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BACKGROUND: The maternal mortality ratio (MMR) in Indonesia is among the highest in Southeast Asia. We aim to describe trends in the MMR and causes of maternal deaths in Indonesia over the past decades, regionally and nationally. METHODS: We performed a systematic review and conducted a search using PubMed, Embase, Global Health, CINAHL, Cochrane, Portal Garuda, and Google Scholar from the inception of the database to April 2023. We included all studies on the incidence and/or the causes of maternal deaths in Indonesia. The MMR was defined as the number of maternal deaths per 100,000 live births. Maternal death causes were assessed and reclassified according to the WHO International Classification of Disease Maternal Mortality (ICD-MM). RESULTS: We included 63 studies that reported the MMR (54 studies) and/or the causes of maternal deaths (44 studies) in Indonesia from 1970 to 2022, with a total of 254,796 maternal deaths. The national MMR declined from 450 to 249 (45%) between 1990 and 2020. Great differences in MMR exist across the country, with the lowest in Java-Bali and the highest (more than twice the national MMR) in Sulawesi and Eastern Indonesia. Between 1990 and 2022, the proportion of deaths due to hemorrhage and sepsis decreased, respectively from 48 to 18% and 15-5%, while the share of deaths due to hypertensive disorders and non-obstetric causes increased, respectively from 8 to 19% and 10-49%. CONCLUSION: Despite the steady decline of maternal deaths in Indonesia, it remains one of the highest in Southeast Asia, with enormous disparities within the country. Hypertensive disorders and non-communicable diseases make up a growing share of maternal deaths, making maternal death reduction strategies increasingly challenging. National Maternal Death Surveillance and Response needs to be prioritized to eliminate preventable maternal deaths in Indonesia. REGISTRATION OF SYSTEMATIC REVIEWS: PROSPERO, CRD42022320213.
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Causas de Muerte , Mortalidad Materna , Humanos , Indonesia/epidemiología , Mortalidad Materna/tendencias , Femenino , Embarazo , Causas de Muerte/tendencias , Complicaciones del Embarazo/mortalidad , Complicaciones del Embarazo/epidemiologíaRESUMEN
BACKGROUND AND OBJECTIVE: SMARCB1-deficient renal medullary carcinoma (RMC) is a rare kidney cancer associated with sickle cell hemoglobinopathies with poor outcomes described only in case reports and small series. We report disease and management characteristics as well as contemporary survival outcomes in a large cohort of patients with RMC. METHODS: Data were extracted retrospectively from all patients with RMC treated at MD Anderson Cancer Center between January 2003 and December 2023. Multivariable Cox regression was used to estimate overall survival (OS) by diagnosis period. KEY FINDINGS AND LIMITATIONS: Among 135 patients (median follow-up of 54.9 mo), only nine did not harbor a sickle hemoglobinopathy and were categorized as having renal cell carcinoma, unclassified with medullary phenotype (RCCU-MP). Most patients (78%) presented with metastatic disease, predominantly to the retroperitoneal lymph nodes (81.7%), and hematuria was the most frequent presenting symptom (60%) in RMC associated with sickle hemoglobinopathy. Survival outcomes improved by diagnosis year (adjusted hazard ratio 0.70, 95% confidence interval 0.53-0.92, p = 0.01). RCCU-MP occurred in slightly older patients with median OS of 19.5 mo from diagnosis, did not show a predilection to the right kidney or male predominance, and afflicted mainly Caucasians (89%). The study is limited by its retrospective nature conducted at one center. CONCLUSIONS AND CLINICAL IMPLICATIONS: RMC frequently presents with hematuria and is highly likely to spread to the retroperitoneal lymph nodes. Survival outcomes are improving with contemporary management. RCCU-MP is very rare and may be slightly less aggressive. PATIENT SUMMARY: Renal medullary carcinoma (RMC) is a rare and aggressive subtype of kidney cancer afflicting primarily young men and women of African descent. There exist limited data regarding patient demographics and disease characteristics. We reported our institution's experience in treating patients with RMC. The first symptom most patients with RMC reported was blood in the urine, and the most common places where the cancer spread were the lymph nodes around the kidney. Patients with RMC are living longer with contemporary treatments.
