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PloS One 2024Nowadays, most fatal diseases are attributed to the malfunction of bodily. Sometimes organ transplantation is the only possible therapy, for instance for patients with...
Nowadays, most fatal diseases are attributed to the malfunction of bodily. Sometimes organ transplantation is the only possible therapy, for instance for patients with end-stage liver diseases, and the preferred treatment, for instance for patients with end-stage renal diseases. However, this surgical procedure comes with inherent risks and effectively managing these risks to minimize the likelihood of complications arising from organ transplantation (maximizing life years from transplant and quality-adjusted life years) is crucial. To facilitate this process, risk ranking is used to identify and promptly address potential risks. Over recent years, considerable efforts have been made, and various approaches have been proposed to enhance Failure Modes and Effects Analysis (FMEA). In this study, taking into account the uncertainty in linguistic variables (F-FMEA), we introduce an approach based on Fuzzy Multi Criteria Decision Making (F-MCDM) for effectively evaluating scenarios and initial failure hazards. Nevertheless, the results of ranking failure modes generated by different MCDM methods may vary. This study is a retrospective study that suggests a comprehensive unified risk assessment model, integrating multiple techniques to produce a more inclusive ranking of failure modes. Exploring a broad spectrum of risks associated with organ transplant operations, we identified 20 principal hazards with the assistance of literature and experts. We developed a questionnaire to examine the impact of various critical factors on the survival of transplanted organs, such as irregularities in immunosuppressive drug consumption, inappropriate dietary habits, psychological disorders, engaging in strenuous activities post-transplant, neglecting quarantine regulations, and other design-related factors. Subsequently, we analyzed the severity of their effects on the durability of transplanted organs. Utilizing the Mamdani algorithm as a fuzzy inference engine and the Center of Gravity algorithm for tooling, we expressed the probability and severity of each risk. Finally, the failure mode ranking obtained from the F-FMEA method, three fuzzy MCDM methods, and the proposed combined method were identified. Additionally, the results obtained from various methods were evaluated by an expert team, demonstrating that the highest consistency and effectiveness among different methods are attributed to the proposed method, as it achieved a 91.67% agreement with expert opinions.
Topics: Humans; Risk Assessment; Fuzzy Logic; Organ Transplantation; Retrospective Studies; Healthcare Failure Mode and Effect Analysis
PubMed: 38781279
DOI: 10.1371/journal.pone.0299655 -
Diagnostic Microbiology and Infectious... Aug 2024In this retrospective cohort study, we aimed to assess clinical effectiveness and viral clearance following the use of molnupiravir, azvudine and paxlovid in...
Real-world effectiveness of molnupiravir, azvudine and paxlovid against mortality and viral clearance among hospitalized patients with COVID-19 infection during the omicron wave in China: A retrospective cohort study.
OBJECTIVES
In this retrospective cohort study, we aimed to assess clinical effectiveness and viral clearance following the use of molnupiravir, azvudine and paxlovid in hospitalized patients with COVID-19 in China dominated by the omicron BA.5.2 and BF.7 subvariant of SARS-CoV-2.
METHODS
Enrolled patients were assigned to the molnupiravir group or the azvudine group or the paxlovid group or the control group (not taking any antiviral drugs). The primary outcome of the cohort study was viral clearance and viral burden rebound after treatment and the secondary outcome was 28-day all-cause mortality. The four groups were propensity score-matched (1:1). We plotted viral load trends for each antiviral drug intervention using locally weighted regression (LOWESS) smoothed data. Multivariate logistic regression (stepwise algorithm) models were used to determine any risk factors for 28-day mortality.
