Early Treatment Research Articles

Residual gastric cancer with a mixed small cell neuroendocrine and keratinizing squamous cell carcinoma: A case report

BACKGROUND Despite advancements in early detection and treatment, the prognosis and histological types for residual gastric cancer (GC) remains poor. CASE SUMMARY This case report presents a rare occurrence of residual GC featuring a combination of small cell neuroendocrine carcinoma (SCNEC) and squamous cell carcinoma (SCC) in a 60-year-old male patient. The patient, with a history of Billroth II gastrectomy for duodenal ulcer bleeding, presented with gastrointestinal bleeding. Preoperative computed tomography and positron emission tomography-computed tomography indicated adenocarcinoma with tumor and abdominal lymph node metastasis. The patient underwent laparoscopic total gastrectomy and lymph node dissection for residual GC. Histological examination of the resected tumor confirmed the presence of both SCNEC and SCC. Postoperatively, the patient underwent adjuvant chemotherapy four times. Two years later, the patient was found to occur esophageal cancer and was performed a small bowel stoma and radical esophagectomy. CONCLUSION In this case report, we detail a rare instance of residual GC with mixed SCNEC and SCC, emphasizing the complexity of diagnosis and treatment, and the need for ongoing research.

Characteristics and trend analysis of cancer mortality among residents of the Xizang autonomous region, 2014–2023

BackgroundThe Xizang Autonomous Region, located in China’s southwestern frontier with an average elevation of 4000 m, faces socioeconomic development challenges influenced by its natural environment and regional disparities. Previous studies have indicated that cancer ranks as the fourth leading cause of death among permanent residents in Xizang. However, there is a paucity of research on the trends and characteristics of cancer mortality in this region. This study aims to analyze mortality data from Xizang between 2014 and 2023 to elucidate the characteristics and trends of cancer deaths and to provide a foundation for developing effective cancer prevention and treatment strategies.MethodsMortality data for cancer patients from 2014 to 2023 were extracted from the Death Information Registration and Management System of the Chinese Center for Disease Control and Prevention (CDC). The population data for Xizang were obtained from the Basic Information System of the Chinese CDC. Crude and age-standardized mortality rates were computed via SPSS software, and joinpoint regression models were employed to estimate the average annual percent change (AAPC) in mortality trends.ResultsBetween 2014 and 2023, the crude mortality rate (CMR) for cancer increased from 31.38 per 100,000 to 49.37 per 100,000, whereas the age-standardized mortality rate (ASMR) rose from 50.15 per 100,000 to 66.42 per 100,000, with annual increases of 4.59% and 2.12%, respectively. The leading causes of cancer death are liver cancer, stomach cancer, lung cancer, esophageal cancer, and cervical cancer.ConclusionCancer mortality in Xizang is increasing, with higher rates in men than in women, although the rate of increase is faster in women. Mortality rates increase with age, predominantly affecting middle-aged and elderly populations. Liver and stomach cancers are the primary contributors to cancer mortality. Given the severe cancer control situation, comprehensive prevention strategies and early diagnosis and treatment for high-risk populations are crucial.

Soluble Thrombomodulin Is Associated With Endothelial Dysfunction Syndromes After Pediatric Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by endothelial dysfunction-related syndromes like sinusoidal obstruction syndrome (SOS), capillary leak syndrome (CLS), and severe acute graft-versus-host disease (aGvHD). We investigated soluble thrombomodulin (sTM), an endothelial damage marker, in relation to endothelial dysfunction syndromes after pediatric HSCT. We measured sTM levels in 113 children before conditioning until Day +180 after HSCT. Plasma levels of sTM increased significantly after conditioning, particularly in patients receiving busulfan-based regimens (Day +7: 5.0 vs. 7.6ng/mL, p = 0.0023), and remained elevated until Day +180 after HSCT. Children diagnosed with SOS (n = 51) had significantly higher sTM levels at Days +7 and +14 than children without SOS (Day +7: 7.3 vs. 5.0ng/mL, p = 0.017). High sTM levels at Day +14 were associated with aGvHD Grade III-IV (n = 8) in multivariable analysis (OR = 3.0 per quartile increase in sTM, p = 0.021). Likewise, children diagnosed with CLS (n = 15) displayed higher sTM levels at Day +7 (5.3 vs. 8.0ng/mL, p = 0.037), while sTM levels were not associated with engraftment syndrome or bacteremia. High sTM levels early after pediatric HSCT are associated with the development of SOS, CLS, and severe aGvHD. These results suggest that conditioning-induced endothelial damage and activation of pro-thrombotic environment play key roles in the pathogenesis of these syndromes, indicating that sTM may prove clinically useful to guide early diagnosis and treatment of endothelial damage syndromes.

