Prophylactic Group Research Articles

A prophylactic tyrosine kinase inhibitor strategy based on measurable residual disease pre-transplantation for Ph+ acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation: A prospective multicenter cohort study.

Relapse is the major cause of treatment failure in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to evaluate the effect of a prophylactic tyrosine kinase inhibitor (TKI) strategy on relapse in this population. Patients were assigned to prophylactic or control groups based on measurable residual disease (MRD) pre-transplantation. The primary endpoint was the cumulative incidence of relapse. A total of 110 patients with Ph+ ALL undergoing allo-HSCT were enrolled in this prospective study. Thirty-eight patients with positive MRD pre-transplantation were included in the prophylactic group, and 72 with negative MRD pre-transplantation were included in the control group. The 4-year cumulative incidence of relapse was 25.3% (95% CI: 12.1%-41.0%) and 20.3% (11.6%-30.7%; HR = 1.272, 95% CI: 0.551-2.940, p = .549), and non-relapse mortality was 10.5% (3.3%-22.7%) and 9.7% (4.2%-17.9%; HR = 1.094, 95% CI: 0.320-3.738, p = .928) in the prophylactic and control groups. The 4-year overall survival was 71.8% (53.2%-84.1%) and 84.1% (72.9%-90.9%; HR = 1.746, 95% CI: 0.741-4.112, p = .196), and leukemia-free survival was 64.1% (45.8%-77.7%) and 70.0% (57.6%-79.4%; HR = 1.212, 95% CI: 0.607-2.421, p = .585) in the prophylactic and control groups. Our results suggest that prophylactic TKI post-HSCT in patients with positive MRD pre-transplantation can produce outcomes comparable to negative MRD pre-transplantation without TKI post-HSCT.

Comparison of Phenylephrine Bolus and Infusion Regimens on Maternal and Fetal Outcomes During Cesarean Delivery: A Systematic Review and Meta-Analysis

BACKGROUND: A systematic review and meta-analysis was conducted to compare phenylephrine boluses versus prophylactic infusion in parturients undergoing cesarean delivery under spinal or combined spinal-epidural anesthesia on feto-maternal outcomes. METHODS: Medline, Embase, Cochrane, and US Clinical registry databases were searched. Studies comparing phenylephrine boluses (both therapeutic and prophylactic) with infusion (both fixed- and variable-rate) assessing various feto-maternal outcomes were included. The primary outcome was the incidence of maternal hypotension. Secondary maternal outcomes included the incidence of reactive hypertension, bradycardia, nausea, or vomiting; secondary neonatal outcomes included umbilical arterial pH, partial pressure of oxygen (paO2), umbilical venous pH, fetal acidosis, Apgar Scores at 1 and 5 minutes. All outcomes were quantitatively analyzed using the random effects model. Risk of bias was assessed using the Cochrane Collaboration R0B 2.0 tool. RESULTS: We included 15 studies with 2153 parturients. The parturients receiving phenylephrine bolus during cesarean delivery under spinal or combined spinal-epidural anesthesia had a significant increase in the incidence of predelivery hypotension compared to phenylephrine infusion (risk ratio [RR], 2.34, 95% confidence interval [CI], 1.72–3.18). Reactive hypertension (RR, 0.48, 95% CI, 0.29–0.79) and bradycardia (RR, 0.57, 95% CI, 0.41–0.79) were less common in the parturients receiving phenylephrine bolus; whereas, vomiting (RR, 2.15, 95% CI, 1.53–3.03) was more common compared to the infusion group. No statistically significant difference was observed in the incidence of nausea or any fetal outcomes (umbilical artery pH, paO2, umbilical venous pH, fetal acidosis, and Apgar scores at 1 and 5 minutes) between either of the groups. Three studies had a high risk of bias. CONCLUSIONS: A prophylactic phenylephrine infusion significantly reduces the incidence of predelivery hypotension in parturients undergoing cesarean delivery under neuraxial anesthesia in comparison to the therapeutic or prophylactic phenylephrine bolus group. A prophylactic phenylephrine infusion may be considered in all parturients without preexisting hypertensive disorder or cardiovascular disorders to reduce the risk of predelivery hypotension. More evidence is needed to guide optimal hemodynamic management for patients with hypertensive or cardiovascular disorders.

Safety of abdominal paracentesis in hospitalised patients receiving uninterrupted therapeutic or prophylactic anticoagulants.

