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2.
Transpl Int ; 37: 12192, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38328616

RESUMO

Pneumocystis pneumonia (PcP) remains life-threatening in kidney transplant recipients (KTR). Our study investigated risk factors one-year before PcP. We conducted a monocentric, case-control study including all KTR at the Dijon University Hospital (France) with a diagnosis of PcP between 2005 and 2022 (cases), and matched control KTR with no history of PcP (3 controls/case). Among all 1,135 KTR, 57 cases (5%) and 169 matched-controls were included. PcP was associated with 18% mortality. Compared to controls, cases were older, with a higher immunological risk, and CMV infection was more frequent in the year preceding the occurrence of PcP (23% vs. 4%; p < 0.001). As early as 1 year before PcP, lymphocyte counts were lower and serum creatinine levels were higher in cases, but immunosuppressive regimens were not significantly different. Multivariable analysis identified lymphocyte count, serum creatinine level, being treated by immunosuppressive therapy other than anti-rejection drugs, and CMV infection in the year preceding the time PcP as independently associated with the occurrence of PcP. PcP was associated with an increased risk of subsequent chronic rejection (27% vs. 3%; p = 0.001) and return to dialysis (20% vs. 3%; p = 0.002). The occurrence of CMV infection and a low lymphocyte count could redefine the indications for continuation or reinitiation of anti-Pneumocystis prophylaxis.


Assuntos
Infecções por Citomegalovirus , Transplante de Rim , Linfopenia , Pneumocystis carinii , Pneumonia por Pneumocystis , Trombocitopenia , Humanos , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/tratamento farmacológico , Estudos de Casos e Controles , Transplante de Rim/efeitos adversos , Creatinina , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Fatores de Risco , Linfopenia/complicações , Trombocitopenia/complicações , Transplantados , Estudos Retrospectivos
3.
Lancet Haematol ; 11(2): e101-e113, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38302221

RESUMO

BACKGROUND: The aim of this trial was to investigate the addition of the anti-SLAMF7 monoclonal antibody elotuzumab to lenalidomide, bortezomib, and dexamethasone (RVd) in induction and consolidation therapy as well as to lenalidomide maintenance treatment in transplant-eligible patients with newly diagnosed multiple myeloma. METHODS: GMMG-HD6 was a phase 3, randomised trial conducted at 43 main trial sites and 26 associated trial sites throughout Germany. Adult patients (aged 18-70 years) with previously untreated, symptomatic multiple myeloma, and a WHO performance status of 0-3, with 3 being allowed only if caused by myeloma disease and not by comorbid conditions, were randomly assigned 1:1:1:1 to four treatment groups. Induction therapy consisted of four 21-day cycles of RVd (lenalidomide 25 mg orally on days 1-14; bortezomib 1·3 mg/m2 subcutaneously on days 1, 4, 8, and 11]; and dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11, 12, and 15 for cycles 1-2) or, RVd induction plus elotuzumab (10 mg/kg intravenously on days 1, 8, and 15 for cycles 1-2, and on days 1 and 11 for cycles 3-4; E-RVd). Autologous haematopoietic stem-cell transplantation was followed by two 21-day cycles of either RVd consolidation (lenalidomide 25 mg orally on days 1-14; bortezomib 1·3 mg/m2 subcutaneously on days 1, 8, and 15; and dexamethasone 20 mg orally on days 1, 2, 8, 9, 15, and 16) or elotuzumab plus RVd consolidation (with elotuzumab 10 mg/kg intravenously on days 1, 8, and 15) followed by maintenance with either lenalidomide (10 mg orally on days 1-28 for cycles 1-3; thereafter, up to 15 mg orally on days 1-28; RVd/R or E-RVd/R group) or lenalidomide plus elotuzumab (10 mg/kg intravenously on days 1 and 15 for cycles 1-6, and on day 1 for cycles 7-26; RVd/E-R or E-RVd/E-R group) for 2 years. The primary endpoint was progression-free survival analysed in a modified intention-to-treat (ITT) population. Safety was analysed in all patients who received at least one dose of trial medication. This trial is registered with ClinicalTrials.gov, NCT02495922, and is completed. FINDINGS: Between June 29, 2015, and on Sept 11, 2017, 564 patients were included in the trial. The modified ITT population comprised 559 (243 [43%] females and 316 [57%] males) patients and the safety population 555 patients. After a median follow-up of 49·8 months (IQR 43·7-55·5), there was no difference in progression-free survival between the four treatment groups (adjusted log-rank p value, p=0·86), and 3-year progression-free survival rates were 69% (95% CI 61-77), 69% (61-76), 66% (58-74), and 67% (59-75) for patients treated with RVd/R, RVd/E-R, E-RVd/R, and E-RVd/E-R, respectively. Infections (grade 3 or worse) were the most frequently observed adverse event in all treatment groups (28 [20%] of 137 for RVd/R; 32 [23%] of 138 for RVd/E-R; 35 [25%] of 138 for E-RVd/R; and 48 [34%] of 142 for E-RVd/E-R). Serious adverse events (grade 3 or worse) were observed in 68 (48%) of 142 participants in the E-RVd/E-R group, 53 (39%) of 137 in the RVd/R, 53 (38%) of 138 in the RVd/E-R, and 50 (36%) of 138 in the E-RVd/R (36%) group. There were nine treatment-related deaths during the study. Two deaths (one sepsis and one toxic colitis) in the RVd/R group were considered lenalidomide-related. One death in the RVd/E-R group due to meningoencephalitis was considered lenalidomide and elotuzumab-related. Four deaths (one pulmonary embolism, one septic shock, one atypical pneumonia, and one cardiovascular failure) in the E-RVd/R group and two deaths (one sepsis and one pneumonia and pulmonary fibrosis) in the E-RVd/E-R group were considered related to lenalidomide or elotuzumab, or both. INTERPRETATION: Addition of elotuzumab to RVd induction or consolidation and lenalidomide maintenance in patients with transplant-eligible newly diagnosed multiple myeloma did not provide clinical benefit. Elotuzumab-containing therapies might be reserved for patients with relapsed or refractory multiple myeloma. FUNDING: Bristol Myers Squibb/Celgene and Chugai.


