Clinical characteristics,treatment intent,and outcome in a consecutive 10-year cohort of oral cancer patients aged 75 years and older

The prevalence of oral squamous cell carcinoma (OSCC) in the elderly is expected to increase by nearly a third in the next decade. Its management in older patients is potentially more challenging due to their pre-existing medical comorbidities, frailty, reduced life expectancy, and social issues. The aim of this retrospective review was to report on treatment given to patients aged 75 years and over, case mix, and survival. All patients aged 75 years and over who were diagnosed with OSCC in Merseyside between 1 January 2007 and 31 December 2016, and treated with either curative or palliative intent, were included. Their hospital notes were reviewed. Fisher’s exact test and Kaplan-Meier analysis were used for data analysis. There were 236 patients (median (IQR) age 81 (78-86) years); 67% were treated curatively and 33% palliatively. Factors associated with palliation included older age, advanced tumour stage, cognitive impairment, and residence in a nursing or residential home. Of the 165 patients who were offered curative treatment, six (4%) declined due to personal or family reasons. Overall survival for palliative patients was 12% at one year and 7% at two years, whereas for patients treated curatively it was 74% at one year, 56% at two years, and 34% at five years. Patients over 85 years of age were less likely to have composite free flaps and postoperative radiotherapy. Perioperative mortality was 2.6%. Improvements in surgical techniques and perioperative management have enabled clinicians to offer treatment with curative intent to older frail patients, and with careful case selection outcomes can be very good.     

New Insights Into Gestational Glucose Metabolism: Lessons Learned From 21st Century Approaches

Pregnancy presents a unique physiological challenge that requires changes coordinated by placentally and non–placentally derived hormones to prepare the mother for the metabolic stress presented by fetal development and to ensure appropriate nutrient allocation between mother and fetus. Of particular importance is the maintenance of normal glucose metabolism during pregnancy. Here, we describe physiological changes in glucose metabolism during pregnancy and highlight new insights into these adaptations that have emerged over the past decade using novel methodologies, specifically genome-wide association studies (GWAS) and metabolomics. While GWAS have identified some novel associations with metabolic traits during pregnancy, the majority of the findings overlap with those observed in nonpregnant populations and individuals with type 2 diabetes (T2D). Metabolomics studies have provided new insight into key metabolites involved in gestational diabetes mellitus (GDM). Both of these approaches have suggested that a strong link exists between GDM and T2D. Most recently, a role of the gut microbiome in pregnancy has been observed, with changes in the microbiome during the third trimester having metabolic consequences for the mother. In this Perspectives in Diabetes article, we highlight how these new data have broadened our understanding of gestational metabolism, and emphasize the importance of future studies to elucidate differences between GDM and T2D.     

Selective inhibition of the carotid body sensory response to hypoxia by the substance P receptor antagonist CP-96,345.

Carotid bodies are sensory organs for monitoring arterial oxygen and CO2. Previous studies have shown that chemoreceptor tissue contains substance P (SP) and exogenously administered SP augments chemosensory discharge. In the present study, we examined the physiological importance of SP in carotid body chemoreception by using a selective nonpeptide SP [neurokinin (NK) 1] receptor antagonist CP-96,345. In experiments performed on anesthetized cats, sensory discharge was recorded from the carotid body in situ. To control for alterations in blood flow, additional studies were conducted on the carotid body in vitro. In in vivo studies, close carotid body (intraarterial) administration of CP-96,345 attenuated the sensory response to hypoxia in a dose-dependent manner with 73% of the response abolished at doses of 0.3-0.6 mg/kg. Comparable doses of the (2R,3R)-enantiomer had no effect on hypoxia-induced excitation, indicating that the effect of CP-96,345 was not due to nonspecific action. In contrast, the carotid body response to high CO2 was not affected by CP-96,345, implying that only the hypoxic response is mediated by NK-1 receptor and confirming that the effect of the SP antagonist was not due to nonspecific actions. Marked attenuation of the sensory response to hypoxia was also obtained in the carotid body in vitro, suggesting that the effects of the NK-1 antagonist were not secondary to cardiovascular changes. These results demonstrate that CP-96,345 attenuates or abolishes the chemosensory response to hypoxia but not to CO2 and suggest that SP mediates the hypoxia-induced sensory excitation in the cat carotid body via NK-1 receptor activation.     

