Percepção profissional sobre tratamento endodôntico em sessão única e múltiplas sessões / Professional perception of single and multi-session endodontic treatment

Na odontologia a decisão do tratamento é exclusiva dos cirurgiões dentistas e suas percepções, incluindo filosofia de tratamento, fazendo com que a prática de novos conceitos, tratamentos ou técnicas dependam não apenas de sua lógica ou eficácia biológica. Sendo assim, este estudo teve como objetivo avaliar os parâmetros envolvidos na tomada de decisão de cirurgiões dentistas clínicos e especialistas para a realização do tratamento endodôntico em sessão única ou múltiplas sessões. Para tanto, este estudo contou com uma coleta de dados através de um questionário online, aplicado cirurgiões dentistas clínicos gerais e especialistas em endodontia. As respostas foram tabuladas e analisadas por meio de estatística descritiva. Os resultados revelaram que a maioria dos endodontistas e dos clínicos gerais prefere realizar tratamento endodôntico em sessão única, devido ao menor desperdício de material, além do melhor domínio da anatomia e tratamento em um único momento. O motivo mais comum para os endodontistas e clínicos gerais escolherem o tratamento com múltiplas visitas é para dentes com prognóstico duvidoso e os casos em que o profissional aguarda a remissão dos sintomas antes da obturação. Em conclusão, a maioria dos endodontistas e dos clínicos gerais preferiu realizar tratamento endodôntico em sessão única.

In dentistry, treatment decisions are made exclusively by dental surgeons and their perceptions, including treatment philosophy, which means that the practice of new concepts, treatments or techniques depends not only on their logic or biological efficacy. Therefore, the aim of this study was to evaluate the parameters involved in clinical and specialist dental surgeons' decision to carry out endodontic treatment in single or multiple sessions. To this end, data was collected using an online questionnaire administered to general dental surgeons and endodontic specialists. The answers were tabulated and analyzed using descriptive statistics. The results revealed that the majority of endodontists and general practitioners prefer to carry out endodontic treatment in a single session, due to less wastage of material, as well as better mastery of the anatomy and treatment at a single time. The most common reason for endodontists and general practitioners to choose treatment with multiple visits is for teeth with a doubtful prognosis and cases in which the professional is waiting for symptoms to remit before filling. In conclusion, the majority of endodontists and general practitioners preferred to carry out endodontic treatment in a single session.

Relevance, Risks, and Benefits of Early-Phases Clinical Trials Participations for Patients With Hematological Malignancies From 2008 to 2023.

BACKGROUND: Early-phases clinical trials (Phases 1 and 2) have evolved from a traditional assessment of toxicity to an adaptive approach based on patients' medical needs and access to effective new therapies. The global risks, benefits, and relevance of early-phases clinical trials participation for patients with hematological malignancies remain poorly evaluated. PATIENTS AND METHODS: All early-phases clinical trials participations for patients with hematological malignancies, from 2008 to 2023, in a tertiary academic center in Europe, were reviewed. Patient's demographics, tumor type categories, therapeutic responses, mortality, overall survival (OS), and investigational product (IP) were assessed. RESULTS: Over the period 2008-2023, 736 patients participating in 92 different early-phases clinical trials, were analyzed. The most common tumor categories were diffuse large B-cell lymphoma (n = 253; 34.4%), acute myeloid leukemia/myelodysplastic syndrome (n = 164; 22.3%) and multiple myeloma (n = 100; 13.6%). The median OS was 14.8 (95% CI: 12.4-17.9) months and response rate 31.9%, including complete responses in 13.5% of patients. By tumor categories, the highest and lowest median duration of OS were observed for patients with Hodgkin lymphoma (99.8; [95% CI: 47.0-not reached] months) and peripheral T-cell lymphoma (8.9 [95% CI: 5.3-12.0] months), respectively. The on-protocol and treatment-related mortality rates were 5.43% and 0.54%, respectively. Overall response rate was 29.1% including 13.5% of complete response. Overall, 202 (27.5%) patients received an IP later approved by the health authorities, and those patients had better OS (18.2 months vs. 12.1 months HR: 1.160 [95% CI; 0.6977-1.391], p = 0.0283). CONCLUSION: In conclusion, patients with hematologic malignancies who have participated in early-phases clinical trials over the past 15 years have achieved variable therapeutic response rates, acceptable risk/benefit ratio and potentially significant therapeutic advantages. This study provides framework material for hematologists to further discuss clinical trial participation with their patients.

