Infectious Mononucleosis-Induced Splenic Infarction: Perhaps More Common in Healthy Individuals Than Previously Thought.

Infectious mononucleosis (IM) is a clinical syndrome that presents as a triad of fever, pharyngitis, and lymphadenopathy. In most cases, it is caused by the Epstein-Barr virus (EBV), which spreads through upper respiratory secretions, particularly saliva, earning its name as the Kissing Disease. In most cases, IM is self-limiting and resolves in two to four weeks without significant sequelae following supportive care. Although rare, IM has been associated with several serious and sometimes life-threatening complications, involving almost any organ system. Splenic infarction is one rare complication of IM due to EBV infection. In the past, IM-induced splenic infarction in the setting of EBV was believed to be rare and mostly limited to patients with underlying hematologic comorbidities. However, we propose this condition to be more common and more likely to occur in individuals without significant medical history than previously suspected. We report a relatively healthy young male patient in his thirties, with no previous history of coagulopathy or complex medical conditions, who was found to have IM-induced splenic infarction.

Assessing Communication Quality in the Intensive Care Unit.

Introduction: Successful shared decision-making for critically ill intensive care unit (ICU) patients requires bidirectional communication. Through observation of ICU conversations, our study aimed to identify communication skill deficiencies in providers who care for patients in the ICU. Methods: This was an observational prospective study performed in a single urban academic medical center (671 beds) from June 2021 through August 2021. Twenty-three providers were recruited from medical and surgical ICU services (56 beds). Thirty-nine surrogate decision makers were identified. Provider skills were assessed using a customized observational tool that examined nonverbal communication, verbal communication, opening the discussion, gathering information, understanding the family's perspective, sharing information, reaching agreements on problems and plans, and providing closure. Results: Thirty-nine conversations were observed for six attending physicians, four fellow physicians, eight resident physicians, two nurse practitioners, and three physician assistants during the coronavirus 19 (COVID19) pandemic. A dedicated critical care provider engaged in 19 observed conversations; 20 discussions occurred with individuals rotating/consulting in the ICU. Communication skill did not depend on experience or area of expertise. Less than half of conversations achieved bidirectional communication proficiency. Scheduled conversations (n = 14) had significantly higher average communication scores than unscheduled encounters (n = 25). Conclusions: Superficial unidirectional communication with decision makers was commonly observed. Providers were less proficient at advanced communication skills needed for shared decision-making. We recommend that providers have more scheduled conversations, which were more productive in achieving bidirectional communication. A targeted simulation curriculum addressing these areas may improve patient, decision maker, and provider satisfaction, while promoting patient-centered care.

Emergency Department Clinician Experience with Embedded Palliative Care.

Background: While the benefits of embedding palliative care (PC) clinicians into the emergency department (ED) are now more widely appreciated, only a handful of programs have been reported in the literature. None has previously evaluated the attitudes and experiences of the multidisciplinary ED team with such an intervention. Objectives: We evaluated the experience of ED attendings, residents, nurses, social workers, and chaplains with an embedded PC clinician in the ED. Design/Subjects: We embedded PC clinicians into an urban, academic ED in the United States and surveyed 142 ED clinicians about their experiences. We analyzed survey results using descriptive analysis for closed-ended responses and thematic analyses for open-ended responses. Measurements/Results: One hundred six of 141 clinicians responded (75% response rate). Quantitative analysis found that 99% of participants found the program valuable. Benefits of embedded PC included changing patients' management or care trajectory, freeing up ED providers for other tasks, contributing to provider education, helping providers feel more supported during their shifts, and adding to providers' skill sets and confidence in practicing primary PC. Most participants reported minimal barriers to engaging with PC. The qualitative analysis identified program approval, desire for expansion/continuation of the program, and ongoing education of ED staff. Important themes for future programs include staff education, PC proactivity, importance of adapting to the needs of the ED, and education regarding PC consultation criteria. Conclusions: ED clinicians' attitudes toward embedded PC reflected overall approval, with underlying themes of providers feeling more supported during their shifts, improved resource management, the perception of better patient care, and nursing empowerment.

Trends in Breast Cancer Survival by Race-Ethnicity in Florida, 1990-2015.

