Diverticulosis and Diverticulitis on YouTube: Is Popular Information the Most Reliable?

Background Patients utilize online health information to inform their medical decision-making. YouTube is one of the most popular media platforms with abundant health-related resources, yet the quality of the disseminated information remains unclear. This study aims to evaluate the quality and reliability of content pertaining to diverticulosis and diverticulitis on YouTube. Methods One author queried the terms "diverticulosis," "diverticulitis," "acute diverticulitis," and "chronic diverticulitis" on YouTube. The first 50 videos per search were selected for analysis. Duplicates, non-English videos, or procedural content were excluded. Video characteristics including view count, likes, comments, duration, days since upload, view ratio, video power index, and video sources (professional organizations (POs), health information websites (HIWs), and entertainment/independent users (EIUs)) were collected. Videos were scored using the mDISCERN and Global Quality Score (GQS). Results Sixty-four videos were included. DISCERN scores significantly differed between POs (n=20, mean=4.35), HIWs (n=29, mean=2.97), and EIUs (n=15, mean=1.83). GQS also significantly differed between POs (n=20, mean=4.47), HIWs (n=29, mean=3.62), and EIUs (n=15, mean=2.5). Video characteristics significantly differed between groups, with most user engagement seen in EIUs. Conclusion POs and HIWs disseminate higher quality health information about diverticular disease on YouTube. The higher viewer engagement with EIUs is concerning, as these sources were found to have lower quality content. Although YouTube has the capability to provide valuable information on diverticulosis and diverticulitis, enhanced content screening is needed to ensure accuracy and validation.

The effect of replacing conventional alfalfa hay with lower-lignin alfalfa hay on feed intake, nutrient digestibility, and energy utilization in lactating Jersey cows.

Lower-lignin (LoL) varieties of alfalfa (Medicago sativa L.) have been developed in recent years, and have the potential to positively impact animal performance. The objective of this study was to evaluate the effects of increasing the proportion of LoL alfalfa hay in diets fed to lactating dairy cows. Research plots were planted with a conventional variety (CON; Dairyland Hybriforce 3400), and 2 LoL varieties (LLG; 54HVX42 and LLB; Aflorex HiGest 460). After harvest, the LoL varieties were blended in equal proportions for feeding. Twelve multiparous Jersey cows (100 ± 4 d in milk) were used in a 3 × 3 Latin square with 3 periods of 28 d. Cows were assigned to 3 diets containing 0 (CNTRL), 16.1 (MdLL), and 32.2% (HiLL) of the diet DM as LoL alfalfa hay, which replaced CON. The CON alfalfa had average CP, NDF, and lignin contents (DM basis) of 20.5 ± 1.15, 42.1 ± 1.37, and 6.81 ± 0.57%, respectively, while the LoL alfalfa averaged 19.8 ± 0.75, 39.9 ± 1.56, and 6.07 ± 0.28%, respectively. No difference was observed in DMI (20.4 ± 0.61 kg/d). No difference in milk yield was observed, averaging 31.0 ± 1.02 kg/d across treatments. Similarly, no difference was observed in ECM yield (averaging 36.2 ± 1.43 kg/d). Feed conversion (ECM/DMI) tended to increase linearly with LoL alfalfa inclusion (1.74 to 1.80 ± 0.03). No difference was observed for milk fat yield and content (1.39 ± 0.075 kg/d and 4.51 ± 0.219%) or milk protein yield and content (1.06 ± 0.041 kg/d and 3.43 ± 0.096%). Total methane production quadratically decreased from CNTRL to MdLL then increased to HiLL (441, 389, 412 ± 18.2 L/d, respectively). No differences were observed on total-tract digestibility of DM (averaging 67.2 ± 0.55%) and NDF (averaging 50.9 ± 1.56%). No difference was observed in the concentration of DE, ME or NEL was observed averaging 2.82 ± 0.021, 2.51 ± 0.027, and 1.72 ± 0.030 Mcal/kg respectively. Our results suggest that replacing CON alfalfa with LoL alfalfa has no effects on milk production, milk composition, or nutrient digestibility but may improve feed efficiency.

Quality of Surgical Care Within the Criminal Justice Health Care System.

