Síncope / Syncope

El síncope es una pérdida transitoria de conciencia y tono postural debido a hipoflujo sanguíneo cerebral que se recupera espontáneamente sin maniobras de RCP. En esta actualización se plantea el síncope vasovagal con sus diagnósticos diferenciales y posibles etiologías, fisiopatología y métodos de estudios. También se presenta la experiencia sobre este tema en nuestro hospital su estudio, tratamiento y diagnostico (tilt test) (AU)

Syncope is a transient loss of consciousness and postural tone due to cerebral blood hypoflow that recovers spontaneously without CPR maneuvers. This update discusses vasovagal syncope with its differential diagnoses and possible etiologies, pathophysiology, and diagnostic methods. Additionally, the experience on this topic of our hospital regarding investigations, treatment, and diagnosis is presented. (AU)

Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up.

PURPOSE: In the initial PALOMA-2 (NCT01740427) analysis with median follow-up of 23 months, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) in women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) [hazard ratio (HR) 0.58; P < 0.001]. Herein, we report results overall and by subgroups with extended follow-up. METHODS: In this double-blind, phase 3 study, post-menopausal women with ER+/HER2- ABC who had not received prior systemic therapy for their advanced disease were randomized 2:1 to palbociclib-letrozole or placebo-letrozole. Endpoints include investigator-assessed PFS (primary), safety, and patient-reported outcomes (PROs). RESULTS: After a median follow-up of approximately 38 months, median PFS was 27.6 months for palbociclib-letrozole (n = 444) and 14.5 months for placebo-letrozole (n = 222) (HR 0.563; 1-sided P < 0.0001). All subgroups benefited from palbociclib treatment. The improvement of PFS with palbociclib-letrozole was maintained in the next 2 subsequent lines of therapy and delayed the use of chemotherapy (40.4 vs. 29.9 months for palbociclib-letrozole vs. placebo-letrozole). Safety data were consistent with the known profile. Patients' quality of life was maintained. CONCLUSIONS: With approximately 15 months of additional follow-up, palbociclib plus letrozole continued to demonstrate improved PFS compared with placebo plus letrozole in the overall population and across all patient subgroups, while the safety profile remained favorable and quality of life was maintained. These data confirm that palbociclib-letrozole should be considered the standard of care for first-line therapy in patients with ER+/HER2- ABC, including those with low disease burden or long disease-free interval. Sponsored by Pfizer; ClinicalTrials.gov: NCT01740427.

Impact of palbociclib plus letrozole on patient-reported health-related quality of life: results from the PALOMA-2 trial.

Background: Patient-reported outcomes are integral in benefit-risk assessments of new treatment regimens. The PALOMA-2 study provides the largest body of evidence for patient-reported health-related quality of life (QOL) for patients with metastatic breast cancer (MBC) receiving first-line endocrine-based therapy (palbociclib plus letrozole and letrozole alone). Patients and methods: Treatment-naïve postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) MBC were randomized 2 : 1 to palbociclib plus letrozole (n = 444) or placebo plus letrozole (n = 222). Patient-reported outcomes were assessed at baseline, day 1 of cycles 2 and 3, and day 1 of every other cycle from cycle 5 using the Functional Assessment of Cancer Therapy (FACT)-Breast and EuroQOL 5 dimensions (EQ-5D) questionnaires. Results: As of 26 February 2016, the median duration of follow-up was 23 months. Baseline scores were comparable between the two treatment arms. No significant between-arm differences were observed in change from baseline in FACT-Breast Total, FACT-General Total, or EQ-5D scores. Significantly greater improvement in pain scores was observed in the palbociclib plus letrozole arm (-0.256 versus -0.098; P = 0.0183). In both arms, deterioration of FACT-Breast Total score was significantly delayed in patients without progression versus those with progression and patients with partial or complete response versus those without. No significant difference was observed in FACT-Breast and EQ-5D index scores in patients with and without neutropenia. Conclusions: Overall, women with MBC receiving first-line endocrine therapy have a good QOL. The addition of palbociclib to letrozole maintains health-related QOL and improves pain scores in treatment-naïve postmenopausal patients with ER+/HER2- MBC compared with letrozole alone. Significantly greater delay in deterioration of health-related QOL was observed in patients without progression versus those who progressed and in patients with an objective response versus non-responders. ClinicalTrials.gov: NCT01740427 (https://clinicaltrials.gov/ct2/show/NCT01740427).

Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases.

Background: This report assesses the efficacy and safety of palbociclib plus endocrine therapy (ET) in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) with or without visceral metastases. Patients and methods: Pre- and postmenopausal women with disease progression following prior ET (PALOMA-3; N = 521) and postmenopausal women untreated for ABC (PALOMA-2; N = 666) were randomized 2 : 1 to ET (fulvestrant or letrozole, respectively) plus palbociclib or placebo. Progression-free survival (PFS), safety, and patient-reported quality of life (QoL) were evaluated by prior treatment and visceral involvement. Results: Visceral metastases incidence was higher in patients with prior resistance to ET (58.3%, PALOMA-3) than in patients naive to ET in the ABC setting (48.6%, PALOMA-2). In patients with prior resistance to ET and visceral metastases, median PFS (mPFS) was 9.2 months with palbociclib plus fulvestrant versus 3.4 months with placebo plus fulvestrant [hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.35-0.61], and objective response rate (ORR) was 28.0% versus 6.7%, respectively. In patients with nonvisceral metastases, mPFS was 16.6 versus 7.3 months, HR 0.53; 95% CI 0.36-0.77. In patients with visceral disease and naive to ET in the advanced disease setting, mPFS was 19.3 months with palbociclib plus letrozole versus 12.9 months with placebo plus letrozole (HR 0.63; 95% CI 0.47-0.85); ORR was 55.1% versus 40.0%; in patients with nonvisceral disease, mPFS was not reached with palbociclib plus letrozole versus 16.8 months with placebo plus letrozole (HR 0.50; 95% CI 0.36-0.70). In patients with prior resistance to ET with visceral metastases, palbociclib plus fulvestrant significantly delayed deterioration of QoL versus placebo plus fulvestrant, whereas patient-reported QoL was maintained with palbociclib plus letrozole in patients naive to endocrine-based therapy for ABC. Conclusions: Palbociclib plus ET prolonged mPFS in patients with visceral metastases, increased ORRs, and in patients previously treated for ABC, delayed QoL deterioration, presenting a standard treatment option among patients with visceral metastases amenable to endocrine-based therapy. Clinical trial registration: NCT01942135, NCT01740427.

Regression of gastric de novo diffuse large B-cell lymphoma following Helicobacter pylori eradication: a case report.

We report a case of primary gastric diffuse large B-cell lymphoma (DLBCL), de novo DLBCL without the features of mucosa-associated lymphoid tissue (MALT) lymphoma, which regressed after Helicobacter pylori (HP) eradication. A 27-year-old Japanese female with epigastralgia was revealed to have ulcerated lesions in the angle and antral regions on gastroscopy. Biopsy specimen was consistent with a diagnosis of DLBCL without MALT lymphoma component, indicating de novo development. Her clinical staging on the Lugano system was Stage I. HP was positive on a rapid urease test, and she received HP eradication therapy twice, because the first therapy was not successful. On gastroscopy performed 1 month after the second HP eradication therapy, no ulcerated lesion was noted, and the lymphoma cells had regressed histopathologically. (Acta gastro-enterol. belg., 2016, 79, 367-369A).

Association Between the Polyomaviruses Titers and Decoy Cell Positivity Rates After Renal Transplantation.

BACKGROUND: Urinary decoy cells develop after renal transplantation and their appearance is attributable primarily to the proliferation of polyomavirus types BK and JC. We measured the levels of these 2 viruses that cause decoy cells to appear in the urine. PATIENTS AND METHODS: BK and JC virus levels were quantified in 1182 urine samples from 335 renal transplant patients using a multiplex Taqman real-time polymerase chain reaction assay. Forty-four samples were excluded from analyses because both viruses were present at ≥10(4) copies/mL. We analyzed the relationship between viral load and the presence of urinary decoy cells. RESULTS: Decoy cells were observed in 237 of 1138 urine samples (21%) and the BK and JC viruses were positive in 205 (18%) and 455 (40%) samples, respectively. Decoy cells were observed in 0%, 21%, 67%, 87%, 100%, and 96% of urine samples when the BK viral load was <10(4), 10(4)-10(5), 10(5)-10(6), 10(6)-10(7), 10(7)-10(8), and ≥10(8) copies/mL, respectively; and in 1%, 13%, 41%, 59%, 87%, and 97% of urine samples when the JC viral load was <10(4), 10(4)-10(5), 10(5)-10(6), 10(6)-10(7), 10(7)-10(8), and ≥10(8) copies/mL, respectively. CONCLUSIONS: BK virus more frequently triggered the appearance of decoy cells than did JC virus at equivalent viral titers.

