Advancing teeth whitening efficacy via dual-phototherapeutic strategy incorporating molybdenum disulfide embedded in carrageenan hydrogel for dental healthcare.

Teeth discoloration poses a widespread challenge in dental health across various regions. Conventional teeth whitening methods often result in enamel deterioration and soft tissue harm due to the utilization of incompatible whitening agents and continuous intense light exposure. Here, we propose an effective phototherapy technique for teeth whitening, employing pathways of energy transition through intersystem crossing. The integration of MoS2 nanosheets into carrageenan gel (MoS2 NSs@Carr) facilitates both photothermal-hyperthermia and the generation of reactive oxygen species (ROS) through photocatalytic processes. The efficacy of ROS generation by the phototherapeutic MoS2 NSs@Carr on teeth whitening in all scenarios. This approach ensures comprehensive teeth whitening by eliminating deep-seated stains on the teeth while preserving structural integrity and avoiding any tissue toxicity. This research highlights the efficacy of the phototherapeutic MoS2 NSs@Carr for dental whitening and underscores the potential of exploring nanostructures based on MoS2 NSs for treating oral ailments.

Connectome-based Brain Marker Moderates the Relationship between Childhood Adversity and Transdiagnostic Psychopathology during Early Adolescence.

Importance: Identifying brain-based markers of resiliency that reliably predict who is and is not at elevated risk for developing psychopathology among children who experience adverse childhood experiences (ACEs) is important for improving our mechanistic understanding of these etiological links between child adversity and psychopathology and guiding precision medicine and prevention efforts for reducing psychiatric impact of ACEs. Objective: To examine associations between ACEs and transdiagnostic psychopathology during the transition from preadolescence to early adolescence and test whether these associations are moderated by a hypothesized resilience factor, a previously identified connectome variate (CV) that is associated with higher cognitive function and lower psychopathology. Design Setting and Participants: This study was conducted in a longitudinal design based on multicenter data from a community cohort of U.S. youth aged of 9-11 at baseline, who participated in the Adolescent Brain Cognitive Development (ABCD) study (N=7,382 at baseline and 6,813 at 2-year follow-up). Linear regression models and moderation analyses were used to characterize concurrent and prospective associations between lifetime ACEs and number of DSM-5 psychiatric disorders (indexing transdiagnostic psychopathology) and to determine if individual variations in these associations were moderated by the CV derived from resting-state fMRI at baseline. Main Outcomes and Measures: Cumulative number of current DSM-5 psychiatric disorders assessed using the computerized self-admin version Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5) and lifetime ACEs assessed from child and parent reports at baseline (9-10 years) and 2-year-follow-up (11-12 years). Results: ACE total scores correlated positively with the cumulative number of current DSM-5 psychiatric disorders at both baseline (r =.258, p < .001) and 2-year follow-up (r =.257, p < .001). The baseline CV score moderated the ACE-disorder associations at baseline (B = -0.021, p < .001) and at 2-year follow-up (B = -0.018, p = .008), as well as the association between the changes in ACE and in the number of disorders from baseline to year 2 (B = -0.012, p = .045). Post-hoc analyses further showed that the moderation effect of CV on ACE-psychopathology associations was specific to the threat-related ACEs and to female youth. Conclusions and Relevance: These findings provide preliminary evidence for a connectome-based resiliency marker and suggest that functional connectivity strength in a broad system including frontal-parietal cortices and subcortical nuclei relevant to cognitive control may protect preadolescents who have experienced lifetime ACEs--especially females and those experiencing threat-related ACEs--from developing transdiagnostic psychopathology.

Effectiveness of a Multifaceted Implementation Strategy to Increase Equitable Hospital at Home Utilization: An Interrupted Time Series Analysis.

