Postoperative Hypoxemia Is Common and Persistent: A Prospective Blinded Observational Study.

BACKGROUND: The incidence, severity, and duration of postoperative oxygen desaturation in the general surgical population are poorly characterized. We therefore used continuous pulse oximetry to quantify arterial oxygen saturation (SpO2) in a cross-section of patients having noncardiac surgery. METHODS: Oxygen saturation, blinded to clinicians, was recorded at 1-minute intervals in patients >45 years old for up to 48 hours after noncardiac surgery in 1250 patients from Cleveland Clinic Main Campus and 250 patients from the Juravinski Hospital. We determined (1) the cumulative minutes of raw minute-by-minute values below various hypoxemic thresholds; and (2) the contiguous duration of kernel-smoothed (sliding window) values below various hypoxemic thresholds. Finally, we compared our blinded continuous values with saturations recorded during routine nursing care. RESULTS: Eight hundred thirty-three patients had sufficient data for analyses. Twenty-one percent had ≥10 min/h with raw SpO2 values <90% averaged over the entire recording duration; 8% averaged ≥20 min/h <90%; and 8% averaged ≥5 min/h <85%. Prolonged hypoxemic episodes were common, with 37% of patients having at least 1 (smoothed) SpO2 <90% for an hour or more; 11% experienced at least 1 episode lasting ≥6 hours; and 3% had saturations <80% for at least 30 minutes. Clinical hypoxemia, according to nursing records, measured only in Cleveland Clinic patients (n = 594), occurred in 5% of the monitored patients. The nurses missed 90% of smoothed hypoxemic episodes in which saturation was <90% for at least one hour. CONCLUSIONS: Hypoxemia was common and prolonged in hospitalized patients recovering from noncardiac surgery. The SpO2 values recorded in medical records seriously underestimated the severity of postoperative hypoxemia.

Internal Medicine Virtual Specialist Assessment Program Reduces Emergency Department Transfers from Long-Term Care.

BACKGROUND: Transfers to emergency departments (EDs) from long-term care (LTC) can expose residents to care discontinuities and risks. Virtual platforms can increase the breadth of care available for residents within their facility, thus replacing transfers to EDs when safe and appropriate. The authors aimed to assess whether leveraging a virtual care platform at an LTC facility would reduce the number of transfers to EDs. METHODS: Data on the number of transfers to EDs were collected from January 2019 to October 2021 at an LTC facility. In June 2020 the home began using a virtual care platform that allowed residents to speak with specialist physicians through video and receive management plans remotely. The authors evaluated the Internal Medicine Virtual Specialist Program (IMVSP) using a pre-post study design by comparing the number of transfers to EDs and the proportion of transfers resulting in hospital admission before and after program implementation. Unstructured phone interviews were conducted with employees at the home to understand their experiences. RESULTS: The median number of transfers to EDs per month after program implementation showed a 13.0% reduction. The median proportion of these transfers resulting in hospital admission per month increased by 26.1%. Employees at the LTC home were satisfied with the program. CONCLUSION: The IMVSP reduced transfers to EDs and allowed for a higher proportion of transfers that resulted in hospital admission. Early access to specialist care via virtual platforms has important implications for improving accessibility to high-quality care for LTC residents and reducing risks associated with transfers.

Pilot study identifying myosin heavy chain 7, desmin, insulin-like growth factor 7, and annexin A2 as circulating biomarkers of human heart failure.

In-depth proteomic analyses offer a systematic way to investigate protein alterations in disease and, as such, can be a powerful tool for the identification of novel biomarkers. Here, we analyzed proteomic data from a transgenic mouse model with cardiac-specific overexpression of activated calcineurin (CnA), which results in severe cardiac hypertrophy. We applied statistically filtering and false discovery rate correction methods to identify 52 proteins that were significantly different in the CnA hearts compared to controls. Subsequent informatic analysis consisted of comparison of these 52 CnA proteins to another proteomic dataset of heart failure, three available independent microarray datasets, and correlation of their expression with the human plasma and urine proteome. Following this filtering strategy, four proteins passed these selection criteria, including myosin heavy chain 7, insulin-like growth factor-binding protein 7, annexin A2, and desmin. We assessed expression levels of these proteins in mouse plasma by immunoblotting, and observed significantly different levels of expression between healthy and failing mice for all four proteins. We verified antibody cross-reactivity by examining human cardiac explant tissue by immunoblotting. Finally, we assessed protein levels in plasma samples obtained from four unaffected and four heart failure patients and demonstrated that all four proteins increased between twofold and 150-fold in heart failure. We conclude that MYH7, IGFBP7, ANXA2, and DESM are all excellent candidate plasma biomarkers of heart failure in mouse and human.

