Examination of plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation in former elite American football players.

INTRODUCTION: Blood-based biomarkers offer a promising approach for the detection of neuropathologies from repetitive head impacts (RHI). We evaluated plasma biomarkers of amyloid, tau, neurodegeneration, and inflammation in former football players. METHODS: The sample included 180 former football players and 60 asymptomatic, unexposed male participants (aged 45-74). Plasma assays were conducted for beta-amyloid (Aß) 40, Aß42, hyper-phosphorylated tau (p-tau) 181+231, total tau (t-tau), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), Aß42/p-tau181 and Aß42/Aß40 ratios. We evaluated their ability to differentiate the groups and associations with RHI proxies and traumatic encephalopathy syndrome (TES). RESULTS: P-tau181 and p-tau231(padj = 0.016) were higher and Aß42/p-tau181 was lower(padj = 0.004) in football players compared to controls. Discrimination accuracy for p-tau was modest (area under the curve [AUC] = 0.742). Effects were not attributable to AD-related pathology. Younger age of first exposure (AFE) correlated with higher NfL (padj = 0.03) and GFAP (padj = 0.033). Plasma GFAP was higher in TES-chronic traumatic encephalopathy (TES-CTE) Possible/Probable (padj = 0.008). DISCUSSION: Plasma p-tau181 and p-tau231, GFAP, and NfL may offer some usefulness for the characterization of RHI-related neuropathologies. HIGHLIGHTS: Former football players had higher plasma p-tau181 and p-tau231 and lower Aß42/ptau-181 compared to asymptomatic, unexposed men. Younger age of first exposure was associated with increased plasma NfL and GFAP in older but not younger participants. Plasma GFAP was higher in participants with TES-CTE possible/probable compared to TES-CTE no/suggestive.

Preoperative Mental Health Disorders Affect Opioid Consumption and Perioperative Complications After Total Shoulder Arthroplasty.

BACKGROUND: Limited evidence exists regarding the influence of mental health disorders (MHDs) on opioid use and complications after total shoulder arthroplasty (TSA). We aimed to identify the prevalence of common MHDs among patients undergoing anatomic TSA (aTSA) and reverse TSA (rTSA). MATERIALS AND METHODS: The Premier Healthcare Database was queried for patients undergoing primary aTSA and rTSA from 2016 to 2020. International Classification of Diseases, Tenth Revision, diagnosis codes were used to identify MHDs. Primary outcomes included the prevalence of MHDs, perioperative opioid consumption, and 90-day risk of postoperative complications, revision, and readmission. Bivariate and multivariate regression analyses were performed to assess 90-day risk of primary endpoints while controlling for potential confounders. Statistical significance was defined as P<.05. RESULTS: From 2016 to 2020, 49,997 of 144,725 (34.55%) patients undergoing primary TSA had at least one diagnosed MHD. The most prevalent were depression (17.03%), anxiety (16.75%), and substance use disorder (10.20%). Patients with a MHD had higher mean hospital costs ($75,984±$43,129 vs $73,316±$39,046, P<.0001), longer mean length of stay (1.95±2.25 days vs 1.61±1.51 days, P<.0001), and higher mean total postoperative opioid use (72.00±231.55 morphine milligram equivalents [MMEs] vs 59.32±127.31 MMEs, P<.0001). Periprosthetic fractures (odds ratio, 1.20; P=.041), dislocation (odds ratio, 1.12; P=.042), and 90-day readmission rates (odds ratio, 1.26; P<.001) were significantly higher among patients with a MHD. CONCLUSION: This study found that MHDs are associated with significantly increased perioperative opioid consumption, medical and surgical complication rates, and risk of readmission after TSA. Recognition and optimization of MHDs is critical to minimizing complications and opioid consumption after TSA. [Orthopedics. 202x;4x(x):xx-xx.].

Multilevel factors drive child exposure to enteric pathogens in animal feces: A qualitative study in northwestern coastal Ecuador.

