Evaluation of characteristics and prognosis of COVID-19 patients requiring invasive mechanical ventilation during dominance of nonvariant, alpha, delta, and omicron variants in tertiary hospitals of Japan.

BACKGROUND: In November 2021, the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in South Africa and subsequently rapidly spread around the world. Despite the reduced severity of the omicron variants, many patients become severely ill after infection and undergo invasive mechanical ventilation, but there are few reports on their background and prognosis throughout all variant periods. This study aimed to evaluate risk factors affecting patients requiring invasive mechanical ventilation with each variant of COVID-19 pandemic in Japan from nonvariants to omicron variants. METHOD: This retrospective observational study was conducted at the Department of Emergency and Critical Care Medicine, Kansai Medical University Hospital and Kansai Medical University Medical Center, Osaka, Japan, from March 2020 to March 2023. Eligible patients were those who underwent invasive ventilation for COVID-19 pneumonia. We set the primary endpoint as in-hospital mortality. Multivariable logistic regression analysis adjusted for clinically important variables was performed to evaluate the clinical outcomes. RESULTS: We included 377 patients: 118 in the Nonvariant group, 154 in the Alpha group, 42 in the Delta group, and 63 patients in the Omicron group. Mortality rates for each group were 23.7% for the Nonvariant group, 12.3% for the Alpha group, 7.1% for the Delta group, and 30.5% for the Omicron group. Patient age was significantly associated with increased mortality (adjusted odds ratio [AOR]: 1.097; 95% confidence interval [CI]: 1.057-0.138, P < 0.001). Immunodeficiency (AOR: 3.388, 95% CI: 1.377-8.333, P = 0.008), initial SOFA score (AOR: 1.190, 95% CI: 1.056-1.341, P = 0.004), dialysis prior to COVID-19 (AOR: 3.695, 95% CI: 1.117-11.663, P = 0.026), and smoking history (AOR: 2.548, 95% CI: 1.153-5.628, P = 0.021) were significantly associated with increased mortality. Differences in variants were not significant factors associated with high mortality. CONCLUSION: We compared the background and prognosis of patients with COVID-19 pneumonia requiring invasive mechanical ventilation between SARS-CoV-2 variants. In these patients, differences in variants did not affect prognosis. Hospital mortality in critically ill COVID-19 patients was significantly higher in the older patients with bacterial coinfection, or patients with immunodeficiency, COPD, and chronic renal failure on dialysis.

The evaluation of risk factors for prolonged viral shedding during anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antivirals in COVID-19 patients with B-cell lymphoma treated by anti-CD20 antibody.

BACKGROUND: The global impact of the coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality. Immunocompromised patients, particularly those treated for B-cell lymphoma, have shown an increased risk of persistent infection with SARS-CoV-2 and severe outcomes and mortality. Multi-mutational SARS-CoV-2 variants can arise during the course of such persistent cases of COVID-19. No optimal, decisive strategy is currently available for patients with persistent infection that allows clinicians to sustain viral clearance, determine optimal timing to stop treatment, and prevent virus reactivation. We introduced a novel treatment combining antivirals, neutralizing antibodies, and genomic analysis with frequent monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection. The aim of this retrospective study was to report and evaluate the efficacy of our novel treatment for immunocompromised B-cell lymphoma patients with persistent COVID-19 infection. METHODS: This retrospective descriptive analysis had no controls. Patients with B-cell lymphoma previously receiving immunotherapy including anti-CD20 antibodies, diagnosed as having COVID-19 infection, and treated in our hospital after January 2022 were included. We selected anti-SARS-CoV-2 monoclonal antibodies according to subvariants. Every 5 days, viral load was tested by RT-PCR, with antivirals continued until viral shedding was confirmed. Primary outcome was virus elimination. Independent predictors of prolonged viral shedding time were determined by multivariate Cox regression. RESULTS: Forty-four patients were included in this study. Thirty-five patients received rituximab, 19 obinutuzumab, and 26 bendamustine. Median treatment duration was 10 (IQR, 10-20) days; 22 patients received combination antiviral therapy. COVID-19 was severe in 16 patients, and critical in 2. All patients survived, with viral shedding confirmed at median 28 (IQR, 19-38) days. Bendamustine use or within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma significantly prolonged time to viral shedding. CONCLUSIONS: Among 44 consecutive patients treated, anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antiviral drugs, switching, and combination therapy resulted in virus elimination and 100% survival. Bendamustine use, within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma were the significant independent predictors of prolonged viral shedding time.

