Efficacy Of Prophylaxis Research Articles

Anti-Factor Xa Level Monitoring for Enoxaparin Prophylaxis and Treatment in High-Risk Patient Groups.

Description Monitoring anti-factor Xa levels is a controversial topic in the inpatient setting due to resource utilization and unclear conditional guideline recommendations regarding this practice. Enoxaparin dosing in certain high-risk patient populations such as those with low body weight, obesity, renal insufficiency, and pregnancy has not been determined. The objective of this review was to assess the safety and efficacy of enoxaparin monitoring via anti-factor Xa levels in high-risk patient populations. The PubMed database was searched for articles related to low-molecular-weight heparin monitoring. Randomized controlled trials and meta-analyses that evaluated the safety and efficacy of enoxaparin prophylaxis and treatment in patients with extremes of weight, renal insufficiency, and pregnancy were selected. Fourteen studies representing four high-risk population patient groups were included. Patients with extremes of weight or who were pregnant were found to have subtherapeutic anti-factor Xa levels due to the weight-based dosing of enoxaparin. Those with renal insufficiency were found to be accumulating enoxaparin, indicating the need for a lower dose. Studies have shown that monitoring may be required in specific high-risk patient groups. Dose adjustments based on anti-factor Xa levels can prevent adverse events associated with enoxaparin. Further research involving larger patient populations would be necessary to determine the clinical efficacy of enoxaparin monitoring with anti-factor Xa levels.

High Rates of Pediatric Venous Thromboembolism After Elective Laparoscopic Splenectomy Suggest Need for Perioperative Prophylaxis

IntroductionIn adult populations, postoperative venous thromboembolism (VTE) is a reported complication of up to 8% of elective laparoscopic splenectomy (LS) cases. VTE is a rare event in the pediatric population, affecting less than 1% of all pediatric surgical patients. We hypothesized that pediatric patients are at a higher risk of postoperative VTE after undergoing elective LS relative to other laparoscopic procedures and may warrant prophylactic treatment. Materials and methodsWe queried the American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database from 2012 to 2020. Patients were identified using the Current Procedural Terminology code 38120 and only elective cases were analyzed. ResultsThe incidence of VTE in all pediatric patients undergoing surgery in the American College of Surgeons NSQIP-P database was 0.13%. The incidence of VTE in pediatric patients undergoing elective laparoscopic abdominopelvic procedures was 0.17%. There were seven total cases of VTE (0.41%) in pediatric patients undergoing elective LS, more than twice the rate of the general population (P = 0.001). Eighty percent of pediatric patients undergoing elective LS had an underlying hematological disorder. ConclusionsBy analyzing the NSQIP-P database, we evaluated the largest cohort of pediatric patients undergoing elective LS to date. We identified a higher incidence of VTE following this procedure relative to the rate of VTE in the overall population in the NSQIP-P database, as well as those undergoing elective laparoscopic abdominopelvic operations. The relatively higher incidence of VTE after elective LS is likely due to the presence of underlying hematological conditions. Given the low incidence of complications associated with pharmacologic VTE prophylaxis, the results of this study suggest that further research is warranted to establish the efficacy of perioperative pharmacological VTE prophylaxis in pediatric patients undergoing elective LS.

Efficacy of perioperative antibiotic prophylaxis in elective soft-tissue-only wrist arthroscopy

Wrist arthroscopy is a standard procedure in hand surgery for diagnosis and treatment of wrist injuries. Even though not generally recommended for similar procedures, general administration of perioperative antibiotic prophylaxis (PAP) is still widely used in wrist arthroscopy. A clinical ambispective dual-centre study was performed to determine whether PAP reduces postoperative infection rates after soft tissue-only wrist arthroscopies. Retrospective and prospective data was collected at two hospitals with departments specialized in hand surgery. During the study period, 464 wrist arthroscopies were performed, of these 178 soft-tissue-only interventions met the study criteria and were included. Signs of postoperative infection and possible adverse drug effects (ADEs) of PAP were monitored. Additionally, risk factors for surgical site infection (SSIs), such as diabetes mellitus and BMI, were obtained. The overall infection rate of SSI was zero. Neither in the PAP group (n = 69) nor in the control group (n = 109) were signs of postoperative infection observed. Observed symptoms of ADEs were three-times higher in the PAP group when compared to the control-group (16.3 vs 5.5%; p = 0.043). No major ADEs were observed, but one in ten patients in the PAP group reported mild to severe intestinal or hypersensitivity symptoms. We demonstrate that the number needed to treat (NNT) with PAP to prevent one postoperative infection in soft-tissue arthroscopies of the wrist is > 109. Conversely, symptoms of ADEs were reported by one out of ten patients given PAP. Considering the high NNT to prevent postoperative infection and the large number of ADEs caused by PAP, we recommend not to use PAP routinely in soft-tissue arthroscopies of the wrist. Subsequent large-scale studies should be conducted to substantiate these results.

