RESUMEN
Hypertrophic scar (HS) tends to raised above skin level with high inflammatory microenvironment and excessive proliferation of myofibroblasts. The HS therapy remains challenging due to dense scar tissue which makes it hard to penetrate, and the side effects resulting from intralesional corticosteroid injection which is the mainstay treatment in clinic. Herein, bilayer microneedle patches combined with dexamethasone and colchicine (DC-MNs) with differential dual-release pattern is designed. Two drugs loaded in commercially available materials HA and PLGA, respectively. Specifically, after administration, outer layer rapidly releases the anti-inflammatory drug dexamethasone, which inhibits macrophage polarization to pro-inflammatory phenotype in scar tissue. Subsequently, inner layer degrades sustainedly, releasing antimicrotubular agent colchicine, which suppresses the overproliferation of myofibroblasts with extremely narrow therapeutic window, and inhibits the overexpression of collagen, as well as promotes the regular arrangement of collagen. Only applied once, DC-MNs directly delivered drugs to the scar tissue. Compared to traditional treatment regimen, DC-MNs significantly suppressed HS at lower dosage and frequency by differential dual-release design. Therefore, this study put forward the idea of integrated DC-MNs accompany the development of HS, providing a non-invasive, self-applicable, more efficient and secure strategy for treatment of HS.
Asunto(s)
Antiinflamatorios , Cicatriz Hipertrófica , Colchicina , Dexametasona , Miofibroblastos , Agujas , Cicatriz Hipertrófica/tratamiento farmacológico , Cicatriz Hipertrófica/patología , Animales , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Dexametasona/farmacología , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Antiinflamatorios/uso terapéutico , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Colchicina/farmacología , Colchicina/administración & dosificación , Ratones , Sistemas de Liberación de Medicamentos , Humanos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/químicaRESUMEN
Inflammation-resident cells within arthritic sites undergo a metabolic shift towards glycolysis, which greatly aggravates rheumatoid arthritis (RA). Reprogramming glucose metabolism can suppress abnormal proliferation and activation of inflammation-related cells without affecting normal cells, holding potential for RA therapy. Single 2-deoxy-d-glucose (2-DG, glycolysis inhibitor) treatment often cause elevated ROS, which is detrimental to RA remission. The rational combination of glycolysis inhibition with anti-inflammatory intervention might cooperatively achieve favorable RA therapy. To improve drug bioavailability and exert synergetic effect, stable co-encapsulation of drugs in long circulation and timely drug release in inflamed milieu is highly desirable. Herein, we designed a stimulus-responsive hyaluronic acid-triglycerol monostearate polymersomes (HTDD) co-delivering 2-DG and dexamethasone (Dex) to arthritic sites. After intravenous injection, HTDD polymersomes facilitated prolonged circulation and preferential distribution in inflamed sites, where overexpressed matrix metalloproteinases and acidic pH triggered drug release. Results indicated 2-DG can inhibit the excessive cell proliferation and activation, and improve Dex bioavailability by reducing Dex efflux. Dex can suppress inflammatory signaling and prevent 2-DG-induced oxidative stress. Thus, the combinational strategy ultimately mitigated RA by inhibiting glycolysis and hindering inflammatory signaling. Our study demonstrated the great potential in RA therapy by reprogramming glucose metabolism in arthritic sites.
Asunto(s)
Artritis Reumatoide , Desoxiglucosa , Dexametasona , Glucosa , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Animales , Glucosa/metabolismo , Dexametasona/farmacología , Dexametasona/uso terapéutico , Ratones , Desoxiglucosa/farmacología , Inflamación/tratamiento farmacológico , Glucólisis/efectos de los fármacos , Polímeros/química , Ácido Hialurónico/química , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Masculino , Humanos , Proliferación Celular/efectos de los fármacosRESUMEN
BACKGROUND: Corticosteroids are commonly used to treat COVID-19 patients with hypoxemia, and clinicians have adjusted the corticosteroid intensity on the basis of clinical needs. However, neither the optimal dose nor the duration of treatment has been recommended. OBJECTIVE: To investigate whether cumulative doses of corticosteroids, measured as dexamethasone-equivalent doses over the first 14 days, impact outcomes in patients with COVID-19 pneumonia. METHODS: We conducted a retrospective cohort study of COVID-19 pneumonia patients admitted between April 1st, 2020, and September 30th, 2021. The study focused on the type and dose of corticosteroid administered during the initial 14 days, clinical outcomes, and complications. The primary outcome was in-hospital mortality. RESULTS: Among 271 patients, the mean cumulative dexamethasone-equivalent dose was 158 (119.9-197.25) mg in survivors and 185 (131.7-222.0) mg in nonsurvivors. Univariate analysis revealed that the cumulative dexamethasone-equivalent dose was a risk factor for in-hospital mortality. However, this association did not hold true in the multivariate analysis. After the cumulative dexamethasone-equivalent dose was categorized into quartiles, the moderate dosage (126.01-165.00 mg) in the second quartile was found to be associated with the lowest in-hospital mortality (16.2%). Higher cumulative dexamethasone-equivalent doses were associated with longer hospital and ICU stays and fewer ventilator-free days (p < 0.001). Doses exceeding 165 mg were associated with an increased risk of hospital-acquired infections (p < 0.001). CONCLUSIONS: The cumulative dexamethasone-equivalent dose during the first 14 days is not associated with in-hospital mortality in hypoxemic COVID-19 patients. However, higher cumulative doses exceeding 165 mg are associated with an increased risk of in-hospital mortality and secondary hospital-acquired infections.
