Extended vertical hemilaryngectomy and reconstruction with a neovascularised tracheal autograft for advanced unilateral laryngeal tumours: a learning curve

Extended vertical hemilaryngectomy and reconstruction with a neovascularised tracheal autograft is a two-stage procedure for advanced unilateral tumours of the larynx. The purpose of this study was to review our early experience of this technique by reporting our clinical outcomes and highlighting some key learning points. Patients were identified from the Liverpool Head and Neck Cancer electronic database. Case notes were reviewed for demographic data, tumour stage, treatment, complications and outcomes. Eleven patients (all males) were identified. The mean age of the cohort was 58.2 years (range 37–78 years). The overall average follow-up period was 41.5 months (range 14 days–75 months). Of the 11 cases, 3 had completed stage 1 only. The most common complications following stage 1 procedure are related to the surgical neck wound (36 % of cases). Of the remaining eight patients who completed the first two surgical stages, closure of tracheostomy stoma was possible in seven; all seven subsequently resumed a normal oral diet. All these patients have subsequently remained free of disease at latest follow-up. There were two cases of post-operative pneumonia and one case of radial forearm free-flap failure. In contrast, only one case of post-operative pneumonia was recorded following the stage 2 procedure. In total, three patients in this cohort were dead at follow-up. This technique has a role in the management of a select group of fit patients presenting with unilateral tumours of the glottis and who are otherwise destined for a total laryngectomy. Whilst the technique is complex, we have shown that its introduction is possible in a suitably specialised and motivated surgical unit.     

Thrombelastography does not predict clinical response to rtPA for acute ischemic stroke

Thrombelastography (TEG) measures coagulation in venous blood. We hypothesized that TEG, by reflecting clot subtype and ex vivo fibrinolysis, might predict fibrinolytic response to tPA as reflected by rapid clinical improvement or hemorrhagic transformation of the infarct. 171 acute ischemic stroke patients treated with tPA were prospectively enrolled. Venous blood for TEG was drawn before and 10 min after tPA bolus. We measured rapid clinical improvement (RCI = 8 point improvement on NIHSS or total NIHSS of 0, 1 at 36 h), Hemorrhagic transformation (HT = any blood on imaging within 36 h), and hyperdense middle cerebral artery sign (HDMCA = biomarker for erythrocyte-rich clot). Multivariable regression models compared TEG parameters after adjusting for potential confounders. No differences in pre- or post-tPA TEG were found between patients with or without RCI. Also, there was no correlation between TEG and HDMCA. Clotting was slightly prolonged in patients with HT (p = 0.046). We failed to find a robust association between TEG and clinical response to tPA. It is likely that arterial clot lysis is determined by factors unrelated to coagulation status as measured by TEG in the venous circulation. It is unlikely that TEG will be useful to predict clinical response to tPA, but may help predict bleeding.     

Usefulness of plasma vitamin B(6), B(12), folate, homocysteine, and creatinine in predicting outcomes in heart transplant recipients

Atherothrombotic complications are frequently seen in patients undergoing heart transplantation. These patients have high plasma total homocysteine concentrations associated with lower folate and vitamin B(6) levels. The relation between these metabolic abnormalities and the development of vascular complications, however, remains unclear. Fasting plasma total homocysteine, folate, vitamin B(12), vitamin B(6), and creatinine were measured in 160 cardiac transplant recipients who were followed for a mean duration of 28 +/- 9 months after blood draw (mean 59 +/- 28 months after transplant). Cardiovascular events and causes of mortality were determined and Cox proportional-hazards regression analysis was used to identify the independent predictors for cardiovascular events and mortality. Twenty-five patients developed cardiovascular events and 17 died (11 cardiovascular deaths). Mean +/- SD total homocysteine value was 18.4 +/- 8.5 (range 4.3 to 63.5 micromol/L). Hyperhomocysteinemia (> or =15 micromol/L) was seen in 99 patients (62%). Levels were no different in patients with or without cardiovascular complications/death (16.8 +/- 6.2 vs 18.9 +/- 9 micromol/L, p = 0.4). However, vitamin B(6) deficiency was seen in 21% of recipients with and in 9% without cardiovascular complications/death (p = 0.05). The relative risk for cardiovascular events, including cardiovascular death, increased 2.7 times (confidence interval 1.2 to 5.9) for B(6) levels < or =20 nmol/L compared with those with normal B(6) levels (p = 0.02). Thus, hyperhomocysteinemia is common in transplant recipients but may have no causal role in the atherothrombotic vascular complications of transplantation. Deficiency of vitamin B(6), however, may predict adverse outcomes, suggesting a possible role for supplementation with this vitamin.     

Trend in the use of drug eluting stents in the United States: Insight from over 8.1 million coronary interventions

Background

Drug eluting stents (DES) reduce the risk of restenosis but are associated with increase in the risk of very late stent thrombosis, especially when antiplatelet therapy is held. The trend in DES use across the US is not fully defined.

Methods

Data from the 2001–2011 Nationwide Inpatient Sample for patients undergoing PCI were used. The trend in DES use was analyzed overall and in subgroups at risk of restenosis (those with diabetes, chronic kidney disease or prior PCI), stent thrombosis (those with acute coronary syndrome) or bleeding (those with history of bleeding peptic ulcer or atrial fibrillation).

Results

Among the 8,150,763 PCI procedures performed, DES use peaked in 2005 at 89% in all patients including groups with a low risk of restenosis, high risk of stent thrombosis or bleeding. A steep drop to 66% was noted in 2007 followed by a progressive rise to 73% in 2011 (P < 0.0001). The 2011 DES use patterns indicate increased DES use in subgroups at risk of restenosis, decreased use in subgroups at risk of thrombosis or bleeding but also lower use in groups at risk for discriminant care such as African Americans, the elderly and patients with Medicaid/self-pay.

