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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]

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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]

In 2011, the American Academy of Orthopaedic Surgeons released a consensus recommending venous thromboembolism (VTE) prophylaxis after total knee arthroplasty (TKA). The purpose of our study was to examine (1) incidences of postoperative complications, including pulmonary embolism (PE), deep vein thrombosis (DVT), and transfusion rates; (2) trends from 2016 to 2021 in VTE prophylaxis; and (3) independent risk factors for 90-day total complications following TKA between aspirin, enoxaparin, rivaroxaban, and warfarin. Using a national, all-payer database from 2016 to 2021, we identified all patients who underwent primary TKA. Exclusions included all patients who had prescribed anticoagulants within 1 year prior to TKA, hypercoagulable states, and cancer. Data were collected on baseline demographics, including age, sex, diabetes, and a comorbidity index, in each of the VTE prophylaxis cohorts. Postoperative outcomes included rates of PE, DVT, and transfusion. Multivariable regressions were performed to determine independent risk factors for total complications at 90 days following TKA. From 2016 to 2021, aspirin was the most used anticoagulant (n = 62,054), followed by rivaroxaban (n = 26,426), enoxaparin (n = 20,980), and warfarin (n = 13,305). The cohort using warfarin had the highest incidences of PE (1.8%) and DVT (5.7%), while the cohort using aspirin had the lowest incidences of PE (0.6%) and DVT (1.6%). The rates of aspirin use increased the most from 2016 to 2021 (32.1% to 70.8%), while the rates of warfarin decreased the most (19.3% to 3.0%). Enoxaparin, rivaroxaban, and warfarin were independent risk factors for total complications at 90 days. An epidemiological analysis of VTE prophylaxis use from 2016 to 2021 shows an increase in aspirin following TKA compared to other anticoagulant cohorts in a nationally representative population. This approach provides more insight and a better understanding of anticoagulation trends over this time period in a nationally representative sample. [ABSTRACT FROM AUTHOR]

There has been a growing interest in venous thromboembolism following spinal surgery over the past few years. However, there currently needs to be a bibliometric report on this field. This study aims to construct the knowledge structure of venous thromboembolism after spinal surgery and explores the current status of research productivity, research directions, hotspots, and trends. All articles related to venous thromboembolism after spinal surgery from the Web of Science Core Collection database for 1990 to 2023 were retrieved. For bibliometric analysis, information extraction involves country/region, institutions, journals, authors, references, and keyword-related data. In this study, a total of 814 articles were identified. Studies related to venous thromboembolism after spinal surgery are showing an increasing trend, with the United States contributing the most. JOHNS HOPKINS UNIVERSITY is a high-productivity institution. The journal "SPINE" is highly productive. Research directions cover venous thromboembolism and bleeding, risk factors and prevention, complications, and perioperative blood protection strategies. Current research hotspots are risk factors, surgical location and approach, and perioperative blood protection strategies. Future research trends include establishing a predictive system for venous thromboembolism after spinal surgery to guide personalized prevention and treatment. This study constructed the knowledge structure of venous thromboembolism after spinal surgery, revealing current research hotspots and future trends. Future research trends include personalized prevention and treatment strategies for venous thromboembolism after spinal surgery, especially safe and effective chemical prophylaxis. It is hoped that this study can lay the foundation for subsequent research. [Display omitted] [ABSTRACT FROM AUTHOR]

There is lack of guidance for immune monitoring and infection prevention after administration of ex vivo genetically modified hematopoietic stem cell therapies (GMHSCT). We reviewed current infection prevention practices as reported by providers experienced with GMHSCTs across North America and Europe, and assessed potential immunologic compromise associated with the therapeutic process of GMHSCTs described to date. Based on these assessments, and with consensus from members of the International Society for Cell & Gene Therapy (ISCT) Stem Cell Engineering Committee, we propose risk-adapted recommendations for immune monitoring, infection surveillance and prophylaxis, and revaccination after receipt of GMHSCTs. Disease-specific and GMHSCT-specific considerations should guide decision making for each therapy. [ABSTRACT FROM AUTHOR]

Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several regimens are available for the prophylaxis of PCP, including trimethoprim-sulfamethoxazole (TMP-SMX), dapsone-based regimens (DBRs), aerosolized pentamidine (AP), and atovaquone. To compare the efficacy and safety of PCP prophylaxis regimens in PWH by network meta-analysis. Embase, MEDLINE, and CENTRAL from inception to June 21, 2023. Comparative randomized controlled trials (RCTs). PWH. Regimens for PCP prophylaxis either compared head-to-head or versus no treatment/placebo. Cochrane risk-of-bias tool for RCTs 2. Title or abstract and full-text screening and data extraction were performed in duplicate by two independent reviewers. Data on PCP incidence, all-cause mortality, and discontinuation due to toxicity were pooled and ranked by network meta-analysis. Subgroup analyses of primary versus secondary prophylaxis, by year, and by dosage were performed. A total of 26 RCTs, comprising 55 treatment arms involving 7516 PWH were included. For the prevention of PCP, TMP-SMX was ranked the most favourable agent and was superior to DBRs (risk ratio [RR] = 0.54; 95% CI, 0.36–0.83) and AP (RR = 0.53; 95% CI, 0.36–0.77). TMP-SMX was also the only agent with a mortality benefit compared with no treatment/placebo (RR = 0.79; 95% CI, 0.64–0.98). However, TMP-SMX was also ranked as the most toxic agent with a greater risk of discontinuation than DBRs (RR = 1.25; 95% CI, 1.01–1.54) and AP (7.20; 95% CI, 5.37–9.66). No significant differences in PCP prevention or mortality were detected among the other regimens. The findings remained consistent within subgroups. TMP-SMX is the most effective agent for PCP prophylaxis in PWH and the only agent to confer a mortality benefit; consequently, it should continue to be recommended as the first-line agent. Further studies are necessary to determine the optimal dosing of TMP-SMX to maximize efficacy and minimize toxicity. [Display omitted] [ABSTRACT FROM AUTHOR]

Tooth extraction has been avoided in patients receiving antiresorptive agent (ARA) therapy. This study aimed to investigate dental findings associated with medication-related osteonecrosis of the jaw (MRONJ) development in patients. First, in patients treated with high-dose ARAs, the relationship between dental findings and MRONJ development was examined. Next, in patients with MRONJ undergoing surgery, the relationship between dental findings and MRONJ occurring at a site distant from the initial site was examined. MRONJ occurred in 13 of 172 patients (80 of 3725 teeth) during observation. Multiple tooth loss, periodontal ligament space enlargement, alveolar bone loss, periapical osteosclerosis, and local infection symptoms were associated with MRONJ development. Tooth extraction significantly reduced MRONJ development. Regarding other-site recurrence, new MRONJ developed at other sites in 54 of 357 patients with MRONJ (171 of 5038 teeth). Multiple tooth loss, apical lesions, periodontal ligament space enlargement, and periapical osteosclerosis were significantly associated with MRONJ development. In patients with malignant tumors, tooth extraction significantly reduced the subsequent incidence of MRONJ, while in patients with osteoporosis, there was no difference in the incidence of MRONJ between patients with and without tooth extraction. MRONJ was more likely to develop from teeth with local infections. Extraction of teeth with local infection in patients with malignancy may be more effective than tooth preservation in preventing MRONJ. [ABSTRACT FROM AUTHOR]

Allogeneic haematopoietic cell transplant (allo-HCT) recipients who are cytomegalovirus (CMV)-seronegative have better post-transplant outcomes than CMV-seropositive recipients. Letermovir (LTV) is approved for CMV primary prophylaxis in adults who are CMV-seropositive after allo-HCT, and its use is associated with improved long-term post-transplant outcomes. We analysed whether LTV has affected the relationship between CMV serostatus and post-transplant outcomes. We conducted a retrospective single-centre cohort study of allo-HCT recipients, stratified according to donor (D) and recipient (R). CMV serostatus and the use of LTV: D−/R−, R+/LTV−, and R+/LTV+. Outcomes measured were all-cause and non-relapse mortality, clinically significant CMV infection, graft-versus-host disease, and relapse up to week 48 after allo-HCT. The D−/R− group served as the reference for comparisons in univariate, competing risk regression, and cumulative incidence functions. The analysis included 1071 consecutive allo-HCT recipients: 131 D−/R−, 557 R+/LTV−, and 383 R+/LTV+. All-cause mortality by day 100 was 6.1% for the D−/R− group, compared with 14.0% (p 0.024) and 7.8% (p 0.7) for the R+/LTV− and R+/LTV + groups, respectively. Non-relapse mortality by day 100 was 11.0%, 6.8% and 3.8% for R+/LTV−, R+/LTV+, and D−/R− groups, respectively, without significant difference. When including relapse as a competing event, the hazard ratio for non-relapse mortality was 1.83 (95% CI: 1.12–2.99, p 0.017) for R+/LTV− compared with D−/R− and 1.05 (95% CI 0.62–1.77, p 0.85) for R+/LTV + compared with D−/R−. CMV primary prophylaxis with LTV abrogated the mortality gap based on CMV serostatus, a protective effect that persisted after discontinuation of primary prophylaxis. [ABSTRACT FROM AUTHOR]

