Early-life inflammation primes a T helper 2 cell-fibroblast niche in skin.

Inflammation early in life can prime the local immune milieu of peripheral tissues, which can cause lasting changes in immunological tone that confer disease protection or susceptibility1. The cellular and molecular mechanisms that prompt changes in immune tone in many nonlymphoid tissues remain largely unknown. Here we find that time-limited neonatal inflammation induced by a transient reduction in neonatal regulatory T cells causes a dysregulation of subcutaneous tissue in mouse skin. This is accompanied by the selective accumulation of type 2 helper T (TH2) cells within a distinct microanatomical niche. TH2 cells are maintained into adulthood through interactions with a fibroblast population in skin fascia that we refer to as TH2-interacting fascial fibroblasts (TIFFs), which expand in response to TH2 cytokines to form subcutaneous fibrous bands. Activation of the TH2-TIFF niche due to neonatal inflammation primes the skin for altered reparative responses to wounding. Furthermore, we identify fibroblasts in healthy human skin that express the TIFF transcriptional signature and detect these cells at high levels in eosinophilic fasciitis, an orphan disease characterized by inflammation and fibrosis of the skin fascia. Taken together, these data define a previously unidentified TH2 cell niche in skin and functionally characterize a disease-associated fibroblast population. The results also suggest a mechanism of immunological priming whereby inflammation early in life creates networks between adaptive immune cells and stromal cells to establish an immunological set-point in tissues that is maintained throughout life.

Early physical rehabilitation dosage in the intensive care unit associates with hospital outcomes after critical COVID-19.

OBJECTIVE: To examine the relationship between physical rehabilitation parameters including an approach to quantifying dosage with hospital outcomes for patients with critical COVID-19. DESIGN: Retrospective practice analysis from March 5, 2020, to April 15, 2021. SETTING: Intensive care units (ICU) at four medical institutions. PATIENTS: n = 3780 adults with ICU admission and diagnosis of COVID-19. INTERVENTIONS: We measured the physical rehabilitation treatment delivered in ICU and patient outcomes: (1) mortality; (2) discharge disposition; and (3) physical function at hospital discharge measured by the Activity Measure-Post Acute Care (AM-PAC) "6-Clicks" (6-24, 24 = greater functional independence). Physical rehabilitation dosage was defined as the average mobility level scores in the first three sessions (a surrogate measure of intensity) multiplied by the rehabilitation frequency (PT + OT frequency in hospital). MEASUREMENTS AND MAIN RESULTS: The cohort was a mean 64 ± 16 years old, 41% female, mean BMI of 32 ± 9 kg/m2 and 46% (n = 1739) required mechanical ventilation. For 2191 patients who received rehabilitation, the dosage and AM-PAC at discharge were moderately, positively associated (Spearman's rho [r] = 0.484, p < 0.001). Multivariate linear regression (model adjusted R2 = 0.68, p < 0.001) demonstrates mechanical ventilation (ß = - 0.86, p = 0.001), average mobility score in first three sessions (ß = 2.6, p < 0.001) and physical rehabilitation dosage (ß = 0.22, p = 0.001) were predictive of AM-PAC scores at discharge when controlling for age, sex, BMI, and ICU LOS. CONCLUSIONS: Greater physical rehabilitation exposure early in the ICU is associated with better physical function at hospital discharge.

Patient and Caregiver-Derived Health Service Improvements for Better Critical Care Recovery.

