Hypercalcemic Crisis Complicated With Acute Respiratory Distress Syndrome Due to Hot Spring Drowning: A Case Report.

Hypercalcemia is generally treated conservatively, including massive fluid administration. However, in cases of acute respiratory distress syndrome (ARDS) associated with drowning, excessive fluid administration may worsen respiratory status. An 81-year-old female was found drowned in a hot spring at an accommodation facility and urgently transported to our hospital. On arrival, the patient exhibited severe respiratory failure, impaired consciousness, and bilateral lung infiltrates on computed tomography (CT), suggesting ARDS. Blood biochemical tests showed calcium (Ca) of 17.4 mg/dL, with altered consciousness attributed to hypercalcemia. Because of concerns about further deterioration of respiratory status, hemodialysis was performed to avoid massive fluid administration. Post-hemodialysis, blood calcium levels quickly decreased, leading to improved consciousness and respiration; the patient was extubated 48 hours post-admission. Subsequent examinations identified hot spring water aspiration as the cause of hypercalcemia. For hypercalcemia from hot spring drowning with acute respiratory distress syndrome, consider early hemodialysis initiation without excessive fluid administration.

External validation of the rCAST for patients after in-hospital cardiac arrest: a multicenter retrospective observational study.

No established predictive or risk classification tool exists for the neurological outcomes of post-cardiac arrest syndrome (PCAS) in patients with in-hospital cardiac arrest (IHCA). This study aimed to investigate whether the revised post-cardiac arrest syndrome for therapeutic hypothermia score (rCAST), which was developed to estimate the prognosis of PCAS patients with out-of-hospital cardiac arrest (OHCA), was applicable to patients with IHCA. A retrospective, multicenter observational study of 140 consecutive adult IHCA patients admitted to three intensive care units. The area under the receiver operating characteristic curves (AUCs) of the rCAST for poor neurological outcome and mortality at 30 days were 0.88 (0.82-0.93) and 0.83 (0.76-0.89), respectively. The sensitivity and specificity of the risk classification according to rCAST for poor neurological outcomes were 0.90 (0.83-0.96) and 0.67 (0.55-0.79) for the low, 0.63 (0.54-0.74) and 0.67 (0.55-0.79) for the moderate, and 0.27 (0.17-0.37) and 1.00 (1.00-1.00) for the high-severity grades. All 22 patients classified with a high-severity grade showed poor neurological outcomes. The rCAST showed excellent predictive accuracy for neurological prognosis in patients with PCAS after IHCA. The rCAST may be useful as a risk classification tool for PCAS after IHCA.

Prediction of the neurological outcomes post-cardiac arrest: A prospective validation of the CAST and rCAST.

INTRODUCTION: The neurologic prognosis of out-of-hospital cardiac arrest (OHCA) patients in whom return of spontaneous circulation (ROSC) is achieved remains poor. The aim of this study was to externally and prospectively validate two scoring systems developed by us: the CAST score, a scoring system to predict the neurological prognosis of OHCA patients undergoing targeted temperature management (TTM), and a simplified version of the same score developed for improved ease of use in clinical settings, the revised CAST (rCAST) score. METHODS: This study was a prospective, multicenter, observational study conducted using the SOS KANTO 2017 registry, an OHCA registry involving hospitals in the Kanto region (including Tokyo) of Japan. The primary outcome was favorable neurological outcome (defined as Cerebral Performance Category score of 1 or 2) at 30 days and the secondary outcomes were favorable neurological outcome at 90 days and survival at 30 and 90 days. The predictive accuracies of the original CAST (oCAST) and rCAST scores were evaluated by using area under the receiver operating characteristic curve (AUC). RESULTS: Of 9909 OHCA patients, 565 showed ROSC and received TTM. Of these, we analyzed the data of 259 patients in this study. The areas under the receiver operating characteristic curve (AUCs) of the oCAST and rCAST scores for predicting a favorable neurological outcome at 30 days were 0.86 and 0.87, respectively, and those for predicting a favorable neurological outcome at 90 days were 0.87 and 0.88, respectively. The rCAST showed a higher predictive accuracy for the neurological outcome as compared with the NULL-PLEASE score. The patients with a favorable neurological outcome who had been classified into the high severity group based on the rCAST tended to have hypothermia at hospital arrival and to not show any signs of loss of gray-white matter differentiation on brain CT. Neurological function at 90 days was correlated with the rCAST (r = 0.63, p < 0.001). CONCLUSIONS: rCAST showed high predictive accuracy for the neurological prognosis of OHCA patients managed by TTM, comparable to that of the oCAST score. The scores on the rCAST were strongly correlated with the neurological functions at 90 days, implying that the rCAST is a useful scale for assessing the severity of brain injury after cardiac arrest.

