Diagnostic performance of [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the spine, and whole-body diagnostic CT and MRI in the detection of spinal bone metastases associated with pheochromocytoma and paraganglioma.

OBJECTIVE: To compare the diagnostic performance of [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the spine, and whole-body CT and MRI for the detection of pheochromocytoma/paraganglioma (PPGL)-related spinal bone metastases. MATERIALS AND METHODS: Between 2014 and 2020, PPGL participants with spinal bone metastases prospectively underwent [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the cervical-thoracolumbar spine (MRIspine), contrast-enhanced MRI of the neck and thoraco-abdominopelvic regions (MRIWB), and contrast-enhanced CT of the neck and thoraco-abdominopelvic regions (CTWB). Per-patient and per-lesion detection rates were calculated. Counting of spinal bone metastases was limited to a maximum of one lesion per vertebrae. A composite of all functional and anatomic imaging served as an imaging comparator. The McNemar test compared detection rates between the scans. Two-sided p values were reported. RESULTS: Forty-three consecutive participants (mean age, 41.7 ± 15.7 years; females, 22) with MRIspine were included who also underwent [68Ga]DOTATATE PET/CT (n = 43), [18F]FDG PET/CT (n = 43), MRIWB (n = 24), and CTWB (n = 33). Forty-one of 43 participants were positive for spinal bone metastases, with 382 lesions on the imaging comparator. [68Ga]DOTATATE PET/CT demonstrated a per-lesion detection rate of 377/382 (98.7%) which was superior compared to [18F]FDG (72.0%, 275/382, p < 0.001), MRIspine (80.6%, 308/382, p < 0.001), MRIWB (55.3%, 136/246, p < 0.001), and CTWB (44.8%, 132/295, p < 0.001). The per-patient detection rate of [68Ga]DOTATATE PET/CT was 41/41 (100%) which was higher compared to [18F]FDG PET/CT (90.2%, 37/41, p = 0.13), MRIspine (97.6%, 40/41, p = 1.00), MRIWB (95.7%, 22/23, p = 1.00), and CTWB (81.8%, 27/33, p = 0.03). CONCLUSIONS: [68Ga]DOTATATE PET/CT should be the modality of choice in PPGL-related spinal bone metastases due to its superior detection rate. CLINICAL RELEVANCE STATEMENT: In a prospective study of 43 pheochromocytoma/paraganglioma participants with spinal bone metastases, [68Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% (377/382), compared to [18F]FDG PET/CT (p < 0.001), MRI of the spine (p < 0.001), whole-body CT (p < 0.001), and whole-body MRI (p < 0.001). KEY POINTS: • Data regarding head-to-head comparison between functional and anatomic imaging modalities to detect spinal bone metastases in pheochromocytoma/paraganglioma are limited. • [68Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% in the detection of spinal bone metastases associated with pheochromocytoma/paraganglioma compared to other imaging modalities: [18]F-FDG PET/CT, MRI of the spine, whole-body CT, and whole-body MRI. • [68Ga]DOTATATE PET/CT should be the modality of choice in the evaluation of spinal bone metastases associated with pheochromocytoma/paraganglioma.

Weakly Supervised Detection of Pheochromocytomas and Paragangliomas in CT.

Pheochromocytomas and Paragangliomas (PPGLs) are rare adrenal and extra-adrenal tumors which have the potential to metastasize. For the management of patients with PPGLs, CT is the preferred modality of choice for precise localization and estimation of their progression. However, due to the myriad variations in size, morphology, and appearance of the tumors in different anatomical regions, radiologists are posed with the challenge of accurate detection of PPGLs. Since clinicians also need to routinely measure their size and track their changes over time across patient visits, manual demarcation of PPGLs is quite a time-consuming and cumbersome process. To ameliorate the manual effort spent for this task, we propose an automated method to detect PPGLs in CT studies via a proxy segmentation task. As only weak annotations for PPGLs in the form of prospectively marked 2D bounding boxes on an axial slice were available, we extended these 2D boxes into weak 3D annotations and trained a 3D full-resolution nnUNet model to directly segment PPGLs. We evaluated our approach on a dataset consisting of chest-abdomen-pelvis CTs of 255 patients with confirmed PPGLs. We obtained a precision of 70% and sensitivity of 64.1% with our proposed approach when tested on 53 CT studies. Our findings highlight the promising nature of detecting PPGLs via segmentation, and furthers the state-of-the-art in this exciting yet challenging area of rare cancer management.

