Administration Protocol Research Articles

The Therapeutic Application of Hydrogen in Cancer: The Potential and Challenges.

Hydrogen therapy has emerged as a possible approach for both preventing and treating cancer. Cancers are often associated with oxidative stress and chronic inflammation. Hydrogen, with its unique physiological functions and characteristics, exhibits antioxidant, anti-inflammatory, and anti-apoptotic properties, making it an attractive candidate for cancer treatment. Through its ability to mitigate oxidative damage, modulate inflammatory responses, and sustain cellular viability, hydrogen demonstrates significant potential in preventing cancer recurrence and improving treatment outcomes. Preclinical studies have shown the efficacy of hydrogen therapy in several cancer types, highlighting its ability to enhance the effectiveness of conventional treatments while reducing associated side effects. Furthermore, hydrogen therapy has been found to be safe and well-tolerated in clinical settings. Nonetheless, additional investigations are necessary to improve a comprehensive understanding of the mechanisms underlying hydrogen's therapeutic potential and refine the administration and dosage protocols. However, further clinical trials are still needed to explore its safety profile and capacity. In aggregate, hydrogen therapy represents an innovative and promising treatment for several malignancies.

Intraoperative intravenous versus periarticular injection of glucocorticoids in improving clinical outcomes after total knee arthroplasty: A prospective, randomized and controlled study.

Glucocorticoids have been widely used in perioperative period for postoperative pain relief after total knee arthroplasty (TKA). However, the optimal administration protocols of glucocorticoids remain controversial. This study aims to compare the efficacy of glucocorticoids between intravenous and periarticular injection on clinical outcomes. A total of 114 patients were randomly assigned to intravenous (IV) group (n = 57) and periarticular injection (PI) group (n = 57). The IV group received 10mg dexamethasone intravenously and the PI group received periarticular injection of 10mg dexamethasone during the procedure. The clinical outcomes were assessed using visual analogue scale (VAS), knee society score (KSS), range of motion (ROM), knee swelling, inflammation markers and complications after TKA. The VAS score during walking at 2nd day postoperatively was lower in the PI group compared with the IV group (2.08 ± 1.45 vs 2.73 ± 1.69, p = .039), and there was no significant difference at the other time points of VAS score in two groups. The inflammation markers, knee swelling, knee ROM and KSS score were not statistically different. Vomiting and other complications occurrence were not significantly different between the two groups. Intraoperative periarticular injection of glucocorticoids has similar analgesic effect compared to intravenous in the postoperative period following TKA and may be even more effective on the second postoperative day. In addition, periarticular injection of glucocorticoids does not impose an excess risk or complication on patients.

Treatment with inhaled Argon: a systematic review of pre-clinical and clinical studies with meta-analysis on neuroprotective effect

Argon (Ar) has been proposed as a potential therapeutic agent in multiple clinical conditions, specifically in organ protection. However, conflicting data on pre-clinical models, together with a great variability in Ar administration protocols and outcome assessments, have been reported. The aim of this study was to review evidence on treatment with Ar, with an extensive investigation on its neuroprotective effect, and to summarise all tested administration protocols. Using the PubMed database, all existing pre-clinical and clinical studies on the treatment with Ar were systematically reviewed (registration: https://doi.org/10.17605/OSF.IO/7983D). Study titles and abstracts were screened, extracting data from relevant studies post full-text review. Exclusion criteria included absence of full text and non-English language. Furthermore, meta-analysis was also performed to assess Ar potential as neuroprotectant agent in different clinical conditions: cardiac arrest, traumatic brain injury, ischemic stroke, perinatal hypoxic-ischemic encephalopathy, subarachnoid haemorrhage. Standardised mean differences for neurological, cognitive and locomotor, histological, and physiological measures were evaluated, through appropriate tests, clinical, and laboratory variables. Invivo studies were evaluated for risk of bias using the Systematic Review Center for Laboratory Animal Experimentation tool, while invitro studies underwent assessment with a tool developed by the Office of Health Assessment and Translation. The systematic review detected 60 experimental studies (16 invitro, 7 exvivo, 31 invivo, 6 with both invitro and invivo) investigating the role of Ar. Only one clinical study was found. Data from six invitro and nineteen invivo studies were included in the meta-analyses. In pre-clinical models, Ar administration resulted in improved neurological, cognitive and locomotor, and histological outcomes without any change in physiological parameters (i.e., absence of adverse events). This systematic review and meta-analysis based on experimental studies supports the neuroprotective effect of Ar, thus providing a rationale for potential translation of Ar treatment in humans. Despite adherence to established guidelines and methodologies, limitations in data availability prevented further analyses to investigate potential sources of heterogeneity due to study design. This study was funded in part by Italian Ministry of Health-Current researchIRCCS and by Ministero della Salute Italiano, Ricerca Finalizzata, project no. RF 2019-12371416.

