Gastric preconditioning via percutaneous angioembolization before esophagectomy in patients at high risk for esophageal leak.

Anastomotic leaks and stenoses remain critical complications in esophagectomy and are related to conduit perfusion. Surgical gastric preconditioning has been described but requires additional surgery and creates scar tissue, potentially hindering future operation. We sought to evaluate the feasibility and safety of percutaneous gastric preconditioning by angioembolization to improve perfusion of gastric conduits before esophagectomy in a high-risk patient cohort. Patients pending an esophagectomy for cancer and deemed to be high risk for anastomotic complications underwent preconditioning by image-guided angioembolization. Preconditioning was performed on an outpatient basis by means of superselective embolization of the left gastric and short gastric arteries. Intraoperative conduit perfusion evaluation with indocyanine green and postoperative surgical outcomes was reviewed. Seventeen patients underwent gastric preconditioning, with no complications observed. Thirteen of the 17 patients ultimately underwent esophagectomy; the remaining four patients were not candidates for an operation. Patients proceeded to surgery a median of 23 days (interquartile range, 21-27 days) after preconditioning. The intraoperative indocyanine green perfusion of all conduits was appropriate, with no tip demarcation and with a median time to dye uptake of 20s (interquartile range, 15-20s). There were no anastomotic stenoses or leaks noted within the series. Gastric conduit preconditioning by percutaneous angioembolization of the left gastric and short gastric arteries can be performed safely and without operative delay in high-risk patients. Further evaluation of preconditioning for conduit optimization is warranted to limit the critical complications of anastomotic leak and stenosis in esophagectomy.

Outpatient elective induction of labour at 39 weeks' gestation (HOME INDUCTION): an open-label, randomised, controlled, phase III, non-inferiority trial.

Background: The increased demand for induction of labour (IOL) at 39 weeks' gestation in normal-risk nulliparous patients creates significant logistical challenges for busy maternity units. A potential innovation is commencing induction by means of outpatient cervical ripening, using either a vaginal prostaglandin preparation (Propess) or an osmotic cervical dilator (Dilapan-S). Methods: A Phase III, open label, single centre non-inferiority trial (EudraCT number 2019-004697-25) randomised healthy nulliparous women who chose elective IOL at 39 weeks to one of three methods of initial cervical ripening, specifically 12 h of Dilapan-S(D12), 24 h of Dilapan-S(D24), or 24 h of Propess(P24) between November 2020 and July 2023. After initial administration of the IOL agent in the hospital, participants returned home for 12 or 24 h, before readmission to complete delivery. The primary outcome was vaginal delivery achieved at any time, and this was compared in a non-inferiority analysis of Dilapan-S compared to Propess, within a 10% non-inferiority margin. Secondary outcomes included pairwise comparisons for each induction agent, and a range of logistical factors, such as time to delivery, the need for an additional cervical ripening agent, and length of hospital stay. Findings: Of the 327 women randomised at 38 weeks, 271 (83%) completed the induction intervention. The D24 and P24 groups showed similarly high rates of vaginal delivery, 75% and 76% respectively. D12 had a lower vaginal delivery rate of 64% and consequently the overall comparison of Dilapan-S to Propess did not demonstrate non-inferiority (difference = -6%, 95% CI = -17%, 5%) because the lower 95% CI exceeded the -10% threshold of non-inferiority. The majority of participants across all groups were delivered by any means within 72 h of starting the induction process, inclusive of time spent at home (89% of the D24 group, 98% of the D12 group, 95% of the P24 group). There were no differences in rates of adverse events between groups. Interpretation: There were similarly high vaginal delivery rates for D24 and P24, with at least 75% of patients successfully delivering vaginally following outpatient cervical ripening, with no significant adverse maternal or neonatal outcomes. Funding: The Rotunda Foundation, Medicem Technology s.r.o.

A Novel Frailty Index Can Predict the Short-Term Outcomes of Esophagectomy in Older Patients with Esophageal Cancer.

