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BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatment. Resmetirom is an oral, liver-directed, thyroid hormone receptor beta-selective agonist in development for the treatment of NASH with liver fibrosis. METHODS: We are conducting an ongoing phase 3 trial involving adults with biopsy-confirmed NASH and a fibrosis stage of F1B, F2, or F3 (stages range from F0 [no fibrosis] to F4 [cirrhosis]). Patients were randomly assigned in a 1:1:1 ratio to receive once-daily resmetirom at a dose of 80 mg or 100 mg or placebo. The two primary end points at week 52 were NASH resolution (including a reduction in the nonalcoholic fatty liver disease [NAFLD] activity score by ≥2 points; scores range from 0 to 8, with higher scores indicating more severe disease) with no worsening of fibrosis, and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score. RESULTS: Overall, 966 patients formed the primary analysis population (322 in the 80-mg resmetirom group, 323 in the 100-mg resmetirom group, and 321 in the placebo group). NASH resolution with no worsening of fibrosis was achieved in 25.9% of the patients in the 80-mg resmetirom group and 29.9% of those in the 100-mg resmetirom group, as compared with 9.7% of those in the placebo group (P<0.001 for both comparisons with placebo). Fibrosis improvement by at least one stage with no worsening of the NAFLD activity score was achieved in 24.2% of the patients in the 80-mg resmetirom group and 25.9% of those in the 100-mg resmetirom group, as compared with 14.2% of those in the placebo group (P<0.001 for both comparisons with placebo). The change in low-density lipoprotein cholesterol levels from baseline to week 24 was -13.6% in the 80-mg resmetirom group and -16.3% in the 100-mg resmetirom group, as compared with 0.1% in the placebo group (P<0.001 for both comparisons with placebo). Diarrhea and nausea were more frequent with resmetirom than with placebo. The incidence of serious adverse events was similar across trial groups: 10.9% in the 80-mg resmetirom group, 12.7% in the 100-mg resmetirom group, and 11.5% in the placebo group. CONCLUSIONS: Both the 80-mg dose and the 100-mg dose of resmetirom were superior to placebo with respect to NASH resolution and improvement in liver fibrosis by at least one stage. (Funded by Madrigal Pharmaceuticals; MAESTRO-NASH ClinicalTrials.gov number, NCT03900429.).
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Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Piridazinas , Uracilo , Adulto , Humanos , Método Doble Ciego , Hígado/diagnóstico por imagen , Hígado/efectos de los fármacos , Hígado/patología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/patología , Piridazinas/uso terapéutico , Resultado del Tratamiento , Uracilo/análogos & derivados , Receptores beta de Hormona Tiroidea/agonistas , Biopsia , Relación Dosis-Respuesta a DrogaRESUMEN
Gastrointestinal (GI) bleeding is one of the most common complications associated with the use of direct oral anticoagulants (DOAC). Clear algorithms exist for the emergency measures in (suspected) GI bleeding, including assessing the medication history regarding anti-platelet drugs and anticoagulants as well as simple coagulation tests during pre-endoscopic management. Platelet transfusions, fresh frozen plasma (FFP), or prothrombin complex concentrate (4F-PCC) are commonly used for optimizing the coagulation status. For severe bleeding under the thrombin inhibitor dabigatran, idarucizumab is available, and for bleeding under the factor Xa inhibitors rivaroxaban or apixaban, andexanet alfa is available as specific antidotes for DOAC antagonization. These antidotes represent emergency drugs that are typically used only after performing guideline-compliant multimodal measures including emergency endoscopy. Antagonization of oral anticoagulants should be considered for severe gastrointestinal bleeding in the following situations: (1) refractory hemorrhagic shock, (2) endoscopically unstoppable bleeding, or (3) nonavoidable delays until emergency endoscopy for life-threatening bleeding. After successful (endoscopic) hemostasis, anticoagulation (DOACs, vitamin K antagonist, heparin) should be resumed timely (i.e. usually within a week), taking into account individual bleeding and thromboembolic risk.
