Erenumab and Topiramate for migraine prevention. Materials and Methods: We conducted a retrospective cohort study of adults with episodic or chronic migraine over a 12-month period, comparing Erenumab (n = 52) and Topiramate (n = 56). Outcomes assessed included changes in the Migraine Disability Assessment (MIDAS) scores from baseline over the last three months of treatment and the proportion of patients achieving a ≥50% reduction in MIDAS scores by the end of the study. Results: The Erenumab group showed significant improvement, with nearly 79% of patients achieving a 50% reduction in their MIDAS score, with a mean reduction of 3.76. Notably, only two patients (3.8.5) discontinued treatment due to adverse events. In contrast, the Topiramate group had over 15% of patients achieve a 50% reduction in MIDAS scores, with a mean reduction of 5.89, and a had discontinuation rate of 14.2% due to adverse events. Conclusions: Both Topiramate and Erenumab are effective for migraine prevention. However, Topiramate has lower tolerability and more side effects, while Erenumab offers better tolerability and safety at a higher cost. Treatment decisions should be individualized based on patient needs, efficacy, safety, and cost considerations. [ABSTRACT FROM AUTHOR]

Introduction: Docusate sodium's efficacy is widely debated. Several studies on opioid induced constipation (OIC) concluded that docusate sodium vs either placebo or in combination with sennosides provided no benefit. Objective: This medication use evaluation aimed to investigate constipation treatment trends within the West Palm Beach VA Healthcare System Community Living Center, and to assess the therapeutic effectiveness of docusate sodium. Methods: This was a retrospective review of data extracted from April 1, 2022, to September 30, 2022. Patients were included if they had oral orders for docusate sodium, sennosides, lactulose, and/or polyethylene glycol. Patients without active bowel regimen medications were excluded. Requirements for rescue constipation medication was evaluated. Results: A total of 98 patients were reviewed. Docusate sodium was used in 43% (n = 42/98) of patients. Rescue medications were needed in 58% (n = 22/38) of patients receiving oral docusate sodium. 52% (n = 29/56) of patients without docusate sodium required rescue medications. For OIC treatment, when docusate sodium was added to other bowel regimens, 59% (n = 17/29) of patients needed a rescue medication, while 66% (n = 19/29) of patients without docusate sodium required a rescue medication. Patients on morphine were given the greatest quantity of rescue constipation medications (73%, n = 16/22). Conclusion: Oral docusate sodium did not reduce the requirement for rescue constipation medications in the WPB VAHCS CLC population. When evaluating constipation treatment, docusate sodium may supply minimal benefit and could be identified as nonessential for deprescribing efforts. Morphine was the most constipating opioid used in this patient population, requiring more aggressive bowel regimens. [ABSTRACT FROM AUTHOR]

