Developing a genetic testing panel for evaluation of morbidities in kidney transplant recipients.

Cardiovascular disease, infection, malignancy, and thromboembolism are major causes of morbidity and mortality in kidney transplant recipients (KTR). Prospectively identifying monogenic conditions associated with post-transplant complications may enable personalized management. Therefore, we developed a transplant morbidity panel (355 genes) associated with major post-transplant complications including cardiometabolic disorders, immunodeficiency, malignancy, and thrombophilia. This gene panel was then evaluated using exome sequencing data from 1590 KTR. Additionally, genes associated with monogenic kidney and genitourinary disorders along with American College of Medical Genetics (ACMG) secondary findings v3.2 were annotated. Altogether, diagnostic variants in 37 genes associated with Mendelian kidney and genitourinary disorders were detected in 9.9% (158/1590) of KTR; 25.9% (41/158) had not been clinically diagnosed. Moreover, the transplant morbidity gene panel detected diagnostic variants for 56 monogenic disorders in 9.1% KTRs (144/1590). Cardiovascular disease, malignancy, immunodeficiency, and thrombophilia variants were detected in 5.1% (81), 2.1% (34), 1.8% (29) and 0.2% (3) among 1590 KTRs, respectively. Concordant phenotypes were present in half of these cases. Reviewing implications for transplant care, these genetic findings would have allowed physicians to set specific risk factor targets in 6.3% (9/144), arrange intensive surveillance in 97.2% (140/144), utilize preventive measures in 13.2% (19/144), guide disease-specific therapy in 63.9% (92/144), initiate specialty referral in 90.3% (130/144) and alter immunosuppression in 56.9% (82/144). Thus, beyond diagnostic testing for kidney disorders, sequence annotation identified monogenic disorders associated with common post-transplant complications in 9.1% of KTR, with important clinical implications. Incorporating genetic diagnostics for transplant morbidities would enable personalized management in pre- and post-transplant care.

Obesity is associated with a higher incidence of rejection in patients on belatacept: A pooled analysis from the BENEFIT/BENEFIT-EXT clinical trials.

Though belatacept is administered with a weight-based dosing schema, there has been higher clearance reported in obese patients. Therefore, we evaluated the association between body mass index (BMI) and transplant outcomes in kidney transplant recipients who were randomized to cyclosporine- or belatacept-based immunosuppression in the BENEFIT and BENEFIT-EXT randomized clinical trials. A total of 666 and 543 patients underwent randomization and transplantation in BENEFIT and BENEFIT-EXT, respectively, of which 1056 had complete data and were included in this analysis. Patients were grouped categorically according to BMI: <25, 25 to <30, and ≥30 kg/m2. BMI did influence both the incidence and severity of acute rejection. Obese patients with BMI >30 kg/m2 in the low intensity belatacept group experienced significantly more rejection at 12 months than did patients with BMI <25 kg/m2 or BMI 25 to <30 kg/m2. In both the moderate intensity belatacept and low intensity belatacept groups, obese patients with BMI >30 kg/m2 experienced significantly more severe acute rejection than did patients with BMI < 25 kg/m2 or BMI 25 to <30 kg/m2. These results suggest that obese kidney transplant recipients are at an increased risk for acute rejection when under belatacept-based immunosuppression when compared to nonobese patients.

Distortionless, free-breathing, and respiratory resolved 3D diffusion weighted imaging of the abdomen.