The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with an increased risk of diabetes-related complications. Hence, it is plausible that Continuous Positive Airway Pressure (CPAP) could have a favorable impact on these complications. To assess the feasibility of conducting a randomized control trial (RCT) in patients with type 2 diabetes (T2D) and OSA over 2 years. METHODS: An open-label multicenter feasibility RCT of CPAP vs no CPAP in patients with T2D and OSA. Patients with resting oxygen saturation <90%, central apnea index >15/hour or Epworth Sleepiness Scale (ESS) ≥11 were excluded. OSA was diagnosed using a multichannel portable device (ApneaLink Air, ResMed). The primary outcome measures were related to feasibility, and the secondary outcomes were changes in various clinical and biochemical parameters related to diabetes outcomes. RESULTS: Eighty-three (40 CPAP vs 43 no CPAP) patients were randomized, with a median (IQR) follow-up of 645 [545, 861] days. CPAP compliance was inadequate, with a median usage of approximately 3.5 hours/night. Early CPAP use predicted longer-term compliance. The adjusted analysis showed a possible favorable association between being randomized to CPAP and several diabetes-related endpoints (chronic kidney disease (CKD), neuropathy, and quality of life (QoL)). CONCLUSIONS: It was feasible to recruit, randomize, and achieve a high follow-up rate over 2 years in patients with OSA and T2D. CPAP compliance might improve by a run-in period before randomization. A full RCT is necessary to assess the observed favorable association between CPAP and CKD, neuropathy, and QoL in patients with T2D. CLINICAL TRIAL REGISTRATION: Registry: ISRCTN; URL: https://www.isrctn.com/ISRCTN12361838; Title: The impact of sleep disorders in patients with type 2 diabetes; Identifier: ISRCTN12361838.

Lobe-specific lymph node sampling is associated with lower risk of cancer recurrence.

Objective: Adequate intraoperative lymph node (LN) assessment is a critical component of early-stage non-small cell lung cancer (NSCLC) resection. The National Comprehensive Cancer Network and the American College of Surgeons Commission on Cancer (CoC) recommend station-based sampling minimums agnostic to tumor location. Other institutions advocate for lobe-specific LN sampling strategies that consider the anatomic likelihood of LN metastases. We examined the relationship between lobe-specific LN assessment and long-term outcomes using a robust, highly curated cohort of stage I NSCLC patients. Methods: We performed a cohort study using a uniquely compiled dataset from the Veterans Health Administration and manually abstracted data from operative and pathology reports for patients with clinical stage I NSCLC (2006-2016). For simplicity in comparison, we included patients who had right upper lobe (RUL) or left upper lobe (LUL) tumors. Based on modified European Society of Thoracic Surgeons guidelines, lobe-specific sampling was defined for RUL tumors (stations 2, 4, 7, and 10 or 11) and LUL tumors (stations 5 or 6, 7, and 10 or 11). Our primary outcome was the risk of cancer recurrence, as assessed by Fine and Gray competing risks modeling. Secondary outcomes included overall survival (OS) and pathologic upstaging. Analyses were adjusted for relevant patient, disease, and treatment variables. Results: Our study included 3534 patients with RUL tumors and 2667 patients with LUL tumors. Of these, 277 patients (7.8%) with RUL tumors and 621 patients (23.2%) with LUL tumors met lobe-specific assessment criteria. Comparatively, 34.7% of patients met the criteria for count-based assessment, and 25.8% met the criteria for station-based sampling (ie, any 3 N2 stations and 1 N1 station). Adherence to lobe-specific assessment was associated with lower cumulative incidence of recurrence (adjusted hazard ratio [aHR], 0.83; 95% confidence interval [CI], 0.70-0.98) and a higher likelihood of pathologic upstaging (aHR, 1.49; 95% CI, 1.20-1.86). Lobe-specific assessment was not associated with OS. Conclusions: Adherence to intraoperative LN sampling guidelines is low. Lobe-specific assessment is associated with superior outcomes in early-stage NSCLC. Quality metrics that assess adherence to intraoperative LN sampling, such as the CoC Operative Standards manual, also should consider lobe-specific criteria.

Exposure to Agent Orange is associated with increased recurrence after surgical treatment of stage I non-small cell lung cancer.