BACKGROUND: This study was conducted to evaluate trends in survival, by race-ethnicity, for women diagnosed with breast cancer in Florida over a 26-year period. METHODS: This was a retrospective cohort study of women diagnosed with invasive breast cancer in Florida between 1990 and 2015. Data were obtained from the Florida Cancer Data System. Women in the study were categorized according to race (white/black) and Hispanic ethnicity (yes/no). Cumulative incidence estimates of 5- and 10-year breast cancer-related death with 95% confidence intervals (CI) were obtained by race-ethnicity, according to diagnosis year. Subdistribution hazard models were used to obtain subdistribution HRs (sHR) for the relative rate of breast cancer death accounting for competing causes. RESULTS: Breast cancer mortality decreased for all racial-ethnic groups, and racial-ethnic minorities had greater absolute and relative improvement for nearly all metrics compared with non-Hispanic white (NHW) women. However, for the most recent time period (2010-2015), black women still experienced significant survival disparities with non-Hispanic black (NHB) women, having twice the rate of 5-year [sHR = 2.04; 95% confidence interval (CI), 1.91-2.19] and 10-year (sHR = 2.02; 95% CI, 1.89-2.16) breast cancer-related death. Adjustment for covariates substantially reduced the excess rate of breast cancer-related death for black women. CONCLUSIONS: Despite efforts to improve disparities in breast cancer outcomes for underserved women in Florida, black women continue to experience significant survival disparities. IMPACT: These results highlight the need for targeted approaches to eliminate disparities in breast cancer survival for black women.

Characterization of outcomes in patients with advanced genitourinary malignancies treated with immune checkpoint inhibitors.

PURPOSE: Several immune checkpoint inhibitors (ICIs) are FDA approved for treatment of genitourinary (GU) malignancies. We aim to determine demographic and clinicopathologic characteristics that significantly affect clinical outcomes in patients with advanced stage GU malignancies treated with ICIs. MATERIALS AND METHODS: We performed a single-center, consecutive, retrospective cohort analysis on patients with metastatic or unresectable GU malignancies who were treated with ICIs at the University of Michigan. Immune-related adverse events (irAEs), putative immune-mediated allergies, and overall response rates (ORR) were assessed. Comorbidity index scores were calculated. Survival analysis was performed to evaluate progression-free survival (PFS) and overall survival (OS), stratifying and controlling for a variety of clinicopathologic baseline factors including site of metastases. RESULTS: A total of 160 patients were identified with advanced renal cell carcinoma (RCC) or urothelial carcinoma. Median PFS and OS were 5.0 and 23.6 months for RCC, and 2.8 and 9.6 months for urothelial carcinoma, respectively. Patients who experienced increased frequency and higher grade irAEs had better ICI treatment response (P < 0.0001). Presence of liver metastases was associated with poor response to ICI therapy (P = 0.001). Multivariable modeling demonstrates that patients with urothelial carcinoma and liver metastases had statistically worse PFS and OS compared to patients with RCC or other sites of metastases, respectively. CONCLUSION: Greater frequency and higher grades of irAEs are associated with better treatment response in patients with RCC and urothelial malignancy receiving ICI therapy. The presence of liver metastases denotes a negative predictive marker for immunotherapy efficacy. SUMMARY: Immune checkpoint inhibitors (ICI) are increasingly used to treat genitourinary (GU) malignancies. However, clinical data regarding patients with advanced-stage GU malignancies treated with ICI is lacking. Thus, we performed a single-center, retrospective cohort study on patients with metastatic and unresectable renal cell carcinoma (RCC) and urothelial carcinoma who were treated with ICIs at the University of Michigan to provide demographic and clinicopathologic data regarding this population. We specifically focused on immune-related adverse events (irAEs), immune-mediated allergies, and the associated overall response rates (ORR). To better assess performance status, we calculated comorbidity scores for all patients. Finally, survival analyses for progression-free survival (PFS) and overall survival (OS) were performed using Kaplan-Meier analysis and Cox proportional hazards modeling, stratifying and controlling for clinicopathologic baseline factors, including sites of metastases, in our multivariable analysis. A total of 160 patients were identified with advanced RCC or urothelial carcinoma. We found decreased PFS (2.8 vs. 5.0 months) and decreased OS (9.8 vs. 23.6 months) for urothelial carcinoma compared to RCC patients. We noted that patients who experienced increased frequency and higher grades of irAEs had better treatment ORR with ICI therapy (P ≤ 0.0001). The presence of liver metastases was associated with worse ORR (P = 0.001), PFS (P = 0.0014), and OS (P = 0.0028) compared to other sites of metastases including lymph node, lung, and CNS/bone. The poor PFS and OS associated with urothelial carcinoma and liver metastases were preserved in our multivariable modeling after controlling for pertinent clinical factors. We conclude that greater frequency and higher grades of irAEs are associated with better treatment response in GU malignancy patients receiving ICI, a finding that is consistent with published studies in other cancers. The presence of liver metastases represents a significantly poor predictive marker in GU malignancy treated with ICI. Our findings contribute to the growing body of literature that seeks to understand the clinicopathologic variables and outcomes associated with ICI therapy.

