Zhang, Nan

AbstractBackgroundPrevious literature on cutaneous squamous cell carcinoma (cSCC) suggests that the incidence, rate of metastasis, and tumour severity of cSCC are higher in immunosuppressed patients than in immunocompetent patients. However, current literature lacks an extensive comparison of cSCC clinical characteristics and outcomes in immunosuppressed patients.ObjectivesWe compared cSCC tumour characteristics and disease‐related outcomes to help guide the clinical management of immunosuppressed patients.MethodsWe conducted a retrospective review of histopathologic and clinical data from 935 cSCC cases (19.5% immunosuppressed) from the Mayo Clinic.ResultsImmunosuppression was associated with younger age (69.3 vs. 74.8 years old, p < 0.0001), male gender (78.6% vs. 67.2%, p = 0.003), and higher grade cSCC tumour characterized by moderate or poor differentiation (25.7% vs. 15.8%, p = 0.009; 9.2% vs. 7.2%, p = 0.009, respectively). No significant differences were found in other tumour characteristics, including clinical tumour dimension, Brigham and Women's Hospital tumour staging or cumulative risk of metastasis and recurrence. Immunosuppressed patients had an increased risk of disease‐specific death on univariate analysis (hazard ratio [HR] [95% confidence interval, CI] 2.05 [1.13–3.74], p = 0.0128). Overall survival in the immunosuppressed population was worse (adjusted HR [95% CI] 1.83 [1.42–2.35], p < 0.001) and, notably, solid organ transplant recipients had the lowest overall survival when stratifying immunosuppressed patients by immunosuppression type (HR [95% CI] 1.62 [1.17–2.24], p < 0.0001).ConclusionsIn our study, immunosuppression status was predictive of poor differentiation of tumours and a reduction in overall and cSCC‐specific survival. Current staging systems for cSCC do not include immunosuppression as a risk factor and incorporating immune status may be beneficial for accurate risk stratification.

Objectives: Gain insights into the pathophysiology of idiopathic subglottic stenosis (iSGS) by investigating differences in transcriptome of subglottic mucosal tissue between patients with iSGS and controls, and between tracheal and subglottic tissue within patients. Methods: RNA sequencing was conducted on biopsied mucosal samples collected from subglottic and tracheal (in-patient control) regions in iSGS patients, and from subglottis in controls. The gene expression differences were validated on a protein level by (1) staining the tissue samples obtained from a second cohort of patients and controls; and (2) in vitro functional assays using primary subglottic epithelial cells from both iSGS patients and healthy donors. Results: We found 7 upregulated genes in the subglottic region of iSGS patients relative to both the tracheal mucosa and subglottic region of controls. A gene ontology enrichment analysis found that the epithelial cell differentiation and cornification pathways are significant, involving specifically 3 of the genes: involucrin ( IVL), small proline rich protein 1B ( SPRR1B), and keratin 16 ( KRT16). Involvement of these pathways suggests squamous metaplasia of the epithelium. Histological analyses of epithelium in subglottic mucosal biopsies revealed squamous metaplasia in 41% of the samples from iSGS patients and in 25% from controls. Immunohistochemical evaluation of the samples presented with squamous epithelium revealed increased expression of the protein encoded by SPRR1B, hyperproliferative basal cells, shedding of apical layers, and accompanying lesions in iSGS compared to CTRL. Cultured primary subglottic epithelial cells from iSGS patients had higher proliferation rates compared to healthy donors and squamous metaplastic differentiation formed thinner epithelia with increased expression proteins encoded by INV, SPRR1B, and KRT16, suggesting intrinsic dysfunction of basal cells in iSGS. Conclusions: Abnormal squamous differentiation of epithelial cells may contribute to the pathogenesis of iSGS. Patients having metaplastic epithelial phenotype may be sensitive to drugs that reverse it to a normal phenotype.

Health insurance literacy (HIL) constructs are related to financial toxicity in patients with cancer.

