Nirmatrelvir-Ritonavir for Acute COVID-19 in Patients With Cardiovascular Disease and Postacute Sequelae of SARS-CoV-2 Infection.

Background: There is limited evidence of association of nirmatrelvir-ritonavir (NMV-r) and incidence of postacute sequelae of SARS-CoV-2 infection (PASC) in patients with pre-existing cardiovascular disease (CVD). Objectives: The objective of this study was to assess the association of NMV-r in nonhospitalized, vaccinated patients with pre-existing CVD and occurrence of PASC. Methods: We conducted a retrospective cohort study utilizing the TriNetX research network, including vaccinated patients with pre-existing CVD who developed COVID-19 between December 2021 and December 2022. Two cohorts were created based on NMV-r administration within 5 days of diagnosis: NMV-r and non-NMV-r cohort. The main outcome was presence of PASC, assessed between 30 to 90 days and 90 to 180 days after index COVID-19 infection. After propensity score matching, both cohorts were compared using t-test and chi-square test for continuous and categorical variables, respectively. Results: A total of 26,953 patients remained in each cohort after propensity score matching. Broadly defined PASC occurred in 6,925 patients (26%) in the NMV-r cohort vs 8,150 patients (30.6%) in the non-NMV-r cohort (OR: 0.80; 95% CI: 0.76-0.82; P < 0.001) from 30 to 90 days and in 6,692 patients (25.1%) as compared to 8,910 patients (33.5%) (OR: 0.25, 95% CI: 0.23-0.29; P < 0.001) from 90 to 180 days. Similarly, narrowly defined PASC occurred in 5,335 patients (20%) in the NMV-r cohort vs 6,271 patients (23.6%) in the non-NMV-r cohort between 30 and 90 days (OR: 0.81, 95% CI: 0.78-0.84, P < 0.001) and in 5,121 patients (19.2%) as compared to 6,964 patients (26.1%) (OR: 0.67, 95% CI: 0.64-0.70, P < 0.001) between 90 and 180 days. Conclusions: NMV-r in nonhospitalized vaccinated patients with pre-existing CVD with COVID-19 was associated with a reduction in PASC and health care utilization.

The Geriatric Patient One Year After Trauma: Palliative Performance Scale Predicts Functional Outcomes.

INTRODUCTION: Frailty in trauma has been found to predict poor outcomes after injury including additional in-hospital complications, mortality, and discharge to dependent care. These gross outcome measures are insufficient when discussing long-term recovery as they do not address what is important to patients including functional status and quality of life. The purpose of this study is to determine if the Palliative Performance Scale (PPS) predicts mortality and functional status one year after trauma in geriatric patients. MATERIAL AND METHODS: Prospective observational study of trauma survivors, age ≥55 years. Patients were stratified by pre-injury PPS high (>70) or low (≤70). Outcomes were functional status at 1 year measured by Glasgow Outcome Scale Extended (GOSE), Euroqol-5D and SF-36. Adjusted relative risks (aRR) were obtained using modified Poisson regression. RESULTS: Follow-up was achieved on 215/301 patients. Mortality was 30% in low PPS group vs 8% in the high PPS group (P<0.001). A greater percentage of patients in the high group had a good functional outcome at one year compared to patients in the low group (78% vs 30% p<0.001). The high PPS patients were more likely to have improvement of GOSE at 1 year from discharge compared to low group (66% vs 27% P<0.001). Low PPS independently predicted poor functional outcome (aRR, 2.64; 95% confidence interval, 1.79-3.89) and death at 1 year (aRR, 3.64; 95% confidence interval 1.68-7.92). An increased percentage of low PPS patients reported difficulty with mobility (91% vs 46% p<0.0001) and usual activities (82% vs 56% p=0.002). Both groups reported pain (65%) and anxiety/depression (47%). CONCLUSION: Low pre-Injury PPS predicts mortality and poor functional outcomes one year after trauma. Low PPS patients were more likely to decline, rather than improve. Regardless of PPS, most patients have persistent pain, anxiety, and limitations in performing daily activities.

Finding New Meaning in the Practice of Medicine: A Quality Improvement Project Evaluating the Remote Communication Liaison Program During the Initial COVID Pandemic Surge.

