A Novel Method for Assessing Risk-Adjusted Diagnostic Coding Specificity for Depression Using a U.S. Cohort of over One Million Patients.

Depression is a prevalent and debilitating mental health condition that poses significant challenges for healthcare providers, researchers, and policymakers. The diagnostic coding specificity of depression is crucial for improving patient care, resource allocation, and health outcomes. We propose a novel approach to assess risk-adjusted coding specificity for individuals diagnosed with depression using a vast cohort of over one million inpatient hospitalizations in the United States. Considering various clinical, demographic, and socioeconomic characteristics, we develop a risk-adjusted model that assesses diagnostic coding specificity. Results demonstrate that risk-adjustment is necessary and useful to explain variability in the coding specificity of principal (AUC = 0.76) and secondary (AUC = 0.69) diagnoses. Our approach combines a multivariate logistic regression at the patient hospitalization level to extract risk-adjusted probabilities of specificity with a Poisson Binomial approach at the facility level. This method can be used to identify healthcare facilities that over- and under-specify diagnostic coding when compared to peer-defined standards of practice.

Human iPSC-derived retinal organoids develop robust Alzheimer's disease neuropathology.

Alzheimer's disease (AD), characterized by memory loss and cognitive decline, affects nearly 50 million people worldwide. Amyloid beta (Aß) plaques and intracellular neurofibrillary tangles (NFTs) of phosphorylated Tau protein (pTau) are key histopathological features of the disease in the brain, and recent advances have also identified AD histopathology in the retina. Thus, the retina represents a central nervous system (CNS) tissue highly amenable to non-invasive diagnostic imaging that shows promise as a biomarker for early AD. Given the devastating effects of AD on patients, their families, and society, new treatment modalities that can significantly alter the disease course are urgently needed. In this study, we have developed and characterized a novel human retinal organoid (RO) model derived from induced pluripotent stem cells (iPSCs) from patients with familial AD due to mutations in the amyloid precursor protein gene (APP). Using immunofluorescence and histological staining, we evaluated the cellular composition and AD histopathological features of AD-ROs compared to control ROs from healthy individuals. We found that AD-ROs largely resemble their healthy control counterparts in cellular composition but display increased levels of Aß and pTau. We also present proof of principle of an assay to quantify amyloid levels in whole ROs. This in vitro model of the human AD retina constitutes a new tool for drug screening, biomarker discovery, and pathophysiological studies.

Deep Proteome Profiling of White Adipose Tissue Reveals Marked Conservation and Distinct Features Between Different Anatomical Depots.

White adipose tissue is deposited mainly as subcutaneous adipose tissue (SAT), often associated with metabolic protection, and abdominal/visceral adipose tissue, which contributes to metabolic disease. To investigate the molecular underpinnings of these differences, we conducted comprehensive proteomics profiling of whole tissue and isolated adipocytes from these two depots across two diets from C57Bl/6J mice. The adipocyte proteomes from lean mice were highly conserved between depots, with the major depot-specific differences encoded by just 3% of the proteome. Adipocytes from SAT (SAdi) were enriched in pathways related to mitochondrial complex I and beiging, whereas visceral adipocytes (VAdi) were enriched in structural proteins and positive regulators of mTOR presumably to promote nutrient storage and cellular expansion. This indicates that SAdi are geared toward higher catabolic activity, while VAdi are more suited for lipid storage. By comparing adipocytes from mice fed chow or Western diet (WD), we define a core adaptive proteomics signature consisting of increased extracellular matrix proteins and decreased fatty acid metabolism and mitochondrial Coenzyme Q biosynthesis. Relative to SAdi, VAdi displayed greater changes with WD including a pronounced decrease in mitochondrial proteins concomitant with upregulation of apoptotic signaling and decreased mitophagy, indicating pervasive mitochondrial stress. Furthermore, WD caused a reduction in lipid handling and glucose uptake pathways particularly in VAdi, consistent with adipocyte de-differentiation. By overlaying the proteomics changes with diet in whole adipose tissue and isolated adipocytes, we uncovered concordance between adipocytes and tissue only in the visceral adipose tissue, indicating a unique tissue-specific adaptation to sustained WD in SAT. Finally, an in-depth comparison of isolated adipocytes and 3T3-L1 proteomes revealed a high degree of overlap, supporting the utility of the 3T3-L1 adipocyte model. These deep proteomes provide an invaluable resource highlighting differences between white adipose depots that may fine-tune their unique functions and adaptation to an obesogenic environment.

