Patient-Centered Framework for Rehabilitation Research in Outpatient Settings.

Conducting high-quality clinical research is dependent on merging scientific rigor with the clinical environment. This is often a complex endeavor that may include numerous barriers and competing interests. Overcoming these challenges and successfully integrating clinical research programs into clinical practice settings serving rehabilitation outpatients is beneficial from both a logistical perspective (eg, supports efficient and successful research procedures) and the establishment of a truly patient-centered research approach. Leveraging our experience with navigating this research-clinical care relationship, this article (1) proposes the Patient-Centered Framework for Rehabilitation Research, a model for integrating patient-centered research in an outpatient clinical setting that incorporates a collaborative, team-based model encompassing patient-centered values, as well as strategies for recruitment and retention, with a focus on populations living with disabilities or chronic diseases; (2) describes application of this framework in a comprehensive specialty multiple sclerosis center with both general strategies and specific examples to guide adaptation and implementation in other settings; and (3) discusses the effect of the framework as a model in 1 center, as well as the need for additional investigation and adaptation for other populations. The 5 interconnected principles incorporated in the Framework and which prioritize patient-centeredness include identifying shared values, partnering with the clinical setting, engaging with the population, building relationships with individuals, and designing accessible procedures. The Patient-Centered Framework for Rehabilitation Research is a model presented as an adaptable roadmap to guide researchers in hopes of not only improving individual patients' experiences but also the quality and relevance of rehabilitation research as a whole. Future investigation is needed to test the Framework in other settings.

Tracking telomere fusions through crisis reveals conflict between DNA transcription and the DNA damage response.

Identifying attributes that distinguish pre-malignant from senescent cells provides opportunities for targeted disease eradication and revival of anti-tumour immunity. We modelled a telomere-driven crisis in four human fibroblast lines, sampling at multiple time points to delineate genomic rearrangements and transcriptome developments that characterize the transition from dynamic proliferation into replicative crisis. Progression through crisis was associated with abundant intra-chromosomal telomere fusions with increasing asymmetry and reduced microhomology usage, suggesting shifts in DNA repair capacity. Eroded telomeres also fused with genomic loci actively engaged in transcription, with particular enrichment in long genes. Both gross copy number alterations and transcriptional responses to crisis likely underpin the elevated frequencies of telomere fusion with chromosomes 9, 16, 17, 19 and most exceptionally, chromosome 12. Juxtaposition of crisis-regulated genes with loci undergoing de novo recombination exposes the collusive contributions of cellular stress responses to the evolving cancer genome.

Neighborhood Disorder, Social Support, and Outcomes Among Violence-Exposed African American Women.

Intimate partner violence (IPV) against women, particularly those living in poverty who have multiple marginalized identities, is a significant public health issue. IPV is associated with numerous mental health concerns including depression, hopelessness, and suicidal behavior. The present study examined the ecological determinants of these mental health outcomes in a high-risk sample of 67 low-income, African American women survivors of IPV. Based on an ecological framework that conceptualizes individuals as nested in multiple, interactive systems, we examined, longitudinally, the main and interactive effects of self-reported neighborhood disorder and social support from family members and friends on participants' mental health (i.e., self-reported depressive symptoms, hopelessness, and suicide intent). In multiple regression analyses, neighborhood disorder interacted with social support from family members to predict depressive symptoms and hopelessness over time. Neighborhood disorder also interacted with social support from friends to predict hopelessness and suicide intent over time. High levels of social support buffered against the dangerous effects of neighborhood disorder on depressive symptoms, hopelessness, and suicide intent; at low levels of social support, there was no significant association between neighborhood disorder and those mental health outcomes. Neighborhood disorder and social support did not yield significant main effects. These findings underscore the importance of interventions that target individuals, families, and communities (e.g., community empowerment programs). Group interventions may also be important for low-income, African American women survivors of IPV, as they can help survivors establish and strengthen relationships and social support.

Distinctive Features of Orbital Adipose Tissue (OAT) in Graves' Orbitopathy.

