Clinical Oral Investigations

Correction to: Induced surface proteins of Staphylococcus epidermidis adhering to titanium implant substrata There is a mistake in the original published version of this article. The word 'Streptococcus' in the article title should have been 'Staphylococcus'.

Clinical investigation of gustatory and neurosensory alterations following mandibular third molar surgery: an observational prospective study Abstract Objective This study aimed to prospectively observe gustatory and neurosensory alterations following surgical removal of mandibular third molars. Material and methods A prospective clinical study was conducted with patients who required mandibular third molar extraction, recruited from the Division of Oral and Maxillofacial Surgery at the Federal University of Ceará (Brazil). Age, sex, and radiographic signs were recorded. The outcome variables were the presence or absence of gustatory and neurosensory alterations. The patients were observed preoperatively and at 7, 30, 90, and 180 days postoperatively by using gustatory and neurosensory tests. Results The response to sweet (p = 0.509) and sour (p = 0.078) stimulus did not alter significantly over time. The salty threshold significantly increased from the preoperative to 7- and 30-day postoperative periods, returning to baseline values at 90 days postoperatively (p = 0.038). The bitter threshold increased significantly from the preoperative to 7-day postoperative period, returning to baseline values at 30 days after surgery (p < 0.001). Regarding neurosensory evaluation, there was an altered response to stimulus at 7 days postoperatively in specific studied areas, returning to baseline values 30 days after surgery (p < 0.05). Conclusion The present study shows that mandibular third molar removal was associated with slight sensory disturbances related to mechanical, tactile, and gustatory perception. Regarding the recovery period, all patients returned to normal function without intervention, over a period ranging from 30 to 90 days. Clinical relevance This study highlighted the importance of a sensory evaluation following removal of third molars, notably regarding mechanical perception and gustatory threshold assessment.

In vivo Raman spectroscopic characteristics of different sites of the oral mucosa in healthy volunteers Abstract Objectives Investigate the biochemistry of in vivo healthy oral tissues through Raman spectroscopy. We aimed to characterize the biochemical features of healthy condition in oral subsites (buccal mucosa, lip, tongue, and gingiva) of healthy subjects. More specifically, we investigated Raman spectral characteristics and biochemical content of in vivo healthy tissues on Brazilian population. This characterization can be used to better define normal tissue and improve the detection of oral premalignant conditions in future studies. Materials and methods For spectroscopic analysis a Raman spectrometer (Kaiser Optical Systems imaging spectrograph Holospec, f / 1.8i-NIR) coupled with a laser 785 nm, 60 mW was used. Raman measurements were obtained by means of an optical fiber (EMVision fiber optic probe) coupled between the laser and the spectrometer. Three spectra per site were acquired from the lip, buccal mucosa, tongue, and gingiva of ten healthy volunteers. This resulted in 30 spectra per oral sub-site and in total 120 spectra. Results We report detailed biochemical information on these subsites and their relative composition based on deconvolution studies of their spectra. Finally, we also report classification efficiency of 61, 83, 41, and 93% for buccal, gingiva, lip, and tongue respectively after applying multivariate statistical tools. Conclusions We quantitated the contribution of various biochemicals in terms of percentage, and this will enable comparison not only across anatomical sites but also across studies. Raman spectroscopy can rapidly probe tissue biochemistry of healthy oral regions. Moreover, the study suggests the possibility of using Raman spectroscopy combined with signal processing and multivariate analysis methods to differentiate the oral sites in healthy conditions and compare with pathological conditions in future studies. Clinical relevance The spectral characterization of the healthy condition of oral tissues by a noninvasive, label-free, and real-time analytical techniques is important to create a spectral reference for future diagnosis of pathological conditions.

Prolyl hydroxylase inhibitor DMOG suppressed inflammatory cytokine production in human gingival fibroblasts stimulated with Fusobacterium nucleatum Abstract Objective Fusobacterium nucleatum (F. nucleatum) is one of the most common bacteria involved in the initiation and progression of periodontal diseases. Pharmacological inhibitor of prolyl hydroxylases (PHDs), dimethyloxallyl glycine (DMOG), has been reported to exert anti-inflammatory effects. The aim of this investigation was to evaluate the role of DMOG in inflammatory cytokine production of human gingival fibroblasts (HGFs) stimulated with F. nucleatum. Material and methods HGFs were pretreated with 10, 50, and 100 μM DMOG for 24 h before infected with F. nucleatum (MOI = 100). Cell morphology and survival after infection with F. nucleatum were determined by crystal violet staining assay. The mRNA levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and IL-1β were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The production of IL-6, IL-8, TNF-α, and IL-1β was assessed by enzyme-linked immunosorbent assay (ELISA). Results F. nucleatum did not affect the morphology and survival of HGFs by the concentrations of MOI (multiplicity of infection) = 10, 50, and 100. The mRNA levels of IL-6, IL-8, TNF-α, and IL-1β were significantly enhanced with the stimulation of F. nucleatum, and the maximal effect reached at 6 h. The secretion of IL-6, IL-8, and TNF-α was significantly upregulated by the infection of F. nucleatum while the production of IL-1β was nearly unchanged. Above all, DMOG suppressed F. nucleatum-stimulated IL-6, IL-8, TNF-α, and IL-1β expressions. Conclusions These data indicate that prolyl hydroxylase inhibitor DMOG partly downregulates inflammatory cytokine expression in F. nucleatum-infected HGFs. Clinical relevance DMOG may provide a novel strategy for the therapy of periodontitis.