AbstractPurposeTo determine whether a 24 MHz transducer significantly improves sensitivity, specificity and accuracy in evaluating flexor tendon repair integrity compared with an 18 MHz transducer.MethodsOne hundred and twelve cadaveric digits were randomised to an intact repair or simulated ‘failed’ repair, and to a two‐ or eight‐strand repair of a flexor digitorum profundus laceration. A blinded sonologist evaluated specimens in static mode using 18 and 24 MHz transducers. Gaps were remeasured after scanning, and final gap width recorded. McNemar's exact test calculated differences between sensitivity, specificity and accuracy, and chi‐squared test to compare sensitivity, specificity and accuracy between number of strands (2 vs. 8) and repair gap (≥4 mm).ResultsThe 24 MHz transducer had higher sensitivity (81 vs. 59%), lower specificity (67 vs. 70%) and higher overall accuracy (74 vs. 64%), than the 18 MHz transducer. The difference for sensitivity was significant (P = 0.011), but not differences for specificity and overall accuracy (P > 0.05). Pearson's correlation (r = 0.61) demonstrated a moderate‐to‐strong positive correlation between measured and true gap sizes. Increased number of suture strands (2 vs. 8) did not impair sensitivity, specificity nor accuracy.DiscussionUltrasound may tend to overestimate gap width, and a slight risk that some intact repairs, or those with small, clinically insignificant gaps may undergo surgical exploration that may not be indicated.ConclusionsA 24 MHz transducer is a more sensitive and accurate transducer for assessing flexor tendon repair integrity and measuring small gaps.

Abstract Objective Our objectives were to examine cross‐sectional correlations of headache disability with measures of resilience, anxiety, and depression, and to determine if resilience modified the association between headache severity/frequency and disability. Background Resilience is associated with quality of life and functioning among patients with chronic conditions. We investigated whether resilience strongly mitigates headache‐related disability as measured by the Migraine Disability Assessment (MIDAS). Methods We prospectively recruited 160 patients with primary headache disorders seen in a tertiary headache medicine program between February 20, 2018 and August 2, 2019. Each participant completed the MIDAS, Conner Davidson Resilience Scale (CDRS‐25), Patient Health Questionnaire‐9 (PHQ‐9), Generalized Anxiety Disorder‐7 (GAD‐7), and WHO‐5 Well‐Being Index. Results The CDRS‐25 score was negatively correlated with the total MIDAS ( r = −0.21, p = 0.009), GAD‐7 ( r = −0.56, p < 0.001), and PHQ‐9 scores ( r = −0.34, p < 0.001). Well‐being inversely correlated with disability ( r = −0.37, p < 0.001). Increases in anxiety and depression increased the odds of disability. A 1 point increase in the CDRS‐25 score decreased the odds of being severely disabled by 4% (OR = 0.96, 95% CI: 0.94 to 0.99, p = 0.001). However, the CDRS‐25 score did not significantly moderate the association between headache days and disability. Conclusion Traits associated with resilience decreased the odds of severe disability from headaches, whereas anxiety, depression, and headache frequency were strongly associated with higher disability from headache.

Background: Essential tremor (ET) is a common movement disorder in which cerebellar microscopic and volume alterations have been repeatedly reported although with disagreement between studies. However, pronounced heterogeneity was found with regard to cerebellar volume alterations. Objective: This study aimed to assess postmortem cerebellar volume in subjects with or without ET, as compared with subjects with multiple system atrophy (MSA), a well-established cerebellar neurodegeneration. Methods: Cases with ET ( n = 29), MSA ( n = 7), and non-demented control cases without any movement disorder ( n = 22) were selected from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), a longitudinal clinicopathological study with annual research-dedicated clinical assessments by neuropsychologists, subspecialist movement disorders, and cognitive/behavioral neurologists, with comprehensive neuropathological examinations after death. Group comparisons were controlled for common age-related neurodegenerative and cerebrovascular pathologies. Cerebellar volumes were calculated using digital images of slices taken at the time of autopsy, immediately after brain removal and before fixation. Results: Cerebellar volume was not reduced in ET subjects compared to controls. The two groups did not differ in terms of incidental cerebrovascular and Alzheimer’s disease neuropathology. In contrast, cerebellar volume was significantly reduced in subjects with MSA when compared to ET and control subjects. Conclusion: In a well-characterized cohort, postmortem cerebellar volume measurements suggest that there are no volume alterations in ET when compared to controls, in contrast to significant cerebellar atrophy in subjects with MSA.

