Prophylactic Administration Research Articles

Enduring modulation of dorsal raphe nuclei regulates (R,S)-ketamine-mediated resilient stress-coping behavior.

Ketamine may be a novel pharmacologic approach to enhance resilience and protect against stress-related disorders, but the molecular targets underlying this response remain to be fully characterized. The multifunctional protein p11 is crucial in the pathophysiology of depression and antidepressant responses. However, it is still unclear whether p11 plays a role in the pro-resilience effects induced by ketamine. Here, we demonstrated that prophylactic administration of ketamine buffers passive stress-induced maladaptive phenotypes induced by chronic stress exposure. Spatial neurotransmitter and metabolite analysis revealed that prophylactic ketamine was also effective in blunting stress-induced disturbances of tryptophan metabolism in dorsal raphe nuclei (DRN). Additionally, we demonstrated that ketamine prevented chronic restraint stress-induced p11 reduction in DRN, a highly p11-enriched region. Furthermore, we provide novel evidence indicating that p11 deficiency regulates susceptibility to stress-induced depression-related phenotypes, and these behavioral maladaptations are dependent, at least in part, on p11 function in serotonergic neurons. Spatial neurotransmitter and metabolite analysis also showed a reduction of tryptophan and dopamine metabolism in DRN of serotonergic p11-deficient mice. Viral-mediated downregulation of p11 within DRN induced a stress-susceptible phenotype. Finally, our results also unveiled that the ability of ketamine to elicit a pro-resilience response against stress-induced maladaptive phenotypes was occluded when p11 was selectively deleted in serotonergic neurons. Altogether, we showed a previously unexplored role of the DRN circuit in regulating stress susceptibility and resilience-enhancing actions of ketamine.

Multidisciplinary standardized protocol decreases time to antibiotic administration for open fractures.

Wound complications after open fracture are common, including superficial and deep infections. Many factors may contribute to outcomes after open fracture, including comorbidities, injury location and characteristics, timing and quality of surgical debridement, and soft tissue coverage. Early prophylactic antibiotic administration is one of the few modifiable factors demonstrated to reduce infection rates. Retrospective comparative study at a single Level 1 Trauma Center evaluated patients age > 18 who presented directly to and were admitted with open long-bone fracture. Primary outcome measure was time from arrival to antibiotic administration pre- and post-implementation of a standardized open fracture protocol. Secondary analysis evaluated percentage of patients receiving antibiotics within one hour for open long-bone fracture, injury characteristics and patient demographics influence on time to antibiotics. Median time to antibiotic administration improved post-protocol (69min vs. 39min, p < 0.001). Patients receiving antibiotics within one hour improved after protocol implementation (42.9% vs. 79.0%, p < 0.001). Antibiotic administration was more often delayed for patients with penetrating injuries compared to blunt injuries (80min vs. 54min, p = 0.003). Patients with penetrating injuries were less likely to receive antibiotics within one hour (46% vs 56%, p < 0.001). The implementation of a standardized protocol reduced the time to antibiotic administration and increased the percentage of patients with open fractures receiving antibiotics within one hour. Penetrating injuries were often not appreciated as open fractures during the initial evaluation, which led to a delay in antibiotic administration. Level III, Therapeutic/Care Management.

Postoperative infections after robotic-assisted radical prostatectomy in a single large institution: Effect of type and duration of prophylactic antibiotic administration.

We evaluated the incidence of and risk factors for postoperative infections after robotic-assisted radical prostatectomy (RARP) according to the type and duration of prophylactic antibiotic administration. A total of 1038 patients underwent RARP at our institution from 2010 to 2021; 1026 patients (201 in the cefazolin [CEZ] group and 825 in the ampicillin/sulbactam [ABPC/SBT] group) were analyzed, and 12 who used other antibiotics were excluded. The primary endpoint was the incidence of urinary tract infection (UTI), surgical site infection (SSI), and remote infection (RI). T-tests, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed. Multivariate logistic regression analysis was performed to evaluate the effect of type and duration of prophylactic antibiotic administration. The incidence of UTI was 2.5% (5/201) in the CEZ group and 3.2% (26/825) in the ABPC/SBT group, with no significant difference between groups (p = 0.622). The rates of SSI and RI were comparable between groups (p = 0.680 and 0.906, respectively). Although the duration of antimicrobial therapy was longer in the ABPC/SBT group (p < 0.001), there was no significant difference in the incidence of UTI/SSI/RI after PSM and IPTW (all p > 0.05). Multivariate logistic regression analysis showed that neither the type of antibiotic nor the duration of administration affected the incidence of UTI/SSI/RI. The risk of postoperative UTI/SSI/RI after RARP did not change with the type and duration of antimicrobial therapy.

