Comparison of Medical Research Abstracts Written by Surgical Trainees and Senior Surgeons or Generated by Large Language Models.

Importance: Artificial intelligence (AI) has permeated academia, especially OpenAI Chat Generative Pretrained Transformer (ChatGPT), a large language model. However, little has been reported on its use in medical research. Objective: To assess a chatbot's capability to generate and grade medical research abstracts. Design, Setting, and Participants: In this cross-sectional study, ChatGPT versions 3.5 and 4.0 (referred to as chatbot 1 and chatbot 2) were coached to generate 10 abstracts by providing background literature, prompts, analyzed data for each topic, and 10 previously presented, unassociated abstracts to serve as models. The study was conducted between August 2023 and February 2024 (including data analysis). Exposure: Abstract versions utilizing the same topic and data were written by a surgical trainee or a senior physician or generated by chatbot 1 and chatbot 2 for comparison. The 10 training abstracts were written by 8 surgical residents or fellows, edited by the same senior surgeon, at a high-volume hospital in the Southeastern US with an emphasis on outcomes-based research. Abstract comparison was then based on 10 abstracts written by 5 surgical trainees within the first 6 months of their research year, edited by the same senior author. Main Outcomes and Measures: The primary outcome measurements were the abstract grades using 10- and 20-point scales and ranks (first to fourth). Abstract versions by chatbot 1, chatbot 2, junior residents, and the senior author were compared and judged by blinded surgeon-reviewers as well as both chatbot models. Five academic attending surgeons from Denmark, the UK, and the US, with extensive experience in surgical organizations, research, and abstract evaluation served as reviewers. Results: Surgeon-reviewers were unable to differentiate between abstract versions. Each reviewer ranked an AI-generated version first at least once. Abstracts demonstrated no difference in their median (IQR) 10-point scores (resident, 7.0 [6.0-8.0]; senior author, 7.0 [6.0-8.0]; chatbot 1, 7.0 [6.0-8.0]; chatbot 2, 7.0 [6.0-8.0]; P = .61), 20-point scores (resident, 14.0 [12.0-7.0]; senior author, 15.0 [13.0-17.0]; chatbot 1, 14.0 [12.0-16.0]; chatbot 2, 14.0 [13.0-16.0]; P = .50), or rank (resident, 3.0 [1.0-4.0]; senior author, 2.0 [1.0-4.0]; chatbot 1, 3.0 [2.0-4.0]; chatbot 2, 2.0 [1.0-3.0]; P = .14). The abstract grades given by chatbot 1 were comparable to the surgeon-reviewers' grades. However, chatbot 2 graded more favorably than the surgeon-reviewers and chatbot 1. Median (IQR) chatbot 2-reviewer grades were higher than surgeon-reviewer grades of all 4 abstract versions (resident, 14.0 [12.0-17.0] vs 16.9 [16.0-17.5]; P = .02; senior author, 15.0 [13.0-17.0] vs 17.0 [16.5-18.0]; P = .03; chatbot 1, 14.0 [12.0-16.0] vs 17.8 [17.5-18.5]; P = .002; chatbot 2, 14.0 [13.0-16.0] vs 16.8 [14.5-18.0]; P = .04). When comparing the grades of the 2 chatbots, chatbot 2 gave higher median (IQR) grades for abstracts than chatbot 1 (resident, 14.0 [13.0-15.0] vs 16.9 [16.0-17.5]; P = .003; senior author, 13.5 [13.0-15.5] vs 17.0 [16.5-18.0]; P = .004; chatbot 1, 14.5 [13.0-15.0] vs 17.8 [17.5-18.5]; P = .003; chatbot 2, 14.0 [13.0-15.0] vs 16.8 [14.5-18.0]; P = .01). Conclusions and Relevance: In this cross-sectional study, trained chatbots generated convincing medical abstracts, undifferentiable from resident or senior author drafts. Chatbot 1 graded abstracts similarly to surgeon-reviewers, while chatbot 2 was less stringent. These findings may assist surgeon-scientists in successfully implementing AI in medical research.

The origins of mammal growth patterns during the Jurassic mammalian radiation.

