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Τετάρτη 13 Φεβρουαρίου 2019

Advanced Pharmaceutical Technology & Research

Nanomedicine in prosthetic dentistry
Upendra Nagaich

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):1-1



Quercetin prevent proteoglycan destruction by inhibits matrix metalloproteinase-9, matrix metalloproteinase-13, a disintegrin and metalloproteinase with thrombospondin motifs-5 expressions on osteoarthritis model rats
Dian Agustina Permatasari, Deantari Karliana, Iskandarsyah Iskandarsyah, Ade Arsianti, Anton Bahtiar

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):2-8

Prior study has shown that Ageratum conyzoides L. extract that containing quercetin has been proved to prevent inflammation and proteoglycan degradation by inhibiting tumor necrosis factor-alpha and matrix metalloproteinase (MMP-9) expression. Target of osteoarthritis (OA) treatment was in the synovial joint that requiring a drug delivery system. The aim of this study was to prove the efficacy of quercetin-loaded lecithin-chitosan nanoparticles on the OA model rats by observed its effect on interleukin (IL-1) β, MMP-9, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-5) expressions. In this study, 70 white male Sprague Dawley rats were divided into 14 groups, 7 groups each for destabilization of medial meniscus (DMM) and monoiodoacetate (MIA)-induced OA. After 28 days from induction, SHAM and negative group received gel base topically; positive group received sodium diclofenac gel; three-dose group received each 0.84, 1.68, 3.36 mg/g quercetin-loaded nanoparticles gel; and A. conyzoides L. group received A. conyzoides L. extract gel. Each group gets treatment until day 70, and then, blood sample was collected for serum analysis; knee joint was isolated and subjected to histology samples treatment. Quercetin-loaded nanoparticle gel dose 1 (0.84 mg/g gel), dose 2 (1.68 mg/g gel), dose 3 (3.36 mg/g), and A. conyzoides L. extract gel could decreased the level of IL-1 β, MMP-9, MMP-13, ADAMTS-5, and increasing color intensity significantly on histopathological observations on DMM and MIA-induced OA. 


High mannoronic acid containing alginate affects the differentiation of Wharton's jelly-derived stem cells to hepatocyte-like cell
Saeed Azandeh, Darioush Bijan Nejad, Vahid Bayati, Foroug Shakoor, Negar Varaa, Bahman Cheraghian

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):9-15

For transplantation of cell into injured tissues, cells should be transferred to the damaged site through an adequate carrier. Nevertheless, the nutrient-limited and hypoxic condition in the carrier can bring about broad cell death. This study set to assess the impact of alginate concentrations on the differentiation and the proliferation of cells encapsulated in alginate hydrogels. Human Wharton's Jelly-derived Mesenchymal Stem Cells (HWJ-MSCs) were encapsulated in two concentrations of alginate hydrogel. Then, the proliferation and the hepatic differentiation were evaluated with an MTT assay and the enzyme-linked immunosorbent assay software and urea production. The results demonstrated that the proliferation of cell and urea production in 1.5% alginate concentration was higher than in 2.5% alginate concentration in the hydrogels of alginate. We deduce that the optimized alginate hydrogel concentration is necessary for achieving comparable cell activities in three-dimensional culture. 


The effect of venous caffeine on the prevention of apnea of prematurity in the very preterm infants in the neonatal intensive care unit of Shahid Motahhari Hospital, Urmia, during a year
Zahra Fakoor, Ali Aghayar Makooie, Zahra Joudi, Rasool Gharaaghaji Asl

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):16-19

Due to the importance of prevention of apnea of prematurity in the very preterm infants and the side effects of using methylxanthines in preterm infants, the present study was conducted and aimed at investigating the effects of prophylactic caffeine on the incident of apnea (short-term consequence). This is a clinical–experimental trial, in which the infants were included after receiving written consent from their parents. The infants were randomly divided into two groups, namely, Group A (receive caffeine) and Group B (did not receive caffeine). After sampling of the collected data, the two groups were analyzed using statistical tests using SPSS software 23. Among the 50 infants in the caffeine group and 50 infants in the control group, 1 (2%) and 2 (4%) infants required long-term oxygen, respectively. Three (6%) infants from the caffeine group and 2 (4%) infants from the control group had an intraventricular hemorrhage. Two (4%) infants from the caffeine group and 1 (2%) infant from the control group had a positive patent ductus arteriosus and needed treatment. Among the 50 infants in the caffeine group and 50 infants in the control group, 7 (14%) and 9 (18%) infants had apnea, respectively. According to the Fisher's exact test, there was no significant difference between the incident of apnea in the two groups (P = 0.58). Ten (20%) infants from the caffeine group and 7 (14%) infants from the control group died. The prescription of prophylactic caffeine had no effect on the incident of apnea in the infants. Hence, the use of that should be limited to the preterm infants lower than 1250 g in the prophylactic form. 


Proniosomal gel-mediated topical delivery of fluconazole: Development, in vitro characterization, and microbiological evaluation
Amal Saber Mohammed Abu El-Enin, Maha Khalifa Ahmed Khalifa, Aya Mohammed Dawaba, Hamdy Mohammed Dawaba

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):20-26

The aim of this study was to explore the potential of proniosomal gel for topical delivery of fluconazole, an antifungal drug used in fungal infections caused by pathogenic fungi. Fluconazole-loaded proniosomal gels were prepared by the coacervation phase separation method using different nonionic surfactants (spans and tweens). The prepared fluconazole proniosomal gels were evaluated for various parameters such as particle size (PS), drug entrapment efficiency percentage (EE%), and in vitro drug release. The experimental results showed that the EE% for the prepared formulae are acceptable (85.14%–97.66%) and they are nanosized (19.8–50.1 nm) and the diffusion from the gels gave the desired sustaining effect. F4, which was prepared from span 60, tween 80 (1:1), and cholesterol showed highest EE% and gave slow release (40.50% ± 1.50% after 6 h), was subjected to zeta potential (ZP) test, transmission electron microscopy as well as microbiological study. The results showed a well-defined spherical vesicle with sharp boundaries with good physical stability of fluconazole within the prepared gel. Moreover, F4 showed an excellent microbiological activity represented by a greater zone of inhibition (5.3 cm) compared to control gel (fluconazole in 2% hydroxy propyl methyl cellulose (HPMC) gel formula) (4.2 cm) and plain gel with no drug (0 cm) against Candida albicans. This study showed the suitability of the proniosomal gel in attaining the desired sustainment effect for topical delivery of fluconazole for the management of fungal infection. The physical stability study showed that there was no significant change in EE%, PS, and ZP of fluconazole proniosomal gel after storage for 6 months. 


The potency of chitosan-Pinus merkusii extract nanoparticle as the antioxidant and anti-caspase 3 on lead acetate-induced nephrotoxicity in rat
Sri Agus Sudjarwo, Koerniasari Eraiko, Giftania Wardani Sudjarwo, Koerniasari 

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):27-32

The current study was carried out to evaluate the antioxidant and anti-caspase 3 activity of chitosan-Pinus merkusii nanoparticle in against lead acetate-induced nephrotoxicity in rats. chitosan-P. merkusii nanoparticle was characterized by dynamic light scattering (DLS) and scanning electron microscope (SEM). The male rats were divided into control group (rats were given with distilled water), lead acetate group (rats were injected with lead acetate 15 mg/kg BW i. p), and the treatment group (rats were given the chitosan-P. merkusii nanoparticle 150 mg, 300 mg, 600 mg/kg BW orally and were injected with lead acetate 15 mg/kg BW). The rats blood samples were measured levels of blood urea nitrogen (BUN) and creatinine. The kidney tissues were collected to evaluate the malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx). Histological to evaluate renal damage, and immunohistochemical to analyze the expression of caspase 3. The results showed that DLS showed the size of chitosan-P. merkusii nanoparticle was 165.9 ± 24.18 nm. SEM images of the chitosan-P. merkusii nanoparticles showed an irregular shape and its the rough surface. Administration of lead acetate resulted in a significant increase in levels of the BUN, creatinine, MDA level, caspase 3 expression, and a decrease in SOD and GPx were compared with the control group. Treatment with the chitosan-P. merkusii nanoparticle 600 mg/kg BW significantly decreased the elevated BUN, creatinine, MDA levels, caspase 3 expression and also increase in SOD and GPx as compared to lead acetate group. The lead acetate induced loss of the normal structure of renal cells and necrosis, whereas treated with chitosan-P. merkusii nanoparticle improved renal cell necrosis. This study indicates that chitosan-P. merkusii nanoparticles appeared to be a promising agent for protection against lead-induced nephrotoxicity through increasing antioxidant and inhibiting caspase 3 expression. 


Effects of rosuvastatin on metabolic profile: Versatility of dose-dependent effect
Hayder M Al-Kuraishy, Ali I Al-Gareeb

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):33-38

Obesity refers to an excess of body fat content causing metabolic and inflammatory disorders. Therefore, the aim of the present study was to investigate dose-dependent effect of rosuvastatin on the metabolic profile of diet-induced obesity in mice model study. A total number of 40 male Albino Swiss mice were used which divided into Group I: Control group, fed normal diet for 8 weeks (n = 10); Group II: High-fat diet (HFD) group, fed on HFD for 8 weeks (n = 10); Group III: HFD + 20 mg/kg rosuvastatin for 8 weeks (n = 10); and Group IV: HFD +40 mg/kg rosuvastatin for 8 weeks (n = 10). Anthropometric and biochemical parameters were estimated, including fasting blood glucose, lipid profile, fasting insulin, and glucose tolerance test (GTT). Mice on HFD fed showed a significant increase in the insulin resistance, body weight, deterioration of lipid profile and significant reduction in the β-cell function, and insulin sensitivity compared to the control P < 0.05. GTT and blood glucose level were significantly high in HFD fed group compared to the control group P < 0.05. Rosuvastatin in a dose of 40 mg/kg illustrated better effect than 20 mg/kg on the glucometabolic profile P < 0.05. Rosuvastatin may has a potential effect on reduction of glucometabolic changes induced by HFD with significant amelioration of pancreatic β-cell function in dose-dependent manner. 


Assessment of the fitness of Cox and parametric regression models of survival distribution for Iranian breast cancer patients' data
Maryam Mohseny, Reza Shekarriz-Foumani, Parastoo Amiri, Marjan Vejdani, Pezhman Farshidmehr, Hossein Zabihi Mahmoudabadi, Farzaneh Amanpour, Pegah Mohaghegh, Farzad Tajdini, Azadeh Sayarifard, Esmat Davoudi-Monfared

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):39-44

Factors affecting the time of survival after breast cancer (BC) diagnosis remain unknown. However, some of the prognostic factors have been identified. The aim of this study was to investigate the effects of biologic and socioeconomic factors on long-term survival of BC patients. This was a descriptive chart review and survey of all women with a confirmed diagnosis of BC registered in Shohada-e-Tajrish Cancer Research Center database from March 2004 to March 2015. The checklist of study consisted of biologic, demographic, reproductive, genetic, medical, and therapeutic information of patients. The minimum time of follow-up was 3 years and the maximum was 10 years. We then evaluated possible associations of these variables with BC survival using Cox and parametric regression models of survival analysis. The study population was 1276 BC patients. Their mean survival was 23 (range 1–120) months. Between the parametric models, Weibull regression model demonstrated the lowest Akaike information criterion and thus the best fit, and tumor size, number of lymph nodes, BC stage, educational level, and high-fat diet were significant in this model. Based on our findings, educational level, consumption of fat, and characteristics of tumor at the time of diagnosis (disease stage, tumor size, number of involved lymph nodes) are the most important prognostic factors affecting long-term survival of BC patients. We suggest that future studies assess the efficacy of possible interventions for these factors. 


