Measuring What Matters: A Qualitative Study of the Relevance and Clinical Utility of PROMIS Surveys in Systemic Lupus Erythematosus.

OBJECTIVE: To evaluate the relevance and clinical utility of the Patient-Reported Outcomes Measurement Information System (PROMIS) surveys in patients with systemic lupus erythematosus (SLE). METHODS: Adults with SLE receiving routine outpatient care at a tertiary care academic medical center participated in a qualitative study. Patients completed PROMIS computerized adaptive tests (CATs) in 12 selected domains and rated the relevance of each domain to their experience with SLE. Focus groups and interviews were conducted to elucidate the relevance of the PROMIS surveys, identify additional domains of importance, and explore the utility of the surveys in clinical care. Focus group and interview transcripts were coded, and a thematic analysis was performed using an iterative inductive process. RESULTS: Twenty-eight women and 4 men participated in 4 focus groups and 4 interviews, respectively. Participants endorsed the relevance and comprehensiveness of the selected PROMIS domains in capturing the effect of SLE on their lives. They ranked fatigue, pain interference, sleep disturbance, physical function, and applied cognition abilities as the most salient health-related quality of life (HRQOL) domains. They suggested that the disease-agnostic PROMIS questions holistically captured their lived experience of SLE and its common comorbidities. Participants were enthusiastic about using PROMIS surveys in clinical care and described potential benefits in enabling disease monitoring and management, facilitating communication, and empowering patients. CONCLUSION: PROMIS includes the HRQOL domains that are of most importance to individuals with SLE. Patients suggest that these universal tools can holistically capture the impact of SLE and enhance routine clinical care.

Baseline demographic, clinical, and cognitive characteristics of the Alzheimer's Prevention Initiative (API) Autosomal-Dominant Alzheimer's Disease Colombia Trial.

INTRODUCTION: The API AutosomalDominant AD (ADAD) Colombia Trial is a placebo-controlled clinical trial of crenezumab in 252 cognitively unimpaired 30 to 60-year-old Presenilin 1 (PSEN1) E280A kindred members, including mutation carriers randomized to active treatment or placebo and non-carriers who receive placebo. METHODS: Of the 252 enrolled, we present data on a total of 242 mutation carriers and non-carriers matched by age range, excluding data on 10 participants to protect participant confidentiality, genetic status, and trial integrity. RESULTS: We summarize demographic, clinical, cognitive, and behavioral data from 167 mutation carriers and 75 non-carriers, 30 to 53 years of age. Carriers were significantly younger than non-carriers ((mean age ± SD) 37 ± 5 vs 42 ± 6), had significantly lower Mini Mental Status Exam (MMSE) scores (28.8 ± 1.4 vs 29.2 ± 1.0), and had consistently lower memory scores. DISCUSSION: Although PSEN1 E280A mutation carriers in the Trial are cognitively unimpaired, they have slightly lower MMSE and memory scores than non-carriers. Their demographic characteristics are representative of the local population.

Developmental origins of nonalcoholic fatty liver disease as a risk factor for exaggerated metabolic and cardiovascular-renal disease.

Intrauterine growth restriction (IUGR) is linked to increased risk for chronic disease. Placental ischemia and insufficiency in the mother are implicated in predisposing IUGR offspring to metabolic dysfunction, including hypertension, insulin resistance, abnormalities in glucose homeostasis, and nonalcoholic fatty liver disease (NAFLD). It is unclear whether these metabolic disturbances contribute to the developmental origins of exaggerated cardiovascular-renal disease (CVRD) risk accompanying IUGR. IUGR impacts the pancreas, adipose tissue, and liver, which are hypothesized to program for hepatic insulin resistance and subsequent NAFLD. NAFLD is projected to become the major cause of chronic liver disease and contributor to uncontrolled type 2 diabetes mellitus, which is a leading cause of chronic kidney disease. While NAFLD is increased in experimental models of IUGR, lacking is a full comprehension of the mechanisms responsible for programming of NAFLD and whether this potentiates susceptibility to liver injury. The use of well-established and clinically relevant rodent models, which mimic the clinical characteristics of IUGR, metabolic disturbances, and increased blood pressure in the offspring, will permit investigation into mechanisms linking adverse influences during early life and later chronic health. The purpose of this review is to propose mechanisms, including those proinflammatory in nature, whereby IUGR exacerbates the pathogenesis of NAFLD and how these adverse programmed outcomes contribute to exaggerated CVRD risk. Understanding the etiology of the developmental origins of chronic disease will allow investigators to uncover treatment strategies to intervene in the mother and her offspring to halt the increasing prevalence of metabolic dysfunction and CVRD.

