Variability of Leser-Trélat Sign Secondary to Melanoma In Situ.

Leser-Trélat sign (LTS) is characterized as an eruptive display of multiple seborrheic keratoses (SKs) in association with malignancy. This case highlights the variable presentation of LTS secondary to melanoma. To our knowledge, this LTS pattern is the first case where the sign manifests as a subtle pattern secondary to melanoma. This stands in contrast to the five documented cases in the literature of LTS-melanoma, which exhibited distinctive and eruptive patterns. A 64-year-old Caucasian female presented for a wellness examination. No personal history of skin cancer was noted. Patient displayed an onset proliferation of SKs with an irregular, sub-centimeter macular nevus over her right lateral mid back. A 6mm punch biopsy was significant for melanoma in situ, arising within a lentiginous compound dysplastic nevus, focally abutting one peripheral tissue edge. A re-excision with a minimum of 5mm margins was completed and the specimen was negative for residual in situ melanoma. Because of the rare occurrence of this delicate pattern at the site of the melanoma, this presentation adds to the knowledge surrounding this diagnosis. This case emphasizes the importance of maintaining vigilance regarding skin manifestations associated with disease and highlights the critical importance of observation and identification of subtle physical exam findings.

Out-of-Pocket Costs and Outpatient Visits Among Patients With Cancer in High-Deductible Health Plans.

Importance: High-deductible health plans (HDHPs) have grown rapidly and may adversely affect access to comprehensive cancer care. Objective: To evaluate the association of HDHPs with out-of-pocket medical costs and outpatient physician visits among patients with cancer. Design, Setting, and Participants: Using 2003 to 2017 data from the deidentified Optum Clinformatics Data Mart database from individuals with employer-sponsored health coverage, adults aged 18 to 64 years with cancer who were enrolled in low-deductible (≤$500 annually) health plans during a baseline year were identified. Patients whose employers then mandated a switch to an HDHP (≥$1000 annual deductible) were assigned to the HDHP group, while contemporaneous individuals with cancer at baseline who had no option but to continue enrollment in low-deductible plans were assigned to the control group. The 2 groups were matched on demographic variables (age, sex, race and ethnicity, US Census region, rural vs urban, and neighborhood poverty level), cancer type, morbidity score, number of baseline physician visits by specialty type, baseline out-of-pocket costs, and employer characteristics. These cohorts were followed up for up to 3 years after the baseline year. Data were analyzed from July 2021 to December 2022. Exposures: Employer-mandated HDHP enrollment. Main Outcomes and Measures: Out-of-pocket medical expenditures and outpatient visits to primary care physicians, cancer specialists, and noncancer specialists. Results: After matching, the sample included 45 708 patients with cancer (2703 patients in the HDHP group and 43 005 matched individuals in the control group); mean (SD) age in the HDHP and control groups was 52.9 (9.3) years and 52.9 (2.3) years, respectively, with 58.5% females in both groups. The matching procedure yielded variable weights for each individual in the control group, resulting in a weighted control group sample of 2703 patients. Patients with cancer who were switched to HDHPs experienced an increase in annual out-of-pocket medical expenditures of 68.1% (95% CI, 51.0%-85.3%; absolute increase, $1349.80 [95% CI, $1060.30-$1639.20]) after the switch compared with those who remained in traditional health plans. At follow-up, the number of oncology visits did not differ between the 2 groups (relative difference, 0.1%; 95% CI, -8.4% to 9.4%); however, the HDHP group had 10.8% (95% CI, -15.5% to -5.9%) fewer visits to primary care physicians and 5.9% (95% CI, -11.2% to -0.3%) fewer visits to noncancer specialists. Conclusions and Relevance: Results of this cohort study suggest that after enrollment in HDHPs, patients with cancer experienced substantial increases in out-of-pocket medical costs. The number of visits to oncologists was unchanged during follow-up, but the number of visits to noncancer physicians was lower. These findings suggest that HDHPs are unlikely to unfavorably affect key oncology services but might lead to less comprehensive care of cancer survivors.

Massachusetts' opioid limit law associated with a reduction in postoperative opioid duration among orthopedic patients.

