RESUMEN
BACKGROUND: Early neurological deterioration (END) occurs in many patients with acute ischemic stroke due to a variety of causes. Although pharmacologically induced hypertension (PIH) and anticoagulants have been investigated in several clinical trials for the treatment of END, the efficacy and safety of these treatments remain unclear. Here, we investigated whether PIH or anticoagulation is better as a rescue therapy for the progression of END in patients with lacunar stroke. METHODS: This study included patients with lacunar stroke who received rescue therapy with END within 3 days of symptom onset between April 2014 and August 2021. In the PIH group, phenylephrine was administered intravenously for 24 h and slowly tapered when symptoms improved or after 5 days of PIH. In the anticoagulation group, argatroban was administered continuously intravenously for 2 days and twice daily for next 5 days. We compared END recovery, defined as improvement in NIHSS from baseline, excellent outcomes (0 or 1 mRS at 3 months), and safety profile. RESULTS: Among the 4818 patients with the lacunar stroke, END occurred in 147 patients. Seventy-nine patients with END received PIH (46.9%) and 68 patients (46.3%) received anticoagulation therapy. There was no significant difference in age (P = 0.82) and sex (P = 0.87) between the two groups. Compared to the anticoagulation group, the PIH group had a higher incidence of END recovery (77.2% vs. 51.5%, P < 0.01) and excellent outcomes (34.2% vs. 16.2%, P = 0.04). PIH was associated with END (HR 2.49; 95% CI 1.06-5.81, P = 0.04). PIH remained associated with END recovery (adjusted HR 3.91; 95% CI 1.19-12.90, P = 0.02). Safety outcomes, like hemorrhagic conversion and mortality, were not significantly different between the two groups. CONCLUSIONS: As a rescue therapy for the progression of END in lacunar stroke patients, PIH with phenylephrine was more effective with similar safety compared to anticoagulation with argatroban.
Asunto(s)
Anticoagulantes , Accidente Vascular Cerebral Lacunar , Humanos , Masculino , Femenino , Accidente Vascular Cerebral Lacunar/tratamiento farmacológico , Anciano , Persona de Mediana Edad , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Hipertensión/tratamiento farmacológico , Hipertensión/complicaciones , Anciano de 80 o más Años , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Arginina/análogos & derivados , Arginina/uso terapéutico , Arginina/administración & dosificación , Resultado del Tratamiento , Antihipertensivos/uso terapéutico , Antihipertensivos/administración & dosificación , Estudios Retrospectivos , Progresión de la Enfermedad , Ácidos PipecólicosRESUMEN
BACKGROUND: We compared efficacy of vonoprazan-dual or triple therapies and bismuth-quadruple therapy for treatment-naive Helicobacter pylori (HP) infection in Southern China, where primary resistance rates of clarithromycin and levofloxacin are >30%. METHODS: This was an investigator-initiated, three-arm, randomized clinical trial in Southern China. Between March 2022 and August 2023, treatment-naïve HP-infected adults were randomly assigned to receive one of three 14-day regimens (1:1:1 ratio): vonoprazan-dual (VA-dual; vonoprazan 20 mg twice daily and amoxicillin 1 g thrice daily), vonoprazan-triple (VAC-triple; vonoprazan 20 mg/amoxicillin 1 g/clarithromycin 500 mg twice daily), or bismuth-quadruple therapy containing bismuth, esomeprazole, tetracycline, and metronidazole. Primary outcome was noninferiority in HP eradication, evaluated by UBT 4-6 weeks post-treatment by intention-to-treat (ITT) and per-protocol (PP) analysis (based on subjects who completed 14-day treatment and rechecked UBT). Bonferroni-adjusted p-value of <0.017 was used to determine statistical significance. RESULTS: A total of 298 subjects (mean age: 35.7 ± 8.4 years; male: 134 [45.0%]; VC-dual: 100, VAC-triple: 98, bismuth-quadruple: 100) were enrolled, and 292 (98.0%) had UBT rechecked. ITT analysis showed that both VA-dual (eradication rate of 96.0%) and VAC-triple therapies (95.9%) were noninferior to bismuth-quadruple therapy (92.0%) (difference: 4.0%, 95% CI: -2.9% to 11.5%, p < 0.001; and 3.9%, 95% CI: -3.1% to 11.5%, p < 0.001, respectively). PP analysis also revealed noninferiority (96.7% or 96.7% vs. 97.4%, with difference: -2.9% and -2.9%, p = 0.009 and 0.010, respectively). The frequency of adverse events was 39.0%, 56.1%, and 71.0% in VA-dual, VAC-triple, and bismuth-quadruple therapies, respectively. CONCLUSIONS: VA-dual and VA-triple therapies are highly effective and noninferior to bismuth-quadruple therapy in Southern China. Given the lower adverse effects and fewer antibiotic use, VA-dual therapy is the preferred first-line treatment for HP infection. TRIAL REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=14131.