Background: Frailty, rather than age, is associated with postoperative morbidity and mortality. We sought to determine whether preoperative frailty as defined by a novel scoring system could predict the outcomes among older patients undergoing esophagectomy. Methods: We identified patients 65 years or older who underwent esophagectomy between 2011 and 2021 at our institution. Frailty was assessed using the MSK-FI, which consists of 1 component related to functional status and 10 medical comorbidities. We used a multivariable logistic regression model to test for the associations between frailty and short-term outcomes, with continuous frailty score as the predictor and additionally adjusted for age and Eastern Cooperative Oncology Group performance status. Results: In total, 447 patients were included in the analysis (median age of 71 years [interquartile range, 68-75]). Most of the patients underwent neoadjuvant treatment (81%), an Ivor Lewis esophagectomy (86%), and minimally invasive surgery (55%). A total of 22 patients (4.9%) died within 90 days of surgery, 144 (32%) had a major complication, 81 (19%) were readmitted, and 31 (7.2%) were discharged to a facility. Of the patients who died within 90 days, 19 had a major complication, yielding a failure-to-rescue rate of 13%. The risk of 30-day major complications (OR, 1.24 [95% CI, 1.09-1.41]; p = 0.001), readmissions (OR, 1.31 [95% CI, 1.13-1.52]; p < 0.001), and discharge to a facility (OR, 1.86 [95% CI, 1.49-2.37]; p < 0.001) increased with increasing frailty. Frailty and 90-day mortality were not associated. Conclusions: Frailty assessment during surgery decision-making can identify patients with a high risk of morbidity.

Evaluating the modulation of peripheral immune profile in people living with HIV and (Neuro)cysticercosis.

BACKGROUND: The parasitic infection caused by Taenia solium represents a significant public health concern in developing countries. Larval invasion of body tissues leads to cysticercosis (CC), while central nervous system (CNS) involvement results in neurocysticercosis (NCC). Both conditions exhibit diverse clinical manifestations, and the potential impact of concomitant HIV infection especially prevalent in sub-Saharan Africa on peripheral and CNS immune responses remains poorly understood. This study aimed to identify the potential impact of HIV coinfection in CC and NCC patients. METHODOLOGY: A nested study within a cross-sectional analysis in two Tanzanian regions was performed and 234 participants (110 HIV+ and 124 HIV-) were tested for cysticercosis antibodies, antigens, CD4 counts and serum Th1 and Th2 cytokines via multiplex bead-based immunoassay. 127 cysticercosis seropositive individuals underwent cranial computed tomography (CCT) and clinical symptoms were assessed. Multiple regression analyses were performed to identify factors associated with cytokine modulation due to HIV in CC and NCC patients. RESULTS: Serologically, 18.8% tested positive for cysticercosis antibodies, with no significant difference HIV+ and HIV+. A significantly higher rate of cysticercosis antigen positivity was found in HIV+ individuals (43.6%) compared to HIV- (28.2%) (p = 0.016). CCT scans revealed that overall 10.3% had active brain cysts (NCC+). Our study found no significant changes in the overall cytokine profiles between HIV+ and HIV- participants coinfected CC and NCC, except for IL-5 which was elevated in HIV+ individuals with cysticercosis. Furthermore, HIV infection in general was associated with increased levels of pro-and some anti-inflammatory cytokines e.g. TNF-α, IL-8, and IFN-γ. However, based on the interaction analyses, no cytokine changes were observed due to HIV in CC or NCC patients. CONCLUSIONS: In conclusion, while HIV infection itself significantly modulates levels of key cytokines such as TNF-α, IL-8, and IFN-γ, it does not modulate any cytokine changes due to CC or NCC. This underscores the dominant influence of HIV on the immune system and highlights the importance of effective antiretroviral therapy in managing immune responses in individuals coinfected with HIV and CC/NCC.

Adenomas from individuals with pathogenic biallelic variants in the MUTYH and NTHL1 genes demonstrate base excision repair tumour mutational signature profiles similar to colorectal cancers, expanding potential diagnostic and variant classification applications.