Effect of sequence and metal ions on UVB-induced anti cyclobutane pyrimidine dimer formation in human telomeric DNA sequences.

Irradiation of G-quadruplex forming human telomeric DNA with ultraviolet B (UVB) light results in the formation of anti cyclobutane pyrimidine dimers (CPDs) between loop 1 and loop 3 in the presence of potassium ions but not sodium ions. This was unexpected because the sequences involved favor the nonphotoreactive hybrid conformations in K(+) solution, whereas a potentially photoreactive basket conformation is favored in Na(+) solution. To account for these contradictory results, it was proposed that the loops are too far apart in the basket conformation in Na(+) solution but close enough in a two G-tetrad basket-like form 3 conformation that can form in K(+) solution. In the current study, Na(+) was still found to inhibit anti CPD formation in sequences designed to stabilize the form 3 conformation. Furthermore, anti CPD formation in K(+) solution was slower for the sequence previously shown to exist primarily in the proposed photoreactive form 3 conformation than the sequence shown to exist primarily in a nonphotoreactive hybrid conformation. These results suggest that the form 3 conformation is not the principal photoreactive conformation, and that G-quadruplexes in K(+) solution are dynamic and able to access photoreactive conformations more easily than in Na(+) solution.

Kinetic intermediates in amyloid assembly.

In contrast to an expected Ostwald-like ripening of amyloid assemblies, the nucleating core of the Dutch mutant of the Aß peptide of Alzheimer's disease assembles through a series of conformational transitions. Structural characterization of the intermediate assemblies by isotope-edited IR and solid-state NMR reveals unexpected strand orientation intermediates and suggests new nucleation mechanisms in a progressive assembly pathway.

Electronic medical record: research tool for pancreatic cancer?

BACKGROUND: A novel data warehouse based on automated retrieval from an institutional health care information system (HIS) was made available to be compared with a traditional prospectively maintained surgical database. METHODS: A newly established institutional data warehouse at a single-institution academic medical center autopopulated by HIS was queried for International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes for pancreatic neoplasm. Patients with ICD-9-CM diagnosis codes for pancreatic neoplasm were captured. A parallel query was performed using a prospective database populated by manual entry. Duplicated patients and those unique to either data set were identified. All patients were manually reviewed to determine the accuracy of diagnosis. RESULTS: A total of 1107 patients were identified from the HIS-linked data set with pancreatic neoplasm from 1999-2009. Of these, 254 (22.9%) patients were also captured by the surgical database, whereas 853 (77.1%) patients were only in the HIS-linked data set. Manual review of the HIS-only group demonstrated that 45.0% of patients were without identifiable pancreatic pathology, suggesting erroneous capture, whereas 36.3% of patients were consistent with pancreatic neoplasm and 18.7% with other pancreatic pathology. Of the 394 patients identified by the surgical database, 254 (64.5%) patients were captured by HIS, whereas 140 (35.5%) patients were not. Manual review of patients only captured by the surgical database demonstrated 85.9% with pancreatic neoplasm and 14.1% with other pancreatic pathology. Finally, review of the 254 patient overlap demonstrated that 80.3% of patients had pancreatic neoplasm and 19.7% had other pancreatic pathology. CONCLUSIONS: These results suggest that cautious interpretation of administrative data rely only on ICD-9-CM diagnosis codes and clinical correlation through previously validated mechanisms.