OBJECTIVE: Approximately 3 million Americans served in the armed forces during the Vietnam War. Veterans have a higher incidence rate of lung cancer compared with the general population, which may be related to exposures sustained during service. Agent Orange, one of the tactical herbicides used by the armed forces as a means of destroying crops and clearing vegetation, has been linked to the development of several cancers including non-small cell lung cancer. However, traditional risk models of lung cancer survival and recurrence often do not include such exposures. We aimed to examine the relationship between Agent Orange exposure and overall survival and disease recurrence for surgically treated stage I non-small cell lung cancer. METHODS: We performed a retrospective cohort study using a uniquely compiled dataset of US Veterans with pathologic I non-small cell lung cancer. We included adult patients who served in the Vietnam War and underwent surgical resection between 2010 and 2016. Our 2 comparison groups included those with identified Agent Orange exposure and those who were unexposed. We used multivariable Cox proportional hazards and Fine and Gray competing risk analyses to examine overall survival and disease recurrence for patients with pathologic stage I disease, respectively. RESULTS: A total of 3958 Vietnam Veterans with pathologic stage I disease were identified (994 who had Agent Orange exposure and 2964 who were unexposed). Those who had Agent Orange exposure were more likely to be male, to be White, and to live a further distance from their treatment facility (P < .05). Tumor size distribution, grade, and histology were similar between cohorts. Multivariable Cox proportional hazards modeling identified similar overall survival between cohorts (Agent Orange exposure hazard ratio, 0.97; 95% CI, 0.86-1.09). Patients who had Agent Orange exposure had a 19% increased risk of disease recurrence (hazard ratio, 1.19; 95% CI, 1.02-1.40). CONCLUSIONS: Veterans with known Agent Orange exposure who undergo surgical treatment for stage I non-small cell lung cancer have an approximately 20% increased risk of disease recurrence compared with their nonexposed counterparts. Agent Orange exposure should be taken into consideration when determining treatment and surveillance regimens for Veteran patients.

Review on Monoclonal Antibodies (mAbs) as a Therapeutic Approach for Type 1 Diabetes.

Monoclonal antibodies have been successfully utilized in a variety of animal models to treat auto-immune illnesses for a long time. Immune system responses will either be less active or more active depending on how the immune system is operating abnormally. Immune system hypoactivity reduces the body's capacity to fight off various invading pathogens, whereas immune system hyperactivity causes the body to attack and kill its own tissues and cells. For maximal patient compliance, we will concentrate on a variety of antibody therapies in this study to treat Type 1 diabetes (an autoimmune condition). T cells are responsible for the auto-immune condition known as T1D, which causes irregularities in the function of ß-cells in the pancreas. As a result, for the treatment and prevention of T1D, immunotherapies that selectively restore continuous beta cell-specific self-tolerance are needed. Utilizing monoclonal antibodies is one way to specifically target immune cell populations responsible for the auto-immune-driven disease (mAb). Numerous mAbs have demonstrated clinical safety and varied degrees of success in modulating autoimmunity, including T1D. A targeted cell population is exhausted by mAb treatments, regardless of antigenic specificity. One drawback of this treatment is the loss of obtained protective immunity. Immune effector cell function is regulated by nondepleting monoclonal antibodies (mAb). The antigen-focused new drug delivery system is made possible by the adaptability of mAbs. For the treatment of T1D and T cell-mediated autoimmunity, different existing and potential mAb therapy methods are described in this article.

Paediatric phaeochromocytoma and paraganglioma: A clinical update.

Paediatric phaeochromocytomas and paragangliomas (PPGLs), though rare tumours, are associated with significant disability and death in the most vulnerable of patients early in their lives. However, unlike cryptogenic and insidious disease states, the clinical presentation of paediatric patients with PPGLs can be rather overt, allowing early diagnosis, granted that salient findings are recognized. Additionally, with prompt and effective intervention, prognosis is favourable if timely intervention is implemented. For this reason, this review focuses on four exemplary paediatric cases, succinctly emphasizing the now state-of-the-art concepts in paediatric PPGL management.

Understanding the Effect of Prescription Isodose in Single-Fraction Stereotactic Radiosurgery on Plan Quality and Clinical Outcomes for Solid Brain Metastases.