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BACKGROUND & AIMS: Based on positive results from small single center studies, granulocyte-colony stimulating factor (G-CSF) is being widely used for the treatment of patients with acute-on-chronic liver failure (ACLF). Herein, we aimed to evaluate the safety and efficacy of G-CSF in patients with ACLF. METHODS: In this multicenter, prospective, controlled, open-label phase II study, 176 patients with ACLF (EASL-CLIF criteria) were randomized to receive G-CSF (5 µg/kg daily for the first 5 days and every third day thereafter until day 26) plus standard medical therapy (SMT) (n = 88) or SMT alone. The primary efficacy endpoint was 90-day transplant-free survival analyzed by Cox regression modeling. The key secondary endpoints were overall and transplant-free survival after 360 days, the development of ACLF-related complications, and the course of liver function scores during the entire observation period. RESULTS: Patients treated with G-CSF had a 90-day transplant-free survival rate of 34.1% compared to 37.5% in the SMT group (hazard ratio [HR] 1.05; 95% CI 0.711-1.551; p = 0.805). Transplant-free and overall survival at 360 days did not differ between the 2 arms (HR 0.998; 95% CI 0.697-1.430; p = 0.992 and HR 1.058; 95% CI 0.727-1.548; p = 0.768, respectively). G-CSF did not improve liver function scores, the occurrence of infections, or survival in subgroups of patients without infections, with alcohol-related ACLF, or with ACLF defined by the APASL criteria. Sixty-one serious adverse events were reported in the G-CSF+SMT group and 57 were reported in the SMT group. In total, 7 drug-related serious adverse reactions occurred in the G-CSF group. The study was prematurely terminated due to futility after conditional power calculation. CONCLUSIONS: In contrast to previous findings, G-CSF had no significant beneficial effect on patients with ACLF in this multicenter controlled trial, which suggests that it should not be used as a standard treatment for ACLF. CLINICALTRIALS. GOV NUMBER: NCT02669680 LAY SUMMARY: Granulocyte-colony stimulating factor was considered as a novel treatment for acute-on-chronic liver failure (ACLF). We performed the first randomized, multicenter, controlled phase II trial, which showed that G-CSF did not improve survival or other clinical endpoints in patients with ACLF. Therefore, G-CSF should not be used to treat liver disease outside clinical studies.
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Insuficiencia Hepática Crónica Agudizada/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/farmacocinética , Insuficiencia Hepática Crónica Agudizada/epidemiología , Insuficiencia Hepática Crónica Agudizada/fisiopatología , Adulto , Anciano , Análisis de Varianza , Distribución de Chi-Cuadrado , Femenino , Alemania/epidemiología , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Placebos , Estudios ProspectivosRESUMEN
BACKGROUND AND AIMS: ARC-520, the first an RNA interference (RNAi) therapeutic, was designed to reduce all RNA transcripts derived from covalently closed circular DNA, leading to a reduction in viral antigens and hepatitis B virus (HBV) DNA. APPROACH AND RESULTS: We aimed to evaluate the depth of hepatitis B surface antigen (HBsAg) decline in response to multiple doses of ARC-520 compared to placebo (PBO) in two randomized, multicenter studies in nucleoside/nucleotide analogue reverse-transcriptase inhibitor (NUC)-experienced patients with hepatitis B early antigen (HBeAg)-negative (E-neg) or HBeAg-positive (E-pos) disease. A total of 58 E-neg and 32 E-pos patients were enrolled and received four monthly doses of PBO (n = 20 E-neg, 11 E-pos), 1 mg/kg ARC-520 (n = 17 E-neg, 10 E-pos), or 2 mg/kg ARC-520 (n = 21 E-neg, 11 E-pos) concomitantly with NUC. HBsAg change from baseline to 30 days after the last ARC-520 dose were compared to PBO. Both E-neg and E-pos high-dose groups significantly reduced HBsAg compared to PBO, with mean reductions of 0.38 and 0.54 log IU/mL, respectively. HBsAg reductions persisted for approximately 85 days and >85 days after the last dose in E-neg and E-pos patients, respectively. The low-dose groups did not reach statistical significance in either study. E-pos patients showed a dose-dependent reduction in HBeAg from baseline. Mean maximum reduction was 0.23 and 0.69 log Paul Ehrlich IUs/mL in the low-dose and high dose ARC-520 groups respectively. ARC-520 was well tolerated, with only two serious adverse events of pyrexia possibly related to study drug observed. CONCLUSIONS: ARC-520 was active in both E-neg and E-pos, NUC-experienced HBV patients; but absolute HBsAg reductions were moderate, possibly due to expression of HBsAg from integrated HBV DNA, indicating the need for RNAi therapeutics that can target viral transcripts regardless of origin.