Dopamine antagonists, 5-HT 3 antagonists, and dexamethasone are frequently used in obstetrics to prevent postoperative nausea and vomiting (PONV). However, the superiority of any drug class is yet to be established. This network meta-analysis aimed to compare the efficacy of these antiemetics for PONV prophylaxis in women receiving neuraxial morphine for Caesarean delivery. We searched PubMed, Embase, CENTRAL, Web of Science, and Wanfang Data for eligible randomised controlled trials. Primary outcomes were the incidences of postoperative nausea (PON) and postoperative vomiting (POV) within 24 h after surgery. We used a Bayesian random-effects model and calculated odds ratios with 95% credible intervals for dichotomous data. We performed sensitivity and subgroup analyses for primary outcomes. A total of 33 studies with 4238 women were included. In the primary analyses of all women, 5-HT 3 antagonists, dopamine antagonists, dexamethasone, and 5-HT 3 antagonists plus dexamethasone significantly reduced PON and POV compared with placebo, and 5-HT 3 antagonists plus dexamethasone were more effective than monotherapy. In the subgroup analyses, similar results were seen in women receiving epidural morphine or intrathecal morphine alone but not in women receiving intrathecal morphine with fentanyl or sufentanil. However, most included studies had some concerns or a high risk of bias, and the overall certainty of the evidence was low or very low. Combined 5-HT 3 antagonists plus dexamethasone are more effective than monotherapy in preventing PONV associated with neuraxial morphine after Caesarean delivery. Future studies are needed to determine the role of prophylactic antiemetics in women receiving intrathecal morphine and lipophilic opioids. PROSPERO CRD42023454602. [ABSTRACT FROM AUTHOR]

Patients undergoing total joint arthroplasty (TJA) who report penicillin allergy (PA) are frequently administered second-line antibiotics, although recent evidence suggests that this may be unnecessary and could increase infection risk. Many institutions have aimed to improve antibiotic deployment via allergy testing and screening; however, there is little standardization to this process. This review aimed to evaluate (1) antibiotic selection in patients who report PA and assess the impact of screening and testing interventions, (2) rates of allergic reactions in patients who report PA, and (3) the association between reported PA and screening or testing programs and odds of surgical site infection or periprosthetic joint infection. PubMed, EBSCOhost, and Google Scholar electronic databases were searched on February 4, 2023 to identify all studies published since January 1, 2000 that evaluated the impact of PA on patients undergoing TJA (PROSPERO study protocol registration: CRD42023394031). Articles were included if full-text manuscripts in English were available, and the study analyzed the impact of PA and related interventions on TJA patients. There were 11 studies evaluating 1,276,663 patients included. Interventions were compared via presentation of key findings regarding rates of clinically relevant or high-risk PA reported upon screenings or testings, cephalosporin utilizations, allergic reactions, and postoperative infections (surgical site infection and periprosthetic joint infection). All 6 studies found that PA screening and testing markedly increase the use of first-line antibiotics. Testing showed low rates of true allergy (0.7 to 3%) and allergic reaction frequency for patients who have reported PA receiving cephalosporins was between 0% and 2%. Although there were mixed findings across studies, there was a trend toward second-line antibiotic prophylaxis being associated with a slightly higher rate of infection in PA patients. Using PA screening and testing can promote antibiotic stewardship by safely increasing the use of first-line antibiotics in patients who have a reported PA. Level III, Therapeutic Study. [ABSTRACT FROM AUTHOR]

Posttraumatic and postsurgical sensory disturbance is a known complication of almost all zygomaticomaxillary (ZMC) complex fractures involving the infraorbital nerve, for which few treatments are effective. Our study used neurosensory assessments to evaluate the efficacy of melatonin on pain and nerve healing following ZMC surgery. Sixty-four randomly allocated ZMC fracture patients were prophylactically administered either oral melatonin or an identical placebo for 15 consecutive days. Pre- and postsurgical clinical parameters included subjective pain, numbness, and objective neurosensory function. Melatonin significantly reduced subjective pain perception in the early postoperative days, with a significant difference in VAS scores between the groups from postoperative day 3 (p = 0.048) until day 7 (p = 0.002). The VAS assessment of subjective numbness perception showed significantly lower self-perceived neurosensory disturbance for patients in the interventional group from the first month (p = 0.039) until the third month (p = 0.005). Objective neurosensory assessment using the pinprick test and two-point discrimination showed statistically significant improvement to almost normal sensation by the first month (p = 0.014) to fully normal sensation by the third month (p = 0.001). The study findings suggest that the prophylactic administration of melatonin confers significant clinical benefits in terms of reduced postoperative pain and improved sensory recovery. [ABSTRACT FROM AUTHOR]

This population based retrospective cohort study aimed to investigate the association between combined treatment with lipid lowering drugs and antiplatelet or anticoagulation therapy and long term survival following vascular surgery in Norway. The study included all patients who were registered for the treatment of carotid stenosis, abdominal aortic aneurysm (AAA), and atherosclerotic lower extremity arterial disease (LEAD) in the Norwegian Registry for Vascular Surgery between 2015 and 2019 and who were discharged alive. Clinical and medication details were retrieved from the register. Survival was assessed with Kaplan–Meier analysis and a multivariable Cox regression model. Stratification was according to treatment group, patient sex, and if patients received the recommended medications or not. Recommended medications were defined as lipid lowering drugs, usually statins, and antiplatelets, or sometimes anticoagulants, when comorbidity indicated anticoagulation therapy. In total, 15 810 patients had LEAD, 4 080 patients AAA, and 2 194 patients had carotid stenosis. In all treatment groups, survival was superior for patients who used the recommended medications upon discharge. The difference was greatest in patients with LEAD with mean survival periods of 4.33 (95% CI 4.29 – 4.36) and 3.7 (95% CI 3.64 – 3.77) years in patients discharged with and without the recommended medications, respectively (p <.001). The mean survival periods were 4.67 (95% CI 4.61 – 4.73) and 4.34 (95% CI 4.24 – 4.44) years in patients with AAA discharged with and without the recommended medications, respectively (p <.001). Cox regression analysis showed a statistically significantly lower mortality rate for patients discharged with the recommended medications for LEAD (HR 0.58; p <.001) and AAA (HR 0.57; p <.001). The recommended medications were associated with improved survival in all treatment groups and both sexes. The survival difference was statistically significant in patients with LEAD and AAA. Patients with LEAD had the greatest improvement; therefore, the recommended secondary prophylaxis is especially important in these patients. [ABSTRACT FROM AUTHOR]

To examine if the use of an antibacterial envelope (TYRX) decreases the rate of postoperative infection in chronic pain patients undergoing treatment with spinal cord stimulation (SCS) involving device implantation. Single-center retrospective cohort study comparing postoperative infections rates in non-TYRX recipients from 2018 to 2020 with recipients of a TYRX antibacterial envelope from 2020 to 2021. Infection was registered if a patient received any form of antibiotic treatment after hospital discharge within a follow-up period of 100 days. A total of 198 patients were included: 100 in the TYRX group and 98 in the non-TYRX group. There were no significant differences between the 2 groups regarding age, body mass index (BMI), smoking, diabetes, and use of immunosuppression. The overall infection rate was 5.6%. The infection rate was 4% in the TYRX group and 7.1% in the non-TYRX group (P = 0.6). However, the 4 cases of postoperative infection in the TYRX group could be effectively managed with oral antibiotics alone, whereas 6 out of the 7 patients in the non-TYRX group required intravenous antibiotics. Moreover, device explantation was necessary in 3 of these patients suggesting the event of more severe infections in the non-TYRX group (P = 0.014). The TYRX antibacterial envelope displayed infection rates reducing capabilities, along with a clear tendency to reduce revision surgeries and system removals due to infections. [ABSTRACT FROM AUTHOR]

