Prognostic factors in mobility disability among elderly patients in the emergency department: A single-center retrospective study.

Aim: We aimed to evaluate the clinical characteristics and outcomes of elderly critically ill patients and identify prognostic factors for mobility disability at discharge. Methods: This single-center, retrospective cohort study investigated the period from April 2020 to January 2021. Patients ≥75 years old transferred to our emergency department and admitted to the intensive care unit (ICU) or intermediate unit in our hospital were eligible. Demographics, clinical characteristics, nutritional indicators, and nutritional screening scores were collected from chart reviews and analyzed. The primary outcome was the prevalence of mobility disability, compared to that of no mobility disability. Results: A total of 124 patients were included in this present study. Median age was 83.0 years (interquartile range [IQR], 79.8-87.0 years) and 48 patients (38.7%) were female. Fifty-two patients (41.9%) could not walk independently at discharge (mobility disability group). The remaining 72 patients were in the no mobility disability group. Multiple logistic regression analyses revealed clinical frailty scale (CFS) score ≥5 (odds ratio [OR] = 6.63, 95% confidence interval [CI] = 2.51-17.52, p < 0.001), SOFA score ≥6 (OR = 6.11, 95% CI = 1.57-23.77, p = 0.009), and neurological disorder as the main cause on admission (OR = 4.48, 95% CI = 1.52-13.20, p = 0.006) were independent and significant prognostic factors for mobility disability at discharge. Conclusion: Among elderly patients admitted to the emergency department, CFS ≥5, SOFA ≥6, and neurological disorders were associated with mobility disability at hospital discharge.

Lymphangioleiomyomatosis as a potent lung cancer risk factor: Insights from a Japanese large cohort study.

BACKGROUND AND OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease associated with the functional tumour suppressor genes TSC1 and TSC2 and causes structural destruction in the lungs, which could potentially increase the risk of lung cancer. However, this relationship remains unclear because of the rarity of the disease. METHODS: We investigated the relative risk of developing lung cancer among patients diagnosed with LAM between 2001 and 2022 at a single high-volume centre in Japan, using data from the Japanese Cancer Registry as the reference population. Next-generation sequencing (NGS) was performed in cases where tumour samples were available. RESULTS: Among 642 patients diagnosed with LAM (sporadic LAM, n = 557; tuberous sclerosis complex-LAM, n = 80; unclassified, n = 5), 13 (2.2%) were diagnosed with lung cancer during a median follow-up period of 5.13 years. All patients were female, 61.5% were never smokers, and the median age at lung cancer diagnosis was 53 years. Eight patients developed lung cancer after LAM diagnosis. The estimated incidence of lung cancer was 301.4 cases per 100,000 person-years, and the standardized incidence ratio was 13.6 (95% confidence interval, 6.2-21.0; p = 0.0008). Actionable genetic alterations were identified in 38.5% of the patients (EGFR: 3, ALK: 1 and ERBB2: 1). No findings suggested loss of TSC gene function in the two patients analysed by NGS. CONCLUSION: Our study revealed that patients diagnosed with LAM had a significantly increased risk of lung cancer. Further research is warranted to clarify the carcinogenesis of lung cancer in patients with LAM.

Functional Recovery and Nutrition Management among Severe COVID-19 Cases during Post-extubation Hospitalization: A Case Series.