Synergistic promotion of angiogenesis after intracerebral hemorrhage by ginsenoside Rh2 and chrysophanol in rats

BackgroundIntracerebral hemorrhage (ICH) is a debilitating condition characterized by the rupture of cerebral blood vessels, resulting in profound neurological deficits. A significant challenge in the treatment of ICH lies in the brain's limited capacity to regenerate damaged blood vessels. This study explores the potential synergistic effects of Ginsenoside Rh2 and Chrysophanol in promoting angiogenesis following ICH in a rat model. MethodsNetwork pharmacology was employed to predict the potential targets and pathways of Ginsenoside Rh2 and Chrysophanol for ICH treatment. Molecular docking was utilized to assess the binding affinity between these compounds and their respective targets. Experimental ICH was induced in male Sprague-Dawley rats through stereotactic injection of type VII collagenase into the right caudate putamen (CPu). The study encompassed various methodologies, including administration protocols, assessments of neurological function, magnetic resonance imaging, histological examination, observation of brain tissue ultrastructure, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunofluorescence staining, Western blot analysis, and statistical analyses. ResultsNetwork pharmacology analysis indicated that Ginsenoside Rh2 and Chrysophanol may exert their therapeutic effects in ICH by promoting angiogenesis. Results from animal experiments revealed that rats treated with Ginsenoside Rh2 and Chrysophanol exhibited significantly improved neurological function, reduced hematoma volume, and diminished pathological injury compared to the Model group. Immunofluorescence analysis demonstrated enhanced expression of vascular endothelial growth factor receptor 2 (VEGFR2) and CD31, signifying augmented angiogenesis in the peri-hematomal region following combination therapy. Importantly, the addition of a VEGFR2 inhibitor reversed the increased expression of VEGFR2 and CD31. Furthermore, Western blot analysis revealed upregulated expression of angiogenesis-related factors, including VEGFR2, SRC, AKT1, MAPK1, and MAPK14, in the combination therapy group, but this effect was abrogated upon VEGFR2 inhibitor administration. ConclusionThe synergistic effect of Ginsenoside Rh2 and Chrysophanol demonstrated a notable protective impact on ICH injury in rats, specifically attributed to their facilitation of angiogenesis. Consequently, this research offers a foundation for the utilization of Ginsenosides Rh2 and Chrysophanol in medical settings and offers direction for the advancement of novel pharmaceuticals for the clinical management of ICH.

Comparison of the Areas Under the Curve of Vancomycin Continuous vs. Intermittent Infusion in Critically Ill Pediatrics: A Randomized Clinical Trial.

Providing data on the superior efficacy of vancomycin administered based on the area under the curve over 24 hours to the minimum inhibitory concentration of vancomycin (AUC24/MIC) is crucial. However, data on dosing and monitoring of vancomycin pharmacokinetics in the pediatric population are limited. Previous findings have showed that intermittent infusion of vancomycin (IIV) may not achieve the desired levels, continous infusions of vancomycin (CIV) reach the desired serum concentration faster than IIV and are associated with reduced nephrotoxicity. This study aimed to compare the serum concentrations, AUC24, clinical variables, and adverse effects of two vancomycin administration methods in the pediatric population. This study was a double-blind, randomized, controlled clinical trial conducted at a tertiary children's teaching hospital. Inclusion criteria were age between 2 months and 15 years and weight less than 67 kilograms, with exclusion criteria including renal impairment. Participants were divided into CIV and IIV groups following distinct administration protocols. Demographic, clinical, and laboratory data, including vancomycin serum concentrations, were compiled. Assessments included pediatric mortality risk, pediatric sequential organ failure assessment, and regular temperature monitoring. Pharmacokinetic analysis was conducted using Monolix software 2023R1. Primary endpoints were vancomycin serum levels and AUC24 between cohorts on day three, with nephrotoxicity and additional adverse drug responses evaluated. Sixty-eight patients in the pediatric intensive care unit (PICU) were allocated to either CIV (33) or IIV (35) for vancomycin treatment. In the CIV group, 82% of patients achieved an AUC24 ≥ 400 mg.h/L, compared to 23% in the IIV group. Continuous infusions of vancomycin demonstrated a greater AUC24 (587.7 ± 184.4 mg.h/L vs. 361.9 ± 113.2 mg.h/L, P < 0.05) compared to IIV. Two cases of nephrotoxicity were reported, one in each group, with mortality and adverse events being comparable between the two groups. This study demonstrated that continuous vancomycin infusion has a higher success rate in safely achieving therapeutic vancomycin levels in PICU patients compared to intermittent vancomycin infusion.