Locoregional CAR T Cells for the Treatment of CNS Tumors in Children: Investigational Drug Service Pharmacy Activities.

BACKGROUND: A major obstacle in translating the therapeutic potential of chimeric antigen receptor (CAR) T cells to children with central nervous system (CNS) tumors is the blood-brain barrier. To overcome this limitation, preclinical and clinical studies have supported the use of repeated, locoregional intracranial CAR T-cell delivery. However, there is limited literature available describing the process for the involvement of an investigational drug service (IDS) pharmacy, particularly in the setting of a children's hospital with outpatient dosing for CNS tumors. OBJECTIVES: To describe Seattle Children's Hospital's experience in clinically producing CAR T cells and the implementation of IDS pharmacy practices used to deliver more than 300 intracranial CAR T-cell doses to children, as well as to share how we refined the processing techniques from CAR T-cell generation to the thawing of fractionated doses for intracranial delivery. METHODS: Autologous CD4+ and CD8+ T cells were collected and transduced to express HER2, EGFR, or B7-H3-specific CAR T cells. Cryopreserved CAR T cells were thawed by the IDS pharmacy before intracranial delivery to patients with recurrent/refractory CNS tumors or with diffuse intrinsic pontine glioma/diffuse midline glioma. RESULTS: The use of a thaw-and-dilute procedure for cryopreserved individual CAR T-cell doses provides reliable viability and is more efficient than typical thaw-and-wash protocols. Cell viability with the thaw-and-dilute protocol was approximately 75% and was always within 10% of the viability assessed at cryopreservation. Cell viability was preserved through 6 hours after thawing, which exceeded the 1-hour time frame from thawing to infusion. CONCLUSION: As the field of adoptive immunotherapy grows and continues to bring hope to patients with fatal CNS malignancies, it is critical to focus on improving the preparatory steps for CAR T-cell delivery.

The Effectiveness of Immersive Virtual Reality as A Complementary Approach and a New Direction in Cancer Related Fatigue Management.

Background: Recent advancements in the field of medical technology have illuminated that the implementation of virtual reality interventions can be highly effective in managing cancer-related fatigue. Moreover, this innovative intervention has demonstrated a substantial improvement in patients' overall well-being and daily functioning. Thus, it represents a promising alternative to traditional pharmacological treatments by effectively addressing symptoms and enhancing quality of life. Therefore, the integration of this approach signifies a significant advancement in patient care. Nevertheless, despite the ongoing efforts to diversify non-pharmacological treatments, pharmacological interventions are still the predominant method for managing cancer-related fatigue. Aim: This systematic review aimed to evaluate the effectiveness of immersive virtual reality in cancer-related fatigue management, and to explore the main side effects of immersive virtual reality. Methods: This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Several online databases were used to find eligible studies in peer-reviewed journals relevant to the study keywords. Specifically, the included studies were systematic reviews and clinical trials that used immersive virtual reality-based intervention among adult patients with cancer and suffering from cancer-related fatigue. As well as were published in the English language from 2014 to 2024. As well as, three researchers independently contributed to study selections, data extraction, and study evaluations from different aspects: including quality assessment, risk of bias, and study synthesis. Results: After an extensive and comprehensive search, a total of ten published studies were included in this review study; 6 articles were quantitative clinical trial studies, and the other 4 were systematic review and meta-analysis studies. The quality of 6 included clinical trials was assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for quantitative studies, the overall result showed that 33.3% of studies rated with moderate quality, no study was rated with low quality, and (66.7%) studies rated as high-quality studies. As well, the quality assessment of all review studies showed that all included systematic reviews and meta-analyses with a low risk of bias and high to moderate power of evidence. The result of this extensive and comprehensive review showed that immersive virtual reality has a significant effect in reducing cancer-related fatigue, however, still, there is a significant variation in the employment of immersive Virtual Reality protocols for cancer symptom management worldwide. Conclusion: Immersive virtual reality is an effective non-pharmacological intervention in reducing and controlling cancer-related fatigue among patients with various types of cancer, as well as being an affordable, cost-effective approach. Nevertheless, there remains a notable gap in the existing literature concerning virtual reality protocols, associated side effects, and the underlying mechanisms by which immersive virtual reality alleviates fatigue. Therefore, further research studies are warranted to address these gaps and advance our understanding in these areas.