Darbepoetin alpha has an anxiolytic and anti-neuroinflammatory effect in male rats

AimsWe aimed to investigate the anxiolytic effect of darbepoetin alpha (DEPO), an erythropoietin derivative, in a neuroinflammation model regarding different behaviors and biological pathways.MethodsForty adult male Wistar albino rats were divided into four groups (control, LPS, DEPO, and DEPO + LPS). The rats were treated with 5 µg /kg DEPO once a week for four weeks, after which neuroinflammation was induced with 2 mg/kg lipopolysaccharide (LPS). The elevated plus maze, open-field, and light‒dark box tests were conducted to assess anxiety levels. Harderian gland secretions were scored via observation. Tumor necrosis factor alpha (TNF-α), Interleukin-1-beta (IL-1β), brain-derived growth factor (BDNF), serotonin, cortisol, total antioxidant/oxidant (TAS/TOS), and total/free thiol levels were measured in the prefrontal cortex, striatum, and serum.ResultsDEPO had a potent anxiolytic effect on both DEPO and DEPO + LPS groups. Compared to the control group, DEPO administration caused an increase in serotonin and BDNF levels and decreased basal cortisol and TNF-α levels in naive rats. IL-1β did not alter after DEPO administration in naive rats. Prophylactic DEPO treatment remarkably downregulated cortisol, IL-1β, and TNF-α in the DEPO + LPS group. In addition, prophylactic DEPO administration significantly attenuated the decrease in serotonin and BDNF levels in the DEPO + LPS group. Furthermore, DEPO ameliorated excessive harderian gland secretion in the DEPO + LPS group. Compared with those in the control group, the free thiol content in the serum increased after DEPO administration. No similar effect was seen in the DEPO + LPS group receiving prophylactic DEPO. TAS showed no difference among all experimental groups. DEPO administration increased TOS and OSI in the serum and prefrontal cortex but not in the striatum. This effect was not seen in the DEPO + LPS group.ConclusionDarbepoetin alpha had an anxiolytic effect on many physiological mechanisms in a neuroinflammation model and naive rats.

Prophylactic 24 versus 48 h cephalosporins in cardiac surgery: A randomized trial.

Recommendations for cardiac surgery advocate for antibiotic prophylaxis for up to 48 hour after surgery. However, recent reports found a significant reduction in surgical site infection with extended duration. We evaluated the effect of the type of prophylactic antibiotics and administration durations on the postoperative surgical site infection rate following cardiac surgery in adults. An investigator-initiated randomized controlled trial was conducted from 2018 to 2022 on adult patients undergoing cardiac surgery. Patients were randomized into four groups based on antibiotic treatment type and duration: 24 h cefazolin, 24 h cefuroxime, 48 h cefazolin, and 48 h cefuroxime. The primary outcome was the rate of surgical site infections within 90 days of surgery. A total of 568 patients were included in this study. The four groups had similar baseline characteristics, including age, sex, EuroSCORE II, and baseline HbA1c. A total of 75 patients developed infection within 90 days postoperative. The overall infection rate was not statistically different across the four groups (p = 0.193). The efficacy of cefazolin and cefuroxime in reducing infection was comparable (p = 0.901). Extended prophylaxis was associated with a significantly reduced overall infection rate within 90 days postoperatively compared to 24-h prophylaxis (10.2% vs. 16.3%; risk ratio = 0.62, 95% confidence interval: 0.40-0.96, p = 0.032). Using cefazolin or cefuroxime for 48 h instead of 24 h was more effective in reducing the overall surgical site infections rate up to 90 days after surgery.

Sternal Wound Reconstruction Following Deep Sternal Wound Infection: Past, Present and Future: A Literature Review.

