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Rapid economic growth in Indonesia and Malaysia has widened the gap in emergency care supply and demand, intensifying challenges. Our study, from August to November 2022, assesses current diverse challenges in both countries' emergency care systems from frontline staff perspectives. The online survey involved emergency department (ED) personnel from 11 hospitals in Indonesia and Malaysia, drawing from an existing network. The survey collected data on respondents' characteristics, factors affecting prehospital and ED care quality, missing clinical information, and factors influencing patients' ED stay duration. With 83 respondents from Indonesia and 109 from Malaysia, the study identified common challenges. In both countries, inadequate clinical information from ambulances posed a primary challenge in prehospital care quality, while crowdedness during night shifts affected ED care quality. Frequent gaps in essential clinical information, such as family and medication history, were observed. Prolonged ED stays were associated with diagnostic studies and their turnaround time. This study offers insights into shared challenges in Indonesia and Malaysia's emergency care systems. Our findings stress recognizing common and country-specific challenges for enhanced emergency care quality in Southeast Asia, supporting tailored interventions., (© 2024. The Author(s).)

Tadashi Kamio,1 Hiroshi Koyama,1 Kiyomitsu Fukaguchi,1 Shuku Sato,2 Wataru Kamata,2 Satomi Okada,2 Yotaro Tamai2 1Division of Critical Care, Shonan Kamakura General Hospital, Kamakura, Kanagawa 247-8533, Japan; 2Department of Hematology, Shonan Kamakura General Hospital, Kamakura, Kanagawa 247-8533, JapanCorrespondence: Tadashi KamioDivision of Critical Care, Shonan Kamakura General Hospital, 1370-1 Okamoto, Kamakura, Kanagawa 247-8533, JapanTel +81-467-46-1717Fax +81-467-47-8243Email tadashi-kamio@mail.goo.ne.jpPurpose: Acute promyelocytic leukemia (APL) constitutes 5– 10% of all cases of newly diagnosed acute myeloid leukemia. However, data on the epidemiology and risk factors for acute kidney injury (AKI) in patients with newly diagnosed APL are lacking. This study determined the incidence rate of AKI during induction chemotherapy for patients with newly diagnosed APL and the risk factors for AKI.Patients and Methods: We conducted a retrospective observational study of patients with newly diagnosed APL in the Shonan Kamakura General Hospital between April 2004 and April 2020. Data of 27 patients with newly diagnosed APL were analyzed. The patients were classified as no AKI and AKI stages 1, 2 or 3.Results: The incidence rate of AKI during induction chemotherapy was 40% (11/27). Among patients who developed AKI, four patients experienced AKI stage 3, and two patients required renal replacement therapy. No significant differences were found in the white blood cell count and baseline renal function between the groups; however, D-dimer and C-reactive protein levels upon admission were significantly higher in patients with AKI than in patients without AKI. Among patients who developed AKI, in hospital mortality at 90 days was 36% (4/11), which was significantly higher than among patients without AKI (p = 0.02). Patients who developed AKI were administered vancomycin more frequently, while almost all blood culture results were negative.Conclusion: Incidence of AKI development in patients with newly diagnosed APL during induction chemotherapy was approximately 40%. Moreover, patients who developed AKI tended to be administered vancomycin more frequently. Unnecessary use of vancomycin should be avoided in patients with newly diagnosed APL, and using alternative non-nephrotoxic drugs should be considered for patients at risk of AKI.Keywords: acute promyelocytic leukemia, acute kidney injury, incidence rate, induction chemotherapy

Optimal timing for intubating patients with coronavirus disease 2019 (COVID-19) has been debated throughout the pandemic. Early use of high-flow nasal cannula (HFNC) can help reduce the need for intubation, but delay can result in poorer outcomes. This study examines trends in laboratory parameters and serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA levels of patients with COVID-19 in relation to HFNC failure. Patients requiring HFNC within three days of hospitalization between July 1 and September 30, 2021 were enrolled. The primary outcome was HFNC failure (early failure ≤Day 3; late failure ≥Day 4), defined as transfer to intensive care just before/after intubation or in-hospital death. We examined changes in laboratory markers and SARS-CoV2-RNAemia on Days 1, 4, and 7, together with demographic data, oxygenation status, and therapeutic agents. We conducted a univariate logistic regression with the explanatory variables defined as 10% change rate in each laboratory marker from Day 1 to 4. We utilized the log-rank test to assess the differences in HFNC failure rates, stratified based on the presence of SARS-CoV2 RNAemia. Among 122 patients, 17 (13.9%) experienced HFNC failure (early: n = 6, late: n = 11). Seventy-five patients (61.5%) showed an initial SpO2/FiO2 ratio ≤243, equivalent to PaO2/FiO2 ratio ≤200, and the initial SpO2/FiO2 ratio was significantly lower in the failure group (184 vs. 218, p = 0.018). Among the laboratory markers, a 10% increase from Day 1 to 4 of lactate dehydrogenase (LDH) and interleukin (IL)-6 was associated with late failure (Odds ratio [OR]: 1.42, 95% confidence interval [CI]: 1.09-1.89 and OR: 1.04, 95%CI: 1.00-1.19, respectively). Furthermore, in patients with persistent RNAemia on Day 4 or 7, the risk of late HFNC failure was significantly higher (Log-rank test, p<0.01). In conclusion, upward trends in LDH and IL-6 levels and the persistent RNAemia even after treatment were associated with HFNC failure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Koyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Although adverse events related to extracorporeal membrane oxygenation have been reported, epidemiological data on life-threatening events are insufficient to study the causes of such adverse events. Data from the Japan Council for Quality Health Care database were retrospectively analyzed. The adverse events extracted from this national database included events associated with extracorporeal membrane oxygenation reported between January 2010 and December 2021. We identified 178 adverse events related to extracorporeal membrane oxygenation. At least 41 (23%) and 47 (26%) accidents resulted in death and residual disability, respectively. The most common adverse events were cannula malposition (28%), decannulation (19%), and bleeding (15%). Among patients with cannula malposition, 38% did not undergo fluoroscopy-guided or ultrasound-guided cannulation, 54% required surgical treatment, and 18% required trans-arterial embolization. In this epidemiological study in Japan, 23% of the adverse events related to extracorporeal membrane oxygenation had fatal outcomes. Our findings suggest that a training system for cannulation techniques may be needed, and hospitals offering extracorporeal membrane oxygenation should perform emergency surgeries., (© 2023. The Author(s).)

Numerous COVID-19 diagnostic imaging Artificial Intelligence (AI) studies exist. However, none of their models were of potential clinical use, primarily owing to methodological defects and the lack of implementation considerations for inference. In this study, all development processes of the deep-learning models are performed based on strict criteria of the "KAIZEN checklist", which is proposed based on previous AI development guidelines to overcome the deficiencies mentioned above. We develop and evaluate two binary-classification deep-learning models to triage COVID-19: a slice model examining a Computed Tomography (CT) slice to find COVID-19 lesions; a series model examining a series of CT images to find an infected patient. We collected 2,400,200 CT slices from twelve emergency centers in Japan. Area Under Curve (AUC) and accuracy were calculated for classification performance. The inference time of the system that includes these two models were measured. For validation data, the slice and series models recognized COVID-19 with AUCs and accuracies of 0.989 and 0.982, 95.9% and 93.0% respectively. For test data, the models' AUCs and accuracies were 0.958 and 0.953, 90.0% and 91.4% respectively. The average inference time per case was 2.83 s. Our deep-learning system realizes accuracy and inference speed high enough for practical use. The systems have already been implemented in four hospitals and eight are under progression. We released an application software and implementation code for free in a highly usable state to allow its use in Japan and globally., (© 2024. The Author(s).)