We use synchrotron x-ray tomography of annual growth increments in the dental cementum of mammaliaforms (stem and crown fossil mammals) from three faunas across the Jurassic to map the origin of patterns of mammalian growth patterns, which are intrinsically related to mammalian endothermy. Although all fossils studied exhibited slower growth rates, longer life spans, and delayed sexual maturity relative to comparably sized extant mammals, the earliest crown mammals developed significantly faster growth rates in early life that reduced at sexual maturity, compared to stem mammaliaforms. Estimation of basal metabolic rates (BMRs) suggests that some fossil crown mammals had BMRs approaching the lowest rates of extant mammals. We suggest that mammalian growth patterns first evolved during their mid-Jurassic adaptive radiation, although growth remained slower than in extant mammals.

TLNRD1 is a CCM complex component and regulates endothelial barrier integrity.

We previously identified talin rod domain-containing protein 1 (TLNRD1) as a potent actin-bundling protein in vitro. Here, we report that TLNRD1 is expressed in the vasculature in vivo. Its depletion leads to vascular abnormalities in vivo and modulation of endothelial cell monolayer integrity in vitro. We demonstrate that TLNRD1 is a component of the cerebral cavernous malformations (CCM) complex through its direct interaction with CCM2, which is mediated by a hydrophobic C-terminal helix in CCM2 that attaches to a hydrophobic groove on the four-helix domain of TLNRD1. Disruption of this binding interface leads to CCM2 and TLNRD1 accumulation in the nucleus and actin fibers. Our findings indicate that CCM2 controls TLNRD1 localization to the cytoplasm and inhibits its actin-bundling activity and that the CCM2-TLNRD1 interaction impacts endothelial actin stress fiber and focal adhesion formation. Based on these results, we propose a new pathway by which the CCM complex modulates the actin cytoskeleton and vascular integrity.

Decision making for health-related research outcomes that alter diagnosis: A model from paediatric brain tumours.

AIMS: The question of how to handle clinically actionable outcomes from retrospective research studies is poorly explored. In neuropathology, this problem is exacerbated by ongoing refinement in tumour classification. We sought to establish a disclosure threshold for potential revised diagnoses as determined by the neuro-oncology speciality. METHODS: As part of a previous research study, the diagnoses of 73 archival paediatric brain tumour samples were reclassified according to the WHO 2016 guidelines. To determine the disclosure threshold and clinical actionability of pathology-related findings, we conducted a result-evaluation approach within the ethical framework of BRAIN UK using a surrogate clinical multidisciplinary team (MDT) of neuro-oncology specialists. RESULTS: The MDT identified key determinants impacting decision-making, including anticipated changes to patient management, time elapsed since initial diagnosis, likelihood of the patient being alive and absence of additional samples since cohort inception. Ultimately, none of our research findings were considered clinically actionable, largely due to the cohort's historic archival and high-risk nature. From this experience, we developed a decision-making framework to determine if research findings indicating a change in diagnosis require reporting to the relevant clinical teams. CONCLUSIONS: Ethical issues relating to the use of archival tissue for research and the potential to identify actionable findings must be carefully considered. We have established a structured framework to assess the actionability of research data relating to patient diagnosis. While our specific findings are most applicable to the pathology of poor prognostic brain tumour groups in children, the model can be adapted to a range of disease settings, for example, other diseases where research is dependent on retrospective tissue cohorts, and research findings may have implications for patients and families, such as other tumour types, epilepsy-related pathology, genetic disorders and degenerative diseases.

Low-Intensity Pulsed Ultrasound Versus Sham in the Treatment of Operatively Managed Scaphoid Nonunions: The SNAPU Randomized Controlled Trial.