This literature review critically examines the historical, current, and prospective dimensions of sternal wound reconstruction in the specific context of deep sternal wound infection (DSWI), aiming to enhance patient outcomes and optimise surgical techniques. Preventive measures, including prophylactic antibiotic administration and surgical site preparation, are crucial in reducing the incidence of DSWI. Effective management necessitates a multidisciplinary approach encompassing surgical debridement, drainage, and sternum repair utilising diverse procedures in conjunction with antibiotic therapy. Traditional approaches to managing DSWI involved closed irrigation and drainage techniques. While these methods exhibited certain advantages, they also exhibited limitations and varying degrees of success. The current care paradigms emphasise prophylactic antibiotic administration and surgical interventions like closed suction and irrigation, vacuum-assisted closure, and flap reconstruction. Future advancements in surgical techniques and technology hold promise for further enhancing sternal wound reconstruction. This review separates and emphasises the distinct roles of prophylaxis, antibiotic treatment, and reconstructive techniques, each relevant specifically to DSWI management. Collaborative efforts between cardiac and plastic surgeons, supported by ongoing research and innovation, are indispensable to advance sternal wound restoration and achieve superior outcomes in terms of patient welfare, morbidity and mortality reduction, and surgical efficacy.

Propensity score-adjusted analysis on early tirofiban administration to prevent thromboembolic complications during stand-alone coil embolization of ruptured aneurysms

The glycoprotein IIb/IIIa antagonist tirofiban has been shown to prevent thromboembolic events during endovascular procedures, but the benefits and risks of its prophylactic early intraprocedural administration for stand-alone coil embolization of acutely ruptured aneurysms are still unclear. We conducted a retrospective single-center analysis of patients treated for aneurysmal subarachnoid hemorrhage with stand-alone coil embolization. Two study cohorts were compared according to the primary prophylactic antithrombotic medication during the procedure: patients receiving only intravenous heparin (HEP) versus patients receiving tirofiban in addition to heparin prior to final aneurysm obliteration (HEP + TF). Outcome endpoints were the incidence of angiographically visible thrombus formation or distal embolization, and the incidence of periprocedural intracranial hemorrhage (ICH). Of 204 cases, 159 were prophylactically treated with HEP and 45 with HEP + TF. Intraprocedural thromboembolic events were less frequent with HEP + TF before and after propensity score matching (PSM) (2.5% vs. 19.7%, p = 0.017). The incidence of ICH and symptomatic ICH did not differ between HEP + TF and HEP before and after PSM (20.5% vs. 30.7%, p = 0.29; and 5.1% vs. 4%, p = 0.88). Early intraprocedural tirofiban administration may be effective in preventing thromboembolic complications during stand-alone coil embolization of acutely ruptured aneurysms without increasing the risk of ICH.

Administration of Adipose Tissue Derived Stem Cells before the Onset of the Disease Lowers the Levels of Inflammatory Cytokines IL-1 and IL-6 in the Rat Model of Necrotizing Enterocolitis.

There is little research concerning the role of stem cells in necrotizing enterocolitis (NEC). Bone marrow-derived mesenchymal stem cells (BMDSC) and amniotic fluid-derived stem cells significantly reduced the amount and severity of NEC in the animal models. ADSCs share similar surface markers and differentiation potential with BMDSCs. Their potential role in the setting of NEC has not been researched before. The hypothesis of the study was that prophylactic intraperitoneal administration of ADSCs before the onset of the disease will result in limiting the inflammatory response, effecting a lower incidence of NEC. On a molecular level, this should result in lowering the levels of inflammatory cytokines IL-1 and IL-6. The local ethical committee for animal experiments approval was acquired (WAW2/093/2021). We utilized a self-modified rat NEC model based on single exposure to hypothermia, hypoxia, and formula feeding. One hundred and twenty-eight rat puppies were divided into two groups-prophylaxis (ADSC-NEC, n = 66) and control group (NEC-PLCB, n = 62)-to measure the influence of ADSCs administration on the inflammatory changes in NEC, the level of cell engraftment, and the histopathology of the disease. The analysis did not show a significant effect on histopathology between groups, H(2) = 2.12; p = 0.347; η²H = 0.00. The intensity of the NEC variable results was similar across the analyzed groups (NEC-PLCB and ADSC-NEC). For IL-1 and IL-6, the difference between the NEC-PLCB group and the ADSC-NEC group was statistically significant, p = 0.002 and p < 0.001, respectively. To conclude, administration of adipose tissue-derived stem cells before the onset of the disease lowers the levels of inflammatory cytokines IL-1 and IL-6 but does not affect the histopathological results in the rat model of NEC.

Prophylactic Administration of Perampanel for Post-Stroke Epilepsy (PROPELLER Study): A Trial Protocol.