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Background: The World Health Organization launched the International Classification of Diseases for Perinatal Mortality (ICD-PM) in 2016 to uniformly report on the causes of perinatal deaths. In this systematic review, we aim to describe the global use of the ICD-PM by reporting causes of perinatal mortality and summarizing challenges and suggested amendments. Methods: We systematically searched MEDLINE, Embase, Global Health, and CINAHL databases using key terms related to perinatal mortality and the classification for causes of death. We included studies that applied the ICD-PM and were published between January 2016 and June 2021. The ICD-PM data were extracted and a qualitative analysis was performed to summarize the challenges of the ICD-PM. We applied the PRISMA guidelines, registered our protocol at PROSPERO [CRD42020203466], and used the Appraisal tool for Cross-Sectional Studies (AXIS) as a framework to evaluate the quality of evidence. Results: The search retrieved 6599 reports. Of these, we included 15 studies that applied the ICD-PM to 44 900 perinatal deaths. Most causes varied widely; for example, "antepartum hypoxia" was the cause of stillbirths in 0% to 46% (median = 12%, n = 95) in low-income settings, 0% to 62% (median = 6%, n = 1159) in middle-income settings and 0% to 55% (median = 5%, n = 249) in high-income settings. Five studies reported challenges and suggested amendments to the ICD-PM. The most frequently reported challenges included the high proportion of antepartum deaths of unspecified cause (five studies), the inability to determine the cause of death when the timing of death is unknown (three studies), and the challenge of assigning one cause in case of multiple contributing conditions (three studies). Conclusions: The ICD-PM is increasingly being used across the globe and gives health care providers insight into the causes of perinatal death in different settings. However, there is wide variation in reported causes of perinatal death across comparable settings, which suggests that the ICD-PM is applied inconsistently. We summarized the suggested amendments and made additional recommendations to improve the use of the ICD-PM and help strengthen its consistency. Registration: PROSPERO [CRD42020203466].
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Muerte Perinatal , Causas de Muerte , Estudios Transversales , Femenino , Humanos , Clasificación Internacional de Enfermedades , Muerte Perinatal/etiología , Mortalidad Perinatal , Embarazo , Mortinato/epidemiologíaRESUMEN
At JADPRO Live Virtual 2021, advanced practitioner experts reviewed clinical updates in the treatment of renal cell carcinoma, key patient counseling and monitoring considerations, and best practices to manage adverse events associated with therapies for renal cell carcinoma.
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BACKGROUND: Latin America and the Caribbean is the region with the highest prevalence of hypertensive disorders of pregnancy worldwide. In Suriname, where the stillbirth rate is the second highest in the region, it is not yet known which maternal factors contribute most substantially. OBJECTIVE: The aims of this study in Suriname were to (1) study the impact of different types of maternal morbidity on adverse perinatal outcomes and (2) study perinatal birth outcomes among women with severe hypertensive disorders of pregnancy. STUDY DESIGN: A case-control study was conducted between March 2017 and February 2018 during which time all hospital births (86% of total) in Suriname were included. We identified babies with adverse perinatal outcomes (perinatal death or neonatal near miss) and women with severe maternal morbidity (according to the World Health Organization Near Miss tool). Stillbirths and early neonatal deaths (<7 days) were considered perinatal death. We defined a neonatal near miss as a birthweight below 1750 g, gestational age <33 weeks, 5-minute Apgar score <7, and preterm intrauterine growth restriction
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BACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of direct maternal mortality globally and in Suriname. We aimed to study the prevalence, risk indicators, causes, and management of PPH to identify opportunities for PPH reduction. METHODS: A nationwide retrospective descriptive study of all hospital deliveries in Suriname in 2017 was performed. Logistic regression analysis was applied to identify risk indicators for PPH (≥ 500ml blood loss). Management of severe PPH (blood loss ≥1,000ml or ≥500ml with hypotension or at least three transfusions) was evaluated via a criteria-based audit using the national guideline. RESULTS: In 2017, the prevalence of PPH and severe PPH in Suriname was 9.2% (n = 808/8,747) and 2.5% (n = 220/8,747), respectively. PPH varied from 5.8% to 15.8% across the hospitals. Risk indicators associated with severe PPH included being of African descent (Maroon aOR 2.1[95%CI 1.3-3.3], Creole aOR 1.8[95%CI 1.1-3.0]), multiple pregnancy (aOR 3.4[95%CI 1.7-7.1]), delivery in Hospital D (aOR 2.4[95%CI 1.7-3.4]), cesarean section (aOR 3.9[95%CI 2.9-5.3]), stillbirth (aOR 6.4 [95%CI 3.4-12.2]), preterm birth (aOR 2.1[95%CI 1.3-3.2]), and macrosomia (aOR 2.8 [95%CI 1.5-5.0]). Uterine atony (56.7%, n = 102/180[missing 40]) and retained placenta (19.4%, n = 35/180[missing 40]), were the main causes of severe PPH. A criteria-based audit revealed that women with severe PPH received prophylactic oxytocin in 61.3% (n = 95/155[missing 65]), oxytocin treatment in 68.8% (n = 106/154[missing 66]), and tranexamic acid in 4.9% (n = 5/103[missing 117]). CONCLUSIONS: PPH prevalence and risk indicators in Suriname were similar to international and regional reports. Inconsistent blood loss measurement, varied maternal and perinatal characteristics, and variable guideline adherence contributed to interhospital prevalence variation. PPH reduction in Suriname can be achieved through prevention by practicing active management of the third stage of labor in every birth and considering risk factors, early recognition by objective and consistent blood loss measurement, and prompt treatment by adequate administration of oxytocin and tranexamic acid according to national guidelines.