sleep alterations strongly influence migraine severity. Prophylactic therapies have a major impact on migraine frequency and associated symptoms. The study purpose was to compare the impact of oral drug therapies or gene-related anti-calcitonin monoclonal antibodies (anti-CGRP mAbs) on sleep alterations. We also evaluated which drug therapies are more effective on sleep quality and the different impact on migraine frequency and life quality. this is a multicenter, prospective study conducted in three specialized headache centers (Marche Polytechnic University, Ancona; University of Palermo, Palermo; Fondazione Policlinico Campus Bio-Medico, Rome). At baseline, we assigned migraine patients to preventive therapy with first-line drugs or anti-CGRP mAbs. The Pittsburgh Sleep Quality Index (PSQI) and Migraine Disability Assessment (MIDAS) scales were administered. After three months, we re-evaluated the patients with the same scales. 214 patients were enrolled. Any prophylaxis was significantly associated with a reduction in PSQI score (mean difference 1.841; 95%CI:1.413–2.269; p < 0.0001), most significantly in the anti-CGRP mAb group (mean difference 1.49; 95%CI:2.617-0.366; p = 0.010). Anti-CGRP mAbs resulted in significant improvement in migraine severity and MIDAS scores. Among oral therapies, calcium antagonists and antidepressants were the most effective in reducing PSQI score between T0 and T1 (p = 0.042; p = 0.049; p < 0.0001, respectively). anti-CGRP mAbs revitalized the management of migraine with stable and well-documented efficacy. Our data also suggest that anti-CGRP mAbs result in a positive effect on sleep quality, with a significant improvement in PSQI scores. Knowing the relevant impact of sleep disruption on migraine severity, these data could help for the management of migraine patients. • Sleep alterations influence migraine severity; no data about therapy are available. • We evaluated migraine prophylaxis impact on sleep quality in 214 patients. • Pittsburgh Sleep Quality Index (PSQI) was calculated at baseline and after 3 months. • Any prophylaxis significantly reduced PSQI, anti-CGRP mAb obtained the best results. • Among oral therapies, calcium antagonists and antidepressants greater reduced PSQI. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the relationship between prophylactic inferior vena cava filter (IVCF) implantation and in-hospital deep vein thrombosis (DVT), pulmonary embolism (PE), and mortality among adults with intracranial, pelvic or lower extremity, and spinal cord injuries. Patients 18 years and older with severe intracranial, pelvic or lower extremity, or spinal cord injuries captured by the Trauma Quality Improvement Program (2010-2019) were identified. IVCFs implanted ≤72 hours after hospital presentation and before performance of lower extremity ultrasonography were defined as prophylactic. Patients were stratified by pharmacologic venous thromboembolism (VTE) prophylaxis status. Logistic regression models estimated prophylactic inferior vena cava (IVC) filtration's effect on selected outcomes and identified attributes associated with prophylactic IVCF implantation. Of 544,739 included patients, 1.3% (n = 7,247) underwent prophylactic IVCF implantation. Among patients who received pharmacologic VTE prophylaxis, prophylactic IVC filtration compared with expectant management was positively associated with DVT (odds ratio [OR], 4.30; P <.001) and PE (OR, 4.30; P <.001) but not associated with mortality (OR, 0.92; P =.43). Among patients who received no pharmacologic prophylaxis, prophylactic IVC filtration was positively associated with DVT (OR, 4.63; P <.001) and PE (OR, 5.02; P <.001) but negatively associated with mortality (OR, 0.43; P <.001). Prophylactic IVC filtration was associated with increased likelihood of VTE among all adults with severe intracranial, pelvic or lower extremity, and spinal cord injuries. In patients who received no pharmacologic VTE prophylaxis, prophylactic IVC filtration was associated with decreased likelihood of in-hospital mortality. [Display omitted] [ABSTRACT FROM AUTHOR]

Brain metastasis (BM) prognosis is incredibly poor and is often associated with considerable morbidity. Seizures are commonly present in these patients, and their biopsychosocial impact can be dangerous. The use of antiepileptic drugs (AEDs) as primary prophylaxis remains controversial. This systematic review and meta-analysis aim to evaluate the efficacy of AED prophylaxis in patients with BM. MEDLINE via PubMed, Web of Science, EMBASE, and Cochrane were searched for articles pertinent to AED prophylaxis use in patients with BM. Patients with BM previously treated for cancer who were seizure naive at the time of inclusion were included. Data regarding patient characteristics, type of AED, prior treatments, and groups at a high risk of seizure were extracted. Seizure prevalence was obtained. Eight studies were included in this systematic review and meta-analysis; 1902 total patients with BM were included, with 381 receiving antiepileptic prophylaxis, and 1521 receiving no prophylaxis. Although the odds of a seizure in the treatment group was found to be 1.158 times the odds of a seizure in the control group, the odds ratio was not statistically significant (t-statistic = 0.62, P value = 0.5543). There was no significant difference in the odds of seizure development in control groups compared to patients receiving prophylactic antiepileptic therapy. As patients with BM present with heterogeneity in tumor characteristics and receive various treatment modalities, future research is needed to identify groups that may benefit more significantly from AED prophylaxis. [ABSTRACT FROM AUTHOR]

Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial. To assess the effect of TMP-SMX in the prevention of nocardiosis after SOT, its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection. A systematic review and individual patient data meta-analysis. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, and Scopus up to 19 September 2023. (a) Risk of nocardiosis between SOT recipients with and without TMP-SMX prophylaxis, or (b) sufficient details to determine the rate of TMP-SMX resistance in breakthrough nocardiosis. SOT recipients. TMP-SMX prophylaxis versus no prophylaxis. Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies. For our primary outcome (i.e. to determine the effect of TMP-SMX on the risk of nocardiosis), a one-step mixed-effects regression model was used to estimate the association between the outcome and the exposure. Univariate and multivariable unconditional regression models were used to adjust for the potential confounding effects. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Individual data from three case-control studies were obtained (260 SOT recipients with nocardiosis and 519 uninfected controls). TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18–0.52, moderate certainty of evidence). Variables independently associated with an increased risk of nocardiosis were older age, current use of corticosteroids, high calcineurin inhibitor concentration, recent acute rejection, lower lymphocyte count, and heart transplant. Breakthrough infections (66/260, 25%) were generally susceptible to TMP-SMX (pooled proportion 98%, 95% CI 92–100). In SOT recipients, TMP-SMX prophylaxis likely reduces the risk of nocardiosis. Resistance appears uncommon in case of breakthrough infection. [Display omitted] [ABSTRACT FROM AUTHOR]