Exposure to animal feces and associated enteric pathogens poses significant risks to child health. However, public health strategies to mitigate enteric infections among children largely aim to reduce exposure to human feces, overlooking transmission pathways related to animal feces. In this study we examine if and how children are exposed to enteric pathogens in animal feces in northwestern coastal Ecuador. We conducted qualitative interviews with mothers of children aged 10-18 months that owned (n = 32) and did not own (n = 26) animals in urban and rural communities. Using thematic analysis, we identified community, household, and child behavioral factors that influence exposure. We also compared child exposure by household animal ownership. Our findings revealed myriad opportunities for young children to be exposed to enteric pathogens in many locations and from multiple animal sources, regardless of household animal ownership. Animal feces management practices (AFM) used by mothers, such as rinsing feces into ditches and throwing feces into surrounding areas, may increase environmental contamination outside their homes and in their communities. Unsafe AFM practices were similar to unsafe child feces management practices reported in other studies, including practices related to defecation location, feces removal and disposal, environmental contamination cleaning, and handwashing. Findings suggest that animal feces may contaminate the environment along similar pathways as human feces. Identification and incorporation of safe AFM practices, similar to those developed for child feces management, would 1) mitigate child exposure to enteric pathogens by reducing animal feces contamination in domestic and public spaces; and 2) enable an integrated approach to address enteric pathogen exposure pathways related to animal and child feces.

The Impact of GeneXpert Cerebrospinal Fluid Testing on Tuberculous Meningitis Diagnosis in Routine Care in Botswana.

Background: Tuberculous meningitis (TBM) disproportionately impacts high-HIV prevalence, resource-limited settings where diagnosis is challenging. The GeneXpert platform has utility in TBM diagnosis, but uptake remains limited. In Botswana, before the introduction of GeneXpert, tuberculosis (TB) testing was only available through mycobacterial culture at the National TB Reference Laboratory. Data describing routine use of Xpert MTB/RIF for cerebrospinal fluid (CSF) testing in resource-limited settings are scarce. Methods: Electronic records for patients with CSF tested in government facilities in Botswana between 2016 and 2022 were obtained from a central online repository as part of ongoing national meningitis surveillance. Samples were excluded from 1 site where Xpert MTB/RIF is performed universally. The proportion receiving TB-specific investigation on CSF and the number positive for Mycobacterium tuberculosis following increased Xpert MTB/RIF capacity were determined. Results: The proportion of CSF samples receiving TB-specific investigation increased from 4.5% (58/1288) in 2016 to 29.0% (201/693) in 2022, primarily due to increased analysis with Xpert MTB/RIF from 0.9% (11/1288) to 23.2% (161/693). There was an overall decline in the annual number of CSF samples analyzed, but the proportion with microbiologically confirmed TBM increased from 0.4% to 1.2%. The proportion of samples tested for TB that were collected from health care facilities >100 km from the National TB Reference Laboratory increased with Xpert MTB/RIF rollout from 65.9% (87/132) to 78.0% (494/633). Conclusions: In Botswana, access to TB culture is challenging in remote populations; more accessible near-patient testing using Xpert MTB/RIF increased the number of patients receiving TB-specific testing on CSF and the number of confirmed TBM cases.

Commercial Insurance Coverage Criteria for Autologous Chondrocyte Implantation Poorly Reflect Current Research.

OBJECTIVE: The aim of this study is to both quantify and qualify the way insurance companies justify their coverage policies for autologous chondrocyte implantation (ACI) and determine whether these policies align with recent research on the subject. DESIGN: The top 11 national commercial health insurance payers for ACI were identified. Coverage policy documents were recovered for 8 payers. These documents were examined, and the type of reference and the level of evidence (LOE) were recorded for each applicable reference. Specific coverage criteria for each individual payer were then extracted and assessed for similarities among commercial payers. Finally, all references cited by each payer were examined to determine whether they mentioned the specific payer criteria. RESULTS: This study found that the majority of cited references were primary journal articles (86, 58.1%) and that only 30 (20.2%) references were level I or level II evidence. This study also found significant homogeneity among payer coverage criteria. Cited sources inconsistently mentioned specific payer coverage criteria. In addition, payer criteria tended to be poorly supported by current evidence on ACI. CONCLUSIONS: This study demonstrates that commercial insurance payers' coverage policies for ACI poorly cite references, cite a majority of references with low LOE, and cite references which infrequently mention their specific coverage criteria. In addition, payer coverage policies have a high degree of homogeneity and many of their specific criteria are poorly supported by current research on ACI.

Flap-Based Lower Extremity Reconstruction in the Elderly-Is It Safe and Does Age Impact Ambulation?