Background: In spring 2020, the COVID-19 pandemic overwhelmed intensive care teams with severely ill patients. Even at the end of life, families were barred from hospitals, relying solely on remote communication. A Remote Communication Liaison Program (RCLP) was established to ensure daily communication for families, while supporting overstretched intensivists. Objectives: To evaluate the effectiveness and impact of the RCLP on participating liaisons and intensivists. Design: Two quality improvement surveys were developed and administered electronically. Setting/Subjects: Based in the United States, all liaisons and intensivists who participated in this program were invited to take the surveys. Measurements: Descriptive statistics were used to analyze the quantitative Likert-scale data, and qualitative analysis was used to assess themes. Results: Among respondents, all (100%) liaisons and more than 90% of intensivists agreed or strongly agreed that the RCLP provided a valuable service to families. More than 70% of intensivists agreed or strongly agreed that the program lessened their workload. More than 90% of liaisons agreed or strongly agreed that participation in the program improved their confidence and skills in end-of-life decision making, difficult conversations, and comprehension of critical care charts. Themes elicited from the liaisons revealed that participation fostered a renewed sense of purpose as physicians, meaningful connection, and opportunities for growth. Conclusions: RCLP successfully trained and deployed liaisons to rapidly develop skills in communication with beleaguered families during COVID-19 surge. Participation in the program had a profound effect on liaisons, who experienced a renewed sense of meaning and connection to the practice of medicine.

Is There a Role for Rib Plating in Thoracic Trauma?

Rib fractures are a morbid consequence of blunt trauma and are associated with a highly variable clinical presentation ranging from nondisplaced rib fractures causing limited, manageable pain to severely displaced rib fractures with concomitant thoracic injuries leading to respiratory failure. Due to an evolution of techniques, hardware technology, and general acceptance, rib plating has increased substantially at trauma centers all throughout the United States over the past decade. This article aims to review the most recent and current reports for rib plating with respect to indications, preoperative evaluation and imaging, approaches, timing for intervention, outcomes in patients with flail chest and nonflail injuries, and the management of complications. From these data, it becomes clear that the surgical stabilization of rib fractures (SSRF) has a firm place in the management of thoracic trauma.

An International Comparison of Presentation, Outcomes and CORONET Predictive Score Performance in Patients with Cancer Presenting with COVID-19 across Different Pandemic Waves.

Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic. We examined differences in features at presentation and outcomes in patients worldwide, depending on the waves of the pandemic: wave 1 D614G (n = 1430), wave 2 Alpha (n = 475), and wave 4 Omicron variant (n = 63, UK and Spain only). The performance of CORONET was evaluated on 258, 48, and 54 patients for each wave, respectively. We found that mortality rates were reduced in subsequent waves. The majority of patients were vaccinated in wave 4, and 94% were treated with steroids if they required oxygen. The stages of cancer and the median ages of patients significantly differed, but features associated with worse COVID-19 outcomes remained predictive and did not differ between waves. The CORONET tool performed well in all waves, with scores in an area under the curve (AUC) of >0.72. We concluded that patients with cancer who present to hospital with COVID-19 have similar features of severity, which remain discriminatory despite differences in variants and vaccination status. Survival improved following the first wave of the pandemic, which may be associated with vaccination and the increased steroid use in those patients requiring oxygen. The CORONET model demonstrated good performance, independent of the SARS-CoV-2 variants.

Assessment of a Crisis Standards of Care Scoring System for Resource Prioritization and Estimated Excess Mortality by Race, Ethnicity, and Socially Vulnerable Area During a Regional Surge in COVID-19.

