Higher Mortality In Patients Research Articles

Clinical characteristics and mortality of mucormycosis in hematological malignancies: a retrospective study in Eastern China

BackgroundMucormycosis is a significant cause of morbidity and mortality in patients with hematological malignancies, but its characteristics are not fully understood. This study aimed to gain a better understanding of the clinical features of mucormycosis in patients with hematological malignancies in eastern China.MethodsA single-center retrospective analysis was conducted on the demographic profile, microbiology, management, and 90-day mortality of mucormycosis patients with hematological malignancies between 2018 and 2023.ResultsA total of 50 cases were included in the study, consisting of 11 proven and 39 probable cases of mucormycosis. The median age of the patients was 39.98 ± 18.52 years, with 52% being male. Among the cases, 46% had acute myeloid leukemia (AML), 16% had acute lymphoblastic leukemia (ALL), and 16% had myelodysplastic syndrome. The most common manifestations of mucormycosis were pulmonary (80%), disseminated (16%), and rhinocerebral (4%). The diagnosis was confirmed through histology, culture, microscopy, and molecular diagnostic techniques. The most commonly identified fungal species were Cunninghamella (40%), Rhizopus (26%), and Rhizomucor (22%). Treatment involved antifungals in 84% of cases and surgery in 10% of cases. The 90-day mortality rate was 76%. Logistic regression analysis revealed that treatment with amphotericin B and surgery was associated with improved survival, while neutropenia and administration of voriconazole prior to diagnosis was associated with higher mortality.ConclusionsMucormycosis continues to have a high mortality rate in patients with hematological malignancies. Early diagnosis using various techniques, including molecular biology, along with the appropriate use of amphotericin B and surgery when possible, is vital for the successful treatment of mucormycosis.

Recent advancements in biomarkers, therapeutics, and associated challenges in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a common type of leukemia that has a high mortality rate. The reasons for high mortality in patients with AML are therapeutic resistance, limited ability to predict duration of response, and likelihood of cancer relapse. Biomarkers, such as leukemic stem cell biomarkers, circulatory biomarkers, measurable residual disease biomarkers, and molecular biomarkers, are used for prognosis, diagnosis, and targeted killing to selectively eliminate AML cells. They also play an indispensable role in providing therapeutic resistance to patients with AML. Therefore, targeting these biomarkers will improve the outcome of AML patients. However, identifying biomarkers that can differentiate between treatment-responsive and non-responsive AML patients remains a challenge. This review discusses recent advancements in AML biomarkers, promising therapeutics, and associated challenges in the treatment of AML.

Dexamethasone for the Treatment of Cardiac Al Amyloidosis: A Case Report and Literature Review

Background: Systemic immunoglobulin light chain (AL) amyloidosis is a condition characterised by the conversion of light chains (LCs) from their soluble states into highly organised fibrillar aggregates that deposit in tissues, resulting in progressive organ damage and dysfunction. While previously considered incurable, treatment strategies are emerging for cardiac amyloidosis, underscoring the importance of early diagnosis. Case Summary: We present the case of a 69-year-old male patient who was admitted with acute onset of dyspnea and diagnosed with heart failure. The diagnosis of cardiac amyloidosis was made on the basis of a discrepancy between the results of the electrocardiogram and the echocardiogram, a conclusion that was further substantiated by the use of scintigraphy and myelogram. Given the poor left ventricular fraction, the standard chemotherapy regimen was replaced with corticosteroid therapy, which led to a significant improvement within the first 48 hours, unfortunately reversible with rapid clinical deterioration followed by sudden death within a week. Conclusion: Our aim is to highlight that early administration of dexamethasone is associated with significant clinical improvement but a high mortality rate in patients with AL cardiac amyloidosis.

Role of flavonoids in inhibiting triple-negative breast cancer.

Increasing incidences of metastasis or recurrence (or both) in triple-negative breast cancer (TNBC) are a growing concern worldwide, as these events are intricately linked to higher mortality rates in patients with advanced breast cancer. Flavonoids possess several pharmaceutical advantages with multi-level, multi-target, and coordinated intervention abilities for treating TNBC, making them viable for preventing tumor growth and TNBC metastasis. This review focused on the primary mechanisms by which flavonoids from traditional Chinese medicine extracts inhibit TNBC, including apoptosis, blocking of cell cycle and movement, regulation of extracellular matrix degradation, promotion of anti-angiogenesis, inhibition of aerobic glycolysis, and improvement in tumor microenvironment. This review aims to improve the knowledge of flavonoids as a promising pharmacological intervention for patients with TNBC.

