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World Journal of Transplantation Jun 2024Transplant recipients commonly harbor multidrug-resistant organisms (MDROs), as a result of frequent hospital admissions and increased exposure to antimicrobials and...
BACKGROUND
Transplant recipients commonly harbor multidrug-resistant organisms (MDROs), as a result of frequent hospital admissions and increased exposure to antimicrobials and invasive procedures.
AIM
To investigate the impact of patient demographic and clinical characteristics on MDRO acquisition, as well as the impact of MDRO acquisition on intensive care unit (ICU) and hospital length of stay, and on ICU mortality and 1-year mortality post heart transplantation.
METHODS
This retrospective cohort study analyzed 98 consecutive heart transplant patients over a ten-year period (2013-2022) in a single transplantation center. Data was collected regarding MDROs commonly encountered in critical care.
RESULTS
Among the 98 transplanted patients (70% male), about a third (32%) acquired or already harbored MDROs upon transplantation (MDRO group), while two thirds did not (MDRO-free group). The prevalent MDROs were (14%), (12%) and (11%). Compared to MDRO-free patients, the MDRO group was characterized by higher body mass index ( = 0.002), higher rates of renal failure ( = 0.017), primary graft dysfunction (10% 4.5%, = 0.001), surgical re-exploration (34% 14%, = 0.017), mechanical circulatory support (47% 26% = 0.037) and renal replacement therapy (28% 9%, = 0.014), as well as longer extracorporeal circulation time (median 210 161 min, = 0.003). The median length of stay was longer in the MDRO group, namely ICU stay was 16 9 d in the MDRO-free group ( = 0.001), and hospital stay was 38 28 d ( = 0.006), while 1-year mortality was higher (28% 7.6%, log-rank- : 7.34).
CONCLUSION
Following heart transplantation, a predominance of Gram-negative MDROs was noted. MDRO acquisition was associated with higher complication rates, prolonged ICU and total hospital stay, and higher post-transplantation mortality.
PubMed: 38947964
DOI: 10.5500/wjt.v14.i2.93567 -
Journal of Surgical Case Reports Jun 2024During breast cancer recurrence, drug therapy is planned based on the biological characteristics of the primary tumor. However, the mechanisms underlying these changes...
During breast cancer recurrence, drug therapy is planned based on the biological characteristics of the primary tumor. However, the mechanisms underlying these changes have not yet been clarified. A 59-year-old woman underwent breast cancer surgery 23 years previously and received postoperative hormone therapy for 2 years. She had abdominal distention and ascites effusion and was diagnosed with carcinomatous peritonitis due to luminal-type breast cancer after ascites puncture. She received up to the fourth line of treatment. Subsequently, pleural effusion was observed and human epidermal growth factor receptor 2 type breast cancer was diagnosed because of pleurodesis. This case suggests that the cell block diagnostic method based on thoracic and ascites fluid cytology is useful not only for confirming the primary tumor but also for diagnosing the biological characteristics of breast cancer. In the treatment of breast cancer recurrence, it is important to plan the treatment, including aggressive re-biopsy of metastases.
PubMed: 38947869
DOI: 10.1093/jscr/rjae432 -
Clinical Case Reports Jul 2024The purpose of this case report is to reveal one of the cardiovascular side effects of favipiravir, sinus bradycardia.
KEY CLINICAL MESSAGE
The purpose of this case report is to reveal one of the cardiovascular side effects of favipiravir, sinus bradycardia.
ABSTRACT
Favipiravir has emerged as a potential treatment for COVID-19, with its antiviral properties showing promise in inhibiting viral replication. However, concerns regarding its safety profile, particularly its cardiac adverse effects, remain a subject of debate. We present the case of a 58-year-old man with a history of diabetes mellitus and chronic obstructive pulmonary disease who developed bradycardia following treatment with favipiravir for COVID-19 pneumonia. Despite being asymptomatic, the patient exhibited sinus bradycardia, which resolved upon discontinuation of favipiravir. Favipiravir has been associated with QT prolongation and sinus bradycardia, though the exact mechanisms remain unclear. Our case adds to the growing body of evidence highlighting the potential cardiac complications of favipiravir therapy in COVID-19 patients. Further research is warranted to clarify the underlying mechanisms and optimize patient management strategies. Clinicians should be cautious for cardiac adverse events when prescribing favipiravir for COVID-19 treatment, especially in patients with preexisting cardiac conditions. Continued research is essential to ensure the safe and effective use of favipiravir in the management of COVID-19.
