Hemophagocytic lymphohistiocytosis triggered by relapsing polychondritis: A case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder caused by abnormal histiocytes and T cell activation. In adults, it is predominantly associated with infections, cancers, and autoimmune diseases. Relapsing polychondritis (RP), another rare disease, is diagnosed based on symptoms without specific tests, featuring cartilage inflammation characterized by swelling, redness, and pain, rarely inducing HLH. CASE SUMMARY: A 74-year-old woman visited the emergency room with a fever of 38.6 °C. Blood tests, cultures, and imaging were performed to evaluate fever. Results showed increased fluorescent antinuclear antibody levels and mild cytopenia, with no other specific findings. Imaging revealed lymph node enlargement was observed; however, biopsy results were inconclusive. Upon re-evaluation of the physical exam, inflammatory signs suggestive of RP were observed in the ears and nose, prompting a tissue biopsy for confirmation. Simultaneously, persistent fever accompanied by cytopenia prompted a bone marrow examination, revealing hemophagocytic cells. After finding no significant results in blood culture, viral markers, and tissue examination of enlarged lymph nodes, HLH was diagnosed by RP. Treatment involved methylprednisolone followed by azathioprine. After two months, bone marrow examination confirmed resolution of hemophagocytosis, with normalization of hyperferritinemia and pancytopenia. CONCLUSION: Thorough physical examination enabled diagnosis and treatment of HLH triggered by RP in patients presenting with fever of unknown origin.

Community-Acquired Solitary Brain Abscesses Caused by Hypervirulent Klebsiella pneumoniae in a Healthy Adult.

A 42-year-old man was admitted to the emergency room complaining of fever and headache. His cerebrospinal fluid showed a cloudy appearance, and his white blood cell count was elevated at 2460/mm3, with a predominance of neutrophils (81%), and abnormal protein and glucose levels (510.7 mg/dL and 5 mg/dL, respectively). A lobulated lesion with rim enhancement, suggestive of abscess, was detected through magnetic resonance imaging. Klebsiella pneumoniae was detected in nasopharyngeal swab and blood cultures. The capsular serotype of K. pneumoniae was K2 and the sequence type determined by multilocus sequence typing was 23. The hypervirulent phenotype was associated with multiple virulent genes, including rmpA, rmpA2, entB, ybtS, kfu, iucA, iutA, iroB mrkD, allS, peg-344, peg-589, and peg-1631. After six weeks of receiving appropriate antibiotics and exhibiting clinical resolution of the brain abscesses, the patient was discharged. We present the first reported case of a healthy community-dwelling adult with solitary brain abscesses, and no other invasive abscesses, related to hypervirulent K. pneumoniae.

Analysis of virulence profiles in clinical isolates of Klebsiella pneumoniae from renal abscesses: clinical significance of hypervirulent isolates.

Introduction: Klebsiella pneumoniae can cause a wide range of infections. Hypervirulent K. pneumoniae (hvKp), particularly associated with the K1 and K2 capsular types, is an increasingly significant microorganism with the potential to cause invasive infections, including renal abscesses. Despite the rising prevalence of hvKp infections, information on renal abscesses caused by K. pneumoniae is limited, and the clinical significance of hvKp associated with specific virulence genes remains elusive. Methods: This study performed at a 1200-bed tertiary hospital sought to identify the clinical and microbiological characteristics of renal abscesses caused by K. pneumoniae, focusing on various virulence genes, including capsular serotypes and multilocus sequence typing (MLST). Results: Over an 8-year period, 64 patients with suspected renal abscesses were reviewed. Ten patients diagnosed with K. pneumoniae-related renal abscesses were ultimately enrolled in the study. Among the isolates from the 10 patients, capsular serotype K2 was predominant (40.0%), followed by K1 (30.0%). The most common sequence type by MLST was 23 (40.0%). In particular, six patients (60.0%) harbored specific genes indicative of hvKp: iucA, peg-344, rmpA, and rmpA2. Conclusions: Our findings highlight the importance of hvKp as a pathogen in renal abscesses. Although the nature of hvKp is relatively unknown, it is widely recognized as a highly virulent pathogen that can infect relatively healthy individuals of various ages and simultaneously cause infections at multiple anatomical sites. Therefore, when treating patients with K. pneumoniae-related renal abscesses, caution is necessary when considering the characteristics of hvKp, such as potential bacteremia, multi-organ abscess formation, and metastatic spread.

