ABSTRACT
The use of high-dose intravenous immune globulin (IVIG) plus anticoagulation is recommended for the treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare side effect of adenoviral vector vaccines against coronavirus disease 2019 (Covid-19). We describe the response to IVIG therapy in three of the first patients in whom VITT was identified in Canada after the receipt of the ChAdOx1 nCoV-19 vaccine. The patients were between the ages of 63 and 72 years; one was female. At the time of this report, Canada had restricted the use of the ChAdOx1 nCoV-19 vaccine to persons who were 55 years of age or older on the basis of reports that VITT had occurred primarily in younger persons. Two of the patients in our study presented with limb-artery thrombosis; the third had cerebral venous and arterial thrombosis. Variable patterns of serum-induced platelet activation were observed in response to heparin and platelet factor 4 (PF4), indicating the heterogeneity of the manifestations of VITT in serum. After the initiation of IVIG, reduced antibody-induced platelet activation in serum was seen in all three patients. (Funded by the Canadian Institutes of Health Research.).
Subject(s)
COVID-19 Vaccines/adverse effects , Immunoglobulins, Intravenous , Thrombocytopenia/therapy , Thrombosis/therapy , Aged , ChAdOx1 nCoV-19 , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Heparin/pharmacology , Humans , Male , Middle Aged , Platelet Count , Platelet Factor 4/pharmacology , Serotonin/blood , Thrombocytopenia/blood , Thrombocytopenia/etiology , Thrombosis/etiology , Thrombosis/immunologyABSTRACT
BACKGROUND: Infective endocarditis (IE) caused by Streptococcus agalactiae (GBS) is increasingly reported and associated with an aggressive course and high mortality rate. Existing literature on GBS IE is limited to case series; we compared the characteristics of patients with GBS IE to patients with GBS bacteremia without IE to identify risk factors for development of IE. METHODS: A nested case-control study in a cohort of adult patients with GBS bacteremia over a 18-year period was conducted across seven centres in three Canadian cities. A chart review identified patients with possible or definite IE (per Modified Duke Criteria) and patients with IE were matched to those without endocarditis in a 1:3 fashion. Multivariate analyses were completed using logistic regression. RESULTS: Of 520 patients with GBS bacteremia, 28 cases of possible or definite IE were identified (5.4%). 68% (19/28) met criteria for definite IE, surgery was performed in 29% (8/28), and the overall in-hospital mortality rate was 29% (8/28). Multivariate analysis demonstrated that IE was associated with injection drug use (OR = 19.6, 95% CI = 3.39-111.11, p = 0.001), prosthetic valve (OR = 11.5, 95% CI = 1.73-76.92, p = 0.011) and lack of identified source of bacteremia (OR = 3.81, 95% CI = 1.24-11.65, p = 0.019). CONCLUSIONS: GBS bacteremia, especially amongst people who inject drugs, those with prosthetic valves, and those with no apparent source of infection, should increase clinical suspicion for IE.
Subject(s)
Endocarditis, Bacterial , Endocarditis , Adult , Canada/epidemiology , Case-Control Studies , Endocarditis/epidemiology , Endocarditis, Bacterial/epidemiology , Humans , Retrospective Studies , Streptococcus agalactiaeABSTRACT
BACKGROUND: Listeriosis is a severe food-borne infection caused by the Gram-positive rod, Listeria monocytogenes. Despite the low incidence (3-8 cases per million), Listeriosis has a case fatality rate of 20-30% as it occurs predominantly in immunocompromised individuals at extremes of age, diabetics and pregnant women. Listeriosis classically presents as a febrile gastroenteritis, isolated bacteremia, meningitis, or maternal-fetal infections. Focal bone and joint infection are rare and primarily involve orthopedic implant devices. Here, we present the first case of Listeria-associated spondylodiscitis. CASE PRESENTATION: A 79-year-old male presents with acute-on-chronic back pain in the absence of risk factors or exposures, aside from age. On radiological imaging, spondylodiscitis of L3-L4 was diagnosed. Subsequently, a CT-guided biopsy was performed to aid in confirming microbiological aetiology. Listeria monocytogenes was grown in culture and patient received appropriate antibacterial therapy. CONCLUSION: The case highlights the utility of image-guided tissue sampling in aiding diagnosis and management in patients with vertebral osteomyelitis. It also encourages consideration of uncommon organisms such as Listeria as an etiology of vertebral osteomyelitis, even in the absence of prosthetic implants.