Background: Overall inferior vena cava filter (IVCF) utilization has decreased in the United States since the 2010 US Food and Drug Administration (FDA) safety communication. The FDA renewed this safety warning in 2014 with additional mandates on reporting IVCF-related adverse events. We evaluated the impact of the FDA recommendations on IVCF placements for different indications from 2010 to 2019 and further assessed utilization trends by region and hospital teaching status. Methods: Inferior vena cava filter placements between 2010 and 2019 were identified in the Nationwide Inpatient Sample database using the associated International Classification of Diseases, Ninth Revision, Clinical Modification, and Tenth Revision codes. Inferior vena cava filter placements were categorized by indication for venous thromboembolism (VTE) "treatment" in patients with VTE diagnosis and contraindication to anticoagulation and "prophylaxis" in patients without VTE. Generalized linear regression was used to analyze utilization trends. Results: A total of 823 717 IVCFs were placed over the study period, of which 644 663 (78.3%) were for VTE treatment and 179 054 (21.7%) were for prophylaxis indications. The median age for both categories of patients was 68 years. The total number of IVCFs placed for all indications decreased from 129 616 in 2010 to 58 465 in 2019, with an aggregate decline rate of −8.4%. The decline rate was higher between 2014 and 2019 than between 2010 and 2014 (−11.6% vs −7.2%). From 2010 to 2019, IVCF placement for VTE treatment and prophylaxis trended downward at rates of −7.9% and −10.2%, respectively. Urban nonteaching hospitals saw the highest decline for both VTE treatment (−17.2%) and prophylactic indications (−18.0%). Hospitals located in the Northeast region had the highest decline rates for VTE treatment (−10.3%) and prophylactic indications (−12.5%). Conclusion: The higher decline rate in IVCF placements between 2014 and 2019 compared with 2010 and 2014 suggests an additional impact of the renewed 2014 FDA safety indications on national IVCF utilization. Variations in IVCF use for VTE treatment and prophylactic indications existed across hospital teaching types, locations, and regions. Clinical Impact: Inferior vena cava filters (IVCF) are associated with medical complications. The 2010 and 2014 FDA safety warnings appeared to have synergistically contributed to a significant decline in IVCF utilization rates from 2010 – 2019 in the US. IVC filter placements in patients without venous thromboembolism (VTE) declined at a higher rate than VTE. However, IVCF utilization varied across hospitals and geographical locations, likely due to the absence of universally accepted clinical guidelines on IVCF indications and use. Harmonization of IVCF placement guidelines is needed to standardize clinical practice, thereby reducing the observed regional and hospital variations and potential IVC filter overutilization. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing non-major orthopedic surgery often face an increased risk of venous thromboembolism due to the necessity of immobilization postoperatively. Current guidelines commonly recommend the use of low-molecular-weight heparin (LMWH) for prophylaxis, but it is associated with low patient compliance and certain side effects. We conducted a meta-analysis of randomized controlled trials (RCTs) to assess the effectiveness and safety of rivaroxaban or LMWH for thromboprophylaxis following non-major orthopedic surgery. Method: Relevant literature was systematically searched in PubMed, Web of Science, Cochrane Library, and Embase from their inception to October 1, 2023, to evaluate the effectiveness and safety of rivaroxaban or LMWH in RCTs for thromboprophylaxis following non-major orthopedic surgery. Results: A total of 5 randomized controlled trials involving 5,101 patients were included. There was no statistically significant difference in the preventive effect against venous thromboembolism (VTE) when using rivaroxaban or LMWH following non-major orthopedic surgery (RR 0.80; 95%CI 0.31 to 2.07). In terms of safety, there was also no statistically significant difference in the incidence of bleeding events in patients undergoing non-major orthopedic surgery when using rivaroxaban or LMWH (RR 1.15; 95% CI 0.75 to 1.76). Conclusion: In non-major orthopedic surgery, the risk of venous thromboembolism and bleeding complications is similar when using rivaroxaban or LMWH. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Coccidioidomycosis may cause severe disseminated disease and mortality among lung transplant recipients. A strategy of lifelong azole prophylaxis was previously associated with low rates of coccidioidomycosis. Whether lung transplant recipients relocating to the Coccidioides endemic region are also at risk and would benefit from antifungal prophylaxis is unknown.Lung transplant recipients transplanted at an outside center with low Coccidioides endemicity before relocating for post‐transplant follow‐up at a transplant center in Phoenix, Arizona from January 2013 to March 2024 were included. The primary outcome was proven or probable coccidioidomycosis per Mycoses Study Group consensus definitions.Forty lung transplant recipients were included, with 62.5% not receiving antifungal prophylaxis at the time of transfer. The median time from transplant to relocation was 34 months. Of those not on prophylaxis, 96% were initiated on azole therapy at the first clinic visit, with 72% prescribed itraconazole. Coccidioides serologic testing was performed in 30% of the cohort, most often in the context of a broad diagnostic work‐up for suspected infection during hospitalization. After a median follow‐up of 31 months, one case (2.5%) of proven pulmonary coccidioidomycosis was identified, occurring 4.8 years post‐transplant and >2 years post‐transfer in a cystic fibrosis patient who had a pause in fluconazole prophylaxis for >1 month prior to diagnosis due to gastrointestinal intolerance and access issues. The patient was treated and maintained on isavuconazole without complications.Azole antifungal prophylaxis was associated with a low rate of coccidioidomycosis among lung transplant recipients relocating to the highly endemic region. [ABSTRACT FROM AUTHOR]

Ibrutinib, a highly effective inhibitor of the Bruton tyrosine kinase, has significantly transformed the therapeutic approach in chronic lymphocytic leukemia (CLL). Despite these advancements, the disease continues to be characterized by immune dysfunction and increased susceptibility to infections, with mortality rates from infections showing no significant improvement over the past few decades. Therefore, timely prevention, recognition, and treatment of infections remains an important aspect of the standard management of a patient with CLL. A panel of hematologists with expertise in CLL met to discuss existing literature and clinical insights for the management of infectious in CLL undergoing ibrutinib treatment. Despite not being a fully comprehensive review on the topic, this work provides a set of practical recommendations that can serve as a guide to healthcare professionals who manage these patients in their daily clinical practice. [ABSTRACT FROM AUTHOR]