Decreased portal vein attenuation and liver enhancement with reduced intravenous contrast dosage during the national iodinated contrast shortage of 2022.

The worldwide shortage of intravenous (IV) Omnipaque iodinated contrast (Iohexol, GE Healthcare; Milwaukee, WI, USA) forced institutions to adopt various policies regarding contrast allocation. We sought to evaluate the impact of our hospital's response to the shortage, which was to decrease the dose of IV contrast from 100 mL to 75 mL for patients weighing between 45.4 and 136 kg (100-300 lbs) undergoing abdominal computed tomography (CT) examinations. The main objective was to assess for any differences in liver attenuation and enhancement between contrast dosages. Secondary outcomes included assessing differences in aortic and portal vein attenuation, the variance in attenuation measurements, and whether radiology reports included the correct IV contrast dose. Consecutive CT abdomen or CT abdomen and pelvis examinations without and with contrast were analyzed for the 3 months before the contrast shortage and for 3 months during the contrast shortage. Attenuation in Hounsfield units (HUs) was measured in the liver on pre-contrast and portal venous phase images. Vessel attenuation was measured in the aorta (arterial phase) and main portal vein (portal venous phase). Standard deviation of liver attenuation measurements was recorded as an indicator of signal-to-noise. Liver enhancement was calculated as the difference between liver portal venous phase attenuation and pre-contrast attenuations. Thirty-nine fixed dose (100 mL) and 36 reduced dose (75 mL) consecutive CT studies were included in the study. There were no significant differences between the two groups with respect to baseline characteristics such as age, weight, body mass index, and gender. There was no significant difference in pre-contrast liver attenuation between groups, but there was statistically significant greater liver attenuation (99.6 vs. 91.2 HU, P = 0.04) and liver enhancement (51.5 vs. 39.1 HU, P < 0.0001) during the portal venous phase for the fixed-dose group compared to the reduced dose group. There was significantly greater main portal vein opacification during the portal venous phase for the fixed dose group (146.6 vs. 122.2 HU, P < 0.0001). No significant difference was found in aortic opacification during the arterial phase (245 vs. 254 HU, P = 0.52). There was no difference in the standard deviation of liver attenuation measurements on the portal venous phase between the groups. The dose was reported correctly in all the patients receiving the fixed dose and in 92% of patients receiving the reduced dose, which was not statistically significant (P = 0.11). Reducing the IV contrast dose from 100 mL to 75 mL Omnipaque 350 in patients weighing 45.4-136 kg (100-300 lbs) undergoing an abdominal CT examination resulted in significantly decreased portal vein opacification and liver enhancement. In particular, liver enhancement and calculated iodine concentrations fell below suggested thresholds for adequate conspicuity of liver lesions. The change in contrast administration protocol also led to more errors in contrast dose reporting in the radiologist's report. These findings are broadly applicable to many practice settings and can help inform strategies in response to any potential future-iodinated contrast shortage.

The Impact of Redosing Antibiotics for Pediatric Patients Undergoing Appendectomy for Complicated Appendicitis.

Currently, there is no universally accepted, standardized protocol for pre-operative antibiotic administration in the setting of appendectomy for complicated appendicitis among pediatric patients. Strategies to mitigate surgical site infections (SSIs) must be balanced with optimal antibiotic use and exposure. We conducted a retrospective chart review to compare outcomes between patients treated pre-operatively with a single pre-operative dose of antibiotics with those who received additional antibiotics prior to laparoscopic appendectomy for complicated appendicitis between 2020 and 2022. Of 124 pediatric patients, 18% received an additional dose of pre-operative antibiotics after initial treatment dose. Surgical site infection rates between the two groups were not statistically significant (P-value = .352), thereby suggesting that redosing antibiotics closer to the time of incision may not impact SSI rates. Additional studies are necessary to make clinical recommendations.