Conclusions

DES trends indicate rapid and broad initial use followed by a sharp decline in 2007 and a progressive rise in 2011. DES use in 2011 seemed based on risk category, but was lower in groups at risk for discriminant care.     

Racial differences in outcomes of the evaluation of potential live kidney donors: a retrospective cohort study

Background: In the USA, the lower rate of live donor kidney transplant among Black transplant candidates may stem from lower rates of donation among potential live donors who are Black. We determined whether outcomes of the evaluation of potential live kidney donors varied according to the potential donors' demographic characteristics. Methods: We performed a single-center, retrospective observational cohort study of 1,179 potential live kidney donors, who came forward between 2000 and 2007. Potential donors' intended recipients were first-time transplant recipients who were evaluated between 2000 and 2005. Results: There were 268 (22.7%) potential live kidney donors who were Black, of whom 93.7% were recruited by Black transplant candidates. Donor outcomes included actual donation (38.3%), exclusion due to blood group or crossmatch incompatibility (20.4%), exclusion due to medical contraindication to donation (13.7%), and lack of further donor interest (11.2%). Black (vs. non-Black) potential donors were less likely to actually donate (27.2 vs. 41.6%, p < 0.001). Black potential donors were more likely to stop pursuing live donation (p = 0.047) or be excluded from donation for medical reasons (p = 0.008) or blood group or crossmatch incompatibility (p = 0.01). These racial differences persisted in a multivariable multinomial logistic regression model of factors associated with outcomes of the donor evaluation. Conclusions: Potential live kidney donors who are Black are less likely to actually donate. Future studies should determine whether paired exchange and desensitization programs decrease these racial differences and why Black potential donors appear more likely to stop pursuing live donation.     

microRNA-31/factor-inhibiting hypoxia-inducible factor 1 nexus regulates keratinocyte differentiation

Notch plays a critical role in the transition from proliferation to differentiation in the epidermis and corneal epithelium. Furthermore, aberrant Notch signaling is a feature of diseases like psoriasis, eczema, nonmelanoma skin cancer, and melanoma where differentiation and proliferation are impaired. Whereas much is known about the downstream events following Notch signaling, factors responsible for negatively regulating Notch receptor signaling after ligand activation are incompletely understood. Notch can undergo hydroxylation by factor-inhibiting hypoxia-inducible factor 1 (FIH-1); however, the biological significance of this phenomenon is unclear. Here we show that FIH-1 expression is up-regulated in diseased epidermis and corneal epithelium. Elevating FIH-1 levels in primary human epidermal keratinocytes (HEKs) and human corneal epithelial keratinocytes (HCEKs) impairs differentiation in submerged cultures and in a "three-dimensional" organotypic raft model of human epidermis, in part, via a coordinate decrease in Notch signaling. Knockdown of FIH-1 enhances keratinocyte differentiation. Loss of FIH-1 in vivo increased Notch activity in the limbal epithelium, resulting in a more differentiated phenotype. microRNA-31 (miR-31) is an endogenous negative regulator of FIH-1 expression that results in keratinocyte differentiation, mediated by Notch activation. Ectopically expressing miR-31 in an undifferentiated corneal epithelial cell line promotes differentiation and recapitulates a corneal epithelium in a three-dimensional raft culture model. Our results define a previously unknown mechanism for keratinocyte fate decisions where Notch signaling potential is, in part, controlled through a miR-31/FIH-1 nexus.     

Comparative effectiveness studies to improve clinical outcomes in end stage renal disease: the DEcIDE patient outcomes in end stage renal disease study

Background

Evidence is lacking to inform providers’ and patients’ decisions about many common treatment strategies for patients with end stage renal disease (ESRD).

Methods/design

The DEcIDE Patient Outcomes in ESRD Study is funded by the United States (US) Agency for Health Care Research and Quality to study the comparative effectiveness of: 1) antihypertensive therapies, 2) early versus later initiation of dialysis, and 3) intravenous iron therapies on clinical outcomes in patients with ESRD. Ongoing studies utilize four existing, nationally representative cohorts of patients with ESRD, including (1) the Choices for Healthy Outcomes in Caring for ESRD study (1041 incident dialysis patients recruited from October 1995 to June 1999 with complete outcome ascertainment through 2009), (2) the Dialysis Clinic Inc (45,124 incident dialysis patients initiating and receiving their care from 2003–2010 with complete outcome ascertainment through 2010), (3) the United States Renal Data System (333,308 incident dialysis patients from 2006–2009 with complete outcome ascertainment through 2010), and (4) the Cleveland Clinic Foundation Chronic Kidney Disease Registry (53,399 patients with chronic kidney disease with outcome ascertainment from 2005 through 2009). We ascertain patient reported outcomes (i.e., health-related quality of life), morbidity, and mortality using clinical and administrative data, and data obtained from national death indices. We use advanced statistical methods (e.g., propensity scoring and marginal structural modeling) to account for potential biases of our study designs. All data are de-identified for analyses. The conduct of studies and dissemination of findings are guided by input from Stakeholders in the ESRD community.

Discussion

The DEcIDE Patient Outcomes in ESRD Study will provide needed evidence regarding the effectiveness of common treatments employed for dialysis patients. Carefully planned dissemination strategies to the ESRD community will enhance studies’ impact on clinical care and patients’ outcomes.