Depot specific expansion of orbital-adipose-tissue (OAT) in Graves' Orbitopathy (GO) is associated with lipid metabolism signaling defects. We hypothesize that the unique adipocyte biology of OAT facilitates its expansion in GO. A comprehensive comparison of OAT and white-adipose-tissue (WAT) was performed by light/electron-microscopy, lipidomic and transcriptional analysis using ex vivo WAT, healthy OAT (OAT-H) and OAT from GO (OAT-GO). OAT-H/OAT-GO have a single lipid-vacuole and low mitochondrial number. Lower lipolytic activity and smaller adipocytes of OAT-H/OAT-GO, accompanied by similar essential linoleic fatty acid (FA) and (low) FA synthesis to WAT, revealed a hyperplastic OAT expansion through external FA-uptake via abundant SLC27A6 (FA-transporter) expression. Mitochondrial dysfunction of OAT in GO was apparent, as evidenced by the increased mRNA expression of uncoupling protein 1 (UCP1) and mitofusin-2 (MFN2) in OAT-GO compared to OAT-H. Transcriptional profiles of OAT-H revealed high expression of Iroquois homeobox-family (IRX-3&5), and low expression in HOX-family/TBX5 (essential for WAT/BAT (brown-adipose-tissue)/BRITE (BRown-in-whITE) development). We demonstrated unique features of OAT not presented in either WAT or BAT/BRITE. This study reveals that the pathologically enhanced FA-uptake driven hyperplastic expansion of OAT in GO is associated with a depot specific mechanism (the SLC27A6 FA-transporter) and mitochondrial dysfunction. We uncovered that OAT functions as a distinctive fat depot, providing novel insights into adipocyte biology and the pathological development of OAT expansion in GO.

Nausea in Numbers: Electronic Medical Record Nausea and Vomiting Assessment for Children With Cancer.

Purpose: Chemotherapy-induced nausea and vomiting (CINV) is a distressing, underrecognized effect of treatment that can occur in up to 80% of patients. The purpose of this quality improvement project was to evaluate the impact of implementation of a standardized nausea assessment tool, the Baxter Animated Retching Faces (BARF) scale, on nursing compliance with nausea assessment and the frequency and severity of patient-reported CINV for children with cancer. Method: The Plan-Do-Study-Act cycle was used to implement this practice change. With stakeholder support and hospital governance council approval, the BARF scale was introduced into the electronic medical record. Nurses were provided education about the assessment tool and were given badge buddy cards to prompt use of the tool, and workstation reminders were created. A root cause analysis was conducted to provide feedback for continuous quality improvement. Results: Retrospective, aggregate electronic medical record data from May 2018 to April 2019 were analyzed for assessment compliance, total number of admissions with vomiting episodes, and average BARF score. Over the 12-month implementation period, run charts demonstrated a shift in nursing practice with increased compliance in documented nausea assessments during the second 6-month period. There was not a significant decrease in patient-reported CINV. Conclusion: The use of standardized nausea assessments based on patient self-reporting can provide useful and consistent feedback for nurses and health care providers. This quality improvement project demonstrated increased compliance with nausea assessment documentation. Further studies are needed to demonstrate that improvements in nausea assessment may reduce the frequency and severity of CINV.

For Whom Does Cognitively Based Compassion Training (CBCT) Work? An Analysis of Predictors and Moderators among African American Suicide Attempters.

OBJECTIVES: Both Cognitively-Based Compassion Training (CBCT) and support-based group intervention have been found to be effective for African American suicide attempters in reducing suicidal ideation and depression, as well as enhancing self-compassion. This study aims to further our understanding of effective interventions by exploring participants' responses to both interventions. METHODS: Exploratory analyses were conducted in a sample of low-income African Americans who had attempted suicide (n=82) to determine how baseline demographic and psychological characteristics would (1) predict outcomes (i.e., suicidal ideation, depression, and self-compassion) regardless of intervention conditions, and (2) moderate outcomes in interaction with intervention condition. RESULTS: Non-reactivity, a mindfulness facet, was identified as an intervention moderator for suicidal ideation and depressive symptoms, suggesting that CBCT outperformed the support group for African American suicide attempters who had low baseline non-reactivity (or high reactivity). Individuals who had high non-reactivity at baseline appeared to benefit more from both conditions in self-compassion as an outcome. There was a pattern that homeless individuals benefited less in terms of their levels of depressive symptoms and self-compassion as outcomes regardless of the assigned condition. When applying Bonferroni corrections, only non-reactivity as an intervention moderator for depressive symptoms was significant. CONCLUSIONS: Findings reveal the relevance of mindfulness and to a lesser extent socioeconomic status in informing compassion-based intervention outcomes with this underserved population and the importance of intervention matching and tailoring to maximize treatment effects. Future large trials are needed to replicate findings and directions indicated from the current pilot study.