JYNNEOS TM vaccine has been used as post-exposure prophylaxis (PEP) during a mpox outbreak in New York City (NYC). Data on effectiveness are limited. Effectiveness of a single dose of JYNNEOS TM vaccine administered subcutaneously ≤ 14 days as PEP for preventing mpox disease was assessed among individuals exposed to case-patients from May 22, 2022–August 24, 2022. Individuals were evaluated for mpox through 21 days post-exposure. An observational study was conducted emulating a sequence of nested "target" randomized trials starting each day after exposure. Results were adjusted for exposure risk and race/ethnicity. Analyses were conducted separately based on last (PEP L) and first (PEP F) exposure date. We evaluated the potential to overestimate PEP effectiveness when using conventional analytic methods due to exposed individuals developing illness before they can obtain PEP (immortal time bias) compared to the target trial. Median time from last exposure to symptom onset (incubation period) among cases that did not receive PEP L was 7 days (range 1–16). Time to PEP L receipt was 7 days (range 0–14). Among 549 individuals, adjusted PEP L and PEP F effectiveness was 19 % (95 % Confidence Interval [CI], −54 % to 57 %) and −7% (95 % CI, −144 % to 53 %) using the target trial emulation, respectively, and 78 % (95 % CI, 50 % to 91 %) and 73 % (95 % CI, 31 % to 91 %) using conventional analysis. Determining PEP effectiveness using real-world data during an outbreak is challenging. Time to PEP in NYC coupled with the observed incubation period resulted in overestimated PEP effectiveness using a conventional method. The target trial emulation, while yielding wide confidence intervals due to small sample size, avoided immortal time bias. While results from these evaluations cannot be used as reliable estimates of PEP effectiveness, we present important methodologic considerations for future evaluations. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) remains a critical issue in the management of patients with multiple myeloma (MM), particularly when immunomodulatory drugs (IMiDs) combined with dexamethasone therapy are being prescribed as first-line and relapse therapy. One possible explanation for the persistent high rates of VTE, is the use of inappropriate thromboprophylaxis strategies for patients starting antimyeloma treatment. To tackle the issue, the Intergroupe francophone du myélome (IFM) offered convenient guidance for VTE thromboprophylaxis in MM patients initiating systemic therapy. This guidance is mainly supported by the results of a large survey on the clinical habits regarding VTE of physicians who are substantially involved in daily care of MM patients. VTE prophylaxis should be considered for all patients treated with IMiDs in combination with dexamethasone, in the absence of significant comorbidities, such as renal failure or bleeding risk. Anticoagulant should be preferred to antiplatelet agents for thromboprophylaxis. Despite the absence of large randomized controlled trials comparing those attitudes/options, available data on direct oral anticoagulants, which are already used in daily management of MM patients, are consistent with their potential usefulness for VTE prophylaxis in such patients. However, in order to implement a personalized continuous improvement strategy, clinicians must to be organized to collect all the data regarding this management. In other situations, thromboprophylaxis should be evaluated by using risk models and after careful evaluation of the risk/benefit ratio. • Proposed guidance for thromboprophylaxis in MM • VTE remains a significant issue in MM care. • Long-term LMWH use has notable side effects. • DOACs offer comfort, efficacy, but need studies. • A holistic VTE management approach is essential. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic continues to pose unprecedented challenges to worldwide health. While vaccines are effective, additional strategies to mitigate the spread/severity of COVID-19 continue to be needed. Emerging evidence suggests susceptibility to respiratory tract infections in healthy subjects can be reduced by probiotic interventions; thus, probiotics may be a low-risk, low-cost, and easily implementable modality to reduce risk of COVID-19. In this initial study, we conducted a randomized, double-blind, placebo-controlled trial across the United States testing probiotic Lacticaseibacillus rhamnosus GG (LGG) as postexposure prophylaxis for COVID-19 in 182 participants who had household exposure to someone with confirmed COVID-19 diagnosed within ≤7 days. Participants were randomized to receive oral LGG or placebo for 28 days. The primary outcome was development of illness symptoms within 28 days of COVID-19 exposure. Stool was collected to evaluate microbiome changes. Intention-to-treat analysis showed LGG treatment led to a lower likelihood of developing illness symptoms versus placebo (26.4 % vs. 42.9 %, p = 0.02). Further, LGG was associated with a statistically significant reduction in COVID-19 diagnosis (log rank, p = 0.049) via time-to-event analysis. Overall incidence of COVID-19 diagnosis did not significantly differ between LGG and placebo groups (8.8 % vs. 15.4 %, p = 0.17). This data suggests LGG is associated with prolonged time to COVID-19 infection, reduced incidence of illness symptoms, and gut microbiome changes when used as prophylaxis ≤7 days post-COVID-19 exposure, but not overall incidence. This initial work may inform future COVID-19 prevention studies worldwide, particularly in developing nations where Lacticaseibacillus probiotics have previously been utilized to reduce other non-COVID infectious-morbidity. ClinicalTrials.gov, NCT04399252, Date: 22/05/2020. https://clinicaltrials.gov/ct2/show/NCT04399252. [ABSTRACT FROM AUTHOR]

Bacterial infection ranks amongst the most common causes of morbidity and mortality in patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT). Although ciprofloxacin (CIP) prophylaxis is recommended, information on serum levels and clinical course is lacking. To investigate relationships between CIP level and failure of prophylaxis, particularly in terms of whether different pharmacokinetic (PK) indices [area under the concentration–time curve (AUC 0–24h) vs single time samples] correlate differently with the outcome. This prospective observational monocentric study was conducted at a 1500-bed teaching hospital (March 2018–March 2019), including 63 adult patients with alloHSCT receiving CIP prophylaxis. Blood samples were drawn at three sampling times (1, 6 and 12 h post-administration), twice per week, and measured via high performance liquid chromatography. The onset of febrile episodes (FEBs) indicated suspected failure of CIP prophylaxis. Positive blood cultures [bloodstream infection (BSI)] indicated confirmed failure of prophylaxis. Seven of 63 patients died without significant differences in their average CIP levels compared with survivors, with patients experiencing FEBs (54/63) displaying a 13% [95% confidence interval (CI) 4–22%] lower probability of survival. In total, 225 sets of three values (triplets) were obtained from 58 primary CIP episodes. Triplets preceding BSI with Gram-negative bacteria (GNB-BSI) showed lower AUC 0–24h on average, but similar single time sample indices. An AUC 0–24h of ≤21.61 mgh/L resulted in four-fold higher odds of GNB-BSI (adjusted odds ratio 3.96, 95% CI 1.21–13.00). These results were independent of the administration route, patient demographics or sampling protocol deviations, indicating reduced CIP exposure upon GNB-BSI events. Monitoring CIP levels, using multiple sampling times, may be useful to reduce alloHSCT-associated bacterial infections. Further analysis is needed to investigate causality. [ABSTRACT FROM AUTHOR]

Sexual partners of youth living with HIV are a key population for pre-exposure prophylaxis (PrEP). Among youth engaged in HIV medical care, we examined awareness of PrEP and experiences with and attitudes toward discussing PrEP with sexual partners. We recruited 25 15–24-year olds from an adolescent/young adult HIV clinic to complete individual interviews. Interviews assessed demographics, PrEP knowledge, sexual behaviors, and experiences with, intentions toward, barriers, and facilitating factors to discussing PrEP with partners. Transcripts were analyzed using framework analysis. Mean age was 18.2 years. Twelve participants were cis-female, 11 cis-male, and two transgender female. Seventeen participants (68%) identified as Black, non-Hispanic. Nineteen acquired HIV sexually. Of 22 participants who had ever had sex, eight reported condomless sex in the prior 6 months. Most youth (17/25) were aware of PrEP. Only 11 participants had discussed PrEP with a partner; 16 reported high intention to discuss PrEP with future partners. Barriers to discussing PrEP with partners included participant-related barriers (i.e., discomfort disclosing HIV status), partner-related barriers (i.e., not open to or unfamiliar with PrEP), relationship-related barriers (i.e., new relationship, lack of trust), and stigma about HIV. Facilitating factors included positive relationship factors, educating partners about PrEP, and partners being receptive to learning about PrEP. Although many youth living with HIV were aware of PrEP, fewer had discussed PrEP with a partner. PrEP use by partners of these youth may be improved by educating all youth about PrEP and offering opportunities for partners to meet with clinicians to discuss PrEP. [ABSTRACT FROM AUTHOR]

• Seizures are commonly seen among meningioma patients and may cause impaired quality of life. • Contains a considerable number of 333 patients. • Three factors were associated with poor seizure control. • Only study which has mentioned regarding the role of presence of intranuclear inclusion bodies. • Advocates a balanced approach. Seizures are commonly seen among meningioma patients and may cause impaired quality of life. These patients can be effectively treated with surgery. Still, many patients have persistent seizure episodes after surgery. The factors which are associated with worsening of seizure episodes remain critical in improving the quality of life for such patients. In this study, we aim to analyze the clinical and histopathological factors to predict the post excision seizure-outcome in meningioma and need of antiepileptic prophylaxis for these patients. Adult patients who underwent primary resection of meningioma at our institute between 2007 and 2020 were included in the study. Eligibility criteria were as follows: (i) Surgery for newly-diagnosed biopsy proven meningioma, (ii) Presence of pre-operative seizure (iii) A follow-up period ≥ 12 months. Of the 1145 patients in this series, 333 patients were recruited in study. The major determinants of prophylactic anti-epileptic were tumour size (S), Oedema (O), location (L), inclusion body (I), antiepileptic drugs (D) and surgical complication (C). The factors independently associated with poor seizure control after surgical resection were presence of brain parenchyma invasion (p < 0.001), pre-operative use of > 2 antiepileptics (p = 0.016) and presence of intranuclear inclusion bodies (p = 0.001). The identification and consideration of factors associated with prolonged seizure control after surgery may help us to guide treatment strategies aimed at improving the quality of life for patients with meningiomas. Authors have proposed a SOLID-C guideline to avoid the blanket approach of prophylactic AED in patients undergoing for meningioma resection. [ABSTRACT FROM AUTHOR]

• Lean body mass was better correlated with plasma cefazolin concentration than either absolute body weight or BMI. • Surgical site cefazolin concentration was directly correlated with entry to the vascular system. • Our hospital antibiotic policy in lumbar spine surgery achieved MIC Staphylococcus aureus in all cases. The aim of this study was to determine the association between measures of body composition and the concentration of plasma and paraspinal muscle cefazolin. Secondly, we aimed to confirm the efficacy of our hospital dosing regimen in achieving the minimum inhibitory concentration (MIC) at the surgical site. Patients undergoing posterior-based lumbar spine surgery had body composition analysed using bioimpedance analysis. All received 2 g of cefazolin at anaesthetic induction in line with hospital guidelines. Cefazolin concentration was measured in plasma (30-minites) and muscle (30- and 60-minuites) using high-performance liquid chromatography. 20 patients were recruited (mean age 61.5 years; 12 female). Mean plasma cefazolin concentrations were 34.1 +/− 10.2 mg/L; mean muscle concentrations 44.4 +/− 18.6 mg/kg and 43.8 +/− 20.4 mg/kg at 30- and 60-minutes respectively. Univariate analysis showed significant correlation between plasma cefazolin concentration and lean mass weight, absolute body weight, height, dry lean mass, total water, total body water, extracellular and intracellular water volume. Linear regression analysis showed lean mass weight the best predictor of plasma cefazolin concentration. Muscle cefazolin concentration was dependent on the plasma concentration. Using a MIC of 2 mg/L and 2 mg/kg for Staphylococcus aureus , MIC was achieved in all samples. In summary, plasma cefazolin concentration was best predicted by lean body mass. Further work should consider the influence of body composition on antibiotic delivery in extremes of body mass index. Local hospital guidelines are effective at achieving MIC against S. aureus. [ABSTRACT FROM AUTHOR]