Rankings versus reality in pancreatic cancer surgery: a real-world comparison.

BACKGROUND: Patients are increasingly confronted with systems for rating hospitals. However, the correlations between publicized ratings and actual outcomes after pancreatectomy are unknown. METHODS: The Massachusetts Division of Health Care Finance and Policy Hospital Inpatient Discharge Database was queried to identify pancreatic cancer resections carried out during 2005-2009. Hospitals performing fewer than 10 pancreatic resections in the 5-year period were excluded. Primary outcomes included mortality, complications, median length of stay (LoS) and a composite outcomes score (COS) combining primary outcomes. Ranks were determined and compared for: (i) volume, and (ii) ratings identified from consumer-directed hospital ratings including the US News & World Report (USN), Consumer Reports, Healthgrades and Hospital Compare. An inter-rater reliability analysis was performed and correlation coefficients (r) between outcomes and ratings, and between rating systems were calculated. RESULTS: Eleven hospitals in which a total of 804 pancreatectomies were conducted were identified. Surgical volume correlated with overall outcome, but was not the strongest indicator. The highest correlation referred to that between USN rank and overall outcome. Mortality was most strongly correlated with Healthgrades ratings (r = 0.50); however, Healthgrades ratings demonstrated poorer correlations with all other outcomes. Consumer Reports ratings showed inverse correlations. CONCLUSIONS: The plethora of publicly available hospital ratings systems demonstrates heterogeneity. Volume remains a good but imperfect indicator of surgical outcomes. Further systematic investigation into which measures predict quality outcomes in pancreatic cancer surgery will benefit both patients and providers.

Synthesis and Photopatterning of Synthetic Thiol-Norbornene Hydrogels.

Hydrogels are a class of soft biomaterials and the material of choice for a myriad of biomedical applications due to their biocompatibility and highly tunable mechanical and biochemical properties. Specifically, light-mediated thiol-norbornene click reactions between norbornene-modified macromers and di-thiolated crosslinkers can be used to form base hydrogels amenable to spatial biochemical modifications via subsequent light reactions between pendant norbornenes in the hydrogel network and thiolated peptides. Macromers derived from natural sources (e.g., hyaluronic acid, gelatin, alginate) can cause off-target cell signaling, and this has motivated the use of synthetic macromers such as poly(ethylene glycol) (PEG). In this study, commercially available 8-arm norbornene-modified PEG (PEG-Nor) macromers were reacted with di-thiolated crosslinkers (dithiothreitol, DTT) to form synthetic hydrogels. By varying the PEG-Nor weight percent or DTT concentration, hydrogels with a stiffness range of 3.3 kPa-31.3 kPa were formed. Pendant norbornene groups in these hydrogels were used for secondary reactions to either increase hydrogel stiffness (by reacting with DTT) or to tether mono-thiolated peptides to the hydrogel network. Peptide functionalization has no effect on bulk hydrogel mechanics, and this confirms that mechanical and biochemical signals can be independently controlled. Using photomasks, thiolated peptides can also be photopatterned onto base hydrogels, and mesenchymal stem cells (MSCs) attach and spread on RGD-functionalized PEG-Nor hydrogels. MSCs encapsulated in PEG-Nor hydrogels are also highly viable, demonstrating the ability of this platform to form biocompatible hydrogels for 2D and 3D cell culture with user-defined mechanical and biochemical properties.

Patterns of genome size diversity in bats (order Chiroptera).

Despite being a group of particular interest in considering relationships between genome size and metabolic parameters, bats have not been well studied from this perspective. This study presents new estimates for 121 "microbat" species from 12 families and complements a previous study on members of the family Pteropodidae ("megabats"). The results confirm that diversity in genome size in bats is very limited even compared with other mammals, varying approximately 2-fold from 1.63 pg in Lophostoma carrikeri to 3.17 pg in Rhinopoma hardwickii and averaging only 2.35 pg ± 0.02 SE (versus 3.5 pg overall for mammals). However, contrary to some other vertebrate groups, and perhaps owing to the narrow range observed, genome size correlations were not apparent with any chromosomal, physiological, flight-related, developmental, or ecological characteristics within the order Chiroptera. Genome size is positively correlated with measures of body size in bats, though the strength of the relationships differs between pteropodids ("megabats") and nonpteropodids ("microbats").