OBJECTIVES: To engage critical care end-users (survivors and caregivers) to describe their emotions and experiences across their recovery trajectory, and elicit their ideas and solutions for health service improvements to improve the ICU recovery experience. DESIGN: End-user engagement as part of a qualitative design using the Framework Analysis method. SETTING: The Society of Critical Care Medicine's THRIVE international collaborative sites (follow-up clinics and peer support groups). SUBJECTS: Patients and caregivers following critical illness and identified through the collaboratives. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-six interviews were conducted. The following themes were identified: 1) Emotions and experiences of patients-"Loss of former self; Experiences of disability and adaptation"; 2) Emotions and experiences of caregivers-"Emotional impacts, adopting new roles, and caregiver burden; Influence of gender roles; Adaptation, adjustment, recalibration"; and 3) Patient and caregiver-generated solutions to improve recovery across the arc of care-"Family-targeted education; Expectation management; Rehabilitation for patients and caregivers; Peer support groups; Reconnecting with ICU post-discharge; Access to community-based supports post-discharge; Psychological support; Education of issues of ICU survivorship for health professionals; Support across recovery trajectory." Themes were mapped to a previously published recovery framework (Timing It Right) that captures patient and caregiver experiences and their support needs across the phases of care from the event/diagnosis to adaptation post-discharge home. CONCLUSIONS: Patients and caregivers reported a range of emotions and experiences across the recovery trajectory from ICU to home. Through end-user engagement strategies many potential solutions were identified that could be implemented by health services and tested to support the delivery of higher-quality care for ICU survivors and their caregivers that extend from tertiary to primary care settings.

Patients Surviving Critical COVID-19 have Impairments in Dual-task Performance Related to Post-intensive Care Syndrome.

OBJECTIVE: The purpose was to examine Dual Task (DT) performance in patients surviving severe and critical COVID-19 compared to patients with chronic lung disease (CLD). Secondarily, we aimed to determine the psychometric properties of the Timed Up and Go (TUG) test in patients surviving COVID-19. DESIGN: Prospective, cross-sectional, observational study. SETTING: Academic medical center within United States. PATIENTS: Ninety-two patients including 36 survivors of critical COVID-19 that required mechanical ventilation (critical-COVID), 20 patients recovering from COVID-19 that required supplemental oxygen with hospitalization (severe-COVID), and 36 patients with CLD serving as a control group. MEASUREMENTS AND MAIN RESULTS: Patients completed the TUG, DT-TUG, Short Physical Performance Battery (SPPB), and Six Minute Walk Test (6MWT) 1-month after hospital discharge. A subset of patients returned at 3-months and repeated testing to determine the minimal detectable change (MDC). Critical-COVID group (16.8 ± 7.3) performed the DT-TUG in significantly slower than CLD group (13.9 ± 4.8 s; P = .024) and Severe-COVID group (13.1 ± 5.1 s; P = .025). Within-subject difference between TUG and DT-TUG was also significantly worse in critical-COVID group (-21%) compared to CLD (-10%; P = .012), even despite CLD patients having a higher comorbid burden (P < .003) and older age (P < .001). TUG and DT-TUG demonstrated strong to excellent construct validity to the chair rise test, gait speed, and 6MWT for both COVID-19 groups (r = -0.84to 0.73, P < .05). One- and 3-months after hospital discharge there was a floor effect of 14% (n = 5/36) and 5.2% (n = 1/19), respectively for patients in the critical-COVID group. Ceiling effects were noted in four (11%) critical-COVID, six (30%) severe-COVID patients for the TUG and DT-TUG at 1-month. CONCLUSION: The ability to maintain mobility performance in the presence of a cognitive DT is grossly impaired in patients surviving critical COVID-19. DT performance may subserve the understanding of impairments related to Post-intensive care syndrome (PICS) for survivors of critical illness.

Transitions of Care After Critical Illness-Challenges to Recovery and Adaptive Problem Solving.