American Indian and Alaska Native Accessibility to Comprehensive Cleft Lip and Palate Treatment.

American Indians and Alaska Natives (AI/AN) have the highest incidence of cleft lip and palate (orofacial clefts [OFCs]) when compared to other ethnic groups. We aim to determine the AI/AN populations' proximity and accessibility to American Cleft Palate-Craniofacial Association accredited centers (ACPA centers) for treatment of OFCs. Our hypothesis is an unacceptable proportion of the AI/AN population lacks reasonable accessibility to ACPA centers and comprehensive craniofacial care.A cross-sectional study of ACPA centers and AI/AN populations were analyzed for possible disparities.ACPA centers were mapped using Geographic Information Systems (GIS) and compared with 2018 census population data and 2017 Tribal Census Tract data to visually display possible disparities. Total annual potential pediatric cleft care need for selected high-density AI/AN populated lands were estimated.GIS mapping demonstrates geographical isolation of AI/AN populations from ACPA centers. Two states with high AI/AN populated lands (ND, WY) have no ACPA centers. 47.1% of ACPA centers in high AI/AN populated lands have no craniofacial trained surgeons versus 78.9% craniofacial staffed ACPA centers nationally. The potential unmet cleft and craniofacial care need in selected high-density AI/AN populated lands is 1042 children.AI/AN populations are likely underserved by ACPA centers and by craniofacial fellowship-trained staffed centers. Not addressing OFCs with comprehensive care can lead to worsened outcomes and further marginalization of these children. With future studies, we will be capable of making data-driven, informed decisions to more effectively ensure AI/AN access to comprehensive cleft and craniofacial care.

Impact of High-Dose Intravenous Vitamin C for Treatment of Sepsis on Point-of-Care Blood Glucose Readings.

BACKGROUND: Intravenous vitamin C therapy has been associated with reduced mortality in patients with sepsis. Of potential concern with this therapy are falsely elevated point-of-care (POC) blood glucose values vs laboratory analyzed (LA) readings. The purpose of this study was to compare POC and LA blood glucose measurements in patients receiving intravenous vitamin C therapy. METHODS: All adults (≥18 years old) admitted from January 2017 to December 2018 who received at least two doses of intravenous vitamin C and had at least one paired blood glucose collection were eligible for inclusion. The primary endpoint was the accuracy in paired blood glucose values determined using the International Organization for Standardization (ISO) 15197:2013 criteria. Paired values were assessed for clinical impact using the Parkes consensus error grid analysis. A subgroup analysis was conducted to determine the impact of impaired renal function on outcomes. RESULTS: Fourteen patients were included for analysis with 46 paired blood glucose levels. Compliance with ISO15197:2013 criteria was met in 34 (73.9%) paired values, which did not meet the minimum criteria for accuracy. Subgroup analysis showed that the paired values from patients with impaired renal function did not meet the minimum requirements for compliance, while those from patients without impaired renal function did. The Parkes error grid showed that the variation in POC measurements likely had minimal clinical impact. CONCLUSIONS: Our study suggests that most patients receiving vitamin C for sepsis may still be monitored at POC with the glucose meter used in our study with minimal clinical impact.

The Ideal Male Nipple-Areola Complex: A Critical Review of the Literature and Discussion of Surgical Techniques for Female-to-Male Gender-Confirming Surgery.