Medical equipment that improve safety and outcomes of inter-facility transportation of critically ill patients: A systematic review.

BACKGROUND: Although many critically ill patients require inter-facility transport for definitive or specialized therapy, the medical equipment required to enhance transport safety remains unclear. This review was performed to summarize the evidence regarding devices used to improve the safety and survival in patients requiring such transport. METHODS: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi for randomized controlled trials and observational studies comparing outcomes according to the presence or absence of devices (or new vs conventional devices) during transfer of critically ill patients. RESULTS: Four studies focusing on continuous blood pressure monitoring, extracorporeal membrane oxygenation, pelvic circumferential compression devices, and cuffed tracheal tubes, respectively, met the inclusion criteria. A meta-analysis was not performed because the 4 studies focused on different devices. Near-continuous blood pressure monitoring increased interventions such as intravenous fluid administration during transport, shortened the intensive care unit and hospital lengths of stay, and reduced the incidence of multiple-organ failure compared with use of oscillometric devices. Despite the small sample size and varying severity of illness among the groups, transport of patients with severe respiratory failure under extracorporeal membrane oxygenation resulted in fewer hypoxemic events during transport than transport on conventional ventilators. During transport of patients with pelvic fractures, pelvic belts may help to reduce mortality and the transfusion volume. Cuffed (vs uncuffed) tracheal tubes may reduce post-transport tube replacement events in pediatric patients. CONCLUSION: Studies on devices needed for inter-facility transport of critically ill patients are scarce, but some devices may be beneficial.

GENETIC DELETION OF TRANSLOCATOR PROTEIN EXACERBATES POST-SEPSIS SYNDROME WITH ACTIVATION OF THE C1Q PATHWAY IN SEPTIC MOUSE MODEL.

ABSTRACT: Significant numbers of patients who survive sepsis exhibit psychiatric and cognitive impairments, termed post-sepsis syndrome. Understanding the underlying pathophysiology is essential to develop effective therapies. Translocator protein 18 kDa (TSPO) is a multifaceted mitochondrial protein implicated in inflammation, oxidative stress, and steroidogenesis in the central nervous system. Despite accumulated evidence demonstrating TSPO is a biomarker in psychiatric and neurodegenerative disorders, the role of this protein in post-sepsis syndrome remains elusive. The aim of this study was to investigate the role of TSPO in the long-term impairment of mouse behavior associated with psychiatric and cognitive impairments following sepsis induced by cecal ligation and puncture (CLP) surgery. Animals were divided into three groups: (i) wild type (WT) + sham, (ii) WT + CLP, and (iii) TSPO knock out + CLP. Survival rate and body weight change were assessed up to 17 days after surgeries. Then, we also assessed anxiety-like behavior, depression-like behavior, cognitive function, locomotor activity, and forelimb muscle strength in surviving mice by elevated plus maze, tail suspension test, y-maze, open field test, and grip strength test, respectively. Deletion of the TSPO gene led to high mortality and prolonged weight loss and exacerbated anxiety-like and depressive-like behavior with cognitive impairment 17 days after, but not before, CLP surgery. RNA-seq analysis of the hippocampus revealed the upregulation of genes (C1qb, C1qc, and Tyrobp) in C1q complement pathways correlated significantly with anxiety-like behavior that appeared long after CLP surgery. The expressions of these genes predicted other behavioral traits, including depressive-like behavior in the tail suspension test and grip power impairment, supporting the role of the C1q pathway in post-sepsis syndrome. Because the C1q pathway has recently attracted interest as a tag for pathological synaptic elimination, the current study suggests the C1q pathway is involved in the psychiatric and cognitive impairments observed in post-sepsis syndrome.