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Antibacterianos , Bismuto , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Pirroles , Sulfonamidas , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Adulto , Helicobacter pylori/efectos de los fármacos , Bismuto/uso terapéutico , Pirroles/uso terapéutico , Pirroles/administración & dosificación , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , China , Resultado del Tratamiento , Claritromicina/uso terapéutico , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Metronidazol/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Adulto Joven , Esomeprazol/uso terapéutico , Esomeprazol/administración & dosificaciónRESUMEN
BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).
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Eptifibatida , Hemorragias Intracraneales , Accidente Cerebrovascular Isquémico , Péptidos , Ácidos Pipecólicos , Sulfonamidas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arginina/administración & dosificación , Arginina/efectos adversos , Arginina/análogos & derivados , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Eptifibatida/administración & dosificación , Eptifibatida/efectos adversos , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Infusiones Intravenosas , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/epidemiología , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/terapia , Péptidos/administración & dosificación , Péptidos/efectos adversos , Péptidos/uso terapéutico , Ácidos Pipecólicos/administración & dosificación , Ácidos Pipecólicos/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Método Simple Ciego , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Terapia Trombolítica/efectos adversos , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Trombectomía/efectos adversos , Trombectomía/métodos , Resultado del Tratamiento , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Incidencia , AdultoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Compuestos Bicíclicos Heterocíclicos con Puentes , Leucemia Linfocítica Crónica de Células B , Sulfonamidas , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of the nine most widely studied Vonoprazan (VPZ)-based treatment regimens along with traditional Proton pump inhibitor (PPI)-based treatment regimens in eradicating Helicobacter pylori (H. pylori) infection. DESIGN: Through searching PubMed, Embase, Cochrane Library, Web of Science, we exclusively included randomized controlled trials (RCTs) to investigate the efficacy of VPZ-based and PPI-based therapies for H. pylori infection. The included studies were evaluated for methodological quality using the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly. RESULTS: The RCTs were collected from the earliest available date up to August 2023. Twenty-one RCTs were included, with a total sample size of 5481. The results of the network meta-analysis showed that the eradication rate of the VPZ-based quadruple 14-day (VPZ-Q14) treatment regimen in Intention-to-treat (ITT) analysis was the highest (SUCRA: 0.874); The eradication rate of the VPZ-based quadruple 10-day (VPZ-Q10) treatment plan in Per-protocol (PP) analysis was the highest (SUCRA: 0.849). All regimens were well tolerated without significant differences. According to the probability ranking of safety, high-dose VPZ-based dual 14-day therapy (H-VPZ-D14) ranked first in SUCRA, reaching 0.952. This indicates that H-VPZ-D14 treatment is the safest with a relatively low incidence of adverse effect. Therefore, VPZ-based therapies not only have a higher eradication rate, but also possess satisfactory safety. CONCLUSION: Compared with traditional PPI-based therapies, VPZ-based therapies have shown superior eradication effects. Based on the Ranking Plot of the Network, the VPZ-Q14 or VPZ-Q10 treatment regimen for H. pylori has a higher eradication rate and acceptable differences compared to other treatment regimens. In addition, for regions with high antibiotic resistance rates, we recommend a 14-day quadruple therapy with bismuth based on VPZ.
