Hepatitis C direct-acting antiviral outcomes in patients 75 years and older.

BACKGROUND AND AIM: Elderly patients with hepatitis C virus (HCV) infection have worse interferon-based treatment outcomes than young patients. Direct-acting antiviral (DAA) regimens have enabled the treatment of previously difficult-to-cure populations. There are few studies that specifically assess DAA treatment outcomes in patients over 75 years of age. METHODS: Design: This was a cohort study. Setting: The setting was three Canadian HCV specialty sites. Participants: Patients aged 75 years and older and treated with DAA without interferon were enrolled. Measurements: Patient demographics, liver fibrosis by transient elastography, treatment regimen, and treatment outcome data were collected. RESULTS: The mean age of 78 patients in our analysis was 78.6 years (SD 3.5; range: 75-88 years). The most common genotype was 1b (35%). The most frequently utilized regimens included sofosbuvir-velpatasvir (33%) and ledipasvir-sofosbuvir (32%). Ribavirin was included for 17% of recipients. Sustained virological response (SVR) was achieved in 94% of patients (69% of those receiving ribavirin and 98% of patients on ribavirin-free regimens). Ribavirin toxicity contributed to the lower SVR rates in ribavirin-exposed patients. Ribavirin dosage was decreased in three patients and ultimately discontinued in two of these patients. All treatment was discontinued in another two patients. CONCLUSION: Ribavirin-free DAA therapy is safe and achieves SVR rates in older adults comparable to those described in the general population. RBV inclusion frequently results in complications, often leads to treatment modification or interruption, and does not improve SVR rates in those with advanced age.

Polymicrobial Clostridioides difficile lung empyema.

Clostridioides (Clostridium) difficile is a well-known cause of enteritis and antibiotic-associated diarrhea. Extraintestinal C. difficile infection is uncommon, with most extraintestinal infections involving the intra-abdominal cavity and anatomic structures adjacent to the colon. Empyema secondary to C. difficile is especially rare, with only a handful of cases reported in the medical literature. A standard antibiotic treatment regimen for C. difficile empyema does not currently exist, and data chronicling successful treatment is limited. We present the case of an 80-year-old woman with a polymicrobial C. difficile empyema who was successfully treated with multiple chest tube insertions and intravenous vancomycin.

Le Clostridioides (Clostridium) difficile est une cause bien connue d'entérite et de diarrhée associée aux antibiotiques. L'infection à C. difficile extra-intestinale est peu courante, et la plupart des infections extra-intestinales touchent la cavité intra-abdominale et les structures adjacentes au colon. L'empyème secondaire au C. difficile est particulièrement rare, et seulement une poignée de cas sont signalés dans les publications médicales. Il n'y a pas d'antibiothérapie standard de l'empyème à C. difficile, et les données sur les traitements réussis sont limitées. Les auteurs présentent le cas d'une femme de 80 ans atteinte d'un empyème polymicrobien à C. difficile qui a été traitée avec succès par l'insertion de multiples drains thoraciques et par de la vancomycine par voie intraveineuse.

Clostridium septicum myonecrosis in a pediatric patient with a self-reported penicillin allergy.

Infections with Clostridium septicum are especially rare in pediatric patients. C. septicum is the most common cause of spontaneous myonecrosis and is usually associated with comorbid malignancy. Treatment of choice for cases of C. septicum myonecrosis is prompt and thorough surgical debridement and antimicrobial therapy with high dose penicillin. The experience and management of C. septicum infections in patients who are unable to take penicillin are not well described, and the optimal duration of therapy is largely unknown. We describe a case of spontaneous myonecrosis in a 14-year-old receiving cytotoxic chemotherapy for Burkitt's lymphoma who had an anecdotal history of a penicillin allergy. Her infection was initially treated with ceftazidime and metronidazole in concert with debridement but was ultimately cured with 3 weeks of intravenous penicillin therapy following a graded penicillin challenge in hospital. We observed a delayed inflammatory tissue response to a C. septicum skin, soft tissue infection that temporally corresponded to neutrophil reconstitution in our patient with severe neutropenia. Our experience demonstrates that C. septicum myonecrosis can present indolently and progress rapidly and highlights the need for clinical vigilance and repeat "second-look" surgeries. Our case also emphasizes the importance of de-labelling penicillin allergies.