BACKGROUND: The primary goal after open reduction and internal fixation of an established scaphoid nonunion is to achieve union. Low-intensity pulsed ultrasound (LIPUS) has been reported to increase the rate of union and to decrease the time to union for multiple fractures and nonunions in clinical and animal models. The evidence for LIPUS in the treatment of scaphoid nonunion, however, is sparse. The aim of this study was to assess whether active LIPUS (relative to sham LIPUS) accelerates the time to union following surgery for scaphoid nonunion. METHODS: Adults with a scaphoid nonunion indicated for surgery were recruited for a multicenter, prospective, double-blinded randomized controlled trial. After surgery, patients self-administered activated or sham LIPUS units beginning at their first postoperative visit. The primary outcome was the time to union on serial computed tomography (CT) scans starting 6 to 8 weeks postoperatively. Secondary outcomes included patient-reported outcome measures, range of motion, and grip strength. RESULTS: A total of 142 subjects completed the study (69 in the active LIPUS group and 73 in the sham group). The average age was 27 years, and the cohort was 88% male. There was no difference in time to union (p = 0.854; hazard ratio, 0.965; 95% confidence interval, 0.663 to 1.405). Likewise, there were no differences between the active LIPUS and sham groups with respect to any of the secondary outcomes, except for wrist flexion at baseline (p = 0.008) and at final follow-up (p = 0.043). CONCLUSIONS: Treatment with LIPUS had no effect on reducing time to union in patients who underwent surgical fixation of established scaphoid nonunions. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Can reproductive health services be used to screen for sexual and gender-based violence in post-conflict Northern Uganda? - a pilot study.

Background: Sexual and gender-based violence (SGBV), including rape and child sexual abuse, remains a significant challenge in post-conflict northern Uganda. Many victims have never sought help. Consequently, the scale of the problem is not known, and SGBV victims' injuries, both psychological and physical, remain hidden and unresolved. Objectives: We aimed to explore whether health workers in rural Reproductive Health Services (RHS), following specific training, could provide a valuable resource for SGBV screening and subsequent referral to targeted services. Methods: Our project had three elements. First, RHS workers were trained to use a questionnaire to screen subjects for past SGBV Second, the screening questionnaire was used by RHS workers over a 3-month period, and the data collected were analysed to explore whether the screening approach was an effective one in this setting, and to record the scale and nature of the problem. Third, victims detected were offered referral as appropriate to hospital services or to a dedicated SGBV ActionAid shelter. Results: Of 1656 women screened, 778 (47%) had suffered SGBV: 123 rape, and 505 non-sexual violence. 1,254 (76%) had been directly or indirectly affected by conflict experiences; 1066 had lived in internally displaced persons camps. 145 (9%) requested referral to Gulu SGBV Shelter; 25 attended the shelter and received assistance, and 20 others received telephone counselling. Conclusion: Undetected SGBV remains a significant problem in post-conflict northern Uganda. RHS workers, following specific training, can effectively screen for and identify otherwise unrecognised survivors of SGBV. This matters because without ongoing detection, survivors have no opportunity for resolution, healing or help.

Health Care Resource Use for Modern First-Line Treatments in Metastatic Renal Cell Carcinoma.

Importance: Immuno-oncology agents have changed the treatment paradigm for metastatic renal cell carcinoma (mRCC). Such therapies improve survival but can impose considerable health care resource use (HCRU) and associated costs, necessitating their examination. Objective: To compare HCRU, costs, and clinical outcomes among patients receiving first-line pembrolizumab plus axitinib (P+A) or ipilimumab plus nivolumab (I+N). Design, Setting, and Participants: This retrospective cohort study used data from an administrative claims database on patients with mRCC receiving first-line P+A or I+N that was initiated between January 2018 and May 2020. Data were analyzed from February 2021 to July 2022. Exposure: First-line P+A or I+N. Main Outcome and Measures: HCRU and costs during the first 90 days, full first-line treatment, and full follow-up periods were assessed. Using Kaplan-Meier analysis, time on treatment, overall survival, time to first emergency department (ED) visit, and time to first inpatient stay were compared. Results: Among 507 patients, there were 126 patients receiving P+A (91 male [72.2%]; mean [SD] age, 67.93 [9.66] y) and 381 patients receiving I+N (271 male [71.1%]; mean [SD] age, 66.52 [9.94] years). The median time on treatment was longer for the P+A compared with I+N group (12.4 months [95% CI, 8.40 months to not estimable] vs 4.1 months [95% CI, 3.07 to 5.30 months]; P < .001). The median time to first ED visit was longer for the P+A than I+N group (7.2 months [95% CI 3.9 to 11.1 months ] vs 3.3 months [95% CI, 2.6 to 3.9 months]; P = .005), as was time to first inpatient stay (9.0 months [95% CI 6.5 months to not estimable] vs 5.6 months [95% CI, 3.9 to 7.9 months]; P = .02). During the first 90 days, a lower proportion of the P+A than N+I group had ED visits (43 patients [34.1%] vs 182 patients [47.8%] and inpatient stays (24 patients [19.1%) vs144 patients [37.8%]; P < .001). During full follow-up, mean total adjusted costs were similar for P+A and I+N groups, but adjusted 12-month estimated total costs were higher for P+A than I+N groups ($325 574 vs $ 263 803; P = .03). Conclusions and Relevance: In this study, treatment with P+A was associated with longer time on treatment, time to first ED visit, and inpatient stay, while 12-month estimated costs were higher for the P+A group. This is among the first clinical studies to evaluate economic burden associated with modern treatments for mRCC.