Effectiveness of immunoglobulin replacement therapy in preventing infections in patients with chronic obstructive pulmonary disease: a systematic review

PurposeImmunoglobulin replacement therapy is a standard treatment for patients with antibody production deficiencies, which is of interest in patients with chronic obstructive pulmonary disease (COPD). This systematic review, registered with PROSPERO (CRD42021281118), assessed the current literature regarding immunoglobulin replacement therapy on COPD clinical outcomes in patients with low immunoglobulin G (IgG) serum concentrations.MethodsLiterature searches conducted from inception to August 23, 2021, in databases including MEDLINE, EMBASE, and CINAHL. Population (sex, age, comorbidities), baseline clinical characteristics (pulmonary function testing results, IgG levels), and outcome (hospitalizations, emergency department visits) were extracted after title/abstract and full text screening. The Cochrane risk of bias assessment form was used for risk of bias assessment of randomized controlled trials and the National Heart, Lung, and Blood Institute (NHLBI) assessment was used for pre and post studies.ResultsA total of 1381 studies were identified in the preliminary search, and 874 records were screened after duplicates were removed. Screening 77 full texts yielded four studies that were included in the review.ConclusionIt is unclear whether immune globulin replacement therapy reduces acute exacerbation frequency and severity in COPD. Current evidence suggests that it is worth considering, but better developed protocols for administration of immune globulin supplementation is required for future randomized controlled trials.

Novel protocol for multiple-dose oral administration of the L-type Ca2+ channel blocker isradipine in mice: A dose-finding pharmacokinetic study

ABSTRACT Studies in genetically modified animals and human genetics have recently provided new insight into the role of voltage-gated L-type Ca2+ channels in human disease. Therefore, the inhibition of L-type Ca2+ channels in vivo in wildtype and mutant mice by potent dihydropyridine (DHP) Ca2+ channel blockers serves as an important pharmacological tool. These drugs have a short plasma half-life in humans and especially in rodents and show high first-pass metabolism upon oral application. In the vast majority of in vivo studies, they have therefore been delivered through parenteral routes, mostly subcutaneously or intraperitoneally. High peak plasma concentrations of DHPs cause side effects, evident as DHP-induced aversive behaviors confounding the interpretation of behavioral readouts. Nevertheless, pharmacokinetic data measuring the exposure achieved with these applications are sparse. Moreover, parenteral injections require animal handling and can be associated with pain, discomfort and stress which could influence a variety of physiological processes, behavioral and other functional readouts. Here, we describe a noninvasive oral application of the DHP isradipine by training mice to quickly consume small volumes of flavored yogurt that can serve as drug vehicle. This procedure does not require animal handling, allows repeated drug application over several days and reproducibly achieves peak plasma concentrations over a wide range previously shown to be well-tolerated in humans. This protocol should facilitate ongoing nonclinical studies in mice exploring new indications for DHP Ca2+ channel blockers.

Retrospective Cohort Study Comparing Efficacy and Safety of Pharmacological Intervention and Phototherapy in Moderate to Severe Psoriasis Patients in a Real-World Setting

Abstract Methotrexate (MTX) is one of the first-line systemic treatment options in patients with moderate-to-severe plaque psoriasis and can be combined with narrow band UVB phototherapy (Nb-UVB). However, such a combination is rarely used for optimal duration due to safety and efficacy concerns. The aim of this study was to assess efficacy and safety of methotrexate (MTX) combination with low doses of Nb-UVB versus MTX monotherapy in patients with moderate-to-severe plaque psoriasis in a real-world setting. Retrospective psoriasis patient medical chart review was performed for the period from 2013 till 2019. The combination therapy group (Group 1, n = 74) received MTX 10 mg s/c once a week for four to six weeks and 311 nm UVB phototherapy according to the skin type and protocol of administration — three times a week; undergoing 10–24 procedures in the treatment course. The monotherapy group (Group 2, n = 57) was treated, using MTX as monotherapy 2.5 mg two times a day orally for five days (4–6 treatment courses in total). The combination therapy group achieved decrease of mean PASI at the end of the 2nd week of treatment by 38% vs monotherapy group 21%. Combination of low dose subcutaneous MTX and Nb-UVB therapy provides better treatment outcomes and normalisation of immunochemical parameters than for MTX monotherapy. This combination also showed a favourable tolerability profile.