PURPOSE: Abdominal imaging is frequently performed with breath holds or respiratory triggering to reduce the effects of respiratory motion. Diffusion weighted sequences provide a useful clinical contrast but have prolonged scan times due to low signal-to-noise ratio (SNR), and cannot be completed in a single breath hold. Echo-planar imaging (EPI) is the most commonly used trajectory for diffusion weighted imaging but it is susceptible to off-resonance artifacts. A respiratory resolved, three-dimensional (3D) diffusion prepared sequence that obtains distortionless diffusion weighted images during free-breathing is presented. Techniques to address the myriad of challenges including: 3D shot-to-shot phase correction, respiratory binning, diffusion encoding during free-breathing, and robustness to off-resonance are described. METHODS: A twice-refocused, M1-nulled diffusion preparation was combined with an RF-spoiled gradient echo readout and respiratory resolved reconstruction to obtain free-breathing diffusion weighted images in the abdomen. Cartesian sampling permits a sampling density that enables 3D shot-to-shot phase navigation and reduction of transient fat artifacts. Theoretical properties of a region-based shot rejection are described. The region-based shot rejection method was evaluated with free-breathing (normal and exaggerated breathing), and respiratory triggering. The proposed sequence was compared in vivo with multishot DW-EPI. RESULTS: The proposed sequence exhibits no evident distortion in vivo when compared to multishot DW-EPI, robustness to B0 and B1 field inhomogeneities, and robustness to motion from different respiratory patterns. CONCLUSION: Acquisition of distortionless, diffusion weighted images is feasible during free-breathing with a b-value of 500 s/mm2, scan time of 6 min, and a clinically viable reconstruction time.

Cognition and psychological wellbeing in hypopituitary patients.

Hypopituitarism (HP) frequently occurs in patients presenting with sellar masses and despite recent advances in therapeutic options, HP patients consistently suffer from impaired quality of life due to psychological distress and cognitive dysfunction. These neurocognitive complications tend to persist in spite of surgical or biochemical remission of the disease making it especially challenging to segregate the effect of HP per se from other comorbidities such as the effect of tumour, surgery, radiation therapy, or complications caused by excess hormone production. Regardless, there is ample evidence to suggest that receptors for various pituitary hormones are abundantly expressed in key areas of central nervous system that are associated with memory and behaviour function and HP is also associated with poor sleep which can further exacerbate neurocognitive dysfunction. There is also evidence that hormonal replacement in HP patients partially restores these neurocognitive functions and improves sleep disorders. However, there is a need for creating better awareness among healthcare providers interacting with HP patients to enhance an earlier recognition of these disorder and their impact on quality of life despite initial remission. Importantly, there is a need to not only develop better and more cost-effective replacement therapies that would closely mimic the physiological hormonal release patterns, but also develop coping strategies for HP patients suffering from these complications.

Neuropsychological complications of hypoprolactinemia.

Prolactin (PRL) is primarily produced by the pituitary lactotrophic cells and while initially named for its role in lactation, PRL has several other biological roles including immunomodulation, osmotic balance, angiogenesis, calcium metabolism, and appetite regulation. Most of the PRL-related literature has traditionally focused on hyperprolactinemia, whereas hypoprolactinemia has received little attention. There is evidence to suggest that PRL receptors are widely distributed within the central nervous system including the limbic system. Furthermore, PRL has been shown to play key role in the stress regulation pathway. Recent data also suggest that hypoprolactinemia may be associated with increased sexual dysfunction, anxiety, and depression. In this paper we discuss the current understanding regarding the neuropsychological impact of hypoprolactinemia and highlight the need for adequately defining hypoprolactinemia as an entity and consideration for future replacement therapies.

Association between donor kidney cysts and donor and recipient outcomes after living donor kidney transplantation.

INTRODUCTION: Incidental kidneys cysts are typically considered benign, but the presence of cysts is more frequent in individuals with other early markers of kidney disease. We studied the association of donor kidney cysts with donor and recipient outcomes after living donor kidney transplantation. METHODS: We retrospective identified 860 living donor transplants at our center (1/1/2011-7/31/2022) without missing data. Donor cysts were identified by review of pre-donation CT scan reports. We used linear regression to study the association between donor cysts and 6-month single-kidney estimated glomerular filtration rate (eGFR) increase, and time-to-event analyses to study the association between donor cysts and recipient death-censored graft failure. RESULTS: Among donors, 77% donors had no kidney cysts, 13% had ≥1 cyst on the kidney not donated, and 11% only had cysts on the donated kidney. In adjusted linear regression, cysts on the donated kidney and kidney not donated were not significantly associated with 6-month single-kidney eGFR increase. Among transplants, 17% used a transplanted kidney with a cyst and 6% were from donors with cysts only on the kidney not transplanted. There was no association between donor cyst group and post-transplant death-censored graft survival. Results were similar in sensitivity analyses comparing transplants using kidneys with no cysts versus 1-2 cysts versus ≥3 cysts. CONCLUSIONS: Kidney cysts in living kidney donors were not associated with donor kidney recovery or recipient allograft longevity, suggesting incidental kidney cysts need not be taken into account when determining living donor candidate suitability or the laterality of planned donor nephrectomy.

