RESUMEN
OBJECTIVE: The prognosis of extra-nodal NK/T cell lymphoma (ENKTL) is poor, and the optimal therapy remains controversial. This study aims to evaluate the safety and efficacy of a new combined modality therapy. METHODS: Phase-2 study of pegaspargase, etoposide and gemcitabine (PEG) combined with involved field radiation therapy (IFRT) in newly-diagnosed patients with early-stage ENKTL. Patients received 4 course of PEG followed by IFRT. The primary endpoints were complete response (CR), partial response (PR), and objective response rate (ORR) after IFRT. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and adverse events. RESULTS: 34 consecutive patients with Ann Arbor stage I/II were enrolled. 3 patients progressed on PEG, while the remaining 31 received IFRT. The ORR was 88.2% (30/34), included 28 (82.4%) complete and 2 (5.8%) partial responses. With a median follow-up of 56.0 months (Interquartile Range [IQR], 36.0-66.9 months), the estimated 5-year PFS and OS were 87.4% (95% Confidence Interval [CI],69.5%-94.8%) and 97.1% (95%CI, 80.1%-99.6%), respectively. Most adverse events were hematological and easily managed. CONCLUSIONS: PEG followed by IFRT is a safe and effective initial therapy for early-stage ENKTL, demonstrating impressive PFS and OS rates. This promising approach warrants further validation in a randomized controlled trial (Registered at Clinicaltrials.gov NCT02705508).Trial registration: ClinicalTrials.gov identifier: NCT02705508.
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Protocolos de Quimioterapia Combinada Antineoplásica , Asparaginasa , Desoxicitidina , Etopósido , Gemcitabina , Linfoma Extranodal de Células NK-T , Polietilenglicoles , Humanos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Linfoma Extranodal de Células NK-T/radioterapia , Linfoma Extranodal de Células NK-T/mortalidad , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Linfoma Extranodal de Células NK-T/terapia , Masculino , Femenino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico , Asparaginasa/administración & dosificación , Asparaginasa/uso terapéutico , Asparaginasa/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Etopósido/uso terapéutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the safety, tolerability, and preliminary efficacy of multiple doses of pegylated irinotecan (JK1201I) as a second-line monotherapy for treating small-cell lung cancer (SCLC) patients. METHODS: According to the "3 + 3" dose-escalation principle, patients received intravenous JK1201I at 180 or 220 mg/m2 once every 3 weeks for four cycles. Progression-free survival (PFS), overall survival (OS), median progression-free survival (mPFS), and median overall survival (mOS) were evaluated. The Kaplan-Meier method was used to analyze PFS and overall OS. Brookmeyer and Crowley's method was used for mPFS and mOS. RESULTS: This study included 29 patients with stage III-IV SCLC (stage IIIa, n = 1; stage IIIb, n = 1; and stage IV, n = 27). Of these, 26 patients were enrolled in the 180 mg/m2 dose group, and 3 patients were enrolled in the 220 mg/m2 dose group. No dose-limiting toxicity (DLT) was noted during the first 28 days of treatment. Grade 3 or higher adverse events were recorded in the 180 mg/m2 group, including diarrhea (11.5%, 3/26), neutropenia (7.7%, 2/26), and leukopenia (7.7%, 2/26). In the 220 mg/m2 group, one patient (33.3%, 1/3) experienced neutropenia or leukopenia. In the 180 mg/m2 group, 38.5% (10/26) of patients achieved an objective response rate (ORR), with a disease control rate (DCR) of 73.1% (19/26). The mPFS and mOS were 3.4 and 12.1 months, respectively. In the 220 mg/m2 group, one patient had stable disease, and one had progressive disease (PD). The ORR, DCR, mPFS, and mOS were 0% (0/3) and 33.3% (1/3), 2.7 months and 2.7 months, respectively. CONCLUSION: JK1201I exhibits promising efficacy and relatively low toxicities as a second-line monotherapy for SCLC, warranting further large-scale clinical studies to evaluate its efficacy in greater detail.
