Arthritis Post-Immunotherapy for Endometrial Cancer: a case report and review of literature on the acute onset of inflammatory arthritis following PD-I inhibitor therapy in a patient with recurrent endometrial cancer

Since gaining FDA approval in 2014, pembrolizumab, a PD-1 immune checkpoint inhibitor, has been utilized in the management of cancers that progress following first-line therapy.While the pathological response to pembrolizumab is favorable, immune related adverse events (irAEs) can be elicited and require prompt diagnosis and management based on grading and severity, which can include discontinuation of immunotherapy.Our case concerns a 66-year-old female with recurrent endometrial cancer who was treated with pembrolizumab, and developed inflammatory arthritis following therapy. We provide a succinct review of the pathogenesis and risk factors associated with irAEs, as well as diagnosis and management strategies

Plasticity and regeneration of gonads in the annelid Pristina leidyi

International audienceGonads are specialized gamete-producing structures that, despite their functional importance, are generated by diverse mechanisms across groups of animals and can be among the most plastic organs of the body. Annelids, the segmented worms, are a group in which gonads have been documented to be plastic and to be able to regenerate, but little is known about what factors influence gonad development or how these structures regenerate. In this study, we aimed to identify factors that influence the presence and size of gonads and to investigate gonad regeneration in the small asexually reproducing annelid, Pristina leidyi.We found that gonad presence and size in asexual adult P. leidyi are highly variable across individuals and identified several factors that influence these structures. An extrinsic factor, food availability, and two intrinsic factors, individual age and parental age, strongly influence the presence and size of gonads in P. leidyi. We also found that following head amputation in this species, gonads can develop by morphallactic regeneration in previously non-gonadal segments. We also identified a sexually mature individual from our laboratory culture that demonstrates that, although our laboratory strain reproduces only asexually, it retains the potential to become fully sexual.Our findings demonstrate that gonads in P. leidyi display high phenotypic plasticity and flexibility with respect to their presence, their size, and the segments in which they can form. Considering our findings along with relevant data from other species, we find that, as a group, clitellate annelids can form gonads in at least four different contexts: post-starvation refeeding, fission, morphallactic regeneration, and epimorphic regeneration. This group is thus particularly useful for investigating the mechanisms involved in gonad formation and the evolution of post-embryonic phenotypic plasticity

Indigenous Cultural Identity Protects Against Intergenerational Transmission of ACEs Among Indigenous Caregivers and Their Children

A large body of empirical research has demonstrated that caregiver adverse childhood experiences (ACEs) predict ACEs in one’s child, a phenomenon known as the intergenerational transmission of ACEs. Little of this empirical research, however, has focused specifically on Indigenous peoples despite a growing body of theoretical literature and the wisdom of Elders and Traditional Knowledge Keepers that speaks to the presence of this phenomenon within Indigenous communities as well as the protective role of Indigenous cultural identity in preventing the intergenerational transmission of ACEs. The purpose of the current study was to conduct an empirical evaluation of this hypothesis, specifically that Indigenous cultural identity and social support protects against the intergenerational transmission of ACEs among Indigenous peoples and their children in the USA. Participants were 106 Indigenous women caregivers of children ages 10 to 14 in South Dakota who completed surveys. Results showed that Indigenous cultural identity moderated the association between caregiver ACEs and child ACEs. At high levels of cultural identity, there was no association between caregiver ACEs and child ACEs. At low levels of Indigenous cultural identity, however, there was a strong and positive relationship between caregiver ACEs and child ACEs. Social support did not moderate the association between caregiver ACEs and child ACEs. These findings underscore the need for initiatives that enhance Indigenous cultural identity and social support among Indigenous caregivers to prevent the intergenerational transmission of ACEs

Rates and Correlates of Intimate Partner Abuse Among Indigenous Women Caregivers

Intimate partner abuse (IPA) is a public health crisis that disproportionately impacts indigenous women. We know little about rates and correlates of IPA victimization (IPAV) and abuse directed at one’s partner (ADP) among indigenous women caregivers (people who take care of children). The purpose of the current study was to address this critical gap in the literature. Participants were 44 indigenous women caregivers in the United States in a current relationship who completed a survey. Most women reported IPAV and ADP experiences in the past 6 months, and IPAV and ADP abuse directed at partner were positively associated. Further, IPAV was positively associated with adverse childhood experiences (ACEs), participants’ engagement in harsh parenting, and depressive symptoms. IPAV was negatively associated with age, income, indigenous cultural identity, and social support. ADP was positively associated with ACEs, harsh parenting, and depressive symptoms. ADP was negatively associated with age and income. ADP was not associated with indigenous cultural identity and social support. These data suggest the urgency with which efforts are needed to prevent and respond to IPA among indigenous women caregivers, especially those who are younger and of lower income, and that culturally grounded initiatives that seek to build social support may be especially impactful

Delays in Appropriate Antibiotic Therapy for Gram-Negative Bloodstream Infections: A Multicenter, Community Hospital Study