MAGE-A4-Responsive Plasma Cells Promote Non-Small Cell Lung Cancer.

Adaptive immunity is critical to eliminate malignant cells, while multiple tumor-intrinsic factors can alter this protective function. Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, is expressed in several solid tumors and correlates with poor survival in non-small cell lung cancer (NSCLC), but its role in altering antitumor immunity remains unclear. We found that expression of MAGE-A4 was highly associated with the loss of PTEN , a tumor suppressor, in human NSCLC. Here we show that constitutive expression of human MAGE-A4 combined with the loss of Pten in mouse airway epithelial cells results in metastatic adenocarcinoma enriched in CD138 + CXCR4 + plasma cells, predominantly expressing IgA. Consistently, human NSCLC expressing MAGE-A4 showed increased CD138 + IgA + plasma cell density surrounding tumors. The abrogation of MAGE-A4-responsive plasma cells (MARPs) decreased tumor burden, increased T cell infiltration and activation, and reduced CD163 + CD206 + macrophages in mouse lungs. These findings suggest MAGE-A4 promotes NSCLC tumorigenesis, in part, through the recruitment and retention of IgA + MARPs in the lungs.

Clinical Outcomes of Immune Checkpoint Inhibitors in Unique Cohorts Underrepresented in Clinical Trials.

Regulatory approval of immune checkpoint inhibitors (ICIs) was based on results of large, randomized clinical trials, resulting in limited outcomes data in patient cohorts typically underrepresented in such trials. The objective of this study was to evaluate the efficacy and safety of ICIs in these unique patient cohorts. This is a multicenter, retrospective analysis of real-world data at six academic and community clinics in the United States from 1 January 2011 to 1 April 2018. Patients were included if they had received at least one cycle of ICI treatment. Unique patient cohorts included age > 75 years, non-White race, positive smoking history, ECOG performance status (PS) ≥ 2, BMI ≥ 30 kg/m2, autoimmune diseases (AIDs), chronic viral infections (CVI), extensive prior lines of therapy (LOTs), or >three metastatic sites. Immune-related adverse events (irAEs), overall survival (OS), and time to treatment failure were evaluated in the entire cohort and in NSCLC patients treated with PD-(L)1 monotherapy. Outcomes and their association with unique patient cohorts were compared on univariate analysis and multivariate analysis to those without a particular characteristic in the entire NSCLC PD-(L)1 monotherapy cohorts. In total, 1453 patients were included: 56.5%-smokers, 30.4%-non-White, 22.8%-elderly, 20.8%-ECOG PS ≥ 2, 15.7%-history of AIDs, and 4.7%-history of CVI. The common ICIs were nivolumab (37.1%) and pembrolizumab (22.2%). Black patients, compared to White patients, experienced fewer irAEs (OR 0.54, p < 0.001). An ECOG PS of ≥2 (HR = 2.01, p < 0.001) and an increased number of previous LOTs were associated with poor OS (the median OS of 26.2 vs. 16.2 vs. 9.6 months for one vs. two vs. three prior LOTs, p < 0.001). The above results were confirmed in anti-PD-(L)1 monotherapy non-small cell lung cancer patients (n = 384). Overall, ICIs were safe and efficacious in these typically underrepresented patient cohorts. We noted ECOG PS ≥ 2 and an increased prior LOTs were associated with poor ICI efficacy, and Black patients, compared to White patients, experienced fewer irAEs.