INTRODUCTION: Lower extremity (LE) reconstruction in the elderly population presents a multifaceted challenge, primarily due to age-related degenerative changes, comorbidities, and functional decline. Elderly individuals often encounter conditions such as osteoarthritis, osteoporosis, and cardiovascular and peripheral artery disease (PAD), which can severely compromise the structural integrity and function of the lower limbs. As such, we aim to assess postoperative complications and functional recovery following LE reconstruction in elderly patients. METHODS: Patients ≥ 18 years who underwent post-traumatic LE reconstruction with flap reconstruction at a Level 1 trauma center between 2007 and 2022 were included. Patient demographics, flap/wound characteristics, complications, and ambulation for the elderly (≥ 60 years old) and the control (< 60 years old) cohorts were recorded. The primary outcome was final ambulation status, modeled with logistic regression. Secondary outcomes included postoperative complications. RESULTS: The mean ages of the control (n = 374) and elderly (n = 49) groups were 37.4 ± 12.6 and 65.8 ± 5.1 years, respectively. Elderly patients more frequently required amputation after flap surgery (p = 0.002). There was no significant difference between the two cohorts in preoperative ambulation status (p = 0.053). Postoperatively, 22.4% of elderly patients were independently ambulatory at final follow-up, compared to 49.5% of patients < 60. Of the elderly, 14.3% could ambulate with an assistance device (cane, walker, etc.), compared to 26.5% in the control group. A wheelchair was required for 46.9% of elderly patients, significantly higher than the 22.7% of those < 60 years of age (p < 0.001). Multivariate regression confirmed an association between older age and nonambulatory final status (p = 0.033). CONCLUSION: LE reconstruction can likely be performed safely in patients 60 years of age or older. However, older age is independently associated with significantly worse postoperative ambulation. Preoperative assessment, including gait and muscle strength, and early initiation of postoperative rehabilitation can potentially improve ambulation in elderly individuals undergoing LE reconstruction.

The development and validation of a survey to measure fecal-oral child exposure to zoonotic enteropathogens: The FECEZ Enteropathogens Index.

Child exposure to animal feces and associated enteropathogens contribute to a significant burden of disease in low- and middle-income countries. However, there are no standardized, validated survey-based approaches to enable accurate assessment of child exposure to zoonotic enteropathogens. We developed and validated a survey-based measure of exposure, the fecal-oral child exposure to zoonotic enteropathogens Index (the FECEZ Enteropathogens Index). First, we identified critical attributes of child exposure through in-depth interviews (IDIs) in Ecuador among individuals who care for animals (n = 29) and mothers of children under two years old (n = 58), and through a systematic review of existing exposure measures. Second, based on these findings, we developed a 105-question survey and administered it to 297 mothers with children under age five. Third, we refined the survey, using principal component analysis to determine the optimal number of components. The final index consisted of 34 items across two sub-domains: the child Environment and child Behavior. Lastly, we compared index scores to two commonly used, unvalidated measures of child exposure-maternal reported household animal ownership and presence of animal feces. Using the FECEZ Enteropathogens Index revealed varying degrees of exposure in our study population, with only two children having no exposure. In contrast, if we had used animal ownership or the presence of animal feces as a measure of exposure, 44% and 33% of children would have been classified as having no exposure, respectively. These common binary exposure measures may be inadequate because they do not provide sufficient information to identify the relative risk of zoonotic pathogen exposure. The FECEZ Enteropathogens Index overcomes this limitation, advancing our ability to assess exposure by quantifying the multiple components of child exposure to zoonotic enteropathogens with higher resolution. Additional testing and evaluation of the index is needed to ensure its reliability, validity, and cross-cultural equivalence in other contexts.

Clinical and Neuropathological Correlates of Substance Use in American Football Players.

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy more frequently found in deceased former football players. CTE has heterogeneous clinical presentations with multifactorial causes. Previous literature has shown substance use (alcohol/drug) can contribute to Alzheimer's disease and related tauopathies pathologically and clinically. Objective: To examine the association between substance use and clinical and neuropathological endpoints of CTE. Methods: Our sample included 429 deceased male football players. CTE was neuropathologically diagnosed. Informant interviews assessed features of substance use and history of treatment for substance use to define indicators: history of substance use treatment (yes vs no, primary variable), alcohol severity, and drug severity. Outcomes included scales that were completed by informants to assess cognition (Cognitive Difficulties Scale, BRIEF-A Metacognition Index), mood (Geriatric Depression Scale-15), behavioral regulation (BRIEF-A Behavioral Regulation Index, Barratt Impulsiveness Scale-11), functional ability (Functional Activities Questionnaire), as well as CTE status and cumulative p-tau burden. Regression models tested associations between substance use indicators and outcomes. Results: Of the 429 football players (mean age = 62.07), 313 (73%) had autopsy confirmed CTE and 100 (23%) had substance use treatment history. Substance use treatment and alcohol/drug severity were associated with measures of behavioral regulation (FDR-p-values<0.05, ΔR2 = 0.04-0.18) and depression (FDR-p-values<0.05, ΔR2 = 0.02-0.05). Substance use indicators had minimal associations with cognitive scales, whereas p-tau burden was associated with all cognitive scales (p-values <0.05). Substance use treatment had no associations with neuropathological endpoints (FDR-p-values>0.05). Conclusions: Among deceased football players, substance use was common and associated with clinical symptoms.

