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Spinal muscular atrophy was recently added to the Wisconsin newborn screening panel. Here we report our screening methods, algorithm, and outcomes. Methods: A multiplex real-time PCR assay was used to identify newborns with homozygous SMN1 exon 7 deletion, and those newborns’ specimens further underwent a droplet digital PCR assay for SMN2 copy number assessment. An independent dried blood spot specimen was collected and tested to confirm the initial screening results for SMN1 and SMN2. Results: From October 15, 2019 to October 14, 2020, a total of 60,984 newborns were screened for spinal muscular atrophy. Six newborns screened positive for and were confirmed to have spinal muscular atrophy, making the Wisconsin spinal muscular atrophy birth prevalence 1 in 10,164. Of these six infants, two have two copies of SMN2, two have three copies of SMN2, and two have four copies of SMN2. Five newborns received Zolgensma therapy, and one newborn received Spinraza therapy. Conclusions: Our screening method'spositive predictive value is 100%. This comprehensive approach, providing both timely SMN2 information and SMN1 and SMN2 confirmation as parts of the algorithm for spinal muscular atrophy newborn screening, facilitated timely clinical follow-up, family counseling, and treatment planning.

Aims: \ud Identifying novel mediators of lethal myocardial reperfusion injury that can be targeted during primary percutaneous coronary intervention (PPCI) is key to limiting the progression of patients with ST-elevated myocardial infarction (STEMI) to heart failure. Here we show through parallel clinical and integrative preclinical studies the significance of the protease cathepsin-L on cardiac function during reperfusion injury.\ud \ud Methods and Results: \ud We found that direct cardiac release of cathepsin-L in STEMI patients (n = 76) immediately post-PPCI leads to elevated serum cathepsin-L levels and that serum levels of cathepsin-L in the first 24 hour post-reperfusion are associated with reduced cardiac contractile function and increased infarct size. Preclinical studies, demonstrate that inhibition of cathepsin-L release following reperfusion injury with CAA0225 reduces infarct size and improves cardiac contractile function by limiting abnormal cardiomyocyte calcium handling and apoptosis.\ud \ud Conclusion: \ud Our findings suggest that cathepsin-L is a novel therapeutic target that could be exploited clinically to counteract the deleterious effects of acute reperfusion injury after an acute STEMI.\ud \ud Translational perspective: \ud New therapeutic targets are urgently required to limit myocardial damage after reperfusion injury. We identified cardiac release of the protease cathepsin-L among patients following primary percutaneous coronary intervention (PPCI). Elevated serum levels of cathepsin-L were associated with reduced contractile function and increased infarct size at 24 hour and 6 months post-PPCI. Work conducted using animal models indicated that cardiac release of cathepsin-L mediated cardiac dysfunction following reperfusion injury. Specific inhibition of cathepsin-L prevented abnormal calcium handling, reduced infarct size and improved contractile function. These novel findings offer the prospect of targeting cathepsin-L-mediated cardiac dysfunction after PPCI.

The robotic platform for cholecystectomy has been extensively studied in comparison to its laparoscopic counterpart with acceptable outcomes. However, wide acceptance of a robotic approach to cholecystectomy has been limited by increased operative room (OR) times and substantially higher cost. This is a single-institution retrospective review of Veteran patients presenting for elective laparoscopic (LC) and robotic (RC) cholecystectomies for benign biliary disease at the Dallas VA Medical Center. The primary goal was to interrogate 30-day morbidity as well as operative room times, estimated blood loss (EBL), hospital length of stay (LOS), and conversion rates. The entire cohort included 612 patients (age = 55.1 ± 12.9 years, men = 77.9%, BMI = 31.2 ± 6.3 kg/m2) undergoing elective cholecystectomy (LC = 441 and RC = 171) for benign biliary disease (biliary colic = 78.8%, history of biliary pancreatitis = 7.8%, history of cholecystitis = 5.7%). Univariate analysis comparing LC and RC showed the two groups to be of similar age (55.4 ± 12.4 vs. 54.4 ± 14.2 years; p = 0.4), male gender (79.4% vs. 74.3%, p = 0.2), and BMI (31.1 ± 6.4 vs. 31.5 ± 6.3 kg/m2; p = 0.5). Except for dyslipidemia (LC = 48.3% vs. RC = 36.8%; p = 0.01), both groups had the same rate of co-morbid conditions. ASA level III and IV (LC = 60.1 vs. RC = 69.0%, p = 0.04) was higher in the RC group. Both groups underwent surgical intervention for similar indications (biliary colic LC = 80.5% vs. RC = 74.3; p = 0.1). Hospital LOS (1.7 ± 3.2 vs. 0.3 ± 0.9 days, p

Accurate clinical staging (CS) of gastric cancer is critical for appropriate treatment selection and prognostication, but CS remains highly imprecise. Our study evaluates factors associated with inaccurate CS, the impact of inaccurate CS on outcomes, and utilization of adjuvant therapy in patients who are understaged. We conducted a retrospective review of NCDB patients diagnosed with clinical early stage gastric adenocarcinoma (cT1-2N0M0) between 2004 and 2016. Patients not undergoing upfront gastrectomy or with missing pathologic staging were excluded. Patients were classified as accurately staged, inaccurately staged with receipt of adjuvant therapy (IS+), and inaccurately staged with no receipt of adjuvant therapy (IS−). Logistic regression was utilized to assess the impact of factors on CS accuracy and receipt of adjuvant therapies. Kaplan–Meier and Cox proportional hazard methods were used for survival analysis. Approximately 40% of patients were inaccurately staged (IS). cT2, moderately/poorly differentiated, and site-overlapping tumors were associated with increased likelihood of being IS. Treatment at an academic facility was associated with decreased likelihood of understaging. Only 54% of patients who were IS received adjuvant therapy. Accurate CS of gastric cancer remains inadequate. Understaging is associated with detrimental effects on receiving guideline-concordant care and, possibly, patient outcomes. Targeted interventions reducing the proportion of understaged patients and ensuring receipt of appropriate therapy is needed to optimize outcomes. Patients with high-risk disease that are frequently understaged may benefit from selective neoadjuvant therapy. Centralization of gastric cancer care may also be a key strategy in improving receipt of guideline-concordant therapies.

Background/Aims Glycogen synthesis and storage are normal hepatocyte functions. However, glycogenosis, defined as excess hepatocyte glycogen visible by routine H&E light microscopy, has not been well characterized in nonalcoholic fatty liver disease (NAFLD). Methods Glycogenosis in NAFLD liver biopsies was graded as “none”, “focal” (in

The CAPER Registry is a voluntary, national safety reporting program that gathers patients' adverse events encountered during dermatologic procedures. This registry is intended as an aid for practitioners, patients, industry, and government regulators, and aims to facilitate safety monitoring for the specialty by identifying resource, process, education, and other systemic gaps associated with adverse events, as well as any potential risk factors for adverse events. CAPER will provide new or corroborating information to help dermatologists improve clinical practices, improve safety and effectiveness, and treat and prevent adverse events. The data generated will also help industry partners and regulatory bodies prevent adverse events from going unnoticed.