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Irinotecán , Neoplasias Pulmonares , Polietilenglicoles , Carcinoma Pulmonar de Células Pequeñas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Anciano , Irinotecán/uso terapéutico , Irinotecán/administración & dosificación , Irinotecán/efectos adversos , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico , Polietilenglicoles/efectos adversos , Adulto , Resultado del Tratamiento , Estadificación de Neoplasias , Supervivencia sin ProgresiónRESUMEN
Primary myelofibrosis (PMF) is the most aggressive of the myeloproliferative neoplasms and patients require greater attention and likely require earlier therapeutic intervention. Currently approved treatment options are limited in their selective suppression of clonal proliferation resulting from driver- and coexisting gene mutations. Janus kinase inhibitors are approved for symptomatic patients with higher-risk PMF. Additionally, most ongoing clinical studies focus on patients with higher-risk disease and/or high rates of transfusion dependency. Optimal treatment of early/lower-risk PMF remains to be identified and needs randomized clinical trial evaluations. Pegylated interferon alfa is recommended for symptomatic lower-risk PMF patients based on phase 2 non-randomized studies and expert opinion. Ropeginterferon alfa-2b (ropeg) is a new-generation pegylated interferon-based therapy with favorable pharmacokinetics and safety profiles, requiring less frequent injections than prior formulations. This randomized, double-blind, placebo-controlled phase 3 trial will assess its efficacy and safety in patients with "early/lower-risk PMF", defined as pre-fibrotic PMF or PMF at low or intermediate-1 risk according to Dynamic International Prognostic Scoring System-plus. Co-primary endpoints include clinically relevant complete hematologic response and symptom endpoint. Secondary endpoints include progression- or event-free survival, molecular response in driver or relevant coexisting gene mutations, bone marrow response, and safety. Disease progression and events are defined based on the International Working Group criteria and well-published reports. 150 eligible patients will be randomized in a 2:1 ratio to receive either ropeg or placebo. Blinded sample size re-estimation is designed. Ropeg will be administered subcutaneously with a tolerable, higher starting-dose regimen. The study will provide important data for the treatment of early/lower-risk PMF for which an anti-clonal, disease-modifying agent is highly needed.
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Interferón alfa-2 , Interferón-alfa , Polietilenglicoles , Mielofibrosis Primaria , Proteínas Recombinantes , Humanos , Mielofibrosis Primaria/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Proteínas Recombinantes/uso terapéutico , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/administración & dosificación , Método Doble Ciego , Interferón-alfa/uso terapéutico , Interferón-alfa/efectos adversos , Interferón-alfa/administración & dosificación , Interferón alfa-2/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , AncianoRESUMEN
BACKGROUND AND AIMS: Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α. METHODS: In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored. RESULTS: As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment. CONCLUSIONS: TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB.
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Antivirales , Quimioterapia Combinada , Hepatitis B Crónica , Interferón-alfa , Polietilenglicoles , Proteínas Recombinantes , Tenofovir , Humanos , Tenofovir/uso terapéutico , Tenofovir/administración & dosificación , Tenofovir/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Masculino , Femenino , Antivirales/uso terapéutico , Antivirales/efectos adversos , Antivirales/administración & dosificación , Niño , Proteínas Recombinantes/uso terapéutico , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Polietilenglicoles/uso terapéutico , Polietilenglicoles/efectos adversos , Polietilenglicoles/administración & dosificación , Interferón-alfa/uso terapéutico , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Preescolar , Resultado del Tratamiento , Interferón alfa-2/uso terapéutico , Interferón alfa-2/administración & dosificación , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/efectos de los fármacos , ADN Viral/sangre , Alanina/uso terapéutico , Alanina/análogos & derivadosRESUMEN
Background and aims: Limited data have been reported on achieving functional cure using pegylated interferon (Peg-IFN) alpha-2b treatment for postpartum hepatitis B e antigen (HBeAg)-negative women with chronic hepatitis B virus (HBV) infection. This study was to assess the effectiveness and safety of Peg-IFN alpha-2b in HBV postpartum women without HBeAg and identify factors linked to the functional cure. Methods: A total of 150 HBeAg-negative postpartum women were retrospectively recruited.47 patients received Peg-IFN alpha-2b [Peg-IFN(+) group] and 103 patients did not [Peg-IFN(-) group]. Propensity score matching (PSM) was used to adjust the baseline imbalance between the two groups. The patients were followed for at least 48 weeks. The primary endpoints were hepatitis B surface antigen(HBsAg) loss and HBsAg seroconversion at 48 weeks. Logistic regression analysis was used to assess factors associated with HBsAg loss at 48 weeks. Results: At week 48,the HBsAg loss and seroconversion rate in Peg-IFN(+) group were 51.06%(24/47) and 40.43%(19/47), respectively. Even after PSM, Peg-IFN(+) group still showed higher HBsAg loss rate (50.00% vs 7.14%,p<0.001) and higher HBsAg seroconversion rate (38.10% vs 2.38%,p<0.001). Baseline HBsAg levels (Odds Ratio [OR]: 0.051, 95% Confidence Interval [CI]: 0.003-0.273, P=0.010), HBsAg at week 24 (OR:0.214, 95%CI:0.033-0.616, P=0.022), HBsAg decline at week 24 (OR:4.682, 95%CI: 1.624-30.198, P=0.022) and postpartum flare (OR:21.181, 95%CI:1.872-633.801, P=0.030) were significantly associated with HBsAg loss at week 48 after Peg-IFN alpha-2b therapy. Furthermore, the receiver operating characteristic curve (ROC) showed that the use of baseline HBsAg<182 IU/mL, HBsAg at week24 < 4 IU/mL and HBsAg decline at week24>12IU/mL were good predictors of HBsAg loss. No serious adverse events were reported. Conclusion: Peg-IFN alpha-2b treatment could achieve a high rate of HBsAg loss and seroconversion in HBeAg-negative postpartum women with reliable safety, particularly for patients experience postpartum flare and have low baseline HBsAg levels.