The Impact of Increased Body Mass Index on Patient Outcomes and Complications in Microsurgical Lower Extremity Reconstruction.

BACKGROUND: Elevated body mass index (BMI) is a known perioperative risk factor for complications such as delayed wound healing and infection. However, there is a gap in understanding how elevated BMI impacts outcomes after posttraumatic lower extremity (LE) microvascular reconstruction. METHODS: A retrospective review was performed at a level 1 trauma center between 2007 and 2022 of patients who underwent posttraumatic microvascular LE reconstruction. Demographics, flap/wound details, complications, and outcomes were recorded. Patients were stratified into BMI Center for Disease Control categories. RESULTS: A total of 398 patients were included with an average BMI of 28.2 ± 5.8. Nearly half (45%) of LE defects were located in the distal third of the leg, 27.5% in the middle third, and 34.4% in the proximal third. Most reconstructions utilized muscle-containing flaps (74.4%) compared with fasciocutaneous flaps (16.8%). Surgical approaches included free flaps (47.6%) and local flaps (52.5%). Class III obese patients were significantly more likely to be nonambulatory than nonobese patients (OR: 4.10, 95% CI 1.10-15.2, p = 0.035). At final follow-up, 30.1% of patients with Class III obesity were ambulatory, requiring either wheelchairs (42.3%) or assistance devices (26.9%). There were no significant differences in complication rates based on obesity status (0.704). The average follow-up time for the entire cohort was 5.8 years. CONCLUSIONS: BMI is critical for patient care and surgical decision-making in LE reconstruction. Further research is warranted to optimize outcomes for higher BMI patients, thereby potentially reducing the burden of postoperative complications and enhancing overall patient recovery.

The use of Reflectance Confocal Microscopy to diagnose Malignant Melanoma and Lentigo Maligna in the United Kingdom: A Prospective Observational Trial at a Single Centre.

BACKGROUND: Previous work with Reflectance Confocal Microscopy (RCM) imaging has shown high sensitivity and specificity for Malignant Melanoma (MM), but to date there have been no studies on a UK cohort. OBJECTIVES: The study hypothesised that RCM could be used prospectively to accurately diagnose MM and lentigo maligna (LM) in a private UK secondary care, single clinician setting. The study assessed the potential for RCM to be used as a routine screening procedure. METHODS: 597 patients were recruited consecutively where MM or LM featured in the differential diagnosis after clinical examination. A sequential record was made of the clinical, dermoscopic, and RCM findings by a single dermatologist [HS] prior to biopsy. Imaging used the arm-mounted confocal microscope unless access was restricted and required the handheld probe. The likelihood of MM was scored for each modality, each diagnosis building on the last. Histology was assessed by a single blinded histopathologist [JJ]. RESULTS: 734 lesions were included in the analysis, including 86 MM and LM with a median diameter of 7.0 mm. The benign to malignant ratio was 3 to 1 (non-melanocytic malignancies included) and 8.3 to 1 for MM and LM only. The sensitivity and specificity for MM and LM was 62.8% (95% CI 51.70% to 72.98%) and 63.2% (59.27% to 66.84%) for clinical examination; 91.9% (83.95% to 96.66%) and 42.1% (38.14% to 45.88%) for dermoscopy; 94.2% (86.95% to 98.09%) and 83.2% (79.91% to 85.84%) for RCM. For RCM, PPV was 42.4% (38.13% to 46.81%) and NPV was 99.1% (97.87% to 99.60%). CONCLUSION: This study demonstrates that RCM can reliably diagnose MM and is fast enough to be integrated into UK pigmented lesion clinics by dermatologists trained in RCM. "Number needed to treat" dropped from 3.9 with clinical examination to 3.0 with dermoscopy to 1.3 with RCM.