BACKGROUND AND OBJECTIVES: There is wide variation in treatment planning strategy for central nervous system (CNS) stereotactic radiosurgery. We sought to understand what relationships exist between intratumor maximum dose and local control (LC) or CNS toxicity, and dosimetric effects of constraining hotspots on plan quality of multiple metastases volumetric modulated arc therapy radiosurgery plans. METHODS: We captured brain metastases from 2015 to 2017 treated with single-isocenter volumetric modulated arc therapy radiosurgery. Included tumors received single-fraction stereotactic radiosurgery, had no previous surgery or radiation, and available follow-up imaging. Our criterion for local failure was 25% increase in tumor diameter on follow-up MRI or pathologic confirmation of tumor recurrence. We defined significant CNS toxicity as Radiation Therapy Oncology Group irreversible Grade 3 or higher. We performed univariate and multivariate analyses evaluating factors affecting LC. We examined 10 stereotactic radiosurgery plans with prescriptions of 18 Gy to all targets originally planned without constraints on the maximum dose within the tumor. We replanned each with a constraint of Dmax 120%. We compared V50%, mean brain dose, and Dmax between plans. RESULTS: Five hundred and thirty tumors in 116 patients were available for analysis. Median prescription dose was 18 Gy, and median prescription isodose line (IDL) was 73%. Kaplan-Meier estimate of 12-month LC only tumor volume (HR 1.43 [1.22-1.68] P < .001) was predictive of local failure on univariate analysis; prescription IDL and histology were not. In multivariate analysis, tumor volume impacted local failure (HR 1.43 [1.22-1.69] P < .001) but prescription IDL did not (HR 0.95 [0.86-1.05] P = .288). Only a single grade 3 and 2 grade 4 toxicities were observed; tumor volume was predictive of CNS toxicity (HR 1.58 [1.25-2.00]; P < .001), whereas prescription IDL was not (HR 1.01 [0.87-1.17] P = .940). CONCLUSION: The prescription isodose line had no impact on local tumor control or CNS toxicity. Penalizing radiosurgery hotspots resulted in worse radiosurgery plans with poorer gradient. Limiting maximum dose in gross tumor causes increased collateral exposure to surrounding tissue and should be avoided.

Is neighborhood deprivation index a risk factor for Staphylococcus aureus infections?

BACKGROUND: We assessed the association between neighborhood area deprivation index (ADI) and community-onset (co) and hospital-onset (ho) Staphylococcus aureus infection. METHODS: Demographic and clinical characteristics of patients admitted to 5 adult hospitals in the mid-Atlantic between 2016 and 2018 were obtained. The association of ADI with methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) S aureus infections was assessed using logistic regression models adjusting for severity of illness and days of admission. RESULTS: Overall, increasing ADI was associated with higher odds of co- and ho-MRSA and MSSA infection. In univariate analysis, Black race was associated with 44% greater odds of ho-MRSA infection (odds ratio [OR] 1.44; 95% CI 1.18-1.76) and Asian race (co-MRSA OR 0.355; Confidence Interval (CI) 0.240-0.525; co-MSSA OR 0.718; CI 0.557-0.928) and unknown race (co-MRSA OR 0.470; CI 0.365-0.606; co-MSSA OR 0.699; CI 0.577-0.848) was associated with lower odds of co-MSSA and co-MRSA infections. When both race and ADI were included in the model, Black race was no longer associated with ho-MRSA infections whereas Asian and unknown race remained associated with lower odds of co-MRSA and co-MSSA infection. In the multivariable logistic regression, ADI was consistently associated with increased odds of S aureus infection (co-MRSA OR 1.132; CI 1.064-1.205; co-MSSA OR 1.089; CI 1.030-1.15; ho-MRSA OR 1.29; CI 1.16-1.43: ho-MSSA OR 1.215; CI 1.096-1.346). CONCLUSIONS: The area deprivation index is associated with community and hospital-onset MRSA and MSSA infections.

Delivering Biopsychosocial Health Care Within Routine Care: Spotlight-AQ Pivotal Multicenter Randomized Controlled Trial Results.

BACKGROUND: Annual national diabetes audit data consistently shows most people with diabetes do not consistently achieve blood glucose targets for optimal health, despite the large range of treatment options available. AIM: To explore the efficacy of a novel clinical intervention to address physical and mental health needs within routine diabetes consultations across health care settings. METHODS: A multicenter, parallel group, individually randomized trial comparing consultation duration in adults diagnosed with T1D or T2D for ≥6 months using the Spotlight-AQ platform versus usual care. Secondary outcomes were HbA1c, depression, diabetes distress, anxiety, functional health status, and healthcare professional burnout. Machine learning models were utilized to analyze the data collected from the Spotlight-AQ platform to validate the reliability of question-concern association; as well as to identify key features that distinguish people with type 1 and type 2 diabetes, as well as important features that distinguish different levels of HbA1c. RESULTS: n = 98 adults with T1D or T2D; any HbA1c and receiving any diabetes treatment participated (n = 49 intervention). Consultation duration for intervention participants was reduced in intervention consultations by 0.5 to 4.1 minutes (3%-14%) versus no change in the control group (-0.9 to +1.28 minutes). HbA1c improved in the intervention group by 6 mmol/mol (range 0-30) versus control group 3 mmol/mol (range 0-8). Moderate improvements in psychosocial outcomes were seen in the intervention group for functional health status; reduced anxiety, depression, and diabetes distress and improved well-being. None were statistically significant. HCPs reported improved communication and greater focus on patient priorities in consultations. Artificial Intelligence examination highlighted therapy and psychological burden were most important in predicting HbA1c levels. The Natural Language Processing semantic analysis confirmed the mapping relationship between questions and their corresponding concerns. Machine learning model revealed type 1 and type 2 patients have different concerns regarding psychological burden and knowledge. Moreover, the machine learning model emphasized that individuals with varying levels of HbA1c exhibit diverse levels of psychological burden and therapy-related concerns. CONCLUSION: Spotlight-AQ was associated with shorter, more useful consultations; with improved HbA1c and moderate benefits on psychosocial outcomes. Results reflect the importance of a biopsychosocial approach to routine care visits. Spotlight-AQ is viable across health care settings for improved outcomes.

