SPLF/SMFU/SRLF/SFAR/SFCTCV Guidelines for the management of patients with primary spontaneous pneumothorax.

INTRODUCTION: Primary spontaneous pneumothorax (PSP) is the presence of air in the pleural space, occurring in the absence of trauma and known lung disease. Standardized expert guidelines on PSP are needed due to the variety of diagnostic methods, therapeutic strategies and medical and surgical disciplines involved in its management. METHODS: Literature review, analysis of the literature according to the GRADE (Grading of Recommendation, Assessment, Development and Evaluation) methodology; proposals for guidelines rated by experts, patients and organizers to reach a consensus. Only expert opinions with strong agreement were selected. RESULTS: A large PSP is defined as presence of a visible rim along the entire axillary line between the lung margin and the chest wall and ≥ 2 cm at the hilum level on frontal chest X-ray. The therapeutic strategy depends on the clinical presentation: emergency needle aspiration for tension PSP; in the absence of signs of severity: conservative management (small PSP), needle aspiration or chest tube drainage (large PSP). Outpatient treatment is possible if a dedicated outpatient care system is previously organized. Indications, surgical procedures and perioperative analgesia are detailed. Associated measures, including smoking cessation, are described. CONCLUSION: These guidelines are a step towards PSP treatment and follow-up strategy optimization in France.

SPLF/SMFU/SRLF/SFAR/SFCTCV Guidelines for the management of patients with primary spontaneous pneumothorax: Endorsed by the French Speaking Society of Respiratory Diseases (SPLF), the French Society of Emergency Medicine (SFMU), the French Intensive Care Society (SRLF), the French Society of Anesthesia & Intensive Care Medicine (SFAR) and the French Society of Thoracic and Cardiovascular Surgery (SFCTCV).

INTRODUCTION: Primary spontaneous pneumothorax (PSP) is the presence of air in the pleural space, occurring in the absence of trauma and known lung disease. Standardized expert guidelines on PSP are needed due to the variety of diagnostic methods, therapeutic strategies and medical and surgical disciplines involved in its management. METHODS: Literature review, analysis of literature according to the GRADE (Grading of Recommendation Assessment, Development and Evaluation) methodology; proposals for guidelines rated by experts, patients, and organizers to reach a consensus. Only expert opinions with strong agreement were selected. RESULTS: A large PSP is defined as presence of a visible rim along the entire axillary line between the lung margin and the chest wall and ≥2 cm at the hilum level on frontal chest x-ray. The therapeutic strategy depends on the clinical presentation: emergency needle aspiration for tension PSP; in the absence of signs of severity: conservative management (small PSP), needle aspiration or chest tube drainage (large PSP). Outpatient treatment is possible if a dedicated outpatient care system is previously organized. Indications, surgical procedures and perioperative analgesia are detailed. Associated measures, including smoking cessation, are described. CONCLUSION: These guidelines are a step towards PSP treatment and follow-up strategy optimization in France.

Acute cholangitis in intensive care units: clinical, biological, microbiological spectrum and risk factors for mortality: a multicenter study.

BACKGROUND: Little is known on the outcome and risk factors for mortality of patients admitted in Intensive Care units (ICUs) for Acute cholangitis (AC). METHODS: Retrospective multicenter study included adults admitted in eleven intensive care units for a proven AC from 2005 to 2018. Risk factors for in-hospital mortality were identified using multivariate analysis. RESULTS: Overall, 382 patients were included, in-hospital mortality was 29%. SOFA score at admission was 8 [5-11]. Biliary obstruction was mainly related to gallstone (53%) and cancer (22%). Median total bilirubin and PCT were respectively 83 µmol/L [50-147] and 19.1 µg/L [5.3-54.8]. Sixty-three percent of patients (n = 252) had positive blood culture, mainly Gram-negative bacilli (86%) and 14% produced extended spectrum beta lactamase bacteria. At ICU admission, persisting obstruction was frequent (79%) and biliary decompression was performed using therapeutic endoscopic retrograde cholangiopancreatography (76%) and percutaneous transhepatic biliary drainage (21%). Adjusted mortality significantly decreased overtime, adjusted OR for mortality per year was 0.72 [0.54-0.96] (p = 0.02). In a multivariate analysis, factors at admission associated with in-hospital mortality were: SOFA score (OR 1.14 [95% CI 1.05-1.24] by point, p = 0.001), lactate (OR 1.21 [95% CI 1.08-1.36], by 1 mmol/L, p < 0.001), total serum bilirubin (OR 1.26 [95% CI 1.12-1.41], by 50 µmol/L, p < 0.001), obstruction non-related to gallstones (p < 0.05) and AC complications (OR 2.74 [95% CI 1.45-5.17], p = 0.002). Time between ICU admission and biliary decompression > 48 h was associated with in-hospital mortality (adjusted OR 2.73 [95% CI 1.30-6.22], p = 0.02). CONCLUSIONS: In this large retrospective multicenter study, we found that AC-associated mortality significantly decreased overtime. Severity of organ failure, cause of obstruction and local complications of AC are risk factors for mortality, as well as delayed biliary drainage > 48 h.