Abdominal paracentesis is a frequently performed procedure in hospitalised patients with ascites. Concurrently, most hospitalised adult patients receive pharmacologic anticoagulation, either for therapeutic purposes or prophylactically to prevent venous thromboembolism. Despite this, minimal evidence exists to guide management of anticoagulant therapy pre- and post-paracentesis. The authors aimed to investigate the safety of abdominal paracentesis in hospitalised patients receiving therapeutic or prophylactic anticoagulation, including in patients for whom these medications were withheld periprocedurally. TriNetX, an electronic health record data set, was queried to identify patients between the ages of 18 and 80 years who received an abdominal paracentesis while hospitalised at the authors' institution between September 2017 and June 2022. Patients receiving prophylactic anticoagulation (137), therapeutic anticoagulation (74) and no anticoagulation because of coagulopathy or thrombocytopenia (15) were compared. Rates of withholding anticoagulation, performing service, pre- and post-paracentesis haemoglobin, bleeding complications, thrombotic complications and need for red blood cell transfusion were analysed. Procedure-related bleeding complications occurred in two (1.4%) patients in the prophylactic group and 0 (0%) patients in the therapeutic group (P = 0.54). No thrombotic complications occurred. Rates of red blood cell transfusions post-paracentesis were similar between groups. Analysis of secondary end-points identified significant differences in rates of withholding anticoagulation and mean change in haemoglobin between performing services. Performance of abdominal paracentesis in patients receiving therapeutic or prophylactic anticoagulation appears to be safe regardless of whether anticoagulation was interrupted periprocedurally, with low rates of bleeding complications, thrombotic complications or need for red blood cell transfusions post-paracentesis.

Efficacy and safety of diclazuril nanoemulsion in control of Eimeria tenella in broilers

BackgroundNanotechnology has the potential to reduce drug dosage while increasing efficacy; thus, the current work intends to synthesize diclazuril nanoemulsion and assess its performance against experimental coccidiosis in broilers.MethodsDiclazuril nanoemulsion (DZN) was formulated and characterized by zeta seizer and zeta potential. The formulated DZN was evaluated in vivo against Eimeria tenella infected chicks. DZN and DZ were used in 2 programs; therapeutic and prophylactic. A total of 210 one-day-old broiler chicks were distributed equally into six groups. The controls were negative uninfected untreated and positive infected untreated (G1 & G2). Therapeutic groups (G3 & G4) treated by DZ and DZN after appearance of the clinical signs of coccidiosis and continued for 5 days. Prophylaxis groups (G5 & G6) received DZ and DZN at 3 days before challenge and continued for 5 days after infection. The treatments dosages were 10 mg/mL for DZ of commercial origin and 2.5 mg/mL for the prepared DZN. All groups (except negative control) orally infected then followed up for clinical signs of coccidiosis, mortality rate, oocysts count, performance, hematological and biochemical parameters in addition to histopathological lesions.ResultsThe therapeutic groups showed that both treated groups (DZ and DZN) revealed similar results including good body weight gain, a low lesion caecal score, a low daily and total oocyst shedding count, and a low mortality rate. Regarding the biochemical parameters, all parameters were affected during infection then restored after the 12th day post infection. However, in the prophylactic groups, showed mild clinical signs and the blood pictures and biochemical parameters were nearly like the control negative without infection.ConclusionDZN at a quarter dose of standard DZ produced the same outcomes as DZ at 10 mg/mL. Furthermore, DZN does not impair the typical safety of diclazuril in treated chicks.

Similar incidence of ICD-shocks in diabetic compared to non-diabetic patients receiving implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D)