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Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Metaanálisis en Red , Inhibidores de la Bomba de Protones , Pirroles , Sulfonamidas , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Pirroles/uso terapéutico , Pirroles/efectos adversos , Pirroles/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Helicobacter pylori/efectos de los fármacos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Lomentospora prolificans is a rare filamentous fungus that causes invasive fungal disease (IFD) in immunocompromised patients with hematological malignancies, as well as hematopoietic cell or solid organ transplant recipients. A 75-year-old woman was diagnosed with acute myeloid leukemia, and started induction therapy with azacitidine and adjusted-dose venetoclax along with antifungal prophylaxis with fluconazole. On day 7, she became febrile and chest CT imaging showed multiple nodules in both lung fields, and the serum galactomannan antigen index became positive, indicating probable IFD. Anti-fungal therapy with liposomal amphotericin B was immediately initiated; however, the patient's condition rapidly deteriorated, and she died on day 15. L. prolificans was later identified in blood culture tests that had been repeatedly performed while she had been febrile. L. prolificans is generally resistant to most antifungal agents, which can make it fatal. As early definitive diagnosis is difficult, it may be appropriate to consider combination therapy when conventional anti-IFD therapy seems inadequate.
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Azacitidina , Compuestos Bicíclicos Heterocíclicos con Puentes , Leucemia Mieloide Aguda , Sulfonamidas , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Anciano , Femenino , Azacitidina/administración & dosificación , Azacitidina/uso terapéutico , Sulfonamidas/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Resultado Fatal , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Quimioterapia de Inducción , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/diagnóstico , Micosis/tratamiento farmacológico , Micosis/diagnósticoAsunto(s)
Antivirales , Tratamiento Farmacológico de COVID-19 , Combinación de Medicamentos , Hospitalización , Huésped Inmunocomprometido , Ritonavir , Humanos , Ritonavir/uso terapéutico , Ritonavir/administración & dosificación , Hospitalización/estadística & datos numéricos , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Citidina/análogos & derivados , Citidina/uso terapéutico , Hidroxilaminas/uso terapéutico , Leucina/análogos & derivados , Leucina/uso terapéutico , Prolina/análogos & derivados , Prolina/uso terapéutico , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , COVID-19/prevención & control , Lactamas , NitrilosRESUMEN
Importance: Serious cutaneous adverse drug reactions (cADRs) are potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. Antibiotics are a recognized cause of these reactions, but no studies have compared relative risks across antibiotic classes. Objectives: To explore the risk of serious cADRs associated with commonly prescribed oral antibiotics, and to characterize outcomes of patients hospitalized for them. Design, Setting, and Participants: Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not. Exposure: Various classes of oral antibiotics. Main Outcomes and Measures: Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group. Results: During the 20-year study period, we identified 21â¯758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87â¯025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital. Conclusion and Relevance: Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate.