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Antivirales , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Hepatitis B Crónica , Interferón alfa-2 , Interferón-alfa , Polietilenglicoles , Periodo Posparto , Proteínas Recombinantes , Humanos , Femenino , Hepatitis B Crónica/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Adulto , Antígenos e de la Hepatitis B/sangre , Antivirales/uso terapéutico , Interferón-alfa/uso terapéutico , Estudios Retrospectivos , Interferón alfa-2/uso terapéutico , Antígenos de Superficie de la Hepatitis B/sangre , Resultado del Tratamiento , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/efectos de los fármacos , Adulto Joven , SeroconversiónRESUMEN
BACKGROUND: Poly-ether-ether-ketone (PEEK) was introduced in dentistry as an alternative to metal alloys. OBJECTIVE: To assess the effectiveness of PEEK-fixed retainers in preserving the stability of mandibular anterior and participant satisfaction as compared to the Dead-soft coaxial fixed retainer (DSC). TRIAL DESIGN: A single-centre, two-arm parallel groups randomized clinical trial. METHODS: The patients treated with pre-adjusted orthodontic appliances who have a Little's Irregularity Index (LII)â ≤â 0.5 mm have been enrolled in the trial. PEEK retainers were prepared to round 0.8 mm wire by computer-aided design and manufacturing, and the DSC wire was carefully adapted to the lingual surface of the lower anterior teeth. The primary outcome was the stability of lower anterior teeth as assessed by LII, while the secondary outcomes were changes in occlusal parameters, retainer failure, and patient satisfaction. The data were collected at the debonding stage (T0), 1 month (T1), 3 months (T3), and 6 months (T6) after starting the trial, except for patient's satisfaction, which was recorded using an electronic form at T1 and T6. BLINDING: Single blinding of participants. RESULTS: A total of 46 participants with an age range of 12-28 years old were randomly allocated to the two groups (nâ =â 23 in each). Only one participant dropped out; therefore, 45 participants were analysed. The DSC group showed a significant increase in LII at T3. Both retainer groups had comparable occlusal measurements, failure frequency, and survival time, with no significant difference. The patients in the DSC group reported a statistically significant perception of change in the position of their teeth compared to those in the PEEK group. HARMS: No harmful effects have been reported. LIMITATIONS: Limited follow-up duration and the inability to blind the operator due to the nature of the intervention. CONCLUSIONS: After 6-month retention, the PEEK retainer was equally effective to DSC retainers in maintaining the teeth alignment, with no significant differences regarding the failure frequency, survival rate, and general patient satisfaction. TRIAL REGISTRATION: https://register.clinicaltrials.gov. (NCT05557136).