Low-Dose TMP-SMX for Pneumocystis jirovecii Pneumonia Prophylaxis in Pediatric Solid Organ Transplant Recipients.

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection that adversely affects solid organ transplant (SOT) recipients. Published guidelines endorse 5 to 10 mg/kg/day (trimethoprim component) trimethoprim-sulfamethoxazole (TMP-SMX) as the recommended regimen for PJP prevention, often resulting in drug-related adverse effects. We investigated the use of a low-dose TMP-SMX regimen given at 2.5 mg/kg/dose once daily every Monday, Wednesday, and Friday at a large pediatric transplantation center. A retrospective chart review was conducted, including patients ages 0 to 21 years who underwent SOT from January 1, 2012, to May 1, 2020, and who were subsequently started on PJP prophylaxis with low-dose TMP-SMX for a minimum of 6 months. The primary end point was the incidence of breakthrough PJP infection on the low-dose TMP-SMX regimen. Secondary end points include the prevalence of adverse effects characteristic of TMP-SMX. A total of 234 patients were included in this study, and 6 of 234 patients (2.6%) were empirically transitioned to treatment dosing of TMP-SMX given a clinical concern for PJP, although none received a diagnosis of PJP. There were 7 patients (2.6%) who experienced hyperkalemia, 36 (13.3%) had neutropenia, and 22 (8.1%) had thrombocytopenia (all grade 4). Clinically significant serum creatinine elevations were seen in 43 of 271 patients (15.9%). Elevations of liver enzymes were seen in 16 of 271 patients (5.9%). Rash was documented in 4 of 271 patients (1.5%). In our patient cohort, low-dose TMP-SMX preserves the efficacy of PJP prophylaxis while providing an acceptable adverse effect profile.

Efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors (ATLAS-INH): a multicentre, open-label, randomised phase 3 trial

Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance haemostasis in people with haemophilia A or haemophilia B, irrespective of inhibitor status. We evaluated the efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors. This multicentre, randomised, open-label phase 3 study was done at 26 sites (primarily secondary or tertiary centres) in 12 countries. Men, boys, and young adults aged 12 years or older with severe haemophilia A or haemophilia B with inhibitors previously treated with on-demand bypassing agents were randomly assigned (2:1) to receive once-a-month 80 mg subcutaneous fitusiran prophylaxis (fitusiran prophylaxis group) or to continue with bypassing agents on-demand (bypassing agents on-demand group) for 9 months. The primary endpoint was mean annualised bleeding rate during the efficacy period in the intention-to-treat population estimated by negative binomial model. Safety was assessed as a secondary endpoint in the safety population. This trial is complete and is registered with ClinicalTrials.gov, NCT03417102. Between Feb 14, 2018, and June 23, 2021, 85 participants were screened for inclusion, of whom 57 (67%; 57 [100%] men; median age 27·0 years [IQR 19·5-33·5]) were randomly assigned: 19 (33%) participants to the bypassing agent on-demand group and 38 (67%) participants to the fitusiran prophylaxis. Negative binomial model-based mean annualised bleeding rate was significantly lower in the fitusiran prophylaxis group (1·7 [95% CI 1·0-2·7]) than in the bypassing agents on-demand group (18·1 [10·6-30·8]), corresponding to a 90·8% (95% CI 80·8-95·6) reduction in annualised bleeding rate in favour of fitusiran prophylaxis (p<0·0001). 25 (66%) participants had zero treated bleeds in the fitusiran prophylaxis group versus one (5%) in the bypassing agents on-demand group. The most frequent treatment-emergent adverse event in the fitusiran prophylaxis group was increased alanine aminotransferase in 13 (32%) of 41 participants in the safety population; there were no increased alanine aminotransferase treatment-emergent adverse events in the bypassing agents on-demand group. Suspected or confirmed thromboembolic events were reported in two (5%) participants in the fitusiran prophylaxis group. No deaths were reported. Subcutaneous fitusiran prophylaxis resulted in statistically significant reductions in annualised bleeding rate in participants with haemophilia A or haemophilia B with inhibitors, with two-thirds of participants having zero bleeds. Fitusiran prophylaxis might show haemostatic efficacy in participants with haemophilia A or haemophilia B with inhibitors; therefore, the therapeutic might have the potential to improve the management of people with haemophilia. Sanofi.