A descriptive study of abdominal complications in patients with mild COVID-19 presenting to the emergency department: a single-center experience in Japan during the omicron variant phase.

BACKGROUND: COVID-19 is widely known to induce a variety of extrapulmonary manifestations. Gastrointestinal symptoms have been identified as the most common extra-pulmonary manifestations of COVID-19, with an incidence reported to range from 3 to 61%. Although previous reports have addressed abdominal complications with COVID-19, these have not been adequately elucidated for the omicron variant. The aim of our study was to clarify the diagnosis of concomitant abdominal diseases in patients with mild COVID-19 who presented to hospital with abdominal symptoms during the sixth and seventh waves of the pandemic of the omicron variant in Japan. METHODS: This study was a retrospective, single-center, descriptive study. In total, 2291 consecutive patients with COVID-19 who visited the Department of Emergency and Critical Care Medicine, Kansai Medical University Medical Center, Osaka, Japan, between January 2022 and September 2022 were potentially eligible for the study. Patients delivered by ambulance or transferred from other hospitals were not included. We collected and described physical examination results, medical history, laboratory data, computed tomography findings and treatments. Data collected included diagnostic characteristics, abdominal symptoms, extra-abdominal symptoms and complicated diagnosis other than that of COVID-19 for abdominal symptoms. RESULTS: Abdominal symptoms were present in 183 patients with COVID-19. The number of patients with each abdominal symptom were as follows: nausea and vomiting (86/183, 47%), abdominal pain (63/183, 34%), diarrhea (61/183, 33%), gastrointestinal bleeding (20/183, 11%) and anorexia (6/183, 3.3%). Of these patients, 17 were diagnosed as having acute hemorrhagic colitis, five had drug-induced adverse events, two had retroperitoneal hemorrhage, two had appendicitis, two had choledocholithiasis, two had constipation, and two had anuresis, among others. The localization of acute hemorrhagic colitis was the left-sided colon in all cases. CONCLUSIONS: Our study showed that acute hemorrhagic colitis was characteristic in mild cases of the omicron variant of COVID-19 with gastrointestinal bleeding. When examining patients with mild COVID-19 with gastrointestinal bleeding, the potential for acute hemorrhagic colitis should be kept in mind.

Clinical experience of treatment of immunocompromised individuals with persistent SARS-CoV-2 infection based on drug resistance mutations determined by genomic analysis: a descriptive study.

BACKGROUND: The efficacy of antiviral drugs that neutralize antibody drugs and fight against SARS-COV-2 is reported to be attenuated by genetic mutations of the virus in vitro. When B-cell immunocompromised patients are infected with SARS-COV-2, the infection can be prolonged, and genetic mutations can occur during the course of treatment. Therefore, for refractory patients with persistent COVID-19 infection, genomic analysis was performed to obtain data on drug resistance mutations as a reference to determine which antiviral drugs and antibody therapies might be effective in their treatment. METHODS: This was a descriptive analysis with no controls. Patients were diagnosed as having COVID-19, examined, and treated in the Kansai Medical University General Medical Center between January 2022 and January 2023. The subjects of the study were B-cell immunocompromised patients in whom genome analysis of SARS-CoV-2 was performed. RESULTS: During the study period, 984 patients with COVID-19 were treated at our hospital. Of those, 17 refractory cases underwent genomic analysis. All 17 patients had factors related to immunodeficiency, such as malignant lymphoma or post-organ transplantation. Eleven patients started initial treatment for COVID-19 at our hospital, developed persistent infection, and underwent genomic analysis. Six patients who were initially treated for COVID-19 at other hospitals became persistently infected and were transferred to our hospital. Before COVID-19 treatment, genomic analysis showed no intrahost mutations in the NSP5, the NSP12, and the RBD regions. After COVID-19 treatment, mutations in these regions were found in 12 of 17 cases (71%). Sixteen patients survived the quarantine, but one died of sepsis. CONCLUSIONS: In genomic analysis, more mutations were found to be drug-resistant after COVID-19 treatment than before COVID-19 treatment. Although it was not possible to demonstrate the usefulness of genome analysis for clinical application, the change of the treatment drug with reference to drug resistance indicated by genomic analysis may lead to good outcome of immunocompromised COVID-19 patients.

