NCCN Guidelines® Insights: Merkel Cell Carcinoma, Version 1.2024.

The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled "Clinical N0 Disease, Locally Advanced MCC." This new algorithm page addresses locally advanced disease, and the panel clarifies the meaning behind the term "nonsurgical" by further defining locally advanced disease. In addition, the guideline includes the management of in-transit disease and updates to the systemic therapy options.

Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States. Due to the high frequency, BCC occurrences are not typically recorded, and annual rates of incidence can only be estimated. Current estimated rates are 2 million Americans affected annually, and this continues to rise. Exposure to radiation, from either sunlight or previous medical therapy, is a key player in BCC development. BCC is not as aggressive as other skin cancers because it is less likely to metastasize. However, surgery and radiation are prevalent treatment options, therefore disfigurement and limitation of function are significant considerations. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline an updated risk stratification and treatment options available for BCC.

Technical note: estimating longer drug shelf-life with reliability plotting.

A graphical plot of drug stability-study data can be extrapolated to estimate the drug's percent degradation and therefore its shelf-life beyond the time period of the study. However, after a statistical confidence limit is applied, that shelf-life estimate is significantly reduced. Such a reduction can be minimized by transforming the data so that it plots as close as possible to linearity, a process that is called reliability plotting. Reliability plotting seems to have been rarely if ever used on drug stability data, despite its being mentioned in relevant guidance documents and its ability to justify longer shelf-life at no additional cost. For example, an 18-month stability study resulted in a 19-month shelf-life using standard extrapolation methods but resulted in a 23 month shelf-life using reliability plotting.

Near doubling of Brazil's intensive row crop area since 2000.

Brazil has become a global leader in the production of commodity row crops such as soybean, sugarcane, cotton, and corn. Here, we report an increase in Brazilian cropland extent from 26.0 Mha in 2000 to 46.1 Mha in 2014. The states of Maranhão, Tocantins, Piauí, Bahia (collectively MATOPIBA), Mato Grosso, Mato Grosso do Sul, and Pará all more than doubled in cropland extent. The states of Goiás, Minas Gerais, and São Paulo each experienced >50% increases. The vast majority of expansion, 79%, occurred on repurposed pasture lands, and 20% was from the conversion of natural vegetation. Area of converted Cerrado savannas was nearly 2.5 times that of Amazon forests, and accounted for more than half of new cropland in MATOPIBA. Spatiotemporal dynamics of cropland expansion reflect market conditions, land use policies, and other factors. Continued extensification of cropland across Brazil is possible and may be likely under current conditions, with attendant benefits for and challenges to development.

NCCN Guidelines® Insights: Squamous Cell Skin Cancer, Version 1.2022.

The NCCN Guidelines for Squamous Cell Skin Cancer provide recommendations for diagnostic workup, clinical stage, and treatment options for patients with cutaneous squamous cell carcinoma. The NCCN panel meets annually to discuss updates to the guidelines based on comments from panel members and the Institutional Review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new surgical recommendation terminology (peripheral and deep en face margin assessment), as well as recent updates on topical prophylaxis, immunotherapy for regional and metastatic disease, and radiation therapy.

Joint cognition and the role of human agency in random number choices.

Joint cognition refers to the mental systems that support group performance when carrying out a shared, or jointly owned task. We focused here on understanding the social configurations that underpin key phenomena in joint cognition, in particular, whether individual cognition in task-sharing environments is mostly shaped by social factors or not. To this end, we investigated, first and mainly, whether human presence is necessary for the creation of joint performance; second and separately, whether prior experience of task sharing has an adaptive influence on subsequent individual choices; and third and additionally, whether individual differences in a social trait mediate joint performance. We describe an experiment in which participants combined with another human or a computer as they attempted to generate a paired sequence that was as random as possible. First, we found little difference in joint performance with regard to whether a human or a computer was the co-participant, except for immediate repetitive response. Second, we found evidence for choice adaptation, but only under the lower time pressure. Third, we replicated previous research in which no systematic link was established between social desirability and joint performance. We conclude that joint cognition phenomena may be rooted primarily in turn-taking configurations rather than in social dynamics per se.

Consistently inconsistent drivers of microbial diversity and abundance at macroecological scales.

Macroecology seeks to understand broad-scale patterns in the diversity and abundance of organisms, but macroecologists typically study aboveground macroorganisms. Belowground organisms regulate numerous ecosystem functions, yet we lack understanding of what drives their diversity. Here, we examine the controls on belowground diversity along latitudinal and elevational gradients. We performed a global meta-analysis of 325 soil communities across 20 studies conducted along temperature and soil pH gradients. Belowground taxa, whether bacterial or fungal, observed along a given gradient of temperature or soil pH were equally likely to show a linear increase, linear decrease, humped pattern, trough-shaped pattern, or no pattern in diversity along the gradient. Land-use intensity weakly affected the diversity-temperature relationship, but no other factor did so. Our study highlights disparities among diversity patterns of soil microbial communities. Belowground diversity may be controlled by the associated climatic and historical contexts of particular gradients, by factors not typically measured in community-level studies, or by processes operating at scales that do not match the temporal and spatial scales under study. Because these organisms are responsible for a suite of key processes, understanding the drivers of their distribution and diversity is fundamental to understanding the functioning of ecosystems.