Post-obturation pain following the use of carrier-based system with AH Plus or iRoot SP sealers: a randomized controlled clinical trial Abstract Objectives The aim of this study was to compare the postoperative pain after root canal treatment using a carrier-based obturation system and two different sealers. Materials and methods In this prospective randomized clinical trial, 160 patients were selected. Patients with vital and devital teeth were randomized into four groups using a randomized block design with block sizes of 10 patients each. The groups were devital/vital teeth treated with iRoot SP sealer and devital/vital teeth treated with AH Plus sealer. Patients were prescribed ibuprofen, a 200-mg analgesic, if needed, and postoperative pain was recorded by visual analogue scale at 6, 12, 24, and 72 h after obturation. Pain score and frequency of tablet intake were recorded and statistically analyzed. Results Results showed that there was no significant difference between groups in the incidence of postoperative pain; however, iRoot SP sealer was associated with less analgesic intake compared to AH Plus sealer. Conclusion The use of different sealers did not significantly affect pain levels. Clinical relevance iRoot SP sealer was associated with less analgesic intake compared to AH Plus sealer.

The role of immediate versus secondary removal of the odontogenic focus in treatment of deep head and neck space infections. A retrospective analysis of 248 patients Abstract Objectives Aim of this study was to investigate conditions and predisposing factors for head and neck infection progress regarding the length of stay (LOS) in hospital, with special emphasis on the time of removal of the odontogenic infection focus. Material and methods A 3-year retrospective study reviewed hospital records of 248 subjects who were treated under inpatient conditions with severe odontogenic infections who received surgical incisions, drainage, and intravenous (IV) antibiotics. Outcomes measured included age, gender, involved fascial spaces, LOS, number of infected spaces, antibiotics administered, and comorbidities. We precisely recorded the time between abscess incision and focus extraction. Results Removal of infection focus (tooth) in the same stay (1 stay, n = 106; group 1; mean 6.5 days ± 3) showed significantly higher (p = 0.042) LOS than extraction in a second stay (2 stays, n = 46; group 2; 5.3 ± 3.1). Group 3 patients showed infection after removal of teeth in outpatient management (1 stay ex-op, n = 96) and presented significantly lower LOS (5.6 ± 2.5) compared to group 1 (p = 0.0216). LOS of group 3 to group 2 patients showed no significance (p = 0.668). Infection expansion and diabetes showed a significant increase of LOS. Conclusion Simultaneous removal of infection focus and abscess incision leads to the lowest LOS. If tooth extraction is performed after incision, subsequent focus extraction performed in a second stay shows lower overall-LOS than extraction at the same stay at later stage. Clinical relevance Multiple factors tend to increase the LOS of patients with severe head and neck infections of odontogenic origin. Our data reveals the role of removal of odontogenic focus and additionally ranks further parameters that influence the LOS. Based on our findings, decisions regarding the surgical treatment can be recommended.

The influence of enamel sandblasting on the shear bond strength and fractography of the bracket-adhesive-enamel complex tested in vitro by the DIN 13990:2017-04 standard Abstract Objectives This study was conducted in order to investigate whether enamel sandblasting as an adjunct or substitute to the acid-etch technique has an effect on the shear bond strength (SBS) and fractography of the bracket-adhesive-enamel complex using the DIN 13990:2017-04 standard. Materials and methods Upper central incisor brackets (discovery®, Dentaurum, Germany) were bonded using Transbond XT™ (3M Unitek, Germany) on bovine incisors prepared by four different methods (15 samples each): sandblasting with 27 μm Al2O3 at 1.2 bar (s), acid etching with 37.4% phosphoric acid (a), sandblasting with 27 μm Al2O3 at 1.2 bar followed by acid etching (s1a), and sandblasting with 50 μm Al2O3 at 5.7 bar followed by acid etching (s2a). The SBS and adhesive remnant index (ARI) were measured, followed by one-way analysis of variance and Fisher's exact tests at 5%. Results The SBS in groups s (5.6 ± 2.2 MPa), a (17.1 ± 4.3 MPa), s1a (18.3 ± 4.3 MPa), and s2a (18.5 ± 4.6 MPa) indicated that the s group was significantly inferior to all the other groups (p < 0.001). Likewise, the ARI analysis indicated a different performance of the s group (mostly ARI of 0) compared to the other groups (p < 0.001) and a tendency for different ARI between the a and s1a/s2a groups. Conclusions In vitro enamel sandblasting could not substitute acid etching and did not offer improved SBS when used before acid etching, regardless of air pressure and powder granulation. Sandblasting without acid etching produced less residual resin on the tooth after debonding. Clinical relevance The clinical use of adjunct enamel sandblasting prior to etching to enhance SBS has to be questioned.