Association of SPOP Mutations with Outcomes in Men with De Novo Metastatic Castration-sensitive Prostate Cancer.

Recently, mutations in speckle-type pox virus and zinc finger protein (SPOP) gene (mutant SPOP [mtSPOP]) have been associated with improved outcomes to abiraterone in the castration-resistant setting. We hypothesized that mtSPOP would be associated with improved outcomes to systemic therapy in men with de novo metastatic castration-sensitive prostate cancer (d-mCSPC). Retrospective data of newly diagnosed d-mCSPC patients were collected from four institutions. Eligibility criteria included standard androgen deprivation therapy without intensification, and SPOP mutational status (mtSPOP or wild-type SPOP [wtSPOP]) determination by targeted next-generation sequencing from tumor biopsies. A total of 121 men (25 mtSPOP [21%] and 96 wtSPOP [79%]) were included. After adjusting for covariates, mtSPOP was significantly associated with better median progression-free survival (35 vs 13 mo; adjusted hazard ratio [HR] 0.47; p = 0.016) and overall survival (97 vs 69 mo; adjusted HR 0.32; p = 0.027), with similar HR and p value on the univariate analysis. These findings, upon external validation, may assist with counseling and prognostication in the clinic, and inform the design of future clinical trials in this setting. PATIENT SUMMARY: : Presence of tumor mutation in speckle-type pox virus and zinc finger protein (SPOP) gene was associated with improved survival outcomes in men with de novo metastatic castration-sensitive prostate cancer receiving standard androgen deprivation therapy.

Mismatch repair deficiency in metastatic prostate cancer: Response to PD-1 blockade and standard therapies.

BACKGROUND: While response rates to anti-PD1 therapy are low in unselected metastatic castration resistant prostate cancer (mCRPC) patients, those with inactivating mutations in mismatch repair (MMR) genes (i.e. MMR deficiency; MMRd) or microsatellite instability (MSI) are thought likely to respond favorably. To date, there is limited published data on this biologically distinct and clinically relevant subgroup's natural history and response to treatment. METHODS: We retrospectively identified patients at two academic institutions who had MMRd/MSI-high metastatic prostate cancer (PC). Clinical and pathologic characteristics at the time of diagnosis as well as response to standard therapies and immune checkpoint therapy were abstracted. Descriptive statistics, including PSA50 response (≥50% decline in PSA from baseline) and clinical/radiographic progression free survival (PFS), are reported. RESULTS: 27 men with MMRd and/or MSI-high metastatic PC were identified. 13 (48%) men had M1 disease at diagnosis and 19 of 24 (79%) men that underwent prostate biopsy had a Gleason score ≥8. Median overall survival from time of metastasis was not reached (95% CI: 33.6-NR mos) after a median follow up of 33.6 mos (95% CI: 23.8-50.5 mos). Seventeen men received pembrolizumab, of which 15 had PSA response data available. PSA50 responses to pembrolizumab occurred in 8 (53%) men. Median PFS was not reached (95% CI: 1.87-NR mos) and the estimated PFS at 6 months was 64.1% (95% CI: 33.7%-83.4%). Of those who achieved a PSA50 response, 7 (87.5%) remain on treatment without evidence of progression at a median follow up of 12 months (range 3-20 months). CONCLUSIONS: MMRd PC is associated with high Gleason score and advanced disease at presentation. Response rates to standard therapies are comparable to those reported in unselected patients and response rate to checkpoint blockade is high. Our study is limited by small sample size, and more research is needed to identify additional factors that may predict response to immunotherapy.

Coprophagic Asphyxiation in an Intellectually Disabled Woman.

