Medicine by Alexandros G.Sfakianakis: 03/24/18

Σάββατο 24 Μαρτίου 2018

Poly ADP-ribose polymerase-1 as a potential therapeutic target in Merkel cell carcinoma.

Poly ADP-ribose polymerase-1 as a potential therapeutic target in Merkel cell carcinoma.

Head Neck. 2018 Mar 23;:

Authors: Ferrarotto R, Cardnell R, Su S, Diao L, Eterovic AK, Prieto V, Morrisson WH, Wang J, Kies MS, Glisson BS, Byers LA, Bell D

Abstract
BACKGROUND: Patients with metastatic Merkel cell carcinoma are treated similarly to small cell lung cancer (SCLC). Poly ADP-ribose polymerase-1 (PARP1) is overexpressed in SCLC and response to PARP inhibitors have been reported in patients with SCLC. Our study explores PARP as a therapeutic target in Merkel cell carcinoma.
METHODS: We evaluated PARP1 expression and Merkel cell polyomavirus (MCPyV) in 19 patients with Merkel cell carcinoma. Target exome-sequencing was performed in 14 samples. Sensitivity to olaparib was tested in 4 Merkel cell carcinoma cell lines.
RESULTS: Most Merkel cell carcinomas (74%) express PARP1 at high levels. Mutations in DNA-damage repair genes were identified in 9 samples (64%), occurred exclusively in head neck primaries, and correlated with TP53/RB1 mutations. The TP53/RB1 mutations were more frequent in MCPyV-negative tumors. Sensitivity to olaparib was seen in the Merkel cell carcinoma line with highest PARP1 expression.
CONCLUSION: Based on PARP1 overexpression, DNA-damage repair gene mutations, platinum sensitivity, and activity of olaparib in a Merkel cell carcinoma line, clinical trials with PARP inhibitors are warranted in Merkel cell carcinoma.

PMID: 29570891 [PubMed - as supplied by publisher]

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Lenalidomide as immune adjuvant to a dendritic cell vaccine in chronic lymphocytic leukemia patients.

Lenalidomide as immune adjuvant to a dendritic cell vaccine in chronic lymphocytic leukemia patients.

Eur J Haematol. 2018 Mar 23;:

Authors: Palma M, Hansson L, Mulder TA, Adamson L, Näsman-Glaser B, Eriksson I, Heimersson K, Mozaffari F, Svensson A, Gentilcore G, Österborg A, Mellstedt H

Abstract
OBJECTIVES: We previously showed that immunization with ex-vivo generated autologous dendritic cells loaded with apoptotic tumor cells (Apo-DC) potentiated tumor-specific immunity in chronic lymphocytic leukemia (CLL) patients. Here, we evaluated safety and immunogenicity of Apo-DC in combination with lenalidomide, granulocyte-macrophage colony-stimulating factor (GM-CSF) and low-dose cyclophosphamide (CTX).
METHODS: Ten previously untreated patients with slowly progressing CLL received 5 Apo-DC vaccinations and lenalidomide orally for 24 weeks either alone (cohort I, n=5) or together with subcutaneous GM-CSF and intravenous CTX (cohort II, n=5). Tumor-specific T-cell responses were measured by proliferation and IFN-γ ELISPOT assays. Immune monitoring was performed by flow-cytometry.
RESULTS: Dose-limiting toxicity was observed in 3/10 patients, two in cohort I and one in cohort II. One patient developed autoimmune hemolytic anemia and another grade 4 thrombocytopenia. Vaccine-induced immune responses were seen in 5/5 and 4/5 patients in cohort I and II, respectively. The expression of immune checkpoints on T cells did not change significantly.
CONCLUSIONS: Lenalidomide alone or in combination with GM-CSF and low-dose CTX as immune adjuvant to the Apo-DC vaccine elicited tumor-specific T-cell responses in CLL patients. However, unexpected toxicity was observed and caution is suggested in further exploring this drug as immune adjuvant in CLL. This article is protected by copyright. All rights reserved.

PMID: 29569742 [PubMed - as supplied by publisher]

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Lipid-Based Particles: Versatile Delivery Systems for Mucosal Vaccination against Infection.

Lipid-Based Particles: Versatile Delivery Systems for Mucosal Vaccination against Infection.

Front Immunol. 2018;9:431

Authors: Corthésy B, Bioley G

Abstract
Vaccination is the process of administering immunogenic formulations in order to induce or harness antigen (Ag)-specific antibody and T cell responses in order to protect against infections. Important successes have been obtained in protecting individuals against many deleterious pathological situations after parenteral vaccination. However, one of the major limitations of the current vaccination strategies is the administration route that may not be optimal for the induction of immunity at the site of pathogen entry, i.e., mucosal surfaces. It is now well documented that immune responses along the genital, respiratory, or gastrointestinal tracts have to be elicited locally to ensure efficient trafficking of effector and memory B and T cells to mucosal tissues. Moreover, needle-free mucosal delivery of vaccines is advantageous in terms of safety, compliance, and ease of administration. However, the quest for mucosal vaccines is challenging due to (1) the fact that Ag sampling has to be performed across the epithelium through a relatively limited number of portals of entry; (2) the deleterious acidic and proteolytic environment of the mucosae that affect the stability, integrity, and retention time of the applied Ags; and (3) the tolerogenic environment of mucosae, which requires the addition of adjuvants to elicit efficient effector immune responses. Until now, only few mucosally applicable vaccine formulations have been developed and successfully tested. In animal models and clinical trials, the use of lipidic structures such as liposomes, virosomes, immune stimulating complexes, gas-filled microbubbles and emulsions has proven efficient for the mucosal delivery of associated Ags and the induction of local and systemic immune reponses. Such particles are suitable for mucosal delivery because they protect the associated payload from degradation and deliver concentrated amounts of Ags via specialized sampling cells (microfold cells) within the mucosal epithelium to underlying antigen-presenting cells. The review aims at summarizing recent development in the field of mucosal vaccination using lipid-based particles. The modularity ensured by tailoring the lipidic design and content of particles, and their known safety as already established in humans, make the continuing appraisal of these vaccine candidates a promising development in the field of targeted mucosal vaccination.