BackgroundGram-negative bacterial bloodstream infection (BSI) is a serious condition with estimated 30% mortality. Clinical outcomes for patients with severe infections improve when antibiotics are appropriately chosen and given early. The objective of this study was to estimate the association of prior healthcare exposure on time to appropriate antibiotic therapy in patients with gram-negative BSI.MethodWe performed a multicenter cohort study of adult, hospitalized patients with gram-negative BSI using time to event analysis in nine community hospitals from 2003-2006. Event time was defined as the first administration of an antibiotic with in vitro activity against the infecting organism. Healthcare exposure status was categorized as community-acquired, healthcare-associated, or hospital-acquired. Time to appropriate therapy among groups of patients with differing healthcare exposure status was assessed using Kaplan-Meier analyses and multivariate Cox proportional hazards models.ResultsThe cohort included 578 patients with gram-negative BSI, including 320 (55%) healthcare-associated, 217 (38%) community-acquired, and 41 (7%) hospital-acquired infections. 529 (92%) patients received an appropriate antibiotic during their hospitalization. Time to appropriate therapy was significantly different among the groups of healthcare exposure status (log-rank p=0.02). Time to first antibiotic administration regardless of drug appropriateness was not different between groups (p=0.3). The unadjusted hazard ratios (HR) (95% confidence interval) were 0.80 (0.65-0.98) for healthcare-associated and 0.72 (0.63-0.82) for hospital-acquired, relative to patients with community-acquired BSI. In multivariable analysis, interaction was found between the main effect and baseline Charlson comorbidity index. When Charlson index was 3, adjusted HRs were 0.66 (0.48-0.92) for healthcare-associated and 0.57 (0.44-0.75) for hospital-acquired, relative to patients with community-acquired infections.ConclusionsPatients with healthcare-associated or hospital-acquired BSI experienced delays in receipt of appropriate antibiotics for gram-negative BSI compared to patients with community-acquired BSI. This difference was not due to delayed initiation of antibiotic therapy, but due to the inappropriate choice of antibiotic

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

The molecular characteristics of colonic neoplasms in serrated polyposis: a systematic review and meta-analysis

Serrated polyposis is a rare disorder characterised by the presence of multiple serrated polyps in the large intestine, and an increased personal and familial risk of colorectal cancer. Knowledge of the molecular characteristics of colonic lesions which develop in this syndrome is fragmented, making it difficult to understand the underlying genetic basis of this condition. We conducted a systematic review and meta-analysis of all studies which evaluated the molecular characteristics of colorectal neoplasms found in individuals with serrated polyposis. We identified 4561 potentially relevant studies, but due to a lack of consensus in the reporting of findings, only fourteen studies were able to be included in the meta-analysis. BRAF mutation was found in 73% (95% CI 65–80%) of serrated polyps, 0% (95% CI 0–3%) of conventional adenomas and 49% (95%CI 33–64%) of colorectal cancers. In contrast, KRAS mutation was present in 8% (95% CI 5–11%) of serrated polyps, 3% (95% CI 0–13%) of conventional adenomas and 6% (95% CI 0–13%) of colorectal cancers. Absence of MLH1 immunostaining was found in 3% (95% CI 0–10%) of serrated polyps and 53% (95% CI 36–71%) of colorectal cancers. Overall, microsatellite instability was found in 40% (95% CI 18–64%) of colorectal cancers arising in the setting of serrated polyposis. Our results indicate that diverse molecular pathways are likely to contribute to the increased predisposition for colorectal cancer in individuals with serrated polyposis. We also propose a set of minimum standards for the reporting of future research in serrated polyposis as this is a rare syndrome and collation of research findings from different centres will be essential to identify the molecular mechanisms involved in the pathogenesis of this condition

Syndromic Surveillance for Emerging Infections in Office Practice Using Billing Data

PURPOSE We wanted to evaluate the feasibility of conducting syndromic surveillance in a primary care office using billing data. METHODS A 1-year study was conducted in a primary care practice; comparison data were obtained from emergency department records of visits by county residents. Within the practice, a computer program converted billing data into de-identified daily summaries of International Classification of Diseases, Ninth Revision (ICD-9) codes by sex and age-group; and a staff member generated daily summaries and e-mailed them to the analysis team. For both the practice and the emergency departments, infection-related syndromes and practice-specific thresholds were calculated using the category 1 syndrome codes and an analyitical method based upon the Early Aberration Reporting System of the Centers for Disease Control and Prevention. RESULTS A mean of 253 ICD-9 codes per day was reported. The most frequently recorded syndromes were respiratory illness, gastrointestinal illness, and fever. Syndromes most commonly exceeding the threshold of 2 standard deviations for the practice were lymphadenitis, rash, and fever. Generating a daily summary took 1 to 2 minutes; the program was written by the software vendor for a fee of $1,500. During the 2003–2004 influenza season, trend line patterns of the emergency department visits reflected a pattern consistent with that of the state, whereas the trend line in primary case practice cases was less consistent, reflecting the variation expected in data from a single clinic. Still, spikes of activity that occurred in the practice before the emergency department suggest the practice may have seen patients with influenza earlier. CONCLUSIONS This preliminary study showed the feasibility of implementing syndromic surveillance in an office setting at a low cost and with minimal staff effort. Although many implementation issues remain, further development of syndromic surveillance systems should include primary care offices