Post-stroke epilepsy can reduce patients' abilities to carry out various activities of daily living. Despite their importance in preventing the onset of post-stroke epilepsy, the prophylactic administration of antiepileptic drugs is controversial due to a lack of high-level clinical research. In this study, we initiated a prospective interventional study of prophylactic antiepileptic drug administration in patients with a subcortical hemorrhage, who are at the highest risk of developing epilepsy after experiencing a stroke. The study was conducted in a single-center setting and was a single-arm study with no control group; the case entry period started in November 2023 and is due to end in March 2025. Only cases with a subcortical hemorrhage will be included. The treatment regimen used in this study is 2 mg of perampanel per day. Perampanel will be administered for one year, followed by two years of follow-up, for a total study period of three years. The primary endpoint will be the development of epilepsy. Perampanel administration is expected to reduce the incidence of post-stroke epilepsy in comparison to the results of previous reports on the use of alternative treatments. The results of this study will provide new insights into the prevention of post-stroke epilepsy. The relatively small size of this study makes it difficult to provide strong evidence of the efficacy of perampanel, but it may serve as a basis for larger clinical trials.

Prophylactic preoperative administration of oral gabapentin versus metoclopramide for prevention of opioid induced pruritis in spinal anesthesia.

Abstract Background Spinal opioids have become a mainstay of clinical pain management in labor, in perioperative care, and in chronic pain management. Spinal opioids are frequently co- administered with local anesthetics to provide analgesia requiring lower doses of each agent, thus minimizing most undesirable side effects. Most opioid-induced side effects such as nausea, vomiting, and respiratory depression are more commonly observed following systemic administration.8 By contrast, pruritus is more commonly observed following intrathecal or epidural administration, particularly in obstetric patients. Aim of the Work to compare the efficacy of gabapentin versus metoclopramide for prevention of intrathecal opioids induced pruritus. Patients and Methods This study is a double blinded prospective randomized controlled clinical trial. This study conducted at Ain Shams University Hospital. The period of the study is a 6 months. 62 adult patients undergoing elective operations under spinal anesthesia at Ain Shams University hospital. Results The demographic data (age, gender, and ASA physical status) was statistically non- significant. The mean age was 35.1 years old in Group G and 36.8 years old in Group M with a P value of 0.569. The female-to-male ratio was 63.1 % in Group G and 82.3% in Group M with a P value of 0.607. In Group G, 71 % were of ASA 1 physical status and 29 % of ASA 2 physical status while in Group M, 67.7% were of ASA 1 physical status and 32% of ASA 2 physical status with a P value of 0.783. The whole incidence of pruritus in the two groups was 31.5%, (48.8% in group G and 45.2% in group M). There is no statistically significant difference, with a p-value 0.799. As for the severity, both drugs showed reduction of VAS score from the first hour after intrathecal fentanyl injection. Gabapentin showed to be more potent in decreasing the severity of pruritus as 2 patients only needed rescue treatment compared to 5 patients from metoclopramide group (but insignificant difference with p value 0.341). The overall incidence of nausea was 17.7% (22.58 in Gabapentin group and 12.9% in metoclopramide group). As for the incidence of vomiting, the whole incidence was 11.29% (16.13% in Gabapentin group and 6.45% in metoclopramide group). There was no statistically significant difference with a p-value 0.118 for nausea and p-value 0.374 for vomtitng. Conclusion The results of the study showed that Gabapentin is as effective as Metoclopramide in prevention of opioid induced pruritus in spinal anesthesia. But, Gabepentin improved to be slightly more effective in reducing the severity of pruritus than Metoclopramide.

Role of Prophylactic N-Acetylcysteine Supplementation on Postoperative Outcomes in Patients Undergoing Elective Double-Valve Replacement (Aortic and Mitral Valve).

The incidence of postoperative liver dysfunction is high in patients undergoing double-valve replacement - mitral and aortic valve replacement (DVR). This study aims to evaluate N-acetylcysteine's free radical scavenging property (NAC) to prevent postoperative liver dysfunction in these patients, thus affecting overall clinical outcomes. A single-center, prospective, randomized, double-blinded interventional study of 60 patients divided into two groups of 30 each. Group N received prophylactic intravenous NAC, and Group C received volume-matched 5% dextrose. Data comprised demographics, liver function tests (LFT), renal function tests (RFT), vasoactive-inotropic scores (VIS) score, and C-reactive protein (CRP) at various time intervals. Postoperative parameters such as ventilation duration, length of stay in ICU (LOS-ICU), length of hospital stay (LOHS), atrial fibrillation (AF), acute kidney injury (AKI) requiring hemodialysis, and mortality were noted. Statistical analysis was performed with the Student's t-test and Chi-square test (SPSS 22 software). All postoperative LFT parameters (total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), and alkaline phosphatase (ALP)) were significantly lower (P < 0.05) at 24, 48, and 72 hours in Group N compared to Group C. RFT and VIS scores were lower in Group N; however, were not statistically significant except for Serum Creatinine at 48 hours (P = 0.0478). Ventilation duration (P = 0.0465) and LOS-ICU (P = 0.0431) were significantly lower in Group N. Other outcomes like AF, LOHS, and mortality were lower in Group N but were not statistically significant. Our study showed that prophylactic administration of NAC in patients undergoing DVR is associated with a reduction in the incidence of postoperative liver dysfunction with a positive impact on postoperative outcomes.

