The COVID-19 outbreak has led to 80,409 diagnosed cases and 3,012 deaths in mainland China based on the data released on March 4, 2020. Approximately 3.2% of patients with COVID-19 required intubation and invasive ventilation at some point in the disease course. Providing best practices regarding intubation and ventilation for an overwhelming number of patients with COVID-19 amid an enhanced risk of cross-infection is a daunting undertaking. The authors presented the experience of caring for the critically ill patients with COVID-19 in Wuhan. It is extremely important to follow strict self-protection precautions. Timely, but not premature, intubation is crucial to counter a progressively enlarging oxygen debt despite high-flow oxygen therapy and bilevel positive airway pressure ventilation. Thorough preparation, satisfactory preoxygenation, modified rapid sequence induction, and rapid intubation using a video laryngoscope are widely used intubation strategies in Wuhan. Lung-protective ventilation, prone position ventilation, and adequate sedation and analgesia are essential components of ventilation management.

Purpose: Ischemic stroke (IS), one of the two main subtypes of stroke, occurs due to brain ischemia as a result of thrombosis of a cerebral blood vessel. IS is one of the most important neurovascular causes of death and disability. It is affected by many risk factors, such as smoking and high body mass index (BMI), which are also critical in the preventive control of other cardiovascular and cerebrovascular diseases. However, there are still few systematic analyses of the current and predicted disease burden, as well as the attributable risk factors for ischemic stroke. Methods: Based on the GBD2019 database, we used age-standardized mortality rate (ASMR) and disability-adjusted life year (ASDR) to systematically present the geographical distribution and trends of ischemic stroke disease burden worldwide from 1990 to 2019 by calculating the estimated annual percentage change (EAPC), and to analyze and predict the death number of IS accounted by seven major risk factors for 2020-2030. Results: Between 1990 and 2019, the global number of IS deaths increased from 2.04 million to 3.29 million and is expected to increase further to 4.90 million by 2030. The downward trend was more pronounced in women, young people, and high social-demographic index (SDI) regions. At the same time, a study of attributable risk factors for IS found that two behavioral factors, smoking and diet in high sodium, and five metabolic factors, including high systolic blood pressure, high low-density lipoprotein cholesterol, kidney dysfunction, high fast plasma glucose, and high BMI, are major contributors to the increased disease burden of IS now and in the future. Conclusions: Our study provides the first comprehensive summary for the last thirty years and the prediction of the global burden of IS and its attributable risk factors until 2030, providing detailed statistics for decision-making on the prevention and control of IS globally. Inadequate control of the seven risk factors would lead to an increased disease burden of IS in young people, especially in low SDI regions. Our study identifies high-risk populations and helps public health professionals develop targeted preventive strategies to reduce the global disease burden of ischemic stroke.

Neuropathic pain is characterized by mechanical allodynia induced by low-threshold myelinated Aβ-fiber activation. The original gate theory of pain proposes that inhibitory interneurons in the lamina II of the spinal dorsal horn (DH) act as “gate control” units for preventing the interaction between innocuous and nociceptive signals. However, our understanding of the neuronal circuits underlying pain signaling and modulation in the spinal DH is incomplete. Using a rat model, we have shown that the convergence of glycinergic inhibitory and excitatory Aβ-fiber inputs onto PKCγ⁺ neurons in the superficial DH forms a feed-forward inhibitory circuit that prevents Aβ input from activating the nociceptive pathway. This feed-forward inhibition was suppressed following peripheral nerve injury or glycine blockage, leading to inappropriate induction of action potential outputs in the nociceptive pathway by Aβ-fiber stimulation. Furthermore, spinal blockage of glycinergic synaptic transmission in vivo induced marked mechanical allodynia. Our findings identify a glycinergic feed-forward inhibitory circuit that functions as a gate control to separate the innocuous mechanoreceptive pathway and the nociceptive pathway in the spinal DH. Disruption of this glycinergic inhibitory circuit after peripheral nerve injury has the potential to elicit mechanical allodynia, a cardinal symptom of neuropathic pain.