A Comparative Analysis of Prophylactic Antibiotic Administration in Emergency Surgery Versus Elective Surgery: A Comprehensive Review.

Surgical site infections (SSIs) contribute to increased patient morbidity, prolonged hospital stays, and substantial healthcare costs. Prophylactic antibiotics play a pivotal role in mitigating the risk of SSIs, with their administration being a standard practice before both emergency and elective surgeries. This paper provides a comprehensive review and comparative analysis of the benefits of prophylactic antibiotic administration in emergency surgery versus elective surgery. Through a systematic literature review and analysis of relevant studies identified through PubMed searches, this paper highlights the specific benefits of prophylactic antibiotics between emergency and elective surgeries. The findings underscore the importance of tailored antibiotic regimens and administration protocols to optimize patient care and promote successful surgical outcomes in diverse clinical settings. Further research is warranted to refine guidelines and enhance understanding of the relationship between prophylactic antibiotics and surgical outcomes across different surgical contexts.

Wild-type lytic bacteriophages against Salmonella Heidelberg: Further characterization and effect of prophylactic therapy in broiler chickens

To characterize wild-type bacteriophages and their effect on Salmonella Heidelberg intestinal colonization in broilers, phages combined in a cocktail were continuously delivered via drinking water since the first day after hatching. After challenge with a field strain, broilers were evaluated at regular intervals for S. Heidelberg and bacteriophages in tissues and cecum, and gross and microscopic lesions in organs. Phages were highly virulent against S. Heidelberg by efficiency of plating. One-step growth curves exhibited eclipse period from 20 to 25 min, whereas the lowest latent period and higher burst size found were 45 min and 54 PFU/cell, respectively. Bacteriophage whole genomic sequencing analyses revealed a lack of genes related to lysogeny, antimicrobial resistance, and virulence factors. Relevant gross or microscopic lesions were absent in tissues analyzed from treated broilers. Although numerically stable bacteriophage concentrations were detected in the cecal contents of treated broilers, no significant difference was found for the S. Heidelberg cecal load in comparison to the untreated group and for the prevalence of positive tissues throughout the evaluated period. The phages produced turbid plaques against some S. Heidelberg re-isolated from treated broilers, suggesting the evolving of a resistant subpopulation. Overall, the results provide new evidence of the safety and in vitro replication of such phages in S. Heidelberg. Nevertheless, continuous administration of the phage suspension most likely induced the development of bacteriophage-resistant mutants, which might have affected the in vivo effect. Therefore, a putative administration protocol should be based on other strategies, such as short-term therapy at pre-harvest age.

ORAL OPIOID ANALGESICS VS SPINAL STEROID INJECTIONS IN THE TREATMENT OF LOW BACK PAIN: A COMPREHENSIVE SYSTEMATIC REVIEW

Introduction: Low back pain (LBP) affects a significant portion of the population worldwide, with distinct treatment needs for acute and chronic cases. Despite widespread opioid use, evidence for their efficacy in LBP remains uncertain, highlighting the need for alternative interventions. Minimally invasive procedures like epidural steroid injections offer potential relief for conditions like lumbar disc herniation, but their effectiveness is debated. To address these complexities, we conducted a comprehensive review encompassing various treatment modalities beyond medication, aiming to optimize outcomes and improve quality of life for individuals with LBP. Method: The researchers in this study followed the 2020 Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines to ensure that their work met the required standards. This was done to ensure the precision and reliability of the conclusions derived from the research. Result: Our search produced 13 results. After looking at the titles and summaries, we found 8 papers that fit our criteria. At first, we excluded several articles because they were written in review style and case reports. But after reading the full papers carefully, we included four papers in our final analysis. These papers included retrospective analysis, a randomized, double blind, placebo controlled cross-over study, noninterventional, retrospective 12-week study using anonymized clinical practice data from the German Pain eRegistry, and a retrospective analysis of anonymized, propensity score–matched data. Conclusion: Favorable post-injection outcomes suggest the blind method for caudal epidural injections is safe and effective, suitable for patients not eligible for surgery or unresponsive to conservative treatments. Interlaminar epidural steroid injections effectively reduce VAS and ODI scores in patients with chronic low back pain and multi-level disc disease, but further research is needed to standardize administration protocols and optimize treatment outcomes, including addressing BMI's impact. The analgesic efficacy of periradicular meloxicam injections for acute/subacute low back pain, indicating a potential new treatment option, while real-world data suggest NBX oromucosal spray may be superior to typical oral LAO analgesics for severe peripheral NBP, pending confirmation in large RCTs.