MR and Ultrasound Elastography for Fibrosis Assessment in Children: Practical Implementation and Supporting Evidence-AJR Expert Panel Narrative Review.

Quantitative MRI and ultrasound biomarkers of liver fibrosis have become important tools in the diagnosis and clinical management of children with chronic liver disease (CLD). In particular, MR elastography (MRE) is now routinely performed in clinical practice to evaluate the liver for fibrosis. Ultrasound shear-wave elastography has also become widely performed for this purpose, especially in young children. These noninvasive methods are increasingly used to replace liver biopsy for the diagnosis, quantitative staging, and treatment monitoring of patients with CLD. Although ultrasound has advantages of portability and lower equipment cost, available evidence indicates that MRI may have greater reliability and accuracy in liver fibrosis evaluation. In this AJR Expert Panel Narrative Review, we describe how, why, and when to use MRI- and ultrasound-based elastography methods for liver fibrosis assessment in children. Practical approaches are discussed for adapting and optimizing these methods in children, with consideration of clinical indications, patient preparation, equipment requirements, acquisition technique, as well as pitfalls and confounding factors. Guidance is provided for interpretation and reporting, and representative case examples are presented.

A digital score of peri-epithelial lymphocytic activity predicts malignant transformation in oral epithelial dysplasia.

Oral squamous cell carcinoma (OSCC) is amongst the most common cancers, with more than 377,000 new cases worldwide each year. OSCC prognosis remains poor, related to cancer presentation at a late stage, indicating the need for early detection to improve patient prognosis. OSCC is often preceded by a premalignant state known as oral epithelial dysplasia (OED), which is diagnosed and graded using subjective histological criteria leading to variability and prognostic unreliability. In this work, we propose a deep learning approach for the development of prognostic models for malignant transformation and their association with clinical outcomes in histology whole slide images (WSIs) of OED tissue sections. We train a weakly supervised method on OED cases (n = 137) with malignant transformation (n = 50) and mean malignant transformation time of 6.51 years (±5.35 SD). Stratified five-fold cross-validation achieved an average area under the receiver-operator characteristic curve (AUROC) of 0.78 for predicting malignant transformation in OED. Hotspot analysis revealed various features of nuclei in the epithelium and peri-epithelial tissue to be significant prognostic factors for malignant transformation, including the count of peri-epithelial lymphocytes (PELs) (p < 0.05), epithelial layer nuclei count (NC) (p < 0.05), and basal layer NC (p < 0.05). Progression-free survival (PFS) using the epithelial layer NC (p < 0.05, C-index = 0.73), basal layer NC (p < 0.05, C-index = 0.70), and PELs count (p < 0.05, C-index = 0.73) all showed association of these features with a high risk of malignant transformation in our univariate analysis. Our work shows the application of deep learning for the prognostication and prediction of PFS of OED for the first time and offers potential to aid patient management. Further evaluation and testing on multi-centre data is required for validation and translation to clinical practice. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Characteristics and health implications of fine particulate matter near urban road site in Islamabad, Pakistan.