Efficacy of the shoelace technique for extremity fasciotomy wounds due to compartment syndrome.

BACKGROUND: The shoelace technique for compartment syndrome allows application of sustained tightening tension to an entire wound and intermittent tightening of the shoelace without requiring its replacement or anesthesia. We retrospectively evaluated the usefulness of the shoelace technique in the management of extremity fasciotomy wounds before and after its introduction in our institution. METHODS: We targeted 25 patients who were diagnosed as having compartment syndrome and underwent extremity fasciotomy at our hospital from April 2012 to December 2021. The N group, comprising 12 patients treated without the shoelace technique, and the S group, comprising 13 patients treated with the shoelace technique, were compared retrospectively for each outcome. RESULTS: There were no significant differences between the two groups in patient background. Compared with the N group patients, all of the S group patients avoided skin grafting (S group: n = 0, 0%; N group: n = 6, 50.0%; p < 0.01). However, there was no significant difference in the number of days to final wound closure (S group: 39.5 [IQR 24.3-58.0] days; N group: 24.0 [IQR 18.5-31.0] days, p = 0.06). CONCLUSIONS: We considered the shoelace technique to be a useful wound closure method for fasciotomy wounds caused by compartment syndrome because it can significantly reduce the need for skin grafting and tends to shorten the wound closure period.

Combined brain and thoracic trauma surgery in a hybrid emergency room system: a case report.

BACKGROUND: A novel trauma workflow system called the hybrid emergency room (Hybrid ER), which combines a sliding CT scanner system with interventional radiology features (IVR-CT), was initially instituted in our emergency department in 2011. Use of the Hybrid ER enables CT diagnosis and emergency therapeutic interventions without transferring the patient to another room. We describe an illustrative case of severe multiple blunt trauma that included injuries to the brain and torso to highlight the ability to perform multiple procedures in the Hybrid ER. CASE PRESENTATION: A 46-year-old man sustained multiple injuries after falling from height. An early CT scan performed in the Hybrid ER revealed grade IIIa thoracic aortic injury, left lung contusion, and right subdural haematoma and subarachnoid haemorrhage. Without relocating the patient, all definitive procedures, including trepanation, total pneumonectomy, and thoracic endovascular aneurysm repair were performed in the Hybrid ER. At 5.72 h after definitive surgery was begun, the patient was transferred to the intensive care unit. CONCLUSIONS: The Hybrid ER has the potential to facilitate the performance of multiple definitive procedures in combination to treat severe multiple blunt trauma including injuries to the brain and torso. Emergency departments with more than one resuscitation room would benefit from a Hybrid ER to treat complex emergency cases.

Hemophagocytic syndrome with severe sepsis caused by Capnocytophaga canimorsus.

Capnocytophaga canimorsus, commonly transmitted by dog bites, can cause severe sepsis, and the mortality rate is very high. We experienced a case of hemophagocytic lymphohistiocytosis (HLH) complicated by severe sepsis caused by C. canimorsus. A 58-year-old man with no remarkable medical history was admitted to another hospital with fever and mild consciousness disorder developed 3 days after being bitten by his dog. The next day, the patient developed disseminated intravascular coagulation and shock and was transferred to our emergency medical center. Blood tests showed hyperferritinemia and cytopenia, and bone marrow aspiration was performed. As a result, we diagnosed severe sepsis and HLH. Once antibiotic and steroid therapy was started, the patient's infection and cytopenia improved. Unfortunately, the patient's fingers and toes required amputation, but his life was saved, and he was discharged from hospital. Because HLH may be hidden in such cases, it may be necessary to measure serum ferritin and perform bone marrow aspiration if hyperferritinemia is suspected.

Cardiopulmonary resuscitation support application on a smartphone - randomized controlled trial.

