Non-Small Cell Lung Cancer, Version 4.2024.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance for relapse, and subsequent treatment. The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. This selection from the NCCN Guidelines for NSCLC focuses on treatment recommendations for advanced or metastatic NSCLC with actionable molecular biomarkers.

Umbravirus-like RNA viruses are capable of independent systemic plant infection in the absence of encoded movement proteins.

The signature feature of all plant viruses is the encoding of movement proteins (MPs) that supports the movement of the viral genome into adjacent cells and through the vascular system. The recent discovery of umbravirus-like viruses (ULVs), some of which only encode replication-associated proteins, suggested that they, as with umbraviruses that lack encoded capsid proteins (CPs) and silencing suppressors, would require association with a helper virus to complete an infection cycle. We examined the infection properties of 2 ULVs: citrus yellow vein associated virus 1 (CY1), which only encodes replication proteins, and closely related CY2 from hemp, which encodes an additional protein (ORF5CY2) that was assumed to be an MP. We report that both CY1 and CY2 can independently infect the model plant Nicotiana benthamiana in a phloem-limited fashion when delivered by agroinfiltration. Unlike encoded MPs, ORF5CY2 was dispensable for infection of CY2, but was associated with faster symptom development. Examination of ORF5CY2 revealed features more similar to luteoviruses/poleroviruses/sobemovirus CPs than to 30K class MPs, which all share a similar single jelly-roll domain. In addition, only CY2-infected plants contained virus-like particles (VLPs) associated with CY2 RNA and ORF5CY2. CY1 RNA and a defective (D)-RNA that arises during infection interacted with host protein phloem protein 2 (PP2) in vitro and in vivo, and formed a high molecular weight complex with sap proteins in vitro that was partially resistant to RNase treatment. When CY1 was used as a virus-induced gene silencing (VIGS) vector to target PP2 transcripts, CY1 accumulation was reduced in systemic leaves, supporting the usage of PP2 for systemic movement. ULVs are therefore the first plant viruses encoding replication and CPs but no MPs, and whose systemic movement relies on a host MP. This explains the lack of discernable helper viruses in many ULV-infected plants and evokes comparisons with the initial viruses transferred into plants that must have similarly required host proteins for movement.

Using machine learning to identify key subject categories predicting the pre-clerkship and clerkship performance: 8-year cohort study.

BACKGROUND: Medical students need to build a solid foundation of knowledge to become physicians. Clerkship is often considered the first transition point, and clerkship performance is essential for their development. We hope to identify subjects that could predict the clerkship performance, thus helping medical students learn more efficiently to achieve high clerkship performance. METHODS: This cohort study collected background and academic data from medical students who graduated between 2011 and 2019. Prediction models were developed by machine learning techniques to identify the affecting features in predicting the pre-clerkship performance and clerkship performance. Following serial processes of data collection, data pre-processing before machine learning, and techniques and performance of machine learning, different machine learning models were trained and validated using the 10-fold cross-validation method. RESULTS: Thirteen subjects from the pre-med stage and ten subjects from the basic medical science stage with an area under the ROC curve (AUC) greater than 0.7 for either pre-clerkship performance or clerkship performance were found. In each subject category, medical humanities and sociology in social science, chemistry and physician scientist-related training in basic science, and pharmacology, immunology-microbiology, and histology in basic medical science have predictive abilities for clerkship performance above the top tertile. Using a machine learning technique based on random forest, the prediction model predicted clerkship performance with 95% accuracy and 88% AUC. CONCLUSION: Clerkship performance was predicted by selected subjects or combination of different subject categories in the pre-med and basic medical science stages. The demonstrated predictive ability of subjects or categories in the medical program may facilitate students' understanding of how these subjects or categories of the medical program relate to their performance in the clerkship to enhance their preparedness for the clerkship.

Superficial parasternal intercostal plane blocks in cardiac surgery: a systematic review and meta-analysis.

