Citations

We report histopathological findings from a human cerebral aneurysm following treatment with a flow diverter. A 75-year-old male underwent flow diversion treatment (Pipeline Embolization Device (PED)) and coil embolization for treatment of an aneurysm at the basilar tip. At four months, angiography showed complete aneurysm occlusion; at 12 months angiography demonstrated that the aneurysm had reopened. The patient expired from brainstem compression. The aneurysm cavity was primarily filled with unorganized thrombus. Thick, interrupted neointima crossed the neck interface indicating blood flow into aneurysm through small channels. Along the parent artery the PED was covered by neointima having a measured thickness of 0.19 ± 0.01 mm; the maximal stenosis of the proximal parent artery was 27%. The perforating arteries that were crossed by the PED remained patent. Findings in this human case are similar to those in the elastase-induced aneurysms in rabbits.

Lifestyle factors can explain many, but not all, of aging-related metabolic disturbances.

AbstractBackgroundNeostigmine, an acetyl cholinesterase inhibitor, stimulates colonic motor activity and may induce vagally mediated cardiovascular effects. Our aim was to evaluate effects of i.v. neostigmine on colonic compliance and its safety in patients with chronic constipation.MethodsWe retrospectively reviewed medical records of a selected group of 144 outpatients with chronic constipation who were refractory to treatment. These patients had undergone intracolonic motility and compliance measurements with an infinitely compliant balloon linked to a barostat. Data abstracted included barostat balloon mean volumes with increases in pressure (4 mmHg steps from 0 to 44 mmHg) before and after i.v. neostigmine. Vital signs and oxygen saturation before and after neostigmine were recorded.Key ResultsOf the 144 patients, 133 were female, mean age was 41.0 ± 15.4 years (SD), and duration of constipation was 12.9 ± 13.8 years. Among patients who had undergone colonic transit measurement by scintigraphy, the overall colonic transit at 24 h (geometric center, GC24 [n = 115]) was 1.5 ± 0.7 (normal >1.3), and at 48 h (GC48 [n = 75]) it was 2.3 ± 0.9 (normal >1.9). Neostigmine decreased colonic compliance at lower distension pressures (e.g., 12 and 20 mmHg [both p < 0.001]), but not at 40 mmHg. There were expected minor changes in vital signs in response to neostigmine in 144 patients; however, one patient developed unresponsiveness, significant bradycardia, hypotension, and muscular rigidity that responded to 400 mcg i.v. atropine.Conclusions & InferencesNeostigmine significantly decreases colonic compliance in patients with refractory chronic constipation. Symptomatic bradycardia in response to neostigmine should be promptly reversed with atropine.

AbstractBackgroundLaparoscopic distal pancreatectomy (LDP) has been shown to have short‐term benefits over open distal pancreatectomy (ODP). Its application for pancreatic ductal adenocarcinoma (PDAC) remains controversial.MethodsFrom 1995 to 2014, 72 patients underwent distal pancreatectomy for PDAC at a single institution and were included in the study. Postoperative and long‐term outcomes of patients undergoing LDP (n = 44) or ODP (n = 28) were compared.ResultsLDP was associated with less blood loss (332 vs. 874 mL, p = 0.0012) and lower transfusion rates than ODP (18.2 vs. 50 %, p = 0.0495). Operative time was similar (254 vs. 266 min) for LDP and ODP; five patients (11.4 %) required conversion to ODP. Pancreatic fistulas (13.6 vs. 7.1 %) and major complications (13.6 vs. 25 %), were similar between LDP and ODP, respectively. Length of hospital stay (5.1 vs. 9.4 days, p = 0.0001) and time to initiate adjuvant therapy (69.4 vs. 95.6 days, p = 0.0441) was shorter for LDP than ODP. Tumor characteristics were similar but LDP was associated with more resected lymph nodes than ODP (25.9 vs. 12.7, p = 0.0001). One‐, three‐, and five‐year survival rates were similar between LDP (69, 41, and 41 %, respectively) and ODP (78, 44, and 32 %, respectively).ConclusionLDP is associated with less blood loss and need for blood transfusion, shorter hospital stay, and faster time to initiate adjuvant therapy than ODP for patients with PDAC. Postoperative outcomes and long‐term survival are similar between the two groups. LDP appears to be safe in the treatment of patients with PDAC.

