Self-reporting of psychoneurophysical (PNP) symptoms in adults with four chronic diseases: a protocol for a scoping review.

BACKGROUND: Patient self-reporting of health-specific information, including symptoms, allows healthcare providers to provide more timely, personalized, and patient-centered care to meet their needs. It is critical to acknowledge that symptom reporting draws from the individual's unique sociocultural background influencing how one perceives health and illness. This scoping review will explore whether racial groups with 4 chronic diseases (cardiovascular diseases, respiratory diseases, cancers, and diabetes) differ in self-reporting of psychoneurophysical (PNP) symptoms. The PNP symptoms of interest include depressive symptoms, fatigue, anxiety, pain, cognitive impairment, sleep impairment, mood impairment, irritability, and shortness of breath. METHODS: Four databases will be searched by a biomedical librarian: CINAHL Plus (EBSCOhost), Embase (Elsevier), PubMed (NLM), Web of Science: Core Collection (Clarivate Analytics), and limited to publications written in the English language. Two independent reviewers will screen the records' title, abstract, and then full text and extract the data from included articles using Covidence. A third reviewer will be used for resolving disagreements. Included articles must comprise adult patients with at least one of the specified chronic diseases who self-report at least one of the specified PNP symptoms. Studies that used clinician-administered questionnaires or obtained symptom responses from primary caregiver or patient designee will be excluded. Articles on patient-reported functionality or perceived quality of life will also be excluded from the review. Two reviewers will independently extract data (e.g., demographics, study design, racial group, chronic disease, measure/scale used for self-report) from each included article using Covidence and Microsoft Excel for data cleaning and analyses. DISCUSSION: This scoping review may potentially identify the relevant and practical implications related to clinical decision-making and health outcomes for patients experiencing the psychoneurophysical symptoms included in this study. The authors will present how the results can be utilized in clinical practice, health policy, and research planning. SYSTEMATIC REVIEW REGISTRATION: The protocol was registered on Open Science Framework (OSF) at: https://osf.io/ps7aw.

Meta-analysis: Incidence of cirrhosis and hepatocellular carcinoma in patients with Fontan palliation.

BACKGROUND AND AIMS: The Fontan palliation is the final stage of surgery for many children born with univentricular physiology. Almost all Fontan patients develop liver fibrosis which may eventually lead to cirrhosis and hepatocellular carcinoma (HCC). These are important causes of morbidity and mortality in these patients. We performed a systematic review and meta-analysis to assess the incidence of cirrhosis and HCC in Fontan patients and stratify it based on time since surgery. METHODS: A literature search of seven databases identified 1158 records. Studies reporting the number of cirrhosis and HCC cases in Fontan patients and time since Fontan surgery were included. In the cirrhosis cohort, we included only those studies where all patients underwent liver biopsy. RESULTS: A total of 23 studies were included: 12 and 13 studies in the cirrhosis and HCC cohorts, respectively, with two studies included in both cohorts. The incidence of cirrhosis was 0.97 per 100 patient-years (95% CI 0.57-1.63), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 1.61 per 100 patient-years (95% CI 1.24-2.08) and 32.2% (95% CI 25.8%-39.4%), respectively. The incidence of HCC was 0.12 per 100 patient-years (95% CI 0.07-0.21), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 0.20 per 100 patient-years (95% CI 0.12-0.35) and 3.9% (95% CI 2.2%-6.8%), respectively. Only about 70% of patients with HCC (20/28) had underlying cirrhosis. CONCLUSION: The incidence of cirrhosis and HCC increases over time, especially at ≥20 years post Fontan surgery. Studies are needed to further identify at-risk patients in order to streamline surveillance for these highly morbid conditions.

The National Cancer Institute's Cancer Disparities Research Partnership Program: a unique funding model 20 years later.

