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Outcomes of Immunotherapy Treatment in Sinonasal Mucosal Melanoma
No full textBACKGROUND: Sinonasal mucosal melanoma has poor survival despite multimodality treatment. While the impact of immunotherapy (IT) on metastatic cutaneous melanoma is well-defined, there are relatively little data on sinonasal mucosal melanoma.
OBJECTIVE: We sought to define immunotherapy outcomes in patients with sinonasal mucosal melanoma.
METHODS: A retrospective cohort study evaluated patients treated with IT during their overall treatment strategy for SNMM. Patient demographics, treatment, and survival outcomes were recorded.
RESULTS: 52 patients had IT treatment for SNMM from 2000 to 2022, with an average age of 69.1 ± 11.9 years. The most common treatment was surgery with radiation and IT (n = 26, 50%). Most regimens consisted of a combination of Nivolumab and Ipilimumab (n = 17, 32.7%) or pembrolizumab (n = 14, 26.9%). 44.2% of patients experienced reported complications. Overall survival at 1-, 2-, and 5 years was 86.9%, 74.1%, and 39.1%, respectively.
CONCLUSION: Approximately half of patients will have a local response following immunotherapy, but it is rare to have improvement at metastatic locations. Further research within our group will assess optimal timing and markers that are predictive of response
Rhinorrhea Recurrence After Posterior Nasal Nerve Cryoablation: A Multicenter Cohort Study
No full textBACKGROUND: Posterior nasal nerve (PNN) cryoablation improves chronic rhinitis (CR) symptoms in 70-80% of cases, including clear thin rhinorrhea (CTR). This study\u27s purpose was to determine time to and degree of CTR recurrence following cryoablation.
METHODS: A multicenter retrospective cohort study was conducted on patients who underwent PNN cryoablation to treat CR-related CTR refractory to ipratropium bromide nasal spray (IBNS). Cryoablation was applied along middle meatal posterolateral walls. Demographic and clinical data were collected at clinic visits or by phone surveys. Patients were followed for either 12 months minimum, or until CTR recurrence. Primary outcome measures were time to and degree of CTR improvement and recurrence based on patient-reported runny nose scores (Likert scale, 0-5). Additionally, patients were asked whether their recurrent CTR was bothersome enough to require treatment, and their preference for subsequent treatments.
RESULTS: Of 74 CR patients, mean age was 58 years, and 53% were female. Regarding CR subtypes, 74% were nonallergic, 22% mixed, and 4% allergic. Additionally, 78% were IBNS responders. Overall, 62 of 74 (84%) initially improved. Of 60 patients with adequate follow-up for recurrence (mean 31.6 months), 57 (95%) recurred to some degree at a mean 5 months post-treatment. Of those who recurred, 37 (65%) recurred completely to preoperative RNSs, and 11 (19%) achieved 20-25% RNS reduction. Almost 90% of those with recurrent CTR were bothered enough to desire further treatment.
CONCLUSION: PNN cryoablation led to CTR improvement in 84% of CR patients, with nearly 90% of patients developing bothersome recurrent CTR by about 5 months post-treatment.
LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2025
Children\u27s executive functioning and health behaviors across pediatric life stages and ecological contexts
No full textExecutive functioning (EF) has been linked to chronic disease risk in children. Health behaviors are thought to partially explain this association. The current cross-sectional study evaluated specific domains of EF and varied health behaviors in three pediatric life stages. Pediatric participants (early childhood n = 2074, M(age) = 6.4 ± 0.9 y; middle childhood n = 3230, M(age) = 9.6 ± 1.2 y; adolescence n = 1416, M(age) = 15.2 ± 1.7 y) were part of the Environmental influences on Child Health Outcomes (ECHO) Program. They completed neurocognitive tasks measuring cognitive flexibility, behavioral inhibition, and working memory. Parent- and/or child-report measures of dietary intake, physical activity, sleep duration and quality, income, and positive parenting were also collected. Neighborhood crime and greenspace were calculated from publicly available census-tract level indices. After adjusting for study site, child body mass index, and demographics, working memory was related in the hypothesized direction to several dietary behaviors within all pediatric life stages. Working memory and cognitive flexibility were positively related to physical activity in middle childhood and adolescence. In adolescence, behavioral inhibition was positively related to physical activity and inversely related to sugar-sweetened beverage and total caloric intake. Associations with sleep were all non-significant. All significant associations reflected small effect sizes. Income, positive parenting, greenspace, and crime did not significantly influence any of the EF-health behavior associations. Findings highlight the need to consider EF domains, specific health behaviors, and developmental stage in creating intervention strategies that target EF to improve health behaviors. The small effect sizes reinforce the need for multi-tiered interventions to maximize health
Classification of female MDD patients with and without suicidal ideation using resting-state functional magnetic resonance imaging and machine learning
No full textSpontaneous blood oxygen level-dependent signals can be indirectly recorded in different brain regions with functional magnetic resonance imaging. In this study resting-state functional magnetic resonance imaging was used to measure the differences in connectivity and activation seen in major depressive disorder (MDD) patients with and without suicidal ideation and the control group. For our investigation, a brain atlas containing 116 regions of interest was used. We also used four voxel-based connectivity models, including degree centrality, the fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity, and voxel-mirrored Homotopic Connectivity. Feature selection was conducted using a sequential backward floating selection approach along with a Random Forest Classifier and Elastic Net. While all four models yield significant results, fALFF demonstrated higher accuracy rates in classifying the three groups. Further analysis revealed three features that demonstrated statistically significant differences between these three, resulting in a 90.00% accuracy rate. Prominent features identified from our analysis, with suicide ideation as the key variable, included the Superior frontal gyrus (dorsolateral and orbital parts), the median cingulate, and the paracingulate gyri. These areas are associated with the Central Executive Control Network (ECN), the Default Mode Network, and the ECN, respectively. Comparing the results of MDD patients with suicidal ideation to those without suicidal ideations suggests dysfunctions in decision-making ability, in MDD females suffering from suicidal tendencies. This may be related to a lack of inhibition or emotion regulation capability, which contributes to suicidal ideations
Factors Associated With Long-term Kidney Allograft Survival: A Contemporary Analysis of the UNOS Database
No full textBACKGROUND: Various clinicopathologic markers, such as 1-year serum creatinine (Cr), have been used to prognosticate kidney allografts after transplantation. However, a contemporary analysis of their relationship with long-term graft survival is lacking. This study aimed to analyze recent data on the association of prognostic factors with kidney allograft survival in patients who underwent transplantation in the modern era.
METHODS: Adult kidney-transplant recipients in the UNOS database (2008-2020) were identified. Living and deceased donor allografts were analyzed separately and stratified by 1-year serum Cr level: ≤ 1.0, 1.0 to 1.5, 1.5 to 2.0, and \u3e2.0 mg/dL. Time-to-event analysis was performed with long-term death-censored graft survival as the primary outcome. In addition, factors associated with raised 1-year serum Cr and with long-term allograft failure were identified.
RESULTS: 174,547 patients were included. Ten-year survival decreased with increasing 1-year creatinine, and these trends persisted on adjusted analysis for both living donor (Cr ≤ 1.0 mg/dL: reference; Cr 1.0-1.5 mg/dL aHR = 1.77 [1.59-1.96]; Cr 1.5-2.0 mg/dL aHR = 3.24 [2.89-3.64] and; Cr \u3e 2.0 mg/dL aHR = 9.78, [8.64-11.07], P \u3c .01) as well as deceased donor allografts (Cr ≤ 1.0 mg/dL: reference; Cr 1.0-1.5 mg/dL aHR = 1.74 [1.63-1.86]; Cr 1.5-2.0 mg/dL aHR = 3.06 [2.84-3.30] and; Cr \u3e 2.0 mg/dL aHR = 8.51, [7.89-9.18], P \u3c .01).