PMID: 29563912 [PubMed]

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Immunogenicity in African Green Monkeys of M Protein Mutant Vesicular Stomatitis Virus Vectors and Contribution of Vector-Encoded Flagellin.

Immunogenicity in African Green Monkeys of M Protein Mutant Vesicular Stomatitis Virus Vectors and Contribution of Vector-Encoded Flagellin.

Vaccines (Basel). 2018 Mar 19;6(1):

Authors: Westcott MM, Smedberg J, Jorgensen MJ, Puckett S, Lyles DS

Abstract
Recombinant vesicular stomatitis virus (VSV) is a promising platform for vaccine development. M51R VSV, an attenuated, M protein mutant strain, is an effective inducer of Type I interferon and dendritic cell (DC) maturation, which are desirable properties to exploit for vaccine design. We have previously evaluated M51R VSV (M51R) and M51R VSV that produces flagellin (M51R-F) as vaccine vectors using murine models, and found that flagellin enhanced DC activation and VSV-specific antibody production after low-dose vaccination. In this report, the immunogenicity of M51R vectors and the adjuvant effect of virus-produced flagellin were evaluated in nonhuman primates following high-dose (10⁸ pfu) and low-dose (10⁵ pfu) vaccination. A single intramuscular vaccination of African green monkeys with M51R or M51R-F induced VSV-specific, dose-dependent humoral immune responses. Flagellin induced a significant increase in antibody production (IgM, IgG and neutralizing antibody) at the low vaccination dose. A VSV-specific cellular response was detected at 6 weeks post-vaccination, but was neither dose-dependent nor enhanced by flagellin; similar numbers of VSV-specific, IFNγ-producing cells were detected in lymph node and spleen of all animals. These results indicate that virus-directed, intracellular flagellin production may improve VSV-based vaccines encoding heterologous antigens by lowering the dose required to achieve humoral immunity.

PMID: 29562688 [PubMed]

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The enhanced antitumor-specific immune response with mannose- and CpG-ODN-coated liposomes delivering TRP2 peptide.

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https:--www.ncbi.nlm.nih.gov-corehtml-pm

The enhanced antitumor-specific immune response with mannose- and CpG-ODN-coated liposomes delivering TRP2 peptide.

Theranostics. 2018;8(6):1723-1739

Authors: Lai C, Duan S, Ye F, Hou X, Li X, Zhao J, Yu X, Hu Z, Tang Z, Mo F, Yang X, Lu X

Abstract
PURPOSE: Dendritic cell (DC)-based cancer vaccines is a newly emerging and potent form of immune therapy. As for any new technology, there are still considerable challenges that need to be addressed. Here, we investigate the antitumor potential of a novel liposomal vaccine, M/CpG-ODN-TRP2-Lipo.
METHODS: We developed a vaccination strategy by assembling the DC-targeting mannose and immune adjuvant CpG-ODN on the surface of liposomes, which were loaded with melanoma-specific TRP2180-188 peptide as liposomal vaccine. M/CpG-ODN-TRP2-Lipo treatment was used to intendedly induce activation of DCs and antitumor- specific immune response in vivo.
RESULTS: Our results demonstrated in vitro that the prepared liposomal particles were efficiently taken up by DCs. This uptake led to an enhanced activation of DCs, as measured by the upregulation of MHC II, CD80, and CD86. Furthermore, M/CpG-ODN-TRP2-Lipo effectively inhibited the growth of implanted B16 melanoma and prolonged the survival of mice. This therapy significantly reduced the number of myeloid-derived suppressor cells (MDSCs) and regulatory T cells, while simultaneously increasing the number of activated T cells, tumor antigen-specific CD8+ cytotoxic T cells, and interferon-γ-producing cells. At the same time, it was found to suppress tumor angiogenesis and tumor cell proliferation, as well as up-regulate their apoptosis. Interestingly, MyD88-knockout mice had significantly shorter median survival times compared to wild-type mice following the administration of M/CpG-ODN-TRP2-Lipo.
CONCLUSIONS: The results suggested that the antitumor activities of the vaccine partially rely on the Myd88 signaling pathway. Interestingly, compared to whole tumor cell lysate-based vaccine, M/CpG-ODN-TRP2-Lipo, tumor specific antigen peptide-based vaccine, improved survival of tumor-bearing mice as well as enhanced their antitumor responses. All in all, we describe a novel vaccine formulation, M/CpG-ODN-TRP2-Lipo, with the aim of improving antitumor responses by alleviating the immunosuppressive environment in tumors.

PMID: 29556352 [PubMed - in process]

https://ift.tt/2HPMnOc

Recognition of microbial viability via TLR8 drives TFH cell differentiation and vaccine responses.

Recognition of microbial viability via TLR8 drives TFH cell differentiation and vaccine responses.

Nat Immunol. 2018 Apr;19(4):386-396

Authors: Ugolini M, Gerhard J, Burkert S, Jensen KJ, Georg P, Ebner F, Volkers SM, Thada S, Dietert K, Bauer L, Schäfer A, Helbig ET, Opitz B, Kurth F, Sur S, Dittrich N, Gaddam S, Conrad ML, Benn CS, Blohm U, Gruber AD, Hutloff A, Hartmann S, Boekschoten MV, Müller M, Jungersen G, Schumann RR, Suttorp N, Sander LE

Abstract
Live attenuated vaccines are generally highly efficacious and often superior to inactivated vaccines, yet the underlying mechanisms of this remain largely unclear. Here we identify recognition of microbial viability as a potent stimulus for follicular helper T cell (TFH cell) differentiation and vaccine responses. Antigen-presenting cells (APCs) distinguished viable bacteria from dead bacteria through Toll-like receptor 8 (TLR8)-dependent detection of bacterial RNA. In contrast to dead bacteria and other TLR ligands, live bacteria, bacterial RNA and synthetic TLR8 agonists induced a specific cytokine profile in human and porcine APCs, thereby promoting TFH cell differentiation. In domestic pigs, immunization with a live bacterial vaccine induced robust TFH cell and antibody responses, but immunization with its heat-killed counterpart did not. Finally, a hypermorphic TLR8 polymorphism was associated with protective immunity elicited by vaccination with bacillus Calmette-Guérin (BCG) in a human cohort. We have thus identified TLR8 as an important driver of TFH cell differentiation and a promising target for TFH cell-skewing vaccine adjuvants.

