Clinical Impact Research Articles

Clinical and histological impact of diffuse inflammation at pouchoscopy

PurposeThe anatomical location of inflammation in and around the ileal pouch affects the pouch survival rate, and diffuse inflammation has poor pouch survival rates. We aimed to clarify the symptoms and histological findings of diffuse inflammation of the pouch.MethodsWe evaluated the symptoms, treatment, and histological findings according to the endoscopic phenotypes of diffuse inflammation, focal inflammation, and normal as the pouch body phenotype and afferent limb involvement, inlet involvement, cuffitis, and fistula as the peripheral findings.ResultsOf the 318 pouchoscopies, 47 had diffuse inflammation, 201 had focal inflammation, and 70 were normal. Symptomatic patients had diffuse inflammation more frequently (46.8%) than focal inflammation (13.4%) and normal (14.2%), with no difference between focal inflammation and normal. Antibiotics and steroids were higher rate administered in cases of diffuse inflammation, but not in cases of focal inflammation or in normal cases. Histological inflammation, inflammatory bowel disease (IBD)–specific finding, and colonic metaplasia showed severity in the order of diffuse inflammation > focal inflammation > normal. The number of peripheral inflammatory findings overlapped in the following order: diffuse inflammation > focal inflammation > normal. The number of symptomatic patients increased as the number of peripheral inflammatory findings increased.ConclusionPouches with diffuse inflammation are more symptomatic, have a higher use of therapeutic agents, and have more severe histological inflammation, IBD-specific finding, and colonic metaplasia accompanying peripheral inflammatory findings than the other groups. The higher the overlap of inflammatory findings in the surrounding tissues, the more symptomatic the patients will appear.

A comprehensive prediction model for central lymph node metastasis in papillary thyroid carcinoma with Hashimoto’s thyroiditis: BRAF may not be a valuable predictor

PurposePapillary thyroid carcinoma (PTC) frequently coexists with Hashimoto’s thyroiditis (HT), which poses challenges in detecting central lymph node metastasis (CLNM) and determining optimal surgical management. Our study aimed to identify the independent predictors for CLNM in PTC patients with HT and develop a comprehensive prediction model for individualized clinical decision-making.Patients and methodsIn this retrospective study, a total of 242 consecutive PTC patients who underwent thyroid surgery and central lymph node dissection between February 2019 and December 2021 were included. 129 patients with HT were enrolled as the case group and 113 patients without HT as control. The results of patients’ general information, laboratory examination, ultrasound features, pathological evaluation, and BRAF mutation were collected. Multivariate logistic regression analysis was used to identify independent predictors, and the prediction model and nomogram were developed for PTC patients with HT. The performance of the model was assessed using the receiver operating characteristic curve, calibration curve, decision curve analysis, and clinical impact curve. In addition, the impact of the factor BRAF mutation was further evaluated.ResultsMultivariate analysis revealed that gender (OR = 8.341, P = 0.013, 95% CI: 1.572, 44.266), maximum diameter (OR = 0.316, P = 0.029, 95% CI: 0.113, 0.888), multifocality (OR = 3.238, P = 0.010, 95% CI: 1.319, 7.948), margin (OR = 2.750, P = 0.046, 95% CI: 1.020, 7.416), and thyrotropin receptor antibody (TR-Ab) (OR = 0.054, P = 0.003, 95% CI: 0.008, 0.374) were identified as independent predictors for CLNM in PTC patients with HT. The area under the curve of the model was 0.82, with accuracy, sensitivity, and specificity of 77.5%, 80.3% and 75.0%, respectively. Meanwhile, the model showed satisfactory performance in the internal validation. Moreover, the results revealed that BRAF mutation cannot further improve the efficacy of the prediction model.ConclusionMale, maximum diameter > 10mm, multifocal tumors, irregular margin, and lower TR-Ab level have significant predictive value for CLNM in PTC patients with HT. Meanwhile, BRAF mutation may not have a valuable predictive role for CLNM in these cases. The nomogram constructed offers a convenient and valuable tool for clinicians to determine surgical decision and prognostication for patients.