Increased Change in Cervical Lordosis is Associated With Decreased Rate of Recovery in Patients With C5 Palsy.

STUDY DESIGN: A retrospective chart review. OBJECTIVE: The authors aim to investigate the role of clinical and radiographic parameters in patients who underwent posterior cervical surgery, and their association with C5 palsy severity and time to recovery. BACKGROUND: Postoperative C5 palsy affects 1%-30% of patients undergoing posterior decompression, with or without fusion. Causation and avoidance of this complication remain widely debated. MATERIALS AND METHODS: A single institution review of patients who underwent posterior cervical spine surgery was focused on using specific Common Procedural Technology codes associated with the patient population of interest. Patients were excluded if they had inadequate pre and postoperative imaging, as well as a history of prior cervical spine surgery, concurrent anterior surgery, intradural pathology, spinal tumor, or spinal trauma. Radiographic measurements of the pre and postoperative images were completed with subsequent intraclass correlation coefficient analysis to confirm the precision of measurements. RESULTS: Out of 105 total patients, 35 (33%) patients developed a C5 palsy. Twenty-four (69%) of those palsies completely resolved, with a median time to recovery of 8 months. Preoperative demographics and radiographic parameters demonstrated heterogeneity among those patients who did and did not have a resolution of palsy. Patients with increased change in C2-C7 lordosis (P = 0.011) after surgery were associated with decreased likelihood of recovery. Patients without a smoking history (P = 0.009) had an increased likelihood of recovering from C5 palsy. CONCLUSIONS: The degree of increased lordosis in the treatment of degenerative cervical disease plays a role in the rate of recovery from C5 palsy. This should be considered during preoperative planning in determining the amount of lordosis desired. In addition, patients without a smoking history were associated with a higher rate of recovery. LEVEL OF EVIDENCE: Level IV.

Identifying clinically meaningful subgroups following open reduction and internal fixation for proximal humerus fractures: a risk stratification analysis for mortality and 30-day complications using machine learning.

Background: Identification of prognostic variables for poor outcomes following open reduction internal fixation (ORIF) of displaced proximal humerus fractures have been limited to singular, linear factors and subjective clinical intuition. Machine learning (ML) has the capability to objectively segregate patients based on various outcome metrics and reports the connectivity of variables resulting in the optimal outcome. Therefore, the purpose of this study was to (1) use unsupervised ML to stratify patients to high-risk and low-risk clusters based on postoperative events, (2) compare the ML clusters to the American Society of Anesthesiologists (ASA) classification for assessment of risk, and (3) determine the variables that were associated with high-risk patients after proximal humerus ORIF. Methods: The American College of Surgeons-National Surgical Quality Improvement Program database was retrospectively queried for patients undergoing ORIF for proximal humerus fractures between 2005 and 2018. Four unsupervised ML clustering algorithms were evaluated to partition subjects into "high-risk" and "low-risk" subgroups based on combinations of observed outcomes. Demographic, clinical, and treatment variables were compared between these groups using descriptive statistics. A supervised ML algorithm was generated to identify patients who were likely to be "high risk" and were compared to ASA classification. A game-theory-based explanation algorithm was used to illustrate predictors of "high-risk" status. Results: Overall, 4670 patients were included, of which 202 were partitioned into the "high-risk" cluster, while the remaining (4468 patients) were partitioned into the "low-risk" cluster. Patients in the "high-risk" cluster demonstrated significantly increased rates of the following complications: 30-day mortality, 30-day readmission rates, 30-day reoperation rates, nonroutine discharge rates, length of stay, and rates of all surgical and medical complications assessed with the exception of urinary tract infection (P < .001). The best performing supervised machine learning algorithm for preoperatively identifying "high-risk" patients was the extreme-gradient boost (XGBoost), which achieved an area under the receiver operating characteristics curve of 76.8%, while ASA classification had an area under the receiver operating characteristics curve of 61.7%. Shapley values identified the following predictors of "high-risk" status: greater body mass index, increasing age, ASA class 3, increased operative time, male gender, diabetes, and smoking history. Conclusion: Unsupervised ML identified that "high-risk" patients have a higher risk of complications (8.9%) than "low-risk" groups (0.4%) with respect to 30-day complication rate. A supervised ML model selected greater body mass index, increasing age, ASA class 3, increased operative time, male gender, diabetes, and smoking history to effectively predict "high-risk" patients.

Access and Cost Trends for Same-Day Plastic Surgery among Propensity-Matched Patients by Site-of-Service.