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Antibacterianos , Erupciones por Medicamentos , Macrólidos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Administración Oral , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificación , Estudios de Casos y Controles , Cefalosporinas/efectos adversos , Cefalosporinas/administración & dosificación , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Fluoroquinolonas/administración & dosificación , Fluoroquinolonas/efectos adversos , Hospitalización/estadística & datos numéricos , Macrólidos/administración & dosificación , Macrólidos/efectos adversos , Nitrofurantoína/administración & dosificación , Nitrofurantoína/efectos adversos , Ontario/epidemiología , Penicilinas/administración & dosificación , Penicilinas/efectos adversos , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Medición de Riesgo/estadística & datos numéricosRESUMEN
BACKGROUND: We previously optimized the duration and dose of vonoprazan and amoxicillin dual therapy in China. The efficacy of vonoprazan with b.i.d. amoxicillin in comparison with vonoprazan-containing quadruple therapy as the first-line treatment of Helicobacter pylori infection has not been adequately evaluated. METHODS: In a non-inferiority, randomized clinical trial, H. pylori infected and treatment-naïve patients were randomly assigned to receive 14 days of either vonoprazan dual (vonoprazan 20 mg and amoxicillin 1 g twice daily) or quadruple therapy (vonoprazan 20 mg + amoxicillin 1 g + furazolidone 100 mg + bismuth potassium citrate 600 mg twice daily). H. pylori status was confirmed using 13C-urea breath tests or fecal antigen test. The primary outcome was the H. pylori eradication rate following vonoprazan dual and quadruple therapy at 4-12 weeks. We also compared drug compliance to either regimen and documented their side effect. RESULTS: A total of 190 subjects were randomized. The eradication rate of vonoprazan dual and quadruple therapy were 87.4% and 92.6% (p = 0.23) by intention-to-treat analysis, respectively, and 96.5% and 97.7% (p = 0.63) by per-protocol analysis, respectively. The efficacy of vonoprazan dual therapy was non-inferior to vonoprazan-containing quadruple therapy in per-protocol analysis (p < 0.001; difference: -1.2%; 90% confidence interval: -5.4% to 3.0%). CONCLUSION: Vonoprazan with b.i.d. amoxicillin for 14 days provided similar satisfactory efficacy with vonoprazan-containing quadruple therapy as a first-line H. pylori treatment in China.
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Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Pirroles , Sulfonamidas , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Pirroles/uso terapéutico , Pirroles/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Femenino , Persona de Mediana Edad , Masculino , Helicobacter pylori/efectos de los fármacos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Adulto , Resultado del Tratamiento , China , Anciano , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificaciónRESUMEN
OBJECTIVE: To evaluate the efficacy and side effects of venetoclax combined with azacitidine chemotherapy in the treatment of previously untreated adult patients with acute myeloid leukemia(AML). METHODS: A retrospective analysis was performed on 48 untreated adult AML patients admitted to the Department of Hematology, Affiliated Hospital of Jinggangshan University from January 2020 to December 2022. Among them, 26 patients received venetoclax combined with azacitidine chemotherapy (observation group), and 22 patients received daunorubicin plus cytarabine chemotherapy (control group). The differences in complete response (CR) rate, objective response rate (ORR), progressionîfree survival (PFS), overall survival(OS) and adverse reactions (AR) were compared between the two groups. RESULTS: There was no significant difference in age, sex ratio, absolute value of triîlineage cell and proportion of bone marrow primordial cells between the two groups before treatment (all P >0.05). The CR rate and the ORR rate of the observation group was significantly higher than that of the control group (P < 0.05). After treatment, there were no significant difference in the adverse reactions such as myelosuppression, granulocytosis, secondary infection, mucosal damage, liver and kidney damage, cardiotoxicity and gastrointestinal toxicity between the two groups (P >0.05). The median PFS and the median OS of the observation group were significantly better than those of the control group (P < 0.05). CONCLUSION: The remission rate of venetoclax combined with azacitidine was higher than that of conventional chemotherapy in previously untreated adult acute myeloid leukemia. Venetoclax combined with azacitidine chemotherapy could reduce hematologic related side reactions and prolong the remission period and survival of AML patients.
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Protocolos de Quimioterapia Combinada Antineoplásica , Azacitidina , Compuestos Bicíclicos Heterocíclicos con Puentes , Leucemia Mieloide Aguda , Sulfonamidas , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Sulfonamidas/administración & dosificación , Azacitidina/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Estudios Retrospectivos , Masculino , Femenino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto , Persona de Mediana Edad , Citarabina/administración & dosificación , Resultado del TratamientoRESUMEN
A 78-year-old woman with rheumatoid arthritis, who was started on baricitinib five or six months earlier, was referred to our hospital due to a subcutaneous abscess in her right axilla. Contrast-enhanced chest, abdomen, and pelvis computed tomography showed subcutaneous abscesses in her right axilla and lymphadenopathy with calcification. Cultures from the subcutaneous abscess and skin biopsy specimens were positive for Mycobacterium tuberculosis. These findings led to the diagnosis of scrofuloderma associated with tuberculous lymphadenitis. She was started on an antitubercular regimen of isoniazid, rifampicin, pyrazinamide, and ethambutol as the initial phase treatment (first 2 months), followed by isoniazid and rifampicin for 4 months (total 6 months). After 6 months of antitubercular treatment, the abscesses and lymphadenitis disappeared. Although cases of tuberculosis during JAK inhibitor treatment are rare, they are serious adverse events that require caution.