N-acetyltransferase 10 mediates cognitive dysfunction through the acetylation of GABABR1 mRNA in sepsis-associated encephalopathy

Sepsis-associated encephalopathy (SAE) is a critical neurological complication of sepsis and represents a crucial factor contributing to high mortality and adverse prognosis in septic patients. This study explored the contribution of NAT10-mediated messenger RNA (mRNA) acetylation in cognitive dysfunction associated with SAE, utilizing a cecal ligation and puncture (CLP)-induced SAE mouse model. Our findings demonstrate that CLP significantly upregulates NAT10 expression and mRNA acetylation in the excitatory neurons of the hippocampal dentate gyrus (DG). Notably, neuronal-specific Nat10 knockdown improved cognitive function in septic mice, highlighting its critical role in SAE. Proteomic analysis, RNA immunoprecipitation, and real-time qPCR identified GABABR1 as a key downstream target of NAT10. Nat10 deletion reduced GABABR1 expression, and subsequently weakened inhibitory postsynaptic currents in hippocampal DG neurons. Further analysis revealed that microglia activation and the release of inflammatory mediators lead to the increased NAT10 expression in neurons. Microglia depletion with PLX3397 effectively reduced NAT10 and GABABR1 expression in neurons, and ameliorated cognitive dysfunction induced by SAE. In summary, our findings revealed that after CLP, NAT10 in hippocampal DG neurons promotes GABABR1 expression through mRNA acetylation, leading to cognitive dysfunction.

VL-HIV co-infection with Leishmania containing skin lesions resembling para-kala-azar dermal leishmaniasis.

Leishmaniases are a group of neglected vector-borne infectious diseases that are among the six priority endemic diseases worldwide. Visceral leishmaniasis (VL) is the most severe clinical manifestation, characterized by systemic and chronic visceral involvement and high mortality in immunosuppressed and untreated patients. VL can be complicated into post-kala-azar dermal leishmaniasis (PKDL), and when dermatologic disorders occur simultaneously with active VL, an intermediate clinical form called para-kala-azar dermal leishmaniasis (para-KDL) occurs. This clinical form is of great epidemiological relevance, as humans act as a source of infection for vectorial transmission. In the Americas, Brazil is among the seven countries responsible for more than 90% of VL cases, though reports of PKDL and para-KDL are rare. This paper presents three cases of VL-HIV co-infection with Leishmania-containing skin lesions resembling para-kala-azar dermal leishmaniasis. The cases were investigated by the team from the Infectious Diseases Department of University Hospital (HUMAP/UFMS) in Mato Grosso do Sul, Brazil. The three patients exhibited skin lesions where amastigote forms of L. (L.) infantum were identified. All cases exhibited similar clinical manifestations of para-KDL, including fever, hepatosplenomegaly, pancytopenia, and disseminated skin lesions. The study described the prevalence of comorbidities, the incidence of VL relapse, and the therapeutic regimen in relation to the outcomes. The study underscores the importance of follow-up and secondary prophylaxis in patients with VL, which are essential for the efficacy of the treatment. Furthermore, the study provides insight into the potential epidemiological profile of para-KDL cases in Brazil, which contributes to the development of more efficient clinical management strategies for patients.

Predicting early appropriate therapy for patients infected by carbapenem-resistant Gram-negative pathogens in intensive care units in Italy