Background: Colorectal cancers (CRCs) from people with biallelic germline likely pathogenic/pathogenic variants in MUTYH or NTHL1 exhibit specific single base substitution (SBS) mutational signatures, namely combined SBS18 and SBS36 (SBS18+SBS36), and SBS30, respectively. The aim was to determine if adenomas from biallelic cases demonstrated these mutational signatures at diagnostic levels. Methods: Whole-exome sequencing of FFPE tissue and matched blood-derived DNA was performed on 9 adenomas and 15 CRCs from 13 biallelic MUTYH cases, on 7 adenomas and 2 CRCs from 5 biallelic NTHL1 cases and on 27 adenomas and 26 CRCs from 46 non-hereditary (sporadic) participants. All samples were assessed for COSMIC v3.2 SBS mutational signatures. Results: In biallelic MUTYH cases, SBS18+SBS36 signature proportions in adenomas (mean±standard deviation, 65.6%±29.6%) were not significantly different to those observed in CRCs (76.2%±20.5%, p-value=0.37), but were significantly higher compared with non-hereditary adenomas (7.6%±7.0%, p-value=3.4×10-4). Similarly, in biallelic NTHL1 cases, SBS30 signature proportions in adenomas (74.5%±9.4%) were similar to those in CRCs (78.8%±2.4%) but significantly higher compared with non-hereditary adenomas (2.8%±3.6%, p-value=5.1×10-7). Additionally, a compound heterozygote with the c.1187G>A p.(Gly396Asp) pathogenic variant and the c.533G>C p.(Gly178Ala) variant of unknown significance (VUS) in MUTYH demonstrated high levels of SBS18+SBS36 in four adenomas and one CRC, providing evidence for reclassification of the VUS to pathogenic. Conclusions: SBS18+SBS36 and SBS30 were enriched in adenomas at comparable proportions observed in CRCs from biallelic MUTYH and biallelic NTHL1 cases, respectively. Therefore, testing adenomas may improve the identification of biallelic cases and facilitate variant classification, ultimately enabling opportunities for CRC prevention.

Determinants of successful minimally invasive surgery (MIS) for resectable non-small cell lung cancer (NSCLC) after neoadjuvant therapy.

OBJECTIVE: MIS (VATS, RATS) for pulmonary resection is standard in early stage NSCLC as it is associated with better perioperative outcomes than thoracotomy. MIS for resection of more advanced NSCLC (Stages IB-IIIB) treated with neoadjuvant therapy has been utilized. However, the determinants of success are not well-defined. METHODS: A single institution retrospective review of a prospectively maintained database was conducted, querying for patients with clinical Stage IB-IIIB NSCLC who had resection after neoadjuvant systemic therapy without radiation from 2013-2022. Patients were grouped by surgical approach, open vs. MIS. Successful MIS was defined by no conversion, R0 resection, and no major (≥grade 3) morbidity. Analyses by intent-to-treat assessed outcomes by Wilcoxon rank sum test and Fisher's exact test. (MVA identified variables that contributed to successful MIS resection. RESULTS: Of 627 eligible patients, 360 (57%) had open and 267 (43%) had MIS procedures. Most patients (79.1%) received neoadjuvant platinum-based chemotherapy, and 21.9% were treated with immunotherapy or targeted therapy alone or combined with chemotherapy. Among MIS resections, 179 (67%) were performed by VATS and 88 (33%) by RATS. The conversion rate was 16% (n=43). Successful MIS resection was achieved in 77% of patients. MVA showed that pre-treatment clinical N stage was a significant determinant of success, but not pre-treatment clinical T stage or type of neoadjuvant therapy. CONCLUSION: Following neoadjuvant systemic therapy for clinical stage IB-IIIB NSCLC, MIS resection can be successfully accomplished and should be considered in appropriate patients. Presence of pre-treatment nodal disease is associated with higher odds of conversion, major morbidity, and incomplete resection.