Tinidazole efficacy for amebic colitis therapeutic prophylaxis in patients with de novo acute leukemia receiving intensive chemotherapy.

In Mexico, seroprevalence of Entamoeba histolytica is 8.4%. The intestinal amebiasis in patients with acute leukemia of novo, after the start of chemotherapy (CT) in the Hematology Service of the CMN 20 de Noviembre is 12%, even if patients show a negative baseline coprological test. To find out if the administration of tinidazole, in patients with acute leukemia and negative coprological test, at the beginning of the CT, decreases the incidence of amoebic colitis during the induction to remission. Prospective and not comparative study. Patients with de novo diagnosis of acute leukemia who initiate induction and initial coprological CT. Tinidazole was indicated, 2 g/day for 5 days in the first week of CT started. They were monitored until the induction was concluded and hematopoietic recovery started. 38 patients, 15 women and 23 men with a mean age of 44 years (16-72), with acute lymphoblastic leukemia 19, myeloblastic 16 and promyelocytic 3. Cases without and with intestinal amebiasis were 35 and 3, respectively. Patients with amebiasis only received tinidazole for 3 days and it was given 2 days after the CT started. Tinidazole, in patients with acute de novo leukemia who initiate induction CT, is effective in the prevention of intestinal amebiasis, during the induction stage, if administered at 2 g/day, for five days, starting on day 1 of the CT.

Fitusiran prophylaxis in people with severe haemophilia A or haemophilia B without inhibitors (ATLAS-A/B): a multicentre, open-label, randomised, phase 3 trial

Fitusiran, a subcutaneous investigational siRNA therapeutic, targets antithrombin with the goal of rebalancing haemostasis in people with haemophilia A or haemophilia B, regardless of inhibitor status. We aimed to evaluate the efficacy and safety of fitusiran prophylaxis in people with severe haemophilia without inhibitors. This multicentre, open-label, randomised phase 3 study was conducted at 45 sites in 17 countries. Male participants aged at least 12 years with severe haemophilia A or B without inhibitors, who had previously been treated on-demand with clotting factor concentrates, were randomly assigned in a 2:1 ratio to receive 80 mg subcutaneous fitusiran prophylaxis once per month or to continue on-demand clotting factor concentrates for a total of 9 months. Randomisation was stratified by the number of bleeding events in the 6 months before screening (≤10 bleeds and >10 bleeds) and by haemophilia type (haemophilia A or B). The primary endpoint was annualised bleeding rate, analysed in the intention-to-treat analysis set. Safety and tolerability were assessed in the safety analysis set. This trial is registered with ClinicalTrials.gov, NCT03417245, and is complete. Between March 1, 2018, and July 14, 2021, 177 male participants were screened for eligibility and 120 were randomly assigned to receive fitusiran prophylaxis (n=80) or on-demand clotting factor concentrates (n=40). Median follow-up was 7·8 months (IQR 7·8-7·8) in the fitusiran group and 7·8 months (7·8-7·8) in the on-demand clotting factor concentrates group. The median annualised bleeding rate was 0·0 (0·0-3·4) in the fitusiran group and 21·8 (8·4-41·0) in the on-demand clotting factor concentrates group. The estimated mean annualised bleeding rate was significantly lower in the fitusiran prophylaxis group (3·1 [95% CI 2·3-4·3]) than in the on-demand clotting factor concentrates group (31·0 [21·1-45·5]; rate ratio 0·101 [95% CI 0·064-0·159]; p<0·0001). In the fitusiran group, 40 (51%) of 79 treated participants had no treated bleeds compared with two (5%) of 40 participants in the on-demand clotting factor concentrates group. Increased alanine aminotransferase concentration (18 [23%] of 79 participants in the safety analysis set) was the most common treatment-emergent adverse event in the fitusiran group and hypertension (four (10%) of 40 participants) was the most common in the on-demand clotting factor concentrates group. Treatment-emergent serious adverse events were reported in five (6%) participants in the fitusiran group (cholelithiasis [n=2, 3%], cholecystitis [n=1, 1%], lower respiratory tract infection [n=1, 1%], and asthma [n=1, 1%]) and five (13%) participants in the on-demand clotting factor concentrates group (gastroenteritis, pneumonia, suicidal ideation, diplopia, osteoarthritis, epidural haemorrhage, humerus fracture, subdural haemorrhage, and tibia fracture [all n=1, 3%]). No treatment-related thrombosis or deaths were reported. In participants with haemophilia A or B without inhibitors, fitusiran prophylaxis resulted in significant reductions in annualised bleeding rate compared with on-demand clotting factor concentrates and no bleeding events in approximately half of participants. Fitusiran prophylaxis shows haemostatic efficacy in both haemophilia A and haemophilia B, and therefore has the potential to be transformative in the management of all people with haemophilia. Sanofi.