PMID: 29556002 [PubMed - in process]

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Texas Hill Country ENT Symposium Scheduled for April 2018

Mark your calendars for the McGovern Medical School Department of Otorhinolaryngology-Head and Neck Surgery's two-day CME meeting in the Texas... Read the full article...

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Branchial Cleft Cyst Resection: A Pediatric Patient Benefits from Texas Medical Center Expertise and the Convenience of Follow-up ENT Care in Southeast Houston

When J. Caleb Simmons, MD, started medical school, he thought he might be a pediatrician. Today as an otolaryngologist, nearly... Read the full article...

https://ift.tt/2pCONIu

Dr. Michael Byrd Named 2017 Physician of the Year at Memorial Hermann Southeast Hospital

Otolaryngologist Michael Byrd, MD, has been recognized as 2017 Physician of the Year at Memorial Hermann Southeast Hospital, a 274-bed... Read the full article...

https://ift.tt/2pCiWZs

2017 Lone Star Rhinology Course Recap

More than 80 physicians participated in Lone Star Rhinology 2017, an intensive two-day CME program dedicated to the study of... Read the full article...

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Future directions in pharmacogenomics discovery in cardiovascular disease

Pharmacogenomics, Ahead of Print.

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Clinical Implant Dentistry and Related Research, Ahead of Print.

Clinical Implant Dentistry and Related Research, Ahead of Print.

https://ift.tt/2pD3Um2

Modulating ion channel function with antibodies and nanobodies

Catelijne Stortelers | Carolina Pinto-Espinoza | Diane Van Hoorick | Friedrich Koch-Nolte

https://ift.tt/2IQ5gSH

Diffuse Gastric Ganglioneuromatosis: Novel Presentation of PTEN Hamartoma Syndrome—Case Report and Review of Gastric Ganglioneuromatous Proliferations and a Novel PTEN Gene Mutation

Gastrointestinal ganglioneuromatous proliferations are rare, most often found in the colon, and are three types: polypoid ganglioneuromas, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. We present a case of diffuse ganglioneuromatosis in the posterior gastric wall in a nine-year-old female. To our knowledge, this is the first reported case of diffuse ganglioneuromatosis located in the stomach. Only six cases of gastric ganglioneuromatous proliferations have previously been reported, two in English and none were diffuse ganglioneuromatosis. A diagnosis of diffuse ganglioneuromatosis is relevant for patient care because, unlike sporadic polypoid ganglioneuromas or ganglioneuromatous polyposis, most are syndromic. Diffuse ganglioneuromatosis is commonly associated with neurofibromatosis type 1, multiple endocrine neoplasia type 2b, and Cowden Syndrome, one of the phenotypes of PTEN hamartoma tumor syndrome. The patient had the noted gastric diffuse ganglioneuromatosis, as well as other major and minor criteria for Cowden syndrome. Genetic testing revealed a novel frameshift mutation in the PTEN gene in the patient, her father, paternal aunt, and the aunt's son who is a paternal first cousin of the patient.

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Effect of Cathodal Transcranial Direct Current Stimulation on a Child with Involuntary Movement after Hypoxic Encephalopathy

The aim of the study was to investigate the effect of cathodal transcranial direct current stimulation to the supplementary motor area to inhibit involuntary movements of a child. An 8-year-old boy who developed hypoxic encephalopathy after asphyxia at the age of 2 had difficulty in remaining standing without support because of involuntary movements. He was instructed to remain standing with his plastic ankle-foot orthosis for 10 s at three time points by leaning forward with his forearms on a desk. He received cathodal or sham transcranial direct current stimulation to the supplementary motor area at 1 mA for 10 min. Involuntary movements during standing were measured using an accelerometer attached to his forehead. The low-frequency power of involuntary movements during cathodal transcranial direct current stimulation significantly decreased compared with that during sham stimulation. No adverse effects were observed. Involuntary movement reduction by cathodal stimulation to supplementary motor areas suggests that stimulations modulated the corticobasal ganglia motor circuit. Cathodal stimulation to supplementary motor areas may be effective for reducing involuntary movements and may be safely applied to children with movement disorders.

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Evaluation of the nephroprotective effect of Glycyrrhiza glabra L aqueous extract on CCl 4 -induced nephrotoxicity in mice

Abstract

In this study, Glycyrrhiza glabra L (GG) aqueous extract was extracted to evaluate its nephroprotective effect on renal structural, hematological, and biochemical changes in CCl₄-induced nephrotoxicity in male mice. Fifty male mice were divided into five groups (n = 10); group I served as control, received 1 mL/kg olive oil intraperitoneally and 0.5 mL distilled water through gavage. Group II served as untreated group, received 1 mg/kg CCl₄ mixed with olive oil in the ratio of 1:1 intraperitoneally and 0.5 mL distilled water orally. Groups III, IV, V, and VI received CCl₄ mixed with olive oil in the ratio of 1:1 intraperitoneally and 30, 90, and 270 mg/kg of GG through gavage for 45 consecutive days. At 45th day, the mice were dissected; blood and kidney samples collected for hematological, biochemical, and histological parameter analysis. The data of this study were analyzed by the SPSS-18 software using one-way analysis of variance (ANOVA) followed by Duncan's post hoc test (p ≤ 0.05). Different doses of GG (especially GG270) could significantly (p ≤ 0.05) reduce the raised levels of urea, creatinine, WBC, and platelet and increased SOD, CAT, and RBC levels as compared to the untreated group. The weight and volume of the renal structures were decreased significantly (p ≤ 0.05) in several doses of GG as compared to the untreated group. In conclusion, GG has nephroprotective effect, thereby reducing the causation of toxicity in experimental mice.