Application of a standard autoclaving protocol does not harm structural integrity of two-piece zirconia abutments under detachment force testing Abstract Objective Aim was to assess the influence of a standard autoclaving protocol on the retention of zirconia abutments glued on titanium bases in two-piece implant abutments. Materials and methods Twenty-four CAD/CAM-generated zirconia abutments were adhesively cemented on prefabricated titanium bases. Before mechanical and thermal aging, the specimens were divided into two groups. Group 1 was subjected to a standard steam autoclaving protocol and Group 2 remained untreated (control). The tensile strength in all specimens was evaluated by a standardized pull-off test limited to a maximum force of 1000 N. Results Eleven samples in both groups could be subjected to pull-off testing. Ten samples in Group 1 and three samples in Group 2 failed, while all others reached the maximum pull-off force. This difference was statistically significant. The mean retention values for the failed samples were 694.53 ± 369.10 N in Group 1 and 890.78 ± 25.90 N in Group 2. This difference was not statistically significant. Conclusions A standard autoclaving protocol does not reduce detachment force of two-piece zirconia abutments. Clinical relevance Clinical sterilization processes as recommended by regulatory authorities seem to be harmless to the structural integrity of two-piece zirconia implant abutments, at least with regard to the retention of the components.

Micro-CT comparison of XP-endo Finisher and passive ultrasonic irrigation as final irrigation protocols on the removal of accumulated hard-tissue debris from oval shaped-canals Abstract Objective To compare the effectiveness of the XP-endo Finisher instrument and passive ultrasonic irrigation (PUI) as final irrigation protocols on the removal of accumulated hard-tissue debris (AHTD) from oval-shaped canals using micro-computed tomographic (micro-CT) analysis. Methods Twenty mandibular incisors were anatomically pair-matched based on similar morphological dimensions (length, volume, aspect ratio, and configuration) through micro-CT analysis, prepared with Reciproc R25 instrument, scanned again, and assigned to one of the two experimental groups (n = 10), according to the final irrigation protocol: XP-endo Finisher and PUI. After the final irrigation protocols, the specimens were rescanned and the registered datasets were examined to quantify the amount of AHTD. Data were statistically analyzed using Student's t test with a significance level of 5%. Results The final irrigation protocols were highly similar in terms of volumetric percentage reduction of AHTD (P = 1.000). Conclusions XP-endo Finisher and PUI showed the same effectiveness on the removal of AHTD. None of the tested final irrigation protocols completely removed the AHTD from oval-shaped root canals. Clinical relevance AHTD may be considered clinically relevant because it could harbor bacterial contents away from the disinfection procedures. Both final irrigation protocols were effective on the removal of AHTD.

Treatment of intrabony defects with modified perforated membranes in aggressive periodontitis: subtraction radiography outcomes, prognostic variables, and patient morbidity Abstract Objectives The main objectives of this study were (1) to evaluate bone/graft density alterations by digital subtraction radiography; (2) to determine factors associated with favorable clinical and radiographic outcomes, and (3) to report on patient morbidity after guided tissue regeneration (GTR) in aggressive periodontitis (AgP) patients. Materials and methods Adapting a split-mouth design, 30 comparative intrabony defects in 15 patients were randomly treated with xenogenic graft plus modified perforated membranes (MPM, tests) or xenogenic graft plus standard collagen membranes (CM, controls). The time period of observation was 12 months. Results There were significant improvements in clinical and radiographic parameters within each group, without intergroup differences. However, higher PPD reduction for three-wall defects was noted in MPM sites (5.22 versus 3.62 mm; p = 0.033). Moreover, a significant gain in bone/graft density of 4.9% from 6 to 12 months post-operatively was observed in test sites. Multivariate analysis demonstrated that morphology of intrabony defects was a predictor of CAL gain (p = 0.06), while independent prognostic variables effecting changes in bone/graft density were radiographic defect depth (p = 0.025) and radiographic angle (p = 0.033). The majority of patients reported some discomfort, pain, and edema with mild intensity without any significant differences between treatment modalities. Conclusions This study demonstrated enhanced bone/graft density gain after GTR with MPM, which may indicate greater area of new bone formation. Independent variables effecting treatment outcomes were intrabony defect morphology, radiographic defect depth, and radiographic angle. Clinical relevance This study supports the regenerative treatment of intrabony defects in AgP patients and identifies some variables with prognostic value.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Cancer