OBJECTIVES: Investigate the challenges experienced by survivors of critical illness and their caregivers across the transitions of care from intensive care to community, and the potential problem-solving strategies used to navigate these challenges. DESIGN: Qualitative design-data generation via interviews and data analysis via the framework analysis method. SETTING: Patients and caregivers from three continents, identified through the Society of Critical Care Medicine's THRIVE international collaborative sites (follow-up clinics and peer support groups). SUBJECTS: Patients and caregivers following critical illness. INTERVENTIONS: Nil. MEASUREMENTS AND MAIN RESULTS: From 86 interviews (66 patients, 20 caregivers), we identified the following major themes: 1) Challenges for patients-interacting with the health system and gaps in care; managing others' expectations of illness and recovery. 2) Challenges for caregivers-health system shortfalls and inadequate communication; lack of support for caregivers. 3) Patient and caregiver-driven problem solving across the transitions of care-personal attributes, resources, and initiative; receiving support and helping others; and acceptance. CONCLUSIONS: Survivors and caregivers experienced a range of challenges across the transitions of care. There were distinct and contrasting themes related to the caregiver experience. Survivors and caregivers used comparable problem-solving strategies to navigate the challenges encountered across the transitions of care.

Prediction Models for Physical, Cognitive, and Mental Health Impairments After Critical Illness: A Systematic Review and Critical Appraisal.

OBJECTIVES: Improved ability to predict impairments after critical illness could guide clinical decision-making, inform trial enrollment, and facilitate comprehensive patient recovery. A systematic review of the literature was conducted to investigate whether physical, cognitive, and mental health impairments could be predicted in adult survivors of critical illness. DATA SOURCES: A systematic search of PubMed and the Cochrane Library (Prospective Register of Systematic Reviews ID: CRD42018117255) was undertaken on December 8, 2018, and the final searches updated on January 20, 2019. STUDY SELECTION: Four independent reviewers assessed titles and abstracts against study eligibility criteria. Studies were eligible if a prediction model was developed, validated, or updated for impairments after critical illness in adult patients. Discrepancies were resolved by consensus or an independent adjudicator. DATA EXTRACTION: Data on study characteristics, timing of outcome measurement, candidate predictors, and analytic strategies used were extracted. Risk of bias was assessed using the Prediction model Risk Of Bias Assessment Tool. DATA SYNTHESIS: Of 8,549 screened studies, three studies met inclusion. All three studies focused on the development of a prediction model to predict (1) a mental health composite outcome at 3 months post discharge, (2) return-to-pre-ICU functioning and residence at 6 months post discharge, and (3) physical function 2 months post discharge. Only one model had been externally validated. All studies had a high risk of bias, primarily due to the sample size, and statistical methods used to develop and select the predictors for the prediction published model. CONCLUSIONS: We only found three studies that developed a prediction model of any post-ICU impairment. There are several opportunities for improvement for future prediction model development, including the use of standardized outcomes and time horizons, and improved study design and statistical methodology.

Society of Critical Care Medicine's International Consensus Conference on Prediction and Identification of Long-Term Impairments After Critical Illness.

BACKGROUND: After critical illness, new or worsening impairments in physical, cognitive, and/or mental health function are common among patients who have survived. Who should be screened for long-term impairments, what tools to use, and when remain unclear. OBJECTIVES: Provide pragmatic recommendations to clinicians caring for adult survivors of critical illness related to screening for postdischarge impairments. PARTICIPANTS: Thirty-one international experts in risk-stratification and assessment of survivors of critical illness, including practitioners involved in the Society of Critical Care Medicine's Thrive Post-ICU Collaboratives, survivors of critical illness, and clinical researchers. DESIGN: Society of Critical Care Medicine consensus conference on post-intensive care syndrome prediction and assessment, held in Dallas, in May 2019. A systematic search of PubMed and the Cochrane Library was conducted in 2018 and updated in 2019 to complete an original systematic review and to identify pre-existing systematic reviews. MEETING OUTCOMES: We concluded that existing tools are insufficient to reliably predict post-intensive care syndrome. We identified factors before (e.g., frailty, preexisting functional impairments), during (e.g., duration of delirium, sepsis, acute respiratory distress syndrome), and after (e.g., early symptoms of anxiety, depression, or post-traumatic stress disorder) critical illness that can be used to identify patients at high-risk for cognitive, mental health, and physical impairments after critical illness in whom screening is recommended. We recommend serial assessments, beginning within 2-4 weeks of hospital discharge, using the following screening tools: Montreal Cognitive Assessment test; Hospital Anxiety and Depression Scale; Impact of Event Scale-Revised (post-traumatic stress disorder); 6-minute walk; and/or the EuroQol-5D-5L, a health-related quality of life measure (physical function). CONCLUSIONS: Beginning with an assessment of a patient's pre-ICU functional abilities at ICU admission, clinicians have a care coordination strategy to identify and manage impairments across the continuum. As hospital discharge approaches, clinicians should use brief, standardized assessments and compare these results to patient's pre-ICU functional abilities ("functional reconciliation"). We recommend serial assessments for post-intensive care syndrome-related problems continue within 2-4 weeks of hospital discharge, be prioritized among high-risk patients, using the identified screening tools to prompt referrals for services and/or more detailed assessments.