Nomogram based on lymphocyte-associated inflammatory indexes predicts portal vein thrombosis after splenectomy with esophagogastric devascularization

ObjectiveThe relationship between lymphocyte-associated inflammatory indices and portal vein thrombosis (PVT) following splenectomy combined with esophagogastric devascularization (SED) is currently unclear. This study aims to investigate the association between these inflammatory indices and PVT, and to develop a nomogram based on these indices to predict the risk of PVT after SED, providing an early warning tool for clinical practice.MethodsWe conducted a retrospective analysis of clinical data from 131 cirrhotic patients who underwent SED at Lanzhou University’s Second Hospital between January 2014 and January 2024. Independent risk factors for PVT were identified through univariate and multivariate logistic regression analyses, and the best variables were selected using the Akaike Information Criterion (AIC) to construct the nomogram. The model’s predictive performance was assessed through receiver operating characteristic (ROC), calibration, decision, and clinical impact curves, with bootstrap resampling used for internal validation.ResultsThe final model incorporated five variables: splenic vein diameter (SVD), D-Dimer, platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and red cell distribution width-to-lymphocyte ratio (RLR), achieving an area under the curve (AUC) of 0.807, demonstrating high predictive accuracy. Calibration and decision curves demonstrated good calibration and significant clinical benefits. The model exhibited good stability through internal validation.ConclusionThe nomogram model based on lymphocyte-associated inflammatory indices effectively predicts the risk of portal vein thrombosis after SED, demonstrating high accuracy and clinical utility. Further validation in larger, multicenter studies is needed.

Understanding the rationale and clinical impact of the revised CLSI 2024 minocycline susceptibility breakpoints against Stenotrophomonas maltophilia

Understanding the rationale and clinical impact of the revised CLSI 2024 minocycline susceptibility breakpoints against Stenotrophomonas maltophilia

Clinical efficacy of unilateral laminotomy for bilateral decompression in the treatment of adjacent segment disease after lumbar fusion

ObjectiveTo assess the clinical impact of unilateral laminotomy for bilateral decompression (ULBD) in managing patients with adjacent vertebrae following lumbar fusion.MethodsA retrospective analysis was conducted on 21 patients, with a mean age of 67.4 years, who underwent ULBD for adjacent vertebra disease at our department from January 2021 to November 2023. We reviewed demographic data, surgical techniques, imaging studies, and patient-reported outcomes. The study compared Visual Analog Scale (VAS) scores, Numeric Rating Scale (NRS) scores, Japanese Orthopaedic Association (JOA) scores, Short Form-36 (SF-36) scores, and imaging outcomes before surgery, immediately post-surgery, and at 1 month, 6 months, and 12 months post-surgery.ResultsEvaluation of 21 patients with adjacent segment disease (ASD) (13 males, 8 females; mean age 67.42 years) was performed with follow-ups at various intervals post-surgery. Postoperative VAS, NRS, JOA, and SF-36 scores showed significant improvements compared to preoperative scores. Immediately after surgery, there were significant improvements in NRS score (2.76 ± 0.70 vs. 3.71 ± 0.85, P < 0.05) and JOA score (15.38 ± 1.02 vs. 9.29 ± 1.01, P < 0.05) compared to preoperative scores. Similarly, at 12 months post-surgery, significant improvements were observed in NRS score (1.52 ± 0.51 vs. 3.71 ± 0.85, P < 0.05) and JOA score (25.0 ± 1.10 vs. 9.29 ± 1.01, P < 0.05) compared to preoperative scores. The clinical satisfaction rate was 95.0% among all patients, with postoperative imaging examinations revealing a significant decompression effect. No complications were reported among the surgical patients.ConclusionsThis study suggests that endoscopic ULBD can be a safe and effective technique for managing symptomatic ASD, providing satisfactory clinical outcomes for patients with ASD. Endoscopic ULBD may serve as an alternative treatment option for ASD with lumbar stenosis.

Prospective Evaluation of Artificial Intelligence Triage of Incidental Pulmonary Emboli on Contrast-Enhanced CT Examinations of the Chest or Abdomen.