Pharmacy And Bioallied Sciences

Date palm (Phoenix dactylifera L.) fruit as potential antioxidant and antimicrobial agents
Hussah A Al-Shwyeh

Journal of Pharmacy And Bioallied Sciences 2019 11(1):1-11

Date palm (Phoenix dactylifera L.) is the most popular fruit in the Middle East and North Africa. It is consumed widely and has been used for traditional medicine purposes for a long time. The fruits are nutrient rich, containing dietary fibers, sugar, protein, vitamins, minerals, flavonoid, and phenolic compounds. Due to the presence of the phenolic compounds, date palm fruits are antioxidant rich with potent bioactivities against several bacterial pathogens. Therefore, on the basis of the available evidence as reviewed in this paper, it was found that date fruits are a good source of natural antioxidants, which can be used for the management of oxidative stress–related and infectious diseases.


Biosimilars in India; current status and future perspectives
Bikash R Meher, Sakthi Balan, Rashmi R Mohanty, Monalisa Jena, Smita Das

Journal of Pharmacy And Bioallied Sciences 2019 11(1):12-15

Many key biologics are scheduled to lose their patent by the year 2020, which will provide the opportunity to other biopharmaceutical companies to develop the similar biologics. Biosimilar or similar biologic used has increased in the recent year following the approval of the first biosimilar in early 2000. India is one of the leading manufacturers of similar biologics. India has developed a new guideline in 2012 for the pre- and post-marketing approval of similar biologics.


High-performance liquid chromatographic analysis explores the potential antioxidative agents of Argyreia argentea ARN. EX CHOISY extract
Md. Nazim Uddin, Md. Atiar Rahman, Hemayet Hossain, Tanzir Ahmed Khan, Rehana Akter

Journal of Pharmacy And Bioallied Sciences 2019 11(1):16-22

Background: Antioxidative properties of medicinal plants play the key role in plant defense mechanism. Argyreia argentea is an evergreen shrub which is used in the treatment of boils, gastric ulcers, tumor, marasmus, paralysis and spermatorrhea, rheumatoid arthritis, cold, painful sensation, and fever. Aims: This research investigates the phytochemical contents and antioxidative effects of optimized crude methanol extract of A. argentea. Materials and Methods: Crude methanol extract of A. argentea prepared in an optimized procedure has been analyzed by high-performance liquid chromatography to quantitatively determine the phytochemical contents. Tannin content of the extract was determined by established method. The extract was also analyzed for in vitro antioxidative actions by spectrophotometric analysis using 2,2’-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) method, N, N-dimethyl-1,4-diaminobenzene (DMPD) free radical scavenging method, superoxide radical scavenging method, and nitric oxide scavenging method. Results: The experimental results showed a high amount of catechin hydrate (348.62mg/100g of dry extract) and moderate amount of gallic acid, p-coumaric acid, and rutin hydrate in the methanol extract of A. argentea. Tannin content was found to be 29.66mg/g tannic acid equivalent. Scavenging effects expressed as inhibition concentrations (IC50) for ABTS assay, DMPD assay, superoxide assay, and NO assay were 1148.3 µg/mL ± 7.32 µmol ascorbic acid/g, 1017.68 µg/mL, 1116.89 µg/mL, 1835.23 µg/mL, respectively. All the values were compared with their respective standards. No β-carotene was detected in the extract. Conclusions: Use of A. argentea extract as a source of functional food as well as an antioxidative agent could be considered with further confirmation.


Cysteine supplementation mitigates the toxicity associated with antitumor therapy of Ehrlich's ascites fluid adsorbed over protein a containing Staphylococcus aureus cowan I†
Ashish S Verma, Anchal Singh, Priyadarshini Mallick, Premendra D Dwivedi

Journal of Pharmacy And Bioallied Sciences 2019 11(1):23-32

Introduction: Previously, we have reported the amelioration of ad-AF induced hepatotoxicity with the exogenous supplementation of glutathione (GSH) without compromising the anti-tumor effect of ad-AF in ascites tumor model of mice with transplantable Ehrlich’s Ascites Tumor cells. Cellular uptake of glutathione (GSH) has its own limitations, therefore exogenous supplementation of L-cysteine (Cys) was tried to reduce the toxicity of ad-AF by providing –SH contents without compromising the anti-tumor property of adsorbed ascites fluid (ad-AF). Results: A significant increase in mean survival time (MST) of tumor bearing mice from 18.1 days to 32.9 days with exogenous supplementation of Cys was observed. Cys supplementation did not alter decline in body-weight gain, tumor cell counts as well as decrease in the viability of tumor cells in ascites tumor bearing animals. Similarly, Cys has been helpful to restore the hepatic –SH contents upto the levels of –SH content in tumor control group. The exogenous supplementation of Cys along with ad-AF has been helpful to restore the decline in the activities of phase-I and enhanced levels of glutathione-S-transferase (GST). The changes in the activities of different enzymes of phase-I and phase-II indicate the reduction in toxic insult induced by the therapeutic material (ad-AF). However, ad-AF treatment could not prevent tumor bearers from natural death due to tumor progression but significantly reduced the rate of tumor progression. Conclusions: Our study suggests that exogenous supplementation of Cys alongwith ad-AF could have a potential to be developed as a modality for the treatment of ascites tumor at least at experimental level.


Effect of Azadirachta indica crude bark extracts concentrations against gram-positive and gram-negative bacterial pathogens
Shreelakshmidevi Singaravelu, Jaikumar Sankarapillai, Abilash Sasidharn Chandrakumari, Pammy Sinha

Journal of Pharmacy And Bioallied Sciences 2019 11(1):33-37

Background: Today’s pharmaceutical markets are crowded with antibacterial agents, yet their toxicities and resistance are always contentious. Azadirachta indica is used in India as an age-old treatment for diverse medical conditions. This study was put forth to analyze the antibacterial action of A. indica bark extract on different bacterial pathogens. Materials and Methods: A. indica bark extract was prepared using Soxhlet extraction method. The bark extract of A. indica was screened for antibacterial activity by agar well diffusion assay technique against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Proteus mirabilis. Ciprofloxacin (5 µg per disc) was used as positive control. All assays were carried out under strict aseptic precautions. All the concentrations included were duplicated, and the results obtained were the average of two independent experiments. Broth microdilution method was used to study the minimum inhibitory concentration of the bark extract of A. indica. Results: A. indica bark extract has shown antibacterial activity against all concentrations of bark extract, whereas antibacterial activity against S. aureus was observed at higher concentration of >500 µg/mL. The bark extract of A. indica showed zone of clearance against E. faecalis, P. aeruginosa, and P. mirabilis at all concentrations. Zone of inhibition was observed in higher concentrations against S. aureus. Conclusion: This study has shown that A. indica bark extract has a potent antibacterial property against S. aureus, E. faecalis, P. aeruginosa, and P. mirabilis. Further isolation of bioactive compounds may lead to a new scope in the treatment of bacterial infections.


Apoptosis-mediated cytotoxic effect of Caralluma adscendens var. attenuata on colon (HT29) and Hepatic (HepG2) cancer cell lines
Mallela Vijaya Jyothi, Eranti Bhargav, Chilamakuru Naresh Babu, Kanala Somasekhar Reddy, Bhupalam Pradeep Kumar, Ravi Prasad Rao

Journal of Pharmacy And Bioallied Sciences 2019 11(1):38-42

Introduction: Caralluma adscendens var. attenuata (Wight) Grav. and Mayur., a member of Apocynaceae, is a perennial stem succulent plant with wide distribution in tropics and subtropics of the world. This plant is reported for the presence of steroids, flavonoids, saponins, triterpenes, and pregnane glycosides, and is known to have antidiabetic and antiulcerogenic properties. Materials and Methods: In this study, an attempt was made to identify antioxidant capacity and cytotoxic potential of n-hexane and aqueous methanolic extracts of total stem part of C. adscendens var. attenuata. Antioxidant activity was evaluated by total phenolic content assay, total flavonoid content assay, free radical scavenging activity, and reducing ability methods. Cytotoxic activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay and nuclear staining methods for colorectal cancer cell lines HT29 and liver cancer cell lines HepG2. Results: MTT assay method has proven that the IC50 value was 10 μg/mL for both extracts, whereas for cisplatin standard, it was 2 μg/mL. By nuclear staining, the apoptotic cells were identified as oval masses with dark cytoplasm and dense green nuclear chromatin fragments indicating the programmed cell death for both n-hexane and aqueous methanolic extracts at the same concentration (10μg/mL). Conclusion: However, aqueous methanolic extract showed prominent cytotoxic potential against both cancer cell lines.


Comparison and evaluation of different seed extracts of Trachyspermum ammi for immunomodulatory effect on cell-mediated immunity through delayed-type hypersensitivity assay skin thickness method
Mohammad Jamshed Siddiqui, Adeel Aslam, Tanveer Khan

Journal of Pharmacy And Bioallied Sciences 2019 11(1):43-48

Objective: The aim and objective of this study was to find the immunostimulant and immunomodulatory effect of T. ammi seed extracts. Methods: Seeds of T. ammi were extracted using three different solvents n-hexane, chloroform, and methanol by using soxhlet apparatus. To assess the immunomodulatory effect, delayed-type hypersensitivity (DTH) assay method was used and by the DTH assay, the effect of T. ammi on the skin thickness of rats was estimated. To find the exact dose for administration, acute toxicity test was performed using crude methanolic extract at a dose of 400, 800, 1600, and 3200mg/kg. After acute toxicity test, 500mg/kg dose was determined as safe for therapeutic effect and immunomodulatory effect was evaluated at this dose. Dose of 500mg/kg was administered to Wistar rats daily for 14 days and skin thickness of rats was measured at 24, 48, and 72h. Results: Results were obtained from six groups of rats, which were positive control group, negative control group, and the groups receiving the test drugs. Standard drug was the combination of sodium selenite, vitamin E, and sodium chloride and it showed more positive results as compared to that of test drug. Furthermore, among the three extracts, methanol extract showed more effectiveness on skin thickness. Conclusion: There was a meaningful difference was observed between the skin thickness of rats which shows that T. ammi have good immunomodulatory as well as immunostimulant activity.