Quantification of respiratory sounds by a continuous monitoring system can be used to predict complications after extubation: a pilot study.

To show that quantification of abnormal respiratory sounds by our developed device is useful for predicting respiratory failure and airway problems after extubation. A respiratory sound monitoring system was used to collect respiratory sounds in patients undergoing extubation. The recorded respiratory sounds were subsequently analyzed. We defined the composite poor outcome as requiring any of following medical interventions within 48 h as defined below. This composite outcome includes reintubation, surgical airway management, insertion of airway devices, unscheduled use of noninvasive ventilation or high-flow nasal cannula, unscheduled use of inhaled medications, suctioning of sputum by bronchoscopy and unscheduled imaging studies. The quantitative values (QV) for each abnormal respiratory sound and inspiratory sound volume were compared between composite outcome groups and non-outcome groups. Fifty-seven patients were included in this study. The composite outcome occurred in 18 patients. For neck sounds, the QVs of stridor and rhonchi were significantly higher in the outcome group vs the non-outcome group. For anterior thoracic sounds, the QVs of wheezes, rhonchi, and coarse crackles were significantly higher in the outcome group vs the non-outcome group. For bilateral lateral thoracic sounds, the QV of fine crackles was significantly higher in the outcome group vs the non-outcome group. Cervical inspiratory sounds volume (average of five breaths) immediately after extubation was significantly louder in the outcome group vs non-outcome group (63.3 dB vs 54.3 dB, respectively; p < 0.001). Quantification of abnormal respiratory sounds and respiratory volume may predict respiratory failure and airway problems after extubation.

Prediction of Prehospital Change of the Cardiac Rhythm From Nonshockable to Shockable in Out-of-Hospital Patients With Cardiac Arrest: A Post Hoc Analysis of a Nationwide, Multicenter, Prospective Registry.

Background Predicting a spontaneous rhythm change from nonshockable to shockable before hospital arrival in patients with out-of-hospital cardiac arrest can help emergency medical services develop better strategies for prehospital treatment. The aim of this study was to identify predictors of spontaneous rhythm change before hospital arrival in patients with out-of-hospital cardiac arrest and develop a predictive scoring system. Methods and Results We retrospectively reviewed data of eligible patients with out-of-hospital cardiac arrest with an initial nonshockable rhythm registered in a nationwide registry between June 2014 and December 2017. We performed a multivariable analysis using a Cox proportional hazards model to identify predictors of a spontaneous rhythm change, and a ridge regression model for predicting it. The data of 25 804 patients were analyzed (derivation cohort, n=17 743; validation cohort, n=8061). The rhythm change event rate was 4.1% (724/17 743) in the derivation cohort, and 4.0% (326/8061) in the validation cohorts. Age, sex, presence of a witness, initial rhythm, chest compression by a bystander, shock with an automated external defibrillator by a bystander, and cause of the cardiac arrest were all found to be independently associated with spontaneous rhythm change before hospital arrival. Based on this finding, we developed and validated the Rhythm Change Before Hospital Arrival for Nonshockable score. The Harrell's concordance index values of the score were 0.71 and 0.67 in the internal and external validations, respectively. Conclusions Seven factors were identified as predictors of a spontaneous rhythm change from nonshockable to shockable before hospital arrival. We developed and validated a score to predict rhythm change before hospital arrival.