The escalating issue of air pollution has become a significant concern in urban regions, including Islamabad, Pakistan, due to the rise in air pollutant emissions driven by economic and industrial expansion. To gain a deeper understanding of air pollution, a study was conducted during winter 2022-2023, assessing physical, chemical, and biological factors in Islamabad. The findings revealed that the average concentration of fine particulate matter (PM2.5) was notably greater than the World Health Organization (WHO) guidelines, reaching 133.39 µg/m³. Additionally, the average concentration of bacteria (308.64 CFU/m³) was notably greater than that of fungi (203.55 CFU/m³) throughout the study. Analytical analyses, including SEM-EDS and FTIR, showed that the PM2.5 in Islamabad is composed of various particles such as soot aggregates, coal fly ash, minerals, bio-particles, and some unidentified particles. EF analysis distinguished PM2.5 sources, enhancing understanding of pollutants origin, whereas Spearman's correlation analysis elucidated constituent interactions, further explaining air quality impact. The results from the Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-OES) indicated a gradual increase in the total elemental composition of PM2.5 from autumn to winter, maintaining high levels throughout the winter season. Furthermore, a significant variation was found in the mass concentration of PM2.5 when comparing samples collected in the morning and evening. The study also identified the presence of semi-volatile organic compounds (SVOCs) in PM2.5 samples, including polycyclic aromatic hydrocarbons (PAHs) and phenolic compounds, with notable variations in their concentrations. Utilizing health risk assessment models developed by the US EPA, we estimated the potential health risks associated with PM2.5 exposure, highlighting the urgency of addressing air quality issues. These findings provide valuable insights into the sources and composition of PM2.5 in Islamabad, contributing to a comprehensive understanding of air quality and its potential environmental and health implications.

Impact of peri-operative red blood cell transfusions for treatment of anemia on acute rejection in renal transplant recipients.

INTRODUCTION: Anemia occurs before and after kidney transplantation. Determining the impact of perioperative transfusion on post-transplant outcomes can help determine best management of anemia. PROJECT AIM: The current study aims to describe clinical outcomes associated with packed red blood cell transfusions in the peri-operative management of anemia after transplantation. DESIGN: This was a single-center, retrospective study of adult kidney recipients with anemia at the time of transplantation. 1271 patients were stratified by donor-type due to the potential variability in underlying recipient and transplant characteristics; living donor (n = 698, 62%) or deceased donor (n = 573, 38%). RESULTS: Living donor recipients that received blood during the index hospitalization were more likely to experience rejection within 30 days (18% vs. 10%, p = 0.008) and 1 year of transplant (32% vs. 16%, p = 0.038). In multivariate analysis, receiving both blood and darbepoetin (HR: 1.89 [1.20,3.00], p = 0.006), age at transplant (HR: 0.98 [0.97, 0.99], p = 0.02), number of HLA mismatches (HR: 1.17 [1.05,1.30], p = 0.003), and whether the case was a repeat transplant (HR: 2.77 [1.93,3.97], p < 0.01) were significantly associated with hazard of rejection. For deceased donor recipients, there were no differences in acute rejection, graft failure or mortality at 30 days or 1 year. When analyzing hazard of rejection in a multivariate model, treatment received was not found to be significantly associated with rejection. CONCLUSION: Our findings suggest there may be a role for more aggressive pre-transplant treatment of anemia for those patients undergoing living donor transplants.

Patient Centered Outcomes of a Lymphedema Pump in Patients with Symptomatic Lower Extremity Edema.

