OBJECTIVE:Diabetic foot ulcer (DFU) is one of the most serious complications of diabetes. Leukocyte- and platelet-rich fibrin (L-PRF) is a second-generation autologous platelet-rich plasma. This study aims to investigate the clinical effects of L-PRF in patients with diabetes in real clinical practice. METHODS:Patients with DFU who received L-PRF treatment and standard of care (SOC) from 2018 to 2019 in Tongji Hospital were enrolled. The clinical information including patient characteristics, wound evaluation (area, severity, infection, blood supply), SOC of DFU, and images of ulcers was retrospectively extracted and analyzed. L-PRF treatment was performed every 7±2 days until the ulcer exhibited complete epithelialization or an overall percent volume reduction (PVR) greater than 80%. Therapeutic effectiveness, including overall PVR and the overall and weekly healing rates, was evaluated. RESULTS:Totally, 26 patients with DFU were enrolled, and they had an ulcer duration of 47.0 (35.0, 72.3) days. The severity and infection of ulcers varied, as indicated by the Site, Ischemia, Neuropathy, Bacterial Infection, and Depth (SINBAD) scores of 2-6, Wagner grades of 1-4, and the Perfusion, Extent, Depth, Infection and Sensation (PEDIS) scores of 2-4. The initial ulcer volume before L-PRF treatment was 4.94 (1.50, 13.83) cm3, and the final ulcer volume was 0.35 (0.03, 1.76) cm3. The median number of L-PRF doses was 3 (2, 5). A total of 11 patients achieved complete epithelialization after the fifth week of treatment, and 19 patients achieved at least an 80% volume reduction after the seventh week. The overall wound-healing rate was 1.47 (0.63, 3.29) cm3/week, and the healing rate was faster in the first 2 weeks than in the remaining weeks. Concurrent treatment did not change the percentage of complete epithelialization or healing rate. CONCLUSION:Adding L-PRF to SOC significantly improved wound healing in patients with DFU independent of the ankle brachial index, SINBAD score, or Wagner grade, indicating that this method is appropriate for DFU treatment under different clinical conditions.

Background:The benefits of early use of norepinephrine in endotoxemic shock remain unknown. We aimed to elucidate the effects of different doses of norepinephrine in early-stage endotoxemic shock using a clinically relevant large animal model.Methods:Vasodilatory shock was induced by endotoxin bolus in 30 Bama suckling pigs. Treatment included fluid resuscitation and administration of different doses of norepinephrine, to induce return to baseline mean arterial pressure (MAP). Fluid management, hemodynamic, microcirculation, inflammation, and organ function variables were monitored. All animals were supported for 6 h after endotoxemic shock.Results:Infused fluid volume decreased with increasing norepinephrine dose. Return to baseline MAP was achieved more frequently with doses of 0.8 µg/kg/min and 1.6 µg/kg/min (P <0.01). At the end of the shock resuscitation period, cardiac index was higher in pigs treated with 0.8 µg/kg/min norepinephrine (P <0.01), while systemic vascular resistance was higher in those receiving 0.4 µg/kg/min (P <0.01). Extravascular lung water level and degree of organ edema were higher in animals administered no or 0.2 µg/kg/min norepinephrine (P <0.01), while the percentage of perfused small vessel density (PSVD) was higher in those receiving 0.8 µg/kg/min (P <0.05) and serum lactate was higher in the groups administered no and 1.6 µg/kg/min norepinephrine (P <0.01).Conclusions:The impact of norepinephrine on the macro- and micro-circulation in early-stage endotoxemic shock is dose-dependent, with very low and very high doses resulting in detrimental effects. Only an appropriate norepinephrine dose was associated with improved tissue perfusion and organ function.

