Sepsis is a life-threatening condition characterized by immune system dysregulation whose pathophysiology still remains incompletely understood. Better outcomes in patients with sepsis have not been reached despite guidelines updates, development of rapid diagnostic tests, and proper hemodynamic and antimicrobial management. Blood cultures are time-consuming and may delay important therapeutic decisions. Nonculture-based techniques overcome some limitations seen with culture-based techniques with early phenotypic identification of resistance remaining as the cornerstone of optimal diagnosis. A new paradigm has started adjusting preemptive therapy for cytomegalovirus (CMV) infection among kidney transplant patients based on monitoring the host immune response. In this review from a PubMed literature search in adults with sepsis or septic shock, we identified newer tests and highlight some advances in monitoring the host immune response for personalized adjunctive therapy. Monitoring the individual host immune response at the bedside is an unmet clinical need to guide immunomodulatory therapy. The coronavirus disease 2019 pandemic has led to a further understanding of the complex immunopathology of sepsis and opened new avenues for mitigating immune dysregulation. In this review, we discuss current evidence regarding the immune response to sepsis along with challenges and directions for future research.

Introduction: Corona virus disease 2019 (COVID-2019) disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2, is having propensity of pulmonary and extrapulmonary involvement. Although dengue virus has a predominant extrapulmonary effect, pulmonary involvement is less common. COVID-19–dengue overlap is a mixture of both diseases sharing few similarities. Methods: A multicentric observational study conducted from May 2021 to October 2021, in MIMSR Medical College and Venkatesh Hospital, Latur, India, included 300 COVID-19 cases with dengue NS1 or dengue immunoglobulin M (IgM) positive, with lung involvement documented and categorized on high-resolution computerized tomography (CT) thorax at the entry point. We have recorded demographic parameters as age, gender, comorbidity, and laboratory parameters such as total white blood cell count, platelet count, lactate dehydrogenase (LDH), C-reactive protein (CRP), interleukin-6 (IL-6), dengue serology, and use of BIPAP/NIV in COVID-19 cases in critical care settings in all study cases. CT severity scoring was done as per universally accepted standard mild if score < 7, moderated if score 8–15, and severe if score > 15. The final radiological outcome as presence or absence of fibrosis with clinical recovery was documented. All cases were subjected to dengue immunoglobulin G (IgG) antibody titers and dengue IgM/IgG antibody titer analysis after 12 weeks of discharge from the hospital after clinical recovery. Statistical analysis is done by using Chi-square test. Results: In a study of 300 COVID-19 pneumonia cases, COVID-19–dengue overlap was documented in 16.3% (49/300) of cases. Predominant age groups between 18–95 years and age ≥ 50 years were 60% (180/300), age < 50 were 40% (120/300). In the gender distribution in the study group, male population was 70.3% (211/300) and females were 29.7% (89/300). The main symptoms in the study group were shortness of breath in 79% of cases, fever in 71%, cough especially dry in 48%, and fatigability in 79%, tachycardia in 72%, tachypnea in 24%, and oxygen desaturation on 6 minutes walk in 29%. Positive dengue serology was documented as per CT severity scoring in 26/42 mild CT severity cases, 16/92 in moderate CT severity cases, and 7/166 in severe CT severity cases (P < 0.00001). Hematological parameters were having a significant association in COVID-19 cases with and without dengue overlap such as abnormal white blood cell count (P < 0.0076) and abnormal platelet count (P < 0.00001). Clinical parameters like hypoxia have a significant association in COVID-19 cases with and without dengue overlap (P < 0.00001). “Inflammatory markers” analysis such as interleukin 6 (IL-6) (P < 0.00001), CRP (P < 0.00001), and LDH (P < 0.00001) has documented significant association in COVID-19 cases with and without dengue overlap. In a study of 49 cases of COVID-19–dengue overlap, post-COVID lung fibrosis was documented in 1 case while 251 COVID-19 patients with negative dengue serology documented post-COVID lung fibrosis in 45 cases (P < 0.004). In a study of 49 cases of COVID-19–dengue overlap, actual serological assessment in dengue IgM/IgG and COVID-19 antibody titers was documented in significant association (P < 0.00001). Conclusion: COVID-19–dengue overlap is very frequently documented in tropical settings and disease of concern in critical care settings as the natural trend of this entity is different and has an impact on clinical outcome if diagnosis is delayed. COVID-19 pneumonia with dengue fever behaves like “two sides of the same coin” or the “polyhedron” nature of COVID-19 due to antigenic cross reactivity. Rationality for coexistent pathology is still undetermined.