BACKGROUND: Same-day surgery is common in plastic surgery. Sites-of-service are associated with cost differences. Freestanding (F-ASCs) and hospital-owned ambulatory surgery centers (HO-ASCs) are less costly than hospital outpatient departments (HOPDs), though access disparities are reported. Trends in cost, access, and outcomes between same-day surgery facilities for common plastic surgeries have not been evaluated. METHODS: Healthcare Cost and Utilization Project State Ambulatory Surgery and Inpatient databases (2016-2019) were queried for patients who underwent laceration repair, local tissue rearrangement, skin grafting, panniculectomy, reduction mammaplasty, breast reconstruction, and revision breast reconstruction. Patients were 1:1:1 propensity-matched by facility type and outcomes were analyzed with a mixed-effects log-linear regression with repeated measures. RESULTS: This study included 120,240 patients. Compared with HOPDs, no change in HO-ASC charges and an 8% quarterly decrease in F-ASC charges (95% CI: 0.89 to 0.96, p<0.001) was found. Relative to White patients, F-ASC use increased among Black (OR: 1.05, 95% CI: 1.03 to 1.06, p<0.001) and Hispanic (OR: 1.05, 95% CI: 1.03 to 1.06, p<0.001) patients. F-ASCs had the lowest rates of unexpected postoperative visits (F-ASC OR: 0.28, 95% CI: 0.25-0.32, p<0.001; HO-ASC OR: 0.52, 95% CI: 0.46-0.58, p<0.001). CONCLUSION: Incentives encouraging ASC use are maligned with same-day surgery payment policy in the US. Policy that narrows differences in ASC reimbursement relative to HOPDs will improve access to same-day plastic surgery and constrain costs. Narrowing F-ASC access disparities and lower rates of unexpected postoperative visits suggest F-ASCs improve access to same-day plastic surgery.

The Influence of Resilience on Outcomes After Total Ankle Arthroplasty.

BACKGROUND: Resiliency is the ability to recover from stressful events and has been shown to correlate with patient outcomes following certain orthopaedic procedures. The purpose of this study was to determine the relationship between resiliency and outcomes following TAA. METHODS: A retrospective analysis of patients undergoing primary TAA between April 2015 and September 2022 was performed (N = 83). Data included demographics, comorbidities, complications, preoperative and postoperative visual analog scale (VAS) pain and Foot and Ankle Ability Measure (FAAM) functional scores, Brief Resilience Scale (BRS) scores, and surgical satisfaction. Patients were defined as having low resilience (LR), normal resilience (NR), or high resilience (HR) based on a BRS score of <3, 3-4.30, and >4.3, respectively. RESULTS: High resilience patients had significantly higher postoperative FAAM ADL, Sports, and Overall scores as well as a significantly greater increase from preoperative scores compared with LR and NR patients. Low resilience patients had significantly lower FAAM Sports and Overall scores compared with normal and high resilience patients. BRS scores positively correlated with postoperative FAAM scores. We found no difference in satisfaction or VAS between the 3 cohorts. Multivariate regression analysis identified BRS scores to be an independent predictor for greater changes in FAAM scores following TAA. CONCLUSION: Although functional improvements following TAA are expected, patients with higher resilience at baseline are more likely to experience greater improvements in functional outcomes following surgery. LEVEL OF EVIDENCE: Level III.

The use of Reflectance Confocal Microscopy to diagnose Basal Cell Carcinoma in the United Kingdom: A Prospective Observational Trial at a Single Centre.