Trajectories of acute graft-versus-host disease and mortality in critically ill allogeneic-hematopoietic stem cell recipients: the Allo-GRRR-OH score.

Acute graft-versus-host disease (aGVHD) is a major cause of morbidity mortality in critically ill hematopoietic stem cell transplantation recipients. We assessed aGVHD trajectories in 191 allogeneic-HSCT recipients (age 42 (27-46)) admitted to our ICU between 2005 and 2015. aGVHD affected 130 (68%) patients (including 90% who underwent steroid therapy at a dose of 2 (2-2) mg/kg) and was graded 3 or 4 in 31% of the patients. Trajectories of aGVHD were clustered in four groups: (1) no aGVHD, (2) controlled aGVHD, (3) uncontrolled aGVHD (active, stable, or worsening), and (4) newly diagnosed and untreated aGVHD. Patients with controlled aGVHD and those admitted at the onset of aGVHD had similar survival than patients who never experienced aGVHD. By multivariable analysis, the dynamic assessment of aGVHD was independently associated with 90-day mortality, in addition to the admission to the ICU for acute respiratory failure, acute kidney injury or acute liver failure, and sepsis-related organ failure assessment score at admission. In conclusion, these findings suggest that GVHD cannot be assessed as a binary variable and at a single time point. Patients in whom GVHD is not uncontrolled with corticosteroids should have the same goals of ICU care than patients without GVHD.

Renal recovery after severe acute kidney injury in critically ill myeloma patients: a retrospective study.

BACKGROUND: Despite substantial improvements in the management of multiple myeloma, renal failure remains an important burden that tremendously impairs prognosis. The purpose of this study was to describe the characteristics and to establish prognostic factors of renal recovery in myeloma patients admitted to the intensive care unit (ICU) for acute kidney injury (AKI) Stage 3 treated with renal replacement therapy (RRT). METHODS: A retrospective single-centre cohort study was performed, including consecutive myeloma patients admitted to one medical ICU between 1 January 2007 and 1 September 2015 and treated with RRT. Patients were evaluated 60 days after initiation of RRT and divided into three groups: alive without dialysis, alive and dialysis-dependent or deceased. A univariate analysis was performed to identify factors associated with renal recovery (alive without dialysis 60 days after initiation of RRT). RESULTS: Fifty patients were included in the study. Mean age was 63 (interquartile range: 58-70) years and 32 (64%) were male. Patients were admitted to the ICU 4 (1-7) years after the diagnosis of myeloma. Twenty-one (42%) had already been treated with high-dose therapy combined with autologous stem cell transplantation. Baseline renal function evaluated by estimated glomerular filtration rate (GFR) before ICU admission was 63 (44-90) mL/min/1.73 m2. The mean SOFA score at Day 1 was 7 (4-8). The three main reasons for ICU admission were AKI (n = 31, 62%), acute pulmonary oedema (n = 17, 32%) and sepsis (n = 10, 20%). During ICU stay, RRT was implemented in all patients, 16 (32%) patients required invasive mechanical ventilation and 12 (24%) received vasopressors. The mean ICU and hospital length of stay were 6 (1-7) and 28 (13-34) days, respectively. At Day 60, 23 (46%) patients were alive without dialysis, 17 (32%) had died and 10 (20%) were still undergoing dialysis. Among the 23 patients who recovered, the mean duration of dialysis was 6 (2-18) days and renal function was not significantly different from baseline [estimated GFR at baseline = 65 (25-74) mL/min/1.73 m2 versus 63 (56-70) mL/min/1.73 m2 at Day 60, P = 0.70]. By univariate analysis, two factors were associated with nonrecovery of renal function at Day 60: a history of high-dose therapy combined with autologous stem cell transplantation [odds ratio (OR) = 6.1, 95% confidence interval (CI) 1.7-21.6; P = 0.008] and a proteinuria at ICU admission >370 mg/mmol creatinine (OR = 4.2, 95% CI 1.1-17; P = 0.02). None of the other variables related to the haematological malignancy or to the ICU stay was associated with renal recovery at Day 60. CONCLUSIONS: AKI Stage 3 in critically ill myeloma patients was associated with a lower than expected hospital mortality. Patients with a high level of proteinuria and a history of high-dose therapy combined with autologous stem cell transplantation were less likely to recover their renal function at Day 60. KEY WORDS: dialysis, intensive care, multiple myeloma, prognosis, proteinuria.