Spontaneous splenic rupture associated with scrub typhus: a case report.

BACKGROUND: Scrub typhus, an acute febrile disease with mild to severe, life-threatening manifestations, potentially presents with a variety of complications, including pneumonia, acute respiratory distress syndrome, cardiac arrhythmias (such as atrial fibrillation), myocarditis, shock, peptic ulcer, gastrointestinal bleeding, meningitis, encephalitis, and renal failure. Of the various complications associated with scrub typhus, splenic rupture has rarely been reported, and its mechanisms are unknown. This study reports a case of scrub typhus-related spontaneous splenic rupture and identifies possible mechanisms through the gross and histopathologic findings. CASE PRESENTATION: A 78-year-old man presented to our emergency room with a 5-day history of fever and skin rash. On physical examination, eschar was observed on the left upper abdominal quadrant. The abdomen was not tender, and there was no history of trauma. The Orientia tsutsugamushi antibody titer using the indirect immunofluorescent antibody test was 1:640. On Day 6 of hospitalization, he complained of sudden-onset left upper abdominal quadrant pain and showed mental changes. His vital signs were a blood pressure of 70/40 mmHg, a heart rate pf 140 beats per min, and a respiratory rate of 20 breaths per min, with a temperature of 36.8 °C. There were no signs of gastrointestinal bleeding, such as hematemesis, melena, or hematochezia. Grey Turner's sign was suspected during an abdominal examination. Portable ultrasonography showed retroperitoneal bleeding, so an emergency exploratory laparotomy was performed, leading to a diagnosis of hemoperitoneum due to splenic rupture and a splenectomy. The patient had been taking oral doxycycline (100 mg twice daily) for 6 days; after surgery, this was discontinued, and intravenous azithromycin (500 mg daily) was administered. No arrhythmia associated with azithromycin was observed. However, renal failure with hemodialysis, persistent hyperbilirubinemia, and multiorgan failure occurred. The patient did not recover and died on the fifty-sixth day of hospitalization. CONCLUSIONS: Clinicians should consider the possibility of splenic rupture in patients with scrub typhus who display sudden-onset abdominal pain and unstable vital signs. In addition, splenic capsular rupture and extra-capsular hemorrhage are thought to be caused by splenomegaly and capsular distention resulting from red blood cell congestion in the red pulp destroying the splenic sinus.

Risk factors and clinical features for pulmonary paragonimiasis-associated pneumothorax.

BACKGROUND: Pulmonary paragonimiasis, a food-borne zoonotic helminthiasis, is a parasitic disease of the lung caused by infection with trematodes species of the genus Paragonimus. Although pneumothorax has been reported as occuring with paragonimiasis, to date no study has been performed concerning the clinical features and predictive risk factors for this condition. METHODS: This retrospective study, which aims to fill this gap, was conducted at Jeonbuk National University Hospital. All patients (aged ≥19 years) were diagnosed with paragonimiasis between May 2011 and December 2021. Medical records were reviewed and information concerning age, sex, vital signs, underlying diseases, clinical signs and symptoms, laboratory findings, radiologic findings, treatment, and clinical outcomes was collected. An odds ratio (OR) for the risk factors associated with pneumothorax was calculated using the binary logistic regression model. RESULTS: Among 179 consecutive patients diagnosed with pulmonary paragonimiasis, the postive rate of pneumothorax was 10.6% (19/179). Pneumothorax occurred mostly in the right lung (78.9%, 15/19), and intrapulmonary parenchymal lesions showed an ipsilateral relationship with pneumothorax (94.7%, 18/19). Fifteen patients (78.9%, 15/19) of pneumothorax associated with pulmonary paragonimiasis are accompanied by pleural effusion. Most of patients with pneumothorax (89.5%, 17/19) underwent chest tube insertion as a first treatment. Three patients (15.8%) showed relapses but in no case was a death recorded. Asthma (odds ratio [OR] 8.10, 95% confidence interval [CI] 1.43-45.91), chest pain (OR 8.15, 95% CI 2.70-24.58), and intrapulmonary lesions (OR 8.94, 95% CI 1.12-71.36) were independent risk factors for pulmonary paragonimiasis-associated pneumothorax. CONCLUSIONS: Our findings suggest that clinicians should keep in mind the possibility of pneumothorax when approached by patients with pulmonary paragonimiasis complaining of chest pain, accompanied by intrapulmonary lesions or with asthma as an underlying disease.