BACKGROUND: The number of Hospital-at-Home (HaH) programs rapidly increased during the COVID-19 pandemic and after issuance of Centers for Medicare and Medicaid Services' (CMS) Acute Hospital Care at Home (AHCaH) waiver. However, there remains little evidence on effective strategies to equitably expand HaH utilization. OBJECTIVE: Evaluate the effects of a multifaceted implementation strategy on HaH utilization over time. DESIGN: Before and after implementation evaluation using electronic health record (EHR) data and interrupted time series analysis, complemented by qualitative interviews with key stakeholders. PARTICIPANTS: Between December 2021 and December 2022, we identified adults hospitalized at six hospitals in North Carolina approved by CMS to participate in the AHCaH waiver program. Eligible adults met criteria for HaH transfer (HaH-eligible clinical condition, qualifying home environment). We conducted semi-structured interviews with 12 HaH patients and 10 referring clinicians. INTERVENTIONS: Two strategies were studied. The discrete implementation strategy (weeks 1-12) included clinician-directed educational outreach. The multifaceted implementation strategy (weeks 13-54) included ongoing clinician-directed educational outreach, local HaH assistance via nurse navigators, involvement of clinical service line executives, and individualized audit and feedback. MEASURES: We assessed weekly averaged HaH capacity utilization, weekly counts of unique referring providers, and patient characteristics. We analyzed themes from qualitative data to determine barriers and facilitators to HaH use. RESULTS: Our evaluation showed week-to-week increases in HaH capacity utilization during the multifaceted implementation strategy period, compared to discrete-period trends (slope-change odds ratio-1.02, 1.01-1.04). Counts of referring providers also increased week to week, compared to discrete-period trends (slope-change means ratio-1.05, 1.03-1.07). The increase in HaH utilization was largest among rural residents (11 to 34%). Barriers included HaH-related information gaps and referral challenges; facilitators included patient-centeredness of HaH care. CONCLUSIONS: A multifaceted implementation strategy was associated with increased HaH capacity utilization, provider adoption, and patient diversity. Health systems may consider similar, contextually relevant multicomponent approaches to equitably expand HaH.

Obesity is associated with adverse outcomes in primary immune thrombocytopenia - a retrospective single-center study.

The pathophysiology of immune thrombocytopenia (ITP) involves immune-mediated platelet destruction. The presence of adipose tissue in obese individuals creates an inflammatory environment that could potentially impact the clinical course and outcomes of ITP. However the relationship between obesity and ITP outcomes has not been well described. We evaluated ITP outcomes in 275 patients diagnosed with primary ITP from 2012 to 2022. Patients were categorized into four groups based on their body mass index (BMI) at diagnosis. Female gender was associated with a lower platelet count at the time of diagnosis at any BMI. Patients with high BMI had lower platelet counts at diagnosis and at platelet nadir (p < 0.001), an increased likelihood of requiring therapy (p < 0.001) and requiring multiple lines of therapy (p = 0.032). Non-obese patients who required corticosteroid treatment experienced a longer remission duration compared to obese patients (p = 0.009) and were less likely to be steroid-dependent (p = 0.048). Our findings suggest that obesity may be a significant risk factor for developing ITP and for ITP prognosis. Future studies are needed to evaluate the role of weight loss intervention in improving ITP outcomes.

Solvent engineering for scalable fabrication of perovskite/silicon tandem solar cells in air.

Perovskite/silicon tandem solar cells hold great promise for realizing high power conversion efficiency at low cost. However, achieving scalable fabrication of wide-bandgap perovskite (~1.68 eV) in air, without the protective environment of an inert atmosphere, remains challenging due to moisture-induced degradation of perovskite films. Herein, this study reveals that the extent of moisture interference is significantly influenced by the properties of solvent. We further demonstrate that n-Butanol (nBA), with its low polarity and moderate volatilization rate, not only mitigates the detrimental effects of moisture in air during scalable fabrication but also enhances the uniformity of perovskite films. This approach enables us to achieve an impressive efficiency of 29.4% (certified 28.7%) for double-sided textured perovskite/silicon tandem cells featuring large-size pyramids (2-3 µm) and 26.3% over an aperture area of 16 cm2. This advance provides a route for large-scale production of perovskite/silicon tandem solar cells, marking a significant stride toward their commercial viability.

A review on revolutionizing ophthalmic therapy: Unveiling the potential of chitosan, hyaluronic acid, cellulose, cyclodextrin, and poloxamer in eye disease treatments.