Background: Whether GPT-4, the conversational artificial intelligence, can accurately diagnose and triage health conditions and whether it presents racial and ethnic biases in its decisions remain unclear., Objective: We aim to assess the accuracy of GPT-4 in the diagnosis and triage of health conditions and whether its performance varies by patient race and ethnicity., Methods: We compared the performance of GPT-4 and physicians, using 45 typical clinical vignettes, each with a correct diagnosis and triage level, in February and March 2023. For each of the 45 clinical vignettes, GPT-4 and 3 board-certified physicians provided the most likely primary diagnosis and triage level (emergency, nonemergency, or self-care). Independent reviewers evaluated the diagnoses as "correct" or "incorrect." Physician diagnosis was defined as the consensus of the 3 physicians. We evaluated whether the performance of GPT-4 varies by patient race and ethnicity, by adding the information on patient race and ethnicity to the clinical vignettes., Results: The accuracy of diagnosis was comparable between GPT-4 and physicians (the percentage of correct diagnosis was 97.8% (44/45; 95% CI 88.2%-99.9%) for GPT-4 and 91.1% (41/45; 95% CI 78.8%-97.5%) for physicians; P=.38). GPT-4 provided appropriate reasoning for 97.8% (44/45) of the vignettes. The appropriateness of triage was comparable between GPT-4 and physicians (GPT-4: 30/45, 66.7%; 95% CI 51.0%-80.0%; physicians: 30/45, 66.7%; 95% CI 51.0%-80.0%; P=.99). The performance of GPT-4 in diagnosing health conditions did not vary among different races and ethnicities (Black, White, Asian, and Hispanic), with an accuracy of 100% (95% CI 78.2%-100%). P values, compared to the GPT-4 output without incorporating race and ethnicity information, were all .99. The accuracy of triage was not significantly different even if patients' race and ethnicity information was added. The accuracy of triage was 62.2% (95% CI 46.5%-76.2%; P=.50) for Black patients; 66.7% (95% CI 51.0%-80.0%; P=.99) for White patients; 66.7% (95% CI 51.0%-80.0%; P=.99) for Asian patients, and 62.2% (95% CI 46.5%-76.2%; P=.69) for Hispanic patients. P values were calculated by comparing the outputs with and without conditioning on race and ethnicity., Conclusions: GPT-4's ability to diagnose and triage typical clinical vignettes was comparable to that of board-certified physicians. The performance of GPT-4 did not vary by patient race and ethnicity. These findings should be informative for health systems looking to introduce conversational artificial intelligence to improve the efficiency of patient diagnosis and triage., (©Naoki Ito, Sakina Kadomatsu, Mineto Fujisawa, Kiyomitsu Fukaguchi, Ryo Ishizawa, Naoki Kanda, Daisuke Kasugai, Mikio Nakajima, Tadahiro Goto, Yusuke Tsugawa. Originally published in JMIR Medical Education (https://mededu.jmir.org), 02.11.2023.)

Background: Invasive pulmonary Aspergillus and invasive bronchial aspergillosis is a life-threatening opportunistic fungal infection that predominantly affects immunocompromised hosts. A case series and review found that the mortality rate of invasive bronchial aspergillosis is high, at about 40%, and 23.7% of invasive bronchial aspergillosis patients require mechanical ventilator management. There are few reports of life-saving cases with venovenous extracorporeal membrane oxygenation as rescue therapy in invasive pulmonary Aspergillus and invasive bronchial aspergillosis. Here, we report a case of invasive bronchial aspergillosis and invasive pulmonary Aspergillus that was successfully treated with venovenous extracorporeal membrane oxygenation, and combined systemic and intratracheal instillation of liposomal amphotericin B., Case Presentation: We present the case of a 61-year-old Japanese man with invasive tracheobronchial-pulmonary aspergillosis while receiving chemotherapy for malignant lymphoma. Bronchoscopy revealed trachea covered with pseudomembranous necrotizing tissue, the culture revealed Aspergillus fumigatus, and the histological findings of pseudomembranous revealed fungal hyphae. The patient required venovenous extracorporeal membrane oxygenation because of respiratory failure for atelectasis and obstructive pneumoniae. While continuing systemic administration of liposomal amphotericin B, intratracheal instillation liposomal amphotericin B was performed by bronchoscopy three times a week. Although the respiratory conditions improved and the patient was discontinued on venovenous extracorporeal membrane oxygenation, he ultimately died of recurrence of malignant lymphoma., Conclusion: Intratracheal instillation of liposomal amphotericin B is safe, and liposomal amphotericin B instillation allowed a targeted high local drug concentration, which led to improvement in the invasive bronchial aspergillosis. In addition, since the patient was supported with venovenous extracorporeal membrane oxygenation, we were able to perform safe bronchoscopic debridement of airway lesions and intratracheal instillation of liposomal amphotericin B., (© 2022. The Author(s).)

BACKGROUND Severe hypothermia has a high mortality rate and necessitates aggressive warming to save lives. One of the most effective treatments for severe hypothermia is intravascular rewarming. Intravascular recuperative warming can be delivered by inserting a catheter through the cervical or femoral veins. Catheter insertion through the femoral vein is a commonly performed procedure with fewer complications than catheter insertion through the internal jugular vein. This procedure is commonly conducted by inserting a central venous catheter through the femoral vein. When a catheter is inserted through the femoral vein, a frontal abdominal radiograph is often used to confirm the position of the catheter tip. CASE REPORT We present the case of a 58-year-old Japanese man who had severe hypothermia. Under ultrasound guidance, a catheter was inserted through the femoral vein into the inferior vena cava for active rewarming. A frontal abdominal radiograph showed that a catheter tip appeared to be in the inferior vena cava. However, a subsequent computed tomography scan revealed that the catheter tip had been misplaced into the right ascending lumbar vein. CONCLUSIONS Catheters may stray into the right ascending lumbar vein if they are placed through the right femoral vein. Frontal abdominal radiographs may be insufficient to confirm catheter placement.

Background: With the aging society, the number of emergency transportations has been growing. Although it is important that a patient be immediately transported to an appropriate hospital for proper management, accurate diagnosis in the prehospital setting is challenging. However, at present, patient information is mainly communicated by telephone, which has a potential risk of communication errors such as mishearing. Sharing correct and detailed prehospital information with emergency departments (EDs) should facilitate optimal patient care and resource use. Therefore, the implementation of an app that provides on-site, real-time information to emergency physicians could be useful for early preparation, intervention, and effective use of medical and human resources., Objective: In this paper, we aimed to examine whether the implementation of a mobile app for emergency medical service (EMS) would improve patient outcomes and reduce transportation time as well as communication time by phone (ie, phone-communication time)., Methods: We performed an interrupted time-series analysis (ITSA) on the data from a tertiary care hospital in Japan from July 2021 to October 2021 (8 weeks before and 8 weeks after the implementation period). We included all patients transported by EMS. Using the mobile app, EMS can send information on patient demographics, vital signs, medications, and photos of the scene to the ED. The outcome measure was inpatient mortality and transportation time, as well as phone-communication time, which was the time for EMS to negotiate with ED staffs for transport requests., Results: During the study period, 1966 emergency transportations were made (n=1033, 53% patients during the preimplementation period and n=933, 47% patients after the implementation period). The ITSA did not reveal a significant decrease in patient mortality and transportation time before and after the implementation. However, the ITSA revealed a significant decrease in mean phone-communication time between pre- and postimplementation periods (from 216 to 171 seconds; -45 seconds; 95% CI -71 to -18 seconds). From the pre- to postimplementation period, the mean transportation time from EMS request to ED arrival decreased by 0.29 minutes (from 36.1 minutes to 35.9 minutes; 95% CI -2.20 to 1.60 minutes), without change in time trends. We also introduced cases where the app allowed EMS to share accurate and detailed prehospital information with the emergency department, resulting in timely intervention and reducing the burden on the ED., Conclusions: The implementation of a mobile app for EMS was associated with reduced phone-communication time by 45 seconds (22%) without increasing mortality or overall transportation time despite the implementation of new methods in the real clinical setting. In addition, real-time patient information sharing, such as the transfer of monitor images and photos of the accident site, could facilitate optimal patient care and resource use., (©Kiyomitsu Fukaguchi, Tadahiro Goto, Tadatsugu Yamamoto, Hiroshi Yamagami. Originally published in JMIR Formative Research (https://formative.jmir.org), 06.07.2022.)