BackgroundAntibiotic resistance among Gram-negative bacteria in intensive care units (ICUs) is linked with high morbidity and mortality in patients. In this study, we estimated the therapeutic coverage of various antibiotics, focusing on cefiderocol and comparators, administered empirically against an infection of unknown origin in the ICU.MethodsIn the ARTEMIS surveillance study, susceptibilities of 624 Italian Gram-negative isolates to amikacin, aztreonam-avibactam, cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, colistin, imipenem-relebactam, meropenem, and meropenem-vaborbactam were tested by broth microdilution, and results were interpreted by European Committee on Antimicrobial Susceptibility Testing breakpoints. The susceptibility rates from the ARTEMIS study were extrapolated to Gram-negative isolates obtained from 5,774 patients in Italian ICUs in 2021. The sum of the predicted susceptibilities of individual pathogens represented the overall likelihood of in vitro activity of each antibiotic as early targeted therapy for ICU patients.ResultsA total of 624 Italian Gram-negative isolates included 206 Pseudomonas aeruginosa, 138 Acinetobacter baumannii, 187 Klebsiella pneumoniae, and 93 Escherichia coli. Against A. baumannii, K. pneumoniae, P. aeruginosa, and E. coli, the overall susceptibility rates for cefiderocol were 87.7%, 96.8%, 99%, and 100%, respectively; and for comparator agents, 8.7–96.4%, 25.7–100%, 73.3–100%, and 89.2–100%, respectively. Among the subset of meropenem-resistant isolates, susceptibility rates of A. baumannii, K. pneumoniae, and P. aeruginosa to cefiderocol were 86.4%, 96.2% and 100%, respectively. Corresponding susceptibility rates to comparator agents were 0–96.8%, 0–100%, and 6.4–100%, respectively. There were no meropenem-resistant isolates of E. coli. The extrapolation of data to isolates from Italian ICUs showed that the highest likelihood of therapeutic coverage, both overall and among meropenem-resistant isolates, was reported for colistin (96.8% and 72.2%, respectively) and cefiderocol (95.7% and 71.4%, respectively). All other antibiotics were associated with a likelihood below 73% overall and between 0% and 41.4% for meropenem-resistant isolates.ConclusionsBased on confirmed susceptibility rates and reported ICU prevalence of multiple Gram-negative species, cefiderocol showed a higher predicted therapeutic coverage and utility in ICUs compared with comparator beta-lactam–beta-lactamase inhibitor antibiotics. Cefiderocol may be a promising early treatment option for patients at high risk of carbapenem-resistant Gram-negative bacterial infections in the ICU.

Diffuse alveolar hemorrhage in patients with systemic lupus erythematosus: data from the Spanish society of rheumathology Lupus Register (RELESSER).

Diffuse alveolar hemorrhage (DAH) is a rare complication with high mortality in patients with systemic lupus erythematosus (SLE). Early diagnosis and treatment are essential to improve patient prognosis.To determine the characteristics of patients with DAH and their mortality in a Spanish cohort of patients with SLE. Patients from the RELESSER (Spanish Society of Rheumatology Lupus Register) who had had at least one confirmed episode of DAH were included. Epidemiological, clinical, and laboratory characteristics were analyzed. 4024 patients were included in the RELESSER register, 37 (0.9%), had at least one recorded episode of DAH. Only further data for 14 patients could be analyzed. In total, 92.9% were women, and for 4 (28.6%) DAH coincided with the debut of SLE. More than 80% of patients had renal involvement and thrombocytopenia. The most frequent manifestations were dyspnea (85.7%) and hypoxemia (100%), with the classic triad of hemoptysis, anemia and pulmonary infiltrates, appearing in 6 (46.2%) patients. The most frequently used treatments were glucocorticoids (85.7%) and cyclophosphamide (69.2%); plasmapheresis was utilized in 5 patients (35.7%) and 8, (57.1%) received intravenous immunoglobulins; 12 (85.7%) patients required admission to the ICU and 5 (35.7%) died. Tobacco use, history of lupus nephritis (LN), concomitant infection, and treatment with cyclophosphamide were more frequent in patients who died. DAH is rare in patients with SLE; in up to one-third of patients, it may appear at the onset of the disease. Some factors, such as smoking, a history of LN, treatment with cyclophosphamide, or concomitant infection, are more prevalent in patients with an unfavorable outcome.