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Effects of bilateral whole vessel ovarian ligation on dogs’ ovarian function and histopathology

Abstract

The most significant postoperative complication of spaying is bleeding from ovarian pedicles. In this study, all of the ovarian vessels were bilaterally ligated; then, ovaries were stimulated by gonadotropins. In a clinical trial and sequential control experiment, five healthy mixed-breed mature female dogs were randomly selected and kept under the new situation for 3 weeks. All ovarian vessels of the dogs were double ligated, bilaterally. For 13 weeks, blood samples, vaginal cytology, and ultrasound examinations continued weekly. All dogs received eCG (200 IU/dog, IM, 5 days) and hCG (500 IU/case IM, 5th day) 1 month after ovarian ligation. After 4 weeks, all dogs were ovariohysterectomized, and ovarian specimens were submitted for histopathological evaluations. Estradiol 17β and progesterone were assayed with ELISA kits. Estradiol concentration decreased after ligation and continued to decrease to the end of study (during 10 weeks). Estradiol concentrations were different before ligation and after hormone stimulation and ovariohysterectomy (P < 0.01). Progesterone concentration decreased suddenly after ligation and had a plateau during the study. Progesterone concentrations were different before ligation period and after ligation and hormone stimulation periods (P < 0.03). An ultrasonographical evaluation showed normal ovarian structures before ligation and ovarian adhesions to bursa and ovarian hyperechogenicity without the presence of active structures. Bleeding, congestion, primordial and primary follicle necrosis, and some degree of fibrosis were observed in the histopathological evaluations. Bilateral whole vessel ovarian ligation could inactivate dogs' ovarian function during 8 weeks. So, we suggest ligation of whole vessels of dogs' ovaries as an alternative method for ovariectomy.

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274 Impact of Tolvaptan on Costs Associated with Renal Pain and Chronic Kidney Disease Among Patients with Autosomal Dominant Polycystic Kidney Disease

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207 FGF-23 and Cardiovascular Risk Factors in Patients with Chronic Kidney Disease: An Indian Perspective

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290 ANCA-Associated Small-Vessel Vasculitis Presenting with Bilateral Leg Pain

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226 A Mobile Application to Evaluate Patient Preference for Nsaid Avoidance Education Media

https://ift.tt/2DQQcR1

258 Urea in the Treatment of Hyponatremia: The First Reported Us Inpatient Experience

https://ift.tt/2G4rHpq

306 CKD Awareness Varies in a Population Based Community Cohort by Question Asked

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67 Hypophosphatemia Following IV Iron - Impact of Varying Renal Function

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210 Hepatorenal Syndrome Redefined Using Inferior Vena Cava Ultrasound to Assess Relative Intravascular Volume

https://ift.tt/2G1w04I

298 X-Linked Alport Syndrome is Not a Disease Exclusive to Males

https://ift.tt/2DRmRWv

282 Extended-Release Calcifediol (ERC) Improves Bone Marker Levels in CKD Patients with Diabetes

https://ift.tt/2G3kuWD

266 C5aR Inhibitor Avacopan in Anti-Neutrophil Cytoplasmic Autoantibody (ANCA) Vasculitis: Phase II Outcomes of Safety, Renal Parameters, and Quality of Life

https://ift.tt/2DVI4yI

250 Delayed Graft Function in Renal Transplantation

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234 Too Much Fiber: A Rare Case of Collagenofibrotic Glomerulopathy

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218 The Role of Self-Efficacy and Coping in ESRD Self-Management Behaviors

https://ift.tt/2G1AJ6q

310 Association of Dermatologic Complaints with Well Being and Lack of Dermatology Referral in Patients with CKD

https://ift.tt/2G6YTZ3

302 Atypical Hemolytic Uremic Syndrome in A Kidney Transplant Recipient Successfully Treated with Eculizumab

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294 Mycophenolate Mofetil Induction Therapy for Crescentic Lupus Nephritis Class IV-G: A Promising Outcome

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286 Severe Symptomatic Hypocalcemia Following Denosumab Administration

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278 Accidental Discovery of Renal Cell Carcinoma with Renal Biopsy in a Patient Presenting with Nephrotic Syndrome: When Luck Saves Lives

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270 Review of Blood Stream Infections Across a Large Academic Dialysis Program

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Adjunct Targeted Biologic Inhibition Agents to Treat Aggressive Multivessel Intraluminal Pediatric Pulmonary Vein Stenosis

To evaluate the use of imatinib mesylate with or without bevacizumab targeting neoproliferative myofibroblast-like cells with tyrosine kinase receptor expression, as adjuncts to modern interventional therapies for the treatment of multivessel intraluminal pulmonary vein stenosis (PVS). We describe the 48- and 72-week outcomes among patients receiving imatinib mesylate with or without bevacizumab for multivessel intraluminal PVS.

https://ift.tt/2DSpaIK

Accuracy of Pulse Oximetry Screening for Critical Congenital Heart Defects after Home Birth and Early Postnatal Discharge

To assess the accuracy of pulse oximetry screening for critical congenital heart defects (CCHDs) in a setting with home births and early discharge after hospital deliveries, by using an adapted protocol fitting the work patterns of community midwives.

https://ift.tt/2Gbhfbm

Attention Deficit Hyperactivity Disorder in Childhood: Healthcare Use in a Danish Birth Cohort during the First 12 Years of Life

To compare the mean number of medical and psychiatric hospital-based services in children with and without attention deficit hyperactivity disorder (ADHD) and to assess the effect of ADHD on hospital-based service use, including child-, parental-, and socioeconomic-related risk factors.

https://ift.tt/2IRi0YS

Prevalence of Nail Scabies: A French Prospective Multicenter Study

To assess the prevalence of nail involvement in children <16 years old with a confirmed diagnosis of scabies.

https://ift.tt/2IM2gXg

Varicocele with an Abdominal Mass

A 4-year-old boy presented with a painless, progressively enlarging abdominal lump associated with hematuria for a month. On examination, there was abdominal fullness with an ill-defined mass measuring 12 × 15 cm, extending from left lumbar to umbilical area. The mass was separate from the liver and did not arise from the pelvis (Figure 1). A left scrotal sac varicocele was noted (Figure 2).

