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Concern about the possibility of inadequate resection and recurrent cancer with the use of laparoscopically assisted colectomy prompted this randomized trial comparing laparoscopically assisted with open surgery for colon cancer. The trial involved 863 patients and 66 surgeons at 48 hospitals. Rates of cancer recurrence, operative complications, and survival were similar in the two groups. Laparoscopically assisted surgery is an acceptable alternative to open surgery for colon cancer. Minimally invasive surgery revolutionized the way operations were performed. Gallbladder procedures that previously required long incisions and extended periods of hospitalization were transformed through the use of laparoscopic techniques. 1 , 2 The possibility that this approach could benefit patients undergoing colectomy for colon cancer was first considered in 1990. 3 However, a number of cancer-specific questions arose, including the following: Could minimally invasive surgery achieve a proper oncologic resection, with the same extent of exploration and information about lymph-node staging provided by a standard open resection? Were patterns of tumor-cell dissemination altered or enhanced by the use of laparoscopic techniques? These concerns . . .

To evaluate the effect of deploying a new electronic medical record (EMR) system on first case starts in the operating room. Data on first case start times were collected after implementation of a new EMR (Epic) from June 2015 to May 2016, which replaced a legacy system of both paper and electronic records. These were compared to data from the same months in the three proceeding years. First patient in room (FPIR) on time was true if the patient was in operating room before 7:35 AM (or 9:35 AM on Wednesdays) and first case on time start (FCOTS) was true if completion of anesthetic induction was less than 20 min after the patient entered the operating room (or 35 min for cardiac and neurosurgery). Times beyond these cutoffs were quantified as FPIR and FCOTS delays in minutes. Average delays were compared by month with two-sample t tests and 95 % confidence intervals. There was a significant increase in FPIR delays in the first month (11.07 vs. 3.47 min, p  < 0.0001), which abated by the fifth month. Post-implementation FCOTS delays improved by the third month (4.53 vs. 7.10 min, p  < 0.0001). Both results persisted throughout the study. First month FPIR delays were not limited to any one specialty. EMRs have the potential to improve hospital workflows, but are not without learning curves. FPIR and FCOTS delays return to baseline after a few months, and in the case of FCOTS, can improve beyond baseline.

Background In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education. Methods Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers. Results Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results. Conclusion Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.

The optimal treatment for neurosarcoidosis myelitis is uncertain. We characterize incident neurosarcoidosis myelitis and assess treatment response by MRI and clinical scales. Incident probable or definite neurosarcoidosis myelitis in adults was retrospectively identified from 13 academic medical centers. Cases were analyzed by initial treatment. The primary outcome was T1 post-contrast gadolinium enhancement resolution at 6 months post-treatment. Secondary outcomes were changes in modified Rankin scale (mRS) and Expanded Disability Status Scale (EDSS) from nadir to final follow-up. Two hundred two patients were identified (median diagnosis age: 47 years (IQR 39-55); male: female 1.3:1). Median nadir mRS and EDSS were 2 (IQR 2-3) and 4 (IQR 2.5-6). At initial treatment, 129 (63.9%) received prolonged corticosteroids ≥ 4 weeks (group A ), 36 (17.8%) received corticosteroids < 4 weeks (B ), 21 (10.4%) received corticosteroids plus sarcoidosis-directed immunosuppressant (E), and 16 (7.9%) received corticosteroids plus non-sarcoidosis-directed agents (F). In 167 cases with sufficient imaging, there were no significant differences in contrast enhancement resolution at 6 months (A 27/106 (25.5%), B 9/28 (32.1%), E 5/19 (26.3%), F 5/14 (35.7%); Fisher's exact p = 0.76). There were no significant differences in changes in mRS or EDSS among treatment groups (Kruskal-Wallis p = 0.69 and 0.63, respectively) after median follow-up of 46.5 months (IQR 18-91.3). Different initial immunosuppression strategies did not correlate with MRI contrast enhancement resolution at 6 months or clinical scales (mRS, EDSS). However, conclusions are limited by retrospective design, imbalanced cohorts, and insensitivity of binary MRI outcomes and available clinical scales for treatment response in neurosarcoidosis.

