Outcomes of Patients Undergoing Segmentectomy for Occult Node-Positive Clinical Stage IA Lung Cancer.

BACKGROUND: Results of recent clinical trials suggest segmentectomy may be an acceptable alternative to lobectomy for selected patients with early-stage non-small cell lung cancer (NSCLC). Increased use of segmentectomy may result in a concomitant increase in occult node-positive (N+) disease on surgical pathology. The optimal management for such patients remains unknown. METHODS: Clinicopathologic data were abstracted from a prospective institutional database to identify patients with pathologic N+ disease after segmentectomy for cT1N0M0 NSCLC. Propensity score matching identified a comparable lobectomy cohort for assessment of cumulative incidence of recurrence and overall survival (OS). RESULTS: Of 759 included patients, 27 (4%) had nodal upstaging on final pathology. Of these, 4 (15%) had skip metastasis to N2 stations, and 20 (74%) received adjuvant therapy; no completion lobectomies were performed. Ten patients (37%) had recurrence: 3 isolated locoregional (11%) and 7 distant (26%). The median time to recurrence among patients with recurrence was 1.8 years; OS after recurrence was 3.4 years. After 5:1 matching with 109 lobectomy patients, all variables were balanced between the groups, except pathologic N2 stage and open surgical approach. Five-year cumulative incidence of recurrence was not significantly different between segmentectomy and lobectomy (42% vs 52%; Gray's p=0.1). Five-year OS (63% and 50%) and rate of locoregional recurrence (12% vs. 13%) were not statistically different between the groups. CONCLUSIONS: Patients with occult N+ disease after segmentectomy for cT1N0M0 NSCLC had limited isolated locoregional recurrences and similar outcomes as patients who underwent lobectomy. Lobectomy may not provide an advantage in these patients.

Assessing the anticholinergic cognitive burden classification of putative anticholinergic drugs using drug properties.

AIMS: This study evaluated the use of machine learning to leverage drug absorption, distribution, metabolism and excretion (ADME) data together with physicochemical and pharmacological data to develop a novel anticholinergic burden scale and compare its performance to previously published scales. METHODS: Experimental and in silico ADME, physicochemical and pharmacological data were collected for antimuscarinic activity, blood-brain barrier penetration, bioavailability, chemical structure and P-glycoprotein (P-gp) substrate profile. These five drug properties were used to train an unsupervised model to assign anticholinergic burden scores to drugs. The model performance was evaluated through 10-fold cross-validation and compared with the clinical Anticholinergic Cognitive Burden (ACB) scale and nonclinical Anticholinergic Toxicity Scores (ATS) scale, which is based primarily on muscarinic binding affinity. RESULTS: In silico software (ADMET Predictor) used for screening drugs for their blood-brain barrier (BBB) penetration correctly identified some drugs that do not cross the BBB. The mean area under the curve for the unsupervised and ACB scale based on the five selected variables was 0.76 and 0.64, respectively. The unsupervised model agreed with the ACB scale on the classification of more than half of the drugs (49 of 88) agreed on the classification of less than half the drugs in the ATS scale (12 of 25). CONCLUSIONS: Our findings suggest that the commonly used ACB scale may misclassify certain drugs due to their inability to cross the BBB. By contrast, the ATS scale would misclassify drugs solely depending on muscarinic binding affinity without considering other drug properties. Machine learning models can be trained on these features to build classification models that are easy to update and have greater generalizability.

Effect of Early Orthodontic Treatment on Long-Term Stability of Class II Malocclusions.

Background: Class II malocclusions are a common orthodontic problem, often requiring comprehensive treatment to achieve proper occlusion and facial harmony. Early orthodontic intervention in the mixed dentition phase has been advocated to address these issues. Materials and Methods: A retrospective analysis was conducted on a cohort of 150 patients with class II malocclusions who underwent early orthodontic treatment between the ages of 7 and 10 years. The treatment included fixed or removable appliances, headgear, and functional appliances, depending on individual needs. Records of their initial malocclusion severity, treatment modalities, and long-term follow-up data (mean follow-up duration of 10 years) were collected and analyzed. Stability was assessed by evaluating overjet and overbite changes from post-treatment to the long-term follow-up. Results: The initial mean overjet and overbite values were 8.5 mm and 4.0 mm, respectively. Following early orthodontic intervention, these values were significantly reduced to 3.0 mm and 1.5 mm, respectively (P < 0.001). At the long-term follow-up, the mean overjet and overbite remained stable at 3.2 mm and 1.6 mm, respectively. Analysis revealed that 85% of patients maintained their corrected class II occlusion within clinically acceptable limits, while 15% experienced minor relapse requiring minimal additional treatment. Conclusion: Early orthodontic treatment in class II malocclusions can lead to significant improvements in overjet and overbite, and these corrections tend to remain stable over the long term.

