Taka-aki Nakada

• MD, PhD
• CEO at Chiba University

The 2024 revised edition of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG 2024) is published by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine. This is the fourth revision since the first edition was published in 2012. The purpose of the guidelines is to...

This study demonstrated that while GPT-4 Turbo had superior specificity when compared to GPT-3.5 Turbo (0.98 vs 0.51), as well as comparable sensitivity (0.85 vs 0.83), GPT-3.5 Turbo processed 100 studies faster (0.9 min vs 1.6 min) in citation screening for systematic reviews, suggesting that GPT-4 Turbo may be more suitable due to its higher spec...

The 2024 revised edition of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J‐SSCG 2024) is published by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine. This is the fourth revision since the first edition was published in 2012. The purpose of the guidelines is to...

Background Lipoproteins and their component apolipoproteins play an important role in sepsis. However, little is known with regard to the association and causal contribution of these proteins to mortality in patients of different ancestries following septic shock. The objective of this study was to determine whether lipoprotein and apolipoprotein l...

Traumatic injury remains a leading cause of death worldwide, with traumatic bleeding being one of its most critical and fatal consequences. The use of whole-body computed tomography (WBCT) in trauma management has rapidly expanded. However, interpreting WBCT images within the limited time available before treatment is particularly challenging for a...

Introduction The survival benefits of treatment at high-volume hospitals (HVHs) are well-documented for several critical pediatric conditions. However, their impact on pediatric sepsis, a leading cause of mortality among children, remains understudied. Aim of the study To investigate the association between hospital case volume and mortality rates...

Background Interleukin-6 (IL-6) is a cytokine that predicts clinical outcomes in critically ill patients, including those with sepsis. Elderly patients have blunted and easily dysregulated host responses to infection, which may influence IL-6 kinetics and alter the association between IL-6 levels and clinical outcomes. Methods This retrospective o...

Staphylococcus aureus can cause outbreaks and becomes multi-drug resistant through gene mutations and acquiring resistance genes. However, why S. aureus easily adapts to hospital environments, promoting resistance and recurrent infections, remains unknown. Here we show that a specific S. aureus lineage evolved from a clone that expresses the access...

Aim This study investigated the correlation between the number of emergency medical service (EMS) dispatches and response time extension. In addition, we conducted a simulation to assess the potential for reducing response times by relocating the ambulance based on the number of dispatches. Methods This retrospective observational study analyzed d...

Background The impact of intensive care unit (ICU) case volume on the mortality and medical costs of sepsis has not been fully elucidated. We hypothesized that ICU case volume is associated with mortality and medical costs in patients with sepsis in Japan. Methodology This retrospective nationwide study used the Japanese administrative data from 20...

Background Timely and effective fluid resuscitation is vital for stabilizing sepsis while avoiding volume overload. We aimed to assess how the administration of a 30 mL/kg bolus fluid affects patients with sepsis within three hours of clinical outcomes. Methods This multicenter observational study included adult patients diagnosed with sepsis in 17...

Importance Large language models (LLMs) are promising as tools for citation screening in systematic reviews. However, their applicability has not yet been determined. Objective To evaluate the accuracy and efficiency of an LLM in title and abstract literature screening. Design, Setting, and Participants This prospective diagnostic study used the...

Background: Systematic reviews require labor-intensive and time-consuming processes. Large language models (LLMs) have been recognized as promising tools for citation screening; however, the performance of LLMs in screening citations remained to be determined yet. This study aims to evaluate the potential of three leading LLMs - GPT-4, Gemini 1.5 P...

This study investigated the accuracy of a machine learning algorithm for predicting mortality in patients receiving rapid response system (RRS) activation. This retrospective cohort study used data from the In-Hospital Emergency Registry in Japan, which collects nationwide data on patients receiving RRS activation. The missing values in the dataset...

Background It is important to determine the prevalence and prognosis of community-acquired infection (CAI) and nosocomial infection (NI) to develop treatment strategies and appropriate medical policies in aging society. Methods Patients hospitalized between January 2010 and December 2019, for whom culture tests were performed and antibiotics were...

Background Systematic reviews require extensive time and effort to manually extract and synthesize data from numerous screened studies. This study aims to investigate the ability of large language models (LLMs) to automate data extraction with high accuracy and minimal bias, using clinical questions (CQs) of the Japanese Clinical Practice Guideline...

