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AbstractIntroductionCurrent National Comprehensive Cancer Network guidelines for Stages II and III rectal cancer recommend neoadjuvant chemoradiation followed by curative intent surgery and adjuvant chemotherapy. It is unclear whether therapies in addition to surgery are truly beneficial in elderly patients. Our aim was to compare the survival of patients over 80 with Stages II and III rectal cancer undergoing curative intent surgery with or without additional therapy.Materials and methodsThe National Cancer Data Base (NCDB 2006–2011) was queried for patients over 80 with Stages II and III rectal cancer. The primary outcome was overall survival. Patients were stratified based upon therapy group. Univariate group comparisons were made. Unadjusted Kaplan–Meier and multivariable Cox proportional hazards modeling survival analyses were performed.ResultsThe query yielded 3098 patients over 80 with Stage II (N = 1566) or Stage III (N = 1532) disease. Approximately, half of the patients received surgery only. Kaplan–Meier analysis showed improved survival for patients receiving neoadjuvant and/or adjuvant therapy in addition to surgery, but there was no significant difference between those that received guideline concordant care (GCC), neoadjuvant chemoradiation only, or post‐operative chemotherapy only. Cox proportional hazard modeling identified age >90 and margin positivity as independent risk factors for decreased overall survival.ConclusionAnalysis of NCDB data for Stages II and III rectal cancer in patients over 80 shows a survival benefit of adjuvant and/or neoadjuvant therapy over surgery alone. There does not appear to be a difference in survival between patients who received neoadjuvant chemoradiation, post‐resection adjuvant chemotherapy, or GCC.

Abstract Rationale Mycobacterium abscessus group lung infection is characterized by low cure rates. Improvement in quality of life may be a reasonable treatment goal. Objectives The objective of this study was to evaluate change in quality of life in response to therapy, predictors of improvement in quality of life, and association of quality of life with traditional outcome measures. Methods Forty-seven patients were treated for Mycobacterium abscessus group lung infection (including one with Mycobacterium chelonae) and were followed prospectively for 2 years between December 2009 and May 2012. St. George’s Respiratory Questionnaire (SGRQ) was administered, chest computed tomography (CT) imaging was carried out, and culture data were collected at multiple time points. Predictors of improvement in the SGRQ total score greater than or equal to a minimal clinically important difference (MCID) at 12 months were evaluated. Measurements and Main Results: Patients were 85% female and 94% white, with a mean age of 65 years. Nine (20%) had a genetic diagnosis of cystic fibrosis (none F508del homozygous). Coinfection with Mycobacterium avium complex occurred in 28% and Pseudomonas in 26%. Chest CT imaging universally indicated bronchiectasis and nodules; 51% had lung cavities. Treatment included a mean of 17 months of antibiotics, and lung resection in 34%. Seventeen patients with M. avium complex (36%) and one with Mycobacterium kansasii were treated for coinfection. The mean SGRQ total score (SD) at baseline was 35 (20). At all follow-up time points, the mean SGRQ total score (SD) was significantly lower (better) than at baseline: 27 (17) at 3 months, P < 0.01; 27 (19) at 6 months, P < 0.01; 27 (20) at 12 months, P < 0.01; and 30 (22) at 24 months, P = 0.02. At 12 and 24 months, respectively, 60% and 56% had improvement greater than or equal to the MCID in SGRQ total score. Improvement greater than or equal to the MCID at 12 months was positively associated with a history of respiratory exacerbation, isolate susceptible to imipenem-cilastatin, and lung resection surgery, and negatively associated with nodules >4 mm in diameter on chest CT imaging, but these associations were not statistically significant in multivariable analysis. At 24 months, 16 patients (48%) with complete data were culture negative for 1 year and had discontinued M. abscessus group treatment. Conclusions Quality of life was a sensitive indicator of treatment response and has the potential to be a useful parameter to guide treatment.