Dyspnea and dystussia in Parkinson’s disease: patient-reported prevalence and determinants

BackgroundThe prevalence of respiratory dysfunction in PD is unknown and a better understanding of determinants contributing to respiratory dysfunction is important to facilitate early recognition and treatment.ObjectiveTo examine the prevalence and determinants of self-reported symptoms of respiratory dysfunction among people with PD.MethodsIn a cross-sectional study, we administered a self-completed questionnaire among a sample of 939 persons with PD. Respiratory dysfunction was defined as experiencing at least one of the following symptoms: breathing difficulties, breathlessness/shortness of breath, tightening of the chest, frequent throat clearing, frequent coughing, or coughing difficulties. A principal component analysis (PCA) was used to define composite constructs of respiratory dysfunction. The association with participant-reported determinants was assessed using multivariable logistic regression models (with adjustment for pulmonary diseases and COVID-19 symptoms).ResultsThe overall prevalence rate of respiratory dysfunction was 44% in persons with PD (42% after excluding pulmonary diseases or COVID-19). The PCA resulted in two constructs of respiratory dysfunction: ‘dyspnea’ and ‘dystussia’ (an impaired cough response), which together explained 68% of the total variance. Female sex (OR = 1.39), higher BMI kg/m2 (OR = 1.04), longer disease duration (OR = 1.35), greater self-reported rigidity (OR = 1.16), previous pulmonary disease(s) (OR = 7.12), and anxiety (OR = 1.04) were independently associated with ‘dyspnea’. Pulmonary disease(s) (OR = 1.81), COVID-19 symptoms (OR = 2.20), swallowing complaints (OR = 1.48), and speech complaints (OR = 1.02) were independently associated with ‘dystussia’.ConclusionsDyspnea and dystussia are common manifestations of respiratory dysfunction among people with PD and deserves more awareness in clinical practice. A proactive screening for the determinants of dyspnea and dystussia may contribute to earlier recognition and treatment of respiratory dysfunction.

Implementation of an electronic early treatment assessment and monitoring questionnaire for oral anticancer medication.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. To evaluate the implementation of an electronic early treatment assessment and monitoring (eTEAM) questionnaire within the electronic health record (EHR) patient portal designed to identify early adverse effects to oral anticancer therapy requiring pharmacist intervention. This quality improvement analysis used the 5 dimensions of the RE-AIM implementation science framework to assess use of an innovative eTEAM questionnaire sent to patients 7 to 14 days after initial counseling on oral anticancer therapy. RE-AIM outcomes included the following: reach and adoption: the number of eTEAM questionnaires sent and the number of eTEAM responses received; effectiveness: the number of pharmacist interventions resulting from the eTEAM questionnaire; implementation: pharmacist responses to a postimplementation survey and semistructured individual interviews; maintenance: responses from postimplementation semistructured individual interviews with pharmacists. Results are reported descriptively. Of the 182 patients sent an eTEAM questionnaire, 47% (n = 85) responded. Pharmacists performed 29 interventions in 25 responding patients, most often due to adverse effects (n = 25) or adherence (n = 4). Most pharmacists agreed that the eTEAM questionnaire was appealing and feasible to use and that its use positively impacted their practice and patient care. Pharmacists recommended that the eTEAM questionnaire be improved by standardizing documentation of patients' actual oral anticancer medication start date in a discrete field. The eTEAM questionnaire was positively received by patients, and pharmacists were supportive of its continued use based on feasibility and impact on practice. The eTEAM questionnaire effectively identified opportunities for pharmacist intervention in patients starting oral anticancer medications.