Ocular disorders, encompassing both common ailments like dry eye syndrome and more severe situations for instance age-related macular degeneration, present significant challenges to effective treatment due to the intricate architecture and physiological barriers of the eye. Polysaccharides are emerging as potential solutions for drug delivery to the eyes due to their compatibility with living organisms, natural biodegradability, and adhesive properties. In this review, we explore not only the recent advancements in polysaccharide-based technologies and their transformative potential in treating ocular illnesses, offering renewed optimism for both patients and professionals but also anatomy of the eye and the significant obstacles hindering drug transportation, followed by an investigation into various drug administration methods and their ability to overcome ocular-specific challenges. Our focus lies on biological adhesive polymers, including chitosan, hyaluronic acid, cellulose, cyclodextrin, and poloxamer, known for their adhesive characteristics enhancing drug retention on ocular surfaces and increasing bioavailability. A detailed analysis of material designs used in ophthalmic formulations, such as gels, lenses, eye drops, nanofibers, microneedles, microspheres, and nanoparticles, their advantages and limitations, the potential of formulations in improving therapeutic outcomes for various eye conditions. Moreover, we underscore the discovery of novel polysaccharides and their potential uses in ocular drug delivery.

Ultrasensitive and multiplexed tracking of single cells using whole-body PET/CT.

In vivo molecular imaging tools are crucially important for elucidating how cells move through complex biological systems; however, achieving single-cell sensitivity over the entire body remains challenging. Here, we report a highly sensitive and multiplexed approach for tracking upward of 20 single cells simultaneously in the same subject using positron emission tomography (PET). The method relies on a statistical tracking algorithm (PEPT-EM) to achieve a sensitivity of 4 becquerel per cell and a streamlined workflow to reliably label single cells with over 50 becquerel per cell of 18F-fluorodeoxyglucose (FDG). To demonstrate the potential of the method, we tracked the fate of more than 70 melanoma cells after intracardiac injection and found they primarily arrested in the small capillaries of the pulmonary, musculoskeletal, and digestive organ systems. This study bolsters the evolving potential of PET in offering unmatched insights into the earliest phases of cell trafficking in physiological and pathological processes and in cell-based therapies.

Increased [18F]FDG uptake of radiation-induced giant cells: a single-cell study in lung cancer models.

Positron emission tomography (PET), a cornerstone in cancer diagnosis and treatment monitoring, relies on the enhanced uptake of fluorodeoxyglucose ([18F]FDG) by cancer cells to highlight tumors and other malignancies. While instrumental in the clinical setting, the accuracy of [18F]FDG-PET is susceptible to metabolic changes introduced by radiation therapy. Specifically, radiation induces the formation of giant cells, whose metabolic characteristics and [18F]FDG uptake patterns are not fully understood. Through a novel single-cell gamma counting methodology, we characterized the [18F]FDG uptake of giant A549 and H1299 lung cancer cells that were induced by radiation, and found it to be considerably higher than that of their non-giant counterparts. This observation was further validated in tumor-bearing mice, which similarly demonstrated increased [18F]FDG uptake in radiation-induced giant cells. These findings underscore the metabolic implications of radiation-induced giant cells, as their enhanced [18F]FDG uptake could potentially obfuscate the interpretation of [18F]FDG-PET scans in patients who have recently undergone radiation therapy.

Lifestyle practices and associated factors among adults with hypertension: Conquering Hypertension in Vietnam-solutions at the grassroots level study.