Nephrolithiasis is one of the most common urinary tract disorders, with the majority of kidney stones composed of calcium oxalate (CaOx). Given its prevalence (US occurrence 10%), it is still poorly understood, lacking progress in identifying new therapies because of its complex etiology. Drosophila melanogaster (fruitfly) is a recently developed model of CaOx nephrolithiasis. Effects of sulfate and thiosulfate on crystal formation were investigated using the Drosophila model, as well as electrophysiological effects on both Drosophila (Slc26a5/6; dPrestin) and mouse (mSlc26a6) oxalate transporters utilizing the Xenopus laevis oocyte heterologous expression system. Results indicate that both transport thiosulfate with a much higher affinity than sulfate Additionally, both compounds were effective at decreasing CaOx crystallization when added to the diet. However, these results were not observed when compounds were applied to Malpighian tubules ex vivo. Neither compound affected CaOx crystallization in dPrestin knockdown animals, indicating a role for principal cell-specific dPrestin in luminal oxalate transport. Furthermore, thiosulfate has a higher affinity for dPrestin and mSlc26a6 compared with oxalate These data indicate that thiosulfate's ability to act as a competitive inhibitor of oxalate via dPrestin, can explain the decrease in CaOx crystallization seen in the presence of thiosulfate, but not sulfate. Overall, our findings predict that thiosulfate or oxalate-mimics may be effective as therapeutic competitive inhibitors of CaOx crystallization.

Objectives/Hypothesis Idiopathic subglottic stenosis (iSGS) is a rare and potentially life‐threatening disease marked by recurrent and progressive airway obstruction frequently requiring repeated surgery to stabilize the airway. Unknown etiology and low disease prevalence have limited the ability to characterize the natural history of iSGS and resulted in variability in surgical management. It is uncertain how this variation relates to clinical outcomes. Study Design Medical record abstraction. Methods Utilizing an international, multi‐institutional collaborative, we collected retrospective data on patient characteristics, treatment, and clinical outcomes. We investigated variation between and within open and endoscopic treatment approaches and assessed therapeutic outcomes; specifically, disease recurrence and need for tracheostomy at last follow‐up. Results Strikingly, 479 iSGS patients across 10 participating centers were nearly exclusively female (98%, 95% confidence interval [CI], 96.1–99.6), Caucasian (95%, 95% CI, 92.2–98.8), and otherwise healthy (mean age‐adjusted Charlson Comorbidity Index 1.5; 95% CI, 1.44–1.69). The patients presented at a mean age of 50 years (95% CI, 48.8–51.1). A total of 80.2% were managed endoscopically, whereas 19.8% underwent open reconstruction. Endoscopic surgery had a significantly higher rate of disease recurrence than the open approach (chi 2 = 4.09, P = 0.043). Tracheostomy was avoided in 97% of patients irrespective of surgical approach (95% CI, 94.5–99.8). Interestingly, there were outliers in rates of disease recurrence between centers using similar treatment approaches. Conclusion Idiopathic subglottic stenosis patients are surprisingly homogeneous. The heterogeneity of treatment approaches and the observed outliers in disease recurrence rates between centers raises the potential for improved clinical outcomes through a detailed understanding of the processes of care. Level of Evidence 4. Laryngoscope , 126:1390–1396, 2016

Abstract B lymphocytes play an essential regulatory role in the adaptive immune response through Ab production during infection. A less known function of B lymphocytes is their ability to respond directly to infectious Ags through stimulation of pattern recognition receptors expressed on their surfaces. β-Glucans are carbohydrates present in the cell wall of many pathogenic fungi that can be detected in the peripheral blood of patients during infection. They have been shown to participate in the innate inflammatory response, as they can directly activate peripheral macrophages and dendritic cells. However, their effect as direct stimulators of B lymphocytes has not been yet fully elucidated. The aim of this study was to examine the molecular mechanisms and cytokine profiles generated following β-glucan stimulation of B lymphocytes, compared with the well-established TLR-9 agonist CpG oligodeoxynucleotide (CpG), and study the participation of β-glucan–stimulated B cells in the innate immune response. In this article, we demonstrate that β-glucan–activated B lymphocytes upregulate proinflammatory cytokines (TNF-α, IL-6, and IL-8). Of interest, β-glucan, unlike CpG, had no effect on B lymphocyte proliferation or IgM production. When compared with CpG (TLR9 agonist), β-glucan–activated cells secreted significantly higher levels of IL-8. Furthermore, IL-8 secretion was partially mediated by Dectin-1 and required SYK, MAPKs, and the transcription factors NF-κB and AP-1. Moreover, we observed that conditioned media from β-glucan–stimulated B lymphocytes elicited neutrophil chemotaxis. These studies suggest that β-glucan–activated B lymphocytes have an important and novel role in fungal innate immune responses.

