Association Between Metastatic Melanoma Response to Checkpoint Inhibitor Therapy and Tumor-Infiltrating Lymphocyte Classification on Primary Cutaneous Melanoma Biopsies.

This cohort study examines the association between tumor-infiltrating lymphocyte classification and disease progression among patients with metastatic primary cutaneous melanoma receiving checkpoint inhibitor therapy.

Thymoglobulin Versus Alemtuzumab Versus Basiliximab Kidney Transplantation From Donors After Circulatory Death.

Introduction: The Campath, Calcineurin inhibitor (CNI) reduction, and Chronic allograft nephropathy (3C), a study comparing alemtuzumab versus basiliximab induction immunosuppression in kidney transplants, has found lower acute rejection rate with alemtuzumab but same graft survival. The aim of the current study is to evaluate the effect of induction immunosuppression (thymoglobulin, alemtuzumab, basiliximab) on the outcome of kidneys of donors after circulatory death (DCD). Methods: Data of the 274 DCD patients of the 3C obtained from the sponsor were compounded with the 140 DCD patients who received thymoglobulin in a single center with the same entry criteria as the 3C, giving 414 patients on 3 induction regimes. Results: There were more male donors (P < 0.05) and human leukocyte antigen and DR mismatched patients in the thymoglobulin group (P < 0.001). Death-censored graft survival at 6 months was 98.6% in the thymoglobulin, 95.5% in the alemtuzumab (P = 0.08), and 95.7% in the basiliximab group (P = 0.09) and at 2 years 97.9% versus 94.8% (P = 0.13, hazard ratio [HR] 2.8, 95% CI 0.7-10.9) versus 94.3% (P = 0.06, HR 3.5, 95% CI 0.9-13.6), respectively.The 2-year overall graft survival was 95% in the thymoglobulin versus 88% in the alemtuzumab (unadjusted P = 0.038, adjusted HR 2.4, 95% CI 0.99-5.9) and 91.4% in the basiliximab group (P = 0.21). The 2-year patient survival was numerically less in the alemtuzumab compared with the thymoglobulin group (91.8% vs. 97.1%, P = 0.052, HR 2.90, 95% CI 0.93-9.2). Acute rejection was 17% in the basiliximab, 4.3% in the thymoglobulin, and 6% in the alemtuzumab group (P < 0.001). Conclusion: In DCD transplants, thymoglobulin induction may provide advantage over alemtuzumab in patient survival and the same advantage as alemtuzumab over basiliximab in terms of acute rejection. Differing maintenance immunosuppression may contribute to the difference found.

An Intrapatient Concordance Study of Mismatch Repair Protein Immunohistochemical Staining Patterns in Patients With Muir-Torre Syndrome.

Importance: Appropriate use criteria for Muir-Torre syndrome (MTS) screening suggest that mismatch repair protein (MMRP) immunohistochemical (IHC) testing is usually appropriate in patients with 2 or more sebaceous neoplasms (SNs). While MTS is known to be caused by a germline mutation in mismatch repair genes, data are limited as to whether individual sebaceous tumors in these patients with multiple lesions show identical MMRP IHC staining patterns. Objective: To determine concordance of MMRP IHC staining patterns in lesions of patients with MTS who have multiple SNs. Design, Setting, and Participants: This retrospective single-center case series evaluated 38 SNs in 11 patients with MTS confirmed by genetic testing for MMRP IHC staining patterns. Tumor sites were classified as either facial or extrafacial. Data were collected between January 1, 2007, and January 1, 2018. Main Outcomes and Measures: In each patient, MMRP IHC staining patterns for SNs were compared with one another to evaluate intrapatient concordance between lesions, and to the patient's known germline mutation. Results: A total of 11 patients (7 women and 4 men) with MTS, with a mean (SD) age of 59.3 (10.6) years at time of SN biopsy, were identified. There was high concordance between MMRP IHC staining results (2-4 lesions per patient) and the patient's mutation status, with 36 of 38 total lesions (95%) matching (sensitivity, 94.7%; 95% CI, 82.3%-99.4%). Extrafacial site tumors represented 16 of 38 total lesions (42%) and demonstrated 100% concordance of IHC results to germline mutation. Only 1 of 11 patients (9%) demonstrated discordant results, with both lesions in this patient occurring on a facial site. Conclusions and Relevance: In patients with known MTS, SNs present with highly concordant MMRP IHC staining profiles across multiple lesions. There is also a strong association with underlying germline mutations. A diagnosis of MTS might be supported by MMRP IHC when the pretest probability is high.