BACKGROUND: This simulation trial aimed to compare the quality of cardiopulmonary resuscitation (CPR) with and without the newly-developed CPR support application on smartphones. METHODS AND RESULTS: In this trial, participants were randomly assigned to either the CPR support application group or the control group, stratified by sex and previous CPR training. Participants' CPR skills were evaluated by a 2-min case-based scenario test using the Leardal Resusci Anne PC Skill reporting Manikin System(®). The outcome measures were the proportion of chest compressions performed in each group and the number of total chest compressions and appropriate chest compressions performed during the 2-min test period. A total of 84 participants were enrolled and completed the protocol. All participants in the CPR support application group performed chest compressions, compared with only 31 (75.6%) in the control group (P<0.001). Among participants who performed chest compressions during the 2-min test period, the number of total chest compressions was significantly higher in the CPR support application group than in the control group (211.6±29.5 vs. 77.0±43.3, P<0.001). The number of appropriate chest compressions tended to be greater in the CPR support application group than in the control group, although it was statistically insignificant (30.3±57.3 vs. 17.2±28.7, P=0.246). CONCLUSIONS: In this cohort of laypersons, the newly-developed CPR support application for smartphones contributed to increasing the implementation rate and the number of total chest compressions performed and may assist in improving the survival rate for out-of-hospital cardiac arrests (UMIN000004740).

Treatment strategy for severe trauma patients requiring aortic occlusion for impending cardiopulmonary arrest in the hybrid emergency room.

Aim: Computed tomography (CT) is useful in trauma care. Severely ill trauma patients may not tolerate whole-body CT even without patient transfer. This study examined clinical flow of severe trauma patients requiring aortic occlusion (AO) such as resuscitative thoracotomy or REBOA in the hybrid emergency room (ER) and investigated patient clinical courses prioritizing CT first versus resuscitation including AO first. Methods: This retrospective, single-center observational study included consecutive trauma patients visiting our ER between May 2016 and February 2023. Patients were divided into the CT first group (whole-body CT preceded AO) and AO first group (AO preceded whole-body CT) and into two subgroups: AO after CT (AO/interventions for hemorrhage performed just after CT in the CT first group), and CT after AO (CT or damage control surgery performed after AO in the AO first group). We investigated 28-day survival rates. Results: Survival probability by TRISS method was 49% (range: 3.3-94) in the CT first group (n = 6) and 20% (range: 0.7-45) in the AO first group (n = 7). Actual 28-day survival rates were 50% and 57%, respectively. Survival rates of the AO after CT subgroup (CT first group) were 75% (3/4) and 0% (0/2), respectively, and those of the CT after AO subgroup (AO first group) were 25% (1/4) and 100% (3/3), respectively. Conclusion: In severe trauma patients with low predicted probability of survival treated in the hybrid ER, survival rates might be better if resuscitation including AO is performed before CT and if damage control surgery is performed first before CT.

Development and validation of a prehospital termination of resuscitation (TOR) rule for out - of hospital cardiac arrest (OHCA) cases using general purpose artificial intelligence (AI).

BACKGROUND: Prehospital identification of futile resuscitation efforts (defined as a predicted probability of survival lower than 1%) for out-of-hospital cardiac arrest (OHCA) may reduce unnecessary transport. Reliable prediction variables for OHCA 'termination of resuscitation' (TOR) rules are needed to guide treatment decisions. The Universal TOR rule uses only three variables (Absence of Prehospital ROSC, Event not witnessed by EMS and no shock delivered on the scene) has been externally validated and is used by many EMS systems. Deep learning, an artificial intelligence (AI) platform is an attractive model to guide the development of TOR rule for OHCA. The purpose of this study was to assess the feasibility of developing an AI-TOR rule for neurologically favorable outcomes using general purpose AI and compare its performance to the Universal TOR rule. METHODS: We identified OHCA cases of presumed cardiac etiology who were 18 years of age or older from 2016 to 2019 in the All-Japan Utstein Registry. We divided the dataset into 2 parts, the first half (2016-2017) was used as a training dataset for rule development and second half (2018-2019) for validation. The AI software (Prediction One®) created the model using the training dataset with internal cross-validation. It also evaluated the prediction accuracy and displayed the ranking of influencing variables. We performed validation using the second half cases and calculated the prediction model AUC. The top four of the 11 variables identified in the model were then selected as prognostic factors to be used in an AI-TOR rule, and sensitivity, specificity, positive predictive value, and negative predictive value were calculated from validation cohort. This was then compared to the performance of the Universal TOR rule using same dataset. RESULTS: There were 504,561 OHCA cases, 18 years of age or older, 302,799 cases were presumed cardiac origin. Of these, 149,425 cases were used for the training dataset and 153,374 cases for the validation dataset. The model developed by AI using 11 variables had an AUC of 0.969, and its AUC for the validation dataset was 0.965. The top four influencing variables for neurologically favorable outcome were Prehospital ROSC, witnessed by EMS, Age (68 years old and younger) and nonasystole. The AUC calculated using the 4 variables for the AI-TOR rule was 0.953, and its AUC for the validation dataset was 0.952 (95%CI 0.949 -0.954). Of 80,198 patients in the validation cohort that satisfied all four criteria for the AI-TOR rule, 58 (0.07%) had a neurologically favorable one-month survival. The specificity of AI-TOR rule was 0.990, and the PPV was 0.999 for predicting lack of neurologically favorable survival, both the specificity and PPV were higher than that achieved with the universal TOR (0.959, 0.998). CONCLUSIONS: The accuracy of prediction models using AI software to determine outcomes in OHCA was excellent and the AI-TOR rule's variables from prediction model performed better than the Universal TOR rule. External validation of our findings as well as further research into the utility of using AI platforms for TOR prediction in clinical practice is needed.