The ingestion of one's own feces is referred to as coprophagia. In this report, the author discusses a case of coprophagia-associated death in a 36-year-old woman. The woman had a history of intellectual disability, bipolar disorder, and schizoaffective disorder and was living in a group home. At autopsy, examination of the upper airway revealed 4 distinct spherical boli of impacted fecal matter in the oral cavity and pharynx. Death was attributed to asphyxia due to aspiration of stool bolus during an episode of coprophagia. This is now the second reported case of coprophagic-related death, illustrating the need for careful monitoring of eating activities in individuals with mental disorders.

Virus Innexins induce alterations in insect cell and tissue function.

Polydnaviruses are dsDNA viruses that induce immune and developmental alterations in their caterpillar hosts. Characterization of polydnavirus gene families and family members is necessary to understand mechanisms of pathology and evolution of these viruses, and may aid to elucidate the role of host homologues if present. For example, the polydnavirus vinnexin gene family encodes homologues of insect gap junction genes (innexins) that are expressed in host immune cells (hemocytes). While the roles of Innexin proteins and gap junctions in insect immunity are largely unclear, we previously demonstrated that Vinnexins form functional gap junctions and alter the junctional characteristics of a host Innexin when co-expressed in paired Xenopus oocytes. Here, we test the effect of ectopic vinnexin expression on host cell physiology using both a lepidopteran cell culture model and a dipteran whole organism model. Vinnexin expression in the cell culture system resulted in gene-specific alterations in cell morphology and a slight, but non-statistically significant, reduction in gap junction activity as measured by dye transfer, while ectopic expression of a lepidopteran innexin2 gene led to morphological alterations and increase in gap junction activity. Global ectopic expression in the model dipteran, Drosophila melanogaster, of one vinnexin (vinnexinG) or D. melanogaster innexin2 (Dm-inx2) resulted in embryonic lethality, while expression of the other vinnexin genes had no effect. Furthermore, ectopic expression of vinnexinG, but not other vinnexin genes or Dm-inx2, in D. melanogaster larval gut resulted in developmental arrest in the pupal stage. These data indicate the vinnexins likely have gene-specific roles in host manipulation. They also support the use of Drosophila in further analysis of the role of Vinnexins and other polydnavirus genes in modifying host physiological processes. Finally, our findings suggest the vinnexin genes may be useful to perturb and characterize the physiological functions of insect Innexins.

Consecutive alkene cross-metathesis/oxonium ylide formation-rearrangement: synthesis of the anti-HIV agent hyperolactone C.

Alpha-diazo-beta-ketoesters bearing allylic ether functionality undergo highly stereoselective Ru-carbene-catalyzed alkene cross-metathesis followed by Rh(2)(OAc)(4)-catalyzed oxonium ylide formation/[2,3] sigmatropic rearrangement in a one-flask operation and in a highly diastereoselective manner. The methodology has been demonstrated in a concise synthesis of the anti-HIV agent hyperolactone C.

Hostility, interpersonal interactions, and ambulatory blood pressure.

OBJECTIVE: This study examined aspects of the transactional model of hostility and health by investigating relationships among hostility, interpersonal interactions, and ambulatory blood pressure in a healthy community sample. MATERIALS AND METHODS: Participants included 65 female and 39 male healthy adults between the ages of 18 and 46 years. Ambulatory blood pressure (ABP) and diary data on mood and social interactions were obtained every 20 minutes for 1 day. Mixed models regression analyses were used to evaluate the relationships among hostility, interpersonal interactions, and ABP. RESULTS: Trait hostility was positively associated with the frequency and intensity of negative interactions and was negatively associated with the frequency and intensity of positive interactions. Interacting with others was associated with increases in systolic blood pressure (SBP) and diastolic blood pressure (DBP). The magnitude of the increase in blood pressure was positively associated with the degree to which the interaction was perceived as negative. Hostility was not directly associated with ABP/heart rate (HR) or ABP/HR responses during any interactions or negative interactions. However, there was an interaction between hostility and negative interaction intensity for DBP, suggesting that hostility moderates the effects of negative interactions on DBP. Specifically, increases in the intensity of negative interactions were associated with increases in DBP for participants with high, but not low, hostility. CONCLUSIONS: The results provide partial support for the notion that hostility may be associated with risk for cardiovascular disease through its effects on interpersonal interactions and their cardiovascular correlates.