Acute skeletal muscle wasting and dysfunction predict physical disability at hospital discharge in patients with critical illness.

BACKGROUND: Patients surviving critical illness develop muscle weakness and impairments in physical function; however, the relationship between early skeletal muscle alterations and physical function at hospital discharge remains unclear. The primary purpose of this study was to determine whether changes in muscle size, strength and power assessed in the intensive care unit (ICU) predict physical function at hospital discharge. METHODS: Study design is a single-center, prospective, observational study in patients admitted to the medicine or cardiothoracic ICU with diagnosis of sepsis or acute respiratory failure. Rectus femoris (RF) and tibialis anterior (TA) muscle ultrasound images were obtained day one of ICU admission, repeated serially and assessed for muscle cross-sectional area (CSA), layer thickness (mT) and echointensity (EI). Muscle strength, as measured by Medical Research Council-sum score, and muscle power (lower-extremity leg press) were assessed prior to ICU discharge. Physical function was assessed with performance on 5-times sit-to-stand (5STS) at hospital discharge. RESULTS: Forty-one patients with median age of 61 years (IQR 55-68), 56% male and sequential organ failure assessment score of 8.1 ± 4.8 were enrolled. RF muscle CSA decreased significantly a median percent change of 18.5% from day 1 to 7 (F = 26.6, p = 0.0253). RF EI increased at a mean percent change of 10.5 ± 21% in the first 7 days (F = 3.28, p = 0.081). At hospital discharge 25.7% of patients (9/35) met criteria for ICU-acquired weakness. Change in RF EI in first 7 days of ICU admission and muscle power measured prior to ICU were strong predictors of ICU-AW at hospital discharge (AUC = 0.912). Muscle power at ICU discharge, age and ICU length of stay were predictive of performance on 5STS at hospital discharge. CONCLUSION: ICU-assessed muscle alterations, specifically RF EI and muscle power, are predictors of diagnosis of ICU-AW and physical function assessed by 5x-STS at hospital discharge in patients surviving critical illness.

Procalcitonin: A promising tool or just another overhyped test?

Sepsis is the leading cause of death worldwide. Timely administration of antibiotics is recognized as the cornerstone in the management of sepsis. However, inappropriate use of antibiotics may lead to adverse effects and the selection of drug-resistant pathogens. Microbiological cultures remain the gold standard to diagnose infection despite their low sensitivity and the intrinsic delay to obtain the results. Certain biomarkers have the benefit of rapid turnover, potentially providing an advantage in timely diagnosis leading to accurate treatment. Over the last few decades, there is an ongoing quest for the ideal biomarker in sepsis. Procalcitonin (PCT), when used alone or alongside additional clinical information, has shown to be a promising tool to aid in the diagnosis and management of patients with sepsis. In February 2017, the Food and Drug Administration (FDA) approved the use of PCT to guide antibiotic treatment in lower respiratory tract infections and sepsis. Despite a good negative predictive value for bacterial infection, the utility of PCT-guided antibiotic initiation is conflicting at best. On the other hand, the use of PCT-guided antibiotic discontinuation has shown to reduce the duration of antibiotic use, the associated adverse effects, and to decrease the overall mortality. The current review discusses the history and pathophysiology of procalcitonin, synthesizes its utility in the diagnosis and management of sepsis, highlights its limitations and compares it with other biomarkers in sepsis.