Abstract Background and aims Recent studies have suggested that diabetes patients with implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) may experience a reduced incidence of appropriate ICD-shocks and an increased mortality rate. This study aims to assess whether there is parity in ATP-treatment and ICD-shocks between patients with and without type 2 diabetes mellitus (T2DM), and to analyze associated mortality rates. Methods Using the Danish pacemaker and ICD registry we included patients who received a first-time ICD or CRT-D implantation with a primary or secondary prophylactic indication, between January 1st 2000 to December 31st 2018. Outcomes were analyzed individually for each outcome. Cause specific Cox was used for i) appropriate ATP therapy or ICD-shock, ii) inappropriate ATP therapy or ICD-shock, and a standard Cox regression model was used for iii) all-cause mortality, iv) mortality rate following an ATP-therapy or ICD-shock. Cumulative incidence curves, generated using the Aalen Johansen estimator, were utilized to compare the incidence rates for ATP therapy and ICD-shock while accounting for competing risk of death, while Kaplan-Meier methodology was utilized for survival curves. Analyses were conducted in the total population and in subgroups divided on indication and device type. Results Out of 14 747 patients who received an ICD or CRT-D, 4377 (30%) had T2DM, 4593 (31%) patients received first-time appropriate ATP therapy or ICD-shock, and 1244 (8,4%) experienced first-time inappropriate treatments, 5 112 (35%) experienced death during the follow-up time (mean 3.9 years (SD 2.7)). T2DM patients were more likely to be male (85% vs 80%), slightly older (66 vs 65 years) and burdened with more comorbidities. No significant differences were seen between T2DM and non-T2DM patients for appropriate ATP therapy (HR 0.96[0.88:1.04] p=0.31), appropriate ICD-shock (HR 0.95[0.86:1.05] p=0.32), inappropriate ATP therapy (HR 0.92 [0.77;1.09] p=0.32) and inappropriate ICD-shock (HR 0.96 [0.78;1.18] p=0.71). In the subgroup analyses, no difference was seen in the primary prophylactic subgroups (Figure 1.), only significant difference was observed in the secondary prophylactic ICD group who received less ATP-therapy at 5-year follow-up (HR0.83[0.70;0.99] p=0.04), and in the secondary prophylactic CRT-D group, were T2DM patients seemed to experience more appropriate ICD-shock treatments (HR 2.07[1.23;3.48] p=0.006). Further, we found a higher mortality rate in T2DM with primary prophylactic ICD (HR 1.46[1.31;1.62] p<0.001) and secondary prophylactic ICD (HR 1.30[1.13;1.51] p<0.001), (Figure 2.) this mortality rate remained largely unchanged post appropriate ATP or ICD-shock in the ICD subgroups. Conclusions Despite similar incidence of ATP-therapy and ICD-shocks, T2DM patients with ICD-device experienced a significantly higher post-treatment mortality and all-cause mortality rate.

Failure of primary prophylaxis: statin use, risk profile, and outcomes in contemporary patients treated with PCI for first atherosclerotic event

Abstract Background Atherosclerosis and coronary artery disease (CAD) are potentially preventable through lifestyle modifications and the use of medical cholesterol-lowering drugs in individuals at risk. However, guidelines for optimal use of statins are debated, and not enough is known about the real-world barriers to effective CAD-prevention. Understanding the mechanisms of prophylactic treatment failure in patients who undergo PCI for their first atherosclerotic event could help improve primary prevention strategies. Purpose To 1) examine the relative contribution of failure mechanisms of medical prophylaxis in patients undergoing PCI for their first atherosclerotic event, 2) examine how clinical characteristics differ between patients with different failure mechanisms, and 3) examine whether long-term outcomes after PCI differ depending on the mechanism of prophylactic failure. Methods A retrospective study was conducted to study electronic healthcare records for all patients ≥18 years treated with PCI at Gentofte Hospital, Denmark in 2019. Data was extracted from electronic health care records. Patients with first atherosclerotic event were divided into cardiovascular risk groups based on the ESC/EAS guidelines and further into four different prophylactic failure mechanism groups based on cardiovascular risk, statin indication, statin use and whether the risk-based LDL-C treatment goals were reached. Results 507 patients were treated with PCI for their first atherosclerotic event. 54% were categorized as low-moderate cardiovascular risk. 41% were not on statin and did not have class I indication for statin treatment (strategy failure). 26% were not on statin treatment despite class I indication for statin treatment (implementation failure). 18% were on statin treatment but had not reached their LDL-C target (efficiency failure), and 16% were on statin treatment, and had reached the LDL-C target (efficacy failure). Patients with strategy failure, were more likely to be younger, mostly males, and often had a smoking history. Patients with implementation failure, were typically elderly, with relatively few comorbidities. The frequency of death, myocardial infarction, stroke, or repeat revascularization over 4 years was 15.3%, with no statistically difference between the groups (p =0.3). Conclusion In this cohort study, patients treated with PCI for first atherosclerotic event were often classified as low or intermediate risk, and a majority had not been on statin treatment before. Improved primary prevention should focus on at-risk groups that are either not included in current recommendation for statin treatment, especially young smokers, or patients not receiving treatment despite recommendations, especially older patients with few medical contacts.Cardiovascular risk & failure mechanismKaplan-Meier MACE

Severe heterotopic ossification after total hip arthroplasty in male patients under 70years of age: effectiveness of prophylactic protocol.