Navigating Post-operative Challenges: A Comprehensive Review of Complications Following Anterior Cruciate Ligament (ACL) Tear Surgery.

Anterior cruciate ligament (ACL) injuries are among the most common and debilitating sports-related injuries, often necessitating surgical intervention to restore knee stability and function. ACL reconstruction surgery, which has evolved significantly over the years, aims to enable patients, particularly those who are young and physically active, to return to their pre-injury activity levels. However, despite advancements in surgical techniques and rehabilitation protocols, post-operative complications remain a significant concern that can adversely affect patient outcomes. This comprehensive review explores the spectrum of complications that can arise following ACL tear surgery, ranging from common issues such as infection, graft failure, and knee stiffness to less frequent but clinically significant complications like osteoarthritis and neurological injuries. The review also delves into the various factors influencing the likelihood of these complications, including patient-related variables, surgical techniques, and the effectiveness of rehabilitation protocols. By providing an in-depth analysis of these post-operative challenges, this review aims to enhance the understanding of ACL reconstruction outcomes and guide healthcare professionals in implementing preventive strategies and optimizing patient care. Through a multidisciplinary approach, the goal is to minimize the risk of complications, improve surgical outcomes, and ultimately enhance the quality of life for patients undergoing ACL reconstruction.

Anastomotic metabolic and bariatric surgeries with same-day discharge: 30-day outcomes of a cohort from a high-volume center in Canada.

BACKGROUND: On the basis of our extensive experience in same-day discharge (SDD) sleeve gastrectomy, we extended this management strategy to anastomotic metabolic and bariatric surgeries (MBS). OBJECTIVES: To retrospectively analyze early outcomes (≤30 d) after anastomotic MBS with planned SDD (≤12 hr). SETTING: University Hospital, Canada; Public Practice. METHODS: SDD anastomotic MBS were proposed with strict preoperative criteria and included single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S), Roux-en-Y gastric bypass (RYGB), one-anastomosis gastric bypass (OAGB), and single-anastomosis sleeve ileal bypass (SASI). Enhanced recovery after bariatric surgery protocols and post-anesthesia care unit criteria were followed. Unplanned overnight stay, emergency department (ED) visit, readmission, morbidity-mortality, and reintervention rates were analyzed. RESULTS: Since 2021, 208 patients (191 female and 17 male) have undergone SDD anastomotic MBS, with 76% conversion procedures: 92 SADI-S, 72 RYGB, 35 OAGB, and 9 SASI (mean age = 41.4 yr and mean preoperative body mass index = 41.9 kg/m2). Unplanned overnight stays and ED visits were 4.8% and 4.3%, respectively. Readmission rate was 5.8% (5 SADI-S, 5 RYGB, 1 OAGB, and 1 SASI). Overall morbidity rate was 14.9%, including 3.9% major complications. Within 30 days postoperatively, there were 2 duodenal leaks, 1 intrabdominal collection, 1 common bile duct stenosis, and 1 acute appendicitis in the SADI-S group. There were 2 occlusions on the jejunojejunal anastomosis and 1 bleeding on the gastrojejunal anastomosis in the RYGB group. Five (2.4%) required reintervention with no mortality. CONCLUSIONS: We report low and acceptable rates of unplanned overnight stay, readmission, and reintervention. Early outcomes suggest that SDD anastomotic MBS seems safe and feasible with an experienced team, selective criteria, and appropriate postoperative follow-up.