Knowledge, attitude and practice towards chemotherapy-related neutropenia and febrile neutropenia among breast cancer patients.

This study aimed to investigate the knowledge, attitude and practice (KAP) towards chemotherapy-related neutropenia and febrile neutropenia (FN) among breast cancer patients. The major hypothesis was that demographic characteristics influence patients' KAP regarding chemotherapy-related neutropenia and FN. A multi-centre cross-sectional study. Conducted in four secondary care hospitals between April and June 2023. The study enrolled 246 breast cancer patients undergoing chemotherapy. Participants were aged 18 years or older, currently on chemotherapy and willing to complete the questionnaire. Exclusion criteria included significant cognitive impairments. Primary outcome measures were KAP scores regarding chemotherapy-related neutropenia and FN. Secondary outcomes included factors associated with adequate knowledge and positive attitudes. A total of 246 patients completed the questionnaire. The mean knowledge score was 12.46±6.21 (range: 0-26), and the mean attitude score was 30.00±2.58 (range: 7-35). Less than half of the patients (45.95%) knew whether their chemotherapy protocol was high risk for FN, while 79.67% were aware of the need for prophylactic administration of leukocyte-raising agents. Multivariate logistic regression analysis revealed that having a junior college education or higher was significantly associated with knowledge scores (OR=4.69, 95% CI 2.23 to 9.89, p<0.001). Living in urban areas was associated with attitude scores (OR=0.58, 95% CI 0.34 to 0.97, p=0.037). Structural equation modelling analysis indicated that experience with chemotherapy-related neutropenia or FN influenced knowledge to some degree (β=1.77, p=0.029). The study found inadequate knowledge, a positive attitude and suboptimal practice towards chemotherapy-related neutropenia and FN among breast cancer patients undergoing chemotherapy. Tailored education programmes are needed to improve KAP in this patient population. Further research should explore additional demographic and psychosocial factors influencing KAP to develop comprehensive educational interventions.

Atropine Prophylaxis before Spinal Anesthesia in Young and Middle Age Males Undergoing Inguinal Hernia Repair

Abstract Background Spinal Anesthesia is a common type of anesthesia used during many surgical procedures. This regional technique can be accomplished by administering an intrathecal dose of hyperbaric local anesthetic solution. The local anesthetic within the subarachnoid space can block sensory, motor and sympathetic pathways. One of the most common complications associated with spinal anesthesia is hypotension with or without bradycardia that can increase risk of perioperative cerebral and cardiovascular events. Aim of the Work to find out the effectiveness of prophylactic administration of intravenous atropine for attenuation of spinal anesthesia induced hypotension in inguinal hernia repair surgeries. Patients and Methods Therefore, A randomized controlled clinical trial was found to be the most suitable design in order to achieve the study objectives. A total of 40 patients males included in the study, aged 15-60 years, and were divided equally into two groups: Group 1 received intravenous injection of 0.01 mg /kg atropine sulphate one minute before spinal anesthesia and fluid preloading 500 ml Ringer solution. Group 2 received the same volume of normal saline intravenous bolus. Results Prophylactic intravenous atropine sulphate 0.01 mg /kg intravenous one minute prior to spinal anesthesia in inguinal hernia repair surgeries was effective in reducing spinal anesthesia induced hypotension, incidence of hypotension was lower in atropine exposed group compared to placebo group. The incidence of ephedrine use and number of boluses of fluids were lower in atropine exposed group compared to placebo group. Conclusion among patients who received spinal anesthesia with bupivacaine for elective inguinal hernia repair, prophylactic intravenous atropine sulphate 0.01 mg /kg prior to spinal anesthesia reduced spinal anesthesia induced hypotension and reduced ephedrine use.

