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Abstract Background Breathlessness is the prominent symptom of chronic obstructive pulmonary disease (COPD). Despite optimal therapeutic management including pharmacological and non-pharmacological interventions, many COPD patients exhibit significant breathlessness. Chronic breathlessness is defined as breathlessness that persists despite optimal treatment of the underlying disease. Because of the major disability related to chronic breathlessness, symptomatic treatments including opioids have been recommended by several authors. The prevalence of chronic breathlessness in COPD and its management in routine clinical practice have been poorly investigated. Our aim was to examine prevalence, associated characteristics and management of chronic breathlessness in patients with COPD recruited in a real-life tertiary hospital-based cohort. Methods A prospective study was conducted among 120 consecutive COPD patients recruited, in stable condition, at Nancy University Hospital, France. In parallel, 88 pulmonologists of the same geographical region were asked to respond to an on-line questionnaire on breathlessness management. Results Sixty four (53%) patients had severe breathlessness (modified Medical Research Council scale≥3), despite optimal inhaled medications for 94% of them; 40% had undergone pulmonary rehabilitation within the past 2 years. The severity of breathlessness increased with increasing airflow limitation. Breathlessness was associated with increased symptoms of anxiety, depression and with osteoporosis. No relation was found with other symptoms, exacerbation rate, or cardiovascular comorbidities. Among the patients with chronic breathlessness and Hospitalized Anxiety and/or Depression score > 10, only 25% were treated with antidepressant or anxiolytic. Among the pulmonologists 46 (52%) answered to the questionnaire and expressed a high willingness to prescribe opioids forchronic breathlessness, which contrasted with the finding that none of these patients received such treatments against breathlessness. Conclusion Treatment approaches to breathlessness and associated psychological distress are insufficient in COPD. This study highlights underuse of pulmonary rehabilitation and symptomatic treatment for breathlessness.

Inflammation plays a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Exposure to cigarette smoke induces the recruitment of inflammatory cells in the airways and stimulates innate and adaptive immune mechanisms. Airway inflammation is involved in increased bronchial wall thickness, increased bronchial smooth muscle tone, mucus hypersecretion and loss of parenchymal elastic structures. Oxidative stress impairs tissue integrity, accelerates lung ageing and reduces the efficacy of corticosteroids by decreasing levels of histone deacetylase-2. Protease–antiprotease imbalance impairs tissues and is involved in inflammatory processes. Inflammation is also present in the pulmonary artery wall and at the systemic level in COPD patients, and may be involved in COPD-associated comorbidities. Proximal airways inflammation contributes to symptoms of chronic bronchitis while distal and parenchymal inflammation relates to airflow obstruction, emphysema and hyperinflation. Basal levels of airways and systemic inflammation are increased in frequent exacerbators. Inhaled corticosteroids are much less effective in COPD than in asthma, which relates to the intrinsically poor reversibility of COPD-related airflow obstruction and to molecular mechanisms of resistance relating to oxidative stress. Ongoing research aims at developing new drugs targeting more intimately COPD-specific mechanisms of inflammation, hypersecretion and tissue destruction and repair. Among new anti-inflammatory agents, phosphodiesterase-4 inhibitors have been the first to emerge.

This review is the summary of a workshop on the role of distal airways in chronic obstructive pulmonary disease (COPD), which took place in 2009 in Vence, France. The evidence showing inflammation and remodelling in distal airways and the possible involvement of these in the pathobiology, physiology, clinical manifestations and natural history of COPD were examined. The usefulness and limitations of physiological tests and imaging techniques for assessing distal airways abnormalities were evaluated. Ex vivo studies in isolated lungs and invasive measurements of airway resistance in living individuals have revealed that distal airways represent the main site of airflow limitation in COPD. Structural changes in small conducting airways, including increased wall thickness and obstruction by muco-inflammatory exudates, and emphysema (resulting in premature airway closure), were important determinants of airflow limitation. Infiltration of small conducting airways by phagocytes (macrophages and neutrophils), dendritic cells and T and B lymphocytes increased with airflow limitation. Distal airways abnormalities were associated with patient-related outcomes (e.g. dyspnoea and reduced health-related quality of life) and with the natural history of the disease, as reflected by lung function decline and mortality. These data provide a clear rationale for targeting distal airways in COPD.

Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance (PVR) due to vascular remodeling of the small pulmonary arteries. In advanced RV failure or severe hypoxemia, extra corporeal life support (ECLS) is now to be considered, with the objective to bridge patients back to their baseline clinical state while waiting or right after lung transplantation, or bridge to pharmacological optimization of PAH (i.e., bridge to recovery). We describe herein a case of a 30-year-old woman (gravida 6, para 6) with an incident case of heritable PAH revealed by refractory hypoxemia. Despite the use of mechanical ventilation and fluid optimization, the patient remained profoundly hypoxemic. ECLS was then initiated to avoid tissue hypoxia. The mechanical option chosen was peripheral femoro-femoral venoarterial extracorporeal membrane oxygen (VA-ECMO), percutaneously implanted. Due to the absence of evidence of chronic respiratory disease or chronic thromboembolic pulmonary hypertension, this severe pre-capillary pulmonary hypertension was attributed to PAH. Therefore, epoprostenol infusion and an association of oral treatments (bosentan and tadalafil) were administered. A dramatic improvement was observed, allowing decannulation 7 days after the initiation of pharmacological treatment. After 29 days, the patient was discharged from the hospital with epoprostenol, bosentan, and tadalafil. The assessment has been completed by positive research on mutations (c.741C > G, p.Tyr247) corresponding to a loss of function of the bone morphogenetic protein receptor 2 (BMPR2) gene. The final diagnosis was heritable PAH. The use of ECLS has been well demonstrated in patients with PAH complicated by acute RV failure or refractory hypoxemia in the “bridge-to-transplantation” strategy. Only a few reports have described the use of ECLS as a “bridge-to-recovery” with PAH drugs in untreated or undertreated PAH patients, but none has described such a rapid improvement with resolution of refractory hypoxemia. More studies are needed to assess the benefits and limitations of the “bridge-to-recovery” strategy and to identify the patients most likely to benefit from it.

Introduction Pulmonary veno-occlusive disease (PVOD) is a rare and severe subtype of pulmonary arterial hypertension (PAH). Although European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines advise assessing PAH severity at baseline and during follow-up, no existing risk assessment methods have been validated for PVOD. This study aimed to identify prognostic factors, examine the impact of treatment strategies and evaluate risk assessment methods for PVOD patients. Methods The study analysed all incident PVOD patients included in the French Pulmonary Hypertension Registry between 2006 and 2021. Survival was assessed based on initial treatment strategy and risk status and compared to a matched (age, sex, pulmonary vascular resistance) PAH group. Six risk assessment methods (number of four low-risk and three noninvasive low-risk variables, ESC/ERS guidelines three-strata and four-strata models, REVEAL 2.0 and Lite 2) were applied at baseline and early follow-up, and their accuracy was compared using Harrell's c-statistic. Results Among the 327 included PVOD patients, survival rates at 1, 3 and 5 years were 86%, 50% and 27%, respectively. Multivariate analysis showed that only 6-min walk distance was associated with survival, with no significant difference based on initial treatment strategy. All six risk assessment methods could discriminate mortality risk, and the ESC/ERS four-strata model was the most accurate at both baseline and follow-up (C-index 0.64 and 0.74). PVOD survival rates were consistently lower than PAH when comparing baseline risk status using the ESC/ERS four-strata model. Conclusion PVOD is associated with poor outcomes, and initial treatment strategies do not significantly affect survival. Risk assessment methods can be useful in predicting survival for PVOD patients.

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56-0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro-brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil-assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12-60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.Clinical trial registered with www.clinicaltrials.gov (NCT01560624).

This paper is a short retrospective review of the predictive methods of turbulent flows in Computational Fluid Dynamics over the last 50 years since the first development of computers. The different schools of turbulence modeling are presented with the aim to guide both users and researchers involved in numerical simulation of turbulent flows.