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Parto , Hemorragia Posparto/mortalidad , Nacimiento Prematuro/mortalidad , Inercia Uterina/mortalidad , Adulto , Femenino , Humanos , Hemorragia Posparto/etiología , Hemorragia Posparto/prevención & control , Embarazo , Nacimiento Prematuro/prevención & control , Estudios Retrospectivos , Suriname/epidemiología , Inercia Uterina/prevención & controlRESUMEN
Constrictive pericarditis is a disease where loss of pericardial elasticity and restriction of filling of the cardiac chambers occurs. It is most often seen as an associated symptom of heart failure. Pericardiectomy provides effective treatment for patients with symptomatic constrictive pericarditis, although high rates of morbidity and mortality are related to the procedure. We present a case with extensive calcification, massive caseous necrosis and an important impairment of right ventricular function successfully operated in our institution.
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Insuficiencia Cardíaca , Pericarditis Constrictiva , Calcificación Vascular/complicaciones , Humanos , Necrosis , Pericardiectomía , Pericarditis Constrictiva/diagnóstico por imagen , Pericarditis Constrictiva/etiología , Pericarditis Constrictiva/cirugía , Pericardio/diagnóstico por imagen , Pericardio/cirugíaRESUMEN
BACKGROUND: Suriname has one of the highest stillbirth rates in Latin America and the Caribbean. To facilitate data comparison of perinatal deaths, the World Health Organization developed the International Classification of Diseases-10 Perinatal Mortality (ICD-PM). OBJECTIVE: We aimed to (1) assess characteristics and risk indicators of women with a stillbirth, (2) determine the timing and causes of stillbirths according to the ICD-PM with critical evaluation of its application and (3) propose recommendations for the reduction of stillbirths in Suriname. METHODS: A hospital-based, nation-wide, cross-sectional study was conducted in all hospitals within Suriname during one-year (2017). The medical files of stillbirths (gestation ≥28 weeks/birth weight ≥1000 grams) were reviewed and classified using ICD-PM. We used descriptive statistics and multiple logistic regression analyses. RESULTS: The stillbirth rate in Suriname was 14.4/1000 births (n=131 stillbirths, n=9089 total births). Medical files were available for 86% (n=113/131) of stillbirths. Women of African descent had the highest stillbirth rate and two times the odds of stillbirth (OR 2.1, 95%CI 1.4-3.1) compared to women of other ethnicities. One third (33%, n=37/113) of stillbirths occurred after hospital admission. The timing was antepartum in 85% (n=96/113), intrapartum in 11% (n=12/113) and unknown in 4% (n=5/113). Antepartum stillbirths were caused by hypoxia in 46% (n=44/96). In 41% (n=39/96) the cause was unspecified. Maternal medical and surgical conditions were present in 50% (n=57/113), mostly hypertensive disorders. CONCLUSION: Stillbirth reduction strategies in Suriname call for targeting ethnic disparities, improving antenatal services, implementing perinatal death audits and improving diagnostic post-mortem investigations. ICD-PM limited the formulation of recommendations due to many stillbirths of 'unspecified' causes. Based on our study findings, we also recommend addressing some challenges with applying the ICD-PM. ABBREVIATIONS: CTG: Cardiotocography; ENAP: Every Newborn Action Plan (ENAP); ICD-PM: The WHO application of ICD-10 to deaths during the perinatal period - perinatal mortality; SBR: Stillbirth rate; SGA: Small for gestational age; WHO: World Health Organization; LMIC: Low- and middle-income countries; FHR: foetal heart rate.