Assuntos
Anticorpos Monoclonais Humanizados , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Pneumonia , Sepse , Adulto , Masculino , Feminino , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/diagnóstico , Lenalidomida/efeitos adversos , Bortezomib/efeitos adversos , Dexametasona/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Autólogo , Pneumonia/etiologia , Sepse/induzido quimicamente , Sepse/tratamento farmacológico
4.
JBJS Rev ; 12(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38315777

RESUMO

¼ The sacroiliac joint (SIJ) is a common cause of low back pain and should be included in the differential diagnosis.¼ Nonoperative treatment of sacroiliac pain is always the first line of therapy; however, when it is unsuccessful and becomes chronic, then recurrent nonoperative treatment becomes expensive.¼ Surgical treatment is cost-effective in appropriately selected patients. High-quality clinical trials have demonstrated statistically and clinically significant improvement compared with nonsurgical management in appropriately selected patients.¼ Spinal fusion to the sacrum increases degeneration of the SIJ and frequency of SIJ pain.


Assuntos
Dor Lombar , Fusão Vertebral , Humanos , Artralgia/etiologia , Dor Lombar/diagnóstico , Dor Lombar/etiologia , Dor Lombar/terapia , Articulação Sacroilíaca/diagnóstico por imagem , Articulação Sacroilíaca/cirurgia , Fusão Vertebral/efeitos adversos , Coluna Vertebral
5.
NEJM Evid ; 3(2): EVIDoa2300144, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38320486

RESUMO

Nab-Paclitaxel plus Gemcitabine and FOLFOXThis randomized, open-label, phase II trial compared nab-paclitaxel/gemcitabine followed by modified FOLFOX versus nab-paclitaxel/gemcitabine alone for the first-line treatment of metastatic pancreatic ductal adenocarcinoma. Patients receiving nab-paclitaxel plus gemcitabine followed by modified FOLFOX-6 (oxaliplatin, leucovorin, and 5-fluorouracil) had a 12-month and 24-month overall survival of 55.3% and 22.4%, respectively, compared with 35.4% and 7.6% in the control group; there was a higher incidence of grade 3 or higher neutropenia and thrombocytopenia. No significant differences in febrile neutropenia, epistaxis or hemorrhage of grade 3 or higher in either group were reported. Two toxic deaths (2.6%) occurred in the experimental group.