Author(s): Hopwood, Christopher J; Krueger, Robert F; Watson, David; Widiger, Thomas A; Althoff, Robert R; Ansell, Emily B; Bach, Bo; Bagby, R Michael; Blais, Mark A; Bornovalova, Marina A; Chmielewski, Michael; Cicero, David C; Conway, Christopher; De Clerq, Barbara; De Fruyt, Filip; Docherty, Anna R; Eaton, Nicholas R; Edens, John F; Forbes, Miriam K; Forbush, Kelsie T; Hengartner, Michael P; Ivanova, Masha Y; Leising, Daniel; Lukowitsky, Mark R; Lynam, Donald R; Markon, Kristian E; Miller, Joshua D; Morey, Leslie C; Mullins-Sweatt, Stephanie N; Ormel, Johan; Patrick, Christopher J; Pincus, Aaron L; Ruggero, Camilo; Samuel, Douglas B; Sellbom, Martin; Tackett, Jennifer L; Thomas, Katherine M; Trull, Timothy J; Vachon, David D; Waldman, Irwin D; Waszczuk, Monika A; Waugh, Mark H; Wright, Aidan GC; Yalch, Mathew M; Zald, David H; Zimmermann, Johannes

Laparoscopy has emerged as a common alternative to the open approach for colorectal operations. Robotic surgery has many advantages, but cost and outcomes are an area of study. There are no randomized-controlled trials of all techniques. The present study evaluated a cohort of veterans undergoing (procto-) colectomy for benign or malignant colorectal disease. This is a single-institution retrospective review. We compared open, laparoscopic, and robotic colectomies. The primary outcome was 30-day mortality. The secondary endpoints included morbidity, operative times, estimated blood loss (EBL), length of stay (LOS), conversion rate, and the learning curve (LC). Subgroup analyses were undertaken for: (1) right hemicolectomies (RHC) and (2) by specific surgeons most familiar with each approach. The cohort included 390 patients (men = 95%, White = 70.8%, BMI = 29.3 ± 6.4 kg/m2, age = 63.7 ± 10.2 years) undergoing (open = 117, laparoscopic = 168, and robotic = 105), colorectal operations for colorectal adenocarcinoma (52.8%) and benign disease. Thirty-day morbidity was similar across all techniques (open = 46.2%, laparoscopic = 42.9%, and robotic = 38.1%; NS). EBL and LOS were decreased with minimally invasive techniques compared to open. Operative time was longer in robotic, but equalized to laparoscopic after 90 cases. The learning curve was reduced to 20 when performed by the surgeon most familiar with the robot. EBL and operative time independently predicted complications for the entire cohort. The best technique for colorectal operations rests on the surgeon’s experience, but minimally invasive techniques are gaining momentum over open colectomies. Robotic colectomy is emerging as a non-inferior approach to laparoscopy in terms of outcomes, while maintaining all its technical advantages.

Background The increasing burden from basal cell carcinoma (BCC) has stimulated the development of alternative treatments for these tumors. Objective This review focuses on upcoming laser treatments for BCC and highlights the limitations of these therapies. Methods A PUBMED search was conducted for articles on laser therapy of BCC. Key studies involving lasers to treat BCC were reviewed. Novel approaches to BCC are also described. Results Vascular-specific laser therapy has increasingly been studied as an addition in the therapeutic armamentarium of BCC. Although these studies demonstrate efficacy for nonaggressive BCC, optimization of this technique is ongoing to minimize scarring. A more targeted approach to the treatment of BCC, such as immunized photothermal therapy or laser-assisted chemotherapeutic delivery, may result in less scarring, while maintaining efficacy similar to that of lasers targeting tumor vasculature. Conclusion Vascular-specific laser therapies show promise in treating low-risk BCC; however, scarring is not an uncommon adverse event. Although only animal studies have been performed to date, laser-activated gold nanoparticle therapy and laser-assisted drug delivery of vismodegib are potential therapies that theoretically confer a more selective approach. Laser modalities demonstrate promise in the treatment of nonaggressive BCC, although long-term studies have yet to be published.

BACKGROUND: The loss of insulin-like growth factor 1 (IGF-1) expression in senescent dermal fibroblasts during aging is associated with an increased risk of nonmelanoma skin cancer (NMSC). We tested how IGF-1 signaling can influence photocarcinogenesis during chronic UVB exposure to determine if fractionated laser resurfacing (FLR) of aged skin, which upregulates dermal IGF-1 levels, can prevent the occurrence of actinic keratosis (AK) and NMSC. METHODS: A human skin/immunodeficient mouse xenografting model was used to test the effects of a small molecule inhibitor of the IGF-1 receptor on chronic UVB radiation. Subsequently, the durability of FLR treatment was tested on a cohort of human participants aged 65 years and older. Finally, 48 individuals aged 60 years and older with considerable actinic damage were enrolled in a prospective randomized clinical trial in which they underwent a single unilateral FLR treatment of one lower arm. Numbers of AKs/NMSCs were recorded on both extremities for up to 36 months in blinded fashion. RESULTS: Xenografting studies revealed that chronic UVB treatment with a topical IGF-1R inhibitor resulted in a procarcinogenic response. A single FLR treatment was durable in restoring appropriate UVB response in geriatric skin for at least 2 years. FLR resulted in sustained reduction in numbers of AKs and decreased numbers of NMSCs in the treated arm (2 NMSCs) versus the untreated arm (24 NMSCs). CONCLUSION: The elimination of senescent fibroblasts via FLR reduced the procarcinogenic UVB response of aged skin. Thus, wounding therapies are a potentially effective prophylaxis for managing high-risk populations. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03906253). FUNDING: National Institutes of Health, Veterans Administration.

Rationale: “Noninfectious” pulmonary complications are significant causes of morbidity and mortality after allogeneic hematopoietic cell transplant. Early-onset viral reactivations or infections ar...