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Muerte Perinatal , Mortalidad Perinatal , Mortinato , Adulto , Región del Caribe , Causas de Muerte , Estudios Transversales , Femenino , Hospitales , Humanos , Recién Nacido , Clasificación Internacional de Enfermedades , Parto , Muerte Perinatal/etiología , Embarazo , Factores de Riesgo , Mortinato/epidemiología , Suriname/epidemiología , Organización Mundial de la SaludRESUMEN
BACKGROUND: Our study aims to evaluate the current perinatal registry, analyze national childbirth outcomes and study ethnic disparities in middle-income country Suriname, South America. METHODS: A nationwide birth registry study was conducted in Suriname. Data were collected for 2016 and 2017 from the childbirth books of all five hospital maternity wards, covering 86% of all births in the country. Multinomial regression analyses were used to assess ethnic disparities in outcomes of maternal deaths, stillbirths, teenage pregnancy, cesarean delivery, low birth weight and preterm birth with Hindustani women as reference group. RESULTS: 18.290 women gave birth to 18.118 (98%) live born children in the five hospitals. Hospital-based maternal mortality ratio was 112 per 100.000 live births. Hospital-based late stillbirth rate was 16 per 1000 births. Stillbirth rate was highest among Maroon (African-descendent) women (25 per 1000 births, aOR 2.0 (95%CI 1.3-2.8) and lowest among Javanese women (6 stillbirths per 1000 births, aOR 0.5, 95%CI 0.2-1.2). Preterm birth and low birthweight occurred in 14 and 15% of all births. Teenage pregnancy accounted for 14% of all births and was higher in Maroon women (18%) compared to Hindustani women (10%, aOR 2.1, 95%CI 1.8-2.4). The national cesarean section rate was 24% and was lower in Maroon (17%) than in Hindustani (32%) women (aOR 0.5 (95%CI 0.5-0.6)). Cesarean section rates varied between the hospitals from 17 to 36%. CONCLUSION: This is the first nationwide comprehensive overview of maternal and perinatal health in a middle income country. Disaggregated perinatal health data in Suriname shows substantial inequities in outcomes by ethnicity which need to be targetted by health professionals, researchers and policy makers.
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Parto Obstétrico/mortalidad , Mortalidad Materna , Parto , Complicaciones del Embarazo/mortalidad , Adolescente , Adulto , Cesárea , Etnicidad , Femenino , Disparidades en el Estado de Salud , Humanos , Edad Materna , Embarazo , Complicaciones del Embarazo/etnología , Resultado del Embarazo , Nacimiento Prematuro/etnología , Nacimiento Prematuro/mortalidad , Sistema de Registros , Factores de Riesgo , Mortinato/etnología , Suriname , Adulto JovenRESUMEN
BACKGROUND: Temsirolimus has level 1 evidence for initial treatment of poor-risk patients with advanced renal cell carcinoma (mRCC), but its efficacy has not been directly compared with an antiangiogenic tyrosine kinase inhibitor (vascular endothelial growth factor receptor tyrosine kinase inhibitor [VEGFR TKi]) in this setting. OBJECTIVE: To evaluate temsirolimus versus pazopanib as first-line therapy in patients with mRCC, predominant clear-cell features, and clinical characteristics of a poor prognosis. DESIGN, SETTING, AND PARTICIPANTS: A randomized (1:1) phase II trial in 69 treatment-naïve mRCC patients and with three or more predictors of short survival for temsirolimus was conducted during 2012-2017 in a single academic cancer center. Crossover to the alternative treatment upon discontinuation of the first-line agent was permitted. INTERVENTION: Mechanistic target of rapamycin inhibitor temsirolimus and VEGFR TKi pazopanib. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), safety, and patient-reported outcomes (PROs). Radiographic response was assessed by blinded radiologists. Efficacy outcomes were adjusted by prior nephrectomy status, prior interleukin-2 treatment, and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score. RESULTS AND LIMITATIONS: Thirty-five patients received temsirolimus and 34 received pazopanib upfront; 72% overall had poor risk by IMDC. Median PFS in the first line was 2.7mo with temsirolimus and 5.2mo with pazopanib (adjusted hazard ratio [HR] 1.36, 95% confidence interval [CI] 0.84-2.22; p=0.210). Median OS was 7.1mo with temsirolimus and 11.9mo with pazopanib (adjusted HR 1.16, 95% CI 0.70-1.93; p=0.558), and ORRs were 5.9% and 21.2%, respectively (adjusted odds ratio 5.2, 95% CI 0.9-29.3; p=0.062). PRO measures favored pazopanib. Five patients discontinued first-line therapy due to adverse events. CONCLUSIONS: Temsirolimus and pazopanib had modest activity in patients with poor-risk clear-cell mRCC, and therefore their use should be discouraged in this setting. PATIENT SUMMARY: We evaluated outcomes of advanced renal cell carcinoma patients presenting with aggressive features when treated with temsirolimus or pazopanib as first-line therapy. Survival was <1yr for most, suggesting that more efficacious alternative treatments should be favored for these patients.