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Benzofenonas , Cetonas , Retenedores Ortodóncicos , Satisfacción del Paciente , Polietilenglicoles , Polímeros , Humanos , Cetonas/química , Cetonas/uso terapéutico , Polietilenglicoles/química , Polietilenglicoles/uso terapéutico , Masculino , Femenino , Polímeros/química , Adolescente , Adulto Joven , Diseño de Aparato Ortodóncico , Adulto , Niño , Recubrimiento Dental Adhesivo/métodosRESUMEN
Objective: This study aimed to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEG-Loxe) compared to those of dapagliflozin in patients with mild-to-moderate diabetic kidney disease (DKD), a prevalent microvascular complication of type 2 diabetes mellitus (T2DM). The study is set against the backdrop of increasing global diabetes incidence and the need for effective DKD management. Methods: This study constituted a single-center, randomized, open-label, clinical trial. The trial included patients with mild-to-moderate DKD and suboptimal glycemic control. Eligible participants were randomly allocated to one of the two groups for treatment with either PEG-Loxe or dapagliflozin. The primary endpoint was the change in UACR from baseline at 24 weeks. Results: Overall, 106 patients were randomized and 80 patients completed the study. Following 24 weeks of treatment, the PEG-Loxe group exhibited a mean percent change in baseline UACR of -29.3% (95% confidence interval [CI]: -34.8, -23.7), compared to that of -31.8% in the dapagliflozin group (95% CI: -34.8, -23.7). Both PEG-Loxe and dapagliflozin showed similar efficacy in reducing UACR, with no significant difference between the groups (p = 0.336). The HbA1c levels decreased by -1.30% (95% CI: -1.43, -1.18) in the PEG-Loxe group and by -1.29% (95% CI: -1.42, -1.17) in the dapagliflozin group (p = 0.905). The TG levels decreased by -0.56 mmol/L (95% CI: -0.71, -0.42) in the PEG-Loxe group and -0.33 mmol/L (95% CI: -0.48, -0.19) in the dapagliflozin group (p = 0.023). Differences in TC, HDL-C, LDL-C, SBP, and DBP levels between the groups were not statistically significant (all p > 0.05). Safety profiles were consistent with previous findings, with gastrointestinal adverse events being more common in the PEG-Loxe group. Conclusions: PEG-Loxe is as effective as dapagliflozin in improving urine protein levels in patients with mild-to-moderate DKD and offers superior benefits in improving lipid profiles. These findings support the use of PEG-Loxe in DKD management, contributing to evidence-based treatment options. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2300070919.
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Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Glucósidos , Polietilenglicoles , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Nefropatías Diabéticas/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Polietilenglicoles/efectos adversos , Polietilenglicoles/administración & dosificación , Glucósidos/uso terapéutico , Glucósidos/efectos adversos , Glucósidos/administración & dosificación , Compuestos de Bencidrilo/uso terapéutico , Compuestos de Bencidrilo/efectos adversos , Anciano , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Resultado del Tratamiento , Hemoglobina Glucada/análisis , Glucemia/efectos de los fármacos , Glucemia/análisis , AdultoRESUMEN
BACKGROUND: Endoscopic rubber band ligation (ERBL) is a nonsurgical technique for the treatment of symptomatic internal hemorrhoids but is limited by recurrence and post-procedural pain. AIM: To evaluate satisfaction, long-term recurrence, and post-procedural pain in managing internal hemorrhoids using a combination of polidocanol foam sclerotherapy and ERBL. METHODS: This was a prospective, multicenter, randomized study. A total of 195 consecutive patients diagnosed with grade II-III internal hemorrhoids were enrolled from four tertiary hospitals and randomly divided into a cap-assisted endoscopic polidocanol foam sclerobanding (EFSB) or an ERBL group. All patients were followed-up for 12 months. Symptom-based severity and post-procedural pain were assessed using a hemorrhoid severity score (HSS) and a visual analog scale (VAS). Continuous variables were reported as medians and interquartile range. RESULTS: One hundred and ninety-five patients were enrolled, with 98 in the EFSB group. HSS was lower in the EFSB group than in the ERBL group at 8 weeks [4.0 (3.0-5.0) vs 5.0 (4.0-6.0), P = 0.003] and 12-month [2.0 (1.0-3.0) vs 3.0 (2.0-3.0), P < 0.001] of follow-up. The prolapse recurrence rate was lower in the EFSB group at 12 months (11.2% vs 21.6%, P = 0.038). Multiple linear regression analysis demonstrated that EFSB treatment [B = -0.915, 95% confidence interval (CI): -1.301 to -0.530, P = 0.001] and rubber band number (B = 0.843, 95%CI: 0.595-1.092, P < 0.001) were negatively and independently associated with the VAS score 24 hours post-procedure. The median VAS was lower in the EFSB group than in the ERBL [2.0 (1.0-3.0) vs 3.0 (2.0-4.0), P < 0.001]. CONCLUSION: Cap-assisted EFSB provided long-term satisfaction and effective relief from the recurrence of prolapse and pain 24 hours post-procedure.
