Citations

Context.— Gynecologic cytopathology is a heavily regulated field, with Clinical Laboratory Improvement Amendments of 1988 mandating the collection of many quality metrics. There is a lack of consensus regarding methods to collect, monitor, and benchmark these data and how these data should be used in a quality assurance program. Furthermore, the introduction of human papilloma virus testing and proficiency testing has provided more data to monitor. Objective.— To determine good laboratory practices in quality assurance of gynecologic cytopathology. Data Sources.— Data were collected through a written survey consisting of 98 questions submitted to 1245 Clinical Laboratory Improvement Amendments–licensed or Department of Defense laboratories. There were 541 usable responses. Additional input was sought through a Web posting of results and questions on the College of American Pathologists Web site. Four senior authors who authored the survey and 28 cytopathologists and cytotechnologists were assigned to 5 working groups to analyze data and present statements on good laboratory practices in gynecologic cytopathology at the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference. Ninety-eight attendees at the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference discussed and voted on good laboratory practice statements to obtain consensus. Conclusions.— This paper describes the rationale, background, process, and strengths and limitations of a series of papers that summarize good laboratory practice statements in quality assurance in gynecologic cytopathology.

The literature on the use of therapeutic apheresis is often criticized for the preponderance of low to very low quality evidence. Shehata et al. examined the apheresis literature published between 1976 and 1999 and found a lack of randomized controlled trials with those identified demonstrating significant limitations. To determine if this has improved, MEDLINE was searched for randomized controlled therapeutic apheresis trials. In addition, the Clinicaltrials.gov database was also searched for actively recruiting randomized controlled therapeutic apheresis trials. The results revealed that the total and average number of publications per year examining therapeutic apheresis has increased substantially in the period 2000–2012 compared to 1976–1999. This was associated with a small increase in the average number of randomized controlled trials reported each year, but these trials represented a smaller percentage of the therapeutic apheresis literature published compared to the 1976–1999 time range. The reported trials continued to have very small numbers of enrolled patients raising questions about their ability to determine whether apheresis represents an effective therapy. Finally, according to the Clinicaltrials.gov database, a small number of randomized controlled trials of therapeutic apheresis are enrolling patients. Despite an increasing emphasis on evidence‐based medicine and the need for quality randomized controlled clinical trials, there is still a lack of such trials when it comes to therapeutic apheresis. There continues to be a need for more and better designed randomized trials in therapeutic apheresis. J. Clin. Apheresis 28:48–55, 2013. © 2013 Wiley Periodicals, Inc.

ABSTRACTInherited neuropathy is a group of common neurologic disorders with heterogeneous clinical presentations and genetic causes. Detailed neuromuscular evaluations, including nerve conduction studies, laboratory testing, and histopathologic examination, can assist in identification of the inherited component beyond family history. Genetic testing increasingly enables definitive diagnosis of specific inherited neuropathies. Diagnosis, however, is often complex, and neurologic disability may have both genetic and acquired components in individual patients. The decision of which genetic test to order or whether to order genetic tests is often complicated, and the strategies to maximize the value of testing are evolving. Apart from rare inherited metabolic neuropathies, treatment approaches remain largely supportive. We provide a clinical update of the various types of inherited neuropathies, their differential diagnoses, and distinguishing clinical features (where available). A framework is provided for clinical evaluations, including the inheritance assessment, electrophysiologic examinations, and specific genetic tests.Muscle Nerve48: 604–622, 2013

ABSTRACTIntroductionThe clinical significance of striational antibodies (StrAbs) detected in the course of paraneoplastic antibody testing is unknown.MethodsWe compared all 203 striational antibody (StrAb)‐seropositive patients identified (2004–2005) during evaluation for paraneoplastic antibodies with age‐ and sex‐matched seronegative controls.ResultsThymoma and myasthenia gravis (MG) were significantly more common among cases (P<0.0001). Cancers more rarely detected after StrAb detection were adenocarcinoma in 5 patients and sarcoma in 3 patients. All patients who had a cancer identified after StrAb testing had a titer of ≥1:7680 or a coexisting muscle AChR‐binding antibody. Autoimmune disorders more commonly observed among cases (with any StrAb value) included: hypothyroidism; rheumatoid arthritis; and pernicious anemia (all P<0.05).ConclusionsStrAbs may serve as a diagnostic clue for an autoimmune diagnosis. There is a low likelihood of oncological significance in patients with StrAb titers <1:7680 without coexisting paraneoplastic Abs. Muscle Nerve, 2013