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Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B Crónica/sangre , Hepatitis B Crónica/tratamiento farmacológico , ARN Interferente Pequeño/uso terapéutico , Tratamiento con ARN de Interferencia , Adulto , Anciano , Antivirales/administración & dosificación , Método Doble Ciego , Combinación de Medicamentos , Femenino , Guanina/administración & dosificación , Guanina/análogos & derivados , Humanos , Masculino , Persona de Mediana Edad , Tenofovir/administración & dosificación , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Uncertainties in detection of oral epithelial dysplasia (OED) frequently result from sampling error especially in inflammatory oral lesions. Endomicroscopy allows non-invasive, "en face" imaging of upper oral epithelium, but parameters of OED are unknown. METHODS: Mucosal nuclei were imaged in 34 toluidine blue-stained oral lesions with a commercial endomicroscopy. Histopathological diagnosis showed four biopsies in "dys-/neoplastic," 23 in "inflammatory," and seven in "others" disease groups. Strength of different assessment strategies of nuclear scoring, nuclear count, and automated nuclear analysis were measured by area under ROC curve (AUC) to identify histopathological "dys-/neoplastic" group. Nuclear objects from automated image analysis were visually corrected. RESULTS: Best-performing parameters of nuclear-to-image ratios were the count of large nuclei (AUC=0.986) and 6-nearest neighborhood relation (AUC=0.896), and best parameters of nuclear polymorphism were the count of atypical nuclei (AUC=0.996) and compactness of nuclei (AUC=0.922). Excluding low-grade OED, nuclear scoring and count reached 100% sensitivity and 98% specificity for detection of dys-/neoplastic lesions. In automated analysis, combination of parameters enhanced diagnostic strength. Sensitivity of 100% and specificity of 87% were seen for distances of 6-nearest neighbors and aspect ratios even in uncorrected objects. Correction improved measures of nuclear polymorphism only. The hue of background color was stronger than nuclear density (AUC=0.779 vs 0.687) to detect dys-/neoplastic group indicating that macroscopic aspect is biased. CONCLUSIONS: Nuclear-to-image ratios are applicable for automated optical in vivo diagnostics for oral potentially malignant disorders. Nuclear endomicroscopy may promote non-invasive, early detection of dys-/neoplastic lesions by reducing sampling error.
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Carcinoma in Situ/patología , Núcleo Celular/patología , Neoplasias de la Boca/patología , Boca/patología , Anciano , Anciano de 80 o más Años , Automatización , Endoscopía , Epitelio/patología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Microscopía , Persona de Mediana Edad , Proyectos PilotoRESUMEN
PURPOSE: TNF blockers are approved for intravenous or subcutaneous systemic therapy of many chronic inflammatory diseases. As it is not possible to achieve a sufficient local clinical improvement through systemic therapy in every patient, diverse approaches of topical therapy using TNF blockers have been investigated in recent years. METHODS: In this paper, we report on long-term clinical results of originator infliximab (IFX) injections into symptomatic combined scarring and inflammatory stenoses of the rectum in two patients with Crohn's disease. Aiming at high tissue IFX levels, 25 mg of IFX was injected into each quadrant of the stenosis after endoscopic balloon dilatation. This off-label treatment was repeated as necessary, depending on the clinical success. RESULTS: Topic IFX injection after balloon dilation reduced imperative stool pressure, isolated episodes of incontinence and incomplete emptying. Improvement lasted between 4 and 14 weeks in one patient and the treatment was repeated 13 times in the following 6.6 years. In the other patient, the technique was necessary only twice with no symptom recurrence in the subsequent 5.3 years. CONCLUSION: Our experience suggests that topic application of a systemically approved anti-TNF substance may be a successful individualized therapy for refractory stenosis of the rectum in patients with Crohn's disease.