Implementation of a Preanesthetic Telehealth Visit to Reduce Day-of-Surgery Cancellations.

PURPOSE: The purpose of the telehealth preanesthesia clinic (PAC) is to reduce the number of day-of-surgery (DOS) cancellations through the implementation of an algorithm-based standardized protocol. DESIGN: A prospective quality improvement project with pre and post assessment. METHODS: One hundred and fifty preoperative and postoperative surgical chart reviews using the Focus, Analyze, Develop, Execute, and Evaluate model. Retrospective chart reviews were conducted via the electronic health record to collect DOS cancellation counts along with reason for cancellation for a 6-week period prior to implementation, and a 6-week period postimplementation based on inclusion and exclusion criteria. FINDINGS: The implementation of a telehealth PAC using TEMPO (transition and action, evaluation and significant history, medications, procedure and condition, and overall plan) protocols resulted in a statistically significant reduction in DOS cancellations from 3.38% to 1.72%. CONCLUSIONS: Postimplementation findings support the use of a telehealth PAC to reduce DOS cancellations.

Fidelity of Enhanced Recovery Protocol Implementation With Assessment of Hospital-Specific Materials.

INTRODUCTION: Variability in implementation of enhanced recovery protocols (ERPs) often reduces the effects of an intervention on clinical outcomes. This study aimed to evaluate hospital-level implementation fidelity to a pediatric gastrointestinal surgery ERP by assessing site-specific implementation materials. METHODS: This document analysis study operationalized implementation fidelity as adherence to the creation of specified materials at each study site. During the 12-mo implementation phase within the stepped-wedge cluster randomized control trial, ENhanced Recovery In CHildren Undergoing Surgery, study sites were provided with materials (e.g., order sets), access to peer-counseling, and given key ERP elements spanning multiple phases of care. Sixteen of the 18 total study sites submitted implementation materials, including 14 anesthesia protocols, 11 order sets, and 16 sets of patient/family education materials. These materials were assessed and graded for fidelity using prespecified criteria. Hospital-level fidelity scores could range from 0 to a maximum score of 18, and were categorized as either high or low, based on whether the score was above or below/equal to the median. Descriptive statistics and Wilcoxon rank sum test were used for analysis. RESULTS: The overall hospital-level median fidelity score for inclusion of ERP elements in the implementation materials was 10.5. The median score was 12.8 at nine high-fidelity sites and was 5.6 at nine low-fidelity sites (P < 0.01). Higher adherence was noted for avoiding prolonged fasting (n = 16/18 hospitals; 89%) and preventing nausea and vomiting (n = 16/18 hospitals; 89%) in anesthesia protocols and/or order sets. Lower adherence was noted for incorporation of minimally invasive surgical techniques (n = 2/18 hospitals, 11%) and of preoperative optimization of medical comorbidities (n = 0/18 hospitals, 0%) in implementation materials. CONCLUSIONS: Despite substantial resources to promote ERP elements, there was wide variation in fidelity for incorporating ERPs into implementation materials among hospital sites. Development of high-fidelity implementation materials for complex ERPs for gastrointestinal surgery in children may require longer than 12 months. Additional implementation strategies, resources, and modification of implementation-focused materials may be needed.

Standardization of robot-assisted radical nephroureterectomy via intraperitoneal approach: insights from a high-volume Japanese Center.

We present the trial-and-error process of standardizing robot-assisted radical nephroureterectomy (RANU) at a high-volume center in Japan. Our urology team performed 53 RANU cases using the Da Vinci Xi system, undergoing five major evolutionary stages. We performed RANU via transperitoneal approach in all cases and lymph-node dissection in selected cases. During the evolution, we adopted a lithotomy position and significantly modified port placement to facilitate lower ureter management. However, we ultimately arrived at a method that minimizes port and patient repositioning during lower ureter processing. By strategically placing ProGrasp™ forceps in the most caudal port, we effectively retracted the bladder and grasped the opened bladder wall during lower ureter manipulation. This approach also allowed us to perform pelvic, para-aortic, and renal portal lymph-node dissection without major changes in patient positioning or port placement. Nevertheless, we acknowledge that some variations in positioning and techniques may be necessary depending on specific case requirements.