Assuntos
Albuminas , Gencitabina , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/efeitos adversos , Paclitaxel/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico
6.
BMC Anesthesiol ; 24(1): 52, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321436

RESUMO

BACKGROUND: Postpartum depression (PPD) following a cesarean delivery is a frequently seen complication. Despite the prophylactic effects of ketamine, the impact of esketamine on PPD in women undergoing cesarean section remains uncertain. This study aimed to assess the effectiveness of esketamine as an adjunct to patient-controlled intravenous analgesia (PCIA) in preventing PPD in women undergoing caesarean section. METHODS: A total of 275 parturients undergoing caesarean section and subsequent patient-controlled intravenous analgesia (PCIA) were randomly assigned to receive either the control treatment (sufentanil 2 µg/kg + tropisetron 10 mg) or the experimental treatment with additional esketamine (1.5 mg/kg). The primary outcome measured was the incidence of postpartum depression (PPD), classified by Edinburgh Postnatal Depression Scale (EPDS) scores equal to or greater than 13 indicating PPD. Secondary outcomes included cumulative sufentanil consumption during specific time periods (0-24 h, 24-48 h, and 0-48 h) after the surgical procedure and numerical rating scale (NRS) scores at rest and during movements. RESULTS: The final analysis included a total of 246 postpartum women who had undergone caesarean delivery. On postoperative day 42, the incidence of depression among the control group was 17.6%, which was significantly higher compared to the esketamine group with a rate of 8.2% (P = 0.02). The EPDS scores also showed a significant difference between the two groups, with a mean score of 9.02 ± 2.21 in the control group and 6.87 ± 2.14 in the esketamine group (p < 0.0001). In terms of pain management, the esketamine group showed lower sufentanil consumption in the 0-24 h (42.5 ± 4.58 µg vs. 50.15 ± 5.47 µg, P = 0.04) and 0-48 h (87.40 ± 9.51 µg vs. 95.10 ± 9.36 µg, P = 0.04) postoperative periods compared to the control group. Differences in movement were also observed between the two groups at 24 and 48 h after the cesarean Sect. (3.39 ± 1.57 vs. 4.50 ± 0.80, P = 0.02; 2.43 ± 0.87 vs. 3.56 ± 0.76, P = 0.02). It is worth noting that the frequency of side effects observed in both groups was comparable. CONCLUSIONS: Esketamine at a dose of 1.5 mg/kg, when used as a supplement in PCIA, has been shown to significantly reduce the occurrence of PPD within 42 days. Additionally, it has been found to decrease cumulative consumption of sufentanil over a 48-hour period following cesarean operation, all without increasing the rate of adverse effects. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry (ChiCTR2200067054) on December 26, 2022.


Assuntos
Depressão Pós-Parto , Ketamina , Feminino , Humanos , Gravidez , Cesárea/efeitos adversos , Depressão Pós-Parto/tratamento farmacológico , Dor/tratamento farmacológico , Manejo da Dor , Dor Pós-Operatória/tratamento farmacológico , Sufentanil , Método Duplo-Cego
7.
Acta Cir Bras ; 39: e390424, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38324800

RESUMO

PURPOSE: To conduct a systematic literature review with meta-analysis to identify whether antibiotic prophylaxis after removal of the indwelling urinary catheter reduces posterior infections. METHODS: A systematic literature review was conducted in the databases PubMed, Embase, Cochrane, Google Scholar, and Latin American and Caribbean Health Sciences Literature, using the keywords "antibiotics" AND "prostatectomy" AND "urinary catheter." RESULTS: Three articles were identified having the scope of our review, with 1,040 patients, which were subjected to our meta-analysis revealing a marginally significant decrease in the risk of urinary infection after indwelling urinary catheter removal (odds ratio-OR = 0.51; 95% confidence interval-95%CI 0.27-0.98; p = 0.04; I2 = 0%). No difference was found regarding the presence of bacteriuria (OR = 0.39; 95%CI 0.12-1.24; p = 0.11; I2 = 73%). CONCLUSIONS: In our meta-analysis, there was a significant decrease in urinary tract infection with antibiotic prophylaxis after indwelling urinary catheter removal following radical prostatectomy.


Assuntos
Antibioticoprofilaxia , Infecções Urinárias , Humanos , Masculino , Cateterismo Urinário/efeitos adversos , Infecções Urinárias/etiologia , Infecções Urinárias/prevenção & controle , Infecções Urinárias/tratamento farmacológico , Antibacterianos/uso terapêutico , Cateteres de Demora/efeitos adversos , Prostatectomia/efeitos adversos
8.
Sci Rep ; 14(1): 3144, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326538