Background: The actual situation and influencing factors of prophylactic use of proton pump inhibitors (PPIs) in internal medicine inpatients receiving glucocorticoid therapy are rarely reported. This study aimed to investigate the current status and influencing factors of prophylactic use of PPIs in internal medicine inpatients receiving glucocorticoid therapy to provide a basis for rational prophylactic use of PPIs. Methods: Internal medicine inpatients receiving glucocorticoid therapy from February 2023 to September 2023 were included. Information on the prophylactic use of PPIs was collected and analyzed by clinical pharmacists. Associated factors with prophylactic use of PPIs were analyzed by univariable and multivariable logistic regression. Results: 980 inpatients were finally included in our study, of which 271 (27.7%) inpatients received prophylactic use of PPIs. Among the inpatients prescribed PPIs, 90 inpatients received a standard dose of PPIs twice a day. Multiple logistic regression analysis showed that age ≥80 years [OR = 7.009, 95% CI (1.424, 34.495), p = 0.017], history of gastroesophageal reflux disease (GERD) [OR = 2.047, 95% CI (1.338, 3.133), p = 0.001], low platelet count [OR = 0.997, 95% CI (0.994, 0.999), p = 0.004], number of concomitant diseases [OR = 1.104, 95% CI (1.056, 1.153), p < 0.001], junior doctors [OR = 1.755, 95% CI (1.248, 2.468), p = 0.001], glucocorticoid dose (higher than 50 mg, measured by methylprednisolone) [OR = 2.455, 95% CI (1.371, 4.395), p = 0.003], antiplatelet agents [OR = 2.567, 95% CI (1.456, 4.524), p = 0.001], immunosuppressants [OR = 1.477, 95% CI (1.014, 2.153), p = 0.042], and betahistine [OR = 5.503, 95% CI (1.124, 26.950), p = 0.035] were associated with more prophylactic use of PPIs. Conclusion: The prophylactic use of PPIs in internal medicine inpatients receiving glucocorticoid therapy is common in China. Clinical pharmacists will take targeted measures to promote the rational use of PPIs according to the results of this study. [ABSTRACT FROM AUTHOR]

Background: Hepatitis A virus (HAV) infection is a significant global cause of viral hepatitis. At present, the anti-HAV vaccine in Italy is proposed exclusively for specific high-risk groups, and a universal vaccination program is not implemented. Objectives: This study aimed to assess the level of immunity against HAV in patients of both sexes across age groups ranging from 0 to 95 years admitted to the San Giovanni di Dio e Ruggi d'Aragona Hospital in Salerno, Italy, over a 9-year period (2015–2023). Methods: The total HAV seroprevalence by chemiluminescence Vitros system immunodiagnostics (ortho-diagnostics) was obtained by database analysis, stratifying patients for gender and age group in both the pre-pandemic (2015–2019) and pandemic (2020–2023) periods. Results: Out of 28,104 samples collected in 2015–2023, 20,613 resulted positive by total HAV immune screening, with a significant reduction in the annualized proportion of events during the pandemic period compared to the pre-pandemic period. HAV was more abundant in males than females in both periods (exceeding the 70%), with a statistically significant decrease in HAV in females in 2015–2019. The 61–70-year-old age group is more susceptible for both genders, with a strong deviation from the 41–50-year-old age group compared to the 51–60-year-old group. The pandemic period affected the number of analyzed samples in 2020. Conclusions: The study revealed high HAV seroprevalence, especially in males and individuals aged 61–70 years. There was a notable decrease in seroprevalence during the pandemic compared to pre-pandemic years. These results emphasize the need for ongoing monitoring and suggest that a universal vaccination program could address regional immunity gaps and lower disease incidence. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous squamous cell carcinoma (cSCC) is a common and potentially dangerous skin cancer, especially for people with weakened immune systems, like those who have had organ transplants or certain blood cancers. These individuals are up to 100 times more likely to develop cSCC compared with the general population. This review discusses the current treatments for cSCC in these high-risk patients, emphasizing the importance of prevention and the variety of treatment options available. Using high-SPF sunscreen and certain medications can help reduce the chances of developing cSCC. Adjusting the medications that suppress the immune system can also lower the risk. Surgery remains the main treatment, with radiation therapy recommended for more serious cases. Other treatments such as chemotherapy and newer targeted therapies have been used, with mixed results. Immunotherapy, which helps the body's own immune system fight the cancer, shows promise but needs more research to ensure it is safe for these vulnerable patients. This study highlights the need for future research to explore personalized treatment plans and combination therapies to improve outcomes for people with weakened immune systems. Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and poses a significant risk to immunosuppressed patients, such as solid organ transplant recipients and those with hematopoietic malignancies, who are up to 100 times more likely to develop cSCC compared with the general population. This review summarizes the current state of treatment for cSCC in immunosuppressed patients, focusing on prevention, prophylaxis, surgical and non-surgical treatments, and emerging therapies. Preventative measures, including high-SPF sunscreen and prophylactic retinoids, are crucial for reducing cSCC incidence in these patients. Adjusting immunosuppressive regimens, particularly favoring mTOR inhibitors over calcineurin inhibitors, has been shown to lower cSCC risk. Surgical excision and Mohs micrographic surgery remain the primary treatments, with adjuvant radiation therapy recommended for high-risk cases. Traditional chemotherapy and targeted therapies like EGFR inhibitors have been utilized, though their efficacy varies. Immunotherapy, particularly with agents like cemiplimab and pembrolizumab, has shown promise, but its use in immunosuppressed patients requires further investigation due to potential risks of organ rejection and exacerbation of underlying conditions. Treatment of cSCC in immunosuppressed patients is multifaceted, involving preventive strategies, tailored surgical approaches, and cautious use of systemic therapies. While immunotherapy has emerged as a promising option, its application in immunosuppressed populations necessitates further research to optimize safety and efficacy. Future studies should focus on the integration of personalized medicine and combination therapies to improve outcomes for this vulnerable patient group. [ABSTRACT FROM AUTHOR]