The burden of cancer and access to effective treatment are not experienced equally by all in the United States. For underserved populations that often access the health-care system when their cancers are in advanced disease stages, radiation oncology services are essential. In 2001, the National Cancer Institute's (NCI's) Radiation Research Program created and implemented the Cancer Disparities Research Partnership Program (CDRP). CDRP was a pioneering funding model whose goal was to increase participation of medically underserved populations in NCI clinical trials. CDRP's Cooperative Agreement funding supported for awardees the planning, development, and conduct of radiation oncology clinical research in institutions not traditionally involved in NCI-sponsored research and cared for a disproportionate number of medically underserved, health-disparities populations. The awardee secured and provided support for mentorship from 1 of 2 NCI comprehensive cancer centers named in its application. Six CDRP awards were made over two 5-year funding periods ending in 2013, with the end-of-program accomplishments previously reported. With the current focus on addressing equity, diversity, and inclusion, the 6 principal investigators were surveyed, 5 of whom responded about the impact of CDRP on their institutions, communities, and personal career paths. The survey that was emailed included 10 questions on a 5-point Likert scale. It was not possible to collect patient data this long after completion of the program. This article provides a 20-year retrospective of the experiences and observations from those principal investigators that can inform those now planning, building, and implementing equity, diversity, and inclusion programs.

Characteristics of Cancer Epidemiology Studies That Employ Metabolomics: A Scoping Review.

An increasing number of cancer epidemiology studies use metabolomics assays. This scoping review characterizes trends in the literature in terms of study design, population characteristics, and metabolomics approaches and identifies opportunities for future growth and improvement. We searched PubMed/MEDLINE, Embase, Scopus, and Web of Science: Core Collection databases and included research articles that used metabolomics to primarily study cancer, contained a minimum of 100 cases in each main analysis stratum, used an epidemiologic study design, and were published in English from 1998 to June 2021. A total of 2,048 articles were screened, of which 314 full texts were further assessed resulting in 77 included articles. The most well-studied cancers were colorectal (19.5%), prostate (19.5%), and breast (19.5%). Most studies used a nested case-control design to estimate associations between individual metabolites and cancer risk and a liquid chromatography-tandem mass spectrometry untargeted or semi-targeted approach to measure metabolites in blood. Studies were geographically diverse, including countries in Asia, Europe, and North America; 27.3% of studies reported on participant race, the majority reporting White participants. Most studies (70.2%) included fewer than 300 cancer cases in their main analysis. This scoping review identified key areas for improvement, including needs for standardized race and ethnicity reporting, more diverse study populations, and larger studies.

How COVID-19 exposed pre-existing roadblocks for cancer control in Africa: strategies, lessons and recommendations from the 2019-2020 Africa Cancer Research and Control ECHO.

Background: The COVID-19 related mitigation measures adversely affected various cancer control activities in Africa, with cancer prevention and screening activities amongst the most significantly impacted. When the COVID-19 pandemic struck, the Africa Cancer Research and Control ECHO utilised their virtual platform to share experiences and knowledge of how to continue cancer service delivery during the pandemic. This analysis describes the evolved strategies, dilemmas, and recommendations to strengthen the health systems for cancer control in Africa. Methods: Eleven 1-hour-long sessions about the then newly emerging coronavirus infection and its impact on cancer control in Africa were held from April 2020 to August 2020, using Zoom®. An average of 39 participants attended the sessions including scientists, clinicians, policymakers and global partners. Sessions were analysed thematically. Results: Most strategies to maintain cancer services during the COVID-19 pandemic centred around cancer treatment, with few strategies on maintaining cancer prevention services, early detection, palliative care and research services. The most mentioned challenge during the pandemic was fear of exposure to COVID-19 infection at the health facility during diagnosis, treatment or follow-up for cancer care. Other challenges were disruptions to service delivery, inaccessibility of cancer treatment, disruption of research activities and a lack of psychosocial support for COVID-19 related fear/anxiety. Significantly, this analysis shows that the COVID-19 related mitigation measures exacerbated existing predicaments in Africa, such as inadequate attention to cancer prevention strategies, psychosocial and palliative services and cancer research. The Africa Cancer ECHO recommends African countries to leverage the infrastructure developed in response to COVID-19 pandemic to strengthen the health system along the entire cancer control continuum. This calls for urgent action to develop and implement evidence-based frameworks and comprehensive National Cancer Control Plans that will withstand any future disruptions.