Urdu Receptive Language Scale (URLS): Modification & development of protocol for administration in Urdu.

To conduct pretesting of Urdu Receptive Language Scale (URLS) for scale modification and development of protocol for administration on children. This exploratory research was conducted from December 2021 to June 2022 in Lahore, Pakistan. Objective was achieved by pretesting in three steps including literature review, expert review and pilot testing on infants, toddlers and children aged 0-6 years utilizing purposive sampling technique. For expert review five experts' speech language pathologists with minimum five years of experience and for pilot study 48 normal developing children age range birth to six years were recruited. The analysis was done using content validity ratio, content validity index and Cronbach alpha. Protocol for administration of test items and stimulus with minimum three correct responses among four children's responses were finalized. Of the 59 items, 57 with CVR = 0.99 were retained. Item number 3 (age 6-11 months) and item 5 (age 3.6-3.11 years) were eliminated as CVR was <0.99. CVI was one for retained items indicating acceptable validity. Cronbach's alpha was 0.95 indicating high level of internal consistency for the scale. Task groups of protocol of administration directions included: Selection of scale items, testing environment, seating arrangements, rapport building and involving the caregiver, handling the scale material and scoring the task responses. The modified 57 items has high validity and internal consistency with suitable protocol of administration. It is linguistically appropriate for the application on larger scale with children of different cultural backgrounds in Pakistan.

Effect of furosemide combined with continuous renal replacement therapy on cardiorenal function and inflammatory response in patients with chronic renal and heart failure after hemodialysis

Purpose: To determine the effect of furosemide combined with continuous renal replacement therapy (CRRT) on cardiorenal function and inflammatory response in patients with chronic renal failure (CRF) and heart failure after hemodialysis. &#x0D; Methods: 130 patients with both CRF and heart failure, who underwent hemodialysis at the Second Hospital Affiliated to Hainan Medical College, China, from October 2020 to October 2022 were recruited as study subjects. They were randomly divided into two groups, with control group administered the Continuous Renal Replacement Therapy (CRRT) while study group received furosemide in addition. The study assessed the clinical outcomes, cardiorenal function and inflammatory factors before and after treatment. Additionally, adverse reactions during treatment were documented for both groups. &#x0D; Results: Study group exhibited a significantly higher (p &lt; 0.001) total response rate compared to control group. Post-treatment, both groups displayed significant increases (p &lt; 0.05) in left ventricular ejection fraction, cardiac output and stroke volume, with study group showing significantly superior results (p &lt; 0.05). Furthermore, post-treatment, both groups experienced significant reductions (p &lt; 0.05) in serum creatinine, blood urea nitrogen, and 24-hour urinary protein levels, with study group displaying significantly lower levels (p &lt; 0.05). Additionally, the interleukin-6, interleukin-1β and tumor necrosis factor-α levels decreased significantly in both groups post-treatment, with study group exhibiting significantly lower levels (p &lt; 0.05). There was no significant difference in adverse reaction incidence between the two groups. &#x0D; Conclusion: Furosemide combined with CRRT significantly improves cardiorenal function and reduces inflammatory response in patients with CRF and heart failure after hemodialysis. Future research could optimize dosage and administration protocols, explore long-term effects and assess applicability in diverse patient populations.