The risk factors for Group B Streptococcus colonization during pregnancy and influences of intrapartum antibiotic prophylaxis on maternal and neonatal outcomes

BackgroundGroup B Streptococcus (GBS), also referred as Streptococcus agalactiae, is one of the leading causes of life-threatening invasive diseases such as bacteremia, meningitis, pneumonia and urinary tract infection in pregnant women and neonates. Rates of GBS colonization vary by regions, but large-sample studies on maternal GBS status are limited in southern China. As a result, the prevalence of GBS among pregnant women and its associated risk factors and the efficacy of intrapartum antibiotic prophylaxis (IAP) intervention in preventing adverse pregnancy and neonatal outcomes remain poorly understood in southern China.MethodsTo fill this gap, we retrospectively analyzed demographic and obstetrical data of pregnant women who have undergone GBS screening and delivered between 2016 and 2018 in Xiamen, China. A total of 43,822 pregnant women were enrolled and only a few GBS-positive women did not receive IAP administration. Possible risk factors for GBS colonization were assayed by univariate and multivariate logistic regression analysis. Generalized linear regression model was applicated to analyze whether IAP is one of the impact factors of the hospital length of stay of the target women.ResultsThe overall GBS colonization rate was 13.47% (5902/43,822). Although women > 35 years old (P = 0.0363) and women with diabetes mellitus (DM, P = 0.001) had a higher prevalence of GBS colonization, the interaction between ages and GBS colonization was not statistically significant in Logistic Regression analysis (adjusted OR = 1.0014; 95% CI, 0.9950, 1.0077). The rate of multiple births was significantly dropped in GBS-positive group than that of GBS-negative group (P = 0.0145), with no significant difference in the rate of fetal reduction (P = 0.3304). Additionally, the modes of delivery and the incidences of abortion, premature delivery, premature rupture of membranes, abnormal amniotic fluid and puerperal infection were not significantly different between the two groups. The hospitalization stays of the subjects were not influenced by GBS infection. As for neonatal outcomes, the cases of fetal death in maternal GBS-positive group did not statistically differ from that in maternal GBS-negative group.ConclusionOur data identified that pregnant women with DM are at high risk of GBS infection and IAP is highly effective in prevention of adverse pregnancy and neonatal outcomes. This stressed the necessity of universal screening of maternal GBS status and IAP administration to the target population in China, and women with DM should be considered as priorities.