BACKGROUND: Vietnam is experiencing an increasing prevalence of hypertension in its adult population. In addition to medical therapy, modifying adverse lifestyle practices is important for effective blood pressure control. There are limited data on unhealthy lifestyle practices in patients with chronic diseases, however, particularly among hypertensive patients living in rural Vietnam. Our study objectives were to examine the prevalence of unhealthy lifestyle practices and associated factors among rural Vietnamese adults with uncontrolled hypertension. METHODS: Data from the baseline survey of a cluster randomized trial among hypertensive Vietnamese adults (2017-2022) were utilized. Information on unhealthy lifestyle practices including smoking, excessive alcohol consumption, physical inactivity, and inadequate fruit and vegetable intake was collected from study participants. The primary study outcome was having ≥2 unhealthy lifestyle practices. A multivariable logistic regression model was used to examine factors associated with the primary study outcome. RESULTS: The mean age of the 671 patients was 67 years and 45.0% were men. Nearly three out of every four participants had one or fewer unhealthy practices, 24.0% had two, and 3.3% had three or all four unhealthy lifestyle practices. Men, individuals who did unpaid work or were unemployed, and individuals with hypertension level III were more likely to have ≥2 unhealthy lifestyle practices, whereas individuals with higher education were less likely to have ≥2 unhealthy lifestyle practices compared with respective comparison groups. CONCLUSIONS: We observed a high prevalence of unhealthy lifestyle practices among rural Vietnamese patients with uncontrolled hypertension. Several demographic factors were associated with a greater number of unhealthy lifestyle practices. Newer interventions and educational programs encouraging lifestyle modification practices are needed to control hypertension among adults living in rural settings of Vietnam.

MPCNN: A Novel Matrix Profile Approach for CNN-based Single Lead Sleep Apnea In Classification Problem.

Sleep apnea (SA) is a significant respiratory condition that poses a major global health challenge. Deep Learning (DL) has emerged as an efficient tool for the classification problem in electrocardiogram (ECG)-based SA diagnoses. Despite these advancements, most common conventional feature extractions derived from ECG signals in DL, such as R-peaks and RR intervals, may fail to capture crucial information encompassed within the complete ECG segments. In this study, we propose an innovative approach to address this diagnostic gap by delving deeper into the comprehensive segments of the ECG signal. The proposed methodology draws inspiration from Matrix Profile algorithms, which generate an Euclidean distance profile from fixed-length signal subsequences. From this, we derived the Min Distance Profile (MinDP), Max Distance Profile (MaxDP), and Mean Distance Profile (MeanDP) based on the minimum, maximum, and mean of the profile distances, respectively. To validate the effectiveness of our approach, we use the modified LeNet-5 architecture as the primary CNN model, along with two existing lightweight models, BAFNet and SE-MSCNN. Our experiment results on the PhysioNet Apnea-ECG dataset (70 overnight recordings), and the UCDDB dataset (25 overnight recordings) revealed that our new feature extraction method achieved per-segment accuracies of up to 92.11% and 81.25%, respectively. Moreover, using the PhysioNet data, we achieved a per-recording accuracy of 100% and yielded the highest correlation of 0.989 compared to state-of-the-art methods. By introducing a new feature extraction method based on distance relationships, we enhanced the performance of certain lightweight models in DL, showing potential for home sleep apnea test (HSAT) and SA detection in IoT devices. The source code for this work is made publicly available in GitHub: https://github.com/vinuni-vishc/MPCNN-Sleep-Apnea.

Record-High Thermoelectric Performance in Al-Doped ZnO via Anderson Localization of Band Edge States.

Oxides are of interest for thermoelectrics due to their high thermal stability, chemical inertness, low cost, and eco-friendly constituting elements. Here, adopting a unique synthesis route via chemical co-precipitation at strongly alkaline conditions, one of the highest thermoelectric performances for ZnO ceramics ( P F max = $PF_{\text{max}} =$  21.5 µW cm-1 K-2 and z T max = $zT_{\text{max}} =$  0.5 at 1100 K in Zn 0.96 Al 0.04 O ${\rm Zn}_{0.96} {\rm Al}_{0.04}{\rm O}$ ) is achieved. These results are linked to a distinct modification of the electronic structure: charge carriers become trapped at the edge of the conduction band due to Anderson localization, evidenced by an anomalously low carrier mobility, and characteristic temperature and doping dependencies of charge transport. The bi-dimensional optimization of doping and carrier localization enable a simultaneous improvement of the Seebeck coefficient and electrical conductivity, opening a novel pathway to advance ZnO thermoelectrics.

A ratiometric substrate for rapid evaluation of transfer hydrogenation efficiency in solution.