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Are Corticosteroids Superior to Nonsteroidal Anti-inflammatory Drugs in the Treatment of Acute Gout?

The search identified 529 references; 6 trials evaluating 817 patients met inclusion criteria. The overall risk of bias was low in these trials, whereas the quality of the evidence was rated as low to moderate according to GRADE criteria. The meta-analysis demonstrated no difference between corticosteroids and nonsteroidal anti-inflammatory drugs for the following outcomes: short-term pain relief (<7 days), long-term pain relief (>7 days), time to resolution of pain, and requirement for additional analgesics (Table 1).

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Femoral arterial and central venous catheters in the trauma resuscitation room

Publication date: Available online 23 March 2018
Source:Injury
Author(s): S.R. Hamada, M. Fromentin, M. Ronot, T. Gauss, A. Harrois, J. Duranteau, C. Paugam-Burtz
BackgroundArterial and central venous femoral catheters (fAC-CVC) use during the initial management of severe trauma patients is not a standard technique in most trauma centers. Arguments in favor of their use are: continuous monitoring of blood pressure, safe drug administration, easy blood sampling and potentially large bore venous access. The lack of evidence makes the practice heterogeneous. The aim of the present study was to describe the use and complications of fAC-CVC in the trauma bay in two centers where they are routinely used.MethodsThis was a retrospective analysis of routine fAC-CVC use from two French trauma centers. All patients admitted directly to the trauma resuscitation room were included. Demographic, clinical and biological data were collected from the scene to discharge to describe the use of catheters during initial trauma management including infectious, mechanical and thrombotic complications.Results243 pairs of femoral catheters were inserted among 692 patients admitted in both trauma centers. Femoral AC-CVC use was more frequent in critically ill patients with higher ISS 26 [17; 41] vs 13 [8; 24], p < 0.001(median [quartile 1–3]), severe traumatic brain injury (AIS head 1[0–4] vs 0[0–3], p < 0.001), lower systolic blood pressure, 92 (37) vs 113 (28) mmHg, p < 0.001 mean (standard deviation), lower haemoglobin on arrival, 10.9 (3) vs 13.3 (2.1) g/dL (p < 0.001), and higher blood lactate concentration, 4.0 (3.9) vs 2.1 (1.8) mmol/L (p < 0.001). In patients with fAC-CVC use time in the trauma room was longer, 46 [40;60] vs 30 [20;40] minutes (p < 0.05). In total 52 colonizations and 3 bloodstream infections were noted in 1000 catheter days. An incidence of 12% of mechanical complications and of 42% deep venous thromboses were observed. Of the latter none was associated with confirmed pulmonary embolism.ConclusionFemoral AC-CVC appeared to be deployed more often in critically ill patients, presenting with shock and/or traumatic brain injury in particular. The observed rate of complications in this sample seems to be low compared to reported rates.

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European evidence-based guidelines on pancreatic cystic neoplasms

Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring <40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter ≥40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule >5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.

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Assessing the ProMCol classifier as a prognostic marker for non-metastatic colorectal cancer within the Melbourne Collaborative Cohort Study

We read with interest the work by Gündert and colleagues, which describes a new prognostic classifier for non-metastatic colorectal cancer (CRC), ProMCol, derived from DNA methylation levels at 20 CpG sites in colorectal tumour tissue.1 Here, we tested the ProMCol classifier on an independent cohort of 526 non-metastatic CRC tumours from the Melbourne Collaborative Cohort Study (MCCS). The MCCS is a prospective cohort study of 41 513 healthy adult volunteers recruited between 1990 and 1994.2 By 31 December 2009, 1046 participants had a first histopathological diagnosis of invasive adenocarcinoma of the colon or rectum identified through the Victorian Cancer Registry (VCR) following the baseline study visit (a total of 1101 CRCs). Characterisation of this CRC-affected cohort is described in Buchanan et al.3 Vital status was ascertained through the VCR and the National Death Index.

From all 1046 participants with a CRC diagnosis, we excluded 26 tumours...

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From Molecules to Materials: Engineering New Ionic Liquid Crystals Through Halogen Bonding

A protocol for the synthesis of a new type of mesogens, based on the halogen-bonded supramolecular anion [CnF2n+1-I···I···I-CnF2n+1]−, is reported.

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CA: A Cancer Journal for Clinicians, Ahead of Print.

CA: A Cancer Journal for Clinicians, Ahead of Print.

https://ift.tt/2IKrCVn

Correction to: Coordination of muscles to control the footpath during over-ground walking in neurologically intact individuals and stroke survivors

Abstract

In the original publication of the article, the corrections for the typographical errors in the equations for variance that affects the footpath (V_ORT) and the total variance (V_TOT) should be as following:

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Optimization of treatment planning workflow and tumor coverage during daily adaptive magnetic resonance image guided radiation therapy (MR-IGRT) of pancreatic cancer

Abstract

Background

To simplify the adaptive treatment planning workflow while achieving the optimal tumor-dose coverage in pancreatic cancer patients undergoing daily adaptive magnetic resonance image guided radiation therapy (MR-IGRT).

