Background
Given the high mortality rate for those with end-stage kidney d sease on dialysis and the efficacy and safety of current hepatitis C virus (HCV) treatments, currently-discarded kidneys from HCV-infected (HCV+) donors may be a neglected public health resource.
Objective
To determine the tolerability and feasibility of kidney transplantation (KT) from HCV+ donors to HCV-uninfected recipients (HCV D+/R−) in combination with direct-acting antivirals (DAAs) as pre- and post-transplant prophylaxis.
Design
Open-label, non-randomized trial. (ClinicalTrials.gov: NCT02781649)
Setting
Single-center.
Participants
10 HCV-uninfected KT candidates over the age of 50 years with no available living donors.
Intervention
KT from deceased donors ages 13–50 years with a positive HCV RNA and HCV antibody test. All recipients received a dose of grazoprevir 100 mg/elbasvir 50 mg (GZR/EBR) immediately prior to transplant. For genotype 1 donors, recipients continued GZR/EBR for 12 weeks post-transplant; for genotype 2 or 3 donors, sofosbuvir 400 mg was added to GZR/EBR for 12 weeks of triple-therapy.
Measurements
The primary safety outcome was the incidence of adverse events related to GZR-EBR. The primary efficacy outcome was the proportion recipients with HCV RNA less than the lower limit of quantification 12 weeks after prophylaxis.
Results
Among 10 HCV D+/R− there were no treatment-related adverse events and HCV RNA was not detected in any recipient 12 weeks after treatment.
Limitations
Nonrandomized study design and small number of patients.
Conclusions
Pre- and post-transplant HCV treatment was safe and prevented chronic hepatitis C in HCV D+/R− KT. If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for HCV− KT candidates.
The final dose investigated (42 Gy) is not recommended for further study considering the occurrence of both acute and late toxicity. However, a phase II trial of this novel gemcitabine-based chemoradiotherapy approach, at a radiation dose of 36 Gy in 2.4-Gy fractions, is recommended on the basis of tolerance, patterns of failure, and survival data.
Purpose-To determine the incidence of cystoid macular edema (CME) after cataract surgery among eyes with and without uveitis using optical coherence tomography (OCT) and to determine risk factors for post-operative CME among eyes with uveitis.
Design-Prospective comparative cohort study.Methods-Single-center, academic practice. Forty-one eyes with and 52 without uveitis underwent clinical examination and OCT testing within 4 weeks before cataract surgery and at 1-month and 3-month post-operative visits. Main outcome was incidence of CME at 1 and 3 months after surgery.Results-Both uveitic and control eyes gained approximately 3 lines of vision (P = 0.6). Incidence of CME at 1 month was 12% (5 eyes) for uveitis and 4% (2 eyes) for controls (P = 0.2). Incidence of CME at 3 months was 8% (3 eyes) for uveitis and 0 % for eyes without uveitis (P = 0.08). Eyes with uveitis treated with peri-operative oral corticosteroids had a 7-fold reduction in post-operative CME (relative risk [RR] = 0.14, P = 0.05). In uveitic eyes, active inflammation within 3 months before surgery increased the risk of CME when compared to eyes without inflammation (RR=6.19, P = 0.04). CME was significantly associated with poorer vision (P = 0.01). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
NIH Public Access
Author ManuscriptAm J Ophthalmol. Author manuscript; available in PMC 2010 July 1. Conclusions-Eyes with well-controlled uveitis may obtain similar outcomes to control eyes after cataract surgery (up to 3 months). Use of peri-operative oral corticosteroids and control of uveitis for ≥ 3 months before surgery appeared to decrease the risk of post-operative CME among uveitic eyes in this study.
Background
Outpatient COVID-19 has been insufficiently characterized. To determine the progression of disease and determinants of hospitalization, we conducted a prospective cohort study.