Acute asymptomatic hyponatraemia following inpatient initiation of angiotensin receptor-neprilysin inhibitor: a case report.

Background: Utilization of sacubitril/valsartan is increasing as a component of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction (HFrEF). Common adverse effects associated with the medication such as hypotension and hyperkalaemia have been described; however, hyponatraemia is very rarely reported to have a potential association with use of the medication. In this report, we describe what we believe to be the first reported case of acute hyponatraemia likely attributable to inpatient initiation of sacubitril/valsartan. Case Summary: A 71-year-old female presented with 2 weeks of progressively worsening dyspnoea and orthopnoea. Bedside echocardiography identified a dilated cardiomyopathy with an estimated left ventricular ejection fraction <30% and diffuse hypokinesis, and given the associated clinical syndrome, she was diagnosed with heart failure with reduced ejection fraction. In conjunction with diuresis, guideline-directed medical therapy was initiated. She developed acute worsening of her previously mild hyponatraemia shortly after starting sacubitril/valsartan, and this improved following discontinuation of the medication. She was subsequently able to tolerate losartan while maintaining eunatraemia, and her ejection fraction improved to 46% on repeat imaging. Discussion: Angiotensin receptor-neprilysin inhibitors are an integral component of guideline-directed medical therapy with proven benefits for patients with heart failure with reduced ejection fraction. Although the association between use of these medications and hyponatraemia appears to be exceedingly rare, clinicians should maintain awareness of this potential adverse effect.

RNA-sequencing attest increased sperm motility in bovine spermatozoa treated with ethanolic extract of Putranjiva roxburghii.

In the course of time, scientific communities have a growing interest in understanding ethano medicines. The Putranjiva roxburghii, a native plant of the Indian Subcontinent is described as a "Child amulet tree" in Ayurveda. Based on the fact that this herbal medicine has an indispensable component of integrative medicine, the present study was planned to assess the effect of ethanolic dried extract of Putranjiva seeds on the motility of X and Y-bearing bovine spermatozoa. The in-vitro effect of seed extract diluted in S-TALP medium on bull semen has been evaluated by Computer Assisted Semen Analysis (CASA) shows a marked increase in the motility of spermatozoa. Motile and non-motile spermatozoa have been separated by glass wool column from the control as well as treated group. The X and Y-bearing sperm quantification have been carried out by droplet digital polymerase chain reaction (ddPCR). The extract didn't exert any differential effect on the motility and viability of X and Y chromosome-bearing spermatozoa. The transcriptome profiling (RNA-Seq) identified 93 differentially expressed genes between the extract treated and control group. It unveils the up-regulation of CATSPER, AKAP3, SPAG, ADAM1B, ADAM2 and ADAM32 genes that are involved in increasing sperm motility. Transcriptome profile also unveil the expression of ZAR1, CYP17A1, APPL2, HOXB4 and SP9 genes involved with embryonic development processes in Putranjiva extract-treated motile spermatozoa. The results envisaged the medicinal value of Putranjiva herb on increased fertility due to combinatory effect like increased sperm motility and favourableness on embryogenesis. The study ruled out the possibility of herbs having any biased effect on the selection of either male or female-bearing spermatozoa in the bull. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03452-4.

Association Between Surgical Quality Metric Adherence and Overall Survival Among US Veterans With Early-Stage Non-Small Cell Lung Cancer.