Background and objective Recent prospective trials have supported treatment of nonfacial BCC with long-pulsed 1064 nm Nd:YAG laser based on short-term histologic clearance rates. Studies have yet to identify the long-term clinical clearance rates of this specific laser therapy for BCC. Study design/material and methods This is a retrospective review of BCC treated with long-pulsed 1064 nm Nd:YAG laser, which have been clinically monitored for at least 6 months, to assess for recurrence and cosmetic outcomes of the treated area. Results 16 BCC lesions (11 subjects) treated with 1064 nm Nd:YAG laser were enrolled. Our analysis revealed 100% clearance rate in all subjects (16 of 16 BCC) treated with long-pulsed Nd:YAG laser based on mean follow-up of 9 months (range 6-15 months). Minimal scarring and no long-term adverse events were noted. Conclusions This study supports the use of 1064 nm Nd:YAG laser as a therapeutic modality for BCC based on the absence of clinical recurrence upon a mean follow-up of 9 months. As studies progress, we are beginning to observe a potential role for laser as an alternative to patients who refuse surgery, have multiple co-morbidities, or decline non-surgical therapies. Laser treatment with 1064 nm Nd:YAG is an evolving, promising story that we continue to investigate to optimize parameters. Lasers Surg. Med. 51:34-39, 2019. © 2018 Wiley Periodicals, Inc.

36 Background: Two recent South Korean studies showed adjuvant therapy (AT) was not associated with improved survival in pT1N1 gastric adenocarcinoma (GAC). We aimed to establish the prognostic utility of lymph node status, determine the pattern of use of AT, and compare survival stratified by type of AT in pT1N1 GAC in a Western patient population. Methods: We identified patients with pT1N0 and pT1N1 GAC using the National Cancer Database from 2004 to 2012. Clinicopathologic variables, treatment regimens, and overall survival (OS) were compared. Results: We compared 4,516 (86.6%) pT1N0 to 696 (13.4%) pT1N1 patients. pT1N1 tumors were larger (median size 2.5 vs. 1.8 cm, p < 0.001), more often poorly differentiated (56.2% vs. 39.6%, p < 0.001), and had higher median retrieved lymph nodes (RLN) (14 vs. 12, p < 0.001) compared to pT1N0. pT1N1 was associated with worse median OS (6.9 years vs. 9.9 years for pT1N0, p < 0.001). pN1 was independently associated with worse OS (HR 2.17 95% CI 1.84-2.56). Increased RLN was associated with improved OS (HR 0.73, 95% CI 0.65-0.83). Among pT1N1 patients, 330 (47.4%) had observation (OBS), 77 (11.1%) received adjuvant chemotherapy (ACT), 68 (9.8%) received adjuvant radiation therapy (ART), and 221 (31.8%) received adjuvant chemoradiation therapy (ACRT). ACT and ACRT were independently associated with improved OS (HR 0.37, 95% CI 0.22-0.65 and HR 0.40, 95% CI 0.28-0.57). Conclusions: pN1 was associated with worse survival and RLN ≥ 15 was associated with improved survival in pT1 GAC. ACT and ACRT were independently associated with improved survival in pT1N1 gastric cancer suggesting a valuable role in Western patients.

Objective Lidocaine acts as a local anesthetic by blocking transmembrane sodium channel permeability, but also induces the synthesis of heat shock proteins and sensitizes cells to hyperthermia. A previous study reported two cases of deep focal skin ulceration at points corresponding to depot local lidocaine injection sites after treatment with non-ablative fractional resurfacing and it was hypothesized that lidocaine had focally sensitized keratinocytes to the thermal damage of laser treatment. The objective of this study was to investigate whether lidocaine potentiates hyperthermia damage to both normal and cancerous skin cells using an in vitro model. Methods Normal skin cell lines (fibroblasts, keratinocytes), skin cancer cell lines (melanoma, basal cell carcinoma), and a mucosal cancer cell line (cervical carcinoma) were exposed to various concentrations of lidocaine (0-0.3%) with or without hyperthermia (37°C, 42°C). Results Compared to normal skin cells, we demonstrate that cancer cell lines show significantly increased cell toxicity when a moderate temperature (42°C) and low lidocaine concentrations (0.1-0.2%) are combined. The toxicity directly correlates with a higher percentage of cells in S-phase (28-57%) in the cancer cell lines compared to normal skin cell lines (13-19%; R-square 0.6752). Conclusion These results suggest that lidocaine potentiates thermal sensitivity of cell cycle active skin cells. The direct correlation between cell toxicity and S-phase cells could be harnessed to selectively treat skin and mucosal cancer cells while sparing the surrounding normal tissue. Additional research pre-clinically and clinically using several different heat sources (e.g., lasers, ultrasound, etc.) and lidocaine concentrations is needed to confirm and optimize these results. Lidocaine-enhanced hyperthermia may provide a non-invasive, alterative treatment option for highly proliferating, superficial skin, and mucosal lesions such as cancer or warts. Lasers Surg. Med. 51:88-94, 2019. © 2018 Wiley Periodicals, Inc.

Background Human immunodeficiency virus (HIV) remains a public health priority in Latin America. While the burden of HIV is historically concentrated in urban areas and high-risk groups, subnational estimates that cover multiple countries and years are missing. This paucity is partially due to incomplete vital registration (VR) systems and statistical challenges related to estimating mortality rates in areas with low numbers of HIV deaths. In this analysis, we address this gap and provide novel estimates of the HIV mortality rate and the number of HIV deaths by age group, sex, and municipality in Brazil, Colombia, Costa Rica, Ecuador, Guatemala, and Mexico. Methods We performed an ecological study using VR data ranging from 2000 to 2017, dependent on individual country data availability. We modeled HIV mortality using a Bayesian spatially explicit mixed-effects regression model that incorporates prior information on VR completeness. We calibrated our results to the Global Burden of Disease Study 2017. Results All countries displayed over a 40-fold difference in HIV mortality between municipalities with the highest and lowest age-standardized HIV mortality rate in the last year of study for men, and over a 20-fold difference for women. Despite decreases in national HIV mortality in all countries—apart from Ecuador—across the period of study, we found broad variation in relative changes in HIV mortality at the municipality level and increasing relative inequality over time in all countries. In all six countries included in this analysis, 50% or more HIV deaths were concentrated in fewer than 10% of municipalities in the latest year of study. In addition, national age patterns reflected shifts in mortality to older age groups—the median age group among decedents ranged from 30 to 45 years of age at the municipality level in Brazil, Colombia, and Mexico in 2017. Conclusions Our subnational estimates of HIV mortality revealed significant spatial variation and diverging local trends in HIV mortality over time and by age. This analysis provides a framework for incorporating data and uncertainty from incomplete VR systems and can help guide more geographically precise public health intervention to support HIV-related care and reduce HIV-related deaths.