BACKGROUND. Artificial intelligence (AI) algorithms improved detection of incidental pulmonary embolism (IPE) on contrast-enhanced CT (CECT) examinations in retrospective studies; however, prospective validation studies are lacking. OBJECTIVE. The purpose of this study was to assess the effect on radiologists' real-world diagnostic performance and report turnaround times of a radiology department's clinical implementation of an AI triage system for detecting IPE on CECT examinations of the chest or abdomen. METHODS. This prospective single-center study included consecutive adult patients who underwent CECT of the chest or abdomen for reasons other than pulmonary embolism (PE) detection from May 12, 2021, to June 30, 2021 (phase 1), or from September 30, 2021, to December 4, 2021 (phase 2). Before phase 1, the radiology department installed a commercially available AI triage algorithm for IPE detection that automatically processed CT examinations and notified radiologists of positive results through an interactive floating widget. In phase 1, the widget was inactive, and radiologists interpreted examinations without AI assistance. In phase 2, the widget was activated, and radiologists interpreted examinations with AI assistance. A review process involving a panel of radiologists was implemented to establish the reference standard for the presence of IPE. Diagnostic performance and report turnaround times were compared using the Pearson chi-square test and Wilcoxon rank sum test, respectively. RESULTS. Phase 1 included 1467 examinations in 1434 patients (mean age, 53.8 ± 18.5 [SD] years; 753 men, 681 women); phase 2 included 3182 examinations in 2886 patients (mean age, 55.4 ± 18.2 years; 1520 men, 1366 women). The frequency of IPE was 1.4% (20/1467) in phase 1 and 1.6% (52/3182) in phase 2. Radiologists without AI, in comparison to radiologists with AI, showed significantly lower sensitivity (80.0% vs 96.2%, respectively; p = .03), without a significant difference in specificity (99.9% vs 99.9%, p = .58), for the detection of IPE. The mean report turnaround time for IPE-positive examinations was not significantly different between radiologists without AI and radiologists with AI (78.3 vs 74.6 minutes, p = .26). CONCLUSION. An AI triage system improved radiologists' sensitivity for IPE detection on CECT examinations of the chest or abdomen without significant change in report turnaround times. CLINICAL IMPACT. This prospective real-world study supports the use of AI assistance for maximizing IPE detection.

Adaptation of the socioecological model to address disparities in engagement of Black men in prostate cancer genetic testing

BackgroundBlack men consistently have higher rates of prostate cancer (PCA)- related mortality. Advances in PCA treatment, screening, and hereditary cancer assessment center around germline testing (GT). Of concern is the significant under-engagement of Black males in PCA GT, limiting the benefit of precision therapy and tailored cancer screening despite longstanding awareness of these disparities. To address these critical disparities, the Socioecological Model (SEM) was employed to develop comprehensive recommendations to overcome barriers and implement equitable strategies to engage Black males in PCA GT.MethodsClinical/research experts, national organization leaders, and community stakeholders spanning multiple regions in US and Africa participated in developing a framework for equity in PCA GT grounded in the SEM. A novel mixed-methods approach was employed to generate key areas to be addressed and informed statements for consensus consideration utilizing the modified Delphi model. Statements achieving strong consensus (> =75% agreement) were included in final equity frameworks addressing clinical/community engagement and research engagement.ResultsAll societal levels of the SEM (interpersonal, institutional, community, and policy/advocacy) must deliver information about PCA GT to Black males that address benefits/limitations, clinical impact, hereditary cancer implications, with acknowledgment of mistrust (mean scores [MS] 4.57-5.00). Interpersonal strategies for information delivery included engagement of family/friends/peers/Black role models to improve education/awareness and overcome mistrust (MS 4.65-5.00). Institutional strategies included diversifying clinical, research, and educational programs and integrating community liaisons into healthcare institutions (MS 4.57-5.00). Community strategies included partnerships with healthcare institutions and visibility of healthcare providers/researchers at community events (MS 4.65–4.91). Policy/advocacy included improving partnerships between advocacy and healthcare/community organizations while protecting patient benefits (MS 4.57-5.00). Media strategies were endorsed for the first time at every level (MS 4.56-5.00).ConclusionThe SEM-based equity frameworks proposed provide the first multidisciplinary strategies dedicated to increase engagement of Black males in PCA GT, which are critical to reduce disparities in PCA-mortality through informing tailored screening, targeted therapy, and cascade testing in families.