RESUMO

The objective of this study was to evaluate the predictive value of the Geriatric Nutritional Risk Index (GNRI) combined with the Systemic Immunoinflammatory Index (SII) for the risk of major adverse cardiovascular events (MACE) following percutaneous coronary intervention in elderly patients with acute coronary syndrome (ACS). We retrospectively reviewed the medical records of 1202 elderly patients with acute coronary syndromes divided into MACE and non-MACE groups according to whether they had a MACE. The sensitivity analysis utilized advanced machine learning algorithms to preliminarily identify the critical role of GNRI versus SII in predicting MACE risk. We conducted a detailed analysis using a restricted cubic spline approach to investigate the nonlinear relationship between GNRI, SII, and MACE risk further. We constructed a clinical prediction model based on three key factors: GNRI, SII, and Age. To validate the accuracy and usefulness of this model, we compared it to the widely used GRACE score using subject work and recall curves. Additionally, we compared the predictive value of models and GRACE scores in assessing the risk of MACE using the Integrated Discriminant Improvement Index (IDI) and the Net Reclassification Index (NRI). This study included 827 patients. The GNRI scores were lower in the MACE group than in the non-MACE group, while the SII scores were higher in the MACE group (P < 0.001). The multifactorial analysis revealed a low GNRI (OR = 2.863, 95% CI: 2.026-4.047, P = 0.001), High SII (OR = 3.102, 95% CI: 2.213-4.348, P = 0.001). The area under the curve (AUC) for the predictive model was 0.778 (95% CI: 0.744-0.813, P = 0.001), while the AUC for the GRACE score was 0.744 (95% CI: 0.708-0.779, P = 0.001). NRI was calculated to be 0.5569, with NRI + at 0.1860 and NRI- at 0.3708. The IDI was found to be 0.0571, with a P-value of less than 0.001. These results suggest that the newly developed prediction model is more suitable for use with the population in this study than the GRACE score. The model constructed using GNRI and SII demonstrated good standardization and clinical impact, as evidenced by the standard, DCA, and clinical impact curves. The study shows that combining GNRI and SII can be a simple, cost-effective, and valuable way to predict the risk of MACE within one year in elderly acute coronary syndromes.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Humanos , Idoso , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/etiologia , Prognóstico , Estudos Retrospectivos , Modelos Estatísticos , Intervenção Coronária Percutânea/efeitos adversos , Medição de Risco
9.
Environ Health ; 23(1): 16, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326853

RESUMO

BACKGROUND: Redlining has been associated with worse health outcomes and various environmental disparities, separately, but little is known of the interaction between these two factors, if any. We aimed to estimate whether living in a historically-redlined area modifies the effects of exposures to ambient PM2.5 and extreme heat on mortality by non-external causes. METHODS: We merged 8,884,733 adult mortality records from thirteen state departments of public health with scanned and georeferenced Home Owners Loan Corporation (HOLC) maps from the University of Richmond, daily average PM2.5 from a sophisticated prediction model on a 1-km grid, and daily temperature and vapor pressure from the Daymet V4 1-km grid. A case-crossover approach was used to assess modification of the effects of ambient PM2.5 and extreme heat exposures by redlining and control for all fixed and slow-varying factors by design. Multiple moving averages of PM2.5 and duration-aware analyses of extreme heat were used to assess the most vulnerable time windows. RESULTS: We found significant statistical interactions between living in a redlined area and exposures to both ambient PM2.5 and extreme heat. Individuals who lived in redlined areas had an interaction odds ratio for mortality of 1.0093 (95% confidence interval [CI]: 1.0084, 1.0101) for each 10 µg m-3 increase in same-day ambient PM2.5 compared to individuals who did not live in redlined areas. For extreme heat, the interaction odds ratio was 1.0218 (95% CI 1.0031, 1.0408). CONCLUSIONS: Living in areas that were historically-redlined in the 1930's increases the effects of exposures to both PM2.5 and extreme heat on mortality by non-external causes, suggesting that interventions to reduce environmental health disparities can be more effective by also considering the social context of an area and how to reduce disparities there. Further study is required to ascertain the specific pathways through which this effect modification operates and to develop interventions that can contribute to health equity for individuals living in these areas.


Assuntos
Poluentes Atmosféricos , Calor Extremo , Humanos , Adulto , Estudos Cross-Over , Calor Extremo/efeitos adversos , Material Particulado/efeitos adversos , Material Particulado/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise
10.
Cancer Biol Ther ; 25(1): 2312602, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38327067