Мeans of restorative treatment of children of younger school age sick of bronchial asthma in rehabilitation institutions

Bronchial asthma is a problem of extreme urgency, as morbidity and mortality from it are constantly increasing throughout the civilized world. Among chronic diseases of respiratory organs, pathology occupies a leading place. In different countries, its prevalence varies from 10 to 15%. This is associated with high disability and mortality of patients with BA. Based on the analysis of literary and other sources of information, theoretical material on the use of means of restorative treatment for children of primary school age with bronchial asthma in rehabilitation institutions was studied and selected. Among the diseases of the respiratory system in children, various forms of bronchial asthma occupy a prominent place in the development of children's disability. Morbidity and mortality from it are constantly increasing throughout the civilized world. The article discusses the issues of non-drug treatment of bronchial asthma in children. The relevance of the problem of rehabilitation of children with bronchial asthma is due to the urgent need to facilitate their life and adaptation to the environment, as well as to improve the level of self-care. Accordingly, physical therapy of such children occupies an important place, because it improves their physical condition, contributes to the effective correction of functional insufficiency of the respiratory system, provides training of the cardiovascular system, which leads to better activity of the child in educational activities and adaptation in society. The aim of the study. Theoretical substantiation of the necessity and essence of the use of physical therapy in the complex rehabilitation of children of primary school age, patients with bronchial asthma, in rehabilitation institutions. Research methods. Analytical review of literary and information sources, study of the state of the issue and systematization of modern scientific and methodological knowledge and results of practical experience of leading specialists in physical rehabilitation regarding the issue of rehabilitation of children with bronchial asthma. Literary sources (scientific articles, textbooks, manuals, dissertation research abstracts) are selected from the electronic databases of the National Library of Ukraine named after V.I. Vernadskyi, Web of Science, PubMed and others.

Association between early blood glucose dynamic trajectory and mortality for critically ill patients with heart failure: Insights from real-world data

AimsThis study endeavors to explore the ramifications of early dynamic blood glucose (BG) trajectories within the initial 48 h of intensive care unit (ICU) admission on mortality among critically ill heart failure (HF) patients. MethodsThe study employed a retrospective observational design, analyzing dynamic BG data of HF patients from the Medical Information Mart for Intensive Care IV database. The BG trajectory subphenotypes were identified using the hierarchical clustering based on the dynamic time-warping algorithm. The primary outcome of the study was 28-day mortality, with secondary outcomes including 180-day and 1-year mortality. ResultsWe screened a total of 21,098 HF patients and finally 15,092 patients were included in the study. Our results identified three distinct BG trajectory subphenotypes: increasing (n = 3503), stabilizing (n = 6250), and decreasing (n = 5339). The increasing subphenotype was associated with the highest mortality risk at 28 days, 180 days, and 1 year. The stabilizing and decreasing subphenotypes showed significantly lower mortality risks across all time points, with hazard ratios ranging from 0.85 to 0.88 (P<0.05 for all). Sensitivity analyses confirmed the robustness of these findings after adjusting for various covariates. ConclusionsIncreasing BG trajectory within 48 h of admission is significantly associated with higher mortality in patients with HF. It is necessary to devote greater attention to the early BG dynamic changes in HF patients to optimize clinical BG management and enhance patient prognosis.

The Alteration Level of VEGF of Colon Cancer Cell After Induction with Mandarin Orange (&lt;i&gt;Citrus Reticulata&lt;/i&gt;) Peel Ethanol Extract

The natural ingredient-based therapy extracted from various plants is assumed more tolerable to cancer patients’ bodies than synthetic drugs. To tell successful novel cancer therapy, an indicator is needed to confirm the result. VEGF is a pro-angiogenic factor that leads the cancer cells’ invasion to another organ and is associated with high mortality in patients. Hence, the VEGF level is widely used as one of the successful cancer therapy indicators. Purposed of research elucidated the effect of Mandarin orange peel ethanol extract (EEKJM) to improve the reduction of VEGF levels in colon cancer in vitro. This study was an experimental posttest and control group design to analyze different level of VEGF on cancer cells at end of the study. Research began with the preparation of EEKJM followed by a cytotoxic extract test using the MTT assay method. Furthermore, the measurement of VEGF levels by the VEGF ELISA kit protocol. One Way ANOVA was performed to analyze data.Results showed the cytotoxic test of the EEKJM and doxorubicin against WiDr cells was 240 g/ml and 1.59 µg/ml. VEGF levels showed decreasing after being induced with EEKJM and doxorubicin with doses ½ IC50 and ¼ IC50. Conclusion: EEKJM was able to reduce VEGF levels and viability of WiDr colon cancer cells. The advantages are as much as initial evidence of the ability of the orange to treat cancer even though further animal studies or evidence of a pathway of decrease of the VEGF or other signals are required.