Postoperative orthopedic patients are a high-risk group for receiving long-duration, large-dosage opioid prescriptions. Rigorous evaluation of state opioid duration limit laws, enacted throughout the country in response to the opioid overdose epidemic, is lacking among this high-risk group. We took advantage of Massachusetts' early implementation of a 2016 7-day-limit law that occurred before other statewide or plan-wide policies took effect and used commercial insurance claims from 2014-2017 to study its association with postoperative opioid prescriptions greater than 7 days' duration among Massachusetts orthopedic patients relative to a New Hampshire control group. Our sample included 14 097 commercially insured, opioid-naive adults aged 18 years and older undergoing elective orthopedic procedures. We found that the Massachusetts 7-day limit was associated with an immediate 4.23 percentage point absolute reduction (95% CI, 8.12 to 0.33 percentage points) and a 33.27% relative reduction (95% CI, 55.36% to 11.19%) in the percentage of initial fills greater than 7 days in the Massachusetts relative to the control group. Seven-day-limit laws may be an important state-level tool to mitigate longer duration prescribing to high-risk postoperative populations.

Clinical findings and outcomes of 153 dogs surgically treated for intestinal intussusceptions.

OBJECTIVE: To describe perioperative characteristics and outcomes of dogs surgically treated for intestinal intussusception. STUDY DESIGN: Multi-institutional, retrospective study. ANIMALS: One hundred fifty-three client-owned dogs with intestinal intussusception. METHODS: Dogs were included when they had undergone surgical treatment of a confirmed intestinal intussusception. Medical records were reviewed for demographics and clinical data, including surgical complications (graded 1-4). Follow-up was obtained via telephone interview with owners and referring veterinarians. RESULTS: Dogs had a median age of 10 months (range, 2-156), and the most common location for intussusception was ileocolic (66/153 [43%]). Most cases had no identifiable cause (104/155 [67%]). Intestinal resection and anastomosis (IRA) was performed in 129 of 153 (84%) dogs; enteroplication was performed in 28 of 153 (18%) dogs, including 13 with and 15 without IRA. Intraoperative complications occurred in 10 of 153 (7%) dogs, all involving intestinal damage during attempted manual reduction. The median duration of follow-up after discharge was 334 days (interquartile range, 15-990; range, 1-3302). Postoperative complications occurred in 53 of 153 (35%) dogs, including 22 of 153 (14%) with severe (grade 3 or 4) events. Diarrhea, regurgitation, and septic peritonitis were the most common postoperative complications; intussusception recurred in four of 153 (3%) dogs, all within 72 hours postoperatively. Fourteen-day postoperative mortality rate was 6%. CONCLUSION: Surgical treatment of intestinal intussusception was curative in most dogs, even when an underlying cause was not identified. Surgical complications were common, including a 14% risk of life-threatening short-term complications. CLINICAL SIGNIFICANCE: Surgical treatment of intestinal intussusception offers an excellent prognosis, but the potential life-threatening complications should be considered.

Response to "How prepared is Africa to face COVID-19?" by Wadoum and Clarke.

A recent commentary published in this journal correctly notes the important challenges that must be addressed to mitigate the effects of the COVID-19 pandemic in Africa. While we agree with the basic assumptions and arguments of their essay, we argue that common social institutional norms in most rural settings could be marshalled for organizing preventive measures.

Response to "How prepared is Africa to face COVID-19? by Wadoum and Clarke

A recent commentary published in this journal correctly notes the important challenges that must be addressed to mitigate the effects of the COVID-19 pandemic in Africa. While we agree with the basic assumptions and arguments of their essay, we argue that common social institutional norms in most rural settings could be marshalled for organizing preventive measures

Development and Implementation of a Comprehensive, Multidisciplinary Emergency Department Extracorporeal Membrane Oxygenation Program.

Despite advances in the medical and surgical management of cardiovascular disease, greater than 350,000 patients experience out-of-hospital cardiac arrest in the United States annually, with only a 12% neurologically favorable survival rate. Of these patients, 23% have an initial shockable rhythm of ventricular fibrillation/pulseless ventricular tachycardia (VF/VT), a marker of high probability of acute coronary ischemia (80%) as the precipitating factor. However, few patients (22%) will experience return of spontaneous circulation and sufficient hemodynamic stability to undergo cardiac catheterization and revascularization. Previous case series and observational studies have demonstrated the successful application of intra-arrest extracorporeal life support, including to out-of-hospital cardiac arrest victims, with a neurologically favorable survival rate of up to 53%. For patients with refractory cardiac arrest, strategies are needed to bridge them from out-of-hospital cardiac arrest to the catheterization laboratory and revascularization. To address this gap, we expanded our ICU and perioperative extracorporeal membrane oxygenation (ECMO) program to the emergency department (ED) to reach this cohort of patients to improve survival. In this report, we illustrate our process and initial experience of developing a multidisciplinary team for rapid deployment of ED ECMO as a template for institutions interested in building their own ED ECMO programs.