Does increasing insurance improve outcomes for US cancer patients?

BACKGROUND: Although debate continues on US healthcare and insurance reform, data are lacking on the effect of insurance on community-level cancer outcomes. Therefore, the objective of the present study was to examine the association of insurance and cancer outcomes. MATERIALS AND METHODS: The US Census Bureau Current Population Survey, Small Area Health Insurance Estimates (2000) were used for the rates of uninsurance. Counties were divided into tertiles according to the uninsurance rates. The data were compared with the cancer incidence and survival for patients residing in counties captured by the Surveillance, Epidemiology, and End Results database (2000-2006). Aggregate patient data were collected of US adults (aged ≥18 y) diagnosed with the following cancers: pancreatic, esophageal, liver or bile duct, lung or bronchial, ovarian, colorectal, breast, prostate, melanoma, and thyroid. The outcomes included the stage at diagnosis, surgery, and survival. Univariate tests and proportional hazards were calculated. RESULTS: The US uninsurance rate was 14.2%, and the range for the Surveillance, Epidemiology, and End Results counties was 8.3%-24.1%. Overall, patients from lower uninsurance rate counties demonstrated longer median survival. Adjusting for patient characteristics and cancer stage (for each cancer), the patients in the higher uninsurance rate counties demonstrated greater mortality (8%-15% increased risk on proportional hazards). The county uninsurance rate was associated with the stage at diagnosis for all cancers, except pancreatic and esophageal, and was also associated with the likelihood of being recommended for cancer-directed surgery (for all cancers). CONCLUSIONS: Health insurance coverage at a community level appears to influence survival for patients with cancer. Additional investigations are needed to examine whether individual versus community associations exist and how best to surmount barriers to cancer care.

Outcomes following resection of pancreatic cancer.

Pancreatic cancer is an aggressive and highly lethal malignancy. Surgical resection is a modest tool, but it provides the only potential for curative therapy and often prolongs survival. This article reviews the progress made on both local and national levels towards an era of safer pancreatic surgery, while discussing both perioperative outcomes and long-term survival after resection.

Imaging mRNA expression levels in living cells with PNA·DNA binary FRET probes delivered by cationic shell-crosslinked nanoparticles.

Optical imaging of gene expression through the use of fluorescent antisense probes targeted to the mRNA has been an area of great interest. The main obstacles to developing highly sensitive antisense fluorescent imaging agents have been the inefficient intracellular delivery of the probes and high background signal from unbound probes. Binary antisense probes have shown great promise as mRNA imaging agents because a signal can only occur if both probes are bound simultaneously to the mRNA target site. Selecting an accessible binding site is made difficult by RNA folding and protein binding in vivo and the need to bind two probes. Even more problematic, has been a lack of methods for efficient cytoplasmic delivery of the probes that would be suitable for eventual applications in vivo in animals. Herein we report the imaging of iNOS mRNA expression in live mouse macrophage cells with PNA·DNA binary FRET probes delivered by a cationic shell crosslinked knedel-like nanoparticle (cSCK). We first demonstrate that FRET can be observed on in vitro transcribed mRNA with both the PNA probes and the PNA·DNA hybrid probes. We then demonstrate that the FRET signal can be observed in live cells when the hybrid probes are transfected with the cSCK, and that the strength of the FRET signal is sequence specific and depends on the mRNA expression level.

A stereoselective cyclization strategy for the preparation of γ-lactams and their use in the synthesis of α-methyl-ß-proline.