Development and validation of liquid chromatography method for determination of glimepiride in presence of (Vimto®) soft drinks in rats: application to pharmacokinetics studies
Mohammed Hamad, Areej Rahhal, Wael Abu Dayyih, Eyad Mallah, Alice Abu Dayyih, Zainab Zakaria, Tawfiq Arafat

Journal of Pharmacy And Bioallied Sciences 2019 11(1):49-59

Context: Diet and beverages are thought to have notable effects on drugs. Recently, this relationship has received significant consideration. Aims: To develop and validate a simple, rapid, and sensitive method for the determination of glimepiride in rat serum. This will be performed using high-performance liquid chromatography–mass spectrometry (HPLC-MS/MS). Potential pharmacokinetic interactions between glimepiride and the soft drink, Vimto, will also be investigated in the serum of experimental rats. Materials and Methods: HPLC-MS/MS was constructed and clarithromycin was used as an internal standard. Results: The method was validated in terms of linearity, precision, accuracy, stability, and system suitability parameters. The method was found to be satisfactory and suitable for the determination of glimepiride. The precision of glimepiride was high (coefficient of variation, CV% <15%), the accuracy over all 3 days of validation was within the accepted criteria. Glimepiride peak serum concentration (Cmax) was 126.01ng/mL and was reached within 1h (Tmax) of administration. Mean area under curve (AUC) was 964.70ng/mL and was reached within 24h of administration. The Vimto soft drink significantly (P < 0.050) reduced glimepiride peak serum concentration to 57.87ng/mL and was reached within 2h of administration. AUC was significantly reduced to 335.04 ng*h/mL (P < 0.050). Conclusion: Glimepiride pharmacokinetic parameters such as Cmax and AUC were significantly affected by the Vimto soft drink. Therefore, this study developed a simple, rapid, and sensitive method for validation and determination of the effects of soft drinks on drugs using the LC-MS/MS method.


Antioxidant potential of Solanum nigrum aqueous leaves extract in modulating restraint stress-induced changes in rat's liver
Syed K Zaidi, Shakeel A Ansari, Shams Tabrez, Muhammad I Naseer, Moyad J Shahwan, Naheed Banu, Muhammad H Al-Qahtani

Journal of Pharmacy And Bioallied Sciences 2019 11(1):60-68

Introduction: This study was carried out to evaluate the antioxidant potential of crude extract of Solanum nigrum leaves and its active constituents as treatment against restraint stress in rat’s liver. Methods: For this purpose, male albino Wistar rats were treated with crude extract of leaves and its alkaloid and flavonoid fractions both before and after 6 h of acute restraint stress. Prooxidant status of rat liver was assessed by determining the levels of thiobarbituric acid reactive substances, reduced glutathione, alkaline phosphatase, alanine transaminase, aspartate aminotransferase, and the activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST). Results: Six hours of restraint stress generated oxidative stress in rat’s liver resulted in a significant rise in the level of the aforementioned liver enzymes. On the other hand, SOD, CAT, and GST enzymatic activities showed a significant decline in their level. The administration of crude leaves extract, both before and after stress exposure, significantly prevented the rise in the level of liver enzymes and reverted the activities of studied biochemical parameters toward their normal control values. However, the reversion was found to be more prominent in after-stress group. Conclusion: The aforementioned results highlight the significant antioxidant potential of S. nigrum extracts. On the basis of our study, we suggest the possible use of S. nigrum leaves extract as a nutritional supplement for combating oxidative stress induced damage.


Impact of pharmacist-directed counseling and message reminder services on medication adherence and clinical outcomes in type 2 diabetes mellitus
Narayana Goruntla, Vijayajyothi Mallela, Devanna Nayakanti

Journal of Pharmacy And Bioallied Sciences 2019 11(1):69-76

Introduction: Medication nonadherence is the most common issue observed in the management of diabetes because of complex and lifelong therapy. The study aimed to assess the effect of pharmacist-directed counseling and daily text message reminder on medication adherence and clinical profile of patients with type II diabetes. Materials and Methods: This prospective, open-labeled, randomized control trial was carried out in outpatient medical department of a secondary care referral hospital. A total of 330 patients who met study criteria were enrolled and randomized into an intervention group (n = 165), received counseling and daily messages about medication intake and control group (n = 165), and usual care by physician. Medication adherence and clinical outcomes such as glycosylated hemoglobin (HbA1C), systolic blood pressure (SBP), low-density lipoprotein (LDL) cholesterol, triglyceride (TG) levels, and body mass index (BMI) were recorded at baseline and follow-up visits. Two-sample Wilcoxon rank sum test was used to compare the mean difference of medication adherence and paired t-test was used to compare clinical outcomes. Results and Discussion: The mean age of intervention and control groups were 57.1±8.55 and 58.5±8.53 years, respectively. The mean difference of medication adherence from baseline to second follow-up visit was significantly more in intervention group (12.2±7.1%) compared to that in control group (0.75±10.2%) with a P < 0.001. From baseline to second follow-up visit, HbA1C (7.79±0.67 to 6.91±0.83%), SBP (136.75±20.09 to 126.23±18.22mm Hg), and LDL cholesterol (104.14±26.23 to 98.29±20.87mg/dL) levels were significantly reduced in intervention group compared to that in control group with a P < 0.01. No significant improvement was observed in TG (169±33.71 to 168 65±33.90mg/dL) and BMI (27.9±4.21 to 27.1±3.12Kg/m2) levels from baseline to second follow-up visit. Conclusion: Pharmacist-directed patient counseling combined with message reminder showed a greater effect on the improvement of medication adherence and control of glycemia, blood pressure, and lipid profile in diabetes.


Hepatotoxicity induced by immune checkpoint inhibitors, Drug–drug interactions of a two-drug regimen of dolutegravir and lamivudine for HIV treatment,Enhancement of lung levels of antibiotics by ambroxol and bromhexine,Pharmacokinetic considerations for anti-epileptic drugs in children

New for Expert Opinion on Drug Metabolism & Toxicology and online now 
   on Taylor & Francis Online 


   Pharmacokinetic considerations for anti-epileptic drugs in children 
   Alberto Verrotti, Giulia Iapadre, Giulia Di Donato, Ludovica Di 
   Francesco, Luca Zagaroli, Sara Matricardi, Vincenzo Belcastro & Maria 
   Laura Iezzi 
   Pages: 1-13 
   DOI: 10.1080/17425255.2019.1575361 
   https://www.tandfonline.com/action/doSecureKeyLogin?uuid=d8594a82-ce8d-4e6c-8a1f-0da062c12f34&dateTime=201902121215&key=VDPNBUIz5a0xwGlHxXUPEU%2BIEkmdS3eDJoUSKBla%2BAE%3D&uri=https%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Ffull%2F10.1080%2F17425255.2019.1575361%3Fai%3D1ws9i%26ui%3D843fx%26af%3DT 

   Enhancement of lung levels of antibiotics by ambroxol and bromhexine 
   Vojo Deretic & Graham S. Timmins 
   Pages: 1-6 
   DOI: 10.1080/17425255.2019.1578748 
   https://www.tandfonline.com/action/doSecureKeyLogin?uuid=d8594a82-ce8d-4e6c-8a1f-0da062c12f34&dateTime=201902121215&key=VDPNBUIz5a0xwGlHxXUPEU%2BIEkmdS3eDJoUSKBla%2BAE%3D&uri=https%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Ffull%2F10.1080%2F17425255.2019.1578748%3Fai%3D1ws9i%26ui%3D843fx%26af%3DT 

   Drug–drug interactions of a two-drug regimen of dolutegravir and 
   lamivudine for HIV treatment 
   Dario Cattaneo, Amedeo Capetti & Giuliano Rizzardini 
   Pages: 1-8 
   DOI: 10.1080/17425255.2019.1577821 
   https://www.tandfonline.com/action/doSecureKeyLogin?uuid=d8594a82-ce8d-4e6c-8a1f-0da062c12f34&dateTime=201902121215&key=VDPNBUIz5a0xwGlHxXUPEU%2BIEkmdS3eDJoUSKBla%2BAE%3D&uri=https%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Ffull%2F10.1080%2F17425255.2019.1577821%3Fai%3D1ws9i%26ui%3D843fx%26af%3DT 

   Hepatotoxicity induced by immune checkpoint inhibitors: a 
   comprehensive review including current and alternative management 
   strategies 
   Joseph J. Jennings, Rohan Mandaliya, Ahmad Nakshabandi & James H. 
   Lewis 
   Pages: 1-14 
   DOI: 10.1080/17425255.2019.1574744 
   https://www.tandfonline.com/action/doSecureKeyLogin?uuid=d8594a82-ce8d-4e6c-8a1f-0da062c12f34&dateTime=201902121215&key=VDPNBUIz5a0xwGlHxXUPEU%2BIEkmdS3eDJoUSKBla%2BAE%3D&uri=https%3A%2F%2Fwww.tandfonline.com%2Fdoi%2Ffull%2F10.1080%2F17425255.2019.1574744%3Fai%3D1ws9i%26ui%3D843fx%26af%3DT 

Outcomes of carotid‐sparing IMRT for T1 glottic cancer: Comparison with conventional radiation

Objectives

We aim to report oncologic outcomes after conventional radiotherapy (ConRT) using opposed lateral beams and intensity‐modulated radiation therapy (IMRT) for tumor (T)1 nodal (N)0 T1 N0 glottic squamous cell carcinoma.

Study Design

Retrospective case‐control study.

Methods

We retrospectively reviewed demographic, disease, and treatment characteristics for patients treated at our institution during 2000 to 2013.

Results

One hundred fifty‐three patients (71%) were treated using ConRT and 62 (29%) using IMRT. The median follow‐up for all patients was 68 months. There was no statistically significant difference in 5‐year local control between patients with T1a versus T1b disease (94% vs. 89%, respectively, P = 0.5). Three‐year locoregional control for patients treated with ConRT was 94% compared to 97% with IMRT (P = 0.4). Three‐year overall survival (OS) for patients treated with ConRT was 92.5% compared with 100% with IMRT (P = 0.1). Twelve of 14 patients with local recurrence underwent salvage surgery with 5‐year ultimate locoregional control of 98.5% and 97.1% in the ConRT and IMRT cohorts, respectively (P = 0.7). Multivariate analysis showed age < 60 years (P < 0.0001) and pretreatment Eastern Cooperative Oncology Group performance status <2 (P = 0.0022) to be independent correlates of improved OS. Postradiation cerebrovascular events were in four patients in the ConRT cohort (3%), whereas no patients in the IMRT cohort suffered any events.

Conclusion

Because the oncologic outcomes for patients treated with IMRT were excellent and IMRT allows for carotid sparing, we have transitioned to IMRT as our standard for most patients with T1 glottic cancer.

Level of Evidence

3b. Laryngoscope, 2019



http://bit.ly/2GlSBsF

Selective reinnervation using phrenic nerve and hypoglossal nerve for bilateral vocal fold paralysis

Objective

To evaluate the extent of airway improvement and voice quality in patients with bilateral vocal fold paralysis (BVFP) who underwent selective laryngeal reinnervation surgery.

Methods

Seven patients with BVFP caused by thyroid surgeries were enrolled. They underwent selective laryngeal reinnervation surgery. Videostroboscopy data, voice perceptual data (grade [G]), acoustic data, laryngeal electromyography data, and pulmonary function test data were obtained preoperatively and postoperatively.

Results

Videostroboscopic videos showed that six patients could achieve moderate‐to‐maximal abduction in the bilateral vocal folds during inspiration, whereas all patients achieved adduction in the bilateral vocal folds during phonation at 4 to 7 months postoperatively. G score was decreased significantly versus preoperative values (P < 0.05), and vocal functional parameters were improved significantly at 12 months postoperatively (P < 0.05). The aerodynamic parameter of maximum phonation time was significantly longer than the preoperative value (P < 0.05). Most parameters in pulmonary function test recovered to normal reference levels as early as 3 months postoperatively, whereas maximal inspiratory pressure (PImax) values were still slightly lower than normal levels 12 months after surgery. All of these parameters improved significantly versus preoperative values. Electromyographic data at 12 months postoperatively showed full interference potentials in bilateral posterior cricoarytenoid muscles during inspiration and full interference potentials in bilateral thyroarytenoid muscles during phonation in all patients. Moderate electric potentials were seen in left interarytenoid muscle in one failed patient.