Dual inhibition of the PI3K and MAPK pathways enhances nab-paclitaxel/gemcitabine chemotherapy response in preclinical models of pancreatic cancer Publication date: 10 September 2019 Source: Cancer Letters, Volume 459 Author(s): Niranjan Awasthi, David Kronenberger, Alexis Stefaniak, Md Sazzad Hassan, Urs von Holzen, Margaret A. Schwarz, Roderich E. Schwarz Abstract Standard chemotherapy for pancreatic ductal adenocarcinoma (PDAC), nab-paclitaxel (NPT) plus gemcitabine (Gem), has led to an average survival of 8.5 months. Presently, no therapeutics exist that effectively target the KRAS oncogene, activated in 95% of PDACs, but alternative strategies focus on inhibition of downstream effectors of KRAS signaling. Through combined inhibition of PI3K and MAPK signaling with MK-2206 (MK) and trametinib (Tra), enhancement of NPT + Gem response was evaluated. Median animal survival was significantly improved by the NPT + Gem combination (67% increase). Addition of MK-2206 or trametinib further increased median survival: NPT + Gem + MK (86%), NPT + Gem + Tra (105%), and NPT + Gem + MK + Tra (129%). In cell line-derived xenografts, the net tumor growth (in mm3) compared to controls (878.5) was significantly reduced by NPT + Gem (191.2), NPT + Gem + MK (150.7), NPT + Gem + Tra (62.2) and NPT + Gem + MK + Tra (49.9) therapies. In patient-derived xenografts, the combination of MK-2206 and trametinib with chemotherapy had an additive response in reducing tumor growth. Effects of therapy on tumor cell proliferation and apoptosis corresponded with tumor growth inhibition. These findings suggest that the standard chemotherapy response of PDAC can be enhanced through dual targeting of PI3K and MAPK signaling, which could lead to improved PDAC therapy.

p53-dependent upregulation of miR-16-2 by sanguinarine induces cell cycle arrest and apoptosis in hepatocellular carcinoma Publication date: 10 September 2019 Source: Cancer Letters, Volume 459 Author(s): Beilei Zhang, Xinan Wang, Jiacong Deng, Haifeng Zheng, Wei Liu, Si Chen, Jie Tian, Fu Wang Abstract MicroRNAs (miRNAs) were involved in cancer progression, and the targeting of miRNAs by natural agents has opened avenues for cancer treatment and drug development. miR-16 functions as a tumor suppressor and is frequently deleted or downregulated in various human cancers, including hepatocellular carcinoma (HCC). In the present study, we employed a miR-16-responsive luciferase reporter to screen candidate compounds that modulate miR-16 expression from a natural product library. One compound, sanguinarine (SG), was capable of activating miR-16 in HCC cells with wildtype or mutated p53 expression but not in p53-deleted HCC cells. Mechanistic investigations revealed that SG increased p53 occupancy on the miR-16-2 promoter and decreased the expression of miR-16 target genes, including Bcl-2 and cyclin D1. Moreover, SG significantly inhibited HCC cell proliferation in a p53-dependent manner by inducing cell cycle arrest and reactive oxygen species (ROS)-associated apoptosis. Silencing miR-16 by treatment with anti-miR16 miRNA inhibitors rescued the cell viability repression effect caused by SG. Importantly, SG dramatically suppressed tumor growth in an HCC xenograft model, with little cytotoxicity. Taken together, our results provide a preclinical proof-of-concept for SG as a potential strategy for HCC treatment based on the restoration of miR-16 tumor suppressor function.

Exosomal transfer of miR-501 confers doxorubicin resistance and tumorigenesis via targeting of BLID in gastric cancer Publication date: 10 September 2019 Source: Cancer Letters, Volume 459 Author(s): Xu Liu, Ying Lu, Yunchao Xu, Sizhu Hou, Jinli Huang, Bo Wang, Jinyao Zhao, Shilin Xia, Shujun Fan, Xiaotang Yu, Yue Du, Li Hou, Zhiyue Li, Zijie Ding, Shuo An, Bo Huang, Lianhong Li, Jianwu Tang, Jingfang Ju, Hongwei Guan Abstract Exosomal transfer of oncogenic miRNAs can enhance recipient cell growth, metastasis and chemoresistance. Currently we found that microRNA-501-5p (miR-501) was overexpressed in doxorubicin-resistant gastric cancer (GC) SGC7901/ADR cell-secreted exosomes (ADR Exo) than that in SGC7901 cell-secreted exosomes (7901 Exo). ADR Exo was internalized by SGC7901, and a Cy3-miR-501 mimic was transferred from SGC7901/ADR to SGC7901 via exosomes. ADR Exo conferred doxorubicin resistance, proliferation, migration and invasion abilities to negative control miRNA inhibitor-expressing GC cells, whereas it inhibited apoptosis. MiR-501 knockdown or BH3-like motif-containing protein, cell death inducer (BLID) overexpression could reverse the effects of ADR Exo on recipient cells. SGC7901 cells cocultured with SGC7901/ADR prior to treatment with GW4869 or transfection of a miR-501 inhibitor were sensitive to doxorubicin and exhibited attenuated proliferation, migration and invasion and increased apoptosis. The intratumoral injection of ADR Exo into negative control miRNA inhibitor-expressing SGC7901 cells induced rapid subcutaneous tumor growth and resistance to doxorubicin compared to that of miR-501 knockdown or BLID-overexpressing cells. This effect is possibly achieved by exosomal miR-501-induced downregulation of BLID, subsequent inactivation of caspase-9/-3 and phosphorylation of Akt. Exosomal miR-501 might be a therapeutic target for GC.