Purpose: Pneumocystis jirovecii pneumonia (PJP) prophylaxis is required by provincial and national drug monographs during glioma treatment using temozolomide (TMZ) concurrently with radiation (TMZ-RT). However, real-world data suggest the potential benefits of PJP prophylaxis may not outweigh its potential harms in this population. Methods: We conducted a single-center patient survey and a national physician survey to explore the role of PJP prophylaxis amongst glioma patients undergoing TMZ-RT. Results: 23% (31/133) of physicians and 60% (44/73) of patients completed a survey. The median patient age was 42 (range 20–77); 85% (34/40) had completed adjuvant TMZ. Although only 2.4% (1/41) of patients received PJP prophylaxis, only one person (without PJP prophylaxis) was hospitalized for pneumonia. When presented with hypothetical PJP risks, 13.2% (5/38) of patients were concerned about PJP infection, while 26% (10/38) were concerned about potential side effects from prophylactic antibiotics. Most physicians (77%, 17/22) perceived the evidence for PJP prophylaxis as weak; 58% (11/19) did not routinely prescribe prophylaxis, and 73% (16/22) felt that PJP prophylaxis should be limited to patients with additional risk factors. Over 95% of physicians estimated that the incidence of PJP was < 1% in their last 5 years of practice regardless of PJP prophylaxis. For 73% (16/22) of physicians, to prescribe PJP prophylaxis, the risk of PJP infection needed to be 3–8%. Conclusion: The current recommendation to routinely prescribe PJP prophylaxis in patients receiving TMZ-RT in the absence of other risk factors warrants reconsideration. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To evaluate the available literature on ureteric stent‐related infections, the use of antibiotics and bacterial colonisation to identify the current incidence of stent‐related infections, unveil knowledge gaps and generate potential hypotheses for future research.A literature review was conducted using PubMed, Cochrane and urological association websites identifying relevant English literature published between 1983 and January 2024.There is a worldwide lack of guidelines for antibiotic prophylaxis for stent placement, exchange or extraction. In patients with a negative preoperative urine culture undergoing ureteroscopy and stent placement, it may be considered to only provide prophylaxis in presence of risk factors. However, in pre‐stented patients a preoperative urine culture is important to guide prophylaxis during endourological surgery. During stent indwell time, antibiotic prophylaxis does not show any advantage in preventing urinary tract infections (UTIs). There is no strong evidence to support the use of antibiotics at time of stent removal. In the absence of any clear evidence, management strategies for treating UTIs in patients with ureteric stents vary widely. Stent exchange could be considered to remove the biofilm as a potential source of bacteria. Stent culture can help to guide treatment during infection as urine culture and stent culture can differ.In terms of good antibiotic stewardship, urologists should be aware that unnecessary use of antibiotics provokes bacterial resistance. There is a great need for further research in the field of antibiotic prophylaxis and stent‐related infections to develop evidence that can help shape clear guidelines for this very common urological practice. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions This study was conducted to assess the efficacy of daily 2000 mg eicosapentaenoic acid (EPA) supplementation in individuals with chronic migraine.Chronic migraine is characterized by a minimum of 15 headache days/month, necessitating a focus on preventive treatment strategies. EPA, a polyunsaturated fatty acid recognized for its anti‐inflammatory properties, is examined for its potential effectiveness in chronic migraine management.A randomized, blinded, placebo‐controlled trial of eligible participants with a confirmed diagnosis of chronic migraine were enrolled. The intervention group received 1000 mg of EPA twice daily for 8 weeks, while the control group received two placebo softgels. Symptoms were recorded at 4 and 8 weeks. The primary outcome was assessed using the Headache Impact Test‐6 to evaluate changes in patients. Secondary outcomes encompassed migraine headache days, headache severity measured via a visual analog scale, and the number of consumed painkillers. Descriptive analyses were reported in mean (± standard deviation [SD]).A total of 60 patients were included in the study and finally, 56 patients completed the study according to the protocol, including 47 (84%) females. The data comparison at baseline did not show any significant difference between the two groups except in the number of patients using valproic acid as prophylaxis (21 patients in the EPA group, and 13 in the placebo group; p = 0.037). The results showed after 8 weeks, a mean (SD) difference of Headache Impact Test‐6 in the EPA and placebo groups was −6.96 (3.34) and −4.43 (5.24), respectively (p = 0.084). Regarding migraine headache days, participants reported a mean (SD) −9.76 (4.15) and −4.60 (4.87) decline in days with headache, respectively (p < 0.001). The number of attacks per month after 8 weeks was 3.0 (95% confidence interval [CI] 2.0–4.0) and 4.0 (95% CI 3.0–6.0), respectively (p < 0.001). Regarding severity, there was no significant difference between the two groups (mean [SD] difference: −0.76 [1.13] and –0.73 [1.04], respectively; p = 0.906). In terms of adverse events, two patients in the EPA group reported intolerable nausea and vomiting, and one patient in the placebo group reported dizziness.This study's findings support the potential of a daily 2000 mg EPA as a prophylactic pharmacotherapy in chronic migraine management, specifically in mitigating migraine attacks, migraine headache days, and overall quality of life. [ABSTRACT FROM AUTHOR]