Conclusion

This new selective laryngeal reinnervation procedure can achieve physiological movements of the bilateral vocal folds in selected patients with BVFP.

Level of Evidence

4. Laryngoscope, 2019



http://bit.ly/2IaBeN6

Safety of office‐based percutaneous injection laryngoplasty with calcium hydroxylapatite

Objective

To evaluate the safety of office‐based calcium hydroxylapatite (CaHA) injection laryngoplasty via the cricothyroid approach through an analysis of all procedures performed over a period of 10 years at a single institution.

Methods

In total, 962 office‐based CaHA injection laryngoplasty via the cricothyroid approach procedures were performed by a single physician at our institution between 2007 and 2016. From these, 955 procedures performed in 617 patients were included in our analysis. The medical records of all 617 patients were retrospectively reviewed. We classified all procedure‐related complications according to the time of onset. Complications that occurred during the procedure were considered intraprocedural complications, whereas complications that developed within 1 week after injection and those that developed after 1 week and were recorded more than twice in the medical records were considered acute and delayed complications, respectively. Failed cases were categorized separately as failure.

Results

Five cases were failed (0.5%). Intraprocedural complications included superficial injection in eight cases (0.8%). Acute and delayed onset of dyspnea was observed in three (0.3%) and two (0.2%) cases, respectively. The incidence of failures and major complications requiring active intervention was 1.6%.

Conclusion

Our findings suggest that office‐based CaHA injection laryngoplasty via the cricothyroid approach is as safe as conventional transoral injection laryngoplasty.

Level of Evidence

4. Laryngoscope, 2019



http://bit.ly/2GmGiMx

The effect of foxp3 on tumor stage, treatment response, recurrence and survivalability in nasopharynx cancer patients

Abstract

Objectives

To investigate the relationship between the cell percentage of T regulator (Treg) cells of patients' specimens and disease severity, survivability, recurrence and metastasis in patients who were diagnosed with nasopharyngeal carcinoma (NPC). Design: Sixty patients who were diagnosed as NPC and treated by the same protocol were enrolled to the study. Patient files were reviewed retrospectively and their clinical and pathological results were recorded. Deparaffinized samples of patients were stained immunohistochemically with anti‐FoxP3 monoclonal antibody. All patients's Anti‐FoxP3 stained slides were evaluated by the same pathologist. Stained Treg lymphocytes around the tumoral foci were investigated. Patients were divided into two groups according to the total anti‐FoxP3‐stained Treg cell counts of the specimens; that is, less than 20% of the total or more than 20% of the total. These groups were compared statistically.

Results

The study group consisted of 42 male patients (70%) and 18 female patients (30%). The mean age was 47 ± 14.9. NPC subtypes among the patients were undifferentiated non‐keratinized type in 54 patients (90%), differentiated non‐keratinized type in 4 patients (6.66%) and keratinized type squamous cell carcinoma (SCC) in 2 patients (3.33%).. When the two groups were compared in terms of pathological subtype, there was no significant variation between the two groups. There was also no significant variation between the two groups when compared on the basis of tumor stage (p = 0.36 for T phase, p = 0.122 for N phase), early stage, late phase (p = 0.15), survival rate (p = 0.69 for general survival), recurrence (p = 0.2 for local recurrence, P = 0.37 for regional recurrence) and distant metastasis (p = 0.3).

Conclusion

There was no significant relationship between the concentration of these cells in the stained specimens and the disease stage, survival rate, recurrence and distant metastasis discovered. Key‐words: Nasopharynx, carcinoma, radiotherapy, staining, immunity, Herpesvirus 4, human.

This article is protected by copyright. All rights reserved.



http://bit.ly/2Dx6UXm

Utility and Practicality of Multi-level Sectioning and Upfront Unstained Slide Cutting in Head and Neck Biopsies: A Critical Analysis

Abstract

Upfront interval sectioning (cutting unstained slides between H&E levels) is used at our institution for biopsies at all sites except the gastrointestinal tract. Very limited data exists in the literature for the need for interval sectioning, and we are aware of no data at all for the head and neck. Biopsies from the larynx, oral cavity, pharynx, and sinonasal tract at our institution have had 5 levels cut. Levels 1, 3, and 5 or levels 2 and 5 had been stained with hematoxylin and eosin (H&E), depending on the subsite, and the remaining slides saved for possible later use. We retrospectively evaluated the use of unstained slides at these sites for clinical utility and efficiency by analyzing 3 years of cases from 1/1/2014 to 12/30/2016. A cutoff of 10% utilization was considered justification for continued upfront unstained slide cutting. We collected 706 larynx, 572 oral cavity, 184 pharynx, and 85 sinonasal tract biopsies over 3 years. The overall rate of unstained slide usage was 18.2%. Usage rates were significantly different by site: 7.8% (55/706) for larynx, 21.9% (125/572) for oral cavity, 30.6% (26/85) for sinonasal tract and 40.8% (75/184) for pharynx (p < 0.0001). The most common stain ordered in the pharynx was p16 immunohistochemistry (59.7%), but it was Grocott methenamine silver staining in the larynx (74.5%), oral cavity (70.4%), and sinonasal tract (35.1%). Usage of unstained slides was lowest for the larynx, and review of the biopsies with unstained slides utilized showed that the lesion was present on the 3rd H&E level in all cases. Removing this practice would have translated to saving 1,378 unstained slides. Upfront interval sectioning makes practical sense for biopsies from most sites in the head and neck, especially the pharynx, but our data suggests it can reasonably be forgone at least for biopsies of the larynx.



http://bit.ly/2BzYLRF

Thyroid Gland Solitary Fibrous Tumor: Report of 3 Cases and a Comprehensive Review of the Literature

Abstract

Solitary fibrous tumors of the thyroid gland are exceptionally rare. In order to further characterize the clinical and pathologic features of solitary fibrous tumor arising at this anatomic site, three cases of thyroid gland solitary fibrous tumor were analyzed in conjunction with 35 cases compiled from the English literature. Thyroid gland solitary fibrous tumors showed an equal sex distribution with a mean age at presentation of 54.4 years (range, 28–88 years). The patients typically presented with an asymptomatic, slow growing neck mass. Microscopically, the tumors were characterized by cytologically bland spindle cells with patternless growth, hypocellular and hypercellular areas, variable amounts of collagen, and ectatic, branching blood vessels. Two previous reported tumors were considered to be histologically malignant on the basis of increased mitotic activity, profound pleomorphism and tumor necrosis. Immunohistochemically, the tumor cells are variably positive with CD34, bcl-2, and CD99. STAT6 immunohistochemistry, performed on the current cases, demonstrated a strong, diffuse nuclear expression in all tumors. Among 26 patients with available follow up data (mean 47.3 months), one developed local recurrence and distant metastasis. Solitary fibrous tumors occurring in the thyroid gland are uncommon, but can be reliably diagnosed based on the presence of characteristic morphologic features as well as immunohistochemical expression of STAT6 and CD34. The majority of thyroid gland solitary fibrous tumors have exhibited an indolent clinical course, however experience is limited. The rare potential for aggressive clinical behavior requires clinical surveillance.



http://bit.ly/2TNNx34

Utility and Practicality of Multi-level Sectioning and Upfront Unstained Slide Cutting in Head and Neck Biopsies: A Critical Analysis

Abstract

Upfront interval sectioning (cutting unstained slides between H&E levels) is used at our institution for biopsies at all sites except the gastrointestinal tract. Very limited data exists in the literature for the need for interval sectioning, and we are aware of no data at all for the head and neck. Biopsies from the larynx, oral cavity, pharynx, and sinonasal tract at our institution have had 5 levels cut. Levels 1, 3, and 5 or levels 2 and 5 had been stained with hematoxylin and eosin (H&E), depending on the subsite, and the remaining slides saved for possible later use. We retrospectively evaluated the use of unstained slides at these sites for clinical utility and efficiency by analyzing 3 years of cases from 1/1/2014 to 12/30/2016. A cutoff of 10% utilization was considered justification for continued upfront unstained slide cutting. We collected 706 larynx, 572 oral cavity, 184 pharynx, and 85 sinonasal tract biopsies over 3 years. The overall rate of unstained slide usage was 18.2%. Usage rates were significantly different by site: 7.8% (55/706) for larynx, 21.9% (125/572) for oral cavity, 30.6% (26/85) for sinonasal tract and 40.8% (75/184) for pharynx (p < 0.0001). The most common stain ordered in the pharynx was p16 immunohistochemistry (59.7%), but it was Grocott methenamine silver staining in the larynx (74.5%), oral cavity (70.4%), and sinonasal tract (35.1%). Usage of unstained slides was lowest for the larynx, and review of the biopsies with unstained slides utilized showed that the lesion was present on the 3rd H&E level in all cases. Removing this practice would have translated to saving 1,378 unstained slides. Upfront interval sectioning makes practical sense for biopsies from most sites in the head and neck, especially the pharynx, but our data suggests it can reasonably be forgone at least for biopsies of the larynx.



http://bit.ly/2BzYLRF

Thyroid Gland Solitary Fibrous Tumor: Report of 3 Cases and a Comprehensive Review of the Literature

Abstract

Solitary fibrous tumors of the thyroid gland are exceptionally rare. In order to further characterize the clinical and pathologic features of solitary fibrous tumor arising at this anatomic site, three cases of thyroid gland solitary fibrous tumor were analyzed in conjunction with 35 cases compiled from the English literature. Thyroid gland solitary fibrous tumors showed an equal sex distribution with a mean age at presentation of 54.4 years (range, 28–88 years). The patients typically presented with an asymptomatic, slow growing neck mass. Microscopically, the tumors were characterized by cytologically bland spindle cells with patternless growth, hypocellular and hypercellular areas, variable amounts of collagen, and ectatic, branching blood vessels. Two previous reported tumors were considered to be histologically malignant on the basis of increased mitotic activity, profound pleomorphism and tumor necrosis. Immunohistochemically, the tumor cells are variably positive with CD34, bcl-2, and CD99. STAT6 immunohistochemistry, performed on the current cases, demonstrated a strong, diffuse nuclear expression in all tumors. Among 26 patients with available follow up data (mean 47.3 months), one developed local recurrence and distant metastasis. Solitary fibrous tumors occurring in the thyroid gland are uncommon, but can be reliably diagnosed based on the presence of characteristic morphologic features as well as immunohistochemical expression of STAT6 and CD34. The majority of thyroid gland solitary fibrous tumors have exhibited an indolent clinical course, however experience is limited. The rare potential for aggressive clinical behavior requires clinical surveillance.



http://bit.ly/2TNNx34

Primary Tonsillar Epithelioid Follicular Dendritic Cell Sarcoma: Report of a Rare Case Mimicking Undifferentiated Carcinoma and a Brief Review of the Literature

