Browsing by Author "Thornton, Christina S"
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- ItemOpen AccessAnother Whipple’s triad? Pericardial, myocardial and valvular disease in an unusual case presentation from a Canadian perspective(2019-12-23) Thornton, Christina S; Wang, Yinong; Köebel, Martin; Bernard, Kathryn; Burdz, Tamara; Maitland, Andrew; Ferraz, Jose G; Beck, Paul L; Ferland, AndreAbstract Background Whipple’s disease is a clinically relevant multi-system disorder that is often undiagnosed given its elusive nature. We present an atypical case of Whipple’s disease involving pan-valvular endocarditis and constrictive pericarditis, requiring cardiac intervention. A literature review was also performed assessing the prevalence of atypical cases of Whipple’s disease. Case presentation A previously healthy 56-year-old male presented with a four-year history of congestive heart failure with weight loss and fatigue. Notably, he had absent gastrointestinal symptoms. He went on to develop pan-valvular endocarditis and constrictive pericarditis requiring urgent cardiac surgery. A clinical diagnosis of Whipple’s disease was suspected, prompting duodenal biopsy sampling which was unremarkable, Subsequently, Tropheryma whipplei was identified by 16S rDNA PCR on the cardiac valvular tissue. He underwent prolonged antibiotic therapy with recovery of symptoms. Conclusions Our study reports the first known case of Whipple’s disease involving pan-valvular endocarditis and constrictive pericarditis. A literature review also highlights this presentation of atypical Whipple’s with limited gastrointestinal manifestations. Duodenal involvement was limited and the gold standard of biopsy was not contributory. We also highlight the Canadian epidemiology of the disease from 2012 to 2016 with an approximate 4% prevalence rate amongst submitted samples. Routine investigations for Whipple’s disease, including duodenal biopsy, in this case may have missed the diagnosis. A high degree of suspicion was critical for diagnosis of unusual manifestations of Whipple’s disease.
- ItemOpen AccessAzithromycin and the microbiota of cystic fibrosis sputum(2021-03-30) Acosta, Nicole; Thornton, Christina S; Surette, Michael G; Somayaji, Ranjani; Rossi, Laura; Rabin, Harvey R; Parkins, Michael DAbstract Background Azithromycin is commonly prescribed drug for individuals with cystic fibrosis (CF), with demonstrated benefits in reducing lung function decline, exacerbation occurrence and improving nutrition. As azithromycin has antimicrobial activity against components of the uncultured microbiome and increasingly the CF microbiome is implicated in disease pathogenesis – we postulated azithromycin may act through its manipulation. Herein we sought to determine if the CF microbiome changed following azithromycin use and if clinical benefit observed during azithromycin use associated with baseline community structure. Results Drawing from a prospectively collected biobank we identified patients with sputum samples prior to, during and after initiating azithromycin and determined the composition of the CF microbial community by sequencing the V3-V4 region of the 16S rRNA gene. We categorized patients as responders if their rate of lung function decline improved after azithromycin initiation. Thirty-eight adults comprised our cohort, nine who had not utilized azithromycin in at least 3 years, and 29 who were completely naïve. We did not observe a major impact in the microbial community structure of CF sputum in the 2 years following azithromycin usage in either alpha or beta-diversity metrics. Seventeen patients (45%) were classified as Responders – demonstrating reduced lung function decline after azithromycin. Responders who were naïve to azithromycin had a modest clustering effect distinguishing them from those who were non-Responders, and had communities enriched with several organisms including Stenotrophomonas, but not Pseudomonas. Conclusions Azithromycin treatment did not associate with subsequent large changes in the CF microbiome structure. However, we found that baseline community structure associated with subsequent azithromycin response in CF adults.
- ItemOpen AccessEpidemiological and genomic characterization of community-acquired Clostridium difficile infections(2018-08-31) Thornton, Christina S; Rubin, Joseph E; Greninger, Alexander L; Peirano, Gisele; Chiu, Charles Y; Pillai, Dylan RAbstract Background Clostridium difficile infection (CDI) is a major cause of morbidity and mortality in North America and Europe. The aim of this study was to identify epidemiologically-confirmed cases of community-acquired (CA)-CDI in a large North American urban center and analyze isolates using multiple genetic and phenotypic methods. Methods Seventy-eight patients testing positive for C. difficile from outpatient clinics were further investigated by telephone questionnaire. CA-CDI isolates were characterized by antibiotic susceptibility, pulsed-field gel electrophoresis and whole genome sequencing. CA-CDI was defined as testing positive greater than 12 weeks following discharge or no previous hospital admission in conjunction with positive toxin stool testing. Results 51.3% (40/78) of the patients in this study were found to have bona fide CA-CDI. The majority of patients were female (71.8% vs. 28.2%) with 50–59 years of age being most common (21.8%). Common co-morbidities included ulcerative colitis (1/40; 2.5%), Crohn’s disease (3/40; 7.5%), celiac disease (2/40; 5.0%) and irritable bowel syndrome (8/40; 20.0%). However, of 40 patients with CA-CDI, 9 (29.0%) had been hospitalized between 3 and 6 months prior and 31 (77.5%) between 6 and 12 months prior. The hypervirulent North American Pulostype (NAP) 1-like (9/40; 22.5%) strain was the most commonly identified pulsotype. Whole genome sequencing of CA-CDI isolates confirmed that NAP 1-like pulsotypes are commonplace in CA-CDI. From a therapeutic perspective, there was universal susceptibility to metronidazole and vancomycin. Conclusions All CA-CDI cases had some history of hospitalization if the definition were modified to health care facility exposure in the last 12 months and is supported by the genomic analysis. This raises the possibility that even CA-CDI may have nosocomial origins.