This study aims to evaluate the incidence of clinically significant heterotopic ossification (HO) in primary total hip arthroplasty (THA), comparing outcomes with and without the adoption of an HO prophylactic protocol in male patients under 70years of age. The prophylactic protocol involved the administration of 50mg of Indomethacin twice daily for 3 weeks. HO presence was classified according to the Brooker classification system, considering "severe" clinically significant HO (Brooker grade 3 and 4). Two hundred and seventy-nine patients were included in our study, and an overall HO rate of 68.2% versus a rate of 61.5% was found respectively in patients not subjected and subjected to prophylactic protocol, without significant difference (PR 0.062). However, patients not subjected to the HO prophylactic protocol exhibited a severe HO rate of 22.4% compared to 7.7% in the prophylactic group, with a statistically significant difference (P = 0.008). Our study demonstrated that prophylactic protocol adoption is significantly associated with lower rate of severe HO in male patients under 70years of age. Currently, there are no orthopedic guidelines for the prevention and management of HO after THA, but in the absence of contraindications, the adoption of a prophylactic protocol for HO should always be considered in high-risk patients.

Mental, emotional and social dimensions of quality of life and their relationship with physical and functional status in adults with haemophilia

IntroductionA comprehensive treatment for patients with haemophilia (PwH) should focus on how the disease interferes with their mental, emotional and social environment to analyse if all the therapeutic efforts invested in their physical status have positive impact on a life worth living. AimTo analyse the correlation between the physical status of a cohort of adults with haemophilia and their mental, emotional and social states regarding their treatment modality; Also, to investigate which variables are most related to quality of life (QoL), joint health and emotional, mental and social states. MethodsIn this cross-sectional, 102 adults with haemophilia divided into a prophylactic group (G1, n = 77) and on-demand group (G2, n = 25) were included. Demographic and clinical characteristics, health joint (HJHS), presence of synovitis with ultrasound, self-perceived functionality (HAL) and QoL (A36-HaemoQoL), were analysed. ResultsIn G1 all the variables that defined the physical status correlated (rho: 0.33 to 0.72) to the mental and social spheres. The emotional state correlated with the self-perceived ones. In G2 physical status did not correlate with the three states. According to the regression models, HAL was the variable that most influenced the QoL (together with the bleedings in the last year, R2 = 0.61), emotional (R2 = 0.16), mental (together with HJHS, R2 = 0.41) and social states (R2 = 0.39). In addition, the HJHS was influenced by synovitis, HAL, mental health, age and the bleeding history (R2 = 0.83). ConclusionEmotional, mental and social states of PwH in prophylaxis are correlated to their physical status, being the self-perceived functionality the variable that most influenced in their QoL.

Gastrostomy tube (g-tube) placement timing and clinical outcomes in patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC) receiving definitive chemoradiation.

37 Background: Patients with HNSCC who undergo definitive chemoradiation (dCRT) frequently require nutritional support via G-tubes; despite this, the factors associated with the timing of G-tube placement remain poorly understood. Methods: We performed a retrospective analysis of patients with HNSCC who received dCRT and required G-tube placement between 01/2018 – 01/2024. We segregated G-tube timing into two groups as determined by the intent of the treating clinician: “prophylactic” placement (ordered in anticipation of dCRT start) or “reactive” placement (ordered in response to weight loss or other adverse clinical indicators). We then evaluated associated clinical variables (patient, disease, treatment) and outcomes (weight loss, G-tube duration, healthcare utilization). Differences across G-tube groups were assessed using t-tests or Wilcoxon Rank Sum tests for continuous measures and Fisher’s exact tests or logistic regression for binary variables. Results: We identified 86 patients; 59 (69%) prophylactic and 27 (31%) reactive G-tubes were placed. At baseline, patients had a mean age of 63, BMI of 28 kg/m 2 , and Charlson Comorbidity Index of 4. Patients were 12% non-White, 2% non-English speaking, and 10% unhoused; 27% had a non-metropolitan address, 67% had public insurance, 31% were smokers and 26% had a history of alcohol dependence. The most common site was the oropharynx (66%; 75% HPV+). Across HNSCC types, 38% had stage IV disease and 60% had preexisting dysphagia/odynophagia. Most received weekly (83%) cisplatin (84%) and bilateral (95%) radiation (RT). We collected RT dose data (parotids, esophagus, pharyngeal constrictors) and found no association between RT dose and G-tube group. Patients with prophylactic G-tubes were significantly more likely to have preexisting odynophagia/dysphagia (69% vs 41%, p = 0.017). Compared to the prophylactic group, reactive G-tube placement occurred more often among patients living in non-metropolitan settings (44% vs 19%, p = 0.018) and was associated with a trend towards a higher mean percent weight loss (12% vs 10%; p = 0.128) and cachexia (per int’l criteria; 89% vs 74%, p = 0.159). We observed no difference in the median G-tube duration or in the rate of persistent G-tube use at last follow-up or death. Notably, we found that patients with reactive G-tubes were hospitalized more frequently (74% vs 36%, p = 0.001) and had a longer median length of stay (LOS; 6 vs 0 days, p = 0.001); these findings remained statistically significant when controlling for other factors (OR 3.76 [95% CI: 1.20-12.65]; p = 0.026). Conclusions: We found that reactive G-tubes were associated with increased hospitalization and LOS, suggesting that select patients may benefit from earlier G-tube placement.