• Vaccines prevent COVID-19; efficacy can be impaired in immunocompromised patients. • Immunocompromised patients need broader protection beyond vaccination. • Monoclonal antibodies have successfully bolstered immune responses to COVID-19. • Recent data shows monoclonal antibodies have limited efficacy against Omicron strains. • This limitation is an important consideration for immunocompromised patients. The objective of this review was to examine the latest literature regarding the effectiveness of monoclonal antibodies as COVID-19 prophylaxis therapy for immunocompromised patient populations. Literature review of published real-world and randomized control trials (RCTs) from 2020 to May 2023. COVID-19 is highly transmissible with potentially serious health outcomes, underscoring the need for effective prevention and treatment strategies. Vaccines are highly effective at preventing COVID-19 for the general population; however, efficacy is often impaired in immunocompromised patients given insufficient response to initial exposure and/or memory for secondary exposures. Some individuals may also have contraindications to vaccination. As such, additional protective measures are needed to bolster the immune response in these populations. Monoclonal antibodies have been effective at bolstering immune system responses to COVID-19 among immunocompromised patients; however, they are proving ineffective against the most recent Omicron strains (BA.4 and BA.5). Several studies have investigated the efficacy of monoclonal antibodies as pre- and post-prophylaxis for COVID-19. Historical evidence is promising; however, new variants of concern are proving challenging for currently available regimens. [ABSTRACT FROM AUTHOR]

Hospitalized patients with cirrhosis frequently undergo multiple procedures. The risk of procedural-related bleeding remains unclear, and management is not standardized. We conducted an international, prospective, multicenter study of hospitalized patients with cirrhosis undergoing nonsurgical procedures to establish the incidence of procedural-related bleeding and to identify bleeding risk factors. Hospitalized patients were prospectively enrolled and monitored until surgery, transplantation, death, or 28 days from admission. The study enrolled 1187 patients undergoing 3006 nonsurgical procedures from 20 centers. A total of 93 procedural-related bleeding events were identified. Bleeding was reported in 6.9% of patient admissions and in 3.0% of the procedures. Major bleeding was reported in 2.3% of patient admissions and in 0.9% of the procedures. Patients with bleeding were more likely to have nonalcoholic steatohepatitis (43.9% vs 30%) and higher body mass index (BMI; 31.2 vs 29.5). Patients with bleeding had a higher Model for End-Stage Liver Disease score at admission (24.5 vs 18.5). A multivariable analysis controlling for center variation found that high-risk procedures (odds ratio [OR], 4.64; 95% confidence interval [CI], 2.44–8.84), Model for End-Stage Liver Disease score (OR, 2.37; 95% CI, 1.46–3.86), and higher BMI (OR, 1.40; 95% CI, 1.10–1.80) independently predicted bleeding. Preprocedure international normalized ratio, platelet level, and antithrombotic use were not predictive of bleeding. Bleeding prophylaxis was used more routinely in patients with bleeding (19.4% vs 7.4%). Patients with bleeding had a significantly higher 28-day risk of death (hazard ratio, 6.91; 95% CI, 4.22–11.31). Procedural-related bleeding occurs rarely in hospitalized patients with cirrhosis. Patients with elevated BMI and decompensated liver disease who undergo high-risk procedures may be at risk to bleed. Bleeding is not associated with conventional hemostasis tests, preprocedure prophylaxis, or recent antithrombotic therapy. [Display omitted] Predicting bleeding in patients with cirrhosis undergoing procedures is challenging. Bleeding caused by procedures was rare, and conventional testing did not predict bleeding. Rather, obese patients with advanced liver disease undergoing high-risk procedures were at the highest risk to bleed. [ABSTRACT FROM AUTHOR]

Approximately 25% of ambulatory surgery patients experience post-discharge nausea and vomiting (PDNV). We aimed to investigate whether palonosetron, a long-acting anti-emetic, decreases the incidence of PDNV in high-risk patients. In this prospective, randomised, double-blind, placebo-controlled trial, 170 male and female patients undergoing ambulatory surgery under general anaesthesia, with a high predicted risk for PDNV, were randomised to receive either palonosetron 75 μg i.v. (n =84) or normal saline (n =86) before discharge. During the first 3 postoperative days (PODs), we measured outcomes using a patient questionnaire. The primary outcome was the incidence of a complete response (no nausea, vomiting, or use of rescue medication) until POD 2. Secondary outcomes included the incidence of PDNV each day until POD 3. The incidence of a complete response until POD 2 was 48% (n =32) in the palonosetron group and 36% (n =25) in the placebo group (odds ratio 1.69 [95% confidence interval: 0.85–3.37]; P =0.131). No significant difference in the incidence of PDNV was observed between the two groups on the day of surgery (47% vs 56%; P =0.31). Significant differences in the incidence of PDNV were found on POD 1 (18% vs 34%; P =0.033) and POD 2 (9% vs 27%; P =0.007). No differences were observed on POD 3 (15% vs 13%; P =0.700). Compared with placebo, palonosetron did not reduce the overall incidence of post-discharge nausea and vomiting up to postoperative day 2. The lower incidence of post-discharge nausea and vomiting on poatoperative days 1 and 2 in the palonosetron group requires further investigation. EudraCT 2015-003956-32. [ABSTRACT FROM AUTHOR]

Surgical site infections (SSI) continue to represent a significant postoperative burden. SSI is associated with an increased risk of morbidity and mortality. Systemic antibiotic prophylaxis (SAP) is used to reduce the risk of SSI. Several factors must be considered for appropriate antibiotic use: antibiotic selection, timing, and duration. The evidence and use of antibiotics differs between closed fractures, open fractures, arthroplasty and percutaneous fixation. The use of SAP is a balance between reducing the incidence of SSI whilst maintaining proper antibiotic stewardship to limit adverse effects and the emergence of antibiotic resistance. This paper will discuss the evidence for the use of SAP in orthopaedic surgery and the potential adverse effects of the injudicious use of antibiotics. [ABSTRACT FROM AUTHOR]

Prophylaxis is the gold standard treatment for children with haemophilia (CWH). MRI studies revealed joint damage, even with this treatment; this suggests the presence of subclinical bleeding. In the case of children with haemophilia, it is relevant to detect early signs of joint damage, as this allows the medical team to provide the appropriate treatment and follow-up, in order to avoid arthropathy development and its consequences. The aim of this study is to detect the hidden joint in children with haemophilia on prophylaxis (CWHP) and analyse, by age group, which joint is the most affected. We define the hidden joint in CWH on prophylaxis as the joint that presents joint damage secondary to repetitive bleeding episodes and is detected in the joint evaluation, despite being asymptomatic or with mild symptoms. It is most commonly caused by repetitive subclinical bleeding. This was an observational, analytical, cross-sectional study of 106 CWH on prophylaxis treated in our centre. Patients were divided according to age and type of treatment. Joint damage was defined as a HEAD-US score ≥ 1. Patients' median age was 12 years. All had severe haemophilia. The median age of onset of prophylaxis was 2.7. Forty-seven (44.3 %) patients received primary prophylaxis (PP) and 59 (55.7 %), secondary prophylaxis. Six hundred and thirty-six joints were analysed. Type of prophylaxis and joint involvement showed statistically significant differences (p < 0.001). However, patients on PP had a greater number of damaged joints at older ages. Twenty-two % (140) of the joints scored ≥1 on HEAD-US. Cartilage was most frequently involved, followed by synovitis, and bone damage. We observed a greater frequency and degree of arthropathy in subjects aged 11 and above. Sixty (12.7 %) joints showed a HEAD-US score ≥ 1, with no history of bleeding. The ankle was the most affected joint, representing the hidden joint according to our definition. Prophylaxis is the best treatment for CWH. However, symptomatic or subclinical joint bleeding may occur. The routine evaluation of joint health is relevant, particularly, of the ankle. In our study, early signs of arthropathy according to age and type of prophylaxis were detected by HEAD-US. • Haemophilic arthropathy, due to the repetitive joint bleeding, leads to disability and loss of quality of life. • Prophylaxis is the best treatment for children with haemophilia. • However, symptomatic or subclinical joint bleeding may occur. • The detection of early signs of arthropathy is relevant, HEAD US has proven to be useful and reliable. • In children with haemophilia on prophylaxis the ankle currently represents the most vulnerable joint. [ABSTRACT FROM AUTHOR]