Factors influencing the incidence of early gastric cancer: a bayesian network analysis

BackgroundThis study aims to establish a Bayesian network risk prediction model for gastric cancer using data mining methods. It explores both direct and indirect factors influencing the incidence of gastric cancer and reveals the interrelationships among these factors.MethodsData were collected from early cancer screenings conducted at the People’s Hospital of Lincang between 2022 and 2023. Initial variable selection was performed using Least Absolute Shrinkage and Selection Operator (Lasso) and Sliding Windows Sequential Forward Selection (SWSFS), and the screened variables and demographic characteristics features were used as variables for constructing the Bayesian network (BN) model. Subsequently, the performance of the models was evaluated, and the optimal model was selected for network mapping and Bayesian inference using the best model.ResultsThe incidence rate of gastric cancer in this region’s high-risk population was determined to be 7.09%. The BN model constructed from the set of variables consisting of Lasso’s selection variables and demographic characteristics had better performance. A total of 12 variables were incorporated into the BN model to form a network structure consisting of 13 nodes and 18 edges. The model shows that age, gender, ethnicity, current address, upper gastrointestinal symptoms (nausea, acid reflux, vomiting), alcohol consumption, smoking, SGIM gastritis, and family history are important risk factors for gastric cancer development.ConclusionThe Bayesian network model provides an intuitive framework for understanding the direct and indirect factors contributing to the early onset of gastric cancer, elucidating the interrelationships among these factors. Furthermore, the model demonstrates satisfactory predictive performance, which may facilitate the early detection of gastric cancer and enhance the levels of early diagnosis and treatment among high-risk populations.

Artificial Intelligence (AI) and the future of Iran’s Primary Health Care (PHC) system

ObjectiveThe rapid adoption of Artificial Intelligence (AI) in health service delivery underscores the need for awareness, preparedness, and strategic utilization of AI’s potential to optimize Primary Health Care (PHC) systems. This study aims to equip Iran’s PHC system for AI integration by envisioning potential futures while addressing past challenges and recognizing current trends.MethodThis study developed a conceptual framework based on the “Future Triangle” (FT) and the “Health Systems Governance” (HSG) models. This framework delineates the characteristics associated with the ‘pulls on the future’ for desired and intelligent PHC, as identified by a panel of experts. Additionally, the ‘weights of the past’—referring to the challenges faced by Iran’s PHC system in utilizing AI—, and the ‘push of the present’—which captures the impacts of AI implementation in global primary care settings—were extracted through a review of relevant literature. The integration and analysis of the collected evidence facilitated the formulation of a range of potential future scenarios, including both optimistic and pessimistic scenarios.FindingsThe interaction between the three elements of the FT will shape the future states of Iran’s PHC, whether optimistic or pessimistic. Building an optimistic scenario for an AI-driven PHC system necessitates addressing past challenges, including deficiencies in the referral and family doctor systems, the absence of evidence-based decision-making, neglect of essential community health needs, fragmented service delivery, high provider workload, and inadequate follow-up on the health status of service recipients. Consideration must also be given to the current impacts of AI in primary care, including comprehensive, coordinated, and need-based service delivery with systematic and integrated monitoring, quality improvement, early disease prevention, precise diagnosis, and effective treatment. Furthermore, fostering a shared vision among stakeholders by defining and advocating for a future system characterized by foresight, resilience, agility, adaptability, and collaboration is essential.ConclusionEnvisioning potential future states requires a balanced consideration of the influence of past, present, and future, recognizing the dual potential of AI to drive either positive or negative outcomes. Achieving the optimistic future or the “utopia of intelligent PHC” and avoiding the pessimistic future or the “dystopia of intelligent PHC” requires coherent planning, attention to the tripartite considerations of the future, past, and present, and a clear understanding of the roles, expectations, and needs of stakeholders.

Anorectal Malformations Associated with Hirschsprung Disease: Insights from a Large Cohort of 2341 ARM Patients in a Single-Center Retrospective Study.