Proceedings of the dengue endgame summit: Imagining a world with dengue control.

The first dengue "endgame" summit was held in Syracuse, NY over August 9 and 10, 2023. Organized and hosted by the Institute for Global Health and Translational Sciences at SUNY Upstate Medical University, the gathering brought together researchers, clinicians, drug and vaccine developers, government officials, and other key stakeholders in the dengue field for a highly collaborative and discussion-oriented event. The objective of the gathering was to discuss the current state of dengue around the world, what dengue "control" might look like, and what a potential roadmap might look like to achieve functional dengue control. Over the course of 7 sessions, speakers with a diverse array of expertise highlighted both current and historic challenges associated with dengue control, the state of dengue countermeasure development and deployment, as well as fundamental virologic, immunologic, and medical barriers to achieving dengue control. While sustained eradication of dengue was considered challenging, attendees were optimistic that significant reduction in the burden of dengue can be achieved by integration of vector control with effective application of therapeutics and vaccines.

Ellagic Acid Reverses Alterations in the Expression of AMPA Receptor and Its Scaffolding Proteins in the Cerebral Cortex and Memory Decline in STZ-sporadic Alzheimer' s Disease Mouse Model.

RATIONALE: Alzheimer's disease (AD), an age-dependent devastating neuropsychiatric disorder, is a leading cause of learning, memory and intellectual disabilities. Current therapeutic approaches for the amelioration of the anomalies of AD are not effective. OBJECTIVE: In the present study, the molecular mechanisms underlying sporadic AD (sAD), the memory related behavioral analysis and neuroprotective effects of Ellagic acid (EA) were investigated. METHOD: sAD mouse model was developed by intracerebroventricular (ICV) injection of Streptozotocin (STZ). The efficacy of EA, a naturally occurring polyphenol, in amelioration of anomalies associated with sAD was assessed. EA was administered once daily for 28 days at a dose of 75 mg/kg body weight followed by neurobehavioral, biochemical, molecular and neuronal count analysis to delineate the mode of action of EA. RESULT: The ICV injection of STZ in mice significantly increased the expression of AD biomarkers in addition to enhanced oxidative stress. A decline in the discrimination index in Novel Object Recognition Test was observed indicating the compromise of recognition memory in AD. Studies on the expression of genes involved in synaptic plasticity reveal the dysregulation of the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of the glutamate and its scaffolding proteins in the postsynaptic density and thereby synaptic plasticity in AD. ICV-STZ led to significant upregulation of apoptotic markers which led to decrease in neuronal density of the cerebral cortex. EA significantly reversed the above and improved anomalies of sAD. CONCLUSION: EA was observed to profoundly modulate the genes involved in AD pathophysiology, restored antioxidant enzymes activity, reduced lipid peroxidation and neuronal loss in the sAD brain. Further, EA was observed to effectively modulate the genes involved in apoptosis and synaptic plasticity. Therefore, EA possesses promising anti-AD properties, which may improve AD-associated anomalies by modulating synaptic plasticity via AMPAR signaling.

High-risk features associated with recurrence in stage I lung adenocarcinoma.