A straightforward stereoselective and enantiodivergent cyclization strategy for the construction of γ-lactams is described. The cyclization strategy makes use of chiral malonic esters prepared from enantiomerically enriched monoesters of disubstituted malonic acid. The cyclization occurs with the selective displacement of a substituted benzyl alcohol as the leaving group. A Hammett study illustrates that the cyclization is under electronic control. The resulting γ-lactam can be readily converted into a novel proline analogue.

Evaluating the Safety and Efficacy of Crenezumab vs Placebo in Adults With Early Alzheimer Disease: Two Phase 3 Randomized Placebo-Controlled Trials.

Importance: Alzheimer disease (AD), a neurodegenerative disease characterized by ß-amyloid plaques and τ tangles in the brain, represents an unmet medical need with no fully approved therapeutics to modify disease progression. Objective: To investigate the safety and efficacy of crenezumab, a humanized monoclonal immunoglobulin G4 antibody targeting ß-amyloid oligomers, in participants with prodromal to mild (early) AD. Design, Setting, and Participants: Two phase 3 multicenter randomized double-blind placebo-controlled parallel-group efficacy and safety studies of crenezumab in participants with early AD, CREAD and CREAD2, were initiated in 2016 and 2017, respectively, and were designed to evaluate the efficacy and safety of crenezumab in participants with early AD. CREAD (194 sites in 30 countries) and CREAD2 (209 sites in 27 countries) were global multicenter studies. A total of 3736 and 3664 participants were screened in CREAD and CREAD2, respectively. A total of 3736 and 3664 participants were screened in CREAD and CREAD2, respectively. Both trials enrolled individuals aged 50 to 85 years with early AD. Participants with some comorbidities and evidence of cerebral infarction or more than 4 microbleeds or areas of leptomeningeal hemosiderosis on magnetic resonance imaging were excluded. After 2923 and 2858 were excluded, respectively, 813 participants in CREAD and 806 in CREAD2 were randomly assigned in a 1:1 ratio to either placebo or crenezumab. In the final analysis, there were 409 participants in the placebo group and 404 in the crenezumab group in CREAD and 399 in the placebo group and 407 in the crenezumab group in CREAD2. Data were analyzed up until January 2019 and August 2019, respectively. Interventions: Participants received placebo or 60 mg/kg crenezumab intravenously every 4 weeks for up to 100 weeks. Main Outcomes and Measures: The primary outcome was change from baseline to week 105 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. Results: There were 813 participants in CREAD (mean [SD] age, 70.7 [8.2] years; 483 female and 330 male) and 806 in CREAD2 (mean [SD] age, 70.9 [7.7] years; 456 female and 350 male). Baseline characteristics were balanced between both groups. The between-group difference in mean change from baseline in CDR-SB score (placebo minus crenezumab) was -0.17 (95% CI, -0.86 to 0.53; P = .63) at week 105 in the CREAD study (88 placebo; 86 crenezumab). Compared with previous trials, no new safety signals were identified, and amyloid-related imaging abnormalities with edema were rare, mild, and transient. No meaningful changes in AD biomarkers were observed. Both studies were discontinued following a preplanned interim analysis indicating that CREAD was unlikely to meet the primary end point. Conclusions and Relevance: Crenezumab was well tolerated but did not reduce clinical decline in participants with early AD. Trial Registration: ClinicalTrials.gov Identifiers: CREAD, NCT02670083; CREAD2, NCT03114657.

Impact of center volume on outcomes of increased-risk liver transplants.