RESULTS
Of the 1537 patients receiving any treatment, 886 (57.6 %) received molnupiravir, 390 (25.4 %) received azvudine, 94 (6.1 %) received paxlovid, and 167 (10.9 %) did not use any antiviral drugs. Our data analysis showed that age (OR = 1.05, 95 % CI: 1.03-1.07, P < 0.001), Charlson comorbidty index (OR = 1.32, 95 % CI: 1.18-1.48, P < 0.001), severity of COVID-19 (P < 0.001), gamma globulin (OR = 2.04, 95 % CI: 1.03-3.99, P = 0.039) and corticosteroids use (OR = 2.3, 95 % CI: 1.19-4.69, P = 0.017) were independent prognostic factors for 28-day mortality in COVID-19 patients. After propensity score matching (PSM), the paxlovid recipients (OR = 0.22, 95 % CI: 0.05-0.83, P = 0.036) or azvudine recipients (OR = 0.27, 95 % CI: 0.07-0.91, P = 0.046) had lower 28-day mortality compared to their matched controls. Viral rebound occurred in the control group around days 9-16, while no viral rebound was found in any of the three oral antiviral groups. We found that molnupiravir group performed comparably in terms of the rate of nucleic acid conversion negative compared with the paxlovid group, while azvudine group performed slightly worse compared with the paxlovid group or molnupiravir group.
CONCLUSIONS
In our retrospective cohort of hospitalized patients with COVID-19 during the wave of omicron strain, the molnupiravir, paxlovid and azvudine recipients showed a faster and more stable decrease in viral load and rare virus rebound in response to antiviral treatments when compared to the controls. The study supported that initiation treatment with paxlovid and azvudine was associated with significantly lower risk of all-cause death within 28 days.
Topics: Humans; Retrospective Studies; Male; Middle Aged; Antiviral Agents; COVID-19 Drug Treatment; Female; China; SARS-CoV-2; Aged; COVID-19; Viral Load; Hospitalization; Adult; Treatment Outcome; Cytidine; Hydroxylamines
PubMed: 38776665
DOI: 10.1016/j.diagmicrobio.2024.116353 -
Cureus Apr 2024Lyme disease is a progressive infectious disease caused by the species that affects multiple organ systems, including the brain, heart, skin, and musculoskeletal...
Lyme disease is a progressive infectious disease caused by the species that affects multiple organ systems, including the brain, heart, skin, and musculoskeletal systems. The cardiac manifestations of Lyme disease typically present with atrioventricular nodal conduction abnormalities and, more rarely, myocarditis. We report a case of an immunocompromised 57-year-old woman who presented with acute onset shortness of breath, hypervolemia, injective conjunctiva, and global vision loss of the left eye in the setting of a recent tick bite. Serologic testing confirmed borreliosis, and cardiac testing demonstrated acute isolated systolic heart failure without any cardiac conduction system abnormalities on the electrocardiogram. The diagnosis of Lyme carditis was made, and the patient was started on doxycycline with complete recovery of cardiac systolic function. This case demonstrates atypical cardiac manifestations of Lyme disease and highlights the difficulty in workup and understanding of Lyme carditis particularly in immunocompromised patients.
PubMed: 38770473
DOI: 10.7759/cureus.58605 -
Surgery Open Science Jun 2024The aim of this study is to determine the correlation between the blood serum mean platelet volume (MPV) and the dynamics of the OF course during the early phase in...
BACKGROUND
The aim of this study is to determine the correlation between the blood serum mean platelet volume (MPV) and the dynamics of the OF course during the early phase in patients with moderately severe and severe acute pancreatitis (AP).
METHODS
The predetermined criterion was the presence of the OF according to the revised Atlanta criteria 2012 for moderately severe and severe AP. A prospective sample of patients was stratified by severity, and two groups were defined based on MPV. Demographic indicators, comorbidities and clinical outcomes were compared between these groups. Multifactorial analysis determined whether an elevated MPV is independently associated with early OF and other unfavorable outcomes.
RESULTS
Out of 108 patients, 20 had moderately severe AP and 88 had severe AP. The blood serum MPV, measured within 72 h of the onset of AP symptoms was lower 11.8 fL in 32 patients and equal to or greater 11.8 fL in 76 patients. Patients with elevated MPV were older (63 vs. 48 years), had obesity (59.2 % vs. 25 %), diabetes mellitus (DM) (51.3 % vs. 12.5 %), ischemic heart disease (70.8 % vs. 28.1 %) and more frequently experienced persistent OF (93.4 % vs. 53.1 %) compared to those with MPV lower 11.8 fL. The incidence of early OF increased proportionally with the severity of MPV (81.6 % vs. 34.4 % in the group with MPV lower 11.8 fL, Ptrend < 0.0001). In multifactorial analysis, adjusted for body mass index and DM, MPV equal to or greater 11.8 fL was independently associated with early OF.