Recurrent urinary tract infection (rUTI) is defined as two or more episodes in a six-month period or, three or more, in one year. Urinary tract infections are more common in women than men at all stages except for the first year of life. rUTIs represent a significant burden on healthcare and account for many lost days of work. The traditional mainstay of acute treatment was with antibiotics, however with increasing resistance patterns, the overuse/misuse of antibiotics, and a shift towards antimicrobial stewardship, we are now leaning more heavily on non-antibiotic and prophylactic strategies. [ABSTRACT FROM AUTHOR]

Background: Intraosseous regional administration (IORA) of antibiotics after tourniquet inflation has recently been introduced as a technique to deliver antibiotics directly to the surgical site among patients undergoing total knee arthroplasty (TKA).Methods: PubMed and Embase were queried for studies reporting on IORA for perioperative prophylaxis during TKA. Primary outcome measures were local tissue antibiotic concentrations and rates of prosthetic joint infection (PJI). Eight studies were included for analysis. Four studies (all randomized controlled trials) compared local tissue concentrations between patients receiving IORA and intravenous (IV) antibiotics. Six studies assessed the rate of PJI among patients receiving IORA versus IV antibiotics.Results: All studies found a statistically significant increase in antibiotic concentration in femoral bone and fat samples in patients who were treated with IORA (44.04 μg/g [fat] and 49.3 μg/g [bone] following 500 mg of intraosseous vancomycin) versus IV (3.5 μg/g [fat] and 5.2 μg/g [bone] following 1 g IV of vancomycin). The two studies powered to determine differences in PJI rates found a statistically significant decrease in the rate of PJI among patients receiving IORA versus IV antibiotics. The incidence of PJI in patients treated with IORA and IV antibiotics across all studies was 0.3 and 1.1%, respectively.Conclusion: Perioperative IORA of antibiotics in TKA provides local tissue concentrations of antibiotics that are on average 10 times higher than IV administration alone. Although more adequately powered investigations are necessary to determine the effectiveness of IORA in reducing PJI rates, adoption of IORA should be considered in high-risk patients where elevated tissue antibiotic concentrations would be of a maximum benefit. [ABSTRACT FROM AUTHOR]

Previous interim data from a phase I study of AKS-452, a subunit vaccine comprising an Fc fusion of the respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (SP/RBD) emulsified in the water-in-oil adjuvant, Montanide™ ISA 720, suggested a good safety and immunogenicity profile in healthy adults. This phase I study was completed and two dosing regimens were further evaluated in this phase II study. This phase II randomized, open-labelled, parallel group study was conducted at a single site in The Netherlands with 52 healthy adults (18 – 72 years) receiving AKS-452 subcutaneously at one 90 µg dose (cohort 1, 26 subjects) or two 45 µg doses 28 days apart (cohort 2, 26 subjects). Serum samples were collected at the first dose (day 0) and at days 28, 56, 90, and 180. Safety and immunogenicity endpoints were assessed, along with induction of IgG isotypes, cross-reactive immunity against viral variants, and IFN-γ T cell responses. All AEs were mild/moderate (grades 1 or 2), and no SAEs were attributable to AKS-452. Seroconversion rates reached 100% in both cohorts, although cohort 2 showed greater geometric mean IgG titers that were stable through day 180 and associated with enhanced potencies of SP/RBD-ACE2 binding inhibition and live virus neutralization. AKS-452-induced IgG titers strongly bound mutant SP/RBD from several SARS-CoV-2 variants (including Omicrons) that were predominantly of the favorable IgG1/3 isotype and IFN-γ-producing T cell phenotype. These favorable safety and immunogenicity profiles of the candidate vaccine as demonstrated in this phase II study are consistent with those of the phase I study (ClinicalTrials.gov: NCT04681092) and suggest that a total of 90 µg received in 2 doses may offer a greater duration of cross-reactive neutralizing titers than when given in a single dose. [ABSTRACT FROM AUTHOR]

The novel coronavirus SARS-CoV-2 and the associated infectious disease COVID-19 pose a significant challenge to healthcare systems worldwide. Patients with cancer have been identified as a high-risk population for severe infections, rendering prophylaxis and treatment strategies for these patients particularly important. Rapidly evolving clinical research, resulting in the recent advent of various vaccines and therapeutic agents against COVID-19, offers new options to improve care and protection of cancer patients. However, ongoing epidemiological changes and rise of new virus variants require repeated revisions and adaptations of prophylaxis and treatment strategies to meet these new challenges. Therefore, this guideline provides an update on evidence-based recommendations with regard to vaccination, pharmacological prophylaxis and treatment of COVID-19 in cancer patients in light of the currently dominant omicron variants. It was developed by an expert panel of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) based on a critical review of the most recent available data. • Changes in epidemiology of SARS-CoV-2 variants require review of strategies. • Vaccination against COVID-19 is of particular importance in cancer patients. • Early treatment of COVID-19 in cancer patients reduces risk of severe disease. • Long-COVID is common in cancer patients and poses a particular challenge. • Evidence-based recommendations can help clinicians make informed decisions. [ABSTRACT FROM AUTHOR]

The use of antibiotic-loaded bone cement (ABC) in the setting of revision arthroplasty for deep infections is a broadly accepted practice. However, its use in the setting of primary arthroplasty continues to be controversial with few studies assessing the efficacy of ABC for primary total shoulder arthroplasty (TSA). The purpose of this study was to determine whether the use of ABC in primary TSA is associated with a difference in the risk of deep infections. A retrospective cohort study was conducted using data from a United States integrated health-care system's shoulder arthroplasty registry. Patients aged ≥18 years who underwent primary elective anatomic TSA for osteoarthritis or reverse TSA (RTSA) for rotator cuff arthropathy with implanted cement information were included in the study (2009-2020). We compared patients that received ABC to those who received plain cement and are at risk of revision due to deep infection within 5 years of follow-up using Cox proportional hazard regression weighted with the inverse propensity score, stratified by procedure type. The study sample included 6409 TSAs for osteoarthritis and 779 RTSAs for rotator cuff arthropathy performed by 198 surgeons at 58 hospitals. In the TSA group, 20% received ABC; the cumulative infection probability at 5 years of follow-up was 0.5% and 0.6% for the ABC and plain cement groups, respectively. After covariate adjustment, no significant difference in infection risk was found (hazard ratio = 0.72, 95% confidence interval = 0.43-1.21, P =.216). In the RTSA group, 19% received ABC; the cumulative infection probability at 5 years of follow-up was 2.7% and 0.9% for the ABC and plain cement groups, respectively. After covariate adjustment, no significant difference in infection risk was found between the 2 cement groups (hazard ratio = 1.47, 95% confidence interval = 0.66-3.26, P =.341). In this study of more than 7000 primary elective shoulder arthroplasties performed in patients with a standard risk of infection, antibiotic bone cement did not confer any risk-reduction for periprosthetic infection when compared to plain bone cement. Different at-risk pathogen profiles may develop with prolonged use of antibiotic bone cement. [ABSTRACT FROM AUTHOR]

This study aimed to measure the cost-effectiveness of prophylaxis with emicizumab in PsHAhri on ITI in Brazil. A cost-effectiveness modeling analysis was used to estimate the costs per PsHAhri on ITI and the number of prevented bleedings from undertaking one intervention (prophylaxis with BpA) over another (prophylaxis with emicizumab), based on the Brazilian Ministry of Health perspective. Costs of ITI with recombinant FVIII, prophylaxis with BpA or emicizumab, and treated bleeding episodes with BpA costs were evaluated for PsHAhri who had ITI success or failure. This study was conducted with the perspective of the Brazilian Ministry of Health (payer). During ITI, prophylaxis with BpA cost US $924 666/PsHAhri/ITI, whereas prophylaxis with emicizumab cost US $488 785/PsHAhri/ITI. During ITI, there was an average of 9.32 bleeding episodes/PsHAhri/ITI when BpA were used as prophylaxis and 0.67 bleeding/PsHAhri/ITI when emicizumab was used. By univariate deterministic sensitivity analysis, emicizumab remained dominant whichever variable was modified. In this study, prophylaxis with emicizumab during ITI is a dominant option compared with prophylaxis with BpA during ITI. • The development of anti-factor VIII antibodies (inhibitor) is related to worse outcomes of treatment of people with severe hemophilia A (PsHA). • Immune tolerance induction (ITI) is the treatment of choice to eradicate inhibitors in PsHA and high-responding inhibitors (PsHAhri). The effectiveness of bypassing agents for preventing bleeding during ITI is already known. Assuming the same effectiveness of emicizumab in preventing bleeding in PsHAhri not under ITI, we evaluated the cost-effectiveness of emicizumab for PsHAhri undergoing ITI according to the Brazilian ITI protocol. • By univariate deterministic and probabilistic sensitivity analyses, emicizumab remained dominant whichever variable was modified. [ABSTRACT FROM AUTHOR]