Longitudinal Quality of Life and Glycemic Outcomes of Total Pancreatectomy With Islet Autotransplantation in Children With Chronic Pancreatitis Followed in a Pediatric Multidisciplinary Pancreas Clinic.

BACKGROUND: Total pancreatectomy with islet autotransplantation (TPIAT) is a potentially curative treatment for patients with chronic pancreatitis (CP) refractory to medical and endoscopic therapies. Patients often receive the initial follow-up medical care at the surgery-performing center, but then may follow up closer to where they live. We sought to describe the characteristics and outcomes of pediatric patients who underwent TPIAT at a national surgical referral center and were subsequently followed at our regional subspecialty center, the Children's Hospital Colorado. METHODS: We performed a retrospective analysis of baseline and outcomes data for the 10 pediatric patients who underwent TPIAT from 2007 to 2020 and received follow-up care at our institution. RESULTS: All patients had a diagnosis of CP, and nine of 10 patients had an identified underlying genetic risk factor. Insulin usage was common immediately following TPIAT, but at 1 year of follow-up, five of nine patients (55.6%) were insulin-independent and nine of nine had an HbA1c below 6.5%. For the four patients on insulin 1 year after TPIAT, total daily insulin dose ranged from 0.06 to 0.71 units/kg/day. All patients who underwent mixed meal tolerance testing had a robust peak C-peptide response at 1 year. There were significant improvements in nausea, school/work absences, narcotic dependence, and pancreas-related hospital admissions 1 year after TPIAT. CONCLUSIONS: Patients followed at our center had long-term improvements with low-insulin usage, detectable C-peptide, and improved pancreatitis-related outcomes after TPIAT. Pediatric patients who undergo TPIAT can be successfully co-managed in conjunction with the original surgery-performing center.

Multi-Subunit Repair With the Nasolabial Burow's Advancement Flap.

AIM: We will describe the use of nasolabial Burow's advancement flaps (perialar crescentic advancements) to repair multi subunit defects of the nasal sidewall including the adjacent cheek, dorsum, tip, and ala without the need of additional flaps. METHODS: This retrospective single centre study analyzed 6 month postoperative photographs using the Manchester Scar scale. The operative technique is described in detail. RESULTS: Of 355 cases, 336 were available for analysis. The median Manchester Scar scale was 7 for both sidewall defects and multi-subunit defects. There were low rates of infection or necrosis. CONCLUSIONS: With the correct technique, the nasolabial Burow's advancement alone is suitable to repair even large multi-subunit defects involving the nasal sidewall, cheek, dorsum, tip, and ala with high-level aesthetic and functional results.

Let-7 restrains an oncogenic epigenetic circuit in AT2 cells to prevent ectopic formation of fibrogenic transitional cell intermediates and pulmonary fibrosis.

Analysis of lung alveolar type 2 (AT2) progenitor stem cells has highlighted fundamental mechanisms that direct their differentiation into alveolar type 1 cells (AT1s) in lung repair and disease. However, microRNA (miRNA) mediated post-transcriptional mechanisms which govern this nexus remain understudied. We show here that the let-7 miRNA family serves a homeostatic role in governance of AT2 quiescence, specifically by preventing the uncontrolled accumulation of AT2 transitional cells and by promoting AT1 differentiation to safeguard the lung from spontaneous alveolar destruction and fibrosis. Using mice and organoid models with genetic ablation of let-7a1/let-7f1/let-7d cluster (let-7afd) in AT2 cells, we demonstrate prevents AT1 differentiation and results in aberrant accumulation of AT2 transitional cells in progressive pulmonary fibrosis. Integration of enhanced AGO2 UV-crosslinking and immunoprecipitation sequencing (AGO2-eCLIP) with RNA-sequencing from AT2 cells uncovered the induction of direct targets of let-7 in an oncogene feed-forward regulatory network including BACH1/EZH2 which drives an aberrant fibrotic cascade. Additional analyses by CUT&RUN-sequencing revealed loss of let-7afd hampers AT1 differentiation by eliciting aberrant histone EZH2 methylation which prevents the exit of AT2 transitional cells into terminal AT1s. This study identifies let-7 as a key gatekeeper of post-transcriptional and epigenetic chromatin signals to prevent AT2-driven pulmonary fibrosis.