PURPOSE: Traditional multimodal analgesic strategies have several contraindications in cardiac surgery patients, forcing clinicians to use alternative options. Superficial parasternal intercostal plane blocks, anesthetizing the anterior cutaneous branches of the thoracic intercostal nerves, are being explored as a straightforward method to treat pain after sternotomy. We sought to evaluate the literature on the effects of superficial parasternal blocks on pain control after cardiac surgery. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched MEDLINE, Embase, CENTRAL, and Web of Science databases for RCTs evaluating superficial parasternal intercostal plane blocks in adult patients undergoing cardiac surgery via midline sternotomy published from inception to 11 March 2022. The prespecified primary outcome was opioid consumption at 12 hr. The risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool, and the quality of evidence was evaluated using the grading of recommendations, assessments, development, and evaluations. Outcomes were analyzed with a random-effects model. All subgroups were prespecified. RESULTS: We reviewed 1,275 citations. Eleven RCTs, comprising 756 patients, fulfilled the inclusion criteria. Only one study reported the prespecified primary outcome, precluding the possibility of meta-analysis. This study reported a reduction in opioid consumption (-11.2 mg iv morphine equivalents; 95% confidence interval [CI], -8.2 to -14.1) There was a reduction in opioid consumption at 24 hr (-7.2 mg iv morphine equivalents; 95% CI, -5.6 to -8.7; five trials; 436 participants; moderate certainty evidence). All five studies measuring complications reported that none were detected, which included a sample of 196 blocks. CONCLUSION: The literature suggests a potential benefit of using superficial parasternal blocks to improve acute postoperative pain control after cardiac surgery via midline sternotomy. Future studies specifying dosing regimens and adjuncts are required. STUDY REGISTRATION: PROSPERO (CRD42022306914); first submitted 22 March 2022.

RéSUMé: OBJECTIF: Il existe plusieurs contre-indications aux stratégies analgésiques multimodales traditionnelles chez la patientèle de chirurgie cardiaque, ce qui oblige les clinicien·nes à se tourner vers d'autres options. Les blocs des plans intercostaux parasternaux superficiels, anesthésiant les branches cutanées antérieures des nerfs intercostaux thoraciques, sont l'une des méthodes simples actuellement explorées pour traiter la douleur après une sternotomie. Nous avons cherché à évaluer la littérature sur les effets des blocs parasternaux superficiels sur le contrôle de la douleur après une chirurgie cardiaque. MéTHODE: Nous avons réalisé une revue systématique et une méta-analyse des études randomisées contrôlées (ERC). Nous avons fait des recherches dans les bases de données MEDLINE, Embase, CENTRAL et Web of Science pour en tirer les ERC évaluant les blocs des plans intercostaux parasternaux superficiels chez les patient·es adultes bénéficiant d'une chirurgie cardiaque par sternotomie médiane publiées depuis leur création jusqu'au 11 mars 2022. Le critère d'évaluation principal préspécifié était la consommation d'opioïdes à 12 heures. Le risque de biais a été évalué à l'aide de l'outil Cochrane Collaboration Risk of Bias, et la qualité des données probantes à l'aide de l'outil GRADE. Les résultats ont été analysés à l'aide d'un modèle à effets aléatoires. Tous les sous-groupes étaient préspécifiés. RéSULTATS: Nous avons examiné 1275 citations. Onze ERC, comprenant 756 patient·es, remplissaient les critères d'inclusion. Une seule étude a rapporté le critère d'évaluation principal préspécifié, ce qui a exclu la possibilité d'une méta-analyse. Cette étude a rapporté une réduction de la consommation d'opioïdes (−11,2 mg équivalents de morphine iv; intervalle de confiance [IC] à 95 %, −8,2 à −14,1). Il y a eu une réduction de la consommation d'opioïdes à 24 heures (−7,2 mg équivalents de morphine iv; IC 95 %, −5,6 à −8,7; cinq études; 436 participant·es; données probantes de certitude modérée). Les cinq études mesurant les complications ont rapporté qu'aucune complication n'avait été détectée, en incluant un échantillon de 196 blocs. CONCLUSION: La littérature suggère un avantage potentiel de l'utilisation de blocs parasternaux superficiels pour améliorer le contrôle de la douleur postopératoire aiguë après une chirurgie cardiaque par sternotomie médiane. Des études futures précisant les schémas posologiques et les adjuvants sont nécessaires. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42022306914); soumis pour la première fois le 22 mars 2022.

Mesothelioma: Pleural, Version 1.2024.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.

Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses.