RESUMO

OBJECTIVE: Axitinib is an oral multi-target tyrosine kinase inhibitor used for the treatment of renal cell carcinoma (RCC). Because of the severe adverse events (AEs) associated with axitinib, patients often need dose reductions or discontinue its use, highlighting the need for effective biomarkers to assess efficacy and/or AEs. The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in genes involved in the pharmacodynamic action of axitinib and clinical prognosis and AEs in metastatic RCC (mRCC) patients. METHODS: This study included 80 mRCC patients treated with first-, second-, or third-line axitinib (5 mg orally twice daily). Clinical parameters and genetic polymorphisms were examined in 75 cases (53 males and 22 females). We assessed three SNPs in each of three candidate genes namely, angiotensin-converting enzyme (ACE), nitric oxide synthase 3 (NOS3), and angiotensin II receptor type 1 (AT1R), all of which are involved in axitinib effects on vascular endothelial function. RESULTS: Axitinib-treated patients carrying the ACE deletion allele suffered more frequently from hand-foot syndrome and a deterioration in kidney function (p = .045 and p = 0.005, respectively) whereas those carrying the NOS3 G allele suffered more frequently from proteinuria and multiple AEs (p = .025 and p = 0.036, respectively). CONCLUSIONS: Our study found that the ACE deletion allele and the NOS3 G allele are associated with increased AEs.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Masculino , Feminino , Axitinibe/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/patologia , Indazóis/efeitos adversos , Polimorfismo de Nucleotídeo Único , Antineoplásicos/uso terapêutico
11.
Clin Exp Med ; 24(1): 33, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329593

RESUMO

Therapy-related myelodysplastic syndrome (t-MDS) is defined as a complication in patients with cancer following exposure to chemotherapy and/or radiotherapy and has an inferior outcome compared with de novo myelodysplastic syndrome (de novo MDS). This study aimed to estimate and compare the clinical outcomes of haploidentical stem cell transplantation (haplo-HSCT) for t-MDS and de novo MDS. We retrospectively analyzed 96 patients with MDS who received haplo-HSCT between January 2015 and December 2021. Eleven patients with t-MDS and 85 patients with de novo MDS were matched using the case-pair method in a 1:8 ratio with the following pairing criteria: (1) sex, (2) age (± 5 years), (3) year of haplo-HSCT (± 2 years), and (4) blast cell counts (≥ 5% or not). The 3-year overall survival and disease-free survival after haplo-HSCT for t-MDS versus de novo MDS patients were 72.7% versus 75.1% (P = 0.99) and 54.5% versus 67.0% (P = 0.50), respectively. The 3-year cumulative incidence of relapse was 36.4% versus 15.5% (P = 0.08), respectively. In multivariate analysis, there was no difference in relapse between t-MDS and de novo MDS. The 3-year cumulative non-relapse mortality rates were 9.1% versus 17.6% (P = 0.45), respectively. This study confirmed the comparable clinical outcomes of haplo-HSCT on the prognosis of t-MDS and de novo MDS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Segunda Neoplasia Primária , Humanos , Estudos Retrospectivos , Síndromes Mielodisplásicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Recidiva
12.
J Glob Health ; 14: 04032, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38299774

RESUMO

*Joint senior authorship. BACKGROUND: Previous studies have observed the adverse effects of ambient fine particulate matter pollution (PM2.5) on heart failure (HF). However, evidence regarding the impacts of specific PM2.5 components remains scarce. METHODS: We included 58 129 patients hospitalised for HF between 2013 and 2017 in 11 cities of Shanxi, China from inpatient discharge database. We evaluated exposure to PM2.5 and its components ((sulphate (SO42-), nitrate (NO3-), ammonium (NH4+), organic matter (OM) and black carbon (BC)), along with meteorological factors using bilinear interpolation at each patients' residential address. We used multivariable logistic and linear regression models to assess the associations of these components with in-hospital case fatality, hospital expenses, and length of hospital stay. RESULTS: Increase equivalents to the interquartile range (IQR) in OM (odds ratio (OR) = 1.13; 95% confidence interval (CI) = 1.02, 1.26) and BC (OR = 1.14; 95% CI = 1.02, 1.26) were linked to in-hospital case fatality. Per IQR increments in PM2.5, SO42-, NO3-, OM, and BC were associated with cost increases of 420.62 (95% CI = 285.75, 555.49), 221.83 (95% CI = 96.95, 346.71), 214.93 (95% CI = 68.66, 361.21), 300.06 (95% CI = 176.96, 423.16), and 303.09 (95% CI = 180.76, 425.42) CNY. Increases of 1 IQR in PM2.5, SO42-, OM, and BC were associated with increases in length of hospital stay of 0.10 (95% CI = 0.02, 0.19), 0.09 (95% CI = 0.02, 0.17), 0.10 (95% CI = 0.03, 0.17), and 0.16 (95% CI = 0.08, 0.23) days. CONCLUSIONS: Our findings suggest that ambient SO42-, OM, and BC might be significant risk factors for HF, emphasising the importance of formulating customised guidelines for the chemical constituents of PM and controlling the emissions of the most dangerous components.