Background. End-stage kidney disease patients with concomitant heart failure (HF) with reduced ejection fraction are often denied kidney transplantation. The aims of this study were to explore factors predictive of suitability for kidney transplant and to assess cardiovascular outcomes in patients with impaired left ventricular ejection fraction (LVEF) after transplant. Methods. We evaluated 109 consecutive adults with LVEF ≤40% at the time of initial kidney transplant evaluation between 2013 and 2018. Posttransplant cardiovascular outcomes were defined as nonfatal myocardial infarction (MI), admission for HF, cardiovascular death, and all-cause mortality. Results. A cardiologist participated in kidney transplant evaluation for 87% of patients and was present at 49% of transplant selection conferences. Twenty-four patients (22%) were denied by a cardiologist for kidney transplant‚ and 59 (54%) were denied by the selection committee, of whom 43 were because of cardiovascular risk. Forty-two (38%) patients were approved for kidney transplant. On univariate analysis, the variables associated with denial for kidney transplant included cardiologist denial, higher cardiac troponin T, prior coronary intervention, cardiovascular event, positive stress study, lower ejection fraction, and lower VO2 max (all P < 0.05). Cardiologist denial was the most significant predictor of denial for kidney transplant in different multivariate models. At a median follow-up of 15 mo, 5 (5%) suffered nonfatal MI, 13 (12%) were hospitalized for HF exacerbation, and 17 (16%) died. Only 22 patients, 52% of those approved, underwent kidney transplant. After kidney transplant, there was 1 death, 1 nonfatal MI, and 3 hospitalizations for HF. Median LVEF improved from 38% before listing to 55% posttransplant. Conclusions. Cardiologist denial was the primary predictor of rejection for kidney transplant. Despite careful selection, prevalence of cardiovascular events and mortality after kidney transplant was 23%. There is need for a structured multidisciplinary approach for patients with impaired LVEF.

ABSTRACT Background Serum cystatin C–based estimated glomerular filtration rate (eGFRcys) generally associates with clinical outcomes better than serum creatinine–based eGFR (eGFRcr) despite similar precision in estimating measured GFR (mGFR). We sought to determine whether the risk of adverse outcomes with eGFRcr or eGFRcys was via GFR alone or also via non-GFR determinants among kidney transplant recipients. Methods Consecutive adult kidney transplant recipients underwent a standardized GFR assessment during a routine follow-up clinic visit between 2011 and 2013. Patients were followed for graft failure or the composite outcome of cardiovascular (CV) events or mortality through 2020. The risk of these events by baseline mGFR, eGFRcr and eGFRcys was assessed unadjusted, adjusted for mGFR and adjusted for CV risk factors. Results There were 1135 recipients with a mean baseline mGFR of 55.6, eGFRcr of 54.8 and eGFRcys of 46.8 ml/min/1.73 m2 and a median follow-up of 6 years. Each 10 ml/min/1.73 m2 decrease in mGFR, eGFRcr or eGFRcys associated with graft failure [hazard ratio (HR) 1.79, 1.68 and 2.07, respectively; P &lt; .001 for all) and CV events or mortality outcome (HR 1.28, 1.19 and 1.43, respectively; P &lt; .001 for all). After adjusting for mGFR, eGFRcys associated with graft failure (HR 1.57, P &lt; .001) and CV events or mortality (HR 1.49, P &lt; .001), but eGFRcr did not associate with either. After further adjusting for CV risk factors, risk of these outcomes with lower eGFRcys was attenuated. Conclusion eGFRcr better represents the true relationship between GFR and outcomes after kidney transplantation because it has less non-GFR residual association. Cystatin C is better interpreted as a nonspecific prognostic biomarker than is eGFR in the kidney transplant setting.

Objectives: To date, there are no specific guidelines on antithrombotic therapy (ATT) management, which includes both anticoagulation and antiplatelet medications, for open tracheostomy. The objective of this study was to evaluate whether the use of perioperative antithrombotic medication during open tracheostomy influences the incidence of perioperative or postoperative complications. Methods: A retrospective review was conducted of all patients who underwent open tracheostomies at a tertiary care medical center from January 2015 to December 2019. Charts were reviewed for demographics, comorbidities, indication for tracheostomy, ATT use, operative details, and complications. Results: A total of 217 tracheostomies were evaluated for this study, of which 148 (68.2%) were not on ATT and 69 (31.8%) were on ATT during surgery. No significant difference was observed based on ATT status in perioperative bleeding ( P = .983), postoperative bleeding ( P = .24), or median days to decannulation ( P = .5986). ATT patients were 2.67 times more likely to experience 30-day mortality than those non-ATT patients ( P = .035). There was only one death due to hemorrhage in the ATT group. This was unrelated to the tracheostomy. This compares to 2 hemorrhage-related deaths in those not on ATT. Conclusion: There was no significant difference in perioperative or postoperative bleeding based on ATT use. Patients on ATT were significantly more likely to experience 30-day mortality, however only one death was due to hemorrhage in the ATT group and was unrelated to tracheostomy. Therefore, continued perioperative ATT use appears to be safe when performing open tracheostomy. Level of Evidence: 4