Pneumocystis pneumonia (PCP) is an opportunistic lung infection and has been reported among patients with rheumatoid arthritis (RA). An animal study revealed that sulfasalazine enhances Pneumocystis clearance from the lung by accelerating macrophage activity. The self-controlled case series (SCCS) method was used to investigate the association between sulfasalazine use and PCP development in patients with RA without the effect of time-invariant, interpatient confounders. PCP episodes which developed in patients with RA at five hospitals between 2003 and 2019 were identified. PCP was defined by the following criteria: 1) detection of Pneumocystis jirovecii in respiratory specimens by polymerase chain reaction; 2) clinical symptoms (pyrexia, dry cough, dyspnea or hypoxia); 3) diffuse interstitial infiltrate on chest imaging; and 4) absence of PCP prophylaxis. The PCP incidence rate ratio (IRR) was compared between periods with and without sulfasalazine use by conditional Poisson regression. Fifty episodes of PCP were identified in 49 patients. Thirty patients received sulfasalazine at some point during their observation. While 49 episodes of PCP developed in 170.3 person-years without sulfasalazine use, only one episode of PCP developed in 103.7 person-years with sulfasalazine use. Sulfasalazine use was associated with a decreased PCP risk (adjusted IRR <0.01; 95% confidence interval <0.01–0.03) after adjusting for age and glucocorticoid, methotrexate, and tumor necrosis factor inhibitor administration. Our study demonstrated a preventive effect of sulfasalazine against PCP in patients with RA. [ABSTRACT FROM AUTHOR]

• Surgical Site Infection (SSI) is a global public health problem with the largest burden in the LMICs. • This is the first study looking into the effectiveness of using soap to prevent SSI in children undergoing surgery. • The intervention may be feasible and sustainable as it is inexpensive, readily available and involves the parent. • There is a need to develop strategies to prevent SSI beyond the hospital settings. Surgical site infections (SSIs) are common and serious complications of surgery. Guidelines on preventing SSIs have been developed, but the role of preoperative bathing with plain soap among paediatric population is unclear. We aimed to assess the effectiveness of pre-operative bathing using plain soap in preventing SSIs among paediatric surgical patients. An open-label, randomised trial was conducted at Muhimbili National Hospital in Tanzania. Preoperatively, patients in the intervention group washed their body using plain soap, while those in the control group did not. The primary outcome was SSI postoperatively. Statistical tests included χ2, Wilcoxon rank sum, and univariate and multivariable logistic regression. Of the 252 patients recruited,114 were randomised to the intervention arm. In the control arm, 40.6% (56/138) of participants developed SSIs compared to 11.4% (13/114) in the intervention arm (p < 0.01). After adjusting for confounding factors in multivariable analysis, the intervention reduced the odds of an SSI by 80% (OR: 0.20 [95% CI: 0.10, 0.41]; p < 0.01). Preoperative antibiotics were deemed to be an effect modifier of the association between the intervention and SSI (p = 0.05). The intervention significantly reduced the odds of an SSI by 88% among participants not given preoperative antibiotics (OR: 0.12 [95% CI: 0.05, 0.30]; p < 0.01). This study has shown that preoperative bathing with soap significantly reduces SSIs in paediatric surgical patients. It is a simple, cost effective and sustainable intervention. Level II [ABSTRACT FROM AUTHOR]

• Reported adherence was highest at the hospital practicing universal decolonization. • Patients vary in their concern about surgical site infections. • Patients vary in the effort they will extend to prevent surgical site infections. • Few patients reported either barriers to adherence or side effects. To improve adherence with pre-surgical screening for Staphylococcus aureus nasal carriage and decolonization, we need more information about patients' experiences with these protocols. We surveyed patients undergoing orthopedic, neurosurgical, or cardiac operations at Johns Hopkins Hospitals (JHH), the University of Iowa Hospitals and Clinics (UIHC) at MercyOne Northeast Iowa Neurosurgery (MONIN) to assess patients' experiences with decolonization protocols. Five hundred thirty-four patients responded. Respondents at JHH were significantly more likely than those at the UIHC to report using mupirocin and were significantly more likely than those at the UIHC and MONIN to feel they received adequate information about surgical site infection (SSI) prevention and decolonization. Respondents at JHH were the least likely to not worry about SSI and they were more willing to do anything they could to prevent SSI. Few patients reported barriers to adherence and side effects of mupirocin or chlorhexidine. Respondents did not report either major side effects or barriers to adherence. Patients varied in their level of concern about SSI, their willingness to invest effort in preventing SSI, and their assessments of preoperative information. To improve patients' adherence, clinicians and hospitals should assess their patients' needs and desires and tailor their preoperative processes, education, and prophylaxis accordingly. [ABSTRACT FROM AUTHOR]

Newborns are susceptible to postnatal Vitamin K deficiencies from limited placental transfer, gastrointestinal absorption, and bioavailability in breast milk and formula preparations. For over 50 years, the American Academy of Pediatrics has recommended prophylactic vitamin K to prevent hemorrhagic disease in newborns. Yet, public skepticism contributes to increasing refusal rates. We present three cases of vitamin K-dependent bleeding following parental refusal of postnatal prophylaxis. Two patients experienced intracranial hemorrhage with resultant neurological devastation and mortality, respectively. The third child presented with symptomatic hematuria. Perinatal providers must partner with families and advocate vitamin K prophylaxis to limit unnecessary morbidity and mortality. [ABSTRACT FROM AUTHOR]

• Pneumocystis jirovecii pneumonia is a life-treating fungal infection. • Trimethoprim-sulfamethoxazole is often recommended as the first-line drug for Pneumocystis jirovecii pneumonia prophylaxis. • Low-dose trimethoprim-sulfamethoxazole has good tolerance and few adverse effects. To evaluate the efficacy and safety of low-dose trimethoprim (TMP)-sulfamethoxazole (SMX) (TMP-SMX) as the primary prophylaxis for Pneumocystis jirovecii pneumonia (PJP) in adult recipients of kidney transplantation. Three kinds of prescriptions in kidney recipients were documented, including 20 mg TMP/100 mg SMX oral daily, 20 mg TMP/100 mg SMX oral every other day, and nonprophylaxis. The primary outcome was the incidence of PJP in the first 180 days of follow-up after kidney transplantation. The secondary outcomes were changes in renal and liver function. Among the 1469 recipients, 1066 (72.56%) received 20 mg TMP/100 mg SMX daily, 127 (8.65%) received 20 mg TMP/100 mg SMX every other day, and 276 (18.79%) did not have prophylaxis prescription. The 276 recipients in the nonprophylaxis group had 124.92 person-years of follow-up, during which PJP occurred in 29 patients, for an incidence rate of 23.21 (95% confidence interval 15.76-32.72) per 100 person-years. The TMP-SMX daily group and the TMP-SMX every other day group had 524.89 and 62.07 person-years of follow-up, respectively, with no occurrence of PJP. There was no significant difference among the three groups in changes in renal and liver function (P >0.05, respectively). A total of 111 recipients in each group were enrolled in the propensity score matching analysis. It was revealed that the 111 nonprophylaxis recipients had 51.27 person-years of follow-up and 10 PJP cases. Prophylaxis was considered effective because there was a significant difference between the three groups (P <0.001). Low-dose TMP-SMX prophylaxis significantly reduces the incidence of PJP within 6 months after kidney transplantation and has a favorable safety profile. [ABSTRACT FROM AUTHOR]

