Respiratory Muscle Strength as a Predictive Biomarker for Survival in Amyotrophic Lateral Sclerosis.

RATIONALE: Biomarkers for survival in amyotrophic lateral sclerosis (ALS) would facilitate the development of novel drugs. Although respiratory muscle weakness is a known predictor of poor prognosis, a comprehensive comparison of different tests is lacking. OBJECTIVES: To compare the predictive power of invasive and noninvasive respiratory muscle strength assessments for survival or ventilator-free survival, up to 3 years. METHODS: From a previously published report respiratory muscle strength measurements were available for 78 patients with ALS. Time to death and/or ventilation were ascertained. Receiver operating characteristic analysis was used to determine the cutoff point of each parameter. MEASUREMENTS AND MAIN RESULTS: Each respiratory muscle strength assessment individually achieved statistical significance for prediction of survival or ventilator-free survival. In multivariate analysis sniff trans-diaphragmatic and esophageal pressure, twitch trans-diaphragmatic pressure (Tw Pdi), age, and maximal static expiratory mouth pressure were significant predictors of ventilation-free survival and Tw Pdi and maximal static expiratory mouth pressure for absolute survival. Although all measures had good specificity, there were differing sensitivities. All cutoff points for the VC were greater than 80% of normal, except for prediction of 3-month outcomes. Sequential data showed a linear decline for direct measures of respiratory muscle strength, whereas VC showed little to no decline until 12 months before death/ventilation. CONCLUSIONS: The most powerful biomarker for mortality stratification was Tw Pdi, but the predictive power of sniff nasal inspiratory pressure was also excellent. A VC within normal range suggested a good prognosis at 3 months but was of little other value.

Decision Making About Gastrostomy and Noninvasive Ventilation in Amyotrophic Lateral Sclerosis.

We used thematic analysis to investigate factors affecting decision making about gastrostomy and noninvasive ventilation (NIV) by people with Amyotrophic Lateral Sclerosis (ALS) from the viewpoint of the health care professionals (HCPs) supporting them. We conducted 20 in-depth interviews with 19 HCPs nominated by people with ALS who had made a decision to accept or decline NIV or gastrostomy. We found the main themes influencing decision making were patient-centric, caregiver-related or related to HCPs' own beliefs, perspectives, and actions. HCPs felt patients should be, and were, in control of decision making, although caregivers and HCPs played a role. The patient's evaluation of quality of life, the desirability of prolonging life, and acceptance of the disease and its progression by both patient and caregiver were the most important factors identified by HCPs. HCPs should be aware of the importance of multiprofessional discussions, and the potential influences (identified above) that might require discussion with patients and caregivers.

Compartmentalized T cell profile in the lungs of patients with HIV-1-associated pulmonary Kaposi sarcoma.

ABSTRACT: Pulmonary Kaposi sarcoma (pKS) caused by Human herpesvirus 8 (HHV-8) is a devastating form of KS in patients with advanced acquired immunodeficiency syndrome (AIDS) and is associated with increased morbidity and mortality. Blood T cells play a central role in the response of HIV-1 and HHV-8. However, little information is available on T cells in the alveolar space of HIV-1-associated pKS patients.Therefore, we examined CD8+ and CD4+ T cells in the alveolar space in comparison with the blood of patients with pKS. We recruited 26 HIV-1 positive patients with KS, including 15 patients with pKS. Bronchoalveolar lavage (BAL) cells and blood mononuclear cells were analyzed for T cell memory phenotypes, surface markers associated with exhaustion, and intracellular cytokine staining (ICS) using flow cytometry. HIV-1 and HHV-8 viral loads were measured in plasma by quantitative PCR.BAL T cells showed reduced inflammatory capacities and significantly diminished polyfunctionality compared to blood T cells from patients with pKS. This was not accompanied by increased expression of exhaustion markers, such as TIM-3 and PD-1.More importantly, we found a negative correlation between the production of MIP1-ß and TNF-α in T cells in BAL and blood, indicating compartmentalised immune responses to pKS and accentuated chronic HIV-1/HHV-8 pathogenesis via T cells in the lungs of people with pKS.

Chest radiography is a poor predictor of respiratory symptoms and functional impairment in survivors of severe COVID-19 pneumonia.