Asunto(s)
Corticoesteroides , Tratamiento Farmacológico de COVID-19 , COVID-19 , Dexametasona , Mortalidad Hospitalaria , Hipoxia , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Dexametasona/efectos adversos , COVID-19/mortalidad , COVID-19/complicaciones , Corticoesteroides/administración & dosificación , Corticoesteroides/efectos adversos , Corticoesteroides/uso terapéutico , Hipoxia/tratamiento farmacológico , SARS-CoV-2/aislamiento & purificación , Resultado del Tratamiento , Relación Dosis-Respuesta a Droga , Anciano de 80 o más AñosAsunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona , Mieloma Múltiple , Talidomida , Humanos , Mieloma Múltiple/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Talidomida/análogos & derivados , Talidomida/administración & dosificación , Talidomida/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Masculino , Femenino , Anciano , Persona de Mediana Edad , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Resistencia a Antineoplásicos/efectos de los fármacosRESUMEN
Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.
Asunto(s)
Anticuerpos Biespecíficos , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia de Inducción , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Biespecíficos/efectos adversos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Adulto Joven , Quimioterapia de Inducción/métodos , Anciano , Adolescente , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Dexametasona/efectos adversos , Inducción de RemisiónRESUMEN
Given the early use of triplet and quadruplet regimens, most patients with multiple myeloma (MM) will be exposed and/or refractory to PIs, IMiDs, and anti-CD38 mAbs after first- or second-line treatment. Effective treatment for this group of triple class exposed/refractory (TCE/R) patients is crucial. Here we present a post-hoc subgroup analysis of TCE/R patients treated on the ALGONQUIN study of belantamab mafodotin plus pomalidomide-dexamethasone (belamaf-Pd) for relapsed MM. Of the 99 patients treated on the ALGONQUIN study, 69 were TCE and 56 were TCR and were included in this analysis. Patients had a median of three prior lines of therapy. The ORR was 86.4% in TCE patients and 84.9% in TCR patients, with ≥ very good partial response rates of 64% and 68% respectively. The median progression free survival was 18.3 months in TCE patients and 19.6 months in TCR patients, with overall survival not yet reached and 34.4 months, respectively for TCE and TCR patients. No new safety signals were identified. The most common Grade ≥ 3 AEs were keratopathy (48%), decreased visual acuity (42%), neutropenia (36%), thrombocytopenia (27%), and infection (25%). In this subgroup analysis of the ALGONQUIN study, patients with TCE/TCR disease treated with belamaf-Pd achieved high clinical response rates with durable remissions, comparable to other novel therapeutics in this space.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona , Mieloma Múltiple , Talidomida , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Talidomida/análogos & derivados , Talidomida/uso terapéutico , Talidomida/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Adulto , Compuestos de Boro/uso terapéutico , Compuestos de Boro/administración & dosificación , Anciano de 80 o más Años , Recurrencia Local de Neoplasia/tratamiento farmacológico , Resistencia a AntineoplásicosRESUMEN
Introduction: Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell therapy approved for patients with relapsed/refractory multiple myeloma (RRMM). In the phase 3 trial, CARTITUDE-4 (NCT04181827), cilta-cel demonstrated improved efficacy vs. standard of care (SOC; daratumumab plus pomalidomide and dexamethasone [DPd] or pomalidomide plus bortezomib and dexamethasone [PVd]) with a ≥ complete response (≥CR) rate of 73.1% vs. 21.8%. Methods: A cost-per-responder model was developed to assess the value of cilta-cel and SOC (87% DPd and 13% PVd) based on the CARTITUDE-4 trial data from a US mixed payer perspective (76.7% commercial, 23.3% Medicare). The model was developed using progression-free survival (PFS), overall survival (OS), and ≥CR endpoints from CARTITUDE-4 over a period of 25.4 months. Inpatient stays, outpatient visits, drug acquisition, administration, and monitoring costs were included. The base-case model assumed an inpatient setting for each cilta-cel infusion; another scenario included 30% outpatient and 70% inpatient infusions. Costs of managing grade 3-4 adverse events (AEs) and grade 1-4 cytokine release syndrome and neurotoxicity were included. Subsequent therapy costs were incurred after disease progression; terminal care costs were considered upon death events. Outcomes included total cost per treated patient, total cost per complete responder, and cost per month in PFS between cilta-cel and SOC. Costs were adjusted to 2024 US dollars. Results: Total cost per treated patient, total cost per complete responder, and total cost per month in PFS were estimated at $704,641, $963,941, and $30,978 for cilta-cel, respectively, and $840,730, $3,856,559, and $42,520 for SOC over the 25.4-month period. Cost drivers included treatment acquisition costs before progression and subsequent treatment costs ($451,318 and $111,637 for cilta-cel; $529,795 and $265,167 for SOC). A scenario analysis in which 30% of patients received an outpatient infusion (assuming the same payer mix) showed a lower cost per complete responder for cilta-cel ($956,523) than those with an infusion in the inpatient setting exclusively. Discussion: This analysis estimated that cost per treated patient, cost per complete responder, and cost per month in PFS for cilta-cel were remarkably lower than for DPd or PVd, highlighting the substantial clinical and economic benefit of cilta-cel for patients with RRMM.