• This manuscript comprehensively explores the versatile nature of biomaterials, emphasizing their dual role in both preventing unwanted bone formation and guiding ectopic bone growth for tissue engineering applications. • Promising future research directions that leverage the dual functionality of biomaterials in orthopedic medicine to improve the management of HO and explore new therapeutic avenues also proposed. Heterotopic ossification (HO) is an abnormal bone formation within non-skeletal tissues, impairing daily functionality and significantly diminishing patient quality of life. This condition presents serious clinical challenges, not only due to its impact on mobility and pain but also due to the complexities involved in its management and treatment. Interestingly, the phenomenon of ectopic bone formation, central to HO, also offers a unique avenue in tissue engineering for the constructive repair of complex bone defects. The exploration of biomaterials in this context reveals a dual potential: they can inhibit unwanted bone growth in HO and strategically direct bone formation to heal skeletal injuries. This review systematically summarizes the applications of biomaterials in preventing HO and promoting ectopic ossification to repair bone defects. It also looks forward to the application of emerging technologies such as artificial intelligence and bio-responsive materials in enhancing ectopic bone formation, providing new perspectives for research in bone tissue engineering and expanding the horizons for innovation and application of biomaterials. [ABSTRACT FROM AUTHOR]

The development of intravenous IgG (IVIG) formulations in the 1970s enabled expanded use for treating primary antibody deficiency syndromes and autoimmune conditions. Recent advancements include the use of IVIG in secondary immune deficiencies related to hematologic malignancies and stem cell transplantation, along with the newly emerging prophylactic applications following chimeric antigen receptor T-cell (CAR-T) therapies. Novel therapeutic areas such as bispecific antibodies (BsAbs) for lymphoma and myeloma have increased the use of IgG, given the associated risks of infections. Today, the concept of a rational personalized clinical use of IgG in the context of evolving clinical indications in high-income countries (HIC) is emerging, as unmet challenges in line with managing shortages due to increasing demands globally. The current work aims to review and link the indications for IgG to their characteristics and formulations, their dose, route and frequency of administrations and duration of therapy to meet the needs of individual patients. It will also explore the means to rationalize and monitor IgG use in HIC in the time of shortage, while explaining pragmatic strategies to improve supply and use in low- and middle-income countries (LMIC). [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) is a recognized postoperative complication of hip or knee arthroplasty and incurs major morbidity and mortality. While anticoagulants are the mainstay of chemoprophylaxis, aspirin has recently emerged as a popular prophylactic agent. However, there is a lack of high-quality evidence comparing aspirin to anticoagulants as a method of VTE prophylaxis, and current guidelines are conflicting regarding using aspirin as first-line chemoprophylaxis. We aimed to investigate guideline characteristics that are associated with the recommendation for or against aspirin as a first-line agent. MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and PubMed databases were searched from 1966 to January 2024 to identify clinical practice guidelines for VTE prophylaxis in adult hip or knee arthroplasty inpatients of average risk. The characteristics of the guideline were collected by 2 independent reviewers. Logistic regression was used to test the association between the recommendation for or against aspirin and guideline characteristics. There were 26 guidelines published from February 2003 to September 2023 and included in this study. There were 5 guidelines that recommended aspirin and 11 guidelines that recommended against aspirin as first-line therapy. With a more recent year of publication, aspirin was more likely to be recommended (odds ratio 1.72, 95% confidence interval: 1.05 to 2.84) and less likely to be recommended against (odds ratio 0.61, 95% confidence interval: 0.41 to 0.90). No other variables, including the level of evidence used, the composition of the guideline working group, or the objective of the guideline, were associated with the recommendation for or against aspirin. Guidelines were inconsistent in their recommendations regarding aspirin as first-line therapy as VTE prophylaxis in arthroplasty patients. Adequately powered randomized controlled trials using modern practices, such as early postoperative mobilization, are needed to better inform clinical practice guidelines. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is the most common complication of cardiac surgery. Cardiac surgery-associated AKI (CSA-AKI) is caused by systemic and renal hemodynamic impairment and parenchymal injury. Prophylaxis of CSA-AKI remains an unmet priority, for which preventive strategies based on drug therapies, hydration procedures, and remote ischemic preconditioning (RIPC) have been tested in pre-clinical and clinical studies, with variable success. Contradicting reports and scarce or insufficiently pondered information have blurred conclusions. Therefore, with an aim to contribute to consolidating the available information, we carried out a wide scope, pan-comparative meta-analysis including the accessible information about the most relevant nephroprotective approaches assayed. After a thorough examination of 1892 documents retrieved from PubMed and Web of Science, 150 studies were used for the meta-analysis. Individual odds ratios of efficacy at reducing AKI incidence, need for dialysis, and plasma creatinine elevation were obtained for each alleged protectant. Also, the combined class effect of drug families and protective strategies was also meta-analyzed. Our results show that no drug family or procedure affords substantial protection against CSA-AKI. Only, a mild but significant reduction in the incidence of CSA-AKI by preemptive treatment with dopaminergic and adrenergic drugs, vasodilators, and the RIPC technique. The integrated analysis suggests that single-drug approaches are unlikely to cope with the variety of individual pathophysiological scenarios potentially underlying CSA-AKI. Accordingly, a theragnostic approach involving the etiopathological diagnosis of kidney frailty is necessary to guide research towards the development of pharmacological combinations concomitantly and effectively addressing the key mechanisms of CSA-AKI. [Display omitted] • Acute kidney injury (AKI) is a common complication of cardiac surgery and a bad prognosis factor. • Prophylactic interventions are needed to improve patient outcome. • Preemptive application of specific drugs or remote ischemic preconditioning affords only mild protection. • Cardiac surgery-associated AKI etiopathology is complex and multifactorial. • Combined prophylaxis concomitantly tackling key pathological mechanisms should be tested. [ABSTRACT FROM AUTHOR]

• Lack of blinding may bias surgical site infection assessment, potentially impacting reported outcomes. • Single-center design and uncontrolled confounders restrict result generalizability. • Patient-reported outcomes and quality of life measures absent, limiting study value. • Antibiotic resistance risks overlooked; crucial safety considerations unaddressed. • 30-day follow-up limits long-term effect insights; delayed complications unexplored. [ABSTRACT FROM AUTHOR]

Illness resulting from influenza is a global health problem that has significant adverse socioeconomic impact. Although various strategies such as flu vaccination have beneficial effects, the risk of this illness has not been eliminated. The use of botanicals may provide a complementary approach by enhancement of the host antiviral immune response. Generate preclinical data using rodent models to determine the most effective utility of a Limnospira (formerly Arthrospira)-derived oral supplement (Immulina®) for enhancing host immunity to improve antiviral resilience. Two non-lethal mouse models (prophylactic and therapeutic) were used to evaluate the impact of Immulina® on increasing host resilience against experimental influenza infection. Mice were fed Immulina® only for the 2 weeks prior to viral infection (prophylactic regime) or starting 3 days post-viral infection (at the onset of symptoms, therapeutic design). Three doses of Immulina® were evaluated in each model using both female and male mice. Significant protective effect of Immulina® against viral illness was observed in the prophylactic model (improved clinical scores, less body weight loss, decreased lung/body weight ratio, lower lung viral load, and increased lung IFN-γ and IL-6). Substantially less (minimal) protective effect was observed in the therapeutic model. This study demonstrates that Immulina® exerts a protective effect against influenza illness when administered using a prophylactic regime and may not be effective if given after the onset of symptoms. The results will help to optimally design future clinical trials. [Display omitted] [ABSTRACT FROM AUTHOR]

• In this study we prescribed rivaroxaban and enoxaparin for VTE chemoprophylaxis after instrumented spine surgeries. • In terms of short term and long term clinical outcomes both drugs showed equal efficacy and safety. Enoxaparin is currently used for VTE prophylaxis. Rivaroxaban is more cost-effective and is as potent as enoxaparin in VTE prophylaxis. The study was held at Al-Zahra and Kashani university hospitals in Isfahan, Iran, from January 2019 to October 2020. Two hundred ninety-six patients requiring instrumented spine surgery were enrolled; 23 were excluded (lack of consent/interfering medical situations). They were randomized into the groups of rivaroxaban (case, n = 137) and enoxaparin receiving (control, n = 136). Medical data were recorded and 244 patients (case = 123, control = 121) were analyzed value < 0.05 was meaningful. 150 patients were males, and 94 were females. The mean age was 52.09 ± 12.6 years. Postoperative drain volume was higher in rivaroxaban received patients than in enoxaparin (p = 0.02). Post-operation epidural hematoma was detected in 3 patients in the case and 1 in the control group, which was not meaningful(p = 0.622). All of them were evacuated surgically. POH was associated with cervical canal stenosis surgery, existing comorbidities, and new medical events. New medical events were associated with postoperative wound dehiscence (p = 0.001). Short and long-term postoperative outcomes were similar in both groups. The mean follow-up duration was 25.8 ± 7.5 months. Rivaroxaban is as effective as enoxaparin in venous thromboembolic event prophylaxis. Regarding postoperative epidural hematoma, statistical analysis showed equal safety of both drugs. Still, the authors would like to recommend more discretion in rivaroxaban administration in cervical spine laminectomy until future studies are conducted. [ABSTRACT FROM AUTHOR]