Importance: Surgical resection remains the preferred treatment for functionally fit patients diagnosed with early-stage non-small cell lung cancer (NSCLC). Process-based intraoperative quality metrics (QMs) are important for optimizing long-term outcomes following curative-intent resection. Objective: To develop a practical surgical quality score for patients diagnosed with clinical stage I NSCLC who received definitive surgical treatment. Design, Setting, and Participants: This retrospective cohort study used a uniquely compiled data set of US veterans diagnosed with clinical stage I NSCLC who received definitive surgical treatment from October 2006 through September 2016. The data were analyzed from April 1 to September 1, 2022. Based on contemporary treatment guidelines, 5 surgical QMs were defined: timely surgery, minimally invasive approach, anatomic resection, adequate lymph node sampling, and negative surgical margin. The study developed a surgical quality score reflecting the association between these QMs and overall survival (OS), which was further validated in a cohort of patients using data from the National Cancer Database (NCDB). The study also examined the association between the surgical quality score and recurrence-free survival (RFS). Exposures: Surgical treatment of early-stage NSCLC. Main Outcomes and Measures: Overall survival and RFS. Results: The study included 9628 veterans who underwent surgical treatment between 2006 and 2016. The cohort consisted of 1446 patients who had a mean (SD) age of 67.6 (7.9) years and included 9278 males (96.4%) and 350 females (3.6%). Among the cohort, 5627 individuals (58.4%) identified as being smokers at the time of surgical treatment. The QMs were met as follows: timely surgery (6633 [68.9%]), minimally invasive approach (3986 [41.4%]), lobectomy (6843 [71.1%]) or segmentectomy (532 [5.5%]), adequate lymph node sampling (3278 [34.0%]), and negative surgical margin (9312 [96.7%]). The median (IQR) follow-up time was 6.2 (2.5-11.4) years. An integer-based score (termed the Veterans Affairs Lung Cancer Operative quality [VALCAN-O] score) from 0 (no QMs met) to 13 (all QMs met) was constructed, with higher scores reflecting progressively better risk-adjusted OS. The median (IQR) OS differed substantially between the score categories (score of 0-5 points, 2.6 [1.0-5.7] years of OS; 6-8 points, 4.3 [1.7-8.6] years; 9-11 points, 6.3 [2.6-11.4] years; and 12-13 points, 7.0 [3.0-12.5] years; P < .001). In addition, risk-adjusted RFS improved in a stepwise manner between the score categories (6-8 vs 0-5 points, multivariable-adjusted hazard ratio [aHR], 0.62; 95% CI, 0.48-0.79; P < .001; 12-13 vs 0-5 points, aHR, 0.39; 95% CI, 0.31-0.49; P < .001). In the validation cohort, which included 107 674 nonveteran patients, the score remained associated with OS. Conclusions and Relevance: The findings of this study suggest that adherence to intraoperative QMs may be associated with improved OS and RFS. Efforts to improve adherence to surgical QMs may improve patient outcomes following curative-intent resection of early-stage lung cancer.

Understanding of molecular basis of histological graded horn cancer by transcriptome profiling.

Horn cancer is most devastating and prominent cancer in Indian zebu cattle that affects socio-economic condition of small-scale farmers who depends on their cattle for farm work. Development in the field for genomics through next generation sequencing and bioinformatics advancement have helped to identify genes which have a role in horn cancer development. Histopathological examination of cancerous tissues of horn revealed myxomatous changes, well, moderate and poorly differentiated squamous cell carcinoma. Differential gene expression analysis showed 40, 11, 66 and 29 upregulated genes and 10, 14, 08 and 07 down-regulated genes in myxomatous, well, moderate and poorly differentiated squamous cell carcinoma as compared to normal. Significant differentially expressed genes are related to cell development, cell proliferation, cell-cell communication, cell signaling and angiogenesis which are linked to Akt pathway, mTOR pathway and Wnt pathway. Activity of these genes and related pathways have already been established about their role in development of cancer. Among the candidate genes; keratin family, keratin family related gene, chemokine signaling and cytokines signaling associated genes could be a prominent target for the development of stage specific prognosis marker after further detailed study at large sample population level. CSTA, PTN, SPP1 genes have upregulation in all stages of cancer and they have enrolled as biomarkers for horn cancer.

Immune signature of pheochromocytoma and paraganglioma in context of neuroendocrine neoplasms associated with prognosis.