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Antituberculosos , Artritis Reumatoide , Inhibidores de las Cinasas Janus , Pirazoles , Sulfonamidas , Tuberculosis Ganglionar , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Femenino , Anciano , Inhibidores de las Cinasas Janus/efectos adversos , Antituberculosos/efectos adversos , Antituberculosos/administración & dosificación , Sulfonamidas/efectos adversos , Sulfonamidas/administración & dosificación , Pirazoles/efectos adversos , Tuberculosis Ganglionar/tratamiento farmacológico , Tuberculosis Ganglionar/diagnóstico , Purinas/efectos adversos , Purinas/administración & dosificación , Azetidinas/efectos adversos , Azetidinas/administración & dosificación , Tuberculosis Cutánea/diagnóstico , Tuberculosis Cutánea/tratamiento farmacológico , Resultado del Tratamiento , Mycobacterium tuberculosis/aislamiento & purificación , Quimioterapia Combinada , Isoniazida/efectos adversos , Isoniazida/administración & dosificaciónRESUMEN
This study aimed to examine the relationship between blood pressure (BP) and blood pressure variability (BPV) during the first 24 hours from admission with 90-day functional outcomes in acute ischemic stroke (AIS) patients whose onset within 24 hours and receiving early argatroban treatment. The study recruited 214 AIS patients. BP was monitored using a cuff at 1-hour fixed intervals, and BP/BPV parameters [standard deviation (SD), coefficient of variation (CV), successive variation (SV), and average real variability (ARV)] were collected. Age, the National Institutes of Health Stroke Scale (NIHSS) score at admission, previous history of diabetes mellitus (DM), and infarction site (located in anterior circulation) were identified as independent factors affecting 90-day outcomes in multiple logistic regression. After adjusting for confounding variables, association between BP/BPV and 90-day modified Rankin Scale (mRS) was assessed using logistic regression models. In model 1 (adjusted for age and NIHSS score at admission), mean-systolic blood pressure (SBP) showed association with 90-day outcomes [1.068 (1.008, 1.131), Pâ =â .025]. In model 2 (adjusted for age, NIHSS score at admission, previous history of DM), mean-SBP [1.061 (1.001, 1.123), Pâ =â .045] and max-SBP [0.951 (0.906, 0.998), Pâ =â .040] showed relatively weak association with outcomes. In model 3 [adjusted for age, NIHSS score at admission, previous history of DM, infarct site (located in anterior circulation)], all BP values were not related with outcomes, meanwhile, none of the BPV parameters calculated from SBP, diastolic blood pressure and mean arterial pressure showed association with 90-day outcomes. Future prospective studies are required to assess the relationship between early BP/BPV parameters with 90-day outcomes and further clarify the reference values for BP parameters. This is important for effective BP/BPV management and improved patient prognosis.