Background Human immunodeficiency virus (HIV) infection in children is a significant public health concern, increasing the risk of infant mortality. Immunodeficiency caused by HIV favors the development of opportunistic infections (OIs), which are responsible for over 90% of HIV-related deaths. This study seeks to determine the primary OIs in children with HIV followed at the Hassan II Regional Hospital Center in Sous Massa, during the period from 2012 to 2023. Materials and Methods This retrospective study is the first in Morocco to investigate OIs among HIV-infected children. It analyzed 76 complete medical records, using a data collection form designed based on existing literature. Results This study revealed that 37% of participants were suffering from OIs, mainly diarrhea (11%), tuberculosis (9%) and pneumonia (7%).There was a significant correlation between OIs and HIV clinical stage (P=0.001), age (P=0.007), and anemia (P=0.001). Despite progress in management, the presence of OIs remains a risk factor for infant morbidity and mortality. Conclusion The study highlights the importance of early detection, prevention, and adherence to treatment in reducing this burden. Management of anemia is essential. [ABSTRACT FROM AUTHOR]

There are conflicting recommendations on whether to use or not to use fluoroquinolone prophylaxis in pediatric oncology patients. An international pediatric clinical practice guideline (CPG) recommends administering levofloxacin prophylaxis in patients with acute myeloblastic leukemia and relapsed acute lymphoblastic leukemia receiving intensive chemotherapy as this practice has been found to reduce episodes of fever and bacteremia. A separate European CPG does not recommend levofloxacin prophylaxis because of concerns for adverse effects, including potentiation of fluoroquinolone resistance and possible increased resistance to other classes of antibiotics. The nuance of the decision to give or not give prophylaxis is discussed in the context of published evidence defining the risks and benefits of levofloxacin prophylaxis for pediatric leukemia patients at high risk for bacterial infection. Knowledge gaps are also identified to guide further investigations to optimize the use of fluoroquinolone prophylaxis in pediatric patients receiving chemotherapy for cancer or undergoing a hematopoietic cell transplantation. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) are the most common bacterial infections in children, occurring both in children with normal urinary tracts and in ones with urinary tract abnormalities. Children with UTIs can present relevant clinical symptoms and risk long-term consequences. Current recommended preventive measures include chemoprophylaxis and dietary supplements such as cranberry, probiotics and vitamins A and E. Although chemoprophylaxis still represents the gold standard, it raises concerns about antimicrobial resistance. N-acetylcysteine (NAC), a precursor of the antioxidant glutathione, has been proven both to inhibit biofilm formation and to destroy developed biofilms. In adults, NAC has been demonstrated to prevent UTIs and to improve the effect of antibiotics, but so far it has not been analyzed as an antimicrobial option for pediatric UTIs. In this work, we aim to discuss the current applications of NAC in adult urology and its future possible evolutions in pediatric urology. [ABSTRACT FROM AUTHOR]