Aortobronchial Fistula after Thoracic Endovascular Aortic Repair (TEVAR) for Descending Thoracic Aortic Aneurysm.

Continued enlargement of the aneurysm sac after thoracic endovascular aortic repair (TEVAR) is a known risk after endovascular treatment of thoracic aortic aneurysms. For this reason, periodic outpatient follow-up is required to identify situations that require repair. Here, we describe an aortobronchial fistula (ABF) in a patient lost to follow-up, that presented 3 years after an elective TEVAR done for a primary, descending thoracic aortic aneurysm. Our patient arrived in extremis and suffered massive hemoptysis leading to her demise. Computed tomography (CT) angiogram near the time of her death demonstrated a bleeding ABF immediately distal to her previous TEVAR repair. Aortic aneurysmal disease remains life threatening even after repair. Improved endovascular techniques and devices have resulted in decreased need for reintervention. However, this case demonstrates the risk of thoracic aortic disease progression and highlights the importance of establishing consistent, long-term follow-up after TEVAR.

Computed Tomography-guided Pericardiocentesis: An alternative approach for accessing the pericardium.

Pericardial effusions compress the heart, decrease cardiac output, and lead to haemodynamic collapse. Ultrasound (US)-guided pericardiocentesis is the gold standard for treating pericardial effusions. Recently, the incorporation of computed tomography (CT) guidance has increased patient safety while entering the pericardium. Despite the superior performance of CT-guided pericardiocentesis in smaller, complex effusions, this procedure is not routinely performed by cardiologists and surgeons. Unlike those with an intact pericardium, patients with mediastinal trauma, pericardial adhesions, temporary pacing wires, and vascular conduits are high risk for pericardiocentesis. Tamponade physiology also increases patient susceptibility to the hypotensive effects of anaesthesia during surgical drainage. Here we illustrate the technique of CT-guided pericardiocentesis and demonstrate its application in specific clinical scenarios. We conclude that CT-guided pericardiocentesis provides a useful, alternative strategy for treating cardiac tamponade in high risk patients.

Alcohol impairs the myeloid proliferative response to bacteremia in mice by inhibiting the stem cell antigen-1/ERK pathway.

Enhancement of stem cell Ag-1 (Sca-1) expression by myeloid precursors promotes the granulopoietic response to bacterial infection. However, the underlying mechanisms remain unclear. ERK pathway activation strongly enhances proliferation of hematopoietic progenitor cells. In this study, we investigated the role of Sca-1 in promoting ERK-dependent myeloid lineage proliferation and the effects of alcohol on this process. Thirty minutes after i.p. injection of alcohol, mice received i.v. challenge with 5 × 10(7) Escherichia coli for 8 or 24 h. A subset of mice received i.v. BrdU injection 20 h after challenge. Bacteremia increased Sca-1 expression, ERK activation, and proliferation of myeloid and granulopoietic precursors. Alcohol administration suppressed this response and impaired granulocyte production. Sca-1 expression positively correlated with ERK activation and cell cycling, but negatively correlated with myeloperoxidase content in granulopoietic precursors. Alcohol intoxication suppressed ERK activation in granulopoietic precursors and proliferation of these cells during bacteremia. Granulopoietic precursors in Sca-1(-/-) mice failed to activate ERK signaling and could not increase granulomacrophagic CFU activity following bacteremia. These data indicate that Sca-1 expression promotes ERK-dependent myeloid cell proliferation during bacteremia. Suppression of this response could represent an underlying mechanism for developing myelosuppression in alcohol-abusing hosts with severe bacterial infection.

Neurological adverse effects of isoxazoline exposure in cats and dogs.

BACKGROUND: Isoxazolines are rarely reported to be associated with neurological adverse events in cats and dogs, but information about the onset and duration of neurological signs is lacking in the summary of product characteristics of these medicines. METHODS: The Veterinary Poisons Information Service and the Dutch Poisons Information Center databases were searched using the Veterinary Dictionary for Drug-Related Affairs terms for ataxia, muscle tremor, convulsions or hyperesthesia in cats and dogs exposed to isoxazolines. RESULTS: There were 22 cases with and 57 cases without outcome information, mostly involving fluralaner or sarolaner. In both groups, muscle tremors and convulsions were the most common signs. In dogs, neurological signs occurred with oral therapeutic dose and overdosage. In cats, most fluralaner cases involved therapeutic topical exposure, and all sarolaner cases involved oral exposure. In all cases with outcome information, the animals recovered. LIMITATIONS: Cases discussed with poison centres tend to involve more severe signs. CONCLUSION: The true incidence of neurological adverse effects from isoxazolines remains unclear. The delay between the administration and onset of signs can be long, and the association may be missed. A lack of timing information in the summary of product characteristics could also contribute to missed attribution of adverse effects.

