Meal Ingestion and Hemodynamic Interactions Regarding Renal Blood Flow on Duplex Sonography: Potential Diagnostic Implications

Publication date: Available online 2 July 2018
Source:Ultrasound in Medicine & Biology
Author(s): Tomonori Kishino, Keiichiro Harashima, Shigeki Hashimoto, Naoya Fukuta, Masayo Seki, Hiroaki Ohnishi, Takashi Watanabe, Junichi Otaki
Splanchnic blood flow changes dramatically after meal ingestion. The present study evaluated physiologic interactions between meal ingestion and hemodynamics with respect to renal blood flow on duplex sonography, assessing the possible influence on Doppler parameters used as diagnostic criteria for renal artery stenosis. Subjects comprised 26 healthy young men (mean age: 22 ± 2 y). Sonographic measurements were made shortly after breakfast and every 1 h thereafter and were compared with values measured before the meal. Peak systolic velocity in the renal artery was elevated post-prandially, peaking at 1 h (90 ± 12 cm/s), compared with pre-prandially (73 ± 10 cm/s, p < 0.01). Similarly, acceleration time at the intra-renal segmental artery shortened to a minimum at 1 h (45 ± 5 ms) compared with baseline (51 ± 6 ms, p < 0.01). The present study indicates that renal blood flow is altered for a few hours after meal ingestion. Attention should be paid to the interpretation of data measured after meals on duplex sonography for diagnosis of renal artery stenosis.



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Stereotactic Body Radiation Therapy (SBRT) for Early-stage Lung Cancer in the Elderly

Publication date: Available online 1 July 2018
Source:Seminars in Oncology
Author(s): Ashwin Shinde, Richard Li, Jae Kim, Ravi Salgia, Arti Hurria, Arya Amini
Early-stage non-small cell lung cancer (NSCLC) is on the rise due to the implementation of screening guidelines for patients at risk for developing lung cancer. It is anticipated that as the United States population continues to age, there will be a higher percentage of medically inoperable early-stage lung cancer patients. For this reason, non-invasive ablative therapies are necessary. Stereotactic body radiation therapy (SBRT) is an effective modality in addressing early-stage NSCLC. SBRT consists of high-dose radiation delivered over three to five treatments. Several randomized trials comparing surgery to SBRT in early-stage operable patients have unfortunately closed early due to poor accrual. However, a recent pooled analysis from two randomized trials (STARS and ROSEL) comparing surgery to SBRT did show comparable local control and overall survival rates between surgery and SBRT, offering a very effective, non-invasive modality for older adult patients with early-stage NSCLC. In this review, we summarize the role of SBRT in early-stage NSCLC, in particularly applying it to the older adult population.



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Chemerin: a multifaceted adipokine involved in metabolic disorders

Metabolic syndrome is a global public health problem and predisposes individuals to obesity, diabetes and cardiovascular disease. Although the underlying mechanisms remain to be elucidated, accumulating evidence has uncovered a critical role of adipokines. Chemerin, encoded by the gene Rarres2, is a newly discovered adipokine involved in inflammation, adipogenesis, angiogenesis and energy metabolism. In humans, local and circulating levels of chemerin are positively correlated with BMI and obesity-related biomarkers. In this review, we discuss both peripheral and central roles of chemerin in regulating body metabolism. In general, chemerin is upregulated in obese and diabetic animals. Previous studies by gain or loss of function show an association of chemerin with adipogenesis, glucose homeostasis, food intake and body weight. In the brain, the hypothalamus integrates peripheral afferent signals including adipokines to regulate appetite and energy homeostasis. Chemerin increases food intake in seasonal animals by acting on hypothalamic stem cells, the tanycytes. In peripheral tissues, chemerin increases cell expansion, inflammation and angiogenesis in adipose tissue, collectively resulting in adiposity. While chemerin signalling enhances insulin secretion from pancreatic islets, contradictory results have been reported on how chemerin links to obesity and insulin resistance. Given the association of chemerin with obesity comorbidities in humans, advances in translational research targeting chemerin are expected to mitigate metabolic disorders. Together, the exciting findings gathered in the last decade clearly indicate a crucial multifaceted role for chemerin in the regulation of energy balance, making it a promising candidate for urgently needed pharmacological treatment strategies for obesity.