Vaccination plays an essential role in preventing diseases, safeguarding the health and welfare of the population. The objective of this review is to design vaccination plans for companion animals and production systems in equines and bovines located in the state of Meta (Colombia). In felines and canines, vaccination can provide protection against possible bacterial, virulent and parasitic agents with infectious and/or zoonotic capacity and thus reduce losses in veterinary expenses associated with the treatment of sick animals. In equines, it is prophylactic against encephalomyelitis and equine influenza, avoiding animal suffering and possible economic losses; while, in bovine production, it can be highly preventive against conditions such as brucellosis and foot-and-mouth disease, which can have serious economic consequences in the industry. Therefore, it is of crucial importance to adopt a solid and clear focus on prevention through contextualized vaccination programs, in this case for the state of Meta, protecting only one health. [ABSTRACT FROM AUTHOR]

Existing literature on best practices to reduce the risk of infectious complications associated with ureteral stent removal in kidney transplant recipients is limited. Prior to 2021, a formal process surrounding stent removal was not in place at our institution. In June 2021, a stent removal protocol was established. This protocol included the following: obtaining a preprocedure urine culture, prescribing universal culture-directed antimicrobial prophylaxis, earlier stent removal posttransplant, and patient education. We performed a retrospective quasi-experimental study of kidney transplant recipients who had their stents removed between July 2020 and June 2022. The primary outcome was the incidence of infectious complications within 30 days. Infectious complications were defined as urinary tract infection and bacteremia due to urinary source, as well as hospitalization, emergency department visit, or outpatient encounter for possible urinary tract infection. Secondary objectives included infectious and immunologic complications within 30 days to 1 year from transplant. During this study period, 239 adult kidney transplant recipients were included: 88 in the preprotocol group and 151 in the protocol group. The median time to stent removal was shorter in the protocol group (25 vs 36 days, P <.001). More patients in the protocol group received preprocedure antibiotics (99% vs 36%, P <.001). Infectious complications were higher in the preprotocol group (9% vs 3%, P =.035). Overall, the stent removal protocol was associated with fewer infectious complications (odds ratio, 0.18; 95% CI, 0.05–0.73). Further investigation is necessary to determine which individual interventions, if any, drive this benefit. [ABSTRACT FROM AUTHOR]

The field of cardio-oncology is an expanding frontier within cardiovascular medicine, and the need for evidence-based guidelines is apparent. One of the emerging focuses within cardio-oncology is the concomitant use of medications for cardioprotection in the setting of chemotherapy regimens that have known cardiovascular toxicity. While clinical trials focusing on cardioprotection during chemotherapy are sparse, an inaugural trial exploring the prophylactic potential of Sodium-Glucose Cotransporter-2 inhibitors (SGLT2is) for anthracycline (ANT)-induced cardiotoxicity has recently commenced. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, though less studied in this oncology demographic, have exhibited promise in preclinical studies for conferring cardiac protection during non-ischemic toxic insults. While primarily used to reduce low-density lipoprotein, PCSK9 inhibitors exhibit pleiotropic effects, including the attenuation of inflammation, reactive oxygen species, and endothelial dysfunction. In ANT-induced cardiotoxicity, these same processes are accelerated, resulting in premature termination of treatment, chronic cardiovascular sequelae, heart failure, and/or death. This review serves a dual purpose: firstly, to provide a concise overview of the mechanisms implicated in ANT-induced cardiotoxicity, and, finally, to summarize the existing preclinical data supporting the theoretical possibility of the cardioprotective effects of PCSK9 inhibition in ANT-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Background: Migraine is characterized by sudden acute episodes of pain, with a global prevalence of 18% among all age groups. It is the second leading cause of years lived with disability worldwide. Prophylactic treatment is important in managing migraine; however, its efficacy and safety are debated. This study aimed to evaluate the efficacy of desvenlafaxine in female patients with migraine. Methods: We conducted a retrospective observational case study involving 10 women diagnosed with migraine who were treated with desvenlafaxine. We measured the number of migraine days per month, average headache duration in minutes, headache severity using a visual analog scale, use of acute medications, and frequency of acute medication use per week. Results: Desvenlafaxine significantly reduced the number of migraine days from 14.70 ± 3.68 at baseline to 2.50 ± 2.50 at follow-up (p < 0.05). The average headache duration dropped from 131.25 ± 32.81 min to 52.50 ± 44.64 min. Headache severity scores improved from 6.80 ± 1.49 at baseline to 0.80 ± 0.92 at follow up, the frequency of acute medication use per week reduced from 3.30 ± 1.49 at baseline to 0.80 ± 0.92, and the frequency of acute medication use decreased from 3.30 ± 1.49 times per week to 0.80 ± 0.92. Conclusions: Desvenlafaxine shows potential as an effective prophylactic therapy for migraine. Larger-scale studies are necessary to further explore its benefits. [ABSTRACT FROM AUTHOR]