Importance: Individuals who are incarcerated represent a vulnerable group due to concerns about their ability to provide voluntary and informed consent, and there are considerable legal protections regarding their participation in medical research. Little is known about the quality of surgical care received by this population. Objective: To evaluate perioperative surgical care provided to patients who are incarcerated within the Texas Department of Criminal Justice (TDCJ) and compare their outcomes with that of the general nonincarcerated population. Design, Setting, and Participants: This cohort study analyzed data from patients who were incarcerated within the TDCJ and underwent general or vascular surgery at the University of Texas Medical Branch (UTMB) from 2012 to 2021. Case-specific outcomes for a subset of these patients and for patients in the general academic medical center population were obtained from the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) and compared. Additional quality metrics (mortality index, length of stay index, and excess hospital days) from the Vizient Clinical Data Base were analyzed for patients in the incarcerated and nonincarcerated groups who underwent surgery at UTMB in 2020 and 2021 to provide additional recent data. Patient-specific demographics, including age, sex, and comorbidities were not available for analysis within this data set. Main Outcome and Measures: Perioperative outcomes (30-day morbidity, mortality, and readmission rates) were compared between the incarcerated and nonincarcerated groups using the Fisher exact test. Results: The sample included data from 6675 patients who were incarcerated and underwent general or vascular surgery at UTMB from 2012 to 2021. The ACS-NSQIP included data (2012-2021) for 2304 patients who were incarcerated and 602 patients who were not and showed that outcomes were comparable between the TDCJ population and that of the general population treated at the academic medical center with regard to 30-day readmission (6.60% vs 5.65%) and mortality (0.91% vs 1.16%). However, 30-day morbidity was significantly higher in the TDCJ population (8.25% vs 5.48%, P = .01). The 2020 and 2021 data from the Vizient Clinical Data Base included 629 patients who were incarcerated and 2614 who were not and showed that the incarcerated and nonincarcerated populations did not differ with regard to 30-day readmission (12.52% vs 11.30%) or morbidity (1.91% vs 2.60%). Although the unadjusted mortality rate was significantly lower in the TDCJ population (1.27% vs 2.68%, P = .04), mortality indexes, which account for case mix index, were similar between the 2 populations (1.17 vs 1.12). Conclusions and Relevance: Findings of this cohort study suggest that patients who are incarcerated have equivalent rates of mortality and readmission compared with a general academic medical center population. Future studies that focus on elucidating the potential factors associated with perioperative morbidity and exploring long-term surgical outcomes in the incarcerated population are warranted.

[Research advances on the prevention and treatment of burn infection in the elderly].

Infection is a common complication after burns and the major cause of death in patients suffering severe burn injury. The infection of the elderly after burns is more serious due to their decreased immune function that is complicated with factors such as multiple chronic diseases and dysfunction of various organs. In addition, the burn infection in the elderly lacks the specific symptoms and signs, which brings great challenges to its diagnosis and treatment. To effectively prevent and control infection is very important for the treatment of elderly burn patients. Combined the clinical characteristics of burn infection in the elderly, this paper summarized the research advances of prevention and treatment for burn infection in the elderly from fluid resuscitation, wound treatment, antibiotic using, organ protection, nutritional support, and infection prevention, aiming to provide reference for clinical practice.

Human Patient-Derived Brain Tumor Models to Recapitulate Ependymoma Tumor Vasculature.

Despite in vivo malignancy, ependymoma lacks cell culture models, thus limiting therapy development. Here, we used a tunable three-dimensional (3D) culture system to approximate the ependymoma microenvironment for recapitulating a patient's tumor in vitro. Our data showed that the inclusion of VEGF in serum-free, mixed neural and endothelial cell culture media supported the in vitro growth of all four ependymoma patient samples. The growth was driven by Nestin and Ki67 double-positive cells in a putative cancer stem cell niche, which was manifested as rosette-looking clusters in 2D and spheroids in 3D. The effects of extracellular matrix (ECM) such as collagen or Matrigel superseded that of the media conditions, with Matrigel resulting in the greater enrichment of Nestin-positive cells. When mixed with endothelial cells, the 3D co-culture models developed capillary networks resembling the in vivo ependymoma vasculature. The transcriptomic analysis of two patient cases demonstrated the separation of in vitro cultures by individual patients, with one patient's culture samples closely clustered with the primary tumor tissue. While VEGF was found to be necessary for preserving the transcriptomic features of in vitro cultures, the presence of endothelial cells shifted the gene's expression patterns, especially genes associated with ECM remodeling. The homeobox genes were mostly affected in the 3D in vitro models compared to the primary tumor tissue and between different 3D formats. These findings provide a basis for understanding the ependymoma microenvironment and enabling the further development of patient-derived in vitro ependymoma models for personalized medicine.

Intravenous Lipid Emulsion does NOT have a role in severe poisoning: CON.

Intravenous lipid emulsion (ILE) has been suggested as a potential universal antidote for cardiovascular and central nervous system toxicity resulting from a multitude of pharmaceutical and nonpharmaceutical poisonings. While there is some evidence to suggest that ILE may have a positive effect in cardiovascular system toxicity after accidental intravenous lipophilic local anaesthetic overdose, this cannot be extrapolated to cases of severe poisoning resulting from oral drug overdose. Treatment recommendations are based upon variable outcome animal studies and low-level clinical evidence with a significant degree of positive reporting bias. Currently, there is a paucity of controlled clinical data to support ILE use to treat severe drug poisoning after oral overdose. ILE use should be limited to well-designed, ethically approved, controlled clinical trials aimed at determining the true effectiveness of this therapy. This should replace the current scattergun clinical use in a multiplicity of poisoning scenarios and subsequent anecdotal reporting approach.