Langerhans cell-like dendritic cells stimulated with an adjuvant direct the development of Th1 and Th2 cells in vivo.

It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of immune responses towards a T helper type 1 (Th1) or Th2 milieu. In this study, we attempted to generate LCs from murine bone marrow cells and elicit a Th1- or Th2-prone immune response through the LCs after stimulation with Th1 or Th2 adjuvant. LCs were generated from murine bone marrow cells using granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and transforming growth factor (TGF)-ß, and were obtained as I-A(d) positive cells. Mice were primed with Th1/Th2 adjuvant- and ovalbumin (OVA)-pulsed LCs and then given a booster injection of OVA 2 days later via the hind footpad. Five days after the OVA injection, the cytokine response in the draining popliteal lymph nodes was investigated by reverse transcription-polymerase chain reaction (RT-PCR) flow cytometry and enzyme-linked immunosorbent assay (ELISA). The generated LCs expressed typical LC surface markers, E-cadherin and Langerin, and were classified accordingly as LC-like dendritic cells (LDCs). Administration of Th1 adjuvant, cytosine-phosphate-guanosine (CpG)-DNA- and OVA-pulsed LDCs into the hind footpads of mice induced a Th1-prone immune response, as represented by up-regulation of IFN-γ production and down-regulation of IL-4 production in the lymph node cells. Conversely, Th2 adjuvant, histamine-pulsed LDCs induced a Th2-prone immune response, as represented by up-regulation of IL-4 production and down-regulation of IFN-γ production. These results suggest that LDCs may be used as a substitute for LCs and have the ability to induce the development of Th1 and Th2 cells in vivo. Our experimental system would therefore be useful for screening of inhibitors of Th1/Th2 differentiation in order to control allergic disease.

Salvage living-donor liver transplantation for liver failure following definitive radiation therapy for recurrent hepatocellular carcinoma: a case report.

A 57-year-old man with a history of hepatitis B virus infection was referred to our hospital for living-donor liver transplantation (LDLT). Five years earlier, right lobectomy had been performed for solitary hepatocellular carcinoma (HCC) with bile duct tumor thrombus in segments 5 and 6 in the liver. Two years later, transarterial chemoembolization and radiofrequency ablation were performed for recurrent HCC. Two years after those local therapies, another recurrent HCC was treated with transhepatic arterial infusion chemotherapy with cisplatin and conventional radiation therapy (RT) with 60 Gy in 20 fractions, because the tumor was contiguous to the trunk of the portal vein. After the completion of RT, symptoms due to liver failure and severe infection caused by multiple liver abscesses developed despite the administration of antibiotics and percutaneous transhepatic cholangiodrainage. Therefore, LDLT was performed with the use of a right lobe graft donated by his wife. Vascular anastomosis was successfully performed with the use of normal procedures. The patient recovered uneventfully, and has since been doing well for 34 months, with no evidence of vascular complications. However, the degree of injury to the anastomotic vessels caused by definitive RT before LDLT remains unclear, whereas the safety and efficacy of some forms of RT as a bridge to deceased-donor LT have been reported. Salvage LDLT is effective for patients with liver failure after multidisciplinary treatment including radiation, while carefully taking radiation-induced vessel injury as a potential late complication into consideration, especially in LDLT cases.

Prediction of the remnant liver hypertrophy ratio after preoperative portal vein embolization.