Emergency umbilical hernia management: scoping review.

BACKGROUND: Umbilical hernias, while frequently asymptomatic, may become acutely symptomatic, strangulated or obstructed, and require emergency treatment. Robust evidence is required for high-quality care in this field. This scoping review aims to elucidate evidence gaps regarding emergency care of umbilical hernias. METHODS: EMBASE, MEDLINE and CENTRAL databases were searched using a predefined strategy until November 2023. Primary research studies reporting on any aspect of emergency umbilical hernia care and published in the English language were eligible for inclusion. Studies were excluded where emergency umbilical hernia care was not the primary focus and subsets of relevant data were unable to be extracted. Two independent reviewers screened abstracts and full texts, resolving disagreements by consensus or a third reviewer. Data were charted according to core concepts addressed by each study and a narrative synthesis was performed. RESULTS: Searches generated 534 abstracts, from which 32 full texts were assessed and 14 included in the final review. This encompassed 52 042 patients undergoing emergency umbilical hernia care. Most were retrospective cohort designs (11/14), split between single (6/14) and multicentre (8/14) with only one randomized trial. Most multicentre studies were from national databases (7/8). Themes arising included risk assessment (n = 4), timing of surgery (n = 4), investigations (n = 1), repair method (n = 8, four mesh versus suture; four laparoscopic versus open) and operative outcomes (n = 11). The most commonly reported outcomes were mortality (n = 9) and morbidity (n = 7) rates and length of hospital stay (n = 5). No studies included patient-reported outcomes specific to emergency umbilical hernia repair. CONCLUSION: This scoping review demonstrates the paucity of high-quality data for this condition. There is a need for randomized trials addressing all aspects of emergency umbilical hernia repair, with patient-reported outcomes.

Relationship between Pulmonary Gas Exchange Function and Brain Uptake Dynamics Investigated with Hyperpolarized 129Xe MR Imaging and Spectroscopy in a Murine Model of Chronic Obstructive Pulmonary Disease.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a complex multisystem disease associated with comorbidities outside the lungs. The aim of this study was to measure changes in metrics of pulmonary gas exchange function and brain tissue metabolism in a mouse model of COPD using hyperpolarized 129Xe (HP 129Xe) MRI/MR spectroscopy (MRS) and investigate the relationship between the metrics of lung and brain. METHODS: COPD phenotypes were induced in 15 mice by 6-week administration of cigarette smoke extract (CSE) and lipopolysaccharide (LPS). A separate negative control (NC) group was formed of 6 mice administered with saline for 6 weeks. After these 6-week administrations, the pulmonary gas exchange function parameter fD (%) and the rate constant, α (s-1), which are composed of the cerebral blood flow Fi and the longitudinal relaxation rate 1/T1i in brain tissue, were evaluated by HP 129Xe MRI/MRS. RESULTS: The fD of CSE-LPS mice was significantly lower than that of NC mice, which was in parallel with an increase in bronchial wall thickness. The α in the CSE-LPS mice decreased with the decrease of fD in contrast to the trend in the NC mice. To further elucidate the opposed trend, the contribution of T1i was separately determined by measuring Fi. The T1i in the CSE-LPS mice was found to correlate negatively with fD as opposed to the positive trend in the NC mice. The opposite trend in T1i between CSE-LPS and NC mice suggests hypoxia in the brain, which is induced by the impaired oxygen uptake as indicated by the reduced fD. CONCLUSION: This study demonstrates the feasibility of using HP 129Xe MRI/MRS to study pathological mechanisms of brain dysfunction in comorbidities with COPD.

Age, sex, and lung volume dependence of dissolved xenon-129 MRI gas exchange metrics.