Methods

In daily adaptive MR-IGRT, the plan objective function constructed during simulation is used for plan re-optimization throughout the course of treatment. In this study, we have constructed the initial objective functions using two methods for 16 pancreatic cancer patients treated with the ViewRay™ MR-IGRT system: 1) the conventional method that handles the stomach, duodenum, small bowel, and large bowel as separate organs at risk (OARs) and 2) the OAR grouping method. Using OAR grouping, a combined OAR structure that encompasses the portions of these four primary OARs within 3 cm of the planning target volume (PTV) is created. OAR grouping simulation plans were optimized such that the target coverage was comparable to the clinical simulation plan constructed in the conventional manner. In both cases, the initial objective function was then applied to each successive treatment fraction and the plan was re-optimized based on the patient's daily anatomy. OAR grouping plans were compared to conventional plans at each fraction in terms of coverage of the PTV and the optimized PTV (PTV OPT), which is the result of the subtraction of overlapping OAR volumes with an additional margin from the PTV.

Results

Plan performance was enhanced across a majority of fractions using OAR grouping. The percentage of the volume of the PTV covered by 95% of the prescribed dose (D₉₅) was improved by an average of 3.87 ± 4.29% while D₉₅ coverage of the PTV OPT increased by 3.98 ± 4.97%. Finally, D₁₀₀ coverage of the PTV demonstrated an average increase of 6.47 ± 7.16% and a maximum improvement of 20.19%.

Conclusions

In this study, our proposed OAR grouping plans generally outperformed conventional plans, especially when the conventional simulation plan favored or disregarded an OAR through the assignment of distinct weighting parameters relative to the other critical structures. OAR grouping simplifies the MR-IGRT adaptive treatment planning workflow at simulation while demonstrating improved coverage compared to delivered pancreatic cancer treatment plans in daily adaptive radiation therapy.

https://ift.tt/2ucfWaY

Altruistic decisions following penetrating traumatic brain injury

Abstract

The cerebral correlates of altruistic decisions have increasingly attracted the interest of neuroscientists. To date, investigations on the neural underpinnings of altruistic decisions have primarily been conducted in healthy adults undergoing functional neuroimaging as they engaged in decisions to punish third parties. The chief purpose of the present study was to investigate altruistic decisions following focal brain damage with a novel altruistic decision task. In contrast to studies that have focused either on altruistic punishment or donation, the Altruistic Decision Task allows players to anonymously punish or donate to 30 charitable organizations involved with salient societal issues such as abortion, nuclear energy and civil rights. Ninety-four Vietnam War veterans with variable patterns of penetrating traumatic brain injury and 28 healthy veterans who also served in combat participated in the study as normal controls. Participants were asked to invest $1 to punish or reward real societal organizations, or keep the money for themselves. Associations between lesion distribution and performance on the task were analysed with multivariate support vector regression, which enables the assessment of the joint contribution of multiple regions in the determination of a given behaviour of interest. Our main findings were: (i) bilateral dorsomedial prefrontal lesions increased altruistic punishment, whereas lesions of the right perisylvian region and left temporo-insular cortex decreased punishment; (ii) altruistic donations were increased by bilateral lesions of the dorsomedial parietal cortex, whereas lesions of the right posterior superior temporal sulcus and middle temporal gyri decreased donations; (iii) altruistic punishment and donation were only weakly correlated, emphasizing their dissociable neuroanatomical associations; and (iv) altruistic decisions were not related to post-traumatic personality changes. These findings indicate that altruistic punishment and donation are determined by largely non-overlapping cerebral regions, which have previously been implicated in social cognition and moral experience such as evaluations of intentionality and intuitions of justice and morality.

https://ift.tt/2G67aMY

High serum levels of caspase-cleaved cytokeratin-18 are associated with malignant middle cerebral artery infarction patient mortality

There have been found apoptotic changes in brain tissue samples from humans after cerebral ischemia. Caspase-cleaved cytokeratin (CCCK)-18 could appears in blood during apoptosis. High circulating levels of CC...

https://ift.tt/2Gn1mSU

Phase I study of combined indomethacin and platinum-based chemotherapy to reduce platinum-induced fatty acids

Abstract

Purpose

Chemotherapy-resistance remains a major obstacle to effective anti-cancer treatment. We previously showed that platinum analogs cause the release of two fatty acids. These platinum-induced fatty acids (PIFAs) induced complete chemoresistance in mice, whereas co-administration of a COX-1 inhibitor, indomethacin, prevented PIFA release and significantly enhanced chemosensitivity. To assess the safety of combining indomethacin with platinum-based chemotherapy, and to explore its efficacy and associated PIFA levels, a multi-center phase I trial was conducted.

Methods

The study was comprised of two arms: oxaliplatin plus capecitabine (CAPOX, arm I) and cisplatin plus gemcitabine, capecitabine or 5FU (arm II) in patients for whom these regimens were indicated as standard care. Indomethacin was escalated from 25 to 75 mg TID, using a standard 3 × 3 design per arm, and was administered orally 8 days around chemo-infusion from cycle two onwards. PIFA levels were measured before and after treatment initiation, with and without indomethacin.

Results

Thirteen patients were enrolled, of which ten were evaluable for safety analyses. In arm I, no dose-limiting toxicities were observed, and all indomethacin dose levels were well-tolerated. Partial responses were observed in three patients (30%). Indomethacin lowered plasma levels of 12-S-hydroxy-5,8,10-heptadecatrienoic acid (12-S-HHT), whereas 4,7,10,13-hexadecatetraenoic acid (16:4(n-3)) levels were not affected. Only one patient was included in arm II; renal toxicity led to closure of this cohort.

Conclusions

Combined indomethacin and CAPOX treatment is safe and reduces the concentrations of 12-S-HHT, which may be associated with improved chemosensitivity. The recommended phase II dose is 75 mg indomethacin TID given 8 days surrounding standard dosed CAPOX.

https://ift.tt/2pDjSfg

Woman recalls trying to save life of stranger hit by truck

Former corrections officer Faith Appelgren and a trauma nurse performed CPR on the victim in the middle of the road while responders were stuck in traffic

https://ift.tt/2I14zER

Comparisons of tumor-infiltrating lymphocyte levels and the 21-gene recurrence score in ER-positive/HER2-negative breast cancer

Abstract

Background

Recent studies have shown that tumors with extensive tumor-infiltrating lymphocytes (TILs) have a higher probability of pathologic complete response, even in luminal/human epidermal growth factor 2 (HER2)-negative breast cancer. We compared TIL levels and the 21-gene recurrence score (RS) in estrogen receptor (ER)-positive/HER2-negative breast cancer.