Background Lymphatic filariasis is a neglected tropical disease that can cause permanent disability through disruption of the lymphatic system. This disease is caused by parasitic filarial worms that are transmitted by mosquitos. Mass drug administration (MDA) of antihelmintics is recommended by WHO to eliminate lymphatic filariasis as a public health problem. This study aims to produce the first geospatial estimates of the global prevalence of lymphatic filariasis infection over time, to quantify progress towards elimination, and to identify geographical variation in distribution of infection. Methods A global dataset of georeferenced surveyed locations was used to model annual 2000–18 lymphatic filariasis prevalence for 73 current or previously endemic countries. We applied Bayesian model-based geostatistics and time series methods to generate spatially continuous estimates of global all-age 2000–18 prevalence of lymphatic filariasis infection mapped at a resolution of 5 km2 and aggregated to estimate total number of individuals infected. Findings We used 14 927 datapoints to fit the geospatial models. An estimated 199 million total individuals (95% uncertainty interval 174–234 million) worldwide were infected with lymphatic filariasis in 2000, with totals for WHO regions ranging from 3·1 million (1·6–5·7 million) in the region of the Americas to 107 million (91–134 million) in the South-East Asia region. By 2018, an estimated 51 million individuals (43–63 million) were infected. Broad declines in prevalence are observed globally, but focal areas in Africa and southeast Asia remain less likely to have attained infection prevalence thresholds proposed to achieve local elimination. Interpretation Although the prevalence of lymphatic filariasis infection has declined since 2000, MDA is still necessary across large populations in Africa and Asia. Our mapped estimates can be used to identify areas where the probability of meeting infection thresholds is low, and when coupled with large uncertainty in the predictions, indicate additional data collection or intervention might be warranted before MDA programmes cease. Funding Bill & Melinda Gates Foundation.

Lung cancer (LC) is an aggressive malignancy with early metastatic spread and poor prognosis. Gastrointestinal metastases from primary LC are extremely rare with highly variable presentations. In this report, we review the case of a patient who presented with peritonitis secondary to perforated sigmoid mass as the first manifestation of metastatic squamous cell LC.

Hepatic angiosarcoma (AS) and hepatic epithelioid hemangioendothelioma (HEHE) are rare primary hepatic vascular malignancies (PHVM) that remain poorly understood. To guide management, we sought to identify factors and trends predicting survival after surgical intervention using a national database.In a retrospective analysis of the National Cancer Database patients with a diagnosis of PHVM were identified. Clinicopathologic factors were extracted and compared. Overall survival (OS) was estimated and predictors of survival were identified.Three hundred ninty patients with AS and 216 with HEHE were identified. Only 16% of AS and 36% of HEHE patients underwent surgery. The median OS for patients who underwent surgical intervention was 97 months, with 5-year OS of 30% for AS versus 69% for HEHE patients (P0.001). Tumor biology strongly impacted OS, with AS histology (Hazard Ratio [HR] of 3.61 [1.55-8.42]), moderate/poor tumor differentiation (HR = 3.86 [1.03-14.46]) and tumor size (HR = 1.01 [1.00-1.01]) conferring worse prognosis. The presence of metastatic disease in the surgically managed cohort (HR = 5.22 [2.01-13.57]) and involved surgical margins (HR = 3.87 [1.59-9.42]), were independently associated with worse survival.In this national cohort of PHVM, tumor biology, in the form of angiosarcoma histology, tumor differentiation and tumor size, was strongly associated with worse survival after surgery. Additionally, residual tumor burden after resection, in the form of positive surgical margins or the presence of metastasis, was also negatively associated with survival. Long-term clinical outcomes remain poor for patients with the above high-risk features, emphasizing the need to develop effective forms of adjuvant systemic therapies for this group of malignancies.

Meckel’s diverticulum (MD) is an anomaly of the small intestine from which malignancy may arise. Among MD neoplasms, neuroendocrine tumors (NETs) are considered the most common. However, their metastatic potential and optimal surgical therapy remain ill-defined. In a retrospective analysis of the National Cancer Database (2004–2015), patients with a diagnosis of MD malignancy were identified. Clinicopathologic factors were extracted and tumors arising in MD were compared. In the subgroup of patients with NET, the association between tumor factors and node involvement was investigated. Three hundred twenty primary MD malignancies were captured in the National Cancer Database, consisting of 280 (87.5%) NET. The median age at diagnosis was 64 years. Patients were predominantly male (207, 73.9%) and white (269, 96.1%). Most tumors were well-differentiated (118, 42.1%) and sub-centimeter (median size, 0.7 cm). Distant metastasis was present in a minority (16, 5.7%), and the median overall survival was 114 months in the entire cohort. The regional lymph node status was known in 87 NET patients, out of which 39 (44.8%) harbored node metastasis. Although the risk of node involvement increased with larger tumor size, it remained significant even among sub-centimeter (9 out of 34, 26.5%) and well-differentiated (18 out of 44, 41%) tumors. Regional node involvement was associated with the presence of distant metastasis (p

Purpose Accurate target definition is critical for the appropriate application of radiation therapy. In 2008, the Radiation Therapy Oncology Group (RTOG) published an international collaborative atlas to define the clinical target volume (CTV) for intensity modulated pelvic radiation therapy in the postoperative treatment of endometrial and cervical cancer. The current project is an updated consensus of CTV definitions, with removal of all references to bony landmarks and inclusion of the para-aortic and inferior obturator nodal regions. Methods and Materials An international consensus guideline working group discussed modifications of the current atlas and areas of controversy. A document was prepared to assist in contouring definitions. A sample case abdominopelvic computed tomographic image was made available, on which experts contoured targets. Targets were analyzed for consistency of delineation using an expectation-maximization algorithm for simultaneous truth and performance level estimation with kappa statistics as a measure of agreement between observers. Results Sixteen participants provided 13 sets of contours. Participants were asked to provide separate contours of the following areas: vaginal cuff, obturator, internal iliac, external iliac, presacral, common iliac, and para-aortic regions. There was substantial agreement for the common iliac region (sensitivity 0.71, specificity 0.981, kappa 0.64), moderate agreement in the external iliac, para-aortic, internal iliac and vaginal cuff regions (sensitivity 0.66, 0.74, 0.62, 0.59; specificity 0.989, 0.966, 0.986, 0.976; kappa 0.60, 0.58, 0.52, 0.47, respectively), and fair agreement in the presacral and obturator regions (sensitivity 0.55, 0.35; specificity 0.986, 0.988; kappa 0.36, 0.21, respectively). A 95% agreement contour was smoothed and a final contour atlas was produced according to consensus. Conclusions Agreement among the participants was most consistent in the common iliac region and least in the presacral and obturator nodal regions. The consensus volumes formed the basis of the updated NRG/RTOG Oncology postoperative atlas. Continued patterns of recurrence research are encouraged to refine these volumes.