Les infections à Clostridium septicum sont particulièrement rares chez les patients d'âge pédiatrique. Le C. septicum, qui est la principale cause de myonécrose spontanée, est généralement associé à des malignités. Le traitement de première intention de la myonécrose à C. septicum consiste à effectuer un débridement chirurgical rapide et minutieux et un traitement antimicrobien au moyen d'une forte dose de pénicilline. L'expérience et la prise en charge des infections à C. septicum ne sont pas bien décrites chez les patients qui ne sont pas en mesure de prendre de la pénicilline, et on ne connaît pas vraiment la durée optimale du traitement. Les auteurs décrivent le cas d'une myonécrose spontanée chez une adolescente de 14 ans qui a reçu une chimiothérapie cytotoxique pour traiter un lymphome de Burkitt et qui a une allergie non démontrée à la pénicilline. Son infection a d'abord été traitée par de la ceftazidime et du métronidazole, conjointement avec le débridement, mais a fini par être guérie au bout de trois semaines de traitement intraveineux à la pénicilline après un test de provocation graduel à la pénicilline à l'hôpital. Les auteurs ont observé une réponse inflammatoire tardive des tissus à une infection de la peau et des tissus mous au C. septicum qui correspondait temporellement à la reconstitution des neutrophiles chez la patiente atteinte d'une grave neutropénie. Selon leur expérience, la myonécrose à C. septicum peut se manifester sous forme indolente et progresser rapidement, ce qui fait ressortir l'importance de la vigilance clinique et des secondes interventions chirurgicales. Ce cas démontre également l'importance de désétiqueter les allergies à la pénicilline.

A Case of Brevibacillus brevis Meningitis and Bacteremia.

Brevibacillus species are environmental organisms that are rarely implicated as human pathogens. We present the case of postsurgical Brevibacillus brevis bacterial meningitis and an associated bacteremia after debulking surgery for a newly diagnosed pilocytic astrocytoma in a 19-year-old woman. The patient experienced clinical cure with a 4-week course of vancomycin, but her postinfectious course was complicated by the development of a pseudomeningocele that required surgical repair. To our knowledge, this is the first described case of a central nervous system infection caused by Brevibacillus brevis in the literature.

An Evaluation of Rapidly Progressive Dementia Culminating in a Diagnosis of Creutzfeldt-Jakob Disease.

Rapidly progressive dementia is a curious and elusive clinical description of a pattern of cognitive deficits that progresses faster than typical dementia syndromes. The differential diagnosis and clinical workup for rapidly progressive dementia are quite extensive and involve searching for infectious, inflammatory, autoimmune, neoplastic, metabolic, and neurodegenerative causes. We present the case of a previously highly functional 76-year-old individual who presented with a 6-month history of rapidly progressive dementia. His most prominent symptoms were cognitive impairment, aphasia, visual hallucinations, and ataxia. Following an extensive battery of tests in hospital, the differential diagnosis remained probable CJD versus autoimmune encephalitis. He clinically deteriorated and progressed to akinetic mutism and myoclonus. He passed away 8 weeks after his initial presentation to hospital, and an autopsy confirmed a diagnosis of sporadic CJD. We use this illustrative case as a framework to discuss the clinical and diagnostic considerations in the workup for rapidly progressive dementia. We also discuss CJD and autoimmune encephalitis, the two main diagnostic possibilities in our patient, in more detail.

Direct-Acting Antiviral Therapy Outcomes in Canadian Chronic Hepatitis C Telemedicine Patients.

INTRODUCTION: Many of the 300,000 HCV-infected Canadians live in under-served and remote areas without access to HCV healthcare specialists. Telemedicine (TM) and advances in HCV management can facilitate linkage of these marginalized patients to healthcare. MATERIALS AND METHODS: A cohort database analysis was performed on patients followed at The Ottawa Hospital and Regional Viral Hepatitis Program between January 2012 and August 2016. We compared patient characteristics, fibrosis work-up and antiviral treatment outcomes in TM (n = 157) and non-TM (n = 1,130) patients (The Ottawa Hospital Viral Hepatitis Outpatient Clinic) residing in Eastern Ontario. RESULTS: TM patients were more often infected with genotype 3 (25.9% vs. 16.4%), were more commonly Indigenous (7.0% vs. 2.2%) had a history of injection drug use (70.1% vs. 54.9%) and incarceration (46.5% vs 35.5%). Groups were comparable in age (48.9 years), gender (63.7% male) and cirrhotic stage (24.0%). 59.2% of TM patients underwent transient elastography during regional outreach blitzes compared to 61.8% of non-TM patients (p = 0.54). Overall, half as many TM patients initiated antiviral therapy as non-TM patients (27.4% vs. 53.8%, p < 0.001). The introduction of DAA regimens is bridging this gap (22.2% of TM patients vs. 34.3% of non-TM patients). SVR rates with interferon-free, DAA regimens were 94.7% and 94.8% in TM and non-TM groups (p = 0.99). CONCLUSION: Our TM program engages and retains a population that faces many barriers to effective HCV treatment. TM patients initiated HCV therapy and achieved High SVR rates comparable to those obtained using traditional models of care.