Sepsis is a syndrome initiated by an infection in which an aberrant host response to the initiating microbe leads to organ dysfunction, and, all too frequently, mortality. An enormous increase in our understanding of sepsis has occurred over the past 25 years. Unfortunately, this increase has not been matched by successful new therapies, and sepsis treatment continues to be centered on timely antibiotics and supportive care. The Surviving Sepsis Campaign has focused practitioners on bundles for quality improvement and guidelines for bedside management. Adhering to standardized care has been associated with improvements in patient outcome. The mainstays of sepsis management, including diagnosis, fluid resuscitation, antimicrobial management, and vasopressors, are critical to successfully treating patients with sepsis and septic shock and play a major role in determining outcome from sepsis. At the same time, there is increasing recognition that a “one size fits all” model cannot always be the best approach to patient management because of the inherent heterogeneity associated with sepsis, both in terms of initiating microbe and the host response. Further, identifying new targets for therapy may allow for improved outcomes. This review study serves to highlight the past and present facets of early clinical management of septic patients and then illustrate future directions that will hopefully improve outcomes in this common and lethal syndrome.

Heterogeneity in clinical presentation for patients with sepsis complicates treatment and prognosis and limits the development of new therapy. Reasons for this heterogeneity is unclear but recent studies have identified sub-types sepsis defined by clinical features. These sub-types may be brought about by certain triggers such as endotoxin and may further require a susceptible host. Treatment with hemoperfusion to remove endotoxin is discussed.

Nutritional support is one of the core issues in the treatment of severe acute pancreatitis (SAP). With the continuous progression of research on nutritional therapy, a large volume of evidence has emerged on the strategies and approaches of nutritional support for SAP patients. At the same time, the pathogenesis of SAP and the metabolic characteristics have been intensified in the acute phase of critically ill patients, which helps better understand the nutritional treatment strategy of SAP in terms of pathophysiology and pathogenesis. In this article, by searching electronic databases (PubMed, EMBASE, and Web of Science) from the earliest achievable date of each database to November 13, 2021, we discuss and analyze recent hot spots of SAP nutritional support to help individualize the implementation of nutritional strategies.

Introduction: The current study is to identify the performance of urinary tissue inhibitors of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) for predicting renal replacement therapy (RRT) initiation and mortality in postoperative acute kidney injury (AKI) patients. Methods: Postoperative AKI patients were prospectively and consecutively enrolled. The biomarkers of urinary TIMP-2 and IGFBP7 were detected at the time AKI diagnosed (day 0) and 24 h later (day 1). The primary endpoint was the initiation of RRT, and the secondary endpoint was 30-day mortality. The receiver operating characteristic (ROC) curve was used to assess the performance of biomarkers for the prediction of RRT requirement. Results: There were 220 AKI patients enrolled in this study. Among the 220 patients, 33 (15.0%) initiated RRT during intensive care units period. Urinary (TIMP-2) × (IGFBP7), TIMP-2 and IGFBP7 on day 1 had fair performance for predict RRT initiation, the predictive area under the ROC curve (AUC) were 0.792 (0.732, 0.843), 0.784 (0.724, 0.837), and 0.770 (0.709, 0.824), respectively, with no significant difference. When they combined with clinically independent risk factors (nonrenal sequential organ failure assessment score, duration of surgery procedure, and serum creatinine at the time of AKI diagnosed) to construct predictive models for predicting RRT. The AUCs were greatly improved to be good. The best AUC was achieved by TIMP-2, which was 0.866 (0.814, 0.908). All of the biomarkers performed poor predictive values for predicting 30-day mortality. Conclusion: Urine concentrations of (TIMP-2) × (IGFBP7), TIMP-2 alone, and IGFBP7 alone on AKI day 1 show fair value for prediction of RRT initiation. However, they fail to predict 30-day mortality.