Evaluation of pancreatic stent and/or suppository indomethacin efficacy in post ERCP pancreatitis prophylaxis: a single center experience

Aim: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a serious complication of ERCP. In this study, we aimed to compare the use of rectal indomethacin, pancreatic stenting or both techniques for prevention of PEP.&#x0D; Material and Method: Patients who underwent ERCP for the first time due to choledocholithiasis between January 2022 and June 2022 were retrospectively reviewed. The clinical findings, demographics, laboratory records, endoscopic intervention characteristics, whether rectal indomethacin was applied before the procedure, whether pancreatic stent was placed or not were evaluated.&#x0D; Results: A total of 367 patients who underwent ERCP for the first time were included in the study. The mean age was 61 (28-92) years and 53.4% were female. In 124 (33.8%) patients, involuntary guide-wire insertion into the pancreatic duct occurred during canulation. Pancreatic stent was placed in 82 (22.3%) of the patients. Rectal indomethacin was administered to 288 patients (78.5%), while indomethacin could not be administered in 79 patients (21.5%), because they did not give consent. When patients with involuntarily pancreatic canulation were evaluated, the rate of PEP was 3.6% in the stented group, while it was 15.3% in the stent-free group (p

Safety and efficacy of nightly nitrofurantoin as prophylaxis in dogs with recurrent urinary tract infections: 13 cases (2015-2021).

To report the protocol, efficacy and adverse events in dogs receiving nightly nitrofurantoin therapy as antimicrobial prophylaxis for recurrent urinary tract infections. Retrospective case series of dogs prescribed nitrofurantoin as prophylaxis for recurrent urinary tract infections. Data on urological history, diagnostic investigation, protocol, adverse events and efficacy (through serial urine cultures) were extracted from medical records. Thirteen dogs were included. Before therapy, dogs had a median of 3 (range 3 to 7) positive urine cultures in the past year. In all but one dog, standard antimicrobial therapy was given before starting the nightly nitrofurantoin. The nightly nitrofurantoin was then prescribed at a median dose of 4.1mg/kg orally every 24 hours for a median of 166 days (range 44 to 1740). The median infection-free interval on therapy was 268 days (95% confidence interval: 165 to undefined). Eight dogs had no positive urine cultures while on therapy. Of these, five (three which discontinued and two which remained on nitrofurantoin) had no return of clinical signs or bacteriuria at time of last follow-up evaluation or death, and three had suspected or confirmed bacteriuria 10 to 70 days after discontinuation. Five dogs developed bacteriuria on therapy, four of which were nitrofurantoin-resistant Proteus spp. Most other adverse events were minor; none were considered likely caused by the drug on causality assessment. Based on this small study group, nightly nitrofurantoin appears well tolerated and might be efficacious prophylaxis for recurrent urinary tract infections in dogs. Infection with nitrofurantoin-resistant Proteus spp. was a common reason for treatment failure.

A Retrospective Case Series on Valproic Acid for Early Post-Traumatic Seizure Prophylaxis After Traumatic Brain Injury in Patients With Concomitant Agitation.

Purpose: Early post-traumatic seizures occur within 7 days following a traumatic brain injury and may lead to additional brain damage and poor outcomes. Levetiracetam or phenytoin is often used for seizure prophylaxis in this patient population, but valproic acid may be an appropriate therapeutic alternative in patients with concomitant agitation. Evidence for the use of valproic acid for both early post-traumatic seizure prophylaxis and agitation is limited. The purpose of this study is to examine the safety and efficacy of valproic acid for both early post-traumatic seizure prophylaxis and agitation. Methods: This single-center, retrospective case series includes 18 patients who received valproic acid for both early post-traumatic seizure prophylaxis and agitation. Efficacy for early post-traumatic seizure prophylaxis is assessed by the incidence of seizures within 7 days of injury. Efficacy for agitation is assessed by changes in Riker Sedation-Agitation Scale scores during valproic acid therapy. The safety of valproic acid is defined by the incidence of selected adverse events. Results: Among 18 patients with traumatic brain injuries receiving valproic acid for both early post-traumatic seizures and agitation, one patient experienced a seizure during the period of prophylaxis and thrombocytopenia was the most common adverse event. Conclusion: In this small cohort of patients, valproic acid appears be a potential option to prevent early post-traumatic seizures in patients with traumatic brain injuries and concomitant agitation with minimal adverse effects. Randomized, controlled studies are needed to further investigate the role of valproic acid for this indication, including standards for dosing regimens, serum drug monitoring, and the relationship between valproic acid treatment and mortality.