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The role of orexin in controlling the activity of the adipo-pancreatic axis

Orexin A and B are two neuropeptides, which regulate a variety of physiological functions by interacting with central nervous system and peripheral tissues. Biological effects of orexins are mediated through two G-protein-coupled receptors (OXR1 and OXR2). In addition to their strong influence on the sleep–wake cycle, there is growing evidence that orexins regulate body weight, glucose homeostasis and insulin sensitivity. Furthermore, orexins promote energy expenditure and protect against obesity by interacting with brown adipocytes. Fat tissue and the endocrine pancreas play pivotal roles in maintaining energy homeostasis. Since both organs are crucially important in the context of pathophysiology of obesity and diabetes, we summarize the current knowledge regarding the role of orexins and their receptors in controlling adipocytes as well as the endocrine pancreatic functions. Particularly, we discuss studies evaluating the effects of orexins in controlling brown and white adipocytes as well as pancreatic alpha and beta cell functions.

https://ift.tt/2tIVhbN

The delayed effects of antibiotics in type 2 diabetes, friend or foe?

An increasing amount of evidence suggests that the delayed effect of antibiotics (abx) on gut microbiota after its cessation is not as favorable as its immediate effect on host metabolism. However, it is not known how the diverse abx-dependent metabolic effects influence diabetic subjects and how gut microbiota is involved. Here, we treated db/db mice with abx cocktail for 12 days and discontinued for 24 days. We found that db/db mice showed decreased body weight and blood glucose after abx treatment, which rapidly caught up after abx cessation. Twenty-four days after abx withdrawal, db/db mice exhibit increased plasma, hepatic total cholesterol (TC) levels and liver weight. The gut microbiota composition at that time showed decreased relative abundances (RAs) of Desulfovibrionaceae and Rikenellaceae, increased RA of Erysipelotrichaceae and Mogibacteriaceae, which were correlating with the reduced short-chain fatty acids (SCFAs) in gut content, such as propionic acid and valeric acid and with the elevated fecal taurine-conjugated bile acids (BAs) levels. The molecular biology studies showed inhibited hepatic BA synthesis from cholesterol, impeded intracellular transportation and biliary excretion of cholesterol that all conferred to liver TC accumulation. The associations among alterations of gut microbiota composition, microbial metabolite profiles and host phenotypes suggested the existence of gut microbiota-linked mechanisms that mediate the unfavorable delayed effects of abx on db/db mice cholesterol metabolism. Thus, we call upon the caution of applying abx in diabetic animal models for studying microbiota-host interaction and in type 2 diabetes subjects for preventing chronic cardiovascular consequences.

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ER{alpha} expression in T lymphocytes is dispensable for estrogenic effects in bone

Estrogen treatment has positive effects on the skeleton, and we have shown that estrogen receptor alpha (ERα) expression in cells of hematopoietic origin contributes to a normal estrogen treatment response in bone tissue. T lymphocytes are implicated in the estrogenic regulation of bone mass, but it is not known whether T lymphocytes are direct estrogen target cells. Therefore, the aim of this study was to determine the importance of ERα expression in T lymphocytes for the estrogenic regulation of the skeleton using female mice lacking ERα expression specifically in T lymphocytes (Lck-ERα^–/–) and ERα^flox/flox littermate (control) mice. Deletion of ERα expression in T lymphocytes did not affect bone mineral density (BMD) in sham-operated Lck-ERα^–/– compared to control mice, and ovariectomy (ovx) resulted in a similar decrease in BMD in control and Lck-ERα^–/– mice compared to sham-operated mice. Furthermore, estrogen treatment of ovx Lck-ERα^–/– led to an increased BMD that was indistinguishable from the increase seen after estrogen treatment of ovx control mice. Detailed analysis of both the appendicular (femur) and axial (vertebrae) skeleton showed that both trabecular and cortical bone parameters responded to a similar extent regardless of the presence of ERα in T lymphocytes. In conclusion, ERα expression in T lymphocytes is dispensable for normal estrogenic regulation of bone mass in female mice.