Despite advances in the detection, surgical care, and systemic treatment of colorectal cancer, many patients develop metastatic disease. Metastasis is the major cause of cancer-related mortality and continues to be a major challenge for clinicians and scientists. Developing earlier detection methods and more effective therapies requires understanding the complex mechanisms that drive colorectal cancer liver metastasis biology. However, due to the limitations of current experimental models and enormous biologic complexity associated with metastatic progression, our understanding of the genetic, epigenetic, transcriptional, and cellular interactions in the native and host microenvironments is in its initial stages. In this chapter, the stages of colorectal cancer liver metastasis are presented and highlighted by our current mechanistic understanding of metastasis biology.

To compare the perioperative outcomes of minimally invasive pancreaticoduodenectomy (MIPD) in comparison with open pancreaticoduodenectomy (OPD) in a national cohort of patients.Limited well-controlled studies exist comparing perioperative outcomes between MIPD and OPD.Patients who underwent MIPD and OPD were abstracted from the 2014 to 2015 pancreas-targeted American College of Surgeons National Surgical Quality Improvement Program. OPD and MIPD patients were matched 3:1 using propensity score, and perioperative outcomes were compared.A total of 4484 patients were identified with 334 (7.4%) undergoing MIPD. MIPD patients were younger, more likely to be White, and had a lower rate of weight loss. They were more likely to undergo classic Whipple and to have a drain placed. After 3:1 matching, 1002 OPD patients were compared with 334 MIPD patients. MIPD was associated with longer mean operative time (426.6 vs 359.6 minutes; P0.01), higher readmission rate (19.2% vs 14.3%; P = 0.04) and lower rate of prolonged length of stay14 days (16.5% vs 21.6%; P = 0.047). The 2 groups had a similar rate of 30-day mortality (MIPD 1.8% vs OPD 1.3%; P = 0.51), overall complications, postoperative pancreatic fistula, and delayed gastric emptying. A secondary analysis comparing MIPD without conversion or open assist with OPD showed that MIPD patients had lower rates of overall surgical site infection (13.4% vs 19.6%; P = 0.04) and transfusion (7.9% vs 14.4%; P = 0.02).MIPD had an equivalent morbidity and mortality rate to OPD, with the benefit of a decreased rate of prolonged length of stay, though this is partially offset by an increased readmission rate.

BACKGROUND A paucity of data exists regarding the natural history and outcome measures of adenosquamous carcinoma of the pancreas (ASCP), a histology distinct from pancreatic adenocarcinoma (PDAC). The aim of this study is to characterize the clinicopathological features of ASCP in a large cohort of patients comparing outcome measures of surgically resected patients to PDAC. METHODS We identified patients diagnosed with ASCP or PDAC from the National Cancer Database from 2004 to 2012. Patient demographics, tumor characteristics, treatment regimens, and overall survival were analyzed between the groups. RESULTS We identified 207 073 patients: 205 328 (99%) in the PDAC group and 1745 (1%) in the ASCP group. ASCP tumors were larger, located more frequently in a body/tail location (36% vs 24%, P

Background and objective Basal cell carcinoma (BCC) is an indolent form of skin cancer that is rarely life threatening, but can cause significant cosmetic and functional morbidity. Surgical treatments often result in disfiguring scars, while topical therapies frequently result in recurrence. The need for a more effective nonsurgical alternative has led to the investigation of laser treatment of BCC. We have previously conducted a pilot study which showed 100% histologic clearance at high fluences. Treatments were well tolerated with no significant adverse events. The objective of this larger study was to confirm preliminary results that the 1064 nm Nd:YAG laser is a safe and effective method for treating non-facial BCC. Design This is an IRB-approved, prospective, multi-center study evaluating the safety and efficacy of the 1064 nm Nd:YAG laser for the treatment of BCC on the trunk and extremities. Thirty-three subjects seeking treatment for biopsy-proven BCC that did not meet the criteria for Mohs surgery were recruited. Subjects on current anticoagulation therapy, or with a history of immunosuppression were excluded. Subjects received one treatment with the 1064 nm Nd:YAG laser as follows: 5-6 mm spot, fluence of 125-140 J/cm2 and a pulse duration of 7-10 ms. Standard excision with 5 mm clinical margins was performed at 30 days after laser treatment to evaluate clinical and histologic clearance of BCC. Standardized photographs and adverse assessments were taken at the baseline visit, immediately after laser treatment and on the day of excision. Results Thirty-one subjects completed the study. BCC tumors had a 90% (28 of 31 BCC tumors) histologic clearance rate after one treatment with the long-pulsed 1064 nm Nd:YAG laser. Treatments were generally well tolerated without any anesthesia. Immediate side effects included edema and erythema. At 1-month follow-up, some patients had residual crusting. No significant adverse events occurred. Conclusion The 1064 nm long-pulsed Nd:YAG laser is an alternative for treating non-facial BCC for those that are poor surgical candidates. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

Chagas disease, also known as American trypanosomiasis, is caused by the flagellate protozoan Trypanosoma cruzi. It is a significant health concern in South and Central America, where millions of people are infected or at risk of infection, and is an emerging health concern in the US. The occurrence of Chagas disease in natural environments is supported by mammal host species, but those primary species may vary based on geographic location. In South Texas, the primary host species for the disease is poorly understood, and required a field study to determine the spatial distribution of T. cruzi prevalence in free-ranging mammals. Our study objectives were to determine the spatial distribution and prevalence of T. cruzi parasites in free-ranging mammals. We compared T. cruzi prevalence among species, among vegetative communities, and among different topographies (i.e., floodplain versus upland). From December 2011 through December 2013, 450 blood and tissue samples from geolocated free-ranging wildlife mammal species were analyzed with the use of polymerase chain reaction to detect protozoan T. cruzi DNA. We also calculated mammal abundance with the use of mark-recapture methodology and recorded capture-site characteristics such as vegetation structure. We found that animals in grasslands had a significantly lower infection rate when summed across all species compared with animals in dense hardwoods and semi-improved woodlands (P=0.001). A higher percentage of infections were found in the lower-elevation floodplain-65% (28/43) of animals sampled, compared to upland areas-25% (9/36) of animals sampled. Our study suggested that common free-ranging meso-mammals supported T. cruzi in natural environments and are of public health concern in South Texas. Mitigation strategies should consider a range of management activities to include vegetation management, selective application of insecticides, and changes in human behavior in high-risk areas.