Development, Implementation, and Satisfaction With a Nurse Practitioner Professional Ladder: A Children's Hospital Experience.

This article describes the development and implementation of a nurse practitioner professional ladder (NPPL) at a large freestanding urban pediatric hospital. The NPPL was created to recognize advanced practice registered nurses and differentiate levels of clinical expertise, role development, leadership, and professional contributions into a three-tiered approach, designated as NP I, NP II, and NP III. The results of a nurse practitioner satisfaction survey at Year 2 and Year 4 after the development of the NPPL are summarized. The NPPL helped create an empowering environment for continued nurse practitioner professional growth.

The Use of Aromatherapy to Reduce Chemotherapy-Induced Nausea in Children With Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial.

INTRODUCTION: Chemotherapy-induced nausea can be distressing and difficult to manage in children with cancer. The purpose of this study was to investigate the utility of ginger aromatherapy in relieving chemotherapy-induced nausea in children with cancer. METHOD: This randomized, double-blind, placebo-controlled study of 49 children with cancer explored whether inhalation of the aroma of essential oil of ginger during chemotherapy decreased nausea compared with a placebo (water) or control (Johnson's baby shampoo) measured by prechemotherapy and postchemotherapy assessment with the Pediatric Nausea Assessment Tool (PeNAT). RESULTS: While well received, well tolerated, nontoxic, and noninvasive, ginger aromatherapy did not significantly decrease nausea in patients enrolled in this study. Among 21 patients who indicated feeling nausea prechemotherapy, 67% reported improvement, 5% worsening, and 28% no change in their postinfusion PeNAT score. We failed to detect a statistical significant difference in the change in PeNAT scores among the three groups.

The -251 A/T Polymorphism in the IL8 Promoter is a Risk Factor for Acute Pancreatitis.

OBJECTIVES: Inflammation in the setting of acute pancreatitis (AP) is partially driven by pathogen recognition receptors that recognize damage-associated molecular patterns. Interleukin (IL)-8 is a chemotactic factor produced by pathogen recognition receptor-expressing cells. A single-nucleotide polymorphism in IL8 promoter region (-251 A/T) has been implicated in inflammatory diseases. We examined whether this IL8 polymorphism confers susceptibility to AP. METHODS: Patients with AP (n = 357) were prospectively recruited. Clinical data and blood were collected in subjects and controls (n = 347). Severity was defined following the Revised Atlanta Classification. Genotypes were assessed by quantitative polymerase chain reaction using TaqMan probes. RESULTS: Patients and controls had similar demographics and had no difference in Hardy-Weinberg (patients, P = 0.29; controls, P = 0.66). Twenty-five percent of patients developed severe AP. Compared with controls, the A/A genotype was more common in AP (P = 0.041; odds ratio, 1.42; 95% confidence interval, 1-1.99). Obese patients with the A/A genotype were more likely to develop mild AP (P = 0.047). CONCLUSIONS: The -251 polymorphism confers susceptibility to AP and disease severity in obese patients. However, its effect is moderate. One potential mechanism for this susceptibility is via increased IL8 production by innate cells, with subsequent enhanced neutrophil influx and pancreatic injury.

Surveillance and Outcomes of Nonresected Presumed Branch-Duct Intraductal Papillary Mucinous Neoplasms: A Meta-analysis.

OBJECTIVES: Guidelines regarding the surveillance of intraductal papillary mucinous neoplasms (IPMNs) are controversial because of uncertain risk of malignancy, agnosticism regarding the use of endoscopic ultrasound, and their recommendation to stop surveillance after 5 years. We present a systematic review and meta-analysis of the risk of malignancy and other end points and estimate the value of endoscopic ultrasound for surveillance. METHODS: We systematically searched MEDLINE for studies with a cohort of patients with presumed branch-duct IPMN who initially were managed nonsurgically. Data regarding study characteristics, surveillance, and outcomes were extracted. Incidence rates of morphologic progression, malignancy, surgery, and death were calculated with a random effects model. RESULTS: Twenty-four studies with 3440 patients and 13,097 patient-years of follow-up were included. Rates of morphologic progression, surgery, malignancy, and death were 0.0379, 0.0250, 0.0098, and 0.0043 per patient-year, respectively. Endoscopic ultrasound was not associated with significantly different rates of these outcomes. CONCLUSIONS: The risk of malignancy calculated in this study was low and in line with recent systematic reviews. Endoscopic ultrasound does not have marginal use in surveillance. Given the limitations of a systematic review of nonrandomized studies, further studies are needed to determine the optimal surveillance of branch-duct IPMNs.