OBJECTIVE: There is a lack of knowledge regarding the use of prognostic features in stage I lung adenocarcinoma (LUAD). Thus, we investigated clinicopathologic features associated with recurrence after complete resection for stage I LUAD. METHODS: We performed a retrospective analysis of patients with pathologic stage I LUAD who underwent R0 resection from 2010 to 2020. Exclusion criteria included history of lung cancer, induction or adjuvant therapy, noninvasive or mucinous LUAD, and death within 90 days of surgery. Fine and Gray competing-risk regression assessed associations between clinicopathologic features and disease recurrence. RESULTS: In total, 1912 patients met inclusion criteria. Most patients (1565 [82%]) had stage IA LUAD, and 250 developed recurrence: 141 (56%) distant and 109 (44%) locoregional only. The 5-year cumulative incidence of recurrence was 12% (95% CI, 11%-14%). Higher maximum standardized uptake value of the primary tumor (hazard ratio [HR], 1.04), sublobar resection (HR, 2.04), higher International Association for the Study of Lung Cancer grade (HR, 5.32 [grade 2]; HR, 7.93 [grade 3]), lymphovascular invasion (HR, 1.70), visceral pleural invasion (HR, 1.54), and tumor size (HR, 1.30) were independently associated with a hazard of recurrence. Tumors with 3 to 4 high-risk features had a higher cumulative incidence of recurrence at 5 years than tumors without these features (30% vs 4%; P < .001). CONCLUSIONS: Recurrence after resection for stage I LUAD remains an issue for select patients. Commonly reported clinicopathologic features can be used to define patients at high risk of recurrence and should be considered when assessing the prognosis of patients with stage I disease.

Diagnostic accuracy of cell-free DNA in maternal blood in detecting chromosomal anomalies in twin pregnancies: systematic review and meta-analysis.

OBJECTIVES: To report the diagnostic accuracy of cell-free DNA (cfDNA) in maternal blood in detecting chromosomal anomalies in twin pregnancies. METHODS: Medline, Embase and Cochrane databases were searched. The inclusion criteria were twin pregnancies undergoing cfDNA screening for Trisomies 13, 18, 21, monosomy X0 and other sex chromosomal anomalies (SCA). The index test was represented by a positive results of cfDNA test. The reference standard was represented by the karyotype results (obtained either pre or postnatally) or, in case of negative cfDNA result, by a normal neonatal phenotype. The quality of the studies was assessed using the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). Summary estimates of sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) and diagnostic odds ratio (DOR), with the corresponding 95% Confidence Intervals (95% CI), were computed using the bivariate random-effects model. RESULTS: Thirty-five studies were included. cfDNA had an overall high accuracy in detecting Trisomy 21 in twin pregnancies with a sensitivity of 98.8% (95% CI 96.5-100), a specificity of 100% (95% CI 99.9-100). Sensitivity and specificity were of 94.9% (95% CI 75.6-99.1) and 100 (95% CI 99.9-100) for Trisomy 18, and 84.6% (95% C% 54.6-98.1) and 100% (95% CI 99.9-100) for Trisomy 13 . We could not compute the diagnostic accuracy of cfDNA in detecting monosomy X0 in twins, while cfDNA had a sensitivity of 100% (95% CI 71.5-100) and a specificity of 99.8% (95% CI 99.7-99.9) in detecting other SCA (11 cases). The accuracy of cfDNA in detecting Trisomy 21, 18 and 13 was similar in dichorionic and monochorionic twin pregnancies. CONCLUSION: cfDNA has a high diagnostic accuracy in detecting Trisomy 18 and 21 in twin pregnancies, irrespective of chorionicity. Accuracy in the detection of Trisomy 13 and SCA was limited by the small number of affected cases and the difficulties in the confirmation of false negative cases in case of SCA and requires confirmation in larger studies. This article is protected by copyright. All rights reserved.

MicroRNA target homeobox messenger RNA in HIV induced hematopoietic inhibition.

