Variable temporoinsular cortex neuroanatomy in primates suggests a bottleneck effect in eastern gorillas

We describe an atypical neuroanatomical feature present in several primate species that involves a fusion between the temporal lobe (often including Heschl's gyrus in great apes) and the posterior dorsal insula, such that a portion of insular cortex forms an isolated pocket medial to the Sylvian fissure. We assessed the frequency of this fusion in 56 primate species (including apes, Old World monkeys, New World monkeys, and strepsirrhines) by using either magnetic resonance images or histological sections. A fusion between temporal cortex and posterior insula was present in 22 species (seven apes, two Old World monkeys, four New World monkeys, and nine strepsirrhines). The temporoinsular fusion was observed in most eastern gorilla (Gorilla beringei beringei and G. b. graueri) specimens (62% and 100% of cases, respectively) but was seen less frequently in other great apes and was never found in humans. We further explored the histology of this fusion in eastern gorillas by examining the cyto‐ and myeloarchitecture within this region and observed that the degree to which deep cortical layers and white matter are incorporated into the fusion varies among individuals within a species. We suggest that fusion between temporal and insular cortex is an example of a relatively rare neuroanatomical feature that has become more common in eastern gorillas, possibly as the result of a population bottleneck effect. Characterizing the phylogenetic distribution of this morphology highlights a derived feature of these great apes. J. Comp. Neurol. 522:844–860, 2014. © 2013 Wiley Periodicals, Inc.     

Active PAI-1 as marker for venous thromboembolism: Case–control study using a comprehensive panel of PAI-1 and TAFI assays

Background

Both activated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) and active Plasminogen Activator Inhibitor-1 (PAI-1) attenuate fibrinolysis and may therefore contribute to the pathophysiology of Venous ThromboEmbolism (VTE). Whether increased TAFI and/or PAI-1 concentrations are associated with VTE is unclear.

Objective

To study an association of impaired fibrinolysis and VTE using a comprehensive panel of in-house developed assays measuring intact TAFI, activation peptide of TAFI (AP-TAFI), PAI-1 antigen, endogenous PAI-1:t-PA complex (PAI-1:t-PA) and active PAI-1 levels in 102 VTE patients and in 113 healthy controls (HC).

Results

Active PAI-1 was significantly higher in VTE patients compared to HC (20.9 [9.6-37.8] ng/ml vs. 6.2 [3.5-9.7] ng/ml, respectively). Active PAI-1 was the best discriminator with an area under the ROC curve and 95% confidence interval (AUROC [95%CI]) of 0.84 [0.79-0.90] compared to 0.75 [0.68-0.72] for PAI-1:t-PA, 0.65 [0.58-0.73] for PAI-1 antigen, 0.62 [0.54-0.69] for AP-TAFI and 0.51 [0.44-0.59] for intact TAFI. Using ROC analysis, we defined an optimal cut-off of 12.8 ng/ml for active PAI-1, with corresponding sensitivity of 71 [61–79] % and specificity of 89 [82–94] %. A lack of association with the time between VTE event and sample collection or with the intake of anticoagulant treatment suggests that active PAI-1 levels are sustainable high in VTE patients.

Conclusions

This case–control study emphasizes the clinical importance of measuring active PAI-1 instead of PAI-1 antigen and identifies active PAI-1 as a potential marker of VTE. Prognostic studies will need to address the clinical significance of active PAI-1 as biomarker.     

Results of a Surgeon-Directed Quality Improvement Project on Breast Cancer Surgery Outcomes in South-Central Ontario

Background

Gaps in breast cancer (BC) surgical care have been identified. We have completed a surgeon-directed, iterative project to improve the quality of BC surgery in South-Central Ontario.

Methods

Surgeons performing BC surgery in a single Ontario health region were invited to participate. Interventions included: audit and feedback (A&F) of surgeon-selected quality indicators (QIs), workshops, and tailoring interviews. Workshops and A&F occurred yearly from 2005–2012. QIs included: preoperative imaging; preoperative core biopsy; positive margin rates; specimen orientation labeling; intraoperative specimen radiography of nonpalpable lesions; T1/T2 mastectomy rates; reoperation for positive margins; sentinel lymph node biopsy (SLNB) rates, number of sentinel lymph nodes; and days to receive pathology report. Semistructured tailoring interviews were conducted to identify facilitators and barriers to improved quality. All results were disseminated to all surgeons performing breast surgery in the study region.

Results

Over 6 time periods, 1,828 BC charts were reviewed from 12 hospitals (8 community and 4 academic). Twenty-two to 40 participants attended each workshop. Sustained improvement in rates of positive margins, preoperative core biopsies, specimen orientation labeling, and SLNB were seen. Mastectomy rates and overall axillary staging rates did not change, whereas time to receive pathology report increased. The tailoring interviews concerning positive margins, SLNB, and reoperation for positive margins identified facilitators and barriers relevant to surgeons.

Conclusions

This surgeon-directed, regional project resulted in meaningful improvement in numerous QIs. There was consistent and sustained participation by surgeons, highlighting the importance of integrating the clinicians in a long-term, iterative quality improvement strategy in BC surgery.     