Ionising radiation and cardiovascular disease: systematic review and meta-analysis.

OBJECTIVE: To systematically review and perform a meta-analysis of radiation associated risks of cardiovascular disease in all groups exposed to radiation with individual radiation dose estimates. DESIGN: Systematic review and meta-analysis. MAIN OUTCOME MEASURES: Excess relative risk per unit dose (Gy), estimated by restricted maximum likelihood methods. DATA SOURCES: PubMed and Medline, Embase, Scopus, Web of Science Core collection databases. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Databases were searched on 6 October 2022, with no limits on date of publication or language. Animal studies and studies without an abstract were excluded. RESULTS: The meta-analysis yielded 93 relevant studies. Relative risk per Gy increased for all cardiovascular disease (excess relative risk per Gy of 0.11 (95% confidence interval 0.08 to 0.14)) and for the four major subtypes of cardiovascular disease (ischaemic heart disease, other heart disease, cerebrovascular disease, all other cardiovascular disease). However, interstudy heterogeneity was noted (P<0.05 for all endpoints except for other heart disease), possibly resulting from interstudy variation in unmeasured confounders or effect modifiers, which is markedly reduced if attention is restricted to higher quality studies or those at moderate doses (<0.5 Gy) or low dose rates (<5 mGy/h). For ischaemic heart disease and all cardiovascular disease, risks were larger per unit dose for lower dose (inverse dose effect) and for fractionated exposures (inverse dose fractionation effect). Population based excess absolute risks are estimated for a number of national populations (Canada, England and Wales, France, Germany, Japan, USA) and range from 2.33% per Gy (95% confidence interval 1.69% to 2.98%) for England and Wales to 3.66% per Gy (2.65% to 4.68%) for Germany, largely reflecting the underlying rates of cardiovascular disease mortality in these populations. Estimated risk of mortality from cardiovascular disease are generally dominated by cerebrovascular disease (around 0.94-1.26% per Gy), with the next largest contribution from ischaemic heart disease (around 0.30-1.20% per Gy). CONCLUSIONS: Results provide evidence supporting a causal association between radiation exposure and cardiovascular disease at high dose, and to a lesser extent at low dose, with some indications of differences in risk between acute and chronic exposures, which require further investigation. The observed heterogeneity complicates a causal interpretation of these findings, although this heterogeneity is much reduced if only higher quality studies or those at moderate doses or low dose rates are considered. Studies are needed to assess in more detail modifications of radiation effect by lifestyle and medical risk factors. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020202036.

Cancer in Costello syndrome: a systematic review and meta-analysis.

BACKGROUND: Costello syndrome (CS) is a cancer-predisposition disorder caused by germline pathogenic variants in HRAS. We conducted a systematic review using case reports and case series to characterise cancer risk in CS. METHODS: We conducted a systematic review to identify CS cases to create a retrospective cohort. We tested genotype-phenotype correlations and calculated cumulative incidence and hazard rates (HR) for cancer and cancer-free death, standardised incidence rates (SIR) and survival after cancer. RESULTS: This study includes 234 publications reporting 621 patients from 35 countries. Over nine percent had cancer, including rhabdomyosarcoma, bladder, and neuroblastoma. The rate of cancer and death associated with p.Gly12Ser were lower when compared to all other variants (P < 0.05). Higher mortality for p.Gly12Cys, p.Gly12Asp, p.Gly12Val and p.Gly60Val and higher malignancy rate for p.Gly12Ala were confirmed (P < 0.05). Cumulative incidence by age 20 was 13% (cancer) and 11% (cancer-free death). HR (death) was 3-4% until age 3. Statistically significant SIRs were found for rhabdomyosarcoma (SIR = 1240), bladder (SIR = 1971), and neuroblastoma (SIR = 60). Survival after cancer appeared reduced. CONCLUSIONS: This is the largest investigation of cancer in CS to date. The high incidence and SIR values found to highlight the need for rigorous surveillance and evidence-based guidelines for this high-risk population.

The influence of telehealth-based cancer rehabilitation interventions on disability: a systematic review.

