Durvalumab-induced thyroiditis in a patient with non-small cell lung carcinoma: a case report and review of pathogenic mechanisms.

BACKGROUND: Immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 and its ligand (PD-1/PD-L1) have become the current standard-of-care for advanced cancers. This novel therapeutic approach comes with its costs in the form of immune-related adverse events (irAE), including endocrinopathy. CASE PRESENTATION: A 63-year-old woman was diagnosed with a non-small cell lung carcinoma of the right superior lobe, cT3N2M0. She developed thyrotoxicosis followed by hypothyroidism induced by consolidation immunotherapy with durvalumab (anti-PD-L1). Analysis of the human leukocyte antigen (HLA) region showed HLA-DR4 (susceptible) and DR13 (protective). The possible mechanisms are subsequently discussed in detail. CONCLUSIONS: The case of a patient with thyroiditis associated with the PD-L1 inhibitor durvalumab is described, highlighting the need for proactive monitoring of thyroid hormone levels. Identifying biomarkers associated with an increased risk of ICI-induced side effects (such as HLA) is of interest for better patient selection, optimal management and improved understanding of the mechanisms involved.

Telemonitoring for the Follow-Up of Obstructive Sleep Apnea Patients Treated with CPAP: Accuracy and Impact on Therapy.

Continuous positive airway pressure (CPAP) telemonitoring (TMg) has become widely implemented in routine clinical care. Objective measures of CPAP compliance, residual respiratory events, and leaks can be easily monitored, but limitations exist. This review aims to assess the role of TMg in CPAP-treated obstructive sleep apnea (OSA) patients. We report recent data related to the accuracy of parameters measured by CPAP and try to determine the role of TMg in CPAP treatment follow-up, from the perspective of both healthcare professionals and patients. Measurement and accuracy of CPAP-recorded data, clinical management of these data, and impacts of TMg on therapy are reviewed in light of the current literature. Moreover, the crucial questions of who and how to monitor are discussed. TMg is a useful tool to support, fine-tune, adapt, and control both CPAP efficacy and compliance in newly-diagnosed OSA patients. However, clinicians should be aware of the limits of the accuracy of CPAP devices to measure residual respiratory events and leaks and issues such as privacy and cost-effectiveness are still a matter of concern. The best methods to focus our efforts on the patients who need TMg support should be properly defined in future long-term studies.

Photoplethysmography in Normal and Pathological Sleep.

This article presents an overview of the advancements that have been made in the use of photoplethysmography (PPG) for unobtrusive sleep studies. PPG is included in the quickly evolving and very popular landscape of wearables but has specific interesting properties, particularly the ability to capture the modulation of the autonomic nervous system during sleep. Recent advances have been made in PPG signal acquisition and processing, including coupling it with accelerometry in order to construct hypnograms in normal and pathologic sleep and also to detect sleep-disordered breathing (SDB). The limitations of PPG (e.g., oxymetry signal failure, motion artefacts, signal processing) are reviewed as well as technical solutions to overcome these issues. The potential medical applications of PPG are numerous, including home-based detection of SDB (for triage purposes), and long-term monitoring of insomnia, circadian rhythm sleep disorders (to assess treatment effects), and treated SDB (to ensure disease control). New contact sensor combinations to improve future wearables seem promising, particularly tools that allow for the assessment of brain activity. In this way, in-ear EEG combined with PPG and actigraphy could be an interesting focus for future research.

Cardiometabolic comorbidities in obstructive sleep apnea patients are related to disease severity, nocturnal hypoxemia, and decreased sleep quality.