Maximal chemiluminescent intensity in response to lipopolysaccharide assessed by endotoxin activity assay on admission day predicts mortality in patients with sepsis.

OBJECTIVE: Sepsis is the leading cause of death among critically ill patients. There are, however, few appropriate biomarkers to predict mortality in patients with sepsis. We focused on maximal chemiluminescent intensity in response to lipopolysaccharide assessed by endotoxin activity assay and evaluated the diagnostic value of maximal chemiluminescent intensity on admission day as a predictor of mortality in patients with sepsis. DESIGN: Prospective, observational study. SETTING: ICU. PATIENTS: One hundred and thirty-two patients with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Within 12 hours after admission, a whole-blood sample was collected, and variables assessed by endotoxin activity assay were measured in each patient. Severity of illness was assessed simultaneously by Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score. The primary outcome was 28-day mortality. One hundred and fifteen patients survived and 17 died. maximal chemiluminescent intensity values were significantly lower in the nonsurvivors than in the survivors (p <0.05). We investigated maximal chemiluminescent intensity, APACHE II score, and SOFA score as predictors of 28-day mortality. Receiver operating characteristic analysis showed that area under the curve for maximal chemiluminescent intensity was 0.902, which was superior to the area under the curves for APACHE II score (0.836) and SOFA score (0.807). At the optimal cutoff value for maximal chemiluminescent intensity, 21,000 RLU/s, the sensitivity for correct prediction of 28-day mortality was 82.4% and the specificity was 92.2%. Kaplan-Meier analysis showed that low maximal chemiluminescent intensity (<21,000 RLU/s) closely correlated with poor overall patient survival compared with high maximal chemiluminescent intensity (>21,000 RLU/s) (p <0.001 by log-rank test). After adjusting for APACHE II score by Cox regression analysis, maximal chemiluminescent intensity was identified as an independent predictor for the probability of 28-day mortality. CONCLUSION: Maximal chemiluminescent intensity level measured on admission day appears to have high predictive value for mortality in patients with sepsis.

Impact on survival of whole-body computed tomography before emergency bleeding control in patients with severe blunt trauma.