Assuntos
Poluentes Atmosféricos , Insuficiência Cardíaca , Humanos , Material Particulado/toxicidade , Material Particulado/análise , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Tempo de Internação , China/epidemiologia , Exposição Ambiental/efeitos adversos
13.
J Clin Invest ; 134(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38299590

RESUMO

Breast implant illness (BII) is a poorly understood disease in which patients develop symptoms typical of autoimmune conditions following breast implantation. There is no known underlying cause, and patients often resort to breast implant removal and capsulectomy to alleviate symptoms. In this issue of the JCI, Khan and colleagues examined 86 breast explants from patients that reported BII symptoms and 55 control explants. The BII group showed a disproportionally high degree of biofilm, which was associated with oxylipin (10-HOME) on the implant surfaces. Injections of 10-HOME in the mammary fat pad of a murine model recapitulated BII symptoms and increased Th1 cell populations. Notably, macrophages in the periprosthetic tissue from BII patients were more likely to exhibit a proinflammatory phenotype, and naive T cells exposed to 10-HOME caused naive macrophages to differentiate to a proinflammatory phenotype. This work provides a pathophysiologic mechanism for a currently understudied and poorly characterized disease.


Assuntos
Implante Mamário , Implantes de Mama , Feminino , Humanos , Camundongos , Animais , Implantes de Mama/efeitos adversos , Oxilipinas , Biofilmes , Imunidade
14.
J Investig Med High Impact Case Rep ; 12: 23247096231210337, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38299604

RESUMO

There have been studies published regarding the association between developing Brugada syndrome after an acute COVID-19 infection. In this case, we present a patient who presented with a syncopal episode and subsequently found to have Type I Brugada pattern on electrocardiogram. The patient underwent placement of a single chamber defibrillator. Genetic analysis demonstrated SCN5A variant which is associated with cardiac conditions including Brugada syndrome.


Assuntos
Síndrome de Brugada , COVID-19 , Humanos , Vacinas contra COVID-19/efeitos adversos
15.
Cereb Cortex ; 34(2)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38300175

RESUMO

Methamphetamine is a highly addictive psychostimulant drug that is abused globally and is a serious threat to health worldwide. Unfortunately, the specific mechanism underlying addiction remains unclear. Thus, this study aimed to investigate the characteristics of functional connectivity in the brain network and the factors influencing methamphetamine use disorder in patients using magnetic resonance imaging. We included 96 abstinent male participants with methamphetamine use disorder and 46 age- and sex-matched healthy controls for magnetic resonance imaging. Compared with healthy controls, participants with methamphetamine use disorder had greater impulsivity, fewer small-world attributes of the resting-state network, more nodal topological attributes in the cerebellum, greater functional connectivity strength within the cerebellum and between the cerebellum and brain, and decreased frontoparietal functional connectivity strength. In addition, after controlling for covariates, the partial correlation analysis showed that small-world properties were significantly associated with methamphetamine use frequency, psychological craving, and impulsivity. Furthermore, we revealed that the small-word attribute significantly mediated the effect of methamphetamine use frequency on motor impulsivity in the methamphetamine use disorder group. These findings may further improve our understanding of the neural mechanism of impulse control dysfunction underlying methamphetamine addiction and assist in exploring the neuropathological mechanism underlying methamphetamine use disorder-related dysfunction and rehabilitation.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Estimulantes do Sistema Nervoso Central , Metanfetamina , Humanos , Masculino , Metanfetamina/efeitos adversos , Encéfalo/diagnóstico por imagem , Transtornos Relacionados ao Uso de Anfetaminas/diagnóstico por imagem , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Mapeamento Encefálico , Imageamento por Ressonância Magnética
16.
BMC Cancer ; 24(1): 163, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302933