Gastroesophageal cancer dynamics and drivers of clinical responses with immune checkpoint inhibitors (ICI) remain poorly understood. Potential synergistic activity of dual programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) inhibition may help improve immunotherapy responses for these tumors. We report a phase Ib trial that evaluated neoadjuvant nivolumab (Arm A, n = 16) or nivolumab-relatlimab (Arm B, n = 16) in combination with chemoradiotherapy in 32 patients with resectable stage II/stage III gastroesophageal cancer together with an in-depth evaluation of pathological, molecular and functional immune responses. Primary endpoint was safety; the secondary endpoint was feasibility; exploratory endpoints included pathological complete (pCR) and major pathological response (MPR), recurrence-free survival (RFS) and overall survival (OS). The study met its primary safety endpoint in Arm A, although Arm B required modification to mitigate toxicity. pCR and MPR rates were 40% and 53.5% for Arm A and 21.4% and 57.1% for Arm B. Most common adverse events were fatigue, nausea, thrombocytopenia and dermatitis. Overall, 2-year RFS and OS rates were 72.5% and 82.6%, respectively. Higher baseline programmed cell death ligand 1 (PD-L1) and LAG-3 expression were associated with deeper pathological responses. Exploratory analyses of circulating tumor DNA (ctDNA) showed that patients with undetectable ctDNA post-ICI induction, preoperatively and postoperatively had a significantly longer RFS and OS; ctDNA clearance was reflective of neoantigen-specific T cell responses. Our findings provide insights into the safety profile of combined PD-1 and LAG-3 blockade in gastroesophageal cancer and highlight the potential of ctDNA analysis to dynamically assess systemic tumor burden during neoadjuvant ICI that may open a therapeutic window for future intervention. ClinicalTrials.gov registration: NCT03044613 .

Computational pathology: A survey review and the way forward.

Computational Pathology (CPath) is an interdisciplinary science that augments developments of computational approaches to analyze and model medical histopathology images. The main objective for CPath is to develop infrastructure and workflows of digital diagnostics as an assistive CAD system for clinical pathology, facilitating transformational changes in the diagnosis and treatment of cancer that are mainly address by CPath tools. With evergrowing developments in deep learning and computer vision algorithms, and the ease of the data flow from digital pathology, currently CPath is witnessing a paradigm shift. Despite the sheer volume of engineering and scientific works being introduced for cancer image analysis, there is still a considerable gap of adopting and integrating these algorithms in clinical practice. This raises a significant question regarding the direction and trends that are undertaken in CPath. In this article we provide a comprehensive review of more than 800 papers to address the challenges faced in problem design all-the-way to the application and implementation viewpoints. We have catalogued each paper into a model-card by examining the key works and challenges faced to layout the current landscape in CPath. We hope this helps the community to locate relevant works and facilitate understanding of the field's future directions. In a nutshell, we oversee the CPath developments in cycle of stages which are required to be cohesively linked together to address the challenges associated with such multidisciplinary science. We overview this cycle from different perspectives of data-centric, model-centric, and application-centric problems. We finally sketch remaining challenges and provide directions for future technical developments and clinical integration of CPath. For updated information on this survey review paper and accessing to the original model cards repository, please refer to GitHub. Updated version of this draft can also be found from arXiv.

Normal postvoid residual urine in healthy adults.

OBJECTIVE: To establish a normal reference value of postvoid residual (PVR) urine volume in "healthy" adults. METHODS: Adults were recruited to undergo uroflowmetry and PVR. Those with neurological disorders, malignancy, diabetes, known lower urinary tract dysfunction, and urinary tract infection within the previous 3 months, were excluded from the study. Constipation was defined as Rome IV ≥ 2. RESULTS: Of the 883 adults enrolled in this study, 194 (22.3%) did not complete the questionnaires or perform the uroflowmetry, 103 (11.7%) met ≥1 exclusion criteria and thus were excluded. In addition, 30 and 38 uroflowmetry were excluded due to artifacts and low bladder volume (BV) (<100 mL), respectively. Finally, 515 uroflowmetry and PVR data from adults aged 36-89 (mean: 59.0 ± 9.5) were examined. There was a significant nonlinear relationship between BV and PVR (p < 0.05), with PVR significantly increased when BV was around 528 mL. Women had lower PVR than men (p < 0.05). PVR also increased as the International Prostatic Symptom Score (IPSS) increased. PVR was unaffected by age and functional constipation. A multivariate analysis revealed that BV (p < 0.05) and IPSS (p < 0.05) had significant influence on PVR, but age, gender, and Rome IV score did not. The 90th and 95th percentiles of PVR for men were 73.2 mL (25% of BV) and 102.6 mL (30% of BV), respectively, while for women they were 60.5 mL (21% of BV) and 93.8 mL (27% of BV), respectively. CONCLUSION: Women had lower PVR than men. The 90th percentile or 95th percentile of normal adults' PVR may serve as the upper limit of normal PVR, and readings above this level may necessitate additional evaluation and treatment. Further studies are required to substantiate these recommendations.

The Society of Thoracic Surgeons Looking to the Future Scholarship Program: A 15-Year Review.