BACKGROUND: A standardised approach to assessing COVID-19 survivors has not been established, largely due to the paucity of data on medium- and long-term sequelae. Interval chest radiography is recommended following community-acquired pneumonia; however, its utility in monitoring recovery from COVID-19 pneumonia remains unclear. METHODS: This was a prospective single-centre observational cohort study. Patients hospitalised with severe COVID-19 pneumonia (admission duration ≥48 h and oxygen requirement ≥40% or critical care admission) underwent face-to-face assessment at 4-6 weeks post-discharge. The primary outcome was radiological resolution of COVID-19 pneumonitis (Radiographic Assessment of Lung Oedema score <5). Secondary outcomes included clinical outcomes, symptom questionnaires, mental health screening (Trauma Screening Questionnaire, seven-item Generalised Anxiety Disorder assessment and nine-item Patient Health Questionnaire) and physiological testing (4-m gait speed (4MGS) and 1-min Sit-to-Stand (STS) tests). RESULTS: 119 patients were assessed between June 3, 2020 and July 2, 2020 at median (interquartile range (IQR)) 61 (51-67) days post-discharge: mean±sd age 58.7±14.4 years, median (IQR) body mass index 30.0 (25.9-35.2) kg·m-2, 62% male and 70% ethnic minority. Despite radiographic resolution of pulmonary infiltrates in 87%, modified Medical Research Council Dyspnoea (breathlessness) scale grades were above pre-COVID-19 baseline in 44%, and patients reported persistent fatigue (68%), sleep disturbance (57%) and breathlessness (32%). Screening thresholds were breached for post-traumatic stress disorder (25%), anxiety (22%) and depression (18%). 4MGS was slow (<0.8 m·s-1) in 38% and 35% desaturated by ≥4% during the STS test. Of 56 thoracic computed tomography scans performed, 75% demonstrated COVID-19-related interstitial and/or airways disease. CONCLUSIONS: Persistent symptoms, adverse mental health outcomes and physiological impairment are common 2 months after severe COVID-19 pneumonia. Follow-up chest radiography is a poor marker of recovery; therefore, holistic face-to-face assessment is recommended to facilitate early recognition and management of post-COVID-19 sequelae.

The effect of treatment on diaphragm contractility in obstructive sleep apnea syndrome.

In untreated obstructive sleep apnea syndrome (OSAS) inspiratory efforts are made against an occluded airway and diaphragm fatigue might therefore complicate OSAS. To test this hypothesis we measured twitch transdiaphragmatic pressure (Tw Pdi) in response to bilateral cervical magnetic stimulation of the phrenic nerve roots in nine patients with OSAS before and one month after successful therapy with nasal continuous positive airways pressure (nCPAP). The mean Tw Pdi before therapy was 23.2cm H2O and after therapy was 22.8cm H2O (P = 0.59); the mean change after initiation of nCPAP was 0.4cm H2O with 95% confidence intervals of -1.3cm H2O and +2.1 cm H2O. We conclude that low frequency diaphragm fatigue does not complicate untreated OSAS.

Psychological as well as illness factors influence acceptance of non-invasive ventilation (NIV) and gastrostomy in amyotrophic lateral sclerosis (ALS): a prospective population study.

Our objective was to identify factors associated with acceptance of non-invasive ventilation (NIV) and gastrostomy in an exploratory population-based study. Seventy-eight people with ALS at least six months post-diagnosis, and 50 caregivers, were recruited from the South-East ALS Register. Baseline physical, cognitive and psychological measures were obtained. Three-monthly follow-ups monitored whether patients had accepted or refused NIV or gastrostomy. Following an intervention decision, post-decision interviews repeated baseline measures and included further intervention-specific questionnaires. Results showed that 32 people with ALS made at least one intervention decision and of these 10 decided about both NIV and gastrostomy. While illness factors predicted those needing to make an intervention decision, cognitive and education status, and level of executive dysfunction were associated with decision-making and acceptance or refusal of interventions. Patients' understanding of their illness, their early approach to considering interventions and carer-related factors were also associated with treatment decisions. In conclusion, our findings highlight the complexity of decision-making and provide a platform for designing further studies. Cognitive and psychosocial factors may assume a greater role in palliative care decisions for people with ALS than has been explicitly recognized. Future work must clarify how to ensure patients are not inadvertently being denied suitable interventions.