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1.
Clin Exp Dermatol ; 47(12): 2333-2335, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36163633

ABSTRACT

We present a case of a patient with bullous pemphigoid presenting with acquired haemophilia A. This is characterized by formation of antibodies or inhibitors against coagulation Factor VIII, leading to a prolonged activated partial thromboplastin time with normal prothrombin time and international normalized ratio. Our case emphasizes the need for increased awareness among dermatologists of this uncommon and potentially life-threatening condition. Click here for the corresponding questions to this CME article.


Subject(s)
Hemophilia A , Pemphigoid, Bullous , Humans , Pemphigoid, Bullous/complications , Pemphigoid, Bullous/diagnosis , Hemoptysis/etiology , Hematoma/complications
2.
Microbiol Spectr ; 10(3): e0079122, 2022 06 29.
Article in English | MEDLINE | ID: mdl-35543562

ABSTRACT

Immunocompromised hosts with prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been implicated in the emergence of highly mutated SARS-CoV-2 variants. Spike mutations are of particular concern because the spike protein is a key target for vaccines and therapeutics for SARS-CoV-2. Here, we report the emergence of spike mutations in two immunocompromised patients with persistent SARS-CoV-2 reverse transcription (RT)-PCR positivity (>90 days). Whole-genome sequence analysis of samples obtained before and after coronavirus disease 2019 (COVID-19) treatment demonstrated the development of partial therapeutic escape mutations and increased intrahost SARS-CoV-2 genome diversity over time. This case series thus adds to the accumulating evidence that immunocompromised hosts with persistent infections are important sources of SARS-CoV-2 genome diversity and, in particular, clinically important spike protein diversity. IMPORTANCE The emergence of clinically important mutations described in this report highlights the need for sustained vigilance and containment measures when managing immunocompromised patients with persistent COVID-19. Even as jurisdictions across the globe start lifting pandemic control measures, immunocompromised patients with persistent COVID-19 constitute a unique group that requires close genomic monitoring and enhanced infection control measures, to ensure early detection and containment of mutations and variants of therapeutic and public health importance.


Subject(s)
COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , COVID-19/virology , Humans , Immunocompromised Host , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
3.
J Intensive Care Med ; 35(6): 527-535, 2020 Jun.
Article in English | MEDLINE | ID: mdl-29552953

ABSTRACT

PURPOSE: To evaluate 1-year mortality in patients with septic acute kidney injury (AKI) and to determine association between initial AKI recovery patterns (reversal within 5 days, beyond 5 days but recovery, or nonrecovery) and chronic kidney disease (CKD) progression. METHODS: Prospective observational study, with retrospective evaluation of initial nonconsenters, of critically ill patients with septic AKI. RESULTS: We studied 207 patients (age, mean [SD]: 64 [16] years, 39% males), of which 56 (27%), 18 (9%), and 9 (4%) died in intensive care unit (ICU), post-ICU in hospital, and posthospitalization, respectively. Infections (including pneumonia) and major adverse cardiac events accounted for 64% and 12% of deaths, respectively. Factors independently associated with 1-year mortality include older age, ischemic heart disease, higher Simplified Acute Physiology Score II, central nervous system or musculoskeletal primary infections, higher daily fluid balance (FB), and frusemide administration during ICU stay (all P < .05). Among 63 patients receiving renal replacement therapy (RRT), hospital mortality was higher with cumulative median FB >8 L versus ≤8 L at RRT initiation (57% vs 24%; P = .009); there was trend for less ICU- and RRT-free days at day 28 in patients with higher FB pre-RRT (P = NS). Chronic kidney disease progression over 1 year developed in 21%, 30%, and 79% of 105 initial survivors with AKI reversal, recovery, and nonrecovery, respectively (P < .001). Acute kidney injury nonrecovery during hospitalization independently predicted CKD progression (P = .001). CONCLUSIONS: Patients with septic AKI had 40% 1-year mortality, mainly associated with infections. High FB and frusemide administration were modifiable risk factors. Risk of CKD progression is high especially with initial AKI nonrecovery.