OBJECT In this clinically based systematic review of cervical facet fractures, the authors’ aim was to determine the optimal clinical care for patients with isolated fractures of the cervical facets through a systematic review. METHODS A systematic review of nonoperative and operative treatment methods of cervical facet fractures was performed. Reduction and stabilization treatments were compared, and analysis of postoperative outcomes was performed. MEDLINE and Scopus databases were used. This work was supported through support received from the Association for Collaborative Spine Research and AOSpine North America. RESULTS Eleven studies with 368 patients met the inclusion criteria. Forty-six patients had bilateral isolated cervical facet fractures and 322 had unilateral isolated cervical facet fractures. Closed reduction was successful in 56.4% (39 patients) and 63.8% (94 patients) of patients using a halo vest and Gardner-Wells tongs, respectively. Comparatively, open reduction was successful in 94.9% of patients (successful reduction of open to closed reduction OR 12.8 [95% CI 6.1–26.9], p < 0.0001); 183 patients underwent internal fixation, with an 87.2% success rate in maintaining anatomical alignment. When comparing the success of patients who underwent anterior versus posterior procedures, anterior approaches showed a 90.5% rate of maintenance of reduction, compared with a 75.6% rate for the posterior approach (anterior vs posterior OR 3.1 [95% CI 1.0–9.4], p = 0.05). CONCLUSIONS In comparison with nonoperative treatments, operative treatments provided a more successful outcome in terms of failure of treatment to maintain reduction for patients with cervical facet fractures. Operative treatment appears to provide superior results to the nonoperative treatments assessed.

AbstractBackgroundRejection of Gal‐free (GTKO) donor pig cardiac xenografts is strongly associated with vascular non‐Gal antibody binding, endothelial cell (EC) injury, and activation and microvascular thrombosis. We adopted a pig‐to‐SCID/beige small animal transplant model to compare the pathogenicity of baboon and human anti‐pig antibody.MethodsWild‐type (GT+) or GTKO porcine coronary arteries (PCAs) were transplanted into the infrarenal aorta of SCID/beige mice. Three days after transplant, recipients were infused with anti‐pig antibody (anti‐SLA class I, an isotype control, naive or sensitized baboon serum, or naive human serum). PCAs were recovered 24 h after antibody infusion and examined using histology, immunohistochemistry, and in situ hybridization.ResultsDose‐dependent intragraft thrombosis occurred after infusion of anti‐SLA I antibody (but not isotype control) in GT+ and GTKO PCA recipients. Naive baboon serum induced thrombosis in GT+ grafts. Thrombosis was significantly reduced by pre‐treating naive baboon serum with Gal polymer and not observed when this serum was infused to GTKO PCA recipients. Naive human serum caused dose‐dependent intragraft thrombosis of GTKO PCAs. In all cases, thrombosis involved graft‐specific vascular antibody and complement deposition, macrophage adherence, EC delamination, and subendothelial thrombus formation.ConclusionsThis study provides the first direct in vivo comparison of the pathogenicity of naive human and baboon serum. The results suggest that human preformed non‐Gal antibody may have increased pathogenicity compared to baboon. This model, which showed a rejected graft histopathology similar to antibody‐mediated rejection in cardiac xenotransplantation, may be useful to assess the pathogenicity of individual protein or carbohydrate specific non‐Gal reactive antibodies.