Healthcare Intensity at Initiation of Chronic Dialysis among Older Adults

Little is known about the circumstances under which older adults initiate chronic dialysis and subsequent outcomes. Using national registry data, we conducted a retrospective analysis of 416,657 Medicare beneficiaries aged ≥67 years who initiated chronic dialysis between January 1995 and December 2008. Our goal was to define the relationship between health care intensity around the time of dialysis initiation and subsequent survival and patterns of hospitalization, use of intensive procedures (mechanical ventilation, feeding tube placement, and cardiopulmonary resuscitation), and discontinuation of dialysis before death. We found that most patients (64.5%) initiated dialysis in the hospital, including 36.6% who were hospitalized for ≥2 weeks and 7.4% who underwent one or more intensive procedures. Compared with patients who initiated dialysis in the outpatient setting, those who received the highest intensity of care at dialysis initiation (those hospitalized ≥2 weeks and receiving at least one intensive procedure) had a shorter median survival (0.7 versus 2.1 years; P<0.001), spent a greater percentage of remaining follow-up time in the hospital (median, 22.9% versus 3.1%; P<0.001), were more likely to undergo subsequent intensive procedures (44.9% versus 26.0%; adjusted hazard ratio, 2.33; 95% confidence interval [CI], 2.27 to 2.39), and were less likely to have discontinued dialysis before death (19.1% versus 26.2%; adjusted odds ratio, 0.68; 95% CI, 0.65 to 0.72). In conclusion, most older adults initiate chronic dialysis in the hospital. Those who have a prolonged hospital stay and receive other forms of life support around the time of dialysis initiation have limited survival and more intensive patterns of subsequent healthcare utilization.Over the last decade, a growing number of older adults are initiating chronic dialysis.¹ Survival among these older patients is extremely limited,^2,3 and many experience functional decline,^4,5 frequent hospitalization,⁶ and a high symptom burden⁷ after initiation of chronic dialysis. In this setting, patients must often make trade-offs between interventions intended to lengthen life and those directed at other treatment goals, such as maximizing quality of life and maintaining independence.Rates of hospitalization and use of intensive procedures, such as mechanical ventilation, feeding tube placement, and cardiopulmonary resuscitation (CPR), at the end of life are exceptionally high in older dialysis patients compared with other older Medicare beneficiaries with life-limiting illness.⁸ Discussions about prognosis, goals, and preferences are often lacking, and patients may have little appreciation of their likelihood of clinical deterioration or knowledge of more conservative alternatives, such as hospice.⁹ Uncertainty about disease trajectory and prognosis can hamper formulation of future plans and treatment preferences.^10–12Prior studies have evaluated the association of patient characteristics (e.g., comorbid conditions and functional status)^5,13,14 and treatment practices (e.g., early nephrology referral and type of vascular access)^15,16 before and at the time of dialysis initiation with subsequent outcomes. However, many of these analyses did not capture information on clinical circumstances around the time of dialysis initiation. In reality, chronic dialysis is often initiated in the context of acute illness^17,18 and rapid or unexpected loss of renal function.¹⁴We hypothesized that illness severity around the time of dialysis initiation—as reflected in measures of health care intensity, such as length of hospitalization and use of intensive procedures—might provide information useful for anticipatory guidance and supporting treatment decisions in older adults newly initiated on chronic dialysis. To evaluate this hypothesis, we used data from the U.S. Renal Data System (USRDS), a national registry of ESRD, to identify 416,657 Medicare beneficiaries aged ≥67 years and describe the intensity of care they experienced around the time of initiation of chronic dialysis and its association with survival and patterns of future healthcare utilization.     

Predictors associated with nonunion and symptomatic malunion following non-operative treatment of displaced midshaft clavicle fractures—a systematic review of the literature

Purpose

The aim of this study was to survey existing literature in order to identify all reported predictors associated with nonunion or symptomatic malunion in adult patients with displaced midshaft clavicle fractures treated non-operatively.

Method

A systematic literature search in Medline was carried out in order to identify publications in English, reporting on predictors for nonunion and malunion in adults with displaced midshaft clavicle fractures. After applying inclusion and exclusion criteria, eight publications were included in this systematic review.

Results

A total of 2,117 midshaft clavicle fractures were included in the eight publications. All publications reported on predictors for nonunion but none were found to report on predictors for malunion. The studies were characterized by different definitions for nonunion and symptomatic malunion if at all present. A total of 13 potential factors associated with nonunion were identified, six of these (displacement, comminution, shortening, age, gender and smoking) were reported as predictors for nonunion. Outcome definitions varied among the studies.

Conclusion

The included publications varied greatly in design, sample size, and quality. Based on the present literature most of the predictors were found to be of limited evidence, however displacement seems to be the most likely factor that can be used to predict for nonunion. Treating all clavicle fractures with displacement surgically would inevitably lead to overtreatment, which is why future studies need to focus on predictive factors in order to differentiate between patients that would benefit from surgery and those who would not.