The clinical features of photoaging include: skin texture changes, laxity, rhytides, pigmentary changes, and vascular changes such as erythema and telangiectasias. In order to meet patients' increasing demands for improving all aspects of photoaging at one office visit, employing a multi-modality treatment for all aspects of photoaging has become increasingly desirable for the physician and patient alike. We examine a novel device that employs bipolar radiofrequency (RF), intense pulsed light (IPL), and infrared diode laser. These laser and light source treatments are performed sequentially. This study aims to evaluate the clinical efficacy and safety of this device (i.e., ELOS Triniti™). Twenty-six subjects received four ELOS Triniti™ treatments at 1-month intervals. They were followed up 1, 3, and 6 months after completing the treatments. Two blinded dermatologists used a comprehensive grading scale to evaluate the degree of the photoaging in terms of rhytides, laxity, dyschromia, erythema, telangiectasias, and texture. Subjects used a 0-10 grading scale for self-assessment of photoaging. Additionally, we measured the Erythema Index (EI), Melanin Index (MI), transepidermal water loss scores (TEWL), stratum corneum moisture scores (SC), and dermis moisture scores (D) before treatment and 1, 3, and 6 months after treatment. There was a statistically significant improvement in all five aspects of the comprehensive grading scale. Overall, it had excellent efficacy for improving erythema, telangiectasias, and skin texture. It also had a relatively long effect on improving skin laxity; however, it had only a limited ability to improve rhytides and dyschromia. It can mildly to moderately improve the global photoaging. This global effect can be noted 1 month after treatment and becomes most clinically apparent 3 months after treatment. This is maintained at least 6 months after treatment. MI index and SC and D values increased while EI index and TEWL values decreased after the treatment. The subjects' self-assessment improved by 2.7 ± 1.2 points. The overall satisfaction rate was 88%. The degree of pain measured 2.5 ± 1.9 points on average. There was no downtime and no severe side effects reported. The sequential implementation of bipolar radiofrequency based optical combination devices (IPL, IR, diode laser) is effective and safe for global facial photoaging.

Purpose To compare overall survival between patients who received neoadjuvant therapy (NAT) followed by resection and those who received upfront resection (UR)—as well as a subgroup of UR patients who also received adjuvant therapy—for early-stage resectable pancreatic adenocarcinoma. Patients and Methods Adult patients with resected, clinical stage I or II adenocarcinoma of the head of the pancreas were identified in the National Cancer Database from 2006 to 2012. Patients who underwent NAT followed by curative-intent resection were matched by propensity score with patients whose tumors were resected upfront. Overall survival was compared by using a Cox proportional hazards regression model. Early postoperative and oncologic outcomes were evaluated. Results We identified 15,237 patients with clinical stage I or II resected pancreatic head adenocarcinoma. From the NAT group, 2,005 patients (95%) were matched with 6,015 patients who underwent UR. The NAT group was associated with improved survival compared with UR (median survival, 26 months v 21 months, respectively; stratified log-rank P < .01; hazard ratio, 0.72; 95% CI, 0.68 to 0.78). Patients in the UR group had higher pathologic T stage (pT3 and T4: 86% v 73%; P < .01), higher positive lymph nodes (73% v 48%; P < .01), and higher positive resection margin (24% v 17%; P < .01). Compared with a subset of UR patients who received adjuvant therapy, NAT patients had a better survival (adjusted hazard ratio, 0.83; 95% CI, 0.73 to 0.89). Conclusion NAT followed by resection has a significant survival benefit compared with UR in early-stage, resected pancreatic head adenocarcinoma. These findings support the use of NAT, particularly as a patient selection tool, in the management of resectable pancreatic adenocarcinoma.

Introduction The FDA issued a statement on July 30, 2018, expressing concern over the marketing of lasers and energy-based devices to promote "vaginal rejuvenation." The FDA stated that there is insufficient data to recommend this modality for optimization of sexual function and alleviation of genitourinary syndrome of menopause (GSM)-related symptoms in postmenopausal or postpartum women. This analysis aims to characterize the mandatory and voluntary reports concerning laser and energy-based procedures marketed for vaginal rejuvenation. Methods Cross-sectional analysis of the FDA database, Manufacturer and User Facility Device Experience (MAUDE), for events related to laser and energy-based devices for vaginal rejuvenation. Results Between October 2015 and January 2019, 45 distinct events describing 46 patients were recorded and reviewed. The most commonly reported adverse event related to the procedure was pain (vulvar, bladder, urethral, or unspecified) (n = 19). The majority of patients sought medical care for their injuries, which included evaluation by urgent care, urology, gynecology, neurology, gastroenterology, pelvic floor therapy, primary care providers, and the device operator. Thirty-three patients indicated chronicity of their injury, which included long-term pain, numbness, burning, bladder disturbances, infections, scarring, dyspareunia, worsening symptoms, aggravation of lichen sclerosis, and disfigurement. Conclusions A variety of adverse events associated with the use of laser and energy-based devices for "vaginal rejuvenation" was reported to the MAUDE database. Although the circumstances surrounding these events were unclear, these reports signify the importance of clinical trials that investigate the efficacy and safety profile of laser and energy-based devices for optimization of sexual function and treatment of GSM-related symptoms. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

BACKGROUND Fragmented cancer care (FC), or care received from multiple institutions, increases systemic health care costs and potentiates cancer care disparities. There is a paucity of data on mechanisms contributing to FC and the resulting effect on patient outcomes. This study characterized patient- and hospital-level factors associated with FC, time to treatment (TTT), and overall survival (OS) in patients with hepatocellular carcinoma (HCC). METHODS Patients newly diagnosed with HCC from 2004 to 2015 and receiving treatment were identified in the Texas Cancer Registry. Patient- and hospital-level factors were compared across 2 cohorts: an FC treatment group and a nonfragmented cancer care (NFC) treatment group. Covariate-adjusted treatment use and OS were compared between the 2 treatment groups. RESULTS Among 4329 patients with HCC, 1185 (27.4%) received FC, and 3144 (72.6%) received NFC. Compared with NFC patients, FC patients had larger tumors (median size ≥4 cm, 52.6% vs 35.2%; P

INTRODUCTION: Gestational ethanol exposure is associated with multiple developmental abnormalities, collectively termed fetal alcohol spectrum disorder (FASD). While the majority of women abstain from ethanol following knowledge of pregnancy, one contributing factor to the high FASD prevalence is that pregnancy is not detected until 4–6 weeks. Thus, ethanol consumption continues during the initial stages of fetal development. METHODS: An experimental protocol is described in which rhesus macaques self-administer 1.5 g/kg/day ethanol (or isocaloric maltose-dextrin) prior to pregnancy and through the first 60 days of a 168-day gestation term. Menstrual cycles were monitored, including measurements of circulating estradiol and progesterone levels. The latency to consume 1.5g/kg ethanol and blood ethanol concentration (BEC) were measured. RESULTS: Twenty-eight fetuses (14 ethanol, 14 controls) were generated in this study. Ethanol did not affect menstrual cycles, or the probability of successful breeding. No ethanol-induced gross adverse effects on pregnancy were observed. Individual variability in latency to complete drinking translated into variability in BEC, measured 90 minutes following session start. Drinking latencies in controls and ethanol-drinkers were longer in the second gestational month than in the first. All pregnancies reached the planned experimental time point of G85, G110, or G135, when in utero MRIs were performed, fetuses were delivered by cesarean section, and brains were evaluated with ex vivo procedures, including slice electrophysiology. Fetal tissues have been deposited to the Monkey Alcohol Tissue Research Resource (MATRR). CONCLUSION: This FASD model takes advantage of the similarities between humans and rhesus macaques in gestational length relative to brain development, as well as similarities in ethanol self-administration and metabolism. The daily 1.5 g/kg dose of ethanol through the first trimester does not influence pregnancy success rates. However, pregnancy influences drinking behavior during the second month of pregnancy. Future publications using this model will describe the effect of early-gestational ethanol exposure on anatomical and functional brain development at subsequent gestational ages.

