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The Right Ventricle During Selective Lung Ventilation for Thoracic Surgery.
No full textThe right ventricle (RV) has been an area of evolving interest after decades of being ignored and considered less important than the left ventricle. Right ventricular dysfunction/failure is an independent predictor of mortality and morbidity in cardiac surgery; however, very little is known about the incidence or impact of RV dysfunction/failure in thoracic surgery. The pathophysiology of RV dysfunction/failure has been studied in the context of acute respiratory distress syndrome (ARDS), cardiac surgery, pulmonary hypertension, and left ventricular failure, but limited data exist in literature addressing the issue of RV dysfunction/failure in the context of thoracic surgery and one-lung ventilation (OLV). Thoracic surgery and OLV present as a unique situation where the RV is faced with sudden changes in afterload, preload, and contractility throughout the perioperative period. The authors discuss the possible pathophysiologic mechanisms that can affect adversely the RV during OLV and introduce the term RV injury to the myocardium that is affected adversely by the various intraoperative factors, which then makes it predisposed to acute dysfunction. The most important of these mechanisms seems to be the role of intraoperative mechanical ventilation, which potentially could cause both ventilator-induced lung injury leading to ARDS and RV injury. Identification of at-risk patients in the perioperative period using focused imaging, particularly echocardiography, is paramount. The authors also discuss the various RV-protective strategies required to prevent RV dysfunction and management of established RV failure
The Role of Stabilin-1 in Lymphocyte Trafficking and Macrophage Scavenging in the Liver Microenvironment.
No full textChronic liver diseases are a major global health burden, and cases of these conditions continue to rise in many countries. A diverse range of insults can lead to chronic liver disease, but they are all characterised by the infiltration and accumulation of immune cells within liver tissue and, if progressive, can lead to tissue fibrosis and cirrhosis. In this review, we focus on the role of stabilin-1 in two key processes that contribute to liver disease, namely, the recruitment of lymphocytes into liver tissue and the response of macrophages to tissue injury. Stabilin-1 is constitutively expressed on the sinusoidal endothelium of the liver and contributes to the homeostatic scavenging function of these cells. Epithelial damage in the context of chronic liver disease leads to the upregulation of stabilin-1 at sites of tissue injury, specifically at sites of immune cell recruitment and on subpopulations of hepatic macrophages. Functionally, stabilin-1 has been shown to mediate transendothelial migration of lymphocyte subsets in the setting of pro-inflammatory-activated human liver endothelium. In experimental models of liver fibrosis, stabilin-1 promotes the uptake of products of chronic oxidative stress by a subset of hepatic macrophages and suppresses their release of pro-inflammatory mediators that regulate tissue remodelling. These studies highlight the active contribution that scavenger receptors such as stabilin-1 can make in regulating chronic inflammation and tissue fibrosis, and their potential as novel therapeutic targets for these conditions
Evidence for the approach to the diagnostic evaluation of squamous cell carcinoma occult primary tumors of the head and neck.
No full textMetastases to the cervical lymph nodes from a occult primary (CUP) of head and neck squamous carcinomas has been increasing in presentation (HNSCC). Modern diagnostic workup, including clinical evaluation, conventional imaging, FDG-PET/CT and panendoscopy/tonsillectomy enables detection of the primary site in over half of all cases, and is associated with significantly improved survival rates. Recent studies have demonstrated the utility of novel molecular pathology and transoral surgical techniques in improving diagnosis and treatment. We present a new, evidence-based protocol incorporating these novel diagnostic modalities. It aims to identify the site of the primary tumor, and determine the stage of the disease, including extranodal extension. This information can personalise treatment recommendations, rationalise combinations of treatment modalities, and thereby potentially minimise toxicity and improving functional outcomes
The role of stem cells in liver injury and repair.
No full text: Liver disease is an increasing cause of worldwide mortality, and currently the only curative treatment for end-stage liver disease is whole organ allograft transplantation. Whilst this is an effective treatment, there is a shortage of suitable grafts and consequently some patients die whilst on the waiting list. Cell therapy provides an alternative treatment to increase liver function and potentially ameliorate fibrosis. : In this review, we discuss the different cellular sources for therapy investigated to date in humans including mature hepatocytes, hematopoietic stem cells, mesenchymal stromal cells and hepatic progenitor cells. Cells investigated in animals include embryonic stem cells, induced pluripotent stem cells and directly reprogrammed cells. We then appraise the experience and evidence base underlying each cell type. : We discuss how this field may evolve in the years to come focusing on opportunities to enhance the intrinsic regenerative response with therapeutic targets and cell therapies. Growing expertise in tissue engineering will likely lead to increasingly complex bio-reactors and bio-artificial livers, which open a further avenue to restore liver function and delay or prevent the need for transplantation
Secukinumab for treatment of psoriasis: does secukinumab precipitate or promote the presentation of cutaneous T-cell lymphoma?
