Ventilator -associated Pneumonia and Lung Ultrasound: Finally,What is between the Ears Matters

How to cite this article: Gopaldas JA, Kumar AKA. Ventilator-associatedPneumonia and Lung Ultrasound: Finally, What is between the EarsMatters. Indian J Crit Care Med 2021;25(9):1075–1076.     

COVID-19 and Sepsis

The COVID-19 pandemic has created a major alteration in the medical literature including the sepsis discussion. From the outset of the pandemic, various reports have indicated that although there are some unique features pertinent to COVID-19, many of its acute manifestations are similar to sepsis caused by other pathogens. As a consequence, the old definitions now require consideration of this new etiologic agent, namely SARS-CoV-2. Although the pathogenesis of COVID-19 has not been fully explained, the data obtained so far in hospitalized patients has revealed that serum cytokine and chemokine levels are high in severe COVID-19 patients, similar to those found with sepsis. COVID-19 may involve multiple organ systems. In addition to the lungs, the virus has been isolated from blood, urine, faeces, liver, and gallbladder. Results from autopsy series in COVID-19 patients have demonstrated a wide range of findings, including vascular involvement, congestion, consolidation, and hemorrhage as well as diffuse alveolar damage in lung tissue consistent with acute respiratory distress syndrome (ARDS). The presence of viral cytopathic-like changes, infiltration of inflammatory cells (mononuclear cells and macrophages), and viral particles in histopathological samples are considered a consequence of both direct viral infection and immune hyperactivation. Thromboembolism and hyper-coagulopathy are other components in the pathogenesis of severe COVID-19. Although the pathogenesis of hypercoagulability is not fully understood, it has been pointed out that all three components of Virchow’s triad (endothelial injury, stasis, and hypercoagulable state) play a major role in contributing to clot formation in severe COVID-19 infection. In severe COVID-19 cases, laboratory parameters such as hematological findings, coagulation tests, liver function tests, D-dimer, ferritin, and acute phase reactants such as CRP show marked alterations, which are suggestive of a cytokine storm. Another key element of COVID-19 pathogenesis in severe cases is its similarity or association with hemophagocytic lymphohistiocytosis (HLH). SARS-CoV-2 induced cytokine storm has significant clinical and laboratory findings overlapping with HLH. Viral sepsis has some similarities but also some differences when compared to bacterial sepsis. In bacterial sepsis, systemic inflammation affecting multiple organs is more dominant than in COVID-19 sepsis. While bacterial sepsis causes an early and sudden onset clinical deterioration, viral diseases may exhibit a relatively late onset and chronic course. Consideration of severe COVID-19 disease as a sepsis syndrome has relevance and may assist in terms of determining treatments that will modulate the immune response, limit intrinsic damage to tissue and organs, and potentially improve outcome.     

Pre-treatment tumor expression of ERCC1 in women with advanced stage epithelial ovarian cancer is not predictive of clinical outcomes: a Gynecologic Oncology Group study

Objective

Excision repair cross-complementation group 1 (ERCC1) is required for the repair of platinum-induced DNA damage. This study sought to assess the prognostic value of ERCC1 expression, measured by immunohistochemistry (IHC) using a highly specific antibody, in advanced epithelial ovarian cancer (EOC) patients treated with platinum-based chemotherapy.

Methods

Formalin-fixed, paraffin-embedded tumors were collected from two GOG phase III trials (GOG-172 and GOG-182) of patients with stage III/IV EOC treated with platinum-based chemotherapy. ERCC1 was detected by (IHC) using FL297 polyclonal antibody and tumors were categorized as negative or positive, based on nuclear staining of tumor cells. ERCC1 genotyping was performed as previously reported. Associations between ERCC1 expression and clinical characteristics, platinum responsiveness, progression-free survival (PFS) or overall survival (OS) were evaluated.