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Carcinoma de Células Renales/tratamiento farmacológico , Indazoles/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Pirimidinas/uso terapéutico , Sirolimus/análogos & derivados , Sulfonamidas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/patología , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Medición de Riesgo , Método Simple Ciego , Sirolimus/uso terapéuticoRESUMEN
Penetrating heart injuries present high mortality rates. Increasing rates of urban violence have contributed to a significant rise in the number of heart injuries by firearm projectiles. Such injuries are associated with the highest mortality rates among penetrating cardiac injuries and may involve one or more cardiac chambers. We present the case of a police officer who, in an approach to five robbers, suffered a transfixed cardiac injury by firearm with the projectile having been lodged inside the right ventricle. This patient was successfully operated, 65 days after the injury, at our institution.
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Lesiones Cardíacas/cirugía , Ventrículos Cardíacos/lesiones , Heridas por Arma de Fuego/cirugía , Adulto , Ecocardiografía , Cuerpos Extraños/cirugía , Lesiones Cardíacas/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Resultado del Tratamiento , Heridas por Arma de Fuego/diagnóstico por imagenRESUMEN
Abstract Penetrating heart injuries present high mortality rates. Increasing rates of urban violence have contributed to a significant rise in the number of heart injuries by firearm projectiles. Such injuries are associated with the highest mortality rates among penetrating cardiac injuries and may involve one or more cardiac chambers. We present the case of a police officer who, in an approach to five robbers, suffered a transfixed cardiac injury by firearm with the projectile having been lodged inside the right ventricle. This patient was successfully operated, 65 days after the injury, at our institution.
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Humanos , Masculino , Adulto , Heridas por Arma de Fuego/cirugía , Lesiones Cardíacas/cirugía , Ventrículos Cardíacos/lesiones , Heridas por Arma de Fuego/diagnóstico por imagen , Ecocardiografía , Resultado del Tratamiento , Cuerpos Extraños/cirugía , Lesiones Cardíacas/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagenRESUMEN
OBJECTIVE: To describe the management strategies and outcomes of patients with renal medullary carcinoma (RMC) and characterise predictors of overall survival (OS). PATIENTS AND METHODS: RMC is a rare and aggressive malignancy that afflicts young patients with sickle cell trait; there are limited data on management to date. This is a study of patients with RMC who were treated in 2000-2015 at eight academic institutions in North America and France. The Kaplan-Meier method was used to estimate OS, measured from initial RMC diagnosis to date of death. Cox regression analysis was used to determine predictors of OS. RESULTS: In all, 52 patients (37 males) were identified. The median (range) age at diagnosis was 28 (9-48) years and 49 patients (94%) had stage III/IV. The median OS for all patients was 13.0 months and 38 patients (75%) had nephrectomy. Patients who underwent nephrectomy had superior OS compared to patients who were treated with systemic therapy only (median OS 16.4 vs 7.0 months, P < 0.001). In all, 45 patients received chemotherapy and 13 (29%) had an objective response; 28 patients received targeted therapies, with 8-week median therapy duration and no objective responses. Only seven patients (13%) survived for >24 months. CONCLUSIONS: RMC carries a poor prognosis. Chemotherapy provides palliation and remains the mainstay of therapy, but <20% of patients survive for >24 months, underscoring the need to develop more effective therapy for this rare tumour. In this study, nephrectomy was associated with improved OS.