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Critical role for the Tsc1-mTORC1 pathway in {beta}-cell mass in Pdx1-deficient mice

Mutations in the pancreatic duodenal homeobox (PDX1) gene are associated with diabetes in humans. Pdx1-haploinsufficient mice also develop diabetes, but the molecular mechanism is unknown. To this end, we knocked down Pdx1 gene expression in mouse MIN6 insulinoma cells. Pdx1 suppression not only increased apoptotic cell death but also decreased cell proliferation, which was associated with a decrease in activity of mechanistic target of rapamycin complex 1 (mTORC1). We found that in Pdx1-deficient mice, tuberous sclerosis 1 (Tsc1) ablation in pancreatic β-cells restores β-cell mass, increases β-cell proliferation and size, decreases the number of TUNEL-positive cells and restores glucose tolerance after glucose challenge. In addition, Tsc1 ablation in pancreatic β-cells increases phosphorylation of initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation and 40S ribosomal protein S6, two downstream targets of mTORC1 indicating that Tsc1 mediates mTORC1 downregulation induced by Pdx1 suppression. These results suggest that the Tsc1-mTORC1 pathway plays an important role in mediating the decrease in β-cell proliferation and growth and the reduction in β-cell mass that occurs in Pdx1-deficient diabetes. Thus, mTORC1 may be target for therapeutic interventions in diabetes associated with reductions in β-cell mass.

https://ift.tt/2z3qDin

Are peptide conjugates the golden therapy against obesity?

Obesity is a worldwide pandemic, which can be fatal for the most extremely affected individuals. Lifestyle interventions such as diet and exercise are largely ineffective and current anti-obesity medications offer little in the way of significant or sustained weight loss. Bariatric surgery is effective, but largely restricted to only a small subset of extremely obese patients. While the hormonal factors mediating sustained weight loss and remission of diabetes by bariatric surgery remain elusive, a new class of polypharmacological drugs shows potential to shrink the gap in efficacy between a surgery and pharmacology. In essence, this new class of drugs combines the beneficial effects of several independent hormones into a single entity, thereby combining their metabolic efficacy to improve systems metabolism. Such unimolecular drugs include single molecules with agonism at the receptors for glucagon, glucagon-like peptide 1 and the glucose-dependent insulinotropic polypeptide. In preclinical studies, these specially tailored multiagonists outperform both their mono-agonist components and current best in class anti-obesity medications. While clinical trials and vigorous safety analyses are ongoing, these drugs are poised to have a transformative effect in anti-obesity therapy and might hopefully lead the way to a new era in weight-loss pharmacology.

https://ift.tt/2tL0K1w

Preliminary Analysis of Pulsed Radiofrequency Therapy Combined with Carpal Tunnel Release for Reducing the Pain in Postoperative Period: Early Outcomes

Carpal tunnel release (CTR) surgery is the main treatment used for moderate and severe CTS. However, despite this treatment, symptoms of pain may continue into the early postoperative period in some cases1.

https://ift.tt/2Nhpfvu

Reply to the Editor: The pedicled internal pudendal artery perforator (PIPAP) flap for ischial pressure sore reconstruction: Technique and long-term outcome of a cohort study

It is with great interest that we have read the recent publication of Legemate CM et al. on the technique and long-term outcome of the pedicled internal pudendal artery perforator (PIPAP) flap for ischial pressure sore reconstruction.1 First described by Hashimoto et al., this flap is an interesting option due to its rich vascular network, easy dissection, feasible primary closure of the donor site, and the fact that the pudendal artery perforators are close to the location of the ischial defect.