Objectives: This observational study was conducted to investigate capillary refill time (CRT) during the early phase of ICU admission in relationship with microvascular flow alteration and outcome in critically ill patients. Design: Prospective, observational, pilot study. Setting: ICU in a university hospital. Patients: Two hundred eighty-two critically ill adult patients admitted to the ICU. Interventions: None. Measurements and Main Results: All patients underwent simultaneous measurements by CRT and sidestream dark field imaging within 24 hours of ICU admission. Other clinical data such as demographic characteristics, hemodynamics, laboratory values, treatment, and physiologic parameters were also included simultaneously. Microcirculatory measurements were performed at 10.2 ± 5.7 hours after ICU admission. Of the 282 included patients, 106 (37.6%) were female, the median (interquartile range) age was 63 years (53–74 yr), and the median Sequential Organ Failure Assessment (SOFA) score was 5 (2–7). The primary finding was the association between CRT and simultaneous the condition of peripheral circulation (microvascular flow index [MFI]: r = –0.4430, p < 0.001; proportion of perfused vessels: r = –0.3708, p < 0.001; heterogeneity index: r = 0.4378, p < 0.001; perfused vessel density: r = –0.1835, p = 0.0020; except total vessel density: p = 0.9641; and De Backer score: p = 0.5202) in critically ill patients. In addition, this relationship was also maintained in subgroups. Microcirculatory flow abnormalities, 28-day mortality, and SOFA score appeared to be more severe for increasing CRT. In a multivariable analysis, prolonged CRT was independently associated with microvascular flow abnormalities (MFI < 2.6; odds ratio [OR], 1.608; 95% CI, 2.1–10.2; p < 0.001). Similarly, multivariable analysis identified CRT as an independent predictor of 28-day mortality (OR, 1.296; 95% CI, 1.078–1.558; p = 0.006). Conclusions: In our ICU population, a single-spot prolonged CRT was independently associated with abnormal microcirculation and increased mortality.

Background:The coronavirus disease 2019 (COVID-19) is an ongoing pandemic. Invasive mechanical ventilation (IMV) is essential for the management of COVID-19 with acute respiratory distress syndrome (ARDS). We aimed to assess the impact of compliance with a respiratory decision support system on the outcomes of patients with COVID-19-associated ARDS who required IMV. Methods:In this retrospective, single-center, case series study, patients with COVID-19-associated ARDS who required IMV at Zhongnan Hospital of Wuhan University, China, from January 8th, 2020, to March 24th, 2020, with the final follow-up date of April 20th, 2020, were included. Demographic, clinical, laboratory, imaging, and management information were collected and analyzed. Compliance with the respiratory support decision system was documented, and its relationship with 28-day mortality was evaluated. Results:The study included 46 COVID-19-associated ARDS patients who required IMV. The median age of the 46 patients was 68.5 years, and 31 were men. The partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio at intensive care unit (ICU) admission was 104 mmHg. The median total length of IMV was 12.0 (interquartile range [IQR]: 6.0-27.3) days, and the median respiratory support decision score was 11.0 (IQR: 7.8-16.0). To 28 days after ICU admission, 18 (39.1%) patients died. Survivors had a significantly higher respiratory support decision score than non-survivors (15.0 [10.3-17.0] vs. 8.5 (6.0-10.3), P = 0.001). Using receiver operating characteristic (ROC) curve to assess the discrimination of respiratory support decision score to 28-day mortality, the area under the curve (AUC) was 0.796 (95% confidence interval [CI]: 0.657-0.934, P = 0.001) and the cut-off was 11.5 (sensitivity = 0.679, specificity = 0.889). Patients with a higher score (>11.5) were more likely to survive at 28 days after ICU admission (log-rank test, P < 0.001). Conclusions:For severe COVID-19-associated ARDS with IMV, following the respiratory support decision and assessing completion would improve the progress of ventilation. With a decision score of >11.5, the mortality at 28 days after ICU admission showed an obvious decrease.