Importance: Crisis standards of care (CSOC) scores designed to allocate scarce resources during the COVID-19 pandemic could exacerbate racial disparities in health care. Objective: To analyze the association of a CSOC scoring system with resource prioritization and estimated excess mortality by race, ethnicity, and residence in a socially vulnerable area. Design, Setting, and Participants: This retrospective cohort analysis included adult patients in the intensive care unit during a regional COVID-19 surge from April 13 to May 22, 2020, at 6 hospitals in a health care network in greater Boston, Massachusetts. Participants were scored by acute severity of illness using the Sequential Organ Failure Assessment score and chronic severity of illness using comorbidity and life expectancy scores, and only participants with complete scores were included. The score was ordinal, with cutoff points suggested by the Massachusetts guidelines. Exposures: Race, ethnicity, Social Vulnerability Index. Main Outcomes and Measures: The primary outcome was proportion of patients in the lowest priority score category stratified by self-reported race. Secondary outcomes were discrimination and calibration of the score overall and by race, ethnicity, and neighborhood Social Vulnerability Index. Projected excess deaths were modeled by race, using the priority scoring system and a random lottery. Results: Of 608 patients in the intensive care unit during the study period, 498 had complete data and were included in the analysis; this population had a median (IQR) age of 67 (56-75) years, 191 (38.4%) female participants, 79 (15.9%) Black participants, and 225 patients (45.7%) with COVID-19. The area under the receiver operating characteristic curve for the priority score was 0.79 and was similar across racial groups. Black patients were more likely than others to be in the lowest priority group (12 [15.2%] vs 34 [8.1%]; P = .046). In an exploratory simulation model using the score for ventilator allocation, with only those in the highest priority group receiving ventilators, there were 43.9% excess deaths among Black patients (18 of 41 patients) and 28.6% (58 of 203 patients among all others (P = .05); when the highest and intermediate priority groups received ventilators, there were 4.9% (2 of 41 patients) excess deaths among Black patients and 3.0% (6 of 203) among all others (P = .53). A random lottery resulted in more excess deaths than the score. Conclusions and Relevance: In this study, a CSOC priority score resulted in lower prioritization of Black patients to receive scarce resources. A model using a random lottery resulted in more estimated excess deaths overall without improving equity by race. CSOC policies must be evaluated for their potential association with racial disparities in health care.

Expressions of conflict following postoperative complications in older adults having major surgery.

BACKGROUND: After serious postoperative complications, patients and families may experience conflict about goals of care. METHODS: We performed a multisite randomized clinical trial to test the effect of a question prompt list on postoperative conflict. We interviewed family members and patients age ≥60 who experienced serious complications. We used qualitative content analysis to analyze conflict and characterize patient experiences with complications. RESULTS: Fifty-six of 446 patients suffered a serious complication. Participants generally did not report conflict relating to postoperative treatments and expressed support for the care they received. We did not appreciate a difference in conflict between intervention and usual care. Respondents reported feeling unprepared for complications, witnessing heated interactions among team members, and a failure to develop trust for their surgeon preoperatively. CONCLUSION: Postoperative conflict following serious complications is well described but its incidence may be low. Nonetheless, patient and family observations reveal opportunities for improvement.

Frequency of Preoperative Advance Care Planning for Older Adults Undergoing High-risk Surgery: A Secondary Analysis of a Randomized Clinical Trial.

Importance: For patients facing major surgery, surgeons believe preoperative advance care planning (ACP) is valuable and routinely performed. How often preoperative ACP occurs is unknown. Objective: To quantify the frequency of preoperative ACP discussion and documentation for older adults undergoing major surgery. Design, Setting, and Participants: This secondary analysis of data from a multisite randomized clinical trial testing the effects of a question prompt list intervention on preoperative communication for older adults considering major surgery was performed at 5 US academic medical centers. Participants included surgeons who routinely perform high-risk surgery and patients 60 years or older with at least 1 comorbidity and an oncological or vascular (cardiac, peripheral, or neurovascular) problem. Data were collected from June 1, 2016, to November 30, 2018. Interventions: Patients received a question prompt list brochure with 11 questions that they might ask their surgeon. Main Outcomes and Measures: For patients who had major surgery, any statement related to ACP from the surgeon, patient, or family member during the audiorecorded preoperative consultation was counted. The presence of a written advance directive (AD) in the medical record at the time of the initial consultation or added preoperatively was recorded. Open-ended interviews with patients who experienced postoperative complications and family members were conducted. Results: Among preoperative consultations with 213 patients (122 men [57%]; mean [SD] age, 72 [7] years), only 13 conversations had any discussion of ACP. In this cohort of older patients with at least 1 comorbid condition, 141 (66%) did not have an AD on file before major surgery; there was no significant association between the presence of an AD and patient age (60-69 years, 26 [31%]; 70-79 years, 31 [33%]; ≥80 years, 15 [42%]; P = .55), number of comorbidities (1, 35 [32%]; 2, 18 [33%]; ≥3, 19 [40%]; P = .62), or type of procedure (oncological, 53 [32%]; vascular, 19 [42%]; P = .22). There was no difference in preoperative communication about ACP or documentation of an AD for patients who were mailed a question prompt list brochure (intervention, 38 [35%]; usual care, 34 [33%]; P = .77). Patients with complications were enthusiastic about ACP but did not think it was important to discuss their preferences for life-sustaining treatments with their surgeon preoperatively. Conclusions and Relevance: Although surgeons believe that preoperative discussion of patient preferences for postoperative life-sustaining treatments is important, these preferences are infrequently explored, addressed, or documented preoperatively. Trial Registration: ClinicalTrials.gov Identifier: NCT02623335.