No full textSecukinumab is an interleukin (IL)-17 monoclonal antibody inhibiting T-helper (Th)1-mediated immune response. It has proven high efficacy for moderate to severe psoriasis but data on its long-term toxicities are limited. We describe two patients who received secukinumab for clinically presumed psoriasis, but were subsequently diagnosed with mycosis fungoides (MF) following skin biopsies triggered by skin deterioration while on secukinumab. Previous studies suggested decreased numbers of regulatory T cells (Tregs) with increasing stage of MF, which may lead to the shift in the Treg/Th17 balance towards the Th17 pathway. Theoretically, the use of IL-17 monoclonal antibodies to inhibit Th17 pathway may lead to further immunosuppression and disease progression in cutaneous T-cell lymphoma (CTCL) by shifting the balance towards Tregs, although this hypothesis has not been proven. With uncertainty over the role of IL-17 and Treg/Th17 as well as diagnostic challenges in CTCL, we recommend that patients should have a confirmatory skin biopsy prior to the commencement of biologic therapy
Prevention of Infectious Complications in Acute Pancreatitis: Results of a Single-Center, Randomized, Controlled Trial.
No full textOBJECTIVES
This study aimed to investigate the efficiency of imipenem to prevent infectious complications in predicted severe acute pancreatitis (AP).
METHODS
Consecutive AP patients were randomized to imipenem 3 × 500 mg intravenously daily or an identical placebo. Exclusion criteria were prior AP, chronic pancreatitis, active malignancy, immune deficiency, active infection, concomitant antibiotic treatment, pregnancy, and patients younger than 18 years. Infectious complications including infected pancreatic necrosis, pneumonia, urinary tract infection, positive blood cultures, sepsis, and other infections were assessed as the primary outcome. Secondary outcomes included mortality, persistent organ failure, systemic inflammatory response syndrome, local complications, serious adverse events, and need for surgical intervention.
RESULTS
Forty-nine patients were randomized to each group. Infectious complications were present in 10 versus 12 of 49 patients (relative risk [RR], 0.833; 95% confidence interval [CI], 0.398-1.747). There were no significant differences in infected pancreatic necrosis (RR, 1.5; 95% CI, 0.262-8.588), pneumonia (RR, 1.5; 95% CI, 0.262-8.588), urinary tract infection (RR, 0.6; 95% CI, 0.152-2.374), positive blood cultures (RR, 0.5; 95% CI, 0.047-5.336), sepsis (RR, 0.333; 95% CI, 0.036-3.095), and other (RR, 1.333; 95% CI, 0.315-5.648). We found no significant differences in secondary outcomes.
CONCLUSIONS
Concordantly to available evidence, there is currently no ground to support prophylactic use of antibiotics in predicted severe AP
Biological variation of measured and estimated glomerular filtration rate in patients with chronic kidney disease.
No full textWhen assessing changes in glomerular filtration rate (GFR) it is important to differentiate pathological change from intrinsic biological and analytical variation. GFR is measured using complex reference methods (e.g., iohexol clearance). In clinical practice measurement of creatinine and cystatin C are used in the Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equations to provide estimated GFR. Here we studied the biological variability of measured and estimated GFR in twenty nephrology outpatients (10 male, 10 female; median age 71, range 50-80 years) with moderate CKD (GFR 30-59 ml/min per 1.73 m). Patients underwent weekly GFR measurement by iohexol clearance over four consecutive weeks. Simultaneously, GFR was estimated using the MDRD, CKD-EPI, CKD-EPI and CKD-EPI equations. Within-subject biological variation expressed as a percentage [95% confidence interval] for the MDRD (5.0% [4.3-6.1]), CKD-EPI (5.3% [4.5-6.4]), CKD-EPI (5.3% [4.5-6.5]), and CKD-EPI (5.0% [4.3-6.2]) equations were broadly equivalent. The within-subject biological variation for MDRD and CKD- EPI estimated GFR were each significantly lower than that of the measured GFR (6.7% [5.6-8.2]). Reference change values, the point at which a true change in a biomarker in an individual can be inferred to have occurred with 95% probability were calculated. By the MDRD equation, positive and negative reference change values were 15.1% and 13.1% respectively. If an individual's baseline MDRD estimated GFR (ml/min per 1.73 m) was 59, significant increases or decreases would be to values over 68 or under 51 respectively. Within-subject variability of estimated GFR was lower than measured GFR. Reference change values can be used to understand GFR changes in clinical practice. Thus, estimates of GFR are at least as reliable as measured GFR for monitoring patients over time
Cerebral Oxygenation in Traumatic Brain Injury: Can a Non-Invasive Frequency Domain Near-Infrared Spectroscopy Device Detect Changes in Brain Tissue Oxygen Tension as Well as the Established Invasive Monitor?