Simple Summary: In daily veterinary practice, canine otitis externa is a common presentation and, therefore, many studies were conducted to evaluate predispositions. This study on the other hand aims to evaluate factors that have potentially statistically reduced risks for developing otitis externa. Regarding the results, Rhodesian Ridgebacks and Collies have shown significantly low odds for otitis externa. Furthermore, regarding dogs with endocrinopathies, it was shown that those who are overweight seem to develop otitis externa more likely than those with a normal weight. Especially the latter result should be used in communication with pet owners to point out the importance of strict weight management and, therefore, increasing the quality of life of their dogs. Background: Canine otitis externa is a common presentation in small animal practice. The clinical signs vary individually from patient to patient. Regardless of the expression, they all decrease the quality of life. Therefore, this study aimed to identify factors that showed reduced odds for otitis externa. Methods: Clinical case records were searched for key terms regarding canine otitis. Statistical analyses were applied to evaluate associations with otitis externa. p-values of <0.05 were considered statistically significant. Results: Rhodesian Ridgeback and dogs with underlying infectious diseases had a reduced risk for otitis externa, while Retrievers and dogs with allergies had an increased risk. Furthermore, in the group of dogs with endocrinopathies, those with normal weight showed a reduced risk of developing canine otitis in comparison to those which were overweight. Conclusions: These results show a new point of view to reduce the prevalence of canine otitis by reducing the animals' weight due to an additional risk of otitis in obese or overweight dogs. Furthermore, for the first time, Rhodesian Ridgebacks were identified in our study population to have a lower risk of developing otitis externa. Thus, breeders should reflect—within other responsibilities for the quality of life in their offspring—on breed-specifics about otitis when planning ahead. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine (CM) significantly impacts both the physical and mental health of patients. Current studies on the safety and effectiveness of different pharmacological prophylaxis interventions for CM are limited. To address this gap, we conducted a network meta-analysis (NMA) to compare and rank the efficacy and safety of various drugs in preventing CM. Methods: Two independent researchers systematically searched four databases from their inception to August 1, 2023, to identify eligible randomized controlled trials (RCTs). Subsequently, they performed data extraction and assessed the risk of bias. A NMA was then performed. Continuous outcomes and binary outcomes were displayed as weighted mean difference (WMD) and risk ratio (RR), respectively, and corresponding 95% confidence intervals (CI) were reported. The surface under the cumulative ranking curve (SUCRA) was used to rank each intervention separately. Results: 24 RCTs involving 8789 patients were included. Compared to placebo, Botulinum toxin A demonstrated the most significant effect in reducing the monthly migraine days for CM patients (MD = 3.88, 95% CI 0.48, 7.28); in terms of improving the response rate by a 50% reduction in monthly migraine days, Topiramate (RR = 50.06, 95% CI 3.18, 787.30) was the most effective; there was no statistically significant difference between all preventive drugs and placebo in improving the migraine disability assessment (MIDAS) score; in terms of the incidence of adverse events, Eptinezumab (RR = 1.09, 95% CI 0.8, 1.54) exhibited the highest safety profile. Conclusion: Among all the drugs for the preventive drugs for CM, Botulinum toxin A has the best efficacy and safety profile, closely followed by calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs). [ABSTRACT FROM AUTHOR]