Regional respiratory sound abnormalities in pneumothorax and pleural effusion detected via respiratory sound visualization and quantification: case report.

Assessment of respiratory sounds by auscultation with a conventional stethoscope is subjective. We developed a continuous monitoring and visualization system that enables objectively and quantitatively visualizing respiratory sounds. We herein present two cases in which the system showed regional differences in the respiratory sounds. We applied our novel continuous monitoring and visualization system to evaluate respiratory abnormalities in patients with acute chest disorders. Respiratory sounds were continuously recorded to assess regional changes in respiratory sound volumes. Because we used this system as a pilot study, the results were not shown in real time and were retrospectively analyzed. Case 1 An 89-year-old woman was admitted to our hospital for sudden-onset respiratory distress and hypoxia. Chest X-rays revealed left pneumothorax; thus, we drained the thorax. After confirming that the pneumothorax had improved, we attached the continuous monitoring and visualization system. Chest X-rays taken the next day showed exacerbation of the pneumothorax. Visual and quantitative findings showed a decreased respiratory volume in the left lung after 3 h. Case 2 A 94-year-old woman was admitted to our hospital for dyspnea. Chest X-rays showed a large amount of pleural effusion on the right side. The continuous monitoring and visualization system visually and quantitatively revealed a decreased respiratory volume in the lower right lung field compared with that in the lower left lung field. Our newly developed continuous monitoring and visualization system enabled quantitatively and visually detecting regional differences in respiratory sounds in patients with pneumothorax and pleural effusion.

A novel system that continuously visualizes and analyzes respiratory sounds to promptly evaluate upper airway abnormalities: a pilot study.

Although respiratory sounds are useful indicators for evaluating abnormalities of the upper airway and lungs, the accuracy of their evaluation may be limited. The continuous evaluation and visualization of respiratory sounds has so far been impossible. To resolve these problems, we developed a novel continuous visualization system for assessing respiratory sounds. Our novel system was used to evaluate respiratory abnormalities in two patients. The results were not known until later. The first patient was a 23-year-old man with chronic granulomatous disease and persistent anorexia. During his hospital stay, he exhibited a consciousness disorder, bradypnea, and hypercapnia requiring tracheal intubation. After the administration of muscle relaxant, he suddenly developed acute airway stenosis. Because we could not intubate and ventilate, we performed cricothyroidotomy. Subsequent review of our novel system revealed mild stridor before the onset of acute airway stenosis, which had not been recognized clinically. The second patient was a 74-year-old woman who had been intubated several days earlier for tracheal burn injury, and was extubated after alleviation of her laryngeal edema. After extubation, she gradually developed inspiratory stridor. We re-intubated her after diagnosing post-extubation laryngeal edema. Subsequent review of our novel system revealed serially increased stridor after the extubation, at an earlier time than was recognized by healthcare providers. This unique continuous monitoring and visualization system for respiratory sounds could be an objective tool for improving patient safety regarding airway complications.

Short- versus prolonged-course antibiotic therapy for sepsis or infectious diseases in critically ill adults: a systematic review and meta-analysis.