Temporal Dynamics of Serum Perforin and Granzyme during the Acute Phase of SARS-CoV-2 Infection.

BACKGROUND: As many SARS-CoV-2 infections are asymptomatic, it could be useful to be able to determine how much time has passed since infection. We explored the changes in the temporal levels of T cell-related proteins (including perforin and granzymes) in the sera of patients with SARS-CoV-2 infection using a commercially available assay. METHODS: This study enrolled 36 patients infected with SARS-CoV-2 and 20 healthy control participants. Blood samples were collected at three different times based on the number of days since symptom onset (early phase: 1-5 days, mid-phase: 6-10 days, late phase: 11-18 days). We assessed the temporal changes in the serum levels of perforin and granzymes in patients with SARS-CoV-2 infection by comparing the results with those obtained in the healthy control group. RESULTS: We identified a significantly low level of perforin in the early phase of SARS-CoV-2 infection (p < 0.01), which was restored to normal during the mid- and late phases of the infection. However, there was no difference in the temporal change in the level of granzymes in SARS-CoV-2-infected patients compared to the healthy control group. CONCLUSIONS: This finding suggests that SARS-CoV-2 infection paralyzed the perforin expression in the early period immediately after infection. Thus, serum perforin is a potential marker for identifying the acute phase of SARS-CoV-2 infection.

Temporal Dynamics of Serum Perforin and Granzymes in Three Different Clinical Stages of Virus-Induced Severe Fever with Thrombocytopenia Syndrome.

Virus-induced severe fever with thrombocytopenia syndrome (SFTS) induces a cell-mediated immune response that likely contributes to virus control in SFTS patients. To identify the temporal changes of the cell-mediated immune response, we investigated the changes in serum levels of perforin and granzymes at early periods after illness onset in SFTS patients. We analyzed 32 SFTS patients and compared the temporal patterns of serum perforin and granzyme A and B to that of 20 healthy control adults using the Mann-Whitney U test. Compared with healthy controls, the mean level of perforin was significantly reduced by 81% (P < 0.01) during the first week after illness onset, whereas granzyme B significantly increased by 4.6-fold (P = 0.02) in the first week after illness onset and decreased to normal afterward. During the study period, there was no significant difference in serum perforin and granzyme. These findings indicate that perforin and granzyme B in serum can be considered possible serologic markers that reflect the clinical stage of SFTS. Additional study is warranted for tracking circulating perforin and granzyme in different ages and for an extended period after illness onset.

Development of an External Control Arm Using Electronic Health Record-Based Real-World Data to Evaluate the Efficacy of COVID-19 Treatment.

To protect people from severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, tremendous research efforts have been made toward coronavirus disease 19 (COVID-19) treatment development. Externally controlled trials (ECTs) may help reduce their development time. To evaluate whether ECT using real-world data (RWD) of patients with COVID-19 is feasible enough to be used for regulatory decision making, we built an external control arm (ECA) based on RWD as a control arm of a previously conducted randomized controlled trial (RCT), and compared it to the control arm of the RCT. The electronic health record (EHR)-based COVID-19 cohort dataset was used as RWD, and three Adaptive COVID-19 Treatment Trial (ACTT) datasets were used as RCTs. Among the RWD datasets, eligible patients were evaluated as a pool of external control subjects of the ACTT-1, ACTT-2, and ACTT-3 trials, respectively. The ECAs were built using propensity score matching, and the balance of age, sex, and baseline clinical status ordinal scale as covariates between the treatment arms of Asian patients in each ACTT and the pools of external control subjects was assessed before and after 1:1 matching. There was no statistically significant difference in time to recovery between ECAs and the control arms of each ACTT. Among the covariates, the baseline status ordinal score had the greatest influence on the building of ECA. This study demonstrates that ECA based on EHR data of COVID-19 patients could sufficiently replace the control arm of an RCT, and it is expected to help develop new treatments faster in emergency situations, such as the COVID-19 pandemic.