Abstract Dunnigan syndrome, or Familial Partial Lipodystrophy type 2 (FPLD2; ORPHA 2348), is a rare autosomal dominant disorder due to pathogenic variants of the LMNA gene. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins), is to provide health professionals with a guide to optimal management and care of patients with FPLD2, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French). Dunnigan syndrome is characterized by a partial atrophy of the subcutaneous adipose tissue and by an insulin resistance syndrome, associated with a risk of metabolic, cardiovascular and muscular complications. Its prevalence, assessed at 1/100.000 in Europe, is probably considerably underestimated. Thorough clinical examination is key to diagnosis. Biochemical testing frequently shows hyperinsulinemia, abnormal glucose tolerance and hypertriglyceridemia. Elevated hepatic transaminases (hepatic steatosis) and creatine phosphokinase, and hyperandrogenism in women, are common. Molecular analysis of the LMNA gene confirms diagnosis and allows for family investigations. Regular screening and multidisciplinary monitoring of the associated complications are necessary. Diabetes frequently develops from puberty onwards. Hypertriglyceridemia may lead to acute pancreatitis. Early atherosclerosis and cardiomyopathy should be monitored. In women, polycystic ovary syndrome is common. Overall, the management of patients with Dunnigan syndrome requires the collaboration of several health care providers. The attending physician, in conjunction with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are described to provide such a support.

Background In burn patients, skin barrier disruption and immune dysfunctions increase susceptibility to invasive fungal diseases (IFDs) like invasive candidiasis (IC) and invasive mold infections (IMI). We provide an in-depth analysis of IFD-related factors and outcomes in a 10-year cohort of severe burn patients. Methods This retrospective cohort study includes adult patients admitted to the burn intensive care unit (BICU) between April 2014 and May 2023 with total burn surface area (TBSA) ≥15%. Patients were classified as proven IFD according to EORTC/MSGERC criteria applicable for IC. Putative IMIs were defined with: ≥2 positive cultures from a skin biopsy/bronchoalveolar lavage or ≥2 positive blood specific-quantitative polymerase chain reactions (qPCRs) or a combination of both. Results Among 1381 patients admitted, 276 consecutive patients with TBSA ≥15% were included. Eighty-seven (31.5%; IC n = 30; IMI n = 43; both n = 14) patients fulfilled the criteria for probable/putative IFD. At Day 30 after the burn injury, the estimated cumulative incidence proven/putative (pr/pu) IFD was 26.4% (95% confidence interval [CI], 21.4%–31.8%). Factors independently associated with IFDs were TBSA, severity scores and indoor burn injury (ie, from confined space fire). Overall mortality was 15.3% and 36.8% in the no IFD, pr/pu IFD groups respectively (P <.0001). IFD was independently associated with a risk of death (hazard ratio [HR]: 1.94 for pr/pu IFD; 95% CI, 1.12–3.36; P =.019). Conclusions This study describes twenty-first-century characteristics of IFDs in severe burn patients confirming known risk factors with thresholds and identifying the indoor injury as an independent factor associated to IFDs. This suggests a link to contamination caused by fire damage, which is highly susceptible to aerosolizing spores. [ABSTRACT FROM AUTHOR]