Surgical protocols for oral leukoplakia and precancerous lesions across three different anatomic sites.

OBJECTIVE: This systematic review and meta-analysis aimed to compare the risk of recurrence and cancer progression after surgical treatment for oral potentially malignant disorders (OPMD) and precancerous lesions in different anatomical sites. MATERIALS AND METHODS: A comprehensive search was conducted in nine databases and grey literature. We included randomized controlled trials assessing surgical treatment efficacy for OPMD and precancerous lesions of cervical, vaginal, anal, and penile sites. Excision or ablation surgical treatments were considered. RESULTS: Overall, 12 studies met the eligibility criteria for oral leukoplakia (OL), proliferative verrucous leukoplakia, cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia, and anal intraepithelial neoplasia (AIN). In qualitative analysis of surgical protocols, the lack of margin description impacts the clinical outcomes of OL and AIN, and the ablative protocols were heterogeneous in both OPMD and precancerous lesions. No significant difference in OL (risk ratio 0.82 [95% CI: 0.59-1.15]) and CIN (risk ratio 0.31 [95% CI: 0.09-1.09]) for recurrence was observed when cold-knife was compared with ablative protocols. OL exhibited higher recurrence and cancer progression rates compared to CIN and AIN. CONCLUSION: There is no difference in recurrence risk post-surgical treatment for OL and CIN. Surgical protocols for oral leukoplakia and CIN/AIN lack standardized approaches.

Impact of Diet Modifications on Body Weight, Body Composition, Treatment Outcomes, and Quality of Life During Primary Treatment for Breast Cancer: A Systematic Review.

CONTEXT: Breast cancer is a significant public health challenge, with 290 000 new cases annually and significant healthcare costs. Treatment advancements have led to improvements in survival, but common adverse effects include weight gain, fatigue, nausea, and taste changes, decreasing quality of life. OBJECTIVE: This review aims to assess the impact of diet and lifestyle interventions during primary treatment for breast cancer and their effects on body weight, body composition, treatment-related adverse outcomes, and patient-reported quality of life. DATA SOURCES AND DATA EXTRACTION: A search of PubMed, CINAHL, and EMBASE conducted through May 10, 2023, identified 31 publications describing 27 interventions including diet or diet plus exercise. The Cochrane Risk of Bias tool assessed the quality of publications. DATA ANALYSIS: The findings suggest that whole foods, aerobic and strength-training exercises, and intermittent fasting during treatment may improve body weight and composition, treatment-related outcomes, and quality of life. Limitations include variation in study duration, small sample sizes, and limited sociodemographic data. CONCLUSION: Improvements seen with increased diet quality and reduced caloric intake, with or without exercise, challenge current standard-of-care recommendations during treatment for breast cancer. While there is a need for additional research, healthcare teams can confidently promote healthy diets and exercise during primary treatment for breast cancer to manage weight and improve treatment-related side effects and quality of life. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. 42023425613.

Allogeneic stem cell transplant with TBI-based myeloablative conditioning in adolescents and young adults with Philadelphia chromosome-negative ALL treated with pediatric protocols.

To investigate the safety of total body irradiation-based myeloablative conditioning (TBI-MAC) in adolescent and young adult (AYA) Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) patients treated with pediatric protocols, treatment outcomes of 106 AYA patients aged 16-39 years old undergoing allogeneic stem cell transplant (allo-SCT) with TBI-MAC in the first remission were compared according to chemotherapy types before transplant. Pediatric and adult protocols were used in 56 and 50 of the patients, respectively. The cumulative incidence (CI) of non-relapse mortality (NRM) and the overall survival (OS) rates were not significantly different between the pediatric-protocol and adult-protocol group (NRM: 4 % vs. 14 % at five years post-transplant, respectively, p = 0.26; OS: 81 % vs. 66 %, respectively, p = 0.14). Multivariate analysis for NRM revealed that a performance status >0 (hazard ratio [HR] = 4.8) and transplant due to chemotherapy toxicities (HR = 3.5) were independent risk factors, but a pediatric protocol was not (HR = 0.48). The CI of NRM and the OS rates were also similar among patients aged over 24 years old. These findings suggested that conventional allo-SCT with TBI-MAC can be performed without increasing NRM in AYA patients with Ph-negative ALL even after pediatric protocols.