Methods

We evaluated the percentage of stromal TILs in 198 ER-positive/HER2-negative patients in whom RS was obtained by examining slides of surgical specimens by standardized methodology proposed by the international TIL Working Group. TIL levels were categorized as high (≥ 60%), intermediate (11–59%), or low (≤ 10%). All tumors were treatment-naïve.

Results

Ninety-seven (49.0%), 88 (44.4%), and 13 patients (6.6%) had low, intermediate, and high TIL levels, respectively. There was a significant but weak correlation between continuous RS and continuous TIL levels (Pearson's R = 0.201, p = 0.004). The mean RS was significantly highest in high TIL tumors (17.8 ± 10.7 in low TIL tumors, 19.4 ± 8.7 in intermediate TIL tumors, and 26.2 ± 8.2 in high TIL tumors; p = 0.014). However, when we compared categorized RS and TIL levels, we found that tumors with high TIL levels tended to have higher RS (≥ 26) but it was not significant (p = 0.155). Furthermore, multivariate analysis revealed that high RS was not an independent factor associated with high TIL levels. Chemo-endocrine therapy was more frequently performed among patients with high TILs and less frequently among those with low or intermediate TILs (p < 0.001).

Conclusions

Despite of a weak correlation between continuous TIL levels and RS, we found that tumors with high TIL levels tended to have a higher RS in ER-positive/HER2-negative breast cancer. Further study is warranted considering the clinical outcomes.

https://ift.tt/2GapiFm

Headache and Its Management in Patients With Multiple Sclerosis

Abstract

Purpose of review

The purpose of this review was to discuss the prevalence, impact, pathophysiology, and treatment of headaches (H/As) in patients with multiple sclerosis (MS).

Recent findings

Headaches and multiple sclerosis are more common in women than in men with the ratio of female to male being 3:1. It is not entirely clear if there is a correlation or an incidental comorbidity of two neurological conditions. A review of the literature shows a variable prevalence of H/As in MS patients. Using the International Classification of Headache Disorders (ICHD) criteria, the primary type of H/As, especially migraine, is the most common type seen in patients with MS. One of the theories of the pathophysiologic mechanisms of migraine in MS patients is inflammation leading to demyelinating lesions in the pain-producing centers in the midbrain. Secondary H/As due to MS medications such as interferons are also frequently present.

Summary

H/As can be a cause for significant comorbidity in patients with MS. The treatment of H/As in patients with MS should be addressed in the same fashion as in the non-MS population, which is a combination of pharmacological and non-pharmacological methods. Preventive medicines for the H/As should be carefully selected because of their side effect profiles. Acute attacks of migraines can be treated with medications such as triptans. Patients with MS who have migraine H/As should be educated about the phenomenon of overuse H/As, keeping headache journals, avoiding stress, and monitoring sleeping habits. The presence of depression in patients with MS and migraine affects quality of life (QOL) and should also be addressed for better outcomes.

https://ift.tt/2G4rOxa

Capillary cerebral amyloid angiopathy in Alzheimer’s disease: association with allocortical/hippocampal microinfarcts and cognitive decline

Abstract

Cerebral amyloid angiopathy (CAA) is caused by the deposition of the amyloid β-protein (Aβ) in the wall of cerebral and leptomeningeal blood vessels and is related to Alzheimer's disease (AD). Capillary Aβ deposition is observed in a subset of CAA cases and represents a distinct type of CAA named capillary CAA or CAA type 1. This type of CAA is strongly associated with the presence of the apolipoprotein E ε4 allele. CAA type 1-associated AD cases often exhibit a more severe Aβ plaque pathology but less widespread neurofibrillary tangle (NFT) pathology. The objective of this study was to analyze whether capillary CAA and its effects on cerebral blood flow have an impact on dementia. To address this objective, we performed neuropathological evaluation of 284 autopsy cases of demented and non-demented individuals. We assessed the presence of CAA and its subtypes as well as for that of hemorrhages and infarcts. Capillary CAA and CAA severity were associated with allocortical microinfarcts, comprising the CA1 region of the hippocampus. Allocortical microinfarcts, capillary CAA and CAA severity were, thereby, associated with cognitive decline. In conclusion, allocortical microinfarcts, CAA severity, and the capillary type of CAA were associated with one another and with the development of cognitive decline. Thus, AD cases with CAA type 1 (capillary CAA) appear to develop dementia symptoms not only due to AD-related Aβ plaque and NFT pathology but also due to hippocampal microinfarcts that are associated with CAA type 1 and CAA severity, and that damage a brain region important for memory function.

https://ift.tt/2ugnsRR

Special Issue on Anaerobic Biological Dehalogenation

https://ift.tt/2pDCBam

Anaerobic Phototrophic Processes of Hydrogen Production by Differents Strains of Microalgae Chlamydomonas sp.

Abstract

Hydrogen is an abundant element and a non-polluting fuel which can be biologically produced by microalgae. The aim of this research was to investigate biological hydrogen production by Chlamydomonas reinhardtii (CC425) and Chlamydomonas moewusii (SAG 24.91) by direct biophotolysis in batch cultures. Strains were cultivated in TAP growth medium (pH 7.2) in two phases: in the first stage, cultures were maintained in an aerobic condition until the middle of the exponential phase; in the second stage, the biomass was transferred to closed anaerobic photobioreactors under sulfur deprived. Gas chromatography and Gompertz model were used to measure the hydrogen production and hydrogen production rate, respectively. We noticed that maximum hydrogen production by biomass of C. reinhardtii was 5.95 ± 0.88 μmol mg⁻¹ and the productivity was 17.02 ± 3.83 μmol L⁻¹ h⁻¹, with hydrogen production five times higher than C. moewusii, approximately, though, C. moewusii obtained a higher ethanol yield compared to C. reinhardtii. The hydrogen production method, with the cultivation of strains in two different phases and sulfur deprivation, was effective for obtaining of biohydrogen for Chlamydomonas, however it depends on the species, strain and growth conditions.