Predicting General Surgery Match Outcomes Using Standardized Ranking Metrics.

INTRODUCTION: Objective measurements for applicant ranking are becoming increasingly important, not only to help address the growing number of general surgery applicants each year but also to minimize bias and ensure consistency. We assessed if our general surgery applicant scoring system was an effective tool for accurately predicting the results of the resident match. METHODS: A retrospective review of applicant rank lists from 2017 to 2020 was conducted. Applicants were ranked based on the sum of preinterview and interview scores. The preinterview score is an objective metric related to the applicant's academic portfolio. The interview score is a standardized score based on interview performance. We reviewed match results from ranked candidates and categorized them as academic categorical (AC), community categorical (CC), preliminary surgical (PS), nonsurgical specialty (NS), or unmatched (UM) positions. RESULTS: A total of 378 applicants were interviewed. Forty-nine percent matched into AC, 22% into CC, 11% into PS, and 5% into NS positions, while 13% of the interviewees were UM. Applicants who matched into AC positions had significantly higher preinterview and interview scores than applicants in other categories. Applicants who matched into CC positions had significantly higher interview scores than those categorized as UM, but their preinterview scores did not differ significantly from the UM group. Applicants who did not match into a categorical position (PS, NS, or UM) did not have significantly different preinterview or interview scores from one another. CONCLUSIONS: Our standardized scoring system was effective in stratifying which applicants would match into categorical general surgery residency programs.

Remote Instruction in Focused Assessment With Sonography in Trauma (FAST) Exams for Surgery Residents: A Pilot Study.

BACKGROUND: The Focused Assessment with Sonography in Trauma (FAST) exam is an important component to the evaluation of trauma patients. With advances in technology and meeting limitations due to COVID-19, remote instruction and learning have gained popularity. We sought to determine whether remote instruction of FAST exams was feasible as sustainable surgical education and a possible alternative to traditional in-person teaching. METHODS: General surgery residents completed a baseline survey and skills assessment on FAST exams and were then randomized to remote or in-person instruction. The remote group participated in an instructional session with a content expert through video conference and then practiced on a simulated mannequin while the expert remotely provided feedback. The in-person group received the experience with the content expert in the room. Both groups completed a post-course survey immediately after the session and a follow-up survey and objective assessment at six-months. Results were compared with two-way analysis of variance (ANOVA). RESULTS: 14 residents underwent the curriculum, seven in each group. There was a significant increase in self-reported confidence when comparing pre- and immediate post-course results for both the remote and in-person groups. At six months, confidence scores remained elevated and skill assessment scores improved, although the latter did not reach significance. There was no significant difference in post-course results between the groups. CONCLUSIONS: Remote instruction of FAST exams was feasible. Pilot data demonstrated an increase in confidence and suggest outcomes that are similar to in-person instruction, which has positive implications for future remote educational and potentially clinical initiatives.

Prevalence and Impact of Infection during Extracorporeal Membrane Oxygenation in Oncologic Patients: A Retrospective Analysis of the Extracorporeal Life Support Organization (ELSO) Registry.

Background: Extracorporeal membrane oxygenation (ECMO) is widely utilized for severe cardiopulmonary insufficiency, but its application to the oncologic population has been debated given concern for increased risk of infection. This study aims to analyze the implications of infections acquired during ECMO runs in patients with malignancy. Methods: The Extracorporeal Life Support Organization (ELSO) database was queried for patients with an International Classification of Diseases code of neoplasms over the last two decades (2000-2019). Culture-proven infections during ECMO runs were analyzed and compared to previously reported data for all ECMO runs. Results: Two thousand, seven hundred and fifty-seven patients met inclusion criteria. Infection acquired during ECMO run was found in 687 patients, a significantly greater proportion compared to all ECMO runs (24.9% vs 11.7%; P = .001). Adult patients had a significantly higher rate of infection (27.0%; P < .001) compared to neonatal (11.0%) and pediatric (21.4%) patients. Prevalence of infection was highest in pulmonary ECMO (29.0%), while the infection rate standardized with ECMO duration was highest in extracorporeal cardiopulmonary resuscitation (55.03/1000-day ECMO run). Compared with ECMO for all diagnoses, the prevalence of Candida and Klebsiella infection was significantly higher in adult and pediatric oncologic patients. Regardless of the pathogen, the presence of infection was not associated with lower survival (38.6% vs 40.0%; P = .522). Conclusions: Oncologic patients had a significantly higher infection rate while on ECMO compared with the general ECMO population. However, the prognostic impact of these infections was minimal, thus ECMO should not be withheld in oncologic patients solely with concern for infection.

Opioid use disorder in adult burn patients: Implications for future mental health, behavioral and substance use patterns.

