Inhaled corticosteroids in chronic obstructive pulmonary disease

The effectiveness of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD) remains controversial. Randomized controlled trials, meta-analyses, medication withdrawal studies, and observational reports have examined this question, with mixed results. Observational studies have been subject to criticism because of study design involving immortal time bias. Some randomized controlled trials suggest small benefits in lung function and health status, and a reduction in the rate of acute exacerbations of COPD and mortality, but their incomplete follow-up and statistical methods have been criticized. The greatest benefits of ICS in COPD have been reported with use of ICS and long-acting beta-agonist combination therapy, although no benefit was found for the primary outcome studied under the most rigorous methodology by the recent TORCH and Optimal randomized trials. Thus, although future randomized trials will need to be conducted with the most rigorous methodology for all outcomes, much uncertainty remains regarding the potential benefits of ICS in COPD.     

Multidetector computed tomography for the detection of left atrial appendage thrombus: a comparative study with transesophageal echocardiography

OBJECTIVE: To determine the diagnostic performance of multidetector computed tomography (MDCT) for the detection of left atrial appendage (LAA) thrombus as compared with transesophageal echocardiography. METHODS: Multidetector computed tomography was evaluated in 43 patients qualitatively for the presence or absence of a filling defect in the LAA and compared with transesophageal echocardiography. Additionally, a ratio of the mean computed tomographic attenuation in the LAA apex to the mean computed tomographic attenuation in the aortic root was used for quantitative evaluation. RESULTS: A filling defect visualized in the LAA by MDCT corresponded to a sensitivity of 70% (7/10), a specificity of 82% (27/33), and a negative predictive value of 90% (27/30) for detection of LAA thrombus. When using quantitative parameters, MDCT demonstrated a sensitivity of 80% (8/10), a specificity of 73% (24/33), and a negative predictive value of 92% (24/26). Multidetector computed tomography was not able to differentiate LAA thrombus from spontaneous echo contrast by either visual evaluation or by quantitative parameters. CONCLUSIONS: Multidetector computed tomography remains limited for the detection of LAA thrombus. However, a subgroup of patients at very high risk for LAA thrombus may benefit from the high negative predictive value of cardiac MDCT.     

PACAP-Mediated Neuroprotection of Neurochemically Identified Cell Types in MSG-Induced Retinal Degeneration

Pituitary adenylate cyclase-activating polypeptide (PACAP) is neuroprotective in animal models of different brain pathologies and injuries, including cerebral ischemia, Parkinson's disease, and different types of retinal degenerations. We have previously shown that PACAP is protective against monosodium glutamate (MSG)-induced retinal degeneration, where PACAP-treated retinas has more retained structure and PACAP induces anti-apoptotic while it inhibits pro-apoptotic signaling pathways. The aim of the present study was to investigate cell-type specific effects of PACAP in MSG-induced retinal degeneration by means of immunohistochemistry. Rat pups received MSG (2 mg/g b.w.) applied on postnatal days 1, 5, and 9. PACAP (100 pmol in 5 microl saline) was injected into the right vitreous body, while the left eye received only saline. Retinas were processed for immunocytochemistry after 3 weeks. Immunolabeling was determined for vesicular glutamate transporter 1, tyrosine hydroxylase, calretinin, calbindin, parvalbumin, and vesicular gamma-aminobutyric acid (GABA) transporter. In the MSG-treated retinas, the cell bodies and processes in the inner nuclear, inner plexiform, and ganglion cell layers displayed less immunoreactivity for all antisera. Apart from photoreceptors, only one major retinal cell type examined in this study; the calbindin-immunoreactive horizontal cell seemed not to be affected by MSG application. After simultaneous application of MSG and PACAP, staining of retinas was similar to that of normal eyes, with no significant alterations in immunoreactive patterns. These findings further support the neuroprotective function of PACAP in MSG-induced retinal degeneration.     

Persistent primitive hypoglossal artery with retrograde flow from the vertebrobasilar system: a case report

The persistent primitive hypoglossal artery (PPHA) is one of the pairs of arterial connections that exist in the human embryo between the developing anterior and posterior circulation. Normally the PPHA arises from the cervical internal carotid artery (ICA) and passes through the hypoglossal canal to join the caudal basilar artery (BA). In most cases the vertebral arteries (VA) are either hypoplastic or aplastic and the posterior communicating arteries (PComA) are absent; thus, the main supply to the posterior circulation comes from the internal carotid via the PPHA in an antegrade fashion. Atherosclerotic plaques in the ICA and PPHA present with ischemic symptoms of both the carotid and vertebrobasilar systems. We report a case of a 53-year-old female who presented with a transient episode of left lower extremity numbness and weakness. Work-up with computed tomography (CT) and magnetic resonance imaging (MRI) showed a small watershed infarct in the right middle cerebral artery (MCA)/posterior cerebral artery (PCA) territory. Diagnostic angiography revealed severe proximal stenosis of the cervical ICA and presence of a PPHA just above the stenosis with retrograde filling from the vertebrobasilar junction to the distal cervical ICA. The patient underwent a carotid endarterectomy with intraoperative EEG monitoring. Intraoperative blood flow measurements were made before and after endarterectomy showing evidence of reversal of blood flow to a normal antegrade fashion. The postoperative angiogram showed resolution of the right ICA stenosis and persistence of the PHA. To our knowledge this is the first case report of a PPHA exhibiting reversal of blood flow from the posterior into the anterior circulation. Awareness of this embryological anomaly and its interaction with acquired atherosclerotic disease will minimize misinterpretation of vascular diagnostic studies.     

Influence of pulsatile perfusion preservation on outcomes in kidney transplantation from expanded criteria donors

BACKGROUND: Expanded criteria donors (ECDs) increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns about diminished survival, poorer renal function, and higher rates of delayed graft function. STUDY DESIGN: Retrospective analysis of intermediate-term outcomes in ECD kidney transplantations according to method of preservation at a single center using a standardized approach. RESULTS: Over a 5-year period, we performed 141 donations-after-brain-death ECD kidney transplantations into adult recipients. A total of 114 kidneys (81%) were managed with combined cold-storage and pulsatile perfusion preservation (PPP), and the remaining 27 (19%) were preserved with cold storage (CS). The PPP group had a higher proportion of kidneys preserved for longer than 30 hours (28% versus 0, p < 0.001) and a longer mean cold ischemia time (24.5 hours PPP versus 19 hours CS, p < 0.01). Other donor and recipient characteristics were similar between groups. Incidence of delayed graft function was 11% in PPP-stored kidneys versus 37% in CS kidneys (p = 0.002). With a mean followup of 27 months, patient (91% PPP versus 96% CS) and kidney graft survival (81% PPP versus 81.5% CS) rates were comparable. Mean 12-month serum creatinine (1.9 mg/dL) and calculated Modification of Diet in Renal Disease glomerular filtration rate (41 mL/min) values were similar between groups. CONCLUSIONS: Despite longer cold ischemia times, recipients of ECD kidneys managed with PPP had similar survival and functional outcomes, but experienced a marked reduction in the rate of delayed graft function.