Human immunodeficiency virus infection is associated with greater risk of pneumonia and readmission after cardiac surgery.

Objective: Human immunodeficiency virus infection (HIV+) is associated with a 2-fold increased risk of cardiovascular disease. Increasingly, patients who are HIV + are being evaluated to undergo cardiac surgery. Current risk-adjusted scoring systems, including the Society of Thoracic Surgeons Predicted Risk of Mortality score, fail to stratify HIV + risk. Unfortunately, there exists a paucity of cardiac surgery outcomes data in modern patients who are HIV+. Methods: We conducted a retrospective review of PearlDiver, an all-payer claims administrative database. In total, 14,714,743 patients were captured between 2010 and 2020. Of these, 59,695 (0.4%) of patients had a history of HIV+, and 1759 (2.95%) of these patients underwent cardiac surgery. Patients who were HIV+ were younger, more often male, and had greater comorbidity, history of hypertension, chronic obstructive pulmonary disease, chronic liver disease, chronic kidney disease, chronic lung disease, and heart failure. Results: Postoperatively, patients who were HIV + had significantly greater rates of pneumonia (relative risk, 1.70; P = .0003) and 30-day all-cause readmission (relative risk, 1.28, P < .0001). After linear regression analysis, these results remained significant. Data also show that a lesser proportion of patients with HIV + underwent coronary artery bypass grafting, aortic valve replacement, and any cardiac surgery compared with controls. Conclusions: Patients who are HIV + undergoing cardiac surgery are at greater risk of pneumonia and readmission. Moreover, we discovered lower rates of cardiac surgery in patients who are HIV+, which may reflect limited access to surgery when indicated. Today's risk-adjusted scoring systems in cardiac surgery need to better account for the modern patient who is HIV+.

Factors Associated With and Characteristics of Patients Receiving Proton Therapy at the End of Life.

Purpose: To identify the characteristics, indications, and toxicities among patients receiving proton beam therapy (PBT) in the final year of life at an academic medical center. Materials and Methods: A retrospective review of patients who received PBT within the final 12 months of life was performed. Electronic medical records were reviewed for patient and treatment details from 2010 to 2019. Patients were followed from the start of PBT until death or last follow-up. Acute (3 months) toxicities were graded using the Common Terminology Criteria for Adverse Events v5.0. Imaging response was assessed using the Response Evaluation Criteria in Solid Tumors v1.1. The χ2 test was used to evaluate factors associated with palliative treatment. Simple logistic regression was used to evaluate factors associated with toxicity. Results: Bet299 patients were treated at the end of life (EOL) out of 5802 total patients treated with PBT (5.2%). Median age was 68 years (19-94 years), 58% male. The most common cancer was nonsmall cell lung cancer (27%). Patients were treated for symptom palliation alone (11%), durable control (57%), curative intent (16%), local recurrence (14%), or oligometastatic disease (2%). Forty-five percent received reirradiation. Median treatment time was 32 days (1-189 days). Acute toxicity was noted in 85% of the patients (31% G1, 53% G2, 15% G3). Thirteen patients (4%) experienced chronic toxicity. Breast and hematologic malignancy were associated with palliative intent χ2 (1, N = 14) = 17, P = .013; (χ2 (1, N = 14) = 18, P = .009). Conclusion: The number of patients treated with PBT at the EOL was low compared to all comers. Many of these patients received treatment with definitive doses and concurrent systemic therapy. Some patients spent a large portion of their remaining days on treatment. A prognostic indicator may better optimize patient selection for PBT at the EOL.

Comparing the Efficacy of Targeted and Blast Portal Messaging in Message Opening Rate and Anticoagulation Initiation in Patients With Atrial Fibrillation in the Preventing Preventable Strokes Study II: Prospective Cohort Study.