Efficacy of pre-exposure prophylaxis to prevent SARS-CoV-2 infection after lung transplantation: a two center cohort study during the omicron era

PurposeLung transplant (LTx) recipients are at risk for poor outcomes from coronavirus disease 2019 (COVID-19). The aim of the study was to assess the outcome of patients receiving pre-exposure prophylaxis (PrEP) with tixagevimab and cilgavimab after LTx.MethodsAll LTx recipients with outpatient visits from February 28th to October 31st, 2022 at two German centers were included. Baseline characteristics were recorded and patients followed until November 30rd, 2022. Infections with SARS-CoV-2, disease severity, and COVID-19-associated death were compared between patients with and without PrEP.ResultsIn total, 1438 patients were included in the analysis, and 419 (29%) received PrEP. Patients receiving PrEP were older and earlier after transplantation, had lower glomerular filtration rates, and lower levels of SARS-CoV-2-S antibodies. In total, 535 patients (37%) developed SARS-CoV-2 infection during a follow-up of median of 209 days. Fewer infections occurred in patients with PrEP during the study period (31% vs. 40%, p = 0.004). Breakthrough SARS-CoV-2 infections after PrEP occurred in 77 patients (19%). In total, 37 infections (8%) were severe or critical. No difference in severity of COVID-19 was observed between patients with and without PrEP. There were 15 COVID-19-associated deaths (n = 1 after PrEP). Compared to matched controls, there was a non-significant difference towards a lower risk for moderate to critical COVID-19 (p 0.184).ConclusionThe number of SARS-CoV-2 infections was lower in LTx recipients with PrEP. Despite being at higher risk for worse outcome severity of COVID-19 and associated mortality were similar in patients with and without PrEP.

Sustained Improvement of Appropriateness in Surgical Antimicrobial Prophylaxis with the Application of Quality Control Circle.

Quality control circle (QCC) has acquired success in many fields in healthcare industry as a process management tool, whereas its efficacy in surgical antimicrobial prophylaxis (SAP) remains unknown. This study aimed to implement QCC interventions to improve the appropriateness of SAP. A QCC activity team was established to grasp the current situation of SAP in clean surgery procedure, set target, formulate corresponding countermeasures and implement and review them in stages. The plan-do-check-act (PDCA) method was cyclically applied. The appropriateness of antibiotic prophylaxis before (January to December 2020) and after (January to December 2021) the implementation of QCC activities were evaluated based on relevant international and Chinese SAP guidelines. The overall SAP appropriateness was significantly improved from 68.72% before QCC to 93.7% post QCC implementation (P<0.01). A significant improvement (P<0.05) was also determined for each category: selection (from 78.82% to 96.06%), duration (from 90.15% to 96.46%), indication (from 94.09% to 97.64%), timing of first dose (from 96.55% to 99.21%), antimicrobial usage (from 96.8% to 99.41%), re-dosing of antimicrobial (from 96.55% to 99.21%). Implementation of a QCC program can optimize the use of antibiotics and improve the appropriateness of SAP and is of practical importance to their standardization.

Pre-exposure prophylaxis of new COVID-19 coronavirus infection with tixagevimab/cilgavimab in adult Moscow patients with primary immunodeficiencies

Primary immunodeficiencies (PIDs), now known as inborn errors of immunity, are a group of inherited diseases caused by defects in the genes that control the immune response. Patients with PIDs have risks of developing a severe course and/or death in COVID-19. Passive immunization with long-acting monoclonal antibodies (MABs) to SARS-CoV-2 should be considered as pre-exposure prophylaxis in patients with PIDs. Tixagevimab/cilgavimab is a combination of MABs that bind to the SARS-CoV-2 spike protein. To evaluate the efficacy and safety of pre-exposure prophylaxis of new SARS-CoV-2 infection in PIDs with the combination of tixagevimab/cilgavimab. Forty eight patients diagnosed with PIDs were included in the study. Median follow-up after drug administration was 174 days. The total number of confirmed coronavirus infections in patients with PIDs as well as 6 months before and after administration of MAT were assessed. In the analyzed cohort, the overall incidence of COVID-19 from pandemic onset to MABs administration was 75% (36/48), with 31% (11/36) of over-infected patients having had the infection more than once. The incidence of COVID-19 immediately 6 months before the introduction of tixagevimab/cilgavimab was 40%. All patients who had COVID-19 after pre-exposure prophylaxis had a mild infection. The incidence of COVID-19 6 months after tixagevimab/cilgavimab administration significantly decreased compared to the incidence 6 months before administration (7 and 40%, respectively; p<0.001). The use of tixagevimab/cilgavimab in patients with PIDs is effective as pre-exposure prophylaxis and reduces the risk of severe COVID-19.