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Presión Sanguínea , Accidente Cerebrovascular Isquémico , Humanos , Femenino , Masculino , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Anciano , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/fisiopatología , Persona de Mediana Edad , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Resultado del Tratamiento , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Arginina/análogos & derivados , Ácidos PipecólicosRESUMEN
PURPOSE OF REVIEW: To analyze the efficacy and safety of Janus kinase inhibitors (JAKi) in the treatment of pediatric AD. RECENT FINDINGS: Adolescents with moderate and severe atopic dermatitis (AD) need systemic therapies, as stated several recent practice guidelines. (JAKi) have shown their efficacy in the treatment of adult AD, however, there is a lack of information concerning efficacy and safety of their use in pediatric AD. We found that the JAKi's abrocitinib (ABRO), baricitinib (BARI), and upadacitinib (UPA), are all an effective treatment option with a very fast onset of action for adolescents with moderate-to-severe AD. BARI was not effective in children between 2 and 10 years with moderate-to-severe AD. Fortunately, major safety issues with JAKi in adolescents with AD have not been documented in the trials, so far, contrasting with the reports in adults with AD, where these events have very rarely occurred. There are some reports of herpes zoster (HZ) infection in adolescents on JAKi, but it is not a major safety concern. Acne is a relatively common AE with UPA in adolescents; however, it is responsive to standard treatment. This review will help the clinician to choose among the JAKi according to the needs and clinical features of patients with moderate and severe AD. In the following years, with the advent of new biologicals and JAKi, these therapies will fall into place in each phase of the evolution of patients with AD.
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Dermatitis Atópica , Inhibidores de las Cinasas Janus , Humanos , Dermatitis Atópica/tratamiento farmacológico , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/efectos adversos , Inhibidores de las Cinasas Janus/administración & dosificación , Niño , Adolescente , Purinas/uso terapéutico , Administración Oral , Azetidinas/uso terapéutico , Azetidinas/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Pirimidinas/uso terapéutico , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Resultado del TratamientoAsunto(s)
Adenina , Protocolos de Quimioterapia Combinada Antineoplásica , Compuestos Bicíclicos Heterocíclicos con Puentes , Linfoma de Células del Manto , Piperidinas , Sulfonamidas , Humanos , Adenina/análogos & derivados , Piperidinas/uso terapéutico , Piperidinas/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/patología , Pirimidinas/uso terapéutico , Pirimidinas/administración & dosificación , Pirazoles/uso terapéutico , Pirazoles/administración & dosificaciónRESUMEN
Glaucoma is caused by high intraocular pressure, which can causes blindness. Combinations of timolol and dorzolamide are used for its treatment with a requirement of multiple dosing with dosing being twice or four times a day. Conventional eye drops have poor pre-corneal retention and is thus less available for action. This study utilizes principles of Quality by Design for formulation of injectable liposomes coloaded with timolol maleate and dorzolamide HCl, which overcomes limitations of conventional eye drops. For implementation of Quality by Design principles a systematic approach involving defining Quality Target Product Profile, identification of Critical Quality Attributes, mapping Critical Quality Attributes to Critical Process Parameters and Critical Material Attributes, Failure Mode and Effect Analysis based risk assessment, Taguchi screening, and 32 full factorial Design of Experiments design were utilized. A robust model for formulation of coloaded liposomes was successfully developed. Design of Experiments approach allowed to obtain optimized batch having particle size of 116.1 nm, encapsulation efficiency of dorzolamide HCl of 72.12 % and encapsulation efficiency of timolol maleate of 71.94 %. In-vitro drug release showed a sustained release for 4 days. The prepared formulation was in the desired osmolarity range. Biosafety was proved using histopathological characterization. In-vivo studies for assessing the Intra Ocular Pressure reduction showed that there was no significant difference in Intra Ocular Pressure reduction between prepared liposomes and marketed formulation but were superior than marketed formulation because of less fluctuations in Intra Ocular Pressure. Prepared coloaded injectable liposomes lays the foundation for further research in the area and can be translated from to bench side for commercial clinical use.