Rationale: Patients with heart failure with preserved ejection fraction (HFpEF) experience elevated filling pressures and reduced ventricular compliance. The splicing factor RNA-binding motif 20 (RBM20) regulates the contour length of titin’s spring region and thereby determines the passive stiffness of cardiomyocytes. Inhibition of RBM20 leads to super compliant titin isoforms (N2BAsc) that reduce passive stiffness. Objective: To determine the therapeutic potential of upregulating compliant titin isoforms in an HFpEF-like state in the mouse. Methods and Results: Constitutive and inducible cardiomyocyte-specific RBM20–inhibited mice were produced on a Ttn ΔIAjxn background to assess the effect of upregulating compliant titin at the cellular and organ levels. Genetic deletion of the I-band–A-band junction ( IAjxn ) in titin increases strain on the spring region and causes a HFpEF-like syndrome in the mouse without pharmacological or surgical intervention. The increased strain represents a mechanical analog of deranged post-translational modification of titin that results in increased passive myocardial stiffness in patients with HFpEF. On inhibition of RBM20 in Ttn ΔIAjxn mice, compliant titin isoforms were expressed, diastolic function was normalized, exercise performance was improved, and pathological hypertrophy was attenuated. Conclusions: We report for the first time a benefit from upregulating compliant titin isoforms in a murine model with HFpEF-like symptoms. Constitutive and inducible RBM20 inhibition improves diastolic function resulting in greater tolerance to exercise. No effective therapies exists for treating this pervasive syndrome; therefore, our data on RBM20 inhibition are clinically significant.

The use of lasers and light devices for the removal of adipose tissue and cellulite represents a new and exciting frontier in the laser field. To date, there are few non-invasive devices in the laser field all of which can only claim limited efficacy. This chapter will review the laser, light sources, as well as devices with radiofrequency and ultrasound devices that currently purport to treat cellulite or adipose tissue.

Purpose: Alcohol misuse is a serious public health issue with conflicting findings relating it to obesity. The purpose of this study was to assess whether alcohol use differs by obesity status in middle aged males in the general population. Methods: This cross sectional analysis used 2016 Behavioral Risk Factor Surveillance System (BRFSS) data for males ages 45 to 64 from Maine (N=1,667), North Dakota (N=1,060), South Carolina (N=1,669), and Wisconsin (N=998). Multiple logistic regression analyses conducted by state were utilized to examine the relationship between alcohol use and obesity while controlling for tobacco use, number of health conditions, mental health, physical activity, education level, employment status, income level, and ethnicity. Results: Across states, about one third of the sample was obese (35%-38%) and about half to two thirds reported alcohol use (55%-69%). Adjusted results indicated that excessive alcohol use was inversely related to weight status. In addition, having multiple health conditions was positively related to weight status while physical activity and tobacco use were inversely related to weight status. Conclusion: The results indicated that obesity differed by alcohol use in 45 to 64 year old males in that excessive alcohol use was related to non-obesity. In primary care settings, about one third of middle-aged males may be obese and up to two-thirds may consume alcohol; however, these should be assessed and treated separately. For those with excessive alcohol use, practitioners should evaluate adequate nutrition. In addition, number of health conditions, tobacco use, and physical activity were significantly related to obesity. Therefore, clinicians should screen for all if middle aged males present with any, coordinate treatment of multiple conditions, and educate patients on the benefits of exercise and smoking cessation.

The evaluation of lymph node involvement is an essential component of cancer staging. Examining an inadequate number of lymph nodes potentially results in understaging. Current guidelines for lymph node retrieval for ampullary adenocarcinoma are based on data extrapolated from other periampullary malignancies and may not be applicable. The aim of this study was to determine the number of lymph nodes that should be examined in resection specimens to optimize staging in ampullary adenocarcinoma. Patients with ampullary adenocarcinoma from 2004 to 2014 were identified in the National Cancer Database. We determined the minimum examined lymph node (ELN) count by modeling each potential ELN count from 2 to 30 in a multivariable regression analysis and confirmed the results with a sensitivity analysis. We identified 7451 patients of whom 52.2% had T3 or T4 disease and 51.4% had lymph node metastases. The median ELN count was 13 (interquartile range, 8–19). Increasing ELNs were independently associated with an increased likelihood of having positive nodal disease (odds ratio, 1.03; 95% confidence interval [CI], 1.03–1.04) and improved overall survival in both node-negative (hazard ratio [HR], 0.98; 95% CI, 0.97–0.99) and node-positive patients (HR, 0.99; 95% CI, 0.986–0.998). We determined that at least 17 lymph nodes should be examined. Overall survival for patients with 17 or more ELNs was superior than for those with fewer than 17 ELNs. Increasing ELNs were independently associated with improved overall survival in patients with resected ampullary adenocarcinoma. At least 17 lymph nodes should be examined for optimal nodal staging.

Background and Objectives Racial and ethnic variations have been described in the different malignancies, but no such data exists for ampullary cancer. The aim of this study was to present an updated report on the epidemiology, treatment patterns, and survival of a national cohort of ampullary cancer patients. Methods Patients diagnosed with ampullary cancer between 2004 and 2014 were identified in the National Cancer Database. Overall survival was estimated and compared between racial/ethnic groups using the log-rank test. Results A total of 14 879 patients were identified; 78% of the patients were White, 9% Hispanic, 8% Black, and 5% Asian. We noted significant differences in disease presentation, socioeconomic status, and outcomes. Blacks had the lowest median overall survival at 18.9 months followed by Whites at 23.9 months, Hispanics at 32.7 months, and Asians at 37.4 months. On a multivariate Cox proportional-hazards model, being Black was associated with worse survival compared to being White while being Asian and Hispanic were associated with better survival. Conclusions Overall survival of ampullary cancer patients was independently associated with race and ethnicity. Further studies are needed to clarify whether these disparities are primarily due to socioeconomic status or biologic factors.