Acquired port-wine stains in six pediatric patients.

BACKGROUND/OBJECTIVES: Port-wine stains, also known as capillary malformations, are due to dermal vascular ectasia and dilation and are most commonly congenital; however, acquired port-wine stains (APWS) developing later in life have been noted in the literature, most commonly in the context of trauma. METHODS/RESULTS: This case series presents 6 pediatric patients with APWS who first developed lesions between ages 3 and 11 years in the absence of a traumatic or other etiologic trigger. CONCLUSIONS: The epidemiology, clinical features, and treatment response of these patients are compared to what has been previously described in other cases in the literature.

Wait times, health care touchpoints, and nonattendance in an academic pediatric dermatology clinic.

BACKGROUND AND OBJECTIVES: Timely access to pediatric dermatology care remains a challenge. While awaiting appointments, many patients and families utilize so-called health care touchpoints outside of the dermatology clinic such as primary care or emergency department visits to address dermatologic concerns. Long waiting periods also factor into nonattendance rates at pediatric dermatology appointments. This observational retrospective study investigated wait times, relevant health care touchpoints, and factors related to nonattendance at a pediatric dermatology clinic. METHODS: We reviewed demographic, health care touchpoint, and nonattendance data for patients referred by a primary care affiliate to the Children's Hospital of Philadelphia (CHOP) pediatric dermatology clinic from February 2016 to May 2017. Descriptive statistics were used to identify trends among analyzed variables. RESULTS: We reviewed 250 patient records. The average number of touchpoints per patient was 0.56, and factors that significantly correlated with increased numbers of touchpoints included younger patient age and longer wait time while payer, primary diagnosis, and time of year were not associated. The nonattendance rate was 26%, and factors significantly associated with increased nonattendance rate included longer wait times and winter and spring appointments. CONCLUSION: Long wait times impact numbers of touchpoints and appointment attendance rate when referring to pediatric dermatology. A platform such as teledermatology may represent an opportunity to improve access to care by allowing for earlier input from the pediatric dermatologist.

'Educational' Deprivation is Associated with PD Peritonitis.

BACKGROUND: Socioeconomic deprivation is an important factor in determining poor health and is associated with a higher prevalence of many chronic diseases, including renal failure, and often poorer outcomes for patients with such conditions. The aim of this study was to investigate the effect of deprivation on peritonitis episodes following peritoneal dialysis (PD)-catheter insertion. METHODS: The Welsh Index of Multiple Deprivation (WIMD) was used to assess the influence of socioeconomic deprivation on outcomes following 233 consecutive first PD-catheter insertions from a single institution in the United Kingdom, performed between 2010 and 2015. The primary outcome measure was the presence of peritonitis episodes. RESULTS: Peritoneal dialysis catheters were inserted in 243 patients, of which data were available for 233. Fifty-four patients experienced at least 1 episode of peritonitis. Overall, more patients in the most deprived group (vs least deprived) experienced peritonitis, although this was not statistically significant. When analyzing the severity of the peritonitis, within the 'Education' domain of the WIMD, significantly more patients from the most deprived group (compared with the least deprived group) experienced '2 or more peritonitis' episodes (p = 0.04) and were hospitalized for antibiotics (p = 0.02). CONCLUSION: This study has shown that patients who live in more 'educationally' deprived areas are more likely to have multiple episodes of peritonitis requiring hospital admission following PD-catheter insertions.

The impact of distance from transplant unit on outcomes following kidney transplantation.

