Recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) is associated with accelerated progression of liver disease, frequently leading to graft loss and early death. Existing treatment options for severe recurrent HCV infection are limited by suboptimal efficacy, poor tolerability, and numerous drug interactions. We provided sofosbuvir (SOF) and ribavirin (RBV) on a compassionate-use basis to patients with severe recurrent hepatitis C, including those with fibrosing cholestatic hepatitis (FCH) and decompensated cirrhosis who had a life expectancy of 1 year or less. All patients were to receive 24-48 weeks of SOF plus RBV. Investigators could add pegylated interferon to the regimen at their discretion. Data from the first 104 patients who completed or prematurely discontinued treatment by January 1, 2014 are presented. Of the 104 patients analyzed, 52 had an early severe recurrence (diagnosed <12 months after LT) and 52 had cirrhosis (diagnosed >12 months after LT). Twelve patients who underwent retransplantation were excluded from our efficacy analysis. Of the 92 patients assessed, 54 (59%) achieved sustained virological response (SVR) at 12 weeks after the end of treatment, with a higher rate (73%; 35 of 48) in patients with early severe recurrence. Of the 103 patients assessed for clinical outcome, 59 (57%) reported clinical improvement at the last study visit, 23 (22%) were unchanged, 3 (3%) had a worsened clinical status, and 13 (13%) died. Overall, 123 serious adverse events (SAEs) occurred in 49 patients (47%). SAEs associated with hepatic decompensation were the most frequent, with 26 SAEs occurring in 19 patients (18%). Conclusion: SOF and RBV provide high rates of SVR in patients with severe recurrent HCV, including patients with early severe recurrence, FCH, and cirrhosis. (HEPATOLOGY 2015;61:1485-1494

IMPORTANCE Many patients with diabetic peripheral neuropathy experience chronic pain and inadequate relief despite best available medical treatments.OBJECTIVE To determine whether 10-kHz spinal cord stimulation (SCS) improves outcomes for patients with refractory painful diabetic neuropathy (PDN). DESIGN, SETTING, AND PARTICIPANTSThe prospective, multicenter, open-label SENZA-PDN randomized clinical trial compared conventional medical management (CMM) with 10-kHz SCS plus CMM. Participants with PDN for 1 year or more refractory to gabapentinoids and at least 1 other analgesic class, lower limb pain intensity of 5 cm or more on a 10-cm visual analogue scale (VAS), body mass index (calculated as weight in kilograms divided by height in meters squared) of 45 or less, hemoglobin A 1c (HbA 1c ) of 10% or less, daily morphine equivalents of 120 mg or less, and medically appropriate for the procedure were recruited from clinic patient populations and digital advertising. Participants were enrolled from multiple sites across the US, including academic centers and community pain clinics, between August 2017 and August 2019 with 6-month follow-up and optional crossover at 6 months. Screening 430 patients resulted in 214 who were excluded or declined participation and 216 who were randomized. At 6-month follow-up, 187 patients were evaluated.INTERVENTIONS Implanted medical device delivering 10-kHz SCS. MAIN OUTCOMES AND MEASURESThe prespecified primary end point was percentage of participants with 50% pain relief or more on VAS without worsening of baseline neurological deficits at 3 months. Secondary end points were tested hierarchically, as prespecified in the analysis plan. Measures included pain VAS, neurological examination, health-related quality of life (EuroQol Five-Dimension questionnaire), and HbA 1c over 6 months. RESULTSOf 216 randomized patients, 136 (63.0%) were male, and the mean (SD) age was 60.8 (10.7) years. Additionally, the median (interquartile range) duration of diabetes and peripheral neuropathy were 10.9 (6.3-16.4) years and 5.6 (3.0-10.1) years, respectively. The primary end point assessed in the intention-to-treat population was met by 5 of 94 patients in the CMM group (5%) and 75 of 95 patients in the 10-kHz SCS plus CMM group (79%; difference, 73.6%; 95% CI, 64.2-83.0; P < .001). Infections requiring device explant occurred in 2 patients in the 10-kHz SCS plus CMM group (2%). For the CMM group, the mean pain VAS score was 7.0 cm (95% CI, 6.7-7.3) at baseline and 6.9 cm (95% CI, 6.5-7.3) at 6 months. For the 10-kHz SCS plus CMM group, the mean pain VAS score was 7.6 cm (95% CI, 7.3-7.9) at baseline and 1.7 cm (95% CI, 1.3-2.1) at 6 months. Investigators observed neurological examination improvements for 3 of 92 patients in the CMM group (3%) and 52 of 84 in the 10-kHz SCS plus CMM group (62%) at 6 months (difference, 58.6%; 95% CI, 47.6-69.6; P < .001).CONCLUSIONS AND RELEVANCE Substantial pain relief and improved health-related quality of life sustained over 6 months demonstrates 10-kHz SCS can s...

Aim: Previous studies of 10 kHz spinal cord stimulation demonstrated its safety and efficacy for treatment of neuropathic pain of the trunk and/or limbs. This study analyzed data from a subset of subjects with painful diabetic neuropathy enrolled in a prospective, multicenter study of peripheral polyneuropathy with various etiologies. Materials & methods: Of the eight subjects that had permanent devices, seven attended the 12-month follow-up assessment. Results & conclusion: At 12 months, 6/7 subjects were treatment responders (≥50% pain relief) and had pain remission (visual analog scale ≤ 3.0 cm). Worsening of neurologic deficits was not reported in any subject. Instead, 5/7 subjects showed improvements in sensory testing and/or reflexes. These results support further investigation of 10 kHz spinal cord stimulation as a safe and effective treatment for intractable painful diabetic neuropathy.

