Pediatric Elective Diagnostic Procedure Complications: A Multicenter Cohort Analysis.

BACKGROUND AND AIM: Increased access to endoscopic procedures have entrenched these investigative tools in routine pediatric gastroenterology practice. Patient outcomes following endoscopy therefore are topical in the decision toward endoscopy. We studied the likelihood and patient characteristics of children admitted following ambulatory endoscopy. METHODS: Hospitalization data were obtained from the Pediatric Hospital Information System including 49 tertiary children's hospitals in the USA. Children who underwent ambulatory diagnostic endoscopy between October 1, 2005 and September 25, 2015 were included. The primary outcomes were post-procedure events resulting in unplanned admission (not for inflammatory bowel disease management) or emergency room visit within 5 days. Unadjusted, univariate analyses were followed by multivariable analysis of the associations between patient characteristics and outcome using the R statistical package, v. 3.2.3. RESULTS: During the study period, 217 817 patients underwent diagnostic endoscopy; 101 (0.05%) patients were admitted directly; 1314 (0.60%) were admitted to the same facility's emergency department with either a respiratory or a gastrointestinal complication as a primary diagnosis within 5 days. None of the procedures resulted in death; female patients were more likely to experience adverse outcomes (P < 0.001), as were patients from an urban setting (P = 0.0004), whereas White, non-Hispanic patients were less likely to represent (P < 0.0001). Patients with chronic comorbidities were more likely to experience complications. The most frequent diagnoses at admission were abdominal pain (30.5%), other gastroenterologic processes (26.8%), respiratory disorders (17.1%), gastrointestinal hemorrhage (8.3%), and fever (4.5%). CONCLUSIONS: Ambulatory pediatric endoscopy is safe; significant adverse outcomes are rare but more likely in female, non-White or Hispanic patients and in patients with significant chronic comorbidities.

Monocyte Subsets Have Distinct Patterns of Tetraspanin Expression and Different Capacities to Form Multinucleate Giant Cells.

Monocytes are able to undergo homotypic fusion to produce different types of multinucleated giant cells, such as Langhans giant cells in response to M. tuberculosis infection or foreign body giant cells in response to implanted biomaterials. Monocyte fusion is highly coordinated and complex, with various soluble, intracellular, and cell-surface components mediating different stages of the process. Tetraspanins, such as CD9, CD63, and CD81, are known to be involved in cell:cell fusion and have been suggested to play a role in regulating homotypic monocyte fusion. However, peripheral human monocytes are not homogenous: they exist as a heterogeneous population consisting of three subsets, classical (CD14++CD16-), intermediate (CD14++CD16+), and non-classical (CD14+CD16+), at steady state. During infection with mycobacteria, the circulating populations of intermediate and non-classical monocytes increase, suggesting they may play a role in the disease outcome. Human monocytes were separated into subsets and then induced to fuse using concanavalin A. The intermediate monocytes were able to fuse faster and form significantly larger giant cells than the other subsets. When antibodies targeting tetraspanins were added, the intermediate monocytes responded to anti-CD63 by forming smaller giant cells, suggesting an involvement of tetraspanins in fusion for at least this subset. However, the expression of fusion-associated tetraspanins on monocyte subsets did not correlate with the extent of fusion or with the inhibition by tetraspanin antibody. We also identified a CD9High and a CD9Low monocyte population within the classical subset. The CD9High classical monocytes expressed higher levels of tetraspanin CD151 compared to CD9Low classical monocytes but the CD9High classical subset did not exhibit greater potential to fuse and the role of these cells in immunity remains unknown. With the exception of dendrocyte-expressed seven transmembrane protein, which was expressed at higher levels on the intermediate monocyte subset, the expression of fusion-related proteins between the subsets did not clearly correlate with their ability to fuse. We also did not observe any clear correlation between giant cell formation and the expression of pro-inflammatory or fusogenic cytokines. Although tetraspanin expression appears to be important for the fusion of intermediate monocytes, the control of multinucleate giant cell formation remains obscure.

Nonresponse to neoadjuvant chemotherapy for muscle-invasive urothelial cell carcinoma of the bladder.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NC) is commonly used in the treatment of muscle-invasive urothelial cell carcinoma of the bladder (UC) and has been shown to improve survival. However, not all patients respond to NC, thus delaying the interval to potentially curative surgical therapy, risking disease progression and subjecting patients to potential morbidity from NC. In this study, we perform a retrospective analysis of patients who received NC prior to cystectomy to identify factors associated with nonresponse. PATIENTS AND METHODS: We identified 80 patients with clinical T2 to T4, N0 to N1 UC of the bladder who received NC and underwent radical cystectomy. Nonresponse was defined as patients with higher pathologic T stage than clinical stage or patients with nodal involvement identified on final pathology. RESULTS: Overall, 20% of patients were considered nonresponders. In multivariate analysis, age was predictive of nonresponse (P(trend) < .05). Compared with those < 60 years of age, those aged 60 to 69 years (odds ratio [OR], 2.9; 95% CI, 0.7-12) and those aged ≥ 70 (OR, 5.0; 95% CI, 0.9-28) had higher odds of nonresponse. Patients who received gemcitabine-carboplatin had higher odds of nonresponse compared with those who received gemcitabine-cisplatin (OR, 4.4; 95% CI, 0.8-21). CONCLUSION: A subset of patients receiving NC prior to cystectomy will experience disease progression. Future study will need to better identify methods to distinguish individuals more likely to benefit from NC and those that should receive upfront cystectomy.

Pathologic Response Rates of Gemcitabine/Cisplatin versus Methotrexate/Vinblastine/Adriamycin/Cisplatin Neoadjuvant Chemotherapy for Muscle Invasive Urothelial Bladder Cancer.

Objectives. To compare pathologic outcomes after treatment with gemcitabine and cisplatin (GC) versus methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) in the neoadjuvant setting. Methods. Data was retrospectively collected on 178 patients with T2-T4 bladder cancer who underwent radical cystectomy between 2003 and 2011. Outcomes of interest included those with complete response (pT0) and any response (≤pT1). Odds ratios were calculated using multivariate logistic regression. Results. Compared to those who did not receive neoadjuvant chemotherapy, there were more patients with complete response (28% versus 9%, OR 3.11 (95% CI: 1.45-6.64), P = 0.03) and any response (52% versus 25%, OR 3.23 (95% CI: 1.21-8.64), P = 0.01). Seventy-two patients received GC (n = 41) or MVAC (n = 31). CR was achieved in 29% and 22% of GC and MVAC patients, respectively (multivariate OR 0.39, 95% CI 0.10-1.58). Any response (≤pT1) was achieved in 56% of GC and 45% of MVAC patients (multivariate OR 0.45, 95% CI 0.12-1.71). Conclusions. We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of patients with muscle invasive urothelial cancer (MIBC). Our findings support the use of GC as an alternative regimen in the neoadjuvant setting.