Citations

Abstract Introduction Patients with metastatic spine disease (MSD) present with varying degrees of systemic illness and frailty. Given the palliative intent of surgery and radiation treatment for MSD, treatment risks must be judiciously weighed against potential benefits. We sought to examine the impact of peroperative nutritional status as measured by the PG-SGA on survival in patients undergoing surgery and radiation for MSD. Methods This study involved an international, multicenter prospective, observational registry of patients with MSD: AO Knowledge Forum Tumor’s Metastatic Tumor Research and Outcomes Network (MTRON). Variables including baseline demographics, oncologic data, adverse events (medical adverse events and surgical complications), length of stay, and nutritional status were prospectively collected. The Patient-Generated Subjective Global Assessment (PG-SGA) was used to evaluate nutritional status. Results A total of 589 patients were included in this study; 469 (80%) of whom underwent surgery and radiation and 120 (20%) of whom underwent radiation alone. The majority of patients (362, 61%) were classified as well nourished, however, 68 patients (12%) were classified as severely malnourished. Among patients that underwent surgery and radiation, the median overall survival of well nourished patients was 491 days compared to 117 days in the severely malnourished patients (p < 0.001). A multivariate analysis demonstrated severe malnourishment and ECOG performance status of 3 or 4 were associated with worse overall survival. Conclusion Malnutrition as measured by the PG-SGA demonstrated to be significantly and independently associated with perioperative survival in patients with MSD. Further studies that investigate optimal pre-treatment optimization for patients with MSD in order to mitigate morbidity and mortality risk are essential.

Abstract Introduction As the incidence of metastatic spine disease (MSD) increases, treatments to manage refractory pain, pathologic vertebral body fractures, and spinal cord compression are becoming increasingly common. Given the palliative nature of surgical intervention used to achieve tumor control and thus mitigate loss of neurologic function and compromised ambulatory function, it is essential to mitigate the risk of such procedures. Methods The AO Spine Knowledge Forum Tumor’s Metastatic Tumor Research and Outcomes Network (MTRON), an international, prospective registry for patients with spinal metastases, was used for this query. Prospective collection included baseline health and demographic information, oncologic data (including Spinal Instability Neoplastic Score (SINS) score and Bilksy epidural compression classification), and baseline functional status (preoperative American Spinal Injury Association (ASIA) and ECOG scores). Health related quality of life (HRQoL) data included Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0) and Euro-QoL measures. Surgery related adverse events (AE’s) were collected using the Spine Adverse Events Severity (SAVES V2) framework. Kaplan-Meir curves were used to assess survival. Results The cohort consisted of 1267 patients, 701 male (55.3%). A total of 245 (19.3%) experienced at least one postoperative AE, the majority of which were considered minor (grade 3 or less). Among the most common were deep wound infections (3.2%), wound dehiscence (2.5%), and urinary infections (2.4%). A multivariate analysis demonstrated that age, smoking status, ECOG performance, prior radiotherapy, presence of multiple metastases at other sites, and multiple spine metastases were significant risk factors for a postoperative AE. Postoperative AE’s (p = 0.049) and major postoperative AE’s (p = 0.0038) were found to be related to survival as well as a significant change in HRQoL scores (p < 0.001). Conclusion Postoperative AE’s are extremely relevant to the care of patients with MSD and impact both HRQoL and survival.

BACKGROUND: Primary aldosteronism (PA) is a common and treatable cause of hypertension, yet data on the durability of medical treatment response beyond the first year are limited. Using the PA medical treatment outcomes framework, we evaluated long-term biochemical and clinical outcomes and factors associated with treatment response. METHODS: We conducted an international, multicenter, observational cohort study across 27 centers on 4 continents. Adults with PA treated with mineralocorticoid receptor antagonists and/or epithelial sodium channel blockers between 2016 and 2021 were included if follow-up data were available at ≥12 months. Biochemical and clinical responses were classified as complete, partial, or absent using PA medical treatment outcomes criteria. Ordinal logistic regression identified determinants of a favorable treatment response. RESULTS: The cohort included 1292 patients (47.5% women, mean age 52 years) with a median follow-up of 34 months (interquartile range, 21–51). At ≥12 months, 58.3% achieved a complete biochemical response, and 20.8% achieved a complete clinical response, with only 5% showing no response. Determinants of a favorable biochemical response included lower aldosterone and lateralization index, and higher renin and potassium levels at baseline. In those taking spironolactone, a higher daily dose was also associated with a favorable biochemical response. Determinants of a favorable clinical response included female sex, lower body mass index, shorter duration of hypertension, and absence of hypertension-mediated organ damage. CONCLUSIONS: Targeted medical therapy for PA can deliver sustained biochemical and clinical benefits. Early disease detection and adequate dose titration are highly actionable determinants of long-term treatment success.