Teaching Residents Communication Skills around Death and Dying in the Trauma Bay.

AbstractBackground: Traumatic events are sudden, unexpected, and often devastating. The delivery of difficult news to patients and families in the trauma setting has unique challenges that necessitate communication skills that may differ from those used in other clinical environments. Objective: Design and implement a novel curriculum to teach, assess, and provide feedback to trauma residents on the communication skills necessary for delivering difficult news to patients and families in the trauma setting. Methods: This communication curriculum was delivered in three separate phases: (1) didactics using a video education e-module, (2) simulated practice of trauma resuscitation with a high-fidelity mannequin followed by role play of delivering difficult news, (3) an observed skills assessment using standardized patients (SPs). Each phase focused on delivery of difficult news of death and of uncertain/poor prognosis after a resuscitation in the trauma bay. Learners were trauma residents that included postgraduate year (PGY) 1-2 general surgery residents and PGY 1-4 emergency medicine residents at a level 1 trauma center. Outcomes include resident comfort, knowledge, and confidence in delivering difficult news in the trauma setting. Results: Thirty-nine trauma residents participated in the three-phase curriculum. There was an increase in the mean scores of resident-reported comfort, knowledge, and confidence in delivering difficult news for the seriously injured. SPs rated 78% of residents as competent to perform delivery of difficult news in the trauma bay independently. Conclusions: A curriculum to teach and assess trauma residents in the skills necessary to deliver difficult news in the trauma setting is both feasible and effective.

Development of a Novel Communication Liaison Program to Support COVID-19 Patients and Their Families.

In the spring of 2020, our hospital faced a surge of critically ill coronavirus disease 2019 patients, with intensive care unit (ICU) occupancy peaking at 204% of the baseline maximum capacity. In anticipation of this surge, we developed a remote communication liaison program to help the ICU and palliative care teams support families of critically ill patients. In just nine days from inception until implementation, we recruited and prepared ambulatory specialty providers to serve in this role effectively, despite minimal prior critical care experience. We report here the primary elements needed to reproduce and scale this program in other hospitals facing similar ICU surges, including a checklist for replication (Appendix I). Keys to success include strong logistical support, clinical reference material designed for rapid evolution, and a liaison team structure with peer coaching.

Outcomes of COVID-19 in Patients With a History of Cancer and Comorbid Cardiovascular Disease.

BACKGROUND: Cancer and cardiovascular disease (CVD) are independently associated with adverse outcomes in patients with COVID-19. However, outcomes in patients with COVID-19 with both cancer and comorbid CVD are unknown. METHODS: This retrospective study included 2,476 patients who tested positive for SARS-CoV-2 at 4 Massachusetts hospitals between March 11 and May 21, 2020. Patients were stratified by a history of either cancer (n=195) or CVD (n=414) and subsequently by the presence of both cancer and CVD (n=82). We compared outcomes between patients with and without cancer and patients with both cancer and CVD compared with patients with either condition alone. The primary endpoint was COVID-19-associated severe disease, defined as a composite of the need for mechanical ventilation, shock, or death. Secondary endpoints included death, shock, need for mechanical ventilation, need for supplemental oxygen, arrhythmia, venous thromboembolism, encephalopathy, abnormal troponin level, and length of stay. RESULTS: Multivariable analysis identified cancer as an independent predictor of COVID-19-associated severe disease among all infected patients. Patients with cancer were more likely to develop COVID-19-associated severe disease than were those without cancer (hazard ratio [HR], 2.02; 95% CI, 1.53-2.68; P<.001). Furthermore, patients with both cancer and CVD had a higher likelihood of COVID-19-associated severe disease compared with those with either cancer (HR, 1.86; 95% CI, 1.11-3.10; P=.02) or CVD (HR, 1.79; 95% CI, 1.21-2.66; P=.004) alone. Patients died more frequently if they had both cancer and CVD compared with either cancer (35% vs 17%; P=.004) or CVD (35% vs 21%; P=.009) alone. Arrhythmias and encephalopathy were also more frequent in patients with both cancer and CVD compared with those with cancer alone. CONCLUSIONS: Patients with a history of both cancer and CVD are at significantly higher risk of experiencing COVID-19-associated adverse outcomes. Aggressive public health measures are needed to mitigate the risks of COVID-19 infection in this vulnerable patient population.