PURPOSE: To characterize the dependence of Xe-MRI gas transfer metrics upon age, sex, and lung volume in a group of healthy volunteers. METHODS: Sixty-five subjects with no history of chronic lung disease were assessed with 129Xe-MRI using a four-echo 3D radial spectroscopic imaging sequence and a dose of xenon titrated according to subject height that was inhaled from a lung volume of functional residual capacity (FRC). Imaging was repeated in 34 subjects at total lung capacity (TLC). Regional maps of the fractions of dissolved xenon in red blood cells (RBC), membrane (M), and airspace (Gas) were acquired at an isotropic resolution of 2 cm, from which global averages of the ratios RBC:M, RBC:Gas, and M:Gas were computed. RESULTS: Data from 26 males and 36 females with a median age of 43 y (range: 20-69 y) were of sufficient quality to analyze. Age (p = 0.0006) and sex (p < 0.0001) were significant predictors for RBC:M, and a linear regression showed higher values and steeper decline in males: RBC:M(Males) = -0.00362 × Age + 0.60 (p = 0.01, R2 = 0.25); RBC:M(Females) = -0.00170 × Age + 0.44 (p = 0.02, R2 = 0.15). Similarly, age and sex were significant predictors for RBC:Gas but not for M:Gas. RBC:M, M:Gas and RBC:Gas were significantly lower at TLC than at FRC (plus inhaled volume), with an average 9%, 30% and 35% decrease, respectively. CONCLUSION: Expected age and sex dependence of pulmonary function concurs with 129Xe RBC:M imaging results, demonstrating that these variables must be considered when reporting Xe-MRI metrics. Xenon doses and breathing maneuvers should be controlled due to the strong dependence of Xe-MRI metrics upon lung volume.

Cabozantinib Plus Nivolumab in Patients with Non-Clear Cell Renal Cell Carcinoma: Updated Results from a Phase 2 Trial.

Treatment options are limited for patients with non-clear cell renal cell carcinoma (nccRCC). Patients with nccRCC experienced a favorable objective response rate (ORR) in a phase 2 trial of cabozantinib plus nivolumab. We now report updated efficacy and safety results at median follow-up of 34 mo for patients with papillary, unclassified, or translocation-associated RCC. Cabozantinib and nivolumab were administered at standard doses to patients with metastatic nccRCC that had progressed on zero or one line of systemic therapy. The primary endpoint was the ORR according to Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Forty patients were treated. At median follow-up of 34 mo for survivors, the ORR was 48% (95% confidence interval [CI] 31.5-63.9%). Median PFS was 13 mo (95% CI 7-16); the 12-mo and 24-mo PFS rates were 51% (95% CI 34-65%) and 23% (95% CI 11-37%), respectively. Median OS was 28 mo (95% CI 23-43); the 18-mo and 36-mo OS rates were 70% (95% CI 53-82%) and 44% (95% CI 28-60%), respectively. No new safety signals were seen with cabozantinib and nivolumab. This extended follow-up analysis demonstrates promising efficacy, and highlights the potential for sustained responses with cabozantinib plus nivolumab in patients with metastatic nccRCC.

Comparison of No Tap (two-step) and tapping robotic assisted cortical bone trajectory screw insertion.

Workflow for cortical bone trajectory (CBT) screws includes tapping line-to-line or under tapping by 1 mm. We describe a non-tapping, two-step workflow for CBT screw placement, and compare the safety profile and time savings to the Tap (three-step) workflow. Patients undergoing robotic assisted 1-3 level posterior fusion with CBT screws for degenerative conditions were identified and separated into either a No-Tap or Tap workflow. Number of total screws, screw-related complications, estimated blood loss, operative time, robotic time, and return to the operating room were collected and analyzed. There were 91 cases (458 screws) in the No-Tap and 88 cases (466 screws) in the Tap groups, with no difference in demographics, revision status, ASA grade, approach, number of levels fused or diagnosis between cohorts. Total robotic time was lower in the No-Tap (26.7 min) versus the Tap group (30.3 min, p = 0.053). There was no difference in the number of malpositioned screws identified intraoperatively (10 vs 6, p = 0.427), screws converted to freehand (3 vs 3, p = 0.699), or screws abandoned (3 vs 2, p = 1.000). No pedicle/pars fracture or fixation failure was seen in the No-Tap cohort and one in the Tap cohort (p = 1.00). No patients in either cohort were returned to OR for malpositioned screws. This study showed that the No-Tap screw insertion workflow for robot-assisted CBT reduces robotic time without increasing complications.