OBJECTIVE The Centers for Medicare & Medicaid Services (CMS) requires a low C-peptide level for insulin pump coverage unless the individual is β-cell autoantibody positive, which precludes coverage of automated insulin delivery (AID) systems for many people with type 2 diabetes. RESEARCH DESIGN AND METHODS In the Randomized Trial Evaluating the Efficacy and Safety of Control-IQ+ Technology in Adults With Type 2 Diabetes Using Basal-Bolus Insulin Therapy study evaluating the t:slim X2 insulin pump with Control-IQ+ technology, adults with insulin-treated type 2 diabetes were categorized into high C-peptide (n = 195) and low C-peptide (n = 59) groups based on CMS criteria. RESULTS In the AID group, mean HbA1c decreased from baseline by 0.8%, which was significantly greater than in the control group with both high (P < 0.001) and low (P = 0.02) C-peptide levels. Results were similar in participants ≥65 years old. CONCLUSIONS The benefit of AID is present with high and low C-peptide levels. Thus, requiring a low C-peptide level as a prerequisite for AID therapy is not warranted.

Abstract Rationale: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a pulmonary condition characterised by neuroendocrine cell proliferation along respiratory bronchioles resulting in tumourlet formation which may progress to pulmonary carcinoid. DIPNECH is a rare and under-recognised condition that predominantly affects females, with an estimated worldwide incidence of 5-6 people per million population. Given it's rarity and the poor understanding around the pathogenesis and treatment of this condition, we undertook the largest international case series to date of DIPNECH patients. We aim to further characterise this patient cohort to better understand the clinical features, identify common pulmonary function test (PFT) patterns and radiographic findings and describe current treatment practices. Methods: We collated data from 17 centres across 8 different countries comprising a total of 258 patients. Data collected included patient demographics, smoking history, symptoms, co-morbidities, pathological diagnosis, imaging findings, PFT pattern and therapies. Results: In total 258 patients were identified. The median age was 65 (SD+/- 10.6). 241 (93%) were female. 39% (n= 94/243) were ex-smokers. 79% (n=186/234) of patients reported pulmonary symptoms with cough being the most common symptom reported in 81% (n=151/186) of patients. Many patients were polysymptomatic, with cough and dyspnoea being the most common combination of symptoms described. (50.54%; n=94/186). Complete spirometry pattern was documented for 180 patients (69.78%) with an obstructive pattern being the most commonly observed (n=76/180; 42%). 27.5% (n=41/139) had clinically significant FEV1 reversibility post bronchodilator administration. Pathology specimens were available in 219 cases. Most common pathological features were neuroendocrine hyperplasia which was observed in 75% (n=165/219) and tumourlets in 74% (n=162/219) of cases. Carcinoid, either typical or atypical, was observed in 64% (n=141/219) of samples. 252 patients had computed tomography (CT) imaging performed. Pulmonary nodules were the most common feature identified in 99.60% of cases (248/250). Mosaic attenuation (69.30%; n=50/173) and airway dilatation (28.90%; n=50/173) were also frequently reported. There was no significant correlation between symptoms (cough, dyspnoea, wheeze) and airway dilatation (p=0.496), mosaic attenuation (p=0.496) and PFT pattern (p=0.837). There was a significant association between presence of symptoms and mosaic attenuation on CT (p=0.003). Conclusions: DIPNECH, while a rare disorder, is understudied. This international case series is the largest performed to date and highlights the complexity in management of these patients.

Abstract The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP‐NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP‐NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP‐NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP‐NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP‐NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.

ABSTRACT Background and hypothesis The MENTOR trial (MEmbranous Nephropathy Trial Of Rituximab) showed that rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria and was superior in maintaining proteinuria remission. However, the cost of rituximab may prohibit first-line use for some patients and health-care payers. Methods A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of rituximab compared with cyclosporine for the treatment membranous nephropathy from the perspective of a health-care payer with a lifetime time horizon. The model was informed by data from the MENTOR trial where possible; additional parameters including cost and utility inputs were obtained from the literature. Sensitivity analyses were performed to evaluate the impact of reduced-cost biosimilar rituximab. Results Rituximab for the treatment of membranous nephropathy was cost effective (assuming a willingness-to-pay threshold of $50 000 per quality-adjusted life year (QALY) gained; in $US 2021) compared with cyclosporine, with an ICER of $8373/QALY over a lifetime time horizon. The incremental cost of rituximab therapy was $28 007 with an additional 3.34 QALYs compared with cyclosporine. Lower cost of rituximab biosimilars resulted in a more favorable ICER, and in some cases resulted in rituximab being dominant (lower cost and great benefit) compared to cyclosporine. Conclusions Despite the greater cost of rituximab, it may be a cost-effective option for the treatment of membranous nephropathy when compared with cyclosporine. The cost-effectiveness of rituximab is further improved with the use of less expensive biosimilars.