Showing papers by "Mark D. Johnson published in 2021"
TL;DR: The REACT trial as mentioned in this paper evaluated the efficacy and safety of continuous glucose monitoring (CGM) in preterm infants requiring intensive care and found that infants managed using CGM had more time in the 2·6-10 mmol/L glucose concentration target range (mean proportion of time 84% [SD 22] vs 94% [11]; adjusted mean difference 8·9% [95% CI 3·4-14·4]), equivalent to 13 h (95%CI 5−21).
32 citations
University Health Network1, University of Ottawa2, University of Toronto3, University of Chicago4, University of Pennsylvania5, Cleveland Clinic6, University of Cape Town7, Royal Melbourne Hospital8, University of Leeds9, University of Manitoba10, McMaster University11, University of Western Australia12, Monash University13
TL;DR: Nine cardiovascular outcomes were rated by the majority of experts as valid, reliable, feasible, and clearly defined and can be confidently used as endpoints in clinical trials designed to evaluate perioperative interventions.
Abstract: Background Adverse cardiovascular events are a leading cause of perioperative morbidity and mortality. The definitions of perioperative cardiovascular adverse events are heterogeneous. As part of the international Standardized Endpoints in Perioperative Medicine initiative, this study aimed to find consensus amongst clinical trialists on a set of standardised and valid cardiovascular outcomes for use in future perioperative clinical trials. Methods We identified currently used perioperative cardiovascular outcomes by a systematic review of the anaesthesia and perioperative medicine literature (PubMed/Ovid, Embase, and Cochrane Library). We performed a three-stage Delphi consensus-gaining process that involved 55 clinician researchers worldwide. Cardiovascular outcomes were first shortlisted and the most suitable definitions determined. These cardiovascular outcomes were then assessed for validity, reliability, feasibility, and clarity. Results We identified 18 cardiovascular outcomes. Participation in the three Delphi rounds was 100% (n=19), 71% (n=55), and 89% (n=17), respectively. A final list of nine cardiovascular outcomes was elicited from the consensus: myocardial infarction, myocardial injury, cardiovascular death, non-fatal cardiac arrest, coronary revascularisation, major adverse cardiac events, pulmonary embolism, deep vein thrombosis, and atrial fibrillation. These nine cardiovascular outcomes were rated by the majority of experts as valid, reliable, feasible, and clearly defined. Conclusions These nine consensus cardiovascular outcomes can be confidently used as endpoints in clinical trials designed to evaluate perioperative interventions with the goal of improving perioperative outcomes.
29 citations
TL;DR: In this article, the authors performed whole exome sequencing of DNA obtained from 53 unrelated iNPH patients and found that two recurrent heterozygous loss of function deletions in CWH43 were observed in 15% of the patients and were significantly enriched 6.6 and 2.7fold, respectively, when compared to the general population.
Abstract: Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder that occurs in about 1% of individuals over age 60 and is characterized by enlarged cerebral ventricles, gait difficulty, incontinence, and cognitive decline. The cause and pathophysiology of iNPH are largely unknown. We performed whole exome sequencing of DNA obtained from 53 unrelated iNPH patients. Two recurrent heterozygous loss of function deletions in CWH43 were observed in 15% of iNPH patients and were significantly enriched 6.6-fold and 2.7-fold, respectively, when compared to the general population. Cwh43 modifies the lipid anchor of glycosylphosphatidylinositol-anchored proteins. Mice heterozygous for CWH43 deletion appeared grossly normal but displayed hydrocephalus, gait and balance abnormalities, decreased numbers of ependymal cilia, and decreased localization of glycosylphosphatidylinositol-anchored proteins to the apical surfaces of choroid plexus and ependymal cells. Our findings provide novel mechanistic insights into the origins of iNPH and demonstrate that it represents a distinct disease entity.
21 citations
TL;DR: Those engaged in social media should consider the background, expertise, and motivation of these influencers as the utilization and impact of this platform grows.
Abstract: BackgroundThe influence of social media and Twitter in general surgery research, mentorship, networking, and education is growing. Limited data exist regarding individuals who control the dialogue....
12 citations
TL;DR: In this paper, the authors show that deletions in CWH43 decrease expression of the cell adhesion molecule, L1CAM, in the brains of mutant mice and in human HeLa cells harboring a CWH 43 deletion.
Abstract: Idiopathic normal pressure hydrocephalus (iNPH) is a common neurological disorder that is characterized by enlarged cerebral ventricles, gait difficulty, incontinence, and dementia. iNPH usually develops after the sixth decade of life in previously asymptomatic individuals. We recently reported that loss-of-function deletions in CWH43 lead to the development of iNPH in a subgroup of patients, but how this occurs is poorly understood. Here, we show that deletions in CWH43 decrease expression of the cell adhesion molecule, L1CAM, in the brains of CWH43 mutant mice and in human HeLa cells harboring a CWH43 deletion. Loss-of-function mutations in L1CAM are a common cause of severe neurodevelopmental defects that include congenital X-linked hydrocephalus. Mechanistically, we find that CWH43 deletion leads to decreased N-glycosylation of L1CAM, decreased association of L1CAM with cell membrane lipid microdomains, increased L1CAM cleavage by plasmin, and increased shedding of cleaved L1CAM in the cerebrospinal fluid. CWH43 deletion also decreased L1CAM nuclear translocation, suggesting decreased L1CAM intracellular signaling. Importantly, the increase in L1CAM cleavage occurred primarily in the ventricular and subventricular zones where brain CWH43 is most highly expressed. Thus, CWH43 deletions may contribute to adult-onset iNPH by selectively downregulating L1CAM in the ventricular and subventricular zone.
5 citations
18 Jan 2021
TL;DR: The case of a 37-year-old nonobese woman who underwent placement of a VP shunt for idiopathic intracranial hypertension, where the distal catheter migrated into the subcutaneous space on three occasions despite the use of multiple surgical techniques.
Abstract: Placement of a ventriculoperitoneal (VP) shunt is an effective treatment for several disorders of cerebrospinal fluid flow. A rare complication involves postoperative migration of the distal catheter out of the intraperitoneal compartment and into the subcutaneous space. Several theories attempt to explain this phenomenon, but the mechanism remains unclear.The authors report the case of a 37-year-old nonobese woman who underwent placement of a VP shunt for idiopathic intracranial hypertension. Postoperatively, the distal catheter of the VP shunt migrated into the subcutaneous space on three occasions despite the use of multiple surgical techniques, including open and laparoscopic methods of abdominal catheter placement. Notably, the patient repeatedly displayed radiographic evidence of chronic bowel distention consistent with increased intraperitoneal pressure.In this case, the mechanism of catheter migration into the subcutaneous space did not appear to be caused by pulling of the catheter from above but rather by expulsion of the catheter from the peritoneum. Space in the subcutaneous tissues caused by open surgical placement of the catheter was permissive for this process. Patients with chronic increased intraabdominal pressure, such as that caused by bowel distention, obesity, or Valsalva maneuvers, may be at increased risk for distal catheter migration.
1 citations