Purpose: Thoracentesis and chest tube insertion are procedures commonly performed in routine clinical practice and are considered mandatory skills for all physicians. Adverse events secondary to these procedures have been widely reported; however, epidemiology data concerning life-threatening events associated with these procedures are lacking., Methods: We retrospectively analyzed data from the Japan Council for Quality Health Care open database regarding subject safety incidents involving thoracentesis and chest tube insertion. The adverse events extracted from the database included only events associated with thoracentesis and chest tube insertion reported between January 2010 and April 2020., Results: We identified 137 adverse events due to thoracentesis or chest tube insertion. Our analysis also revealed at least 15 fatal adverse events and 17 cases of left/right misalignment. Not only resident doctors but also physicians with 10 years or more of clinical experience had been mentioned in these reports. The most common complications due to adverse events were lung injury (55%), thoracic vascular injury (21%), and liver injury (10%). Surgical treatment was required for 43 (31%) of the 137 cases, and the mortality risk was significantly higher for thoracic vascular injury than for other complications (p = 0.02)., Conclusion: We identified at least 15 fatal adverse events and 17 cases of left/right misalignment over a 10-year period in the Japan Council for Quality Health Care open database. Our findings also suggest that care should be taken to avoid thoracic vascular injury during chest tube insertion and that immediate intervention is required should such an injury occur., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Serum potassium levels are considered as a marker of cerebrovascular emergencies but there is less clarity on the association between initial serum potassium levels recorded on patient's arrival at the emergency department with the type of stroke. This is a case-control study using data of a tertiary care hospital in Japan from April 2018 to September 2019. We identified adult patients with hemorrhagic stroke including subarachnoid hemorrhage (cases) and those with ischemic stroke (controls). Data on age, sex, chief complaints, vital signs, and initial blood tests were collected. We analyzed the association between serum potassium levels and the type of stroke by drawing a LOWESS curve. Additionally, we fitted a logistic regression model to examine the association of interest. There were 416 stroke patients (158 hemorrhagic and 258 ischemic). The median age was 77 years (IQR: 68, 84), and 54% were male. The mean potassium level was 3.69 ± 0.55 mEq/L for hemorrhagic stroke and 4.08 ± 0.65 mEq/L for ischemic stroke. The LOWESS curve showed that the lower initial potassium level was linearly associated with a greater likelihood of hemorrhagic stroke. In the logistic regression model, the odds ratio for the risk of hemorrhagic stroke per 1 mEq/L lower potassium level was 3.31 (95% confidence interval [CI]: 2.24-5.04). This association remained significant in a multivariable model adjusting for other covariates (OR: 2.62 [95% CI: 1.70-4.16]). Initial potassium level was lower in patients with hemorrhagic stroke compared to those with ischemic stroke., Competing Interests: Declaration of Competing Interest Dr. Fukaguchi, Dr. Soeno, Dr. Hara, Dr. Shirakawa are contracted researchers of TXP Medical Co. Ltd. Dr. Goto is the Chief Scientific Officer of TXP Medical Co. Ltd. Dr. Sonoo is the Chief Executive Officer of TXP Medical Co. Ltd., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: The coronavirus disease (COVID-19) pandemic massively impacted emergency department (ED) visits. The unavailability of specific therapies or vaccines has made non-pharmaceutical interventions (NPIs) an alternative strategy for COVID-19. We assessed the impact of NPIs (nationwide school closures and state of emergency) on ED visits during the COVID-19 pandemic in Japan., Methods: This retrospective study compared the trends in ED visits from 1 January to 25 May, 2020 (during the pandemic) with the average during 2015-2019 (before the pandemic). The primary end-point was the change in the number of ED visits during the COVID-19 pandemic with those from before the pandemic, with the NPI application stratified across four periods in 2020: Period 0 (1-15 January), no COVID-19 cases detected in Japan; Period I (16 January-1 March), initial COVID-19 outbreak; Period II (2 March-15 April), nationwide school closures; Period III (16 April-25 May), state of emergency., Results: Compared with before the pandemic, the number of walk-in ED visits significantly decreased by 23.1%, 12.4%, and 24.0% (4,047 versus 3,111; 3,211 versus 2,813; and 3,384 versus 2,573; P  < 0.001 for all) in Periods I, II, and III, respectively. The number of ambulance ED visits during the pandemic significantly increased by 8.3% in Period I (1,814 versus 1,964, P  = 0.002), whereas there was no significant change in Periods II and III with 2.7% and -3.1% (1,547 versus 1,589 and 1,389 versus 1,346; P  = 0.335 and P  = 0.284, respectively)., Conclusions: The application of an NPI during the COVID-19 pandemic could have significantly reduced patient attendance in the ED., Competing Interests: Approval of the research protocol: This study was approved by the Tokushukai Group Ethical Committee (TGE01518‐024). Informed consent: N/A. Registry and the registration no. of the study: UMIN Clinical Trials Registry, UMIN000041073. Animal studies: N/A. Conflict of interest: None., (© 2020 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Aim: In patients with thunderclap headaches, reversible cerebral vasoconstriction syndrome (RCVS) should be considered as a differential diagnosis. However, RCVS diagnosis in the emergency department (ED) remains challenging. This report describes the clinical features and factors related to RCVS diagnosis and suggests diagnostic strategies for its management., Methods: We retrospectively reviewed the medical records of eight patients diagnosed with RCVS from January 2010 to March 2019 (aged 18-69 years, 5 women)., Results: The median duration from the ED visit to RCVS diagnosis was 6 days (range, 1-11 days). Of the eight patients, seven were middle-aged, six had apparent triggers, six had subarachnoid hemorrhage (SAH), five had high systolic blood pressure, and none had any specific abnormality observed upon physical examination. At the initial visit, RCVS was diagnosed in only one patient who had a history of RCVS. Of the other patients, SAH was diagnosed in two, and primary headache was diagnosed in four patients with negative computed tomography (CT) findings. Based on follow-up angiography (e.g., magnetic resonance angiography), seven of eight patients with convexal SAH were diagnosed with RCVS (as the cause of SAH)., Conclusion: Reversible cerebral vasoconstriction syndrome with negative CT findings at the ED visit was likely to be misdiagnosed as a primary headache. In patients with thunderclap headache and negative CT findings, physicians should consider RCVS as a differential diagnosis, inform patients of the risk of RCVS, and undertake follow-up imaging within 2 weeks., Competing Interests: Approval of the Research Protocol: This study was approved by the hospital’s Institutional Review Board. Informed Consent: The requirement of written informed consent was waived. Registry and the Registration no. of the study/trial: N/A. Animal Studies: N/A. Conflict of Interest: None., (© 2020 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Background: Maintaining the patient awake and not intubated during the venovenous extracorporeal membrane oxygenation (VV ECMO) reduces the risk of ventilation-induced lung injury in patients with ARDS. Currently, there is a lack of data on outcomes and complications associated with the awake ECMO approach. Objectives: To evaluate outcomes and the occurrence of complications of awake ECMO approach guided by local safety protocol comprising ultrasound-guided cannulation, argatroban-based anticoagulation, respiratory support, and routine sedation targeted to reduce respiratory effort and keeping nurse-to-patient ratio of 1:1. Design: A single-center retrospective case series analysis. Methods: Consecutive patients with COVID-19-related acute respiratory distress syndrome (ARDS) (CARDS) treated by full awake VV ECMO approach from April 2019 to December 2023 were eligible. Results: Our center treated 10 patients (mean age 54.7 ± 11.6 years) with CARDS with an awake ECMO approach. The reasons for awake ECMO included the presence of barotrauma in six patients, a team consensus to prefer awake ECMO instead of mechanical ventilation in three patients, and the patient's refusal to be intubated in one case. Before ECMO, patients were severely hypoxemic, with a mean value of Horowitz index of 48.9 ± 9.1 mmHg and a mean respiratory rate of 28.8 ± 7.3 breaths per minute on high-flow nasal cannula or noninvasive ventilation support. The mean duration of awake VV ECMO was 558.0 ± 173.6 h. Seven patients (70%) were successfully disconnected from ECMO and fully recovered. Intubation from respiratory causes was needed in three patients (30%), all of whom died eventually. In total, three episodes of delirium, two episodes of significant bleeding, one pneumothorax requiring chest tube insertion, and one oxygenator acute exchange occurred throughout the 5580 h of awake ECMO. No complications related to cannula displacement or malposition occurred. Conclusion: The awake ECMO strategy guided by safety protocol appears to be a safe approach in conscious, severely hypoxemic, non-intubated patients with COVID-19-related ARDS. Plain language summary: Enhancing the safety and effectiveness of extracorporeal membrane oxygenation (ECMO) therapy in awake, spontaneously breathing patients with the most severe form of COVID-19-related acute respiratory distress syndrome (ARDS) Why Was the Study Done? Extracorporeal membrane oxygenation (ECMO) represents a life-saving therapeutic approach that ensures appropriate gas exchange in patients with the most severe form of respiratory failure – acute respiratory distress syndrome (ARDS). Typically, patients are connected to ECMO when already deeply sedated and mechanically ventilated. The awake ECMO approach (keeping the patient awake, not intubated, and breathing spontaneously during ECMO support) minimizes the risks associated with mechanical ventilation and provides several relevant physiological benefits. However, the awake ECMO approach is also associated with several significant risks, including delirium, bleeding, and cannula displacement. Published papers have reported relatively frequent complications and method failures. What Did the Researchers Do? To address safety concerns regarding the awake ECMO approach, we present a single-center retrospective analysis of ten COVID-19-related ARDS patients treated with the awake ECMO approach, guided by the local safety protocol. What Did the Researchers Find? The awake ECMO approach yielded success (i.e., the patient was not intubated for respiratory causes, was successfully disconnected from ECMO, and fully recovered in seven patients (70.0%), outperforming previously published efficacy ranges. Three patients were intubated due to the progression of respiratory failure and eventually died. The incidence of adverse events during the 5,580 hours of awake ECMO was considered low. No cannula displacement or malposition occurred despite routine active physiotherapy, including walking during ECMO treatment in three patients. What Do the Findings Mean? The general applicability of the study is limited by the low number of patients and the retrospective monocentric design. However, the presented data illustrate real-life clinical scenarios and could aid clinicians in managing severely hypoxemic but still conscious and cooperative patients. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Reversible cerebral vasoconstriction syndrome (RCVS) is a rare disease that is classified as a condition of diffuse cerebral artery constriction. RCVS can be complicated with transient neurological deficits, seizures, ischemic strokes, and hemorrhagic strokes. A thunder-clap headache, described as being the worst headache a patient can experience, is the predominant symptom in RCVS, which contributes to why RCVS is underdiagnosed as an ischemic stroke or migraine. Case Report: In this case study, we present a healthy 34-year-old Black woman who presented to the Emergency Department 3 times over a period of 4 days with concerns of severe headaches. In her first Emergency Department visit, she had a normal computed tomography scan of the brain. Her third Emergency Department visit resulted in hospitalization due to seizures, and a computed tomography brain scan done then showed acute intracranial hemorrhaging. The patient ultimately received a diagnosis of RCVS during her hospitalization. Conclusions: RCVS is the most notable mimicker of other similar-presenting vasculopathies, such as primary angiitis of the central nervous system and posterior reversible encephalopathy syndrome. It is important to note that thunder-clap headache, as well as complications such as intracranial hemorrhaging and seizures, can arise not just from other diseases but from RCVS as well; hence, an early diagnosis is critical to avoid complications, especially if initial imaging is negative. [ABSTRACT FROM AUTHOR]