Evaluating the added value of concurrent contrast-enhanced diagnostic CT for PSMA-PET/CT Interpretation.

RATIONALE AND OBJECTIVES: To determine whether concurrent contrast-enhanced diagnostic CT (DxCT) confers added diagnostic certainty compared to PSMA-PET/CT alone. MATERIALS AND METHODS: This retrospective multi-reader study analyzed imaging comprising combined F-18-piflufolastat PSMA-PET/CT with diagnostic chest/abdominopelvic CT from prostate cancer patients within the first 6 months of FDA-approval of the PET agent. Six nuclear radiology readers were randomly presented with PSMA-PET/CT studies with or without DxCT and asked to report their diagnostic certainty for PSMA-avid lesions found on PET. Subsequently, readers re-reviewed the same study after an interlude (with the CT if not previously presented and vice-versa) to determine if DxCT altered their diagnostic assessment. Inter-rater concordance was assessed on a subset of images read by all readers. Diagnostic certainties for PSMA-PET/CT with and without DxCT were compared, and the variables for which DxCT may add value were examined. RESULTS: Good inter-rater concordance across readers was noted for both PET/CT (Finn's coefficient of reliability for overall scan certainty: 0.85,p < 0.01) and combined DxCT-PET/CT (0.59,p < 0.01). Overall certainty and concordance between PET/CT and combined DxCT-PET/CT datasets were similar (overall scan certainty: 92% ± 16 vs. 92% ± 17,p = 0.43), with no significant advantage for adding DxCT across different anatomic locations or clinical parameters. A slight predilection for combined DxCT-PET/CT was noted when interpreting images acquired for the initial staging of prostate cancer (89% ± 16 vs. 93% ± 17,p = 0.08). CONCLUSION: Good inter-reader concordance can be achieved across different training levels with PSMA-PET/CT. Furthermore, using DxCT concurrent with PSMA-PET/CT does not significantly improve diagnostic certainty for most indications but may be useful for initial staging.

Participation in a High-Risk Program Is Associated with a Diagnosis of Earlier-Stage Disease Among Women at Increased Risk for Breast Cancer Development.

BACKGROUND: High-risk programs provide recommendations for surveillance/risk reduction for women at elevated risk for breast cancer development. This study evaluated the impact of high-risk surveillance program participation on clinicopathologic breast cancer features at the time of diagnosis. METHODS: Women followed in the authors' high-risk program (high-risk cohort [HRC]) with a diagnosis of breast cancer from January 2015 to June 2021 were identified and compared with the general population of women undergoing breast cancer surgery at Memorial Sloan Kettering Cancer Center (MSK; general cohort [GC]) during the same period. Patient and tumor factors were collected. Clinicopathologic features were compared between the two cohorts and in a subset of women with a family history of known BRCA mutation. RESULTS: The study compared 255 women in the HRC with 9342 women in the GC. The HRC patients were slightly older and more likely to be white and have family history than the GC patients. The HRC patients also were more likely to present with DCIS (41 % vs 23 %; p < 0.001), to have smaller invasive tumors (pT1: 100 % vs 77 %; p < 0.001), and to be pN0 (95 % vs 81 %; p < 0.001). The HRC patients had more invasive triple-negative tumors (p = 0.01) and underwent less axillary surgery (p < 0.001), systemic therapy (p < 0.001), and radiotherapy (p = 0.002). Among those with a known BRCA mutation, significantly more women in the HRC underwent screening mammography (75 % vs 40 %; p < 0.001) or magnetic resonance imaging (MRI: 82 % vs 9.9 %; p < 0.001) in the 12 months before diagnosis. CONCLUSIONS: Women followed in a high-risk screening program have disease diagnosed at an earlier stage and therefore require less-intensive breast cancer treatment than women presenting to a cancer center at the time of diagnosis. Identification of high-risk women and implementation of increased surveillance protocols are vital to improving outcomes.