OBJECTIVES: Phlebolymphedema is a challenging condition to manage, with limited options for effective treatment. For patients, this may be debilitating and lead to infection, loss of independence and affect quality of life (QOL). This study aims to evaluate patient-reported outcomes of an advanced pneumatic compression device (APCD) in the treatment of lower extremity phlebolymphedema. METHODS: Patients with diagnosis of lower extremity phlebolymphedema at an acute care facility within the New York City Health and Hospitals Cooperation treated with the Flexitouch (FLX; Tactile Systems Technology, Inc, Minneapolis, Minnesota) APCD from December 2021 to March 2023 were evaluated. Patient-perceived subjective outcomes were assessed via a short questionnaire, with subsequent analysis using Chi-squared test. Primary endpoints were subjective improvements in 1) swelling, 2) pain, and 3) ease of use of device as surrogates for patient satisfaction. Secondary endpoint was subjective patient-reported compliance, obtained by investigating 1) if patients were trained to use device, and 2) if patients were using the device. RESULTS: A total of 52 participants were included in this study, consisting of 30.8% male and 69.2% female patients with a mean age of 71.7 years. While selection criteria did not exclude unilateral disease or alternative etiologies, we note that the entire study population had been diagnosed with bilateral lower extremity lymphedema in the setting of chronic venous insufficiency. Other patient characteristics including race, comorbidities and smoking status were documented in Table 1. Table 2 demonstrates the results of Chi-squared analysis. This study noted significant patient-perceived improvement in swelling and pain (91.4% with P < 0.00001; 85.7% with P = 0.00002 respectively) as well as patient-reported ease of use of the FLX device (85.7% with P = 0.00002). Additional secondary findings included a majority of patients reporting being trained on how to use FLX and also maintaining compliance with the device (69.2% with P = 0.005; 67.3% with P = 0.012 respectively). CONCLUSIONS: FLX APCD use has been found to demonstrate desirable patient-reported outcomes as a general trend. The participants in this study noted statistically significant subjective improvement in swelling and pain, ease of use of device as well as adherence to training and compliance with device. FLX appears to be positively received by patients, and the authors recommend its consideration for management of bilateral lower extremity phlebolymphedema.

A model for delivery of extracorporeal life support in a stand-alone veterans affairs medical center.

INTRODUCTION: For the Veterans Health Administration (VHA) to continue to perform complex cardiothoracic surgery, there must be an established pathway for providing urgent/emergent extracorporeal life support (ECLS). Partnership with a nearby tertiary care center with such expertise may be the most resource-efficient way to provide ECLS services to patients in post-cardiotomy cardiogenic shock or respiratory failure. The goal of this project was to assess the efficiency, safety, and outcomes of surgical patients who required transfer for perioperative ECLS from a single stand-alone Veterans Affairs Medical Center (VAMC) to a separate ECLS center. METHODS: Cohort consisted of all cardiothoracic surgery patients who experienced cardiogenic shock or refractory respiratory failure at the local VAMC requiring urgent or emergent institution of ECLS between 2019 and 2022. The primary outcomes are the safety and timeliness of transport. RESULTS: Mean time from the initial shock call to arrival at the ECLS center was 2.8 h. There were no complications during transfer. Six patients (86%) survived to decannulation. CONCLUSION: These results suggest that complex cardiothoracic surgery can be performed within the VHA system and when there is an indication for ECLS, those services can be safely and effectively provided at an affiliated, properly equipped center.

Differences in psychological treatment outcomes by ethnicity and gender: an analysis of individual patient data.

PURPOSE: There are discrepancies in mental health treatment outcomes between ethnic groups, which may differ between genders. NHS Talking Therapies for anxiety and depression provide evidence-based psychological therapies for common mental disorders. This study examines the intersection between ethnicity and gender as factors associated with psychological treatment outcomes. Aims were to explore by gender: (1) differences in psychological treatment outcomes for minoritized ethnic people compared to White-British people, (2) whether differences are observed when controlling for clinical and socio-demographic factors associated with outcomes, and (3) whether organization-level factors moderate differences in outcomes between ethnic groups. METHODS: Patient data from eight NHS Talking Therapies for anxiety and depression services (n = 98,063) was used to explore associations between ethnicity and outcomes, using logistic regression. Stratified subsamples were used to separately explore factors associated with outcomes for males and females. RESULTS: In adjusted analyses, Asian (OR = 0.82 [95% CI 0.78; 0.87], p < .001, 'Other' (OR = 0.79 [95%CI 0.72-0.87], p < .001) and White-other (0.93 [95%CI 0.89-0.97], p < .001) ethnic groups were less likely to reliably recover than White-British people. Asian (OR = 1.48 [95% CI 1.35-1.62], p < .001), Mixed (OR = 1.18 [95% CI 1.05-1.34], p = .008), 'Other' (OR = 1.60 [95% CI 1.38-1.84], p < .001) and White-other (OR = 1.18 [95% CI 1.09-1.28], p < .001) groups were more likely to experience a reliable deterioration in symptoms. Poorer outcomes for these groups were consistent across genders. There was some evidence of interactions between ethnic groups and organization-level factors impacting outcomes, but findings were limited. CONCLUSIONS: Across genders, Asian, 'Other' and White-other groups experienced worse treatment outcomes across several measures in adjusted models. Reducing waiting times or offering more treatment sessions might lead to increased engagement and reduced drop-out for some patient groups.

