Stenotrophomonas maltophilia pneumonia in critical COVID-19 patients.

Stenotrophomonas maltophilia, an environmental aerobic non-fermentative Gram-negative bacilli, has gained attention in many nosocomial outbreaks. COVID-19 patients in intensive care unit have extended hospital stay and are severely immunosuppressed. This study aimed to determine the prevalence and risk factors of S. maltophilia pneumonia in critical COVID-19 patients. A total of 123 COVID-19 patients in ICU admitted between March 2020 and March 2021 were identified from the authors' institutional database and assessed for nosocomial pneumonia. Demographic data and factors predisposing to S. maltophilia pneumonia were collected and analyzed. The mean age was 66 ± 13 years and 74% were males. Median APACHE and SOFA scores were 13 (IQR = 8-19) and 4 (3-6), respectively. The Median NEWS2 score was 6 (Q1 = 5; Q3 = 8). The Median ICU stay was 12 (Q1 = 7; Q3 = 22) days. S. maltophilia was found in 16.3% of pneumonia patients, leading to a lengthier hospital stay (34 vs. 20 days; p < 0.001). Risk factors for S. maltophilia pneumonia included previous treatment with meropenem (p < 0.01), thrombopenia (p = 0.034), endotracheal intubation (p < 0.001), foley catheter (p = 0.009) and central venous catheter insertion (p = 0.016). S. maltophilia nosocomial pneumonia is frequent in critical COVID-19 patients. Many significant risk factors should be addressed to reduce its prevalence and negative impact on outcomes.

Pirfenidone mitigates TGF-ß1-mediated fibrosis in an idiopathic inflammatory myositis-associated interstitial lung disease model.

Idiopathic inflammatory myositis (IIM) is a group of rare diseases of unknown etiology, with a pathognomonic muscular deficiency. Antisynthetase syndrome is a subtype of IIM with an associated interstitial lung disease (ILD), characterized by pulmonary inflammation and fibrosis mediated by TGF-ß. Pirfenidone is a new molecule with anti-inflammatory and anti-fibrotic properties, used for the treatment of idiopathic ILD, but has never been assessed in IIM. The aim of our study is to evaluate the effect of pirfenidone on IIM-associated ILD. Thirty-two BALB/c male mice were divided into three groups: Sham, IIM-untreated (IIM), and IIM pirfenidone-treated (IIM + PIR). IIM was induced by intramuscular injections of guinea pig muscle myosin extract and intraperitoneal injections of Pertussis toxin. Pirfenidone was given orally at a dose of 30 mg kg-1 day-1 for two months. Muscle force, blood and bronchoalveolar lavage fluid samples, as well as muscle and lung tissues, were analyzed. Progressive deterioration of muscle force and infiltration of the muscular tissue by inflammatory cells were observed with IIM. Auto-immune antibodies specific to the antisynthetase syndrome were also increased in IIM mice. Pirfenidone attenuated IIM-associated ILD with anti-inflammatory properties evidenced by decreased peribronchial inflammation and TGF-ß1 in bronchoalveolar lavage fluid. Likewise, pirfenidone attenuated pulmonary fibrosis by fine-tuning TGF-ß1-mediated epithelial-to-mesenchymal and fibrotic signaling pathways; pro-fibrotic SMAD3, ZEB2 and STAT1 expression and activation were decreased, whereas anti-fibrotic SMAD2 activation was increased. This study unravels for the first time that pirfenidone has the potential to fine-tune TGF-ß1 fibrotic signaling in IIM-associated ILD.

Hydrocortisone mitigates ICU-AW by fine-tuning of muscle atrophic and hypertrophic signaling pathways in a sepsis model with limb immobilization.

AIMS: Intensive care unit-acquired weakness (ICU-AW) is a complex spectrum of disability that delays recovery of critically ill-immobilized patients with sepsis. Much discrepancy remain on the use of corticosteroids and their impact on muscle regeneration in critical illness management. Therefore, the aim of this study is to investigate whether hydrocortisone (HCT) modulates muscle mass turnover in ICU-AW induced by sepsis with limb immobilization (SI). MAIN METHODS: Sepsis by cecal ligation puncture (CLP) with forelimb-immobilization were performed in rats. The study consisted of four groups: Sham (left forelimb-immobilization), Sham HCT (left forelimb-immobilization + HCT), SI (CLP + left forelimb-immobilization) and SI HCT (CLP + left forelimb-immobilization + HCT). Motor force, blood and muscle sampling were assessed. KEY FINDINGS: HCT prevented body weight loss associated with SI and attenuated systemic and muscular inflammation. Besides, myosin was restituted in SI HCT group in conjunction to muscle mass and strength restoration. Pro-hypertrophic calcineurin (PP2B-Aß) and nuclear factor of activated T-cells C3 (NFATc3) but not protein kinase B (Akt) were re-activated by HCT. Finally, pro-atrophic extracellular signal-regulated kinases (ERK1/2) and p38 mitogen-activated protein kinases (p38) but not nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) were inhibited in SI HCT group. SIGNIFICANCE: This study unravels new molecular events thought to control muscle protein synthesis in ICU-AW induced by sepsis and limb immobilization. HCT has a potential to fine-tune muscle-signaling pathways and to reduce the negative outcomes of ICU-AW.

Post-transfusion platelet responses in critically ill cancer patients with hypoproliferative thrombocytopenia.

