Antihypertensive drugs and the kidney

In the United States, 50 million Americans are estimated to have hypertension. Over the past several decades, it has become clear that hypertension is both a cause and a consequence of kidney disease. In contrast to the striking decline in mortality rates from both stroke and coronary heart disease, the prevalence of hypertension as a cause of end-stage renal disease (ESRD) has increased such that it is now the second most common cause of ESRD in the United States. Hypertension and proteinuria occur in most patients with chronic kidney disease and are risk factors for faster progression of kidney disease. Antihypertensive agents reduce blood pressure and urine protein excretion and slow the progression of kidney disease. The level of blood pressure achieved and use of renin-angiotensinaldosterone system-blocking agents is critical for delaying progression of renal disease in all ethnic groups.     

Missing the obvious: psychosocial obstacles in Veterans with hepatocellular carcinoma

BackgroundSocioeconomic disparities in patients with hepatocellular carcinoma (HCC) influence medical treatment. In addition to socioeconomic barriers, the Veteran population suffers from significant psychosocial obstacles. This study identifies the social challenges that Veterans face while undergoing treatment for HCC.MethodsOne hundred Veterans at the Palo Alto VA treated for HCC from 2009 to 2014 (50 consecutive patients who underwent a surgical procedure; 50 treated with intra‐arterial therapy) were retrospectively reviewed.ResultsSubstance abuse history was identified in 96%, and half were unemployed. Most patients survived on a limited income [median $1340, interquartile range (IQR) 900–2125]; 36% on ≤ $1000/month, 37% between $1001–2000/month and 27% with >$2000/month. A history of homelessness was found in 30%, more common in those of the lowest income (57% of ≤$1K/month group, 23% of $1–2K/month group and 9% of >$2K/month group, P< 0.01). Psychiatric illness was present in 64/100 patients; among these the majority received ongoing psychiatric treatment. Transportation was provided to 23% of patients who would otherwise have been unable to attend medical appointments.ConclusionsPsychiatric disease and substance abuse are highly prevalent among Veterans with HCC. Most patients survive on a very meager income. These profound socioeconomic and psychosocial problems must be recognized when providing care for HCC to this population to provide adequate treatment and surveillance.     

Pancreatectomy with vein reconstruction: technique matters

BackgroundA variety of techniques have been described for portal vein (PV) and/or superior mesenteric vein (SMV) resection/reconstruction during a pancreatectomy. The ideal strategy remains unclear.MethodsPatients who underwent PV/SMV resection/reconstruction during a pancreatectomy from 2005 to 2014 were identified. Medical records and imaging were retrospectively reviewed for operative details and outcomes, with particular emphasis on patency.ResultsNinety patients underwent vein resection/reconstruction with one of five techniques: (i) longitudinal venorrhaphy (LV, n = 17); (ii) transverse venorrhaphy (TV,n = 9); (iii) primary end‐to‐end (n = 28); (iv) patch venoplasty (PV, n = 17); and (v) interposition graft (IG, n = 19). With a median follow‐up of 316 days, thrombosis was observed in 16/90 (18%). The rate of thrombosis varied according to technique. All patients with primary end‐to‐end or TV remained patent. LV, PV and IG were all associated with significant rates of thrombosis (P = 0.001 versus no thrombosis). Comparing thrombosed to patent, there were no differences with respect to pancreatectomy type, pre‐operative knowledge of vein involvement and neoadjuvant therapy. Prophylactic aspirin was used in 69% of the total cohort (66% of patent, 81% of thrombosed) and showed no protective benefit.ConclusionsPrimary end‐to‐end and TV have superior patency than the alternatives after PV/SMV resection and should be the preferred techniques for short (<3 cm) reconstructions.     

3D Microfabricated Scaffolds and Microfluidic Devices for Ocular Surface Replacement: a Review

In recent years, there has been increased research interest in generating corneal substitutes, either for use in the clinic or as in vitro corneal models. The advancement of 3D microfabrication technologies has allowed the reconstruction of the native microarchitecture that controls epithelial cell adhesion, migration and differentiation. In addition, such technology has allowed the inclusion of a dynamic fluid flow that better mimics the physiology of the native cornea. We review the latest innovative products in development in this field, from 3D microfabricated hydrogels to microfluidic devices.     

Treatment with anti‐OX40L or anti‐TSLP does not alter the frequency of T regulatory cells in allergic asthmatics

OX40‐OX40L interactions and thymic stromal lymphopoietin (TSLP) are important in the induction and maintenance of Th2 responses in allergic disease, whereas T regulatory cells (Treg) have been shown to suppress pro‐inflammatory Th2 responses. Both OX40L and TSLP have been implicated in the negative regulation of Treg. The effect of anti‐asthma therapies on Treg is not well known. Our aim was to assess the effects of two monoclonal antibody therapies (anti‐OX40L and anti‐TSLP) on Treg frequency using a human model of allergic asthma. We hypothesized that the anti‐inflammatory effects of these therapies would result in an increase in circulating Treg (CD4⁺CD25⁺CD127^lowFoxp3⁺ cells) frequency. We measured Treg using flow cytometry, and our results showed that neither allergen challenge nor monoclonal antibody therapy altered circulating Treg frequency. These data highlight the need for assessment of airway Treg and for a more complete understanding of Treg biology so as to develop pharmacologics/biologics that modulate Treg for asthma therapy.     

Plasmodium falciparum cysteine protease falcipain-2 cleaves erythrocyte membrane skeletal proteins at late stages of parasite development

Plasmodium falciparum-derived cysteine protease falcipain-2 cleaves host erythrocyte hemoglobin at acidic pH and specific components of the membrane skeleton at neutral pH. Analysis of stage-specific expression of these 2 proteolytic activities of falcipain-2 shows that hemoglobin-hydrolyzing activity is maximum in early trophozoites and declines rapidly at late stages, whereas the membrane skeletal protein hydrolyzing activity is markedly increased at the late trophozoite and schizont stages. Among the erythrocyte membrane skeletal proteins, ankyrin and protein 4.1 are cleaved by native and recombinant falcipain-2 near their C-termini. To identify the precise peptide sequence at the hydrolysis site of protein 4.1, we used a recombinant construct of protein 4.1 as substrate followed by MALDI-MS analysis of the cleaved product. We show that falcipain-2-mediated cleavage of protein 4.1 occurs immediately after lysine 437, which lies within a region of the spectrin-actin-binding domain critical for erythrocyte membrane stability. A 16-mer peptide containing the cleavage site completely inhibited the enzyme activity and blocked falcipain-2-induced fragmentation of erythrocyte ghosts. Based on these results, we propose that falcipain-2 cleaves hemoglobin in the acidic food vacuole at the early trophozoite stage, whereas it cleaves specific components of the red cell skeleton at the late trophozoite and schizont stages. It is the proteolysis of skeletal proteins that causes membrane instability, which, in turn, facilitates parasite release in vivo.     

Imaging findings in a rare case of extra-articular chondrocalcinosis

We report the imaging findings in extra-articular chondrocalcinosis in a 53-year-old man with swelling and pain in right scapular area for 1 year. Plain radiography showed a right scapular area calcific mass. The clinical suspicion was of a soft tissue sarcoma. As a part of diagnostic workup, a bone scan and a PET/CT scan were done. Bone scan revealed intense MDP uptake in the right scapular area. FDG PET/CT revealed intense FDG uptake in the mass. The biopsy revealed chondrocalcinosis. This is an addition to our long list of causes of extraosseous uptake of MDP.