Transcriptional regulation of the IL-7Rα gene by dexamethasone and IL-7 in primary human CD8 T cells.

Interleukin-7 is essential for the development and maintenance of T cells, and the expression of the IL-7 receptor is tightly regulated at every stage of the T cell's lifespan. In mature CD8 T cells, IL-7 plays important roles in cell survival, peripheral homeostasis, and cytolytic function. The IL-7 receptor alpha-chain (CD127) is expressed at high levels on naïve and memory cells, but it is rapidly downregulated upon IL-7 stimulation. In this study, we illustrate the dynamicity of the CD127 promoter and show that it possesses positive as well as negative regulatory sites involved in upregulating and downregulating CD127 expression, respectively. We cloned the CD127 gene promoter and identified key cis-regulatory elements required for CD127 expression in mature resting primary CD8 T cells. The core promoter necessary for efficient basal transcription is contained within the first 262 bp upstream of the TATA box. Additional positive regulatory elements are located between -1200 and -2406 bp, conferring a further 2- to 4-fold enhancement in gene expression. While transcription of the CD127 gene is increased directly through a glucocorticoid response element located between -2255 and -2269 bp upstream of the TATA box, we identified a suppressive region that lies upstream of 1760 bp from the TATA box, which is likely involved in the IL-7-mediated suppression of CD127 transcription. Finally, we illustrated IL-7 does not bias alternative splicing of CD127 transcripts in primary human CD8 T cells.

Distribution of Hepatitis C Risk Factors and HCV Treatment Outcomes among Central Canadian Aboriginal.

Background. Aboriginal Canadians face many lifestyle risk factors for hepatitis C exposure. Methods. An analysis of Ottawa Hospital Viral Hepatitis Clinic (Ottawa, Canada) patients between January 2000 and August 2013 was performed. HCV infection risk factors and HCV treatment outcomes were assessed. Socioeconomic status markers were based on area-level indicators linked to postal codes using administrative databases. Results. 55 (2.8%) Aboriginal and 1923 (97.2%) non-Aboriginal patients were evaluated. Aboriginals were younger (45.6 versus 49.6 years, p < 0.01). The distribution of gender (63.6% versus 68.3% male), HIV coinfection (9.1% versus 8.1%), advanced fibrosis stage (29.2% versus 28.0%), and SVR (56.3% versus 58.9%) was similar between groups. Aboriginals had a higher number of HCV risk factors, (mean 4.2 versus 3.1, p < 0.001) with an odds ratio of 2.5 (95% confidence interval: 1.4-4.4) for having 4+ risk factors. This was not explained after adjustment for income, social deprivation, and poor housing. Aboriginal status was not related to SVR. Aboriginals interrupted therapy more often due to loss to follow-up, poor adherence, and substance abuse (25.0% versus 4.6%). Conclusion. Aboriginal Canadians have higher levels of HCV risk factors, even when adjusting for socioeconomic markers. Despite facing greater barriers to care, SVR rates were comparable with non-Aboriginals.

Suppressor of cytokine signaling (SOCS) proteins are induced by IL-7 and target surface CD127 protein for degradation in human CD8 T cells.

Given the essential role interleukin (IL)-7 plays in T-cell survival, homeostasis and function, it is no surprise expression of the IL-7 receptor alpha-chain (CD127) is tightly regulated. We have previously shown IL-7 binding to its receptor on the surface of CD8 T cells leads to both suppression of CD127 gene transcription and loss of existing CD127 protein from the cell membrane. Indeed upon binding IL-7, CD127 is rapidly internalized into early endosomes where phosphorylation by JAK targets the receptor for degradation. We now show that IL-7 induces the expression of suppressor of cytokine signaling (SOCS) proteins CIS, SOCS1 and SOCS2 through the JAK/STAT-5 pathway and that CIS and SOCS2 specifically interact with CD127 in early endosomes and direct the receptor complex to the proteasome for degradation. These results illustrate how expression of the IL-7 receptor and thus IL-7 signaling is modulated in human CD8 T cells by a negative feedback mechanism dependent on members of the SOCS family of proteins.

Use of telemedicine technologies in the management of infectious diseases: a review.

Telemedicine technologies are rapidly being integrated into infectious diseases programs with the aim of increasing access to infectious diseases specialty care for isolated populations and reducing costs. We summarize the utility and effectiveness of telemedicine in the evaluation and treatment of infectious diseases patients. The use of telemedicine in the management of acute infectious diseases, chronic hepatitis C, human immunodeficiency virus, and active pulmonary tuberculosis is considered. We recapitulate and evaluate the advantages of telemedicine described in other studies, present challenges to adopting telemedicine, and identify future opportunities for the use of telemedicine within the realm of clinical infectious diseases.