PURPOSE: To characterize delivery features and explore effectiveness of telehealth-based cancer rehabilitation interventions that address disability in adult cancer survivors. METHODS: A systematic review of electronic databases (CINAHL Plus, Cochrane Library: Database of Systematic Reviews, Embase, National Health Service's Health Technology Assessment, PubMed, Scopus, Web of Science) was conducted in December 2019 and updated in April 2021. RESULTS: Searches identified 3,499 unique studies. Sixty-eight studies met inclusion criteria. There were 81 unique interventions across included studies. Interventions were primarily delivered post-treatment and lasted an average of 16.5 weeks (SD = 13.1). They were most frequently delivered using telephone calls (59%), administered delivered by nursing professionals (35%), and delivered in a one-on-one format (88%). Risk of bias of included studies was primarily moderate to high. Included studies captured 55 measures of disability. Only 54% of reported outcomes had data that allowed calculation of effect sizes ranging -3.58 to 15.66. CONCLUSIONS: The analyses suggest small effects of telehealth-based cancer interventions on disability, though the heterogeneity seen in the measurement of disability makes it hard to draw firm conclusions. Further research using more diverse samples, common measures of disability, and pragmatic study designs is needed to advance telehealth in cancer rehabilitation. IMPLICATIONS FOR CANCER SURVIVORS: Telehealth-based cancer rehabilitation interventions have the potential to increase access to care designed to reduce disability across the cancer care continuum.

Cancer incidence and surveillance strategies in individuals with RASopathies.

RASopathies are a set of clinical syndromes that have molecular and clinical overlap. Genetically, these syndromes are defined by germline pathogenic variants in RAS/MAPK pathway genes resulting in activation of this pathway. Clinically, their common molecular signature leads to comparable phenotypes, including cardiac anomalies, neurologic disorders and notably, elevated cancer risk. Cancer risk in individuals with RASopathies has been estimated from retrospective reviews and cohort studies. For example, in Costello syndrome, cancer incidence is significantly elevated over the general population, largely due to solid tumors. In some forms of Noonan syndrome, cancer risk is also elevated over the general population and is enriched for hematologic malignancies. Thus, cancer surveillance guidelines have been developed to monitor for the occurrence of such cancers in individuals with some RASopathies. These include abdominal ultrasound and urinalyses for individuals with Costello syndrome, while complete blood counts and splenic examination are recommended in Noonan syndrome. Improved cancer risk estimates and refinement of surveillance recommendations will improve the care of individuals with RASopathies.

Team-Based Care for Cancer Survivors With Comorbidities: A Systematic Review.

Coordination of quality care for the growing population of cancer survivors with comorbidities remains poorly understood, especially among health disparity populations who are more likely to have comorbidities at the time of cancer diagnosis. This systematic review synthesized the literature from 2000 to 2022 on team-based care for cancer survivors with comorbidities and assessed team-based care conceptualization, teamwork processes, and outcomes. Six databases were searched for original articles on adults with cancer and comorbidity, which defined care team composition and comparison group, and assessed clinical or teamwork processes or outcomes. We identified 1,821 articles of which 13 met the inclusion criteria. Most studies occurred during active cancer treatment and nine focused on depression management. Four studies focused on Hispanic or Black cancer survivors and one recruited rural residents. The conceptualization of team-based care varied across articles. Teamwork processes were not explicitly measured, but teamwork concepts such as communication and mental models were mentioned. Despite team-based care being a cornerstone of quality cancer care, studies that simultaneously assessed care delivery and outcomes for cancer and comorbidities were largely absent. Improving care coordination will be key to addressing disparities and promoting health equity for cancer survivors with comorbidities.

The State of Preclinical Modeling for Early Phase Cancer Trials Using Molecularly Targeted Agents with Radiation.

