Deciphering Early-Stage Molecular Mechanisms of Negative Pressure Wound Therapy in a Murine Model.

Negative Pressure Wound Therapy (NPWT) is a commonly employed clinical strategy for wound healing, yet its early-stage mechanisms remain poorly understood. To address this knowledge gap and overcome the limitations of human trials, we establish an NPWT C57BL/6JNarl mouse model to investigate the molecular mechanisms involved in NPWT. In this study, we investigate the intricate molecular mechanisms through which NPWT expedites wound healing. Our focus is on NPWT's modulation of inflammatory immune responses and the concurrent orchestration of multiple signal transduction pathways, resulting in shortened coagulation time and reduced inflammation. Notably, we observe a significant rise in dickkopf-related protein 1 (DKK-1) concentration during NPWT, promoting the differentiation of Hair Follicle Stem Cells (HFSCs) into epidermal cells, expediting wound closure. Under negative pressure, macrophages express and release DKK-1 cytokines, crucial for stimulating HFSC differentiation, as validated in animal experiments and in vitro studies. Our findings illuminate the inflammatory dynamics under NPWT, revealing potential signal transduction pathways. The proposed framework, involving early hemostasis, balanced inflammation, and macrophage-mediated DKK-1 induction, provides a novel perspective on enhancing wound healing during NPWT. Furthermore, these insights lay the groundwork for future pharmacological advancements in managing extensive wounds, opening avenues for targeted therapeutic interventions in wound care.

Laparoscopic vs. open feeding jejunostomy: a systemic review and meta-analysis.

BACKGROUND: Feeding jejunostomy is a solid way for patients to maintain enteral nutrition. However, debate over the superiority of the laparoscopic vs. laparotomic method has raised concerns in recent years. This systemic review and meta-analysis aimed to compare the postoperative outcomes between these two approaches. METHODS: We searched PubMed, Embase, and Scopus from the date of inception to April 2022 for studies comparing laparoscopic and open feeding jejunostomy. Study characteristics and outcomes were extracted from the included articles. The primary outcome was the relative risk (RR) of postoperative complications in each group. We also analyzed the major/minor complication rates and operations, excluding major concomitant procedures. The risk of bias of included studies were assessed using the ROBINS-I tool. The certainty of evidence was rated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: A total of seven retrospective studies with 1195 patients in total were included in this systemic review and meta-analysis. Laparoscopic feeding jejunostomy carried a significantly lower postoperative complication rate (RR: 0.62; 95% CI, 0.42-0.91, p = 0.02, low certainty of evidence) compared with laparotomy, and the heterogeneity was moderate (I2 = 34%, p = 0.18). After excluding major concomitant procedures, the RR between the laparoscopic and open group was 0.48 (95% CI, 0.33-0.70, p < 0.001, low certainty of evidence), suggesting that the laparoscopic approach was superior in terms of postoperative complications. CONCLUSIONS: Our results indicate that laparoscopic feeding jejunostomy might reduce the postoperative overall complication rate compared with open feeding jejunostomy.

Reduced-port robotic radical gastrectomy for gastric cancer: a single-institute experience.

BACKGROUND: Reduced-port laparoscopic gastrectomy can potentially reduce postoperative pain and improve recovery time. However, the inherent difficulty caused by the narrow manipulation angle makes this operation difficult, especially during lymph node dissection. The intrinsic advantage of the da Vinci® robotic system might offset this difficulty, maintaining adequate surgical quality with risks of surgical complications equal to those by the conventional four-port robotic approach. The aim of this study was to compare the reduced-port robotic approach and the conventional four-port approach in terms of postoperative pain and short-term surgical outcomes. METHODS: All patients who underwent radical gastrectomy with D2 lymph node dissection using the da Vinci Xi robotic system, including reduced-port or conventional four-port approach, were analyzed retrospectively. The primary outcome was postoperative pain assessed using the numerical rating scale (NRS). The secondary outcomes were the number of harvested lymph nodes, operation time, length of hospital stay, and postoperative 30-day complications. RESULTS: Forty-eight patients were enrolled in the study, 10 cases in the reduced-port and 38 in the conventional four-port group. Postoperative NRS revealed no significant difference between the reduced-port and conventional four-port groups [postoperative day (POD) 1: 4.5 vs. 3, p = 0.047, POD 3: 4 vs. 3, p = 0.178]. After propensity score matching, there were no significant differences in the median number of harvested lymph nodes, operation time, and length of hospital stay between the groups. The postoperative 30-day complications were more frequent in the conventional four-port group, but there was no significant difference compared with the reduced-port group after propensity score matching. CONCLUSIONS: Reduced-port robotic gastrectomy with D2 lymph node dissection might be comparable to the conventional four-port robotic operation in terms of postoperative pain, surgical quality, and short-term outcomes. However, further studies are required to confirm our results and clarify the advantages of the robotic reduced-port approach.