Background: Many patients with coronavirus disease 2019 (COVID-19) develop malnutrition after a prolonged stay in the intensive care unit (ICU) with mechanical ventilation. Early enteral nutrition is recommended, but optimal nutrition management during post-extubation recovery remains challenging. Cases: The subjects were 12 acute respiratory distress syndrome patients with COVID-19 (9 men, 3 women; median age, 55.6 years). We reviewed patient characteristics, physical function, and nutrient intake during hospitalization from just after extubation to discharge. During this period, the median Functional Oral Intake Scale score improved from 4.5 (interquartile range [IQR] 3.3-5.3) to 7.0 (IQR 5.8-7.0), the median Medical Research Council (MRC) scale score improved from 45.0 (IQR 39.3-48.5) to 53.5 (IQR 47.5-59.3), and the median Barthel index improved from 7.5 (IQR 0-16.3) to 72.5 (IQR 42.5-95.0). In 3 patients, the MRC scale score remained below 48 before discharge, indicating that ICU-acquired weakness had been prolonged. The median daily caloric intake during this phase increased from 6.9 kcal/kg per day (3.5-10.2 kcal/kg per day) to 24.8 kcal/kg per day (21.0-27.9 kcal/kg per day). About half of these patients showed caloric intake below 25 kcal/kg per day before discharge. Based on the Global Leadership Initiative on Malnutrition (GLIM) diagnostic scheme, 10 patients were diagnosed with malnutrition during hospitalization. Discussion: Physical function improved in more than half of the patients, but nutritional status was not recovered. More studies for nutritional management are required to prevent malnutrition and to enhance functional recovery during the post-extubation rehabilitation phase.

IFN-λ3 and CCL17 as predictors of disease progression in patients with mild to moderate COVID-19: A cohort study in a real-world setting.

Coronavirus disease 2019 (COVID-19) has overwhelmed hospitals worldwide. In Japan, serum interferon lambda 3 (IFN-λ3) and C-C motif ligand (CCL) 17 levels have been used as predictive markers for disease progression to severe COVID-19. However, the relationship between these predictive markers and the disease progression of COVID-19 has not been well evaluated. We retrospectively evaluated the patient characteristics, serum IFN-λ3 and CCL17 levels, and comorbidities of 92 patients with mild (n = 20) and moderate (n = 72) COVID-19 who were hospitalized in our institution. The results of the multivariable analysis showed that the positive rates of IFN-λ3, CCL17, and the combination of these markers were significantly elevated in patients with progressed COVID-19. Furthermore, patients who were negative for both markers did not experience disease progression. This study illustrates the importance of measuring these markers to predict disease severity and progression in patients with COVID-19.

A Case of Tuberculosis-related Cerebral Venous Sinus Thrombosis and Pulmonary Thromboembolism Successfully Treated with Edoxaban.

A 22-year-old woman was admitted to the hospital with complaints of headache and vomiting. Radiological examinations revealed cerebral sinus venous thromboses, pulmonary thromboembolism, and cavities in the left upper lung. Pulmonary tuberculosis was diagnosed based on sputum and gastric aspirate culture. Heparin followed by warfarin was administered. Anti-tuberculosis agents including rifampicin were also initiated. Since the effect of warfarin did not reach the therapeutic level because of interaction with rifampicin, edoxaban was administered and thromboses were ameliorated. This report illustrates rare thrombotic complications in a TB-induced hypercoagulable state and the potential benefits and safety of edoxaban in combination with rifampicin.

Eleven-year retrospective study characterizing patients with severe brain damage and poor neurological prognosis -role of physicians' attitude toward life-sustaining treatment.