Abstract

We present a 52 years old male with a left tonsillar follicular dendritic cell sarcoma with prominent epithelioid features that on light microscopical examination bore a striking resemblance to a lymphoepithelial or undifferentiated carcinoma. The tumor was immunohistochemically positive for CD21 and CD35 and negative for cytokeratins. Two distinct histopathological features (both present in our case) that may serve as clues to the correct diagnosis on light microscopical examination were formation of ectatic pseudovascular spaces lined by malignant cells and the presence of non-neoplastic multinucleated giant cells. Familiarity with the above-mentioned morphological clues, and awareness that this tumour may occur in anatomical sites outside the lymph node, are essential for accurate diagnosis.



http://bit.ly/2N1Pjeo

Τρίτη 12 Φεβρουαρίου 2019

Primary Osteosarcoma of Sphenoid and Ethmoid Sinus in a 17 Year Female: Case Report

Abstract

Primary osteosarcoma of sphenoid and ethmoid sinus present as a challenge in head neck cancer. A 17 year female presented with left sided hemifacial pain, headache with nasal discharge. Clinico-radiological finding showed mass in sphenoethmoid recess spreading to adjacent structures. Endoscopic resection was done. Histopathological diagnosis was osteosarcoma of sphenoid and ethmoid sinus. Adjuvant chemotherapy administered. Osteosarcomas of sphenoid and ethmoid sinus are aggressive tumors with variable clinical features warranting high clinical suspicion.



http://bit.ly/2ByXs5E

Primary Tonsillar Epithelioid Follicular Dendritic Cell Sarcoma: Report of a Rare Case Mimicking Undifferentiated Carcinoma and a Brief Review of the Literature

Abstract

We present a 52 years old male with a left tonsillar follicular dendritic cell sarcoma with prominent epithelioid features that on light microscopical examination bore a striking resemblance to a lymphoepithelial or undifferentiated carcinoma. The tumor was immunohistochemically positive for CD21 and CD35 and negative for cytokeratins. Two distinct histopathological features (both present in our case) that may serve as clues to the correct diagnosis on light microscopical examination were formation of ectatic pseudovascular spaces lined by malignant cells and the presence of non-neoplastic multinucleated giant cells. Familiarity with the above-mentioned morphological clues, and awareness that this tumour may occur in anatomical sites outside the lymph node, are essential for accurate diagnosis.



http://bit.ly/2N1Pjeo

Primary Osteosarcoma of Sphenoid and Ethmoid Sinus in a 17 Year Female: Case Report

Abstract

Primary osteosarcoma of sphenoid and ethmoid sinus present as a challenge in head neck cancer. A 17 year female presented with left sided hemifacial pain, headache with nasal discharge. Clinico-radiological finding showed mass in sphenoethmoid recess spreading to adjacent structures. Endoscopic resection was done. Histopathological diagnosis was osteosarcoma of sphenoid and ethmoid sinus. Adjuvant chemotherapy administered. Osteosarcomas of sphenoid and ethmoid sinus are aggressive tumors with variable clinical features warranting high clinical suspicion.



http://bit.ly/2ByXs5E

Contribution of Nitric oxide synthase 3 genetic variants to nasopharyngeal carcinoma risk and progression in a Tunisian population

Abstract

Purpose

We conduct this study to evaluate the clinical and functional impact of Nitric Oxide Synthase 3 (NOS3) T-786C and G894T genetic variants on nasopharyngeal carcinoma (NPC) risk and progression in a Tunisian population.

Methods

259 NPC patients and 169 healthy controls were enrolled into our case–control study. Blood samples were genotyped by the RFLP-PCR analysis. The levels of Nitric oxide (NO) were measured by a colorimetric assay kit in the plasma of NPC patients, healthy controls and according to NOS3 genotypes. The correlation between the NOS3 variants and the clinicopathological parameters was examined.

Results

We found no linkage disequilibrium between NOS3 T-786C and G894T variants. These results showed that NOS3 variants were genetically independent. In contrast to NOS3 T-786C, a significant association was found between NOS3 G894T polymorphism and NPC risk. The 894T allele decreased significantly in NPC patients and appeared as protective factor (OR = 0.65, CI 95%= 0.48–0.88, p = 0.006). NPC patients had significantly higher levels of plasma NO as compared to healthy controls (p = 0.0011). The T-786C mutation reduced the levels of plasma NO and decreased risk of lymph node metastasis in NPC patients (OR = 0.64, 95% CI = 0.43–0.96; p = 0.03). In contrast, NOS3 G894T polymorphism had no effects neither on NO plasma levels nor clinical parameters.

Conclusions

This is the first study to associate NPC with significantly higher levels of plasma NO. NOS3-derived NO could play key roles in NPC pathogenesis. NOS3 variants differently contribute to NPC risk and progression in a Tunisian population. NOS3 G894T was associated with NPC risk. NOS3 T-786C decreased the levels of plasma NO and reduced the development of regional lymph node metastasis.



http://bit.ly/2GnioAv

β-Catenin nuclear expression discriminates deep penetrating nevi from other cutaneous melanocytic tumors

Abstract

Recent advances in genomics have improved the molecular classification of cutaneous melanocytic tumors. Among them, deep penetrating nevi (DPN) and plexiform nevi have been linked to joint activation of the MAP kinase and dysregulation of the β-catenin pathways. Immunohistochemical studies have confirmed cytoplasmic and nuclear expression of β-catenin and its downstream effector cyclin D1 in these tumors. We assessed nuclear β-catenin immunohistochemical expression in a large group of DPN as well as in the four most frequent differential diagnoses of DPN: "blue" melanocytic tumors, Spitz tumors, nevoid and SSM melanomas, and pigmented epithelioid melanocytomas (PEM). Nuclear β-catenin expression was positive in 98/100 DPN and 2/16 of melanomas (one SSM and one nevoid melanoma with a plexiform clone) and was negative in all 30 Spitz, 26 blue, and 6 PEM lesions. In 41% DPN, β-catenin expression was positive in more than 30% nuclei. No differences were observed in cytoplasmic and nuclear cyclin D1 expression between these tumor groups, suggesting alternate, β-catenin-independent, activation pathways. We have subsequently studied nuclear β-catenin expression in a set of 13 tumors with an ambiguous diagnosis, for which DPN was part of the differential diagnosis. The three out of four patients showing canonical DPN mutation profiles were the only β-catenin-positive cases. We conclude that nuclear β-catenin expression, independently from CCND1 expression, in a dermal melanocytic tumor is an argument for its classification as DPN. In ambiguous cases and in early combined DPN lesions, this antibody can be helpful as a screening tool. β-Catenin is also potentially expressed in a subset of malignant melanomas with CTNNB1 mutations.



http://bit.ly/2N0SP8M

Recent success and limitations of immune checkpoint inhibitors for cancer: a lesson from melanoma

Abstract

Several researches have been carried over the last few decades to understand of how cancer evades the immune system and thus to identify therapies that could directly act on patient's immune system in the way of restore or induce a response to cancer. As a consequence, "cancer immunotherapy" is conquering predominantly the modern scenario of the fight against cancer. The recent clinical success of immune checkpoint inhibitors (ICIs) has created an entire new class of anti-cancer drugs and restored interest in the field of immuno-oncology, leading to regulatory approvals of several agents for the treatment of a variety of malignancies. The first to be approved in 2011 was the anti-CTLA-4 antibody ipilimumab for the treatment of unresectable or metastatic melanoma. Subsequently, the anti-PD-1s, nivolumab and pembrolizumab, received regulatory approvals for the treatment of melanoma and several other cancers. More recently, three anti-PD-L1 antibodies have received approval: atezolizumab and durvalumab for locally advanced or metastatic urothelial carcinoma and metastatic non-small cell lung cancer (NSCLC) and avelumab for the treatment of locally advanced or metastatic urothelial carcinoma and metastatic Merkel cell carcinoma. This review, starting from the results of melanoma trials, highlights in turn different ICIs and data for different indications in several malignancies are included under each drug class.



http://bit.ly/2SKodO7

Two rare cases of endosalpingiosis in the axillary sentinel lymph nodes: evaluation of immunohistochemical staining and one-step nucleic acid amplification (OSNA) assay in patients with breast cancer

Abstract

Benign inclusions, such as endosalpingiosis, in an axillary sentinel lymph node (SLN) can be misdiagnosed as metastatic breast carcinoma. However, endosalpingiosis is rare in lymph nodes above the diaphragm. Among 792 patients with breast carcinoma who underwent sentinel lymph node biopsy at our center, 2 patients have experienced benign glandular inclusions in 3 SLNs, and all of these glandular inclusions were lined with columnar and ciliated epithelial cells. Immunohistochemistry revealed that the epithelial cells were positive for Müllerian markers (e.g., PAX8 and WT-1) and negative for mammary markers (e.g., mammaglobin, GCDFP-15, and GATA3), which confirm the diagnosis of endosalpingiosis. The epithelial cells were positive for CK19 but the one-step nucleic acid amplification assay revealed negative results for the axillary SLNs. Although endosalpingiosis is rare in axillary SLNs, care is needed to identify these rare cases and avoid unnecessary axillary lymph node dissection, overstaging, and overtreatment.



http://bit.ly/2N3kPbT

Non Familial Cherubism: A Case Report

Abstract

Cherubism might occur in solitary cases or in several members of the family, often in many generations. Treatment depends on the clinical course of the disease. The reported case is an example of solitary sporadic occurrence within a family, which is a less documented condition in the literature.



http://bit.ly/2N0BFIs

Safety of outpatient admission and comparison of different surgical techniques in adult tonsillectomy

Abstract

Purpose

To investigate the safety of outpatient admission and the effects of surgical technique in tonsillectomy operations of adult patients.

Methods

The digital database was scanned for patients aged ≥ 15 years that underwent tonsillectomy in our institution between years 2014 and 2018. Demographic and clinical characteristics, the surgical technique, length of stay (LOS) in hospital, re-admissions after discharge, complications and interventions performed were recorded.

Results

A total of 276 patients met the inclusion criteria, comprising 139 (50.4%) females and 137 (49.6%) males with a mean age of 27.17 ± 9.41 years. The most common indication was recurrent tonsillitis (n = 223, 80.8%), and surgical techniques used were bipolar scissors (CURIS®, Sutter Medizintechnik, Germany) (n = 137, 49.6%), cold dissection (n = 75, 27.2%) and/or plasma blade (PEAK Surgical, Medtronic, USA) (n = 64, 23.2%). A total of 43 (15.5%) re-admissions from 37 (13.4%) patients were recorded because of bleeding (n = 33, 70.2%) and/or odynodysphagia (n = 13, 27.7%). Non-surgical interventions were sufficient in 32 (74.4%) cases, while surgical interventions were required in 11 (25.6%) patients. In patients where "hot" techniques (bipolar scissors, plasma blade) were used and in patients with complaints in the first 24 h postoperatively, significantly increased rates of elongated LOS values for more than 1 day were determined (p < 0.01, p < 0.001).