Optimizing of a suitable protocol for isolating tissue-derived extracellular vesicles and profiling small RNA patterns in hepatocellular carcinoma.

BACKGROUND: Extracellular vesicles (EVs) facilitate cell-cell interactions in the tumour microenvironment. However, standard and efficient methods to isolate tumour tissue-derived EVs are lacking, and their biological functions remain elusive. METHODS: To determine the optimal method for isolating tissue-derived EVs, we compared the characterization and concentration of EVs obtained by three previously reported methods using transmission electron microscopy, nanoparticle tracking analysis, and nanoflow analysis (Nanoflow). Additionally, the differential content of small RNAs, especially tsRNAs, between hepatocellular carcinoma (HCC) and adjacent normal liver tissues (ANLTs)-derived EVs was identified using Arraystar small RNA microarray. The targets of miRNAs and tsRNAs were predicted, and downstream functional analysis was conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, non-negative matrix factorization and survival prediction analysis. RESULTS: A differential centrifugation-based protocol without cell cultivation (NC protocol) yielded higher EV particles and higher levels of CD9+ and CD63+ EVs compared with other isolation protocols. Interestingly, the NC protocol was also effective for isolating frozen tissue-derived EVs that were indistinguishable from fresh tissue. HCC tissues showed significantly higher EV numbers compared with ANLTs. Furthermore, we identified different types of small RNAs in HCC tissue-derived EVs, forming a unique multidimensional intercellular communication landscape that can differentiate between HCC and ANLTs. ROC analysis further showed that the combination of the top 10 upregulated small RNAs achieved better diagnostic performance (AUC = .950 [.895-1.000]). Importantly, most tsRNAs in HCC tissue-derived EVs were downregulated and mitochondria-derived, mainly involving in lipid-related metabolic reprogramming. CONCLUSION: The NC protocol was optimal for isolating EVs from HCC, especially from frozen tissues. Our study emphasized the different roles of small-RNA in regulating the HCC ecosystem, providing insights into HCC progression and potential therapeutic targets.

A systematic review of immunosuppressive protocols used in AAV gene therapy for monogenic disorders.

The emergence of adeno-associated virus (AAV)-based gene therapy has brought hope to patients with severe monogenic disorders. However, immune responses to AAV vectors and transgene products present challenges that require effective immunosuppressive strategies. This systematic review focuses on the immunosuppressive protocols used in 38 clinical trials and 35 real-world studies, considering a range of monogenic diseases, AAV serotypes, and administration routes. The review underscores the need for a deeper understanding of immunosuppressive regimens to enhance the safety and effectiveness of AAV-based gene therapy. Characterizing the immunological responses associated with various gene therapy treatments is crucial for optimizing treatment protocols and ensuring the safety and efficacy of forthcoming gene therapy interventions. Further research and understanding of the impact of immunosuppression on disease, therapy, and route of administration will contribute to the development of more effective and safer gene therapy approaches in the future.

Dedicated anticoagulation management protocols in fragility femoral fracture care - a source of significant variance and limited effectiveness in improving time to surgery: The hip and femoral fracture anticoagulation surgical timing evaluation (HASTE) study.