(117) Is Platelet-Rich Plasma Effective and Safe for Managing Erectile Dysfunction? A Meta-Analysis of Before-After Data from Clinical Studies

Abstract Introduction Erectile dysfunction (ED) is common health issues among men with increasing prevalence along with age. With the advancement of technology, the aim of therapy for ED is start to shift in reversing the pathology and not only relieving the symptoms. Platelet-rich plasma (PRP) are one of the regenerative modalities that has gained popularity in many medical disciplines. Many studies have been conducted that favour PRP in improving erectile function. However, no relevant meta-analysis of PRP have been performed to date. Objective A single-arm meta-analysis were conducted to evaluate the outcome of PRP for the treatment of ED based on the data before and after the procedures. Methods We systematically searched PubMed, Embase, Scopus in June 2023 to find the relevant articles based on the Preferred Reporting Items for Systematic Review and Meta-analysis statement. All randomized controlled trials (RCTs), observational, and case control studies in English with 10 or more subjects and a minimum of 1 month follow-up after PRP treatment reporting International Index of Erectile Function-Erectile Function (IIEF-EF) score were included. Pooled analysis on outcomes that were reported in at least 2 studies were performed using RevMan 5.4 and STATA18 with 95% confidence intervals (CIs). We also conduct heterogeneity test and a leave-one-out sensitivity analysis. Results A total of three RCTs, three observational studies and one case-control study, comprising 236 patients, were included from 183 studies identified. The pooled analysis showed that PRP injection significantly increased the IIEF-EF score by 3.87 (95% CI: 2.92, 4.83, p&amp;lt;0.00001), 3.01 (95% CI: 2.27, 3.74, p&amp;lt;0.0001), 3.29 (95% CI: 2.26, 4.32, p&amp;lt;0.00001), at 1, 3, and 6, months follow-up. Subgroup analysis of IIEF-EF based on the use of PDE5i in the protocol or during follow-up period also found the same finding result. The proportion of patient who met MCID after 6 months of follow of was 70% (95% CI: 59%, 80%). In term of penile hemodynamic, a significant improvement was found in peak systolic velocity and end diastolic velocity at the end-point of follow-up. On contrary, there was no significant improvement were found for IIEF score of intercourse satisfaction and overall satisfaction domain. The most common complication reported were transient subcutaneous bruising. Two cases reported a formation of painless plaque but no other major adverse events were reported. Consistent result was found after a leave-one-out sensitivity analysis. Conclusions PRP is a promising restorative modality for ED with improvement in IIEF-EF score and penile hemodynamic. However, further studies and human trials are required to confirm the efficacy and durability of this novel treatment as well as to find out the best protocol of administration. Disclosure No.

Development of A Micro-CT Scanner with Dual-Energy Option and Endovascular Contrast Agent Administration Protocol for Fetal and Neonatal Virtual Autopsy.

The rate of parental consent for fetal and perinatal autopsy is decreasing, whereas parents are more likely to agree to virtual autopsy by non-invasive imaging methods. Fetal and perinatal virtual autopsy needs high-resolution and good soft-tissue contrast for investigation of the cause of death and underlying trauma or pathology in fetuses and stillborn infants. This is offered by micro-computed tomography (CT), as opposed to the limited resolution provided by clinical CT scanners, and this is one of the most promising tools for non-invasive perinatal postmortem imaging. We developed and optimized a micro-CT scanner with a dual-energy imaging option. It is dedicated to post-mortem CT angiography and virtual autopsy of fetuses and stillborn infants in that the chamber can be cooled down to around 5 °C; this increases tissue rigidity and slows decomposition of the native specimen. This, together with the dedicated gantry-based architecture, attempts to reduce potential motion artifacts. The developed methodology is based on prior endovascular injection of a BaSO4-based contrast agent. We explain the design choices and considerations for this scanner prototype. We give details of the treatment of the optimization of the dual-energy and virtual mono-energetic imaging option that has been based on minimizing noise propagation and maximizing the contrast-to-noise ratio for vascular features. We demonstrate the scanner capabilities with proof-of-concept experiments on phantoms and stillborn piglets.

Strategy to optimize PeriproCeduraL AnticOagulation in structural transseptal interventions: Design and rationale of the STOP CLOT trial