CONCLUSIONS
Elevated blood serum MPV of patients with AP are independently and proportionally correlated with early organ failure in patients with alcoholic and idiopathic etiology of AP.
KEY MESSAGE
The study provides an evaluation of MPV as a prognostic marker for organ failure within the initial 7 days following the onset of acute pancreatitis symptoms. Additionally, alterations in MPV were identified in patients with acute pancreatitis who had diabetes or ischemic heart disease within the first 24 h of hospitalization.
PubMed: 38770184
DOI: 10.1016/j.sopen.2024.04.011 -
Transplantation Direct Jun 2024A stable, minimum physiological health status is required for patients to qualify for transplant or artificial organ support eligibility to ensure the recipient has...
A stable, minimum physiological health status is required for patients to qualify for transplant or artificial organ support eligibility to ensure the recipient has enough reserve to survive the perioperative transplant period. Herein, we present a novel strategy to stabilize and improve patient clinical status through extracorporeal immunomodulation of systemic hyperinflammation with impact on multiple organ systems to increase eligibility and feasibility for transplant/device implantation. This involves treatment with the selective cytopheretic device (SCD), a cell-directed extracorporeal therapy shown to adhere and immunomodulate activated neutrophils and monocytes toward resolution of systemic inflammation. In this overview, we describe a case series of successful transition of pediatric and adult patients with multiorgan failure to successful transplant/device implantation procedures by treatment with the SCD in the following clinical situations: pediatric hemophagocytic lymphohistiocytosis, and adult hepatorenal and cardiorenal syndromes. Application of the SCD in these cases may represent a novel paradigm in increasing clinical eligibility of patients to successful transplant outcomes.
PubMed: 38769980
DOI: 10.1097/TXD.0000000000001627 -
Journal of Cancer Research and Clinical... May 2024Carfilzomib, commonly used for relapsed/refractory multiple myeloma (RRMM), has been associated with various adverse events in randomized controlled trials (RCTs).... (Observational Study)
Observational Study
PURPOSE
Carfilzomib, commonly used for relapsed/refractory multiple myeloma (RRMM), has been associated with various adverse events in randomized controlled trials (RCTs). However, real-world safety data for a more diverse population are needed, as carfilzomib received expedited approval. This study aimed to evaluate carfilzomib's safety in Korea by comparing new users of KRd (carfilzomib, lenalidomide, and dexamethasone) to Rd (lenalidomide and dexamethasone) using a nationwide administrative claims database.
METHODS
The retrospective cohort study utilized target trial emulation, focusing on adverse events in various organ systems similar to the ASPIRE trial.
RESULTS
This study included 4,580 RRMM patients between 2007 and 2020, and the KRd group showed significantly higher risks of hematologic adverse events (anemia, neutropenia, thrombocytopenia) and some non-hematologic adverse events (cough, hypokalemia, constipation, hypertension, heart failure) compared to the Rd group. Among non-hematologic adverse events, cardiovascular events (heart failure [HR 2.04; 95% CI 1.24-3.35], hypertension [HR 1.58; 95% CI 1.15-2.17]) had the highest risk in the KRd group.
CONCLUSION
The safety profile of carfilzomib in Korean patients was similar to previous RCTs. Therefore, caution should be exercised when using carfilzomib in Asian individuals with RRMM due to the increased risk of cardiovascular adverse events.
Topics: Humans; Multiple Myeloma; Oligopeptides; Male; Female; Republic of Korea; Retrospective Studies; Middle Aged; Aged; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Neoplasm Recurrence, Local; Lenalidomide
PubMed: 38769166
DOI: 10.1007/s00432-024-05800-8 -
PloS One 2024Sepsis-Associated Liver Injury (SALI) is an independent risk factor for death from sepsis. The aim of this study was to develop an interpretable machine learning model...