BACKGROUND: Portal vein embolization (PVE) is considered to improve the safety of major hepatectomy. Various conditions might affect remnant liver hypertrophy after PVE. The aim of the present study was to clarify the factors that affect remnant liver hypertrophy and to establish a prediction formula for the hypertrophy ratio. METHODS: Fifty-nine patients who underwent preoperative PVE for cholangiocarcinoma (39 patients), metastatic carcinoma (10 patients), hepatocellular carcinoma (8 patients), and other diseases (2 patients) were enrolled in this study. For the prediction of the hypertrophy ratio, a formula with stepwise multiple regression analysis was set up. The following parameters were used: age, gender, future liver remnant ratio to total liver (FLR%), plasma disappearance rate of indocyanine green (ICGK), platelet count, prothrombin activity, serum albumin, serum total bilirubin at the time of PVE and the maximum value before PVE (Max Bil), as well as a history of cholangitis, diabetes mellitus, and chemotherapy. RESULTS: The mean hypertrophy ratio was 28.8%. The 5 parameters detected as predictive factors were age (p = 0.015), FLR% (p < 0.001), ICGK (p = 0.112), Max Bil (p < 0.001), and history of chemotherapy (p = 0.007). The following prediction formula was established: 101.6 - 0.78 × age - 0.88 × FLR% + 128 × ICGK - 1.48 × Max Bil (mg/dl) - 21.2 × chemotherapy. The value obtained using this formula significantly correlated with the actual value (r = 0.72, p < 0.001). A 10-fold cross validation also showed significant correlation (r = 0.62, p < 0.001), and a hypertrophy ratio <20% was predictable with a sensitivity of 100% and a specificity of 90.9%. Moreover, technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy showed a significantly smaller increase in the uptake ratio of the remnant liver in patients with prediction values <20% than in those with values ≥20% (6.8 vs. 20.8%, p = 0.030). CONCLUSIONS: The prediction formula can prognosticate the hypertrophy ratio after PVE, which may provide a new therapeutic strategy for major hepatectomy.

Impact of sarcopenia on survival in patients undergoing living donor liver transplantation.

Skeletal muscle depletion, referred to as sarcopenia, predicts morbidity and mortality in patients undergoing digestive surgery. However, the impact on liver transplantation is unclear. The present study investigated the impact of sarcopenia on patients undergoing living donor liver transplantation (LDLT). Sarcopenia was assessed by a body composition analyzer in 124 adult patients undergoing LDLT between February 2008 and April 2012. The correlation of sarcopenia with other patient factors and the impact of sarcopenia on survival after LDLT were analyzed. The median ratio of preoperative skeletal muscle mass was 92% (range, 67-130%) of the standard mass. Preoperative skeletal muscle mass was significantly correlated with the branched-chain amino acids to tyrosine ratio (r = -0.254, p = 0.005) and body cell mass (r = 0.636, p < 0.001). The overall survival rate in patients with low skeletal muscle mass was significantly lower than in patients with normal/high skeletal muscle mass (p < 0.001). Perioperative nutritional therapy significantly increased overall survival in patients with low skeletal muscle mass (p = 0.009). Multivariate analysis showed that low skeletal muscle mass was an independent risk factor for death after transplantation. In conclusion, sarcopenia was closely involved with posttransplant mortality in patients undergoing LDLT. Perioperative nutritional therapy significantly improved overall survival in patients with sarcopenia.

IFPA Meeting 2012 Workshop Report III: trophoblast deportation, gestational trophoblastic disease, placental insufficiency and fetal growth restriction, trophoblast over-invasion and accreta-related pathologies, placental thrombosis and fibrinolysis.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2012 there were twelve themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of clinical research and pregnancy disorders: 1) trophoblast deportation; 2) gestational trophoblastic disease; 3) placental insufficiency and fetal growth restriction; 4) trophoblast overinvasion and accreta-related pathologies; 5) placental thrombosis and fibrinolysis.

Feasibility of duodenal balloon-assisted direct cholangioscopy with an ultrathin upper endoscope.

BACKGROUND AND STUDY AIMS: We have previously developed duodenal balloon-assisted direct cholangioscopy (DBA-DC) with an ultrathin endoscope (UTE). Here, we further evaluated the feasibility, safety, and diagnostic and therapeutic usefulness of DBA-DC using UTE. PATIENTS AND METHODS: 40 consecutive patients with biliary diseases were enrolled in a prospective observational feasibility study. We assessed the success rate, procedure time, durability of the UTE, and usefulness in diagnosis and therapy. We also evaluated safety, including cardiovascular alterations and biliary injury as complications of the procedure. RESULTS: DBA-DC was performed successfully in 37/40 patients (92.5%). The mean time to reach either biliary bifurcation or stricture was 11.8 ± 6.3 minutes. The procedure revealed 26 biliary stones, 5 cholangiocarcinomas, and 3 benign biliary strictures. Therapeutic procedures were performed in 16 patients (10 biliary lithotomies, 3 holmium-YAG laser lithotripsies, and 3 intraductal stent placements). No significant clinical complications related to DBA-DC were observed. Changes in cardiovascular responses and biliary biochemical parameters were minimal, except for leukocytosis in 8 patients. CONCLUSIONS: DBA-DC appears to be sufficiently feasible and may be useful as an alternative technique in cases that elude successful diagnosis and/or therapy with conventional endoscopic retrograde cholangiopancreatography (ERCP).