Despite recent advances in antibiotic therapy and intensive care, sepsis is still considered to be the most common cause of death in intensive care units. Excessive production of reactive oxygen species plays an important role in the pathogenesis of sepsis. Recently, it has been suggested that molecular hydrogen (H₂) exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radicals (•OH, the most cytotoxic reactive oxygen species) and effectively protects against organ damage induced by I/R. Therefore, we hypothesized that H₂ treatment had a beneficial effect on sepsis. In the present study, we found that H₂ inhalation starting at 1 and 6 h after cecal ligation and puncture (CLP) or sham operation significantly improved the survival rate of septic mice with moderate or severe CLP in a concentration- and time-dependent manner. Furthermore, moderate or severe CLP mice showed significant multiple organ damage characterized by the increases of lung myeloperoxidase activity, wet-to-dry weight ratio, protein concentration in bronchoalveolar lavage, serum biochemical parameters, and organ histopathologic scores at 24 h after CLP operation, which was significantly attenuated by 2% H₂ treatment. In addition, we found that the beneficial effects of H₂ treatment on sepsis and sepsis-associated organ damage were associated with the decreased levels of oxidative product, increased activities of antioxidant enzymes, and reduced levels of high-mobility group box 1 in serum and tissue. Thus, H₂ inhalation may be an effective therapeutic strategy for patients with sepsis. ABBREVIATIONS-ALI-acute lung injury; ALT-alanine aminotransferase; AST-aspartate aminotransferase; BAL-bronchoalveolar lavage; BUN-blood urea nitrogen; CAT-catalase; CLP-cecal ligation and puncture; Cr-creatinine; H₂-hydrogen; H₂O₂-hydrogen peroxide; HMGB1-high-mobility group box 1; 8-iso-PGF2α-8-iso-prostaglandin F2α; MPO-myeloperoxidase; •OH-hydroxyl radicals; ROS-reactive oxygen species; SOD-superoxide dismutase; W/D-wet-to-dry

Rationale: No medical intervention has been identified that decreases acute kidney injury and improves renal outcome at 1 year after cardiac surgery. Objectives: To determine whether administration of nitric oxide reduces the incidence of postoperative acute kidney injury and improves long-term kidney outcomes after multiple cardiac valve replacement requiring prolonged cardiopulmonary bypass. Methods: Two hundred and forty-four patients undergoing elective, multiple valve replacement surgery, mostly due to rheumatic fever, were randomized to receive either nitric oxide (treatment) or nitrogen (control). Nitric oxide and nitrogen were administered via the gas exchanger during cardiopulmonary bypass and by inhalation for 24 hours postoperatively. Measurements and Main Results: The primary outcome was as follows: oxidation of ferrous plasma oxyhemoglobin to ferric methemoglobin was associated with reduced postoperative acute kidney injury from 64% (control group) to 50% (nitric oxide group) (relative risk [RR], 0.78; 95% confidence interval [CI], 0.62–0.97; P = 0.014). Secondary outcomes were as follows: at 90 days, transition to stage 3 chronic kidney disease was reduced from 33% in the control group to 21% in the treatment group (RR, 0.64; 95% CI, 0.41–0.99; P = 0.024) and at 1 year, from 31% to 18% (RR, 0.59; 95% CI, 0.36–0.96; P = 0.017). Nitric oxide treatment reduced the overall major adverse kidney events at 30 days (RR, 0.40; 95% CI, 0.18–0.92; P = 0.016), 90 days (RR, 0.40; 95% CI, 0.17–0.92; P = 0.015), and 1 year (RR, 0.47; 95% CI, 0.20–1.10; P = 0.041). Conclusions: In patients undergoing multiple valve replacement and prolonged cardiopulmonary bypass, administration of nitric oxide decreased the incidence of acute kidney injury, transition to stage 3 chronic kidney disease, and major adverse kidney events at 30 days, 90 days, and 1 year. Clinical trial registered with ClinicalTrials.gov (NCT01802619).