Recurrent right hepatic artery pseudoaneurysm after robotic-assisted cholecystectomy in a patient with Mirizzi syndrome: a case report.

BACKGROUND: Iatrogenic hepatic artery pseudoaneurysm is a rare complication following laparoscopic cholecystectomy. Trans-arterial embolization (TAE) is an effective way to control bleeding after a ruptured aneurysm. But uncommonly, rebleeding may occur which will require a second embolization or even laparotomy. CASE PRESENTATION: We report a case of a 45-year-old woman who underwent robotic-assisted cholecystectomy after the diagnosis of type II Mirizzi syndrome. During the operation, the anterior branch of the right hepatic artery was damaged and Hem-o-lok clips were applied to control the bleeding. The postoperative course was smooth, and the patient was discharged 6 days after the procedure. However, one week after hospital discharge, she presented to the emergency department with right upper abdominal tenderness, melena, and jaundice. After examination, the computed tomography angiography (CTA) revealed a 3 cm pseudoaneurysm at the distal stump of the right hepatic artery anterior branch. TAE with gelfoam material was performed. Three days later, the patient had an acute onset of abdominal pain. A recurrent pseudoaneurysm was found at the same location. She underwent TAE again but this time with a steel coil. No further complication was noted, and she was discharged one week later. CONCLUSIONS: Even with the assistance of modern technologies such as the robotic surgery system, one should still take extra caution while handling the vessels. Also, embolization of the pseudoaneurysm with steel coils may be suitable for preventing recurrence.

Inferior Vena Cava Volume Is an Independent Predictor of Massive Transfusion in Patients With Trauma.

OBJECTIVES: Early adequate resuscitation of patients with trauma is crucial in preventing shock and early mortality. Thus, we aimed to determine the performance of the inferior vena cava (IVC) volume and other risk factors and scores in predicting massive transfusion and mortality. METHODS: We included all patients with trauma who underwent computed tomography (CT) scan of the torso, which included the abdominal area, in our emergency department (ED) from January 2014 to January 2017. We calculated the 3-dimensional IVC volume from the left renal vein to the IVC bifurcation. The primary outcome was the performance of IVC volume in predicting massive transfusion, and the secondary outcome was the performance of IVC volume in predicting 24-hour and 30-day in-hospital mortality. RESULTS: Among the 236 patients with trauma, 7.6% received massive transfusions. The IVC volume and revised trauma score (RTS) were independent predictors of massive transfusion (adjusted odds ratio [OR]: 0.79 vs 1.86, 95% confidence interval [CI], 0.71-0.89 vs 1.4-2.47, respectively). Both parameters showed the good area under the curve (AUC) for the prediction of massive transfusion (adjusted AUC: 0.83 and 0.82, 95% CI, 0.74-0.92 vs 0.72-0.93, respectively). Patients with a large IVC volume (fourth quartile) were less likely to receive massive transfusion than those with a small IVC volume (first quartile, ≥28.29 mL: 0% vs <15.08 mL: 20.3%, OR: 0.13, 95% CI, 0.03-0.66). CONCLUSIONS: The volume of IVC measured on CT scan and RTS are independent predictors of massive transfusion in patients with trauma in the ED.

Transoral robotic thyroidectomy versus transoral endoscopic thyroidectomy: a propensity-score-matched analysis of surgical outcomes.