Effect of maintenance therapy with low-dose peginterferon for recurrent hepatitis C after living donor liver transplantation.

Approximately 30% of patients who have recurrent hepatitis C after liver transplantation achieve sustained virological response (SVR) by taking a combination therapy of pegylated interferon and ribavirin. For the remaining non-SVR patients, an effective management treatment has not yet been established. In this study, efficacy of long-term peginterferon maintenance therapy for non-SVR patients was evaluated. Forty patients who had previously received the combination therapy for hepatitis C after living donor liver transplantation were classified into one of the following three groups: the SVR group (n = 11); the non-SVR-IFN group (n =17), which received low-dose peginterferon maintenance therapy for non-SVR patients; and the non-SVR-Withdrawal group (n = 12), which discontinued the interferon treatment. We then compared histological changes among these three groups after 2 or more years follow-up. Activity grade of liver histology improved or remained stable in patients in the SVR and non-SVR-IFN groups, but deteriorated in half of the patients in the non-SVR-Withdrawal group. Fibrosis improved or remained stable in 10 of 11 SVR patients and in 13 of 17 non-SVR-IFN patients, but deteriorated in all non-SVR-Withdrawal patients. Mean changes in fibrosis stage between pretreatment and final liver biopsy were -0.18, +0.06 and +2.2 in the SVR, non-SVR-IFN and non-SVR-Withdrawal groups, respectively. Fibrosis stage deteriorated to F3 or F4 significantly more rapidly in the non-SVR-Withdrawal group than in the other two groups. In conclusion, continuing long-term maintenance therapy with peginterferon prevented histological progression of hepatitis C in patients who had undergone living donor liver transplantation.

Cavernous malformations of the central nervous system in children: presentation, treatment and outcome of 20 cases.

BACKGROUND: Cavernous malformations (CM) of the central nervous system are vascular malformations responsible for symptoms such as seizures, headache, and neurological deficits: 25% of cases already present in childhood. MATERIAL AND METHODS: Retrospective study including all CMs of the central nervous system in childhood diagnosed in the period 1993-2008 in 3 paediatric hospitals in Switzerland, focusing on clinical manifestations, neuroimaging findings, treatment, and outcome. RESULTS: 20 children (13 females) were diagnosed with CM, with an average age at presentation of 8.5 years (range 7 months-16 years). 17/20 presented with acute haemorrhage, 9/17 with seizures, 5/17 with focal neurological symptoms, and 3/17 with severe headache only. Localisation was supratentorial in 15/20, infratentorial in 2/20, supra- and infratentorial in 2/20, and spinal in 1 child. Five children had multiple CMs. Treatment was conservative in 10 cases and surgery was indicated in 10: for acute haemorrhage in 5; recurrent bleeding in 3; and epilepsy in 2. Follow-up after diagnosis was 0.5 years-10 years (mean 4 years), revealing neurological sequelae in 6 patients. The CM increased in size in 2 cases with an increase in number also in 1 of these. CONCLUSIONS: We confirm that CMs in childhood mainly present with seizures, severe headache, or focal symptoms due to acute haemorrhage. During infancy they may appear as dynamic lesions increasing in size and/or number. The regular application of newer neuroimaging techniques such as susceptibility weighted imaging will detect more lesions but not necessarily resolve problems concerning optimum treatment.

Unsedated transnasal ultrathin esophagogastroduodenoscopy may provide better diagnostic performance in gastroesophageal reflux disease.