Changes in Physiopathological Markers in Myotonic Dystrophy Type 1 Skeletal Muscle: A 3-Year Follow-up Study.

Background: Myotonic dystrophy type 1 (DM1) is a slowly progressive disease caused by abnormal CTG repetitions on the dystrophia myotonica protein kinase (DMPK) gene. Long mRNA from CTG repetitions stabilizes in nuclear foci and sequester muscleblind-like splicing regulator 1 (MBNL1). Cardinal signs of DM1 include muscle wasting and weakness. The impacts of DM1 progression on skeletal muscle are under-researched. Objective: Identifying physiopathological markers related to maximal strength loss over time in DM1. Methods: Twenty-two individuals with DM1 participated in two maximal isometric muscle strength (MIMS) evaluations of their knee extensors and two vastus lateralis muscle biopsies, 3 years apart. Muscle fiber typing, size (including minimal Feret's diameter [MFD] and atrophy/hypertrophy factors [AF/HF]), and nuclear foci and MBNL1 colocalization (foci/MBNL1+) were evaluated. Immunoblotting was used to measure glycogen synthase kinase-3 beta (GSK3ß), p62, LC3BI, LC3BII, and oxidative phosphorylation proteins. Results: There are significant correlations between the fold changes of MIMS with type 1 fiber MFD (ρ= 0.483) and AF (ρ= -0.514). Regression analysis shows that baseline percentage of foci/MBNL1+ nuclei and strength training explain 44.1% of foci/MBNL1+ nuclei percentage variation over time. There are fair to excellent correlations between the fold changes of MIMS and GSK3ß (ρ= 0.327), p62 (ρ= 0.473), LC3BI (ρ= 0.518), LC3BII (ρ= -0.391) and LC3BII/LC3BI (ρ= -0.773). Conclusion: Type 1 MFD decrease and AF increase are correlated with MIMS loss. There seems to be a plateau effect in foci/MBNL1+ nuclei accumulation and strength training helps decrease this accumulation. Autophagy marker LC3BII/LC3BI ratio has a good biomarker potential of MIMS loss, but more investigations are needed.

Spatial extent as a sensitive amyloid-PET metric in preclinical Alzheimer's disease.

INTRODUCTION: Spatial extent-based measures of how far amyloid beta (Aß) has spread throughout the neocortex may be more sensitive than traditional Aß-positron emission tomography (PET) measures of Aß level for detecting early Aß deposits in preclinical Alzheimer's disease (AD) and improve understanding of Aß's association with tau proliferation and cognitive decline. METHODS: Pittsburgh Compound-B (PIB)-PET scans from 261 cognitively unimpaired older adults from the Harvard Aging Brain Study were used to measure Aß level (LVL; neocortical PIB DVR) and spatial extent (EXT), calculated as the proportion of the neocortex that is PIB+. RESULTS: EXT enabled earlier detection of Aß deposits longitudinally confirmed to reach a traditional LVL-based threshold for Aß+ within 5 years. EXT improved prediction of cognitive decline (Preclinical Alzheimer Cognitive Composite) and tau proliferation (flortaucipir-PET) over LVL. DISCUSSION: These findings indicate EXT may be more sensitive to Aß's role in preclinical AD than level and improve targeting of individuals for AD prevention trials. HIGHLIGHTS: Aß spatial extent (EXT) was measured as the percentage of the neocortex with elevated Pittsburgh Compound-B. Aß EXT improved detection of Aß below traditional PET thresholds. Early regional Aß deposits were spatially heterogeneous. Cognition and tau were more closely tied to Aß EXT than Aß level. Neocortical tau onset aligned with reaching widespread neocortical Aß.

Hypertrophic cardiomyopathy detection with artificial intelligence electrocardiography in international cohorts: an external validation study.