Abstracting ICU Nursing Care Quality Data From the Electronic Health Record.

The electronic health record is a potentially rich source of data for clinical research in the intensive care unit setting. We describe the iterative, multi-step process used to develop and test a data abstraction tool, used for collection of nursing care quality indicators from the electronic health record, for a pragmatic trial. We computed Cohen's kappa coefficient (κ) to assess interrater agreement or reliability of data abstracted using preliminary and finalized tools. In assessing the reliability of study data ( n = 1,440 cases) using the finalized tool, 108 randomly selected cases (10% of first half sample; 5% of last half sample) were independently abstracted by a second rater. We demonstrated mean κ values ranging from 0.61 to 0.99 for all indicators. Nursing care quality data can be accurately and reliably abstracted from the electronic health records of intensive care unit patients using a well-developed data collection tool and detailed training.

Electrophysiological Correlates of Aberrant Motivated Attention and Salience Processing in Unaffected Relatives of Schizophrenia Patients.

Patients with schizophrenia (SCZ) exhibit debilitating deficits in attention and affective processing, which are often resistant to treatment and associated with poor functional outcomes. Impaired orientation to task-relevant target information has been indexed by diminished P3b event-related potentials in patients, as well as their unaffected first-degree relatives, suggesting that P3b may be a vulnerability marker for schizophrenia. Despite intact affective valence processing, patients are unable to employ cognitive change strategies to reduce electrophysiological responses to aversive stimuli. Less is known about the attentional processing of emotionally salient task-irrelevant information in patients and unaffected first-degree relatives. The goal of the present study was to examine the neural correlates of salience processing, as indexed by the late positive potential (LPP), during the processing of emotionally salient distractor stimuli in 31 patients with SCZ, 28 first-degree relatives, and 47 control participants using an oddball paradigm. Results indicated that despite intact novelty detection (P3a), both SCZ and first-degree relatives demonstrated deficiencies in attentional processing, reflected in attenuated target-P3b, and aberrant motivated attention, with reduced early-LPP amplitudes for aversive stimuli relative to controls. First-degree relatives revealed a unique enhancement of the late-LPP response, possibly underlying an exaggerated evaluation of salient information and a compensatory engagement of neural circuitry. Furthermore, reduced early-LPP and target-P3b amplitudes were associated with enhanced symptom severity. These findings suggest that, in addition to P3b, LPP may be useful for monitoring clinical state. Future studies will explore the value of P3 and LPP responses as vulnerability markers for early detection and prediction of psychopathology.

High prevalence of "Candidatus Rickettsia andeanae" and apparent exclusion of Rickettsia parkeri in adult Amblyomma maculatum (Acari: Ixodidae) from Kansas and Oklahoma.

Amblyomma maculatum (the Gulf Coast tick), an aggressive, human-biting, Nearctic and Neotropical tick, is the principal vector of Rickettsia parkeri in the United States. This pathogenic spotted fever group Rickettsia species has been identified in 8-52% of questing adult Gulf Coast ticks in the southeastern United States. To our knowledge, R. parkeri has not been reported previously from adult specimens of A. maculatum collected in Kansas or Oklahoma. A total of 216 adult A. maculatum ticks were collected from 18 counties in Kansas and Oklahoma during 2011-2014 and evaluated by molecular methods for evidence of infection with R. parkeri. No infections with this agent were identified; however, 47% of 94 ticks collected from Kansas and 73% of 122 ticks from Oklahoma were infected with "Candidatus Rickettsia andeanae" a spotted fever group Rickettsia species of undetermined pathogenicity. These preliminary data suggest that "Ca. R. andeanae" is well-adapted to survival in populations of A. maculatum in Kansas and Oklahoma, and that its ubiquity in Gulf Coast ticks in these states may effectively exclude R. parkeri from their shared arthropod host, which could diminish markedly or preclude entirely the occurrence of R. parkeri rickettsiosis in this region of the United States.

Prognostic significance of NPM1 mutations in the absence of FLT3-internal tandem duplication in older patients with acute myeloid leukemia: a SWOG and UK National Cancer Research Institute/Medical Research Council report.