Gastric ulcer and duodenitis associated with coinfection of human herpesvirus-8 and cytomegalovirus in a renal transplant recipient: a case report.

BACKGROUND: The coinfection between cytomegalovirus (CMV) and either human herpesvirus-6 (HHV-6) or HHV-7 in renal transplant recipients is well known; however, there have been few reports of coinfection of CMV associated with HHV-8. This paper presents a first case of acute gastric ulcer and duodenitis associated with CMV and HHV-8 coinfection after renal transplantation. CASE PRESENTATION: A 33-year-old male with a history of kidney transplantation was admitted to hospital because of postural epigastric pain. The recipient was CMV seropositive prior to transplantation and received trimethoprim-sulfamethoxazole without universal prophylaxis. Approximately 5 months after renal transplant, the recipient complained postural epigastric pain. An endoscopy revealed diffuse ulcerative lesions in the lower body and in the antrum of the stomach, as well as several erythematous mucosal lesions in the duodenum. Histopathologic examination identified CMV inclusions consistent with invasive CMV disease and immunohistochemical staining showed positive results for HHV-8 and CMV. No tumorous diseases such as Kaposi's sarcoma were detected. After 3 weeks of intravenous ganciclovir treatment, we observed that serum CMV PCR remained within the normal range and clinical symptoms improved. A follow-up endoscopy performed 3 weeks later showed that the severity of the above mentioned lesions had improved. CONCLUSIONS: We report the first case of a renal transplant recipient diagnosed with acute gastric ulcer and duodenitis associated with coinfection of CMV and HHV-8. Ganciclovir appears to be effective in diseases associated with coinfection of CMV and HHV-8.

Treatment outcomes of oral doxycycline versus intravenous azithromycin in adults hospitalized with scrub typhus: A retrospective study using inverse probability treatment weighting (IPTW) propensity analysis.

OBJECTIVE: Only a few well-designed studies that have investigated the effectiveness of azithromycin in treating adult patients hospitalized with scrub typhus are currently available. The purpose of our study was to compare the effects of intravenous azithromycin administration with those of oral doxycycline, and to evaluate cardiovascular death associated with intravenous azithromycin in adult patients hospitalized with scrub typhus. METHODS: This retrospective study investigated Korean National Infectious Disease Cohort Collaborative-registered scrub typhus-infected patients who were hospitalized between January 1, 2013, and December 31, 2021, and who were ≥18 years old. The primary outcome was time to fever clearance and the secondary outcomes were treatment failure, relapse, scrub typhus-related death, or azithromycin-related cardiovascular death. To address any indication bias, inverse probability of treatment weighting (IPTW) analysis was performed. Times to fever clearance between the doxycycline and azithromycin groups were compared using log-rank tests and Kaplan-Meier curves. RESULTS: A total of 326 consecutive patients with laboratory-confirmed scrub typhus were included in this study of whom 109 were treated with azithromycin and 217 with doxycycline. Using IPTW, there were no statistically significant differences in the following end points between the azithromycin and doxycycline groups: median time to fever clearance (3 days vs. 3 days, P = 0.649), treatment failure (0.71% vs. 0.42%, P = 0.702), relapse (0.0% vs. 0.0%), and scrub typhus-related death (5.12% vs. 0.0%, P = 0.155). No azithromycin-related cardiovascular deaths occurred. In the sensitivity analyses, there were no significant changes in effect size. CONCLUSIONS: Our study showed that the therapeutic effects and safety of intravenous azithromycin are comparable to those of oral doxycycline administration in patients hospitalized with scrub typhus. A well-designed randomized controlled trial may help further evaluate the most adequate route of administration, dose and duration of treatment with azithromycin.

Influenza viral infection is a risk factor for severe illness in COVID-19 patients: a nationwide population-based cohort study.