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Hemorroides , Polidocanol , Recurrencia , Soluciones Esclerosantes , Escleroterapia , Humanos , Polidocanol/administración & dosificación , Polidocanol/uso terapéutico , Hemorroides/terapia , Hemorroides/diagnóstico , Hemorroides/cirugía , Persona de Mediana Edad , Femenino , Masculino , Estudios Prospectivos , Escleroterapia/métodos , Resultado del Tratamiento , Ligadura/métodos , Soluciones Esclerosantes/administración & dosificación , Adulto , Anciano , Índice de Severidad de la Enfermedad , Dolor Postoperatorio/etiología , Dolor Postoperatorio/diagnóstico , Satisfacción del Paciente , Dimensión del Dolor , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéuticoRESUMEN
The efficacy of different pegylated interferon (PEG-IFN) treatment strategies for achieving sustained hepatitis B surface antigen (HBsAg) clearance in chronic hepatitis B (CHB) remains controversial. This study assesses the efficacy of different PEG-IFN treatment regimens and factors influencing sustained HBsAg clearance after PEG-IFN discontinuation. PubMed , Embase , Web of Science , and the Cochrane Library databases were searched from inception to June 2023, regarding PEG-IFN therapy in CHB. Methodological quality was assessed using the Cochrane risk of bias tool. We explored sources of heterogeneity through univariate meta-regression. Frequentist network meta-analyses were used to compare the efficacy of different PEG-IFN treatment strategies. We analyzed 53 studies (including 9338 CHB patients). After PEG-IFN withdrawal, the annual rates of HBsAg clearance and seroconversion were 6.9% [95% confidence interval (CI), 5.10-9.31] and 4.7% (95% CI, 2.94-7.42). The pooled 1-, 3-, and 5-year sustained HBsAg clearance rates were 7.4%, 9.9%, and 13.0%, and the sustained HBsAg seroconversion rates were 6.6%, 4.7%, and 7.8%, respectively. HBsAg quantification, hepatitis B e antigen status, and PEG-IFN treatment protocols were major sources of heterogeneity. Baseline HBsAg quantification was significantly lower in patients with sustained HBsAg clearance versus those without ( P â <â 0.046). PEG-IFN combined with tenofovir has the highest probability of achieving HBsAg seroconversion (surface under the cumulative ranking of 81.9%). Sustained HBsAg clearance increased approximately linearly from years 1 to 5 after PEG-IFN discontinuation. Low baseline HBsAg quantification has a significant impact on sustained HBsAg clearance. PEG-IFN combined with tenofovir may be optimal in achieving sustained HBsAg seroconversion.
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Antivirales , Antígenos de Superficie de la Hepatitis B , Hepatitis B Crónica , Interferón-alfa , Metaanálisis en Red , Polietilenglicoles , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Antivirales/uso terapéutico , Polietilenglicoles/uso terapéutico , Interferón-alfa/uso terapéutico , Seroconversión , Respuesta Virológica Sostenida , Tenofovir/uso terapéutico , Virus de la Hepatitis B/inmunología , Proteínas Recombinantes/uso terapéutico , Quimioterapia Combinada , Resultado del TratamientoRESUMEN
BACKGROUND: Patients with cirrhosis commonly undergo endoscopic cyanoacrylate injection for gastric and esophageal variceal bleeding. However, postoperative infections can increase the risk of rebleeding and mortality. AIM: This study aimed to determine the risk of postoperative infections and its associated factors following cyanoacrylate injection treatment in these patients. METHODS: A retrospective analysis was conducted on 57 patients treated with ligation (ligation group), 66 patients treated with cyanoacrylate injection (injection group), and 91 patients treated with conservative treatment (control group) at the Nanchong Central Hospital. RESULTS: The rate of postoperative infection was similar among the cyanoacrylate, ligation, and conservative treatment groups, with no significant statistical difference observed ( P â =â 0.97). Multivariate analysis identified postoperative Child-Pugh score and renal insufficiency as two independent risk factors for postoperative infection. The rebleeding rate in the injection group was significantly lower than in the other groups ( P â =â 0.01). Mortality was significantly higher in the control group compared with the ligation and injection groups ( P â =â 0.01). CONCLUSION: Cyanoacrylate combined with lauromacrogol injection did not significantly increase the risk of infection compared with ligation and conservative treatments, and it was more effective in reducing the risk of rebleeding. This method is safe, effective, and holds clinical value for broader application.
