Although open esophagectomy (OE) is considered the “gold standard” treatment for esophageal cancer, robotic-assisted minimally invasive esophagectomy (RAMIE), and laparoscopic/thoracoscopic minimally ...invasive esophagectomy (MIE) are becoming more common. This study aimed to compare short-term outcomes and overall survival of patients undergoing RAMIE, MIE, and OE.
The National Cancer Data Base was queried for patients who had OE, RAMIE, or MIE for esophageal cancer from 2010 to 2013. Three propensity-matched cohorts were generated, one for each surgical approach. Survival was examined in the unmatched and matched cohorts.
We identified 9,217 patients who underwent RAMIE (581; 6.3%), MIE (2,379; 25.8%), or OE (6,257; 67.9%). In the unmatched cohort, 30-day mortality was higher after RAMIE. The RAMIE and MIE patients had more lymph nodes harvested than OE patients. Median survival was 48 months after RAMIE, 44 months after MIE, and 41 months after OE (p = 0.121). The propensity-matched groups contained 569 patients each. There was a trend toward higher 30-day mortality in the RAMIE group. The number of lymph nodes harvested was similar among the groups. There were no significant differences in survival, with a median survival of 48 months after RAMIE, 49 months after MIE, and 44 months after OE (p = 0.53).
We were unable to find significant differences in long-term survival of patients with esophageal cancer undergoing RAMIE, OE, or MIE. Surgeon experience and expertise may be more important than surgical approach for esophageal cancer.
Sequencing of gene-coding regions (the exome) is increasingly used for studying human disease, for which copy-number variants (CNVs) are a critical genetic component. However, detecting copy number ...from exome sequencing is challenging because of the noncontiguous nature of the captured exons. This is compounded by the complex relationship between read depth and copy number; this results from biases in targeted genomic hybridization, sequence factors such as GC content, and batching of samples during collection and sequencing. We present a statistical tool (exome hidden Markov model XHMM) that uses principal-component analysis (PCA) to normalize exome read depth and a hidden Markov model (HMM) to discover exon-resolution CNV and genotype variation across samples. We evaluate performance on 90 schizophrenia trios and 1,017 case-control samples. XHMM detects a median of two rare (<1%) CNVs per individual (one deletion and one duplication) and has 79% sensitivity to similarly rare CNVs overlapping three or more exons discovered with microarrays. With sensitivity similar to state-of-the-art methods, XHMM achieves higher specificity by assigning quality metrics to the CNV calls to filter out bad ones, as well as to statistically genotype the discovered CNV in all individuals, yielding a trio call set with Mendelian-inheritance properties highly consistent with expectation. We also show that XHMM breakpoint quality scores enable researchers to explicitly search for novel classes of structural variation. For example, we apply XHMM to extract those CNVs that are highly likely to disrupt (delete or duplicate) only a portion of a gene.
Research has shown that Black parents are more likely than White parents to have conversations about race with their children, but few studies have directly compared the frequency and content of ...these conversations and how they change in response to national events. Here we examine such conversations in the United States before and after the killing of George Floyd. Black parents had conversations more often than White parents, and they had more frequent conversations post-Floyd. White parents remained mostly unchanged and, if anything, were less likely to talk about being White and more likely to send colorblind messages. Black parents were also more worried than White parents-both that their children would experience racial bias and that their children would perpetrate racial bias, a finding that held both pre- and post-Floyd. Thus, even in the midst of a national moment on race, White parents remained relatively silent and unconcerned about the topic.