In order to prepare for the twindemic of influenza and SARS-CoV-2 infection, we investigated the association between influenza infection and subsequent severity of SARS-CoV-2 infection. A population-based nationwide cohort study was performed using data from the National Health Insurance Service (NHIS) in the Republic of Korea. This study included 274,126 individuals who underwent SARS-CoV-2 PCR testing between 20 January 2020 and 1 October 2020. Among these patients, 28,338 tested positive for SARS-CoV-2, and 4,003 of these individuals had a history of influenza. The control group was selected through 1:1 propensity score matching. In the group of 4,003 COVID-19-positive individuals with no history of influenza, 192 (4.8%) experienced severe illness from COVID-19 infection. In the group of 4,003 COVID-19-positive individuals with a history of influenza, 260 (6.5%) had severe illness from COVID-19, and the overall adjusted odds ratio (aOR) was 1.29 (95% confidence interval 1.04-1.59). Among the 4,003 COVID-19-positive individuals with a history of influenza, severe COVID-19 infection was experienced by 143 of 1,760 (8.1%) with an influenza history within 1 year before the onset of COVID-19, 48 of 1,129 (4.3%) between 1 and 2 years, and 69 of 1,114 (6.2%) between 2 and 3 years before COVID-19 onset, and the aORs were 1.54 (1.20-1.98), 1.19 (0.84-1.70), and 1.00 (0.73-1.37), respectively. In conclusion, individuals who had an influenza infection less than 1 year before COVID-19 infection were at an increased risk of experiencing severe illness from the SARS-CoV-2 infection. To control the public health burden, it is essential that effective public health control measures, which include influenza vaccination, hand washing, cough etiquette, and mask use are in place.

Invasive Hypervirulent Klebsiella pneumoniae Syndrome Originating from an Anorectal Abscess as Opposed to a Pyogenic Liver Abscess.

An immunocompetent 49-year-old man presented with swelling and pain in the lower region of his left leg that had lasted for 4 weeks. The diagnosis was severe pyomyositis and osteomyelitis in the lower left leg caused by hypervirulent Klebsiella pneumoniae (hvKP) along with multiple metastatic infections in the kidneys, lungs, and brain originating from an anorectal abscess. A virulence-gene analysis revealed that the isolated K. pneumoniae harbored rmpA, entB, ybtS, kfu, iutA, mrkD, and allS-virulence genes and belonged to the K1 capsular serotype. After repeated abscess drainage procedures, intravenous ceftriaxone was administered for more than 10 weeks, and the patient's infection was controlled. We focused on the clinical features of hvKP originating from an anorectal abscess without a pyogenic liver abscess. We suggest that hvKP be considered a causative pathogen of pyomyositis and osteomyelitis resulting in multiple metastatic infections in an immunocompetent patient, and more information on the unexpected multiple metastatic infections should be obtained from a virulence analysis of K. pneumoniae.

Pyogenic spondylitis caused by Klebsiella pneumoniae: should the possibility of hypervirulent Klebsiella pneumoniae be considered?

BACKGROUND: Klebsiella pneumoniae is rare but the second most common causative agent among gram-negative bacteria that cause pyogenic spondylitis. However, there are no available studies on the serotype, virulence factors, and clinical characteristics associated with K. pneumoniae-caused pyogenic spondylitis. Accordingly, we investigated the clinical characteristics of pyogenic spondylitis, K1 and K2 serotypes, and virulence factors of K. pneumoniae. METHODS: We reviewed the microbiological reports of specimens collected between January 2014 and December 2019 as well as the medical records of patients with pyogenic spondylitis caused by K. pneumoniae. We also evaluated K1 and K2 serotypes and the virulent genes rmpA, iutA, mrkD, ybtS, entB, and kfu. Strains that possessed rmpA and iutA were defined as hypervirulent K. pneumoniae. RESULTS: Six patients with pyogenic spondylitis caused by K. pneumoniae were enrolled in the study. The capsular serotypes K1 and K2 were present in 66.7% (4/6) of cases, and the hypervirulent strains were present in 88.3% (5/6) of cases. All patients had community-acquired infections, and all strains isolated were susceptible to antimicrobial agents. Intravenous antibiotic treatment continued for 2-7 weeks, and no patient underwent decompressive operation or surgical debridement. There was no recurrence. One patient died from pneumonia with a septic lung. CONCLUSION: Hypervirulent K. pneumoniae is a rare but possible causative agent associated with pyogenic spondylitis.