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681 Chronic ITP is characterized by increased platelet destruction and suboptimal platelet production. Immunosuppressive ITP therapies may produce only short-term responses and may have issues with toxicity. Romiplostim is a novel peptibody that increases platelet production by a mechanism similar to thrombopoietin; and is approved for the treatment of chronic ITP. We report data from adult patients with chronic ITP treated with romiplostim in an open-label extension study. Collection of safety and efficacy data from long-term treatment of these patients is ongoing. Eligible patients had completed a prior romiplostim study. Romiplostim was administered once weekly by subcutaneous injection, with dose adjustments to maintain platelet counts in the target range (50 to 200 × 109/L). Patients who achieved a stable dose of romiplostim for 3 consecutive weeks were eligible to administer romiplostim at home (by self-injection or by a caregiver); these patients returned to the clinic every 4 weeks for study evaluations. As of May 2009, 291 adult patients had been treated with romiplostim; most were female (63%) and their median time since diagnosis was 4.9 years (range, 1 to 46 years). Thirty-three percent had previously undergone a splenectomy. Patients were treated with romiplostim for a median of 48 weeks (range, 1 to 244 weeks). Two hundred and nineteen patients (75%) were continuing the study at the data cut-off. Home administration of romiplostim was able to be started by 75% of patients; 8/218 patients (4%) discontinued home administration and resumed study-site injection. The median of the average weekly dose across the overall study population was 4 mcg/kg (interquartile range: 2 to 7 mcg/kg). The weekly dose among individual patients remained stable: after week 12, 79% (228/288) of patients were administered a dose of romiplostim within 2 mcg/kg of their most frequent dose at least 90% of the time. Almost all patients (94%) experienced a platelet count ≥50 × 109/L during the study, and more than 50% of patients had platelet counts ≥50 × 109/L on 95% of all study visits. After the first week, median platelet counts remained within the target range (50 to 200 × 109/L) for the duration of the study. Of patients receiving concurrent ITP medication at baseline, 78% (29/37) were able to discontinue or reduce their dose by >25%. Adverse events were reported in 92% of patients overall; the most common were headache (32%); nasopharyngitis (30%); and contusion and fatigue (each 28%). The frequency of adverse events did not increase with time on study (Table). The patient incidence of bleeding events of moderate or greater severity (≥Grade 2) and of clinical significance (≥Grade 3) did not increase over time (Table). Thrombotic events were experienced by 17 (6%) patients and did not increase in frequency over time (Table). Bone marrow reticulin was present or increased in 9 patients with no evidence of progression to collagen fibrosis or chronic idiopathic myelofibrosis. Two patients developed neutralizing antibodies to romiplostim that were absent on retesting after drug withdrawal, with no cross-reactive antibodies to thrombopoietin. Thirteen patients died; 2 deaths were considered by the investigator as possibly related to treatment (unstable angina, myocardial infarction). In conclusion, romiplostim-treated patients were able to maintain platelet counts within the target range, with minimal dose adjustments for up to almost 5 years. Romiplostim was well-tolerated and adverse events did not increase with longer duration of treatment.Table.Summary of patient incidence of adverse events by study periodStudy periodAdverse eventsAny n (%)Serious n (%)Treatment related n (%)Bleeding n (%)Bleeding ≥Grade 2 n (%)Bleeding ≥Grade 3 n (%)Thrombotic events n (%) <24 wks N = 291245 (84)41 (14)68 (23)93 (32)36 (12)12 (4)7 (2) 24 to <48 wks N = 271215 (79)32 (12)31 (11)66 (24)23 (9)5 (2)5 (2) 48 to <72 wks N = 151113 (75)14 (9)18 (12)41 (27)12 (8)2 (1)3 (2) 72 to <96 wks N = 12498 (79)11 (9)4 (11)38 (31)6 (5)1 (1)2 (2) 96 to <120 wks N = 11283 (74)19 (17)8 (7)31 (28)9 (8)1 (1)4 (4) 120 to <144 wks N = 10176 (75)8 (8)7 (7)21 (21)7 (7)1 (1)1 (1) 144 to <168 wks N = 8151 (63)6 (7)2 (3)15 (19)4 (5)00 68 to <192 wks N = 4726 (55)3 (6)2 (4)9 (19)4 (9)1 (2)1 (2) 192 to <216 wks N = 2619 (73)2 (8)010 (39)2 (8)00 216 to <240 wks N = 2417 (71)2 (8)07 (29)2 (8)1 (4)0 >240 wks N = 61 (17)000000 Disclosures: Bussel: Genzyme: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai, Inc: Research Funding; Sysmex: Research Funding; Scienta: Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees. Kuter:Amgen Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Esehi: Consultancy; Shionagi: Consultancy, Honoraria, Speakers Bureau; ONO: Consultancy, Honoraria, Speakers Bureau; MGI Pharma: Consultancy, Research Funding; Ligand: Honoraria, Speakers Bureau. Newland:Amgen Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pangenetics: Consultancy; Schering Plough: Consultancy; Baxter: Research Funding; Genentech: Research Funding; Gilead: Research Funding. Wasser:Amgen Inc.: Speakers Bureau. Chang:Amgen Inc.: Employment, Equity Ownership. Nie:Amgen Inc.: Employment, Equity Ownership. Berger:Amgen Inc.: Employment, Equity Ownership.