BACKGROUND: It has been postulated that a possible barrier to pursuing cardiothoracic surgery is a lack of exposure and mentorship during training. In 2006, The Society of Thoracic Surgeons began the Looking to the Future Scholarship to expand interest in the field. Undecided trainees with limited exposure were prioritized in the selection process. This report summarizes the career outcomes of general surgery resident and medical student recipients. METHODS: Scholarship recipients and nonrecipients (control) were queried in a Google search. The percentage of those who were cardiothoracic surgeons or in cardiothoracic training (%CTS) was calculated, as well as the percentage of female surgeons in cardiothoracic surgery. RESULTS: From 2006 to 2021, there were 669 awardees. The %CTS was 63.7% for resident recipients and 31.4% for students, respectively. There was no significant difference in %CTS between resident and student recipients compared to nonrecipients. Notably, the percentage of female cardiothoracic surgeons was significantly greater for both resident and student recipients. CONCLUSIONS: The majority of resident recipients are now in cardiothoracic surgery, comparable to nonrecipients. While there was no significant difference between the percentage of recipients and non-recipients in cardiothoracic surgery, these groups differed substantially as nonrecipients had greater exposure and commitment to the field at the time of application.

Albuminuria Is Affected by Urinary Tract Infection: A Comparison between Biochemical Quantitative Method and Automatic Urine Chemistry Analyzer UC-3500.

The automated urine reagent strip test is a cost-effective tool for detecting albuminuria in patients. However, prior research has not investigated how urinary tract infections (UTIs) affect the test's accuracy. Therefore, this study aims to assess the impact of UTIs on albuminuria diagnosis using both the biochemical quantitative method and the test strip method of the Fully Automatic Urine Chemistry Analyzer, UC-3500 (Sysmex, Kobe, Japan). From March to December 2019, we prospectively collected midstream urine from adult female UTI patients before and after one week of cephalexin treatment. The urine samples were subjected to culture, routine urinalysis, and albuminuria diagnosis using the biochemical quantitative method and UC-3500. Albuminuria was defined as a urine albumin to creatinine ratio (UACR) ≥ 30 mg/g in the biochemical quantitative method. The results were compared between the two methods. Among fifty-four female patients (average age: 50.5 ± 4.4 years) with UTIs, 24 (44.44%) had transient albuminuria. The quantitative UACR significantly decreased after one week of antibiotic treatment (median: 53 mg/g to 9 mg/g; median difference: -0.54, p < 0.0001). UC-3500 exhibited a higher false positive rate for diagnosing albuminuria during UTIs (42%) compared to after treatment (19%). Its agreement with the biochemical quantitative method was moderate during UTI (κ = 0.49, 95% confidence interval [CI]: 0.24-0.73) and good after treatment (κ = 0.65, 95% CI: 0.45-0.86). UC-3500's accuracy in diagnosing albuminuria is influenced by UTIs, leading to either transient albuminuria or a false positive reaction of the test strip. UTI should be excluded or treated before its application in albuminuria screening.

Effectiveness of various treatment modalities in children with vesicoureteral reflux grades II-IV: a systematic review and network meta-analysis.

BACKGROUND: Vesicoureteral reflux (VUR) is one of the most common risk factors of urinary tract infection (UTI) among children. Various treatment modalities including antibiotic prophylaxis, surgical or endoscopic corrections and conservative treatment were used depending on the severity of VUR. The aim of this study is to compare the effectiveness of these treatment modalities in children with VUR grades II-IV by conducting a systematic review and network meta-analysis. METHODS: A systematic search from different databases was performed from their earliest records to December 2022 without any language restriction. Only randomised controlled trials were included in this study. Effectiveness of treatment modalities was mainly compared by UTI. Other outcomes for renal scarring and resolution by renal units were also measured between treatments. RESULTS: A total of 11 studies with 1447 children were included in this study. While comparing with antibiotic prophylaxis in network meta-analysis for UTI recurrence, surgical treatment probably lowers the rate of UTI recurrence (Log OR -0.26, 95% CI -0.54 to 0.02, high quality). However, endoscopic treatment (Log OR 0.2, 95% CI -1.41 to 1.81, high quality) and conservative treatment (Log OR 0.15, 95% CI -0.45 to 0.75, high quality) revealed probably inferior to antibiotic treatment. CONCLUSION: Both pairwise and network meta-analytic results probably showed no difference between the treatments in terms of their impact on UTI recurrence, progression of previous renal scars, or formation of new renal scars in children with VUR grades II-IV. These findings may offer a better understanding of each treatment and evidence-based suggestions for the choice of treatment, which should be individualised and based on the patient's risk factors.

Differences Between Attending and Trainee Surgeon Performance Using Objective Performance Indicators During Robot-Assisted Lobectomy.