Renal Pathology of Ciliopathies.

Renal ciliopathies are a group of genetic disorders that affect the function of the primary cilium in the kidney, as well as other organs. Since primary cilia are important for regulation of cell signaling pathways, ciliary dysfunction results in a range of clinical manifestations, including renal failure, cyst formation, and hypertension. We summarize the current understanding of the pathophysiological and pathological features of renal ciliopathies in childhood, including autosomal dominant and recessive polycystic kidney disease, nephronophthisis, and Bardet-Biedl syndrome, as well as skeletal dysplasia associated renal ciliopathies. The genetic basis of these disorders is now well-established in many cases, with mutations in a large number of cilia-related genes such as PKD1, PKD2, BBS, MKS, and NPHP being responsible for the majority of cases. Renal ciliopathies are broadly characterized by development of interstitial fibrosis and formation of multiple renal cysts which gradually enlarge and replace normal renal tissue, with each condition demonstrating subtle differences in the degree, location, and age-related development of cysts and fibrosis. Presentation varies from prenatal diagnosis of congenital multisystem syndromes to an asymptomatic childhood with development of complications in later adulthood and therefore clinicopathological correlation is important, including increasing use of targeted genetic testing or whole genome sequencing, allowing greater understanding of genetic pathophysiological mechanisms.

Identification of connective tissue disease autoantibodies and a novel autoantibody anti-annexin A11 in patients with "idiopathic" interstitial lung disease.

BACKGROUND: Autoantibodies are a hallmark feature of Connective Tissue Diseases (CTD). Their presence in patients with idiopathic interstitial lung disease (ILD) may suggest covert CTD. We aimed to determine the prevalence of CTD autoantibodies in patients diagnosed with idiopathic ILD. METHODS: 499 patient sera were analysed: 251 idiopathic pulmonary fibrosis (IPF), 206 idiopathic non-specific interstitial pneumonia (iNSIP) and 42 cryptogenic organising pneumonia (COP). Autoantibody status was determined by immunoprecipitation. RESULTS: 2.4% of IPF sera had a CTD-autoantibody compared to 10.2% of iNSIP and 7.3% of COP. 45% of autoantibodies were anti-synthetases. A novel autoantibody targeting an unknown 56 kDa protein was found in seven IPF patients (2.8%) and two NSIP (1%) patients. This was characterised as anti-annexin A11. CONCLUSION: Specific guidance on autoantibody testing and interpretation in patients with ILD could improve diagnostic accuracy. Further work is required to determine the clinical significance of anti-annexin A11.

Artificial Intelligence-Assisted Cancer Status Detection in Radiology Reports.

Cancer research is dependent on accurate and relevant information of patient's medical journey. Data in radiology reports are of extreme value but lack consistent structure for direct use in analytics. At Memorial Sloan Kettering Cancer Center (MSKCC), the radiology reports are curated using gold-standard approach of using human annotators. However, the manual process of curating large volume of retrospective data slows the pace of cancer research. Manual curation process is sensitive to volume of reports, number of data elements and nature of reports and demand appropriate skillset. In this work, we explore state of the art methods in artificial intelligence (AI) and implement end-to-end pipeline for fast and accurate annotation of radiology reports. Language models (LM) are trained using curated data by approaching curation as multiclass or multilabel classification problem. The classification tasks are to predict multiple imaging scan sites, presence of cancer and cancer status from the reports. The trained natural language processing (NLP) model classifiers achieve high weighted F1 score and accuracy. We propose and demonstrate the use of these models to assist in the manual curation process which results in higher accuracy and F1 score with lesser time and cost, thus improving efforts of cancer research. SIGNIFICANCE: Extraction of structured data in radiology for cancer research with manual process is laborious. Using AI for extraction of data elements is achieved using NLP models' assistance is faster and more accurate.