PURPOSE: To understand prognostic immune cell infiltration signatures in neuroendocrine neoplasms (NENs), particularly pheochromocytoma and paraganglioma (PCPG), we analyzed tumor transcriptomic data from The Cancer Genome Atlas (TCGA) and other published tumor transcriptomic data of NENs. METHODS: We used CIBERSORT to infer immune cell infiltrations from bulk tumor transcriptomic data from PCPGs, in comparison to gastroenteropancreatic neuroendocrine tumors (GEPNETs) and small cell lung carcinomas (SCLCs). PCPG immune signature was validated with NanoString immune panel in an independent cohort. Unsupervised clustering of the immune infiltration scores from CIBERSORT was used to find immune clusters. A prognostic immune score model for PCPGs and the other NENs were calculated as a linear combination of the estimated infiltration of activated CD8+/CD4+ T cells, activated NK cells, and M0 and M2 macrophages. RESULTS: In PCPGs, we found five dominant immune clusters, associated with M2 macrophages, monocytes, activated NK cells, M0 macrophages and regulatory T cells, and CD8+/CD4+ T cells respectively. Non-metastatic tumors were associated with activated NK cells and metastatic tumors were associated with M0 macrophages and regulatory T cells. In GEPNETs and SCLCs, M0 macrophages and regulatory T cells were associated with unfavorable outcomes and features, such as metastasis and high-grade tumors. The prognostic immune score model for PCPGs and the NENs could predict non-aggressive and non-metastatic diseases. In PCPGs, the immune score was also an independent predictor of metastasis-free survival in a multivariate Cox regression analysis. CONCLUSION: The transcriptomic immune signature in PCPG correlates with clinical features like metastasis and prognosis.

Association between imaging surveillance frequency and outcomes following surgical treatment of early-stage lung cancer.

BACKGROUND: Recent studies have suggested that more frequent postoperative surveillance imaging via computed tomography following lung cancer resection may not improve outcomes. We sought to validate these findings using a uniquely compiled dataset from the Veterans Health Administration, the largest integrated health-care system in the United States. METHODS: We performed a retrospective cohort study of veterans with pathologic stage I non-small cell lung cancer receiving surgery (2006-2016). We assessed the relationship between surveillance frequency (chest computed tomography scans within 2 years after surgery) and recurrence-free survival and overall survival. RESULTS: Among 6171 patients, 3047 (49.4%) and 3124 (50.6%) underwent low-frequency (<2 scans per year; every 6-12 months) and high-frequency (≥2 scans per year; every 3-6 months) surveillance, respectively. Factors associated with high-frequency surveillance included being a former smoker (vs current; adjusted odds ratio [aOR] = 1.18, 95% confidence interval [CI] = 1.05 to 1.33), receiving a wedge resection (vs lobectomy; aOR = 1.21, 95% CI = 1.05 to 1.39), and having follow-up with an oncologist (aOR = 1.58, 95% CI = 1.42 to 1.77), whereas African American race was associated with low-frequency surveillance (vs White race; aOR = 0.64, 95% CI = 0.54 to 0.75). With a median (interquartile range) follow-up of 7.3 (3.4-12.5) years, recurrence was detected in 1360 (22.0%) patients. High-frequency surveillance was not associated with longer recurrence-free survival (adjusted hazard ratio = 0.93, 95% CI = 0.83 to 1.04, P = .22) or overall survival (adjusted hazard ratio = 1.04, 95% CI = 0.96 to 1.12, P = .35). CONCLUSIONS: We found that high-frequency surveillance does not improve outcomes in surgically treated stage I non-small cell lung cancer. Future lung cancer treatment guidelines should consider less frequent surveillance imaging in patients with stage I disease.

Development and Validation of the VA Lung Cancer Mortality (VALCAN-M) Score for 90-Day Mortality Following Surgical Treatment of Clinical Stage I Lung Cancer.

OBJECTIVE: The aim was to develop and validate the Veterans Administration (VA) Lung Cancer Mortality (VALCAN-M) score, a risk prediction model for 90-day mortality following surgical treatment of clinical stage I nonsmall-cell lung cancer (NSCLC). BACKGROUND: While surgery remains the preferred treatment for functionally fit patients with early-stage NSCLC, less invasive, nonsurgical treatments have emerged for high-risk patients. Accurate risk prediction models for postoperative mortality may aid surgeons and other providers in optimizing patient-centered treatment plans. METHODS: We performed a retrospective cohort study using a uniquely compiled VA data set including all Veterans with clinical stage I NSCLC undergoing surgical treatment between 2006 and 2016. Patients were randomly split into derivation and validation cohorts. We derived the VALCAN-M score based on multivariable logistic regression modeling of patient and treatment variables and 90-day mortality. RESULTS: A total of 9749 patients were included (derivation cohort: n=6825, 70.0%; validation cohort: n=2924, 30.0%). The 90-day mortality rate was 4.0% (n=390). The final multivariable model included 11 factors that were associated with 90-day mortality: age, body mass index, history of heart failure, forced expiratory volume (% predicted), history of peripheral vascular disease, functional status, delayed surgery, American Society of Anesthesiology performance status, tumor histology, extent of resection (lobectomy, wedge, segmentectomy, or pneumonectomy), and surgical approach (minimally invasive or open). The c statistic was 0.739 (95% CI=0.708-0.771) in the derivation cohort. CONCLUSIONS: The VALCAN-M score uses readily available treatment-related variables to reliably predict 90-day operative mortality. This score can aid surgeons and other providers in objectively discussing operative risk among high-risk patients with clinical stage I NSCLC considering surgery versus other definitive therapies.