BACKGROUND: Obstructive sleep apnea syndrome (OSA) is currently recognized as an independent risk factor for hypertension, arrhythmia, coronary heart disease, stroke, and metabolic disorders (e.g. diabetes, dyslipidemia). In clinical practice, apnea-hypopnea index (AHI) is the marker used to classify disease severity and guide treatment. However, AHI alone does not sufficiently identify OSA patients at risk for cardiometabolic comorbidities. With this in mind, the aim of this retrospective study was to determine whether some polysomnographic parameters (e.g. apnea-hypopnea duration, sleep structure, nocturnal hypoxemia) are specifically associated with cardiometabolic comorbidities in OSA. METHODS: In this retrospective study, 1717 patients suffering from moderate/severe OSA were included between 2013 and 2017. Data on demographics, comorbidities, and polysomnographic characteristics were collected and analyzed to identify factors associated with cardiometabolic complications. RESULTS: The medical files of 1717 patients (68% male) were reviewed. The mean AHI was 43.1 +/- 27.7 with 57.3% of patients suffering from severe OSA, and 52% from at least one cardiovascular comorbidity (CVCo). Diabetes affected 22% of the patients and 27% exhibited dyslipidemia. Patients affected by CVCos were older, and more often women and non-smokers. These patients also had worse sleep quality, and a more marked intermittent/global nocturnal hypoxemia. With regard to diabetes, diabetics were older, more often non-smoker, non-drinker women, and were more obese. These patients also exhibited more severe OSA, especially in non-REM (NREM) sleep, worse sleep quality, and a more marked intermittent/global nocturnal hypoxemia. Dyslipidemia was more frequent in the absence of alcohol consumption, and was associated with OSA severity, decreased sleep quality, and longer AH in REM sleep. CONCLUSIONS: This study identifies demographic and polysomnographic factors associated with cardiometabolic comorbidities. Patients (especially women) suffering from more severe OSA, longer sleep apneas and hypopneas, worse sleep quality, and marked intermittent/global nocturnal hypoxemia are more likely to develop cardiometabolic comorbidities. This should stimulate clinicians to obtain adequate treatment in this population.

African ethnicity is associated with a higher prevalence of diabetes in obstructive sleep apnea patients: results of a retrospective analysis.

PURPOSE: Obstructive sleep apnea (OSA) syndrome is a well-recognized independent risk factor for cardiovascular disease and its prevalence is increasing. OSA symptomology, polysomnographic features, and comorbidities are heterogeneous among patients. Ethnicity is thought to influence OSA phenotypes, but extensive knowledge of OSA ethnic patterns is lacking. The primary aim of the present study was to compare comorbidities in Caucasian and African OSA. Secondary aims were to observe OSA symptomatology, polysomnographic characteristics, and CPAP adherence in these two ethnic groups. METHODS: In this retrospective study, 1717 patients suffering from moderate/severe OSA were included between 2013 and 2017. Data on demographics, symptomatology, comorbidities, polysomnographic characteristics, and CPAP adherence were collected. Data were analyzed to identify potential differences between Caucasians and Africans. RESULTS: Despite healthier lifestyles and lower BMI, a higher prevalence of diabetes but less cardiac comorbidities and dyslipidemia was observed in the African population. Younger African patients (< 56 years) suffered more from cognitive impairment than Caucasians and both younger and older Africans complained more of nighttime choking than Caucasians. In analysis of polysomnographic data, Africans had higher apnea-hypopnea index (AHI) in REM sleep, lower supine AHI, lower desaturation time, and lower periodic leg movements index. CONCLUSIONS: Compared with Caucasians, African OSA showed a particular comorbidity profile. There are younger patients who exhibit more diabetes but less cardiac comorbidities than the Caucasians. African diabetics should be more promptly referred for OSA testing. Moreover, as they suffer more often from choking and cognitive impairment, OSA treatment could positively impact their quality of life.

Pulmonary Functional Outcomes at 3 Months in Critical COVID-19 Survivors Hospitalized during the First, Second, and Third Pandemic Waves.