Conclusions

Adult tonsillectomy is a safe surgical procedure with low complication, re-operation and mortality rates. Significantly increased rates of elongated LOS values for more than 1 day and re-admissions after discharge were determined in those patients having complications in the first 24 h postoperatively. Cold dissection seems to be more advisable than hot techniques for outpatient tonsillectomy among adult patients.



http://bit.ly/2BrR687

Non Familial Cherubism: A Case Report

Abstract

Cherubism might occur in solitary cases or in several members of the family, often in many generations. Treatment depends on the clinical course of the disease. The reported case is an example of solitary sporadic occurrence within a family, which is a less documented condition in the literature.



http://bit.ly/2N0BFIs

Development of an Experimental System “Computer-Aided Diagnosis in Neurotology (CADINO)” for Vertigo

Abstract

Computer-based medical diagnosis expert systems, when used by clinicians, familiar with the limitations of the system, were found both accurate and educationally helpful. Vertigo is one of the most common complaints of the patients and the specialists who manage these patients are not easily available. Diagnostic expert system can help clinicians including general practitioners in providing reasonable diagnostic suggestions while dealing with patients with vertigo/dizziness when the specialist doctors are not available. To provide an understanding about the method of making an expert system "Computer-Aided Diagnosis in Neurotology (CADINO)" for dizzy patients and highlight its potential uses. CADINO, developed during this original research project, is an expert computer program which is capable of making diagnoses in patients with vertigo. CADINO includes more than 100 causes of vertigo. It was developed in Microsoft Office using hyperlinks. CADINO has the potential of making diagnoses in patients with vertigo. It differs from most other programs for computer-assisted diagnosis in the generality of its approach and knowledge base. Specific deficiencies of CADINO include its inability to explain its thinking. CADINO can broaden the clinicians' scope and awareness regarding the findings which are important for making the differential diagnoses in patients with vertigo/dizziness. Though the CADINO on its face value seems to improve patient safety and quality of care by enhancing knowledge and cognitive skills of the clinicians, yet it remains a research tool and will need clinical evaluation in terms of diagnostic accuracy.



http://bit.ly/2TKQEsK

Roles of Ki-67 and p16 as biomarkers for unknown primary head and neck squamous cell carcinoma

Abstract

Purpose

Treatment guidelines have not been established for unknown primary head and neck squamous cell carcinoma (SCC). For these patients, chemoradiotherapy (CRT) can provide a better prognosis than that for patients with other head and neck cancers. The presence of HPV in the tumor is associated with a better outcome. However, not all patients with HPV-positive unknown primary head and neck SCC experience good treatment outcomes in actual clinical settings.

Methods

We thus retrospectively determined the Ki-67 proliferation index and p16 expression status to assess the associations of these parameters with treatment outcomes of patients with unknown primary head and neck SCC.

Results

The subjects were 13 patients who underwent CRT after surgery or excision biopsy between 1999 and 2016. The 2- and 5-year overall survival (OS) rate was 76.9% and 68.4%, respectively. The prognostic factor was age. There was no significant difference in survival between patients with a high Ki-67 vs. low Ki-67 or between patients with p16-positive vs. p16-negative metastases OS. However, all p16-positive patients with low Ki-67 showed good locoregional control.

Conclusions

The combination of ki67 expression and p16 expression status may allow prediction of local control more accurately than p16 expression status alone.



http://bit.ly/2TM1Bdl

HPV as a marker for molecular characterization in head and neck oncology: Looking for a standardization of clinical use and of detection method(s) in clinical practice

Abstract

Background

A consensus about the most appropriate diagnostic method(s) for head and neck human papillomavirus (HPV)‐induced carcinogenesis is still lacking because most of the commercially available assays have been designed for the cervix.

Methods

This article summarizes current data and trends concerning HPV diagnostic strategies in oropharyngeal squamous cell carcinoma (OPSCC). Six main approaches are described.

Results

The diagnostic gold standard for HPV‐related OPSCC, focusing on E6/E7 mRNA detection, requires fresh samples. Because most frequently available samples are formalin‐fixed paraffin‐embedded (FFPE), the pros and cons of the different approaches were analyzed.

Conclusions

In the FFPE samples, the immunohistochemistry of p16, which is considered appropriate to assess HPV‐driven carcinogenesis in OPSCC according to the 8th American Joint Committee on Cancer TNM classification, may not be specific enough to become the diagnostic standard in the perspective of treatment deintensification. p16 may play a safer role in combination with another highly sensible assay. Other promising approaches are based on DNA detection through real‐time polymerase chain reaction and RNAscope.



http://bit.ly/2GFdCxO

Development of an Experimental System “Computer-Aided Diagnosis in Neurotology (CADINO)” for Vertigo

Abstract

Computer-based medical diagnosis expert systems, when used by clinicians, familiar with the limitations of the system, were found both accurate and educationally helpful. Vertigo is one of the most common complaints of the patients and the specialists who manage these patients are not easily available. Diagnostic expert system can help clinicians including general practitioners in providing reasonable diagnostic suggestions while dealing with patients with vertigo/dizziness when the specialist doctors are not available. To provide an understanding about the method of making an expert system "Computer-Aided Diagnosis in Neurotology (CADINO)" for dizzy patients and highlight its potential uses. CADINO, developed during this original research project, is an expert computer program which is capable of making diagnoses in patients with vertigo. CADINO includes more than 100 causes of vertigo. It was developed in Microsoft Office using hyperlinks. CADINO has the potential of making diagnoses in patients with vertigo. It differs from most other programs for computer-assisted diagnosis in the generality of its approach and knowledge base. Specific deficiencies of CADINO include its inability to explain its thinking. CADINO can broaden the clinicians' scope and awareness regarding the findings which are important for making the differential diagnoses in patients with vertigo/dizziness. Though the CADINO on its face value seems to improve patient safety and quality of care by enhancing knowledge and cognitive skills of the clinicians, yet it remains a research tool and will need clinical evaluation in terms of diagnostic accuracy.



http://bit.ly/2TKQEsK

Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer

Condition:   Medullary Thyroid Cancer
Intervention:   Drug: Ponatinib
Sponsors:   Antonio Fojo;   Millennium Pharmaceuticals, Inc.
Not yet recruiting

http://bit.ly/2Ia7foi

Radiotherapy Plus Concurrent Nimotuzumab or Cisplatin in Stage II-III Nasopharyngeal Carcinoma

Conditions:   Nasopharyngeal Carcinoma;   Nasopharyngeal Neoplasms;   Nasopharyngeal Diseases;   Head and Neck Neoplasm
Interventions:   Drug: Nimotuzumab;   Drug: Cisplatin
Sponsors:   Sun Yat-sen University;   Affiliated Cancer Hospital & Institute of Guangzhou Medical University;   Guangdong General Hospital;   First Affiliated Hospital, Sun Yat-Sen University
Recruiting

http://bit.ly/2Go1ge2

Feasibility and Tolerance of Nivolumab Neoadjuvant Immunotherapy in High Risk HPV Driven Oropharynx Cancer

Condition:   Oropharynx Cancer
Interventions:   Drug: Nivolumab;   Radiation: Chemoradiation
Sponsor:   UNICANCER
Not yet recruiting

http://bit.ly/2Ia764e

Role of Microbiome as a Biomarkers in Locoregionally-Advanced Oropharyngeal Squamous Cell Carcinoma 2

Condition:   Head and Neck Squamous Cell Carcinoma
Intervention:   Drug: MET-4
Sponsors:   University Health Network, Toronto;   NuBiyota
Not yet recruiting

http://bit.ly/2GpiFTq

A Single Dry Needling Session of the Obliquus Capitis Inferior for the Altered Sensorimotor Function in People With Neck Pain

Conditions:   Whiplash Syndrome;   Neck Pain
Interventions:   Other: dry needling;   Other: Sham needling
Sponsor:   University of Valencia
Recruiting

http://bit.ly/2Ia6XxI

Factors of success of low‐dose macrolides in chronic sinusitis: Systematic review and meta‐analysis

Objective

To assess the prognostic factors that predict favorable outcomes of low‐dose macrolides (LDMs) in treating chronic rhinosinusitis (CRS).

Methods

Randomized controlled trials studying the effects of LDMs in treating CRS were included. Data were pooled for meta‐analysis. Primary outcome was Sino‐Nasal Outcome Test (SNOT). Six prognostic factors: CRS subtypes, serum immunoglobulin (Ig)E level, membered lactone ring of macrolides, concurrent endoscopic sinus surgery (ESS), and dosage and duration of the LDMs were assessed by subgroup analyses.

Results

Ten studies (608 patients) met the inclusion criteria. LDMs and placebo were not different in SNOT improvement (standardized mean difference [SMD] = −0.23, 95% confidence interval [CI]: −0.69 to 0.24). Subgroup analyses showed that the effects favored LDMs in the patients with CRS without polyps (SMD = −0.64, 95% CI: −1.01 to −0.27) compared to CRS with polyps, and the patients receiving a half dose (SMD = −0.64, 95% CI: −1.01 to −0.27) compared to a very low dose. There was no difference in SNOT improvement between LDMs plus standard treatment compared to standard treatment (SMD = −0.52, 95% CI: −1.57 to 0.53). Subgroup analyses showed that the effects favored LDMs in the patients receiving LDMs for a duration of 24 weeks (SMD = −1.68, 95% CI: −2.40 to −0.95) compared to 8 and 12 weeks. There was no difference between the 14‐membered and 15‐membered ring LDMs. Assessment of concurrent ESS found mixed results. Serum IgE level could not be assessed.

Conclusions

LDMs provided favorable outcomes in patients with CRS without polyps. A half dose of macrolides should be given for a duration of 24 weeks.

Level of Evidence

1a Laryngoscope, 2019



http://bit.ly/2Sq8YL3

In reference to pH‐neutralizing esophageal irrigations as a novel mitigation strategy for button battery injury



http://bit.ly/2DumByC

Identification of Four Novel Mutations in MYO7A Gene and Their Association with Nonsyndromic Deafness and Usher Syndrome 1B

Publication date: Available online 11 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Yunlong Li, Jie Su, Chao Ding, Fangqing Yu, Baosheng Zhu

Abstract
Introduction

MYO7A gene has been shown to be associated with Usher syndrome 1B and nonsyndromic deafness. Although a lot of mutations have been reported in MYO7A gene, novel MYO7A mutations are continuously to be identified.

Methods

Targeted next generation sequencing was performed on the two unrelated patients with Usher syndrome 1B and nonsyndromic deafness respectively. The identified mutations from targeted next generation sequencing were further validated by Sanger sequencing, and analyzed by bioinformatics tools, like SIFT, Polyphen-2, PyMOL, I-Mutant 2.0 and so on.

Results

By analyzing the sequencing data of these two patients, four novel MYO7A mutations were revealed: (i) MYO7A p.Tyr560Ser and p.Ala2039Pro were associated with Usher syndrome 1B. (ii) MYO7A c.2187 +2_+8 delTGAGCAC and p.Leu728Pro were related to nonsyndromic hearing loss. These mutations were further proved to be possibly disease-causing by segregation analysis, conservation analysis and bioinformatics tools.

Conclusions

Four novel MYO7A mutations were identified in the present study. These findings provided new evidence for the genetic counseling of Usher syndrome 1B and nonsyndromic deafness.



http://bit.ly/2UUitia

Comparison of three different surgical techniques for designing pharyngeal flaps according to findings of videonasopharyngoscopy and multiplanar videofluoroscopy

Publication date: Available online 11 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Pablo Antonio Ysunza, Kongkrit Chaiyasate, Matthew Rontal, Kenneth Shaheen, Blake Bartholomew

Abstract
Background

Velopharyngeal insufficiency (VPI) occurs when the velopharyngeal sphincter (VPS) is unable to completely seal anatomical closure between the nasal and oral cavities during speech. Palatal repair can restore VPS function but the prevalence of VPI after repair has been reported ranging from 20% to 40%. The combination of flexible videonasopharyngoscopy (FVNP) and multiplanar videofluoroscopy (MPVF) has been reported as the best approach for assessing the VPS mechanism and planning effective surgical procedures aimed to correct VPI.