Enablers and Barriers to Implementing ICU Follow-Up Clinics and Peer Support Groups Following Critical Illness: The Thrive Collaboratives.

OBJECTIVES: Data are lacking regarding implementation of novel strategies such as follow-up clinics and peer support groups, to reduce the burden of postintensive care syndrome. We sought to discover enablers that helped hospital-based clinicians establish post-ICU clinics and peer support programs, and identify barriers that challenged them. DESIGN: Qualitative inquiry. The Consolidated Framework for Implementation Research was used to organize and analyze data. SETTING: Two learning collaboratives (ICU follow-up clinics and peer support groups), representing 21 sites, across three continents. SUBJECTS: Clinicians from 21 sites. MEASUREMENT AND MAIN RESULTS: Ten enablers and nine barriers to implementation of "ICU follow-up clinics" were described. A key enabler to generate support for clinics was providing insight into the human experience of survivorship, to obtain interest from hospital administrators. Significant barriers included patient and family lack of access to clinics and clinic funding. Nine enablers and five barriers to the implementation of "peer support groups" were identified. Key enablers included developing infrastructure to support successful operationalization of this complex intervention, flexibility about when peer support should be offered, belonging to the international learning collaborative. Significant barriers related to limited attendance by patients and families due to challenges in creating awareness, and uncertainty about who might be appropriate to attend and target in advertising. CONCLUSIONS: Several enablers and barriers to implementing ICU follow-up clinics and peer support groups should be taken into account and leveraged to improve ICU recovery. Among the most important enablers are motivated clinician leaders who persist to find a path forward despite obstacles.

Multidisciplinary Prerounding Meeting as a Continuous Quality Improvement Tool: Leveraging to Reduce Continuous Benzodiazepine Use at an Academic Medical Center.

BACKGROUND: Evidence-based medicine often has many barriers to overcome prior to implementation in practice, hence the importance of continuous quality improvement. We report on a brief (≤10 minutes) multidisciplinary meeting prior to rounds to establish a dashboard for continuous quality improvement and studied the success of this meeting on a particular area of focus: continuous infusion benzodiazepine minimization. METHODS: This was a prospective observational study of patients admitted to the medical intensive care unit (MICU) of a large academic medical center over a 4-month period. A morning multidisciplinary prerounding meeting was implemented to report on metrics required to establish a dashboard for MICU care for the previous 24 hours. Fellows and nurse practitioners on respective teams reported on key quality metrics and other important data related to patient census. Continuous benzodiazepines were tracked daily as the number of patients per team who had orders for a continuous benzodiazepine infusion. The aim of this report is to describe the development of the morning multidisciplinary prerounding meeting and its impact on continuous benzodiazepine use, along with associated clinical outcomes. RESULTS: The median number of patients prescribed a continuous benzodiazepine daily decreased over this time period and demonstrated a sustained reduction at 1 year. Furthermore, sedation scores improved, corresponding to a reduction in median duration of mechanical ventilation. The effectiveness of this intervention was mapped post hoc to conceptual models used in implementation science. CONCLUSIONS: A brief multidisciplinary meeting to review select data points prior to morning rounds establishes mechanisms for continuous quality improvement and may serve as a mediating factor for successful implementation when initiating and monitoring practice change in the ICU.