Total quality management (TQM) is a strategic philosophy that has adopted kaizen activities which drives the business to carry out activities effectively to yield the best desired output, hence, a profitable organization. The kaizen philosophy acts as a catalyst in productivity rate and integrated management systems (IMS) which results in drastic improvements. When the nonconformity arises within the process, the accuracy of the problem solving determines quality of preventive action, therefore the preventive action should be accompanied by the opportunity of improvement from the raised nonconformance. This research seeks to add more knowledge and upgrade technology of problem-solving models relating to the integrated management systems by examining various troubleshooting models for problem solving and preventive action related to quality nonconformances, safety incidents and engineering breakdowns. Hence, the aim of this research is for troubleshooting model technique enhancement for issues related to process engineering, quality management systems and occupational health and safety by creating a model which analyses kaizen projects from the corrective and preventive action analysis of nonconformances. The proposed troubleshooting model was developed using lean techniques and risk rating tools; it was then applied to the case study company for simulation and the outcomes resulted in the closure of nonconformances and continual improvement of future projects. The proposed model is more advantageous to the manufacturing industries seeking to improve their Corrective Action and Preventive Action (CAPA) systems. [ABSTRACT FROM AUTHOR]

The tetraspanin CD151 forms a stable complex with integrin alpha3beta1, a widely expressed laminin receptor, and is implicated in the regulation of integrin alpha3beta1-mediated cellular responses, including cell attachment, spreading and migration. However, the molecular mechanism by which CD151 regulates integrin alpha3beta1 functions remains unclear. To address this issue, we knocked down CD151 expression in A549 human lung adenocarcinoma cells by RNA interference. When plated on laminin-511 (laminin-10), the CD151-knocked-down cells showed aberrant membrane protrusions and exhibited reductions in the tyrosine phosphorylation of focal adhesion kinase, Src, p130Cas and paxillin. The formation of membrane protrusions was attenuated when the cells were either plated on surfaces coated with higher concentrations of laminin-511 or treated with the integrin beta1-activating mAb TS2/16; however, neither treatment could rescue the reduced tyrosine phosphorylation. These results indicate that CD151 knockdown weakens the integrin alpha3beta1-mediated adhesion to laminin-511 and thereby provokes an aberrant morphology, but this reduced adhesive activity is not involved in the decline of signaling events in CD151-knocked-down cells. Thus, our results suggest that CD151 regulates integrin alpha3beta1 functions in two independent aspects: potentiation of integrin alpha3beta1-mediated cell adhesion and promotion of integrin alpha3beta1-stimulated signaling events involving tyrosine phosphorylation.