BACKGROUND: Burn patients continue to have a high opioid requirement, despite current national trends to decrease opioid prescribing. While effective, long-term opioid use results in opioid dependence and possibly other mental health comorbidities. This retrospective cohort study seeks to evaluate implications of diagnosed opioid use disorder in the development of subsequent psychiatric, behavioral and substance abuse patterns. METHODS: The TriNetX database was queried for patients 18 years and older with a diagnosis of thermal or chemical burn who developed opioid use disorder after their burn injury. Two matched cohorts were studied, opioid use disorder versus non-opioid use disorder, to evaluate risk of developing subsequent mental health and behavioral conditions, use of psychiatric health services, and future substance abuse. RESULTS: A total of 2020 patients were identified in each cohort, matched for demographics, external trauma, and burn size. Patients in the opioid use disorder group had a significantly higher incidence of mental health diagnoses (79.7 % versus 57.7 %, OR 1.973, CI 1.741-2.236, p < 0.0001), including major depressive disorder, generalized anxiety disorder, and post-traumatic stress disorder. This group was also more likely to utilize psychiatric services (16.0 % versus 10.3 %, OR 1.926, CI 1.595-2.326, p < 0.0001) and psychotherapy (12.6 % versus 7.2 %, OR 2.046, CI 1.650-2.536, p<0.0001). Furthermore, the opioid use disorder group had higher rates of polysubstance abuse (29.9 % versus 12.3 %, OR 3.048, CI 2.588-3.589, p<0.0001), suicidal / homicidal ideations (8.2 % versus 3.2 %, OR 3.057, CI 2.274-4.109, p<0.0001), and suicide attempts (2.0 % versus 0.7 %, OR 2.971, CI 1.611-5.478, p = 0.003). CONCLUSIONS: Burn patients who develop opioid use disorder have significantly higher rates of future psychiatric diagnoses, behavioral disturbances, and polysubstance abuse. A multidisciplinary team approach, including early involvement of pain and mental health services, could potentially reduce the development of opioid use disorder and its consequences.

Percutaneous Sacroplasty with or without Radiofrequency Ablation for Treatment of Painful Sacral Metastases.

BACKGROUND AND PURPOSE: Percutaneous sacroplasty is a variation of percutaneous vertebroplasty that has gained attention as a therapeutic option for patients with painful sacral insufficiency fractures due to osteoporosis or metastases. Additionally, percutaneous sacroplasty can also be used to treat painful sacral metastases without a pathologic fracture. The purpose of this retrospective study was to compare the efficacy and safety of fluoroscopy-guided percutaneous sacroplasty alone versus percutaneous sacroplasty plus radiofrequency ablation for the treatment of painful sacral metastases. MATERIALS AND METHODS: For this retrospective study, 126 patients (with a total of 162 painful sacral metastases) were enrolled from October 2012 to February 2021 and assigned to receive either percutaneous sacroplasty plus radiofrequency ablation (n = 51, group A) or percutaneous sacroplasty alone (n = 75, group B). Four different approaches were used for percutaneous sacroplasty: transiliac, interpedicular, anterior-oblique, and posterior. The Visual Analog Scale, Oswestry Disability Index, and Karnofsky Performance Scale were used to evaluate outcomes. RESULTS: The Visual Analog Scale, Oswestry Disability Index, and Karnofsky Performance Scale scores showed significant improvement in both groups after treatment (P < .05). The overall pain relief rate was significantly better in group A than in group B (90% versus 76%, P = .032). There were no significant differences in the incidence of polymethylmethacrylate leakage between the 2 groups or among the 4 different approaches (P > .05). CONCLUSIONS: Both percutaneous sacroplasty alone and the combination of percutaneous sacroplasty and radiofrequency ablation are safe and effective for treatment of painful sacral metastases. The combination of percutaneous sacroplasty and radiofrequency ablation appears to be more effective than percutaneous sacroplasty alone.

Reviewing ACGME Plastic Surgery Fellowship Case Logs: Is Surgical Experience Increasing?

INTRODUCTION: Over the last decade, there has been a 32% decrease in independent plastic surgery fellowships. The growing prevalence of 6-year integrated plastic surgery residencies, duty hour restrictions, and new subspecialty training fellowships for general surgeons have changed the training experience of plastic surgery fellows. METHODS: A retrospective review of the Accreditation Council for Graduate Medical Education (ACGME) case logs for graduating fellows of independent plastic surgery fellowships in the United States was conducted from 2011 to 2019. A linear regression analysis was conducted for each case log code and category, and a 95% level of confidence was assumed (α = 0.05). RESULTS: In 2011, 141 residents from 69 programs graduated with an average of 1469.7 cases. In 2019, 84 residents from 47 programs graduated with an average of 1952 cases. Index procedures significantly increased overall during the 9 y (P < 0.001). Categorical cases increased in esthetics (P < 0.001), including facelift, browlift, blepharoplasty, and more. Categorical cases increased in reconstructive surgery (P < 0.001), including treatment of deformities of the skin, lower extremities, and trunk, nerve decompression, and hand reconstruction. In breast procedures, an increase was seen in the reduction of mammoplasty, reconstruction, and treatment of other breast deformities. In head and neck procedures, an increase was seen in resection of head and neck neoplasms and secondary cleft lip repair. Decreases in procedural numbers were seen in primary cleft lip repair and hand reconstruction by primary closure. CONCLUSIONS: Despite a 32% decline in the number of independent plastic surgery fellowships over the last 9 y, plastic surgery fellows are obtaining significantly more surgical experience, both in esthetic and reconstructive surgery.