Preclinical studies inform and guide the development of novel treatment combination strategies that bridge the laboratory with the clinic. We aimed to evaluate approaches cancer researchers used to justify advancing new combinations of molecularly targeted agents and radiation treatment into early-phase human clinical trials. Unsolicited early phase clinical trial proposals submitted to the National Cancer Institute's Cancer Therapy Evaluation Program between January 2016 and July 2020 were curated to quantify key characteristics and proportion of preclinical data provided by trialists seeking to conduct molecularly targeted agent-radiation combination studies in cancer patients. These data elucidate the current landscape for how the rationale for a molecularly targeted agent-radiation combination therapy is supported by preclinical research and illustrate unique challenges faced in translation at the intersection of precision medicine and radiation oncology.

A bibliometric analysis of cancer research funders and collaborators in Kenya: 2007-2017.

AIM: Cancer research is essential to the development and implementation of effective control strategies and interventions. In Kenya, cancer is the third leading cause of death. Country specific research conducted by local and international investigators can inform a national plan to address local needs across the cancer care continuum. This analysis aims to provide information about the trends and types of cancer research collaborations, funding, and outputs from 2007 to 2017, to understand gaps and opportunities to strengthen Kenya-led cancer research capacity. METHODS: This analysis included 243 studies from a previously published phase 1 scoping review of oncology research conducted and published in Kenya from 2007 to 2017. The citation metadata was drawn from the Web of Science and PubMed and normalized in Microsoft Excel. Using Sci2, a series of bibliometric network analyses were conducted to identify funding patterns, collaborations between authors and institutions, and the types of cancer research conducted in Kenya. Gephi and Excel provided descriptive analyses and graphs of the network. The analyses are categorized into three themes: article production, collaboration, and research topics. RESULTS: The bibliometric analysis found 5 US-based government agencies are funding cancer research in Kenya. Kenya-Kenya institutional collaborations were most common, and half of authors with the most co-authored publications were from Kenya. The publication trend showed a gradual increase from 2011 to 2014 with a subsequent drop through 2017. CONCLUSION AND POLICY SUMMARY STATEMENT: This study identifies the funders and most often published Kenyan authors and Kenyan-based institutions publishing oncology research in Kenya. It also identifies future areas to focus research and the importance of continuing to build the writing and publishing capacity on oncology research by Kenyans.

Exposure to Outdoor Particulate Matter Air Pollution and Risk of Gastrointestinal Cancers in Adults: A Systematic Review and Meta-Analysis of Epidemiologic Evidence.

BACKGROUND: Outdoor air pollution is a known lung carcinogen, but research investigating the association between particulate matter (PM) and gastrointestinal (GI) cancers is limited. OBJECTIVES: We sought to review the epidemiologic literature on outdoor PM and GI cancers and to put the body of studies into context regarding potential for bias and overall strength of evidence. METHODS: We conducted a systematic review and meta-analysis of epidemiologic studies that evaluated the association of fine PM [PM with an aerodynamic diameter of ≤2.5µm (PM2.5)] and PM10 (aerodynamic diameter ≤10µm) with GI cancer incidence or mortality in adults. We searched five databases for original research published from 1980 to 2021 in English and summarized findings for studies employing a quantitative estimate of exposure overall and by specific GI cancer subtypes. We evaluated the risk of bias of individual studies and the overall quality and strength of the evidence according to the Navigation Guide methodology, which is tailored for environmental health research. RESULTS: Twenty studies met inclusion criteria and included participants from 14 countries; nearly all were of cohort design. All studies identified positive associations between PM exposure and risk of at least one GI cancer, although in 3 studies these relationships were not statistically significant. Three of 5 studies estimated associations with PM10 and satisfied inclusion criteria for meta-analysis, but each assessed a different GI cancer and were therefore excluded. In the random-effects meta-analysis of 13 studies, PM2.5 exposure was associated with an increased risk of GI cancer overall [risk ratio (RR)=1.12; 95% CI: 1.01, 1.24]. The most robust associations were observed for liver cancer (RR=1.31; 95% CI: 1.07, 1.56) and colorectal cancer (RR=1.35; 95% CI: 1.08, 1.62), for which all studies identified an increased risk. We rated most studies with "probably low" risk of bias and the overall body of evidence as "moderate" quality with "limited" evidence for this association. We based this determination on the generally positive, but inconsistently statistically significant, effect estimates reported across a small number of studies. CONCLUSION: We concluded there is some evidence of associations between PM2.5 and GI cancers, with the strongest evidence for liver and colorectal cancers. Although there is biologic plausibility for these relationships, studies of any one cancer site were few and there remain only a small number overall. Studies in geographic areas with high GI cancer burden, evaluation of the impact of different PM exposure assessment approaches on observed associations, and investigation of cancer subtypes and specific chemical components of PM are important areas of interest for future research. https://doi.org/10.1289/EHP9620.