Methods
Outpatient adults with positive RT-PCR results for SARS-CoV-2 were recruited by phone between April 21 to July 23, 2020 after receiving outpatient or emergency department testing within a large health network in Maryland, USA. Symptoms were collected by participants on days 0, 3, 7, 14, 21, and 28 and portable pulse oximeter oxygen saturation (SaO2), heart rate, and temperature were collected for 15 consecutive days. Baseline demographics, comorbid conditions, and vital signs were evaluated for risk of subsequent hospitalization using negative binomial, and logistic regression.
Results
Among 118 SARS-CoV-2 infected outpatients, the median age was 56.0 years (IQR, 50.0 to 63.0) and 50 (42.4%) were male. Among individuals in the first week of illness (N=61), the most common symptoms included weakness/fatigue (65.7%), cough (58.8%), headache (45.6%), chills (38.2%), and anosmia (27.9%). Participants returned to their usual health a median of 20 days (IQR, 13 to 38) from symptom onset, and 66.0% of respondents were at their usual health during the fourth week of illness. Over 28 days, 10.9% presented to the emergency department and 7.6% required hospitalization. The area under the receiving operating characteristic curve for the initial home SaO2 for predicting subsequent hospitalization was 0.86 (CI, 0.73 to 0.99).
Conclusions
Symptoms often persisted but uncommonly progressed to hospitalization among outpatients with COVID-19. Home SaO2 may be a helpful tool to stratify risk of hospitalization.
Purpose
To describe viral retinitis following intravitreal and periocular
corticosteroid administration.
Methods
Retrospective case series and comprehensive literature review.
Results
We analyzed 5 unreported and 25 previously published cases of viral
retinitis following local corticosteroid administration. Causes of retinitis
included 23 CMV (76.7%), 5 HSV (16.7%), and 1 each VZV and
unspecified (3.3%). Two of 22 tested patients (9.1%) were
HIV positive. Twenty-one of 30 (70.0%) cases followed one or more
intravitreal injections of triamcinolone acetonide (TA), 4 (13.3%)
after one or more posterior sub-Tenon injections of TA, 3 (10.0%)
after placement of a 0.59-mg fluocinolone acetonide implant (Retisert), and
1 (3.3%) each after an anterior subconjunctival injection of TA
(together with IVTA), an anterior chamber injection, and an anterior
sub-Tenon injection. Mean time from most recent corticosteroid
administration to development of retinitis was 4.2 months (median 3.8; range
0.25–13.0). Twelve patients (40.0%) had type II diabetes
mellitus. Treatments used included systemic antiviral agents (26/30,
86.7%), intravitreal antiviral injections (20/30, 66.7%),
and ganciclovir intravitreal implants (4/30, 13.3%).
Conclusions
Viral retinitis may develop or reactivate following intraocular or
periocular corticosteroid administration. Average time to development of
retinitis was 4 months, and CMV was the most frequently observed agent.
Diabetes was a frequent co-morbidity and several patients with uveitis who
developed retinitis were also receiving systemic immunosuppressive
therapy.
Cisplatin at doses up to 40 mg/m(2) may be safely added to full-dose gemcitabine and conformal RT. The Time-to-Event Continual Reassessment Method trial design allowed rapid completion of the study and confidence in the conclusion about the maximum tolerated dose, but accrued more patients to a dose level above the maximum tolerated dose than the typical phase I design. Local and systemic disease control and survival in this study cohort supports further investigation of gemcitabine-based RT and combination chemotherapy in this disease.
Colchicine inhibited amylase secretion by isolated rat parotid glands only 6 h after administration of the drug in vivo. This delayed effect was not the result of the inability of the drug to reach its reaction site. When parotid glands were emptied of their secretory granules by isoproterenol treatment, the subsequent replenishment of cells with granules was inhibited by colchicine. Colchicine concomitantly produced alterations of the Golgi complexes, the cisternae of which were reduced in size and surrounded by clusters of microvesicles.
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