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Antiinflamatorios/administración & dosificación , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/administración & dosificación , Infliximab/administración & dosificación , Obstrucción Intestinal/tratamiento farmacológico , Enfermedades del Recto/tratamiento farmacológico , Adulto , Colonoscopía , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Femenino , Humanos , Inyecciones Intralesiones , Obstrucción Intestinal/diagnóstico , Obstrucción Intestinal/etiología , Masculino , Enfermedades del Recto/diagnóstico , Enfermedades del Recto/etiología , Recurrencia , Retratamiento , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: Co-occurrence of oral lichen planus (OLP) and chronic hepatitis C virus (HCV) infection suggests a strong association, but the relation between mucocutaneus, autoimmune lichen planus and HCV infection remains unclear. In areas with higher prevalence of HCV infection in general population, like Japan and southern Europe, 20 to 40 % of patients with OLP test positive for anti-HCV antibodies, whereas in German populations, a co-occurrence of 4.2 to 16 % was reported. MATERIAL AND METHODS: We screened 143 patients with histopathologically proven OLP for prevalence of anti-HCV antibodies. Additionally, we examined 51 anti-HCV-positive subjects with current or past HCV infection for clinical symptoms of OLP. In all patients, confirmatory diagnosis was made by the detection of HCV RNA via reverse transcription-polymerase chain reaction (RT-PCR). A randomized control group comprised 109 blood sera samples of patients without any characteristics of OLP. RESULTS: The results of all patients showed no co-occurrence in either cohort. CONCLUSION: In conclusion, no association between oral lichen planus and chronic HCV infection in our study population was found. CLINICAL RELEVANCE: Anti-HCV antibody screening in patients with confirmed oral lichen planus is not indicated routinely in central Germany.
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Hepatitis C/epidemiología , Liquen Plano Oral/epidemiología , Estudios Transversales , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
OBJECTIVES: Prucalopride is effective at alleviating symptoms of chronic constipation in women. The aim of this study was to assess the efficacy of 12 weeks of prucalopride treatment compared with placebo in men with chronic constipation. METHODS: This was a multicenter, stratified, randomized, parallel-group, double-blind, placebo-controlled, phase 3 study (ClinicalTrials.gov identifier: NCT01147926). The primary end point was the proportion of patients with a mean of three or more spontaneous complete bowel movements (SCBMs) per week across the treatment period. Efficacy end points were assessed using daily electronic diaries, global assessment of the severity of constipation and efficacy of treatment, and Patient Assessment of Constipation-Symptoms (PAC-SYM) and Patient Assessment of Constipation-Quality of Life (PAC-QOL) questionnaires. RESULTS: In total, 374 patients were enrolled in the study. Significantly more patients achieved a mean of three or more SCBMs per week in the prucalopride group (37.9%) than in the placebo group (17.7%, P<0.0001). The proportion of patients rating their constipation treatment as "quite a bit" to "extremely" effective at the final on-treatment visit was 46.7 and 30.4% in the prucalopride and placebo groups, respectively. The difference between treatment groups was statistically significant (P<0.0001). The proportion of patients with an improvement of at least 1 point in PAC-QOL satisfaction subscale score was 52.7 and 38.8% in the prucalopride and placebo groups, respectively (P=0.0035). Prucalopride had a good safety profile and was well tolerated. CONCLUSIONS: Prucalopride is effective, has a good safety profile, and is well tolerated for the treatment of men with chronic constipation.