Mucorales are ubiquitous environmental molds responsible for mucormycosis in diabetic, immunocompromised, and severely burned patients. Small outbreaks of invasive wound mucormycosis (IWM) have already been reported in burn units without extensive microbiological investigations. We faced an outbreak of IWM in our center and investigated the clinical isolates with whole-genome sequencing (WGS) analysis. We analyzed M. circinelloides isolates from patients in our burn unit (BU1, Hôpital Saint-Louis, Paris, France) together with nonoutbreak isolates from Burn Unit 2 (BU2, Paris area) and from France over a 2-year period (2013 to 2015). A total of 21 isolates, including 14 isolates from six BU1 patients, were analyzed by whole-genome sequencing (WGS). Phylogenetic classification based on de novo assembly and assembly free approaches showed that the clinical isolates clustered in four highly divergent clades. Clade 1 contained at least one of the strains from the six epidemiologically linked BU1 patients. The clinical isolates were specific to each patient. Two patients were infected with more than two strains from different clades, suggesting that an environmental reservoir of clonally unrelated isolates was the source of contamination. Only two patients from BU1 shared one strain, which could correspond to direct transmission or contamination with the same environmental source. In conclusion, WGS of several isolates per patients coupled with precise epidemiological data revealed a complex situation combining potential cross-transmission between patients and multiple contaminations with a heterogeneous pool of strains from a cryptic environmental reservoir.IMPORTANCE Invasive wound mucormycosis (IWM) is a severe infection due to environmental molds belonging to the order Mucorales. Severely burned patients are particularly at risk for IWM. Here, we used whole-genome sequencing (WGS) analysis to resolve an outbreak of IWM due to Mucor circinelloides that occurred in our hospital (BU1). We sequenced 21 clinical isolates, including 14 from BU1 and 7 unrelated isolates, and compared them to the reference genome (1006PhL). This analysis revealed that the outbreak was mainly due to multiple strains that seemed patient specific, suggesting that the patients were more likely infected from a pool of diverse strains from the environment rather than from direct transmission among them. This study revealed the complexity of a Mucorales outbreak in the settings of IWM in burn patients, which has been highlighted based on WGS combined with careful sampling.

Compartment syndrome is a serious complication of high voltage electrical burns, limb carbonization and deep circular burns with delayed escharotomy. Without treatment, ischemic tissue damage leads to irreversible necrosis. Treatment is emergency surgical decompression. The burned patient is usually not searchable and cannot always be readily examined because of bulky dressings; diagnosis of compartment syndrome is always hard to make. The pressure transducer used in central arterial catheters is easy available. We used it to measure pressure in muscular compartments. We measured compartment pressure three times at different depths in all cases of electrical burn, carbonization and deep circumferential burns with delayed escharotomy. We also took the pressure in the uninjured limb. The pressure assessment device was composed of a blood pressure transducer commonly used in arterial catheters for arterial pressure monitoring with three connecting branches. The first branch was connected to the 'arterial pressure exit' in the monitoring device. The second, an IV tube, was connected to one litre of physiological serum in a pressure bag inflated to 200 mmHg. The third, also an IV tube with a sterile extension cable, was directly connected to an 18G standard straight needle to be inserted in the tissues for which interstitial pressure had to be measured. In patients with thermal burns, we measured pressure before and after escharotomy. Threshold intracompartmental pressure was 35 mmHg. We carried out pressure assessment of all muscular compartments during and at the end of surgery. The pressure transducer provides a pressure value in all muscular compartments with a time of installation and measuring of less than 5 minutes. Sensitivity is measured at +/- 1 mmHg. Operation is simple, non-operator dependent, and accessible to medical and paramedic teams. The pressure transducer allows accurate diagnosis of early or established compartment syndrome. It requires no additional equipment and its application does not delay therapeutic management. Its use helps with fasciotomy decision, especially after escharotomy, guides the surgeon in the exploration of different compartments and verifies the effectiveness of surgery.

BackgroundIntravascular haemolysis has been associated with acute kidney injury (AKI) in different clinical settings (cardiac surgery, sickle cell disease). Haemolysis occurs frequently in critically ill burn patients. The aim of this study was to assess the predictive value of haptoglobin at admission to predict major adverse kidney events (MAKE) and AKI in critically ill burn patients.MethodsWe conducted a retrospective, single-centre cohort study in a burn critical care unit in a tertiary centre, including all consecutive severely burned patients (total burned body surface > 20% and/or shock and/or mechanical ventilation at admission) from January 2012 to April 2017 with a plasmatic haptoglobin dosage at admission.ResultsA total of 130 patients were included in the analysis. Their mean age was 49 (34-62) years, their median total body surface area burned was 29% (15-51%) and the intensive care unit (ICU) mortality was 25%. Early haemolysis was defined as an undetectable plasmatic haptoglobin at admission. We used logistic regression to identify MAKE and AKI risk factors. In multivariate analysis, undetectable haptoglobin was associated with MAKE and AKI (respectively, OR 6.33, 95% CI 2.34-16.45, p