Emerging Targets in Non-Small Cell Lung Cancer

Lung cancer is responsible for a high burden of disease globally. Over the last two decades, the discovery of targetable oncogenic genomic alterations has revolutionized the treatment landscape for early-stage and advanced non-small cell lung cancer (NSCLC). New molecular drivers continue to emerge as promising therapeutic targets, including KRAS non-G12C, RAF/MEK, HER3, Nectin-4, folate receptor alpha, ITGB6, and PRMT5. In this review, we summarize the emerging molecular targets with a potential clinical impact in advanced NSCLC, elaborating on their clinical characteristics and specific mechanisms and molecular pathways for which targeted treatments are currently available. Additionally, we present an aggregate of ongoing clinical trials investigating the available treatment options targeting such alterations, in addition to their current recruitment status and preliminary efficacy data. These advancements may guide further research endeavors and inform future treatment strategies to improve the management of and transform outcomes for patients with advanced NSCLC.

Constitutional mosaicism of pathogenic variants in SMARCB1 in a subset of patients with sporadic rhabdoid tumors.

Malignant rhabdoid tumors are aggressive malignancies predominantly affecting very young children. The characteristic genetic alteration is biallelic inactivation of SMARCB1. In approximately 30% of patients one SMARCB1 allele is constitutionally altered conferring a particularly unfavourable prognosis. Constitutional mosaicism for pathogenic SMARCB1 mutations has recently been reported in distinct cases of allegedly sporadic rhabdoid tumors. We aimed to systematically investigate the frequency and clinical impact of constitutional mosaicism in patients with sporadic rhabdoid tumors included in the EU-RHAB registry. We selected 29 patients with rhabdoid tumors displaying at least one pathogenic small variant in SMARCB1 in the tumor DNA and absence of a germline mutation. We re-screened blood-derived patient and control DNA for the respective small variant by PCR with unique molecular identifiers and ultra-deep next generation sequencing. Clinical data in patients with and without mosaicism and 174 EU-RHAB controls were compared. Employing an ultra-deep sequencing approach, we detected tumor-associated SMARCB1 variants in blood-derived DNA in 9/29 patients. In 6/29 patients (21%), whose variant allele frequency (VAF) exceeded 2%, constitutional mosaicism was assumed whereas tumor DNA contamination was documented in 1/3 patients with VAF below 1%. No significant differences were observed between 6 mosaic-positive and 20 -negative patients regarding age at diagnosis, presence of metastases, event-free or overall survival. Constitutional mosaicism for pathogenic small SMARCB1 variants is recurrent in patients with allegedly sporadic rhabdoid tumors. The clinical implications of such variants need to be determined in larger, prospective cohorts also including detection of structural variants of SMARCB1.

Targeted therapy guided by circulating tumor DNA analysis in advanced gastrointestinal tumors.

Although comprehensive genomic profiling has become standard in oncology for advanced solid tumors, the full potential of circulating tumor DNA (ctDNA)-based profiling in capturing tumor heterogeneity and guiding therapy selection remains underexploited, marked by a scarcity of evidence on its clinical impact and the assessment of intratumoral heterogeneity. The GOZILA study, a nationwide, prospective observational ctDNA profiling study, previously demonstrated higher clinical trial enrollment rates using liquid biopsy compared with tissue screening. This updated analysis of 4,037 patients further delineates the clinical utility of ctDNA profiling in advanced solid tumors, showcasing a significant enhancement in patient outcomes with a 24% match rate for targeted therapy. Patients treated with matched targeted therapy based on ctDNA profiling demonstrated significantly improved overall survival compared with those receiving unmatched therapy (hazard ratio, 0.54). Notably, biomarker clonality and adjusted plasma copy number were identified as predictors of therapeutic efficacy, reinforcing the value of ctDNA in reflecting tumor heterogeneity for precise treatment decisions. These new insights into the relationship between ctDNA characteristics and treatment outcomes advance our understanding beyond the initial enrollment benefits. Our findings advocate for the broader adoption of ctDNA-guided treatment, signifying an advancement in precision oncology and improving survival outcomes in advanced solid tumors.

Outcomes and predictors of intraprocedural rupture in patients with cerebral aneurysm.