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Liberación de Fármacos , Presión Intraocular , Liposomas , Sulfonamidas , Tiofenos , Timolol , Timolol/administración & dosificación , Timolol/química , Timolol/farmacocinética , Sulfonamidas/administración & dosificación , Sulfonamidas/química , Sulfonamidas/farmacocinética , Tiofenos/administración & dosificación , Tiofenos/química , Animales , Presión Intraocular/efectos de los fármacos , Composición de Medicamentos/métodos , Tamaño de la Partícula , Conejos , Masculino , Combinación de Medicamentos , Química Farmacéutica/métodos , Antihipertensivos/administración & dosificación , Antihipertensivos/química , Antihipertensivos/farmacocinética , Glaucoma/tratamiento farmacológicoRESUMEN
The FMS-related tyrosine kinase 3 (FLT3) inhibitor gilteritinib is standard therapy for relapsed/refractory (R/R) FLT3-mutated (FLT3mut) acute myeloid leukemia (AML) but the overall survival (OS) is only approximately 20â¯% and few patients achieve deep and/ or durable response. We retrospectively analyzed 29â¯R/R FLT3mut AML patients treated on triplet regimens (gilteritinib+ venetoclaxï¼»VEN] +azacitidineï¼»AZA]). Nineteen patients (65.5â¯%) had received prior FLT3 inhibitor therapy. The modified composite complete remission (mCRc) rate was 62.1â¯% (n = 18; CR, 4/29,13.8â¯%; CRi, 6/29, 20.7â¯%; MLFS, 8/29, 27.6â¯%). Among 18 patients achieved mCRc, FLT3-PCR negativity was 94.4â¯% (n=17), and flow-cytometry negativity was 77.7â¯% (n=14). The mCRc rate was 70â¯% (n=7) in 10 patients without prior FLT3 TKI exposure and 57.8â¯% (n=11) in 19 patients with prior FLT3 TKI exposure (P=0.52). At the end of the first cycle, the median time to ANC > 0.5× 109/L was 38 days and platelet > 50× 109/L was 31 days among responders, but 60-day mortality was 0â¯%. The estimated 2-year OS was 60.9â¯% for all R/R FLT3mut patients. The 1-year OS was 80â¯% and 58.8â¯% in patients without and with prior FLT3 TKI exposure, respectively (P=0.79). The estimated 2-year OS was 62â¯% in 19 (65.5â¯%) patients who received allo-HSCT after triplet therapy and 37â¯% in 10 patients who did not receive allo-HSCT (P=0.03). In conclusion, triplet therapy with gilteritinib, VEN, and AZA is effective and safe and an excellent frontline option for R/R FLT3mut AML.
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Compuestos de Anilina , Protocolos de Quimioterapia Combinada Antineoplásica , Azacitidina , Compuestos Bicíclicos Heterocíclicos con Puentes , Leucemia Mieloide Aguda , Pirazinas , Sulfonamidas , Tirosina Quinasa 3 Similar a fms , Humanos , Tirosina Quinasa 3 Similar a fms/genética , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Masculino , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/genética , Femenino , Persona de Mediana Edad , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Estudios Retrospectivos , Compuestos de Anilina/uso terapéutico , Adulto , Pirazinas/uso terapéutico , Pirazinas/administración & dosificación , Azacitidina/uso terapéutico , Azacitidina/administración & dosificación , Mutación , Tiofenos/uso terapéutico , Tiofenos/administración & dosificación , Resistencia a AntineoplásicosAsunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Puntaje de Propensión , Sulfonamidas , Humanos , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/diagnóstico , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Masculino , Anciano , Femenino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Anciano de 80 o más AñosRESUMEN
The aim of this study was to observe the effects of different conditioning regimens on fine immune indices after microtransplantation (MST) in patients with acute myeloid leukaemia (AML). This article discusses the possible immune mechanism of microtransplantation and describes a more optimized conditioning regimen. A total of 55 AML patients who received MST treatment at the Second Hospital of Lanzhou University from August 2015 to October 2023 were included in this study, and 13 AML patients who did not receive MST but directly received the maintenance therapy were included as the control group (C). The MST patients were divided into a conditioning regimen with venetoclax group (A) and a conditioning regimen without venetoclax group (B). The fine immune indices were detected by flow cytometry and cytometric bead array analysis. Changes in the immune indices before and after treatment were observed, and the progression-free survival (PFS) and overall survival (OS) of patients in the MST group were analysed. Compared with those in Group B, patients in Group A had better PFS and OS. The proportion of Treg cells and the expression level of IL-2 were increased, while TNF-α and IFN-α were decreased after MST (P < 0.05). In Group B, total T cells, CD4+T cells and CD4+/CD8+T cells decreased; NK cells and total B cells increased; and IL-17A first increased and then decreased during the MST (P < 0.05). There were significant differences in total B cells, IL-4 and IFN-γ between Group A and Group B during MST. Moreover, there were significant differences in total T cells, CD4+T cells, Treg cells, IL-17A, IFN-γ and IL-2 between the patients in the MST group and those in the control group (P < 0.05). The MST conditioning regimen containing venetoclax significantly changed the fine immune indices and showed improved efficacy, which is worthy of further study and clinical application.