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Cianoacrilatos , Várices Esofágicas y Gástricas , Hemorragia Gastrointestinal , Recurrencia , Humanos , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/terapia , Masculino , Femenino , Estudios Retrospectivos , Cianoacrilatos/efectos adversos , Cianoacrilatos/administración & dosificación , Cianoacrilatos/uso terapéutico , Persona de Mediana Edad , Factores de Riesgo , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Ligadura , Anciano , Resultado del Tratamiento , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico , Polietilenglicoles/efectos adversos , Adulto , Infección de la Herida Quirúrgica/etiología , Cirrosis Hepática/complicacionesRESUMEN
OBJECTIVE: Selected populations of patients with chronic hepatitis B (CHB) may benefit from a combined use of pegylated interferon-alpha (pegIFN-α) and nucleos(t)ides (NUCs). The aim of our study was to assess the immunomodulatory effect of pegIFN-α on T and natural killer (NK) cell responses in NUC-suppressed patients to identify cellular and/or serological parameters to predict better T cell-restoring effect and better control of infection in response to pegIFN-α for a tailored application of IFN-α add-on. DESIGN: 53 HBeAg-negative NUC-treated patients with CHB were randomised at a 1:1 ratio to receive pegIFN-α-2a for 48 weeks, or to continue NUC therapy and then followed up for at least 6 months maintaining NUCs. Serum hepatitis B surface antigen (HBsAg) and hepatitis B core-related antigen (HBcrAg) levels as well as peripheral blood NK cell phenotype and function and HBV-specific T cell responses upon in vitro stimulation with overlapping HBV peptides were measured longitudinally before, during and after pegIFN-α therapy. RESULTS: Two cohorts of pegIFN-α treated patients were identified according to HBsAg decline greater or less than 0.5 log at week 24 post-treatment. PegIFN-α add-on did not significantly improve HBV-specific T cell responses during therapy but elicited a significant multispecific and polyfunctional T cell improvement at week 24 post-pegIFN-α treatment compared with baseline. This improvement was maximal in patients who had a higher drop in serum HBsAg levels and a lower basal HBcrAg values. CONCLUSIONS: PegIFN-α treatment can induce greater functional T cell improvement and HBsAg decline in patients with lower baseline HBcrAg levels. Thus, HBcrAg may represent an easily and reliably applicable parameter to select patients who are more likely to achieve better response to pegIFN-α add-on to virally suppressed patients.
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Antivirales , Antígenos e de la Hepatitis B , Hepatitis B Crónica , Interferón-alfa , Células Asesinas Naturales , Polietilenglicoles , Proteínas Recombinantes , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/sangre , Interferón-alfa/uso terapéutico , Antivirales/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Femenino , Adulto , Masculino , Polietilenglicoles/uso terapéutico , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/efectos de los fármacos , Persona de Mediana Edad , Antígenos e de la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos del Núcleo de la Hepatitis B/sangre , Quimioterapia Combinada , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Resultado del Tratamiento , Nucleósidos/uso terapéuticoAsunto(s)
Interferón alfa-2 , Interferón-alfa , Policitemia Vera , Polietilenglicoles , Proteínas Recombinantes , Adulto , Humanos , Aberraciones Cromosómicas , Interferón alfa-2/uso terapéutico , Interferón-alfa/uso terapéutico , Policitemia Vera/tratamiento farmacológico , Policitemia Vera/genética , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes/uso terapéuticoRESUMEN
Axons successfully repaired with polyethylene glycol (PEG) fusion tecnology restored axonal continuity thereby preventing their Wallerian degeneration and minimizing muscle atrophy. PEG fusion studies in animal models and preliminary clinical trials involving patients with digital nerve repair have shown promise for this therapeutic approach. PEG fusion is safe to perform, and given the enormous potential benefits, there is no reason not to explore its therapeutic potential.
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Traumatismos de los Nervios Periféricos , Polietilenglicoles , Humanos , Polietilenglicoles/uso terapéutico , Polietilenglicoles/administración & dosificación , Traumatismos de los Nervios Periféricos/cirugía , Animales , Regeneración NerviosaAsunto(s)
Antivirales , Humanos , Antivirales/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Polietilenglicoles/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Interferón-alfa/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B/tratamiento farmacológicoAsunto(s)
Antivirales , Humanos , Antivirales/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Polietilenglicoles/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Interferón-alfa/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B/tratamiento farmacológicoRESUMEN
BACKGROUND: Trabectedin in combination with pegylated liposomal doxorubicin (PLD) is approved for the treatment of patients with platinum-sensitive relapsed ovarian cancer. Nevertheless, there is currently limited information regarding this treatment in elderly patients with ovarian cancer in a real-world setting. METHODS: This observational and multicentric study retrospectively evaluated trabectedin plus PLD in a real-world setting treatment of elderly patients diagnosed with platinum-sensitive relapsed ovarian cancer, treated according to the Summary of Product Characteristics (SmPC) from 15 GEICO-associated hospitals. Patients ≥ 70 years old at the time of treatment initiation and platinum-free intervals ≥ 6 months were considered eligible. RESULTS: Forty-three patients with a median age of 74.0 years were treated between January 1st, 2015, and December 31st, 2019 in 15 Spanish centers. Four patients achieved complete response (9.3%), 14 (32.6%) partial response, and 13 (30.2%) stable disease as the best radiological response. In the analysis of biological overall response according to CA125 serum levels (i.e., Rustin criteria), 14 responded to the treatment (32.6%), 11 responded and normalized (25.6%), three patients stabilized (7.0%) and three progressed (7.0%). Median progression-free survival (PFS) and overall survival (OS) in the study population were 7.7 and 19.5 months, respectively. The most common grade 3/4 adverse events were neutropenia (n = 8, 18.7%) and asthenia (n = 5, 11.6%). CONCLUSIONS: This analysis demonstrated that trabectedin combined with PLD is a feasible and effective treatment in elderly patients with platinum-sensitive relapsed ovarian cancer, showing an acceptable safety profile, which is crucial in the palliative treatment of these patients.