Cytopenias are a common occurrence due to abnormal hematopoiesis persistent in patients suffering from and advancing with HIV/AIDS. In order to develop efficacious therapies against cytopenias, it is necessary to understand the mechanisms by which HIV infection affects the differentiation of hematopoietic stem-progenitor cells (HSPCs), causing hematopoietic inhibition, that leads to hematological disorders. Currently, only the antiretrovirals that are being used to treat HIV infection and indirectly lower the levels of virus replication also co-attenuate cytopenias. The evidence available suggests that this indirect efficacy may not prevail for the lifetime of the infected patients, and the acquired immunodeficiency can overtake the beneficial consequences of decreased virus replication. As cited in this article, we and our colleagues are the first to make a foray into the involvement of microRNAs and their use as potential interventional treatments for the cytopenias that occur with HIV/AIDS. Herein, we progressed further in the direction of the mechanisms of the involvement of homeobox gene regulation to cause cytopenias. We had previously shown that HIV-1 inhibits multi-lineage hematopoiesis of the CD34+ cells using SCID-hu Thy/Liv animals in vivo. Furthermore, we demonstrated that the virus-induced hematopoietic inhibition occurred despite the CD34+ cells being resistant to HIV-1 infection. We set out to search for the specific host factors secreted by CD4+ T-cells that likely participate in the inhibition of hematopoiesis of the HIV infection-resistant CD34+ cells. More recently, we reported the identification of virus-infected CD4+ thymocyte-secreted miRNA-15a and miRNA-24 and that their differential expression following HIV infection causes the indirect inhibition of hematopoiesis. We then hypothesized that the observed miRNA differential expression in the virus-infected T-cells causes the abnormal regulation of homeobox (HOX) gene-encoded transcriptomes in the CD34+ cells, affecting specific MAPK signaling and CD34+ cell fate, thereby disrupting normal hematopoiesis. We present that in HIV infection, miRNA-mediated post-transcriptional dysregulation of HOXB3 mRNA inhibits multi-lineage hematopoiesis, which translates into hematological disorders in virus-infected patients with HIV/AIDS. These observations portend specific microRNA candidates for potential efficacy against the virus-induced cytopenias that are otherwise not treatable by the existing HAART/ART regimens, which are primarily designed and applicable for the attenuation of virus replication.

A New Functional Threshold for Minimally Invasive Lobectomy.

OBJECTIVE: To assess the performance of a lower predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1) or diffusion capacity of the lung for carbon monoxide (DLCO) (ppoFEV1/ppoDLCO) threshold to predict cardiopulmonary complications after minimally invasive surgery (MIS) lobectomy. SUMMARY BACKGROUND DATA: Although MIS is associated with better postoperative outcomes than open surgery, MIS uses risk-assessment algorithms developed for open surgery. Moreover, several different definitions of cardiopulmonary complications are used for assessment. METHODS: All patients who underwent MIS lobectomy for clinical stage I-II lung cancer from 2018 to 2022 at our institution were considered. The performance of a ppoFEV1/ppoDLCO threshold of <45% was compared against that of the current guideline threshold of <60%. Three different definitions of cardiopulmonary complications were compared: Society of Thoracic Surgeons (STS), European Society of Thoracic Surgeons (ESTS), and Berry et al. RESULTS: In 946 patients, the ppoFEV1/ppoDLCO threshold of <45% was associated with a higher proportion correctly classified (79% [95% CI, 76%-81%] vs. 65% [95% CI, 62%-68%]; P<0.001). The complication with the biggest difference in incidence between ppoFEV1/ppoDLCO of 45%-60% and >60% was prolonged air leak (33 [13%] vs. 34 [6%]; P<0.001). The predicted probability curves for cardiopulmonary complications were higher for the STS definition than for the ESTS or Berry definitions across ppoFEV1 and ppoDLCO values. CONCLUSIONS: The ppoFEV1/ppoDLCO threshold of <45% more accurately classified patients for cardiopulmonary complications after MIS lobectomy, emphasizing the need for updated risk-assessment guidelines for MIS lobectomy to optimize additional cardiopulmonary function evaluation.

Leveraging the pleural space for anticancer therapies in pleural mesothelioma.

Most patients with pleural mesothelioma (PM) present with symptomatic pleural effusion. In some patients, PM is only detectable on the pleural surfaces, providing a strong rationale for intrapleural anticancer therapy. In modern prospective studies involving expert radiological staging and specialist multidisciplinary teams, the population incidence of stage I PM (an approximate surrogate of pleura-only PM) is higher than in historical retrospective series. In this Viewpoint, we advocate for the expansion of intrapleural trials to serve these patients, given the paucity of data supporting licensed systemic therapies in this setting and the uncertainties involved in surgical therapy. We begin by reviewing the unique anatomical and physiological features of the PM-bearing pleural space, before critically appraising the evidence for systemic therapies in stage I PM and previous intrapleural PM trials. We conclude with a summary of key challenges and potential solutions, including optimal trial designs, repurposing of indwelling pleural catheters, and new technologies.