Short- and long-term outcomes of AL amyloidosis patients admitted into intensive care units.

Amyloidosis is a rare and threatening condition that may require intensive care because of amyloid deposit-related organ dysfunction or therapy-related adverse events. Although new multiple myeloma drugs have dramatically improved outcomes in AL amyloidosis, the outcomes of AL patients admitted into intensive care units (ICUs) remain largely unknown. Admission has been often restricted to patients with low Mayo Clinic staging and/or with a complete or very good immunological response at admission. In a retrospective multicentre cohort of 66 adult AL (n = 52) or AA (n = 14) amyloidosis patients, with similar causes of admission to an ICU, the 28-d and 6-month survival rates of AA patients were significantly higher compared to AL patients (93% vs. 60%, P = 0·03; 71% vs. 45%, P = 0·02, respectively). In AL patients, the simplified Index of Gravity Score (IGS2) was the only independent predictive factor for death by day 28, whereas the Mayo-Clinic classification stage had no influence. In Cox's multivariate regression model, only cardiac arrest and on-going chemotherapy at ICU admission significantly predicted death at 6 months. Short-term outcomes of AL patients admitted into an ICU were mainly related to the severity of the acute medical condition, whereas on-going chemotherapy for active amyloidosis impacted on long-term outcomes.

Sleep in the intensive care unit / Sono na unidade de terapia intensiva

ABSTRACT Poor sleep quality is a consistently reported by patients in the ICU. In such a potentially hostile environment, sleep is extremely fragmented and sleep architecture is unconventional, with a predominance of superficial sleep stages and a limited amount of time spent in the restorative stages. Among the causes of sleep disruption in the ICU are factors intrinsic to the patients and the acute nature of their condition, as well as factors related to the ICU environment and the treatments administered, such as mechanical ventilation and drug therapy. Although the consequences of poor sleep quality for the recovery of ICU patients remain unknown, it seems to influence the immune, metabolic, cardiovascular, respiratory, and neurological systems. There is evidence that multifaceted interventions focused on minimizing nocturnal sleep disruptions improve sleep quality in ICU patients. In this article, we review the literature regarding normal sleep and sleep in the ICU. We also analyze sleep assessment methods; the causes of poor sleep quality and its potential implications for the recovery process of critically ill patients; and strategies for sleep promotion.

RESUMO O sono de má qualidade é uma situação persistentemente descrita em UTIs. O sono nesse ambiente potencialmente hostil é caracterizado pela sua extrema fragmentação e arquitetura não convencional, com predomínio de fases leves e limitada quantidade de tempo nos estágios reparadores. Entre as causas da privação do sono na UTI estão fatores intrínsecos aos pacientes e à condição aguda de sua doença, assim como fatores relacionados ao ambiente da UTI e ao tratamento em curso, como o suporte ventilatório e a terapia medicamentosa. Embora as consequências da má qualidade do sono no processo de recuperação desses pacientes ainda sejam desconhecidas, ela parece influenciar os sistemas imune, metabólico, cardiovascular, respiratório e neurológico. Evidências sugerem que intervenções multifacetadas, focadas na minimização das perturbações do sono noturno, promovem melhora na qualidade do sono nesses pacientes. Este artigo revisa a literatura acerca do sono normal e do sono na UTI. Também analisa seus métodos de avaliação, as causas da má qualidade do sono, suas potenciais implicações no processo de recuperação de pacientes críticos e estratégias para sua promoção.

A case of melphalan sustained accumulation in an 80-year old patient.

Case We report the case of melphalan accumulation in an 80-year old female with multiple myeloma. Her initial health status was good except for a moderate chronic renal failure (estimated glomerular filtration rate: 31 ml/min) and anemia. Among other drugs, her usual treatment included trimethoprim/sulfamethoxazole and the patient received melphalan from day 1 to day 4 for multiple myeloma. On day 13, she was admitted in intensive care unit for acute renal failure and severe sepsis with pancytopenia. Usual treatments were stopped. Melphalan blood concentrations were 123.6 ng/ml on day 16 and 87.5 ng/ml on day 17 while cerebrospinal fluid concentration was 173.8 ng/ml on day 25. Patient recovered on day 30. Melphalan accumulation may be explained by substrate competition between sulfamethoxazole and melphalan in metabolism pathway and chronic renal failure. Conclusion close clinical and renal monitoring should be performed in patient receiving melphalan and sulfamethoxazole.