Intraprocedural rupture (IPR) is a devastating complication of cerebral aneurysm treatment. While several studies have investigated its risk factors and clinical impact, further research with larger populations is warranted. We retrospectively reviewed data from 4,039 patients with 4,233 cerebral aneurysms treated at our institution between January 2009 and December 2018. Multivariate logistic regression with stepwise elimination was performed to identify the independent risk factors of IPR. Unfavorable clinical outcome was defined as a Modified Rankin Scale (mRS) ≥ 3 points at 3months post-treatment. IPR occurred in 61 (1.44%) of the 4,233 aneurysms. Multivariate analysis showed that previously ruptured aneurysms (odds ratio [OR] 3.182; 95% confidence interval [CI] 1.851-5.470; p < 0.001), surgical clipping (OR 3.598; 95% CI 1.894-6.836; p < 0.001), and higher aspect ratio (OR 1.310; 95% CI 1.032-1.663; p = 0.024) were independent risk factors for IPR. Patients with IPR had significantly higher rates of unfavorable clinical outcomes (mRS ≥ 3) compared to those without (18.0% vs. 3.3%, p < 0.001). However, within the ruptured aneurysm subgroup, the rate of unfavorable outcomes did not differ significantly between IPR and non-IPR groups (22.7% vs. 19.2%, p = 0.594). Ruptured aneurysms, surgical clipping, and higher aspect ratio were independently associated with IPR. IPR significantly increased the risk of unfavorable clinical outcomes regardless of treatment approach, except in the subgroup of ruptured aneurysms.

Comparison between clinical and cytological findings in chronic rhinosinusitis with nasal polyps treated with Dupilumab.

Biologics represent a new therapeutic strategy for severe and recurrent chronic rhinosinusitis with nasal polyps (CRSwNP). Usually, their actual therapeutic effectiveness is assessed by reduction in nasal polyps and/or improvement in nasal symptoms and quality of life. However, these measures do not consider nasal immunophlogosis, which can be evaluated through nasal cytology. The purpose of this study was to assess not only the clinical impact but also the cellular changes in the nasal inflammatory infiltrate observed through nasal cytology of CRSwNP patients treated with Dupilumab for 24 months. Fifty-five CRSwNP patients treated with Dupilumab were collected. Patients were evaluated before starting treatment and at one, three, six, nine months, one year, one and a half years, and two years after the first drug administration. During follow-up visits patients underwent endoscopic evaluation, nasal symptoms and quality of life assessment, complete blood count and nasal cytology. During follow-up, significant improvement was found in Nasal Polyps Score (NPS), nasal patency, olfaction, Sino-Nasal Outcome Test (SNOT-22) score, and Visual Analogue Scale (VAS). Regarding nasal cytology, a reduction in eosinophils and mast cells in the cellular infiltrate was observed over the two-year follow-up period compared to baseline. Dupilumab has demonstrated broad efficacy in the management of CRSwNP from both clinical and cytological findings. Further studies are needed to confirm our findings and evaluate the biologics' impact on nasal mucosal inflammatory cells by nasal cytology with the aim of better identifying each patient's endotype and predicting the response to biologics.

Incorporating patient-specific information for the development of rectal tumor auto-segmentation models for online adaptive magnetic resonance Image-guided radiotherapy

Background and purposeIn online adaptive magnetic resonance image (MRI)-guided radiotherapy (MRIgRT), manual contouring of rectal tumors on daily images is labor-intensive and time-consuming. Automation of this task is complex due to substantial variation in tumor shape and location between patients. The aim of this work was to investigate different approaches of propagating patient-specific prior information to the online adaptive treatment fractions to improve deep-learning based auto-segmentation of rectal tumors. Materials and methods243 T2-weighted MRI scans of 49 rectal cancer patients treated on the 1.5T MR-Linear accelerator (MR-Linac) were utilized to train models to segment rectal tumors. As benchmark, an MRI_only auto-segmentation model was trained. Three approaches of including a patient-specific prior were studied: 1. include the segmentations of fraction 1 as extra input channel for the auto-segmentation of subsequent fractions, 2. fine-tuning of the MRI_only model to fraction 1 (PSF_1) and 3. fine-tuning of the MRI_only model on all earlier fractions (PSF_cumulative). Auto-segmentations were compared to the manual segmentation using geometric similarity metrics. Clinical impact was assessed by evaluating post-treatment target coverage. ResultsAll patient-specific methods outperformed the MRI_only segmentation approach. Median 95th percentile Hausdorff (95HD) were 22.0 (range: 6.1–76.6) mm for MRI_only segmentation, 9.9 (range: 2.5–38.2) mm for MRI+prior segmentation, 6.4 (range: 2.4–17.8) mm for PSF_1 and 4.8 (range: 1.7–26.9) mm for PSF_cumulative. PSF_cumulative was found to be superior to PSF_1 from fraction 4 onward (p = 0.014). ConclusionPatient-specific fine-tuning of automatically segmented rectal tumors, using images and segmentations from all previous fractions, yields superior quality compared to other auto-segmentation approaches.