Radiolabeling and preclinical animal model evaluation of DTPA coupled 99mTc-labelled flutamide complex ([99mTc]DTPA-FLUT) as a potential radiotracer for cancer imaging.

BACKGROUND: Advances in molecular imaging strategies have had an effect on precise diagnosis and treatment. Research has been intensified to develop more effective and versatile radiopharmaceuticals to uplift diagnostic efficiency and, consequently, the treatment. PURPOSE: To label the flutamide (FLUT) coupled with diethylenetriamine pentaacetate (DTPA) with technetium-99 m (99mTc) and to evaluate its binding efficiency with rhabdomyosarcoma (RMS) cancer cells. MATERIAL AND METHODS: Radiolabeling of FLUT with 185 MBq freshly eluted 99mTcO4-1 was carried out via DTPA bifunctional chelating agent using stannous chloride reducing agent at pH 5. The labeled compound was assessed for its purity using chromatography analysis, stability in saline and blood serum, AND charge using paper electrophoresis. Normal biodistribution was studied using a mouse model, while binding affinity with RMS cancer cells was studied using an internalization assay. The in vivo accumulation of RMS cancer cells in a rabbit model was monitored using a SPECT gamma camera. RESULTS: Radiolabeling reaction displayed a pharmaceutical yield of 97% and a stability assay showed >95% intact radiopharmaceutical up to 6 h in saline and blood serum. In vitro internalization studies showed the potential of [99mTc]DTPA-FLUT to enter into cancer cells. This biodistribution study showed rapid blood clearance and minimum uptake by body organs, and scintigraphy displayed the [99mTc]DTPA-FLUT uptake by lesion, induced by RMS cancer cell lines in rabbit. CONCLUSION: Stable, newly developed [99mTc]DTPA-FLUT seeks its way to internalize into RMS cancer cells, indicating it could be a potential candidate for the diagnosis of RMS cancer.

Short-term patency of iliofemoral to tibial bypass with vascular allografts in a minority population: A retrospective analysis of a single center acute care facility.

OBJECTIVE: The aim of this study was to examine the short-term patency rates and associated factors of open lower limb, iliofemoral to tibial bypass using cryopreserved saphenous vein (CSV) in a minority population at an acute care hospital in New York City. METHODS: A retrospective analysis of patients undergoing infra-inguinal bypass from iliofemoral vessels to tibial arteries with CSV between March 2020-April 2022 at an acute care facility (Harlem Hospital Center, Harlem, New York) was performed. Data including patient demographics, comorbidities, type of operation, follow-up surveillance, and salvage procedures were collected. Results were presented in patency line graphs and a life table. Target limb revascularization (TLR) and amputation free survival (AFS) were also calculated. RESULTS: Eleven bypass procedures were included in the analysis. Patients were followed for a mean of 10.8 months. Cumulative primary patency rates at 1, 6, and 12 months were 72.7%, 54.5%, and 40.9%, respectively. TLR was 36.4% and the AFS was 66.67% at the mean 10.8-month follow-up. CONCLUSIONS: The patency rates of minority patients undergoing bypass with CSV were analyzed with creation of a life table and calculation of patency rates, TLR and AFS. The short-term primary patency rates and post-operative outcomes were found to be comparable to larger studies in non-minority cohorts. These results suggest that larger studies as well as prospective analyses and randomized controlled trials in this patient cohort and demographic are needed, as well as optimal selection of patients to determine true clinical implications.