BACKGROUND: The gap in anticoagulation use among patients with atrial fibrillation (AF) is a major public health threat. Inadequate patient education contributes to this gap. Patient portal-based messaging linked to educational materials may help bridge this gap, but the most effective messaging approach is unknown. OBJECTIVE: This study aims to compare the responsiveness of patients with AF to an AF or anticoagulation educational message between 2 portal messaging approaches: sending messages targeted at patients with upcoming outpatient appointments 1 week before their scheduled appointment (targeted) versus sending messages to all eligible patients in 1 blast, regardless of appointment scheduling status (blast), at 2 different health systems: the University of Massachusetts Chan Medical School (UMass) and the University of Florida College of Medicine-Jacksonville (UFL). METHODS: Using the 2 approaches, we sent patient portal messages to patients with AF and grouped patients by high-risk patients on anticoagulation (group 1), high-risk patients off anticoagulation (group 2), and low-risk patients who may become eligible for anticoagulation in the future (group 3). Risk was classified based on the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age between 65 and 74 years, and sex category (CHA2DS2-VASc) score. The messages contained a link to the Upbeat website of the Heart Rhythm Society, which displays print and video materials about AF and anticoagulation. We then tracked message opening, review of the website, anticoagulation use, and administered patient surveys across messaging approaches and sites using Epic Systems (Epic Systems Corporation) electronic health record data and Google website traffic analytics. We then conducted chi-square tests to compare potential differences in the proportion of patients opening messages and other evaluation metrics, adjusting for potential confounders. All statistical analyses were performed in SAS (version 9.4; SAS Institute). RESULTS: We sent 1686 targeted messages and 1450 blast messages. Message opening was significantly higher with the targeted approach for patients on anticoagulation (723/1156, 62.5% vs 382/668, 57.2%; P=.005) and trended the same in patients off anticoagulation; subsequent website reviews did not differ by messaging approach. More patients off anticoagulation at baseline started anticoagulation with the targeted approach than the blast approach (adjusted percentage 9.3% vs 2.1%; P<.001). CONCLUSIONS: Patients were more responsive in terms of message opening and subsequent anticoagulation initiation with the targeted approach.

Prevention of postpartum traumatic stress in mothers with preterm infants: manual development and evaluation.

Premature birth has been associated with multiple adverse maternal psychological outcomes that include depression, anxiety, and trauma as well as adverse effects on maternal coping ability and parenting style. Infants who are premature are more likely to have poorer cognitive and developmental functioning and, thus, may be harder to parent, both as infants and as they get older. In response to these findings, a number of educational and behavioral interventions have been developed that target maternal psychological functioning, parenting, and aspects of the parent-infant relationship. The current study aimed to both develop and evaluate a treatment that integrates, for the first time, effective interventions for reducing symptoms of posttraumatic stress disorder (PTSD) and enhancing maternal-infant interactions. Conclusions from the study indicate that the intervention is feasible, able to be implemented with a high level of fidelity, and is rated as highly satisfactory by participants. Though encouraging, these findings are preliminary, and future studies should strive to reproduce these findings with a larger sample size and a comparison group.

Cannabinoids function in defense against chewing herbivores in Cannabis sativa L.

In the decades since the first cannabinoids were identified by scientists, research has focused almost exclusively on the function and capacity of cannabinoids as medicines and intoxicants for humans and other vertebrates. Very little is known about the adaptive value of cannabinoid production, though several hypotheses have been proposed including protection from ultraviolet radiation, pathogens, and herbivores. To test the prediction that genotypes with greater concentrations of cannabinoids will have reduced herbivory, a segregating F2 population of Cannabis sativa was leveraged to conduct lab- and field-based bioassays investigating the function of cannabinoids in mediating interactions with chewing herbivores. In the field, foliar cannabinoid concentration was inversely correlated with chewing herbivore damage. On detached leaves, Trichoplusia ni larvae consumed less leaf area and grew less when feeding on leaves with greater concentrations of cannabinoids. Scanning electron and light microscopy were used to characterize variation in glandular trichome morphology. Cannabinoid-free genotypes had trichomes that appeared collapsed. To isolate cannabinoids from confounding factors, artificial insect diet was amended with cannabinoids in a range of physiologically relevant concentrations. Larvae grew less and had lower rates of survival as cannabinoid concentration increased. These results support the hypothesis that cannabinoids function in defense against chewing herbivores.

Effectiveness of therapeutic behavioral interventions for parents of low birth weight premature infants: A review.

Premature birth has been associated with a number of adverse maternal psychological outcomes that include depression, anxiety, and trauma as well as adverse effects on maternal coping ability and parenting style. Infants and children who were premature are more likely to have poorer cognitive and developmental functioning and, thus, may be harder to parent. In response to these findings, there have been a number of educational and behavioral interventions developed that target maternal psychological functioning, parenting and aspects of the parent-infant relationship. Since the last comprehensive review of this topic in 2002, there have been a significant number of developments in the quality of the studies conducted and the theoretical models that address the experience of parents of premature infants. In the current review, eighteen new interventions were identified and grouped into four categories based on treatment length and the target of the intervention. Findings suggest a trend towards early, brief interventions that are theoretically based, specifically target parent trauma, and utilize cognitive behavioral techniques. Although it is difficult to generalize study findings, conclusions from the review suggest that targeted interventions may have positive effects on both maternal and infant outcomes.