Pro: "Is Spread Through Air Spaces an In Vivo Phenomenon or an Inducible Artifact?"

In this PRO-CON debate, you will read very different perspectives about a simple question regarding an observation under the microscope: What is the significance of tumor cells in the air spaces of the lung parenchyma beyond the tumor edge of a resected lung cancer? An important underlying question is whether this entire PRO-CON debate is a mere academic exercise or whether spread through air spaces (STAS), as currently defined, describes a clinically useful phenomenon. The journey of STAS began with a complete paradigm shift to reverse the thinking that all air space tumor cells beyond the edge of lung cancers are an artifact. This led to a new concept where STAS could be separated from artifacts with a definition that has proven to be clinically useful. As with any major change in thinking, it is understandable that there would be some disagreement with this paradigm shift. Nevertheless, after a decade since it was described, many pathologists and clinicians around the world have found STAS to provide important information about the behavior of lung cancer. Numerous PRO-STAS articles supporting the usefulness of STAS have been published with clinical data on many thousands of patients from numerous institutions all over the world. In contrast, for the CON-STAS articles, widespread international representation and data are limited. It is now difficult to ignore the numerous reports and is reasonable to consider how to use the presence of STAS in clinical decisions. Hopefully, this PRO-CON debate will further stimulate clinical and scientific investigations aimed at a better understanding of STAS.

Machine learning prediction of hypertension and diabetes in twin pregnancies using characteristics at prenatal care entry: a nationwide study.

OBJECTIVES: To develop a prediction model for hypertensive disorders in pregnancy (HDP) and gestational diabetes (GDM) in twin pregnancies utilizing characteristics at the prenatal care entry level. METHODS: Cross-sectional study using the US national live birth data between 2016 and 2021. The association of all prenatal candidate variables with HDP and GDM was tested with uni- and multi-variable logistic regression analyses. Prediction models were built with generalized linear models using the logit link function and classification and regression tree approach (XGboost) machine learning (ML) algorithm. Performance was assessed with repeated 2-fold cross-validation and performance metrics we considered were area under the curve (AUC). P value <0.001 was considered statistically significant. RESULTS: A total of 707,198 twin pregnancies were included in the HDP analysis and 723,882 twin pregnancies for the GDM analysis. The incidence of HDP and GDM significantly increased from 12.2% in 2016 to 15.4% in 2021 and from 8.1% in 2016 to 10.7% in 2021, respectively. Factors that increase the risk of HDP in twin gestations are maternal age <20, age≥35, infertility, prepregnancy DM, non-Hispanic Black population, obesity, and those with Medicaid insurance (p<0.001). Factors that more than doubled the risk are obesity class II and III (p<0.001). Factors that increase the risk of GDM in twin gestations are age <25, age≥30, history of infertility, prepregnancy hypertension, non-Hispanic Asian population, non-US nativity, and obesity (p<0.001). Factors that more than doubled the risk are maternal age ≥ 30 years, non-Hispanic Asian, and class I, II, and III maternal obesity ( p<0.001). For both HDP and GDM, the performance of the ML and logistic regression model was mostly similar with negligible difference in terms of all tested performance domains. The AUC of the final ML model for HDP and GDM were 0.62±0.004, and 0.67±0.004, respectively. CONCLUSIONS: The incidence of HDP and GDM in twin gestations is increasing. The predictive accuracy of the machine learning model for both HDP and GDM in twin gestations is similar to that of the logistic regression model. Both models had modest performance, well-calibrated, and neither had a poor fit. This article is protected by copyright. All rights reserved.

Determinants of radiation exposure during mobile cone-beam CT-guided robotic-assisted bronchoscopy.