Prophylactic antibiotic therapy during endovascular closure of patent foramen ovale: a clinical study

Purpose of the study. To study the effect of prophylactic antibiotic therapy on the course of the postoperative period in patients undergoing endovascular closure of patent foramen ovale (PFO). Material and methods. The study included 276 patients who were submitted to endovascular closure of PFO. The follow-up duration was 12 months. Depending on prophylactic antibiotic therapy the patients were divided into 2 groups - those who did not receive and those who received prophylactic antibiotic therapy (115 and 161 patients, respectively). Results. Cephalosporins were prescribed to patients as prophylactic antibiotic therapy, and in the presence of allergic reactions they were replaced by glycopeptides. In total, patients received 1 to 2 drugs per prophylaxis course. Postoperative complications were present in 37 (22.98 %) patients who received prophylactic antibiotic therapy and 12 (10.43 %) who did not receive prophylaxis (p = 0.007). Access site complications were the most identified, but they were not inflammatory in nature. An elevation of body temperature over 37.1 °C was observed in 19 (11.80 %) patients receiving prophylactic antibiotic therapy compared to 5 (4.35 %) who did not receive prophylaxis (p = 0.03). Meanwhile, marked leukocytosis was absent in both groups. The duration of body temperature elevation did not differ between the groups. They also had a longer duration of hospitalization, 7.00 [6.00; 8.00] bed days, compared to 6.00 [4.00; 7.00]. Discussion. It has been suggested that hyperthermia may be associated with prophylactic administration of antibacterial drugs causing death of persistent microflora. In patients who did not receive prophylactic antibiotic therapy, their concentration was lower, which did not lead to an increase in body temperature. Since there are no indications on the necessity of prophylactic antibiotic therapy before endovascular closure of PFO in clinical recommendations, it is suggested to evaluate its appropriateness for each patient individually.

Hepatoprotective effects of vildagliptin mitigates lung biochemical and histopathological changes in experimental hepatopulmonary syndrome model in rat

Hepatopulmonary syndrome (HPS) is a liver disease-induced pulmonary complication manifested with arterial hypoxemia. Hepatic cholestasis, encountered in several clinical situations, leads to biliary cirrhosis and HPS, both of which are best reproduced by rat common bile duct ligation (CBDL). Experience from liver transplantation suggests hepatoprotective-based therapy would be most effective in HPS treatment Dipeptidyl peptidase-4 (DPP-4) enzyme is involved in different pathogenic mechanisms of liver diseases. Vildagliptin (Vild) is a DPP-4 inhibitor which possesses favorable anti-inflammatory, anti-oxidant and anti-fibrotic effects. The present work explored hepatoprotective mechanisms of Vild and their participation in its prophylactic effectiveness in HPS induced by CBDL in rats. Male Wistar rats weighing 220–280 g were allocated into 4 groups: normal control, sham, CBDL and CBDL + Vild groups. i.p. saline was administered to the first 3 groups and i.p. Vild (10 mg/kg/day) was given to the fourth group for 6 weeks starting 2 week before CBDL. CBDL produced liver fibrosis, arterial hypoxemia and decreased survivability of rats. It altered liver functions and induced oxidative stress, pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)], vasodilatory molecules [endothelin-1 (ET-1), and inducible and endothelial nitric oxide synthases] and angiogenesis-associated protein [vascular endothelial growth factor-A (VEGF-A)] in liver and lung. Vild ameliorated liver fibrosis, and improved hypoxemia and survivability of CBDL rats and reversed these biochemical alterations. Prophylactic Vild administration attenuated CBDL-induced HPS in rats via direct hepatoprotective effects in the form of anti-oxidant, anti-inflammatory, anti-angiogenic and anti-fibrotic effects beside inhibition of pathological intrahepatic vasodilatation.

Systemic administration of a potent mouse monoclonal antibody provides multisite protection against HPV16 infection

Although preventive vaccines for Human Papillomaviruses (HPV) are available, a definitive cure for the viral infection itself is currently lacking. There is a sizable population that remains inaccessible to HPV vaccination due to reasons such as high costs or lack of availability of the vaccines. Therefore, there remains a significant population susceptible to HPV infection. Persistent multisite infections with high-risk HPV types can cause cancer at several different anatomic sites.Especially HPV16 is a key etiologic factor for cervical, other ano-genital and oropharyngeal cancers. Therefore, it is imperative to develop pharmaceutical interventions for the treatment of viral infections. In this study, a panel of 9 neutralizing antibodies was screened using the hybridoma technique, with 20F6 being identified as the representative antibody. The purified 20F6 exhibited an IC50 of 0.0011 μg/ml against HPV16, demonstrating potent viral inhibitory activity. Moreover, it displayed cross-neutralizing efficacy towards other Alphapapillom 9 subtypes including HPV31, HPV33, HPV52, and HPV58 with respective IC50 values of 2.0 μg/ml, 7.3 μg/ml, 1.7 μg/ml, and 3.0 μg/ml. 20F6 recognizes the linear epitope MSLW, the first four amino-acids located at the very N-terminus of the HPV16 L1 protein. Administration of 20F6, 24 h prior to and following HPV16 pseudo-virion (PSV) challenge, conferred protection against infection in mice at doses as low as 1 mg/kg. Following intraperitoneal administration of 20F6, neutralizing antibodies were consistently detected at both oral and vaginal sites, indicating that prophylactic systemic administration of 20F6 may confer efficient protection against multiple susceptible mucosal sites.