BackgroundImpact of early systemic hemodynamic alterations and fluid resuscitation on outcome in the modern burn care remains controversial. We investigate the association between acute-phase systemic hemodynamics, timing of fluid resuscitation and outcome in critically ill burn patients.MethodsRetrospective, single-center cohort study was conducted in a university hospital. Forty critically ill burn patients with total body surface area (TBSA) burn-injured >20 % with invasive blood pressure and cardiac output monitoring (transpulmonary thermodilution technique) within 8 h from trauma were included. We retrospectively examined hemodynamic variables during the first 24 h following admission, and their association with 90-day mortality.ResultsThe median (interquartile range 25th-75th percentile) TBSA, Simplified Acute Physiology Score II (SAPS II) and Abbreviated Burn Severity Index of the study population were 41 (29-56), 31 (23-50) and 9 (7-11) %, respectively. 90-Day mortality was 42 %. There was no statistical difference between the median pre-hospital and 24-h administered fluid volume in survivors and non-survivors. On admission, stroke volume (SV), cardiac index (CI), oxygen delivery index and mean arterial pressure (MAP) were significantly lower in patients who died despite similar fluid resuscitation volume. ROC curves comparing the ability of initial SV, CI, MAP and lactate to discriminate 90-day mortality gave areas under curves of, respectively, 0.89 (CI 0.77-1), 0.77 (CI 0.58-0.95), 0.73 (CI 0.53-0.93) and 0.78 (CI 0.63-0.92); (p value

There is a paucity of articles addressing the management strategy for perineal burns. Pelvic floor burns present a multitude of problems. These relate to the management of stool, urine, areas of maceration, significant strain, and the risk of infection. The objective of this study was to analyze a consecutive series of perineal burns by studying their characteristics, treatment, and management of urine and feces. This was a retrospective study including 100 patients between January 2018 and December 2022. The patients had all been hospitalized after suffering burns to the perineum. In 28% of the patients, the perineal burn was complicated by infection. In 61% of cases, a cutaneous infection, in 32% of cases, a urinary tract infection, in 25% of cases, a respiratory tract infection, and in 7% of cases, an infection of the digestive tract. Superinfection is associated with an increased risk of poor engraftment. A total of 100% of the patients with poor or average engraftment had an infection in the aftermath of the burn, compared with 20% of the patients with excellent engraftment and 61% of the patients with good engraftment. In our series, the analysis revealed that, in 95% of cases, no specific procedures were implemented for stool management. Perianal involvement was associated with a risk of sub-excellent engraftment. The results were statistically significant, with P =.005 and an OR = 8.72 after multivariate analysis. We favor the least invasive approach to stool management. Indications for a rectal catheter arise in patients with the following characteristics: the patient must be sedated, the burns must be deep and close to the anal opening, and the stools must be watery and abundant. In 95% of cases, we do not install a stool management device. Colostomies should remain exceptional. [ABSTRACT FROM AUTHOR]

Deep soft tissue defects next to the joints can rapidly lead to irreversible damages and have to be covered urgently and effectively. In severely burned patients the usual approach is to use a flap even though it has its limitations in regards to the extent of the burn and the general condition of the patient. A 27-year-old male was admitted at the Burn Treatment Center for a thermic burn of 72% of his BSA. At first he has benefited from several skin grafts and later on a major open right elbow had to be treated urgently to rescue the joint. After the burn, a revascularization of the donor site was noticed, sufficient to use the radial forearm pedicled flap as a cover for the elbow. This case reports an innovative approach based on the use of an irrigation and drainage system placed underneath the flap. The elbow was rigidly immobilized with an external fixator in order to facilitate an optimal healing of the flap. In this case, the choice of this flap, combined with the irrigation and drainage system and the immobilization by external fixation, provided an original and efficient treatment. Postoperatively the healing of the flap and of the donor site was complete. The functional results exceeded the expectations with a complete recovery of the joint amplitude. Thus, in case of no other therapeutic options, it is probably possible to use a variety of flaps recently healed. [ABSTRACT FROM AUTHOR]

The idea that one can report on one's own death is paradoxical, if not preposterous. As Epicurus wrote in his Letter to Menoeceus, 'When we exist, death is not; and [...]