Subject(s)
Discitis/diagnostic imaging , Listeriosis/diagnosis , Aged , Anti-Bacterial Agents/therapeutic use , Arthritis, Infectious/drug therapy , Back Pain , Bacteremia/microbiology , Discitis/drug therapy , Humans , Listeria monocytogenes/isolation & purification , Listeria monocytogenes/pathogenicity , Listeriosis/drug therapy , Male , Osteomyelitis/diagnostic imaging , Risk FactorsABSTRACT
BACKGROUND: Alopecia areata (AA) is a common T cell-mediated disorder with limited therapeutics. A molecular profile of cytokine pathways in AA tissues is lacking. Although studies have focused on TH1/IFN-γ responses, several observations support a shared genetic background between AA and atopy. OBJECTIVE: We sought to define the AA scalp transcriptome and associated biomarkers with comparisons with atopic dermatitis (AD) and psoriasis. METHODS: We performed microarray and RT-PCR profiling of 27 lesional and 17 nonlesional scalp samples from patients with AA for comparison with normal scalp samples (n = 6). AA gene expression was also compared with samples from patients with lesional or nonlesional AD and those with psoriasis. A fold change of greater than 1.5 and a false discovery rate of less than 0.05 were used for differentially expressed genes (DEGs). RESULTS: We established the AA transcriptomes (lesional vs nonlesional: 734 DEGs [297 upregulated and 437 downregulated]; lesional vs normal: 4230 DEGs [1980 upregulated and 2250 downregulated]), including many upregulated immune and downregulated hair keratin genes. Equally impressive as upregulation in TH1/interferon markers (IFNG and CXCL10/CXCL9) were those noted in TH2 (IL13, CCL18, CCL26, thymic stromal lymphopoietin, and periostin), TH9/IL-9, IL-23 (p40 and p19), and IL-16 mediators (all P < .05). There were no increases in TH17/TH22 markers. Hair keratin (KRT) expressions (ie, KRT86 and KRT85) were significantly suppressed in lesional skin. Greater scalp involvement (>25%) was associated with greater immune and keratin dysregulation and larger abnormalities in nonlesional scalp samples (ie, CXCL10 and KRT85). CONCLUSIONS: Our data associate the AA signature with TH2, TH1, IL-23, and IL-9/TH9 cytokine activation, suggesting consideration of anti-TH2, anti-TH1, and anti-IL-23 targeting strategies. Similar to psoriasis and AD, clinical trials with selective antagonists are required to dissect key pathogenic pathways.