BACKGROUND: Previous work with Reflectance Confocal Microscopy (RCM) imaging has shown high sensitivity and specificity for Basal Cell Carcinoma (BCC), but to date there have been few studies on a UK cohort. OBJECTIVES: The study hypothesised that RCM could be used prospectively to accurately diagnose BCC in a private UK secondary care, single clinician setting. The study assessed the potential for RCM to be used as a routine diagnostic procedure. METHODS: 522 lesions were recruited prospectively where BCC featured in the differential diagnosis after clinical examination. 78 were subsequently excluded. Imaging used the arm-mounted confocal microscope unless access was restricted and required the handheld probe. The likelihood of BCC was scored for each modality, each diagnosis building on the last. Histology was assessed by a single blinded histopathologist [JJ]. RESULTS: 444 lesions from 326 patients were included in the analysis, including 327 BCCs. Median maximum diameter was 6 mm. The sensitivity and specificity for BCC was 69.42% (64.11% to 74.37%) and 52.99% (43.55% to 62.28%) for clinical examination alone; 91.77% (88.25% to 94.51%) and 41.03% (32.02% to 50.50%) plus dermoscopy; 98.78% (96.91% to 99.67%) and 85.47% (77.76% to 91.30%) plus RCM. For RCM PPV was 95.01% (92.14% to 97.07%) and NPV was 96.15% (90.44% to 98.94%). Area under the curve increased from 0.61 to 0.66 to 0.92 as modalities were added. CONCLUSION: This study demonstrates that RCM can, reliably and quickly, diagnose BCC, and that the addition of RCM to dermoscopy permits higher diagnostic accuracy for BCC in the UK. The specificity and sensitivity of the RCM diagnosis did not alter significantly with experience, reflecting the ease and speed of acquiring the skill. CLINICAL TRIAL REGISTRATION: NCT03509415.

A Comparison of Postoperative Outcomes Based on Muscle versus Fasciocutaneous Flaps in Scalp Reconstruction: A Systematic Review and Meta-analysis.

BACKGROUND: Scalp reconstruction in plastic and reconstructive surgery often necessitates the transfer of soft-tissue flaps to restore form and function. The critical decision lies in choosing between muscle-containing (MC) and fasciocutaneous (FC) flaps for scalp reconstruction, and while both variants have their merits, flap composition remains a subject of ongoing debate. This scientific discussion aims to explore this contentious issue through a comprehensive meta-analysis, shedding light on the rationale behind the choice of these flaps and the potential impact on clinical outcomes. METHODS: A comprehensive systematic review was conducted following PRISMA-P guidelines, encompassing six prominent databases up to the year 2023. Data were collected from studies assessing outcomes of MC and FC flaps for scalp reconstruction. Quality evaluation was performed using ASPS criteria and the ROBINS-I tool. Statistical analysis included descriptive statistics, meta-analysis, sensitivity analysis, and assessment of bias using STATA software. RESULTS: The meta-analysis included 28 nonrandomized studies, totaling 594 flaps (MC: 380, FC: 214). MC flaps were significantly larger than FC flaps. There were no significant differences in flap loss, flap necrosis, or wound dehiscence between the two flap types. However, the incidence of venous congestion was significantly higher in FC flaps. Sensitivity analysis confirmed the robustness of results, and publication bias assessment showed no significant evidence of bias. CONCLUSION: While both MC and FC flaps offer viable options for scalp reconstruction, the choice should be tailored to individual patient characteristics and defect size. FC flaps may provide advantages such as shorter operative times and reduced morbidity, whereas MC flaps could be preferred for addressing larger defects. Future research should focus on prospective studies and strategies to mitigate venous congestion in FC flaps, enhancing their safety and efficacy in scalp reconstruction.

Engaging Undergraduate Students in Course-based Research Improved Student Learning of Course Material.

Course-based undergraduate research experiences (CUREs) offer students opportunities to engage in critical thinking and problem solving. However, quantitating the impact of incorporating research into undergraduate courses on student learning and performance has been difficult since most CUREs lack a comparable traditional course as a control. To determine how course-based research impacts student performance, we compared summative assessments of the traditional format for our upper division immunology course (2013-2016), in which students studied known immune development and responses, to the CURE format (2017-2019), in which students studied the effects of genetic mutations on immune development and responses. Because the overall class structure remained unaltered, we were able to quantitate the impact of incorporating research on student performance. Students in the CURE format class performed significantly better on quizzes, exams, and reports. There were no significant differences in academic levels, degree programs, or grade point averages, suggesting improved performance was due to increased engagement of students in research.

Studies with Direct Industry Affiliation are More Likely to Report Positive Results in Randomized Controlled Trials for Platelet-Rich Plasma Use in Rotator Cuff Pathology: A Systematic Review.