Abstract Background: Recent studies demonstrate the advantage of peripheral perfusion-targeted resuscitation protocols based on capillary refill time (CRT) assessment in critically ill patients. Additionally, sidestream dark field (SDF) imaging could direct visualize sublingual microcirculation of critically ill patients. This study aimed to determine the association between the sublingual microcirculation and CRT in critically ill patients in the early phase of intensive care unit (ICU) admission. Methods: This prospective, observational, pilot study included 282 patients in the ICU of Zhongnan Hospital of Wuhan University between October 2021 and January 2022. All patients underwent simultaneous measurements by CRT and SDF imaging within 24 hours of ICU admission. Additionally, other clinical data such as demographic variables, hemodynamics, laboratory values, treatment, and physiological parameters were also included. The primary outcome was the association between CRT and simultaneous sublingual microcirculation parameters in critically ill patients.Results: Of the 282 included patients, 106 (37.6%) were female, the median (IQR) age was 63 (53-74) years, and the median (IQR) SOFA score was 5 (2-7). Microcirculatory measurements (CRT and SDF imaging) were performed at 10.2 ± 5.7 hours after ICU admission. Significant relationships were observed between the CRT and MFI (r = -0.4430, p < 0.001), PPV (r = -0.3708, p < 0.001), PVD (r = -0.1835, p = 0.0020), and HI (r = 0.4378, p < 0.001). Neither TVD (p = 0.9641) nor De Backer score (p = 0.5202) were related to the CRT. Compare to CRT< 3s group, MFI (2.60 vs. 2.88, p < 0.001), PPV (91.35% vs. 99.10%, p < 0.001), PVD (13.36 mm/mm2 vs. 14.55 mm/mm2, p = 0.002), and HI (0.46 vs. 0.15, p < 0.001) were significantly worse in the CRT ≥ 3s group. The similar results were also found in the sepsis subgroup and the hyperlactatemia subgroup. Prolonged CRT was an independent predictor of 28-days mortality (OR = 1.296; (95%CI, 1.078-1.558); p = 0.006).Conclusions: Our findings suggested that there was a significant and moderate association between CRT and some sublingual microcirculation parameters more related to perfusion (MFI, PPV, and HI) in heterogeneous ICU patients at the early phase of admission.Trial registration: The study was retrospectively registered on November 7, 2021, ChiCTR2100052999.

Background:The aim of this study was to determine the efficacy of interferon (IFN)-based therapy for coronavirus disease 2019 (COVID-19) based on relevant qualified studies. We searched for pertinent studies using keywords via PubMed, Cochrane and Embase databases. Studies from other pertinent sources and that were published before September 2021 were also reviewed.Methods:For each study, we assessed and synthesized the outcomes by relative risk (RR) or weighted mean difference (WMD) combined with a 95% confidence interval (CI). A total of 8 studies involving 2442 patients with COVID-19 were evaluated in this meta-analysis.Results:The IFN group had a significant decrease in ICU admissions (RR: 0.705; 95% CI, 0.515-0.964) and death (RR: 0.416; 95% CI, 0.217-0.797), and increased duration of ICU stay (WMD: 0.996; 95% CI, 0.834-1.158) compared with the control group in the randomized clinical trial (RCT) subgroup analysis. In non-RCT subgroup analysis, the IFN group showed a significant increase in discharge rate (RR: 1.052; 95% CI, 1.004-1.101) compared with the control group.Conclusion:IFN therapy appears to have better efficacy than non-IFN therapy as sedatives in patients with COVID-19 in terms of decreasing ICU admissions and death and increasing discharge. However, more high-quality RCTs are needed to confirm these findings.

RationaleCerebrospinal fluid (CSF) leakage is a common condition after spinal surgery and is also the most common cause of intracranial hypotension. Intracranial hypotension (IH) is typically characterized by an orthostatic headache with associated nausea, vomiting, tinnitus, vertigo, hypoacusis, neck stiffness, and photophobia. There have been limited case reports describing surgery-associated IH presenting with seizures and disorder of consciousness. Due to the atypia of symptoms, these clinical manifestations are usually ignored or even misdiagnosed. As a result, clinicians face a significant challenge in detecting IH early and understanding its various clinical presentations. Meanwhile, we summarize the cases of IH presenting as seizures in recent years, including its clinical characteristics and effective treatment, which will be very helpful for the early diagnosis of IH. Patient concernsA 72-year-old Chinese male patient developed status epilepticus, a disorder of consciousness, and quadriplegia when he finished spinal surgery, although he had no previous seizures or any seizure risk factors. DiagnosisAfter MRI and CT examination, subdural hygromas were found under both sides of the skull, and combined with the clinical manifestations of the patient, intracranial hypotension due to cerebrospinal fluid leakage was diagnosed. InterventionsIn the early stage, we carried out strict perioperative critical care for the patient. Trendelenburg position was conducted to relieve intracranial hypotension. The dural repair surgery was performed after the diagnosis of CSF leakage. OutcomesSeizures in the patient were resolved. Three months after discharge, he was gradually returning to normal life. LessonsOne possible cause of unexplained seizures and disorder of consciousness after spinal surgery is cerebrospinal fluid leakage associated with intracranial hypotension syndrome. Trendelenburg position and dural repair surgery are effective ways to relieve intracranial hypotension and associated symptoms. Better awareness of the association between IH (intracranial hypotension) and seizures may help us improve early recognition of the syndrome.