Development of antisense technology has focused in part on creating improved methods for delivering oligodeoxynucleotides (ODNs) to cells. In this report, we describe a cationic lipid that, when formulated with the fusogenic lipid dioleoylphosphatidylethanolamine, greatly improves the cellular uptake properties of antisense ODNs, as well as plasmid DNA. This lipid formulation, termed GS 2888 cytofectin, (i) efficiently transfects ODNs and plasmids into many cell types in the presence or absence of 10% serum in the medium, (ii) uses a 4- to 10-fold lower concentration of the agent as compared to the commercially available Lipofectin liposome, and (iii) is ≥ 20-fold more effective at eliciting antisense effects in the presence of serum when compared to Lipofectin. Here we show antisense effects using GS 2888 cytofectin together with C-5 propynyl pyrimidine phosphorothioate ODNs in which we achieve inhibition of gene expression using low nanomolar concentrations of ODN. This agent expands the utility of antisense ODNs for their use in understanding gene function and offers the potential for its use in DNA delivery applications in vivo.

Background Perinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review and meta-analysis of potential precision markers for GDM. Methods Systematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m 2 ) with offspring macrosomia or large-for-gestational age (LGA). Results A total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies [ n  = 28,763]; odds ratio [OR] 2.65; 95% Confidence Interval [CI] 1.91, 3.68), and LGA (10 studies [ n  = 20,070]; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers. Conclusions Maternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted. Plain language summary Gestational Diabetes (GDM) is high blood sugar that develops during pregnancy and may cause complications. GDM diagnosis is centered on blood sugar levels. Despite everyone receiving standard treatment, the clinical outcomes may vary from one individual to another. This indicates a need to identify factors that may help GDM diagnosis and result in improved classification of those at greatest risk for complications. Here, we systematically analyzed all published evidence for potential markers that could identify those with GDM who have greater risk of complications. We find that high maternal weight is a risk factor for offspring born larger for their gestational age. Other promising markers were identified, but further analysis is needed before they can be applied in the clinic. Francis et al. perform a systematic review and meta-analysis to evaluate studies comparing perinatal outcomes among individuals with gestational diabetes mellitus (GDM). Their review and post hoc analysis find that maternal preconception weight and non-glucose-dependent biochemical markers could be a precision diagnostic approach to reducing variability in clinical outcomes following treatment.

Addictive behavior threatens not just the addict's happiness and health but also the welfare and well-being of others. It represents a loss of self-control and a variety of other cognitive impairments and behavioral deficits. An addict may say, \"I couldn't help myself.\" But questions arise: are we responsible for our addictions? And what responsibilities do others have to help us? This volume offers a range of perspectives on addiction and responsibility and how the two are bound together. Distinguished contributors -- from theorists to clinicians, from neuroscientists and psychologists to philosophers and legal scholars -- discuss these questions in essays using a variety of conceptual and investigative tools. Some contributors offer models of addiction-related phenomena, including theories of incentive sensitization, ego-depletion, and pathological affect; others address such traditional philosophical questions as free will and agency, mind-body, and other minds. Two essays, written by scholars who were themselves addicts, attempt to integrate first-person phenomenological accounts with the third-person perspective of the sciences. Contributors distinguish among moral responsibility, legal responsibility, and the ethical responsibility of clinicians and researchers. Taken together, the essays offer a forceful argument that we cannot fully understand addiction if we do not also understand responsibility.

Revised and updated by a new editorial team, the Sixth Edition of this text will remain the leading reference on the clinical care of the newborn. It provides complete, authoritative information on the biology of the newborn and the pathophysiology and management of diseases during the neonatal period. This edition has five new chapters on the role of telemedicine in neonatology, the impact of labor and delivery on the fetus, fetal determinants of adult disease, breast feeding, and control of breathing and apnea. Also included is a full-color insert illustrating key signs and symptoms, selected imaging techniques, and dermatologic conditions.