Methylated tirilazad may mitigate oligofructose-induced laminitis in horses.

Laminitis is a serious health condition that can cause severe pain and lameness in horses. Due to lack of understanding of laminitis, treatments often fail to achieve the desired results. In recent years, we have begun to recognize that laminitis may involve a complex interaction between local and systemic inflammation. Dysbiosis of the gut microbiota has been linked in the development of systemic inflammation, and our previous findings suggest that the development of laminitis is closely linked to the production of harmful metabolites of the gut microbiota. In addition, it was found that localized lesions in the hoof, especially lamellar injuries, are the most direct cause of laminitis. Matrix metalloproteinases have been found to be strongly associated with the development of laminitis. Recent discovery has found that methylated tirilazad has a role in repairing laminar tissue in vitro. However, its efficacy in horses never has been studied. Therefore, we aimed to investigate the efficacy of methylated tirilazad (product name: PTP-102) in the prevention/treatment of oligofructose-induced laminitis. The results showed that oligofructose successfully induced laminitis in horses, resulting in detreated clinical signs. Blood indices (including inflammation-related indices and other related indices) were significantly increased. Observations of dissection and staining showed significant bleeding, swelling, and damage to hoof tissue. Analysis of the gut microbiota showed a significant decrease in abundance and diversity, and a significant increase in the relative abundance of specific bacteria. Following methylated tirilazad intervention, there were a significant improvement in clinical signs, blood markers and lamellar tissue damage. Additionally, methylated tirilazad positively influenced the gut microbiota structure by reducing the relative abundance of genera closely associated with the development of equine laminitis. This suggests that some of the therapeutic mechanism of methylated tirilazad may be linked to its effects on the gut microbiota. Notably, methylated tirilazad had better effect in the treatment group than the prophylactic group, indicating the post-diagnosis utility of methylated tirilazad for laminitis management.

The role of prophylactic transfusion on the maternal and fetal outcomes in pregnant women with sickle cell disease: A systematic review and meta-analysis.

In the present review, we aimed to synthesize evidence from studies on the safety and effectiveness of prophylactic blood transfusion in pregnant women with sickle cell disease. To gather relevant information, we conducted systematic electronic searches of databases such as SCOPUS, Medline via PubMed, Web of Science, and Cochrane Central Register of Controlled Trials. We included both retrospective and prospective studies that examined the impact of prophylactic blood transfusions during pregnancy. The collected data were analyzed using Review Manager, version 5.3. The review included 15 cohort studies. The overall findings indicated a preference for the prophylactic blood transfusion group over the control group across several key parameters. Specifically, the prophylactic group demonstrated lower rates of maternal mortality (odds ratio [OR] = 0.33; 95% confidence interval [CI] = 0.10-1.13; P = .08), reduced incidence of vaso-occlusive painful events (OR = 0.31; 95% CI = 0.14-0.73; P = .007), fewer pulmonary complications (OR = 0.21; 95% CI = 0.08-0.53; P = .001), decreased perinatal mortality (OR = 0.35; 95% CI = 0.17-0.75; P = .03), and lower likelihood of preterm birth (OR = 0.67; 95% CI = 0.47-0.96; P = .02). Notably, statistically significant heterogeneities were observed in the pooled effect estimates. The present meta-analysis indicated that prophylactic blood transfusion in pregnant women with sickle cell disease may improve maternal and fetal outcomes. However, substantial variations in the methodology and transfusion protocols among the included studies limited the credibility of the current evidence supporting the routine clinical use of prophylactic transfusion for SCD during pregnancy.

Emergency and prophylactic uterine artery embolization in gynecology and obstetrics - a retrospective analysis.