Can Community Members Identify Tropical Tree Species for REDD+ Carbon and Biodiversity Measurements?

Biodiversity conservation is a required co-benefit of REDD+. Biodiversity monitoring is therefore needed, yet in most areas it will be constrained by limitations in the available human professional and financial resources. REDD+ programs that use forest plots for biomass monitoring may be able to take advantage of the same data for detecting changes in the tree diversity, using the richness and abundance of canopy trees as a proxy for biodiversity. If local community members are already assessing the above-ground biomass in a representative network of forest vegetation plots, it may require minimal further effort to collect data on the diversity of trees. We compare community members and trained scientists' data on tree diversity in permanent vegetation plots in montane forest in Yunnan, China. We show that local community members here can collect tree diversity data of comparable quality to trained botanists, at one third the cost. Without access to herbaria, identification guides or the Internet, community members could provide the ethno-taxonomical names for 95% of 1071 trees in 60 vegetation plots. Moreover, we show that the community-led survey spent 89% of the expenses at village level as opposed to 23% of funds in the monitoring by botanists. In participatory REDD+ programs in areas where community members demonstrate great knowledge of forest trees, community-based collection of tree diversity data can be a cost-effective approach for obtaining tree diversity information.

Practice characteristics of Emergency Department extracorporeal cardiopulmonary resuscitation (eCPR) programs in the United States: The current state of the art of Emergency Department extracorporeal membrane oxygenation (ED ECMO).

PURPOSE: To characterize the current scope and practices of centers performing extracorporeal cardiopulmonary resuscitation (eCPR) on the undifferentiated patient with cardiac arrest in the emergency department. METHODS: We contacted all US centers in January 2016 that had submitted adult eCPR cases to the Extracorporeal Life Support Organization (ELSO) registry and surveyed them, querying for programs that had performed eCPR in the Emergency Department (ED ECMO). Our objective was to characterize the following domains of ED ECMO practice: program characteristics, patient selection, devices and techniques, and personnel. RESULTS: Among 99 centers queried, 70 responded. Among these, 36 centers performed ED ECMO. Nearly 93% of programs are based at academic/teaching hospitals. 65% of programs are less than 5 years old, and 60% of programs perform ≤3 cases per year. Most programs (90%) had inpatient eCPR or salvage ECMO programs prior to starting ED ECMO programs. The majority of programs do not have formal inclusion and exclusion criteria. Most programs preferentially obtain vascular access via the percutaneous route (70%) and many (40%) use mechanical CPR during cannulation. The most commonly used console is the Maquet Rotaflow(®). Cannulation is most often performed by cardiothoracic (CT) surgery, and nearly all programs (>85%) involve CT surgeons, perfusionists, and pharmacists. CONCLUSIONS: Over a third of centers that submitted adult eCPR cases to ELSO have performed ED ECMO. These programs are largely based at academic hospitals, new, and have low volumes. They do not have many formal inclusion or exclusion criteria, and devices and techniques are variable.

Variation in Postpartum Glycemic Screening in Women With a History of Gestational Diabetes Mellitus.