BACKGROUND: The 2016 International Guidelines for the Management of Sepsis and Septic Shock recommend antibiotic therapy for 7-10 days for most patients with sepsis. However, evidence on critically ill patients is limited. Thus, we conducted the first systematic review and meta-analysis comparing the effectiveness and adverse events of shorter- (≤1 week) with longer-course antibiotics in adults with critical infections including sepsis. METHODS: We searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases for randomised controlled trials (RCTs) and observational studies (OSs) from inception to 31 March 2021. RESULTS: We included 6 of 3,766 identified articles, incorporating data from 4 RCTs and 2 OSs (1,721 patients) in meta-analyses. Three RCTs and one OS focussed on ventilator-associated pneumonia, and one RCT and one OS investigated intra-abdominal infections. The severity score levels were similar to that of sepsis, but no study comprehensively focussing on sepsis was found. There were no significant differences in mortality at a maximum follow-up of 30 days (RR 1.08, 95%CI 0.80-1.46); 28-day mortality, clinical cure, the occurrence of new events, and the emergence of resistant organisms between the groups in the RCTs. The OSs findings were consistent. The quality of evidence was assessed as very low to moderate using the GRADE approach, with no uniform description of severity scores, sepsis, or adverse events. CONCLUSIONS: Shorter, fixed-duration antibiotic therapy for clinically heterogeneous sepsis or severe infections was not associated with poorer outcomes, but the overall quality of evidence was poor.

Differential Effectiveness of Hypothermic Targeted Temperature Management According to the Severity of Post-Cardiac Arrest Syndrome.

International guidelines recommend targeted temperature management (TTM) to improve the neurological outcomes in adult patients with post-cardiac arrest syndrome (PCAS). However, it still remains unclear if the lower temperature setting (hypothermic TTM) or higher temperature setting (normothermic TTM) is superior for TTM. According to the most recent large randomized controlled trial (RCT), hypothermic TTM was not found to be associated with superior neurological outcomes than normothermic TTM in PCAS patients. Even though this represents high-quality evidence obtained from a well-designed large RCT, we believe that we still need to continue investigating the potential benefits of hypothermic TTM. In fact, several studies have indicated that the beneficial effect of hypothermic TTM differs according to the severity of PCAS, suggesting that there may be a subgroup of PCAS patients that is especially likely to benefit from hypothermic TTM. Herein, we summarize the results of major RCTs conducted to evaluate the beneficial effects of hypothermic TTM, review the recent literature suggesting the possibility that the therapeutic effect of hypothermic TTM differs according to the severity of PCAS, and discuss the potential of individualized TTM.

A Novel Microcontroller-Based System for the Wheel-Running Activity in Mice.

Voluntary wheel-running activity is a way to assess rodents' circadian rhythm and motivation for exercise. Deficits in these behaviors are implicated in the pathophysiology of sleep and psychiatric disorders. Limited space in animal facilities can hamper long-term monitoring of running wheel activity outside of the home cage. To address this issue, we provide a stand-alone solution to monitor the wheel-running activity of mice in their home cage. This system, named the wheel-running activity acquisition (WRAQ) system, is based on a microcontroller driven by a lithium polymer battery. With the WRAQ, we can record the wheel-running activity and illumination data for at least 30 d. Applying the WRAQ to an endotoxemia mouse model robustly detected the altered wheel-running activity and its recovery. With wireless data transfer capability extension, the system also allows for online monitoring and reporting of the circadian time (CT). We used the online monitoring of wheel-running activity with this extended WRAQ system and observed a significant shift of the active period in the circadian rhythm following a temporal chemogenetic activation of the suprachiasmatic nucleus (SCN)-subparaventricular zone (SPZ). Together, these findings indicate that the WRAQ system is a novel and cost-effective solution for the analysis of wheel-running activity in mice.

Pharmacological and Genetic Inhibition of Translocator Protein 18 kDa Ameliorated Neuroinflammation in Murine Endotoxemia Model.