Oncoplastic reconstruction of a large chest wall defect using dual fasciocutaneous flaps: A case report.

INTRODUCTION AND IMPORTANCE: Large chest wall defects in the context of breast cancer or its sequelae can be challenging to address. Oncoplastic techniques have been demonstrated to be safe and feasible options for immediate reconstruction. We describe the use of dual fasciocutaneous flaps for coverage following resection of a large chest wall mass in an area with a remote history of radiation therapy. CASE PRESENTATION: A 67-year-old woman with a distant history of bilateral mastectomies and adjuvant chemoradiation for Stage IIB triple negative invasive ductal carcinoma presented with an enlarging left chest wall mass and chronic wound. The mass was excised with adequate margins, and the resulting defect was reconstructed with two locoregional fasciocutaneous flaps. Pathology returned negative for malignancy and follow-up demonstrated viable flaps that were healing well. CLINICAL DISCUSSION: Fasciocutaneous flaps are one of many techniques for breast reconstruction and offer advantages of a relatively superficial dissection, shorter operative time, and decreased risk of functional impairment. They are consequently an attractive option for patients with multiple comorbidities and high risk of perioperative complications. Historically used for immediate reconstruction at the time of oncologic resection, we present its successful use decades after the index cancer operation to manage a chest wall defect secondary to radiation injury. CONCLUSIONS: Oncoplastic reconstruction with dual fasciocutaneous flaps is a feasible option for a large chest wall defect in the setting of previous radiation.

3D patient-derived tumor models to recapitulate pediatric brain tumors In Vitro.

Brain tumors are the leading cause of cancer-related deaths in children. Tailored therapies need preclinical brain tumor models representing a wide range of molecular subtypes. Here, we adapted a previously established brain tissue-model to fresh patient tumor cells with the goal of establishing3D in vitro culture conditions for each tumor type.Wereported our findings from 11 pediatric tumor cases, consisting of three medulloblastoma (MB) patients, three ependymoma (EPN) patients, one glioblastoma (GBM) patient, and four juvenile pilocytic astrocytoma (Ast) patients. Chemically defined media consisting of a mixture of pro-neural and pro-endothelial cell culture medium was found to support better growth than serum-containing medium for all the tumor cases we tested. 3D scaffold alone was found to support cell heterogeneity and tumor type-dependent spheroid-forming ability; both properties were lost in 2D or gel-only control cultures. Limited in vitro models showed that the number of differentially expressed genes between in vitro vs. primary tissues, are 104 (0.6%) of medulloblastoma, 3,392 (20.2%) of ependymoma, and 576 (3.4%) of astrocytoma, out of total 16,795 protein-coding genes and lincRNAs. Two models derived from a same medulloblastoma patient clustered together with the patient-matched primary tumor tissue; both models were 3D scaffold-only in Neurobasal and EGM 1:1 (v/v) mixture and differed by a 1-mo gap in culture (i.e., 6wk versus 10wk). The genes underlying the in vitrovs. in vivo tissue differences may provide mechanistic insights into the tumor microenvironment. This study is the first step towards establishing a pipeline from patient cells to models to personalized drug testing for brain cancer.

[Fluid resuscitation strategy and efficacy evaluation in shock stage in severely burned children with different burn areas in different age groups].