Nonalcoholic steatohepatitis (NASH) is a serious disease threatening public health, and its pathogenesis remains largely unclear. Recent scientific research has shown that intestinal microbiota and its metabolites have an important impact on the development of NASH. A balanced intestinal microbiota contributes to the maintenance of liver homeostasis, but when the intestinal microbiota is disequilibrated, it serves as a source of pathogens and molecules that lead to NASH. In this review, we mainly emphasize the key mechanisms by which the intestinal microbiota and its metabolites affect NASH. In addition, recent clinical trials and animal studies on the treatment of NASH by regulating the intestinal microbiota through prebiotics, probiotics, synbiotics and FMT have also been briefly elaborated. With the increasing understanding of interactions between the intestinal microbiota and liver, accurate and personalized detection and treatment methods for NASH are expected to be established.

Nonalcoholic steatohepatitis (NASH) is a progressive liver disease and has become a leading indication for liver transplantation in the United States. The development of effective therapies for NASH is a major unmet need. Here, we identified a small molecule, IMA-1, that can treat NASH by interrupting the arachidonate 12-lipoxygenase (ALOX12)–acetyl-CoA carboxylase 1 (ACC1) interaction. IMA-1 markedly blocked diet-induced NASH progression in both male mice and Cynomolgus macaque therapeutic models. The anti-NASH efficacy of IMA-1 was comparable to ACC inhibitor in both species. Protein docking simulations and following functional experiments suggested that the anti-NASH effects of IMA-1 were largely dependent on its direct binding to a pocket in ALOX12 proximal to its ACC1-interacting surface instead of inhibiting ALOX12 lipoxygenase activity. IMA-1 treatment did not elicit hyperlipidemia, a known side effect of direct inhibition of ACC enzymatic activity, in both mice and macaques. These findings provide proof of concept across multiple species for the use of small molecule–based therapies for NASH.

BACKGROUND AND AIMS:NAFLD has become the most common liver disease worldwide but lacks a well-established pharmacological therapy. Here, we aimed to investigate the role of an E3 ligase SH3 domain-containing ring finger 2 (SH3RF2) in NAFLD and to further explore the underlying mechanisms.METHODS AND RESULTS:In this study, we found that SH3RF2 was suppressed in the setting of NAFLD across mice, monkeys, and clinical individuals. Based on a genetic interruption model, we further demonstrated that hepatocyte SH3RF2 deficiency markedly deteriorates lipid accumulation in cultured hepatocytes and diet-induced NAFLD mice. Mechanistically, SH3RF2 directly binds to ATP citrate lyase, the primary enzyme promoting cytosolic acetyl-coenzyme A production, and promotes its K48-linked ubiquitination-dependent degradation. Consistently, acetyl-coenzyme A was significantly accumulated in Sh3rf2-knockout hepatocytes and livers compared with wild-type controls, leading to enhanced de novo lipogenesis, cholesterol production, and resultant lipid deposition.CONCLUSION:SH3RF2 depletion in hepatocytes is a critical aggravator for NAFLD progression and therefore represents a promising therapeutic target for related liver diseases.