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Benzofuranos/uso terapéutico , Agonistas del Receptor de Serotonina 5-HT4/uso terapéutico , Dolor Abdominal/inducido químicamente , Adulto , Anciano , Benzofuranos/efectos adversos , Enfermedad Crónica , Defecación , Diarrea/inducido químicamente , Método Doble Ciego , Cefalea/inducido químicamente , Humanos , Masculino , Registros Médicos , Persona de Mediana Edad , Náusea/inducido químicamente , Calidad de Vida , Agonistas del Receptor de Serotonina 5-HT4/efectos adversos , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
UNLABELLED: The natural course of HCV infection remains controversial. The German HCV (1b)-contaminated anti-D cohort provides an ideal population to investigate the natural course of HCV infection in a large, homogenous cohort of young women from the date of HCV inoculation. Our previous follow-up studies at 20 and 25 years after infection suggested slow fibrosis progression rates in this unique cohort. The aim of our prospective, community-based, multicenter study was to reevaluate the liver disease progression in 718 patients of the original anti-D cohort at 35 years after infection. Patients with self-limited HCV infection (n = 189) were compared to those who failed to eliminate the virus spontaneously (n = 529), comprising patients who were treatment naïve (n = 197) or achieved a sustained virological response (SVR; n = 149), respectively, failed to clear the virus (non-SVR; n = 183) after antiviral therapy. In the overall cohort, 9.3% of patients showed clinical signs of liver cirrhosis at 35 years after infection. Liver disease progression largely depended on HCV infection status. The highest proportion of patients with clinical signs of end-stage liver disease was observed in the non-SVR group (15.3%), whereas decreased cirrhosis rates were detected in the SVR group (6%) and in patients with self-limited HCV infection (1.1%; P = 6.2 × 10(-6)). Overall survival was significantly enhanced after SVR, compared to treatment-naïve patients or non-SVR (P = 0.027). CONCLUSION: The present study provides further evidence for a mild, but significant, disease progression at 35 years after infection in the German HCV (1b)-contaminated anti-D cohort. Patients with self-limited HCV infection or SVR after antiviral treatment were protected from progressive liver disease and showed the best clinical long-term outcome.
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Hepatitis C/epidemiología , Adolescente , Adulto , Anciano , Antivirales/uso terapéutico , Progresión de la Enfermedad , Contaminación de Medicamentos , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Hepatitis C/tratamiento farmacológico , Hepatitis C/etiología , Humanos , Enfermedad Iatrogénica/epidemiología , Isoanticuerpos , Cirrosis Hepática/epidemiología , Cirrosis Hepática/etiología , Persona de Mediana Edad , Estudios Prospectivos , Globulina Inmune rho(D) , Análisis de Supervivencia , Adulto JovenAsunto(s)
Fuga Anastomótica/cirugía , Neoplasias del Colon/cirugía , Colonoscopía/métodos , Obesidad Mórbida , Anciano , Drenaje , Humanos , Masculino , Reoperación , VacioRESUMEN
BACKGROUND & AIMS: Teduglutide is a Glucagon-like peptide-2 (GLP-2) agonist indicated for the treatment of patients with parenteral support (PS) dependent short bowel syndrome (SBS) with chronic intestinal failure (cIF). Its application is accompanied by a structured nation-wide home-care service program in Germany. We investigated care characteristics and outcome parameters in a clinical real-world observational setting. METHODS: Data generated within a therapy-accompanying home-care service program for adult SBS-cIF patients were analyzed retrospectively for patients treated up to 1 year (data cut: April 2020). RESULTS: In total, 52 teduglutide-treated patients were included by 6 German cIF centers. At teduglutide administration start, 49/52 patients were on PS, 3 of them without macronutrients. The majority of patients received individualized parenteral nutrition (PN) (n = 32/46), while 13/46 were on commercial premixed bags. PS application was done by patients themselves (37%), home-care nurses (19%), relatives (8%) or by a combination of those (16%). In patients with PS dependency at baseline and available follow-up data (n = 40-44), teduglutide treatment resulted in significantly reduced PN days, caloric needs, infusion time, and infusion volume after 6 and 12 months. After 1 year, reduction of infusion time was positively correlated with a reduction of PN calories and volume; 30 patients (68%) were responders (PS-volume reduction ≥20%), and 6 patients (14%) were completely weaned off PS. Sleep disturbances per night were significantly reduced after 3 months of treatment and stool characteristics improved in consistency and significantly in frequency, while meal frequency remained stable. CONCLUSIONS: Teduglutide treatment associated reduction in PS volume and calories was accompanied by reduced infusion days, infusion times, sleep disturbances, stable oral intake surrogates, and improved stool characteristics, all of these potential parameters for improving quality of life. Furthermore, analyzed care characteristics reflect SBS-cIF treatment as a complex, resource-intensive and demanding task for both, healthcare system and patients.