Subject(s)
Alopecia Areata/immunology , Dermatitis, Atopic/immunology , Psoriasis/immunology , Th1 Cells/immunology , Th2 Cells/immunology , Adult , Biomarkers/metabolism , Chemokines/genetics , Chemokines/metabolism , Female , Humans , Interleukin-23/metabolism , Keratins, Hair-Specific/genetics , Keratins, Hair-Specific/metabolism , Lymphocyte Activation , Male , Microarray Analysis , Middle Aged , Transcriptome , Young AdultABSTRACT
Complicated Staphylococcus aureus infections, including bacteremia, are often associated with treatment failures, prolonged hospital stays, and the emergence of resistance to primary and even secondary therapies. Daptomycin is commonly used as salvage therapy after vancomycin failure for the treatment of methicillin-resistant S. aureus (MRSA) infections. Unfortunately, the emergence of daptomycin resistance, especially in deep-seated infections, has been reported, prompting the need for alternative or combination therapy. Numerous antibiotic combinations with daptomycin have been investigated clinically and in vitro. Of interest, the combination of daptomycin and trimethoprim-sulfamethoxazole (TMP-SMX) has proved to be rapidly bactericidal in vitro to strains that are both susceptible and nonsusceptible to daptomycin. However, to date, there is limited clinical evidence supporting the use of this combination. This was a multicenter, retrospective case series of patients treated with the combination of daptomycin and TMP-SMX for at least 72 h. The objective of this study was to describe the safety and effectiveness of this regimen in clinical practice. The most commonly stated reason that TMP-SMX was added to daptomycin was persistent bacteremia and/or progressive signs and symptoms of infection. After the initiation of combination therapy, the median time to clearance of bacteremia was 2.5 days. Microbiological eradication was demonstrated in 24 out of 28 patients, and in vitro synergy was demonstrated in 17 of the 17 recovered isolates. Further research with this combination is necessary to describe the optimal role and its impact on patient outcomes.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Daptomycin/therapeutic use , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Infections/drug therapy , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Anti-Bacterial Agents/adverse effects , Daptomycin/adverse effects , Drug Synergism , Drug Therapy, Combination , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Retrospective Studies , Treatment Outcome , Trimethoprim, Sulfamethoxazole Drug Combination/adverse effectsABSTRACT
A 70-year-old male with a complex past medical history presents with confusion and slurred speech for 24 hours. His exam was unremarkable, and his CT head was negative. Both his C-reactive protein and white blood cell count were elevated. As part of the delirium workup, blood cultures were done which grew Streptococcus pyogenes with no obvious source. He was treated with appropriate antibiotics. To determine the source, a white blood cell scan was done, which showed increased localization within a left-sided upper mediastinum mass. Subsequently, chest CT scan with contrast showed an acute type B aortic dissection with mycotic aneurysm. Consequently, he was taken urgently for surgical management. He completed 6 weeks of penicillin G and was discharged to a rehabilitation center. This case illustrates both a rare entity, mycotic aneurysm secondary to Streptococcus pyogenes, and the importance of getting an Infectious Diseases consult in the setting of an unknown source of bacteremia.
ABSTRACT
In this article, we present a case of pyoderma gangrenosum (PG), misdiagnosed initially as a necrotizing infection that significantly worsened due to repeated surgical debridement and aggressive wound care therapy, almost resulting in limb amputation despite antibiotic therapy. The PG lesions improved after pancytopenia were further investigated, and the diagnosis and treatment of an underlying hematologic malignancy was initiated. The diagnosis and management of PG is challenging given the paucity of robust clinical evidence, lack of standard diagnostic criteria, and absence of clinical practice guidelines. It is imperative that clinicians recognize PG as a clinical diagnosis that must be considered in any patient with enlarging, sterile, necrotic lesions that are unresponsive to prolonged and appropriate antibiotics. Early recognition can prevent devastating sequelae such as deep tissue and bone infections associated with a chronic open wound, severe cosmetic morbidity, and potential limb amputation.
ABSTRACT
BACKGROUND: Chronic hand and foot eczema (CHFE), a prevalent debilitating disorder affecting approximately 15% of the population, presents a socioeconomic and psychosocial burden for patients and often follows a chronic course, refractory to conventional therapies. Thus, a large need exists for more effective therapeutics; the excimer laser (308 nm) is effective for some inflammatory skin diseases, but its efficacy has not been evaluated for CHFE. METHODS: The study is a retrospective chart review conducted on 30 patients with recalcitrant CHFE (19 with hand involvement, four with foot involvement, and seven with both) treated twice weekly with excimer laser (308 nm) single wavelength ultraviolet (UV)B radiation between January 2013 and December 2014. RESULTS: Improvements in clinical scores included a 69% reduction in average physician's global assessment (PGA) scores (from 2.77 at baseline to 0.87 after treatment, P < 0.0001) with a parallel reduction in average modified total lesion/symptom scores of 70% (from 10.2 to 3.1, P < 0.0001). Only mild sunburn-like reactions were observed. CONCLUSION: This report evaluates excimer laser for patients with refractory CHFE and shows excellent and sustained efficacy for this treatment. Compared to other UV therapies, excimer laser offers lower cumulative doses of UV radiation by targeting specific areas. This effective treatment should be considered alone or in combination with other established or newer therapies.