Objective

To study the outcome of three different techniques for performing pharyngeal flaps with the common denominator of individually designing the flap according to findings of VFNP and MPVF.

Material and Methods

A total of 140 cases of pharyngeal flap surgery were reviewed. Three surgeons performed 3 different surgical techniques. All cases underwent nasometry, VNP and MPVF preoperatively. All surgical procedures were carefully planned and designed according to findings of VNP and MPVF.

Results

Nasal emission was completely eliminated in all cases. One-hundred-thirty-four patients (95%) demonstrated mean nasalance within normal limits after the surgical procedure whereas 6 patients persisted with mean nasalance scores above reference values postoperatively. There were no intraoperative or postoperative complications in any of the cases. No clinical data of sleep disordered breathing was detected in any of the cases after 2 months of postoperative follow-up. However, one case presented with clinical data of sleep disordered breathing 8 months postoperatively.

Conclusions

The results of this study suggest that as long as pharyngeal flaps are being designed according to the findings of imaging procedures, different surgical techniques can provide similar successful outcomes with minimal complications.



http://bit.ly/2E4cxO4

The anatomical and radiological evaluation of the Vidian canal on cone-beam computed tomography images

Abstract

Introduction

The aim of this study is to explore the anatomy of the Vidian nerve to elucidate the appropriate surgical approach based on preoperative cone-beam computed tomography (CBCT) images.

Materials and methods

The Vidian canal and its surrounding structures were morphometrically evaluated retrospectively in CBCT images of 400 cases by the Planmeca Romexis program. The types of the Vidian canal were determined and seven parameters were measured from the images.

Results

Three types of the Vidian canal according to the relationship with the sphenoid bone were found as follows: the Vidian canal totally protruded into the sphenoid sinus (19.75%), partially protruded into sphenoid sinus (44.37%) and embedded inside bony tissue of the body of sphenoid bone (35.87%). The position of the Vidian canal was medial (34.62%), on the same line (55.12%) and lateral (10.25%) to the medial plate of the pterygoid process. The distance between the Vidian canal and the vomerine crest, the mid-sagittal plane, the round foramen, the palatovaginal canal, and the superior wall of the sphenoid sinus, the length of the Vidian canal and the angle between the Vidian canal and the sagittal plane was found to be 16.69 ± 2.14, 13.80 ± 2.00, 8.88 ± 1.60, 5.83 ± 1.37, 23.98 ± 2.68, 13.29 ± 1.71 mm and 25.78° ± 3.68° in males, 14.62 ± 1.66, 11.43 ± 1.28, 8.51 ± 1.63, 5.78 ± 0.57, 22.37 ± 2.07, 12.91 ± 1.26 mm and 23.43° ± 3.07° in females, respectively.

Conclusions

Our results may assist with proper treatment for surgical procedures around the Vidian canal with a high success rate and minimal complications. Therefore, the results obtained in this study contribute to the literature.



http://bit.ly/2BxwJ9H

Sialendoscopy plus laser lithotripsy in sialolithiasis of the submandibular gland in 64 patients: A simple and safe procedure

Publication date: Available online 11 February 2019

Source: Auris Nasus Larynx

Author(s): Thomas Guenzel, Stephan Hoch, Niels Heinze, Thomas Wilhelm, Christian Gueldner, Achim Franzen, Annekathrin Coordes, Anja Lieder, Susanne Wiegand

Abstract
Objective

To demonstrate the safety and efficiency of holmium laser-assisted lithotripsy during sialendoscopy of the submandibular gland using a retrospective, interventional consecutive case series.

Methods

We performed 374 sialendoscopies between 2008 and 2015 and evaluated all patients regarding clinical symptoms, clinical findings, therapy and outcome. We performed 109 procedures of holmium laser-assisted lithotripsy in 64 patients whose sialoliths measured 5 mm or more in diameter. In addition to retrospective case note reviews, we performed telephone interviews of all patients in January 2017.

Results

We performed 374 consecutive submandibular gland sialendoscopy procedures in 276 patients between 2008 to 2015. Sialolithiasis had either previously been diagnosed, or symptoms highly suggestive of sialolithiasis of the submandibular gland presented in 197 patients.

Holmium laser-assisted Laser lithotripsy was performed in 109 cases (64.9%). Smaller mobile concrement was removed directly either by forceps or wire basket, or following marsupialisation of the submandibular duct. This was the case in 88 patients (29.1%). Three patients (0.8%) required surgical removal of the submandibular gland due to early abscess. The majority of patients (n = 374 procedures; 90.1%) remained symptom-free after two or more years following intervention. In the remaining procedures (n = 37 procedures; 9.9%), patients reported discreet postprandial problems but did not seek medical attention. In total, we managed to preserve the submandibular gland and avoid open surgery in 99% of patients through endoscopic management of submandibular concrement and duct stenosis.

Conclusion

Holmium laser-assisted lithotripsy is a simple, safe, and effective procedure for treating patients with sialolithiasis of the submandibular gland. Removal of the gland is rarely required, and removing the gland without prior sialendoscopy is no longer recommended. It should be offered to all patients with submandibular gland sialolithiasis, or such patients should be referred to the appropriate centre for sialendoscopy before submandibulectomy is considered.



http://bit.ly/2IaND3t

Feasibility of transnasal flexible carbon dioxide laser surgery for laryngopharyngeal lesions

Publication date: Available online 11 February 2019

Source: Auris Nasus Larynx

Author(s): Koji Araki, Masayuki Tomifuji, Kosuke Uno, Hiroshi Suzuki, Yuya Tanaka, Shingo Tanaka, Eiko Kimura, Akihiro Shiotani

Abstract
Objective

The fiber-guided carbon dioxide (CO2) laser is a useful device for laryngopharyngeal surgery. The flexible CO2 wave-guide laser has been developed and commercially available for several years. However, the transnasal use of CO2 flexible wave-guided laser surgery through the instrument channel of a flexible endoscope (CO2 TNFLS) is not permitted in Japan. This feasibility study aimed to assess the value and the safety of an in-office CO2 TNFLS procedure.

Methods

Patients with small laryngopharyngeal diseases were enrolled from June 2015. Eligible patients had indications with lesions generally localized superficial lesions such as the benign tumor, leukoplakia, and premalignant lesion-like carcinoma in situ (CIS). Patients were locally well anesthetized using xylocaine. After removing as much of the lesion(s) as possible with flexible forceps, the remainder of the lesions were evaporated using CO2 TNFLS through the instrument channel of a flexible endoscope under local anesthesia.

Results

Eighteen surgeries involving 13 patients, including 9 papilloma (7 recurrent respiratory papilloma [RRP]), 2 carcinoma in situ, 1 leukoplakia, and 1 large epiglottic cyst), were performed. Four patients with RRP required multiple surgeries. Except for 3 patients with RRP, all patients achieved disease control without additional intervention. All procedures were completed with no severe adverse events.

Conclusion

Office-based CO2 TNFLS is safe and feasible for patients with laryngopharyngeal pathologies. It is especially valuable for RRP patients with small lesions to avoid surgery under general anesthesia.



http://bit.ly/2BrmpzV

Standardisation of Tinnitus Handicap Inventory in Hindi

Abstract

Tinnitus is defined as perception of sound in ear continuously without presence of any external stimuli. It is mainly due to the activity within central nervous system without any mechanical or vibratory activity that stimulates the cochlea. It is purely subjective phenomenon that cannot be measured by the any physical scale. Tinnitus handicap inventory is very useful tool to measure the severity of impact of tinnitus on person's life. There is lack of questionnaire in Hindi and this work will help a lot in future. The English THI was translated to Hindi by person expert in both English and Hindi. The translated THI was given to 40 people with Hindi as mother tongue for rechecking the words. The final THI (Hindi) was used in assessment of severity in 100 tinnitus patient. The observed data was analysed by using Microsoft excel. Reliability of THI Hindi was high (Pearson correlation .98, test and retest method), factor analysis indicated that TH1 Hindi has unified. The THI Hindi version is reliable. THI Hindi can be used to assessment of severity of tinnitus in Hindi speaking population.



http://bit.ly/2TJ3kAk

A functional gene expression analysis in epithelial sinonasal cancer: Biology and clinical relevance behind three histological subtypes

Publication date: March 2019

Source: Oral Oncology, Volume 90

Author(s): Loris De Cecco, Mara Serena Serafini, Carla Facco, Roberta Granata, Ester Orlandi, Carlo Fallai, Lisa Licitra, Edoardo Marchesi, Federica Perrone, Silvana Pilotti, Pasquale Quattrone, Cesare Piazza, Fausto Sessa, Mario Turri-Zanoni, Paolo Battaglia, Paolo Castelnuovo, Paolo Antognoni, Silvana Canevari, Paolo Bossi

Abstract

Epithelial sinonasal cancers (SNCs) are rare diseases with overlapping morphological features and a dismal prognosis. We aimed to investigate the expression differences among the histological subtypes for discerning their molecular characteristics.

We selected 47 SNCs: (i) 21 nonkeratinizing squamous cell carcinomas (NKSCCs), (ii) 13 sinonasal neuroendocrine cancers (SNECs), and (iii) 13 sinonasal undifferentiated cancers (SNUCs). Gene expression profiling was performed by DASL (cDNA-mediated annealing, selection, extension, and ligation) microarray analysis with internal validation by quantitative RT-PCR (RT-qPCR). Relevant molecular patterns were uncovered by sparse partial-least squares discriminant analysis (sPLS-DA), microenvironment cell type (xCell), CIBERSORT, and gene set enrichment (GSEA) analyses.

The first two sPLS-DA components stratified samples by histological subtypes. xCell highlighted increased expression of immune components (CD8+ effector memory cells, in SNUC) and "other cells": keratinocytes and neurons in NKSCC and SNEC, respectively. Pathway enrichment was observed in NKSCC (six gene sets, proliferation related), SNEC (one gene set, pancreatic β-cells), and SNUC (twenty gene sets, some of them immune-system related). Major neuroendocrine involvement was observed in all the SNEC samples.

Our high-throughput analysis revealed a good diagnostic ability to differentiate NKSCC, SNEC, and SNUC, but indicated that the neuroendocrine pathway, typical and pathognomonic of SNEC is also present at lower expression levels in the other two histological subtypes. The different and specific profiles may be exploited for elucidating their biology and could help to identify prognostic and therapeutic opportunities.



http://bit.ly/2I7amxt

Associations between pre-, post-, and peri-operative variables and health resource use following surgery for head and neck cancer

Publication date: March 2019

Source: Oral Oncology, Volume 90

Author(s): Hoda Badr, Maximiliano Sobrero, Joshua Chen, Tamar Kotz, Eric Genden, Andrew G. Sikora, Brett Miles

Abstract
Objective

We examined associations between pre-, post-, and peri-operative variables and health resource use in head and neck cancer patients.