Asunto(s)
Análisis Costo-Beneficio , Inmunoterapia Adoptiva , Lenalidomida , Mieloma Múltiple , Talidomida , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/mortalidad , Mieloma Múltiple/tratamiento farmacológico , Lenalidomida/uso terapéutico , Lenalidomida/administración & dosificación , Inmunoterapia Adoptiva/economía , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Talidomida/análogos & derivados , Talidomida/uso terapéutico , Talidomida/economía , Talidomida/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Receptores Quiméricos de Antígenos/uso terapéutico , Receptores Quiméricos de Antígenos/inmunología , Masculino , Femenino , Bortezomib/uso terapéutico , Bortezomib/administración & dosificación , Persona de Mediana Edad , Supervivencia sin Progresión , Resultado del Tratamiento , Anciano , Resistencia a Antineoplásicos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/economíaRESUMEN
BACKGROUND: Systemic corticosteroids have become the standard of care for severe to critically ill patients with coronavirus disease 2019 (COVID-19). However, the real-world efficacy and safety outcomes associated with a higher dose of corticosteroids remain uncertain. METHODS: We conducted a nationwide, population-based, matched cohort study of severe to critically ill adult patients with COVID-19 between January 2020 and June 2021 in Korea using the National Health Information Database. Patients using systemic corticosteroids were included and high-dose corticosteroid use was defined as a daily mean prescribed dose of more than 6 mg of dexamethasone. We then employed a proportional hazard regression model to identify prognostic factors for 28-day all-cause mortality and conducted a Fine and Gray regression model to assess risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA). RESULTS: During the study period, 102,304 patients with COVID-19 were screened, 5,754 met the eligibility criteria, and 2,138 were successfully matched. The mean prescribed daily dose was 4.2 mg and 13.4 mg in the standard- and high-dose groups, respectively, and the mean duration of use was not different between the groups. High-dose corticosteroid use independently increased all-cause mortality at 28 days (adjusted hazard ratio [aHR], 1.48; 95% confidence interval [CI], 1.25-1.76) and 90 days (aHR, 1.63; CI, 1.44-1.85) after admission. Subgroup analysis revealed a statistically significant elevation in the risk of mortality among patients using low-flow or high-flow nasal cannulas, with aHRs of 1.41 and 1.46, respectively. No significant impact of high-dose steroids was observed, even in patients who underwent mechanical ventilation at 28 days (aHR, 1.17; CI, 0.79-1.72). As a safety outcome, high-dose corticosteroid use showed an association with the development of CAPA (aHR, 2.97; 95% CI, 0.94-9.43). CONCLUSION: Among severe to critically ill patients with COVID-19, high-dose corticosteroid use was associated with increased 28-day all-cause mortality and showed a trend toward the development of CAPA.
Asunto(s)
Corticoesteroides , Tratamiento Farmacológico de COVID-19 , COVID-19 , Enfermedad Crítica , Dexametasona , SARS-CoV-2 , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , COVID-19/mortalidad , COVID-19/complicaciones , COVID-19/epidemiología , República de Corea , Corticoesteroides/uso terapéutico , Corticoesteroides/administración & dosificación , SARS-CoV-2/aislamiento & purificación , Estudios de Cohortes , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Modelos de Riesgos Proporcionales , Adulto , Factores de RiesgoRESUMEN
Lenalidomide, bortezomib, and dexamethasone (RVd) have previously been established as standard-of-care induction therapy for newly diagnosed multiple myeloma (NDMM). More recently, randomized phase 3 data have demonstrated the benefit of the addition of daratumumab (Dara-RVd) to the RVd backbone in terms of improved both depth of response and long-term survival benefit as measured by progression-free survival (PFS). Our group has previously published on a historical cohort of 1000 NDMM patients uniformly treated with RVd induction with impressive both PFS and overall survival. Here, we present a comparative analysis of our RVd cohort with a recent cohort of 326 patients induced with Dara-RVd at our institution with intent to transplant. This analysis demonstrates the utility of this regimen in real-world clinical practice and provides additional insights into D-RVd performance in patient subsets often underrepresented in clinical trials, as well as the impact of daratumumab in maintenance for NDMM patients.