The complex relationship between human herpesvirus 6 and acute graft-versus-host disease.

The most frequent manifestation of human herpesvirus 6 (HHV-6) reactivation after allogeneic hematopoietic stem cell transplantation (HSCT) is febrile rash, raising the question of its relationship with graft-versus-host disease (GVHD). In this retrospective analysis of 365 patients who underwent allogeneic HSCT, HHV-6 reactivation was significantly associated with cord blood transplantation (hazard ratio [HR], 3.20; P < .0001) and the use of unrelated donors (HR, 2.02; P = .008). On multivariate analysis, previous GVHD was a predictive factor for HHV-6 reactivation (HR, 1.80; P = .01), and previous HHV-6 reactivation was a predictive factor for acute GVHD (HR, 1.66; P = .03). Nineteen patients with no pathological evidence of GVHD later developed severe clinical GVHD (grade III-IV), suggesting the role of HHV-6 as a trigger for severe GVHD. Furthermore, 17 patients without histopathological GVHD demonstrated a significant lymphoid infiltrate suggesting "pure" HHV-6-related manifestations, and these patients could have been spared steroid therapy.

Th17/Treg ratio in human graft-versus-host disease.

Th17 cells have never been explored in human graft-versus-host disease (GVHD). We studied the correlation between the presence of Th17 cells with histologic and clinical parameters. We first analyzed a cohort of 40 patients with GVHD of the gastrointestinal tract. Tumor necrosis factor (TNF), TNF receptors, and Fas expression, and apoptotic cells, CD4(+)IL-17(+) cells (Th17), and CD4(+)Foxp3(+) cells (Treg) were quantified. A Th17/Treg ratio less than 1 correlated both with the clinical diagnosis (P < .001) and more than 2 pathologic grades (P < .001). A Th17/Treg ratio less than 1 also correlated with the intensity of apoptosis of epithelial cells (P = .03), Fas expression in the cellular infiltrate (P = .003), TNF, and TNF receptor expression (P < .001). We then assessed Th17/Treg ratio in 2 other independent cohorts; a second cohort of 30 patients and confirmed that Th17/Treg ratio less than 1 correlated with the pathologic grade of GI GVHD. Finally, 15 patients with skin GVHD and 11 patients with skin rash but without pathologic GVHD were studied. Results in this third cohort of patients with skin disease confirmed those found in patients with GI GVHD. These analyses in 96 patients suggest that Th17/Treg ratio could be a sensitive and specific pathologic in situ biomarker of GVHD.

Mutations of the selenoprotein N gene, which is implicated in rigid spine muscular dystrophy, cause the classical phenotype of multiminicore disease: reassessing the nosology of early-onset myopathies.

Multiminicore disease (MmD) is an autosomal recessive congenital myopathy characterized by the presence of multiple, short core lesions (known as "minicores") in most muscle fibers. MmD is a clinically heterogeneous condition, in which four subgroups have been distinguished. Homozygous RYR1 mutations have been recently identified in the moderate form of MmD with hand involvement. The genes responsible for the three other forms (including the most prevalent phenotype, termed the "classical" phenotype) remained, so far, unknown. To further characterize the genetic basis of MmD, we analyzed a series of 62 patients through a combined positional/candidate-gene approach. On the basis of clinical and morphological data, we suspected a relationship between classical MmD and the selenoprotein N gene (SEPN1), which is located on chromosome 1p36 (RSMD1 locus) and is responsible for the congenital muscular dystrophy with rigid spine syndrome (RSMD). A genomewide screening, followed by the analysis of 1p36 microsatellite markers in 27 informative families with MmD, demonstrated linkage to RSMD1 in eight families. All showed an axial myopathy with scoliosis and respiratory failure, consistent with the most severe end of the classical MmD spectrum; spinal rigidity was evident in some, but not all, patients. We excluded linkage to RSMD1 in 19 families with MmD, including 9 with classical MmD. Screening of SEPN1 in the 8 families that showed linkage and in 14 patients with classical sporadic disease disclosed 9 mutations affecting 17 patients (12 families); 6 were novel mutations, and 3 had been described in patients with RSMD. Analysis of three deltoid biopsy specimens from patients with typical RSMD revealed a wide myopathological variability, ranging from a dystrophic to a congenital myopathy pattern. A variable proportion of minicores was found in all the samples. The present study represents the first identification of a gene responsible for classical MmD, demonstrates its genetic heterogeneity, and reassesses the nosological boundaries between MmD and RSMD.