Primary prophylaxis of variceal hemorrhage

Figure 3 shows an algorithm for the primary prevention of variceal hemorrhage. Pharmacologic therapy is the current standard of treatment for the primary prophylaxis of esophageal variceal bleeding. Patients with medium or large varices should be treated with a nonselective beta-blocker with the dose titrated to achieve a 25% decrement in resting heart rate or a heart rate of 55 to 60 bpm. The development of symptoms will, of course, limit the dose used. As discussed previously, these therapeutic endpoints are not well correlated with decreases in portal pressure. Measurement of the HVPG before therapy and after 3 months of therapy provides a rational approach to drug dosing. If the HVPG decreases by 20% or to less than 12 mm Hg, the medication dose will be effective in preventing hemorrhage. If, however, the HVPG is not appropriately lowered, a long-acting nitrate may be added. Patients with small varices should be observed, with endoscopic examinations every 2 years to assess progression of variceal size. Endoscopic therapy is not indicated for the primary prevention of variceal bleeding.     

Cardiac rupture caused by Staphylococcus aureus septicaemia and pericarditis: an incidental finding

A 35 year old woman with a long history of intravenous drug abuse presented to a local hospital with severe anaemia, fever, raised markers of inflammation, and positive blood cultures for Staphylococcus aureus. She responded to treatment with antibiotics with improvement in her symptoms and markers of inflammation. Four weeks later a "routine" echocardiogram showed a rupture of her left ventricular apex and a large pseudoaneurysm. There had been no deterioration in her symptoms or haemodynamic status to herald this new development. It was successfully repaired surgically and the patient made a good recovery.


Keywords: ventricular rupture; pseudoaneurysm; staphylococcal septicaemia     

An L-selectin ligand distinct from P-selectin glycoprotein ligand-1 is expressed on endothelial cells and promotes neutrophil rolling in inflammation

Neutrophils recruited from the blood are key players in the innate immune response. Selectins play critical roles in neutrophil recruitment by mediating their tethering and rolling in inflamed venules. While the roles of P- and E-selectin in this process are well established, the mechanisms of L-selectin-mediated neutrophil recruitment remain elusive. One proposal is that tethering is mediated by L-selectin on flowing neutrophils interacting with P-selectin glycoprotein ligand-1 (PSGL-1) on adherent neutrophils. To clarify whether L-selectin-mediated neutrophil recruitment depends entirely on PSGL-1, we examined the impact of L-selectin deficiency in mice with a PSGL-1-deficient background. L-selectin and PSGL-1 double-knockout mice exhibited a higher increase in their peripheral blood neutrophil count and a worse defect in neutrophil recruitment into the inflamed peritoneum than PSGL-1-deficient mice. Intravital microscopy of inflamed cremaster muscle venules showed that L-selectindeficiency or antibody blockade of L-selectin reduced the residual leukocyte rolling in PSGL-1-deficient mice. Flow cytometric analyses showed that the endothelial cells from the cremaster muscle bound L-selectin in a PSGL-1-independent manner. These results provide evidence for the existence of an L-selectin ligand distinct from PSGL-1 in inflammation and indicate that such a ligand is expressed on endothelial cells, promoting neutrophil rolling in vivo.     

Social Network Analysis to Assess the Impact of the CTSA on Biomedical Research Grant Collaboration

Success of the Clinical Translational Science Award (CTSA) program implicitly demands team science efforts and well‐orchestrated collaboration across the translational silos (T1–T4). Networks have proven to be useful abstractions of research collaborations. Networks provide novel system‐level insights and exhibit marked changes in response to external interventions, making them potential evaluation tools that complement more traditional approaches. This study is part of our ongoing efforts to assess the impact of the CTSA on Biomedical Research Grant Collaboration (BRGC). Collaborative research grants are a complex undertaking and an outcome of sustained interaction among researchers. In this report, BRGC networks representing collaborations among CTSA‐affiliated investigators constructed from grants management system data at the University of Kentucky across a period of six years (2007–2012) corresponding to pre‐ and post‐CTSA are investigated. Overlapping community structure detection algorithms, in conjunction with surrogate testing, revealed the presence of intricate research communities rejecting random graphs as generative mechanisms. The deviation from randomness was especially pronounced post‐CTSA, reflecting an increasing trend in collaborations and team‐science efforts potentially as a result of CTSA. Intercommunity cross talk was especially pronounced post‐CTSA.     

Case Report: Cysticercosis with an Orbital Tropism in Twins

Two fraternal twin sisters developed cysticercosis localizing to the right lateral orbit over the same period after a presumed common-source exposure in China. This case demonstrates that cysticercosis can be related to travel. Similar temporal and spatial occurrences of these infections suggest a genetic tropism of the infecting organism in these twins.