The use of high-risk donor livers, which is reflective of the gross national shortage of organs available for transplantation, has gained momentum. Despite the demand, many marginal livers are discarded annually. We evaluated the impact of center volume on survival outcomes associated with liver transplantation using high-donor risk index (DRI) allografts. We queried the Scientific Registry of Transplant Recipients database for deceased donor liver transplants (n = 31,576) performed between 2002 and 2008 for patients who were 18 years old or older, and we excluded partial and multiple liver transplants. A high-DRI cohort (n = 15,668), which was composed of patients receiving grafts with DRIs > 1.90, was analyzed separately. Transplant centers (n = 102) were categorized into tertiles by their annual procedure volumes: high-volume centers (HVCs; 78-215 cases per year), medium-volume centers (MVCs; 49-77 cases per year), and low-volume centers (LVCs; 5-48 cases per year). The endpoints were allograft survival and recipient survival. In comparison with their lower volume counterparts, HVCs used donors with higher mean DRIs (2.07 for HVCs, 2.01 for MVCs, and 1.91 for LVCs), more donors who were 60 years old or older (18.02% for HVCs, 16.85% for MVCs, and 12.39% for LVCs), more donors who died after a stroke (46.52% for HVCs, 43.71% for MVCs, and 43.36% for LVCs), and more donation after cardiac death organs (5.04% for HVCs, 4.45% for MVCs, and 3.51% for LVCs, all P values < 0.001). Multivariate risk-adjusted frailty models showed that increased procedure volume at a transplant center led to decreased risks of allograft failure [hazard ratio (HR) = 0.93, 95% confidence interval (CI) = 0.89-0.98, P = 0.002] and recipient death (HR = 0.90, 95% CI = 0.83-0.97, P = 0.004) for high-DRI liver transplants. In conclusion, HVCs more frequently used higher DRI livers and achieved better risk-adjusted allograft and recipient survival. A greater understanding of the outcomes of transplantation with high-DRI livers may improve their utilization, the postoperative outcomes, and future allocation practices.

Colectomy performance improvement within NSQIP 2005-2008.

BACKGROUND: All open and laparoscopic colectomies submitted to the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) were evaluated for trends and improvements in operative outcomes. METHODS: 48,247 adults (≥18 y old) underwent colectomy in ACS NSQIP, as grouped by surgical approach (laparoscopic versus open), urgency (emergent versus elective), and operative year (2005 to 2008). Primary outcomes measured morbidity, mortality, perioperative, and postoperative complications. RESULTS: The proportion of laparoscopic colectomies performed increased annually (26.3% to 34.0%), while open colectomies decreased (73.7% to 66.0%; P < 0.0001). Most emergent colectomies were open procedures (93.5%) representing 24.3% of all open cases. The overall risk-adjusted morbidity and mortality for all colectomy procedures did not show a statistically significant change over time, however, morbidity and mortality increased among open colectomies (r = 0.03) and decreased among laparoscopic colectomies (r = -0.04; P < 0.0001). Postoperative complications reduced significantly including superficial surgical site infections (9.17% to 8.20%, P < 0.004), pneumonia (4.60% to 3.97%, P < 0.0001), and sepsis (4.72%, 2005; 6.81%, 2006; 5.62%, 2007; 5.09%, 2008; P < 0.0002). Perioperative improvements included operative time (169.2 to 160.0 min), PRBC transfusions (0.27 to 0.25 units) and length of stay (10.5 to 6.61 d; P < 0.0001). CONCLUSION: It appears that laparoscopic colectomies are growing in popularity over open colectomies, but the need for emergent open procedures remains unchanged. Across all colectomies, however, key postoperative and perioperative complications have improved over time. Participation in ACS NSQIP demonstrates quality improvement and may encourage greater enrollment.

Effect of centre volume and high donor risk index on liver allograft survival.