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Carcinoma Medular , Neoplasias Renales , Adolescente , Adulto , Carcinoma Medular/tratamiento farmacológico , Carcinoma Medular/epidemiología , Carcinoma Medular/mortalidad , Carcinoma Medular/cirugía , Niño , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/epidemiología , Neoplasias Renales/mortalidad , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Nefrectomía , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
The outcome of triple therapy with protease inhibitors (PI) depends on the intrinsic response to interferon. Interferon-stimulated gene (ISG) expression differs by cell type in the liver and is a strong predictor of interferon responsiveness. Patients who respond well to interferon have low/absent ISG expression in hepatocytes but significant ISG expression in macrophages. Nonresponders (NRs) show the opposite pattern. We aimed to determine the association between cell-type-specific ISG staining and treatment outcome with PI-based triple therapy. Liver biopsy tissue from consecutive patients treated with boceprevir or telaprevir with peginterferon and ribavirin was stained for myxovirus A (MxA). Staining was scored 0-3 in macrophages (M-MxA) and hepatocytes (H-MxA), and IL28B genotyping was performed. Of 56 patients included 41 achieved SVR (73%) (sustained virological response), 2 (4%) relapsed, 10 (18%) were NRs, and 3 (5%) were lost to follow-up. Median M-MxA staining was stronger and H-MxA staining was weaker in patients who achieved SVR. MxA staining correlated with IL28B genotype and with the HCV RNA decline during lead-in phase. However, unlike with dual therapy, the negative predictive value (NPV) of absent or weak M-MxA staining was poor (42%), while the positive predictive value improved (93%). Although by multivariable logistic regression M-MxA staining was significantly associated with SVR (OR 4.35, 1.32-14.28, P = 0.012), the predictive ability was inadequate to withhold therapy. The interaction between macrophages and hepatocytes plays a critical role in interferon responsiveness; however, the addition of a PI at least partially overcomes the interferon nonresponse phenotype making the predictive ability of ISG staining less clinically useful.
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/inmunología , Interferón-alfa/uso terapéutico , Inhibidores de Proteasas/uso terapéutico , Adulto , Anciano , Biopsia , Femenino , Perfilación de la Expresión Génica , Hepatocitos/inmunología , Humanos , Interferón-alfa/inmunología , Hígado/patología , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Oligopéptidos/uso terapéutico , Prolina/análogos & derivados , Prolina/uso terapéutico , Ribavirina/uso terapéutico , Coloración y EtiquetadoRESUMEN
We report a patient with metastatic clear-cell renal cell carcinoma (mRCC) who presented with primary tumor in situ in the left kidney and metastases to bone, liver, lungs, and brain. After over 5 years of sunitinib therapy and subsequent cytoreductive left nephrectomy, the patient achieved radiographic complete response (CR) and had pathologic CR in the nephrectomy specimen. Durable clinical and pathological CRs are possible with targeted agents, even with primary tumor in situ and widely disseminated metastases. Ongoing research will define the optimal duration of systemic therapy in exceptional responders and identify the molecular determinants of response and resistance.
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Carcinoma de Células Renales/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Fluorouracilo/uso terapéutico , Interferón-alfa/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Antimetabolitos Antineoplásicos/uso terapéutico , Desoxicitidina/uso terapéutico , Humanos , Factores Inmunológicos/uso terapéutico , Masculino , Persona de Mediana Edad , Inducción de Remisión , GemcitabinaRESUMEN
OBJECTIVE: To determine the clinical activity and safety of the combination of pemetrexed and gemcitabine in advanced nonclear cell renal cell carcinoma (nccRCC). METHODS: In this phase II study, patients received pemetrexed 500 mg/m intravenous infusion over 10 minutes on day 1 followed immediately by gemcitabine 1500 mg/m intravenously over 30 minutes on day 1, with cycles repeated every 14 days. Planned enrollment was 40 patients. The primary endpoints were objective response rate and progression-free survival (PFS). The secondary endpoints were safety and overall survival. RESULTS: Between December 2005 and December 2008, 16 patients with locally advanced or metastatic nccRCC were enrolled. The trial was stopped early due to low efficacy and excessive toxicity. The objective response rate was 0% [95% confidence interval (CI), 0%-18%]. The median number of cycles administered was 4 (range, 1 to 12). Median PFS was 3.2 months (95% CI, 1.9-6+), and the 16-week PFS rate was 46.7% (95% CI, 19.8%-100%). Median overall survival was 23.2 months (95% CI, 12.9-38.1). The most common grade 3 or 4 adverse events were neutropenia (53%), leukopenia (53%), anemia (13%), fatigue (40%), and renal insufficiency (13%). CONCLUSIONS: In this phase II trial in nccRCC, the combination of pemetrexed and gemcitabine was toxic and ineffective. Further development of this regimen in nccRCC is not warranted.