To efficiently allocate medical resources at disaster sites, medical workers perform triage to prioritize medical treatments based on the severity of the wounded or sick. In such instances, evaluators often assess the severity status of the wounded or sick quickly, but their measurements are qualitative and rely on experience. Therefore, we develop...

Objectives We aimed to describe empiric antimicrobial options for patients with community-onset sepsis using nationwide real-world data from Japan. Methods This retrospective cohort study used nationwide Japanese data from a medical reimbursement system database. Patients aged ≥20 years with both presumed infections and acute organ dysfunction who...

Capillary refill time (CRT) is an internationally accepted indicator of peripheral circulation. The CRT is measured by applying compression to the fingernail for a few seconds, releasing it, and observing the process of refilling of blood at the fingertip. The international guidelines for the management of sepsis and septic shock 2021 contains an a...

A stroke is a medical emergency and thus requires immediate treatment. Paramedics should accurately assess suspected stroke patients and promptly transport them to a hospital with stroke care facilities; however, current assessment procedures rely on subjective visual assessment. We aim to develop an automatic evaluation system for central facial p...

This retrospective cohort study aimed to develop and evaluate a machine-learning algorithm for predicting oliguria, a sign of acute kidney injury (AKI). To this end, electronic health record data from consecutive patients admitted to the intensive care unit (ICU) between 2010 and 2019 were used and oliguria was defined as a urine output of less tha...

Background: The development of clinical practice guidelines requires a meticulous literature search and screening process. This study aims to explore the potential of large language models in the development of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG), focusing on enhancing literature search quali...

Background: We evaluated the applicability of automated citation screening in developing clinical practice guidelines. Methods: We prospectively compared the efficiency of citation screening between the conventional (Rayyan) and semi-automated (ASReview software) methods. We searched the literature for five clinical questions (CQs) in the developme...

Background The effect of hospital spending on the mortality rate of patients with sepsis has not yet been fully elucidated. We hypothesized that hospitals that consume more medical resources would have lower mortality rates among patients with sepsis. Methods This retrospective study used administrative data from 2010 to 2017. The enrolled hospita...

Background Although coagulopathy is often observed in acute respiratory distress syndrome (ARDS), its clinical impact remains poorly understood. Objectives This study aimed to clarify the coagulopathy parameters that are clinically applicable for prognostication and to determine anticoagulant indications in sepsis-induced ARDS. Method This study...

Background The efficacy of therapeutic drug monitoring (TDM)-based antimicrobial dosing optimization strategies on pharmacokinetics/pharmacodynamics and specific drug properties for critically ill patients is unclear. Here, we conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effectiveness of TDM-based...

Increased fluid overload (FO) is associated with poor outcomes in critically ill patients, especially in acute kidney injury (AKI). However, the exact timing from when FO influences outcomes remains unclear. We retrospectively screened intensive care unit (ICU) admitted patients with AKI between January 2011 and December 2015. Logistic or linear re...

Sepsis is the leading cause of death worldwide. Considering regional variations in the characteristics of patients with sepsis, a better understanding of the epidemiology in Japan will lead to further development of strategies for the prevention and treatment of sepsis. To investigate the epidemiology of sepsis, we conducted a systematic literature...

Increased fluid overload (FO) is associated with poor outcomes in critically ill patients, especially in acute kidney injury (AKI). However, the exact timing from when FO influences outcomes remains unclear. We retrospectively screened intensive care unit (ICU) admitted patients with AKI between January 2011 and December 2015. Logistic or linear re...

Predicting out-of-hospital cardiac arrest (OHCA) events might improve outcomes of OHCA patients. We hypothesized that machine learning algorithms using meteorological information would predict OHCA incidences. We used the Japanese population-based repository database of OHCA and weather information. The Tokyo data (2005–2012) was used as the traini...

Background Oliguria is an important indicator for the early detection of acute kidney injury (AKI) and prediction of poor outcomes in critically ill patients; however, the accuracy of a prediction model using machine learning has rarely been investigated. This study aimed to develop and evaluate a machine learning algorithm for predicting oliguria...

Introduction: Capillary refill time (CRT) is an indicator of peripheral circulation and is recommended in the 2021 guidelines for treating and managing sepsis. Study objective: This study developed a portable device to realize objective CRT measurement. Assuming that peripheral blood flow obstruction by the artery occlusion test (AOT) or venous...

While the development of prehospital diagnosis scales has been reported in various regions, we have also developed a scale to predict stroke type using machine learning. In the present study, we aimed to assess for the first time a scale that predicts the need for surgical intervention across stroke types, including subarachnoid haemorrhage and int...