Aims: Recently, deep learning artificial intelligence (AI) models have been trained to detect cardiovascular conditions, including hypertrophic cardiomyopathy (HCM), from the 12-lead electrocardiogram (ECG). In this external validation study, we sought to assess the performance of an AI-ECG algorithm for detecting HCM in diverse international cohorts. Methods and results: A convolutional neural network-based AI-ECG algorithm was developed previously in a single-centre North American HCM cohort (Mayo Clinic). This algorithm was applied to the raw 12-lead ECG data of patients with HCM and non-HCM controls from three external cohorts (Bern, Switzerland; Oxford, UK; and Seoul, South Korea). The algorithm's ability to distinguish HCM vs. non-HCM status from the ECG alone was examined. A total of 773 patients with HCM and 3867 non-HCM controls were included across three sites in the merged external validation cohort. The HCM study sample comprised 54.6% East Asian, 43.2% White, and 2.2% Black patients. Median AI-ECG probabilities of HCM were 85% for patients with HCM and 0.3% for controls (P < 0.001). Overall, the AI-ECG algorithm had an area under the receiver operating characteristic curve (AUC) of 0.922 [95% confidence interval (CI) 0.910-0.934], with diagnostic accuracy 86.9%, sensitivity 82.8%, and specificity 87.7% for HCM detection. In age- and sex-matched analysis (case-control ratio 1:2), the AUC was 0.921 (95% CI 0.909-0.934) with accuracy 88.5%, sensitivity 82.8%, and specificity 90.4%. Conclusion: The AI-ECG algorithm determined HCM status from the 12-lead ECG with high accuracy in diverse international cohorts, providing evidence for external validity. The value of this algorithm in improving HCM detection in clinical practice and screening settings requires prospective evaluation.

Effects of a passive upper-body exoskeleton on whole-body kinematics, leg muscle activity, and discomfort during a carrying task.

OBJECTIVE: To compare whole-body kinematics, leg muscle activity, and discomfort while performing a 10-min carrying task with and without a passive upper-body exoskeleton (CarrySuitⓇ), for both males and females. BACKGROUND: Diverse commercial passive exoskeletons have appeared on the market claiming to assist lifting or carrying task. However, evidence of their impact on kinematics, muscle activity, and discomfort while performing these tasks are necessary to determine their benefits and/or limitations. METHOD: Sixteen females and fourteen males carried a 15kg load with and without a passive exoskeleton during 10-min over a round trip route, in two non-consecutive days. Whole-body kinematics and leg muscle activity were evaluated for each condition. In addition, leg discomfort ratings were quantified before and immediately after the task. RESULTS: The gastrocnemius and vastus lateralis muscle activity remained constant over the task with the exoskeleton. Without the exoskeleton a small decrease of gastrocnemius median activation was observed regardless of sex, and a small increase in static vastus lateralis activation was observed only for females. Several differences in sagittal, frontal, and transverse movements' ranges of motion were found between conditions and over the task. With the exoskeleton, ROM in the sagittal plane increased over time for the right ankle and pelvis for both sexes, and knees for males only. Thorax ROMs in the three planes were higher for females only when using the exoskeleton. Leg discomfort was lower with the exoskeleton than without. CONCLUSION: The results revealed a positive impact on range of motion, leg muscle activity, and discomfort of the tested exoskeleton.

Late recurrence of completely resected stage I to IIIA lung adenocarcinoma.

OBJECTIVE: Research into the risk factors associated with late recurrence (>2 years after surgery) of lung adenocarcinoma is limited. We investigated the incidence of and clinicopathologic and genomic features associated with late recurrence of resected stage I-IIIA lung adenocarcinoma. METHODS: We performed a retrospective analysis of patients with completely resected pathologic stage I-IIIA lung adenocarcinoma (2010-2019). Patients with a history of lung cancer, neoadjuvant therapy, or mucinous or noninvasive lung adenocarcinoma, or with follow-up of less than 2 years were excluded. Cox and logistic regression modeling were used to compare clinicopathologic variables among patients with no, early (≤2 years), and late recurrence. Comparisons of genomic mutations were corrected for multiple testing. RESULTS: Of the 2349 patients included, 537 developed a recurrence during follow-up. Most recurrences (55% [297/537]) occurred early; 45% (240/537) occurred late. A larger proportion of late recurrences than early recurrences were locoregional (37% vs 29%; P = .047). Patients with late recurrence had more aggressive pathologic features (International Association for the Study of Lung Cancer grade 2 and 3, lymphovascular invasion, visceral pleural invasion) and higher stage than patients without recurrence. Pathologic features were similar between patients with early and late recurrence, except stage IIIA disease was more common in the early cohort. No genomic mutations were associated with late recurrence. CONCLUSIONS: Late recurrence of lung adenocarcinoma after resection is more common than previously reported. Patients without disease more than 2 years after surgery who had aggressive pathologic features at the time of resection have an elevated risk of recurrence and may benefit from more aggressive follow-up.