INTRODUCTION: Whole-body computed tomography (CT) has gained importance in the early diagnostic phase of trauma care. However, the diagnostic value of CT for seriously injured patients is not thoroughly clarified. This study assessed whether preoperative CT beneficially affected survival of patients with blunt trauma who required emergency bleeding control. METHODS: This retrospective study was conducted from January 2004 to December 2010 in two tertiary trauma centers in Japan. The primary inclusion criterion was patients with blunt trauma who required emergency bleeding control (surgery or transcatheter arterial embolization). CT before emergency bleeding control was performed at the attending physician's discretion based on individual patient condition (for example, hemodynamic stability or certain abnormalities in the primary survey). We assessed covariates associated with 28-day mortality with multivariate logistic regression analysis and evaluated standardized mortality ratio (SMR, ratio of observed to predicted mortality by Trauma and Injury Severity Score (TRISS) method) in two subgroups of patients who did or did not undergo CT. RESULTS: The inclusion criterion was fulfilled by 152 patients with a median Injury Severity Score of 35.3. During the early resuscitation phase, 132 (87%) patients underwent CT and 20 (13%) did not. Severity of injury was significantly higher in the non-CT versus CT group patients. Observed mortality rate was significantly lower in the CT versus non-CT group (18% vs. 80%, P <0.001). Multivariate adjustment for the probability of survival (Ps) by TRISS method confirmed CT as an independent predictor for 28-day mortality (adjusted OR, 7.22; 95% CI, 1.76 to 29.60; P = 0.006). In the subgroup with less severe trauma (TRISS Ps ≥50%), SMR in the CT group was 0.63 (95% CI, 0.23 to 1.03; P = 0.066), indicating no significant difference between observed and predicted mortality in the CT group. In contrast, in the subgroup with more severe trauma (TRISS Ps <50%), SMR was 0.65 (95% CI, 0.41 to 0.90; P = 0.004) only in the CT group, whereas the difference between observed and predicted mortality was not significant in the non-CT group, suggesting a possible beneficial effect of CT on survival only in trauma patients at high risk of death. CONCLUSION: CT performed before emergency bleeding control might be associated with improved survival, especially in severe trauma patients with TRISS Ps of <50%.

Probiotic/synbiotic therapy for treating critically ill patients from a gut microbiota perspective.

The gut is an important target organ for stress caused by severe insults such as sepsis, trauma, burn, shock, bleeding and infection. Severe insult to the gut is considered to have an important role in promoting infectious complications and multiple organ dysfunction syndrome. These are sequelae of interactions between deteriorated intestinal epithelium, the immune system and commensal bacteria. The gut is the "motor" of multiple organ failure, and now it is recognized that gut dysfunction is a causative factor in disease progression. The gut flora and environment are significantly altered in critically ill patients, and the number of obligate anaerobes is associated with prognosis. Synbiotic therapy is a combination of probiotics and prebiotics. Probiotic, prebiotic and synbiotic treatment has been shown to be a promising therapy to maintain and repair the gut microbiota and gut environment. In the critically ill, such as major abdominal surgery, trauma and ICU patients, synbiotic therapy has been shown to significantly reduce septic complications. Further basic and clinical research would clarify the underlying mechanisms of the therapeutic effect of probiotic/synbiotic treatment and define the appropriate conditions for use.

Reduction of thoracic aorta motion artifact with high-pitch 128-slice dual-source computed tomographic angiography: a historical control study.

OBJECTIVES: Electrocardiogram-gated imaging combined with multi-detector row computed tomography (MDCT) has reduced cardiac motion artifacts, but it was not practical in the emergency setting. The purpose of this study was to evaluate the ability of a high-pitch, 128-slice dual-source CT (DSCT) scanner to reduce motion artifacts in patients admitted to the emergency room. METHODS: This study comprised 100 patients suspected of having thoracic aorta lesions. We examined 47 patients with the 128-slice DSCT scanner (DSCT group), and 53 patients were examined with a 64-slice MDCT scanner (MDCT group). Six anatomic areas in the thoracic aorta were evaluated. RESULTS: Computed tomography images in the DSCT group were distinct, and significant differences were observed in images of all areas between the 2 groups except for the descending aorta. CONCLUSIONS: The high-pitch DSCT scanner can reduce motion artifacts of the thoracic aorta and enable radiological diagnosis even in patients with tachycardia and without breath hold.

Prognostic impact of fecal pH in critically ill patients.

INTRODUCTION: We have reported that altered gut flora is associated with septic complications and eventual death in critically ill patients with systemic inflammatory response syndrome. It is unclear how fecal pH affects these patients. We sought to determine whether fecal pH can be used as an assessment tool for the clinical course of critically ill patients. METHODS: Four hundred ninety-one fecal samples were collected from 138 patients who were admitted to the Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Japan. These patients were treated in the intensive care unit for more than 2 days. Fecal pH, fecal organic acids, and fecal bacteria counts were measured and compared by survived group and nonsurvived group, or nonbacteremia group and bacteremia group. Logistic regression was used to estimate relations between fecal pH, age, sex, or APACHE II score and mortality, and incidence of bacteremia. Differences in fecal organic acids or fecal bacteria counts among acidic, neutral, and alkaline feces were analyzed. RESULTS: The increase of fecal pH 6.6 was significantly associated with the increased mortality (odds ratio, 2.46; 95% confidence interval, 1.25 to 4.82) or incidence of bacteremia (3.25; 1.67 to 6.30). Total organic acid was increased in acidic feces and decreased in alkaline feces. Lactic acid, succinic acid, and formic acid were the main contributors to acidity in acidic feces. In alkaline feces, acetic acid was significantly decreased. Propionic acid was markedly decreased in both acidic and alkaline feces compared with neutral feces. No differences were noted among the groups in bacterial counts. CONCLUSIONS: The data presented here demonstrate that the fecal pH range that extended beyond the normal range was associated with the clinical course and prognosis of critically ill patients.