Background and Objective Standard surgical and destructive treatments for basal cell carcinoma (BCC) can result in significant morbidity and scarring, stimulating the investigation of alternative non-surgical options. The objective of this study was to determine the safety, clinical, and histological efficacy of pulsed, high-fluence 1064 nm Nd:YAG laser therapy for the treatment of BCC on the trunk and extremities. Study Design/Materials and Methods This was a prospective, non-randomized, open-label clinical trial. Ten subjects with a biopsy-proven BCC less than 1.5 cm in diameter on the trunk or extremities received one treatment with a 10 milliseconds pulsed 1064 nm Nd:YAG laser. Standard excision was performed 1 month after laser treatment to confirm histologic clearance. Results The laser treatment was quick and well tolerated. There was complete histologic clearance after one treatment in 92% of the BCC tumors, overall. At higher fluences, there was 100% histologic clearance after one treatment. No significant adverse events were seen, including scarring. Conclusions The 1064 nm long-pulsed Nd:YAG laser may offer a safe alternative for treating BCC off the face. A larger study is highly warranted to confirm these preliminary results. Lasers Surg. Med. 47:106–110, 2015. © 2015 Wiley Periodicals, Inc.

Objective To investigate the effect of pulsed dye laser (PDL 595 nm) on the proliferation and expression of connective tissue growth factor (CTGF) in cultured keloid fibroblasts. Materials and Methods Cultured keloid fibroblasts were exposed to pulsed dye laser irradiation at fluences of 6, 8, and 10 J/cm2, with pulse durations of 1.5, 3, and 10 ms. The viability of keloid fibroblasts was measured with CCK-8 at 72, 24, and 12 hours prior to irradiation. Subsequently, viability was measured at 12, 24, and 72 hours post-irradiation. Additionally, the fibroblast cell cycle and apoptosis rate were measured by flow cytometry. Finally, keloid fibroblasts underwent real-time polymerase chain reaction (PCR) and Western blot to investigate the CTGF mRNA and protein expression after PDL irradiation. The untreated cultured keloid fibroblasts served as controls. Results The proliferation of keloid fibroblasts was significantly inhibited after PDL irradiation. Both CTGF mRNA and protein expression were significantly down-regulated in 1.5, 3, and 10 ms pulse duration groups, in a dose dependent manner (P 0.05). Conclusions Within certain fluence ranges, pulsed dye laser can effectively suppress the growth of keloids and significantly down-regulate CTGF mRNA and CTGF expression. Lasers Surg. Med. 47:203–209, 2015. © 2015 Wiley Periodicals, Inc.

Background and Objective It is essential for physicians to be fully informed regarding adverse events and malfunctions associated with medical devices that occur in routine practice. There is limited information on this important issue in the medical literature, and it is mostly based on initial studies and case reports. More advanced knowledge regarding device adverse events is necessary to guide physicians towards providing safe treatments. The FDA requires that manufacturers and device users submit medical device reports (MDRs) for suspected injuries from device use or malfunction. The database of MDRs, entitled Manufacturer and User Facility Device Experience (MAUDE) enables the FDA to monitor device performance and identify potential safety issues. Study Design/Materials and Methods We employed the following search strategy to identify reported adverse events. We searched the MAUDE electronic database on the FDA website in December 2013: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/search.cfm We collected all reported cases between 1991 and December 2013. The search terms utilized included a comprehensive list of device manufacturers, specific product names, and the wavelengths/technology of the devices used in the field of dermatology. Results Our search yielded 1257 MDRs. Forty-five MDRs were excluded due to insufficient data. The data is broken down into the adverse events observed, such as, but not limited to: blistering, burns, scarring, dyschromia, fat loss, and nerve palsy. The MDRs describe the adverse event and attempt to determine if it was related to device malfunction versus operator error. Radiofrequency devices, diode lasers, and intense pulsed light devices were the most commonly reported devices related to injuries. Conclusion 1257 MDRs, from a myriad of devices used in dermatology, have been reported to the FDA as of December 2013. Despite the underreporting of adverse events, the MAUDE database is an untapped resource of post-market surveillance of medical devices. The database can offer additional information, which combined with the initial device studies and published case reports from our colleagues, will help raise awareness and improve patient safety. Lasers Surg. Med. 47:133–140, 2015. © 2015 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Non-ablative fractional laser procedures have become increasingly popular since their introduction in 2004. The fractional 1,927 nm thulium laser is a non-ablative device that penetrates up to 300 μm in the skin and the 1,550 nm erbium:glass laser penetrates up to 1,400 μm. These procedures are considered minimally invasive with a high safety profile; therefore, infectious complications are exceedingly rare. However, we report five recent cases of bacterial infection with both gram-positive and gram-negative organisms following treatment with the fractional 1550/1927 nm laser approximately 1 day to 1 week post-procedure. One patient had a rapidly progressing pustular eruption with symptoms of sepsis. These patients were seen immediately, cultures were obtained and empiric antibiotic therapy was initiated. They recovered without long-term complications. Rapid-onset bacterial infections following non-ablative laser resurfacing with the 1550/1927 nm laser have not been previously reported in the literature. The infections can progress quickly and lead to serious sequelae, including systemic illness and severe scarring, if not identified and appropriately treated. We present these cases to highlight the importance of close surveillance and when appropriate, rapid intervention, following non-ablative fractional procedures, especially when patients present with atypical symptoms and signs. Lasers Surg. Med. 47:128–132, 2015. © 2015 Wiley Periodicals, Inc.

Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients.In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle.The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P=0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet.In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis. (Funded by Amgen; EVOLVE ClinicalTrials.gov number, NCT00345839.).

Oxidative stress suppresses host immunity by generating oxidized lipid agonists of the platelet-activating factor receptor (PAF-R). Because many classical chemotherapeutic drugs induce reactive oxygen species (ROS), we investigated whether these drugs might subvert host immunity by activating PAF-R. Here, we show that PAF-R agonists are produced in melanoma cells by chemotherapy that is administered in vitro, in vivo, or in human subjects. Structural characterization of the PAF-R agonists induced revealed multiple oxidized glycerophosphocholines that are generated nonenzymatically. In a murine model of melanoma, chemotherapeutic administration could augment tumor growth by a PAF-R–dependent process that could be blocked by treatment with antioxidants or COX-2 inhibitors or by depletion of regulatory T cells. Our findings reveal how PAF-R agonists induced by chemotherapy treatment can promote treatment failure. Furthermore, they offer new insights into how to improve the efficacy of chemotherapy by blocking its heretofore unknown impact on PAF-R activation. Cancer Res; 74(23); 7069–78. ©2014 AACR.