A cyclometalated iridium(III) complex bearing a self-immolative quinolinium moiety was developed as a ratiometric substrate for transfer hydrogenation studies. This photoluminescent probe allowed the rapid screening of a variety of Ir catalysts using a microplate reader, offering a convenient method to assess activity using a minimum amount of catalyst sample.

Heterologous expression of pediocin PA-1 in Pichia pastoris: cloning, expression, characterization, and application in pork bologna preservation.

OBJECTIVE: Pediocin PA-1, an antimicrobial peptide derived from Pediococcus acidilactici PAC1.0, has a potential application as a food preservative thanks to its strong inhibitory activity against the foodborne pathogen L. monocytogenes. This study aimed to produce Pediocin PA-1 from the yeast P. pastoris and evaluate its characteristics. METHODS: Gene encoding Pediocin PA-1 was integrated into P. pastoris X33 genome to establish the strain X33::ped, which could produce and secrete this peptide into culture medium. The antimicrobial activity of Pediocin PA-1 was examined using agar diffusion assay. The stability of pediocin PA-1 was determined based on its remaining antibacterial activity after exposure to proteases and extreme pH and temperatures. The potential use of this bacteriocin in food preservation was demonstrated using the L. monocytogenes infected pork bologna. The anticancer activity of Pediocin PA-1 was also investigated on some cancer cells using MTT assay. RESULTS: We established the yeast P. pastoris X33::ped capable of producing pediocin PA-1 with antimicrobial activity against L. monocytogenes and some other harmful bacteria. Pediocin PA-1 was stable at 100˚C and resistant against pH 1-12 for 1 h, but susceptible to trypsin, α-chymotrypsin, and proteinase K. This peptide could reduce the number of L. monocytogenes in pork bologna by 3.59 log CFU/g after 7 days of storage at 4˚C. Finally, Pediocin PA-1 (25 µg/ml) inhibited the proliferation of A549 and Hela cancer cells. CONCLUSION: We succeeded in producing active Pediocin PA-1 from P. pastoris and demonstrated its potential use in food preservation and pharmaceutical industry.

Description of Trypoxylonsicklum sp. nov. from Vietnam and a key to species in the Trypoxylonfulvocollare group (Hymenoptera, Crabronidae).

Background: Trypoxylon Latreille, 1796 (Hymenoptera, Crabronidae) consists of 633 known species worldwide and the genus is divided into numerous species groups. In Vietnam, 19 species of Trypoxylon have been recorded to date. In this study, a new species, Trypoxylonsicklum Pham and Antropov sp. nov. is described and illustrated from Vinh Phuc Province, Vietnam. The new species is the second member of the Trypoxylonfulvocollare species group. A key to species in the Trypoxylonfulvocollaris group is presented. New information: Trypoxylonsicklum Pham and Antropov sp. nov., is described as a new species and is the second member of the Trypoxylonfulvocollare species group. A key to species in the Trypoxylonfulvocollaris group is presented.

A regionally tailored epidemiological forecast and monitoring program to guide a healthcare system in the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, analytics and predictive models built on regional data provided timely, accurate monitoring of epidemiological behavior, informing critical planning and decision-making for health system leaders. At Atrium Health, a large, integrated healthcare system in the southeastern United States, a team of statisticians and physicians created a comprehensive forecast and monitoring program that leveraged an array of statistical methods. METHODS: The program utilized the following methodological approaches: (i) exploratory graphics, including time plots of epidemiological metrics with smoothers; (ii) infection prevalence forecasting using a Bayesian epidemiological model with time-varying infection rate; (iii) doubling and halving times computed using changepoints in local linear trend; (iv) death monitoring using combination forecasting with an ensemble of models; (v) effective reproduction number estimation with a Bayesian approach; (vi) COVID-19 patients hospital census monitored via time series models; and (vii) quantified forecast performance. RESULTS: A consolidated forecast and monitoring report was produced weekly and proved to be an effective, vital source of information and guidance as the healthcare system navigated the inherent uncertainty of the pandemic. Forecasts provided accurate and precise information that informed critical decisions on resource planning, bed capacity and staffing management, and infection prevention strategies. CONCLUSIONS: In this paper, we have presented the framework used in our epidemiological forecast and monitoring program at Atrium Health, as well as provided recommendations for implementation by other healthcare systems and institutions to facilitate use in future pandemics.