Renal artery stenosis (RAS) is an important cause of chronic renal dysfunction. Recent studies have underscored a critical role for CCL2 (MCP-1)-mediated inflammation in the progression of chronic renal damage in RAS and other chronic renal diseases. In vitro studies have implicated p38 MAPK as a critical intermediate for the production of CCL2. However, a potential role of p38 signaling in the development and progression of chronic renal disease in RAS has not been previously defined. We sought to test the hypothesis that inhibition of p38 MAPK ameliorates chronic renal injury in mice with RAS. We established a murine RAS model by placing a cuff on the right renal artery and treated mice with the p38 inhibitor SB203580 or vehicle for 2 wk. In mice treated with vehicle, the cuffed kidney developed interstitial fibrosis, tubular atrophy, and interstitial inflammation. In mice treated with SB203580, the RAS-induced renal atrophy was reduced (70% vs. 39%, P < 0.05). SB203580 also reduced interstitial inflammation and extracellular matrix deposition but had no effect on the development of hypertension. SB203580 partially blocked the induction of CCL2, CCL7 (MCP-3), CC chemokine receptor 2 (CCR2), and collagen 4 mRNA expression in the cuffed kidneys. In vitro, blockade of p38 hindered both TNF-α and TGF-β-induced CCL2 upregulation. Based on these observations, we conclude that p38 MAPK plays a critical role in the induction of CCL2/CCL7/CCR2 system and the development of interstitial inflammation in RAS.

Introduction: Collaborative care management (CCM) for the treatment of depression has been shown to be an effective therapy. CCM can be seen as a resource intensive treatment. Early identification of patients who would not be effectively treated with CCM could allow for alteration of therapy or change in modality. Methods: A retrospective case-controlled study used 132 patients with prolonged enrollment (>1 year) in CCM (cases) and 396 randomized CCM patients who achieved remission within 6 months (controls). The hypothesis was that by studying the epidemiology of patients in prolonged care management (PCM), characteristics could be determined to help define this group. Results: With regression modeling, the odds of a patient having PCM at 1 year was highly significant for those unmarried patients (odds ratio [OR] = 1.736, confidence interval [CI] = 1.115-2.703, P = .015) with dysthymia (OR = 2.362, CI = 1.104-5.052, P = .027) and severe depression (OR = 2.856, CI = 1.551-5.260, P = .001). The adjusted baseline Patient Health Questionnaire–9 (PHQ-9) score showed a difference of 16.0 for the cases versus 14.8 for the controls ( P < .001). By 10 weeks, the difference is much larger at (10.7 vs 4.9, P < .001). At 26 weeks, the control group had an adjusted average PHQ-9 score of 2.0, whereas the case group was still elevated at 10.2 ( P < .001). Conclusions: Case-controlled analysis of PCM patients demonstrated independent predictors (such as unmarried status, diagnosis of dysthymia or severe depression), however, no baseline data was of sufficient clarity to suggest changes in clinical practice. The trend of the patient’s PHQ-9 over time was strongly suggestive of allowing differentiation between the groups.

BackgroundPrevalence and risk factors for focal hemosiderin deposits are important considerations when planning amyloid‐modifying trials for treatment and prevention of Alzheimer's disease (AD).MethodsSubjects were cognitively normal (n = 171), early‐mild cognitive impairment (MCI) (n = 240), late‐MCI (n = 111), and AD (n = 40) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Microhemorrhages and superficial siderosis were assessed at baseline and on all available MRIs at 3, 6, and 12 months. β‐amyloid load was assessed with 18F‐florbetapir positron emission tomography.ResultsPrevalence of superficial siderosis was 1% and prevalence of microhemorrhages was 25% increasing with age (P < .001) and β‐amyloid load (P < .001). Topographic densities of microhemorrhages were highest in the occipital lobes and lowest in the deep/infratentorial regions. A greater number of microhemorrhages at baseline was associated with a greater annualized rate of additional microhemorrhages by last follow‐up (rank correlation = 0.49; P < .001).ConclusionsFocal hemosiderin deposits are relatively common in the ADNI cohort and are associated with β‐amyloid load.

Traumatic brain injury (TBI) is a global public health epidemic. In the US alone, more than 3 million people sustain a TBI annually. It is one of the most disabling injuries as it may cause motor and sensory deficits and lead to severe cognitive, emotional, and psychosocial impairment, crippling vital areas of higher functioning. Fueled by the recognition of TBI as the “signature injury” in our wounded soldiers in Iraq and Afghanistan, and its often devastating impact on athletes playing contact sports, interest in TBI and TBI research has increased dramatically. Unfortunately, despite increased awareness of its detrimental consequences, there has been little progress in developing effective TBI interventions. Recent evidence, however, strongly indicates that nutritional intervention may provide a unique opportunity to enhance the neuronal repair process after TBI. To date, two omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have the most promising laboratory evidence for their neuro-restorative capacities in TBI. Although both animal models and human studies of brain injuries suggest they may provide benefits, there has been no clinical trial evaluating the effects of n-3 fatty acids on resilience to, or treatment, of TBI. This article reviews the known functions of n-3 fatty acids in the brain and their specific role in the cellular and biochemical pathways underlying neurotraumatic injury. We also highlight recent studies on the therapeutic impact of enhanced omega 3 intake in vivo , and how this may be a particularly promising approach to improving functional outcome in patients with TBI.