Systematic Review of Functional Outcomes in Cancer Rehabilitation.

OBJECTIVE: To systematically review the evidence regarding rehabilitation interventions targeting optimal physical or cognitive function in adults with a history of cancer and describe the breadth of evidence as well as strengths and limitations across a range of functional domains. DATA SOURCES: PubMed, Cumulative Index to Nursing and Allied Health Plus, Scopus, Web of Science, and Embase. The time scope was January 2008 to April 2019. STUDY SELECTION: Prospective, controlled trials including single- and multiarm cohorts investigating rehabilitative interventions for cancer survivors at any point in the continuum of care were included, if studies included a primary functional outcome measure. Secondary data analyses and pilot/feasibility studies were excluded. Full-text review identified 362 studies for inclusion. DATA EXTRACTION: Extraction was performed by coauthor teams and quality and bias assessed using the American Academy of Neurology (AAN) Classification of Evidence Scheme (class I-IV). DATA SYNTHESIS: Studies for which the functional primary endpoint achieved significance were categorized into 9 functional areas foundational to cancer rehabilitation: (1) quality of life (109 studies), (2) activities of daily living (61 studies), (3) fatigue (59 studies), (4) functional mobility (55 studies), (5) exercise behavior (37 studies), (6) cognition (20 studies), (7) communication (10 studies), (8) sexual function (6 studies), and (9) return to work (5 studies). Most studies were categorized as class III in quality/bias. Averaging results found within each of the functional domains, 71% of studies reported statistically significant results after cancer rehabilitation intervention(s) for at least 1 functional outcome. CONCLUSIONS: These findings provide evidence supporting the efficacy of rehabilitative interventions for individuals with a cancer history. The findings should be balanced with the understanding that many studies had moderate risk of bias and/or limitations in study quality by AAN criteria. These results may provide a foundation for future work to establish clinical practice guidelines for rehabilitative interventions across cancer disease types.

BTK inhibitors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Systematic Review.

ImportanceThe Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. BTK inhibition was shown to protect against lethal influenza-induced acute lung injury in mice. Inhibiting BTK has been hypothesized to ameliorate lung injury in patients with severe coronavirus disease 2019 (COVID-19). ObjectiveTo evaluate the use of BTK inhibitors (BTKinibs) during COVID-19 and assess how they may affect patient outcomes.Evidence ReviewWe searched PubMed, Embase, and Web of Science: Core on December 30, 2020. Clinical studies with at least 5 COVID-19 patients treated with BTKinibs were included. Case reports and reviews were excluded.FindingsOne hundred twenty-five articles were identified, 6 of which met inclusion criteria. Sample size ranged from 6 to 126 patients. Patient populations included subjects hospitalized with COVID-19 (6/6) and admitted to the intensive care unit (5/6). Patient age ranged between 35 and 98 years. Four studies included patients already receiving BTKinibs for their lymphoproliferative disease, 1 for Waldenstrom's macroglobulinemia and 3 for chronic lymphocytic leukemia (CLL). The most common clinical outcomes measured were oxygen requirements (4/6) and hospitalization rate or duration (3/6). Differences in standard-of-care reflected the date of study and pre-existing conditions in the various patient cohorts. Full-dose acalabrutinib was evaluated in 2 studies, one study evaluated full-dose ibrutinib, and another study evaluated both ibrutinib and acalabrutinib. The remainder 2 studies described outcomes in CLL patients on multiple BTKinibs and other CLL-targeted treatments. Three studies showed decreased oxygen requirements in patients who started or continued BTKinibs. All three studies that evaluated hospitalization rate or duration found favorable outcomes in those on BTKinibs. Conclusions and RelevanceBTKinib use was associated with decreased oxygen requirements and decreased hospitalization rates and duration. However, randomized clinical trials are needed to validate the beneficial effects of BTKinibs for acute SARS-CoV-2 infection.