PURPOSE: To perform a systematic review to evaluate the effect of industry affiliation on the outcomes of randomized controlled trials (RCTs) for platelet-rich plasma (PRP) injections in rotator cuff tears. METHODS: PubMed, SPORTdiscus, and Scopus databases were searched from 2010 to the present for terms "rotator cuff" and "platelet-rich plasma." Inclusion criteria were RCTs comparing PRP to controls for treatment of rotator cuff tears and exclusion criteria were systematic reviews, meta-analyses, case reports, cohort studies, basic science studies, other level 3 and below studies, and studies not in English. Degree of industry affiliation was categorized into three groups: direct, indirect, and not affiliated. Direct affiliation required the study or its authors to receive financial support from the company manufacturing the devices used in the study to prepare or administer PRP. Indirect affiliation required financial association with a different company that produces or administers PRP than the one used in the study. Studies were classified as favorable if study outcomes achieved significance (p < 0.05) of PRP over the control, or analogous if there was no statistical significance between PRP and control. Data was analyzed using chi-squared and fisher's exact tests. RESULTS: Of the 47 studies selected for analysis, 8 (17.0%) had no direct industry affiliation, 9 (19.1%) indirect affiliation and 30 (63.8%) no industry affiliation. 22 (46.8%) studies reported favorable results with PRP compared to the control and 25 (53.2%) showed analogous results between PRP and control. Degree of industry affiliation was significantly associated with increased likelihood of reporting favorable study outcomes (p = 0.041). Directly affiliated studies had a significantly increased likelihood of reporting favorable results (p = 0.024) compared to indirectly affiliated. CONCLUSIONS: Studies that used PRP produced by companies that directly fund the study or were financially affiliated with the authors were significantly more likely to report favorable results. LEVEL OF EVIDENCE: Systematic review of Level I and II studies.

Shared sanitation facilities and risk of respiratory virus transmission in resource-poor settings: A COVID-19 modeling case study.

Water supply and sanitation are essential household services frequently shared in resource-poor settings. Shared sanitation can increase the risk of enteric pathogen transmission due to suboptimal cleanliness of facilities used by large numbers of individuals. It also can potentially increase the risk of respiratory disease transmission. As sanitation is an essential need, shared sanitation facilities may act as important respiratory pathogen transmission venues even with strict control measures such as stay-at-home recommendations in place. This analysis explores how behavioral and infrastructural conditions surrounding shared sanitation may individually and interactively influence respiratory pathogen transmission. We developed an individual-based community transmission model using COVID-19 as a motivating example parameterized from empirical literature to explore how transmission in shared latrines interacts with transmission at the community level. We explored mitigation strategies, including infrastructural and behavioral interventions. Our review of empirical literature confirms that shared sanitation venues in resource-poor settings are relatively small with poor ventilation and high use patterns. In these contexts, shared sanitation facilities may act as strong drivers of respiratory disease transmission, especially in areas reliant on shared facilities. Decreasing dependence on shared latrines was most effective at attenuating sanitation-associated transmission. Improvements to latrine ventilation and handwashing behavior were also able to decrease transmission. The type and order of interventions are important in successfully attenuating disease risk, with infrastructural and engineering controls being most effective when administered first, followed by behavioral controls after successful attenuation of sufficient alternate transmission routes. Beyond COVID-19, our modeling framework can be extended to address water, sanitation, and hygiene measures targeted at a range of environmentally mediated infectious diseases.

Effect of drought acclimation on sugar metabolism in millet.

Drought stress triggers sugar accumulation in plants, providing energy and aiding in protection against oxidative damage. Plant hardening under mild stress conditions has been shown to enhance plant resistance to severe stress conditions. While sugar accumulation and metabolism under drought stress have been well-documented in crop plants, the effect of drought acclimation treatment on sugar accumulation and metabolism has not yet been explored. In this study, we investigated the impact of drought stress acclimation on sugar accumulation and metabolism in the leaves and root tissues of two commonly cultivated foxtail millet (Setaria italica L.) genotypes, 'PI 689680' and 'PI 662292'. Quantification of total sugars (soluble sugar, fructose, glucose, and sucrose), their related enzymes (SPS, SuSy, NI, and AI), and the regulation of their related transcripts (SiSPS1, SiSuSy1, SiSWEET6, SiA-INV, and SiC-INV) revealed that drought-acclimated (DA) plants exhibited levels of these indicators comparable to those of control plants. However, under subsequent drought stress conditions, both the leaves and roots of non-acclimated plants accumulated higher levels of total sugars, displayed increased activity of sugar metabolism enzymes, and showed elevated expression of sugar metabolism-related transcripts compared to drought-acclimated plants. Thus, acclimation-induced restriction of sugar accumulation, transport, and metabolism could be one of the metabolic processes contributing to enhanced drought tolerance in millet. This study advocates for the use of acclimation as an effective strategy to mitigate the negative impacts of drought-induced metabolic disturbances in millet, thereby enhancing global food security and promoting sustainable agricultural systems.