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Patients with Abdominal-based Free Flap Breast Reconstruction a Decade after Surgery - A Comprehensive Long-term Follow-up Study

Abdominal-based free flap breast reconstruction has increasingly become the gold standard, however long-term evidence of aesthetic outcome and quality of life is lacking. Our study aims to gain an overview of patients with abdominal-based free flap breast reconstructions in a long-term perspective.

https://ift.tt/2tNzBuU

Autoimmune pituitary involvement in Prader–Willi syndrome: new perspective for further research

Abstract

The role of antipituitary antibodies in the pathophysiology of pituitary hormone deficiency has been increasingly elucidated over the last decade. Prader-Willi syndrome is a genetic disorder which includes hypothalamic/pituitary dysfunction as one of its main features. We looked for autoimmune pituitary involvement in 55 adults with Prader-Willi syndrome, discovering that about 30% of them have a positive titer of antipituitary antibodies. Although the presence of these autoantibodies could only be an "epiphenomenon", our results suggest that autoimmune mechanisms might contribute, at least in part, to the pituitary impairment of Prader-Willi syndrome, and in addition to genetically determined dysfunction of the central nervous system. This paper provides a new perspective on pituitary impairment in these patients, suggesting that the search for hypophisitis could be a reasonable and interesting field for further research.

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Sentinel lymph node biopsy in small papillary thyroid cancer. A review on novel surgical techniques

Abstract

Purpose

Sentinel lymph node biopsy (SNB) in patients with papillary thyroid carcinoma (PTC) and negative for clinically neck lymph node metastatic involvement (N0) has emerged as a promising minimally invasive procedure to detect metastatic nodes.

Methods

The MEDLINE database was searched via the PubMed interface on 10 January 2018 for the MeSH headings "sentinel lymph node biopsy" and "thyroid carcinoma".

Results

Vital blue dye, radioisotope, and the combination of both techniques are used in PTC patients. These methods and the emerging role of SPECT/CT are discussed in this review. The sentinel lymph node (SLN) identification rates ranged from 0 to 100% for blue dye, 83 to 100% for radioisotopes, and 66 to 100% for the combination of both techniques, respectively.

Conclusions

SNB based on radioisotope technique with the use of intraoperative gamma-probe is an accurate and safe method that allows the highest SLN detection rate. There is sufficient evidence to propagate the increasing use of SNB procedure that has the potential to avoid prophylactic lymph node surgery in patients clinically N0.

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Perioperative serum cortisol levels in ACTH sufficient and ACTH deficient patients during transsphenoidal surgery of pituitary adenoma

Abstract

Purpose

No previous study has analyzed serum cortisol levels during transsphenoidal endoscopic pituitary surgery in patients with and without hydrocortisone (HC) substitution.

Methods

A total of 15 patients undergoing surgery for a pituitary adenoma were studied. Those with normal ACTH function were either not given HC (n = 7) or received 50 mg intravenous HC at the start of surgery (n = 4). Patients with ACTH deficiency received intravenous HC of 100 mg in the morning before surgery (n = 4) with the additional 50 mg for an afternoon operation (n = 2). Propofol and remifentanil were used as anesthetics. Serum cortisol was measured at the start of and every 30 min during surgery.

Results

Among 7 patients with normal ACTH function without HC substitution, cortisol levels before surgery were 126–244 nmol/L, among the 4 patients undergoing surgery in the morning, whereas the 3 who underwent surgery in the afternoon had lower levels, 38–76 nmol/L. During nose/sinus surgery cortisol levels decreased to 79–139 and 24–54 nmol/L, respectively. At intrasellar manipulation a distinct rise was noted. Also, in the 4 ACTH sufficient patients receiving HC, cortisol levels decreased during nose/sinus surgery, but only with a slight increase during intrasellar surgery. In the 4 ACTH deficient patients cortisol peaked at 1914–2582 nmol/L.