Tertiary lymphoid structures sustain cutaneous B cell activity in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic skin condition affecting approximately 1% of the US population. HS skin lesions are highly inflammatory and characterized by a large immune infiltrate. While B cells and plasma cells comprise a major component of this immune milieu, the biology and the contribution of these cells in HS pathogenesis are unclear. We aimed to investigate the dynamics and microenvironmental interactions of B cells within cutaneous HS lesions. Combining histological analysis, single-cell RNA sequencing, and spatial transcriptomics profiling of HS lesions, we defined the tissue microenvironment relative to B cell activity within this disease. Our findings identified tertiary lymphoid structures (TLSs) within HS lesions and described organized interactions among T cells, B cells, antigen-presenting cells, and skin stroma. We found evidence that B cells within HS TLSs actively underwent maturation, including participation in germinal center reactions and class switch recombination. Moreover, skin stroma and accumulating T cells were primed to support the formation of TLSs and facilitate B cell recruitment during HS. Our data definitively demonstrated the presence of TLSs in lesional HS skin and point to ongoing cutaneous B cell maturation through class switch recombination and affinity maturation during disease progression in this inflamed nonlymphoid tissue.

Early physical rehabilitation dosage in the IntensiveCare Unit predicts hospital outcomes after criticalCOVID-19.

Objective: to examine the relationship between physical rehabilitation parameters including a novel approach to quantifying dosage with hospital outcomes for patients with critical COVID-19. Design: Retrospective practice analysis from March 5, 2020, to April 15, 2021. Setting: Intensive care units (ICU) at four medical institutions. Patients: n = 3,780 adults with ICU admission and diagnosis of COVID-19. Interventions: We measured the physical rehabilitation treatment delivered in ICU and patient outcomes: 1) mortality; 2) discharge disposition; and 3) physical function at hospital discharge measured by the Activity Measure-Post Acute Care (AM-PAC) "6-Clicks" (6-24, 24=greater functional independence). Physical rehabilitation dosage was defined as the average mobility level scores in the first three sessions (a surrogate measure of intensity) multiplied by the rehabilitation frequency (PT + OT frequency in hospital). Measurements and Main Results: The cohort was a mean 64 ± 16 years old, 41% female, mean BMI of 32 ± 9 kg/m2 and 46% (n=1739) required mechanical ventilation. For 2191 patients with complete data, rehabilitation dosage and AM-PAC at discharge were moderately, positively associated (Spearman's rho [r] = 0.484, p < 0.001). Multivariate linear regression (model adjusted R2= 0.68, p <0.001) demonstrates mechanical ventilation (ß = -0.86, p = 0.001), average mobility score in first three sessions (ß = 2.6, p <0.001) and physical rehabilitation dosage (ß = 0.22, p = 0.001) were predictive of AM-PAC scores at discharge when controlling for age, sex, BMI, and ICU LOS. Conclusions: Greater physical rehabilitation exposure early in the ICU is associated with physical function at hospital discharge.

Tertiary Lymphoid Structures Sustain Cutaneous B cell Activity in Hidradenitis Suppurativa.

Background: Hidradenitis suppurativa (HS) skin lesions are highly inflammatory and characterized by a large immune infiltrate. While B cells and plasma cells comprise a major component of this immune milieu the biology and contribution of these cells in HS pathogenesis is unclear. Objective: We aimed to investigate the dynamics and microenvironmental interactions of B cells within cutaneous HS lesions. Methods: We combined histological analysis, single-cell RNA-sequencing (scRNAseq), and spatial transcriptomic profiling of HS lesions to define the tissue microenvironment relative to B cell activity within this disease. Results: Our findings identify tertiary lymphoid structures (TLS) within HS lesions and describe organized interactions between T cells, B cells, antigen presenting cells and skin stroma. We find evidence that B cells within HS TLS actively undergo maturation, including participation in germinal center reactions and class switch recombination. Moreover, skin stroma and accumulating T cells are primed to support the formation of TLS and facilitate B cell recruitment during HS. Conclusion: Our data definitively demonstrate the presence of TLS in lesional HS skin and point to ongoing cutaneous B cell maturation through class switch recombination and affinity maturation during disease progression in this inflamed non-lymphoid tissue.

Nutrition in the intensive care unit and early recovery influence functional outcomes for survivors of critical illness: A prospective cohort study.