Identifying longitudinal cognitive resilience from cross-sectional amyloid, tau, and neurodegeneration.

BACKGROUND: Leveraging Alzheimer's disease (AD) imaging biomarkers and longitudinal cognitive data may allow us to establish evidence of cognitive resilience (CR) to AD pathology in-vivo. Here, we applied latent class mixture modeling, adjusting for sex, baseline age, and neuroimaging biomarkers of amyloid, tau and neurodegeneration, to a sample of cognitively unimpaired older adults to identify longitudinal trajectories of CR. METHODS: We identified 200 Harvard Aging Brain Study (HABS) participants (mean age = 71.89 years, SD = 9.41 years, 59% women) who were cognitively unimpaired at baseline with 2 or more timepoints of cognitive assessment following a single amyloid-PET, tau-PET and structural MRI. We examined latent class mixture models with longitudinal cognition as the dependent variable and time from baseline, baseline age, sex, neocortical Aß, entorhinal tau, and adjusted hippocampal volume as independent variables. We then examined group differences in CR-related factors across the identified subgroups from a favored model. Finally, we applied our favored model to a dataset from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 160, mean age = 73.9 years, SD = 7.6 years, 60% women). RESULTS: The favored model identified 3 latent subgroups, which we labelled as Normal (71% of HABS sample), Resilient (22.5%) and Declining (6.5%) subgroups. The Resilient subgroup exhibited higher baseline cognitive performance and a stable cognitive slope. They were differentiated from other groups by higher levels of verbal intelligence and past cognitive activity. In ADNI, this model identified a larger Normal subgroup (88.1%), a smaller Resilient subgroup (6.3%) and a Declining group (5.6%) with a lower cognitive baseline. CONCLUSION: These findings demonstrate the value of data-driven approaches to identify longitudinal CR groups in preclinical AD. With such an approach, we identified a CR subgroup who reflected expected characteristics based on previous literature, higher levels of verbal intelligence and past cognitive activity.

Neurocysticercosis Prevalence and Characteristics in Communities of Sinda District in Zambia: A Cross-Sectional Study.

BACKGROUND: This study aimed at describing the epidemiology of (neuro)cysticercosis as well as its clinical and radiological characteristics in a Taenia solium endemic district of Zambia. METHODS: This was part of a cross-sectional community-based study conducted in Sinda district to evaluate an antibody-detecting T. solium point-of-care (TS POC) test for taeniosis and (neuro)cysticercosis. All TS POC cysticercosis positive (CC+) participants and a subset of the TS POC cysticercosis negative (CC-) received a clinical evaluation and cerebral computed tomography (CT) examination for neurocysticercosis (NCC) diagnosis and staging. RESULTS: Of the 1249 participants with a valid TS POC test result, 177 (14%) were TS POC CC+ . Cysticercosis sero-prevalence was estimated to be 20.1% (95% confidence intervals [CI] 14.6-27.0%). In total, 233 participants received a CT examination (151 TS POC CC+ , 82 TS POC CC-). Typical NCC lesions were present in 35/151 (23%) TS POC CC+ , and in 10/82 (12%) TS POC CC- participants. NCC prevalence was 13.5% (95% CI 8.4-21.1%) in the study population and 38.0% (95% CI 5.2-87.4%) among people reporting epileptic seizures. Participants with NCC were more likely to experience epileptic seizures (OR = 3.98, 95% CI 1.34-11.78, p = 0.01) than those without NCC, although only 7/45 (16%) people with NCC ever experienced epileptic seizures. The number of lesions did not differ by TS POC CC status (median: 3 [IQR 1-6] versus 2.5 [IQR 1-5.3], p = 0.64). Eight (23%) of the 35 TS POC CC+ participants with NCC had active stage lesions; in contrast none of the TS POC CC- participants was diagnosed with active NCC. CONCLUSION: NCC is common in communities in the Eastern province of Zambia, but a large proportion of people remain asymptomatic.