Effects of exchange transfusion with liposome-encapsulated hemoglobin on VO2/DO2.

We clarified the effect of exchange transfusion with liposome-encapsulated hemoglobin (neo red cells, NRCs) with low O2 affinity (P50O2 = 50 mm Hg) on O2 metabolism. Rabbits were randomly assigned to receive serial exchange transfusions with NRC (NRC group, n = 5), shed blood diluted 1:1 with saline (red blood cell (RBC) group, n = 5), or saline alone (plasma group, n = 4) under hemodynamic monitoring. Cardiac tamponade was then induced and successively reversed to determine relationships between O2 consumption (VO2) and O2 delivery (DO2) using the dual-line method. Mean values of Hb concentration after exchange transfusion were 5.7 (NRC), 6.0 (RBC), and 1.5 (plasma) g/dL. The plasma group could not even survive the initial exchange hemodilution due to a critical decrease in DO2. The NRC, but not the RBC group, developed progressive metabolic acidosis and lactatemia, as well as increases in PaCO2 and decreases in tissue PO2 in skeletal muscle after exchange transfusion. Nonetheless, systemic O2 uptake indices obtained from an analysis of the VO2/DO2 relationship in the NRC and RBC groups were comparable. These findings suggested that systemic O2 uptake was maintained in rabbits after exchange transfusion with NRC, although progressive tissue hypoxia with systemic acidosis is indicative of inadequate peripheral circulation and insufficient aerobic metabolism during extended hemodilution in which 86% of the circulating blood is replaced.

EFFECTS OF 2-METHYL-2-THIAZOLINE ON CIRCULATORY DYNAMICS AND INTESTINAL VASCULAR SYSTEM IN RABBITS WITH ENDOTOXIC SHOCK.

ABSTRACT: We hypothesized that circulatory and jejunal mucosal blood flow would improve after 2-methyl-2thiazoline (2MT) administration in endotoxic shock. This study aimed to evaluate changes in systemic circulation and in superior mesenteric venous (SMV) blood flow and jejunal mucosal tissue blood flow of the intestinal vascular system over time after administration of 2MT in rabbits with endotoxic shock. We created four groups (n = 6 each): control group, LPS (1 mg/kg) group, 2MT (80 mg/kg) group, and LPS-2MT group. As indicators of circulation, we measured MAP, heart rate, cardiac index, lactic acid level, SMV blood flow, and jejunal mucosal tissue blood flow every 30 min from 0 to 240 min. The drop in MAP observed in the LPS group was suppressed by 2MT administration. Superior mesenteric venous blood flow dropped temporarily with LPS administration but then rose thereafter. After administration of 2MT to the LPS group, SMV blood flow began to rise earlier than that in the LPS group and did not decline below that of the control group thereafter. In the LPS group, jejunal mucosal tissue blood flow transiently decreased and then increased but at a lower level than that in the control group. However, in the LPS-2MT group, although a transient decrease in jejunal mucosal tissue blood flow was observed, its flow then improved to the level of the control group. An interaction between 2MT and LPS was observed for jejunal mucosal tissue blood flow from 90 to 180 min and at 240 min (P < 0.05). We showed that 2MT maintained MAP and improved SMV blood flow and jejunal mucosal tissue blood flow. In a rabbit model of endotoxic shock, 2MT had a positive effect on MAP and jejunal mucosal tissue blood flow.

Novel treatment combining antiviral and neutralizing antibody-based therapies with monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection.