Objective: To explore the fluid resuscitation strategy in shock stage in severely burned children with different burn areas in different age groups, and to evaluate the curative effect. Methods: A retrospective cohort study was conducted. From January 2015 to June 2020, 235 children with severe and above burns who met the inclusion criteria were hospitalized in the First Affiliated Hospital of Nanchang University, including 150 males and 85 females, aged 3 months to 12 years. After admission, it was planned to rehydrate the children with electrolyte, colloid, and water according to the domestic rehydration formula for pediatric burn shock, and the rehydration volume and speed were adjusted according to the children's mental state, peripheral circulation, heart rate, blood pressure, and urine output, etc. The actual input volume and planned input volume of electrolyte, colloid, water, and total fluid of all the children were recorded during the 8 hours since fluid replacement and the first and second 24 hours after injury. According to urine output during the 8 hours since fluid replacement, all the children were divided into satisfactory urine output maintenance group (119 cases) with urine output ≥1 mL·kg-1·h-1 and unsatisfactory urine output maintenance group (116 cases) with urine output <1 mL·kg-1·h-1, and the electrolyte coefficient, colloid coefficient, and water coefficient of the children were calculated during the 8 hours since fluid replacement. According to the total burn area, children aged <3 years (155 cases) and 3-12 years (80 cases) were divided into 15%-25% total body surface area (TBSA) group and >25%TBSA group, respectively. The electrolyte coefficient, colloid coefficient, water coefficient, and urine output of the children were calculated or counted during the first and second 24 hours after injury, and the non-invasive monitoring indicators of body temperature, heart rate, respiratory rate, and percutaneous arterial oxygen saturation and efficacy indicators of hematocrit, platelet count, hemoglobin, albumin, creatinine, and alanine aminotransferase (ALT) of the children were recorded 48 hours after injury. The prognosis and outcome indicators of all the children during the treatment were counted, including complications, cure, improvement and discharge, automatic discharge, and death. Data were statistically analyzed with independent sample or paired sample t test, Mann-Whitney U test, chi-square test, and Fisher's exact probability test. Results: During the 8 hours since fluid replacement, the actual input volume of electrolyte of all the children was significantly more than the planned input volume, and the actual input volumes of colloid, water, and total fluid were significantly less than the planned input volumes (Z=13.094, 5.096, 13.256, 7.742, P<0.01). During the first and second 24 hours after injury, the actual input volumes of electrolyte of all the children were significantly more than the planned input volumes, and the actual input volumes of water and total fluid were significantly less than the planned input volumes (Z=13.288, -13.252, 3.867, 13.183, -13.191, 10.091, P<0.01), while the actual input volumes of colloid were close to the planned input volumes (P>0.05). During the 8 hours since fluid replacement, compared with those in unsatisfactory urine output maintenance group, there was no significant change in electrolyte coefficient or colloid coefficient of children in satisfactory urine output maintenance group (P>0.05), while the water coefficient was significantly increased (Z=2.574, P<0.05). Among children <3 years old, compared with those in >25%TBSA group, the electrolyte coefficient and water coefficient of children were significantly increased and the urine output of children was significantly decreased in 15%-25%TBSA group during the first and second 24 hours after injury (Z=-3.867, -6.993, -3.417, -5.396, -5.062, 1.503, P<0.05 or P<0.01), while the colloid coefficient did not change significantly (P>0.05); the levels of efficacy indicators of hematocrit, platelet count, and hemoglobin at 48 h after injury were significantly increased, while ALT level was significantly decreased (Z=-2.720, -3.099, -2.063, -2.481, P<0.05 or P<0.01); the levels of the rest of the efficacy indicators and non-invasive monitoring indicators at 48 h after injury did not change significantly (P>0.05). Among children aged 3-12 years, compared with those in >25%TBSA group, the electrolyte coefficient and water coefficient of children in 15%-25%TBSA group were significantly increased during the first and second 24 hours after injury, the colloid coefficient during the second 24 h was significantly decreased (Z=-2.042, -4.884, -2.297, -3.448, -2.480, P<0.05 or P<0.01), while the colloid coefficient during the first 24 hours after injury, urine output during the first and second 24 hours after injury, and the non-invasive monitoring indicators and efficacy indicators at 48 hours after injury did not change significantly (P>0.05). Complications occurred in 17 children during the treatment. Among the 235 children, 211 cases were cured, accounting for 89.79%, 5 cases were improved and discharged, accounting for 2.13%, 16 cases were discharged automatically, accounting for 6.81%, and 3 cases died, accounting for 1.28%. Conclusions: The electrolyte volume in early fluid resuscitation in severely burned children exceeding the volume calculated by the formula can obtain a good therapeutic effect. Among children <3 years old, the volume of fluid resuscitation should be appropriately increased in children with extremely severe burns compared with children with severe burns during fluid resuscitation; among children aged 3-12 years, the colloid volume should be appropriately increased in children with extremely severe burns compared with children with severe burns during fluid resuscitation; non-invasive monitoring indicators can be used to monitor hemodynamics and guide fluid resuscitation in severely burned children.

Conventional oxygen therapy versus CPAP as a ceiling of care in ward-based patients with COVID-19: a multi-centre cohort evaluation.

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is commonly used for respiratory failure due to severe COVID-19 pneumonitis, including in patients deemed not likely to benefit from invasive mechanical ventilation (nIMV). Little evidence exists demonstrating superiority over conventional oxygen therapy, whilst ward-level delivery of CPAP presents practical challenges. We sought to compare clinical outcomes of oxygen therapy versus CPAP therapy in patients with COVID-19 who were nIMV. METHODS: This retrospective multi-centre cohort evaluation included patients diagnosed with COVID-19 who were nIMV, had a treatment escalation plan of ward-level care and clinical frailty scale ≤ 6. Recruitment occurred during the first two waves of the UK COVID-19 pandemic in 2020; from 1st March to May 31st, and from 1st September to 31st December. Patients given CPAP were compared to patients receiving oxygen therapy that required FiO2 ≥0.4 for more than 12 hours at hospitals not providing ward-level CPAP. Logistic regression modelling was performed to compare 30-day mortality between treatment groups, accounting for important confounders and within-hospital clustering. FINDINGS: Seven hospitals provided data for 479 patients during the UK COVID-19 pandemic in 2020. Overall 30-day mortality was 75.6% in the oxygen group (186/246 patients) and 77.7% in the CPAP group (181/233 patients). A lack of evidence for a treatment effect persisted in the adjusted model (adjusted odds ratio 0.84 95% CI 0.57-1.23, p=0.37). 49.8% of patients receiving CPAP-therapy (118/237) chose to discontinue it. INTERPRETATION: No survival difference was found between using oxygen alone or CPAP to treat patients with severe COVID-19 who were nIMV. A high patient-initiated discontinuation rate for CPAP suggests a significant treatment burden. Further reflection is warranted on the current treatment guidance and widespread application of CPAP in this setting. FUNDING: L Pearmain is supported by the MRC (MR/R00191X/1). TW Felton is supported by the NIHR Manchester Biomedical Research Centre.