Cardiovascular and neurological diseases are a major cause of mortality and morbidity worldwide. Such diseases require careful monitoring to effectively manage their progression. Artificial intelligence (AI) offers valuable tools for this purpose through its ability to analyse data and identify predictive patterns. This review evaluated the application of AI in cardiac and neurological diseases for their clinical impact on the general population. We reviewed studies on the application of AI in the neurological and cardiological fields. Our search was performed on the PubMed, Web of Science, Embase and Cochrane library databases. Of the initial 5862 studies, 23 studies met the inclusion criteria. The studies showed that the most commonly used algorithms in these clinical fields are Random Forest and Artificial Neural Network, followed by logistic regression and Support-Vector Machines. In addition, an ECG-AI algorithm based on convolutional neural networks has been developed and has been widely used in several studies for the detection of atrial fibrillation with good accuracy. AI has great potential to support physicians in interpretation, diagnosis, risk assessment and disease management. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: Lung cancer is the most common malignant neoplasm diagnosed worldwide. Early diagnosis and treatment are of great importance for patient’s prognosis. A wide variety of pulmonary conditions display clinical and radiological presentation similar to that of lung cancer, and the awareness of their existence can help in making correct diagnoses. Case Reports: This article presents a description of 4 patients with an insidious type of lesions mimicking pulmonary carcinomas. The first patient was referred to Department with a tumor-like lesion in the right lung. After CT of the chest and core-needle biopsy, the lesion turned out to be an ectopic thyroid tissue. The second patient reported a dry cough and weight loss. A lung nodule mass was revealed in chest CT and the patient was diagnosed with pulmonary tuberculoma. The remaining 2 patients, despite the suspicion of lung cancer, were subsequently diagnosed with a post-traumatic pleural hematoma and diffuse large B cell lymphoma. Conclusions: Low-dose computed tomography of the chest plays a significant role in the diagnosis of newly detected lesions in the lungs. However, due to the similarity of the image of cancer to that of other diseases, the ultimate diagnosis should be based on the interpretation of full imaging diagnostic tests, clinical presentation, and histopathological examination of the material obtained from the lesion. Analysis of cases enables us to expand our understanding of the diseases that need to be considered in differential diagnosis of a patient with a detected tumor-like lesion in the lungs. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) is a life-saving technique used in critical care medicine for patients with severe respiratory or cardiac failure. This review examines the treatment and prophylaxis of fungal infections in ECMO patients, proposing specific regimens based on available data for different antifungals (azoles, echinocandins, amphotericin B/liposomal amphotericin B) and invasive fungal infections. Currently, isavuconazole and posaconazole have the most supported data, while modified dosages of isavuconazole are recommended in ECMO. Echinocandins are preferred for invasive candidiasis. However, choosing echinocandins is challenging due to limited and varied data on concentration loss in the ECMO circuit. Caution is likewise advised when using liposomal amphotericin B due to uncertain concentrations and potential ECMO dysfunction based on scarce data. We further conclude with the importance of further research on the impact of ECMO on antifungal drug concentrations to optimize dosing regimens in critically ill patients. [ABSTRACT FROM AUTHOR]

Introduction: Acute promyelocytic leukemia (APL), classified as Subtype M3 of acute myeloid leukemia, is known for its relatively favorable prognosis, primarily due to the high effectiveness of all-trans retinoic acid (ATRA) in treating the maturation block. However, it is essential to be aware of potential complications such as ATRA syndrome, which can affect 5%–25% of patients and manifest with symptoms such as fever, interstitial pulmonary infiltration, pleural/pericardial effusion, and acute renal failure. Methods: We present the case of a 47-year-old female with a history of hypertension, who experienced rash, fever, and reduced urine output during the induction phase with ATRA. Her serum creatinine levels exhibited a rapid increase from 2.63 mg/dL on October 07, 2022, to 7 mg/dL on October 18, 2022, despite having normal-sized kidneys and normal corticomedullary differentiation. A renal biopsy conducted on October 20, 2022, revealed features consistent with active tubulointerstitial nephritis, with direct immunofluorescence showing no significant glomerular immune deposits. A total of 17 hemodialysis sessions were performed. Results: A subsequent bone marrow examination conducted on October 26, 2022, demonstrated a hypercellular aspirate with normal morphology. However, due to the persistence of renal failure, a repeat biopsy was performed, revealing severe acute tubular injury. Pulse steroids were initiated, and ATRA was discontinued, resulting in an improvement in renal function. Conclusion: This case highlights an instance of acute, early, and severe differentiation syndrome (DS) occurring after induction therapy in a patient with APL. The DS in this case was particularly severe, leading to renal failure necessitating hemodialysis. The prompt initiation of pulse steroids and discontinuation of ATRA proved to be effective in managing this complication. Clinicians should remain vigilant for DS and its potential complications, including acute kidney injury and acute tubulointerstitial nephritis, when treating patients with APL. [ABSTRACT FROM AUTHOR]

Digital advancements can reduce the burden of recording clinical information. This intra-subject experimental study compared the time and error rates for recording vital signs and prescriptions between an optical character reader (OCR) and manual typing. This study was conducted at three community hospitals and two fire departments in Japan. Thirty-eight volunteers (15 paramedics, 10 nurses, and 13 physicians) participated in the study. We prepared six sample pictures: three ambulance monitors for vital signs (normal, abnormal, and shock) and three pharmacy notebooks that provided prescriptions (two, four, or six medications). The participants recorded the data for each picture using an OCR or by manually typing on a smartphone. The outcomes were recording time and error rate defined as the number of characters with omissions or misrecognitions/misspellings of the total number of characters. Data were analyzed using paired Wilcoxon signed-rank sum and McNemar's tests. The recording times for vital signs were similar between groups (normal state, 21 s [interquartile range (IQR), 17–26 s] for OCR vs. 23 s [IQR, 18–31 s] for manual typing). In contrast, prescription recording was faster with the OCR (e.g., six-medication list, 18 s [IQR, 14–21 s] for OCR vs. 144 s [IQR, 112–187 s] for manual typing). The OCR had fewer errors than manual typing for both vital signs and prescriptions (0/1056 [0%] vs. 14/1056 [1.32%]; p<0.001 and 30/4814 [0.62%] vs. 53/4814 [1.10%], respectively). In conclusion, the developed OCR reduced the recording time for prescriptions but not vital signs. The OCR showed lower error rates than manual typing for both vital signs and prescription data. [ABSTRACT FROM AUTHOR]