Transnasal ultrathin esophagogastroduodenoscopy (N-EGD) with less gagging reflexes under non-sedation is likely suitable for the diagnosis of gastroesophageal reflux disease (GERD), however, N-EGD might have drawbacks, including its low image resolution. Limited information is available regarding the diagnosability of N-EGD for GERD. We compared the utility and gagging reflexes of three different endoscopies, including N-EGD, ultrathin transoral EGD (UTO-EGD) and conventional oral EGD (CO-EGD), in the diagnosis of GERD. We performed screening endoscopy in 1580 patients (N-EGD n=727, UTO-EGD n=599, CO-EGD n=254) and compared the frequency distributions of the severity of reflux esophagitis, hiatus hernia, and Barrett's epithelium to estimate the diagnostic performance of each endoscopy. We also analyzed patients' tolerability of endoscopy by the subjective evaluation of gagging reflexes. In the diagnosis of reflux esophagitis and Barrett's epithelium, there was no significant difference in the frequency distributions of the severity of the diseases among three EGDs. However, the incidence of Barrett's epithelium was higher than that in the previous nationwide survey of GERD in Japan. The evaluated size of hiatus hernia was smaller in N-EGD than in two other peroral endoscopies. The size of hiatus hernia correlated significantly with severity of gagging reflexes that was also lowest when diagnosed with N-EGD. N-EGD had an equivalent performance in the diagnosis of reflux esophagitis and Barrett's epithelium compared with CO-EGD. Enlargement of hiatus hernia induced by gagging reflexes was minimal in N-EGD, resulting in its better performance in the diagnosis of Barrett's epithelium.

Coupled regulation of interleukin-12 receptor beta-1 of CD8+ central memory and CCR7-negative memory T cells in an early alloimmunity in liver transplant recipients.

This study investigated how CD8(+) T cell subsets respond to allo- and infectious immunity after living donor liver transplantation (LDLT). Early alloimmunity: 56 recipients were classified into three types according to the post-transplant course; type I demonstrated uneventful post-transplant course, type II developed severe sepsis leading to multiple organ dysfunction syndrome or retransplantation and type III with acute rejection. In 23 type I recipients, the interleukin (IL)-12 receptor beta-1 (R beta 1)(+) cells of central memory T cells (Il-12R beta 1(+) T(CM)) were increased above the pretransplant level. In 16 type II recipients, IL-12R beta 1(+) T(CM) was decreased markedly below the pretransplant level on postoperative day (POD) 5. In 17 type III recipients, IL-12R beta 1(+) T(CM) was decreased for a more prolonged period until POD 10. Along with down-regulation of IL-12R beta 1(+) T(CM), the IL-12R beta 1(+) cells of CCR7-negative subsets (CNS) as well as perforin, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha decreased gradually, resulting in the down-regulation of effectors and cytotoxicity. The down-regulation of IL-12R beta 1(+) T(CM) was suggested to be due to the recruitment of alloantigen-primed T cells into the graft, and then their entry into the secondary lymphoid organ, resulting in graft destruction. Infectious immunity: immunocompetent memory T cells with the capacity to enhance effectors and cytotoxicity were generated in response to post-transplant infection along with both up-regulation of the IL-12R beta 1(+) T(CM) and an increase in the CNS showing the highest level of IL-12R beta 1(+) cells. In conclusion, this work demonstrated that the IL-12R beta 1(+) cells of T(CM) and CNS are regulated in a tightly coupled manner and that expression levels of IL-12R beta 1(+) T(CM) play a crucial role in controlling allo- and infectious immunity.

Istradefylline as monotherapy for Parkinson disease: results of the 6002-US-051 trial.

OBJECTIVE: 6002-US-051 was a 12-week, double-blind study evaluating the safety and efficacy of istradefylline, a selective A(2A) adenosine receptor antagonist, as monotherapy in patients with Parkinson's disease (PD). METHODS: Patients with Hoehn-Yahr stages 1-2.5 who had not received dopaminergic drugs in the past 30 days or levodopa for >30 days at anytime were randomized to 40 mg/day istradefylline or placebo. The primary efficacy outcome was the change from Baseline to Endpoint in the Unified Parkinson's Disease Rating Scale (UPDRS) Subscale III score. Safety was assessed by physical examination, laboratory tests, electrocardiograms, and adverse event monitoring. RESULTS: 176 patients comprised the intent-to-treat population. Although istradefylline showed numerically greater improvements in UPDRS Subscale III at each time point and reached statistical significance at Week 2 (LS mean difference = -1.47), it did not show statistically significant improvement from placebo for the primary endpoint (least square [LS] mean difference = -1.11). Similar proportions of patients in each group experienced treatment-emergent adverse events (63% istradefylline, 65% placebo). CONCLUSIONS: Istradefylline, as monotherapy in patients with PD, is safe and well tolerated. However, efficacy in improving motor symptoms in early PD was not statistically demonstrated by this study.