RESUMO

BACKGROUND: Despite advancements in managing metastatic clear cell renal carcinoma (mccRCC) through antiangiogenic tyrosine kinase inhibitors and immunotherapy, there remains a demand for novel treatments for patients experiencing progression despite the use of these medications. There is currently no established standard treatment for patients receiving third therapy line. Prostate Specific Membrane Antigen (PSMA) whose high expression has been demonstrated in metastatic aggressive prostate adenocarcinoma is also highly expressed in neovessels of various solid tumors including renal cell carcinoma (RCC): 86% of clear cell RCC, 61% of chromophobe RCC, and 28% of papillary RCC. Therefore, PSMA may be a target expressed in metastatic ccRCC for radionuclide therapy using PSMA ligands radiolabeled with Lutetium-177 (PRLT). 177Lu-PSMA delivers ß-particle radiation to PSMA-expressing cells and the surrounding microenvironment with demonstrated efficacy in metastatic prostate cancer. METHODS: This is a multicenter phase I/II study designed to assess the tolerability and effectiveness of 177Lu-PSMA-1 in individuals with PSMA-positive metastatic clear cell renal cell carcinoma (ccRCC), identified through 68Ga-PSMA PET, conducted in France (PRadR). 48 patients will be treated with 4 cycles of 7.4 GBq of 177Lu-PSMA-1 every 6 weeks. The primary objective is to evaluate the safety of 177Lu-PSMA-1 (phase I) and the efficacy of 177Lu-PSMA-1 in mccRCC patients (phase II). Primary endpoints are incidence of Severe Toxicities (ST) occurring during the first cycle (i.e. 6 first weeks) and disease Control Rate after 24 weeks of treatment (DCR24w) as per RECIST V1.1. Secondary objective is to further document the clinical activity of 177Lu-PSMA-1 in mccRCC patients (duration of response (DoR), best overall response rate (BORR), progression fee survival (PFS) and overall survival (OS). DISCUSSION: Our prospective study may lead to new potential indications for the use of 177Lu-PSMA-1 in mccRCC patients and should confirm the efficacy and safety of this radionuclide therapy with limited adverse events. The use of 177Lu-PSMA-1may lead to increase disease control, objective response rate and the quality of life in mccRCC patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06059014.


Assuntos
Antígenos de Superfície , Carcinoma de Células Renais , Glutamato Carboxipeptidase II , Neoplasias Renais , Lutécio , Radioisótopos , Compostos Radiofarmacêuticos , Humanos , Masculino , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/tratamento farmacológico , Dipeptídeos/efeitos adversos , Dipeptídeos/uso terapêutico , Compostos Heterocíclicos com 1 Anel/efeitos adversos , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Lutécio/efeitos adversos , Lutécio/uso terapêutico , Estudos Prospectivos , Qualidade de Vida , Radioisótopos/efeitos adversos , Radioisótopos/uso terapêutico , Resultado do Tratamento , Microambiente Tumoral , Feminino , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/radioterapia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Estudos Multicêntricos como Assunto , Antígenos de Superfície/metabolismo , Glutamato Carboxipeptidase II/antagonistas & inibidores , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/uso terapêutico
17.
Cancer Prev Res (Phila) ; 17(2): 47-49, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38303649

RESUMO

From risk association between acute promyelocytic leukemia (APL) and obese-overweight individuals, Mazzarella and colleagues hypothesized that a high-fat diet (HFD) promotes development of APL. Using mouse APL model (PML-RARα knock-in), the authors demonstrated that linoleic acid drives activation of PPARδ in hematopoietic progenitors, and that activation of PPARδ increases proliferation of progenitor cells with PML-RARA expression toward APL. Involvements of PPARδ on regulation of stem cell renewal and proliferation were shown in colorectal cancers earlier, but this study newly demonstrates in hematopoietic progenitors, while suggesting use of diet rich in linoleic acid with caution. See related article by Mazzarella et al., p. 59.


Assuntos
Leucemia Promielocítica Aguda , PPAR delta , Camundongos , Animais , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácido Linoleico , Proteínas de Fusão Oncogênica , Tretinoína
18.
Clin Transl Med ; 14(2): e1529, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38303609

RESUMO

OBJECTIVE: Our study was to elucidate the role of RNA helicase DEAD-Box Helicase 17 (DDX17) in NAFLD and to explore its underlying mechanisms. METHODS: We created hepatocyte-specific Ddx17-deficient mice aim to investigate the impact of Ddx17 on NAFLD induced by a high-fat diet (HFD) as well as methionine and choline-deficient l-amino acid diet (MCD) in adult male mice. RNA-seq and lipidomic analyses were conducted to depict the metabolic landscape, and CUT&Tag combined with chromatin immunoprecipitation (ChIP) and luciferase reporter assays were conducted. RESULTS: In this work, we observed a notable increase in DDX17 expression in the livers of patients with NASH and in murine models of NASH induced by HFD or MCD. After introducing lentiviruses into hepatocyte L02 for DDX17 knockdown or overexpression, we found that lipid accumulation induced by palmitic acid/oleic acid (PAOA) in L02 cells was noticeably weakened by DDX17 knockdown but augmented by DDX17 overexpression. Furthermore, hepatocyte-specific DDX17 knockout significantly alleviated hepatic steatosis, inflammatory response and fibrosis in mice after the administration of MCD and HFD. Mechanistically, our analysis of RNA-seq and CUT&Tag results combined with ChIP and luciferase reporter assays indicated that DDX17 transcriptionally represses Cyp2c29 gene expression by cooperating with CCCTC binding factor (CTCF) and DEAD-Box Helicase 5 (DDX5). Using absolute quantitative lipidomics analysis, we identified a hepatocyte-specific DDX17 deficiency that decreased lipid accumulation and altered lipid composition in the livers of mice after MCD administration. Based on the RNA-seq analysis, our findings suggest that DDX17 could potentially have an impact on the modulation of lipid metabolism and the activation of M1 macrophages in murine NASH models. CONCLUSION: These results imply that DDX17 is involved in NASH development by promoting lipid accumulation in hepatocytes, inducing the activation of M1 macrophages, subsequent inflammatory responses and fibrosis through the transcriptional repression of Cyp2c29 in mice. Therefore, DDX17 holds promise as a potential drug target for the treatment of NASH.