OBJECTIVE: To assess patterns and predictors of postpartum diabetes screening in a commercially insured, geographically and sociodemographically diverse sample of women with gestational diabetes mellitus. METHODS: Using commercial insurance claims (2000-2012) from all 50 states, we conducted a retrospective cohort study in 447,556 women with at least one delivery and continuous enrollment 1 year before and after delivery. We identified women with a gestational diabetes mellitus pregnancy and examined postpartum diabetes screening type and timing and performed logistic regression to identify screening predictors. RESULTS: Gestational diabetes mellitus was diagnosed in 32,253 (7.2%) women during the study timeframe. Three fourths received no screening within 1 year postpartum. Rates of recommended 75-g oral glucose tolerance testing within 6-12 weeks were low but increased over time (27 [2%] in 2001 compared with 249 [7%] in 2011, adjusted odds ratio [OR] 3.1, 95% confidence interval [CI] 2.0-47). Among women screened, those in the Northeast (19%) and South (18%) were least likely to receive a 75-g oral glucose tolerance test within 0-12 weeks (adjusted OR 0.4 for each, CI 0.4-0.5) compared with the West (36%). Asian women were most likely to receive any screening (18%; adjusted OR 1.5, CI 1.3-1.6) compared with white women (12%). Black women were most likely to receive hemoglobin A1c (21%; adjusted OR 2.0, CI 1.3-3.2) compared with white women (11%). Antepartum antiglycemic medication (21%; adjusted OR 2.1, CI 2.0-2.3) or visit to a nutritionist-diabetes educator (19%; adjusted OR 1.6, CI 1.4-1.7) or endocrinologist (23%; adjusted OR 1.7, CI 1.6-1.9) predicted screening within 12 weeks postpartum. CONCLUSION: Postpartum diabetes screening remains widely underused among commercially insured women with gestational diabetes mellitus. Differences in screening by geography, race, and antepartum care can inform health system and public health interventions to increase diabetes detection in this high-risk population.

A Novel Epigenetic Silencing Pathway Involving the Highly Conserved 5'-3' Exoribonuclease Dhp1/Rat1/Xrn2 in Schizosaccharomyces pombe.

Epigenetic gene silencing plays a critical role in regulating gene expression and contributes to organismal development and cell fate acquisition in eukaryotes. In fission yeast, Schizosaccharomyces pombe, heterochromatin-associated gene silencing is known to be mediated by RNA processing pathways including RNA interference (RNAi) and a 3'-5' exoribonuclease complex, the exosome. Here, we report a new RNA-processing pathway that contributes to epigenetic gene silencing and assembly of heterochromatin mediated by 5'-3' exoribonuclease Dhp1/Rat1/Xrn2. Dhp1 mutation causes defective gene silencing both at peri-centromeric regions and at the silent mating type locus. Intriguingly, mutation in either of the two well-characterized Dhp1-interacting proteins, the Din1 pyrophosphohydrolase or the Rhn1 transcription termination factor, does not result in silencing defects at the main heterochromatic regions. We demonstrate that Dhp1 interacts with heterochromatic factors and is essential in the sequential steps of establishing silencing in a manner independent of both RNAi and the exosome. Genomic and genetic analyses suggest that Dhp1 is involved in post-transcriptional silencing of repetitive regions through its RNA processing activity. The results describe the unexpected role of Dhp1/Rat1/Xrn2 in chromatin-based silencing and elucidate how various RNA-processing pathways, acting together or independently, contribute to epigenetic regulation of the eukaryotic genome.

Development of a mouse model for sulfur mustard-induced ocular injury and long-term clinical analysis of injury progression.

CONTEXT: Sulfur mustard (SM) is a highly reactive vesicating agent that can induce severe ocular injury. The clinical features of this injury have been well documented, but the molecular basis for this pathology is not well understood. Identification and validation of specific targets is necessary in the effort to develop effective therapeutics for this injury. Currently used rabbit models are not well suited for many molecular studies because the necessary reagents are not widely available. However, these reagents are widely available for the mouse model. OBJECTIVE: Our objective is to develop a mouse model of SM-induced ocular injury suitable for the study of the molecular mechanisms of injury and the evaluation of therapeutics. MATERIALS AND METHODS: Ocular exposure to sulfur mustard vapor was accomplished by using a vapor cup method. Dose response studies were conducted in female BALB/c mice. An exposure dose which produced moderate injury was selected for further study as moderate injury was determined to be amenable to studying the beneficial effects of potential therapeutics. Histopathology and inflammatory markers were evaluated for up to 28 days after exposure, while clinical injury progression was evaluated for 1 year post-exposure. RESULTS: A biphasic ocular injury was observed in mice exposed to SM. Acute phase SM ocular injury in mice was characterized by significant corneal epithelium loss, corneal edema, limbal engorgement, and ocular inflammation. This was followed by a brief recovery phase. A delayed injury phase then ensued in the following weeks to months and was characterized by keratitis, stromal edema, infiltrates, neovascularization, and eventual corneal scarring. DISCUSSION AND CONCLUSIONS: SM-induced ocular injury in mice is consistent with observations of SM-induced ocular injury in humans and rabbit models. However, in the mouse model, the SM ocular injury, a more rapid onset of the delayed injury phase was observed. We have developed an animal model of SM injury that is suitable for studies to elucidate molecular mechanisms of injury and identify potential therapeutic targets.