Subject(s)
Eczema/radiotherapy , Foot Dermatoses/radiotherapy , Hand Dermatoses/radiotherapy , Lasers, Excimer , Low-Level Light Therapy/methods , Adolescent , Adult , Aged , Child , Chronic Disease , Cohort Studies , Eczema/diagnosis , Female , Follow-Up Studies , Foot Dermatoses/diagnosis , Hand Dermatoses/diagnosis , Humans , Male , Middle Aged , Patient Satisfaction/statistics & numerical data , Retrospective Studies , Severity of Illness Index , Statistics, Nonparametric , Treatment Outcome , Young AdultABSTRACT
Fibrosis is defined as increased fibroblast proliferation and deposition of extracellular matrix components with potential clinical ramifications including organ dysfunction and failure. Fibrosis is a characteristic finding of various skin diseases which can have life-threatening consequences. These implications call for research into this topic as only a few treatments targeting fibrosis are available. In this review, we discuss oxidative stress and its role in skin fibrosis. Recent studies have implicated the importance of oxidative stress in a variety of cellular pathways directly and indirectly involved in the pathogenesis of skin fibrosis. The cellular pathways by which oxidative stress affects specific fibrotic skin disorders are also reviewed. Finally, we also describe various therapeutic approaches specifically targeting oxidative stress to prevent skin fibrosis. We believe oxidative stress is a relevant target, and understanding the role of oxidative stress in skin fibrosis will enhance knowledge of fibrotic skin diseases and potentially produce targeted therapeutic options.
ABSTRACT
Colonoscopy is the preferred modality for colon cancer screening. A successful colonoscopy requires proper bowel preparation. Adequate bowel preparation continues to remain a limiting factor. One hundred thirty-three patients scheduled for an outpatient colonoscopy were prospectively randomized in a single-blinded manner to video or nonvideo group. In addition to written bowel preparation instructions, patients in the video group viewed a brief instructional video. Quality of colon preparation was measured using the Ottawa Bowel Preparation Quality scale, while patient satisfaction with preparation was evaluated using a questionnaire. Statistical analyses were used to evaluate the impact of the instructional colonoscopy video. There were significant differences in the quality of colonoscopy preparation between the video and the nonvideo groups. Participants who watched the video had better preparation scores in the right colon (P=0.0029), mid-colon (P=0.0027), rectosigmoid (P=0.0008), fluid content (P=0.03) and aggregate score (median score 4 versus 5; P=0.0002). There was no difference between the two groups with regard to patient satisfaction. Income, education level, sex, age and family history of colon cancer had no impact on quality of colonoscopy preparation or patient satisfaction. The addition of an instructional bowel preparation video significantly improved the quality of colon preparation.
Subject(s)
Colonoscopy/education , Patient Education as Topic/methods , Patient Satisfaction , Video Recording , Adult , Aged , Aged, 80 and over , Cathartics/therapeutic use , Colonoscopy/standards , Female , Humans , Male , Middle Aged , Patient Compliance , Single-Blind Method , Young AdultABSTRACT
The cutaneous manifestations of thyroid disease can be present in the hair, nails, and local or diffuse locations throughout the skin. Traditionally, thyroid-associated mucin deposition is present in a pretibial location on bilateral lower legs. We present a case of a growing plaque on the lower back of a 10-year-old girl, whose appearance coincided with a recent diagnosis of Hashimoto's thyroiditis.