PubMed: 38947534
DOI: 10.1002/ccr3.9052 -
Heliyon Jun 2024Cholangiocarcinoma is a malignant invasive biliary tract carcinoma with a poor prognosis. Anoikis-related genes are prognostic features of a variety of cancers. However,...
BACKGROUND
Cholangiocarcinoma is a malignant invasive biliary tract carcinoma with a poor prognosis. Anoikis-related genes are prognostic features of a variety of cancers. However, the value of prognostication and therapeutic effect of anoikis-related genes in cholangiocarcinoma have not been reported. The aim of this research was developing an ARGs signature associated with cholangiocarcinoma patients.
METHODS
We introduced transcriptome data to discover genes that were differentially expressed in cholangiocarcinoma. Subsequently, WGCNA was utilized to screen critical module genes in reference to anoikis. The univariate Cox, Lasso regression and Kaplan-Meier survival were executed to build a prognostic signature. We further performed gene functional enrichment, immune microenvironment and immunotherapy analysis between two risk subgroups. Finally, the pRRophetic algorithm was applied to compare the half inhibitory concentration value of several drugs.
RESULTS
A grand total of 1844 genes with differential expression related to the cholangiocarcinoma patients were identified. Furthermore, we obtained 2678 key module genes related to anoikis. Then, a prognostic signature was developed using the 6 prognostic genes (, , , , and ) Independent prognostic analysis showed that risk score and alcohol could function as separate prognostic variables. We found cetain distinction in the immune microenvironment between the two risk subgroups. Moreover, immunotherapy evaluation showed that the anoikis-related gene signature could be applied as a therapy predictor. Finally, Chemotherapeutic drug sensitivity results showed that the low-risk group responded better to bosutinib, gefitinib, gemcitabine, and paclitaxel, while the high-risk group responded better to axitinib, cisplatin, and imatinib.
CONCLUSION
The prognostic signature comprised of , , , , and based on anoikis-related genes was established, which provided theoretical basis and reference value for the research and treatment of cholangiocarcinoma.
PubMed: 38947446
DOI: 10.1016/j.heliyon.2024.e32337 -
Global Health & Medicine Jun 2024The recent dramatic progress in systemic therapy for hepatocellular carcinoma (HCC) provides the possibility of a combination of surgery and systemic therapy including...
The recent dramatic progress in systemic therapy for hepatocellular carcinoma (HCC) provides the possibility of a combination of surgery and systemic therapy including adjuvant, neoadjuvant, or conversion settings. Since the turn of the century, at least three negative studies have tested adjuvant therapies after curative resection or ablation, including uracil-tegafur, which is an oral chemotherapeutic drug, sorafenib, and peretinoin, which a synthetic retinoid that may induce the apoptosis and differentiation of liver cancer cells. Using more potent immuno-checkpoint inhibitors (ICIs), at least 4 phase III trials of adjuvant immunotherapy are ongoing: nivolumab, durvalumab/ bevacizumab, pembrolizumab, and atezolizumab+bevacizumab. Very recently, the last trial indicated a significantly better recurrence-free survival (RFS) for adjuvant atezolizumab+bevacizumab. Another promising combination of surgery and systemic therapy is neoadjuvant therapy for potentially resectable cases or a conversion strategy for oncologically unresectable cases. There are 2 neoadjuvant trials for technically or oncologically unresectable HCCs ongoing in Japan: the LENS-HCC trial using lenvatinib and the RACB study using atezolizumab+bevacizumab. A longer follow-up may be needed, but the overall survival (OS) in resected cases seems much higher than that in unresectable cases. Recently, the Japan Liver Cancer Association (JLCA) and the Japanese Society of HPB Surgery (JSHPBS) created a joint working group on "so-called borderline resectable HCC". They obtained a Japanese consensus on this issue that has been published on the websites of JLCA and JSHPBS. The definition of resectability or borderline resectability provides a common language regarding advanced HCC for investigators and is a useful tool for future clinical trials.
PubMed: 38947413
DOI: 10.35772/ghm.2024.01002 -
Journal of Cancer 2024Hepatocellular carcinoma (HCC) is the main type of primary liver cancer, and its related death ranks third worldwide. The curative methods and progress prediction...