Differences between atrial fibrillation diagnosed before and after stroke: A large real-world cohort study.

The clinical characteristics and long-term outcomes of patients with ischemic stroke (IS) and atrial fibrillation detected after stroke (AFDAS) have not been clearly established. Previous studies evaluating patients with AFDAS were limited by the low prescription rates of anticoagulants and short follow-up periods. Consecutive patients hospitalized for IS between 2014 and 2017 were identified from a National Health Insurance Research Database. The included patients were categorized into three groups: (1) known diagnosis of AF (KAF) before the index stroke, (2) AFDAS, and (3) without AF (non-AF). Univariable and multivariable Cox regression analyses were performed to estimate the hazard ratio (HR) for independent variables and recurrent IS, hemorrhagic stroke, or all-cause mortality. We identified 158,909 patients with IS of whom 16,699 (10.5%) had KAF and 7,826 (4.9%) had AFDAS. The patients with AFDAS were younger, more often male, and had lower CHA2DS2-VASc scores (3.8 ± 1.9 versus 4.9 ± 1.8, p < 0.001) than the patients with KAF. Anticoagulant treatment significantly reduced the risks of all outcomes. The standardized mortality rates were 40.4, 28.6, and 18.4 (per 100 person-years) for the patients with KAF, AFDAS, and non-AF, respectively. Compared with AFDAS, KAF was associated with lower risks of recurrent IS [hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.86-0.97, p < 0.01] and hemorrhagic stroke (HR: 0.88, 95% CI: 0.79-0.99, p < 0.01) and a higher risk of all-cause mortality (HR: 1.11, 95% CI: 1.07-1.16, p < 0.001). The risks of recurrent IS and hemorrhagic stroke were higher and of all-cause mortality was lower for patients with AFDAS than with KAF. There is a strong need to refine treatment modalities to reduce the high mortality in patients with KAF and AFDAS.

High expression of L-GILZ transcript variant 1 (GILZ TV 1) is associated with increased 30-day sepsis mortality, and a high expression ratio possibly contraindicates hydrocortisone administration

BackgroundSepsis presents a challenge due to its complex immune responses, where balance between inflammation and anti-inflammation is critical for survival. Glucocorticoid-induced leucine zipper (GILZ) is key protein in achieving this balance, suppressing inflammation and mediating glucocorticoid response. This study aims to investigate GILZ transcript variants in sepsis patients and explore their potential for patient stratification and optimizing glucocorticoid therapy.MethodsSepsis patients meeting the criteria outlined in Sepsis-3 were enrolled, and RNA was isolated from whole blood samples. Quantitative mRNA expression of GILZ transcript variants in both sepsis patient samples (n = 121) and the monocytic U937 cell line (n = 3), treated with hydrocortisone and lipopolysaccharides, was assessed using quantitative PCR (qPCR).ResultsElevated expression of GILZ transcript variant 1 (GILZ TV 1) serves as a marker for heightened 30-day mortality in septic patients. Increased levels of GILZ TV 1 within the initial day of sepsis onset are associated with a 2.2-[95% CI 1.2–4.3] fold rise in mortality, escalating to an 8.5-[95% CI 2.0–36.4] fold increase by day eight. GILZ TV1 expression is enhanced by glucocorticoids in cell culture but remains unaffected by inflammatory stimuli such as LPS. In septic patients, GILZ TV 1 expression increases over the course of sepsis and in response to hydrocortisone treatment. Furthermore, a high expression ratio of transcript variant 1 relative to all GILZ mRNA TVs correlates with a 2.3-fold higher mortality rate in patients receiving hydrocortisone treatment.ConclusionHigh expression of GILZ TV 1 is associated with a higher 30-day sepsis mortality rate. Moreover, a high expression ratio of GILZ TV 1 relative to all GILZ transcript variants is a parameter for identifying patient subgroups in which hydrocortisone may be contraindicated.

