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.

No abstract

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.

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 4 proteins. We verified antibody cross reactivity by examining human cardiac explant tissue by immunoblotting. Finally, we assessed protein levels in plasma samples obtained from 4 unaffected and 4 heart failure patients and demonstrated that all four proteins increased between 2-fold 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.

THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCESOccipital condyle fracture (OCF) is a rare injury that was first described by Bell in 1817. In fact, there have been only 96 more reported cases of occipital condyle fractures from 1817 to 1994 of which only 58 survived. 1 Occipital condyle fractures can sometimes go unnoticed or under-diagnosed as they are not always evident on plain radiographs of the cervical spine. Also, in rare cases OCFs can cause damage to the hypoglossal nerve which passes through the hypoglossal canal which is near the occipital condyle. The presence of specific symptoms and clinical signs should lead to the correct diagnosis. This paper describes a patient who was diagnosed with OCFs, but not hypoglossal nerve damage until 20 days following admission to hospital. We point out many factors that contributed to this delayed diagnosis, which ultimately caused severe discomfort to the patient.A 25-year-old male was involved in a motor vehicle accident in which he was the passenger. When admitted he had a Glasgow Coma Score (GCS) of E4V4M6 and had a hemotympanum on the left. He was also complaining of cervical pain and tenderness as well as difficulty breathing and speaking. Radiographic investigation revealed that the patient had suffered fractures of the 9th and 10th ribs. Furthermore, this individual had undisplaced fractures of the anterior arch of C1 and of both occipital condyles. A computerized tomographic (CT) scan of the cranial vertebral junction showed that the occipital condyles were medially and inferiorly fractured. The CT scans revealed no other spinal fracture.Although the patient was conscious on admission he had respiratory obstruction which was due to a retropharyngeal hematoma and also to pharyngeal edema. The patient was intubated the same day and attempts to extubate the patient failed twice. Because of these problems (swallowing difficulty in both oral phase and pharyngeal phase) which were confirmed by bedside testing and a video swallow study done 20 days after admission, bilateral hypoglossal nerve palsy was diagnosed.The patient was managed expectantly and mobilized in an Aspen collar. Because the patient could not move his tongue, a percutanous endogastric (PEG) tube was inserted until hypoglossal nerve function recovered. Three weeks following insertion, his tongue movements appeared to be improving to the point that he was no longer having difficulty swallowing secretions.Fracture of the occipital condyle is a rare entity. As a result, there is very limited knowledge concerning this subject. We can speculate that this injury is more common than reported. The

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.

For patients with chronic renal failure, peritoneal dialysis (PD) is a common, life sustaining form of renal replacement therapy that is used worldwide. Exposure to nonbiocompatible dialysate, inflammation, and uremia induces longitudinal changes in the peritoneal membrane. Application of molecular biology techniques has led to advances in our understanding of the mechanism of injury of the peritoneal membrane. This understanding will allow for the development of strategies to preserve the peritoneal membrane structure and function. This may decrease the occurrence of PD technique failure and improve patient outcomes of morbidity and mortality.

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.