BACKGROUND: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) has been shown to be safe and has similar outcomes as open thyroidectomy for selected patients. It is not clear if transoral robotic thyroidectomy (TORT) may extend transoral endoscopic thyroidectomy to more complex thyroid operations. The study aimed to compare the safety and outcomes of TORT with those of TOETVA. METHODS: We retrospectively reviewed all patients who had TORT and TOETVA performed by a single surgeon from June 2017 to May 2019. Intrathoracic goiter and combined operations were excluded. Surgical outcomes were compared after propensity score matching. Learning curves, as measured by operating time, were evaluated. RESULTS: A total of 150 patients underwent 154 transoral (55 TORT and 99 TOETVA) thyroidectomy. Of the 154 operations, 28 (18.2%) were bilateral total thyroidectomy and 126 (81.8%) were unilateral thyroid lobectomy. After propensity score matching, we found a longer operative time (median [interquartile range]) for TORT (n = 53) than for the TOETVA (308 [284-388] vs 228 [201-267] min, P < 0.001). Blood loss and visual analog scale scores for pain were not significantly different between the two groups. Central neck lymph node dissection was performed more frequent in the TORT group (28 of 53 [52.8%] vs 10 of 53 [18.9%], P = 0.001), and when performed, the numbers of total and positive lymph nodes did not differ significantly between the two groups. The rates of hypoparathyroidism and recurrent laryngeal nerve injury did not differ significantly between the two groups. There was no conversion to open thyroidectomy, mental nerve injury, or surgical site infection. The learning curve for TORT was 25 cases, but no obvious learning curve was observed for TOETVA. CONCLUSIONS: TORT requires a longer operative time, but is as safe as TOETVA and may be useful for more complex thyroid operations.

Predictive Analytics for Care and Management of Patients With Acute Diseases: Deep Learning-Based Method to Predict Crucial Complication Phenotypes.

BACKGROUND: Acute diseases present severe complications that develop rapidly, exhibit distinct phenotypes, and have profound effects on patient outcomes. Predictive analytics can enhance physicians' care and management of patients with acute diseases by predicting crucial complication phenotypes for a timely diagnosis and treatment. However, effective phenotype predictions require several challenges to be overcome. First, patient data collected in the early stages of an acute disease (eg, clinical data and laboratory results) are less informative for predicting phenotypic outcomes. Second, patient data are temporal and heterogeneous; for example, patients receive laboratory tests at different time intervals and frequencies. Third, imbalanced distributions of patient outcomes create additional complexity for predicting complication phenotypes. OBJECTIVE: To predict crucial complication phenotypes among patients with acute diseases, we propose a novel, deep learning-based method that uses recurrent neural network-based sequence embedding to represent disease progression while considering temporal heterogeneities in patient data. Our method incorporates a latent regulator to alleviate data insufficiency constraints by accounting for the underlying mechanisms that are not observed in patient data. The proposed method also includes cost-sensitive learning to address imbalanced outcome distributions in patient data for improved predictions. METHODS: From a major health care organization in Taiwan, we obtained a sample of 10,354 electronic health records that pertained to 6545 patients with peritonitis. The proposed method projects these temporal, heterogeneous, and clinical data into a substantially reduced feature space and then incorporates a latent regulator (latent parameter matrix) to obviate data insufficiencies and account for variations in phenotypic expressions. Moreover, our method employs cost-sensitive learning to further increase the predictive performance. RESULTS: We evaluated the efficacy of the proposed method for predicting two hepatic complication phenotypes in patients with peritonitis: acute hepatic encephalopathy and hepatorenal syndrome. The following three benchmark techniques were evaluated: temporal multiple measurement case-based reasoning (MMCBR), temporal short long-term memory (T-SLTM) networks, and time fusion convolutional neural network (CNN). For acute hepatic encephalopathy predictions, our method attained an area under the curve (AUC) value of 0.82, which outperforms temporal MMCBR by 64%, T-SLTM by 26%, and time fusion CNN by 26%. For hepatorenal syndrome predictions, our method achieved an AUC value of 0.64, which is 29% better than that of temporal MMCBR (0.54). Overall, the evaluation results show that the proposed method significantly outperforms all the benchmarks, as measured by recall, F-measure, and AUC while maintaining comparable precision values. CONCLUSIONS: The proposed method learns a short-term temporal representation from patient data to predict complication phenotypes and offers greater predictive utilities than prevalent data-driven techniques. This method is generalizable and can be applied to different acute disease (illness) scenarios that are characterized by insufficient patient clinical data availability, temporal heterogeneities, and imbalanced distributions of important patient outcomes.

A deep learning-based, unsupervised method to impute missing values in electronic health records for improved patient management.

