This consensus statement provides 17 different recommendations pertaining to the monitoring and caring of patients with shock. There were some important questions that could not be fully addressed using an evidence-based approach, and areas needing further research were identified.

The use of NPPV in patients with chronic obstructive pulmonary disease and acute respiratory failure requiring ventilatory support after failure of medical treatment avoided ETI in 48% of the patients, had the same ICU mortality as conventional treatment and, at 1-year follow-up was associated with fewer patients readmitted to the hospital or requiring for long-term oxygen supplementation. An editorial regarding this article can be found in the same issue (http://dx.doi.org/10.1007/s00134-002-1503-3).

We tested the effectiveness of protected bronchoalveolar lavage (PBAL), performed through a protected transbronchoscopic balloon-tipped (PBT) catheter, in collecting distal airway secretions with a minimal degree of contamination. The PBAL had less than or equal to 1% squamous epithelial cells in 91% of specimens and an absence of bacterial growth in 59% of patients without pneumonia. Using a threshold of 10(4) cfu/ml we had one false positive result in 33 patient without pneumonia and one false negative in 13 patients with pneumonia. Quantitative bacterial cultures of the PBAL specimens had a diagnostic sensitivity of 97% and a specificity of 92%, with a positive predictive value of 97% and a negative predictive value of 92%. The diagnostic efficiency was 96%. The presence of intracellular organisms in much greater than or equal to 2% of the recovered alveolar cells (Giemsa stain) was seen in all but two patients with pneumonia (on corticosteroids) and in none of the patients without pneumonia. Gram stains of the PBAL specimens were positive in all but one patient with pneumonia and negative in all but one patient without infection (patient with endobronchial narrowing secondary to neoplasm with false positive cultures). Either the Giemsa or the Gram stain was positive in all patients with pneumonia, allowing early and accurate diagnosis of lower respiratory tract infection before the results of cultures were available. The time off antibiotic therapy before bronchoscopy did not affect the result of PBAL cultures, contrary to what we observed for the protected brush specimen.

In March 2020, an expert panel called the Front Line COVID-19 Critical Care Alliance (FLCCC) was created and led by Professor Paul E. Marik, with the goal of continuously reviewing the rapidly emerging basic science, translational, and clinical data in order to gain insight into and to develop a treatment protocol for COVID-19. At the same time, many centers and groups employed a multitude of novel therapeutic agents empirically, and within clinical trials, often during inappropriate time points during this now well-described multi-phase disease. Either as a result of these frequent trial design failures, or due to the lack of their insufficient anti-viral or anti-inflammatory properties, nearly all trialed agents have proven ineffective in treating COVID-19 as of November 11, 2020. Based on a recent series of negative published therapeutic study results, in particular the SOLIDARITY trial, they now virtually eliminate any treatment role for remdesivir, hydroxychloroquine, lopinavir/ritonavir, interferon, convalescent plasma, tocilizumab, and monoclonal antibody therapy. Despite this growing list of failed therapeutics in COVID-19, the FLCCC recently discovered that ivermectin, an anti-parasitic medicine, has highly potent real-world, anti-viral, and anti-inflammatory properties against SARS-CoV-2 and COVID-19. This conclusion is based on the increasing numbers of study results reporting effectiveness, not only within vitro and animal models, but also in numerous randomized and observational controlled clinical trials. Repeated, large magnitude improvements in clinical outcomes have now been recorded when ivermectin is used not only as a prophylactic agent but also in mild, moderate, and even severe disease states. The review that follows of the existing evidence for ivermectin relies on “emerging” data in that, although compelling, only a minority of studies have been published in peer-reviewed publications with the majority of results compiled from manuscripts uploaded to medicine pre-print servers or posted on clinicaltrials.gov.

Introduction: COVID-19 disease progresses through a number of distinct phases. The management of each phase is unique and specific. The pulmonary phase of COVID-19 is characterized by an organizing pneumonia with profound immune dysregulation, activation of clotting, and a severe microvascular injury culminating in severe hypoxemia. The core treatment strategy to manage the pulmonary phase includes the combination of methylprednisolone, ascorbic acid, thiamine, and heparin (MATH+ protocol). The rationale for the MATH+ protocol is reviewed in this paper. Areas covered: We provide an overview on the pathophysiological changes occurring in patients with COVID-19 respiratory failure and a treatment strategy to reverse these changes thereby preventing progressive lung injury and death. Expert opinion: While there is no single 'Silver Bullet' to cure COVID-19, we believe that the severely disturbed pathological processes leading to respiratory failure in patients with COVID-19 organizing pneumonia will respond to the combination of Methylprednisone, Ascorbic acid, Thiamine, and full anticoagulation with Heparin (MATH+ protocol).We believe that it is no longer ethically acceptable to limit management to 'supportive care' alone, in the face of effective, safe, and inexpensive medications that can effectively treat this disease and thereby reduce the risk of complications and death.

To assess markers of lung inflammation, we used SELDI-TOF and 2-DE to study changes in bronchoalveolar lavage (BAL) protein in 33 subjects challenged with local bronchial lung endotoxin and saline and in 11 patients with acute respiratory distress syndrome (ARDS). Differences in the SELDI-TOF spectra were assessed by t-test after baseline subtraction, normalization to total ion current and alignment by m/z calibration. The temporal changes in acute inflammatory BAL (6, 24 and 48 h following endotoxin challenge) on hydrophobic binding chip surfaces revealed the differential presence of proteins of 9, 14, 18 and 28 kDa (all p <0.001) in the inflammatory BAL. This differential pattern was also found in the ARDS BAL. Principal component analysis of the entire SELDI-TOF spectra separated normal BAL, experimental and clinical lung inflammation supporting the notion of a distinctive protein pattern associated with acute lung inflammation. An analysis of the hydrophobic fraction of the inflammatory BAL using 2-DE, identified increased levels of apolipoprotein A1, and S100 calcium-binding proteins A8 and A9 in the inflammatory BAL. This pattern was also found in ARDS BAL after immunoblot analysis. These approaches will be useful to improve current methods of monitoring lung inflammation and to identify new therapeutic targets.

In early acute respiratory distress syndrome, administration of methylprednisolone was associated with improvement in important biomarkers of inflammation and coagulation and clinical outcomes. Biomarker changes varied with the precipitating cause of acute respiratory distress syndrome, suggesting that the underlying mechanisms and response to anti-inflammatory therapy may vary with the cause of acute respiratory distress syndrome.

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