Methods

Patients (N = 183) who were seen for a pre-surgical consult between January 2012 and December 2014 completed surveys that assessed medical history, a patient-reported outcome measure (PROM) of dysphagia, and quality of life (QOL). After surgery, peri-operative (e.g., tracheostomy, feeding tube) and post-operative (e.g., complications) variables were abstracted from patients' medical records.

Results

Multivariate regression models using backward elimination showed that pre-surgical University of Washington Quality of Life (UW-QOL) Inventory and M.D. Anderson Dysphagia Inventory (MDADI) composite scores, documented surgical complications, and having a tracheostomy, were all significant predictors of hospital length of stay, explaining 57% of the total variance (F(5, 160) = 18.71, p < .001). Male gender, psychiatric history, and lower pre-surgical MDADI scores significantly predicted thirty-day unplanned readmissions (30dUR). Pre-surgical MDADI composite scores also significantly predicted emergencey department (ED) visits within 30 days of initial hospital discharge (p = .02).

Conclusions

Assessment of PROMs and QOL in the pre-surgical setting may assist providers in identifying patients at risk for prolonged LOS and increased health resource use after hospital discharge.



http://bit.ly/2Gm8ZJE

Standardisation of Tinnitus Handicap Inventory in Hindi

Abstract

Tinnitus is defined as perception of sound in ear continuously without presence of any external stimuli. It is mainly due to the activity within central nervous system without any mechanical or vibratory activity that stimulates the cochlea. It is purely subjective phenomenon that cannot be measured by the any physical scale. Tinnitus handicap inventory is very useful tool to measure the severity of impact of tinnitus on person's life. There is lack of questionnaire in Hindi and this work will help a lot in future. The English THI was translated to Hindi by person expert in both English and Hindi. The translated THI was given to 40 people with Hindi as mother tongue for rechecking the words. The final THI (Hindi) was used in assessment of severity in 100 tinnitus patient. The observed data was analysed by using Microsoft excel. Reliability of THI Hindi was high (Pearson correlation .98, test and retest method), factor analysis indicated that TH1 Hindi has unified. The THI Hindi version is reliable. THI Hindi can be used to assessment of severity of tinnitus in Hindi speaking population.



http://bit.ly/2TJ3kAk

Extension patterns of vestibular schwannomas towards the middle ear: three new cases and review of the literature

Abstract

Objective

Middle ear extension of vestibular schwannomas is not a common occurrence, and only a few cases have been described so far in past publications. We report three new cases of vestibular schwannomas extending to the middle ear and reviewed the literature to specify the patterns of such an extension.

Materials and methods

We analysed databases of previously published articles to search for additional cases of middle ear extension of vestibular schwannomas and compared them to the cases we have documented. Extension patterns of the tumours were analysed, especially focusing on the extension through the round and oval windows.

Results and conclusion

Middle ear vestibular schwannomas are uncommon tumours and only 13 cases have been published so far. The vestibular schwannoma (internal auditory canal or intralabyrinthine) has to invade the labyrinth first (complete invasion in 88% of the cases, n = 14), before reaching the middle ear. In the majority of cases (69%, n = 11/16), internal auditory canal vestibular schwannomas or intralabyrinthine schwannomas extended in the middle ear though the round window.



http://bit.ly/2E5NLxh

Post-contrast 3D-FLAIR in idiopathic sudden sensorineural hearing loss

Abstract

Purpose

Our study investigated correlations between clinical characteristics, particularly hearing recovery, interval time between onset and three-dimensional fluid attenuation inversion recovery magnetic resonance imaging (3D-FLAIR MRI), and the signal intensity of post-contrast 3D-FLAIR MRI in patients with idiopathic sudden sensorineural hearing loss (SSNHL).

Methods

The study enrolled 100 SSNHL patients. The signal intensities and asymmetry ratios of the inner ear structures, including the cochleae, vestibules and vestibulocochlear nerve, were evaluated and calculated. The relationships between the clinical characteristics and MRI findings were assessed.

Results

After intravenous gadolinium (Gd) injection, 3D-FLAIR revealed high signal intensities in 65 patients. The corrected asymmetry ratios of cochlea correlated closely with interval time between onset and MRI. The asymmetry ratios of the inner ear structures were significantly lower in patients with final complete to partial hearing recovery. The corrected asymmetry ratios of the inner ear structures correlated with initial/final pure tone audiometry (PTA) and hearing recovery in the affected ear. Notably, it was shown that the corrected asymmetry ratios identified a poor prognosis for hearing recovery, with a sensitivity and specificity of 67.9% and 75.0% in the cochlea, 83.3% and 75.0% in the vestibule, and 52.4% and 81.2% in the vestibulocochlear nerve, respectively.

Conclusions

Post-contrast 3D-FLAIR after intravenous Gd injection in SSNHL can be used to assess the permeability of the blood–labyrinth and blood–nerve barriers. The asymmetry ratios of the inner ear structures may identify patients with poor prognosis for hearing recovery. Signal characteristics are closely related to interval time between onset and MRI.



http://bit.ly/2UUcrhI

The speed limit of outer hair cell electromechanical activity

Abstract

The outer hair cell of Corti's organ provides mechanical feedback into the organ to boost auditory perception. The fidelity of voltage-dependent motility has been estimated to extend beyond 50 kHz, where its force generation is deemed a requirement for sensitive high-frequency mammalian hearing. Recent investigations have shown, however, that the frequency response is substantially more low pass at physiological membrane potentials where the kinetics of prestin impose their speed limit. Nevertheless, it is likely that the reduced magnitude of electromotility is sufficient to drive cochlear amplification at high frequencies.



http://bit.ly/2SL7HxA

In Response to pH‐Neutralizing Esophageal Irrigations as a Novel Mitigation Strategy



http://bit.ly/2SN9K3W

Δευτέρα 11 Φεβρουαρίου 2019

The microRNA-375 as a potentially promising biomarker to predict the prognosis of patients with head and neck or esophageal squamous cell carcinoma: a meta-analysis

Abstract

Background

The prognostic value of microRNA-375 (miR-375) expression in squamous cell carcinoma (SCC) had been reported in the previous studies; however, the results remain inconsistent. This study was performed to investigate the prognostic significance of miR-375 expression in SCC based on all eligible evidences.

Methods

Relevant studies were identified by searching PubMed, Embace, Medline, Cochrane Library, and China Biology Medicine disk. Survival outcome including overall survival (OS) and other survival outcomes were used as the primary endpoint to evaluate the prognostic outcome of patients with SCC. All statistical analyses were performed in RevMan software version 5.3 and STATA software version 14.1. Furthermore, the quality of included studies was assessed by The Newcastle–Ottawa Scale.

Results

In total, 13 studies, including 1340 patients, met the inclusion criteria for our meta-analysis. The pooled analysis results indicated that downregulation of miR-375 significantly predicted poor OS (HR 1.58, 95% CI 1.34–1.88, P < 0.001). Downregulated miR-375 was also correlated with the other survival outcomes. Subgroup analysis based on tumor type found that lower expression of miR-375 was significantly related with poor OS in patients with esophageal squamous cell carcinoma (ESCC) (HR 1.58, 95% CI 1.29–1.94, P < 0.001) and head and neck squamous cell carcinoma (HNSCC) (HR 1.59, 95% CI 1.16–2.18, P = 0.004).

Conclusions

This meta-analysis demonstrated that the downexpression of miR-375 was significantly correlated with poor OS in patients with SCCs and indicated the potential clinical use of miR-375 as a molecular biomarker, particularly in assessing prognosis for patients with ESCC and HNSCC.



http://bit.ly/2E58DVf

Propofol and isoflurane on intraoperative motor evoked potentials

The effects of propofol and isoflurane on intraoperative motor evoked potentials during spinal cord tumour removal surgery - A prospective randomised trial p. 92
Parthiban Velayutham, Verghese T Cherian, Vedantam Rajshekhar, Krothapalli S Babu
DOI:10.4103/ija.IJA_421_18  
Background and Aims: Transcranial electrical stimulation (TES) elicited intraoperative motor evoked potentials (iMEPs), are suppressed by most anaesthetic agents. This prospective randomised study was carried out to compare the effects of Isoflurane and Propofol on iMEPs during surgery for spinal cord tumours. Methods: A total of 110 patients were randomly divided into two groups. In group P, anaesthesia was maintained with intravenous propofol (6.6 ± 1.5 mg/kg/hr) and in group I anaesthesia was maintained with isoflurane (0.8 ± 0.1% minimal alveolar concentration (MAC). An Oxygen- air mixture (FiO2-0.3) was used in both groups. TES-iMEPs were recorded from tibialis anterior, quadriceps, soleus and external anal sphincter muscles in 60 of 90 patients. Statistical analysis was performed with Pearson correlation and Paired 't' tests. Results: Successful baseline iMEPs were recorded in 74% of patients in Group P and in 50% of patients in Group I. Age and duration of symptoms influenced the elicitation of baseline iMEPs under isoflurane (r = −0.71, −0.66 respectively, P < 0.01) as compared to propofol (r = −0.60, −0.50 respectively, P < 0.01). The mean stimulus strength required to elicit the baseline iMEPs were lesser in propofol (205 ± 55Volts) as compared to isoflurane (274 ± 60 Volts). Suppression of the iMEP responses was less under propofol (7.3%) as compared to isoflurane anaesthesia (11.3%) in patients with no preoperative neurological deficits. Conclusion: iMEPs are better maintained under propofol anaesthesia (6-8 mg/kg/hr) when compared with isoflurane (0.7-0.9 MAC). in patients undergoing surgery for excision of spinal cord tumours.

Analgesia nociception index and systemic haemodynamics during anaesthetic induction and tracheal intubation

: A secondary analysis of a randomised controlled trial p. 100
Kamath Sriganesh, Kaushic A Theerth, Madhusudan Reddy, Dhritiman Chakrabarti, Ganne Sesha Umamaheswara Rao
DOI:10.4103/ija.IJA_656_18  
Background and Aims: Direct laryngoscopy and tracheal intubation is a noxious stimulation that induces significant stress response. Currently, this nociceptive response is assessed mainly by haemodynamic changes. Recently, analgesia nociception index (ANI) is introduced into anaesthesia practice and provides objective information about parasympathetic (low nociceptive stress) and sympathetic (high nociceptive stress) balance, which reflects the degree of intraoperative nociception/analgesia. This study evaluated the changes in ANI and haemodynamics during anaesthetic induction and intubation, and their correlation during tracheal intubation. Methods: Sixty adult patients scheduled for elective brain tumour surgery under general anaesthesia were studied for changes in ANI, heart rate (HR) and mean blood pressure (MBP) during anaesthetic induction and intubation. This was a secondary analysis of a previously published trial. Linear mixed effects model was used to evaluate changes in ANI, HR and MBP and to test correlation between ANI and haemodynamics. Results: Anaesthetic induction reduced ANI (but not below the critical threshold of nociception of 50) and MBP, and increased the HR (P < 0.001). Direct laryngoscopy and tracheal intubation resulted in increase in HR and MBP with decrease in ANI below the threshold of 50 (P < 0.001). A linear negative correlation was observed between ANI and HR; r = −0.405, P < 0.001, and ANI and MBP; r = −0.415, P= 0.001. Conclusion: Significant changes are observed in ANI during anaesthetic induction and intubation. There is a negative linear correlation between ANI and systemic haemodynamics during intubation.