Invasive Fungal Breakthrough Infections under Targeted Echinocandin Prophylaxis in High-Risk Liver Transplant Recipients

Invasive fungal infections (IFIs) are frequent and outcome-relevant complications in the early postoperative period after orthotopic liver transplantation (OLT). Recent guidelines recommend targeted antimycotic prophylaxis (TAP) for high-risk liver transplant recipients (HR-LTRs). However, the choice of antimycotic agent is still a subject of discussion. Echinocandins are increasingly being used due to their advantageous safety profile and the increasing number of non-albicans Candida infections. However, the evidence justifying their use remains rather sparse. Recently published data on breakthrough IFI (b-IFI) raise concerns about echinocandin efficacy, especially in the case of intra-abdominal candidiasis (IAC), which is the most common infection site after OLT. In this retrospective study, we analyzed 100 adult HR-LTRs undergoing first-time OLT and receiving echinocandin prophylaxis between 2017 and 2020 in a tertiary university hospital. We found a breakthrough incidence of 16%, having a significant impact on postoperative complications, graft survival, and mortality. The reasons for this may be multifactorial. Among the pathogen-related factors, we identified the breakthrough of Candida parapsilosis in 11% of patients and one case of persistent IFI due to the development of a secondary echinocandin resistance of an IAC caused by Candida glabrata. Consequently, the efficacy of echinocandin prophylaxis in liver transplantation should be questioned. Further studies are necessary to clarify the matter of breakthrough infections under echinocandin prophylaxis.

Lupus – Prevention and Treatment with a Plant-Based Diet

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune rheumatic disease in which disease flares are interspersed with episodes of remission. In contrast to organ-specific autoimmune diseases, SLE comprises a constellation of signs and symptoms that can affect multiple organ systems. A plant-based diet may have a beneficial effect on SLE patients, due not only to the direct action of nutrients on the immune system and inflammation, but also to an indirect effect on insulin resistance, obesity and associated co-morbidities. Accelerated atherosclerosis is a significant comorbidity and the leading cause of death for patients with SLE. Patients are also more likely to experience metabolic syndrome leading to type II diabetes, obesity, and chronic kidney disease. A plant-based diet is a safe and efficacious prophylaxis and treatment for all these comorbidities. Three small interventional studies with a plant-based diet showed a beneficial effect on patients’ symptoms and therefore their quality of life. A plant-based diet has the advantage of having no adverse reactions or contraindications and can be an effective adjunct to standard treatments.

Multi-probiotic consumption sex-dependently interferes with MSG-induced obesity and concomitant phagocyte pro-inflammatory polarization in rats: Food for thought about personalized nutrition

Epidemic scope which obesity has reached in many countries necessitates shifting the emphasis in medicine from traditional reaction to individualized and personalized prevention. Numerous trials convincingly prove sexual dimorphism of obesity in morbidity, pathophysiology, comorbidity, outcomes and prophylaxis efficacy. Obesity is characterized by chronic systemic low-grade inflammation that creates the preconditions for the emergence of numerous comorbidities. Leading role in the initiation, propagation and resolution of inflammation belongs to tissue resident and circulating phagocytes. The outcome of inflammation largely depends on phagocyte functional polarization, which in turn is governed by environmental stimuli. Gut microbiota (GM), whose disturbances are one of the key pathogenetic features in obesity, substantially affect phagocyte functions and can either aggravate or calm obesity-associated inflammation. Probiotics possess promising physiological functions, including microbiota-restoring and anti-inflammatory traits, that may possibly help prevent obesity. However, sex-specific effects of probiotic supplementation for targeted obesity prevention remain unknown. The aim of the current study was aimed to compare the effect of multi-probiotic preparation used in prophylactic regimen on the adiposity, profile of culturable GM and its short-chain fatty acids as well as on functional profile of phagocytes from different locations in male and female rats with monosodium glutamate (MSG)-induced obesity. Obesity was induced by neonatal MSG injections in male and female rats, who were given the multi-species probiotic during juvenile and adult developmental stages. Culturable fecal and mucosa-associated microbiota of the intestine were examined using selective diagnostic media. Short-chain fatty acid profile in fecal samples was determined by GC-MS. Phagocyte functional profile was evaluated using flow cytometry and colorimetric methods. Probiotic supplementation after the administration of MSG prevented weight gain and fat accumulation, inflammatory phagocyte activation and alterations in GM in female rats. In male MSG-injected rats, probiotic supplementation restricted but did not prevent weight gain and fat deposition, alleviated but did not prevent systemic inflammation, prevented the alterations in GM, but with residual imbalance in the ratio of obligate anaerobic to facultative anaerobic bacteria. Our findings emphasize the necessity of sex-centered approaches to the prophylactic use of probiotics in obesity in the context of predictive preventive and personalized medicine.