BACKGROUND AND OBJECTIVE: Robotic-assisted bronchoscopy (RAB) is an emerging modality to sample pulmonary lesions. Cone-beam computed tomography (CBCT) can be incorporated into RAB. We investigated the magnitude and predictors of patient and staff radiation exposure during mobile CBCT-guided shape-sensing RAB. METHODS: Patient radiation dose was estimated by cumulative dose area product (cDAP) and cumulative reference air kerma (cRAK). Staff equivalent dose was calculated based on isokerma maps and a phantom simulation. Patient, lesion and procedure-related factors associated with higher radiation doses were identified by logistic regression models. RESULTS: A total of 198 RAB cases were included in the analysis. The median patient cDAP and cRAK were 10.86 Gy cm2 (IQR: 4.62-20.84) and 76.20 mGy (IQR: 38.96-148.38), respectively. Among staff members, the bronchoscopist was exposed to the highest median equivalent dose of 1.48 µSv (IQR: 0.85-2.69). Both patient and staff radiation doses increased with the number of CBCT spins and targeted lesions (p < 0.001 for all comparisons). Patient obesity, negative bronchus sign, lesion size <2.0 cm and inadequate sampling by on-site evaluation were associated with a higher patient dose, while patient obesity and inadequate sampling by on-site evaluation were associated with a higher bronchoscopist equivalent dose. CONCLUSION: The magnitude of patient and staff radiation exposure during CBCT-RAB is aligned with safety thresholds recommended by regulatory authorities. Factors associated with a higher radiation exposure during CBCT-RAB can be identified pre-operatively and solicit procedural optimization by reinforcing radiation protective measures. Future studies are needed to confirm these findings across multiple institutions and practices.

A Real-World Assessment of Stage I Lung Cancer Through Electronic Nose Technology.

INTRODUCTION: Electronic nose (E-nose) technology has reported excellent sensitivity and specificity in the setting of lung cancer screening. However, the performance of E-nose specifically for early-stage tumors remains unclear. Therefore, the aim of our study was to assess the diagnostic performance of E-nose technology in clinical stage I lung cancer. METHODS: This phase IIc trial (NCT04734145) included patients diagnosed with a single greater than or equal to 50% solid stage I nodule. Exhalates were prospectively collected from January 2020 to August 2023. Blinded bioengineers analyzed the exhalates, using E-nose technology to determine the probability of malignancy. Patients were stratified into three risk groups (low-risk, [<0.2]; moderate-risk, [≥0.2-0.7]; high-risk, [≥0.7]). The primary outcome was the diagnostic performance of E-nose versus histopathology (accuracy and F1 score). The secondary outcome was the clinical performance of the E-nose versus clinicoradiological prediction models. RESULTS: Based on the predefined cutoff (<0.20), E-nose agreed with histopathologic results in 86% of cases, achieving an F1 score of 92.5%, based on 86 true positives, two false negatives, and 12 false positives (n = 100). E-nose would refer fewer patients with malignant nodules to observation (low-risk: 2 versus 9 and 11, respectively; p = 0.028 and p = 0.011) than would the Swensen and Brock models and more patients with malignant nodules to treatment without biopsy (high-risk: 27 versus 19 and 6, respectively; p = 0.057 and p < 0.001). CONCLUSIONS: In the setting of clinical stage I lung cancer, E-nose agrees well with histopathology. Accordingly, E-nose technology can be used in addition to imaging or as part of a "multiomics" platform.

Novel Insights Into the International Association for the Study of Lung Cancer Grading System for Lung Adenocarcinoma.

The new grading system for lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) defines prognostic subgroups on the basis of histologic patterns observed on surgical specimens. This study sought to provide novel insights into the IASLC grading system, with particular focus on recurrence-specific survival (RSS) and lung cancer-specific survival among patients with stage I adenocarcinoma. Under the IASLC grading system, tumors were classified as grade 1 (lepidic predominant with <20% high-grade patterns [micropapillary, solid, and complex glandular]), grade 2 (acinar or papillary predominant with <20% high-grade patterns), or grade 3 (≥20% high-grade patterns). Kaplan-Meier survival estimates, pathologic features, and genomic profiles were investigated for patients whose disease was reclassified into a higher grade under the IASLC grading system on the basis of the hypothesis that they would strongly resemble patients with predominant high-grade tumors. Overall, 423 (29%) of 1443 patients with grade 1 or 2 tumors classified based on the predominant pattern-based grading system had their tumors upgraded to grade 3 based on the IASLC grading system. The RSS curves for patients with upgraded tumors were significantly different from those for patients with grade 1 or 2 tumors (log-rank P < .001) but not from those for patients with predominant high-grade patterns (P = .3). Patients with upgraded tumors had a similar incidence of visceral pleural invasion and spread of tumor through air spaces as patients with predominant high-grade patterns. In multivariable models, the IASLC grading system remained significantly associated with RSS and lung cancer-specific survival after adjustment for aggressive pathologic features such as visceral pleural invasion and spread of tumor through air spaces. The IASLC grading system outperforms the predominant pattern-based grading system and appropriately reclassifies tumors into higher grades with worse prognosis, even after other pathologic features of aggressiveness are considered.