Electronic health records (EHRs) often suffer missing values, for which recent advances in deep learning offer a promising remedy. We develop a deep learning-based, unsupervised method to impute missing values in patient records, then examine its imputation effectiveness and predictive efficacy for peritonitis patient management. Our method builds on a deep autoencoder framework, incorporates missing patterns, accounts for essential relationships in patient data, considers temporal patterns common to patient records, and employs a novel loss function for error calculation and regularization. Using a data set of 27,327 patient records, we perform a comparative evaluation of the proposed method and several prevalent benchmark techniques. The results indicate the greater imputation performance of our method relative to all the benchmark techniques, recording 5.3-15.5% lower imputation errors. Furthermore, the data imputed by the proposed method better predict readmission, length of stay, and mortality than those obtained from any benchmark techniques, achieving 2.7-11.5% improvements in predictive efficacy. The illustrated evaluation indicates the proposed method's viability, imputation effectiveness, and clinical decision support utilities. Overall, our method can reduce imputation biases and be applied to various missing value scenarios clinically, thereby empowering physicians and researchers to better analyze and utilize EHRs for improved patient management.

Diabetes poses a higher risk of hepatocellular carcinoma and mortality in patients with chronic hepatitis B: A population-based cohort study.

Diabetes mellitus may be a risk factor of HCC development in chronic hepatitis B infected patients and affect the all-cause mortality. This study aimed to examine whether DM was associated with the development of HCC with CHB and affected the all-cause mortality. A total of 2966 CHB patients newly diagnosed with DM in 2000 were retrieved from the Longitudinal Cohort of Diabetes Patients database and used propensity scores matching based on age, sex-gender, alcohol-related liver disease and baseline liver cirrhosis to compare with the non-DM patients from the Taiwanese National Health Insurance Research Database. The CHB patients with DM compared to the non-DM had significantly increased (3.3%) risk for HCC development and significantly increased (2.8%) risk of HCC-related mortality. Interestingly, the all-cause mortality was significantly higher in the DM cohort (16.9%) compared to the non-DM cohort (8.2%). In a multivariable transition-specific Cox model to investigate the adjusted hazard ratio of CHB patients with DM or non-DM during the transitions from start to HCC was 1.35; 95% CI (1.16-1.57) and from HCC to death was 1.31; 95% CI (1.06-1.62). All-cause mortality between CHB patients with DM or non-DM during the transitions from start to death was 2.32; 95% CI (1.84-2.92). Taken together, DM is an independent risk factor associated with increasing disease development of HCC, HCC-related mortality and all-cause mortality in CHB patients. This study may provide a clinical strategy for strict DM control in order to reduce the risk of disease development in CHB patients.

Predicting hepatocellular carcinoma recurrences: A data-driven multiclass classification method incorporating latent variables.

Hepatocellular carcinoma (HCC), a malignant form of cancer, is frequently treated with surgical resections, which have relatively high recurrence rates. Effective recurrence predictions enable physicians' timely detections and adequate therapeutic measures that can greatly improve patient care and outcomes. Toward that end, predictions of early versus late HCC recurrences should be considered separately to reflect their distinct onset time horizons, clinical causes, underlying clinical etiology, and pathogenesis. We propose a novel Bayesian network-based method to predict different HCC recurrence outcomes by considering the respective recurrence evolution paths. Typical patient information obtained in early stages is insufficiently informative to predict recurrence outcomes accurately, due to the lack of subsequent patient progression information. Our method alleviates such information deficiency constraints by incorporating an independent latent variable, dominant recurrence type, to regulate recurrence outcome predictions (early, late, or no recurrence). We use a real-world HCC data set to evaluate the proposed method, relative to three prevalent benchmark techniques. Overall, the results show that our method consistently and significantly outperforms all the benchmark techniques in terms of accuracy, precision, recall, and F-measures. For increased robustness, we use another data set to perform an out-of-sample evaluation and obtain similar results. This study thus contributes to HCC recurrence research and offers several implications for clinical practice.

Diabetes, hepatocellular carcinoma, and mortality in hepatitis C-infected patients: A population-based cohort study.