Asunto(s)
Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Dexametasona , Lenalidomida , Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Bortezomib/administración & dosificación , Bortezomib/uso terapéutico , Lenalidomida/uso terapéutico , Lenalidomida/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Adulto , Anciano de 80 o más Años , Estudios de CohortesRESUMEN
Although COVID-19 infection is an immunosuppressant disease, many immunosuppressant agents, such as pulse methylprednisolone (PMP), dexamethasone (DXM), and tocilizumab (TCZ), were used during the pandemic. Secondary infections in patients with COVID-19 have been reported recently. This study investigated these agents' effects on secondary infections and outcomes in patients with COVID-19 in intensive care units (ICUs). This study was designed retrospectively, and all data were collected from the tertiary intensive care units of six hospitals between March 2020 and October 2021. All patients were divided into three groups: Group I [GI, PMP (-), DXM (-) and TCZ (-)], Group II [GII, PMP (+), DXM (+)], and Group III [GIII, PMP (+), DXM (+), TCZ (+)]. Demographic data, PaO/FiO2 ratio, laboratory parameters, culture results, and outcomes were recorded. To compare GI-GII and GI-GIII, propensity score matching (PSM) was used by matching 14 parameters. Four hundred twelve patients with COVID-19 in the ICU were included in the study. The number of patients with microorganisms ≥ 2 was 279 (67.7%). After PSM, in GII and GIII, the number of (+) tracheal cultures and (+) bloodstream cultures detected different microorganisms ≥ 2 during the ICU period, neuropathy, tracheotomized patients, duration of IMV, and length of ICU stay were significantly higher than GI. The mortality rate was similar in GI and GII, whereas it was significantly higher in GIII than in GI. The use of immunosuppressant agents in COVID-19 patients may lead to an increase in secondary infections. In addition, increased secondary infections may lead to prolonged ICU stay, prolonged IMV duration, and increased mortality.
Asunto(s)
COVID-19 , Inmunosupresores , Unidades de Cuidados Intensivos , Humanos , Masculino , Femenino , Estudios Retrospectivos , COVID-19/mortalidad , COVID-19/complicaciones , COVID-19/epidemiología , Persona de Mediana Edad , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Anciano , Dexametasona/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Metilprednisolona/uso terapéutico , SARS-CoV-2/aislamiento & purificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , AdultoRESUMEN
Bortezomib, lenalidomide, and dexamethasone (VRD), and bortezomib, doxorubicin, and dexamethasone (PAD), are commonly used in induction regimens for patients with newly diagnosed multiple myeloma (NDMM) in China. This real-world study enrolled 390 patients, 195 receiving VRD and 195 receiving PAD induction. The primary endpoint was progression-free survival (PFS) and stringent complete remission/complete remission. Across the entire cohort, VRD demonstrated significantly improved five-year overall survival (OS) (74% vs. 59%, p = 0.0024) and five-year PFS (67% vs. 37%, p = 0.0018) compared to PAD. Notably, the median OS and PFS were not reached for VRD-treated patients, while they were 77 months (60-not reached [NR]) and 46 months (36-NR), respectively, for PAD. In patients with standard-risk cytogenetics, VRD showed superior five-year OS (83% vs. 58%, p = 0.0038) and PFS (78% vs. 48%, p = 0.0091) compared to PAD. However, these differences were not statistically significant in high-risk patients. For transplanted patients, VRD was associated with superior five-year OS (91% vs. 67%, p = 0.014) and PFS (79% vs. 47%, p = 0.015) compared to PAD. In non-transplanted patients, VRD showed a trend towards improved five-year OS (p = 0.085) and PFS (p = 0.073) compared to the PAD group. In conclusion, VRD displayed superior OS and PFS outcomes in standard-risk patients and those who underwent transplantation. These findings suggest potential advantages of VRD over PAD in real-world clinical settings for NDMM treatment. However, due to the imbalance in transplantation rates between the VRD and PAD groups, limitations in testing for high-risk cytogenetic abnormalities (HRA), and the difference between the received cycles and salvage therapies, the conclusions of this study should be interpreted with caution.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Dexametasona , Doxorrubicina , Lenalidomida , Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Bortezomib/uso terapéutico , Bortezomib/administración & dosificación , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Lenalidomida/uso terapéutico , Lenalidomida/administración & dosificación , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Masculino , Anciano , Adulto , Estudios Retrospectivos , Supervivencia sin Progresión , Anciano de 80 o más AñosRESUMEN