Phytochemicals, Health-Promoting Effects, and Enzyme Inhibition Traits of Phlomis stewartii Extracts.

Phlomis stewartii is a wild, perennial woody plant used for diverse therapeutic targets. The present work evaluated the influence of independent variables such as extraction time, solvent concentration, and speed in the range of (100 mL, 150 mL, and 200 mL), (2 h, 5 h, and 8 h), and (100 rpm, 150 rpm, and 200 rpm), respectively, on extraction yields, phytochemical components, total phenolic contents (TPC), and total flavonoid contents (TFC) of P. stewartii extract. In the present work, response surface methodology (RSM) was applied to optimize the extraction yield. High-performance liquid chromatography (HPLC) was performed to detect the bioactive constituents of the extracts. The potent extracts were analyzed to study α-amylase and α-glucosidase inhibitory activities. Under the optimized conditions of solvent concentration (200 mL), extraction time (8 h), and speed (150 rpm), the whole plant methanol extract (WPME) showed a maximum extraction yield of 13.5%, while the leaves methanol extract (LME) showed a maximum TPC of 19.5 ± 44 mg of gallic acid equivalent (GAE) per gram of extract and a maximum TFC of 4.78 ± 0.34 mg of quercetin equivalent (QE) per gram of extract. HPLC analysis showed the presence of p-coumaric, gallic acid, quercetin, salicylic acid, sinapic acid, and vanillic acid. LME showed the highest α-amylase inhibitory activity (IC50 = 46.86 ± 0.21 µg/mL) and α-glucosidase inhibitory activity (IC50 value of 45.81 ± 0.17 µg/mL). Therefore, in conclusion, LME could be considered to fix the α-amylase and α-glucosidase-mediated disorders in the human body to develop herbal phytomedicine.

ChatGPT and dentistry: a step toward the future.

This article aims to explore the integration of ChatGPT, an advanced conversational artificial intelligence model, in the field of dentistry. The review primarily consists of information related to the capabilities and functionalities of ChatGPT and how these abilities can aid dental professionals. This study includes data from research papers, case studies, and relevant literature on language models, as well as papers on dentistry, patient communication, dental education, and clinical decision-making. A systematic approach was used to select relevant studies and literature. The selection criteria focused on papers that specifically discussed the integration of language models, ChatGPT in particular, in dentistry and their applications. The study findings revealed that ChatGPT has significant potential to revolutionize dentistry by offering various applications and benefits. It can enhance patient engagement and understanding through personalized oral health information and guidance. In dental education, ChatGPT can provide interactive learning, case studies, and virtual patient simulations. ChatGPT can also assist researchers in analyzing dental literature, identifying patterns, and generating insights. Moreover, it supports dentists with evidence-based recommendations, treatment options, and diagnostic support. Integrating ChatGPT in dentistry can be highly beneficial, but it is crucial to address ethical considerations, accuracy, and privacy concerns. Responsible implementation and continuous improvement of its functionalities are necessary to ensure that patient care and outcomes are improved.

Large Language Models for Intraoperative Decision Support in Plastic Surgery: A Comparison between ChatGPT-4 and Gemini.