INTRODUCTION: Approximately 20 % of femoral fragility fracture patients take anticoagulants, typically warfarin or Direct Oral AntiCoagulant (DOAC). These can impact timing of surgery affecting patient survival. Due to several possible approaches and numerous factors to consider in the preoperative workup of anticoagulated patients, potential for variations in clinical practice exist. Some hospitals employ dedicated anticoagulation management protocols to address this issue, and to improve time to surgery. This study aimed to determine the proportion of hospitals with such protocols, compare protocol guidance between hospitals, and evaluate the effectiveness of protocols in facilitating prompt surgery. METHODS: Data was prospectively collected through a collaborative, multicentre approach involving hospitals across the UK. Femoral fragility fracture patients aged ≥60 years and admitted to hospital between 1st May to 31st July 2023 were included. Information from dedicated anticoagulation management protocols were collated on several domains relating to perioperative care including administration of reversal agents and instructions on timing of surgery as well as others. Logistic regression was used to evaluate effects of dedicated protocols on time to surgery. RESULTS: Dedicated protocols for management of patients taking warfarin and DOACs were present at 41 (52.6 %) and 43 (55.1 %) hospitals respectively. For patients taking warfarin, 39/41 (95.1 %) protocols specified the dose of vitamin k and the most common was 5 milligrams intravenously (n=21). INR threshold values for proceeding to surgery varied between protocols; 1.5 (n=28), 1.8 (n=6), and 2 (n=6). For patients taking DOACs, 35/43 (81.4 %) and 8/43 (18.6 %) protocols advised timing of surgery based on renal function and absolute time from last dose respectively. Analysis of 10,197 patients from 78 hospitals showed fewer patients taking DOACs received surgery within 36 h of admission at hospitals with a dedicated protocol compared to those without (adjusted OR 0.73, 95% CI 0.54-0.99, p=0.040), while there were no differences among patients taking warfarin (adjusted OR 1.64, 95% CI 0.75-3.57, p=0.219). CONCLUSIONS: Around half of hospitals employed a dedicated anticoagulation management protocol for femoral fragility fracture patients, and substantial variation was observed in guidance between protocols. Dedicated protocols currently being used at hospitals were ineffective at improving the defined targets for time to surgery.

Trends in Medicare Costs of Hyperbaric Oxygen Therapy, 2013 through 2022.

Objective: To analyze Hyperbaric Oxygen Therapy Registry (HBOTR) data to estimate the Medicare costs of hyperbaric oxygen therapy (HBO2) based on standard treatment protocols and the annual mean number of treatments per patient reported by the registry. Methods: We performed a secondary analysis of deidentified data for all payers from 53 centers registered in the HBOTR from 2013 to 2022. We estimated the mean annual per-patient costs of HBO2 based on Medicare (outpatient facility + physician) reimbursement fees adjusted to 2022 inflation using the Medicare Economic Index. Costs were calculated for the annual average number of treatments patients received each year and for a standard 40-treatment series. We estimated the 2022 costs of standard treatment protocols for HBO2 indications treated in the outpatient setting. Results: Generally, all costs decreased from 2013 to 2022. The facility cost per patient per 40 HBO2 treatments decreased by 10.7% from $21,568.58 in 2013 to $19,488.00 in 2022. The physician cost per patient per 40 treatments substantially decreased by -37.8%, from $5,993.16 to $4,346.40. The total cost per patient per 40 treatments decreased by 15.6% from $27,561.74 to $23,834.40. In 2022, a single HBO2 session cost $595.86. For different indications, estimated costs ranged from $2,383.4-$8,342.04 for crush injuries to $17,875.80-$35,751.60 for diabetic foot ulcers and delayed radiation injuries. Conclusions: This real-world analysis of registry data demonstrates that the actual cost of HBO2 is not nearly as costly as the literature has insinuated, and the per-patient cost to Medicare is decreasing, largely due to decreased physician costs.

A Comprehensive on Synthesis and Antimicrobial Evaluation of Substituted-Arylideneamino-5-(5-Chlorobenzofuran-2-yl)-1, 2, 4-Triazole-3-Thiol Derivatives/ Schiff Bases.

Schiff bases are well known and popular classes of organic compounds containing imine (R2C = NH) group that are widely used as catalysts and intermediates in numerous organic transformations. Schiff bases are medicinally very important because they exhibit antimicrobial like antibacterial, antiviral and anticancer activities. Benzofuran based Schiff bases have been found as interesting scaffolds for the synthesis and design of biologically active agents. Moreover, they possess a wide range of biological activities against fungal, bacterial, malarial, inflammatory and viral diseases. In this reviw, substituted-arylideneamino-5-(5-chlorobenzofuran-2-yl)-1,2,4-triazole-3-thiols have been synthesized by using efficient synthetic protocols. The synthesized derivatives are also evaluated against different bacterial strains.