Subject(s)
Acute Kidney Injury/mortality , Hospital Mortality , Renal Insufficiency, Chronic/mortality , Sepsis/mortality , Acute Kidney Injury/complications , Aged , Critical Care Outcomes , Critical Illness/mortality , Female , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Prospective Studies , Renal Insufficiency, Chronic/etiology , Renal Replacement Therapy/mortality , Retrospective Studies , Risk Factors , Sepsis/complications , Simplified Acute Physiology Score
5.
Cytometry B Clin Cytom ; 94(1): 159-168, 2018 01.
Article in English | MEDLINE | ID: mdl-28431200

ABSTRACT

BACKGROUND: The WHO defines three categories of NK cell malignancies; extra nodal NK/T cell lymphoma (NKTCL), aggressive NK cell leukemia, and the provisional entity chronic lymphoproliferative disorder of NK cells (CLPD-NK). Although the flow cytometric (FC) phenotype of CLPD-NK has been described, studies on FC phenotype of NKTCL are limited. To the best of our knowledge ours is the first study to compare the phenotype of NKTCL, CLPD-NK, reactive NK lymphocytosis (RNKL), and normal NK cells using eight color (8C) FC. METHODS: Specimens analyzed using the Euroflow8C NK Lymphoproliferative Disorder (NKLPD) panel between 2011 and 2014 were identified from our database. All samples were analyzed on the FACSCantoII cytometer. NK cells were identified as CD45+, smCD3-, CD19-, CD56+ and normal T-cells served as internal controls. RESULTS: The majority of NKTCL were CD56 bright, CD16 dim, CD57-, and CD94+. CLPD-NK and RNKL were predominantly CD56+ or dim with positive expression of CD16 and CD57 and weak CD94 expression. Antigen based statistical analyses showed robust division of samples along the NKTCL/normal CD56 bright NK cell and CLPD-NK/RNKL/normal CD56 positive NK cell groups. CONCLUSIONS: It was concluded that FC can reliably distinguish NKTCL from CLPD-NK, normal NK cells of CD56+ phenotype, and RNKL. It was proposed that the typical phenotype for NKTCL is: CD56 bright, CD16 dim with positive CD2, CD7, CD94, HLADR, CD25, CD26, and absent CD57. This resembles the phenotype of the CD56 bright immunoregulatory subset of NK cells which we therefore hypothesize is the cell of origin of NKTCL. © 2017 International Clinical Cytometry Society.


Subject(s)
Cell Proliferation/physiology , Killer Cells, Natural/physiology , Lymphoma, T-Cell/physiopathology , Antigens, CD/metabolism , Flow Cytometry/methods , Humans , Killer Cells, Natural/metabolism , Lymphoma, T-Cell/metabolism , Lymphoproliferative Disorders/metabolism , Lymphoproliferative Disorders/physiopathology , Phenotype
6.
Int J Hematol ; 104(1): 92-8, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27106479

ABSTRACT

Increasing awareness and availability of tests for anti-PF4/heparin complex antibodies has raised concerns about indiscriminate testing and inappropriate diagnosis of heparin-induced thrombocytopenia. A retrospective review of HITS testing at a large tertiary centre was performed to determine test patterns and incidence of HITS. Records of anti-PF4 tests over 4 years were reviewed. Positive results were matched against patient medical records and records of heparin utilisation for the diagnosis of HITS. Total of 33,308 patients (9.89 % of admissions) were exposed to at least 1 day of unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Of 346 anti-PF4 antibody assays performed, 52 (15 %) were positive. Seventeen patients (4.9 % of total) were determined to have HITS. Of these, 13 cases (76 %) were patients who were initiated on haemodialysis via central venous catheters. Five patients (29 %) subsequently experienced thrombosis. The rate of HITS in patients given UFH was 0.33 %. HITS occurred in only one patient given LMWH. Of 1337 patients with chronic renal failure initiated on long term haemodialysis, the incidence of HITS was 0.97 %. Despite increased awareness of HITS, testing frequency remains conservative. An overwhelming majority of HITS cases were diagnosed among patients initiated on haemodialysis.


Subject(s)
Heparin/adverse effects , Thrombocytopenia/etiology , Antibodies/analysis , Heparin, Low-Molecular-Weight/adverse effects , Humans , Incidence , Medical Records , Platelet Factor 4/immunology , Renal Dialysis/adverse effects , Retrospective Studies , Tertiary Care Centers , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis
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