Key Clinical MessageRasburicase for the treatment of tumor lysis syndrome has been associated with hemolytic anemia and methemoglobinemia, usually in patients with G6PD deficiency. Risks and benefits should be considered prior to use of rasburicase in at‐risk patients. Methylene blue will worsen the hemolytic anemia in G6PD deficiency and should be avoided.

ABSTRACTBackgroundCerebellar ataxia is an exclusion criterion for the clinical diagnosis of progressive supranuclear palsy, but a variant with predominant cerebellar ataxia has been reported. The aims of this study were to estimate the frequency of progressive supranuclear palsy with predominant cerebellar ataxia in an autopsy series from the United States and to compare clinical, pathologic, and genetic differences between progressive supranuclear palsy with and without predominant cerebellar ataxia.MethodWe selected 100 consecutive patients with pathologically confirmed progressive supranuclear palsy who had been evaluated at the Mayo Clinic (referred to as the Mayo Clinic patient series) from our brain bank database (N = 1085). We next enriched in cases likely to have cerebellar ataxia by searching the remaining 985 cases for (1) an antemortem diagnosis of multiple system atrophy or (2) neuropathologic evidence of prominent degeneration of the cerebellum or cerebellar afferent nuclei. Subsequently, clinical, pathologic, and genetic features were compared between the two groups.ResultsOne patient in the Mayo Clinic patient series (1%) met criteria for progressive supranuclear palsy with predominant cerebellar ataxia and had both cerebellar and mild midbrain atrophy on MRI. Four patients were identified with the targeted search. Four of the five patients were clinically misdiagnosed as multiple system atrophy. The severity of tau‐related pathology and cerebellar degeneration were not different between the two groups. No differences were detected in tau genotypes.ConclusionAlthough our data cannot provide definitive information about how to make an accurate clinical diagnosis, they should serve to raise awareness of progressive supranuclear palsy with predominant cerebellar ataxia in the differential diagnosis of multiple system atrophy. © 2016 Movement Disorder Society

The Protein Kinase D (PKD) isoforms PKD1, PKD2, and PKD3 are effectors of the novel Protein Kinase Cs (nPKCs) and diacylglycerol (DAG). PKDs impact diverse biological processes like protein transport, cell migration, proliferation, epithelial to mesenchymal transition (EMT) and apoptosis. PKDs however, have distinct effects on these functions. While PKD1 blocks EMT and cell migration, PKD2 and PKD3 tend to drive both processes. Given the importance of EMT and cell migration to the initiation and progression of various malignancies, abnormal expression of PKDs has been reported in multiple types of cancers, including breast, pancreatic and prostate cancer. In this review, we discuss how EMT and cell migration are regulated by PKD isoforms and the significance of this regulation in the context of cancer development.

Because tests that do not alter management (i.e., influence decisions and actions) should not be performed, data on the consequences of assessment constitute a critical source of validity evidence. Consequences validity evidence is challenging for many educators to understand, perhaps because it has no counterpart in the older framework of content, criterion, and construct validity. The authors’ purpose is to explain consequences validity evidence and propose a framework for organizing its collection and interpretation. Both clinical and educational assessments can be viewed as interventions. The act of administering or taking a test, the interpretation of scores, and the ensuing decisions and actions influence those being assessed (e.g., patients or students) and other people and systems (e.g., physicians, teachers, hospitals, schools). Consequences validity evidence examines such impacts of assessments. Despite its importance, consequences evidence is reported infrequently in health professions education (range 5%–20% of studies in recent systematic reviews) and is typically limited in scope and rigor. Consequences validity evidence can derive from evaluations of the impact on examinees, educators, schools, or the end target of practice (e.g., patients or health care systems); and the downstream impact of classifications (e.g., different score cut points and labels). Impact can result from the uses of scores or from the assessment activity itself, and can be intended or unintended and beneficial or harmful. Both quantitative and qualitative research methods are useful. The type, quantity, and rigor of consequences evidence required will vary depending on the assessment and the claims for its use.