Chronic upper abdominal pain occurs as a complication of various malignant and benign diseases including pancreatic cancer and chronic pancreatitis, and when present may contribute to lower quality of life and higher mortality. Though various pain management strategies are available as part of a multimodal approach, they are often incompletely effective and accompanied by side effects. Pain originating in upper abdominal viscera is transmitted through the celiac plexus, which is an autonomic plexus located in the retroperitoneum at the root of the celiac trunk. Direct intervention at the level of the plexus, referred to as celiac plexus block or neurolysis depending on the injectate, is a minimally invasive therapeutic strategy which has been demonstrated to decrease pain, improve function, and reduce opiate dependence. Various percutaneous techniques have been reported, but, with appropriate preprocedural planning, use of image guidance (usually computed tomography), and postprocedural care, the frequency and severity of complications is low and the success rate high regardless of approach. The main benefit of the intervention may be in reduced opiate dependence and opiate-associated side effects, which in turn improves quality of life. Celiac plexus block and neurolysis are safe and effective treatments for chronic upper abdominal pain and should be considered early in patients experiencing such symptoms.
BackgroundNeural tube defects (NTDs) are common birth defects (~1 in 1000 pregnancies in the US and Europe) that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and MTHFD1 rs2236225 (R653Q)) have been found to increase NTD risk. We hypothesized that variants in additional folate/B12 pathway genes contribute to NTD risk.MethodsA tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents), including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects.ResultsNearly 70 SNPs in 30 genes were found to be associated with NTDs at the p < 0.01 level. The ten strongest association signals (p-value range: 0.0003–0.0023) were found in nine genes (MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury)) and included the known NTD risk factor MTHFD1 R653Q (rs2236225). The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele). Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing.ConclusionsTo our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the stringency of correction are likely to have contributed to real associations failing to survive correction. We have produced a ranked list of variants with the strongest association signals. Variants in the highest rank of associations are likely to include true associations and should be high priority candidates for further study of NTD risk.
BackgroundTen million Americans enter jails annually. The objective was to evaluate new CDC guidelines for routine opt-out HIV testing and examine the optimal time to implement routine opt-out HIV testing among newly incarcerated jail detainees.MethodsThis prospective, controlled trial of routine opt-out HIV testing was conducted among 323 newly incarcerated female inmates in Connecticut's only women's jail. 323 sequential entrants to the women's jail over a five week period in August and September 2007 were assigned to be offered routine opt-out HIV testing at one of three points after incarceration: immediate (same day, n = 108), early (next day, n = 108), or delayed (7 days, n = 107). The primary outcome was the proportion of women in each group consenting to testing.ResultsRoutine opt-out HIV testing was significantly highest (73%) among the early testing group compared to 55% for immediate and 50% for 7 days post-entry groups. Other factors significantly (p = 0.01) associated with being HIV tested were younger age and low likelihood of early release from jail based on bond value or type of charge for which women were arrested.ConclusionsIn this correctional facility, routine opt-out HIV testing in a jail setting was feasible, with highest rates of testing if performed the day after incarceration. Lower testing rates were seen with immediate testing, where there is a high prevalence of inability or unwillingness to test, and with delayed testing, where attrition from jail increases with each passing day.Trial RegistrationClinicalTrials.gov NCT00624247
Background The Liver Imaging Reporting and Data System (LI‐RADS) is being adapted by many clinical practices. To support continuation of its use, LI‐RADS (LR) is in need of multicenter validation studies of recent LI‐RADS iterations. Furthermore, while both gadoxetate and extracellular agents have been incorporated into LI‐RADS, comparison of the diagnostic performance between the two has yet to be determined. Purpose/Hypothesis To evaluate the rate, diagnostic performance, and interreader reliability (IRR) of LI‐RADS 2017 for hepatocellular carcinoma, including LR major and ancillary features, with both gadoxetate and extracellular agent‐enhanced MRI against a reference standard of histopathology or imaging follow‐up. Study Type Retrospective. Population In all, 114 patients with 144 observations were included who met LR 2017 criteria for at risk and had at least one hepatic observation on liver MRI performed with either gadoxetate (n = 52) or an extracellular agent (n = 92) between 2010–2016, with histopathology (n = 103) or follow‐up imaging (n = 41). Field Strength/Sequence 1.5 and 3.0T/T1‐T2WI, diffusion‐weighted imaging. Assessment Three radiologists independently assessed major/ancillary features and assigned overall LI‐RADS category for every observation. Statistical Tests Diagnostic performance of LR5/TIV+LR5 for identifying hepatocellular carcinoma (HCC) was compared between contrast agents with a generalized estimating equation. Weighted kappa was performed for interrater reliability. Results The frequency of HCCs among LR1, LR2, LR3, L4, LR5, LRTIV+LR5, and LRM observations were: 0% (all readers), 0–12.5%, 11.4–26.9%, 50–76%, 83.0–95.1%, 83.3–100.0%, and 45.0–65.0%, respectively. Sensitivity of LR5/LRTIV+LR5 for HCC was 59.7–71.4% and specificity 85.0–96.8%. LI‐RADS specificity and positive predictive value for observations imaged with gadoxetate was higher than extracellular agent for the most inexperienced reader (R3) (P = 0.009–0.034). IRR for LI‐RADS categorization was substantial (k = 0.661). Data Conclusion Increasing numerical LI‐RADS 2017 categories demonstrate a greater percentage of HCCs. LR5/TIV+LR5 demonstrates excellent specificity and fair sensitivity for HCC. MRI with gadoxetate in liver transplant candidates may be beneficial for less experienced readers, although further large‐scale prospective studies are needed. Level of Evidence: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:e205–e215.
We prospectively identified 96 women consuming at least 4 drinks/day during pregnancy by screening 9628 pregnant women. In these women with heavy prenatal alcohol use, there were three stillbirths and one preterm delivery; 98 matched nondrinking women had no stillbirths and two preterm births. Preterm rates did not differ significantly. The stillbirth rate was higher in the exposed group (p = 0.06). Additional investigation showed the stillbirth rate in the exposed population (3.1%) was significantly higher (p = 0.019) than the reported Chilean population rate (0.45%). Our data suggest that heavy alcohol consumption may increase the risk for stillbirth but not preterm delivery.
Future liver remnant (FLR) size and function is a critical limiting factor for treatment eligibility and postoperative prognosis when considering surgical hepatectomy. Pre-operative portal vein embolization (PVE) has been proven effective in modulating FLR and now widely accepted as a standard of care. However, PVE is not always effective due to potentially inadequate augmentation of the FLR as well as tumor progression while awaiting liver growth. These concerns have prompted exploration of alternative techniques: associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), transarterial embolization-portal vein embolization (TAE-PVE), liver venous deprivation (LVD), and radiation lobectomy (RL). The article aims to review the principles and applications of PVE and these newer hepatic regenerative techniques.
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Homologous recombination provides a means for the in vivo construction of recombinant DNA molecules that may be problematic to assemble in vitro. We have investigated the efficiency of recombination within the Caenorhabditis elegans germ line as a function of the length of homology between recombining molecules. Our findings indicate that recombination can occur between molecules that share only 10 bp of terminal homology, and that 25 bp is sufficient to mediate relatively high levels of recombination. Recombination occurs with lower efficiency when the location of the homologous segment is subterminal or internal. As in yeast, recombination can also be mediated by either single- or double-stranded bridging oligonucleotides. We find that ligation between cohesive ends is highly efficient and does not require that the ends be phosphorylated; furthermore, precise intermolecular ligation between injected molecules that have blunt ends can also occur within the germ line.
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