Bloodstream infections (BSI) are one of the leading causes of morbidity and mortality in children and young adults receiving chemotherapy for malignancy or undergoing hematopoietic stem cell transplantation (HSCT). Antibiotic prophylaxis is commonly used to decrease the risk of BSI; however, antibiotics carry an inherent risk of complications. The aim of this manuscript is to review levofloxacin prophylaxis in pediatric oncology patients and HSCT recipients. We reviewed published literature on levofloxacin prophylaxis to prevent BSI in pediatric oncology patients and HSCT recipients. Nine manuscripts were identified. The use of levofloxacin is indicated in neutropenic children and young adults receiving intensive chemotherapy for leukemia or undergoing HSCT. These results support the efficacy of levofloxacin in pediatric patients with leukemia receiving intensive chemotherapy and should be considered in pediatric patients undergoing HSCT prior to engraftment. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis is one of the infectious diseases with greater morbidity and mortality worldwide. Cancer causes an important immunosuppression with increased risk of infections. There is an enlarged bidirectional incidence between tuberculosis and cancer, mainly due to latent tuberculosis. Guidelines review: There is great discrepancy between recommendations for screening and prophylaxis of latent tuberculosis in patients with solid tumors and systemic cancer therapy among different medical societies and guidelines. Most infectious diseases guidelines recommend it, while most oncology guidelines do not. Discussion: Patients with solid tumours generally have a limited life expectancy and a state of intermittent immunosuppression, resulting in a lower risk of tuberculosis reactivation than other risky populations. There is a lack of prospective and retrospective studies analysing the benefit of screening and prophylaxis in this population. The first step is to study the incidence of active tuberculosis in this population to estimate the real magnitude of the problem. [ABSTRACT FROM AUTHOR]

Although COVID-19 transmission has been reduced by the advent of vaccinations and a variety of rapid monitoring techniques, the SARS-CoV-2 virus itself has shown a remarkable ability to mutate and persist. With this long track record of immune escape, researchers are still exploring prophylactic treatments to curtail future SARS-CoV-2 variants. Specifically, much focus has been placed on the antiviral lectin Griffithsin in preventing spike protein-mediated infection via the hACE2 receptor (direct infection). However, an oft-overlooked aspect of SARS-CoV-2 infection is viral capture by attachment receptors such as DC-SIGN, which is thought to facilitate the initial stages of COVID-19 infection in the lung tissue (called trans-infection). In addition, while immune escape is dictated by mutations in the spike protein, coronaviral virions also incorporate M, N, and E structural proteins within the particle. In this paper, we explored how several structural facets of both the SARS-CoV-2 virion and the antiviral lectin Griffithsin can affect and attenuate the infectivity of SARS-CoV-2 pseudovirus. We found that Griffithsin was a better inhibitor of hACE2-mediated direct infection when the coronaviral M protein is present compared to when it is absent (possibly providing an explanation regarding why Griffithsin shows better inhibition against authentic SARS-CoV-2 as opposed to pseudotyped viruses, which generally do not contain M) and that Griffithsin was not an effective inhibitor of DC-SIGN-mediated trans-infection. Furthermore, we found that DC-SIGN appeared to mediate trans-infection exclusively via binding to the SARS-CoV-2 spike protein, with no significant effect observed when other viral proteins (M, N, and/or E) were present. These results provide etiological data that may help to direct the development of novel antiviral treatments, either by leveraging Griffithsin binding to the M protein as a novel strategy to prevent SARS-CoV-2 infection or by narrowing efforts to inhibit trans-infection to focus on DC-SIGN binding to SARS-CoV-2 spike protein.

Biosafety hazards can trigger a host immune response after infection, invasion, or contact with the host. Whether infection with a microorganism results in disease or biosafety concerns depends to a large extent on the immune status of the population. Therefore, it is essential to investigate the immunological characteristics of the host and the mechanisms of biological threats and agents to protect the host more effectively. Emerging and re-emerging infectious diseases, such as the current coronavirus disease 2019 (COVID-19) pandemic, have raised concerns regarding both biosafety and immunology worldwide. Interdisciplinary studies involved in biosafety and immunology are relevant in many fields, including the development of vaccines and other immune interventions such as monoclonal antibodies and T-cells, herd immunity (or population-level barrier immunity), immunopathology, and multispecies immunity, i.e., animals and even plants. Meanwhile, advances in immunological science and technology are occurring rapidly, resulting in important research achievements that may contribute to the recognition of emerging biosafety hazards, as well as early warning, prevention, and defense systems. This review provides an overview of the interdisciplinary field of biosafety and immunology. Close collaboration and innovative application of immunology in the field of biosafety is becoming essential for human health.