Pulmonary complications in trauma patients with obstructive sleep apnea undergoing pelvic or lower limb operation.

BACKGROUND: Obstructive sleep apnea (OSA) is increasingly prevalent in the range of 2% to 24% in the US population. OSA is a well-described predictor of pulmonary complications after elective operation. Yet, data are lacking on its effect after operations for trauma. We hypothesized that OSA is an independent predictor of pulmonary complications in patients undergoing operations for traumatic pelvic/lower limb injuries (PLLI). METHODS: Nationwide Inpatient Sample (2009-2013) was queried for International Classification of Diseases, Ninth Revision, Clinical Modification codes for PLLI requiring operation. Elective admissions and those with concurrent traumatic brain injury with moderate to prolonged loss of consciousness were excluded. Outcome measures were pulmonary complications including ventilatory support, ventilator-associated pneumonia, pulmonary embolism (PE), acute respiratory distress syndrome (ARDS), and respiratory failure. Multivariable logistic regression analysis was used, adjusting for OSA, age, sex, race/ethnicity, and specific comorbidities (obesity, chronic lung disease, and pulmonary circulatory disease). P<0.01 was considered statistically significant. RESULTS: Among the 337 333 patients undergoing PLLI operation 3.0% had diagnosed OSA. Patients with OSA had more comorbidities and were more frequently discharged to facilities. Median length of stay was longer in the OSA group (5 vs 4 days, p<0.001). Pulmonary complications were more frequent in those with OSA. Multivariable logistic regression showed that OSA was an independent predictor of ventilatory support (adjusted odds ratio (aOR), 1.37; 95% CI,1.24 to 1.51), PE (aOR 1.40; 95% CI, 1.15 to 1.70), ARDS (aOR 1.36; 95% CI,1.23 to 1.52), and respiratory failure (aOR 1.90; 95% CI, 1.74 to 2.06). CONCLUSION: OSA is an independent and underappreciated predictor of pulmonary complications in those undergoing emergency surgery for PLLI. More aggressive screening and identification of OSA in trauma patients undergoing operation are necessary to provide closer perioperative monitoring and interventions to reduce pulmonary complications and improve outcomes. LEVEL OF EVIDENCE: Prognostic Level IV.

The Palliative Performance Scale predicts mortality in hospitalized patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a substantial mortality risk with increased rates in the elderly. We hypothesized that age is not sufficient, and that frailty measured by preadmission Palliative Performance Scale would be a predictor of outcomes. Improved ability to identify high-risk patients will improve clinicians' ability to provide appropriate palliative care, including engaging in shared decision-making about life-sustaining therapies. AIM: To evaluate whether preadmission Palliative Performance Scale predicts mortality in hospitalized patients with COVID-19. DESIGN: Retrospective observational cohort study of patients admitted with COVID-19. Palliative Performance Scale was calculated from the chart. Using logistic regression, Palliative Performance Scale was assessed as a predictor of mortality controlling for demographics, comorbidities, palliative care measures and socioeconomic status. SETTING/PARTICIPANTS: Patients older than 18 years of age admitted with COVID-19 to a single urban public hospital in New Jersey, USA. RESULTS: Of 443 admitted patients, we determined the Palliative Performance Scale score for 374. Overall mortality was 31% and 81% in intubated patients. In all, 36% (134) of patients had a low Palliative Performance Scale score. Compared with patients with a high score, patients with a low score were more likely to die, have do not intubate orders and be discharged to a facility. Palliative Performance Scale independently predicts mortality (odds ratio 2.89; 95% confidence interval 1.42-5.85). CONCLUSIONS: Preadmission Palliative Performance Scale independently predicts mortality in patients hospitalized with COVID-19. Improved predictors of mortality can help clinicians caring for patients with COVID-19 to discuss prognosis and provide appropriate palliative care including decisions about life-sustaining therapy.

The Center for Trauma Survivorship: Addressing the great unmet need for posttrauma center care.