Objective We evaluated the clinical differences in coronavirus disease 2019 (COVID-19) patients between the sixth wave with the Omicron BA.1/BA.2 dominant variant (from January to April 2022) and seventh wave with the Omicron BA.5 dominant variant (from July to August 2022). Methods This retrospective, single-center, observational study included CO...

Background: Patients with severe acute kidney injury (AKI) who require continuous venovenous hemodiafiltration (CVVHDF) in intensive care unit (ICU) are at high mortality risk. Little is known about clinical biomarkers for risk prediction, optimal initiation, and optimal discontinuation of CVVHDF. Methods: This prospective observational study wa...

Data collection on adverse reactions in recipients after vaccination is vital to evaluate potential health issues, but health observation diaries are onerous for participants. Here, we present a protocol to collect time series information using a smartphone or web-based platform, thus eliminating the need for paperwork and data submission. We descr...

Background: Dysbiosis, an imbalance of the intestinal microbiota in critically ill patients, reportedly contributes to poor outcomes. Controlling the disruption of intestinal homeostasis could be promising tactics for infectious complications in severe acute pancreatitis. To improve the mortality rate of severe acute pancreatitis with high frequenc...

Background The effect of hospital spending on the mortality rate of patients with sepsis has not yet been fully elucidated. We hypothesized that hospitals that consume more medical resources would have lower mortality rates among patients with sepsis. Methods This retrospective study used administrative data from 2010 to 2017. The enrolled hospita...

Objectives: The pharmacokinetics of vancomycin and meropenem in patients treated with continuous online hemodiafiltration (OL-HDF) are not well understood. Case: We evaluated dialytic clearance and serum concentrations of vancomycin and meropenem by OL-HDF in a critically ill patient with soft tissue infection. The mean clearance of OL-HDF and m...

Background and Aims Acute liver injury (ALI) due to autoimmune hepatitis (AIH) can be treated by immunosuppression. In contrast, idiosyncratic drug-induced liver injury (DILI) had a poor prognosis. DILI thus needs to be distinguished from non-DILI. Methods Twenty-nine patients with DILI and 77 with non-DILI (42 of AIH and 35 with undetermined caus...

Background: Genome-wide association studies have identified sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing 1 ( SVEP1 ) polymorphism as a genetic risk factor for sepsis, as well as acute coronary syndrome. However, research on the role of SVEP1 in systemic inflammation, such as surgical invasion and sepsis, remains insuffi...

Background A substantial number of sepsis patients require specialized care, including multidisciplinary care, close monitoring, and artificial organ support in the intensive care unit (ICU). However, the efficacy of ICU management on clinical outcomes remains insufficiently researched. Therefore, we tested the hypothesis that ICU admission would i...

Background: Sepsis is the leading cause of death worldwide. Although the mortality of sepsis patients has been decreasing over the past decade, the trend of medical costs and cost-effectiveness for sepsis treatment remains insufficiently determined. Methods: We conducted a retrospective study using the nationwide medical claims database of sepsi...

Background: This study aims to investigate the quality of the literature search and workload saving using the semi-automatic software for citation screening in the development of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG). Methods: We will conduct a prospective study to compare the efficiency of cit...

Background: Microcirculation is a vital sign that supplies oxygen and nutrients to maintain normal life activities. Sepsis typically influences the operation of microcirculation, which is recovered by the administration of medicine injection. Objective: Sepsis-induced variation and recovery of microcirculation are quantitatively detected using micr...

Objectives The aim of this study was to reveal the neurological outcomes of choking-induced out-of-hospital cardiac arrest (OHCA) and evaluate the presence of witnesses, cardiopulmonary resuscitation (CPR) performed by a witness (bystander-witnessed CPR), and the proportion of patients with favourable neurological outcomes by the time from CPR by e...

Background The Japan Society for Blood Purification in Critical Care (JSBPCC) has reported survey results on blood purification therapy (BPT) for critically ill patients in 2005, 2009, and 2013. To clarify the current clinical status, including details of the modes used, treated diseases, and survival rate, we conducted this cohort study using data...

We aimed to investigate the impact of hospital volume on the mortality rate and medical costs in sepsis. This retrospective study used the administrative data from 2010 to 2017. The hospital volume categorization into quartiles was performed according to the annual number of sepsis cases. The primary and secondary outcome was in-hospital mortality...

Background: The appropriate duration of antibiotic treatment in patients with bacterial sepsis remains unclear. The purpose of this study was to evaluate the association of a shorter course of antibiotics on 28-day mortality in comparison with a longer course using a national database in Japan. Methods: We conducted a post hoc analysis from the...