Background Neuroendocrine tumors of the thymus (NETT) constitute less than 5% of all anterior mediastinal masses but are aggressive and lead to poor overall survival. This study was designed to ...evaluate factors that influence the prognosis of patients with NETT and the role of surgical intervention in survival. Methods We analyzed the Surveillance, Epidemiology, and End Results cancer database to identify patients with NETT. We performed univariate and multivariate analyses to identify prognostic factors among demographic, tumor, and treatment variables. Results In 254 patients identified with NETT, the median overall survival time was 73 months, with a 5-year survival rate of 56%. Patients who underwent surgical therapy had a significantly longer median survival time than did those who did not undergo surgical therapy (109 months vs 46 months, p < 0.001). In multivariate analysis, surgical resection, Masaoka-Koga stage, and tumor size were significant predictors of survival. Conclusions Our study found that surgical resection, Masaoka-Koga stage, and tumor size are significant prognostic factors in patients with NETT. Complete surgical resection continues, rightfully, to be the mainstay in the treatment of this rare disease.
Our understanding of gene regulation in plants is constrained by our limited knowledge of plant cis-regulatory DNA and its dynamics. We mapped DNase I hypersensitive sites (DHSs) in A. thaliana ...seedlings and used genomic footprinting to delineate ∼700,000 sites of in vivo transcription factor (TF) occupancy at nucleotide resolution. We show that variation associated with 72 diverse quantitative phenotypes localizes within DHSs. TF footprints encode an extensive cis-regulatory lexicon subject to recent evolutionary pressures, and widespread TF binding within exons may have shaped codon usage patterns. The architecture of A. thaliana TF regulatory networks is strikingly similar to that of animals in spite of diverged regulatory repertoires. We analyzed regulatory landscape dynamics during heat shock and photomorphogenesis, disclosing thousands of environmentally sensitive elements and enabling mapping of key TF regulatory circuits underlying these fundamental responses. Our results provide an extensive resource for the study of A. thaliana gene regulation and functional biology.
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•A. thaliana regulatory DNA, TF footprints, and cis-regulatory lexicon are elucidated•TF binding in protein-coding exons may have shaped A. thaliana codon usage•A. thaliana TF network architecture is strikingly similar to human•Light- and heat-cued regulatory DNA dynamics and TF network remodeling are revealed
Our understanding of plant gene regulation is constrained by our limited knowledge of plant cis-regulatory DNA and its dynamics in response to environmental cues. Sullivan et al. now establish nucleotide-resolution regulatory DNA landscapes for A. thaliana seedlings before and after exposure to light and heat, key environmental cues shaping plant growth and development. This study generates genome-wide, condition- and tissue-specific maps of TF occupancy, constructs condition-specific TF networks, and identifies hundreds of de novo TF motif models.
With increased life expectancy for HIV-infected persons, there is concern regarding comorbid depression because of its common occurrence and association with behaviors that may facilitate HIV ...transmission. Our objectives were to estimate the prevalence of current depression among HIV-infected persons receiving care and assess the burden of major depression, relative to that in the general population.
We used data from the Medical Monitoring Project (MMP) and the Behavioral Risk Factors Surveillance System (BRFSS). The eight-item Patient Health Questionnaire was used to identify depression. To assess the burden of major depression among HIV-infected persons receiving care, we compared the prevalence of current major depression between the MMP and BRFSS populations using stratified analyses that simultaneously controlled for gender and, in turn, each of the potentially confounding demographic factors of age, race/ethnicity, education, and income. Each unadjusted comparison was summarized as a prevalence ratio (PR), and each of the adjusted comparisons was summarized as a standardized prevalence ratio (SPR). Among HIV-infected persons receiving care, the prevalence of a current episode of major depression and other depression, respectively, was 12.4% (95% CI: 11.2, 13.7) and 13.2% (95% CI: 12.0%, 14.4%). Overall, the PR comparing the prevalence of current major depression between HIV-infected persons receiving care and the general population was 3.1. When controlling for gender and each of the factors age, race/ethnicity, and education, the SPR (3.3, 3.0, and 2.9, respectively) was similar to the PR. However, when controlling for gender and annual household income, the SPR decreased to 1.5.