BACKGROUND AND AIM: The effect of diabetes mellitus (DM) on the development of hepatocellular carcinoma (HCC) and all-cause mortality after HCC development in chronic hepatitis C virus (HCV)-infected patients remains inconclusive. This cohort study aimed to investigate these issues using the Taiwanese National Health Insurance Research Database. METHODS: We retrieved and enrolled newly diagnosed DM patients with HCV from the Longitudinal Cohort of Diabetes Patients database. Propensity score matching-including age, sex, alcohol-related liver disease, and baseline liver cirrhosis-was used to identify and enroll HCV patients without DM from the Longitudinal Health Insurance Database (n = 1686). A multi-state model was used to investigate transitions from "start-to-HCC," "start-to-death," and "HCC-to-death." RESULTS: The multi-state model showed higher cumulative hazards for "start-to-HCC," "start-to-death," and "HCC-to-death" transitions in the DM (vs non-DM) cohort. The cumulative probability of death with or without HCC after 10 years of follow-up was higher in the DM cohort than in the non-DM cohort. Multivariable transition-specific Cox models demonstrated that DM significantly increased the risk for transition from "start-to-HCC" (adjusted hazard ratio [aHR] 1.36; 95% confidence interval [CI] 1.16-1.59; P < 0.001), "start-to-death" (aHR 2.61; 95% CI: 2.05-3.33; P < 0.001), and "HCC-to-death" (aHR 1.36; 95% CI 1.10-1.68; P = 0.005). The effect of liver cirrhosis on "start-to-HCC" and "start-to-death" transitions decreased over time, particularly within 2 years. CONCLUSIONS: Diabetes mellitus increased the risk of HCC development in HCV-infected patients and the risk of all-cause mortality in patients with or without HCC.

Serum Glutamine Levels as a Potential Diagnostic Biomarker in Sepsis following Surgery for Peritonitis.

Few diagnostic biomarkers for sepsis after emergency peritonitis surgery are available to clinicians, and, thus, it is important to develop new biomarkers for patients undergoing this procedure. We investigated whether serum glutamine and selenium levels could be diagnostic biomarkers of sepsis in individuals recovering from emergency peritonitis surgery. From February 2012 to March 2013, patients who had peritonitis diagnosed at the emergency department and underwent emergency surgery were screened for eligibility. Serum glutamine and selenium levels were obtained at pre-operative, post-operative and recovery time points. The average level of pre-operation serum glutamine was significantly different from that on the recovery day (0.317 ± 0.168 vs. 0.532 ± 0.155 mM, P < 0.001); moreover, serum glutamine levels were unaffected by surgery. Selenium levels were significantly lower on the day of surgery than they were at recovery (106.6 ± 36.39 vs. 130.68 ± 56.98 ng/mL, P = 0.013); no significant difference was found between pre-operation and recovery selenium levels. Unlike selenium, glutamine could be a sepsis biomarker for individuals with peritonitis. We recommend including glutamine as a biomarker for sepsis severity assessment in addition to the commonly used clinical indicators.

miR-122-mediated translational repression of PEG10 and its suppression in human hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC), a primary liver malignancy, is the most common cancer in males and fourth common cancer in females in Taiwan. HCC patients usually have a poor prognosis due to late diagnosis. It has been classified as a complex disease because of the heterogeneous phenotypic and genetic traits of the patients and a wide range of risk factors. Micro (mi)RNAs regulate oncogenes and tumor suppressor genes that are known to be dysregulated in HCC. Several studies have found an association between downregulation of miR-122, a liver-specific miRNA, and upregulation of paternally expressed gene 10 (PEG10) in HCC; however, the correlation between low miR-122 and high PEG10 levels still remains to be defined and require more investigations to evaluate their performance as an effective prognostic biomarker for HCC. METHODS: An in silico approach was used to isolate PEG10, a potential miR-122 target implicated in HCC development. miR-122S binding sites in the PEG10 promoter were evaluated with a reporter assay. The regulation of PEG10 by miR-122S overexpression was examined by quantitative RT-PCR, western blotting, and immunohistochemistry in miR-122 knockout mice and liver tissue from HCC patients. The relationship between PEG10 expression and clinicopathologic features of HCC patients was also evaluated. RESULTS: miR-122 downregulated the expression of PEG10 protein through binding to 3'-untranslated region (UTR) of the PEG10 transcript. In miR-122 knockout mice and HCC patients, the deficiency of miR-122 was associated with HCC progression. The expression of PEG10 was increased in 57.3 % of HCC as compared to paired non-cancerous tissue samples. However, significant upregulation was detected in 56.5 % of patients and was correlated with Okuda stage (P = 0.05) and histological grade (P = 0.001). CONCLUSIONS: miR-122 suppresses PEG10 expression via direct binding to the 3'-UTR of the PEG10 transcript. Therefore, while PEG10 could not be an ideal diagnostic biomarker for HCC but its upregulation in HCC tissue still has predictive value for HCC prognosis.