BACKGROUND: Severe brain hemorrhage/infarction and cardiac arrest constitute the most critical situations leading to poor neurological prognosis. Characterization of these patients is required to offer successful end-of-life care, but actual practice is affected by multiple confounding factors, including ethicolegal issues, particular in Japan and Asia. The aim of this study is to evaluate the clinical courses of patients with severe brain damage and to assess the preference of end-of-life care for these patients in Japanese hospitals. METHODS: A retrospective observational study was conducted between 2008 and 2018. All intracranial hemorrhage/infarction and cardiac arrest out-patients (n = 510) who were admitted to our two affiliated hospitals and survived but with poor neurologic outcomes were included. Demographic characteristics as well as prognosis and treatment policies were also assessed. RESULTS: Patients were divided into two categories; cases with absent brainstem reflex (BSR) (BSR[-]) and those with preserved BSR (BSR[ +]). The survival rate was higher and the length of hospitalization was longer in patients with BSR[ +] than in those with BSR[-]. Among three life-sustaining policies (i.e., aggressive treatment, withdrawal of treatment, and withholding of treatment), withholding of treatment was adopted to most patients. In BSR[-], the proportion of three treatment policies performed at the final decision did not differ from that at the initial diagnosis on neurological status (p = 0.432). In contrast, this proportion tended to be altered in BSR[ +] (p = 0.072), with a decreasing tendency of aggressive treatment and a modest increasing tendency of withdrawal of treatment. Furthermore, the requests from patients' families to withdraw life-sustaining treatment, including discontinuation of mechanical ventilation, increased, but actual implementation of withdrawal by physicians was less than half of the requests. CONCLUSIONS: BSR constitutes a crucial determinant of mortality and length of hospitalization in comatose patients with severe brain damage. Although the number of withdrawal of life-sustaining treatment tends to increase over time in BSR[ +] patients, there are many more requests from patients' families for withdrawal. Since physicians has a tendency to desist from withdrawing life-sustaining treatment, more in-depth communication between medical staff and patients' families will facilitate mutual understanding over ethicolegal and religious issues and may thus improve end-of-life care.

Mortality associated with new risk classification of developing refeeding syndrome in critically ill patients: A cohort study.

BACKGROUND & AIMS: Although refeeding syndrome (RFS) has been recognized as a potentially fatal metabolic complication, the definition of RFS has remained unclear. Recently, European researchers suggested an evidence-based and consensus-supported algorithm that consisted of a new RFS risk classification and treatment strategies for medical inpatients. The classification was based on the National Institute for Health and Clinical Excellence (NICE) criteria for patients at risk of developing RFS. In this study, we aimed to investigate the frequency of each applied new risk group and the association between the new classification and mortality in critically ill patients. METHODS: This cohort study was conducted at a Japanese metropolitan tertiary-care university hospital from December 2016 to December 2018. We included critically ill adult patients who were admitted to the intensive care unit (ICU) via the emergency department and who stayed in the ICU for 24 h or longer. We applied the new risk classification based on the NICE RFS risk factors on ICU admission. The main exposure was risk classification of RFS: no risk, low risk, high risk, or very high risk. The primary outcome was in-hospital mortality censored at day 30 after ICU admission. We performed a multivariable analysis using Cox proportional hazard regression. RESULTS: We analyzed 542 patients who met the eligibility criteria. The prevalence of the four RFS risk classification groups was 25.8% for no risk, 25.7% for low risk, 46.5% for high risk, and 2.0% for very high risk. The 30-day mortality was 5.0%, 7.2%, 16.3%, and 27.3%, respectively (log-rank trend test: p < 0.001). In the multivariable Cox regression, adjusted hazard ratios with no risk group as a reference were 1.28 (95% CI 0.48-3.38) for low risk, 2.81 (95% CI 1.24-6.35) for high risk, and 3.17 (95% CI 0.78-12.91) for very high risk. CONCLUSIONS: Approximately half the critically ill patients were categorized as high or very high risk based on the new risk classification. Furthermore, as the risk categories progressed, the 30-day in-hospital mortality increased. Early recognition of patients at risk of developing RFS may improve patient outcomes through timely and optimal nutritional treatment.

Herpes simplex virus type 2 myelitis mimicking ICU-acquired weakness as a complication of meningococcal meningitis: A case report.

Herpes simplex virus 2 (HSV-2) is a well-known cause of neurological complications. This case study describes the first reported case of reactivated HSV-2 myelitis, which was induced by immunosuppression due to sepsis. During the treatment of meningococcal meningitis, the patient developed quadriparesis and was later diagnosed as HSV-2 myelitis, mimicking ICU-acquired weakness. The case emphasizes the importance of excluding viral myelitis before making the diagnosis of ICU-acquired weakness.