Background: Patients with severe thalassemia may experience adverse effects from transfusion such as fever, rash, and iron overload after long-term transfusion therapy. Severe headaches as a side effect of blood transfusion in patients with thalassemia are not commonly observed, especially when combined with superficial siderosis of the central nervous system, which is easily misdiagnosed and requires excessive examination and treatment. Case Presentation: A 31-year-old woman was admitted with severe headache and vomiting over 3 days following blood transfusion. She was diagnosed with intermediate α-thalassemia at 2 years of age and had a history of irregular blood transfusions. Physical examination revealed horizontal nystagmus with no other abnormal neurological signs. Magnetic resonance (MR) imaging, MR venography, MR arteriography, and cerebrospinal fluid analysis were normal. However, susceptibility-weighted imaging showed abnormal signals in the bilateral and fourth ventricles. Initial antibiotics, antivirals, decompression of intracranial pressure, iron chelation, and symptomatic treatments were administered; subsequently, small intermittent blood transfusions were cautiously administered for severe anemia. The patient's headache was gradually relieved, and she was discharged on day 9. At the 5-month follow-up, the patient's headache recurred following another transfusion. Conclusions: Severe post-transfusion headache in patients with thalassemia has not been fully recognized and is easily misdiagnosed, leading to excessive examination and treatment. Understanding the clinical features of transfusion-related headaches can help identify this complication, but the exact pathophysiological mechanism requires further research. [ABSTRACT FROM AUTHOR]

Background: Invasive aspergillosis (IA) can lead to life-threatening respiratory failure necessitating extracorporeal membrane oxygenation (ECMO) support. However, data on ECMO experience in the management of IA patients are scarce., Objectives: The purpose of this systematic review was to evaluate the potential benefits and risks of ECMO as a supportive intervention for critically ill patients with IA., Methods: We conducted a systematic review of the literature using the search terms ECMO, extracorporeal membrane oxygenation, Aspergillus and Aspergillosis in two databases (Medline and Scopus). Clinical data were extracted by two independent investigators. Clinical parameters, such as mode of ECMO support, duration of treatment and clinical outcomes, were assessed., Results: Overall, 32 patients were included in the analysis. The age ranged from 5 to 69 years, 59% were male, and 38% were female. The majority of patients suffered from ARDS (82%). 82% received VV-ECMO, and 18% received VA-ECMO. Aspergillus fumigatus was the most frequent cause of IA, coinfections were frequently observed (51%). The overall mortality was 78%. Complications during ECMO support were observed in 21 of the 39 cases (53.8%)., Conclusions: IA poses significant management challenges for critically ill ICU patients, even with ECMO support. Although ECMO appears to improve survival of patients at high risk of AI, potential risks such as bacterial superinfection and altered pharmacokinetics of antifungal drugs must be carefully considered., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Abstract: Understanding how large language model (LLM) recommendations vary with patient race/ethnicity provides insight into how LLMs may counter or compound bias in opioid prescription. Forty real-world patient cases were sourced from the MIMIC-IV Note dataset with chief complaints of abdominal pain, back pain, headache, or musculoskeletal pain and amended to include all combinations of race/ethnicity and sex. Large language models were instructed to provide a subjective pain rating and comprehensive pain management recommendation. Univariate analyses were performed to evaluate the association between racial/ethnic group or sex and the specified outcome measures-subjective pain rating, opioid name, order, and dosage recommendations-suggested by 2 LLMs (GPT-4 and Gemini). Four hundred eighty real-world patient cases were provided to each LLM, and responses included pharmacologic and nonpharmacologic interventions. Tramadol was the most recommended weak opioid in 55.4% of cases, while oxycodone was the most frequently recommended strong opioid in 33.2% of cases. Relative to GPT-4, Gemini was more likely to rate a patient's pain as "severe" (OR: 0.57 95% CI: [0.54, 0.60]; P < 0.001), recommend strong opioids (OR: 2.05 95% CI: [1.59, 2.66]; P < 0.001), and recommend opioids later (OR: 1.41 95% CI: [1.22, 1.62]; P < 0.001). Race/ethnicity and sex did not influence LLM recommendations. This study suggests that LLMs do not preferentially recommend opioid treatment for one group over another. Given that prior research shows race-based disparities in pain perception and treatment by healthcare providers, LLMs may offer physicians a helpful tool to guide their pain management and ensure equitable treatment across patient groups., (Copyright © 2024 International Association for the Study of Pain.)

The inhibition of mammalian target of rapamycin (mTOR) with rapamycin (RAPA) provides protection against myocardial ischemia/reperfusion (I/R) injury in diabetes. Since interactions between transcripts, including long non-coding RNA (lncRNA), microRNA(miRNA) and mRNA, regulate the pathophysiology of disease, we performed unbiased miRarray profiling in the heart of diabetic rabbits following I/R injury with/without RAPA treatment to identify differentially expressed (DE) miRNAs and their predicted targets of lncRNAs/mRNAs. Results showed that among the total of 806 unique miRNAs targets, 194 miRNAs were DE after I/R in diabetic rabbits. Specifically, eight miRNAs, including miR-199a-5p, miR-154-5p, miR-543-3p, miR-379-3p, miR-379-5p, miR-299-5p, miR-140-3p, and miR-497-5p, were upregulated and 10 miRNAs, including miR-1-3p, miR-1b, miR-29b-3p, miR-29c-3p, miR-30e-3p, miR-133c, miR-196c-3p, miR-322-5p, miR-499-5p, and miR-672-5p, were significantly downregulated after I/R injury. Interestingly, RAPA treatment significantly reversed these changes in miRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated the participation of miRNAs in the regulation of several signaling pathways related to I/R injury, including MAPK signaling and apoptosis. Furthermore, in diabetic hearts, the expression of lncRNAs, HOTAIR, and GAS5 were induced after I/R injury, but RAPA suppressed these lncRNAs. In contrast, MALAT1 was significantly reduced following I/R injury, with the increased expression of miR-199a-5p and suppression of its target, the anti-apoptotic protein Bcl-2. RAPA recovered MALAT1 expression with its sponging effect on miR-199-5p and restoration of Bcl-2 expression. The identification of novel targets from the transcriptome analysis in RAPA-treated diabetic hearts could potentially lead to the development of new therapeutic strategies for diabetic patients with myocardial infarction. [ABSTRACT FROM AUTHOR]

Intra-abdominal candidiasis (IAC) is one of the most common of invasive candidiasis observed in critically ill patients. It is associated with high mortality, with up to 50% of deaths attributable to delays in source control and/or the introduction of antifungal therapy. Currently, there is no comprehensive guidance on optimising antifungal dosing in the treatment of IAC among the critically ill. However, this form of abdominal sepsis presents specific pharmacokinetic (PK) alterations and pharmacodynamic (PD) challenges that risk suboptimal antifungal exposure at the site of infection in critically ill patients. This review aims to describe the peculiarities of IAC from both PK and PD perspectives, advocating an individualized approach to antifungal dosing. Additionally, all current PK/PD studies relating to IAC are reviewed in terms of strength and limitations, so that core elements for the basis of future research can be provided. Highlights: Intra-abdominal candidiasis presents specific pharmacokinetic (PK) and pharmacodynamic (PD) challenges where suboptimal antifungal concentrations are likely to occur leading to high risk of treatment failure. The intra-abdominal cavity has been highlighted as a hidden reservoir for resistance to antifungals including echinocandins. To date, all antifungal PK/PD studies in intra-abdominal candidiasis have enrolled small cohorts and have only provided post-operative antifungal concentrations analysis. Based on current evidence, high dosing regimens of antifungals should be strongly considered, especially at the onset of infection. The place of new antifungals (rezafungin, ibrexafungerp) requires more robust clinical studies including PK/PD analysis in critically ill patients. [ABSTRACT FROM AUTHOR]

