Convalescent plasma for COVID-19: a meta-analysis, trial sequential analysis, and meta-regression.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, particularly those preventing interaction between the viral spike receptor-binding domain and the host angiotensin-converting enzyme 2 receptor, may prevent viral entry into host cells and disease progression. METHODS: We performed a systematic review, meta-analysis, trial sequential analysis (TSA), and meta-regression of RCTs to evaluate the benefit of convalescent plasma for COVID-19. The primary outcome was 28-30 day mortality. Secondary outcomes included need for mechanical ventilation and ICU admission. Data sources were PubMed, Embase, MedRxiv, and the Cochrane library on July 2, 2021. RESULTS: We identified 17 RCTs that recruited 15 587 patients with 8027 (51.5%) allocated to receive convalescent plasma. Convalescent plasma use was not associated with a mortality benefit (24.7% vs 25.5%; odds ratio [OR]=0.94 [0.85-1.04]; P=0.23; I2=4%; TSA adjusted confidence interval [CI], 0.84-1.05), or reduction in need for mechanical ventilation (15.7% vs 15.4%; OR=1.01 [0.92-1.11]; P=0.82; I2=0%; TSA adjusted CI, 0.91-1.13), or ICU admission (22.4% vs 16.7%; OR=0.80 [0.21-3.09]; P=0.75; I2=63%; TSA adjusted CI, 0.0-196.05). Meta-regression did not reveal association with titre of convalescent plasma, timing of administration, or risk of death and treatment effect (P>0.05). Risk of bias was high in most studies. CONCLUSIONS: In patients with COVID-19, there was no clear mortality benefit associated with convalescent plasma treatment. In patients with mild disease, convalescent plasma did not prevent either the need for mechanical ventilation or ICU admission. CLINICAL TRIAL REGISTRATION: CRD42021234201 (PROSPERO).

Selective mitochondrial antioxidant MitoTEMPO reduces renal dysfunction and systemic inflammation in experimental sepsis in rats.

BACKGROUND: Excess mitochondrial reactive oxygen species (mROS) in sepsis is associated with organ failure, in part by generating inflammation through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. We determined the impact of a mitochondrial-targeted antioxidant (MitoTEMPO) on mitochondrial dysfunction in renal proximal tubular epithelial cells, peritoneal immune cell function ex vivo, and organ dysfunction in a rat model of sepsis. METHODS: The effects of MitoTEMPO were assessed ex vivo using adenosine triphosphate and lipopolysaccharide-stimulated rat peritoneal immune cells and fresh rat kidney slices exposed to serum from septic rats. We assessed mROS production and phagocytotic capacity (flow cytometry), mitochondrial functionality (multiphoton imaging, respirometry), and NLRP3 inflammasome activation in cell culture. The effect of MitoTEMPO on organ dysfunction was evaluated in a rat model of faecal peritonitis. RESULTS: MitoTEMPO decreased septic serum-induced mROS (P<0.001) and maintained normal reduced nicotinamide adenine dinucleotide redox state (P=0.02) and mitochondrial membrane potential (P<0.001) in renal proximal tubular epithelial cells ex vivo. In lipopolysaccharide-stimulated peritoneal immune cells, MitoTEMPO abrogated the increase in mROS (P=0.006) and interleukin-1ß (IL-1ß) (P=0.03) without affecting non-mitochondrial oxygen consumption or the phagocytotic-induced respiratory burst (P>0.05). In vivo, compared with untreated septic animals, MitoTEMPO reduced systemic IL-1ß (P=0.01), reduced renal oxidative stress as determined by urine isoprostane levels (P=0.04), and ameliorated renal dysfunction (reduced serum urea (P<0.001) and creatinine (P=0.05). CONCLUSIONS: Reduction of mROS by a mitochondria-targeted antioxidant reduced IL-1ß, and protected mitochondrial, cellular, and organ functionality after septic insults.

Effect of Extracorporeal Blood Purification on Mortality in Sepsis: A Meta-Analysis and Trial Sequential Analysis.