Drug Burden Index is a Modifiable Predictor of 30-Day-Hospitalization in Community-Dwelling Older Adults with Complex Care Needs: Machine Learning Analysis of InterRAI Data.

BACKGROUND: Older adults (≥ 65 years) account for a disproportionately high proportion of hospitalization and in-hospital mortality, some of which may be avoidable. Although machine learning (ML) models have already been built and validated for predicting hospitalization and mortality, there remains a significant need to optimise ML models further. Accurately predicting hospitalization may tremendously impact the clinical care of older adults as preventative measures can be implemented to improve clinical outcomes for the patient. METHODS: In this retrospective cohort study, a dataset of 14,198 community-dwelling older adults (≥ 65 years) with complex care needs from the Inter-Resident Assessment Instrument database was used to develop and optimise three ML models to predict 30-day-hospitalization. The models developed and optimized were Random Forest (RF), XGBoost (XGB), and Logistic Regression (LR). Variable importance plots were generated for all three models to identify key predictors of 30-day-hospitalization. RESULTS: The area under the receiver operating characteristics curve for the RF, XGB and LR models were 0.97, 0.90 and 0.72, respectively. Variable importance plots identified the Drug Burden Index and alcohol consumption as important, immediately potentially modifiable variables in predicting 30-day-hospitalization. CONCLUSIONS: Identifying immediately potentially modifiable risk factors such as the Drug Burden Index and alcohol consumption is of high clinical relevance. If clinicians can influence these variables, they could proactively lower the risk of 30-day-hospitalization. ML holds promise to improve the clinical care of older adults. It is crucial that these models undergo extensive validation through large-scale clinical studies before being utilized in the clinical setting.

Association of fetal growth restriction and stillbirth in twin compared with singleton pregnancies.