Sensory cue reactivity: Sensitization in alcohol use disorder and obesity.

Neuroimaging techniques to measure the function of the human brain such as electroencephalography (EEG), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI), are powerful tools for understanding the underlying neural circuitry associated with alcohol use disorder (AUD) and obesity. The sensory (visual, taste and smell) paradigms used in neuroimaging studies represent an ideal platform to investigate the connection between the different neural circuits subserving the reward/executive control systems in these disorders, which may offer a translational mechanism for novel intervention predictions. Thus, the current review provides an integrated summary of the recent neuroimaging studies that have applied cue-reactivity paradigms and neuromodulation strategies to explore underlying alterations in neural circuitry as well in treatment strategies in AUD and obesity. Finally, we discuss literature on mechanisms associated with increased alcohol sensitivity post-bariatric surgery (BS) which offers guidance for future research to use sensory percepts in elucidating the relation of reward signaling in AUD development post-BS.

A Panoply of Rheumatological Manifestations in Patients with GATA2 Deficiency.

PURPOSE: To characterize rheumatological manifestations of GATA2 deficiency. METHODS: Single-center, retrospective review of 157 patients with GATA2 deficiency. Disease course, laboratory results, and imaging findings were extracted. In-person rheumatological assessments were performed on selected, available patients. A literature search of four databases was conducted to identify additional cases. RESULTS: Rheumatological findings were identified in 28 patients, out of 157 cases reviewed (17.8%). Twenty-two of those patients (78.6%) reported symptom onset prior to or in conjunction with the molecular diagnosis of GATA2 deficiency. Notable rheumatological manifestations included: piezogenic pedal papules (PPP), joint hyperextensibility, early onset osteoarthritis, ankylosing spondylitis, and seronegative erosive rheumatoid arthritis. In peripheral blood of patients with rheumatological manifestations and GATA2 deficiency, CD4+ CD3+ helper T cells and naïve CD3+ CD4+ CD62L+ CD45RA+ helper T cell subpopulation fractions were significantly lower, while CD8+ cytotoxic T cell fractions were significantly higher, compared to those without rheumatological manifestations and with GATA2 deficiency. No changes in CD19, CD3, or NK populations were observed. CONCLUSION: GATA2 deficiency is associated with a broad spectrum of rheumatological disease manifestations. Low total helper T lymphocyte proportions and low naïve helper T cell proportions are associated with those most at risk of overt rheumatological manifestations. Further, PPP and joint hyperextensibility may explain some of the nonimmunologically-mediated joint problems encountered in patients with GATA2 deficiency. This catalogue suggests that rheumatological manifestations and immune dysregulation are relatively common in GATA2 deficiency.

Chemical, Biological, Radiological, Nuclear, and Explosive (CBRNE) Science and the CBRNE Science Medical Operations Science Support Expert (CMOSSE).

A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.

Allocation of scarce resources after a nuclear detonation: setting the context.

The purpose of this article is to set the context for this special issue of Disaster Medicine and Public Health Preparedness on the allocation of scarce resources in an improvised nuclear device incident. A nuclear detonation occurs when a sufficient amount of fissile material is brought suddenly together to reach critical mass and cause an explosion. Although the chance of a nuclear detonation is thought to be small, the consequences are potentially catastrophic, so planning for an effective medical response is necessary, albeit complex. A substantial nuclear detonation will result in physical effects and a great number of casualties that will require an organized medical response to save lives. With this type of incident, the demand for resources to treat casualties will far exceed what is available. To meet the goal of providing medical care (including symptomatic/palliative care) with fairness as the underlying ethical principle, planning for allocation of scarce resources among all involved sectors needs to be integrated and practiced. With thoughtful and realistic planning, the medical response in the chaotic environment may be made more effective and efficient for both victims and medical responders.