PURPOSE: Younger patients with acute myeloid leukemia (AML) harboring NPM1 mutations without FLT3-internal tandem duplications (ITDs; NPM1-positive/FLT3-ITD-negative genotype) are classified as better risk; however, it remains uncertain whether this favorable classification can be applied to older patients with AML with this genotype. Therefore, we examined the impact of age on the prognostic significance of NPM1-positive/FLT3-ITD-negative status in older patients with AML. PATIENTS AND METHODS: Patients with AML age ≥ 55 years treated with intensive chemotherapy as part of Southwest Oncology Group (SWOG) and UK National Cancer Research Institute/Medical Research Council (NCRI/MRC) trials were evaluated. A comprehensive analysis first examined 156 patients treated in SWOG trials. Validation analyses then examined 1,258 patients treated in MRC/NCRI trials. Univariable and multivariable analyses were used to determine the impact of age on the prognostic significance of NPM1 mutations, FLT3-ITDs, and the NPM1-positive/FLT3-ITD-negative genotype. RESULTS: Patients with AML age 55 to 65 years with NPM1-positive/FLT3-ITD-negative genotype treated in SWOG trials had a significantly improved 2-year overall survival (OS) as compared with those without this genotype (70% v 32%; P < .001). Moreover, patients age 55 to 65 years with NPM1-positive/FLT3-ITD-negative genotype had a significantly improved 2-year OS as compared with those age > 65 years with this genotype (70% v 27%; P < .001); any potential survival benefit of this genotype in patients age > 65 years was marginal (27% v 16%; P = .33). In multivariable analysis, NPM1-positive/FLT3-ITD-negative genotype remained independently associated with an improved OS in patients age 55 to 65 years (P = .002) but not in those age > 65 years (P = .82). These results were confirmed in validation analyses examining the NCRI/MRC patients. CONCLUSION: NPM1-positive/FLT3-ITD-negative genotype remains a relatively favorable prognostic factor for patients with AML age 55 to 65 years but not in those age > 65 years.

Pregnancy in a Patient With a Malignant Brain Tumor Taking Temozolomide: Case Report and Review of the Literature.

Temozolomide (TMZ), an alkylating agent used in the treatment of malignant gliomas, is a pregnancy category D medication that is not advised for use in pregnant women. We report the case of a 19-year-old woman with anaplastic oligodendroglioma (high-grade glioma) who became pregnant during maintenance chemotherapy consisting of TMZ 200 mg/m(2) administered 5 days monthly. The TMZ was immediately discontinued after she developed a positive pregnancy test. She delivered a full-term healthy baby boy with no prenatal or perinatal complications. Adolescents and young adults with brain tumors are often sexually active and should receive intensive and repeated anticipatory guidance regarding contraception while receiving chemotherapy. Pediatric oncology nurses are in a unique position to provide this education for patients and ensure that young women have appropriate pregnancy testing prior to chemotherapy administration.

Attenuated auditory event-related potentials and associations with atypical sensory response patterns in children with autism.

Neurobiological underpinnings of unusual sensory features in individuals with autism are unknown. Event-related potentials elicited by task-irrelevant sounds were used to elucidate neural correlates of auditory processing and associations with three common sensory response patterns (hyperresponsiveness; hyporesponsiveness; sensory seeking). Twenty-eight children with autism and 39 typically developing children (4-12 year-olds) completed an auditory oddball paradigm. Results revealed marginally attenuated P1 and N2 to standard tones and attenuated P3a to novel sounds in autism versus controls. Exploratory analyses suggested that within the autism group, attenuated N2 and P3a amplitudes were associated with greater sensory seeking behaviors for specific ranges of P1 responses. Findings suggest that attenuated early sensory as well as later attention-orienting neural responses to stimuli may underlie selective sensory features via complex mechanisms.

Significance of FAB subclassification of "acute myeloid leukemia, NOS" in the 2008 WHO classification: analysis of 5848 newly diagnosed patients.