CONCLUSION: These results characterize the association between 1-year serum creatinine levels and other clinicopathologic factors with long-term kidney allograft survival. We demonstrate the ability of prognostic factors to stratify patients by risk of graft failure in a contemporary patient cohort that is representative of current practice and outcomes
Defining an NK Cell-enriched Rejection-like Phenotype in Liver Transplant Biopsies From the INTERLIVER Study
No full textBACKGROUND: Initial analysis of liver transplant biopsies in the INTERLIVER study (ClinicalTrials.gov; unique identifier NCT03193151) using rejection-associated transcripts failed to find an antibody-mediated rejection state (ie, rich in natural killer [NK] cells and with interferon-gamma effects). We recently developed an optimization strategy in lung transplants that isolated an NK cell-enriched rejection-like (NKRL) state that was molecularly distinct from T cell-mediated rejection (TCMR). Here we apply the same strategy to a liver transplant biopsy population.
METHODS: We used this strategy to search for a molecular NKRL state in 765 consented liver transplant biopsies collected at participating international centers for gold-standard histology and molecular assessment by genome-wide microarrays. Validation through a training set-test set approach of an optimized selection of variables as inputs into unsupervised rejection classification identified an NKRL state in livers.
RESULTS: The full model classified 765 biopsies into the following molecular phenotypes, characterized by their gene expression: no-rejection 54%, TCMR 16%, NKRL 13%, and injury 16%. Top TCMR transcripts were expressed in effector T cells; top NKRL transcripts were almost exclusively expressed in NK cells; and both had increased interferon-γ-inducible transcripts, which were more pronounced in TCMR. Most TCMR biopsies had significant parenchymal injury, molecular fibrosis, and abnormal biochemistry. NKRL biopsies had no excess of injury, fibrosis, or biochemistry abnormalities.
CONCLUSIONS: Optimized rejection algorithms indicate that some liver transplants manifest an NKRL state that is well tolerated in the short term postbiopsy and with minimal injury and relatively normal biochemistry, while also underscoring the potential of TCMR to produce extensive parenchymal injury
Treatment decision regret after precision prostatectomy: An analysis of patient-reported outcomes predicting decision regret
No full textOBJECTIVES: This study aimed to assess postoperative decision regret (DR) after precision prostatectomy (PP), a novel subtotal surgical technique for prostate cancer (PCa) that involves the preservation of the unilateral capsule and seminal vesicle, and to identify factors predictive of DR after PP.
MATERIALS AND METHODS: After a shared decision-making process, 128 patients underwent PP for the treatment of localised PCa. Given the subtotal nature of the surgery, patients were informed about the possibility of a detectable prostate-specific antigen and secondary treatment. Between 6 and 12 months of follow-up, DR was analysed using the previously validated decision regret score (DRS). A univariable linear regression analysis was performed to analyse factors predictive of DR after PP.
RESULTS: Between 6 and 12 months after PP, objective measurements of DR were obtained on 64 patients who completed the DRS. At the time of DRS, 16 patients were impotent (SHIM \u3c 17), while six were incontinent (≥1 pad/day). The median time to DRS was 10 months (IQR 7.5-11.8). Only two patients (3.1%) reported significant DR after PP (DRS \u3e 25), while 53 patients (83%) reported no regret (DRS = 0). The median DRS was 0 (0-0). Incontinence and impotence at the time of DRS predicted higher DR after PP (incontinence estimate: 11.3 ± 3.2, p \u3c 0.001; impotence estimate: 5.4 ± 2.3, p = 0.02).