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Enfermedades Intestinales , Insuficiencia Intestinal , Síndrome del Intestino Corto , Adulto , Enfermedad Crónica , Fármacos Gastrointestinales/uso terapéutico , Péptidos Similares al Glucagón/uso terapéutico , Humanos , Enfermedades Intestinales/tratamiento farmacológico , Péptidos , Calidad de Vida , Estudios Retrospectivos , Síndrome del Intestino Corto/tratamiento farmacológicoRESUMEN
BACKGROUND & AIMS: The CCR5Δ32 mutation has been suspected to adversely affect outcomes of HCV infection, although reports have remained controversial. Here, we investigated the relative genetic contributions of the CCR5Δ32 deletion and the IL28B rs12979860 polymorphisms to spontaneous clearance of hepatitis C in a single-source outbreak. METHODS: We retrieved 396 Caucasian women (119 women with spontaneous HCV clearance) who had been infected with HCV genotype 1-contaminated anti-D immunoglobulin in 1978, and determined their IL28B and CCR5 alleles. RESULTS: IL28B CC, CT, and TT genotypes were found in 35.4%, 50%, and 14.6% of patients and corresponded to spontaneous clearance rates of 50%, 21.2%, and 12.1% (Chi(2)=38.7, p=5.0×10(-10)), respectively. CCR5 WT/WT, WT/Δ32, and Δ32/Δ32 genotypes were observed in 76%, 22.7%, and 1.3% of patients and corresponded to clearance rates of 33.2%, 21.2%, and 0% (Chi(2)=6.9, p=0.009), respectively. In a stepwise forward-conditional multivariate regression model both CCR5 (OR 2.1, p=0.01 for WT/WT) and IL28B genetic variants (OR 4.3, p=4.6×10(-10) for the C/C genotype) were identified as independent predictors of spontaneous HCV clearance. Importantly, favorable response rates were associated with the IL28B CC genotype only in CCR5 wild-type homozygous women, while HCV clearance in CCR5Δ32 carriers remained poor even in patients with the rs12979860 CC genotype. CONCLUSIONS: Both IL28B rs1297860 and CCR5Δ32 allelic variants are independent genetic determinants of spontaneous HCV clearance. The variable relative distribution between IL28B rs1297860 and CCR5Δ32 allelic variants in different populations may have masked the role of the CCR5Δ32 mutation in some studies.
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Hepatitis C/genética , Interleucinas/genética , Receptores CCR5/genética , Alelos , Estudios de Casos y Controles , Estudios de Cohortes , Brotes de Enfermedades , Contaminación de Medicamentos , Femenino , Frecuencia de los Genes , Genotipo , Alemania/epidemiología , Hepatitis C/epidemiología , Hepatitis C/inmunología , Hepatitis C/transmisión , Hepatitis C/virología , Humanos , Interferones , Polimorfismo de Nucleótido Simple , Eliminación de SecuenciaRESUMEN
BACKGROUND & AIMS: A single nucleotide polymorphism (SNP) upstream of the IL28B gene has been associated with response of patients with chronic hepatitis C to therapy with pegylated interferon and ribavirin and also with spontaneous clearance of acute hepatitis C in a heterogeneous population. We analyzed the association between IL28B and the clinical presentation of acute hepatitis C virus (HCV) infection in a homogeneous population. METHODS: We analyzed the SNP rs12979860 in 190 women from the German anti-D cohort (infected with HCV genotype 1b via contaminated rhesus prophylaxis) and its association with spontaneous clearance. Clinical data were available in 136 women with acute infection who were also evaluated for IL28B genotype. Based on results of a TaqMan polymerase chain reaction assay, the rs12979860 SNP genotypes studied were C/C, C/T, or T/T. RESULTS: Spontaneous clearance was more common in patients with the C/C genotype (43/67; 64%) compared with C/T (22/90; 24%) or T/T (2/33; 6%) (P < .001). Jaundice during acute infection was more common among patients with C/C genotype (32.7%) than non-C/C patients (with C/T or T/T) (16.1%; P = .032). In C/C patients, jaundice during acute infection was not associated with an increased chance of spontaneous clearance (56.3%) compared with those without jaundice (60.6%). In contrast, in non-C/C patients, jaundice was associated with a higher likelihood of spontaneous clearance (42.9%) compared with those without jaundice (13.7%). CONCLUSIONS: The SNP rs12979860 upstream of IL28B is associated with spontaneous clearance of HCV. Women with the C/T or T/T genotype who did not develop jaundice had a lower chance of spontaneous clearance of HCV infection.