RATIONALE: Cytokine release syndrome (CRS) is a common adverse event of chimeric antigen receptor T (CAR-T) cell therapy. CRS is generally a systemic inflammatory reaction, but in rare cases, it can occur in specific body areas and is referred to as "local CRS (L-CRS)." A case of laryngeal edema due to L-CRS that required tracheal intubation because of the lack of response to tocilizumab (TCZ) and dexamethasone (DEX) is reported. PATIENT CONCERNS: A 67-year-old woman with relapsed transformed follicular lymphoma was treated with CAR-T cell therapy. Although she had been given TCZ and DEX for CRS, neck swelling appeared on day 4 after infusion. DIAGNOSES: Laryngoscopy showed severe laryngeal edema, which was presumed to be due to L-CRS, since there were no other apparent triggers based on history, physical examination, and computed tomography. INTERVENTIONS: Tracheal intubation was performed because of the risk of upper airway obstruction. Ultimately, 4 doses of tocilizumab (8 mg/kg) and 6 doses of dexamethasone (10 mg/body) were required to improve the L-CRS. OUTCOMES: On day 7, laryngeal edema improved, and the patient could be extubated. LESSONS: The lessons from this case are, first, that CAR-T cell therapy may induce laryngeal edema in L-CRS. Second, TCZ alone may be ineffective in cervical L-CRS. Third, TCZ, as well as DEX, may be inadequate. In such cases, we should recognize L-CRS and manage it early because it may eventually progress to laryngeal edema that requires securing the airway.
Asunto(s)
Intubación Intratraqueal , Edema Laríngeo , Linfoma Folicular , Humanos , Femenino , Anciano , Edema Laríngeo/etiología , Edema Laríngeo/terapia , Intubación Intratraqueal/métodos , Intubación Intratraqueal/efectos adversos , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/terapia , Linfoma Folicular/complicaciones , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Síndrome de Liberación de Citoquinas/etiología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversosRESUMEN
RATIONALE: Anaphylactic shock, a severe and rapid systemic allergic reaction, poses significant treatment challenges. Epinephrine, the first-line treatment, effectively reverses symptoms but can complicate the clinical picture by elevating lactate levels, blurring the distinction between shock-induced hypoperfusion and drug-induced metabolic effects. PATIENT CONCERNS: A 26-year-old female presented with anaphylactic shock following an antibiotic infusion, experiencing chest tightness, hypotension, and pulmonary edema, without significant past medical history apart from a noted allergy to fish and shrimp. DIAGNOSES: Anaphylaxis was diagnosed based on clinical presentation and supported by imaging that revealed pulmonary edema, despite normal troponin levels and electrocardiogram. INTERVENTIONS: Treatment included 0.5 mg of intramuscular epinephrine and 5 mg of intravenous dexamethasone, with subsequent intubation and mechanical ventilation in the intensive care unit. An intravenous epinephrine infusion was also administered for hemodynamic support. OUTCOMES: While epinephrine resolved the pulmonary edema and stabilized circulation, it led to a significant, albeit transient, increase in lactate levels, which normalized following discontinuation of epinephrine, indicating the metabolic effect of the drug rather than ongoing tissue hypoperfusion. LESSONS: This case illustrates the importance of recognizing epinephrine-induced lactate elevation in anaphylactic shock, necessitating a nuanced interpretation of lactate dynamics. Clinicians must differentiate between lactate elevations due to tissue hypoperfusion and those arising from epinephrine's pharmacologic effects to optimize patient care.
Asunto(s)
Anafilaxia , Epinefrina , Ácido Láctico , Humanos , Anafilaxia/tratamiento farmacológico , Anafilaxia/sangre , Femenino , Adulto , Epinefrina/administración & dosificación , Ácido Láctico/sangre , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Edema Pulmonar/inducido químicamente , Edema Pulmonar/tratamiento farmacológico , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificaciónRESUMEN
A woman in her mid-60s who is a high hypermetrope presented with bilateral eye pain and headache approximately 1 hour after taking a single dose of a widely available decongestant containing paracetamol, guaifenesin and phenylephrine hydrochloride for coryzal symptoms. She had previous successful bilateral peripheral iridotomies performed for narrow angles. At presentation, her intraocular pressures (IOPs) were significantly raised at 72 mm Hg and 66 mm Hg in the right and left eye, respectively, with bilateral corneal oedema. Her IOP was normalised with urgent treatment using 500 mg intravenous acetazolamide, pilocarpine 2%, dexamethasone 0.1% and IOP-lowering drops. She was listed for cataract surgery and was advised to avoid the precipitating agent and other over-the-counter decongestants. This is the first reported case of bilateral angle closure triggered by a decongestant with such a combination of ingredients. Clinicians should be aware of this rare side effect for prompt diagnosis and management.