Introduction Anorectal malformation (ARM) and Hirschsprung disease (HSCR) are common congenital gastrointestinal defects, but their co-occurrence is rare. This retrospective study analyzed clinical characteristics of patients with ARM associated with HSCR for early diagnosis and treatment guidance to reduce the occurrence of severe complications. Materials and Methods A single-center retrospective cohort analysis from 2010 to 2024 identified 2341 patients with ARM and 1721 with HSCR. The histopathologic assessment included hematoxylin and eosin (H&E) staining and immunohistochemical staining. Results Seven patients (0.3%) out of 2341 cases of ARM were diagnosed with concurrent HSCR, three males (42.9%) and four females (57.1%). Seven cases are rectoperineal fistula. All cases developed constipation with abdominal distension within one month to one year after anoplasty, even following aggressive bowel management. Barium enema showed obvious transition zones, and anorectal manometry revealed absent rectoanal inhibitory reflex in seven cases. All patients underwent the Swenson procedure. The mean duration of postoperative follow-up was 7.5 ± 2.8 years. Seven cases had no constipation, no soiling, voluntary bowel movements by Krickenbeck classification, and excellent continence by Rintala scoring system in recent follow-up. Conclusions The association between ARM and HSCR may be rarer than previously reported. Low-type ARM and short or rectosigmoid aganglionosis appeared more common in these cases. Persistent postoperative constipation and abdominal distension unresponsive to conservative treatment should raise suspicion for HSCR, prompting timely diagnostic evaluations. Postoperative bowel function needs to be interpreted carefully, and prospective studies are needed to confirm these findings and guide standardized care.

Clinical Values of Combined Detection of Serum Cystatin C, β2-Microglobulin, and Urine Transferrin in Diagnosing Early Primary Glomerulonephritis.

Despite primary glomerulonephritis (PGN) being a leading cause of chronic kidney disease and end-stage renal disease, specific and sensitive biomarkers for the early detection and monitoring of this condition are lacking. We evaluated the value of the combined detection of serum cystatin C (CYSC), β2-microglobulin (β2-MG), and urine transferrin (TRF) for diagnosing early-stage PGN. From May 2021 to May 2023, we enrolled 105 patients in our hospital as the observation group and 50 healthy volunteers as the control group. Their serum expression levels of CYSC, β2-MG, and TRF were evaluated. We plotted separate ROC curves and calculated the area under the curve (AUC) values of CYSC, β2-MG, and TRF to assess their diagnostic performance in PGN. The levels of CYSC, β2-MG, and TRF were significantly higher (P <0.05) in the observation group than in the healthy control group. CYSC, β2-MG, and TRF were expressed at significantly higher levels in G2, G3a, and G3b of PGN than in G1. The combined use of CYSC, β2-MG, and TRF as biomarkers could significantly improve the early diagnosis and monitoring of PGN and may lead to better patient outcomes by facilitating earlier intervention and treatment strategies.

Early treatment with inhibitors of P2Y12 receptor in patients with ST-segment elevation myocardial infarction - 2023 ESC recommendations and scientific evidence. Is clinical evidence sufficient to suggest a move towards precision medicine? The ELECTRA-SIRIO 2 investigators' viewpoint.

The 2023 ESC guidelines changed previously recommended a strategy of early treatment in patients with STEMI. Pre-treatment with a P2Y12 receptor inhibitor may be considered in patients undergoing a primary PCI strategy (Class IIb, Level of evidence B). However, the available scientific evidence justifies a personalized approach differentiating the indications for pre-treatment with oral P2Y12 receptor inhibitors depending on the concomitant administration of opioids. In our opinion, in patients undergoing primary PCI not treated with opioids, pre-treatment with an oral P2Y12 receptor inhibitor should be applied, while in patients undergoing primary PCI treated with opioids, pre-treatment with an oral P2Y12 receptor inhibitor should be considered.

Haematology results, inflammatory haematological ratios, and inflammatory indices in cervical cancer: How is the difference between cancer stage?