INTRODUCTION: Top surgery (mastectomy and masculinization of the chest) is a key gender affirming operation for many female-to-male transgender patients. Positioning of the nipple-areola complex (NAC) is a crucial part of this procedure. To date, there are no standards as to where to place the new NAC based on the patient's anatomy, to achieve the most aesthetically pleasing result. OBJECTIVE: The objectives of this study were to review the literature and analyze the anatomical averages for NAC shape, width, and height as well as vertical and horizontal placement and to compile the recommendations and proposed equations of NAC placement based on chest wall measurements, chest wall landmarks, and body habitus. METHODS: A systematic review of the literature was conducted in the spring of 2018. Eleven articles met the inclusion criteria, with objective measurements of, and guidelines for, positioning the male NAC in men that had not been preselected for being aesthetically perfect. RESULTS: The average diameter for a round NAC was 25.9 mm (SD, 2.5 mm), and the width and height of the oval-shaped NAC were found to be 25.3 mm (SD, 2.6 mm) and 20.1 mm (SD, 0.75 mm), respectively. The average sternal notch to nipple distance was found to be 19.3 cm (SD, 1.7 cm). The average internipple distance was 22.3 cm (SD, 1.6 cm). CONCLUSIONS: The data are inconclusive about the effects of anatomical measurements on NAC vertical and horizontal position, but areola diameter is reasonably consistent. There are a wide variety of guidelines and algorithms offered for determining these measurements.

Influenza epidemiology in patients admitted to sentinel Australian hospitals in 2018: the Influenza Complications Alert Network (FluCAN).

The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all jurisdictions in Australia. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2018 influenza season. In this observational surveillance system, cases were defined as patients admitted to any of the 17 sentinel hospitals with influenza confirmed by nucleic acid detection. Data were also collected on a frequency-matched control group of influenza-negative patients admitted with acute respiratory infection. During the period 3 April to 31 October 2018 (the 2018 influenza season), 769 patients were admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 30% were elderly (≥65 years), 28% were children (<16 years), 6.4% were Aboriginal and Torres Strait Islander peoples, 2.2% were pregnant and 66% had chronic comorbidities. A small proportion of FluCAN admissions were due to influenza B (13%). Estimated vaccine coverage was 77% in the elderly (≥65 years), 45% in non-elderly adults with medical comorbidities and 26% in children (<16 years) with medical comorbidities. The estimated vaccine effectiveness (VE) in the target population was 52% (95% CI: 37%, 63%). There were a smaller number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2018 than in 2017, with the demographic profile reflecting the change in circulating subtype from A/H3N2 to A/H1N1.

Influenza epidemiology in patients admitted to sentinel Australian hospitals in 2017: the Influenza Complications Alert Network (FluCAN).

The Influenza Complications Alert Network (FluCAN) is a sentinel-hospital-based surveillance program that operates at sites in all jurisdictions in Australia. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2017 influenza season. In this observational surveillance system, cases were defined as patients admitted to any of the 17 sentinel hospitals with influenza confirmed by nucleic acid detection. Data are also collected on a frequency-matched control group of influenza-negative patients admitted with acute respiratory infection. During the period 3 April to 31 October 2017 (the 2017 influenza season), 4,359 patients were admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 52% were elderly (≥65 years), 14% were children (<16 years), 6.5% were Aboriginal and Torres Strait Islander peoples, 1.6% were pregnant and 78% had chronic comorbidities. A significant proportion were due to influenza B (31%). Estimated vaccine coverage was 72% in the elderly (≥65 years), 50% in non-elderly adults with medical comorbidities and 24% in children (<16 years) with medical comorbidities. The estimated vaccine effectiveness (VE) in the target population was 23% (95% CI: 7%, 36%). There were a large number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2017, with case numbers more than twice that reported in 2016.

The role of collagenase ointment in acute burns: a systematic review and meta-analysis.

OBJECTIVE:: A systematic review and meta-analysis was performed to summarise the state of the literature in regard to the efficacy and uses of clostridial collagenase ointment (CCO) in the burn patient. METHOD:: A systematic review of articles available on PubMed, Scopus and OvidSP Medline was performed. Keywords used in the search process included burns, thermal injury, collagenase, enzymatic debridement, wound care. Reviews, case reports, independent abstracts, consensus and opinion papers were excluded. A meta-analysis was performed for articles fitting inclusion criteria. RESULTS:: Following screening, six relevant articles were identified for systematic review. Few studies, with limited sample sizes, argue that CCO may be an effective debriding agent. It may also accelerate wound healing and avoid the pain associated with mechanical debridement. CCO lacks antimicrobial activity but the risk of burn wound infection does not appear to be significantly different than when using silver-impregnated products. CCO is more expensive than traditional wound care products but may help halt burn depth conversion and prevent the need for surgery. CONCLUSION:: CCO may be a safe and effective debridement agent for burn wounds with respect to decreasing wound healing time and minimising pain without increasing the risk of infection. It should be used on a case-by-case basis due to its financial cost, which may be offset by its ability to manage burns non-operatively.