Alginate Oligosaccharides Enhance Gut Microbiota and Intestinal Barrier Function, Alleviating Host Damage Induced by Deoxynivalenol in Mice

BackgroundAlginate oligosaccharides (AOS) exhibits notable effects in terms of anti-inflammatory, antibacterial, and antioxidant properties. Deoxynivalenol (DON) has the potential to trigger intestinal inflammation by upregulating pro-inflammatory cytokines and apoptosis, thereby compromising the integrity of the intestinal barrier function and perturbing the balance of the gut microbiota. ObjectivesWe assessed the impact of AOS on mitigating DON-induced intestinal damage and systemic inflammation in mice. MethodsAfter a 1-wk acclimatization period, the mice were divided into 4 groups. For 3 wk, the AOS and AOS + DON groups were gavaged daily with 200 μL of AOS [200 mg/kg body weight (BW)], whereas the CON and DON groups received an equivalent volume of sterile Phosphate-Buffered Saline (PBS). Subsequently, for 1 wk, the DON and AOS + DON groups received 100 μL of DON (4.8 mg/kg BW) daily, whereas the control (CON) and AOS groups continued receiving PBS. ResultsAfter administering DON via gavage to mice, there was a significant decrease (P < 0.05) in body weights compared with the CON group. Interestingly, AOS exhibited a tendency to mitigate this weight loss in the AOS + DON group. In the feces of mice treated with both AOS and DON, the concentration of DON significantly increased (P < 0.05) compared with the DON group alone. Histological analysis revealed that DON exposure caused increased intestinal damage, including shortened villi and eroded epithelial cells, which was ameliorated by presupplementation with AOS, alleviating harm to the intestinal barrier function. In both jejunum and colon tissues, DON exposure significantly reduced (P < 0.05) the expression of tight junction proteins (claudin and occludin in the colon) and the mucin protein mucin 2, compared with the CON group. Prophylactic administration of AOS alleviated these reductions, thereby improving the expression levels of these key proteins. Additionally, AOS supplementation protected DON-exposed mice by increasing the abundance of probiotics such as Bifidobacterium, Faecalibaculum, and Romboutsia. These gut microbes are known to enhance (P < 0.05) anti-inflammatory responses and the production of short-chain fatty acids (SCFAs), including total SCFAs, acetate, and valerate, compared with the DON group. ConclusionsThis study unveils that AOS not only enhances gut microbiota and intestinal barrier function but also significantly mitigates DON-induced intestinal damage.

The effects of prophylactic administration of tranexamic acid on the operative time and the amount of blood transfused during open fixation of pelvis and acetabulum fractures

BackgroundOrthopedic surgeons face challenges regarding perioperative bleeding during the operations of pelvic and acetabular fracture cases. Although the recently popular tranexamic acid (TXA) has proven to be a useful tool, this study primarily aimed to conduct a retrospective comparative analysis of the results of the prophylactic administration of tranexamic acid during open fixation of pelvis and acetabulum fractures, especially regarding operative time and the amount of blood transfused; and in addition, share the results related to other findings including the management of the erythrocyte suspension use and overall cost as secondary aims and thus providing a comprehensive point of view.MethodsThe files of patients with pelvis or acetabulum fractures admitted to the Emergency Clinic of the Adana City Training and Research Hospital between January 1, 2020, and December 31, 2023, were analyzed retrospectively. The inclusion criteria were as follows: patients aged 18 years or older who had undergone open reduction for pelvis or acetabulum fractures.ResultsThere were 78 files identified for analysis. Among the fractures, 27 were located at the pelvis (34.61%) and 51 at the acetabulum (65.38%). The pelvic fracture cases’ age and preoperative hemoglobulin levels were significantly lower (p = 0.019 and p = 0.006, respectively). When all cases were dichotomized into two groups, ones requiring ICU monitoring and the remaining, there were statistically significant differences in terms of the preoperative hemoglobin levels (p = 0.0446), intraoperative bleeding (p = 0.0134), units of erythrocyte suspension used (p = 0.0066), drain output (p = 0.0301), hospitalization duration (p = 0.0008), and the overall cost (p = 0.0002). The comparison regarding TXA use showed that the use of blood products was significantly higher in the pelvic fractures not treated with TXA (6.44 ± 4.42 units, p = 0.0029). The duration of surgery was shorter for pelvic fractures treated with TXA (98.33 ± 21.76 min, p = 0.047).ConclusionAmong the variables, the amount of intraoperative bleeding emerged as the most correlated element, which strongly suggests that in managing open reduction internal fixation surgeries performed for pelvis and acetabulum fractures, intraoperative bleeding should be considered as the crucial factor. Therefore, the administration of TXA, by effectively reducing the amount of intraoperative bleeding, should be considered as an essential tool for orthopedic surgeons.