Because prolonged viral replication of SARS-CoV-2 is increasingly being recognized among immunocompromised patients, subacute or chronic COVID-19 pneumonia can cause persistent lung damage and may lead to viral escape phenomena. Highly efficacious antiviral therapies in immunosuppressed hosts with COVID-19 are urgently needed. From February 2022, we introduced novel treatment combining antiviral therapies and neutralizing antibodies with frequent monitoring of spike-specific antibody and RT-PCR cycle threshold (Ct) values as indicators of viral load for immunocompromised patients with persistent COVID-19 infection. We applied this treatment to 10 immunosuppressed patients with COVID-19, and all completed treatment without relapse of infection. This may be a potentially successful treatment strategy that enables us to sustain viral clearance, determine optimal timing to stop treatment, and prevent virus reactivation in immunocompromised patients with persistent COVID-19.

Peak value of serum KL-6 may be useful for predicting poor prognosis of severe COVID-19 patients.

BACKGROUND: Serum Krebs von den Lungen 6 (KL-6), which reflects alveolar epithelial injury, was reported to be useful to predict the progression of pneumonitis induced by COVID-19 in the early phase. This study aimed to evaluate the peak value of serum KL-6 during hospitalization for COVID-19 to discover a more useful biomarker for predicting prognosis in COVID-19 patients. METHODS: In this retrospective, single-center, observational study, we analyzed the data of 147 hospitalized patients who required supplemental oxygen, high-flow oxygen therapy, or invasive mechanical ventilation for respiratory failure due to COVID-19 from March 2020 to February 2021. We extracted data on patient sex, age, comorbidities, treatment, and biomarkers including the initial and peak values of KL-6. Inclusion criteria were examination of the studied biomarkers at least once within 3 days of admission, then at least once a week, and at a minimum, at least twice during the entire hospitalization. Area under the receiver operating curve (AUC) was analyzed to determine the accuracy of several biomarkers including KL-6 and LDH for predicting poor prognosis defined as survivors requiring invasive mechanical ventilation for over 28 days or non-survivors of COVID-19. Univariable and multivariate logistic regression analyses were performed to investigate the prognostic value of the baseline characteristics and biomarkers. RESULTS: Among the 147 patients, 108 (73.5%) had a good prognosis and 39 (26.5%) had a poor prognosis. The AUC analysis indicated that peak KL-6 showed precise accuracy in the discrimination of patients with poor prognosis (AUC 0.89, p < 0.001). The best cut-off value for KL-6 concentration was 966 U/mL (sensitivity 81.6%, specificity84.3%). After adjustment, increasing peak values of KL-6 or LDH were associated with a high risk of poor prognosis, with an adjusted odds ratio of 1.35 for peak value of KL-6, per 100 U/mL increase (95% CI 1.17-1.57, p < 0.001) and 2.16 for peak value of LDH, per 100 U/L increase (95% CI 1.46-3.20, p < 0.001). CONCLUSIONS: Peak values of KL-6 and LDH measured during hospitalization might help to identify COVID-19 patients with respiratory failure who are at higher risk for a poor prognosis.

Profile and Outcome of Victims of an Earthquake in an Aging Society: A Population-Based Descriptive Study of the Earthquake in Osaka, Japan, on June 18, 2018.

OBJECTIVE: The aim of this study is to reveal the characteristics and outcomes of patients injured in a major earthquake and who were transported to a hospital by ambulance. METHODS: This study was a retrospective descriptive epidemiological study including all patients who were injured after a major earthquake struck Osaka Prefecture on June 18, 2018, and were transported to a hospital by ambulance. The main outcome was the prognosis at each hospital's emergency department. RESULTS: In total, 214 patients were included in the analysis. Their median age was 74 years (IQR, 54-82); 53 (24.8%) were men and 161 (75.2%) were women. The median time from ambulance call to arrival at the scene was 10 min (IQR, 7-15), and the median time from ambulance call to the hospital arrival was 37 min (IQR, 30-51). Ninety-seven patients (45.3%) were admitted to a hospital, 114 patients (53.3%) were discharged home to and from the emergency department, and 3 patients (1.4%) died. Among the patients discharged to home from the emergency department, the most common pathological condition was head bruising in 16 patients. CONCLUSIONS: This study revealed the profile of injured patients transported by ambulances after an earthquake that struck an aging society.