CMOS Gaussian Monocycle Pulse Transceiver for Radar-Based Microwave Imaging.

A single-chip Gaussian monocycle pulse (GMP) transceiver was developed for radar-based microwave imaging by the use of 65-nm complementary metal oxide semiconductor (CMOS) technology. A transmitter (TX) generates GMP signals, whose pulse widths and -3 dB bandwidths are 192 ps and 5.9 GHz, respectively. A 102.4 GS/s equivalent time sampling receiver (RX) performs the minimum jitter, input referred noise, signal-to-nose-ratio (SNR), signal-to-noise and distortion ratio (SNDR) effective number of bits (ENOB) of 0.58 ps, 0.24 mVrms, 28.4 dB, 26.6 dB and 4.1 bits, respectively. The SNR for the bandwidth of 3.6 GHz is 36.3 dB. The power dissipations of transmitter and receiver circuits are 19.79 mW and 48.87 mW, respectively. The GMP transceiver module can differentiate two phantom targets with the size of 1 cm and the spacing of 1 cm by confocal imaging.

Independent lung ventilation with use of a double-lumen endotracheal tube for refractory hypoxemia and shock complicating severe unilateral pneumonia: A case report.

BACKGROUND: The indications for independent lung ventilation (ILV) in critical care settings have not been fully clarified, especially because extracorporeal membrane oxygenation (ECMO) is being used increasingly in cases of severe respiratory failure. CASE REPORT: A 90-year-old man presented with severe unilateral pneumonia, and despite conventional mechanical ventilation management with use of a single lumen endotracheal tube and high positive endo-expiratory pressure (PEEP), oxygenation and hemodynamics deteriorated. We then performed ILV using a double-lumen endotracheal tube (DLT) and two ventilators, each set at a different respiratory mode. With continuous administration of a neuromuscular blocking agent, the ventilator for the left lung (non-affected lung) was set to pressure-controlled ventilation (PCV) mode, whereas the ventilator for the right lung (affected lung) was set to bi-level mode, 1 breath/min, and high PEEP. ILV and the high PEEP applied to the affected lung prevented hyperinflation of the non-affected lung and increased pulmonary blood perfusion on the non-affected side. Thus, ILV immediately improved oxygenation and hemodynamics by correcting ventilation/perfusion mismatch. DISCUSSION: Although ECMO is a valid treatment option for patients with severe respiratory failure, it is highly invasive intervention. ILV performed with use of a DLT is less invasive and more useful than ECMO. Thus, ILV should be kept in mind as a treatment option, especially in cases of refractory respiratory failure and circulatory failure in which the pathophysiology of the left and right lungs differs markedly.

Exploratory Observational Study of Extracorporeal Cardiopulmonary Resuscitation for Nonshockable Out-Of-Hospital Cardiac Arrest Occurring After an Emergency Medical Services Arrival: SOS-KANTO 2012 Study Report.

BACKGROUND: The outcomes of patients with nonshockable out-of-hospital cardiac arrest (OHCA) are poor, but may be improved by extracorporeal cardiopulmonary resuscitation (E-CPR). OBJECTIVE: To examine the effects of veno-arterial extracorporeal membranous oxygenation (ECMO) as E-CPR in patients with nonshockable OHCA after emergency medical services (EMS) arrival for whom satisfactory cardiopulmonary resuscitation (CPR) was immediately performed. METHODS: Among 16,452 patients enrolled in the SOS-KANTO 2012 study, we examined data on 531 patients aged ≥ 18 years who performed activities of daily living (ADL) well or had moderate disability before the onset of cardiac arrest (CA) and those with normal spontaneous respiration or pulse palpation upon EMS arrival. CPR was performed immediately after CA onset, and advanced life support was provided upon hospital arrival for these patients. We divided patients into ECMO and non-ECMO groups. We retrospectively analyzed background factors and clinical outcomes. RESULTS: E-CPR was performed on 38 (7.2%) patients. In the univariate analysis, the mean age of the ECMO group was lower, ADL function before onset was more favorable, mean body weight was higher, and the mean interval from onset until hospital arrival was shorter than those in the non-ECMO group. One-to 3-month survival or favorable cerebral function outcome rates were higher in the ECMO group than in the non-ECMO group. In the multivariate analysis, ECMO use and the interval from onset until hospital arrival were independent prognostic factors for favorable cerebral functional outcomes at 1 and 3 months. CONCLUSION: E-CPR may be associated with favorable outcomes in carefully selected patients with nonshockable OHCA.