Safety and effectiveness of intraosseous regional prophylactic antibiotics in total knee arthroplasty: a systematic review and meta-analysis.

Intraosseous regional administration (IORA) as a widely applicable and clinically valuable route of administration has gained significant attention in the context of total knee arthroplasty (TKA) for the prophylactic administration of antibiotics. However, there is still controversy regarding its effectiveness and safety. The latest meta-analysis reports that the use of IORA for antibiotics in TKA is as safe and effective as IV administration in preventing prosthetic joint infection (PJI), but they did not separate the statistics for primary TKA and revision TKA, which may be inappropriate. There is currently a lack of evidence specifically comparing the outcomes of prophylactic antibiotic administration via IORA or IV route in primary/revision TKA, respectively, and new research evidence has emerged. In this study, we conducted a systematic review and meta-analysis with the primary objective of comparing the local drug tissue concentration and the incidence of PJI between preoperative IORA and intravenous (IV) administration of prophylactic antibiotics in TKA. Additionally, the occurrence of complications between the two administration routes was also compared. This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement (PRISMA) guidelines. Retrospective cohort studies and prospective randomized controlled trials that utilized intraosseous local drug delivery for prophylactic antibiotics in knee arthroplasty were included. English literature from PubMed, Embase, and Cochrane Library databases was searched from the inception of each database until December 2023. Two researchers independently screened the literature, assessed the quality, and extracted data according to the inclusion criteria. The primary outcomes were local antibiotic tissue concentration and postoperative PJI incidence, while the secondary outcome was the occurrence of postoperative complications. Statistical analysis was performed using Review Manager 5.3 software. This study included 7 prospective randomized controlled trials and 5 retrospective cohort studies. A total of 4091 patients participated in the 12 included studies, with 1,801 cases receiving IORA and 2,290 cases in the control group. In terms of local drug tissue concentration, intraosseous infusion (IO) 500mg vancomycin significantly increased the drug concentration in the periarticular adipose tissue (SMD: 1.36; 95% CI: 0.87-1.84; P < 0.001; I2 = 0%) and bone tissue (SMD: 0.94; 95% CI: 0.49-1.40; P < 0.001; I2 = 0%) compared to IV 1g vancomycin. Regarding the incidence of postoperative PJI after primary TKA, IO 500mg vancomycin was more effective in reducing the occurrence of PJI compared to IV 1g vancomycin (OR: 0.19; 95% CI: 0.06-0.59; P < 0.001; I2 = 36%). Finally, no significant differences were found between the two groups in terms of postoperative pulmonary embolism (PE) (OR: 1.72; 95% CI: 0.22-13.69; P = 0.59; I2 = 0%) and vancomycin-related complications (OR: 0.54; 95% CI: 0.25-1.19; P = 0.44; I2 = 0%). Preoperative prophylactic antibiotic administration via IORA in TKA significantly increases local drug tissue concentration without significantly increasing systemic drug-related complications compared to traditional IV administration. In primary TKA, low-dose vancomycin via IORA is more effective in reducing the incidence of PJI compared to traditional IV regimens. However, its effectiveness remains controversial in high-risk populations for PJI, such as obese, diabetic, and renal insufficiency patients, as well as in revision TKA.

Protective Effect of Modified Ginseng Baidu Powder Prophylactic Administration on LPS-Induced Acute Respiratory Distress Syndrome in Mice

Protective Effect of Modified Ginseng Baidu Powder Prophylactic Administration on LPS-Induced Acute Respiratory Distress Syndrome in Mice