The Chemo-Immunotherapeutic Roles of Tumor-Derived Extracellular Vesicle-Based Paclitaxel Delivery System in Hepatocarcinoma.

As a first-line chemotherapeutic agent, albumin-bound paclitaxel (PA) has a considerable effect on the treatment of various cancers. However, in chemotherapy for hepatocarcinoma, the sensitivity to PA is low owing to the innate resistance of hepatocarcinoma cells; the toxicity and side effects are severe, and the clinical treatment impact is poor. In this study, we present a unique nanodrug delivery system. The ultraviolet (UV)-induced tumor-cell-derived extracellular vesicles (EVs) were isolated and purified by differential centrifugation. Then, PA was loaded by coextrusion to create a vesicle drug delivery system (EVPA). By employing the EV-dependent enhanced retention effect and specific homing effect, EVPA would passively and actively target tumor tissues, activate the immune response to release PA, and achieve the combination therapeutic effect of chemo-immunotherapy on hepatocarcinoma. We demonstrated that the tumor-killing effect of EVPA is superior to that of PA, both in vivo and in vitro and that EVPA can be effectively taken up by hepatocarcinoma and dendritic cells, activate the body's specific immune response, promote the infiltration of CD4+ and CD8+ T cells in tumor tissues, and exert a precise killing effect on hepatocarcinoma cells via chemo-immunotherapy.

Outcome of Levofloxacin in the Treatment of Lower Respiratory Tract Infection

Background: Levofloxacin, a broad-spectrum fluoroquinolone antibiotic, is commonly used in treating lower respiratory tract infections (LRTIs) like pneumonia and chronic bronchitis. Its effectiveness lies in its ability to inhibit bacterial DNA gyrase, leading to bacterial cell death. Clinical outcomes of levofloxacin in LRTI treatment have generally been positive, with high rates of bacterial eradication and symptom resolution. Objective: The present research aimed to determine whether levofloxacin is an effective and safe option for treating lower respiratory tract infections. Method: From January 2022 to January 2023, researchers analyzed data from 120 patients with a lower respiratory tract infection at a tertiary hospital. Sixty patients were split evenly between a control group and an observation group. Levofloxacin was administered at the standard dosage to the control group and at a significantly higher dose to the observation group. Both the clinical efficacy and adverse reaction rates were compared and contrasted between the two groups statistically. Results: The cure rate in the observation group was 53.33 percent, which was substantially greater than the cure rate in the control group, which was 36.67 percent. There is a statistically significant difference between them (P 0.05). The overall efficacy rate of the observation group was 93.33%, significantly higher than that of the control group (73.33%). There is a statistically significant difference between them (P 0.05). There was no statistically significant difference (P&gt;0.05) between the two groups due to the low incidence of adverse responses in both the observation and control groups. Conclusion: This research demonstrates that large dosages of levofloxacin have a stronger clinical curative impact on treating lower respiratory infections than lesser doses. It is worthwhile to promote the widespread adoption of this technique since it has the potential to greatly enhance the quality of patient care

Risk factor analysis and prediction model to establish recurrence or progression of non-functioning pituitary adenomas in men after transnasal sphenoidal surgery