BACKGROUND AND AIMS:NAFLD is the most prevalent chronic liver disease without any Food and Drug Administration-approved pharmacological intervention in clinic. Fatty acid synthase (FASN) is one of the most attractive targets for NAFLD treatment because of its robust rate-limiting capacity to control hepatic de novo lipogenesis. However, the regulatory mechanisms of FASN in NAFLD and potential therapeutic strategies targeting FASN remain largely unknown.METHODS AND RESULTS:Through a systematic interactomics analysis of FASN-complex proteins, we screened and identified sorting nexin 8 (SNX8) as a binding partner of FASN. SNX8 directly bound to FASN and promoted FASN ubiquitination and subsequent proteasomal degradation. We further demonstrated that SNX8 mediated FASN protein degradation by recruiting the E3 ligase tripartite motif containing 28 (TRIM28) and enhancing the TRIM28-FASN interaction. Notably, Snx8 interference in hepatocytes significantly deteriorated lipid accumulation in vitro, whereas SNX8 overexpression markedly blocked hepatocyte lipid deposition. Furthermore, the aggravating effect of Snx8 deletion on NAFLD was validated in vivo as hepatic steatosis and lipogenic pathways in the liver were significantly exacerbated in Snx8-knockout mice compared to wild-type controls. Consistently, hepatocyte-specific overexpression of Snx8 in vivo markedly suppressed high-fat, high-cholesterol diet (HFHC)-induced hepatic steatosis. Notably, the protective effect of SNX8 against NAFLD was largely dependent on FASN suppression.CONCLUSIONS:These data indicate that SNX8 is a key suppressor of NAFLD that promotes FASN proteasomal degradation. Targeting the SNX8-FASN axis is a promising strategy for NAFLD prevention and treatment.

Myocardial ischemia-reperfusion (MIR) injury is a major cause of adverse outcomes of revascularization after myocardial infarction. To identify the fundamental regulator of reperfusion injury, we performed metabolomics profiling in plasma of individuals before and after revascularization and identified a marked accumulation of arachidonate 12-lipoxygenase (ALOX12)-dependent 12-HETE following revascularization. The potent induction of 12-HETE proceeded by reperfusion was conserved in post-MIR in mice, pigs, and monkeys. While genetic inhibition of Alox12 protected mouse hearts from reperfusion injury and remodeling, Alox12 overexpression exacerbated MIR injury. Remarkably, pharmacological inhibition of ALOX12 significantly reduced cardiac injury in mice, pigs, and monkeys. Unexpectedly, ALOX12 promotes cardiomyocyte injury beyond its enzymatic activity and production of 12-HETE but also by its suppression of AMPK activity via a direct interaction with its upstream kinase TAK1. Taken together, our study demonstrates that ALOX12 is a novel AMPK upstream regulator in the post-MIR heart and that it represents a conserved therapeutic target for the treatment of myocardial reperfusion injury.

Lipotoxicity is a recognized pathological trigger and accelerator of nonalcoholic steatohepatitis (NASH). However, the molecular basis of lipotoxicity-induced NASH remains elusive. Here, we systematically mapped the changes in hepatic transcriptomic landscapes in response to lipotoxic insults across multiple species. Conserved and robust activation of the arachidonic acid pathway, in particular the arachidonate 12-lipoxygenase (ALOX12) gene, was closely correlated with NASH severity in humans, macaques with spontaneously developed NASH, as well as swine and mouse dietary NASH models. Using gain- and loss-of-function studies, we found that ALOX12 markedly exacerbated NASH in both mice and Bama pig models. ALOX12 was shown to induce NASH by directly targeting acetyl-CoA carboxylase 1 (ACC1) via a lysosomal degradation mechanism. Overall, our findings reveal a key molecular driver of NASH pathogenesis and suggest that ALOX12-ACC1 interaction may be a therapeutic target in NASH.

This single-center case series describes the demographics, symptoms, laboratory and imaging findings, treatment, and clinical course of 138 patients hospitalized with 2019 novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) in Wuhan, China, highlighting presumed human-to-human hospital-associated transmission in many cases. Importance In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. Objective To describe the epidemiological and clinical characteristics of NCIP. Design, Setting, and Participants Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. Exposures Documented NCIP. Main Outcomes and Measures Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. Results Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 x 10(9)/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). Conclusions and Relevance In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%. Question What are the clinical characteristics of hospitalized patients with 2019 novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) in Wuhan, China? Findings In this single-center case series involving 138 patients with NCIP, 26% of patients required admission to the intensive care unit and 4.3% died. Presumed human-to-human hospital-associated transmission of 2019-nCoV was suspected in 41% of patients. Meaning In this case series in Wuhan, China, NCIP was frequently associated with presumed hospital-related transmission, 26% of patients required intensive care unit treatment, and mortality was 4.3%.

We aim to explore the safety and feasibility of umbilical cord mesenchymal stem cells (UC‐MSCs) transplantation in patients with severe and critically severe coronavirus disease‐2019 (COVID‐19).