This study aimed to evaluate the safety and efficacy of emergency and prophylactic uterine artery embolization (UAE) in our clinical practice, including technical success, clinical success, and associated complications. In this retrospective study, we analyzed 64 women who underwent emergency (n =18) and prophylactic (n = 46) UAE. Indications for emergency UAE included postpartum hemorrhage or severe hemorrhage during pregnancy termination, while prophylactic UAE was performed prior to surgical removal of retained products of conception (RPOC), delivery with abnormal placental implantation, or pregnancy termination (cervical pregnancy or fetal anomalies accompanied by abnormal placental implantation). Technical success of UAE was defined as complete exclusion of the vascular lesion and contrast stasis on the final angiogram, while clinical success was defined as cessation of bleeding after UAE Termination without a hysterectomy. The overall clinical success of UAE in our study was 97% (62/64). All embolization procedures were technically and clinically successful in the prophylactic group without life-threatening hemorrhages or hysterectomies (100% success rate, 46/46). However, while 100% technical success was similarly attained in the emergency group, bleeding was successfully controlled in 89% of cases (16/18). In two patients with significant blood loss (over 2000 mL), embolization failed to achieve hemostasis, resulting in persistent bleeding and subsequent hysterectomy. UAE is a safe and effective procedure for managing primary postpartum hemorrhage or severe hemorrhage during pregnancy termination and for decreasing the risk of severe hemorrhage during surgical removal of RPOC, delivery with abnormal placental implantation, or pregnancy.

Ureteral stenting in patients with locally advanced cervical cancer: Predictors of low success rate

ObjectiveCervical cancer is the leading gynecologic malignancy in Ethiopia. The diagnosis is often delayed and many patients present with locally advanced disease. Involvement of the ureters with or without the development of hydroureteronephrosis is a common finding. Ureteral stent placement is a modality utilized to relieve an established obstruction (therapeutic) or to prevent its early occurrence (prophylactic). However, the procedure may not be successful in all patients. The objective of this study is to assess the factors associated with low success rate of ureteral stenting in these patients with locally advanced disease. MethodsThis is a hospital based cross-sectional study of patients diagnosed with locally advanced cervical cancer for whom a retrograde ureteral stent placement is attempted from January 2019 to March 2020. Data of 175 patients were retrieved by a retrospective chart review and analyzed for factors associated with low procedural success. ResultsSocio-demographic data were similar between patients regardless of procedural success. The overall success rate of stenting was 54.2 %. In the prophylactic group (with no hydronephrosis and normal creatinine) success rate was 94 % and in the therapeutic group 42.6 %. Logistic regression analysis showed that bilateral hydronephrosis and increased serum creatinine were indicators of significant ureteral obstruction and were predictors of stent placement failure. ConclusionIncreased serum creatinine and presence of hydronephrosis are risk factors for failed ureteral stenting. For these patients, other options of urinary diversion such as percutaneous nephrostomy should be considered from the outset.

Simvastatin exerts neuroprotective effects post-stroke by ameliorating endoplasmic reticulum stress and regulating autophagy/apoptosis balance through pAMPK/LC3B/ LAMP2 axis

Statins have evident neuroprotective role in acute ischemic stroke(AIS). The pleiotropic effect by which statin exerts neuroprotective effects, needs to be explored for considering it as one of the future adjunctive therapies in AIS. Endoplasmic reticulum(ER) assists cellular survival by reducing protein aggregates during ischemic conditions. ER-stress mediated apoptosis and autophagy are predominant reasons for neuronal death in AIS. Statin exerts both anti-apoptotic and anti-autophagic effect in neurons under ischemic stress. Although the influence of statin on autophagic neuroprotection has been reported with contradictory results. Thus, in our study we have attempted to understand its influence on autophagic protection while inhibiting upregulation of autophagic death(autosis). Previously we reported, statin can alleviate apoptosis via modulating cardiolipin mediated mitochondrial dysfunction. However, the clearance of damaged mitochondria is essential for prolonged cell survival. In our study, we tried to decipher the mechanism by which statin leads to neuronal survival by the mitophagy mediated cellular clearance. Simvastatin was administered to Sprague Dawley(SD) rats both as prophylaxis and treatment. The safety and efficacy of the statin was validated by assessment of infarct size and functional outcome. A reduction in oxidative and ER-stress were observed in both the prophylactic and treatment groups. The influence of statin on autophagy/apoptosis balance was evaluated by molecular assessment of mitophagy and cellular apoptosis. Statin reduces the post-stroke ER-stress and predominantly upregulated autophagolysosome mediated mitophagy than apoptotic cell death by modulating pAMPK/LC3B/LAMP2 axis. Based on the above findings statin could be explored as an adjunctive therapy for AIS in future.