Clinical outcomes of urinary tract infection caused by extended spectrum beta-lactamase producing Enterobacteriaceae: a retrospective observational study comparing patients with and without systemic inflammatory response syndrome.

AIM: In severe urinary tract infection (UTI), susceptible antibiotics should be given. With the recent increase of multidrug-resistant bacteria, especially extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E), broad-spectrum antibiotics, such as carbapenems, are used more frequently, which could lead to a further increase of multidrug-resistant bacteria. We aimed to analyze the relationship between initial empirical antibiotic appropriateness and clinical outcomes in UTI, especially in patients with systemic inflammatory response syndrome (SIRS) and ESBL-E. METHODS: A retrospective observational study from 2012 to 2017. RESULTS: Among urine culture-positive cases with ≥105 colony-forming units/mL (n = 1,880), true UTI cases were extracted (n = 844) and divided into the SIRS group (n = 336 [ESBL-E12.8% (43/336)]) and non-SIRS group (n = 508 [ESBL-E12.6% (64/508)]). In the SIRS ESBL-E group, the initial antibiotics were susceptible in 55.8% (24/43), among which 91.7% (22/24) improved and 8.3% (2/24) deteriorated or died. The initial antibiotics were resistant in 44.2% (19/43), among which 47.4% (9/19) improved with the initial antibiotics, 47.4% (9/19) improved after escalating antibiotics, and 5.3% (1/19) deteriorated or died. In the SIRS group, 14 cases had true bacteremia with ESBL-E. Seven cases were initiated with inappropriate antibiotics; four cases showed improvement before or without antibiotic change and three cases improved after antibiotic escalation. CONCLUSION: Initiation of narrow-spectrum antibiotics in septic UTI with ESBL-E might not deteriorate the clinical outcome if promptly escalated on clinical deterioration or with ESBL-E culture results. Further investigation is warranted to guide judicious use of initial antibiotics.

Association Between Therapeutic Hypothermia and Outcomes in Patients with Non-shockable Out-of-Hospital Cardiac Arrest Developed After Emergency Medical Service Arrival (SOS-KANTO 2012 Analysis Report).

BACKGROUND/OBJECTIVE: The outcomes of patients with non-shockable out-of-hospital cardiac arrest (non-shockable OHCA) are poorer than those of patients with shockable out-of-hospital cardiac arrest (shockable OHCA). In this retrospective study, we selected patients from the SOS-KANTO 2012 study with non-shockable OHCA that developed after emergency medical service (EMS) arrival and analyzed the effect of therapeutic hypothermia (TH) on non-shockable OHCA patients. METHODS: Of 16,452 patients who have definitive data on the 3-month outcome in the SOS-KANTO 2012 study, we selected 241 patients who met the following criteria: age ≥ 18 years, normal spontaneous respiration or palpable pulse upon emergency medical services arrival, no ventricular fibrillation or pulseless ventricular tachycardia before hospital arrival, and achievement of spontaneous circulation without cardiopulmonary bypass. Patients were divided into two groups based on the presence or absence of TH and were analyzed. RESULTS: Of the 241 patients, 49 underwent TH. Univariate analysis showed that the 1-/3-month survival rates and favorable 3-month cerebral function outcome rates in the TH group were significantly better than the non-TH group (46% vs 19%, respectively, P < 0.001, 35% vs 12%, respectively, P < 0.001, 20% vs 7%, respectively, P = 0.01). Multivariate logistic regression analysis showed that TH was a significant, independent prognostic factor for cerebral function outcome. CONCLUSIONS: In this study, TH was an independent prognostic factor for the 3-month cerebral function outcome. Even in patients with non-shockable OHCA, TH may improve outcome if the interval from the onset of cardiopulmonary arrest is relatively short, and adequate cardiopulmonary resuscitation is initiated immediately after onset.