Constitutively active calcineurin induces cardiac endoplasmic reticulum stress and protects against apoptosis that is mediated by alpha-crystallin-B.

Cardiac-specific overexpression of a constitutively active form of calcineurin A (CNA) leads directly to cardiac hypertrophy in the CNA mouse model. Because cardiac hypertrophy is a prominent characteristic of many cardiomyopathies, we deduced that delineating the proteomic profile of ventricular tissue from this model might identify novel, widely applicable therapeutic targets. Proteomic analysis was carried out by subjecting fractionated cardiac samples from CNA mice and their WT littermates to gel-free liquid chromatography linked to shotgun tandem mass spectrometry. We identified 1,918 proteins with high confidence, of which 290 were differentially expressed. Microarray analysis of the same tissue provided us with alterations in the ventricular transcriptome. Because bioinformatic analyses of both the proteome and transcriptome demonstrated the up-regulation of endoplasmic reticulum stress, we validated its occurrence in adult CNA hearts through a series of immunoblots and RT-PCR analyses. Endoplasmic reticulum stress often leads to increased apoptosis, but apoptosis was minimal in CNA hearts, suggesting that activated calcineurin might protect against apoptosis. Indeed, the viability of cultured neonatal mouse cardiomyocytes (NCMs) from CNA mice was higher than WT after serum starvation, an apoptotic trigger. Proteomic data identified α-crystallin B (Cryab) as a potential mediator of this protective effect and we showed that silencing of Cryab via lentivector-mediated transduction of shRNAs in NCMs led to a significant reduction in NCM viability and loss of protection against apoptosis. The identification of Cryab as a downstream effector of calcineurin-induced protection against apoptosis will permit elucidation of its role in cardiac apoptosis and its potential as a therapeutic target.

Patient safety incident analysis in healthcare: a novel curricular session for medical students.

Patient safety incident analysis is a tool which allows for the identification of and learning from patient safety incidents, which are common in healthcare settings. The University of Toronto introduced a patient safety incident analysis session for graduating medical students in the form of a lecture and subsequent student presentations of incident analyses. Student respondents to evaluation rated the session highly and felt that feedback on their presentations was helpful to reinforce material. Medical schools can incorporate this innovative session as an interactive addition to quality improvement and patient safety curricula to provide students with hands-on experience in incident analysis.

L'analyse des incidents liés à la sécurité des patients permet de repérer et d'apprendre de tels incidents qui sont fréquents dans les établissements de santé. L'Université de Toronto a introduit une séance d'analyse des incidents liés à la sécurité des patients pour les étudiants en médecine en fin de cursus, sous la forme d'un cours magistral suivi de présentations d'analyses d'incidents par les étudiants. Les étudiants qui ont évalué la formation ont rapporté un haut taux de satisfaction par rapport à la séance et ont trouvé que les commentaires reçus sur leurs présentations étaient utiles pour mieux assimiler le contenu du cours. Les facultés de médecine peuvent intégrer cette formation innovante et interactive comme complément aux programmes d'amélioration de la qualité et à ceux axés sur la sécurité des patients afin de fournir aux étudiants une expérience pratique en ce qui concerne l'analyse des incidents.

Rituximab plus standard of care for treatment of primary immune thrombocytopenia: a systematic review and meta-analysis.