Both transcatheter edge-to-edge repair (TEER) of mitral regurgitation or left atrial appendage closure (LAAC) require periprocedural anticoagulation with unfractionated heparin (UFH) that is administered either before or immediately after transseptal puncture (TSP). The optimal timing of UFH administration (before or after TSP) is unknown. The Strategy To Optimize PeriproCeduraL AnticOagulation in Structural Transseptal Interventions trial (STOP CLOT Trial) was designed to determine if early anticoagulation is effective in reducing ischemic complications without increasing the risk of periprocedural bleeding.The STOP CLOT trial is a multicenter, prospective, double-blind, placebo-controlled, randomized trial. A total of 410 patients scheduled for TEER or LAAC will be randomized 1:1 either early UFH administration (iv. bolus of 100Units/kg UFH or placebo, given after obtaining femoral vein access and at least 5 minutes prior to the start of the TSP) or late UFH administration (iv. bolus of 100Units/kg UFH or placebo given immediately after TSP). Prespecified preliminary statistical analysis will be performed after complete follow-up of the first 196 randomized subjects. To ensure blinding, a study nurse responsible for randomization and UFH/placebo preparation is not involved in the care of the patients enrolled into the study. The primary study endpoint is a composite of (1) major adverse cardiac and cerebrovascular events (death, stroke, TIA, myocardial infarction, or peripheral embolization) within 30 days post-procedure, (2) intraprocedural fresh thrombus formation in the right or left atrium as assessed with periprocedural transesophageal echocardiography, or (3) occurrence of new ischemic lesions (diameter ≥4 mm) on brain magnetic resonance imaging performed 2-5 days after the procedure. The safety endpoint is the occurrence of moderate or severe bleeding complications during the index hospitalization. Protocols of periprocedural anticoagulation administration during structural interventions have never been tested in a randomized clinical trial. The Stop Clot trial may help reach consensus on the optimal timing of initiation of periprocedural anticoagulation.

Assessment of Microplastics in Hanumante River of Kathmandu Valley

Plastic debris is one of the most significant organic pollutants in the aquatic environment. Researchers are currently focusing on the impact of micro and nano-scale plastic waste on aquatic systems. In this study, we investigated the distribution of plastic pellets and fragments present in the freshwater ecosystem. The goal was to assess microplastic (MP) abundance in the Hanumante River, a tributary of the Bagmati River, and analyze their properties. Sample collection involved the bottle sampling method. Filtration, wet peroxide oxidation, density separation, gravimetric analysis, and microscopic examination were performed to study the characteristics of microplastics. The study was conducted by following the guidelines of the National Oceanic and Atmospheric Administration (NOAA) protocol. Gravimetric analysis was applied to calculate the reduced mass of the sample after total organic carbon reduction. Results showed that the maximum amount of reduced sample was obtained from the sample taken from sample taken from Madhyapur Thimi area (~3.593g) and the minimum amount of reduced sample was obtained from the sample taken from the Shiva temple Jagati area (~2.130g). Microscopic inspection showed that samples taken from different locations were composed of an average of 14–23 microplastics per liter of sample. FT-IR analysis was performed to analyze the characteristics of microplastics and the type of polymers present in the sample which showed the abundance of polymer materials like polyethylene, polypropylene, and polycarbonates. The findings imply that appropriate plastic waste management measures be implemented in the communities to safeguard the ecosystem benefits derived from the river.

Comparison of Hyaluronidase-Mediated Degradation Kinetics of Commercially Available Hyaluronic Acid Fillers In Vitro.

The ability to degrade hyaluronic acid (HA)-based fillers with hyaluronidase allows for better management of adverse effects and reversal of suboptimal treatment outcomes. The aim of this study was to compare the enzymatic degradation kinetics of 16 commercially available HA-based fillers, representing 6 manufacturing technologies. In this nonclinical study, a recently developed in vitro multidose hyaluronidase administration protocol was used to induce degradation of HA-based fillers, enabling real-time evaluation of viscoelastic properties under near-static conditions. Each filler was exposed to repeated doses of hyaluronidase at intervals of 5 minutes to reach the degradation threshold of G' ≤ 30 Pa. Noticeable differences in degradation characteristics were observed based on the design and technology of different filler classes. Vycross fillers were the most difficult to degrade and the Cohesive Polydensified Matrix filler was the least difficult to degrade. Preserved Network Technology products demonstrated proportional increases in gel degradation time and enzyme volume required for degradation across the individual resilient hyaluronic acid (RHA) products and indication categories. No obvious relationship was observed between gel degradation characteristics and the individual parameters of HA concentration, HA chain length, or the degree of modification of each filler when analyzed separately; however, a general correlation was identified with certain physicochemical properties. Manufacturing technology was the most important factor influencing the reversibility of an HA product. An understanding of the differential degradation profiles of commercially available fillers will allow clinicians to select products that offer a higher margin of safety due to their preferential reversibility.