Prostatic Abscess Caused by Klebsiella pneumoniae: A 6-Year Single-Center Study.

Hypervirulent Klebsiella pneumoniae (hvKp) is an important strain that can cause multiple organ infections. Although hvKp infection cases are increasing, there is limited information on the prostatic abscesses caused by K. pneumoniae. Furthermore, the clinical significance of hvKp associated with K1 or K2 capsular types or virulence genes in prostatic abscesses remains unclear. Therefore, we aimed to elucidate the clinical and microbiological characteristics of prostatic abscesses caused by K. pneumoniae in relation to various virulence genes. A retrospective study was performed at a 1200-bed tertiary hospital between January 2014 and December 2019. Patients diagnosed with prostatic abscesses with K. pneumoniae isolated from blood, urine, pus, or tissue cultures were enrolled in this study. Our results demonstrate that 30.3% (10/33) of the prostatic abscesses were caused by K. pneumoniae. All strains isolated from patients with prostatic abscesses due to K. pneumoniae were the K1 capsular type, and eight patients (80.0%) carried rmpA and iutA genes that identified hvKp. These findings suggest that hvKp is an important pathogen in prostatic abscesses. Therefore, when treating patients with K. pneumoniae prostatic abscesses, attention should be paid to the characteristics of hvKp, such as bacteremia, multiorgan abscess formation, and metastatic spread.

Bean Extract-Based Gargle for Efficient Diagnosis of Active COVID-19 Infection Using Rapid Antigen Tests.

The antigen-based rapid diagnostic test (Ag-RDT) using saliva specimens is fast, noninvasive, and suitable for SARS-CoV-2 self-testing, unlike nasopharyngeal swab (NPS) testing. We evaluated a novel Beanguard gargle (BG)-based virus collection method that can be applied to Ag-RDT as an alternative to the current RT-PCR with an NPS for early diagnosis of COVID-19. This clinical trial comprised 102 COVID-19-positive patients hospitalized after a governmental screening process and 100 healthy individuals. Paired NPS and BG-based saliva specimens from COVID-19 patients and healthy individuals were analyzed using NPS-RT-PCR, BG-RT-PCR, and BG-Ag-RDTs, whose diagnostic performance for detecting SARS-CoV-2 was compared. BG-Ag-RDTs showed high sensitivity (97.8%) and specificity (100%) in 45 patients within 6 days of illness and detected all cases of SARS-CoV-2 Alpha and Delta variants. In 11 asymptomatic active COVID-19 cases, both BG-Ag-RDTs and BG-RT-PCR showed sensitivities and specificities of 100%. Sensitivities of BG-Ag-RDT and BG-RT-PCR toward salivary viral detection were highly concordant, with no discrimination between symptomatic (97.0%), asymptomatic (100%), or SARS-CoV-2 variant (100%) cases. The intermolecular interactions between SARS-CoV-2 spike proteins and truncated canavalin, an active ingredient from the bean extract (BE), were observed in terms of physicochemical properties. The detachment of the SARS-CoV-2 receptor-binding domain from hACE2 increased as the BE concentration increased, allowing the release of the virus from hACE2 for early diagnosis. Using BG-based saliva specimens remarkably enhances the Ag-RDT diagnostic performance as an alternative to NPS and enables noninvasive, rapid, and accurate COVID-19 self-testing and mass screening, supporting efficient COVID-19 management. IMPORTANCE An Ag-RDT is less likely to be accepted as an initial test method for early diagnosis owing to its low sensitivity. However, our self-collection method, Ag-RDT using BG-based saliva specimens, showed significantly enhanced detection sensitivity and specificity toward SARS-CoV-2 including the Alpha and Delta variants in all patients tested within 6 days of illness. The method represents an attractive alternative to nasopharyngeal swabs for the early diagnosis of symptomatic and asymptomatic COVID-19 cases. The evidence suggests that the method could have a potential for mass screening and monitoring of COVID-19 cases.