The great social and economic impact that the COVID-19 pandemic has had on a global level has encouraged the development of new mathematical models that make it possible to better manage this and future pandemics. Here, we propose an extension of the classical epidemiological compartmental model SIR, the SEIAMD model (Susceptible–Exposed–Identified–Asymptomatic–iMmunized–Deceased), which considers the appearance of new virus variants, the use of vaccines, the existence of nonidentified asymptomatic individuals, and the loss of immunity acquired by infection or vaccination. Using an optimization model coded in Python that allows us to determine the change points that represent different behaviors of infected people, the SEIAMD model calculates, from official data, the different effective contact rates that were observed during the first seven waves of the COVID-19 pandemic in Tokyo due to the application of Non-Pharmaceutical Interventions (NPIs) and social habits. The closeness of the results obtained with our model and the real data, as well as the accuracy of predictions and observations, confirm the suitability of our model for studying the evolution of the COVID-19 pandemic in Tokyo. [ABSTRACT FROM AUTHOR]

Introduction: The coronavirus disease 2019 (COVID-19) pandemic accelerated the provision of telepharmacy services. However, little is known about the knowledge, perception, and willingness of pharmacy students as future key players in telepharmacy adoption to provide such a service, particularly in a setting without well-established telepharmacy services before the COVID-19 pandemic. Objective: With this survey we aimed to assess the level of knowledge, perception, and willingness to provide telepharmacy services and to identify associated factors among pharmacy students in Indonesia. Methods: We applied a multicenter cross-sectional study design with convenience sampling technique among pharmacy students in three public universities in Bandung City, Surabaya City, and Special Region of Yogyakarta, Indonesia. The knowledge, perception, and willingness to provide telepharmacy services were assessed using an online questionnaire. Ordinal regression analysis was performed to determine factors associated with a high knowledge level, whereas binary logistic regression analyses were performed to determine factors associated with a positive perception of telepharmacy services. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported. Results: Among 313 respondents, 83.4% were female, and the mean age was 20 years. Although only 13.2% showed a high knowledge level, 66.5% showed a positive perception of telepharmacy services and 97.4% were willing to provide telepharmacy services in the future. An increase in age (OR 1.33; 95% CI 1.14–1.54) and being advance in smartphone usage (OR 5.21; 95% CI 2.03–13.42) are associated with an increased likelihood of having a high knowledge level about telepharmacy services. Male students had a lower likelihood of having a positive perception of telepharmacy services than females (OR 0.46; 95% CI 0.24–0.85). Conclusion: Despite limited knowledge of telepharmacy, the majority of pharmacy students reported a positive perception and willingness to provide telepharmacy services in their future careers. Therefore, telepharmacy practice models must be included as a subject course in the curriculum, better preparing future pharmacists to perform their roles effectively. Furthermore, student-specific factors such as age and expertise in smartphone usage that associated with knowledge and gender that associated with perception should be considered to facilitate telepharmacy adoption in Indonesia. [ABSTRACT FROM AUTHOR]

Objective: Data about the contribution of drugs to the development of acute kidney injury are scarce in hematological cancer patients. The current study evaluated the relationship between the use of different medications and acute kidney injury development in hematological cancer patients. Methods: This study was designed as a prospective observational cross-sectional study. All patients admitted to hematology wards of Shariati Hospital of Tehran University of Medical Sciences were evaluated, and patients younger than 18 years of age, those who were not able to consent to participate and those who presented with acute kidney injury were excluded. Acute kidney injury was diagnosed per KDIGO criteria. Results: Overall, 450 patients were evaluated in this study and 138 cases of acute kidney injury were detected; this translates into 30.6% incidence rate in hematology wards of the study center. The median age of the patients with acute kidney injury was 49 years and 84 (60.9%) of them were men. Length of hospital stay and mortality rate was significantly higher in patients with acute kidney injury than those without (P < .001 and < .001, respectively). Results of the multivariate analysis showed that treatment with vancomycin (odds ratio 1.77), the combination of vancomycin and amphotericin B deoxycholate (odds ratio 3.10), and idarubicin (odds ratio 2.10) could significantly increase the odds of acute kidney injury development in patients with hematological malignancy, but treatment with hydrocortisone (odds ratio 0.26) could have significant nephroprotective effects. Conclusion: This study showed that treatment with vancomycin, the combination of vancomycin and amphotericin B deoxycholate, and idarubicin could significantly increase the odds of acute kidney injury development. Hydrocortisone treatment showed significant nephroprotective effects. Mortality and duration of hospital stay were significantly higher in patients with acute kidney injury. [ABSTRACT FROM AUTHOR]

Reversible cerebral vasoconstriction syndrome (RCVS) is a condition with variable outcomes presenting a new onset thunderclap headache accompanied by focal neurological symptoms or seizures. It can be idiopathic or arise secondarily to a variety of trigger factors. The condition is increasingly recognized in clinical practice, but many facets remain poorly understood. This article aims to clarify the headache characteristics in RCVS, the temporal association of angiographic findings, the potential association of the condition with SARS-CoV-2 infection, and the clinical presentation of RCVS in children and is based on a systematic PRISMA search for published analytical or large descriptive observational studies. Data from 60 studies that fulfilled specific criteria were reviewed. Most people with RCVS exhibit a typical thunderclap, explosive, or pulsatile/throbbing headache, or a similar acute and severe headache that takes longer than 1 min to peak. Atypical presentations or absence of headaches are also reported and may be an underrecognized phenotype. In many cases, headaches may persist after resolution of RCVS. Focal deficits or seizures are attributed to associated complications including transient ischemic attacks, posterior reversible encephalopathy syndrome, ischemic stroke, cerebral edema, and intracranial hemorrhage. The peak of vasoconstriction occurs usually within two weeks after clinical onset, possibly following a pattern of centripetal propagation, and tends to resolve completely within 3 months, well after symptoms have subsided. There are a few reports of RCVS occurring in relation to SARS-CoV-2 infection, but potential underlying pathophysiologic mechanisms and etiological associations have not been confirmed. RCVS occurs in children most often in the context of an underlying disease. Overall, the available data in the literature are scattered, and large-scale prospective studies and international collaborations are needed to further characterize the clinical presentation of RCVS. [ABSTRACT FROM AUTHOR]

Background: The global outbreak of COVID-19, and the limited availability of clinical treatments, forced researchers around the world to search for the pathogenesis and potential treatments. Understanding the pathogenesis of SARS-CoV-2 is crucial to respond better to the current coronavirus disease 2019 (COVID-19) pandemic. Methods: We collected sputum samples from 20 COVID-19 patients and healthy controls. Transmission electron microscopy was used to observe the morphology of SARS-CoV-2. Extracellular vesicles (EVs) were isolated from sputum and the supernatant of VeroE6 cells, and were characterized by transmission electron microscopy, nanoparticle tracking analysis and Western-Blotting. Furthermore, a proximity barcoding assay was used to investigate immune-related proteins in single EV, and the relationship between EVs and SARS-CoV-2. Result: Transmission electron microscopy images of SARS-COV-2 virus reveal EV-like vesicles around the virion, and western blot analysis of EVs extracted from the supernatant of SARS-COV-2-infected VeroE6 cells showed that they expressed SARS-COV-2 protein. These EVs have the infectivity of SARS-COV-2, and the addition can cause the infection and damage of normal VeroE6 cells. In addition, EVs derived from the sputum of patients infected with SARS-COV-2 expressed high levels of IL6 and TGF-β, which correlated strongly with expression of the SARS-CoV-2 N protein. Among 40 EV subpopulations identified, 18 differed significantly between patients and controls. The EV subpopulation regulated by CD81 was the most likely to correlate with changes in the pulmonary microenvironment after SARS-CoV-2 infection. Single extracellular vesicles in the sputum of COVID-19 patients harbor infection-mediated alterations in host and virus-derived proteins. Conclusions: These results demonstrate that EVs derived from the sputum of patients participate in virus infection and immune responses. This study provides evidence of an association between EVs and SARS-CoV-2, providing insight into the possible pathogenesis of SARS-CoV-2 infection and the possibility of developing nanoparticle-based antiviral drugs. [ABSTRACT FROM AUTHOR]