- ItemOpen AccessGroup B streptococcus (GBS) is an important pathogen in human disease- but what about in cystic fibrosis?(2017-10-02) Skolnik, Kate; Nguyen, Austin; Thornton, Christina S; Waddell, Barbara; Williamson, Tyler; Rabin, Harvey R; Parkins, Michael DAbstract Background Group B Streptococcus (GBS) is a common commensal capable of causing severe invasive infections. Most GBS infections occur in neonates (often as pneumonia). GBS can also cause infection in adults with diabetes and other immunological impairments but rarely leads to pneumonia in adults. GBS has occasionally been found in the sputum of Cystic Fibrosis (CF) patients, an inherited condition known for progressive lung disease. However, the epidemiology and clinical significance of GBS in CF are not understood. Methods We retrospectively reviewed a large single-centre adult CF population with an associated comprehensive, prospectively collected bacterial biobank beginning in 1978. We identified all individuals with GBS isolated from their sputum on at least one occasion. The primary outcome was risk of pulmonary exacerbation (PEx) at the time of the first GBS isolate compared to the preceding visit. Secondary outcomes included determining: prevalence of GBS infection in a CF population, whether GBS infections where transient or persistent, whether GBS strains were shared among patients, change in % predicted FEV1 at the time of GBS isolate compared to the preceding visit, PEx frequency after the first GBS isolate, change in % predicted FEV1 after the first GBS isolate, and complications of GBS infection. Results GBS was uncommon, infecting 3.5% (11/318) adults within our cohort. Only three individuals developed persistent GBS infection, all lasting > 12 months. There were no shared GBS strains among patients. PEx risk was not increased at initial GBS isolation (RR 5.0, CI 0.69–36.1, p=0.10). In the two years preceding initial GBS isolation compared to the two following years, there was no difference in PEx frequency (median 2, range 0–4 vs 1, range 0 to 5, respectively, p=0.42) or lung function decline, as measured by % predicted FEV1, (median −1.0%, range −19 to 7% vs median −6.0%, range −18 to 22%, p=0.86). There were no invasive GBS infections. Conclusion In adults with CF, GBS is uncommon and is generally a transient colonizer of the lower airways. Despite the presence of structural lung disease and impaired innate immunity in CF, incident GBS infection did not increase PEx risk, PEx frequency, rate of lung function decline, or other adverse clinical outcomes.
- ItemOpen AccessPulmonary Cryptococcus infections as a manifestation of idiopathic CD4 lymphocytopenia: case report and literature review(2019-10-17) Thornton, Christina S; Larios, Oscar; Grossman, Jennifer; Griener, Thomas P; Vaughan, StevenAbstract Background Idiopathic CD4 lymphocytopenia (ICL) is a rare clinical disease with relative CD4 deficiency in the absence of HIV infection. The pathogenicity of ICL is poorly understood with an unclear incidence rate in the general population. Sequelae of ICL includes AIDS-defining infections, which most commonly includes Cryptococcus neoformans. Typically, C. neoformans infections present with CNS involvement but rarely with extra-CNS manifestations. Here, we present a rare case of ICL with exclusively primary pulmonary cryptococcus and a review of the literature. Case presentation A 56-year-old female presented to our tertiary care hospital requiring a right hip open reduction intervention. The patient became febrile during admission, prompting a work-up that included a chest X-ray showing a peripheral pulmonary solitary nodule. Transthoracic biopsy revealed encapsulated yeast forms in keeping with C. neoformans. CD4 counts, repeated at least one month apart, were < 200 cells/mm3, with negative HIV testing. Flow cytometry and genetic testing were completed to elucidate the etiology of the immune deficiency, both of which were unremarkable. She was subsequently treated with 12 months of posaconazole with clinical resolution. Conclusions Our patient highlights a rare clinical disease, which a review of literature revealed only five cases in the literature with exclusive pulmonary Cryptococcus in ICL/ This case demonstrates the strong clinical acumen required to properly diagnose and ultimately manage the patient.
- ItemOpen AccessSevere skin disease in lupus associated with hemophagocytic lymphohistiocytosis: case reports and review of the literature(2019-02-08) Thornton, Christina S; Minoo, Parham; Schneider, Michelle; Fifi-Mah, AuroreAbstract Background Hemophagocytic lymphohistiocytosis (HLH) is a severe clinical entity associated with high mortality in the adult population. HLH has been associated with infections, malignancy and autoimmune conditions such as Systemic Lupus Erythematosus (SLE), however this is often in the context of a disease flare. Currently, there are limited reports of inaugural SLE manifesting as HLH with a lack of consensus on treatment and management of these patients. Case presentation Here, we present two rare case reports of severe cutaneous manifestation of lupus associated with HLH. Both patients presented with sinister clinical courses with primarily rheumatologic complaints including malaise, arthralgia, and myalgia with biochemical abnormalities. Both patients were diagnosed with HLH as a result of first presentation from cutaneous lupus. A comprehensive literature review using the PubMed database with cases comprising keywords of HLH and SLE up to September 2017 was conducted, with an emphasis on inaugural cutaneous SLE cases. Conclusions Ultimately, we highlight that a keen clinical acumen is required as misdiagnosis may lead to insufficient treatment with adverse clinical outcomes with the unique presentation of HLH from inaugural cases of SLE.