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ADN/genética , Hepatitis C/genética , Interleucinas/genética , Ictericia/genética , Polimorfismo Genético , Enfermedad Aguda , Adulto , Femenino , Estudios de Seguimiento , Genotipo , Hepatitis C/complicaciones , Hepatitis C/metabolismo , Humanos , Interferones , Interleucinas/metabolismo , Ictericia/etiología , Ictericia/metabolismo , Reacción en Cadena de la Polimerasa , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
Iron deficiency is a common cause of morbidity and can arise as a consequence or complication from many diseases. The use of intravenous iron has increased significantly in the last decade, but concerns remain about indications and administration. Modern intravenous iron preparations can facilitate rapid iron repletion in one or two doses, both for absolute iron deficiency and, in the presence of inflammation, functional iron deficiency, where oral iron therapy is ineffective or has not worked. A multidisciplinary team of experts experienced in iron deficiency undertook a consensus review to support healthcare professionals with practical advice on managing iron deficiency in gastrointestinal, renal and cardiac disease, as well as; pregnancy, heavy menstrual bleeding, and surgery. We explain how intravenous iron may work where oral iron has not. We provide context on how and when intravenous iron should be administered, and informed opinion on potential benefits balanced with potential side-effects. We propose how intravenous iron side-effects can be anticipated in terms of what they may be and when they may occur. The aim of this consensus is to provide a practical basis for educating and preparing staff and patients on when and how iron infusions can be administered safely and efficiently. Key messages Iron deficiency treatment selection is driven by several factors, including the presence of inflammation, the time available for iron replenishment, and the anticipated risk of side-effects or intolerance. Intravenous iron preparations are indicated for the treatment of iron deficiency when oral preparations are ineffective or cannot be used, and therefore have applicability in a wide range of clinical contexts, including chronic inflammatory conditions, perioperative settings, and disorders associated with chronic blood loss. Adverse events occurring with intravenous iron can be anticipated according to when they typically occur, which provides a basis for educating and preparing staff and patients on how iron infusions can be administered safely and efficiently.
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Administración Intravenosa , Compuestos de Hierro/administración & dosificación , Deficiencias de Hierro , Administración Oral , Toma de Decisiones Clínicas , Consenso , Femenino , Humanos , Masculino , Guías de Práctica Clínica como Asunto , EmbarazoRESUMEN
BACKGROUND: Endoscopic band ligation (EBL) is generally accepted as the treatment of choice for bleeding from esophageal varices. It is also used for secondary prophylaxis of esophageal variceal hemorrhage. However, there is no data or guidelines concerning endoscopic control of ligation ulcers. We conducted a retrospective study of EBL procedures analyzing bleeding complications after EBL. METHODS: We retrospectively analyzed data from patients who underwent EBL. We analyzed several data points, including indication for the procedure, bleeding events and the time interval between EBL and bleeding. RESULTS: 255 patients and 387 ligation sessions were included in the analysis. We observed an overall bleeding rate after EBL of 7.8%. Bleeding events after elective treatment (3.9%) were significantly lower than those after treatment for acute variceal hemorrhage (12.1%). The number of bleeding events from ligation ulcers and variceal rebleeding was 14 and 15, respectively. The bleeding rate from the ligation site in the group who underwent emergency ligation was 7.1% and 0.5% in the group who underwent elective ligation. Incidence of variceal rebleeding did not vary significantly. Seventy-five percent of all bleeding episodes after elective treatment occurred within four days after EBL. 20/22 of bleeding events after emergency ligation occurred within 11 days after treatment. Elective EBL has a lower risk of bleeding from treatment-induced ulceration than emergency ligation. CONCLUSIONS: Patients who underwent EBL for treatment of acute variceal bleeding should be kept under medical surveillance for 11 days. After elective EBL, it may be reasonable to restrict the period of surveillance to four days or even perform the procedure in an out-patient setting.