Symptoms of adverse reactions to vaccines evolve over time, but traditional studies have focused only on the frequency and intensity of symptoms. Here, we attempt to extract the dynamic changes in vaccine adverse reaction symptoms as a small number of interpretable components by using non-negative tensor factorization. We recruited healthcare worke...

Rapid and precise prehospital recognition of acute coronary syndrome (ACS) is key to improving clinical outcomes. The aim of this study was to investigate a predictive power for predicting ACS using the machine learning-based prehospital algorithm. We conducted a multicenter observational prospective study that included 10 participating facilities...

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analy...

The mortality of coronavirus disease 2019 (COVID-19) is strongly correlated with pulmonary vascular pathology accompanied by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection–triggered immune dysregulation and aberrant activation of platelets. We combined histological analyses using field emission scanning electron microscopy w...

Background The impact of hospital volume on the mortality rate and medical costs in sepsis has not been fully elucidated. We hypothesized that high-volume hospitals have low mortality rates and high medical costs in sepsis cases. Methods This retrospective study used the administrative data from 2010 to 2017. The hospital volume categorization int...

Identifying the factors underlying severe COVID-19 in the host genetics is an emerging issue1–5. We conducted a genome-wide association study (GWAS) involving 2,393 Japanese COVID-19 cases collected in initial pandemic waves with 3,289 controls, which identified a variant on 5q35 (rs60200309-A) near DOCK2 associated with severe COVID-19 in younger...

Tranexamic acid (TXA) reduces the risk of bleeding trauma death without altering the need for blood transfusion. We examined the effects of TXA on coagulation and fibrinolysis dynamics and the volume of transfusion during the early stage of trauma. This subanalysis of a prospective multicenter study of severe trauma included 276 patients divided in...

Machine learning can predict outcomes and determine variables contributing to precise prediction, and can thus classify patients with different risk factors of outcomes. This study aimed to investigate the predictive accuracy for mortality and length of stay in intensive care unit (ICU) patients using machine learning, and to identify the variables...

Background: Predicting out-of-hospital cardiac arrest (OHCA) events might contribute to the improvement of OHCA patients’ outcomes. We hypothesized that machine learning algorithms using meteorological and chronological information would predict high OHCA incidence. Methods: We used the large Japanese population-based repository database of OHCA an...

Background There is currently limited evidence to guide prehospital identification of patients with cardiopulmonary arrest on arrival (CPAOA) to hospital who have potentially favourable neurological function. This study aimed to develop a simple scoring system that can be determined at the contact point with emergency medical services to predict ne...

Disseminated intravascular coagulation (DIC) is one of the major organ dysfunctions associated with sepsis. This retrospective secondary analysis comprised data from a prospective multicenter study to investigate the age-related differences in the survival benefit of anticoagulant therapy in sepsis according to the DIC diagnostic criteria. Adult pa...

Background: A substantial number of sepsis patients require specialized care, including multidisciplinary care, close monitoring, and artificial organ support in the intensive care unit (ICU). However, the efficacy of ICU management on clinical outcomes remains insufficiently researched. Therefore, we tested the hypothesis that ICU admission would...

Background: Heart rate (HR) predicts outcomes in patients with acute coronary syndrome (ACS), whereas the impact of HR on outcomes after out-of-hospital cardiac arrest (OHCA) remains unclear. This study aimed to investigate the impact of HR after resuscitation on outcomes after OHCA and whether the impact differs with OHCA etiology.Methods and Res...

Soon after the emergence and global spread of the SARS-CoV-2 Omicron lineage, BA.1, another Omicron lineage, BA.2, began outcompeting BA.1. The results of statistical analysis showed that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralization experiments revealed that immunity induced by COVID vaccines widely...

Background: Sepsis is the leading cause of death worldwide. Although the mortality of sepsis patients has been decreasing over the past decade, the trend of medical costs and cost-effectiveness for sepsis treatment remains insufficiently determined. Methods: We conducted a retrospective study using the nationwide medical claims database of sepsis p...

Introduction The usefulness of smartphone-based application software as a way to manage adverse events (AEs) after vaccination is well known. The purpose of this study is to clarify the usefulness and precautions of employing a smartphone application for collecting AEs after the administration of Comirnaty®️. Methods Healthcare workers (HCWs) who...