The incremental contribution of mobile cone-beam computed tomography to the tool-lesion relationship during shape-sensing robotic-assisted bronchoscopy.

Introduction: This study aims to answer the question of whether adding mobile cone-beam computed tomography (mCBCT) imaging to shape-sensing robotic-assisted bronchoscopy (ssRAB) translates into a quantifiable improvement in the tool-lesion relationship. Methods: Data from 102 peripheral lung lesions with ≥2 sequential mCBCT orbital spins and from 436 lesions with 0-1 spins were prospectively captured and retrospectively analysed. The primary outcome was the tool-lesion relationship status across the first and the last mCBCT spins. Secondary outcomes included 1) the change in distance between the tip of the sampling tool and the centre of the lesion between the first and the last spins and 2) the per-lesion diagnostic yield. Results: Compared to lesions requiring 0-1 spins, lesions requiring ≥2 spins were smaller and had unfavourable bronchus sign and intra-operative sonographic view. On the first spin, 54 lesions (53%) were designated as non-tool-in-lesion (non-TIL) while 48 lesions (47%) were designated as TIL. Of the 54 initially non-TIL cases, 49 (90%) were converted to TIL status by the last spin. Overall, on the last spin, 96 out of 102 lesions (94%) were defined as TIL and six out of 102 lesions (6%) were defined as non-TIL (p<0.0001). The mean distance between the tool and the centre of the lesion decreased from 10.4 to 6.6 mm between the first and last spins (p<0.0001). The overall diagnostic yield was 77%. Conclusion: Targeting traditionally challenging lung lesions, intra-operative volumetric imaging allowed for the conversion of 90% of non-TIL status to TIL. Guidance with mCBCT resulted in a significant decrease in the distance between the tip of the needle to lesion centre.

Ten-Year Trend of Oral Anticoagulation Use in Postoperative and Nonpostoperative Atrial Fibrillation in Routine Clinical Practice.

BACKGROUND: The study aimed to describe the patterns and trends of initiation, discontinuation, and adherence of oral anticoagulation (OAC) in patients with new-onset postoperative atrial fibrillation (POAF), and compare with patients newly diagnosed with non-POAF. METHODS AND RESULTS: This retrospective cohort study identified patients newly diagnosed with atrial fibrillation or flutter between 2012 and 2021 using administrative claims data from OptumLabs Data Warehouse. The POAF cohort included 118 366 patients newly diagnosed with atrial fibrillation or flutter within 30 days after surgery. The non-POAF cohort included the remaining 315 832 patients who were newly diagnosed with atrial fibrillation or flutter but not within 30 days after a surgery. OAC initiation increased from 28.9% to 44.0% from 2012 to 2021 in POAF, and 37.8% to 59.9% in non-POAF; 12-month medication adherence increased from 47.0% to 61.8% in POAF, and 59.7% to 70.4% in non-POAF. The median time to OAC discontinuation was 177 days for POAF, and 242 days for non-POAF. Patients who saw a cardiologist within 90 days of the first atrial fibrillation or flutter diagnosis, regardless of POAF or non-POAF, were more likely to initiate OAC (odds ratio, 2.92 [95% CI, 2.87-2.98]; P <0.0001), adhere to OAC (odds ratio, 1.08 [95% CI, 1.04-1.13]; P <0.0001), and less likely to discontinue (odds ratio, 0.83 [95% CI, 0.82-0.85]; P <0.0001) than patients who saw a surgeon or other specialties. CONCLUSIONS: The use of and adherence to OAC were higher in non-POAF patients than in POAF patients, but they increased over time in both groups. Patients managed by cardiologists were more likely to use and adhere to OAC, regardless of POAF or non-POAF.

Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study.

BACKGROUND: Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population. METHODS: This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4-5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4-9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population. FINDINGS: In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9-63·9], p<0·001) or MACE (12·6 [8·5-18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17-8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93-5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events. INTERPRETATION: The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators. FUNDING: British Heart Foundation, NHS-AI award, Innovate UK, National Institute for Health and Care Research, and the Oxford Biomedical Research Centre.

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

BACKGROUND: Results of recent clinical trials suggest that 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 examination. 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 cT1 N0 M0 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 the final pathology report. Of these 27 patients, 4 (15%) had skip metastasis to N2 stations, and 20 (74%) received adjuvant therapy; no completion lobectomies were performed. Ten patients (37%) had disease 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 patients who underwent lobectomy, all variables were balanced between the groups, except pathologic N2 stage and open surgical approach. The 5-year cumulative incidence of recurrence was not significantly different between segmentectomy and lobectomy (42% vs 52%, respectively; Gray's P = .1). The 5-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 cT1 N0 M0 NSCLC had limited isolated locoregional recurrences and outcomes similar to those in patients who underwent lobectomy. Lobectomy may not provide an advantage in these patients.

Lower in vivo locus coeruleus integrity is associated with lower cortical thickness in older individuals with elevated Alzheimer's pathology: a cohort study.

BACKGROUND: Autopsy work indicates that the widely-projecting noradrenergic pontine locus coeruleus (LC) is among the earliest regions to accumulate hyperphosphorylated tau, a neuropathological Alzheimer's disease (AD) hallmark. This early tau deposition is accompanied by a reduced density of LC projections and a reduction of norepinephrine's neuroprotective effects, potentially compromising the neuronal integrity of LC's cortical targets. Previous studies suggest that lower magnetic resonance imaging (MRI)-derived LC integrity may signal cortical tissue degeneration in cognitively healthy, older individuals. However, whether these observations are driven by underlying AD pathology remains unknown. To that end, we examined potential effect modifications by cortical beta-amyloid and tau pathology on the association between in vivo LC integrity, as quantified by LC MRI signal intensity, and cortical neurodegeneration, as indexed by cortical thickness. METHODS: A total of 165 older individuals (74.24 ± 9.72 years, ~ 60% female, 10% cognitively impaired) underwent whole-brain and dedicated LC 3T-MRI, Pittsburgh Compound-B (PiB, beta-amyloid) and Flortaucipir (FTP, tau) positron emission tomography. Linear regression analyses with bootstrapped standard errors (n = 2000) assessed associations between bilateral cortical thickness and i) LC MRI signal intensity and, ii) LC MRI signal intensity interacted with cortical FTP or PiB (i.e., EC FTP, IT FTP, neocortical PiB) in the entire sample and a low beta-amyloid subsample. RESULTS: Across the entire sample, we found a direct effect, where lower LC MRI signal intensity was associated with lower mediolateral temporal cortical thickness. Evaluation of potential effect modifications by FTP or PiB revealed that lower LC MRI signal intensity was related to lower cortical thickness, particularly in individuals with elevated (EC, IT) FTP or (neocortical) PiB. The latter result was present starting from subthreshold PiB values. In low PiB individuals, lower LC MRI signal intensity was related to lower EC cortical thickness in the context of elevated EC FTP. CONCLUSIONS: Our findings suggest that LC-related cortical neurodegeneration patterns in older individuals correspond to regions representing early Braak stages and may reflect a combination of LC projection density loss and emergence of cortical AD pathology. This provides a novel understanding that LC-related cortical neurodegeneration may signal downstream consequences of AD-related pathology, rather than being exclusively a result of aging.