https://ift.tt/2Gn7iuX

Transcriptional and Post-translational Regulation of AccD6 in Mycobacterium smegmatis

Abstract

AccD6 is an important component of acetyl-CoA/propionyl-CoA carboxylase, which acts as a key role in mycolic acid synthesis and short chain fatty acyl-coenzyme A metabolism. In this study, we demonstrated that AccD6 of Mycobacterium smegmatis associates with AccA3 (α subunit of acetyl-CoA carboxylase, MSMEG_1807) and AccE (ε subunit, MSMEG_1812) to form the acetyl-CoA (propionyl-CoA) carboxylase. Results showed that the MSMEG_4331 subunit is a regulator that interacts with the promoter region of accD6 to inhibit its transcription. Transcription of accD6 was reduced by 50% in the mutant M. smegmatis strain overexpressing MSMEG_4331. Moreover, the activity of AccD6 was inhibited by acylation (such as acetylation and propionylation). These results demonstrate that AccD6 of M. smegmatis is regulated at both the transcriptional and post-translational levels. Our findings highlight the novel regulatory mechanism underlying mycolic acid biosynthesis in mycobacteria.

https://ift.tt/2DQRhYT

Quantitative Imaging and Spectroscopic Technologies for Microbiology

Abstract

Light microscopy has enabled the observation of the structure and organization of biofilms. Typically, the contrast in an image obtained from light microscopy is given by the time-averaged intensity that is effective in visualizing the overall structure. Technological advancements in light microscopy have led to the creation of techniques that not only provide a static intensity image of the biofilm, but also enable one to quantify various dynamic physicochemical properties of biomolecules in microbial biofilms. Such light microscopy based techniques can be grouped into two main classes, those that are based on luminescence and those that are based on scattering. Here we review the fundamentals and applications of luminescence and scattering based techniques, specifically, Fluorescence Lifetime Imaging (FLIM), Förster Resonance Energy Transfer (FRET), Fluorescence Correlation Spectroscopy (FCS), Fluorescence Recovery after Photobleaching (FRAP), Single Particle Tracking (SPT), Transient State Imaging (TRAST), Brillouin and Raman microscopy. These techniques provide information about the abundance, interactions and mobility of various molecules in the biofilms and also properties of the local microenvironment at optical resolution. Further, one could use any of these techniques to probe the real-time changes in these physical parameters upon the addition of external agents or at different stages during the growth of biofilms.

https://ift.tt/2GmNurO

D-dimer predicts postoperative recurrence and prognosis in patients with liver metastasis of colorectal cancer

Abstract

Background

Colorectal cancer is common, and its incidence is increasing throughout the world. The liver is a major metastatic site, and colorectal liver metastasis (CRLM) has a poor prognosis. Although liver resection is the most effective therapy for CRLM, postoperative recurrence is common. Thus, prognostic markers for CRLM are greatly needed. D-dimer, a fibrin cleavage product, has been shown to be related to colorectal tumor progression, and is also associated with malignant progression and recurrence in various cancers. Therefore, we evaluated the value of D-dimer in predicting the prognosis in CRLM.

Methods

We retrospectively evaluated 90 cases of resected CRLM to determine the correlation between D-dimer and patient survival. The cut-off value for D-dimer levels was determined using receiver operating characteristic curve analysis.

Results

Significant differences occurred in the recurrence group with higher D-dimer levels (P = 0.00736*), while the optimal cut-off value was 0.6 µg/mL. High D-dimer levels (≥ 0.6 µg/mL) were associated with poor recurrence-free survival (RFS; P = 0.0000841*) and cancer-specific survival (CSS; P = 0.00615*). In the multivariate analysis, D-dimer correlated with CRLM prognosis and independently predicted RFS (P = 0.0179*).

Conclusion

High D-dimer levels were associated with poor RFS and CSS. D-dimer was an independent prognostic factor of RFS. Therefore, D-dimer may help predict recurrence and prognosis in patients with CRLM.

https://ift.tt/2ufsNJo

What foods can I eat after wisdom tooth extraction?

People are advised to eat soft or liquid foods after having a wisdom tooth removed. Learn about the best foods to eat after having this type of surgey, including soups, smoothies, and mashed vegetables. We also look at foods to avoid, other recovery self-care tips, and possible complications, such as dry socket.

https://ift.tt/2HXAeHe

Best Protocol for Combined Contrast-Enhanced Thoracic and Abdominal CT for Lung Cancer: A Single-Institution Randomized Crossover Clinical Trial

American Journal of Roentgenology, Ahead of Print.

https://ift.tt/2I2Vtr3

Comparison of DWI Methods in the Pediatric Brain: PROPELLER Turbo Spin-Echo Imaging Versus Readout-Segmented Echo-Planar Imaging Versus Single-Shot Echo-Planar Imaging

American Journal of Roentgenology, Ahead of Print.

https://ift.tt/2INCC4v

Shear Wave Elastography as a Quantitative Biomarker of Clinically Significant Portal Hypertension: A Systematic Review and Meta-Analysis

American Journal of Roentgenology, Ahead of Print.

https://ift.tt/2DRbjlT

Improving the Quality of MRI Reports of Preoperative Patients With Rectal Cancer: Effect of National Guidelines and Structured Reporting

American Journal of Roentgenology, Ahead of Print.

https://ift.tt/2GoyedE

Initial Experience of Tomosynthesis-Guided Vacuum-Assisted Biopsies of Tomosynthesis-Detected (2D Mammography and Ultrasound Occult) Architectural Distortions

American Journal of Roentgenology, Ahead of Print.

https://ift.tt/2GnfriU

Αρχειοθήκη ιστολογίου

Αναζήτηση αυτού του ιστολογίου

Σάββατο 24 Μαρτίου 2018

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