No full textThe cost and highly invasive nature of brain monitoring modality in traumatic brain injury patients currently restrict its utility to specialist neurological intensive care settings. We aim to test the abilities of a frequency domain near-infrared spectroscopy (FD-NIRS) device in predicting changes in invasively measured brain tissue oxygen tension. Individuals admitted to a United Kingdom specialist major trauma center were contemporaneously monitored with an FD-NIRS device and invasively measured brain tissue oxygen tension probe. Area under the curve receiver operating characteristic (AUROC) statistical analysis was utilized to assess the predictive power of FD-NIRS in detecting both moderate and severe hypoxia (20 and 10 mm Hg, respectively) as measured invasively. Sixteen individuals were prospectively recruited to the investigation. Severe hypoxic episodes were detected in nine of these individuals, with the NIRS demonstrating a broad range of predictive abilities (AUROC 0.68-0.88) from relatively poor to good. Moderate hypoxic episodes were detected in seven individuals with similar predictive performance (AUROC 0.576-0.905). A variable performance in the predictive powers of this FD-NIRS device to detect changes in brain tissue oxygen was demonstrated. Consequently, this enhanced NIRS technology has not demonstrated sufficient ability to replace the established invasive measurement
Hypocapnia Alone Fails to Provoke Important Electrocardiogram Changes in Coronary Artery Diseased Patients.
No full textBackground
There is still an urgent clinical need to develop non-invasive diagnostic tests for early ischemic heart disease because, once angina occurs, it is too late. Hypocapnia has long been known to cause coronary artery vasoconstriction. Some new cardiology tests are accompanied by the claim that they must have potential diagnostic value if hypocapnia enhances their cardiac effects in healthy subjects. But no previous study has tested whether hypocapnia produces bigger cardiac effects in patients with angina than in healthy subjects.
Methods
Severe hypocapnia (a PetCO level of 20 mmHg) lasting >15 min was mechanically induced by facemask, while conscious and unmedicated, in 18 healthy subjects and in 10 patients with angina and angiographically confirmed coronary artery disease, awaiting by-pass surgery. Each participant was their own control in normocapnia (where CO was added to the inspirate) and the order of normocapnia and hypocapnia was randomized. Twelve lead electrocardiograms (ECG) were recorded and automated measurements were made on all ECG waveforms averaged over >120 beats. 2D echocardiography was also performed on healthy subjects.
Results
In the 18 healthy subjects, we confirm that severe hypocapnia (a mean PetCO of 20 ± 0 mmHg, 0.05) on their electro- or echocardiogram. All 10 angina patients tolerated the mechanical hyperventilation well, with minimal discomfort. Hypocpania caused a similar increase in V1 (by 39%, 0.05 vs. healthy controls) and did not induce angina. Its effects were no greater in patients who did not take β-blockers, or did not take organic nitrates, or had the worst Canadian Cardiovascular Society scores.
Conclusion
Non-invasive mechanical hyperventilation while awake and unmedicated is safe and acceptable, even to patients with angina. Using it to produce severe and prolonged hypocapnia alone does produce significant ECG changes in angina patients. But its potential diagnostic value for identifying patients with coronary stenosis requires further evaluation
Pharmacy-based sexual health services: a systematic review of experiences and attitudes of pharmacy users and pharmacy staff.
No full textBACKGROUND
Pharmacies are increasingly providing services related to contraception and STIs. Identifying pharmacy staff' and users' experiences and attitudes relating to sexual health services is critical to understand users' needs and examining how pharmacy staff can most effectively contribute to patient-centred care. This systematic review aimed to examine pharmacy staff and pharmacy users' experiences and attitudes towards the delivery of a large range of sexual health services.
METHODS
Seven electronic databases and the reference lists of all included studies were searched in September 2018. Studies giving insight into pharmacy users' and pharmacy staff's experiences and attitudes towards the delivery of services related to contraception and STIs were included. The Mixed Methods Appraisal Tool was used to assess the quality of included studies and a narrative synthesis applied to analyse evidence.
RESULTS
Nineteen studies were included. Eleven studies looked at pharmacy staff, four at users and four at both groups. Users found services accessible and convenient and staff found service provision feasible. However, several barriers to service delivery were identified including lack of privacy for delivering services, lack of trained staff available to provide services and subjective judgements being made on who should be provided or offered a service.
DISCUSSION
Barriers to service delivery need to be addressed to allow pharmacies to deliver their full potential. Future research on pharmacy-based gonorrhoea and syphilis screening, and hepatitis B vaccination is needed.
PROSPERO REGISTRATION NUMBER
CRD42018106807