Cervical cancer is a prevalent form of cancer affecting women worldwide and it is the second most common cancer among women in Indonesia, accounting for 8.5% of all cancer-related deaths. Cervical cancer progression can be evaluated through laboratory tests to detect anaemia, an increased platelet count, and elevated inflammatory markers, therefore, effective laboratory examination is crucial for early detection and treatment of cervical cancer. To evaluate the association between laboratory findings (haematology, haematology index, and inflammatory index) and the clinical stage of cervical cancer. This cross-sectional study analyzed adult cervical cancer patients' data from medical records and laboratory results including sociodemographic status, histopathological finding, clinical stage, and complete haematology examination. Numerical data was analyzed by the one-way ANOVA (normal data distribution), while the Kruskal-Wallis test was used for non-parametric data (abnormal distribution), followed by appropriate post-hoc analysis. The categorical data was analyzed by the Chi-square or Fisher Exact tests. The significance level was established at a P value < 0.05. This study involved the data of 208 adult cervical cancer patients and found no association between age, marital history, parity history, hormonal contraceptive use and cervical cancer stages. There were significant differences in the clinical laboratory test results based on the clinical stage of cervical cancer, including haemoglobin levels (P < 0.001), leucocytes (P < 0.001), neutrophils (P < 0.001), monocytes (P = 0.002), lymphocytes (P = 0.006), platelets (P < 0.001), neutrophil-lymphocyte ratio/NLR (P < 0.001), lymphocyte-monocyte ratio/LMR (P < 0.001), and platelet-lymphocyte ratio/PLR (P < 0.001). There were also significant differences in the systemic inflammatory index (SII) and systematic inflammatory response index (SIRI) between stage III + IV cervical cancer and stage II (SII P < 0.001; SIRI P = 0.001) and stage I (SII P < 0.001; SIRI P = 0.016), associated with the shifts in previously mentioned complete haematological values with cancer advancement. The haematological parameters, inflammatory haematological ratios, and inflammatory indices exhibited significant differences between cervical cancer stages, therefore these tests can be utilized to evaluate cervical cancer progression.

Retrospective evaluation of the results of ultrasound-accelerated catheter-directed tombolysis in acute-subacute pulmonary embolism patients.

ObjectivesAcute pulmonary embolism (PE) is one of the most serious forms of venous thromboembolism (VTE) with high mortality and morbidity. PE may present with right ventricular dysfunction and hemodynamic disturbances. Early diagnosis and appropriate treatment approaches play a critical role in improving survival. In this study, we evaluated the efficacy and safety of catheter-mediated thrombolytic therapy in intermediate-high-risk PE patients.MethodsOur retrospective study was conducted at Ankara University between 2015 and 2020 and 66 intermediate-high-risk PE patients were analyzed. Clinical, biochemical and echocardiographic data of the patients were analyzed and their response to treatment was evaluated. The primary endpoint was 30-day mortality and secondary endpoints were hemodynamic improvement, length of hospitalization and complication rates.ResultsThe mean age of the patients was 65years and all of them presented with a diagnosis of symptomatic PE. After treatment, significant improvement was observed in right ventricular function, RV/LV ratio, ProBNP and Troponin I levels decreased significantly. Pulmonary artery pressures decreased and hemodynamic parameters improved. The early mortality rate after the procedure was 3% and the rate of major bleeding was low.ConclusionsCatheter-mediated thrombolytic therapy provides hemodynamic improvement in intermediate-high-risk PE patients, while offering a low bleeding risk. Our results suggest that this therapy may be a safe and effective alternative. However, long-term results should be evaluated in large-scale, randomized studies.

What would Hippocrates have sworn upon witnessing the COVID-19 mandates and mortality paradox.

For the first time in human history, hundreds of millions of people all over the world have been subjected to compulsory vaccination with a new type of nucleic acid based vaccines in order to keep their jobs or be able to travel due to some notorious coronavirus disease 2019 (COVID-19) mandates. The vast majority of African countries were either initially deprived of these vaccines, or later, a majority of the population was too skeptical to receive them and preferred a safe early treatment pharmacological approach. Yet, Africa had the lowest COVID-19 mortality rate compared to those countries that adopted mass vaccination. This letter to the editor adds African insights that should be helpful in future pandemics to save millions of precious lives.