Lipid oxidation and peroxidation in CNS health and disease: from molecular mechanisms to therapeutic opportunities.

Reactive oxygen species (ROS) are produced at low levels in mammalian cells by various metabolic processes, such as oxidative phosphorylation by the mitochondrial respiratory chain, NAD(P)H oxidases, and arachidonic acid oxidative metabolism. To maintain physiological redox balance, cells have endogenous antioxidant defenses regulated at the transcriptional level by Nrf2/ARE. Oxidative stress results when ROS production exceeds the cell's ability to detoxify ROS. Overproduction of ROS damages cellular components, including lipids, leading to decline in physiological function and cell death. Reaction of ROS with lipids produces oxidized phospholipids, which give rise to 4-hydroxynonenal, 4-oxo-2-nonenal, and acrolein. The brain is susceptible to oxidative damage due to its high lipid content and oxygen consumption. Neurodegenerative diseases (AD, ALS, bipolar disorder, epilepsy, Friedreich's ataxia, HD, MS, NBIA, NPC, PD, peroxisomal disorders, schizophrenia, Wallerian degeneration, Zellweger syndrome) and CNS traumas (stroke, TBI, SCI) are problems of vast clinical importance. Free iron can react with H(2)O(2) via the Fenton reaction, a primary cause of lipid peroxidation, and may be of particular importance for these CNS injuries and disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Atherosclerosis, the major risk factor for ischemic stroke, involves accumulation of oxidized LDL in the arteries, leading to foam cell formation and plaque development. This review will discuss the role of lipid oxidation/peroxidation in various CNS injuries/disorders.

Integration of cytokine biology and lipid metabolism in stroke.

Cytokines regulate the innate and adaptive immune responses and are pleiotropic, redundant and multifunctional. Expression of most cytokines, including TNF-alpha and IL-1alpha/beta, is very low in normal brain. Metabolism of lipids is of particular interest due to their high concentration in the brain. Inflammatory response after stroke suggests that cytokines (TNF-alpha, IL-1alpha/beta, IL-6), affect the phospholipid metabolism and subsequent production of eicosanoids, ceramide, and ROS that may potentiate brain injury. Phosphatidylcholine and sphingomyelin are source for lipid messengers. Sphingomyelin synthase serves as a bridge between metabolism of glycerolipids and sphingolipids. TNF-alpha and IL-1alpha/beta can induce phospholipases (A2, C, and D) and sphingomyelinases, and concomitantly proteolyse phosphatidylcholine and sphingomyelin synthesizing enzymes. Together, these alterations contribute to loss of phosphatidylcholine and sphingomyelin after stroke that can be attenuated by inhibiting TNF-alpha or IL-1alpha/beta signaling. Inflammatory responses are instrumental in the formation and destabilization of atherosclerotic plaques. Secretory PLA2 IIA is found in human atherosclerotic lesions and is implicated in initiation, progression and maturation of atherosclerosis, a risk factor for stroke. Lipoprotein-PLA2, part of apolipoprotein B-100 of LDL, plays a role in vascular inflammation and coronary endothelial dysfunction. Cytokine antagonism attenuated secretory PLA2 IIA actions, suggesting cytokine-lipid integration studies will lead to new concepts contributing to bench-to-bedside transition for stroke therapy.

Youth working alliance: a core clinical construct in need of empirical maturity.

The therapeutic alliance has long been recognized as an important component of successful psychotherapy for adults; research has established robust links to outcome. Until recently, however, research on the alliance between youth and their therapists has been sparse. The present review synthesizes the existing findings regarding the youth alliance and utilizes the adult alliance literature and the child and adolescent developmental literatures to suggest future avenues of research. Weak alliance was found to predict premature termination, and strong alliance predicted symptom reduction, with some support for differential effects of the youth-therapist and parent-therapist alliances. In addition, the youth alliance is moderated by several patient and therapist characteristics, including the particular problems of patients and the interpersonal skills of therapists. The field has yet to coalesce around a single definition of the youth alliance, however, making it difficult to assess research results. Adult models of the alliance continue to be used heuristically despite some evidence that the alliance operates differently for youth. Tightening the operational definition of the youth alliance and addressing methodological issues will be essential in future efforts to understand how the alliance develops and what role it may play in the treatment process for youth.