Investigation and treatment of pulmonary embolism as a potential etiology may be important to improve post-resuscitation prognosis in non-shockable out-of-hospital cardiopulmonary arrest: report on an analysis of the SOS-KANTO 2012 study.

Background: The prognosis of non-shockable out-of-hospital cardiac arrest is worse than that of shockable out-of-hospital cardiac arrest. We investigated the associations between the etiology and prognosis of non-shockable out-of-hospital cardiac arrest patients who experienced the return of spontaneous circulation after arriving at hospital. Methods and Results: All subjects were extracted from the SOS-KANTO 2012 study population. The subjects were 3,031 adults: (i) who had suffered out-of-hospital cardiac arrest, (ii) for whom there were no pre-hospital data on ventricular fibrillation/pulseless ventricular tachycardia until arrival at hospital, (iii) who experienced the return of spontaneous circulation after arriving at hospital. We compared the patients' prognosis after 1 and 3 months between various etiological and presumed cardiac factors. The proportion of the favorable brain function patients that developed pulmonary embolism or incidental hypothermia was significantly higher than that of the patients with presumed cardiac factors (1 month, P < 0.0001 and P < 0.0001, respectively; 3 months, P = 0.0018 and P < 0.0001, respectively). In multiple logistic regression analysis, pulmonary embolism and incidental hypothermia were found to be significant independent prognostic factors for 1- and 3-month survival and the favorable brain function rate. Conclusions: In patients who suffer non-shockable out-of-hospital cardiac arrest, but who experience the return of spontaneous circulation after arriving at hospital, the investigation and treatment of pulmonary embolism as a potential etiology may be important for improving post-resuscitation prognosis.

STAT3 polymorphism predicts interferon-alfa response in patients with metastatic renal cell carcinoma.

PURPOSE: To clarify the effect of genetic polymorphisms on the response to interferon alfa (IFN-alpha) for metastatic renal cell carcinoma (MRCC), and to find a reliable molecular marker to select those patients with MRCC who would benefit from IFN-alpha immunotherapy. PATIENTS AND METHODS: We carried out an association study in which 463 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped in 75 Japanese patients who had received IFN-alpha for MRCC. RESULTS: After adjusting for lung metastasis, stepwise logistic regression analysis revealed that the SNPs in signal transducer and activator 3 (STAT3) were most significantly associated with better response to IFN-alpha. Linkage disequilibrium mapping revealed that the SNP in the 5' region of STAT3, rs4796793, was the most significant predictor of IFN-alpha response (odds ratio [OR] = 2.73; 95% CI, 1.38 to 5.78). The highest OR was shown in the CC genotype at rs4796793 compared to the GG + GC genotypes (OR = 8.38, 95% CI, 1.63 to 42.96). Genotype-dependent expressions of STAT3 in B lymphocyte cell lines and the enhanced growth inhibitory effects of IFN- by STAT3 suppression in an RCC cell line supported the results of the present association study. CONCLUSION: The present study suggested that the STAT3 polymorphism is a useful diagnostic marker to predict the response to IFN-alpha therapy in patients with MRCC. An efficient response marker for IFN-alpha needs to be utilized to establish individual optimal treatment strategies, even when newer drug therapies are used as first line treatments for MRCC.