Application and advantages of a joystick-controlled robotic scope holder in transoral endoscopic thyroidectomy vestibular approach: a comparative study.

Transoral endoscopic thyroidectomy has gained popularity due to its scarless nature, but the use of a handheld endoscope can lead to an unstable visual field. Soloassist II, a robotic scope holder, enables precise control using a joystick, ensuring stable vision. This study aims to evaluate the application and the advantages of Soloassist II in transoral thyroidectomy. Patients who underwent transoral thyroidectomy with Soloassist II or human assistance between June 2019 and May 2021 were reviewed. Patient demographics and surgical outcomes were compared. The ergonomic stress of the assistant in both groups was also measured. A total of 100 consecutive patients were included: 32 were assisted by Soloassist II and 68 by humans. The Soloassist II group demonstrated significantly shorter operation times (median [IQR]) (165 [149,179] vs. 181 [165,204] min, P = 0.004) in unilateral lobectomy and less blood loss (median [IQR]) (2 [2,2] vs. 2 [2,3] ml, P = 0.002) than the human-assisted group. Postoperative course and complication rates were similar. The musculoskeletal pain of the assistant was significantly higher and involved more areas in the human-assisted group. The utilization of Soloassist II in transoral endoscopic thyroidectomy is easy to set up and leads to shorter operation times, reduced blood loss, and decreased musculoskeletal pain compared to human handheld endoscope. These findings support the potential of Soloassist II in improving surgical outcomes and minimizing physical strain during transoral thyroidectomy.

Surgical intervention may provides better outcomes for hip fracture in nonagenarian patients: A retrospective observational study.

Background: Hip fracture is a common disease in the elderly. Among these patients, surgical intervention for hip fracture should be carefully considered because of old age and multiple comorbidities. There are still insufficient comparisons between nonagenarian patients treated with surgery and those treated non-surgically. We studied hip fracture nonagenarian patients to compare the different outcomes between surgical and non-surgical treatments. Materials and methods: Nonagenarian patients visiting the emergency department with hip fractures between March 2010 and December 2020 were identified. Overall survival was estimated using multivariate Cox proportional hazards models. The mortality rates, the length of hospital stay, complication and readmission rates were also recorded. Results: A total of 173 patients who underwent surgery and 32 who received conservative treatments were included. The median survival time was 58.47 months in the OP group, which was significantly higher than the 24.28 months in the non-OP group. After adjusting for covariates, including age, sex, Charlson Comorbidity Index (CCI), injury severity score, and fracture type, the risk of death was reduced by surgery (hazard ratio [HR] = 0.427; 95 % confidence interval [CI]: 0.207-0.882; p = 0.021). CCI was also an independent risk factor for poor survival rate (HR = 1.3; 95 % CI: 1.115-1.515; p = 0.001). After adjusting for several factors, surgery within 48 h improved overall survival (HR: 2.518; 95 % CI: 1.299-4.879; p = 0.006) in operative group. Conclusion: Our study suggests that surgical treatment may provide better survival for nonagenarian patients with hip fractures than non-operation, especially patients with less concurrent comorbidities.

High-Intensity Interval Training Is Associated With Improved 10-Year Survival by Mediating Left Ventricular Remodeling in Patients With Heart Failure With Reduced and Mid-Range Ejection Fraction.