CONCLUSIONS: The incidence of DR after PP is low, with only 3% of patients reporting significant regret. Patients who are either incontinent or impotent after PP are more likely to regret their decision. Further studies with larger sizes and longer follow-ups are required to measure the longitudinal trends in DR after PP
Influence of air quality on lung cancer in people who have never smoked
No full textObjective: Lung cancer is the leading cause of cancer-related death. The percentage of people who have never smoked with lung cancer has risen recently, but alternative risk factors require further study. Our goal was to determine the influence of air quality on incidence of lung cancer in people who have smoked or never smoked. Methods: The cancer registry from a large urban medical center was queried to include every new diagnosis of lung cancer from 2013 to 2021. Air quality and pollution data for the county were obtained from the US Environmental Protection Agency from 1980 to 2018. Patient demographics, location of residence, smoking history, and tumor stage were recorded. Bivariate comparison analyses were conducted in R (R Foundation for Statistical Computing). Results: A total of 2223 new cases of lung cancer were identified. Mean age was 69.2 years. There was a nonsmoking rate of 8.1%. A total of 37% of patients identified as a racial minority. People who have never smoked were more likely to be diagnosed at an advanced stage. When analyzing geographic distribution, incidence of lung cancer among people who have never smoked was more closely associated with highly polluted areas. People who have never smoked with lung cancer had significantly higher exposure levels of multiple pollutants. Conclusions: Newly diagnosed lung cancer appears to be more related to poor air quality among people who have never smoked than people who have smoked. Future studies are needed to examine the associations of specific pollutants with lung cancer incidence
Exploring Machine Learning Algorithms to Revise the Kidney Donor Risk Index
No full textIntroduction: The Kidney Donor Risk Index (KDRI), originally based on patients transplanted between 1995-2005, has been demonstrated as a poor predictor of graft failure (C-statistic: 0.62). Recent policy developments have removed race and Hepatitis C virus from the model with recalculation of the variable coefficients, but without re-analysis of the variables included. We sought to develop an updated KDRI in a modern cohort of kidney transplant recipients using both conventional and machine learning algorithms. Methods: Kidney transplant alone recipients transplanted between 2016-2023 were included. To minimize the impact of recipient factors on death-censored graft failure, recipients who were \u3c35 or \u3e65 years, had diabetes, peripheral vascular disease or prior transplant were excluded. The remaining recipients were randomized into development (80%) and testing (20%) cohorts. Regular Cox, Lasso Cox, Elastic Net Cox models, and Random Forest, XgBoost, and Neural Network models were fitted to predict the risk of 1-year death-censored graft failure with their respective C-statistics compared. Shapley plots were generated post-hoc from machine learning models for feature interpretability. Results: In this modern cohort, the original KDRI was a poor predictor of graft failure with a C-statistic of 0.594 but higher than the race-neutral KDRI (C-statistic 0.589). Regular Cox, Lasso Cox, Elastic Net Cox models, and Random Forest all performed equally well, with C-statistic of 0.62. XgBoost and Neural Net survival analysis performed less well (C-statistic 0.55 and 0.59, respectively). Variables included in the new model overlapped with original KDRI (donor age, height, weight, creatinine, diabetes, hypertension) but also included new variables (donor pH and \u3e20% glomerulosclerosis on biopsy), while some models excluded CVA as a cause of death. Conclusion: The discriminatory powe
Benefits of Earlier Apremilast Initiation in Patients with Psoriasis and Limited Skin Involvement: Results from a Real-World Retrospective Study
No full textINTRODUCTION: Many patients with psoriasis remain on topical therapy despite meeting criteria for systemic therapy. Our objective was to estimate the effect of earlier initiation of apremilast on attaining body surface area (BSA) treatment targets in patients with psoriasis in a real-world setting.
METHODS: This retrospective cohort study conducted in the OM1 database analyzed patients with psoriasis and a BSA value between ≥ 1 and ≤ 10% (on index date) who had initiated apremilast or a topical treatment. Relative risks were used to compare achieved BSA targets across treatment groups. Confounding, selection bias, and missing data may have been present, but measures were taken to limit their impact.
RESULTS: Of 3589 apremilast initiators, 2073 (57.8%) initiated early (≤ 6 months after index date) and 1516 (42.2%) initiated late (\u3e 6 months); separately, 9777 patients initiated their second or later topical treatment (topical users). Compared with early initiators, late initiators had higher BSA values at treatment initiation. Early apremilast initiators were more likely than topical users to achieve BSA ≤ 1% or ≥ 75% improvement in BSA (BSA-75) at 6 and 12 months after treatment initiation: for early apremilast initiators, the relative risks of achieving BSA ≤ 1% and BSA-75 compared with topical users were 1.54 (95% confidence interval [CI]: 1.27, 1.87) and 1.52 (95% CI: 1.21, 1.89), respectively, at 6 months, and 1.49 (95% CI: 1.23, 1.80) and 1.50 (95% CI: 1.22, 1.85), respectively, at 12 months.
CONCLUSIONS: Earlier initiation of apremilast, an oral systemic treatment, was associated with lower cumulative disease burden and increased likelihood of attaining BSA goals compared with topical users