INTRODUCTION: Despite improved management of patients with COVID-19, we still ignore whether pharmacologic treatments and improved respiratory support have modified outcomes for intensive care unit (ICU) surviving patients of the three first consecutive waves (w) of the pandemic. The aim of this study was to evaluate whether developments in the management of ICU COVID-19 patients have positively impacted respiratory functional outcomes, quality of life (QoL), and chest CT scan patterns in ICU COVID-19 surviving patients at 3 months, according to pandemic waves. METHODS: We prospectively included all patients admitted to the ICU of two university hospitals with acute respiratory distress syndrome (ARDS) related to COVID-19. Data related to hospitalization (disease severity, complications), demographics, and medical history were collected. Patients were assessed 3 months post-ICU discharge using a 6 min walking distance test (6MWT), a pulmonary function test (PFT), a respiratory muscle strength (RMS) test, a chest CT scan, and a Short Form 36 (SF-36) questionnaire. RESULTS: We included 84 ARDS COVID-19 surviving patients. Disease severity, complications, demographics, and comorbidities were similar between groups, but there were more women in wave 3 (w3). Length of stay at the hospital was shorter during w3 vs. during wave 1 (w1) (23.4 ± 14.2 days vs. 34.7 ± 20.8 days, p = 0.0304). Fewer patients required mechanical ventilation (MV) during the second wave (w2) vs. during w1 (33.3% vs. 63.9%, p = 0.0038). Assessment at 3 months after ICU discharge revealed that PFTs and 6MWTs scores were worse for w3 > w2 > w1. QoL (SF-36) deteriorated (vitality and mental health) more for patients in w1 vs. in w3 (64.7 ± 16.3 vs. 49.2 ± 23.2, p = 0.0169). Mechanical ventilation was associated with reduced forced expiratory volume (FEV1), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO), and respiratory muscle strength (RMS) (w1,2,3, p < 0.0500) on linear/logistic regression analysis. The use of glucocorticoids, as well as tocilizumab, was associated with improvements in the number of affected segments in chest CT, FEV1, TLC, and DLCO (p < 0.01). CONCLUSIONS: With better understanding and management of COVID-19, there was an improvement in PFT, 6MWT, and RMS in ICU survivors 3 months after ICU discharge, regardless of the pandemic wave during which they were hospitalized. However, immunomodulation and improved best practices for the management of COVID-19 do not appear to be sufficient to prevent significant morbidity in critically ill patients.

Health-Related Quality of Life Improves in Parallel with FEV1 and 6-Minute Walking Distance Test at Between 3 and 12 Months in Critical COVID-19 Survivors.

Background: In COVID-19 intensive care unit (ICU)-admitted patients, multiorgan acute complications lead to long-lasting sequelae. The aim of this study was to assess (1) changes in chest CT, pulmonary function test (PFT), functional capacity (6-minute walking distance test (6MWT)), and health-related quality of life (HR-QoL) among ICU COVID-19 survivors at 3, 6, and 12 months after ICU discharge and (2) predictors of persistent impairment/improvement in 6MWT and HR-QoL. Methods: ICU COVID-19 survivors were prospectively included. Outcomes at 3, 6, and 12 months included PFT, 6MWT, respiratory muscle strength (RMS), HR-QoL (SF-36), Medical Research Council dyspnea scale (mMRC), and post-COVID Functional Status scale. Results: Eighty-seven survivors were included, from June 3, 2020, to September 2, 2021. At 12 months, 50% of PFT were normal, 46% were restrictive, and 22% showed reduced diffusing capacity for carbon monoxide (DLCO). Impaired DLCO was associated with ICU length of stay and age. In mixed linear model analysis, improvements in RMS and mMRC persisted over time regardless of the adjustments applied (P ≤ .050). SF-36 improved in parallel with FEV1 and 6MWT between 3 and 12 months (P ≤ .044), while increment in DLCO correlated with changes in FEV1 and total lung capacity (TLC) (p ≤ 0.026). Conclusions: This longitudinal study demonstrated that improvements in SF-36 occur in parallel with improvements in FEV1 and 6MWT between 3 and 12 months post-ICU discharge in a sample of critically ill COVID-19 patients. However, PFT remained, however, abnormal in 50% of patients. Based on continued improvements observed from 3 to 12 months, it is anticipated that COVID-19 ICU patients will continue to recover similarly to ARDS patients.