Tumour size predicts risk of recurrence in tall cell subtype papillary thyroid carcinoma.

BACKGROUND: The tall cell subtype of papillary thyroid cancer (TCPTC) is the most common aggressive subtype and often treated aggressively. This approach may not be necessary in smaller tumours without adverse histological characteristics. METHODS: 97 patients with TCPTC defined as a height-to-width ratio of ≥3:1 and at least 30% tall cells were compared against 390 classical papillary thyroid carcinoma (CPTC) based on tumour size with recurrence free survival (RFS) as the primary outcome. RESULTS: TCPTC are more likely to present with adverse histological characteristics. In smaller tumours (<2 â€‹cm), only central lymph node metastasis (HR7.16 p â€‹= â€‹0.03) and multifocality (HR10.11 p â€‹= â€‹0.026) increased recurrence risk. In larger tumours, TCPTC histology (HR3.78 p â€‹= â€‹0.002), lymphovascular invasion (HR3.02 p â€‹= â€‹0.014) and central lymph node metastasis (HR3.24 p â€‹< â€‹0.001) significantly increased recurrence risk. CONCLUSION: TCPTC tumours <2 â€‹cm without central lymph node metastasis and multifocality are similar in risk of recurrence to classical PTC and could be managed with lobectomy.

Morusacerane: A new gammacerane triterpenoid from the trunk of Morus Alba linn. with α-glucosidase inhibitory activity.

This phytochemistry investigation on the trunk of Morus alba L. resulted in the isolation of three triterpenoids, including a new gammacerane triterpenoid - morusacerane (1); along with two known compounds of betulinic acid (2) and ursolic acid (3). The structure elucidation was thoroughly conducted based on 1D, 2D-NMR and HRESIMS spectra, followed by a comparison with existing literatures. The evaluation on α-glucosidase inhibitory exhibited the great potential of the application of these isolated compounds in diabetes treatments. The results show that morusacerane (1), betulinic acid (2), and ursolic acid (3) demonstrate the strong inhibitory with the IC50 values of 106.1, 11.12, and 7.20 µM, respectively. All of these compounds interacted well with the allosteric site enzyme α-glucosidase MAL32 through H-bonds and hydrophobic interaction.

Water adsorption on surfaces of calcium aluminosilicate crystal phase of stone wool: a DFT study.

Stone wool is widely used as an efficient thermal insulator within the construction industry; however, its performance can be significantly impacted by the presence of water vapor. By altering the material's characteristics and effective thermo-physical properties, water vapor can reduce overall efficacy in various environmental conditions. Therefore, understanding water adsorption on stone wool surfaces is crucial for optimizing insulation properties. Through the investigation of interaction between water molecules and calcium aluminosilicate (CAS) phase surfaces within stone wool using density functional theory (DFT), we can gain insight into underlying mechanisms governing water adsorption in these materials. This research aims to elucidate the molecular-level interaction between water molecules and CAS surfaces, which is essential for understanding fundamental properties that govern their adsorption process. Both dissociative and molecular adsorptions were investigated in this study. For molecular adsorption, the adsorption energy ranged from -  84 to -  113 kJ mol - 1 depending on surface orientation. A wider range of adsorption energy ( -  132 to -  236 kJ mol - 1 ) was observed for dissociative adsorption. Molecular adsorption was energetically favored on (010) surfaces while dissociative adsorption was most favorable on (111) surfaces. This DFT study provides valuable insights into the water adsorption behavior on low index surfaces of CAS phase in stone wool, which can be useful for designing effective strategies to manage moisture-related issues in construction materials. Based on these findings, additional research on the dynamics and kinetics of water adsorption and desorption processes of this thermal isolation material is suggested.

Phosphorylation-Driven Epichaperome Assembly: A Critical Regulator of Cellular Adaptability and Proliferation.