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Protocolos de Quimioterapia Combinada Antineoplásica , Doxorrubicina , Recurrencia Local de Neoplasia , Neoplasias Ováricas , Polietilenglicoles , Trabectedina , Humanos , Trabectedina/uso terapéutico , Trabectedina/administración & dosificación , Femenino , Doxorrubicina/análogos & derivados , Doxorrubicina/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/administración & dosificación , Anciano , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/mortalidad , Estudios Retrospectivos , Polietilenglicoles/uso terapéutico , Polietilenglicoles/efectos adversos , Polietilenglicoles/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano de 80 o más Años , Recurrencia Local de Neoplasia/tratamiento farmacológico , Resultado del TratamientoRESUMEN
PURPOSE: The management of bowel bladder disorder (BBD) has only been indicated for subjective constipation without objective evidence. We attempted to highlight the radiological findings in patients with BBD and construct a scoring system to identify patients with BBD prior to treatment. MATERIALS AND METHODS: Forty-five patients with lower urinary tract dysfunction (LUTD) received polyethylene glycol for 2 months before bladder medication for LUTD. Based on partial response to LUTD following treatment, we divided the patients into LUTD-fecal impaction (FI) and LUTD not attributed to FI (LUTD-NFI) groups. Pre/post-treatment kidney, ureter, and bladder (KUB) were compared with respect to several radiographic parameters. Items with significant changes after treatment were included in the scoring system. The accuracy and inter-rater agreement were also evaluated. RESULTS: Cecal dilation, descending colon dilation, fecal quality, and overall haziness were found to undergo significant changes after laxative treatment. We assigned 0 to 2 points for each item, with a total score of 8. Receiver operating characteristic curve analysis revealed a cutoff value of 5 between LUTD-FI and LUTD-NFI, with 79% sensitivity and 88% specificity. The scoring system was instructed to six doctors who were unaware of it and was then tested on previous patients, which showed a substantial concordance rate (κ=0.79, p<0.05). CONCLUSIONS: Fecal scoring system based on KUB was beneficial in identifying children with LUTD attributed to FI. This may provide an opportunity to obtain objective FI data as an alternative to subjective assessment of constipation.
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Impactación Fecal , Síntomas del Sistema Urinario Inferior , Humanos , Impactación Fecal/diagnóstico por imagen , Femenino , Masculino , Síntomas del Sistema Urinario Inferior/diagnóstico por imagen , Síntomas del Sistema Urinario Inferior/etiología , Persona de Mediana Edad , Laxativos/uso terapéutico , Anciano , Polietilenglicoles/uso terapéutico , Radiografía , Adulto , Estreñimiento/diagnóstico por imagenRESUMEN
OBJECTIVES: to assess the variability in expenditure compared to 2022 assuming different rates of shifting of therapy days from current active ingredients used for the treatment of haemophilia B to nonacog beta pegolDesign: descriptive cross-sectional study. SETTING AND PARTICIPANTS: consumption in the year 2022 (data source: Medicines Utilisation Monitoring Centre, Italian Medicines Agency) of all medicinal products available in Italy containing coagulation factor IX. MAIN OUTCOMES MEASURES: for each active ingredient, the total number of therapy days and the variability in expenditure compared to 2022 were estimated on the basis of a switch of therapy days, between 5% and 20%, to nonacog beta pegol. RESULTS: on the basis of considered scenarios, the analysis shows that the total annual expenditure for clotting factors used in the treatment of haemophilia B could remain at most unchanged or reduced. Particularly, the extent of the reduction in spending could vary from 0.11% to 2.26%. This trend would be in contrast to the stable increase seen in recent years, particularly in 2022. CONCLUSIONS: this predictive spending assessment may be useful in evaluating the economic impact from new treatment options, such as etranacogene dezaparvovec gene therapy already approved by the European Medicines Agency and the Food and Drug Administration, and to improve pharmaceutical governance.