MLKL attenuates colon inflammation and colitis-tumorigenesis via suppression of inflammatory responses Publication date: 10 September 2019 Source: Cancer Letters, Volume 459 Author(s): Qun Zhao, XianJun Yu, Ming Li, YongBo Liu, YaMei Han, XiXi Zhang, Xiao Ming Li, XiaoXia Wu, Jun Qin, Jing Fang, Haibing Zhang Abstract The mixed lineage kinase domain-like protein (MLKL) has emerged as a critical mediator of necroptosis, which results in the release of cellular damage-associated molecular patterns (DAMPs). However, its physiological role in regulating inflammation is not fully understood. We herein showed that Mlkl−/− mice were highly susceptible to colitis and colitis-associated tumorigenesis (CAT), which was associated with massive leukocyte infiltration and increased inflammatory responses. Moreover, we used bone marrow transplantation to reveal that MLKL in inflammatory cells is crucial for its role on colitis. Intestinal mucosal tissue and polyps isolated from Mlkl−/− mice exhibited increased ERK activation and elevated expression of genes associated with inflammation and cancer. Mechanistically, enhanced inflammation in Mlkl−/− mice was due to MEK/ERK activation particularly in dendritic cells (DCs). Our results demonstrate the role of MLKL in maintaining intestinal homeostasis and protecting against colitis and tumorigenesis.

Interferon-inducible lncRNA IRF1-AS represses esophageal squamous cell carcinoma by promoting interferon response Publication date: 10 September 2019 Source: Cancer Letters, Volume 459 Author(s): Jianbing Huang, Jiagen Li, Yuan Li, Zhiliang Lu, Yun Che, Shuangshuang Mao, Yuanyuan Lei, Ruochuan Zang, Sufei Zheng, Chengming Liu, Xinfeng Wang, Ning Li, Nan Sun, Jie He Abstract Interferons (IFNs) play crucial roles in the development and treatment of cancer. Long non-coding RNAs (lncRNAs) are emerging molecules involved in cancer progression. Here, we identified and characterized an IFN-inducible nuclear lncRNA IRF1-AS (Interferon Regulatory Factor 1 Antisense RNA) which was positively correlated with IRF1 expression. IFNs upregulate IRF1-AS via the JAK-STAT pathway. Knockdown and overexpression of IRF1-AS revealed that IRF1-AS inhibits oesophageal squamous cell carcinoma (ESCC) proliferation and promotes apoptosis in vitro and in vivo. Mechanistically, IRF1-AS activates IRF1 (Interferon Regulatory Factor 1) transcription through interacting with ILF3 (Interleukin Enhancer Binding Factor 3) and DHX9 (DExH-Box Helicase 9). In turn, IRF1 binds to the IRF1-AS promoter directly and activates IRF1-AS transcription. Global analysis of IRF1-AS–regulated genes indicated that IRF1-AS activates the IFN response in vitro and in vivo. IRF1 knockdown in IRF1-AS–overexpressing cells abolished the antiproliferative effect and activation of the IFN response. Furthermore, IRF1-AS was downregulated in ESCC tissues, and low expression correlated with poor prognosis. In conclusion, the interferon-inducible lncRNA IRF1-AS represses esophageal squamous cell carcinoma progression by promoting interferon response through a positive regulatory loop with IRF1.

Stress hormone-mediated acceleration of breast cancer metastasis is halted by inhibition of nitric oxide synthase Publication date: 10 September 2019 Source: Cancer Letters, Volume 459 Author(s): Renée L. Flaherty, Haya Intabli, Marta Falcinelli, Giselda Bucca, Andrew Hesketh, Bhavik A. Patel, Marcus C. Allen, Colin P. Smith, Melanie S. Flint Abstract Stress hormones have been shown to be important mediators in driving malignant growth and reducing treatment efficacy in breast cancer. Glucocorticoids can induce DNA damage through an inducible nitric oxide synthase (iNOS) mediated pathway to increase levels of nitric oxide (NO). Using an immune competent mouse breast cancer model and 66CL4 breast cancer cells we identified a novel role of NOS inhibition to reduce stress-induced breast cancer metastasis. On a mechanistic level we show that the glucocorticoid cortisol induces expression of keys genes associated with angiogenesis, as well as pro-tumourigenic immunomodulation. Transcriptomics analysis confirmed that in the lungs of tumour-bearing mice, stress significantly enriched pathways associated with tumourigenesis, some of which could be regulated with NOS inhibition. These results demonstrate the detrimental involvement of NOS in stress hormone signalling, and the potential future benefits of NOS inhibition in highly stressed patients.

