Mayo Clinic proceedings
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Mayo Clinic proceedings · Oct 2016
ReviewThe Promise and Peril of Precision Medicine: Phenotyping Still Matters Most.
We illustrate the work necessary to reverse course after identification of a KCNQ1 variant interpreted erroneously as causing long QT syndrome (LQTS) and to identify the true cause of a case of sudden death in the young. Surrogate genetic testing of a decedent's living brother identified a rare KCNQ1-V133I variant, which prompted an implantable cardioverter defibrillator and subsequent diagnosis of LQTS in other family members. Subsequently, this presumed LQT1 family came to our institution for further clinical evaluation and research-based investigations, including KCNQ1-V133I variant-specific analysis of the decedent, heterologous expression studies of KCNQ1-V133I, and a whole-exome molecular autopsy along with genomic triangulation using his unaffected parents' DNA. ⋯ Although the root cause of the decedent's tragic death would have remained a mystery, the unintended consequences for the living relatives described herein might have been avoided based on clinical grounds alone. All family members had electrocardiograms with normal QT intervals, making the diagnosis of familial LQTS unlikely. As such, if the clinicians caring for these patients had focused solely on clinical data from the survivors, there might have been no reason to embark on a path of inappropriate treatment based on genetic testing.
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There are a number of changes underway in modern clinical bacteriology laboratories. Panel-based molecular diagnostics are now available for numerous applications, including, but not limited to, detection of bacteria and select antibacterial resistance markers in positive blood culture bottles, detection of acute gastroenteritis pathogens in stool, and detection of selected causes of acute meningitis and encephalitis in the cerebrospinal fluid. Today, rapid point-of-care nucleic acid amplification tests are bringing the accuracy of sophisticated molecular diagnostics closer to patients. ⋯ Laboratory automation, common in chemistry laboratories, is now available for clinical bacteriology laboratories. Finally, there are several technologies under development, such as rapid phenotypic antimicrobial susceptibility testing, whole-genome sequencing, and metagenomic analysis for the detection of bacteria in clinical specimens. It is helpful for clinicians to be aware of the pace of new development in their bacteriology laboratory to enable appropriate test ordering, to enable test interpretation, and to work with their laboratories and antimicrobial stewardship programs to ensure that new technology is implemented to optimally improve patient care.
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Mayo Clinic proceedings · Oct 2016
Survival, Risk Factors, and Effect of Treatment in 101 Patients With Calciphylaxis.
To report on the survival and the associations of treatments upon survival of patients with calciphylaxis seen at a single center. ⋯ Calciphylaxis is associated with a high mortality rate. Significantly effective treatments included surgical debridement and subtotal parathyroidectomy in patients with stage 5/5D CKD with hyperparathyroidism. Treatments with tissue-plasminogen activator, sodium thiosulfate, and hyperbaric oxygen therapy were not associated with higher mortality.
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To identify coagulation risk factors in patients with calciphylaxis and the relationship between anticoagulation use and overall survival. ⋯ Laboratory testing reveals a strikingly high prevalence of severe thrombophilias in patients with calciphylaxis, underscoring the importance of congenital and acquired thrombotic propensity potentially contributing to the pathogenesis of this disease. These findings may have therapeutic implications; however, to date, survival differences did not vary by therapeutic choice.