The intricate protein-chaperone network is vital for cellular function. Recent discoveries have unveiled the existence of specialized chaperone complexes called epichaperomes, protein assemblies orchestrating the reconfiguration of protein-protein interaction networks, enhancing cellular adaptability and proliferation. This study delves into the structural and regulatory aspects of epichaperomes, with a particular emphasis on the significance of post-translational modifications in shaping their formation and function. A central finding of this investigation is the identification of specific PTMs on HSP90, particularly at residues Ser226 and Ser255 situated within an intrinsically disordered region, as critical determinants in epichaperome assembly. Our data demonstrate that the phosphorylation of these serine residues enhances HSP90's interaction with other chaperones and co-chaperones, creating a microenvironment conducive to epichaperome formation. Furthermore, this study establishes a direct link between epichaperome function and cellular physiology, especially in contexts where robust proliferation and adaptive behavior are essential, such as cancer and stem cell maintenance. These findings not only provide mechanistic insights but also hold promise for the development of novel therapeutic strategies targeting chaperone complexes in diseases characterized by epichaperome dysregulation, bridging the gap between fundamental research and precision medicine.

Lean body mass index is a marker of advanced tumor features in patients with hepatocellular carcinoma.

BACKGROUND: Obesity is an independent risk factor for the development of hepatocellular carcinoma (HCC) and may influence its outcomes. However, after diagnosis of HCC, like other malignancies, the obesity paradox may exist where higher body mass index (BMI) may in fact confer a survival benefit. This is frequently observed in patients with advanced HCC and cirrhosis, who often present late with advanced tumor features and cancer related weight loss. AIM: To explore the relationship between BMI and survival in patients with cirrhosis and HCC. METHODS: This is a retrospective cohort study of over 2500 patients diagnosed with HCC between 2009-2019 at two United States academic medical centers. Patient and tumor characteristics were extracted manually from medical records of each institutions' cancer registries. Patients were stratified according to BMI classes: < 25 kg/m2 (lean), 25-29.9 kg/m2 (overweight), and > 30 kg/m2 (obese). Patient and tumor characteristics were compared according to BMI classification. We performed an overall survival analysis using Kaplan Meier by the three BMI classes and after adjusting for Milan criteria. A multivariable Cox regression model was then used to assess known risk factors for survival in patients with cirrhosis and HCC. RESULTS: A total of 2548 patients with HCC were included in the analysis of which 11.2% (n = 286) were classified as non-cirrhotic. The three main BMI categories: Lean (n = 754), overweight (n = 861), and obese (n = 933) represented 29.6%, 33.8%, and 36.6% of the total population overall. Within each BMI class, the non-cirrhotic patients accounted for 15% (n = 100), 12% (n = 94), and 11% (n = 92), respectively. Underweight patients with a BMI < 18.5 kg/m2 (n = 52) were included in the lean cohort. Of the obese cohort, 42% (n = 396) had a BMI ≥ 35 kg/m2. Out of 2262 patients with cirrhosis and HCC, 654 (29%) were lean, 767 (34%) were overweight, and 841 (37%) were obese. The three BMI classes did not differ by age, MELD, or Child-Pugh class. Chronic hepatitis C was the dominant etiology in lean compared to the overweight and obese patients (71%, 62%, 49%, P < 0.001). Lean patients had significantly larger tumors compared to the other two BMI classes (5.1 vs 4.2 vs 4.2 cm, P < 0.001), were more likely outside Milan (56% vs 48% vs 47%, P < 0.001), and less likely to undergo transplantation (9% vs 18% vs 18%, P < 0.001). While both tumor size (P < 0.0001) and elevated alpha fetoprotein (P < 0.0001) were associated with worse survival by regression analysis, lean BMI was not (P = 0.36). CONCLUSION: Lean patients with cirrhosis and HCC present with larger tumors and are more often outside Milan criteria, reflecting cancer related cachexia from delayed diagnosis. Access to care for hepatitis C virus therapy and liver transplantation confer a survival benefit, but not overweight or obese BMI classifications.