Efficacy of lyophilized Lactobacillus sakei as a potential candidate for preventing carbapenem-resistant Klebsiella infection

BackgroundAntimicrobial resistance is considered one of the greatest threats to human health, according to the World Health Organization (WHO). Gram-negative bacteria, especially carbapenem-resistant Enterobacteriaceae (CRE), have become a significant concern in antimicrobial-resistant bacteria’s global emergence and spread. Among CRE pathogens, carbapenem-resistant Klebsiella pneumoniae (CRKP) has recently been reported as a highly infectious strain associated with high mortality and morbidity in adults and immunocompromised patients. Additionally, CRKP-related infections are challenging to treat, as carbapenems are the last resort of antibiotics. Therefore, developing novel drugs with different mechanisms of action from existing drugs is urgently required to defeat this lethal menace. Under such circumstances, probiotics can be therapeutic candidates for inhibiting pathogens. Thus, our research team has been focusing on probiotics for a long time to develop potential anti-CRKP drug agents.MethodsAfter extensive efforts, we finally found a novel probiotic strain, Lactobacillus sakei PMC104, suitable for treating CRKP infection. It was isolated from kimchi. As part of our expansion into therapeutic development, we evaluated the L. sakei strain effect against CRKP pathogens in both in vitro and in vivo experiments. Moreover, we conducted media optimization at food grade and then established a scale-up process on a pilot scale. Subsequently, a lyophilizate was obtained and used in a mouse model infected with CRKP.ResultsData demonstrated that the L. sakei strain has an inhibitory effect against CRKP infection both in in vitro and in vivo experiments and also increases the level of short-chain fatty acids in the feces of mice after receiving L. sakei strain treatment for 10 days. Furthermore, treatment with L. sakei powder remarkably diminished body weight loss, mortality, and illness severity in CRKP-infected mice, showing a preventive effect of our PMC 104 against CRKP infection.DiscussionOur results demonstrate the potential therapeutic effect of our candidate probiotic strain against CRKP, suggesting that L. sakei PMC 104 could be considered an antimicrobial candidate for treating CRKP infections. However, extensive studies, including additional toxicity tests and clinical trials, are still essential to develop it as a new anti-CRKP therapeutic agent.

Synergistic antifungal effect of thiophene derivative as an inhibitor of fluconazole-resistant Candida spp. biofilms.

Candida species resistant to fluconazole have raised concern in the scientific medical community due to high mortality in patients with invasive disease. In developing countries, such as Brazil, fluconazole is the most commonly used antifungal, and alternative treatments are expensive or not readily available. Furthermore, the occurrence of biofilms is common, coupled with their inherent resistance to antifungal therapies and the host's immune system, these microbial communities have contributed to making infections caused by these yeasts an enormous clinical challenge. Therefore, there is an urgent need to develop alternative medicines, which surpass the effectiveness of already used therapies, but which are also effective against biofilms. Therefore, the present study aimed to describe for the first time the antifungal and antibiofilm action of the derivative 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-isopropyl carboxylate (2AT) against clinical strains of Candida spp. resistant to fluconazole (FLZ). When determining the minimum inhibitory concentrations (MIC), it was found that the compound has antifungal action at concentrations of 100 to 200µg/mL, resulting in 100% inhibition of yeast cells. Its synergistic effect with the drug FLZ was also observed. The antibiofilm action of the compound in subinhibitory concentrations was detected, alone and in association with FLZ. Moreover, using scanning electron microscopy, it was observed that the compound 2AT in isolation was capable of causing significant ultrastructural changes in Candida. Additionally, it was also demonstrated that the compound 2AT acts by inducing characteristics compatible with apoptosis in these yeasts, such as chromatin condensation, when visualized by transmission electron microscopy, indicating the possible mechanism of action of this molecule. Furthermore, the compound did not exhibit toxicity in J774 macrophage cells up to a concentration of 4000µg/mL. In this study, we identify the 2AT derivative as a future alternative for invasive candidiasis therapy, in addition, we highlighted the promise of a strategy combined with fluconazole in combating Candida infections, especially in cases of resistant isolates.

Is advanced age still a risk factor for recurrence of C. difficile infection in the era of new treatments?