Objective: To evaluate the effect of online objective structured clinical examination (OSCE) in critical care teaching. Methods: This is a self-controlled prospective study performed in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 2020 to 2021. Consecutive students came from various surgical departments. Online tests were conducted for each student pre-and post-ICU round. There were three spots in online OSCE including clinical case, electrocardiography and chest X-ray. Results: Twenty-four students completed the tests. The median age is 27 years (24–28) in the cohort. There are 18 males and 6 females. Of twenty-four students, 7 came from department of neurologic or head-neck surgery, 3 from department of thoracic surgery, 12 from department of abdominal surgery, and 2 from others. There was significant difference in scores between pre-round and post-round ICU test in the chest X-ray spot, which was 3.33±4.81 and 6.67±4.81 respectively (P = 0.029). Scores in the postround ICU test in the electrocardiography spot was higher than that in the pre-round test (5.85±5.05 vs. 8.33±3.80)however no significance was reached (P = 0.056). There was no significant difference in the scores between pre-round and post-round ICU test in the clinical case spot (63.33±18.33 vs 71.67 ± 13.07, P = 0.116). Lastly, there were significant differences in total scores between pre-round and post-round ICU test (72.50±19.83 vs 86.67±13.40, P = 0.019). Conclusions: Online OSCE was feasible in the teaching evaluation of surgical rotation residents in ICU. Surgery rotation residents in ICU should receive more training in electrocardiography and chest X-ray.

Pain is common in severe acute pancreatitis (SAP) and is associated with the disease severity and outcomes. The management of pain in SAP may not only relieve pain but also improve outcomes. However, pancreatic pain in SAP involves several complicated mechanisms. Poor understanding about the pain mechanism in SAP and lack of enough high-quality data on pharmacological and nonpharmacological intervention lead to a limited analgesia strategy in patients with SAP mainly managed using nonsteroidal anti-inflammatory drugs and opioids. This makes pain management in SAP challenging and may cause potential harm. This article reviewed the current management of pain in SAP by combining pain mechanisms with animal or clinical studies and proposed an analgesic ladder based on available evidence to improve pain management in patients with SAP.

Acute pancreatitis (AP) is an acute inflammation of the pancreas. Many of the mild AP and moderately severe AP (SAP) are self-limiting with a good prognosis, but the management of 15%–20% of SAP is very difficult and results in a mortality rate of 36%–50%. It poses a great challenge in clinical diagnosis and treatment. Infected pancreatic necrosis develops in approximately 20% to 30% of patients with AP, which is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated.

Background: Vasopressin receptor antagonists increase serum sodium through increased aquaresis via inhibition of V2 receptors. The purpose of this study was to compare the efficacy and safety of conivaptan versus tolvaptan for the treatment of hyponatremia. Subject and Methods: This was a retrospective study of patients who received conivaptan or tolvaptan for hyponatremia admitted to the neurocritical care unit. Serum sodium values were collected at baseline and daily up to 4 days after the last dose. The primary efficacy outcome was an increase in serum sodium ≥4 mEq/L in 24 h after the first vaptan dose. The primary safety outcome was overcorrection defined by an increase in serum sodium >12 mEq/L in 24 h. Results: Thirty-four encounters (14 conivaptan and 20 tolvaptan) were included. Baseline serum sodium was similar between groups (conivaptan 126 mEq/L and tolvaptan 125 mEq/L). Each group received a median of one vaptan dose received on days 5 and 7 of hospitalization for conivaptan and tolvaptan, respectively. The primary efficacy outcome was similar between conivaptan (9 of 14, 64.3%) and tolvaptan (14 of 20, 70%) groups, P = 1.0, and the median change in serum sodium 24 h after the first vaptan dose was 5 versus 7 mEq/L (P = 0.377), respectively. The rate of overcorrection was similar between conivaptan and tolvaptan patients (7.1% vs. 15% P = 0.627). Conclusion: In this study, conivaptan compared to tolvaptan for the treatment of hyponatremia in patients admitted with a primary neurological diagnosis appears efficacious and safe. Further studies are warranted given the sample size of this cohort.

Acute pancreatitis (AP) is one of the common gastrointestinal diseases requiring hospitalization. Once AP develops into severe AP, the mortality markedly increases. Animal studies have confirmed that thoracic epidural analgesia (TEA) has many benefits for AP and can provide the survival rate of experimental animals. Existing clinical studies have also shown the safety and effectiveness of TEA in AP. This paper reviews the potential benefits and possible mechanisms of TEA for AP.

Diaphragm weakness develops in up to 80% of the critically ill patients, and is associated with adverse clinical outcomes. Mechanical ventilation has been proposed to play a role in the development of diaphragm weakness in critically ill patients, especially by ventilator under-assist or ventilator over-assist. Therefore, in addition to the concept of lung-protective ventilation to protect the lung, diaphragm-protective ventilation has been recently proposed to limit the development of diaphragm weakness. In this concise review, we will discuss the current evidence for diaphragm-protective ventilation and the clinical consequences.