Sepsis-Associated Liver Injury (SALI) is an independent risk factor for death from sepsis. The aim of this study was to develop an interpretable machine learning model for early prediction of 28-day mortality in patients with SALI. Data from the Medical Information Mart for Intensive Care (MIMIC-IV, v2.2, MIMIC-III, v1.4) were used in this study. The study cohort from MIMIC-IV was randomized to the training set (0.7) and the internal validation set (0.3), with MIMIC-III (2001 to 2008) as external validation. The features with more than 20% missing values were deleted and the remaining features were multiple interpolated. Lasso-CV that lasso linear model with iterative fitting along a regularization path in which the best model is selected by cross-validation was used to select important features for model development. Eight machine learning models including Random Forest (RF), Logistic Regression, Decision Tree, Extreme Gradient Boost (XGBoost), K Nearest Neighbor, Support Vector Machine, Generalized Linear Models in which the best model is selected by cross-validation (CV_glmnet), and Linear Discriminant Analysis (LDA) were developed. Shapley additive interpretation (SHAP) was used to improve the interpretability of the optimal model. At last, a total of 1043 patients were included, of whom 710 were from MIMIC-IV and 333 from MIMIC-III. Twenty-four clinically relevant parameters were selected for model construction. For the prediction of 28-day mortality of SALI in the internal validation set, the area under the curve (AUC (95% CI)) of RF was 0.79 (95% CI: 0.73-0.86), and which performed the best. Compared with the traditional disease severity scores including Oxford Acute Severity of Illness Score (OASIS), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction Score (LODS), Systemic Inflammatory Response Syndrome (SIRS), and Acute Physiology Score III (APS III), RF also had the best performance. SHAP analysis found that Urine output, Charlson Comorbidity Index (CCI), minimal Glasgow Coma Scale (GCS_min), blood urea nitrogen (BUN) and admission_age were the five most important features affecting RF model. Therefore, RF has good predictive ability for 28-day mortality prediction in SALI. Urine output, CCI, GCS_min, BUN and age at admission(admission_age) within 24 h after intensive care unit(ICU) admission contribute significantly to model prediction.
Topics: Humans; Sepsis; Machine Learning; Male; Female; Middle Aged; Aged; Liver Diseases; Risk Factors; Prognosis
PubMed: 38768153
DOI: 10.1371/journal.pone.0303469 -
ArXiv Jun 2024On December 15, 2023, The National Academies of Sciences, Engineering and Medicine (NASEM) released a report entitled: "Foundational Research Gaps and Future Directions...
A design specification for Critical Illness Digital Twins (CIDTs) to cure sepsis: responding to the National Academies of Sciences, Engineering and Medicine Report "Foundational Research Gaps and Future Directions for Digital Twins".
On December 15, 2023, The National Academies of Sciences, Engineering and Medicine (NASEM) released a report entitled: "Foundational Research Gaps and Future Directions for Digital Twins." The ostensible purpose of this report was to bring some structure to the burgeoning field of digital twins by providing a working definition and a series of research challenges that need to be addressed to allow this technology to fulfill its full potential. In the work presented herein we focus on five specific findings from the NASEM Report: 1) definition of a Digital Twin, 2) using "fit-for-purpose" guidance, 3) developing novel approaches to Verification, Validation and Uncertainty Quantification (VVUQ) of Digital Twins, 4) incorporating control as an explicit purpose for a Digital Twin and 5) using a Digital Twin to guide data collection and sensor development, and describe how these findings are addressed through the design specifications for a Critical Illness Digital Twin (CIDT) aimed at curing sepsis.
PubMed: 38764598
DOI: No ID Found -
Phytomedicine : International Journal... Jul 2024The proinflammatory response induced by macrophages plays a crucial role in the development of sepsis and the resulting multiorgan dysfunction. Identifying new...
BACKGROUND
The proinflammatory response induced by macrophages plays a crucial role in the development of sepsis and the resulting multiorgan dysfunction. Identifying new regulatory targets for macrophage homeostasis and devising effective treatment strategies remains a significant challenge in contemporary research.
PURPOSE
This study aims to identify new regulatory targets for macrophage homeostasis and develop effective strategies for treating sepsis.