Assuntos
Transtornos do Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Masculino , Camundongos , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fibrose , Expressão Gênica , Metabolismo dos Lipídeos/genética , Transtornos do Metabolismo dos Lipídeos/genética , Lipídeos , Luciferases/metabolismo , Macrófagos/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Progressão da Doença
19.
J Drugs Dermatol ; 23(2): 9-16, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306138

RESUMO

BACKGROUND: Modified Kligman's formula (mKF) is the gold standard treatment for melasma; however, its prolonged use is not recommended due to side effects. Cysteamine is a potent, safe, and effective depigmenting agent. Here, we conducted a double-blind, randomized, and placebo-controlled clinical trial to assess the efficacy of cysteamine isobionic-amide -- a complex with enhanced depigmenting efficacy -- and compared it to mKF for the treatment of melasma. METHODS: This study involved a total of 80 patients divided into 3 groups: cysteamine-isobionic amide, placebo, or mKF. The modified Melasma Area Severity Index (mMASI) score and spectrophotometric evaluation were conducted at baseline, week 4, week 8, and week 16. Dermatological assessment, patients’ feedback, and satisfaction including quality-of-life scores were also collected. RESULTS: At week 4, cysteamine isobionic-amide and mKF groups showed an equivalent onset of action in terms of mMASI and skin pigmentation contrast reduction. The 2 groups significantly reduced melasma severity and improved the overall skin condition with a comparable efficacy at week 16. Quality of life of melasma patients was significantly improved in the cysteamine isobionic-amide group at week 8 and further at week 16 (P<0.001) compared to the mKF group. Patients’ feedback and satisfaction were higher with the cysteamine isobionic-amide product compared to mKF. CONCLUSION: Cysteamine isobionic-amide provided a rapid onset of action and was as effective as the mKF for the treatment of melasma. The data suggest that cysteamine isobionic-amide could potentially be an acceptable alternative to mKF for the long-term treatment of melasma. J Drugs Dermatol. 2024;23(2):9-16.  doi:10.36849/JDD.7428.


Assuntos
Cisteamina , Melanose , Humanos , Cisteamina/efeitos adversos , Resultado do Tratamento , Qualidade de Vida , Melanose/diagnóstico , Melanose/tratamento farmacológico , Método Duplo-Cego
20.
Sci Rep ; 14(1): 2801, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307870

RESUMO

Several reports stated that erythema multiforme (EM) was associated with COVID-19 with detrimental outcomes in patients. However, since most of these are case reports, it is challenging to quantitively assess their associations. Therefore, our study aims to determine the prevalence of EM in the context of COVID-19. The study was designed as a retrospective cross-sectional hospital-based study of registered patients at the University of Florida Health Hospital. The ICD-10 codes for EM, COVID-19 infection, and COVID-19 vaccines were searched in the database. The odds ratio was calculated to assess the risk of EM after COVID-19 infection or vaccination. Our study included 43,547 patients with a history of COVID-19 infection, of whom 92 developed EM. Patients with COVID-19 infection were 6.68 times more likely to have EM than those without COVID-19 (P < 0.0001). Similarly, the risk of developing EM after COVID-19 vaccination was 2.7, significantly higher than the general population (P < 0.0001). The prevalence of EM following COVID-19 infection or vaccination significantly differs from the general population, highlighting the importance of monitoring patients for EM after COVID-19 infection and/or vaccination. It is imperative to disseminate awareness to clinicians and patients regarding the impact of COVID-19 on EM.


Assuntos
COVID-19 , Eritema Multiforme , Humanos , Vacinas contra COVID-19/efeitos adversos , Estudos Retrospectivos , Prevalência , Estudos Transversais , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/complicações , Eritema Multiforme/epidemiologia , Eritema Multiforme/etiologia , Vacinação/efeitos adversos
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