ABSTRACT: Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction associated with sepsis. The development of an effective strategy for early diagnosis and therapeutic intervention is essential for the prevention of poor prognosis of SAE. Translocator protein 18 kDa (TSPO) is a mitochondrial protein implicated in steroidogenesis and inflammatory responses. Despite accumulating evidence that implicates TSPO in the neuroinflammatory response of the central nervous system, the possible role of TSPO in SAE remains unclear. The aim of this study is to address a role of TSPO in neuroinflammation using mice 24 h after systemic injection of LPS, which consistently demonstrated microglial activation and behavioral inhibition. Quantitative polymerase chain reaction analysis revealed that hippocampal TSPO expression was induced following the systemic LPS injection, associated with an increase in pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-1ß. Interestingly, pretreatment with the TSPO antagonist, ONO-2952, or germ-line deletion of the TSPO gene exhibited an anti-inflammatory effect with significant suppression of LPS-induced production of those cytokines. These effects demonstrated by the ONO-2952 or TSPO knockout were associated with significant recovery from behavioral inhibition, as shown by improved locomotor activity in the open field analysis. Histological analysis revealed that ONO-2952 pretreatment suppressed the LPS-induced activation of TSPO-expressing microglia in the hippocampus of mice. Collectively, these results suggest that TSPO plays a critical role in the SAE mouse model. Based on this finding, monitoring TSPO activity, as well as the progress of endotoxemia and its sequelae in the animal model, would deepen our understanding of the underlying molecular mechanism of SAE.

Microglial translocator protein and stressor-related disorder.

Despite the prevalence of neuroinflammation in psychiatric disorders, molecular mechanism underlying it remains elusive. Translocator protein 18 kDa (TSPO), also known as peripheral benzodiazepine receptor, is a mitochondrial protein implicated in the synthesis of steroids in a variety of tissues. Multiple reports have shown increased expression of TSPO in the activated microglia in the CNS. Radioactive probes targeting TSPO have been developed and used for imaging assessment in neurological and psychiatric disorders to examine neuroinflammation. Recent studies revealed that the wide range of stressors ranging from psychological to physical insults induced TSPO in human, suggesting that this protein could be an important tool to explore the contribution of microglia in stressor-related disorders. In this review, we first overview the microglial activation with TSPO in a wide range of stressors in human and animal models to discuss prevalent roles of TSPO in response of CNS to stressors. With recent update of the signaling pathway revealing link connecting TSPO with neuroinflammatory effectors such as reactive oxygen species, we discuss TSPO as a therapeutic targeting tool for suppression of adverse effect of stressors on long-lasting changes in animal behaviors and activities. Targeting TSPO which mediates neuroinflammation under the stress might pave the way to develop therapeutic intervention and prophylaxis of stressor-related disorder.

A Ruptured Mediastinal Bronchial Artery Aneurysm Treated with Urgent Thoracic Endovascular Aortic Repair.

Bronchial artery aneurysms (BAA) are a rare but potentially life-threatening complications because of the massive hemothorax or hemoptysis that occurs with ruptures. A 79-year-old woman was transferred to our hospital because of the sudden onset of back pain, syncope, and subsequent hypotension. Computed tomography showed a left BAA with bilateral hemothorax and hemomediastinum. Transcatheter bronchial artery embolization failed because of the anatomical location, and she went into cardiopulmonary arrest. Cardiopulmonary resuscitation was performed with successful revival. Urgent thoracic endovascular aortic repair to cover the root of the left bronchial artery was successful, and she survived without any neurological deficits.

Appendicitis complicated by appendiceal metastasis via peritoneal dissemination from lung cancer.

Peritoneal disseminations from lung cancer are difficult to detect during the patient's clinical course. Therefore, complications of this condition are unclear. We report a case in which peritoneal dissemination from lung cancer complicated appendicitis. A 74-year-old man with lung cancer who was receiving maintenance therapy presented at our hospital because of abdominal pain. It was the seventh day after the 14th cycle of maintenance therapy with bevacizumab. He was diagnosed with acute appendicitis. The resected appendix showed acute appendicitis complicated by appendiceal metastasis from lung cancer. Adenocarcinoma was observed predominantly in the serous membrane from the neck to the tail of the appendix. The distribution of the adenocarcinoma was diffuse. Peritoneal dissemination was considered the route of metastasis. He was admitted to the palliative care unit 10 months after appendectomy. Appendiceal metastasis via peritoneal dissemination from lung cancer complicated appendicitis in our patient who had been receiving bevacizumab.