BACKGROUND: Returning patients to preinjury status is the goal of a trauma system. Trauma centers (TCs) provide inpatient care, but postdischarge treatment is fragmented with clinic follow-up rates of <30%. Posttraumatic stress disorder (PTSD) and depression are common, but few patients ever obtain necessary behavioral health services. We postulated that a multidisciplinary Center for Trauma Survivorship (CTS) providing comprehensive care would meet patient's needs, improve postdischarge compliance, deliver behavioral health, and decrease unplanned emergency department (ED) visits and readmissions. METHODS: Focus groups of trauma survivors were conducted to identify issues following TC discharge. Center for Trauma Survivorship eligible patients are aged 18 to 80 years and have intensive care unit stay of >2 days or have a New Injury Severity Score of ≥16. Center for Trauma Survivorship visits were scheduled by a dedicated navigator and included physical and behavioral health care. Patients were screened for PTSD and depression. Patients screening positive were referred for behavioral health services. Patients were provided 24/7 access to the CTS team. Outcomes include compliance with appointments, mental health visits, unplanned ED visits, and readmissions in the year following discharge from the TC. RESULTS: Patients universally felt abandoned by the TC after discharge. Over 1 year, 107 patients had 386 CTS visits. Average time for each appointment was >1 hour. Center for Trauma Survivorship "no show" rate was 17%. Eighty-six percent screening positive for PTSD/depression successfully received behavioral health services. Postdischarge ED and hospital admissions were most often for infections or unrelated conditions. Emergency department utilization was significantly lower than a similarly injured group of patients 1 year before the inception of the CTS. CONCLUSION: A CTS fills the vast gaps in care following TC discharge leading to improved compliance with appointments and delivery of physical and behavioral health services. Center for Trauma Survivorship also appears to decrease ED visits in the year following discharge. To achieve optimal long-term recovery from injury, trauma care must continue long after patients leave the TC. LEVEL OF EVIDENCE: Therapeutic, Level III.

Directional X Chromosome Skewing of White Blood Cells from Subjects with Heterozygous Mosaicism for the Variant IRAK1 Haplotype.

Random X chromosome (ChrX) inactivation and consequent cellular mosaicism for the active ChrXs in white blood cells (WBCs) is unique to females and may contribute to sex-biased modulation of the innate immune response. Polymorphic differences between the two parental ChrXs may result in ChrX skewing of circulating WBCs (ChrX inactivation-ratio (XCI) > 3) driven by differences in stem cell selection and activity in the bone marrow or WBC trafficking at the periphery. Independent of the mechanism, ChrX skewing may result in genotype-phenotype discrepancies. This study aimed to develop an allele-specific assay and test its applicability in clinical samples to determine the "direction" of ChrX skewing in the variant IRAK1 haplotype, a common X-linked polymorphism with major clinical impacts. Because alternative splice variants of IRAK1 are also produced in the region surrounding the critical single-nucleotide polymorphism (SNP, rs1059703), we also tested the abundance of alternative splice variant IRAK1 transcripts. The expression of splice variants IRAK1-B and IRAK1-C was about 30 and 50% of the full-length (IRAK1-A) in WBCs from healthy subjects (n = 53). IRAK1-A, B, and C showed about 30% lower expression level in males (n = 25) than females (n = 28). By contrast, the expression levels of IRAK1-A, B, and C were not affected by the variant IRAK1 haplotype in either sex. Allele-specific primers generated WT and variant-IRAK1 amplicons with high selectivity, and on average produced about half the expression levels of each transcript in heterozygous IRAK1-mosaic females. Because injury was shown to induce de novo ChrX skewing of WBCs, we tested the directional XCI ratio changes in WBC in a sample of trauma patients heterozygous for the variant IRAK1 haplotype (n = 18). Using the allele-specific assay in combination with the DNA methylation status at the polymorphic HUMARA locus, we found that at admission, about 60% the patients presented XCI ratios skewed toward WBCs with active ChrXs carrying the variant-IRAK1 similar to healthy controls. De novo, trauma-induced XCI ratio changes showed increased extravasation of the more abundant mosaic WBC subset without reversal in the direction of ChrX skewing during the injury course.

Emergency abdominal surgery in patients presenting from skilled nursing facilities: Opportunities for palliative care.