This paper aims to analyze the risk factors for the recurrence or progression of non-functioning pituitary adenomas (NFPAs) in male patients after transnasal sphenoidal surgery and to develop a predictive model for prognosis. Clinical and follow-up data of 126 male patients with NFPAs treated by transnasal sphenoidal surgery from January 2011 to January 2021 in Fuzhou 900th Hospital were retrospectively analyzed. Lasso regression analysis was used to screen the best predictors, and the predictors were further screened by multivariate logistic regression analysis, and the nomogram prediction model was constructed. The performance of the model was verified by three aspects: discrimination, calibration and clinical utility by using the consistency index (C-index), receiver operating characteristic curve (ROC), calibration curve, clinical decision curve (DCA) and Clinical impact curve (CIC). Out of 126 cases, 7 (5.56%) showed postoperative tumor recurrence, and 18 (14.29%) exhibited postoperative residual regrowth (progression). Age (P = 0.024), maximum tumor diameter (P < 0.001), modified Knosp grade (P < 0.001), resection extent (P < 0.001), Ki67 (P < 0.001), pressure symptom (P < 0.001), Pre-op hypopituitarism (P = 0.048), Post-op new hypopituitarism (P = 0.017) showed significant differences among the recurrence group, the progression group, and the alleviation group. Three independent risk factors (Ki67, modified Knosp grade, and resection extent) affecting postoperative remission were used to construct a predictive model for long-term postoperative failure to remit. The C-index of the nomogram model was 0.823, suggesting that the model had a high discriminatory power, and the AUC of the area under the ROC curve was 0.9[95% CI (0.843, 0.958)]. A nomogram prediction model based on modified Knosp grading (grades 3B-4), resection extent (partial resection), and Ki-67 (≥ 3%) predicts the recurrence or progression of NFPAs in men after transnasal sphenoidal surgery.

Clinical impact of concomitant BIO-three use in advanced or recurrent non-small cell lung cancer treated with immune-checkpoint inhibitor.

Immune checkpoint inhibitors (ICIs) have been approved as first-line therapy for advanced non-small cell lung cancer (NSCLC). The probiotic MIYAIRI 588 can potentially improve the outcomes of patients with advanced NSCLC treated with ICI. However, the impact of other probiotics on ICI-treatment efficacy remains unclear. Thus, we aimed to clarify the association between BIO-three use and treatment outcomes in patients with advanced NSCLC treated with ICI. This retrospective study included patients aged ≥ 18years with advanced or recurrent NSCLC who had received ICI monotherapy or ICI plus chemotherapy. Concomitant therapy with probiotic bacteria was defined as receiving it within 180days before ICI therapy. Here, 289 patients were enrolled, including 23 (8.0%) receiving BIO-three. In the multivariable analysis, the progression-free survival (PFS) and overall survival (OS) of patients receiving BIO-three tended to be longer than those of patients not receiving probiotic therapy (PFS, hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.43-1.30; p = 0.33; OS, HR 0.69; 95% CI 0.37-1.28; p = 0.24). After propensity score matching with weighted adjustment, patients receiving BIO-three tended to have prolonged PFS (median PFS [range] 7.6months [2.6-17.4] vs 3.2months [1.6-7.0]; HR 0.53; 95% CI 0.25-1.12; p = 0.09) and OS (median OS [range] 25.6months [10.8-not reached] vs 10.9months [7.3-not reached]; HR 0.57; 95% CI 0.24-1.36; p = 0.20) than those not receiving probiotic therapy. This study suggests the prognostic impact of concomitant BIO-three use in patients with advanced NSCLC on ICI treatment.

Clinical evaluation of a machine learning-based early warning system for patient deterioration.