Assessment of Duration of Smoking Cessation Prior to Surgical Treatment of Non-small Cell Lung Cancer.

OBJECTIVE: To define the relationship between the duration of smoking cessation and postoperative complications for patients with lung cancer undergoing surgical treatment. BACKGROUND: Smoking increases the risk of postoperative morbidity and mortality in patients with lung cancer undergoing surgical treatment. Although smoking cessation before surgery can mitigate these risks, the ideal duration of preoperative smoking cessation remains unclear. METHODS: Using a uniquely compiled Veterans Health Administration dataset, we performed a retrospective cohort study of patients with clinical stage I non-small cell lung cancer undergoing surgical treatment between 2006 and 2016. We characterized the relationship between duration of preoperative smoking cessation and risk of postoperative complications or mortality within 30-days using multivariable restricted cubic spline functions. RESULTS: The study included a total of 9509 patients, of whom 6168 (64.9%) were smoking at the time of lung cancer diagnosis. Among them, only 662 (10.7%) patients stopped smoking prior to surgery. Longer duration between smoking cessation and surgery was associated with lower odds of major complication or mortality (adjusted odds ratio [aOR] for every additional week, 0.919; 95% confidence interval [CI], 0.850-0.993; P = 0.03). Compared to nonsmokers, patients who quit at least 3 weeks before surgery had similar odds of death or major complication (aOR, 1.005; 95% CI, 0.702-1.437; P = 0.98) whereas those who quit within 3 weeks of surgery had significantly higher odds of death or major complication (aOR, 1.698; 95% CI, 1.203-2.396; P = 0.003). CONCLUSION: Smoking cessation at least 3 weeks prior to the surgical treatment of lung cancer is associated with reduced morbidity and mortality. Providers should aggressively encourage smoking cessation in the preoperative period, since it can disproportionately impact outcomes in early-stage lung cancer.

Comparison Between Veteran and Non-Veteran Populations With Clinical Stage I Non-small Cell Lung Cancer Undergoing Surgery.

OBJECTIVE: The aim of this study was to compare quality of care and outcomes between Veteran and non-Veteran patients undergoing surgery for clinical stage I non-small cell lung cancer (NSCLC). BACKGROUND: Prior studies and the lay media have questioned the quality of care that Veterans with lung cancer receive through the VHA. We hypothesized Veterans undergoing surgery for early-stage NSCLC receive high quality care and have similar outcomes compared to the general population. METHODS: We performed a retrospective cohort study of patients with clinical stage I NSCLC undergoing resection from 2006 to 2016 using a VHA dataset. Propensity score matching for baseline patient- and tumor-related variables was used to compare operative characteristics and outcomes between the VHA and the National Cancer Database (NCDB). RESULTS: The unmatched cohorts included 9981 VHA and 176,304 NCDB patients. The VHA had more male, non-White patients with lower education levels, higher incomes, and higher Charlson/Deyo scores. VHA patients had inferior unadjusted 30-day mortality (VHA 2.1% vs NCDB 1.7%, P = 0.011) and median overall survival (69.0 vs 88.7 months, P < 0.001). In the propensity matched cohort of 6792 pairs, VHA patients were more likely to have minimally invasive operations (60.0% vs 39.6%, P < 0.001) and only slightly less likely to receive lobectomies (70.1% vs 70.7%, P = 0.023). VHA patients had longer lengths of stay (8.1 vs 7.1 days, P < 0.001) but similar readmission rates (7.7% vs 7.0%, P = 0.132). VHA patients had significantly better 30-day mortality (1.9% vs 2.8%, P < 0.001) and median overall survival (71.4 vs 65.2 months, P < 0.001). CONCLUSIONS: Despite having more comorbidities, Veterans receive exceptional care through the VHA with favorable outcomes, including significantly longer overall survival, compared to the general population.