OBJECTIVE: Existing approaches for assessing surgical performance are subjective and prone to bias. In contrast, utilizing digital kinematic and system data from the surgical robot allows the calculation of objective performance indicators (OPIs) that may differentiate technical skill and competency. This study compared OPIs of trainees and attending surgeons to assess differences during robotic lobectomy (RL). METHODS: There were 50 cardiothoracic surgery residents and 7 attending surgeons who performed RL on a left upper lobectomy of an ex vivo perfused model. A novel recorder simultaneously captured video and data from the system and instruments. The lobectomy was annotated into discrete tasks, and OPIs were analyzed for both hands during 6 tasks: exposure of the superior pulmonary vein, upper division of the pulmonary artery and bronchus, and the stapling of these structures. RESULTS: There were significant differences between attendings and trainees in all tasks. Among 20 OPIs during exposure tasks, significant differences were observed for the left hand in 31 of 60 (52%) of OPIs and for the right hand in 42 of 60 (70%). During stapling tasks, significant differences were observed for the stapling hand in 28 of 60 (47%) of OPIs and for the nonstapling hand in 14 of 60 (25%). CONCLUSIONS: Use of a novel data and video recorder to generate OPIs for both hands revealed significant differences in the operative gestures performed by trainees compared to attendings during RL. This method of assessing performance has potential for establishing objective competency benchmarks and use for tracking progress.

Lung tumor-infiltrating Treg have divergent transcriptional profiles and function linked to checkpoint blockade response.

Regulatory T cells (Treg) are conventionally viewed as suppressors of endogenous and therapy-induced antitumor immunity; however, their role in modulating responses to immune checkpoint blockade (ICB) is unclear. In this study, we integrated single-cell RNA-seq/T cell receptor sequencing (TCRseq) of >73,000 tumor-infiltrating Treg (TIL-Treg) from anti-PD-1-treated and treatment-naive non-small cell lung cancers (NSCLC) with single-cell analysis of tumor-associated antigen (TAA)-specific Treg derived from a murine tumor model. We identified 10 subsets of human TIL-Treg, most of which have high concordance with murine TIL-Treg subsets. Only one subset selectively expresses high levels of TNFRSF4 (OX40) and TNFRSF18 (GITR), whose engangement by cognate ligand mediated proliferative programs and NF-κB activation, as well as multiple genes involved in Treg suppression, including LAG3. Functionally, the OX40hiGITRhi subset is the most highly suppressive ex vivo, and its higher representation among total TIL-Treg correlated with resistance to PD-1 blockade. Unexpectedly, in the murine tumor model, we found that virtually all TIL-Treg-expressing T cell receptors that are specific for TAA fully develop a distinct TH1-like signature over a 2-week period after entry into the tumor, down-regulating FoxP3 and up-regulating expression of TBX21 (Tbet), IFNG, and certain proinflammatory granzymes. Transfer learning of a gene score from the murine TAA-specific TH1-like Treg subset to the human single-cell dataset revealed a highly analogous subcluster that was enriched in anti-PD-1-responding tumors. These findings demonstrate that TIL-Treg partition into multiple distinct transcriptionally defined subsets with potentially opposing effects on ICB-induced antitumor immunity and suggest that TAA-specific TIL-Treg may positively contribute to antitumor responses.

Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term "malignant" is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.

The differences in the adrenergic receptors of proximal urethra between sexes.

Objectives: The bladder and urethra work as a physiologically functional unit to facilitate continence in the storage and voiding phase. Sex differences have been found in the urethral contraction in response to α-adrenergic receptor activation. This study aimed to investigate the role of adrenergic receptors in the proximal urethra of male and female mice. Materials and Methods: Urinary bladder and proximal urethral smooth muscle (USM) samples from male and female C57BL/6 mice were isolated and mounted in an organ bath. Results: Acetylcholine-induced contraction of the urinary bladder was compared in male and female mice. Phenylephrine and norepinephrine (NE) induced little contraction at a lower concentration, but a relaxing phase of female proximal USM was observed at a higher concentration. This contraction profile was inhibited by NG-nitro-L-arginine, lidocaine, and capsaicin. In addition, the NE-induced contraction was greater in the incubation of propranolol than that of L-NNA or lidocaine. These results suggested that the ß-adrenoceptor may be the dominant receptor of female proximal USM, and the activity of calcitonin gene-related peptide sensory nerves and nitrergic nerves may pose an anti-contraction effect on the proximal urethra in female mice. Conclusion: ß-adrenoceptor may be the dominant receptor of female proximal USM. The use of ß-adrenergic receptor blocker agents might have the potential for the treatment of female voiding dysfunction.