Reversible cerebral vasoconstriction syndrome (RCVS) is a group of disorders characterized by segmental narrowing and dilatation of medium-to-large cerebral arteries, clinically presenting with recurrent episodes of sudden-onset thunderclap headaches, with or without focal neurological deficits. Cerebral vasoconstriction is typically reversible, with spontaneous resolution within 3 months. Although the syndrome has generally a benign course, patients with neurological deficits may experience worse outcome. The main imaging finding is segmental constriction of intracranial arteries, which can be associated with subarachnoid hemorrhage and/or ischemic foci. Other possible findings are intracranial hemorrhage, subdural bleeding and cerebral edema. The latter may have a pattern which can resemble that of posterior reversible encephalopathy syndrome, a condition that can overlap with RCVS. New imaging techniques, such as vessel wall imaging and arterial spin labeling, are proving useful in RCVS and are giving new insights into the pathophysiology of this condition. In this paper, we aim to review neuroimaging findings of RCVS. [ABSTRACT FROM AUTHOR]

A large language model (LLM), in the context of natural language processing and artificial intelligence, refers to a sophisticated neural network that has been trained on a massive amount of text data to understand and generate human-like language. These models are typically built on architectures like transformers. The term "large" indicates that the neural network has a significant number of parameters, making it more powerful and capable of capturing complex patterns in language. One notable example of a large language model is ChatGPT. ChatGPT is a large language model developed by OpenAI that uses deep learning techniques to generate human-like text. It can be trained on a variety of tasks, such as language translation, question answering, and text completion. One of the key features of ChatGPT is its ability to understand and respond to natural language inputs. This makes it a powerful tool for generating a wide range of text, including medical reports, surgical notes, and even poetry. Additionally, the model has been trained on a large corpus of text, which allows it to generate text that is both grammatically correct and semantically meaningful. In terms of applications in neurosurgery, ChatGPT can be used to generate detailed and accurate surgical reports, which can be very useful for sharing information about a patient's case with other members of the medical team. Additionally, the model can be used to generate detailed surgical notes, which can be very useful for training and educating residents and medical students. Overall, LLMs have the potential to be a valuable tool in the field of neurosurgery. Indeed, this abstract has been generated by ChatGPT within few seconds. Potential applications and pitfalls of the applications of LLMs are discussed in this paper., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The coronavirus disease 2019 (COVID-19) pandemic disrupted global healthcare systems. The present study aimed to determine the impact of lockdown restrictions on the time required to transport patients with urological diseases with fever to the hospital during the early stages of the COVID-19 pandemic. The present retrospective, observational study analyzed information about the transport of 2,811 patients with urological emergencies to hospitals retrieved from a prefectural database, an emergency medical and disaster information system. Differences in emergency transport in terms of duration were analyzed using Student's t-tests. Bivariate associations before and after the onset of COVID-19 were assessed using simple linear and multiple regression analyses. The results indicated a significant association between the mean transport duration and fever in these patients before quarantine (β=5.57; 95% confidence interval, 1.93-9.21). The duration of emergency transport for patients with urological diseases with fever in significantly increased. This was attributed to lifestyle changes brought about by the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Tetraspanin-enriched microdomains (TEMs) are specialized membrane platforms driven by protein-protein interactions that integrate membrane receptors and adhesion molecules. Tetraspanins participate in antigen recognition and presentation by antigenpresenting cells (APCs) through the organization of pattern-recognition receptors (PRRs) and their downstream-induced signaling, as well as the regulation of MHC-II-peptide trafficking. T lymphocyte activation is triggered upon specific recognition of antigens present on the APC surface during immunological synapse (IS) formation. This dynamic process is characterized by a defined spatial organization involving the compartmentalization of receptors and adhesion molecules in specialized membrane domains that are connected to the underlying cytoskeleton and signaling molecules. Tetraspanins contribute to the spatial organization and maturation of the IS by controlling receptor clustering and local accumulation of adhesion receptors and integrins, their downstream signaling, and linkage to the actin cytoskeleton. This review offers a perspective on the important role of TEMs in the regulation of antigen recognition and presentation and in the dynamics of IS architectural organization. [ABSTRACT FROM AUTHOR]

Post-translational protein modifications, such as tyrosine phosphorylation, regulate protein-protein interactions ( PPIs) critical for signal processing and cellular phenotypes. We extended an established yeast two-hybrid system employing human protein kinases for the analyses of phospho-tyrosine ( pY)-dependent PPIs in a direct experimental, large-scale approach. We identified 292 mostly novel pY-dependent PPIs which showed high specificity with respect to kinases and interacting proteins and validated a large fraction in co-immunoprecipitation experiments from mammalian cells. About one-sixth of the interactions are mediated by known linear sequence binding motifs while the majority of pY- PPIs are mediated by other linear epitopes or governed by alternative recognition modes. Network analysis revealed that pY-mediated recognition events are tied to a highly connected protein module dedicated to signaling and cell growth pathways related to cancer. Using binding assays, protein complementation and phenotypic readouts to characterize the pY-dependent interactions of TSPAN2 (tetraspanin 2) and GRB2 or PIK3R3 (p55γ), we exemplarily provide evidence that the two pY-dependent PPIs dictate cellular cancer phenotypes. [ABSTRACT FROM AUTHOR]

Tetraspanins are a family of proteins with four transmembrane domains that play a role in many aspects of cell biology and physiology; they are also used by several pathogens for infection and regulate cancer progression. Many tetraspanins associate specifically and directly with a limited number of proteins, and also with other tetraspanins, thereby generating a hierarchical network of interactions. Through these interactions, tetraspanins are believed to have a role in cell and membrane compartmentalization. In this Cell Science at a Glance article and the accompanying poster, we describe the basic principles underlying tetraspanin-based assemblies and highlight examples of how tetraspanins regulate the trafficking and function of their partner proteins that are required for the normal development and function of several organs, including, in humans, the eye, the kidney and the immune system. [ABSTRACT FROM AUTHOR]

Understanding how the immune response is activated and amplified requires detailed knowledge of the stages in the formation of the immunological synapse (IS) between T lymphocytes and antigen-presenting cells (APCs). We show that tetraspanins CD9 and CD151 congregate at the T-cell side of the IS. Silencing of CD9 or CD151 blunts the IL-2 secretion and expression of the activation marker CD69 by APC-conjugated T lymphocytes, but does not affect the accumulation of CD3 or actin to the IS, or the translocation of the microtubule-organizing center toward the T-B contact area. CD9 or CD151 silencing diminishes the relocalization of α4β1 integrin to the IS and reduces the accumulation of high-affinity β1 integrins at the cell-cell contact. These changes are accompanied by diminished phosphorylation of the integrin downstream targets FAK and ERK1/2. Our results suggest that CD9 and CD151 support integrin-mediated signaling at the IS. [ABSTRACT FROM AUTHOR]