OBJECTIVE: The objective of this study was to conduct a meta-analysis and trial sequential analysis (TSA) of published randomized controlled trials (RCTs) to determine whether mortality benefit exists for extracorporeal blood purification techniques in sepsis. DATA SOURCES: A systematic search on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs was performed. STUDY SELECTION: RCTs investigating the effect of extracorporeal blood purification device use on mortality among critically ill septic patients were selected. DATA EXTRACTION: Mortality was assessed using Mantel-Haenszel models, and I2 was used for heterogeneity. Data are presented as odds ratios (OR); 95% confidence intervals (CIs); p values; I2. Using the control event mortality proportion, we performed a TSA and calculated the required information size using an anticipated intervention effect of a 14% relative reduction in mortality. DATA SYNTHESIS: Thirty-nine RCTs were identified, with 2,729 patients. Fourteen studies used hemofiltration (n = 789), 17 used endotoxin adsorption devices (n = 1,363), 3 used nonspecific adsorption (n = 110), 2 were cytokine removal devices (n = 117), 2 used coupled plasma filtration adsorption (CPFA) (n = 207), 2 combined hemofiltration and perfusion (n = 40), and 1 used plasma exchange (n = 106). On conventional meta-analysis, hemofiltration (OR 0.56 [0.40-0.79]; p < 0.001; I2 = 0%), endotoxin removal devices (OR 0.40 [0.23-0.67], p < 0.001; I2 = 71%), and nonspecific adsorption devices (OR 0.32 [0.13-0.82]; p = 0.02; I2 = 23%) were associated with mortality benefit, but not cytokine removal (OR 0.99 [0.07-13.42], p = 0.99; I2 = 64%), CPFA (OR 0.50 [0.10-2.47]; p = 0.40; I2 = 64%), or combined hemofiltration and adsorption (OR 0.71 [0.13-3.79]; p = 0.69; I2 = 0%). TSA however revealed that based on the number of existing patients recruited for RCTs, neither hemofiltration (TSA-adjusted CI 0.29-1.10), endotoxin removal devices (CI 0.05-3.40), nor nonspecific adsorption devices (CI 0.01-14.31) were associated with mortality benefit. CONCLUSION: There are inadequate data at present to conclude that the use of extracorporeal blood purification techniques in sepsis is beneficial. Further adequately powered RCTs are required to confirm any potential mortality benefit, which may be most evident in patients at greatest risk of death.

High-sensitivity troponin level pre-catheterization predicts adverse cardiovascular outcomes after primary angioplasty for ST-elevation myocardial infarction.

BACKGROUND: Cardiac troponins are the preferred biomarkers for diagnosing myocardial infarction (MI). High-sensitivity troponin T (hs-TnT) assays have increased sensitivity and enable more rapid diagnosis of infarction. We assessed the prognostic utility of admission hs-TnT to detect outcomes after primary angioplasty for ST-elevation/new left bundle branch block myocardial infarction (STEMI). METHODS: Patients admitted to Auckland City Hospital for acute coronary catheterization with a diagnosis of STEMI between October 2010 and September 2011 were identified, and included if hs-TnT levels were measured at admission. Clinical characteristics and major adverse cardiovascular events (MACE: death, myocardial infarction and revascularization) at 30 days and 1 year were collected from national statistics and electronic medical records. RESULTS: Median admission hs-TnT level in the 173 STEMI patients studied was 59 ng/L (interquartile range (IQR) 19-310). Incidences of MACE at 30 days and 1 year were 10% (n=17) and 18% (n=31), respectively. C-statistics and 95% confidence interval (CI) (95% CI) for hs-TnT on admission at detecting MACE at 30 days and 1 year were 0.800 (0.696-0.904) and 0.750 (0.655-0.845) respectively, with the optimal cut-point of 225 ng/L giving sensitivities/specificities of 76.5%/75.6% and 64.5%/78.2% respectively. Admission log(hs-TnT) independently predicted both MACE at 30 days with hazards ratio 5.16, 95% CI (2.25-11.9) and 1 year with hazards ratio 2.88, 95% CI (1.79-4.63), as did age and cardiogenic shock. Age, Maori or Pacific ethnicity and chronic respiratory disease were independent predictors of hs-TnT>225 ng/L. CONCLUSION: Admission hs-TnT measured in primary angioplasty is strongly prognostic of MACE at 30 days and 1 year, even following adjustment for potential confounding variables.

A Case of Breathlessness during Pregnancy: The Difficulty in Diagnosing Heart Failure.

We present the case of a 33-year-old woman in her second pregnancy who was transferred to our unit following a one-month history of worsening fatigue and a three-day history of worsening symptoms of heart failure. Shortly after presentation she developed ventricular fibrillation and arrested. At an emergency caesarean section a placental abruption was noted and the baby was stillborn, unable to be resuscitated. The patient required a prolonged intensive and coronary care stay. Echocardiographic findings were consistent with dilated cardiomyopathy and as all investigations to ascertain a cause were negative she was diagnosed with peripartum cardiomyopathy. Her case highlights a potential fatal cause of breathlessness during pregnancy and the role of B-type natriuretic peptide to assist in the differential diagnosis of these cases.

Myocardial infarction following sclerotherapy in a patient with a patent foramen ovale.

A case is reported of myocardial infarction occurring following sclerotherapy for varicose veins in a patient with a patent foramen ovale (PFO). It is believed that microemboli crossed the PFO as a result of the procedure and caused coronary artery embolisation, resulting in the symptoms, electrocardiographic and biochemical evidence of myocardial infarction.