New medications to mitigate attacks of hereditary angioedema: does one size fit all?

Hereditary angioedema has received renewed attention in the past two decades, with the elucidation of the biochemical pathways resulting in bradykinin overproduction in patients with congenital C1esterase inhibitor (C1INH) deficiency, leading to recurrent attacks of tissue swelling due to uncontrolled vascular permeability. 1 Busse PJ Christiansen SC Hereditary angioedema. N Engl J Med. 2020; 382: 1136-1148 Crossref PubMed Scopus (132) Google Scholar Oedema attacks affecting the lingual or laryngeal area can become lethal as a result of asphyxiation. 2 Minafra FG Gonçalves TR Alves TM Pinto JA The mortality from hereditary angioedema worldwide: a review of the real-world data literature. Clin Rev Allergy Immunol. 2022; 62: 232-239 Crossref PubMed Scopus (4) Google Scholar Several new treatments have emerged, 143 years after Quincke's first description of hereditary angioedema and 15 years after the introduction of the first specific bradykinin B2 receptor inhibitor (icatibant). These drugs specifically target crucial steps in the kallikrein–kinin (contact) cascade downstream of bradykinin production. 3 Fijen LM Bork K Cohn DM Current and prospective targets of pharmacologic treatment of hereditary angioedema types 1 and 2. Clin Rev Allergy Immunol. 2021; 61: 66-76 Crossref PubMed Scopus (0) Google Scholar Many of these agents have shown their efficacy and safety in acute (on-demand) treatment and prophylaxis of hereditary angioedema attacks, saving lives and revolutionising patients’ quality of life. 4 Lumry WR Settipane RA Hereditary angioedema: epidemiology and burden of disease. Allergy Asthma Proc. 2020; 41: S08-S Crossref Google Scholar These modalities fit well into the modern paradigm in hereditary angioedema treatment, supporting patients’ autonomy, recommending self-administration, and reducing reliance on hospital emergency rooms, health-care providers, and medical points of care. 5 Maurer M Magerl M Betschel S et al. The international WAO/EAACI guideline for the management of hereditary angioedema—the 2021 revision and update. Allergy. 2022; 77: 1961-1990 Crossref PubMed Scopus (32) Google Scholar An investigational oral plasma kallikrein inhibitor for on-demand treatment of hereditary angioedema: a two-part, randomised, double-blind, placebo-controlled, crossover phase 2 trialOral administration of sebetralstat was well tolerated and led to rapid suppression of plasma kallikrein activity, resulting in increased time to use of conventional attack treatment and faster symptom relief versus placebo. Based on these results, a phase 3 trial to evaluate the efficacy and safety of two dose levels of sebetralstat in adolescent and adult participants with hereditary angioedema has been initiated ( NCT05259917 ). Full-Text PDF

142 - Safety and Efficacy of Oral Vancomycin Prophylaxis Against Clostridioides Difficile Infection in Stem Cell Transplant Recipients

142 - Safety and Efficacy of Oral Vancomycin Prophylaxis Against Clostridioides Difficile Infection in Stem Cell Transplant Recipients

342 - Safety and Efficacy of Gvhd Prophylaxis with Abatacept and Reduced Dose Post-Transplant Cytoxan in Matched Unrelated and Matched Related Allogeneic Peripheral Stem Cell Transplants

342 - Safety and Efficacy of Gvhd Prophylaxis with Abatacept and Reduced Dose Post-Transplant Cytoxan in Matched Unrelated and Matched Related Allogeneic Peripheral Stem Cell Transplants