Expression and prognosis of NR3C1 in uterine corpus endometrial carcinoma based on multiple datasets

Uterine corpus endometrial carcinoma (UCEC), a prevalent malignancy in the female reproductive system, has witnessed a 30% increase in recent year. Recognizing the significance of early treatment in reducing patient mortality, the identification of potential biomarkers for UCEC plays a crucial role in early diagnosis. This study was to identify key genes associated with UCEC utilizing the Gene Expression Omnibus database, followed by validating their prognostic value across multiple databases. Analysis of four UCEC databases (GSE17025, GSE36389, GSE63678, GSE115810) yielded 72 co-expressed genes. KEGG and GO enrichment analyses revealed their involvement in physiological processes such as transcriptional misregulation in cancer. Constructing a protein–protein interaction network for these 72 genes, the top 10 genes with significant interactions were identified. Survival regression analysis highlighted NR3C1 as the gene with a substantial impact on UCEC prognostic outcomes. Differential expression analysis indicated lower expression of NR3C1 in UCEC compared to normal endometrial tissue. Cox regression analysis, performed on clinical datasets of UCEC patients, identified clinical stage III, clinical stage IV, age, and NR3C1 as independent prognostic factors influencing UCEC outcomes. The LinkedOmics online database revealed the top 50 positively and negatively correlated genes with NR3C1 in UCEC. Subsequent investigations into the relationship between NR3C1 and tumor-infiltrating immune cells were conducted using R software. Gene set enrichment analysis provided insights into NR3C1-related genes, showing enrichment in processes such as Ribosome, Oxidative phosphorylation in UCEC. Collectively, these comprehensive analyses suggest that NR3C1 may serve as a potential biomarker indicating the prognosis of UCEC.

Examining why therapists add sessions to the written exposure therapy protocol and whether it improves treatment outcome: A mixed-methods analysis.

Written exposure therapy (WET) is a brief psychotherapy for posttraumatic stress disorder (PTSD). Although WET is designed to be delivered in five sessions, implementation data collected from trained mental health care providers suggest that therapists sometimes add more sessions without sufficient justification. We conducted a mixed-methods examination to understand why therapists added WET sessions and whether adding sessions improved treatment outcomes. Participants were drawn from a larger trial where therapists were permitted to deliver five to seven WET sessions. This study included 77 client participants who were randomly assigned to receive WET and nine therapist participants who delivered WET during the trial. Results showed that PTSD symptom severity trajectories at follow-up assessment were not significantly different between client participants who received five sessions and those who received more than five. Only 15.7% of participants who received supplemental WET sessions displayed a clinically meaningful reduction in PTSD symptom severity, while 11.8% displayed a clinically meaningful increase in PTSD symptom severity. Qualitative interviews with therapists indicated that their decision to add sessions was largely driven by the client avoiding writing about the traumatic event in early treatment sessions or due to a very complex or lengthy traumatic event that required additional sessions to provide repeated exposure to the trauma memory. Taken together, the findings suggest that adding WET sessions is unnecessary most of the time, but therapists have a strong preference for having flexibility in adding treatment sessions. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Bioenergetic markers in cerebrospinal fluid in first-episode psychosis: Are they predictors of early antipsychotic response and 1-year outcomes?

Bioenergetic markers in cerebrospinal fluid in first-episode psychosis: Are they predictors of early antipsychotic response and 1-year outcomes?

Liquid biopsy in lung cancer.

Precision medicine based on biomarkers, such as genetic abnormalities and PD-L1 expression, has been established for the treatment of nonsmall cell lung cancer. Recently, liquid biopsy has emerged as a valuable and minimally invasive alternative. This method analyzes blood and other bodily fluids to detect cancer-related genetic abnormalities and molecular residual disease (MRD). Liquid biopsy, which includes testing for circulating tumor cells, circulating tumor DNA (ctDNA), and microRNA (miRNA), offers several advantages over conventional methods. It is minimally invasive, can be performed repeatedly, and provides crucial information for early cancer diagnosis, genotyping, and treatment monitoring. Elevated ctDNA levels and miRNA markers show promise for early diagnosis. Liquid biopsy complements traditional tissue biopsy during genotyping, particularly when tumor samples are insufficient. Tests such as Cobas® EGFR Mutation Test v2 and Guardant360® CDx have been shown to be effective in detecting genetic mutations and guiding treatment decisions. Although the accuracy of liquid biopsy is still lower than that of tissue biopsy, its clinical utility continues to improve. For cancer prediction recurrence and treatment monitoring, ctDNA analysis can detect MRD earlier than conventional imaging, offering potential benefits for treatment adjustment and early relapse detection. The continuous development and validation of liquid biopsy methods are essential for improving personalized lung cancer treatment strategies.