The effect of prophylactic tranexamic acid on the incidence of postoperative hemorrhage in greyhounds

To investigate whether the incidence of postoperative hemorrhage in greyhounds was reduced when a standardized protocol for prophylactic tranexamic acid (TXA) administration to greyhounds undergoing surgery was followed, a retrospective clinical study at a private referral and first opinion hospital group was performed. Patient records of client-owned greyhounds undergoing elective surgery or dental procedures involving extractions were examined retrospectively, and 58 incidents of surgery considered eligible were documented, along with any subsequent reports of hemorrhage and whether the TXA protocol was followed.The use of TXA was not associated with a reduction in the incidence of postoperative hemorrhage in this population of greyhounds. In the group that did not receive TXA, post-operative hemorrhage was reported in 7/37 (18.9 %) cases and in the prophylactic TXA group, post-operative hemorrhage was reported in 11/21 (52.4 %) cases, a significantly higher number than in the group that did not receive TXA. Interestingly, in our population, prophylactic administration of TXA was not associated with a reduction in post-operative hemorrhage, but with a higher incidence of hemorrhage. We belief that descrepencies in our dataset may explain these findings, and a prospective randomized-controlled trial should be performed to further investigate the efficacy of TXA as an antifibrinolytic agent in greyhounds.

Nephroprotective effect of pioglitazone in a Wistar rat model of adenine‑induced chronic kidney disease.

Chronic kidney disease (CKD) is a progressive disease with a high mortality rate and a worldwide prevalence of 13.4%, triggered by various diseases with high incidence. The aim of the present study was to investigate the anti-inflammatory and antifibrotic effect of pioglitazone on kidney in an adenine-induced Wistar rats and the mechanisms possibly involved. CKD was induced in 40 rats. Rats were divided into two groups, which were split into the following sub-groups: i) Therapeutic (pioglitazone administered after renal damage) divided into intact (healthy), adenine (CKD) and adenine/pioglitazone (treatment) and ii) prophylactic (adenine and pioglitazone administered at the same time) split into intact (healthy), adenine (CKD), endogenous reversion (recovery without treatment), adenine/pioglitazone (treatment) and pioglitazone sub-groups. Reverse transcription-quantitative PCR (collagen I, α-SMA and TGF-β), and hematoxylin-eosin, Masson's trichrome and Sirius red staining were performed to measure histological markers of kidney damage, also the serum markers (urea, creatinine and uric acid) were performed, for analyze the effects of pioglitazone. In the adenine/pioglitazone rats of the therapeutic group, renal function parameters such as eGFR increased and serum creatinine decreased from those of untreated rats (CKD), however the renal index, serum urea, abnormalities in renal morphology, inflammatory cells and relative gene expression of collagen I, α-SMA and TGF-β did not change relative to the CKD rats. In adenine/pioglitazone rats, extracellular matrix collagen accumulation was significantly lower than the CKD rats. On the other hand, in adenine/pioglitazone rats of the prophylactic group, the renal index, creatinine, urea, uric acid serum and relative gene expression of collagen I, α-SMA, and TGF-β were significantly lower, as well as the presence of 2,8-dihydroxyadenine crystals, and extracellular matrix collagen compared with CKD rats. In addition, the eGFR in the treatment group was similar to healthy rats, renal morphology was restored, and inflammatory cells were significantly lower. In conclusion, pioglitazone has a nephroprotective effect when administered in the early stages of kidney damage, reducing inflammatory and fibrotic processes and improving glomerular filtration rate. Furthermore, in the late phase of treatment, a tendency to decrease creatinine and increase eGFR was observed.

Prophylactic therapy using epigenetic agents for RUNX1::RUNXT1-positive high-risk AML after Allo-HSCT.

Disease recurrence is the leading cause of treatment failure in patients with RUNX1::RUNXT1-positive acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Post-transplant maintenance therapy, guided by monitoring minimal residual disease (MRD), is commonly administered; however, relapse rates remain high. This prospective study aimed to assess the effectiveness and safety of epigenetic agents as prophylactic therapy in patients with RUNX1::RUNXT1-positive AML. Thirty high-risk patients received prophylactic therapy (n = 17 and n = 13 in the chidamide and AZA groups, respectively) between January 2019 and July 2023. 34 high-risk patients who received preemptive treatment due to molecular relapse were included in the analysis. The two-year relapse-free survival (RFS) and overall survival (OS) were significantly higher in the prophylactic group compared to the preemptive group (82.82% vs. 51.38%, P = 0.014; 86.42% vs. 56.16%, P = 0.025, respectively); 2-year cumulative incidence of relapse rates were 13.8% and 36.40%, respectively (P = 0.037). In conclusion, prophylactic therapy with epigenetic agents may improve long-term prognosis and is well-tolerated in patients with RUNX1::RUNXT1-positive high-risk AML. Timely post-transplant prophylactic therapy may be more effective than preemptive therapy based on positive MRD results.

