RESUMEN
BACKGROUND: This study aimed to determine whether paromomycin plus miltefosine (PM/MF) is noninferior to sodium stibogluconate plus paromomycin (SSG/PM) for treatment of primary visceral leishmaniasis in eastern Africa. METHODS: An open-label, phase 3, randomized, controlled trial was conducted in adult and pediatric patients at 7 sites in eastern Africa. Patients were randomly assigned to either 20 mg/kg paromomycin plus allometric dose of miltefosine (14 days), or 20 mg/kg sodium stibogluconate plus 15 mg/kg paromomycin (17 days). The primary endpoint was definitive cure after 6 months. RESULTS: Of 439 randomized patients, 424 completed the trial. Definitive cure at 6 months was 91.2% (155 of 170) and 91.8% (156 of 170) in the PM/MF and SSG/PM arms in primary efficacy modified intention-to-treat analysis (difference, 0.6%; 97.5% confidence interval [CI], -6.2 to 7.4), narrowly missing the noninferiority margin of 7%. In the per-protocol analysis, efficacy was 92% (149 of 162) and 91.7% (155 of 169) in the PM/MF and SSG/PM arms (difference, -0.3%; 97.5% CI, -7.0 to 6.5), demonstrating noninferiority. Treatments were well tolerated. Four of 18 serious adverse events were study drug-related, and 1 death was SSG-related. Allometric dosing ensured similar MF exposure in children (<12 years) and adults. CONCLUSIONS: PM/MF and SSG/PM efficacies were similar, and adverse drug reactions were as expected given the drugs safety profiles. With 1 less injection each day, reduced treatment duration, and no risk of SSG-associated life-threatening cardiotoxicity, PM/MF is a more patient-friendly alternative for children and adults with primary visceral leishmaniasis in eastern Africa. CLINICAL TRIALS REGISTRATION: NCT03129646.
Asunto(s)
Antiprotozoarios , Leishmaniasis Visceral , Adulto , Humanos , Niño , Paromomicina/efectos adversos , Antiprotozoarios/efectos adversos , Gluconato de Sodio Antimonio/efectos adversos , Leishmaniasis Visceral/tratamiento farmacológico , Resultado del Tratamiento , Quimioterapia Combinada , África Oriental , Fosforilcolina/efectos adversosRESUMEN
Patients with hematologic malignancies undergoing chemotherapy and requiring blood transfusion usually have an elevated serum ferritin. These findings have led to the suggestion that iron overload is common and may have deleterious effects in these patients. However, the relationship between serum ferritin and parenchymal iron overload in such patients is unknown. Therefore, we measured the liver iron content (LIC) by the FerriScan® method and investigated the liver function and some endocrine tests in 27 patients with acute leukemia (AL) or myelodysplastic syndromes (MDS). Using FerriScan® method, the normal mean LIC levels are: 4.3 ± 2.9 mg Fe/g dry weight (d.w.). In our patients, the mean serum ferritin level was 1965 ± 2428 ng/mL. In our patients, the mean total iron in the blood received by them was 7177 ± 5009 mg. In 6 out of 27 patients LIC was > 7 mg Fe/g d.w. and in 11/27 serum ferritin was > 1000 ng/ml. Measuring fasting blood glucose revealed 3/27 with diabetes mellitus and 4/27 with impaired fasting glucose (IFG). All patients had normal serum concentrations of calcium, parathormone (PTH), free thyroxine (FT4) and thyrotropin (TSH). Four patients had elevated serum alanine transferase (ALT). LIC was correlated significantly with ferritin level (r = 0.5666; P < 0.001) and the cumulative amount of iron in the transfused blood (r = 0.523; P <0.001). LIC was correlated significantly with ALT (r = 0.277; P = 0.04) and fasting blood glucose (FBG) was correlated significantly with the amount of iron transfused (r = 0.52, p < 0.01) and ALT level (r = 0.44; P< 0.01). The age of patients did not correlate with LIC, FBG or ALT. In conclusions, these results contribute to our understanding of the prevalence of dysglycemia and hepatic dysfunction in relation to parenchymal iron overload in patients with hematologic malignancies undergoing chemotherapy and requiring blood transfusions.
Asunto(s)
Transfusión Sanguínea , Sistema Endocrino/fisiopatología , Sobrecarga de Hierro/fisiopatología , Leucemia/complicaciones , Hígado/fisiopatología , Síndromes Mielodisplásicos/complicaciones , Enfermedad Aguda , Adulto , Alanina Transaminasa/sangre , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Biomarcadores , Glucemia/análisis , Diabetes Mellitus/sangre , Diabetes Mellitus/etiología , Ferritinas/sangre , Hormonas/sangre , Humanos , Hipotiroidismo/etiología , Hierro/análisis , Sobrecarga de Hierro/etiología , Leucemia/tratamiento farmacológico , Leucemia/terapia , Hígado/química , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/terapiaRESUMEN
PATIENT: Male, 66. FINAL DIAGNOSIS: Hepatocellular carcinoma. SYMPTOMS: Abdominal distension ⢠painful right facial swelling ⢠weight loss. MEDICATION: -. CLINICAL PROCEDURE: -. SPECIALTY: -. OBJECTIVE: Rare disease. BACKGROUND: Hepatocellular carcinoma is a common cancer, but it rarely metastasizes to the salivary glands. A review of the literature revealed only 5 reported cases of hepatocellular carcinoma metastatic to parotid glands. We here report an additional case of this rare association. CASE REPORT: A 66-year-old male with a background of type 2 diabetes mellitus and post-alcoholic decompensated liver cirrhosis presented with a progressively enlarging painful right facial swelling for 2 months that was eventually found to be due to hepatocellular carcinoma metastatic to the right parotid gland. Fine needle aspiration from the right parotid showed sheets and single malignant cells that were interpreted as carcinoma not otherwise specific. However, biopsy showed metastatic hepatocellular carcinoma into the right parotid gland. CONCLUSIONS: We report an additional case of the rare metastasis of hepatocellular carcinoma to the parotid glands. It should therefore be considered in a patient with decompensated liver cirrhosis presenting with a parotid swelling. Furthermore, the present case demonstrates the importance of the tissue biopsy for obtaining an accurate final diagnosis.