BACKGROUND: Patients who are critically ill may receive suboptimal nutrition that leads to weight loss and increased risk of functional deficits. METHODS: Our overarching hypothesis is that nutrition in the intensive care unit (ICU) and the early recovery phase associates with functional outcomes at short-term follow-up. We enrolled adult patients who attended the University of Kentucky ICU recovery clinic (ICU-RC) from November 2021 to June 2022. Patients participated in muscle and functional assessments. Nutrition intake and status during the ICU stay were analyzed. The Subjective Global Assessment and a nutrition questionnaire were used to identify changes in intake, ongoing gastrointestinal symptoms, and patient's access to food at the ICU-RC appointment. RESULTS: Forty-one patients enrolled with a median hospital length of stay (LOS) of 23 days. Patients with 0 days of nil per os (NPO) status throughout hospitalization had a shorter LOS (P = 0.05), were able to complete the five times sit-to-stand test (P = 0.02), and were less likely to experience ICU-acquired weakness (P = 0.04) at short-term follow-up compared with patients with ≥1 day of NPO status. Twenty (48%) patients reported changes in nutrition intake in early recovery compared with before hospitalization. Eight (20%) patients reported symptoms leading to decreased intake and four (10%) reported access to food as a barrier to intake. CONCLUSION: Barriers to nutrition exist during critical illness and persist after discharge, with almost half of patients reporting a change in intake. Inpatient nutrition intake is associated with functional outcomes and warrants further exploration.

Construct and criterion validity of muscle ultrasonography for assessment of skeletal muscle in patients recovering from COVID-19.

Background: The purpose was to investigate the content, construct, and criterion validity of muscle ultrasound in a mixed cohort of participants recovering from mild and critical COVID-19. Methods: A secondary analysis of a prospective cross-sectional study was conducted on data obtained from a battery of muscle and physical function assessments including a muscle biopsy and muscle ultrasonography (US). Rectus femoris (RF) muscle thickness (mT), quadricep complex (QC) mT, RF muscle cross-sectional area (CSA) using 2D freeform trace and estimated from Feret's diameter, and RF echo intensity (EI) were assessed with US. Muscle fiber CSA, fiber type, protein content in muscle fibers, extracellular matrix content (ECM; wheat-germ agglutin), and percent area of collagen in ECM (picrosirius red) were examined from vastus lateralis muscle biopsies. Spearman rho correlations (r) were performed to assess validity of ultrasound parameters. Results: Thirty-three individuals participated including 11 patients surviving critical COVID-19, 15 individuals recovering from mild-COVID, and 7 controls. There were several significant correlations between RF mT, QC mT, RF CSA, and RF EI with age, comorbid burden, body-mass index, and measures of muscle strength, muscle power, and physical function (range r = 0.35-0.83). RF Feret's CSA correlated to CSA of type II muscle fibers (r = 0.41, p = 0.022) and the average size of all muscle fibers (r = 0.39, p = 0.031). RF EI was correlated with collagen in muscle ECM (r = 0.53, p = 0.003) and protein content in muscle tissue (r = -0.52, p = 0.012). Conclusion: Muscle size and quality measured using US has moderate content and construct validity, and to lesser extent, fair to moderate criterion validity in a mixed cohort of individuals recovering from COVID. Muscle ultrasound quality (EI) appears to be sensitive at detecting muscle dysfunction as it is associated with strength, power, physical function, and collagen distribution in a mixed group of individuals recovering from COVID-19.

Post-intensive care syndrome and pulmonary fibrosis in patients surviving ARDS-pneumonia of COVID-19 and non-COVID-19 etiologies.