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Factor IX , Hemofilia B , Italia , Humanos , Estudios Transversales , Hemofilia B/tratamiento farmacológico , Hemofilia B/economía , Factor IX/uso terapéutico , Factor IX/economía , Costos de los Medicamentos , Proteínas Recombinantes/uso terapéutico , Proteínas Recombinantes/economía , Polietilenglicoles/uso terapéutico , Polietilenglicoles/economía , Gastos en Salud/estadística & datos numéricosRESUMEN
BACKGROUND: This study aimed to investigate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for primary prophylaxis of neutropenia in patients with cervical cancer receiving concurrent chemoradiotherapy. METHODS: In this prospective, single-center, single-arm study, we enrolled patients (18-70 years) with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1r-IVA and IVB (distant metastasis only with inguinal lymph node metastasis) cervical cancer. Eligible patients should have normal function of the bone marrow (absolute neutrophil count (ANC) ≥ 2.0 × 109/L) and adequate hepatic and renal functions. Key exclusion criteria included: previous chemotherapy and/or radiotherapy; a history of bone marrow dysplasia or other hematopoietic abnormalities. All patients underwent radical radiotherapy (pelvic radiotherapy or extended-field irradiation) plus brachytherapy. The chemotherapy regimen included four cycles of 3-weekly paclitaxel and cisplatin. PEG-rhG-CSF was administered 48-72 h after each treatment cycle. Salvage granulocyte colony-stimulating factor (G-CSF) was only permitted in certain circumstances. The primary endpoint was the incidence of grade 3-4 neutropenia. The secondary endpoints included frequency of febrile neutropenia (FN), chemotherapy completion rate in cycles 2-4, time to complete radiotherapy, and safety. RESULTS: Overall, 52 patients were enrolled in this study from July 2019 to October 2020. The incidence of grade 3-4 neutropenia was 28.8%, with an average duration of grade 3-4 neutropenia persistence of 3.85 days (1-7 days). The incidence rate of FN was 3.8%. The chemotherapy completion rate was 94.2%, 82.7%, and 75.0% for cycles 2-4, respectively. The incidences of grade 3-4 neutropenia for cycles 1-4 were 9.6% (5/52), 8.2% (4/49), 14.0% (6/43), and 2.6% (1/39), respectively. All patients completed radiotherapy within 8 weeks (median, 48 days; range: 41-56 days), except one patient who withdrew consent and did not receive radiotherapy. Severe non-hematologic toxicity was not observed in any patient. CONCLUSION: PEG-rhG-CSF is an effective and safe prophylactic treatment for neutropenia in patients with cervical cancer undergoing concurrent chemoradiotherapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024494. Date of Registration:13/July/2019.
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Quimioradioterapia , Factor Estimulante de Colonias de Granulocitos , Neutropenia , Polietilenglicoles , Proteínas Recombinantes , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/terapia , Femenino , Persona de Mediana Edad , Adulto , Estudios Prospectivos , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico , Polietilenglicoles/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Anciano , Neutropenia/prevención & control , Neutropenia/etiología , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Cisplatino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto Joven , Adolescente , Paclitaxel/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéuticoRESUMEN
Polycythemia vera (PV) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by clonal erythrocytosis. A phase 2 study reported that ropeginterferon alfa-2b is a well-tolerated and effective treatment for PV in Japanese patients. This post hoc analysis of the phase 2 data further evaluated outcomes in patients at low risk of thrombosis (low-risk PV). Among 20 patients with low-risk PV, 60.0% (12/20) and 85.0% (17/20) achieved < 45% hematocrit by weeks 24 and 52, respectively. The proportion of responders with complete hematologic response (CHR) was 60.0% (12/20) at week 52, and the median time to response was 11.9 months. The mean JAK2 V617F allele burden decreased from 75.8% at baseline to 53.7% at week 52. No patient experienced thrombosis or bleeding episodes. All patients experienced treatment-emergent adverse events (TEAEs) related to ropeginterferon alfa-2b, but no grade ≥ 3 TEAEs or deaths related to ropeginterferon alfa-2b occurred, and no new safety concerns arose. This analysis indicated that ropeginterferon alfa-2b may be an effective treatment option for Japanese patients with low-risk PV.