BACKGROUND: This study aimed to assess the left ventricular (LV) remodeling response and long-term survival after high-intensity interval training (HIIT) in patients with various heart failure (HF) phenotypes during a 10-year longitudinal follow-up. METHODS AND RESULTS: Among 214 patients with HF receiving guideline-directed medical therapy, those who underwent an additional 36 sessions of aerobic exercise at alternating intensities of 80% and 40% peak oxygen consumption (V̇$$ \dot{\mathrm{V}} $$O2peak) were considered HIIT participants (n=96). Patients who did not undergo HIIT were considered participants receiving guideline-directed medical therapy (n=118). Participants with LV ejection fraction (EF) <40%, ≥40% and <50%, and ≥50% were considered to have HF with reduced EF, HF with mid-range EF, and HF with preserved EF, respectively. V̇$$ \dot{\mathrm{V}} $$O2peak, serial LV geometry, and time to death were recorded. In all included participants, 10-year survival was better (P=0.015) for participants who underwent HIIT (80.3%) than for participants receiving guideline-directed medical therapy (68.6%). An increased V̇$$ \dot{\mathrm{V}} $$O2peak, decreased minute ventilation carbon dioxide production slope, and reduced LV end-diastolic diameter were protective factors against all-cause mortality. Regarding 138 patients with HF with reduced EF (P=0.044) and 36 patients with HF with mid-range EF (P=0.036), 10-year survival was better for participants who underwent HIIT than for participants on guideline-directed medical therapy. Causal mediation analysis showed a significant mediation path for LV end-diastolic diameter on the association between HIIT and 10-year mortality in all included patients with HF (P<0.001) and those with LV ejection fraction <50% (P=0.006). HIIT also had a significant direct association with 10-year mortality in patients with HF with LV ejection fraction <50% (P=0.027) but not in those with LV ejection fraction ≥50% (n=40). CONCLUSIONS: Reversal of LV remodeling after HIIT could be a significant mediating factor for 10-year survival in patients with HF with reduced EF and those with HF with mid-range EF.

A hierarchical multilabel graph attention network method to predict the deterioration paths of chronic hepatitis B patients.

OBJECTIVE: Estimating the deterioration paths of chronic hepatitis B (CHB) patients is critical for physicians' decisions and patient management. A novel, hierarchical multilabel graph attention-based method aims to predict patient deterioration paths more effectively. Applied to a CHB patient data set, it offers strong predictive utilities and clinical value. MATERIALS AND METHODS: The proposed method incorporates patients' responses to medications, diagnosis event sequences, and outcome dependencies to estimate deterioration paths. From the electronic health records maintained by a major healthcare organization in Taiwan, we collect clinical data about 177 959 patients diagnosed with hepatitis B virus infection. We use this sample to evaluate the proposed method's predictive efficacy relative to 9 existing methods, as measured by precision, recall, F-measure, and area under the curve (AUC). RESULTS: We use 20% of the sample as holdouts to test each method's prediction performance. The results indicate that our method consistently and significantly outperforms all benchmark methods. It attains the highest AUC, with a 4.8% improvement over the best-performing benchmark, as well as 20.9% and 11.4% improvements in precision and F-measures, respectively. The comparative results demonstrate that our method is more effective for predicting CHB patients' deterioration paths than existing predictive methods. DISCUSSION AND CONCLUSION: The proposed method underscores the value of patient-medication interactions, temporal sequential patterns of distinct diagnosis, and patient outcome dependencies for capturing dynamics that underpin patient deterioration over time. Its efficacious estimates grant physicians a more holistic view of patient progressions and can enhance their clinical decision-making and patient management.

Prognosis of chronic kidney disease in patients with non-alcoholic fatty liver disease: a Northeastern Taiwan community medicine research cohort.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with incident chronic kidney disease (CKD). We aimed to investigate outcomes and risk factors of CKD progression and regression. METHODS: This is a longitudinal community-based cohort study of patients with NAFLD. Exclusion criteria included alcoholic liver diseases, sero-positive for hepatitis B surface antigen, sero-positive for hepatitis C virus antibodies, fatty liver index <60, individuals with only one year of data, missing data for fibrosis-4 score (FIB-4 score) and NAFLD fibrosis score (NFS), and advanced CKD at baseline. Main outcomes were stratified according to estimated glomerular filtration rate (eGFR) and albuminuria categories as state 1 (low risk), state 2 (moderately increased risk), and state 3 (high-risk/very-high risk of progression). The multi-state Markov model was used for outcome analysis. RESULTS: This study included 1628 patients with NAFLD with a median follow-up of 3.4 years. State 2 CKD was found in 9.3% of patients at 5 years (95% CI, 8.1%-10.6%). Most patients with state 2 CKD recovered to state 1 (69%; 95% CI, 63.7%-74%), while 17.6% progressed to state 3 (95% CI, 13.4%-22.7%). Advanced liver fibrosis was found to be associated with the risk of transitioning from state 1 to state 2 ((FIB-4 score) ≥1.3; hazard ratio (HR), 1.42; 95% CI, 1.02-2.00), and reduced recovery from state 2 to state 1 (NFS≥-1.455; HR, 0.56; 95% CI, 0.34-0.91). CONCLUSION: NAFLD severity is associated with CKD, which may be reversible before becoming high-risk. Controlling metabolic risk factors and preventing advanced liver fibrosis are recommended.