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Acondicionamiento Pretrasplante , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Acondicionamiento Pretrasplante/métodos , Adulto , Trasplante de Células Madre Hematopoyéticas/métodos , Antígenos HLA/inmunología , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Adulto Joven , Linfocitos T Reguladores/inmunología , Anciano , AdolescenteRESUMEN
Background: Chronic myelomonocytic leukemia is a clonal hematological disorder with an inherent risk of transformation to acute myeloid leukemia. Recently, there has been exponential discovery of molecular abnormalities in patients with chronic myelomonocytic leukemia. Some of these mutations independently contribute to a higher risk of transformation and result in inferior overall survival. Treatment strategies for patients undergoing blastic transformation in chronic myelomonocytic leukemia, especially after progressing on hypomethylating agents, are currently limited.Case presentation: We present a case of a 70-year-old male patient with chronic myelomonocytic leukemia blastic transformation with RUNX1 mutation following azacitidine monotherapy. Notably, he achieved hematological complete remission after the first course of venetoclax plus azacitidine, leading to the disappearance of RUNX1 mutation. We performed serial assessments of molecular analysis by next generation sequencing throughout his clinical course.Conclusion: The presence of RUNX1 mutation is associated with higher response rates to venetoclax-based combination therapies in chronic myelomonocytic leukemia with blastic transformation. Our findings suggest that even after azacitidine monotherapy, venetoclax plus azacitidine is effective in targeting leukemic clones harboring RUNX1 mutations. Furthermore, we emphasize the significance of molecular analysis, including next-generation sequencing, in providing insights into the detailed dynamics of clonal evolution and guiding treatment decisions.
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Compuestos Bicíclicos Heterocíclicos con Puentes , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Leucemia Mielomonocítica Crónica , Mutación , Sulfonamidas , Humanos , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Leucemia Mielomonocítica Crónica/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Masculino , Anciano , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Azacitidina/uso terapéutico , Azacitidina/administración & dosificación , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, has demonstrated greater potency and a longer duration of acid suppression when compared to the proton pump inhibitors. However, data regarding the comparison between vonoprazan-based triple therapy with standard treatment for first-line Helicobacter pylori treatment are limited. This study aimed to compare the efficacy between 7-day vonoprazan-based triple therapy with high-dose amoxicillin (VAC-7) and 14-day extended sequential therapy (S-14). MATERIALS AND METHODS: This was a single-center prospective randomized controlled trial following a noninferiority design. Subjects over 20 years old with confirmed H. pylori infection were enrolled prospectively from Fu Jen Catholic University Hospital. They were randomly assigned to the VAC-7 or S-14 group. The primary endpoint was the eradication rate in first-line treatment, evaluated by urea breath test, with noninferiority determined using the Farrington-Manning method. The secondary outcome included adverse effect rates and compliance, assessed through self-administered questionnaires. RESULTS: Between December 2021 and June 2023, a total of 628 patients were recruited. The eradication rates by per-protocol analysis and intention-to-treat analysis were 88.6%/81.8% for VAC-7 and 90.3%/81.4% for S-14, respectively. The VAC-7 was non-inferior to S-14 in terms of ITT analysis. Subjects experienced fewer incidences of nausea, anorexia, dizziness, fatigue, and any severe adverse events in the VAC-7 group. Compliance was higher in the VAC-7 group, with 94% taking all the pills correctly. CONCLUSIONS: Our findings supported the use of 7-day vonoprazan triple therapy with high-dose amoxicillin as the standard first-line treatment for H. pylori infection. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05371249.