Simultaneous blocking of the pan-RAF and S100B pathways as a synergistic therapeutic strategy against malignant melanoma.

Melanoma is a very aggressive form of skin cancer. Although BRAF inhibitors have been utilized for melanoma therapy, advanced melanoma patients still face a low five-year survival rate. Recent studies have shown that CRAF can compensate for BRAF depletion via regulating DNA synthesis to remain melanoma proliferation. Hence, targeting CRAF either alone or in combination with other protein pathways is a potential avenue for melanoma therapy. Based on our previously reported CRAF-selective inhibitor for renal cancer therapy, we have herein discovered an analogue (complex 1) from the reported CRAF library suppresses melanoma cell proliferation and melanoma tumour growth in murine models of melanoma via blocking the S100B and RAF pathways. Intriguingly, we discovered that inhibiting BRAF together with S100B exerts a novel synergistic effect to significantly restore p53 transcription activity and inhibit melanoma cell proliferation, whereas blocking BRAF together with CRAF only had an additive effect. We envision that blocking the pan-RAF and S100B/p53 pathways might be a novel synergistic strategy for melanoma therapy and that complex 1 is a potential inhibitor against melanoma via blocking the pan-RAF and S100B pathways.

Potential anti-ageing effect of chondroitin sulphate through skin regeneration.

OBJECTIVE: Skin ageing is inevitably exposed through its typical features such as wrinkles and sagging. Therefore, skin anti-ageing is a major issue in cosmetic research to prevent and improve ageing symptoms using effective ingredients. Chondroitin sulphate (CS), a type of glycosaminoglycan, is an important structural component of the extracellular matrix (ECM) and is involved in various biological processes, such as cell proliferation, differentiation and migration. Here, we aimed to investigate the effects of CS on skin regeneration and examine its efficacy as a potential safe and effective skin anti-ageing ingredient. METHODS: We investigated the effects of CS on cell proliferation in normal human keratinocytes and fibroblasts. Then, cell migration, ECM synthesis and related signalling pathways were examined in fibroblasts through gene and protein expression analysis. Finally, the effect on skin wound healing and regeneration was validated using a full-thickness skin wound model and an aged skin model. RESULTS: Chondroitin sulphate treatment increased the proliferation of keratinocytes and fibroblasts. It also stimulated the migration and synthesis of ECM components of fibroblasts. Further analysis revealed that CS induced the expression of type I procollagen by activating the extracellular signal-regulated kinase pathway. Using a full-thickness skin wound model and an aged skin model, we confirmed that CS treatment promoted skin wound healing and regeneration. CONCLUSION: Together, our results indicated that CS has the potential to facilitate skin regeneration, implying that CS could be clinically applied to improve skin ageing.

OBJECTIF: Le vieillissement cutané est inévitable, dans ses caractéristiques intrinsèques nous trouvons l'apparition des rides et l'affaissement de la peau. Sachant cela, l'anti-âge cutané est un enjeu majeur de la recherche cosmétique où sa prévention ou son amélioration sont faites à l'aide d'ingrédients efficaces. Le sulfate de chondroïtine (CS), un type de glycosaminoglycane, est un composant structurel important de la matrice extracellulaire (ECM) et il est aussi impliqué dans les divers processus biologiques, tels que la prolifération, la différenciation et la migration cellulaire. Dans le travail présenté ici, nous avons étudié les effets du CS sur la régénération de la peau et son efficacité en tant qu'ingrédient anti-âge cutané sûr. MÉTHODES: Nous avons étudié les effets du CS sur la prolifération cellulaire des kératinocytes et fibroblastes humains normaux. Ensuite, la migration cellulaire, la synthèse de la ECM et les voies de signalisation associées ont été examinées dans les fibroblastes par l'analyse de l'expression des gènes et des protéines. Finalement, l'effet sur la cicatrisation et la régénération cutanées a été validé à l'aide d'un modèle de plaie cutanée « full thickness ¼ et d'un modèle de peau âgée. RÉSULTATS: Le traitement au sulfate de chondroïtine a augmenté la prolifération des kératinocytes et des fibroblastes. Il a également stimulé la migration et la synthèse des composants de la MEC des fibroblastes. Une analyse plus approfondie a démontré que CS induisait l'expression du procollagène du type I en activant la voie de la kinase régulée par le signal extracellulaire. En utilisant un modèle de plaie cutanée « full thickness ¼ et un modèle de peau âgée, nous avons confirmé que le traitement CS favorisait la cicatrisation et la régénération des blessures cutanées. CONCLUSION: Dans l'ensemble, nos résultats ont indiqué que le CS a le potentiel de faciliter la régénération de la peau, ce qui implique que le CS pourrait être appliqué cliniquement pour améliorer le vieillissement cutané.