DEPTOR inhibits cell proliferation and confers sensitivity to dopamine agonist in pituitary adenoma Publication date: 10 September 2019 Source: Cancer Letters, Volume 459 Author(s): Hong Yao, Hao Tang, Yong Zhang, Qiu Fen Zhang, Xin Yi Liu, Yan Ting Liu, Wei Ting Gu, Yong Zhi Zheng, Han Bing Shang, Yu Wang, Jin Yan Huang, Yong Xu Wei, Xun Zhang, Jian Zhang, Zhe Bao Wu Abstract DEP domain-containing mechanistic target of rapamycin (mTOR)-interacting protein (DEPTOR) is an important modulator of mTOR, a highly conserved kinase whose hyperactivation is critically involved in a variety of human tumors. The role of DEPTOR playing in pituitary adenoma (PA) is largely unknown. Here, we reported that DEPTOR was downregulated in PA tissues, especially dopamine-resistant prolactinomas. Consistently, overexpression of DEPTOR inhibited pituitary tumor GH3 and MMQ cells proliferation in vitro and in vivo, and sensitized GH3 and MMQ cells to cabergoline (CAB), a dopamine agonist (DA). Conversely, knockdown of DEPTOR promoted GH3 and MMQ cells proliferation, and conferred cells resistance to CAB. Mechanistically, DEPTOR inhibited both mTOR Complex 1 (mTORC1) and 2 (mTORC2) activities in PA cells. In addition, DEPTOR expression level was increased to suppress mTOR kinase activity via decreasing E3 ubiquitin ligase, βTrCP1, in response to CAB. Furthermore, DEPTOR enhanced autophagy-dependent cell death to confer cells sensitivity to CAB. Taken together, our results suggest that DEPTOR may be a potential target for the treatment of PAs.

Oncolytic Ad co-expressing decorin and Wnt decoy receptor overcomes chemoresistance of desmoplastic tumor through degradation of ECM and inhibition of EMT Publication date: 10 September 2019 Source: Cancer Letters, Volume 459 Author(s): Yan Li, JinWoo Hong, Bo-Kyeong Jung, Eonju Oh, Chae-Ok Yun Abstract Pancreatic cancer is a highly lethal disease. Excessive accumulation of tumor extracellular matrix (ECM) and epithelial-to-mesenchymal transition (EMT) phenotype are two main contributors to drug resistance in desmoplastic pancreatic tumors. To overcome desmoplasia and chemoresistance of pancreatic cancer, we utilized an oncolytic adenovirus (Ad) co-expressing decorin and soluble Wnt decoy receptor (HEmT-DCN/sLRP6). An orthotopic pancreatic xenograft tumor model was established in athymic nude mice using Mia PaCa-2 cells, and the antimetastatic and antitumor efficacy of systemically administered HEmT-DCN/sLRP6 was evaluated. Immunohistochemical analysis of tumor tissues was performed to assess ECM degradation, induction of apoptosis, viral dispersion, and inhibition of the Wnt/β-catenin signaling pathway. HEmT-DCN/sLRP6 effectively degraded tumor ECM and inhibited EMT, leading to enhanced viral distribution, induction of apoptosis, and attenuation of tumor cell proliferation in tumor tissue. HEmT-DCN/sLRP6 prevented metastasis of pancreatic cancer. Importantly, HEmT-DCN/sLRP6 sensitized pancreatic tumor to gemcitabine treatment. Furthermore, HEmT-DCN/sLRP6 augmented drug penetration and dispersion within pancreatic tumor xenografts and patient-derived tumor spheroids. Collectively, these results illustrate that HEmT-DCN/sLRP6 can enhance the dispersion of both oncolytic Ad and a chemotherapeutic agent in chemoresistant and desmoplastic pancreatic tumor, effectively overcoming the preexisting limitations of standard treatments.

Patient-derived cell line models revealed therapeutic targets and molecular mechanisms underlying disease progression of high grade serous ovarian cancer Publication date: 10 September 2019 Source: Cancer Letters, Volume 459 Author(s): Caroline Kreuzinger, Isabel von der Decken, Andrea Wolf, Magdalena Gamperl, Julia Koller, Jasmine Karacs, Stephanie Pfaffinger, Thomas Bartl, Alexander Reinthaller, Christoph Grimm, Christian F. Singer, Elena Ioana Braicu, Paula Cunnea, Charlie Gourley, Dominiek Smeets, Bram Boeckx, Diether Lambrechts, Paul Perco, Reinhard Horvat, Els M.J.J. Berns Abstract High grade serous ovarian cancer (HGSOC) is the most frequent type of ovarian cancer. Most patients have primary response to platinum-based chemotherapy but frequently relapse, which leads to patient death. A lack of well documented and characterized patient-derived HGSOC cell lines is so far a major barrier to define tumor specific therapeutic targets and to study the molecular mechanisms underlying disease progression. We established 34 patient-derived HGSOC cell lines and characterized them at cellular and molecular level. Particularly, we demonstrated that a cancer-testis antigen PRAME and Estrogen Receptor could serve as therapeutic targets. Notably, data from the cell lines did not demonstrate acquired resistance due to tumor recurrence that matched with clinical observations. Finally, we presented that all HGSOC had no or very low CDKN1A (p21) expression due to loss of wild-type TP53, suggesting that loss of cell cycle control is the determinant for tumorigenesis and progression. In conclusion, patient-derived cell lines reveal that PRAME is a potential tumor specific therapeutic target in HGSOC and counteracting the down-regulation of p21 caused by loss of wild-type TP53 might be the key to impede disease progression.