Anatomical Basis of the Gastroepiploic Vascularized Lymph Node Transfer: A Radiographic Evaluation Using Computed Tomographic Angiography.

BACKGROUND: The omentum, nourished by the gastroepiploic vessels, has gained popularity as an option for vascularized lymph node transfer. The anatomy of the gastroepiploic vessels, omentum, and lymph nodes has not been investigated. The purpose of this article is to describe the right gastroepiploic artery and related structures by using computed tomographic angiography. METHODS: A retrospective analysis was conducted on 34 patients who underwent computed tomographic angiography. Statistical models were applied to identify right gastroepiploic artery and lymph node anatomical characteristics. RESULTS: The right gastroepiploic artery was identified in 33 of 34 patients. It was found to have a diameter of 2.49 ± 0.66 mm at its origin. The gastroduodenal artery length before right gastroepiploic artery takeoff was 3.09 ± 1.31 cm. Twenty-five patients had lymph nodes in the right gastroepiploic artery lymphosome. There were 2.7 ± 2.12 lymph nodes identified per patient. The distance from the right gastroepiploic artery origin to the most proximal lymph node was 3.99 ± 2.21 cm. The distance from the gastroepiploic artery origin to the third lymph node was 9.12 ± 5.06 cm. Each lymph node was within 7.00 ± 6.2 mm of the right gastroepiploic artery. CONCLUSIONS: When using the right gastroepiploic artery donor site for vascularized lymph node transfer, the plastic surgeon should anticipate using a pedicle length of 4 cm, a total flap length of 9 cm, and 3 cm of surrounding tissue to obtain at least three lymph nodes for transfer. Computed tomographic angiography is an effective imaging modality that can be used for patient-specific surgical navigation before vascularized lymph node transfer.

Updates on the Management of Non-Melanoma Skin Cancer (NMSC).

Non-melanoma skin cancers (NMSCs) are the most common malignancy worldwide, of which 99% are basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of skin. NMSCs are generally considered a curable diseases, yet they currently pose an increasing global healthcare problem due to rising incidence. This has led to a shift in emphasis on prevention of NMSCs with development of various skin cancer prevention programs worldwide. This article aims to summarize the most recent changes and advances made in NMSC management with a focus on prevention, screening, diagnosis, and staging.

Biological control of Eotetranychus lewisi and Tetranychus urticae (Acari: Tetranychidae) on strawberry by four phytoseiids (Acari: Phytoseiidae).

The spider mite, Eotetranychus lewisi (McGregor) (Acari: Tetranychidae), is a new emerging pest in California commercial strawberries. The predatory mite Phytoseiulus persimilis (Athias-Henriot) (Acari: Phytoseiidae), typically used for biocontrol of Tetranychus urticae (Koch) (Acari: Tetranychidae), provided growers little to no control of E. lewisi. Four commonly used phytoseiid predatory mites: P. persimilis, Neoseiulus californicus (McGregor), N. fallacis (Garman), and Amblyseius andersoni (Chant), were used in lab studies to investigate which is best at managing E. lewisi populations. We als o investigated t he interactions between T. urticae and E. lewisi and in relation to phytoseiid efficiency given the potential for indirect effects of biocontrol. When E. lewisi and T. urticae are present on the same leaf, T. urticae populations increase and begin displacing E. lewisi. P. persimilis did not feed on E. lewisi, but the other three predatory mites consumed the spider mites and lowered their populations. When both E. lewisi and T. urticae are present on the same leaf, N. fallacis and A. andersoni fed on both types of mites equally and were capable of decreasing both populations. N. californicus fed on E. lewisi first and decreased its population, but allowed T. urticae populations to increase. P. persimilis may be insufficient at controlling E. lewisi and its use may instead enhance E. lewisi populations.