BACKGROUND: Residents of skilled nursing facilities (SNF) with acute abdomen present with more comorbidities and frailty than community-dwelling (CD) counterparts. Outcomes in this population are poorly described. METHODS: We hypothesized that SNF patients have higher mortality and morbidity than CD patients. This retrospective review of the NSQIP database from 2011 to 2015 compared outcomes of SNF and CD patients presenting with bowel obstruction, ischemia and perforation. Primary outcomes were in-hospital and 30-day mortality and failure-to-rescue (FTR). RESULTS: 18,326 patients met inclusion criteria. 904 (5%) presented from SNF. In-hospital (26% vs 10%) and 30-day mortality (33% vs 26%) was higher in SNF patients (p < 0.001). The FTR rate was 34% for SNF patients and 20% for CD patients (p < 0.001). CONCLUSIONS: Presentation from SNF is an independent predictor of mortality and FTR. Presentation from SNF is a potential trigger for early, concurrent palliative care to assist surgeons, patients, and families in decision making and goal-concordant treatment.

Older Patients With Severe Traumatic Brain Injury: National Variability in Palliative Care.

BACKGROUND: Older patients with traumatic brain injury (TBI) have higher mortality and morbidity than their younger counterparts. Palliative care (PC) is recommended for all patients with a serious or life-limiting illness. However, its adoption for trauma patients has been variable across the nation. The goal of this study was to assess PC utilization and intensity of care in older patients with severe TBI. We hypothesized that PC is underutilized despite its positive effects. MATERIALS AND METHODS: The National Inpatient Sample database (2009-2013) was queried for patients aged ≥55 y with International Classification of Diseases, Ninth Revision codes for TBI with loss of consciousness ≥24 h. Outcome measures included PC rate, in-hospital mortality, discharge disposition, length of stay (LOS), and intensity of care represented by craniotomy and or craniectomy, ventilator use, tracheostomy, and percutaneous endoscopic gastrostomy. RESULTS: Of 5733 patients, 78% died in hospital with a median LOS of 1 d, and 85% of the survivors were discharged to facilities. The overall PC rate was 35%. Almost 40% of deaths received PC, with nearly half within 48 h of admission. PC was used in 26% who had neurosurgical procedures, compared with 35% who were nonoperatively managed (P = 0.003). PC was associated with less intensity of care in the entire population. For survivors, those with PC had significantly shorter LOS, compared with those without PC. CONCLUSIONS: Despite high mortality, only one-third of older patients with severe TBI received PC. PC was associated with decreased use of life support and lower intensity of care. Significant efforts need to be made to bridge this quality gap and improve PC in this high-risk population.

X-Linked IRAK1 Polymorphism is Associated with Sex-Related Differences in Polymorphonuclear Granulocyte and Monocyte Activation and Response Variabilities.

Common X-linked genetic polymorphisms are expected to alter cellular responses affecting males and females differently through sex-linked inheritance pattern as well as X chromosome (ChrX) mosaicism and associated ChrX skewing, which is unique to females. We tested this hypothesis in ex vivo lipopolysaccharide and phorbol ester-stimulated polymorphonuclear granulocytes (PMNs) and monocytes from healthy volunteers (n = 51). Observations were analyzed after stratification by sex alone or the presence of variant IRAK1 haplotype a common X-linked polymorphism with previously demonstrated major clinical impacts. Upon cell activation, CD11b, CD45, CD66b, CD63, and CD14 expression was markedly and similarly elevated in healthy males and females. By contrast, PMN and monocyte activation measured by CD11b, CD66b, and CD63 was increased in variant-IRAK1 subjects as compared with WT. Stratification by IRAK1 genotype and sex showed similar cell activation effect on variant-IRAK1 subjects and an intermediate degree of cell activation in heterozygous mosaic females. The increased membrane expression of these proteins in variant-IRAK1 subjects was associated with similar or increased intersubject but uniformly decreased intrasubject cell response variabilities as compared with WT. We also tested white blood cell ChrX skewing in the healthy cohort as well as in a sample of female trauma patients (n = 201). ChrX inactivation ratios were similar in IRAK1 WT, variant, and heterozygous healthy subjects. Trauma patients showed a trend of blunted ChrX skewing at admission in homozygous variant-IRAK1 and heterozygous mosaic-IRAK1 female subjects as compared with WT. Trauma-induced de novo ChrX skewing was also depressed in variant-IRAK1 and mosaic-IRAK1 female trauma patients as compared with WT. Our study indicates that augmented PMN and monocyte activation in variant-IRAK1 subjects is accompanied by decreased intrasubject cellular variability and blunted de novo ChrX skewing in response to trauma. A more pronounced cell activation of PMNs and monocytes accompanied by decreased response variabilities in variant-IRAK1 subjects may be a contributing mechanism affecting the course of sepsis and trauma and may also impact sex-based outcome differences due to its X-linked inheritance pattern and high prevalence.