CFIm25 and alternative polyadenylation: Conflicting roles in cancer Publication date: 10 September 2019 Source: Cancer Letters, Volume 459 Author(s): Mohammad Hassan Jafari Najaf Abadi, Rana Shafabakhsh, Zatollah Asemi, Hamid Reza Mirzaei, Roxana Sahebnasagh, Hamed Mirzei, Michael R. Hamblin Abstract Alternative polyadenylation (APA) is now widely recognized to regulate gene expression. APA is an RNA-processing mechanism that generates distinct 3′ termini on mRNAs, producing mRNA isoforms. Different factors influence the initiation and development of this process. CFIm25 (among others) is a cleavage and polyadenylation factor that plays a key role in the regulation of APA. Shortening of the 3′UTRs on mRNAs leads to enhanced cellular proliferation and tumorigenicity. One reason may be the up-regulation of growth promoting factors, such as Cyclin D1. Different studies have reported a dual role of CFIm25 in cancer (both oncogenic and tumor suppressor). microRNAs (miRNAs) may be involved in CFIm25 function as well as competing endogenous RNAs (ceRNAs). The present review focuses on the role of CFIm25 in cancer, cancer treatment, and possible involvement in other human diseases. We highlight the involvement of miRNAs and ceRNAs in the function of CFIm25 to affect gene expression. The lack of understanding of the mechanisms and regulation of CFIm25 and APA has underscored the need for further research regarding their role in cancer and other diseases.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Medical Physics

Investigation of internal target volumes using device and deviceless four-dimensional respiratory monitoring systems for moving targets in four-dimensional computed tomography acquisition Raghavendra Holla, D Khanna, Shubhangi Barsing, Bhaskaran K Pillai, Tharmarnadar Ganesh Journal of Medical Physics 2019 44(2):77-83 Aims and Objectives: The influence of target motion on the reconstructed internal target volume (ITV) for device-based (DB) external surrogate system and Smart deviceless (DL) 4-dimensional (4D) system were compared in a controlled phantom experiment. The volumetric changes in reconstructed ITVs from the average intensity projection (AveIP) images using DB method (Anzai Respiratory Gating System, ANZAI MEDICAL CO., LTD, Japan) and DL method (Smart deviceless 4D system by GE Medical Systems (Chicago, USA)) with the theoretical true volume (ITVth) for moving target with the increasing target motion in anterior-posterior (A-P), lateral (left-right [L-R]) and inferior-superior (S-I) directions were assessed. Materials and Methods: 4D computed tomography (4DCT) of CIRS dynamic phantom (Computerized Imaging Reference Systems Inc., Norfolk, VA, USA) with 2.5 cm diameter spherical target of volume 8.2 cc programmed to move in a cos4(x) motion pattern placed in the lung volume were acquired for various target motion pattern using DB and DL method of gating. AveIP images of 10 phase binned image sets were generated and ITVs were delineated. Results: The maximum absolute percent differences between ITVaveand ITVthfor DL and DB methods were 15.91% and 4.94 % respectively for target motion of 5 mm in AP with 15 mm S-I direction. When the S-I motion was decreased to 10 mm, the observed % difference of the ITVs were also decreased to 12.5% and 0.3% for DL and DB method. When the lateral [L-R] motion was varied from 0 mm to 5 mm for S-I motion of 5 mm to 15 mm, the differences in the ITVs were significant (P = 0.004) with the maximum absolute percent difference of 18.61% and 4.94 % for DL and DB gating. With the simultaneous motion of the target in all the 3 directions, the difference in the reconstructed ITVs were statistically significant for DL method (P = 0.0002) and insignificant for DB method (P = 0.06) with an average increase of 10% in ITVDL against 2% in the ITVDB. The difference in ITVDL was significant for the target motion above 3 mm in A-P and L-R directions for S-I movement of above 10 mm (P = 0.0002). However, for low excursions of the target movement, no significant difference in the ITVs were observed (P > 0.06). In general, ITVDBs were closer to the ITVth (within 7.8%) than ITVDL (18.61%). Conclusion: The results showed that the DL method is an effective way of image sorting in 4D acquisition for smaller target excursion. When the target motion exceeds 3 mm in A-P and L-R directions with S-I more than 10 mm, DB method is the choice due to its accuracy in reproducing the absolute target volume.