Soon after the emergence and global spread of a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron lineage, BA.1 (ref 1, 2 ), another Omicron lineage, BA.2, has initiated outcompeting BA.1. Statistical analysis shows that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralisation experiments...

Background Rapid and precise prehospital recognition of acute coronary syndrome (ACS) is key to improving clinical outcomes. We tested the hypothesis that the machine learning-based prehospital algorithm shows a high predictive power for predicting ACS. Methods We conducted a multicenter observational prospective study that included 10 participati...

Rapid and precise prehospital recognition of acute coronary syndrome (ACS) is key to improving clinical outcomes. We tested the hypothesis that the machine learning-based prehospital algorithm shows a high predictive power for predicting ACS. We conducted a multicenter observational prospective study that included 10 participating facilities in an...

Background The updated Surviving Sepsis Campaign guidelines recommend a 1-hour window for completion of a sepsis care bundle; however, the effectiveness of the hour-1 bundle has not been fully evaluated. The present study aimed to evaluate the impact of hour-1 bundle completion on clinical outcomes in sepsis patients. Methods This was a multicente...

Capillary refilling time (CRT) is defined as the time taken for the distal capillary bed to regain its color after the capillaries have been blanched through external skin compression. Measuring the CRT is a simple method of evaluating peripheral circulation in the clinic. Typically, the CRT is measured by manually recording the time taken for the...

Introduction: Propofol infusion syndrome (PRIS) is rare but a potentially lethal adverse event. The pathophysiologic mechanism is still unknown. Patient concerns: A 22-year-old man was admitted for the treatment of Guillain-Barré syndrome. On day six, he required mechanical ventilation due to progressive muscle weakness; propofol (3.5 mg/kg/hour) w...

Background Acute mesenteric ischemia (AMI) is challenging to diagnose in the early phase. We tested the hypothesis that blood levels of cell-free DNA would increase early after AMI. In addition, proteome analysis was conducted as an exploratory analysis to identify other potential diagnostic biomarkers. Methods Mesenteric ischemia, abdominal sepsi...

Introduction: Cytomegalovirus (CMV) infection is associated with increased length of hospital stay and mortality in critically ill patients. We evaluated the efficacy of periodic monitoring of CMV antigenemia in intensive care units (ICU). Methods: During the four-year study period, CMV antigenemia tests were conducted in 341 cases. The tests were...

Background Cellular patterns in bronchoalveolar lavage fluid (BALF) are used to distinguish or rule out particular diseases in patients with acute respiratory failure (ARF). However, whether BALF cellular patterns can predict mortality or not is unknown. We test the hypothesis that BALF cellular patterns have predictive value for mortality in patie...

This is a response to the issues raised in the commentary by Dr. Yifu Si et al.

Background: Trends in the incidence and outcomes of sepsis using a Japanese nationwide database were investigated. Methods: This was a retrospective cohort study. Adult patients, who had both presumed serious infections and acute organ dysfunction, between 2010 and 2017 were extracted using a combined method of administrative and electronic heal...

Introduction The purpose of this study was to explore factors influencing meropenem pharmacokinetics (PKs) in critically ill patients by developing a population PK model and to determine the optimal dosing strategy. Methods This prospective observational study involved 12 critically ill patients admitted to the intensive care unit and treated with...

Background: Traumatic brain injury (TBI)-associated coagulopathy is a widely recognized risk factor for secondary brain damage and contributes to poor clinical outcomes. Various theories, including disseminated intravascular coagulation (DIC), have been proposed regarding its pathomechanisms; no consensus has been reached thus far. This study aimed...

Background Shock and organ damage occur in critically ill patients in the emergency department because of biological responses to invasion, and cytokines play an important role in their development. It is important to predict early multiple organ dysfunction (MOD) because it is useful in predicting patient outcomes and selecting treatment strategie...

本邦ではRRS（rapid response system）が多くの施設で導入されつつある。RRSオンラインレジストリ（第1版）は本邦におけるRRSの状況を把握するため2014年に開始，35施設が参加し，6,784症例が蓄積されている。敗血症は，予後を改善するために早期の発見と早期の介入が必要とされている疾患であり，RRSの主な対象疾患の1つである。また，病院の特性によって有害事象が異なるという報告がある。本邦におけるRRS症例で敗血症を対象にした研究は未だに見られない。今回我々は，レジストリのデータから敗血症の状況とRRSチーム体制に対する考察を行った。【対象と結果】5,827症例のうち，535症例（9.1%）が敗血症であった。SEPSIS–2から3への定義変更によって，敗血症の占める割合...