Advanced age has been widely identified as a risk factor for recurrent Clostridioides difficile infection (CDI), but most related studies were performed before the introduction of novel therapies. The aim of this study was to compare CDI characteristics and outcomes in patients over and under 80years old with CDI and their outcomes in the era of new treatments. This was a retrospective cohort study of patients diagnosed with CDI from January 2021 to December 2022 in an academic hospital. We compared recurrence and mortality at 12weeks after the end of treatment. An extension of the Fine and Grey model adjusted for competing events was used to assess the effect of age on recurrence. Four hundred seventy-six patients were considered to have CDI (320 in patients <80years and 156 in ≥80years). CDI in older patients was more frequently healthcare-associated and was more severe. Although the Charlson index was almost identical between populations, comorbidities clearly differed. New treatments (bezlotoxumab, fidaxomicin and faecal microbiota transplantation) were more frequently used in older patients without statistical significance (41.3% vs. 33.4%, P= .053). There were 69 (14.5%) recurrences, with no differences by age group after adjusting for competing events. Mortality was greater in the oldest (35.3%) than in the youngest (13.1%); P< .001. No differences in CDI recurrence rates were found between age groups. However, there was a high mortality rate in patients ≥80years old, which emphasises the urgent need to improve the prevention and treatment of CDI in this group.

Liver Retransplantation Using Living Donor Grafts: A Feasible Approach for Chronic Allograft Failure.

The indication of living donor liver retransplantation (re-LDLT) for retransplant candidates with chronic allograft failure (CAF) is increasing because of the high mortality rate of patients on the waiting list. However, evidence supporting re-LDLT for CAF remains scarce because of technical difficulties. We aimed to examine the feasibility based on our significant case experience. A total of 95 retransplant cases (adult: 53, pediatric: 42) between 2000 and 2020 were retrospectively reviewed. Graft survival after re-LDLT and deceased donor liver retransplantation (re-DDLT) was compared among recipients with CAF and acute allograft failure (AAF). Re-LDLTs for CAF were performed in 58 (61.1%) cases, re-DDLTs for CAF in 16 (16.8%) cases, re-LDLTs for AAF in 13 (13.7%) cases, and re-DDLTs for AAF in 8 (8.4%) cases. Re-DDLTs have become increasingly prevalent over time. Retransplantation for AAF results in lower graft survival than that for CAF in both adult and pediatric cases. All adult recipients who underwent re-LDLT for AAF died within 1 y after retransplantation. The 5-y graft survival between re-LDLT and re-DDLT for CAF was not significantly different (73.8% versus 75.0%, P = 0.84). Operation time and blood loss were not significantly different. The survival rate of re-LDLT for recipients with CAF is permissible. Re-LDLT may be another treatment option for recipients with CAF.

Acid sphingomyelinase deficiency in France: a retrospective survival study

BackgroundAcid sphingomyelinase deficiency (ASMD) or Niemann–Pick disease types A, A/B, and B is a progressive, life-limiting, autosomal recessive disorder caused by sphingomyelin phosphodiesterase 1 (SMPD1) gene mutations. There is a need to increase the understanding of morbidity and mortality across children to adults diagnosed with ASMD.MethodsThis observational retrospective survey analysed medical records of patients with ASMD with retrievable data from 27 hospitals in France, diagnosed/followed up between 1st January 1990 and 31st December 2020. Eligible records were abstracted to collect demographic, medical/developmental history, and mortality data. Survival outcomes were estimated from birth until death using Kaplan–Meier survival analyses; standardised mortality ratio (SMR) was also explored.ResultsA total of 118 medical records of patients with ASMD (type B [n = 94], type A [n = 15], and type A/B [n = 9]) were assessed. The majority of patients were males (63.6%); the median [range] age at diagnosis was 8.0 [1.0–18.0] months (type A), 1.0 [0–3] year (type A/B), and 5.5 [0–73] years (type B). Overall, 30 patients were deceased at the study completion date; the median [range] age at death for patients with ASMD type A (n = 14) was 1 [0–3.6] year, type A/B (n = 6) was 8.5 [3.0–30.9] years, and type B (n = 10) was 57.6 [3.4–74.1] years. The median [95% confidence interval (CI)] survival age from birth in patients with ASMD type A and type A/B was 2.0 [1.8–2.7] years and 11.4 [5.5–18.5] years, respectively. Survival analysis in ASMD type B was explored using SMR [95% CI] analysis (3.5 [1.6–5.9]), which showed that age-specific deaths in the ASMD type B population were 3.5 times more frequent than those in the general French population. The causes of death were mostly severe progressive neurodegeneration (type A: 16.7%), cancer (type B: 16.7%), or unspecified (across groups: 33.3%).ConclusionsThis study illustrated a substantial burden of illness with high mortality rates in patients with ASMD, including adults with ASMD type B, in France.