BACKGROUND: Following transplantation, many patients travel long distances for follow-up care. Many studies have examined the influence of distance from transplant centre on access to transplantation, but few have examined post-transplant outcomes. MATERIALS AND METHODS: Distance from transplant centre was calculated for all kidney transplant recipients transplanted over a 5-year period. Outcomes measured were rates of acute rejection, graft and patient survival. RESULTS: Complete follow up data was available for 571 of the 585 kidney transplants performed over the study period. Distance from home to transplant centre ranged from 1.3 to 257.4 km (median 33.7 km). Patients were divided into quartiles according to their distance from the transplant centre. Distance from the transplant centre did not influence rates of acute rejection (p = 0.102). One-year graft survival for 'nearest' and 'farthest' quartiles was 99% and 97% respectively and five-year graft survival was 78% and 89% respectively (log rank p-value of 0.212). There were no differences in patient survival at 1 and 5 years between the 'nearest' and 'farthest' groups. CONCLUSION: Distance from transplant centre does not affect early outcomes following kidney transplantation. The centralized practice which involves a low threshold for rapid assessment and readmission of patients post-transplantation appears to provide good outcomes for kidney transplant recipients.

The influence of socioeconomic deprivation on early outcomes in vascular access surgery.

INTRODUCTION: Socioeconomic deprivation is an important factor in determining poor health and is associated with a higher prevalence of many chronic diseases including diabetes and renal failure, and often poorer outcomes for patients with such conditions. The influence of deprivation on outcomes following vascular access surgery has not previously been reported. METHODS: The Welsh Index of Multiple Deprivation was used to assess the influence of socioeconomic deprivation on outcomes following 507 consecutive first upper limb arteriovenous (AV) fistulas from a single institution in the United Kingdom, performed between 2011 and 2014. The primary outcome measures were early failure and maturation into a working fistula. RESULTS: Four hundred and five (80%) patients had a patent AV fistula at the 2-week follow-up clinic. Three hundred and fifty-nine (71%) patients developed a functionally mature AV fistula as determined by clinical assessment and a Doppler scan. There were no differences in either early failure rates (p = 0.95) or maturation rates (p = 0.77) between the least and most deprived groups of patients. CONCLUSIONS: In conclusion, this study has shown that socioeconomic deprivation does not influence outcomes following vascular access surgery.

The influence of socioeconomic deprivation on outcomes in pancreas transplantation.

Socioeconomic deprivation is an important factor in determining poor health and is associated with a higher prevalence of many chronic diseases including diabetes and renal failure, with poorer outcomes of their treatments. The influence of deprivation on outcomes following pancreas transplantation has not previously been reported. The Welsh Index of Multiple Deprivation was used to assess the influence of socioeconomic deprivation on outcomes for 119 consecutive pancreas transplant recipients from a single center in the United Kingdom, transplanted between 2004 and 2013. Outcomes measured were rate of acute rejection and graft survival. Thirty-five (29.4%) patients experienced at least one episode of acute rejection following their transplant. Rejection rates in least deprived were 37% and most deprived 24% (p = 0.29). Within the individual domains, rejection rate was higher for the "physical environment" domain (least deprived 40% vs. most deprived 17% (p = 0.053). Five-year graft survival for least and most deprived groups was 75% and 88%, respectively (log-rank test p-value 0.24). This study has not demonstrated any significant differences in outcomes following pancreas transplantation in Wales in relation to socioeconomic deprivation with the exception possibly of the "physical environment" domain. Further studies with larger patient population or concentrating on physical environment deprivation would be of interest.

Generation of eosinophils from cryopreserved murine bone marrow cells.