Jing Zhang Wuhan University Zhongnan Hospital Xin Rao Wuhan University Zhongnan Hospital Yiming Li Wuhan University Zhongnan Hospital Yuan Zhu Wuhan University Zhongnan Hospital Fang Liu Wuhan University Zhongnan Hospital Guangling Guo Taihe Hospital Guoshi Luo Taihe Hospital Zhongji Meng Taihe Hospital Daniel De Backer CHIREC Hui Xiang Wuhan University Zhongnan Hospital Zhi-Yong Peng (  pengzy5@hotmail.com ) Wuhan University Zhongnan Hospital https://orcid.org/0000-0002-3873-9607

Importance: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections outbreak in China is now a global issue. There is only a limited understanding of the clinical characteristics of patients with SARS-CoV-2 infections is available. Objective: To describe the characteristics, management strategies, and outcomes of critically ill patients with SARS-CoV-2 infection. Design, Setting, and Patients: This is aretrospective, multi-center case series of 50 critically ill patients with confirmed SARS-CoV-2 infection who were admitted at Zhongnan Hospital of Wuhan University and Wuhan Pulmonary Hospital in Wuhan, China, from January 8 to February 9, 2020. Exposures: Documented Corona Virus Disease, 2019 (COVID-19). Main Outcome Measures: Demographic, clinical, laboratory, imaging data were collected along with management strategies, complications and outcomes of enrolled individuals. Results Fifty critically ill patients with SARS-CoV-2 infections were enrolled. Their median age was 62 (range, 29-92) [IQR,49.5-69.0] years, 68% were male, and 28 (56%) patients had comorbidities, the most common being hypertension. In this cohort, 20(40%) patients survived ,16(32%) patients died, and the rest remained hospitalized. The invasive mechanical ventilator was used in 36(72%) patients with 15(30%) of them requiring prone positioning, and 17(34%) switched to ECMO. The compliance scores of lungs (Cstat)on the day of ICU admission among survivors were higher than those in non-survivors [42.0(18.0-47.0), vs. 19.5(14.0-24.2), p=0.038].The blood IL-6 levels and neutrophils counts at the first day of ICU admission were significantly higher in non-survivors compared to survivors [123.7(85.3-228.8), vs. 20.2(6.8-67.2) ng/ml, p=0.025 for IL-6, and 20.2(6.8-67.2) vs. 4.01(1.99-7.05) × 10⁹/L, p=0.02 for neutrophils counts].The heart rates, PaCO2, lung injury scale (LIS), and positive end-expiratory pressure levels were constantly higher for 10 days in non-survivors than those who survived (p<0.05). The frequency of vasopressor uses and neuromuscular blockers was higher in non-survivors from day 1 to day 10 compared to survivors (p<0.05). In the whole cohort, the most common complications were ARDS (97%), shock (44%), arrhythmia (38%), acute cardiac injury (26%), and acute kidney injury (22%). A secondary bacterial infection was noted in 17(34%) patients. Univariate analysis indicated that lower lung complianceand higher neutrophil counts at the day of ICU admission were related to higher mortality (p-0.03, and 0.04, respectively) Conclusion We demonstrated that SARS-CoV-2 infection-related critical illness predominantly affected old individuals with comorbidities and characterized by severe hypoxemic respiratory failure, often requiring prolonged mechanical ventilation and rescue therapies. Low lung compliance and persistently elevated PaCO2 indicated poor outcomes.

Purpose: To assess the impact of the timeline of sepsis bundle completion with clinical outcomes in septic shock. Materials and methods: We retrospectively studied adult (>= 18 years) patients with septic shock from January 1, 2006, through May 31, 2018, who were admitted to the intensive care unit in Mayo Clinic, Rochester. We divided patients into three groups based on the SSC compliant 1) <1h, 2) 1.1 to 3 h, 3) >3 h after the time of septic shock diagnosis. Results: We enrolled 1052 septic shock patients, among 8% were in group 1, 26% in group 2, and the remaining in group 3. Those who completed all bundle components within 3 h had the lowest 28-day mortality (17.5% vs. 31.4%, p<.001) and higher survival at 90 days (HR = 0.67; 95% CI 0.55-0.80; p<.001). Sepsis bundle completion in <1 h had no significant advantage in 28-day mortality (21.5% vs.15.9%, p = .4) or 90-day survival compared with group 2 (HR = 1.08; 95% CI 0.77-1.53; p = .6). Conclusions: We showed an association between the completion of SSC bundle components within three hours with lower mortality or earlier shock reversal. This relationship was not evident when compared to bundle completion in 1 h vs. within 3 h. (C) 2020 Elsevier Inc. All rights reserved.