The impact of early standard therapy on dyspnoea in patients with acute heart failure: the URGENT-dyspnoea study.

AIMS: The vast majority of acute heart failure (AHF) trials to date have targeted dyspnoea. However, they enrolled patients relatively late and did not standardize their methods of dyspnoea measurement. URGENT Dyspnoea was designed to determine changes in dyspnoea in response to initial, standard therapy in patients presenting with AHF using a standardized approach. METHODS AND RESULTS: URGENT Dyspnoea was an international, multi-centre, observational cohort study of AHF patients managed conventionally and enrolled within 1 h of first hospital medical evaluation. Patient-assessed dyspnoea was recorded in the sitting position at baseline and at 6 hours by Likert and visual analog scales. Less symptomatic patients were placed supine to determine whether this provoked worsening dyspnoea (orthopnoea). Of the 524 patients with AHF, the mean age was 68 years, 43% were women, and 83% received intravenous diuretics. On a 5-point Likert scale, dyspnoea improvement was reported by 76% of patients after 6 h of standard therapy. Supine positioning (orthopnoea test) led to worse dyspnoea in 47% of patients compared to sitting upright. CONCLUSION: When sitting upright, dyspnoea in the sitting position improves rapidly and substantially in patients with AHF after administration of conventional therapy, mainly intra-venous diuretics. However, many patients remain orthopnoeic. Improving the methodology of clinical trials in AHF by standardizing the conditions under which dyspnoea is assessed could enhance their ability to identify effective treatments. Relief of orthopnoea is clinically valuable and may represent a useful goal for clinical trials.

Midregional pro-atrial natriuretic peptide for the diagnosis of cardiac-related dyspnea according to renal function in the emergency department: a comparison with B-type natriuretic peptide (BNP) and N-terminal proBNP.

BACKGROUND: Although renal dysfunction influences the threshold values of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in diagnosis of cardiac-related dyspnea (CRD), its effects on midregional pro-atrial natriuretic peptide (MR-proANP) threshold values are unknown. We evaluated the impact of renal function on MR-proANP concentrations and compared our results to those of BNP and NT-proBNP. METHODS: MR-proANP, BNP, and NT-proBNP concentrations were measured in blood samples collected routinely from dyspneic patients admitted to the emergency department. Patients were subdivided into tertiles based on their estimated glomerular filtration rate [eGFR, in mL · min(-1) · (1.73 m(2))(-1)]: tertiles 1 (<44.3), 2 (44.3-58.5), and 3 (≥58.6). RESULTS: Of 378 patients studied, 69% (n = 260) had impaired renal function [<60 mL · min(-1) · (1.73 m(2))(-1)] and 30% (n = 114) had CRD. MR-proANP, BNP, and NT-proBNP concentrations were significantly increased in patients with impaired renal function. In each tertile, all peptides remained significantly increased in CRD patients by comparison with non-CRD patients. By ROC analysis, MR-proANP, BNP, and NT-proBNP threshold values for the diagnosis of CRD increased as eGFR decreased from tertile 3 to tertile 1. Areas under the ROC curve for all peptides were significantly lower in tertile 1. Using adapted thresholds, MR-proANP, BNP, and NT-proBNP remained independently predictive of CRD, even in tertile 1 patients. CONCLUSIONS: Renal function influences optimum cutoff points of MR-proANP for the diagnosis of CRD. With use of an optimum threshold value adapted to the eGFR category, MR-proANP remains as effective as BNP and NT-proBNP in independently predicting a diagnosis of CRD in the emergency department.

Febrile neutropenia in French emergency departments: results of a prospective multicentre survey.