Depression remains a common comorbidity among HIV-infected persons. The overall excess burden among HIV-infected persons receiving care is about three-times that among the general population and is associated with differences in annual household income between the two populations. Relevant efforts are needed to reduce this burden.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An urgent need exists to better understand the transition from short-term opioid use to unintended prolonged opioid use (UPOU). The purpose of this work is to propose a conceptual framework for ...understanding UPOU that posits the influence of 3 principal domains that include the characteristics of (1) individual patients, (2) the practice environment, and (3) opioid prescribers. Although no standardized method exists for developing a conceptual framework, the process often involves identifying corroborative evidence, leveraging expert opinion to identify factors for inclusion in the framework, and developing a graphic depiction of the relationships between the various factors and the clinical problem of interest. Key patient characteristics potentially associated with UPOU include (1) medical and mental health conditions; (2) pain etiology; (3) individual affective, behavioral, and neurophysiologic reactions to pain and opioids; and (4) sociodemographic factors. Also, UPOU could be influenced by structural and health care policy factors: (1) the practice environment, including the roles of prescribing clinicians, adoption of relevant practice guidelines, and clinician incentives or disincentives, and (2) the regulatory environment. Finally, characteristics inherent to clinicians that could influence prescribing practices include (1) training in pain management and opioid use; (2) personal attitudes, knowledge, and beliefs regarding the risks and benefits of opioids; and (3) professionalism. As the gatekeeper to opioid access, the behavior of prescribing clinicians directly mediates UPOU, with the 3 domains interacting to determine this behavior. This proposed conceptual framework could guide future research on the topic and allow plausible hypothesis-based interventions to reduce UPOU.
By analyzing the exomes of 12,332 unrelated Swedish individuals, including 4,877 individuals affected with schizophrenia, in ways informed by exome sequences from 45,376 other individuals, we ...identified 244,246 coding-sequence and splice-site ultra-rare variants (URVs) that were unique to individual Swedes. We found that gene-disruptive and putatively protein-damaging URVs (but not synonymous URVs) were more abundant among individuals with schizophrenia than among controls (P = 1.3 × 10
). This elevation of protein-compromising URVs was several times larger than an analogously elevated rate for de novo mutations, suggesting that most rare-variant effects on schizophrenia risk are inherited. Among individuals with schizophrenia, the elevated frequency of protein-compromising URVs was concentrated in brain-expressed genes, particularly in neuronally expressed genes; most of this elevation arose from large sets of genes whose RNAs have been found to interact with synaptically localized proteins. Our results suggest that synaptic dysfunction may mediate a large fraction of strong, individually rare genetic influences on schizophrenia risk.
Thoracic surgery can cause significant pain, and multiple strategies have been developed to control pain after surgery. We compared 2 bupivacaine formulations given intraoperatively: bupivacaine with ...epinephrine (1,200,000) or liposomal bupivacaine.
This was a randomized, open-label study (NCT03560362). Eligible patients were adults scheduled for a minimally invasive lung procedure. Incision sites were injected with bupivacaine with epinephrine or liposomal bupivacaine before incision, and each intercostal space was injected with 1 mL of bupivacaine with epinephrine or liposomal bupivacaine entering the thoracic cavity. Patient-controlled analgesia was initiated in the recovery room. Pain was recorded using a visual analog scale. The primary outcome was the amount of narcotics taken during the postoperative hospital stay.
We recruited 50 patients; 25 received bupivacaine with epinephrine, and 25 received liposomal bupivacaine. The treatment groups were similar in age, histology, and procedure performed. There were no statistical differences between the treatment groups in the amount of narcotics required during the hospital stay (36.3 mg for bupivacaine and 38 mg for liposomal bupivacaine) or in pain assessed the day of surgery (5 and 5), the first day (3.5 and 2.3), second day (3 and 2.6), 2 weeks (0 and 1), or 3 months (0 and 0) postoperatively. Hospital length of stay and complications were also similar.
In a small, randomized study, we did not find significant differences between bupivacaine with epinephrine or liposomal bupivacaine in mitigating pain after minimally invasive lung resection. We currently favor using the less expensive nonliposomal bupivacaine preparations until additional data are available.
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Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%. We performed a ...genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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