Asunto(s)
Acetaminofén , Acetazolamida , Glaucoma de Ángulo Cerrado , Humanos , Glaucoma de Ángulo Cerrado/inducido químicamente , Glaucoma de Ángulo Cerrado/tratamiento farmacológico , Femenino , Persona de Mediana Edad , Acetazolamida/uso terapéutico , Acetazolamida/administración & dosificación , Acetaminofén/efectos adversos , Acetaminofén/administración & dosificación , Acetaminofén/uso terapéutico , Fenilefrina/efectos adversos , Fenilefrina/administración & dosificación , Fenilefrina/uso terapéutico , Medicamentos sin Prescripción/efectos adversos , Medicamentos sin Prescripción/administración & dosificación , Guaifenesina/efectos adversos , Guaifenesina/administración & dosificación , Guaifenesina/uso terapéutico , Descongestionantes Nasales/efectos adversos , Descongestionantes Nasales/administración & dosificación , Presión Intraocular/efectos de los fármacos , Medicamentos Compuestos contra Resfriado, Gripe y Alergia/efectos adversos , Pilocarpina/uso terapéutico , Pilocarpina/administración & dosificación , Pilocarpina/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Dexametasona/efectos adversos , Dolor Ocular/inducido químicamente , Dolor Ocular/etiología , Enfermedad AgudaRESUMEN
Histiocytic sarcoma (HS) is a rare hematopoietic neoplasm with an aggressive clinical course and a poor response to conventional chemotherapy. Currently, no standard treatment paradigms are available. Herein, we present a case of de novo HS treated with pembrolizumab combined with a GDP regimen (gemcitabine, cisplatin, and dexamethasone) that resulted in sustained complete remission with progression-free survival exceeding 4 years. Immunohistochemical analysis demonstrated significant overexpression of programmed death ligand 1 (PD-L1) on biopsy samples. Additionally, fluorescence in situ hybridization (FISH) with a JAK-2 probe indicated 9p24.1 amplification, suggesting reliance on the JAK-STAT pathway. Polymerase chain reaction (PCR) analysis did not reveal any BRAF-V600 mutations. Consequently, an immune checkpoint inhibitor (ICI) was administered alongside chemotherapy, resulting in sustained complete remission and progression-free survival for over 4 years. Our findings suggest that a combination of ICI and chemotherapy could represent a promising therapeutic approach for HS.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Desoxicitidina , Dexametasona , Gemcitabina , Sarcoma Histiocítico , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Sarcoma Histiocítico/tratamiento farmacológico , Sarcoma Histiocítico/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Desoxicitidina/administración & dosificación , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/administración & dosificación , Inducción de Remisión , Masculino , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Persona de Mediana Edad , Supervivencia sin Progresión , FemeninoRESUMEN
BACKGROUND: In nephrotic syndrome, protein leaks from the blood into the urine through the glomeruli, resulting in hypoproteinaemia and generalised oedema. While most children with nephrotic syndrome respond to corticosteroids, 80% experience a relapsing course. Corticosteroids have reduced the death rate to around 3%; however, corticosteroids have well-recognised potentially serious adverse events such as obesity, poor growth, hypertension, diabetes mellitus, osteoporosis, cataracts, glaucoma and behavioural disturbances. This is an update of a review first published in 2000 and updated in 2002, 2005, 2007, 2015 and 2020. OBJECTIVES: The aim of this review was to assess the benefits and harms of different corticosteroid regimens in children with steroid-sensitive nephrotic syndrome (SSNS). The benefits and harms of therapy were studied in two groups of children: 1) children in their initial episode of SSNS and 2) children who experience a relapsing course of SSNS. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 9 July 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) performed in children (one to 18 years) during their initial or subsequent episode of SSNS, comparing different durations, total doses or other dose strategies using any corticosteroid agent. DATA COLLECTION AND ANALYSIS: Summary estimates of effects were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: In this 2024 update, we included five new studies, resulting in 54 studies randomising 4670 children. Risk of bias methodology was often poorly performed, with only 31 studies and 28 studies respectively assessed to be at low risk for random sequence generation and allocation concealment. Ten studies were at low risk of performance bias (blinding of participants and personnel), and 12 studies were at low risk of detection bias (blinding of outcome assessment); nine of these studies were placebo-controlled RCTs. Twenty-seven studies (fewer than 50%) were at low risk for attrition bias, and 26 studies were at low risk for reporting bias (selective outcome reporting). In studies at low risk of selection bias evaluating children in their initial episode of SSNS, there is little or no difference in the number of children with frequent relapses when comparing two months of prednisone with three months or more (RR 0.96, 95% CI 0.83 to 1.10; 755 children, 5 studies; I2 = 0%; high certainty evidence) or when comparing three months with five to seven months of therapy (RR 0.99, 95% CI 0.74 to 1.33; 376 children, 3 studies; I2 = 35%; high certainty evidence). In analyses of studies