Objective: The information about the critically ill coronavirus disease 2019 (COVID-19) was limited and controversy. This study was to analyze the clinical feature and predictors for outcome in critically ill COVID-19. Design: This was a descriptive study from two hospitals. Setting: This study was conducted in intensive care units (ICUs) from university hospitals. Methods: Critically ill COVID-19 patients admitted in ICU from Zhongnan Hospital of Wuhan University and Wuhan Pulmonary Hospital from January 8 to February 20, 2020, were screened. Interventions: None. Measurements and Main Results: Clinical, laboratory data were collected with management strategies and outcomes. Sixty-eight critically ill patients were enrolled. Their median age was 64 (interquartile range, 54-72) years, and 67.65% were male. In this cohort, 44 (65%) patients survived for 28 days. The invasive mechanical ventilator was used in 51 (75%) patients, with 20 of them requiring prone positioning, and 17 switched to extracorporeal membrane oxygenation. The compliance scores of lungs on the day of intubation among survivors were higher than those in nonsurvivors (25.00 [13.50-39.00] vs. 17.00 [12.00-22.00], P = 0.01). The blood interlukin-6 (IL-6) levels at the ICU admission were significantly higher in nonsurvivors compared to survivors (71.27 [51.48-144.15] vs. 18.15 [7.55-68.02] ng/ml, P = 0.025). The heart rates, lung injury scale, and positive end-expiratory pressure were constantly higher for 10 days in nonsurvivors. The frequency of vasopressor uses and neuromuscular blockers was higher in nonsurvivors from day 5 to day 10 (P < 0.05). In the whole cohort, the most common complications were acute respiratory distress syndrome (95.59%), shock (48.53%), arrhythmia (33.82%), acute cardiac injury (33.82%), and acute kidney injury (27.94%). Multivariate analysis indicated that lower lung compliance at the day of intubation and higher Acute Physiology and Chronic Health Evaluation II (APACHE II) at ICU admission were related to higher mortality (P = 0.02 and 0.05, respectively). Conclusion: COVID-19-related critical illness predominantly affected old individuals and was characterized by severe hypoxemic respiratory failure, often requiring prolonged mechanical ventilation and rescue therapies. High APACHE II scores and low lung compliance indicated poor outcomes.

Objective: We investigated the epidemiology, risk factors, and predictive parameters for ischemic or hemorrhagic stroke-associated acute kidney injury (AKI) and mortality in a general intensive care unit (ICU) in China. Methods: During 5 years, 479 stroke patients were screened, and 381 were enrolled. AKI was diagnosed within 7 days after ICU admission, based on the Kidney Disease Improving Global Outcomes criteria. Risk factors of AKI were assessed by Logistic regression analyses, and the predictive biomarkers for AKI were determined using receiver operating characteristic (ROC) curves. Also examined were factors influencing 28-day mortality, using Cox regression analyses and Kaplan-Meier curves. Results: Among all, 115 (30.18%) patients developed AKI. Multivariate regression analyses revealed that the following features at ICU admission significantly increased the risk of developing AKI: an increased National Institutes of Health Stroke Scale score (OR 1.136, p < 0.001) and Acute Physiology and Chronic Health Evaluation II score (OR 1.107, p = 0.042); hypertension (OR 2.346, p = 0.008); use of loop diuretics (OR 1.961, p = 0.032); and higher serum cystatin C (sCysC; OR 8.156, p = 0.001). The area under the ROC curves for predicting AKI using sCysC was 0.772, slightly better than that of other biomarkers. The sCysC ≥0.93 mg/L (hazard ratio 1.844, p = 0.004) significantly predicted 28-day mortality. Conclusions: Among stroke patients in ICU, we identified significant risk factors of stroke-associated AKI. Serum CysC level at ICU admission was an important biomarker for predicting AKI and 28-day mortality.