BACKGROUND: Platelet transfusion is aimed at increasing platelet counts to prevent or treat bleeding. Critically ill cancer patients with hypoproliferative thrombocytopenia are high consumers of blood products. We herein described their post-transfusion platelet responses in the intensive care unit (ICU) and analyzed the determinants of poor post-transfusion increments. STUDY DESIGN AND METHODS: This was a single-center 9-year (2009-2017) retrospective observational study. Patients with malignancies and presumed or proven hypoproliferative thrombocytopenia who had received at least one platelet transfusion in the ICU were included. Poor post-transfusion platelet increments were defined as body surface-adjusted corrected count increment (CCI) <7, or alternatively as weight-adjusted platelet transfusion recovery (PTR) <0.2. Patients were deemed refractory to platelet transfusions when two consecutive ABO-compatible transfusions resulted in poor platelet increments. RESULTS: A total of 1470 platelet transfusions received by 326 patients were analyzed. Indications for platelet transfusions were distributed into prophylactic (44.5%), peri-procedural (18.1%) and therapeutic (37.4%). Regardless of indications, 54.6% and 55.4% of transfusion episodes were associated with a CCI <7 or a PTR <0.2. Factors independently associated with poor post-transfusion increments were lower body mass index, spleen enlargement, concurrent severity of clinical condition, fever ≥39°C, antibiotic therapy and increased storage duration of platelet concentrates. Eventually, 48 patients developed refractoriness to platelet transfusion, which was associated increased incidence of bleeding events. CONCLUSION: Platelet transfusions are often associated with poor increments in critically ill cancer patients with hypoproliferative thrombocytopenia. The findings suggest amenable interventions to improve the platelet transfusion practices in this setting.

A randomized double-blind controlled trial comparing three sedation regimens during flexible bronchoscopy: Dexmedetomidine, alfentanil and lidocaine.

INTRODUCTION: No standardized sedation protocol is available for flexible bronchoscopy (FB). OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of three regimens used for sedation during FB. METHODS: This randomized double-blind controlled trial assessed patients undergoing bronchoscopy and receiving lidocaine alone (C) or combined with dexmedetomidine (D) or alfentanil (A). Tolerance was assessed using the bronchoscopy score, and level of sedation was assessed using the Nursing Instrument for the Communication of Sedation. Safety was evaluated in terms of pulmonary function and vital signs. RESULTS: A total of 162 patients were enrolled. The bronchoscopy score was identical in all groups. Group D subjects were the most sedated (P = .013), whereas group A subjects were the least agitated. Linear regression showed a negative association between bronchoscopy score and age in A (ß = -0.06; P = .001). Positive predictors of bronchoscopy score were female gender (ß = 1.96; P = .003) in D and obesity (ß = 2.41; P = .012), longer procedures (ß = 0.08; P = .009) and female gender (ß = 1.15; P = .038) in C. Longer procedures (ß = -0.12; P = .010) was a negative predictor of bronchoscopy score in D. Desaturation, hypoxia and heart rate changes were most prevalent in group A. Hypotension was mostly observed in D. CONCLUSIONS: No consistent differences were present between the three regimens; however, each was more appropriate in certain patient profiles. We consequently proposed a protocol as a first step towards standardizing sedation practice in FB in a patient-tailored manner. A more comprehensive and detailed protocol including other sedative agents with their corresponding doses should be developed.

Platelet transfusions in cancer patients with hypoproliferative thrombocytopenia in the intensive care unit.

BACKGROUND: Thrombocytopenia is a frequent finding in critically ill cancer patients for whom indications of platelet transfusions are unclear. We herein addressed the current practices in platelet transfusion and the risk of bleeding in cancer patients with hypoproliferative thrombocytopenia in the intensive care unit (ICU). METHODS: A retrospective monocenter study over a 7-year period was conducted in a medical ICU. Adult patients with malignancies and hypoproliferative thrombocytopenia, and who received at least one platelet concentrate during their ICU stay, were included. RESULTS: 296 patients were included and received a total of 904 platelet transfusions, for prophylactic indications in 300 (33.2 %) episodes, for securing an invasive procedure in 257 (28.4 %), and for treatment of minor to major bleeding manifestations in 347 (38.4 %). Most prophylactic transfusions (80 %) were performed at platelet count thresholds below 10-20 × 10(9)/L. Platelet increments were generally low in all three indications, 10 (interquartile range 2-25), 11 (2-25), and 8 (0-21) × 10(9)/L, respectively. A total of 97 major ICU-acquired bleeding events occurred in 40 patients. About half of those bleeding episodes (54.7 %) occurred at platelet counts below 20 × 10(9)/L. However, neither low admission platelet count nor low nadir platelet counts were predictive of ICU-acquired bleeding. The in-ICU mortality rate tended to be higher in patients with severe ICU-acquired bleeding events (50 vs. 36 %). CONCLUSIONS: Most prophylactic platelet transfusions were given using thresholds of 10-20 × 10(9)/L in critically ill thrombocytopenic cancer patients. The individual risk of ICU-acquired severe bleeding appears hardly predictable with the depth of thrombocytopenia.

Shoshin Beriberi in Critically-Ill patients: case series.

Thiamine plays a fundamental role in cellular metabolism. The classical syndrome caused by thiamine deficiency is beriberi, and its fulminant variant, once considered an uncommon finding, is now encountered among the critically ill.We present a case series of four critically ill non-septic non-alcoholic patients with severe lactic acidosis and refractory cardio-circulatory collapse caused by acute fulminant beriberi, which drastically responded to thiamine administration.In critical care settings, increased awareness of this life-threatening but reversible condition is a requirement, especially among patients receiving parenteral nutrition and those with unexplained recalcitrant lactic acidosis.