OBJECTIVE: Twin pregnancies are at an increased risk of stillbirth compared to singletons. Fetal growth restriction (FGR) is a leading cause of perinatal mortality and morbidity, in both singleton and multiple pregnancies. Whether the contribution of FGR to stillbirth in twin pregnancies differs from that in singletons is yet to be determined. The main aim of this study was to determine the association between FGR and stillbirth in twin compared to singleton pregnancies. The secondary objectives include an assessment of the contribution of FGR to stillbirths, stratified by gestational age at delivery. Furthermore, we aimed to compare the association between FGR and stillbirth in twin pregnancies using the twin-specific versus singleton birthweight charts, stratified by chorionicity. METHODS: This was a cross-sectional study including pregnancies receiving obstetric care and birth at St George's Hospital, London. The exclusion criteria included triplet and higher order pregnancies, those resulting in miscarriage or livebirths at or prior to 23+6 weeks, or had a termination of pregnancy, or with missing data on the gestational age at birth. FGR and small for gestational age (SGA) were defined as birthweight <5th and <10th centile, respectively. While standard logistic regression was used for singleton pregnancies, the association of FGR and SGA designation with stillbirth in twin pregnancies was investigated with mixed-effects logistic regression models. For twin pregnancies, intercepts were allowed to vary for twin pairs to account for inter-twin dependency. Analyses were stratified by gestational age at delivery and chorionicity. RESULTS: The study included 95,342 singleton and 3,576 twin pregnancies. There were 494 (0.52%) stillbirths in singleton and 41 (1.15%) stillbirths in twin pregnancies (17 dichorionic and 24 monochorionic). FGR and SGA were significantly associated with stillbirth in singleton pregnancies, across all gestational ages at delivery (before 32 weeks- SGA: OR 2.36; 95% CI 1.78-3.13, p<0.001 and FGR: OR 2.67; 95% CI 2.02- 3.55, p<0.001; between 32-36 weeks- SGA: OR 2.70; 95% CI 1.71-4.31, p<0.001 and FGR: OR 2.82; 95% CI 1.78- 4.47, p<0.001; above 36 weeks- SGA: OR 3.85; 95% CI 2.83 - 5.21, p<0.001 and FGR: OR 4.43; 95% CI 3.16 - 6.12, p<0.001) A greater proportion of fetuses from twin pregnancies were diagnosed as SGA and FGR when singleton compared to the twin-specific chart was used (48.43% vs. 9.12%, and 36.73% vs. 6.23%, respectively). When stratified by gestational age at delivery, both SGA and FGR determined by the twin-specific charts were associated with significantly increased odds of having a stillbirth for those delivered before 32 weeks (SGA: OR 3.87; 95% CI 1.56-9.50, p=0.003 and FGR: OR 5.26; 95% CI 2.11-13.01, p<0.001), those delivered between 32-36 weeks (SGA: OR 6.67; 95% CI 2.11-20.41, p=0.001 and FGR: OR 9.54; 95% CI 3.01-29.40, p<0.001) and those delivered beyond 36 weeks (SGA: OR 12.68 95% CI 2.47-58,15, p=0.001 and FGR: OR 23.84; 95% CI 4.62-110.25, p<0.001), whereas the association of stillbirth with either SGA or FGR was inconsistent when analysed using singleton charts (before 32 weeks- SGA: p=0.014 and FGR: p=0.005; between 32-36 weeks- SGA: p=0.036 and FGR: p=0.008; above 36 weeks- SGA: p=0.080 and FGR: p=0.063). For dichorionic twins delivered before 32 weeks, the odds of an SGA or FGR fetus having a stillbirth was increased when analysed using twin-specific charts. In contrast, monochorionic twins delivered before 32 weeks showed lower and non-significant associations with stillbirth for both SGA and FGR cases using either twin-specific or singleton charts. In dichorionic twin pregnancies delivered between 32-36 weeks, the OR for stillbirth of SGA using twin birthweight chart was 6.70 (95% CI 0.80-56.46, p=0.059), and using singleton chart was 0.92 (95% CI 0.11-7.71, p=0.934) and statistically non-significant. Similarly, the OR for stillbirth of FGR using twin birthweight chart and singleton chart was 9.59 (95% CI 1.14-81.06, p=0.025), and 1.40 (95% CI 0.17-11.76, p=0.735), respectively. On the other hand, in monochorionic twin pregnancies delivered between 32-36 weeks, the OR for stillbirth of SGA and FGR using twin birthweight chart was 9.37 (95% CI 2.20- 37.72, p=0.001), and 13.55 (95% CI 3.12 - 55.94 p < 0.001) respectively. CONCLUSIONS: Our study demonstrates a significant association between SGA, particularly for FGR, with increased odds of stillbirths in singleton pregnancies across all gestational ages. For twin pregnancies, when twin-specific charts were used, SGA and in particular FGR were associated with a significantly increased risk of stillbirth, across all gestational ages at delivery. This article is protected by copyright. All rights reserved.

A smartphone-based standalone fluorescence spectroscopy tool for cervical precancer diagnosis in clinical conditions.

Real-time prediction about the severity of noncommunicable diseases like cancers is a boon for early diagnosis and timely cure. Optical techniques due to their minimally invasive nature provide better alternatives in this context than the conventional techniques. The present study talks about a standalone, field portable smartphone-based device which can classify different grades of cervical cancer on the basis of the spectral differences captured in their intrinsic fluorescence spectra with the help of AI/ML technique. In this study, a total number of 75 patients and volunteers, from hospitals at different geographical locations of India, have been tested and classified with this device. A classification approach employing a hybrid mutual information long short-term memory model has been applied to categorize various subject groups, resulting in an average accuracy, specificity, and sensitivity of 96.56%, 96.76%, and 94.37%, respectively using 10-fold cross-validation. This exploratory study demonstrates the potential of combining smartphone-based technology with fluorescence spectroscopy and artificial intelligence as a diagnostic screening approach which could enhance the detection and screening of cervical cancer.