INTRODUCTION: Febrile neutropenia (FN) is common in cancer patients receiving myelotoxic therapy. The procedures to treat FN are well established in oncology, but it is unclear whether management is adequate in the emergency department (ED). METHODS: This prospective, multicentre, observational study was carried out in 47 French EDs for 6 months. Patients were adults presenting at the ED with FN after myelotoxic treatment for cancer. Severity of infection was defined according to Bone criteria for severe sepsis and septic shock (SS/SSh) and risk was determined according to Multinational Association of Supportive Care in Cancer (MASCC) criteria. The end point was the implementation of guidelines. Management of patients with SS/SSh required: (i) adequate intravenous (IV) antimicrobial therapy for the first 90 min (broad-spectrum beta-lactam with or without an aminoglycoside); (ii) fluid challenge (500 mL); (iii) lactate measurement; (iv) at least one blood culture; and (v) hospitalization. Management of patients without SS/SSh required: (1) no initiation of granulocyte - cell stimulating factor (G-CSF); (2) adequate IV antimicrobial therapy (broad-spectrum beta-lactam) and hospitalization if the patient was high-risk according to MASCC criteria; (3) adequate oral antimicrobial therapy (quinolone or amoxicillin/clavulanate or cephalosporin) and hospital discharge if the patient was low-risk. RESULTS: 198 patients were enrolled; 89 patients had SS/SSh, of whom 19 received adequate antimicrobial therapy within 90 min and 42 received appropriate fluid challenge. Blood cultures were obtained from 87 and lactate concentration was measured in 29. Overall, only 6 (7%) patients with SS/SSh received adequate management. Among 108 patients without SS/SSh, 38 (35%) were high-risk and 70 (65%) low-risk. In the high-risk group, adequate antimicrobial therapy was given to 31 patients, G-CSF was initiated in 4 and 35 were hospitalized. In the low-risk group, 4 patients received adequate oral antimicrobial therapy, IV antimicrobial therapy was prescribed in 59, G-CSF was initiated in 12 and six patients were discharged. Adequate management was given to 26/38 (68%) high-risk and 1/70 low-risk patients. Factors associated with adequate management were absence of SS/SSh (P = 0.0009) and high-risk according to MASCC criteria (P < 0.0001). CONCLUSIONS: In this French sample of cancer patients presenting to the ED with FN, management was often inadequate and severity was under-evaluated in the critically ill.

Accuracy of oxygen tissue saturation values in assessing severity in patients with sepsis admitted to emergency departments.

INTRODUCTION: Near-infrared spectrometry assesses hemoglobin saturation of oxygen in tissues (StO2). Although it may provide additional information on local microcirculation function, the usefulness of near-infrared spectrometry in septic patients is debated. This study evaluated whether baseline StO2 value is useful in septic patients admitted to the emergency department with a diagnosis of severe sepsis. MATERIALS AND METHODS: We carried out a prospective multicenter study in three emergency departments in Paris, France. Triage nurses were to record StO2, the results were blinding to the emergency physicians. Patients were eligible when presenting with at least two of the following parameters: temperature higher than 38°C or less than 36°C, respiratory rate greater than 30/min, heart rate greater than 120/min, and systolic arterial blood pressure less than 110 mmHg. Patients with a final diagnosis of sepsis and severe sepsis were analyzed. RESULTS: We analyzed 98 patients (70 with sepsis and 28 with severe sepsis). Thirty-day mortality was 2.9 versus 14.3% (P=0.048) in the sepsis and the severe sepsis group, respectively. No significant difference in the median StO2 was observed in patients with sepsis and severe sepsis [79% (74-85%) vs. 77% (72-83%), respectively; P=0.66]. The area under the curve of the receiver operating characteristic curve for StO2 to predict severe sepsis was 0.53 (0.39-0.66; P=0.5) and the cutoff value was 77%. Median StO2 did not differ in patients admitted to the ICU [80% (60-88%) vs. 79% (74-84%); P=0.78] and in nonsurvivors compared with that of survivors [79% (74-85%) vs. 76% (73-83%); P=0.64]. CONCLUSION: This study fails to show any value of StO2 baseline at triage for early detection of severe sepsis in emergency patients.