Biofilm-Mediated Infections; Novel Therapeutic Approaches and Harnessing Artificial Intelligence for Early Detection and Treatment of Biofilm-Associated Infections.

Biofilm-Mediated Infections; Novel Therapeutic Approaches and Harnessing Artificial Intelligence for Early Detection and Treatment of Biofilm-Associated Infections.

Alpha-1-Antitrypsin Enhances Fat Graft Survival in a Murine Model.

Objective: Fat grafting is widely applied for various purposes, including volume restoration, improving tissue quality, and promoting wound healing, but it has poor long-term graft survival predictability. Alpha-1-antitrypsin (AAT) administration is hypothesized to improve fat graft outcomes by expediting inflammatory resolution and graft vascularity and reducing necrosis. Approach: Mice heterozygote to human AAT was grafted fat under the scalp alongside 400 µg/graft AAT or albumin (ALB) on days 0 and 3. Graft volume was determined by micro-magnetic resonance imaging, and explants were assessed for viability, histology, immunohistochemistry, and expression of selected genes. AAT expression was examined in hypoxia-exposed adipose-derived stem cells (ADSCs). Results: After 90 days, AAT-treated grafts maintained higher volumes (70.06% vs. 34.54%, n = 8, p = 0.02) and displayed improved tissue quality. On day 10 after grafting, grafts exhibited more blood vessels (mean 1.94/mm2 vs. 0.33/mm2) and 6.25-fold more adiponectin transcript levels (n = 12, p = 0.02). Although day-3 interleukin (IL)-1β expression was 5-fold greater in AAT-treated grafts (n = 6, p = 0.4), day-10 IL-1β expression was 2-fold lower compared to ALB-treated grafts (n = 22, p = 0.01). In the Methoxynitrosulfophenyl-tetrazolium carboxanilide (XTT) assay, day-3 AAT-treated grafts were 1.56-fold more metabolically functional (n = 6, p = 0.04) and exhibited greater perilipin-positive regions (18.5% versus 3.1%). Hypoxia-exposed ADSC expressed 9-fold higher AAT transcript levels (p = 0.04). Innovation: Fat grafting outcomes improved by early AAT treatment, probably by accelerating inflammatory resolution. Due to its marked safety profile, the study's findings are for adjunct clinical-grade AAT therapy. Conclusion: AAT has a promising potential to be utilized as a fat graft outcome enhancer in terms of volume retention predictability and tissue quality.

Efficacy of intravenous thrombolysis in patients with mild acute ischemic stroke and large vessel occlusion with different hypoperfusion volumes.

To investigate early treatment strategies for patients with mild acute ischemic stroke and large vessel occlusion, we evaluated the efficacy of intravenous thrombolysis in patients with mild stroke and large vessel occlusion in different hypoperfusion volumes. Cohort data of consecutive patients (October 2021 to June 2024) with anterior circulation large vessel occlusion mild stroke (NIHSS ≤ 5) with onset < 24h were retrospectively analyzed. We compared the outcomes of patients treated with intravenous thrombolysis (IVT) and dual antiplatelet therapy (DAPT). The outcomes of patients on IVT and DAPT were then compared between the large-volume hypoperfusion group (> 65ml) and the small-volume hypoperfusion group (≤ 65ml) based on the hypoperfusion volume of CT perfusion (Tmax > 6s). A total of 222 patients were enrolled in the study (62 IVT, 160 DAPT). In 111 patients with small-volume hypoperfusion, there was no statistically significant difference in the rate of good prognosis (mRS0-1) at 90 days, the rate of early neurological deterioration and the rate of intracranial hemorrhage between the IVT and DAPT groups (P > 0.05). In another 111 patients with large-volume hypoperfusion, the IVT group had a higher rate of good prognosis (mRS0-1) at 90 days (OR:3.639,95%CI:1.249 ~ 10.601, P:0.018) and a higher rate of intracranial hemorrhage (OR:11.029, 95%CI:1.015 ~ 119.873, P:0.049) compared to the DAPT group. In mild acute ischemic stroke patients with large-volume hypoperfusion and large-vessel occlusion, IVT has a higher rate of intracranial hemorrhage but a higher proportion of excellent functional outcomes compared with DAPT. Further randomized controlled trials are needed.