The potential prophylactic and therapeutic efficacy of progesterone and mifepristone on experimental trichinellosis with ultra-structural studies

Right up to now, there has not been an effective or safe therapy for trichinellosis. Thus, this study aimed to determine the efficacy of prophylactic and therapeutic regimens of progesterone and mifepristone on the intestinal and muscular phases of experimental Trichinella spiralis infection compared to albendazole. Seven distinct groups of mice were divided as follows: negative, positive, and drug control groups, as well as prophylactic and treatment groups using mifepristone and progesterone. Mice were sacrificed on the 7th and 37th days after infection. Treatment efficacy was evaluated using parasitological techniques, histopathological examination, immunohistochemical staining, and ultrastructural morphological analysis of adult worms by scanning electron microscopy. The mice groups received progesterone (300 ng/ml) and mifepristone (100 ng/ml). They demonstrated a significant improvement in intestinal and muscular inflammation and a statistically significant decline in the adult worm burden and encysted larvae (P < 0.001). Moreover, immunohistochemical staining of vascular endothelial growth factor and mucosal mast cell analyses were coincided with the obtained parasitological results. There was notable destruction and degeneration of the adult worm tegument by using both drugs. The current study pointed out that progesterone and mifepristone may provide new insights regarding the development of vaccines and drug protocols to treat trichinellosis through their combined action in reducing the inflammation, affecting the intestinal immune cell, and decreasing the adult worm burden, and larval capsule development.

Prevention of bone dehiscence associated with orthodontic tooth movement by prophylactic injection of bone anabolic agents in mice

Although bone dehiscence may occur during orthodontic tooth movement into the narrow alveolar ridge, a non-invasive prevention method is yet to be fully established. We show for the first time prevention of bone dehiscence associated with orthodontic tooth movement by prophylactic injection of bone anabolic agents in mice. In this study, we established a bone dehiscence mouse model by applying force application and used the granular type of scaffold materials encapsulated with bone morphogenetic protein (BMP)-2 and OP3-4, the receptor activator of NF-κB ligand (RANKL)-binding peptide, for the prophylactic injection to the alveolar bone. In vivo micro-computed tomography revealed bone dehiscence with decreased buccal alveolar bone thickness and height after force application, whereas no bone dehiscence was observed with the prophylactic injection after force application, and alveolar bone thickness and height were kept at similar levels as those in the control group. Bone histomorphometry analyses revealed that both bone formation and resorption parameters were significantly higher in the injection with force application group than in the force application without the prophylactic injection group. These findings suggest that the prophylactic local delivery of bone anabolic reagents can prevent bone dehiscence with increased bone remodelling activity.

Evaluation of the Efficacy of Targeted Microbiome Therapy in Non-Alcoholic Steatohepatitis Rat Model

Abstract Non-alcoholic steatohepatitis (NASH) is the clinically aggressive variant of non-alcoholic fatty liver disease. Hippo pathway dysregulation can contribute to NASH development and progression. The use of probiotics is effective in NASH management. Our aim is to investigate the efficacy of kefir Milk in NASH management via modulation of hepatic mRNA-miRNA based panel linked to NAFLD/NASH Hippo signaling and gut microbita regulated genes which was identified using bioinformatics tools. Firstly, we analyzed mRNAs (SOX11, SMAD4 and AMOTL2), and their epigenetic regulator (miR-6807) followed by validation of target effector proteins (TGFB1, IL6 and HepPar1). Molecular, biochemical, and histopathological, analyses were used to evaluate the effects of kefir on high sucrose high fat (HSHF) diet -induced NASH in rats. We found that administration of Kefir proved to prevent steatosis and development of the inflammatory component of NASH. Moreover, Kefir improved liver function and lipid panel. At the molecular level, kefir down-regulated the expression of miR 6807-5p with subsequent increase in the expression of SOX 11, AMOTL2 associated with downregulated SMAD4, resulting in reduction in the expression of the inflammatory and fibrotic markers, IL6 and TGF-β1 in the treated and prophylactic groups compared to the untreated rats. In conclusion, Kefir suppressed NASH progression and improved both fibrosis and hepatic inflammation. The produced effect was correlated with modulation of SOX11, SMAD4 and AMOTL2 mRNAs) – (miR-6807-5p) – (TGFB, IL6 and, HepPar1) expression.