Synergy Through Integration of Wearable EEG and Virtual Reality for Mild Cognitive Impairment and Mild Dementia Screening.

Virtual reality (VR) technologies have shown promising potential in the early diagnosis of dementia by enabling accessible and regular assessment. However, previous VR studies were restricted to the analysis of behavioral responses, so information about degenerated brain dynamics could not be directly acquired. To address this issue, we provide a cognitive impairment (CI) screening tool based on a wearable EEG device integrated into a VR platform. Subjects were asked to use a hardware setup consisting of a frontal six-channel EEG device mounted on a VR device and to perform four cognitive tasks in VR. Behavioral response profiles and EEG features were extracted during the tasks, and classifiers were trained on extracted features to differentiate subjects with CI from healthy controls (HCs). Notably, the performance of the patient classification consistently improved when EEG characteristics measured during cognitive tasks were additionally included in feature attributes than when only the task scores or resting-state EEG features were used, suggesting that our protocol provides discriminative information for screening. These results propose that the integration of EEG devices into a VR framework could emerge as a powerful and synergistic strategy for constructing an easily accessible EEG-based CI screening tool.

A Clinical Decision Support System for Sleep Staging Tasks With Explanations From Artificial Intelligence: User-Centered Design and Evaluation Study.

BACKGROUND: Despite the unprecedented performance of deep learning algorithms in clinical domains, full reviews of algorithmic predictions by human experts remain mandatory. Under these circumstances, artificial intelligence (AI) models are primarily designed as clinical decision support systems (CDSSs). However, from the perspective of clinical practitioners, the lack of clinical interpretability and user-centered interfaces hinders the adoption of these AI systems in practice. OBJECTIVE: This study aims to develop an AI-based CDSS for assisting polysomnographic technicians in reviewing AI-predicted sleep staging results. This study proposed and evaluated a CDSS that provides clinically sound explanations for AI predictions in a user-centered manner. METHODS: Our study is based on a user-centered design framework for developing explanations in a CDSS that identifies why explanations are needed, what information should be contained in explanations, and how explanations can be provided in the CDSS. We conducted user interviews, user observation sessions, and an iterative design process to identify three key aspects for designing explanations in the CDSS. After constructing the CDSS, the tool was evaluated to investigate how the CDSS explanations helped technicians. We measured the accuracy of sleep staging and interrater reliability with macro-F1 and Cohen κ scores to assess quantitative improvements after our tool was adopted. We assessed qualitative improvements through participant interviews that established how participants perceived and used the tool. RESULTS: The user study revealed that technicians desire explanations that are relevant to key electroencephalogram (EEG) patterns for sleep staging when assessing the correctness of AI predictions. Here, technicians wanted explanations that could be used to evaluate whether the AI models properly locate and use these patterns during prediction. On the basis of this, information that is closely related to sleep EEG patterns was formulated for the AI models. In the iterative design phase, we developed a different visualization strategy for each pattern based on how technicians interpreted the EEG recordings with these patterns during their workflows. Our evaluation study on 9 polysomnographic technicians quantitatively and qualitatively investigated the helpfulness of the tool. For technicians with <5 years of work experience, their quantitative sleep staging performance improved significantly from 56.75 to 60.59 with a P value of .05. Qualitatively, participants reported that the information provided effectively supported them, and they could develop notable adoption strategies for the tool. CONCLUSIONS: Our findings indicate that formulating clinical explanations for automated predictions using the information in the AI with a user-centered design process is an effective strategy for developing a CDSS for sleep staging.

Elevated Extracellular Levels of Granzymes in Patients with Scrub Typhus.

Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi, which is transmitted through chigger mites. Delayed treatment results in various complications and, in severe cases, death. Granzymes are secreted by cytotoxic T lymphocytes or natural killer cells and are known to play an important role in controlling intracellular pathogens. To date, few studies have been done on granzymes in patients with scrub typhus. In this study, granzymes A and B showed a significant increase during the acute stage of scrub typhus compared with healthy control subjects, and decreased sharply after treatment. In addition, granzymes A and B were significantly high in the moderately elevated liver enzyme group. In conclusion, it appears that the host during the acute phase of scrub typhus increases cytotoxic T-cell activity to control infection.