Hepatocellular carcinoma (HCC) is the main type of primary liver cancer, and its related death ranks third worldwide. The curative methods and progress prediction markers of HCC are not sufficient enough. Nevertheless, little progress has been made in the signature of mA-, mC-, mA-, mG-, and DNA methylation of HCC. We calibrated a risk gene signature model that can be used to categorize HCC patients based on univariate, multivariate, and LASSO Cox regression analysis. This gene signature classified the patients into high- and low-risk subgroups. Patients in the high-risk group showed significantly reduced overall survival (OS) compared with patients in the low-risk group. The gene set variation analysis (GSVA), immune infiltration, and immunotherapy response were analyzed. The results demonstrated that an immunosuppressive environment was exited and the high-risk group had higher sensitivity to 5-fluorouracil, cisplatin, sorafenib, tamoxifen, and epirubicin. These results indicated personalized therapy should be taken into consideration. Our findings enriched our understanding of the molecular heterogeneity, tumor microenvironment (TME), and drug susceptibility of HCC. mA-, mC-, mA-, mG-, and DNA methylation-related regulators may be promising biomarkers for future research.
PubMed: 38947378
DOI: 10.7150/jca.95730 -
Frontiers in Public Health 2024The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in...
Epidemiology and antimicrobial resistance of spp. in the United Arab Emirates: a retrospective analysis of 12 years of national antimicrobial resistance surveillance data.
INTRODUCTION
The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in the United Arab Emirates (UAE) to 204 per 100,000 in Djibouti. The national surveillance data from the Middle East and North Africa (MENA) region on the epidemiology and antimicrobial resistance trends of TB, including MDR-TB remains scarce.
METHODS
A retrospective 12-year analysis of = 8,086 non-duplicate diagnostic complex (MTB complex) isolates from the UAE was conducted. Data were generated through routine patient care during the 2010-2021 years, collected by trained personnel and reported by participating surveillance sites to the UAE National Antimicrobial Resistance (AMR) Surveillance program. Data analysis was conducted with WHONET, a windows-based microbiology laboratory database management software developed by the World Health Organization Collaborating Center for Surveillance of Antimicrobial Resistance, Boston, United States (https://whonet.org/).
RESULTS
A total of 8,086 MTB-complex isolates were analyzed. MTB-complex was primarily isolated from respiratory samples (sputum 80.1%, broncho-alveolar lavage 4.6%, pleural fluid 4.1%). Inpatients accounted for 63.2%, including 1.3% from ICU. Nationality was known for 84.3% of patients, including 3.8% Emiratis. Of UAE non-nationals, 80.5% were from 110 countries, most of which were Asian countries. India accounted for 20.8%, Pakistan 13.6%, Philippines 12.7%, and Bangladesh 7.8%. Rifampicin-resistant MTB-complex isolates (RR-TB) were found in 2.8% of the isolates, resistance to isoniazid, streptomycin, pyrazinamide, and ethambutol, was 8.9, 6.9, 3.4 and 0.4%, respectively. A slightly increasing trend of resistance among MTB-complex was observed for rifampicin from 2.5% (2010) to 2.8% (2021).
CONCLUSION
Infections due to MTB-complex are relatively uncommon in the United Arab Emirates compared to other countries in the MENA region. Most TB patients in the UAE are of Asian origin, mainly from countries with a high prevalence of TB. Resistance to first line anti-tuberculous drugs is generally low, however increasing trends for MDR-TB mainly rifampicin linked resistance is a major concern. MDR-TB was not associated with a higher mortality, admission to ICU, or increased length of hospitalization as compared to non-MDR-TB.
Topics: United Arab Emirates; Humans; Retrospective Studies; Tuberculosis, Multidrug-Resistant; Male; Mycobacterium tuberculosis; Female; Adult; Antitubercular Agents; Middle Aged; Drug Resistance, Bacterial; Adolescent; Microbial Sensitivity Tests; Young Adult; Population Surveillance
PubMed: 38947352
DOI: 10.3389/fpubh.2024.1244353 -
Frontiers in Immunology 2024The interaction between pyroptosis-a form of programmed cell death-and tumor immunity represents a burgeoning field of interest. Pyroptosis exhibits a dual role in... (Review)
Review
BACKGROUND
The interaction between pyroptosis-a form of programmed cell death-and tumor immunity represents a burgeoning field of interest. Pyroptosis exhibits a dual role in cancer: it can both promote tumor development and counteract it by activating immune responses that inhibit tumor evasion and encourage cell death. Current tumor immunotherapy strategies, notably CAR-T cell therapy and immune checkpoint inhibitors (ICIs), alongside the potential of certain traditional Chinese medicinal compounds, highlight the intricate relationship between pyroptosis and cancer immunity. As research delves deeper into pyroptosis mechanisms within tumor therapy, its application in enhancing tumor immune responses emerges as a novel research avenue.