BACKGROUND: Rituximab is commonly used as a treatment for primary immune thrombocytopenia to induce and maintain remission. The benefit of adding rituximab to standard-of-care treatment is uncertain. METHODS: We did a systematic review and meta-analysis of randomised controlled trials assessing the efficacy and safety of rituximab for treatment of adults with primary immune thrombocytopenia. We searched Medline, Embase, and the Cochrane database in duplicate and independently from inception up to July 31, 2014, for relevant studies. Primary outcomes were the proportion of patients achieving a complete platelet count response and a partial platelet count response (as defined in primary studies) that was maintained until the end of follow-up. We also assessed bleeding, infection, and infusion reactions. FINDINGS: Our database search returned 468 abstracts, of which five trials (with total of 463 patients) were eligible for analysis. No patients had splenectomy at the time of enrolment. Median follow-up was 6 months (IQR 6-12). Complete response (>100 × 10(9) platelets per L without rescue therapy) was more common with rituximab than with standard of care (weighted proportions: 46·8% vs 32·5%; relative risk [RR] 1·42, 95% CI 1·13-1·77; p=0·0020). Partial response was not significantly different between groups (57·6% vs 46·7%; RR 1·26, 95% CI 0·95-1·67; p=0·11). Rituximab was not associated with a reduction in bleeding (9·2% vs 5·2%; RR 1·34, 95% CI 0·63-2·87; p=0·44) or an increase in infections (20·1% vs 12·1%; RR 1·40, 95% CI 0·87-2·26; p=0·17). INTERPRETATION: Rituximab can improve complete platelet count responses by 6 months in patients with immune thrombocytopenia. Evidence for sustained responses beyond 6-12 months is limited. Clinicians must consider the goals of treatment before prescribing rituximab. FUNDING: None.

Improving prognosis estimation in patients with heart failure and the cardiorenal syndrome.

The coexistence of heart failure and renal dysfunction constitutes the "cardiorenal syndrome" which is increasingly recognized as a marker of poor prognosis. Patients with cardiorenal dysfunction constitute a large and heterogeneous group where individuals can have markedly different outcomes and disease courses. Thus, the determination of prognosis in this high risk group of patients may pose challenges for clinicians and for researchers alike. In this paper, we discuss the cardiorenal syndrome as it pertains to the patient with heart failure and considerations for further refining prognosis and outcomes in patients with heart failure and renal dysfunction. Conventional assessments of left ventricular function, renal clearance, and functional status can be complemented with identification of coexistent comorbidities, medication needs, microalbuminuria, anemia, biomarker levels, and pulmonary pressures to derive additional prognostic data that can aid management and provide future research directions for this challenging patient group.

Proteomics and mass spectrometry: what have we learned about the heart?

The emergence of new platforms for the discovery of innovative therapeutics has provided a means for diagnosing cardiac disease in its early stages. Taking into consideration the global health burden of cardiac disease, clinicians require innovations in medical diagnostics that can be used for risk stratification. Proteomic based studies offer an avenue for the discovery of proteins that are differentially regulated during disease; such proteins could serve as novel biomarkers of the disease state. For instance, in clinical practice, the abundance of such biomarkers in blood could be correlated with the severity of the disease state. As such, early detection of biomarkers would enable an improvement in patient prognosis. In this review, we outline advancements in various proteomic platforms used to study the disease proteome and their applications to the field of clinical medicine. Specifically, we highlight the contributions of proteomic-based profiling experiments to the analysis of cardiovascular diseases.

Large-scale studies to identify biomarkers for heart disease: a role for proteomics?

BACKGROUND: In clinical practice, timely detection of disease and accurate diagnosis are highly important for the effective treatment of various patient populations. Biomarkers offer a new and innovative means of assessing the disease state during early, mid and late stages of progression. OBJECTIVE: Advancements in various proteomic platforms used to study the disease proteome and their applications to the field of clinical medicine are reviewed. METHODS: A literature review was done to study proteomic technology and its contribution to the discovery of cardiac biomarkers. CONCLUSION: Proteomic profiling experiments can allow for the establishment of cardiac biomarkers, which can often offer information regarding the severity of the disease state. As high-throughput evaluation of various cardiac disease proteomes continues to improve in precision, the prospect of offering medical treatment that is tailored to the individual could follow.