at low risk of selection bias, there is little or no difference in the number of children with any relapse by 12 to 24 months when comparing two months of prednisone with three months or more (RR 0.93, 95% CI 0.81 to 1.06; 808 children; 6 studies; I2 = 47%) or when comparing three months with five to seven months of therapy (RR 0.88, 95% CI 0.70 to 1.11; 377 children, 3 studies; I2 = 53%). Little or no difference was noted in adverse events between the different treatment durations. Amongst children with relapsing SSNS, four small studies (177 children) utilising lower doses of prednisone compared with standard regimens found little or no differences between groups in the numbers with relapse (RR 1.01, 95% CI 0.85 to 1.20; I2 = 0%). A fifth study (117 children) reported little or no difference between two weeks and four weeks of alternate-day prednisone after remission with daily prednisone. A recent large, well-designed study with 271 children found that administering daily prednisone compared with alternate-day prednisone or no prednisone during viral infection did not reduce the risk of relapse. In contrast, four previous small studies in children with frequently relapsing disease had reported that daily prednisone during viral infections compared with alternate-day prednisone or no treatment reduced the risk of relapse. AUTHORS' CONCLUSIONS: There are four well-designed studies randomising 823 children, which have demonstrated that there is no benefit of prolonging prednisone therapy beyond two to three months in the first episode of SSNS. Small studies in children with relapsing disease have identified no differences in efficacy using lower induction doses or shorter durations of prednisone therapy. Large, well-designed studies are required to confirm these findings. While previous small studies had suggested that changing from alternate-day to daily prednisone therapy at the onset of infection reduced the likelihood of relapse, a much larger and well-designed study found no reduction in the number relapsing when administering daily prednisone at the onset of infection.
Asunto(s)
Síndrome Nefrótico , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Síndrome Nefrótico/tratamiento farmacológico , Humanos , Niño , Preescolar , Adolescente , Lactante , Corticoesteroides/uso terapéutico , Corticoesteroides/efectos adversos , Sesgo , Glucocorticoides/uso terapéutico , Glucocorticoides/efectos adversos , Dexametasona/uso terapéuticoRESUMEN
Importance: The role of olanzapine has not been adequately evaluated in moderately emetogenic chemotherapy (MEC) regimens with or without neurokinin-1 receptor antagonists. Objective: To evaluate whether addition of olanzapine to an MEC regimen reduces nausea, vomiting, and use of nausea rescue medications among patients with solid malignant tumors. Design, Setting, and Participants: This multicenter, open-label phase 3 randomized clinical trial included patients aged 18 years or older with solid malignant tumors who were receiving oxaliplatin-, carboplatin-, or irinotecan-based chemotherapy. The trial was conducted at 3 institutes in India from March 26, 2019, to August 26, 2023; the final cutoff date for analysis was September 10, 2023. Exposure: Patients were randomized 1:1 to dexamethasone, aprepitant, and palonosetron with olanzapine (experimental group) or without olanzapine (observation group). The experimental group received 10 mg of olanzapine orally once at night on days 1 through 3 of the chemotherapy regimen. Main Outcomes and Measures: The primary end point was complete response (CR), defined as the proportion of patients with no vomiting, no significant nausea (scored as <5 on a visual analog scale of 1 to 100), and no use of rescue medications for nausea. Secondary end points included the proportion of patients experiencing nausea and chemotherapy-induced nausea and vomiting (CINV), receiving rescue medications, and experiencing adverse events. Results: A total of 560 patients (259 [64%] male; median age, 51 years [range, 19-80 years]) were randomized. The analysis included 544 patients with evaluable data (274 assigned to olanzapine and 270 to observation). Baseline characteristics were evenly matched between the 2 groups. The proportion of patients with CR was significantly greater in the group with (248 [91%]) than without (222 [82%]) olanzapine in the overall 120-hour treatment period (P = .005). Likewise, there were significant differences between the olanzapine and observation groups for nausea control (264 [96%] vs 234 [87%]; P < .001) and CINV (262 [96%] vs 245 [91%]; P = .02) during the overall assessment period, and the proportion of patients receiving rescue medications significantly increased in the observation group (30 [11%]) compared with the olanzapine group (11 [4%]) (P = .001). Grade 1 somnolence was reported by 27 patients (10%) following administration of chemotherapy and olanzapine and by no patients in the observation group. Conclusions and Relevance: In this randomized clinical trial, the addition of olanzapine significantly improved CR rates as well as nausea and vomiting prevention rates in chemotherapy-naive patients who were receiving MEC regimens containing oxaliplatin, carboplatin, or irinotecan. These findings suggest that use of olanzapine should be considered as one of the standards of care in these chemotherapy regimens. Trial Registration: Clinical Trials Registry-India (CTRI) Identifier: CTRI/2018/12/016643.