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Endoscopía Gastrointestinal/métodos , Várices Esofágicas y Gástricas/cirugía , Hemorragia Gastrointestinal/prevención & control , Ligadura/métodos , Urgencias Médicas , Endoscopía Gastrointestinal/mortalidad , Endoscopía Gastrointestinal/estadística & datos numéricos , Hemorragia Gastrointestinal/epidemiología , Humanos , Incidencia , Estimación de Kaplan-Meier , Ligadura/mortalidad , Ligadura/estadística & datos numéricos , Persona de Mediana Edad , Recurrencia , Estudios RetrospectivosAsunto(s)
Anemia Ferropénica/diagnóstico , Anemia Ferropénica/tratamiento farmacológico , Compuestos de Hierro/uso terapéutico , Administración Oral , Anemia Ferropénica/etiología , Diagnóstico Diferencial , Alemania , Adhesión a Directriz , Hemoglobinometría , Humanos , Inyecciones Intravenosas , Compuestos de Hierro/efectos adversos , Resultado del TratamientoRESUMEN
Ferric carboxymaltose (FCM) has been shown to achieve rapid replenishment of iron stores and correction of anaemia in various populations with iron deficiency. A decrease in serum phosphate (PO43-) levels, which in most cases is asymptomatic, has been reported with IV iron preparations. Hypophosphataemia (HP) is a known adverse drug reaction with FCM. This post hoc pooled analysis investigates the frequency, duration, risk factors, and clinical signs of HP as reported in interventional clinical trials with FCM. Pooled data from subjects enrolled across 45 clinical trials in different therapy areas were included. A three-step adjudication process was utilised to identify adverse events of HP. Stratified analyses by therapy group and stepwise logistic regression analysis were used to identify predictors of HP. This pooled analysis confirms that FCM is associated with increased rates of serum PO43- lowering, but mean serum PO43- values were seen to recover at Week 4 and further recover at Week 8. Among all subjects receiving FCM therapy (n = 6879), 41.4% (n = 2847) reached a PO43- nadir value <2.5 mg/dL at any point on study and 0.7% (n = 49) reached a nadir <1 mg/dL. Although gastroenterology and women's health subjects were identified to be at higher risk, occurrence of severe HP (<1 mg/dL [0.3 mmol/L]) following FCM administration was not observed to be common among subjects in these studies. Furthermore, there was no correlation between laboratory serum PO43- values and the occurrence of reported adverse events related to low PO43- levels.
RESUMEN
BACKGROUND: Knowledge about cancer-related malnutrition and the use of clinical nutrition (CN) in the real-world setting are lacking. We investigated diagnosis and treatment frequency of malnutrition in a multinational survey to identify unmet needs in cancer patients' care. METHODS: Retrospective analyses were conducted on data from three administrative healthcare datasets from France (n = 570,727), Germany (n = 4642) and Italy (n = 58,468). Data from France described frequency and timing of malnutrition diagnosis in hospitalized gastrointestinal cancer patients. The German data detailed home parenteral nutrition (HPN) use in cancer patients with stage III/IV cancers. The Italian data analysed three cohorts: metastatic with CN, metastatic without CN, and patients without metastatic disease. RESULTS: In France, malnutrition diagnosis at first hospitalization occurred in 10% of patients, 13% were subsequently diagnosed, and 77% had no malnutrition diagnosis. In Germany, 16% of patients received HPN. Patients started HPN around 3 months before death. In Italy, 8.4% of metastatic cancer patients received CN; average time between metastasis diagnosis and first CN prescription was 6.6 months. Average time between first CN prescription and death was 3.5 months. CONCLUSIONS: These data indicate that in the real-world clinical practice, cancer-related malnutrition is under-recognized and undertreated. CN often appears to be prescribed as an end-of-life intervention or is not prescribed at all.Appropriate CN use remains challenging, and current practice may not allow optimal oncologic outcomes for patients at nutritional risk. Improving awareness of malnutrition and generating further evidence on clinical and economic benefits of CN are critical priorities in oncology.