The World Health Organization (WHO) classifies acute myeloid leukemia (AML) via genetic, immunophenotypic, biological, and clinical features. Still, "AML, not otherwise specified (NOS)" is further subdivided based on morphologic criteria similar to those of the French-American-British (FAB) classification. We analyzed the relevance of this practice in patients with newly diagnosed "AML, NOS" with available FAB information undergoing curative-intent therapy in trials of 3 cooperative study groups (Dutch-Belgian Cooperative Trial Group for Hematology/Oncology [HOVON], UK Medical Research Council/National Cancer Research Institute [MRC/NCRI], and the US cooperative group Southwest Oncology Group [SWOG]) or at MD Anderson Cancer Center. Ignoring information on NPM1 and CEBPA, 5848 patients met criteria for "AML, NOS." After multivariate adjustment, FAB M0 was independently associated with significantly lower likelihood of achieving complete remission and inferior relapse-free and overall survival as compared with FAB M1, M2, M4, M5, and M6, with inconclusive data regarding M7. However, restricting attention to known NPM1(neg) patients, FAB M0 was no longer associated with worse outcomes; restricting attention to patients known to be NPM1(neg)/CEPBA(neg) (ie, honoring the provisional entities of "AML with mutated NPM1" and "AML with mutated CEBPA") did not affect this result. In conclusion, in the 2008 WHO classification scheme, FAB subclassification does not provide prognostic information for "AML, NOS" cases if data on NPM1 and CEBPA mutations are available.

Investigating developmental changes in sensory processing: visual mismatch response in healthy children.

The ability to detect small changes in one's visual environment is important for effective adaptation to and interaction with a wide variety of external stimuli. Much research has studied the auditory mismatch negativity (MMN), or the brain's automatic response to rare changes in a series of repetitive auditory stimuli. But recent studies indicate that a visual homolog to this component of the event-related potential (ERP) can also be measured. While most visual mismatch response (vMMR) studies have focused on adult populations, few studies have investigated this response in healthy children, and little is known about the developmental nature of this phenomenon. We recorded EEG data in 22 healthy children (ages 8-12) and 20 healthy adults (ages 18-42). Participants were presented with two types of task irrelevant background images of black and gray gratings while performing a visual target detection task. Spatial frequency of the background gratings was varied with 85% of the gratings being of high spatial frequency (HSF; i.e., standard background stimulus) and 15% of the images being of low spatial frequency (LSF; i.e., deviant background stimulus). Results in the adult group showed a robust mismatch response to deviant (non-target) background stimuli at around 150 ms post-stimulus at occipital electrode locations. In the children, two negativities around 150 and 230 ms post-stimulus at occipital electrode locations and a positivity around 250 ms post-stimulus at fronto-central electrode locations were observed. In addition, larger amplitudes of P1 and longer latencies of P1 and N1 to deviant background stimuli were observed in children vs. adults. These results suggest that processing of deviant stimuli presented outside the focus of attention in 8-12-year-old children differs from those in adults, and are in agreement with previous research. They also suggest that the vMMR may change across the lifespan in accordance with other components of the visual ERP.

TNF-alpha gene (TNFA) variants increase risk for multi-organ dysfunction syndrome (MODS) in acute pancreatitis.

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) is a complex inflammatory syndrome with unpredictable progression to systemic inflammation and multi-organ dysfunction syndrome (MODS). Tumor necrosis factor alpha (TNF-α) is a cytokine that may link inflammation to the systemic inflammatory response syndrome (SIRS), which usually precedes MODS. Small genetic cohort studies of the TNFA promoter in AP produced ambiguous results. We performed a comprehensive evaluation of TNFA promoter variants to assess both susceptibility to AP and risk of progression to MODS. METHODS: We prospectively ascertained 401 controls and 211 patients with AP that were assessed for persistent SIRS (>48 h) and MODS. MODS was defined as failure of ≥2 organ systems (cardiovascular, pulmonary, and/or renal) persisting more than 48 h. Subjects were genotyped by DNA sequencing and analyzed for SNPs at -1031 C/T (rs1799964), -863 A/C (rs1800630), -857 C/T (rs1799724), -308 A/G (rs1800629), and -238 A/G (rs361525). RESULTS: Twenty-three of 211 AP patients (11%) developed MODS. TNFA promoter variants were not associated with susceptibility to AP, but progression to MODS was associated with the minor allele at -1031C (56.5% vs. 32.4% P = 0.022, OR: 2.7; 95%CI: 1.12-6.51) and -863A (43.5% vs. 21.8% P = 0.022, OR: 2.76; 95%CI: 1.12-6.74). CONCLUSION: TNFA promoter variants do not alter susceptibility to AP, but rather the TNF-α expression-enhancing -1031C and -863A alleles significantly increased the risk of AP progression to MODS. These data, within the context of previous studies, clarify the risk of specific genetic variants in TNFA and therefore the role of TNF-α in the overall AP syndrome.