Abstract Tu102: The Role of the β IV -spectrin/STAT3 Complex in Regulating Ischemic Cardiac Remodeling

Adverse fibrotic remodeling contributes to high morbidity and mortality in patients following myocardial infarction (MI). The healing process after MI requires necrotic tissue to be cleared and replaced with fibrosis, which is driven by the coordinated effort of several distinct cardiac cell populations, including macrophages and cardiac fibroblasts (CFs). While previous studies have focused on identifying the stimuli that drives fibrotic remodeling in the infarcted myocardium, the contribution of specific cell populations to the signaling cascade and the manner of how these communication networks are tuned in response to chronic stress remains unclear. Prior work has identified a role for the cytoskeletal protein, β IV -spectrin, in coordinating the activity of the transcription factor, STAT3, with implications for CF activation and profibrotic signaling. Specifically, it was found that mice expressing truncated β IV -spectrin ( qv 3J ) are resistant to cardiac fibrosis in the setting of chronic pressure overload, with maintained β IV -spectrin expression and STAT3 localization/activity in CFs. Further, β IV -spectrin deficiency causes increased secretion of profibrotic and proinflammatory factors, including matrix metallopeptidases (MMPs). Therefore, we hypothesized that stress-induced loss of β IV -spectrin and subsequent dysregulation of STAT3 signaling in CFs proximal to the infarct promotes fibroblast activation, an important first step in repairing the infarct region. In this study, we subjected WT and qv 3J mice to permanent ligation of the left anterior descending artery and assessed cardiac function and survival through 28 days. A subset of mice were sacrificed at 7 days for histology, qPCR, and flow cytometry. Compared to WT, qv 3J mice showed a significant decrease in 28-day survival with increased mortality in the first week post-MI. Autopsy identified increased incidence of cardiac rupture in qv 3J animals. Immunohistochemistry revealed impaired scar formation at 7 days post-MI in qv 3J compared to WT. Quantitative PCR showed altered expression of matrix metallopeptidases (MMPs 3, 8, 9, and 14) in the qv 3J hearts at day 7. MMP activity was assessed in whole heart lysates using gelatin-zymography. Collagen uptake was assessed in CFs and bone marrow-derived macrophages isolated from WT and qv 3J mice. Our work identifies a novel role of the spectrin-based pathway in facilitating fibrotic remodeling in response to ischemic stress.

Prognostic impact of peripheral artery disease-related parameters in patients with acute coronary syndrome.

Lower extremity arterial disease (LEAD) and increased aortic stiffness are associated with higher mortality in patients with chronic coronary syndrome, while their prognostic significance after an acute coronary syndrome (ACS) is less known. We analyzed prevalence, clinical phenotypes and association of LEAD - assessed by the ankle-brachial index (ABI) - and increased aortic stiffness - assessed by the aortic pulse wave velocity (PWV) - with all-cause mortality and major adverse cardiovascular events (MACE) in patients admitted with an ACS. Among 270 patients admitted for ACS (mean age 67 years, 80% males), 41 (15%) had an ABI ≤0.9, with 14 of them (34%) presenting with intermittent claudication (symptomatic LEAD). Patients with symptomatic LEAD, compared with those with asymptomatic LEAD or without LEAD, had higher prevalence of cardiovascular risk factors, lower estimated glomerular filtration rate and higher high-sensitivity C-reactive protein. Patients with LEAD, either symptomatic or asymptomatic, more frequently presented with non-ST-elevation myocardial infarction and more frequently had multivessel coronary artery disease. Both symptomatic and asymptomatic LEAD were significantly associated with all-cause mortality after adjustment for confounders, including multivessel disease or carotid artery disease (hazard ratio 4.03, 95% confidence interval 1.61-10.08, P < 0.01), whereas PWV was not associated with the outcome in the univariable model. LEAD and PWV were not associated with a higher risk of MACE (myocardial infarction or unstable angina, stroke, or transient ischemic attack). LEAD, either clinical or subclinical, but not increased aortic stiffness, is an independent predictor of all-cause mortality in patients admitted for ACS.