PURPOSE
This review aims to elucidate the mechanisms underlying pyroptosis, its impact on tumor biology, and the advancements in tumor immunotherapy research.
METHODS
A comprehensive literature review was conducted across PubMed, Embase, CNKI, and Wanfang Database from the inception of the study until August 22, 2023. The search employed keywords such as "pyroptosis", "cancer", "tumor", "mechanism", "immunity", "gasdermin", "ICB", "CAR-T", "PD-1", "PD-L1", "herbal medicine", "botanical medicine", "Chinese medicine", "traditional Chinese medicine", "immunotherapy", linked by AND/OR, to capture the latest findings in pyroptosis and tumor immunotherapy.
RESULTS
Pyroptosis is governed by a complex mechanism, with the Gasdermin family playing a pivotal role. While promising for tumor immunotherapy application, research into pyroptosis's effect on tumor immunity is still evolving. Notably, certain traditional Chinese medicine ingredients have been identified as potential pyroptosis inducers, meriting further exploration.
CONCLUSION
This review consolidates current knowledge on pyroptosis's role in tumor immunotherapy. It reveals pyroptosis as a beneficial factor in the immunotherapeutic landscape, suggesting that leveraging pyroptosis for developing novel cancer treatment strategies, including those involving traditional Chinese medicine, represents a forward-looking approach in oncology.
Topics: Pyroptosis; Humans; Neoplasms; Immunotherapy; Animals; Immune Checkpoint Inhibitors; Tumor Microenvironment
PubMed: 38947336
DOI: 10.3389/fimmu.2024.1381778 -
Frontiers in Immunology 2024Epithelioid hemangioendothelioma is a rare vascular malignancy, and currently, there is no standard treatment regimen for this disease and existing treatment options...
Epithelioid hemangioendothelioma is a rare vascular malignancy, and currently, there is no standard treatment regimen for this disease and existing treatment options have limited efficacy. In this case report, we present a patient with lung and lymph node metastases from prostate epithelioid hemangioendothelioma who achieved a significant partial response. This was accomplished through alternating nivolumab therapy with ipilimumab and liposomal doxorubicin, resulting in a progression-free-survival more than 6 months to date. The treatment was well-tolerated throughout. Our report suggests that dual immunotherapy alternating with anti-PD-1antibody plus doxorubicin may be a potential treatment modality for epithelioid hemangioendothelioma. However, larger sample studies are necessary to ascertain the effectiveness of this treatment strategy and it is essential to continue monitoring this patient to sustain progression-free survival and overall survival.
Topics: Humans; Male; Doxorubicin; Hemangioendothelioma, Epithelioid; Nivolumab; Prostatic Neoplasms; Programmed Cell Death 1 Receptor; Antineoplastic Combined Chemotherapy Protocols; Immunotherapy; Immune Checkpoint Inhibitors; Ipilimumab; Treatment Outcome; Polyethylene Glycols; Middle Aged
PubMed: 38947327
DOI: 10.3389/fimmu.2024.1384111 -
Frontiers in Immunology 2024Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC... (Comparative Study)
Comparative Study
INTRODUCTION
Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency.
METHODS
We retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m and cyclophosphamide 500 mg/m for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m and cyclophosphamide 500 mg/m for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity.
RESULTS
From June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin's lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2-4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026).
DISCUSSION
As the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen.
Topics: Humans; Immunotherapy, Adoptive; Male; Middle Aged; Female; Antigens, CD19; Vidarabine; Retrospective Studies; Lymphoma, Non-Hodgkin; Aged; Cyclophosphamide; Adult; Lymphocyte Depletion; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; Biological Products; Receptors, Antigen, T-Cell
PubMed: 38947326
DOI: 10.3389/fimmu.2024.1403145