Prognostic factors in non-exertional heatstroke.

PURPOSE: To identify the prognostic factors associated with mortality in heat-related illness. METHODS: Multi-center observational cohort-study in 16 emergency departments (ED) belonging to the teaching hospital network of the Paris area. The cohort comprised all patients admitted to one of the EDs during the August 2003 heat wave in Paris and having a core temperature >38.5 degrees C. Baseline clinical and biological data in ED, patient's course and 1-year survival rate were recorded. Potential prognostic factors associated with death were assessed by Cox proportional-hazards analysis. RESULTS: A total of 1,456 patients were included. Mean age was 79 +/- 19 years. Critically ill conditions were noted in 391 patients (27%), but only 72 (5%) were admitted into an intensive care unit. The survival rate was 57% at 1 year as compared to an expected 90% (P < 0.001). Nine independent prognostic factors were identified: previous treatment with diuretics, living in an institution, age >80 years, cardiac disease, cancer, core temperature >40 degrees C, systolic arterial pressure <100 mmHg, Glasgow coma scale <12 and transportation to hospital by ambulance. We defined three risk groups: low, intermediate and high risk, with a 1-year survival rate of 85, 61 and 18%, respectively. CONCLUSIONS: We observed a low survival rate and developed a risk score based on easily obtained variables that may be useful to clinicians managing casualties from future heat waves.

Extra-hematopoietic effects of erythropoietin.

Erythropoietin (Epo) has a long-lasting history as the hormon that allows production of red blood cells. It is now well established that, besides erythropoiesis, Epo has the ability to sustain proliferation of myeloid lineages. More recently, extra-haematological roles have been described for Epo. Its receptor, EpoR, has been detected at the membrane of several neoplastic and normal cell types from the central nervous system and other non haematological cell lines. Whereas Epo-EpoR have been detected several years ago in some extra-haematological normal lineages, their role has long been underestimated whereas they may be crucial for proliferation and survival. Consequently, efforts have recently increased to identify the precise role of Epo-EpoR in a variety of cell types. This allowed identification of physiologically relevant targets that led to original therapeutic strategies.

Accuracy study of Angiotensin 1-7 composite index test to predict pulmonary fibrosis and guide treatment.

BACKGROUND: Pulmonary fibrosis can develop after acute respiratory distress syndrome (ARDS). The hypothesis is we are able to measure phenotypes that lie at the origin of ARDS severity and fibrosis development. The aim is an accuracy study of prognostic circulating biomarkers. METHODS: A longitudinal study followed COVID-related ARDS patients with medical imaging, pulmonary function tests and biomarker analysis, generating 444 laboratory data. Comparison to controls used non-parametrical statistics; p < 0·05 was considered significant. Cut-offs were obtained through receiver operating curve. Contingency tables revealed predictive values. Odds ratio was calculated through logistic regression. RESULTS: Angiotensin 1-7 beneath 138 pg/mL defined Angiotensin imbalance phenotype. Hyper-inflammatory phenotype showed a composite index test above 34, based on high Angiotensin 1-7, C-Reactive Protein, Ferritin and Transforming Growth Factor-ß. Analytical study showed conformity to predefined goals. Clinical performance gave a positive predictive value of 95 % (95 % confidence interval, 82 %-99 %), and a negative predictive value of 100 % (95 % confidence interval, 65 %-100 %). Those severe ARDS phenotypes represented 34 (Odds 95 % confidence interval, 3-355) times higher risk for pulmonary fibrosis development (p < 0·001). CONCLUSIONS: Angiotensin 1-7 composite index is an early and objective predictor of ARDS evolving to pulmonary fibrosis. It may guide therapeutic decisions in targeted phenotypes.