Asunto(s)
Antieméticos , Náusea , Neoplasias , Olanzapina , Vómitos , Humanos , Olanzapina/uso terapéutico , Antieméticos/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Vómitos/inducido químicamente , Vómitos/prevención & control , Náusea/inducido químicamente , Náusea/prevención & control , Adulto , Neoplasias/tratamiento farmacológico , Anciano , Aprepitant/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Dexametasona/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Palonosetrón/uso terapéutico , IndiaAsunto(s)
Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona , Mieloma Múltiple , Oligopéptidos , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Oligopéptidos/administración & dosificación , Oligopéptidos/uso terapéutico , Oligopéptidos/efectos adversos , Masculino , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Femenino , Anciano , Persona de Mediana Edad , Amplificación de Genes , Resultado del TratamientoRESUMEN
BACKGROUND: Intimal hyperplasia is a normal adaptive feature of arteries in response to injuries, which include invasive vascular interventions. Its development limits the long-term success of bypass grafts. Various pharmacological agents have been successfully employed in experimental models to reduce the degree of intimal hyperplasia. In our study, we investigated the efficacy of dexamethasone in reducing intimal hyperplasia in rat abdominal aortas after partial transection and primary repair. METHODS: In this study, 20 Wistar Albino rats were randomly selected and divided into four groups to compare the effects of low- and high-dose dexamethasone on intima and media thickness compared to the control. Group A (n=5) was the control group, where only skin incision and laparotomy were performed. For Group B (n=5), a median laparotomy was performed, the abdominal aorta was partially transected, and repaired with an 8.0 prolene suture. Doses of 0.1 mg/kg and 0.2 mg/kg dexamethasone were administered in Group C (n=5) and Group D (n=5), respectively. After two weeks, all rats were euthanized, and the repaired abdominal aortas were excised and examined histopathologically. Intima and media thicknesses were measured using the 'Olympus AnalySIS 5' program (Olympus Corporation, Japan) after digital photos were taken. RESULTS: Based on the measurements, we demonstrated that after transection and repair of the abdominal aorta, the intima/media ratio was not significantly different between the low-dose dexamethasone and non-dexamethasone groups. The intima/media ratio was significantly lower in the high-dose dexamethasone group than in the non-dexamethasone and low-dose dexamethasone groups. CONCLUSION: After vascular interventions, dexamethasone treatment may reduce intimal hyperplasia and increase patency by providing vascular remodeling.
Asunto(s)
Aorta Abdominal , Dexametasona , Hiperplasia , Ratas Wistar , Túnica Íntima , Animales , Dexametasona/farmacología , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Aorta Abdominal/cirugía , Aorta Abdominal/patología , Ratas , Hiperplasia/tratamiento farmacológico , Hiperplasia/patología , Hiperplasia/prevención & control , Túnica Íntima/patología , Túnica Íntima/efectos de los fármacos , Modelos Animales de Enfermedad , MasculinoRESUMEN
RATIONALE: Kawasaki disease (KD) manifests as an acute, self-limited vasculitis disease that constitutes the primary cause of acquired heart disease in children under 5 years of age. Facial nerve palsy (FNP) is a rare complication associated with coronary artery lesions (CALs) in patients with KD. Patients with KD and FNP usually present atypically, leading to a delayed diagnosis and treatment of KD. PATIENT CONCERNS: A 4-month-old boy with fever, left FNP and bilateral conjunctival injection with spontaneous resolution, was admitted to the hospital, received a short course of intravenous dexamethasone, and experienced rapid FNP recovery on the first admission. The patient experienced a resurgence of fever, bilateral conjunctival injection, and right FNP, which led to readmission. Physical examination revealed redness at the site of Bacillus Calmette-Guérin inoculation, reddening of lips, and desquamation of the distal extremities. Echocardiography revealed right-sided CALs. DIAGNOSES: The patient initially missed KD on the first admission, and was later diagnosed with complete KD with FNP on the second admission. INTERVENTIONS AND OUTCOMES: After a short course of intravenous dexamethasone, the left FNP resolved quickly. However, right FNP recurred after corticosteroids withdrawal. Meanwhile, more typical symptoms were observed, and KD was diagnosed. Treatment ensued with intravenous immunoglobulin (IVIG), aspirin, and dexamethasone. The patient achieved rapid remission, without recurrence. Echocardiography continued to show normal findings during 1-year follow-up after discharge. LESSONS: The clinical symptoms of FNP complicating KD in children are atypical and can easily lead to delayed diagnosis and treatment. FNP in patients with KD may serve as a risk factor for CALs, which are more challenging to resolve than the FNP itself. Adding corticosteroids to IVIG may be recommended to reduce IVIG resistance, decrease the risk of developing CALs, and alleviate CALs.