STUDY DESIGN AND METHODS
Macrophage infiltration in septic patients and in lungs, kidneys, and brains of caecum ligation and puncture (CLP)-induced septic mice was observed using CIBERSORT and immunofluorescence (IF). Upon integrating the MSigDB database and GSE65682 dataset, differently expressed macrophage-associated genes (DEMAGs) were identified. Critical DEMAGs were confirmed through machine learning. The protein level of the critical DEMAG was detected in PBMCs of septic patients, RAW264.7 cells, and mice lungs, kidneys, and brains using ELISA, western blot, immunohistochemistry, and IF. siRNA was applied to investigate the effect of the critical DEMAG in RAW264.7 cells. A natural product library was screened to find a compound targeting the critical DEMAG protein. The binding of compounds and proteins was analyzed through molecular docking, molecular dynamics simulations, CETSA, and MST analysis. The therapeutic efficacy of the compounds against sepsis was then evaluated through in vitro and in vivo experiments.
RESULTS
Macrophage infiltration was inversely correlated with survival in septic patients. The critical differentially expressed molecule RasGRP1 was frequently observed in the PBMCs of septic patients, LPS-induced RAW264.7 cells, and the lungs, kidneys, and brains of septic mice. Silencing RasGRP1 alleviated proinflammatory response and oxidative stress in LPS-treated RAW264.7 cells. Catechin Hydrate (CH) was identified as an inhibitor of RasGRP1, capable of maintaining macrophage homeostasis and mitigating lung, kidney, and brain damage during sepsis.
CONCLUSION
This study demonstrates that RasGRP1, a novel activator of macrophage proinflammatory responses, plays a crucial role in the excessive inflammation and oxidative stress associated with sepsis. CH shows potential for treating sepsis by inhibiting RasGRP1.
Topics: Animals; Sepsis; Mice; Humans; RAW 264.7 Cells; Macrophages; Male; Guanine Nucleotide Exchange Factors; Catechin; Multiple Organ Failure; Molecular Docking Simulation; Kidney; Mice, Inbred C57BL; Disease Models, Animal; Lung
PubMed: 38759314
DOI: 10.1016/j.phymed.2024.155733 -
Frontiers in Immunology 2024Drug-induced immune hemolytic anemia (DIIHA) is a rare but serious condition, with an estimated incidence of one in 100,000 cases, associated with various antibiotics....
BACKGROUND
Drug-induced immune hemolytic anemia (DIIHA) is a rare but serious condition, with an estimated incidence of one in 100,000 cases, associated with various antibiotics. This study reports on a case of ceftizoxime-induced hemolysis observed in a patient in China.
CASE DESCRIPTION
A Chinese patient diagnosed with malignant rectal cancer underwent antimicrobial therapy after laparoscopic partial recto-sigmoid resection (L-Dixon). After receiving four doses of ceftizoxime, the patient developed symptoms including rash, itchy skin, and chest distress, followed by a rapid decline in hemoglobin levels, the presence of hemoglobin in the urine (hemoglobinuria), renal failure, and disseminated intravascular coagulation. Laboratory analysis revealed high-titer antibodies against ceftizoxime and red blood cells (RBCs) in the patient's serum, including immunoglobulin M (IgM) (1:128) antibodies and immunoglobulin G (IgG) (1:8) antibodies, with noted crossreactivity to ceftriaxone. Significant improvement in the patient's hemolytic symptoms was observed following immediate discontinuation of the drug, two plasma exchanges, and extensive RBC transfusion.
CONCLUSION
This case, together with previous reports, underscores the importance of considering DIIHA in patients who exhibit unexplained decreases in hemoglobin levels following antibiotic therapy. A thorough examination of the patient's medical history can provide crucial insights for diagnosing DIIHA. The effective management of DIIHA includes immediate cessation of the implicated drug, plasma exchange, and transfusion support based on the identification of specific drug-dependent antibodies through serological testing.
Topics: Humans; Rectal Neoplasms; Hemoglobins; Anti-Bacterial Agents; Male; Ceftizoxime; Multiple Organ Failure; Middle Aged; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; China; East Asian People
PubMed: 38756782
DOI: 10.3389/fimmu.2024.1390082