Results

Of 408 eligible patients, 27% had tumors that were ERCC1 positive. ERCC1 expression was not associated with clinical characteristics or platinum-responsiveness. Women with ERCC1-positive versus -negative tumors had similar median PFS (17.9 months versus 17.5 months, respectively, p = 0.59), median OS (52.0 months versus 47.0 months, respectively, p = 0.30), risk of disease progression (adjusted hazard ratio [HR] = 0.90, 95% confidence interval (CI): 0.71-1.15, p = 0.41), and risk of death (adjusted HR = 0.81, 95% CI: 0.61-1.07, p = 0.14). ERCC1 expression, as measured by IHC, was not associated with single nucleotide polymorphisms (SNPs), in codon 118 and C8092A, of the ERCC1 gene.

Conclusions

ERCC1 expression, measured by IHC in pre-treatment tumor specimens, using a highly specific antibody, has limited clinical value in patients with advanced EOC treated with platinum and taxane based chemotherapy.     

Systematic review comparing endoscopic,percutaneous and surgical pancreatic pseudocyst drainage

AIM: To perform a systematic review comparing the outcomes of endoscopic, percutaneous and surgical pancreatic pseudocyst drainage.METHODS: Comparative studies published between January 1980 and May 2014 were identified on Pub Med, Embase and the Cochrane controlled trials register and assessed for suitability of inclusion. The primary outcome was the treatment success rate. Secondary outcomes included were the recurrence rates, re-interventions, length of hospital stay, adverse events and mortalities.RESULTS: Ten comparative studies were identified and 3 were randomized controlled trials. Four studies reported on the outcomes of percutaneous and surgical drainage. Based on a large-scale national study, surgical drainage appeared to reduce mortality and adverse events rate as compared to the percutaneous approach. Three studies reported on the outcomes of endoscopic ultrasound(EUS) and surgical drainage. Clinical success and adverse events rates appeared to be comparable but the EUS approach reduced hospital stay, cost and improved quality of life. Three other studies comparedEUS and esophagogastroduodenoscopy-guided drainage. Both approaches were feasible for pseudocyst drainage but the success rate of the EUS approach was better for non-bulging cyst and the approach conferred additional safety benefits.CONCLUSION: In patients with unfavorable anatomy, surgical cystojejunostomy or percutaneous drainage could be considered. Large randomized studies with current definitions of pseudocysts and longer-term follow-up are needed to assess the efficacy of the various modalities.     

Reduction in circulating markers of endothelial dysfunction in HIV-infected patients during antiretroviral therapy

Objectives

Antiretroviral therapy (ART) in HIV‐infected patients is associated with increased cardiovascular risk. Circulating markers of endothelial dysfunction may be used to study early atherogenesis. The aim of our study was to investigate changes in such markers during initiation of ART.

Methods

In 115 HIV‐positive treatment‐naïve patients, plasma lipids, E‐selectin, soluble intercellular adhesion molecule 1 (sICAM‐1), soluble vascular cell adhesion molecule 1 (sVCAM‐1), tissue‐type plasminogen activator inhibitor 1 (tPAI‐1) and high‐sensitivity C‐reactive protein (hsCRP) were measured before and after 2 and 14 months of ART. A control group of 30 healthy subjects was included. Values are mean±standard error of the mean.

Results

Prior to treatment, HIV‐infected patients had elevated levels of sICAM‐1 (296±24 vs. 144±12 ng/mL), tPAI‐1 (18 473±1399 vs. 5490±576 pg/mL) and hsCRP (28 060±5530 vs. 6665±2063 ng/mL) compared with controls (P<0.001). In contrast, sVCAM‐1 and E‐selectin did not differ between the groups. Initiation of ART resulted in significantly lower levels of E‐selectin (15.1±0.8; P<0.01), sICAM‐1 (248±12 ng/mL; P<0.05), sVCAM‐1 (766±33 ng/mL; P<0.001) and hsCRP (14 708±2358 ng/mL; P<0.001) after 2 months, which remained reduced at 14 months. tPAI‐1 was not influenced by initiation of ART.

Conclusions

Markers of endothelial dysfunction were elevated in treatment‐naïve HIV‐infected patients and were related to HIV RNA viral load. Initiation of ART reduced the levels of the majority of these markers. The positive effect of ART initiation was dependent on the duration of HIV infection prior to treatment.