Background and Objectives: Large language models (LLMs) are emerging as valuable tools in plastic surgery, potentially reducing surgeons' cognitive loads and improving patients' outcomes. This study aimed to assess and compare the current state of the two most common and readily available LLMs, Open AI's ChatGPT-4 and Google's Gemini Pro (1.0 Pro), in providing intraoperative decision support in plastic and reconstructive surgery procedures. Materials and Methods: We presented each LLM with 32 independent intraoperative scenarios spanning 5 procedures. We utilized a 5-point and a 3-point Likert scale for medical accuracy and relevance, respectively. We determined the readability of the responses using the Flesch-Kincaid Grade Level (FKGL) and Flesch Reading Ease (FRE) score. Additionally, we measured the models' response time. We compared the performance using the Mann-Whitney U test and Student's t-test. Results: ChatGPT-4 significantly outperformed Gemini in providing accurate (3.59 ± 0.84 vs. 3.13 ± 0.83, p-value = 0.022) and relevant (2.28 ± 0.77 vs. 1.88 ± 0.83, p-value = 0.032) responses. Alternatively, Gemini provided more concise and readable responses, with an average FKGL (12.80 ± 1.56) significantly lower than ChatGPT-4's (15.00 ± 1.89) (p < 0.0001). However, there was no difference in the FRE scores (p = 0.174). Moreover, Gemini's average response time was significantly faster (8.15 ± 1.42 s) than ChatGPT'-4's (13.70 ± 2.87 s) (p < 0.0001). Conclusions: Although ChatGPT-4 provided more accurate and relevant responses, both models demonstrated potential as intraoperative tools. Nevertheless, their performance inconsistency across the different procedures underscores the need for further training and optimization to ensure their reliability as intraoperative decision-support tools.

Development and validation of a multivariable model for prediction of malignant transformation and recurrence of oral epithelial dysplasia.

BACKGROUND: Oral epithelial dysplasia (OED) is the precursor to oral squamous cell carcinoma which is amongst the top ten cancers worldwide. Prognostic significance of conventional histological features in OED is not well established. Many additional histological abnormalities are seen in OED, but are insufficiently investigated, and have not been correlated to clinical outcomes. METHODS: A digital quantitative analysis of epithelial cellularity, nuclear geometry, cytoplasm staining intensity and epithelial architecture/thickness is conducted on 75 OED whole-slide images (252 regions of interest) with feature-specific comparisons between grades and against non-dysplastic/control cases. Multivariable models were developed to evaluate prediction of OED recurrence and malignant transformation. The best performing models were externally validated on unseen cases pooled from four different centres (n = 121), of which 32% progressed to cancer, with an average transformation time of 45 months. RESULTS: Grade-based differences were seen for cytoplasmic eosin, nuclear eccentricity, and circularity in basal epithelial cells of OED (p < 0.05). Nucleus circularity was associated with OED recurrence (p = 0.018) and epithelial perimeter associated with malignant transformation (p = 0.03). The developed model demonstrated superior predictive potential for malignant transformation (AUROC 0.77) and OED recurrence (AUROC 0.74) as compared with conventional WHO grading (AUROC 0.68 and 0.71, respectively). External validation supported the prognostic strength of this model. CONCLUSIONS: This study supports a novel prognostic model which outperforms existing grading systems. Further studies are warranted to evaluate its significance for OED prognostication.

BK DNAemia and native kidney polyomavirus nephropathy following lung transplantation.

BK virus DNAemia (BKPyV) and nephropathy are common after kidney transplant; however, there are limited data on BK infections in nonrenal solid organ transplant recipients. We examined the frequency, clinical and pathologic features, and kidney and lung outcomes of BKPyV and BK virus native kidney nephropathy (BKVN) in lung transplant recipients at our center. Among 878 recipients transplanted from 2003 to 2019, 56 (6%) developed BKPyV at a median of 30.1 months after transplant (range, 0.6-213) and 11 (1.3%) developed BKVN at a median of 46 months after transplant (range, 9-213). The incidence of end-stage kidney disease was significantly higher in patients with peak viral load ≥10 000 copies/mL (39% vs 8%, P < .001). All cases of BKVN were in patients with peak viral load of ≥10 000 copies/mL, and 55% of these patients developed end-stage kidney disease. Despite the reduction of immunosuppression to treat BKVN, only 1 patient developed acute rejection, and lung function was stable >1 year. BKPyV and nephropathy are more common after lung transplantation than previously reported. Routine screening for BKPyV should be considered in all lung transplant recipients.