The purpose was to examine patient-centered outcomes and the occurrence of lung fibrotic changes on Chest computed tomography (CT) imaging following pneumonia-related acute respiratory distress syndrome (ARDS). We sought to investigate outpatient clinic chest CT imaging in survivors of COVID19-related ARDS and non-COVID-related ARDS, to determine group differences and explore relationships between lung fibrotic changes and functional outcomes. A retrospective practice analysis of electronic health records at an ICU Recovery Clinic in a tertiary academic medical center was performed in adult patients surviving ARDS due to COVID-19 and non-COVID etiologies. Ninety-four patients with mean age 53 ± 13 and 51% male were included (n = 64 COVID-19 and n = 30 non-COVID groups). There were no differences for age, sex, hospital length of stay, ICU length of stay, mechanical ventilation duration, or sequential organ failure assessment (SOFA) scores between the two groups. Fibrotic changes visualized on CT imaging occurred in a higher proportion of COVID-19 survivors (70%) compared to the non-COVID group (43%, p < 0.001). Across both groups, patients with fibrotic changes (n = 58) were older, had a lower BMI, longer hospital and ICU LOS, lower mean RASS scores, longer total duration of supplemental oxygen. While not statistically different, patients with fibrotic changes did have reduced respiratory function, worse performance on the six-minute walk test, and had high occurrences of anxiety, depression, emotional distress, and mild cognitive impairment regardless of initial presenting diagnosis. Patients surviving pneumonia-ARDS are at high risk of impairments in physical, emotional, and cognitive health related to Post-Intensive Care Syndrome. Of clinical importance, pulmonary fibrotic changes on chest CT occurred in a higher proportion in COVID-ARDS group; however, no functional differences were measured in spirometry or physical assessments at ICU follow-up. Whether COVID infection imparts a unique recovery is not evident from these data but suggest that long-term follow up is necessary for all survivors of ARDS.

Meeting the Challenges of Establishing Intensive Care Unit Follow-up Clinics.

Intensive care unit follow-up clinics are becoming an increasingly widespread intervention to facilitate the physical, cognitive, psychiatric, and social rehabilitation of survivors of critical illness who have post-intensive care syndrome. Developing and sustaining intensive care unit follow-up clinics can pose significant challenges, and clinics need to be tailored to the physical, personnel, and financial resources available at a given institution. Although no standard recipe guarantees a successful intensive care unit aftercare program, emerging clinics will need to address a common set of hurdles, including securing an adequate space; assembling an invested, multidisciplinary staff; procuring the necessary financial, information technology, and physical stuff; using the proper screening tools to identify patients most likely to benefit and to accurately identify disabilities during the visit; and selling it to colleagues, hospital administrators, and the community at large.

Establishing a Cardiac ICU Recovery Clinic: Characterizing a Model for Continuity of Cardiac Critical Care.

BACKGROUND: Care in the cardiovascular intensive care unit (CICU) has become increasingly intricate due to a temporal rise in noncardiac diagnoses and overall clinical complexity with high risk for short-term rehospitalization and mortality. Survivors of critical illness are often faced with debility and limitations extending beyond the index hospitalization. Comprehensive ICU recovery programs have demonstrated some efficacy but have primarily targeted survivors of acute respiratory distress syndrome or sepsis. The efficacy of dedicated ICU recovery programs on the CICU population is not defined. METHODS: We aim to describe the design and initial experience of a novel CICU-recovery clinic (CICURC). The primary outcome was death or rehospitalization in the first 30 days following hospital discharge. Self-reported outcome measures were performed to assess symptom burden and independence in activities of daily living. RESULTS: Using standardized criteria, 41 patients were referred to CICURC of which 78.1% established care and were followed for a median of 88 (56-122) days. On intake, patients reported a high burden of heart failure symptoms (KCCQ overall summary score 29.8 [18.0-47.5]), and nearly half (46.4%) were dependent on caretakers for activities of daily living. Thirty days postdischarge, no deaths were observed and the rate of rehospitalization for any cause was 12.2%. CONCLUSIONS: CICU survivors are faced with significant residual symptom burden, dependence upon caretakers, and impairments in mental health. Dedicated CICURCs may help prioritize treatment of ICU related illness, reduce symptom burden, and improve outcomes. Interventions delivered in ICU recovery clinic for patients surviving the CICU warrant further investigation.