Background: There are controversies regarding corticosteroids using in coronavirus disease-2019 (COVID-19) pneumonia in the current pandemic. Objectives: This study investigates the efficacy and safety profiles of corticosteroids therapy in COVID-19 patients. Methods: Retrospective, multicenter study case series of consecutive patients with confirmed COVID-19 infection at the whole hospital from January 1 to March 1, 2020, were enrolled. Demographic, clinical, radiological, laboratory, and treatment data were collected and analyzed. The effect of corticosteroids therapy on death and organ-failure complications of pneumonia were analyzed by logistic regression. Results: A total of 470 COVID-19 patients at the whole hospital were enrolled. According to the time of corticosteroids initiation and severity of illness, there were 159 patients stratified into critical ill group and 64% (102 of 159) patients received corticosteroids treatments. Ninety-four percent (166 of 176) of corticosteroids were methylprednisolone. The median cumulative corticosteroids dosage was 300 mg equivalent of methylprednisolone over a median duration of 6 days. Multivariate regression analysis showed that corticosteroids use did not affect the mortality. However, corticosteroids therapy at moderate cumulative doses (total exposure 480 mg to 1200 mg) was associated with deceased occurrence of organ-failure complications in critically ill COVID-19. Conclusions: Corticosteroids have no effect to mortality in COVID-19 patients. The moderate cumulative doses of corticosteroids might decrease organ-failure complications in critically ill COVID-19. Further large-scale randomized controlled trials are warranted to confirm our findings, until then use of corticosteroids should be used with caution COVID-19 patients.

Background: Extracorporeal membrane oxygenation (ECMO) has been used for treating myocarditis for years. To extubate and be awake have been proven to be useful in adult patients supported with ECMO, especially for long-term pulmonary support. However, the role of awake ECMO remains still unclear in pediatric patients with acute fulminant myocarditis (AFM). Objectives: The objective is to summarize the application of awake ECMO during the treatment of pediatric AFM. Methods: Seven patients with AFM received ECMO from October 2018 to March 2020 in the Pediatric Intensive Care Unit, Senior Department of Pediatrics, the Seventh Medical Center of PLA General Hospital. During the process, the patients were extubated and supported with awake ECMO. Retrospective analysis of basic characteristics, clinical vital signs, outcomes, and parameters of ECMO was carried out. Results: All the patients received venoarterial mode ECMO during the treatment, and awake ECMO was implemented after the patients were stable. During the period, all the patients were fed with enteral nutrition. The respiratory and circulatory conditions were improved during the awake ECMO. Finally, all the patients successfully weaned from ECMO and survived to discharge from hospital. Conclusion: It is possible for pediatric ECMO-supported patients with AFM to extubation and keep awake. The choice of patients, close monitoring during process, and good coordination are key factors for the successful implementation of awake ECMO.

Background: We aimed to establish a modified cecal ligation and puncture (CLP) rat model with omentectomy for simulating moderate-to-severe septic kidney injury (AKI). Subjects and Methods: Rats were randomly divided into four groups subjected to: Traditional CLP (n = 40); the modified CLP procedure (n = 40); sham surgery (abdominal incision only) (n = 6); and abdominal incision and omentectomy only (n = 6). We evaluated the severity of renal injury according to serum creatinine levels at 0, 24, and 48 h postoperatively and cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) levels at 12 h postoperatively, graded the severity of sepsis, monitored the degree of peritonitis, and examined animal survival. Results: Compared with the traditional CLP group, the modified CLP group developed more severe sepsis at postoperative 48 h, had more severe renal pathology, and developed more severe AKI with high homogeneity. Most rats in the traditional CLP group exhibited complete wrapping of the puncture site by omentum with limited peritonitis, while partial wrapping with pus spreading was observed in some. All rats in the modified CLP group developed puncture site necrosis, with pus spreading without formation of an encapsulated abscess, and a consistent degree of peritonitis. The 7-day survival rates in the traditional and modified CLP groups were 65.0% and 50.0%, respectively. Conclusion: The traditional CLP approach was associated with an even distribution of different AKI severities among treated animals, whereas the modified CLP approach established a consistently more severe rat model of septic AKI, constituting an important advance for optimizing septic AKI animal models.