Conclusions

Patients with normal ACTH function without HC substitution had very low cortisol levels during the first part of surgery, likely suppressed by the anesthetics. After mechanical impact in the sella, a marked increase in cortisol was noted. Supraphysiological cortisol levels were achieved with our routine HC substitution, advising us to reduce the supplementation.

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Decision support system for detection of hypertensive retinopathy using arteriovenous ratio

Publication date: Available online 2 July 2018
Source:Artificial Intelligence in Medicine
Author(s): Shahzad Akbar, Muhammad Usman Akram, Muhammad Sharif, Anam Tariq, Shoab A. Khan
Hypertensive Retinopathy (HR) caused by hypertension is a retinal disease which may leads to vision loss and blindness. Computer aided diagnostic systems for various diseases are being used in clinics but there is a need to develop an automated system that detects and grades HR disease. In this paper, an automated system is presented that detects and grades HR disease using Arteriovenous Ratio (AVR).The presented system includes three modules i.e. main component extraction, artery/vein (A/V) classification and finally AVR calculation and grading of HR. Proposed system uses vascular map and a set of hybrid features for A/V classification. The evaluation of proposed system is carried out using three datasets. The proposed system shows average accuracies of 95.14% for images of INSPIRE-AVR database, 96.82% for images of VICAVR database and 98.76% for local dataset AVRDB. These results support that the proposed system is trustworthy for clinical use in detection and grading of HR disease. Main contribution of proposed system is that it utilizes complete blood vessel map for A/V classification. These arteries and veins are then used to calculate AVR and grade HR cases based on AVR values. Another contribution of this article is that it presents a new dataset AVRDB for A/V classification and HR detection.



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Gabapentin, Methadone, and Oxycodone With or Without Venlafaxine Hydrochloride in Managing Pain in Participants With Stage II-IV Squamous Cell Head and Neck Cancer Undergoing Chemoradiation Therapy

Conditions:   Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8;   Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
Interventions:   Drug: Gabapentin;   Drug: Methadone;   Drug: Oxycodone;   Other: Quality-of-Life Assessment;   Other: Questionnaire Administration;   Drug: Venlafaxine;   Drug: Venlafaxine Hydrochloride Extended Release
Sponsors:   Roswell Park Cancer Institute;   National Cancer Institute (NCI)
Recruiting

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Wearable Sensor for Biometrics During Locoregional Therapy for Head and Neck Cancer

Condition:   Cancer of Head and Neck
Intervention:   Device: wearable sensor
Sponsor:   University of Texas Southwestern Medical Center
Recruiting

https://ift.tt/2KpbxsB

Sitravatinib (MGCD516) and Nivolumab in Oral Cavity Cancer Window Opportunity Study

Conditions:   Squamous Cell Carcinoma, Head And Neck;   Squamous Cell Carcinoma Mouth;   Squamous Cell Carcinoma of the Oral Cavity
Interventions:   Drug: Sitravatinib;   Biological: Nivolumab
Sponsors:   University Health Network, Toronto;   Mirati Therapeutics Inc.
Not yet recruiting

https://ift.tt/2MGV1ky

Nivolumab & IRX-2 With Surgery for Resectable Stage III-IVA Oral Cavity Cancer or HPV-Positive Oropharyngeal Cancer

Conditions:   Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma;   Stage II Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7;   Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7;   Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7
Interventions:   Drug: Cyclophosphamide;   Biological: IRX-2;   Biological: Nivolumab;   Procedure: Surgery
Sponsors:   Emory University;   Bristol-Myers Squibb;   IRX Therapeutics
Not yet recruiting

https://ift.tt/2Ko15BP

TPF Induction Chemotherapy vs PF Adjuvant Chemotherapy Combined With Concurrent Chemoradiotherapy in the Treatment of Locally Advanced NPC

Condition:   Locally Advanced Nasopharyngeal Carcinoma
Interventions:   Drug: TPF+CCRT;   Drug: CCRT+PF
Sponsor:   Guiyang Medical University
Recruiting

https://ift.tt/2MH8FEo