BACKGROUND: A growth in the utilization of high-risk allografts is reflective of a critical national shortage and the increasing waiting list mortality. Using risk-adjusted models, the aim of the present study was to determine whether a volume-outcome relationship existed among liver transplants at high risk for allograft failure. METHODS: From 2002 to 2008, the Scientific Registry of Transplant Recipients (SRTR) database for all adult deceased donor liver transplants (n = 31 587) was queried. Transplant centres (n = 102) were categorized by volume into tertiles: low (LVC; 31 cases/year), medium (MVC: 64 cases/year) and high (HVC: 102 cases/year). Donor risk comparison groups were stratified by quartiles of the Donor Risk Index (DRI) spectrum: low risk (DRI ≤ 1.63), moderate risk (1.64 > DRI > 1.90), high risk (1.91 > DRI > 2.26) and very high risk (DRI ≥ 2.27). RESULTS: HVC more frequently used higher-risk livers (median DRI: LVC: 1.82, MVC: 1.90, HVC: 1.97; P < 0.0001) and achieved better risk adjusted allograft survival outcomes compared with LVC (HR: 0.90, 95%CI: 0.85-0.95). For high and very high risk groups, transplantation at a HVC did contribute to improved graft survival [high risk: hazard ratio (HR): 0.85, 95% confidence interval (CI): 0.76-0.96; Very High Risk: HR: 0.88, 95%CI: 0.78-0.99]. CONCLUSION: While DRI remains an important aspect of allograft survival prediction models, liver transplantation at a HVC appears to result in improved allograft survival with high and very high risk DRI organs compared with LVC.

A Scalable Strand-Specific Protocol Enabling Full-Length Total RNA Sequencing From Single Cells.

RNA sequencing (RNAseq) has been widely used to generate bulk gene expression measurements collected from pools of cells. Only relatively recently have single-cell RNAseq (scRNAseq) methods provided opportunities for gene expression analyses at the single-cell level, allowing researchers to study heterogeneous mixtures of cells at unprecedented resolution. Tumors tend to be composed of heterogeneous cellular mixtures and are frequently the subjects of such analyses. Extensive method developments have led to several protocols for scRNAseq but, owing to the small amounts of RNA in single cells, technical constraints have required compromises. For example, the majority of scRNAseq methods are limited to sequencing only the 3' or 5' termini of transcripts. Other protocols that facilitate full-length transcript profiling tend to capture only polyadenylated mRNAs and are generally limited to processing only 96 cells at a time. Here, we address these limitations and present a novel protocol that allows for the high-throughput sequencing of full-length, total RNA at single-cell resolution. We demonstrate that our method produced strand-specific sequencing data for both polyadenylated and non-polyadenylated transcripts, enabled the profiling of transcript regions beyond only transcript termini, and yielded data rich enough to allow identification of cell types from heterogeneous biological samples.

Complications after pancreatectomy for neuroendocrine tumors: a national study.

BACKGROUND: Although resection of pancreatic neuroendocrine tumors (PNETs) has a demonstrated survival advantage, further evaluation of the overall morbidity of these procedures is needed. Our objective was to examine a composite outcome of major postoperative complications, including in-hospital mortality. MATERIALS AND METHODS: The Nationwide Inpatient Sample (NIS), 1998-2006, was used to identify all patients with a diagnosis of PNET who had undergone pancreatectomy. Candidate predictors consisted of patient and hospital characteristics. Univariate analyses included chi(2) tests. Multivariate analyses were performed with logistic regression to determine which predictors were independently associated with the composite outcome. RESULTS: A total of 463 (2274 nationally weighted) patients were identified. Overall composite postoperative complication rate was 29.6%. The majority of complications involved infections (11.1%), digestive complications (8.8%), or pulmonary compromise (7.3%). In-hospital mortality rate was 1.7%. High Charlson comorbidity score, procedure type of Whipple or total pancreatectomy, and urban hospital location were all associated with significantly increased complication rate. Logistic regression analysis demonstrated: Charlson score of > or =3 versus score of 0 (adjusted odds ratio (OR) 4.1, 95% confidence interval (CI) 2.1-8.3), surgery type of Whipple or total pancreatectomy versus partial pancreatectomy (adjusted OR 2.7, 95% CI 1.8-4.1), and hospital location of urban versus rural (adjusted OR 4.5, 95% CI 3.0-6.9). CONCLUSIONS: While in-hospital mortality rates are low for surgical resection of PNETs, there is a considerable overall postoperative complication rate associated with these procedures. Careful patient and surgery selection may be the key to a surgical treatment approach for PNETs that may optimize outcomes.