The implementation and clinical impact of machine learning-based early warning systems for patient deterioration in hospitals have not been well described. We sought to describe the implementation and evaluation of a multifaceted, real-time, machine learning-based early warning system for patient deterioration used in the general internal medicine (GIM) unit of an academic medical centre. In this nonrandomized, controlled study, we evaluated the association between the implementation of a machine learning-based early warning system and clinical outcomes. We used propensity score-based overlap weighting to compare patients in the GIM unit during the intervention period (Nov. 1, 2020, to June 1, 2022) to those admitted during the pre-intervention period (Nov. 1, 2016, to June 1, 2020). In a difference-indifferences analysis, we compared patients in the GIM unit with those in the cardiology, respirology, and nephrology units who did not receive the intervention. We retrospectively calculated system predictions for each patient in the control cohorts, although alerts were sent to clinicians only during the intervention period for patients in GIM. The primary outcome was non-palliative in-hospital death. The study included 13 649 patient admissions in GIM and 8470 patient admissions in subspecialty units. Non-palliative deaths were significantly lower in the intervention period than the pre-intervention period among patients in GIM (1.6% v. 2.1%; adjusted relative risk [RR] 0.74, 95% confidence interval [CI] 0.55-1.00) but not in the subspecialty cohorts (1.9% v. 2.1%; adjusted RR 0.89, 95% CI 0.63-1.28). Among high-risk patients in GIM for whom the system triggered at least 1 alert, the proportion of non-palliative deaths was 7.1% in the intervention period, compared with 10.3% in the pre-intervention period (adjusted RR 0.69, 95% CI 0.46-1.02), with no meaningful difference in subspecialty cohorts (10.4% v. 10.6%; adjusted RR 0.98, 95% CI 0.60-1.59). In the difference-indifferences analysis, the adjusted relative risk reduction for non-palliative death in GIM was 0.79 (95% CI 0.50-1.24). Implementing a machine learning-based early warning system in the GIM unit was associated with lower risk of non-palliative death than in the pre-intervention period. Machine learning-based early warning systems are promising technologies for improving clinical outcomes.

The potential of a nomogram risk assessment model for the diagnosis of abdominal aortic aneurysm: a multicenter retrospective study

The incidence of abdominal aortic aneurysm (AAA) is very high, but there is no risk assessment model for early identification of AAA in clinic. The aim of this study was to develop a nomogram risk assessment model for predicting AAA. The data of 280 patients diagnosed as AAA and 385 controls in The Affiliated Suzhou Hospital of Nanjing Medical University were retrospectively reviewed. The LASSO regression method was applied to filter variables, and multivariate logistic regression was used to construct a nomogram. The discriminatory ability of the model was determined by calculating the area under the curve (AUC). The calibration capability of the model is evaluated by using bootstrap (resampling = 1000) internal validation and Hosmer–Lemeshow test. The clinical utility and clinical application value were evaluated by decision curve analysis (DCA) and clinical impact curve (CIC). In addition, a retrospective review of 133 AAA patients and 262 controls from The First Affiliated Hospital of Soochow University was performed as an external validation cohort. Eight variables are selected to construct the nomogram of AAA risk assessment model. The nomogram predicted AAA with AUC values of 0.928 (95%CI, 0.907–0.950) in the training cohort, and 0.902 (95%CI, 0.865–0.940) in the external validation cohort, the risk prediction model has excellent discriminative ability. The calibration curve and Hosmer–Lemeshow test proved that the nomogram predicted outcomes were close to the ideal curve, the predicted outcomes were consistent with the real outcomes, the DCA curve and CIC curve showed that patients could benefit. This finding was also confirmed in the external validation cohort. In this study, a nomogram was constructed that incorporated eight demographic and clinical characteristics of AAA patients, which can be used as a practical approach for the personalized early screening and auxiliary diagnosis of the potential risk factors.

Hiding in plain sight: Misinterpretation of immunogenic DPB epitopes within G/P groups

The clinical impact of HLA DP antibodies is poorly understood, resulting in variable clinical strategies for transplant candidates and recipients with donor-directed HLA-DP antibodies. Complicating matters further, the DPB naming convention is not based on allelic homology and requires sequence alignments to identify potential immunogenic epitopes. Historically, G and P codes, which consolidated alleles that were identical over Exon 2, were used to simplify the reporting of HLA Class II typing as differences outside of Exon 2 have not been considered immunogenic (i.e., able to induce an antibody response). Herein, we present four cases demonstrating that polymorphisms at codons 96R/K and 170I/T, in Exon 3 of DPB, are targets for alloantibody recognition. These regions “hide in plain sight” due to the current use of G/P code-level typing, potentially leading to incorrect compatibility assessments (i.e., virtual crossmatches) and misinterpreted antibody responses. The unintentional crossing of an HLA-DPB donor-specific antibody (DSA) in a solid organ or hematopoietic stem cell transplant may lead to unforeseen deleterious clinical outcomes. Our data underscore the complexities of DPB histocompatibility assessments and highlight the need for adaptable systems that align with evolving research and clinical outcomes.