Eosinophils are produced in the bone marrow from CD34+ eosinophil lineage-committed progenitors, whose levels in the bone marrow are elevated in a variety of human diseases. These findings suggest that increased eosinophil lineage-committed progenitor production is an important process in disease-associated eosinophilia. The pathways central to the biology of the eosinophil lineage-committed progenitor remain largely unknown. Thus, developing new methods to investigate the regulators of eosinophil lineage-committed progenitor differentiation is needed to identify potential therapeutic targets to specifically inhibit eosinophil production. We tested cytokine regimens to optimize liquid cultures for the study of eosinophil lineage-committed progenitor and eosinophil precursor differentiation into mature eosinophils. Stem cell factor (but not fms-related tyrosine kinase 3 ligand) was required for optimal yield of eosinophils. Furthermore, we evaluated the effects of cell preservation and scale on the culture, successfully culturing functional eosinophils from fresh and frozen murine bone marrow cells and in a standard-sized and 96-well culture format. In summary, we have developed an adaptable culture system that yields functionally competent eosinophils from murine low-density bone marrow cells and whose cytokine regime includes expansion of progenitors with stem cell factor alone with subsequent differentiation with interleukin 5.

Improved motion detection method using spot localization - biomed 2011.

The common house fly may be able to process certain features of images much faster than that of typical human vision. A computer model as well as a hardware model has been developed to simulate parts of the fly eye. One particular area of study in the software model has been motion detection. A new method is being developed that focuses on spot localization before motion detection. Models have been developed that can localize a spot in cylindrical coordinates with respect to the center receptor. Relative motion can be detected by analyzing the changes in the location of the spots. The advantage of this method is that it requires almost no memory. By reducing the memory required, faster frame rates can be achieved. Motion detection and spot localization will serve as the foundation for additional processing for segmentation and object recognition.

Early cholecystectomy after acute admission with cholecystitis: how much work?

BACKGROUND: This study was designed to determine the number of cases and amount of operating room time required, for a population of 600,000, to provide definitive treatment in the form of cholecystectomy for all patients admitted as an emergency with cholecystitis. METHODS: The total number of patients admitted to a single NHS trust in South East Wales with the diagnosis of cholecystitis during a 1-year period was assessed. The number of laparoscopic cholecystectomies performed and the time taken was investigated with the conversion rates. RESULTS: There were a total of 787 individual emergency admissions attributed to cholecystitis, and 224 patients (36%) underwent cholecystectomy on the same admission. The median operative time was 77 (range, 23-238) min, and the median operating room time was 108 (range, 37-278) min. To treat all patients definitively would necessitate 12 cholecystectomies per week, requiring 1,296 min or 5.4 sessions of operating room time. CONCLUSIONS: A population of 600,000 could be expected to generate enough emergency cholecystectomies to require more than one operating session per day. A significant increase in emergency operating room availability would be necessary to allow the provision of definitive treatment for all emergency admissions with cholelithiasis.

Prognostic significance of gastrin expression in patients undergoing R0 gastrectomy for adenocarcinoma.

BACKGROUND: Gastrointestinal (GI) hormones regulate several GI functions, including the proliferation and repair of normal mucosa, and hormone receptors may therefore be implicated in the growth, invasion, and metastasis of cancers of the GI tract. The aim of this study was to determine the cellular distribution of gastrin in intestinal-type gastric cancers, and to determine its relationship to outcomes after R0 gastrectomy. METHODS: Eighty-six consecutive patients undergoing R0 gastrectomy for adenocarcinoma were studied. Normal gastric mucosa and tumor were stained for gastrin and their specific cellular distribution was determined. RESULTS: The duration of survival of patients whose tumors exhibited well-differentiated gastrin-positive tumor (GPT) cells (n = 12) was significantly poorer than that of patients whose tumors were GPT-negative (5-year survival, 30% vs 54%; P = 0.037). Patients with GPT-positive intestinal-type gastric cancer (5 of 47 patients) had the poorest survival of all (median, 14 months; 5-year survival, 0%; P = 0.006). In a multivariate analysis, only lymph node metastases (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.2 to 3.79; P = 0.01) and the presence of GPT cells (HR, 6.61; 95% CI, 1.74 to 25.09; P = 0.01) were independently and significantly associated with durations of survival in patients with intestinal-type gastric cancer. CONCLUSION: The presence of GPT cells in patients with gastric adenocarcinoma is a significant and independent prognostic indicator.