The shape change index (SCI) of inferior vena cava (IVC) measuring by transabdominal ultrasound to predict the presence of septic shock in intensive care unit (ICU) patients.

OBJECTIVE: This study is designed as prospective and observational research of patients with sepsis. It was carried out in the intensive care unit (ICU). We investigated the shape change index (SCI) of inferior vena cava (IVC) measured with trans-abdominal ultrasound to detect the signs of septic shock. The aim of this research was to find the most effective tool in predicting shock in patients compared with that of other parameters such as brain natriuretic peptide (BNP), lactate, variation index of inferior vena cava IVC-VI, and extravascular lung water index (EVLWI). PATIENTS AND METHODS: We suppose that SCI can be used as the safest and most sensitive tool in the early recognition of septic dysfunction. The observational study was conducted in the Department of ICU, Shandong Provincial Hospital Affiliated to Shandong University from January 2016 to December 2017. SCI of IVC, serum lactate, BNP, IVC-VI, and EVLWI concentrations were measured in 30 sepsis patients. All studied biomarkers were analyzed and contrasted according to the score of the Sequential Organ Failure Assessment (SOFA). Pearson correlation analysis was analyzed to statistic the relationship between variables. RESULTS: We showed the correlation of BNP value, lactic acid value, IVC-VI, EVLWI, and SCI of IVC in sick patients suffering septic shock. Positive correlation was observed in the BNP value, lactic acid value, IVC-VI, EVLWI, and SCI of IVC (r=0.447, p=0.013; r=0.484, p=0.007; r=0.423, p=0.023; r=0.638, p<0.001; r=0.599, p<0.001; respectively). However, the SCI and EVLWI showed a stronger correlation with the SOFA than the others. SCI of IVC, as estimated by transabdominal ultrasound, was more accurate than the other commonly used non-invasive predictors. EVLWI, as an accurate and classical predictor, was an invasive predictor. SCI of IVC was faster, more convenient and safer than the other. CONCLUSIONS: SCI of IVC was faster, more convenient and safer than the other commonly used non-invasive predictors. Early recognition and diagnosis of sepsis may improve patient outcome.

Film interface for drug testing for delivery to cells in culture and in the brain.

Brain access remains a major challenge in drug testing. The nearly 'impermeable' blood-brain-barrier (BBB) prevents most drugs from gaining access to brain cells via systematic intravenous (IV) injection. In this study, silk fibroin films were used as drug carrier as well as cell culture substrate to simulate the in vivo interface between drug reservoir and brain cells for testing drug delivery in the brain. In in vitro studies, film-released arabinofuranosyl cytidine (AraC), a mitotic inhibitor, selectively killed glial cells in film-supported mixed neural cell cultures; with widened dosage windows for drug efficacy and tolerance compared to drugs in solution. In the brain, the presence of silk films was well tolerated with no signs of acute neuroinflammation, cell death, or altered brain function. Topical application of silk films on the cortical surface delivered Evans blue, a BBB-impenetrable fluorescent marker, through the intact dura matter into the parenchyma of the ipsilateral hemisphere as deep as the hippocampal region, but not the contralateral hemisphere. In a mouse traumatic brain injury (TBI) model, necrosis markers by film delivery accessed more cells in the lesion core than by con-current IV delivery; whereas the total coverage including the peri-lesional area appeared to be comparable between the two routes. The complementary distribution patterns of co-delivered markers provided direct evidence of the partial confinement of either route's access to brain cells by a restrictive zone near the lesion border. Finally, film-delivered necrostatin-1 reduced overall cell necrosis by approximately 40% in the TBI model. These findings from representative small molecules of delivery route-dependent drug access are broadly applicable for evaluating drug actions both in vitro and in vivo. Combined with its demonstrated role of supporting neuron-electrode interfaces, the film system can be further developed for testing a range of neuromodulation approaches (i.e., drug delivery, electrical stimulation, cell graft) in the brain. STATEMENT OF SIGNIFICANCE: This study demonstrated that silk fibroin films can be used to evaluate drug actions both in vitro and in vivo, partially overcoming the significant delivery barriers of the brain. This system can be adapted for efficient drug access to specific brain regions and/or cell types. The film system can be further developed for testing a range of interventions with drugs, electrical signals or cell graft for analysis of treatment outcomes including cell responses and brain function.