Dosimetric effect of rotational setup errors in single-isocenter volumetric-modulated arc therapy of multiple brain metastases Kasirajan Tamil Selvan, Ganesan Padma, Murugesan Kesavan Revathy, N Arunai Nambi Raj, K Senthilnathan, P Ramesh Babu Journal of Medical Physics 2019 44(2):84-90 Aim: The aim of this study is to investigate the dosimetric effects of rotational uncertainties in patient positioning on target coverage in stereotactic radiosurgery (SRS) of multiple brain metastases using single isocenter volumetric modulated arc therapy (VMAT). Materials and Methods: Ten SRS cases with multiple brain metastases(2-8) planned with single isocenter non-coplanar VMAT technique were investigated in this study. Pitch, yaw and roll displacements of 1, 3 and 5° were simulated about isocenter along each axes and nine plans were obtained for each case. Gross tumor volume (GTV) coverage obtained on simulated plans were compared with the original plan on four metrics of mean dose (Dmean), minimum dose to GTV (Dmin), dose to 95% of GTV (D95) and the volume covered by the 95% of the prescribed dose (V95). Results: At 1° rotation about 4% of the PTV had V95 and D95 values <95%. The minimum dose obtained across all PTV was 85.1% and there was not much change in the mean dose values obtained. The PTV volume which had V95 and D95 values <95% were in the range of 0.05 - 0.07cc and at a radial distance of 6.2 cm - 7.2 cm. At 3° rotation almost 50% of the PTV had V95 and D95 values <95%. The minimum dose obtained across all PTV was 48.3% and the mean dose reduced to as low as 78.8%. At 5° rotation almost 74% of the PTV had V95and D95 values <95%. The minimum dose obtained across all PTV was 21.2% and the mean dose reduced to as low as 49.2%. Conclusion: Our results indicate that correcting rotational uncertainties is critical in single-isocenter, multi-target SRS. For rotational deviations, radial distance of the target from isocenter along the respective axis has a strong influence on target coverage. For rotational setup deviation at a given radial distance larger targets tend to have lesser geometric miss compared to smaller targets. Mathematical model for spherical targets can be used to estimate V95 for given rotational errors.

Clinical evaluation of a two-dimensional liquid-filled ion chamber detector array for verification of high modulation small fields in radiotherapy Miljenko Markovic, Ganesh Narayanasamy, Sotirios Stathakis, Panayiotis Mavroidis, Ines-Ana Jurkovic, Daniel Saenz, Niko Papanikolaou Journal of Medical Physics 2019 44(2):91-98 Introduction: Clinical evaluation of a two-dimensional (2D) liquid-filled ion chamber detector array used in the verification of highly modulated small beams of stereotactic body radiation therapy (SBRT) has been conducted. Materials and Methods: Measurements with the Octavius 1000 SRS (PTW, Freiburg, Germany) detector with 977 liquid-filled ion chambers were compared against EDR2 film and PTW Octavius Seven29. The performance of detector array has been evaluated on ten SBRT patient plans. Dose profiles of individual and composite fields' calculated using Pinnacle3 treatment planning system were compared against measurements with Octavius 1000 SRS detector array, EDR2 film, and Octavius Seven29 detector. Gamma index and profile comparison were used in the evaluation and assessment of the detector's performance. Results: The Gamma index measurements show agreement between Pinnacle3 computations and Octavius 1000 SRS array, PTW Octavius Seven29, and EDR2 film for >90% of the points using 2%, 2 mm tolerance criteria. Profiles obtained with the Octavius 1000 SRS were in agreement with the EDR2 film profiles, demonstrating the detector's superior sampling rate. Conclusions: The Octavius 1000 SRS is a dosimetrically accurate device to perform quality assurance checks in SBRT treatments. The broad range of measurements performed in this study quantified the dosimetric accuracy of Octavius 1000 SRS detector in the clinical setup of the small fields in radiotherapy.

Performance validation of in-house developed four-dimensional dynamic phantom Rahul Kumar Chaudhary, Rajesh Kumar, SD Sharma, Soumen Bera, Vikram Mittal, Sudesh Deshpande Journal of Medical Physics 2019 44(2):99-105 Objective: The objective of this study was to validate the performance characteristics of in-house developed four-dimensional (4D) dynamic phantom (FDDP). Materials and Methods: There are three target inserts of 1.0, 1.5 and 2.0 cm diameter. The targets were driven in sinusoidal pattern in the longitudinal direction, using the combinations of amplitudes of 0.5, 1.0, and 1.5 cm with frequencies of 0.2 and 0.25 Hz. The amplitude and frequency of motion were measured manually, and by using Real-Time Position Management (RPM) system also. The static, free-breathing, and 4D computed tomography (CT) scans of the phantom were acquired with 1.0 mm slice thickness. The 4DCT scans were sorted into 0%–90% phase, and the maximum intensity projection (MIP) images were also generated. The static, free-breathing, and 4DCT data sets and MIP images were contoured to get VStatic, VFB, V00......V90, and internal target volume ITVMIP, respectively. The individual phase volumes were summed to obtain V4D. The length of the target in the motion was measured using MIP image and compared with theoretical length (TL). The variation of 3D displacement vector of individual phase volume with respect to V00with the phase of motion was studied at amplitude and frequency of 1.0 cm and 0.25 Hz, respectively. The degree of similarity between VFBand V4Dand VFBand ITVMIPwas also studied for all the target sizes at amplitude and frequency of 1.0 cm and 0.2 Hz and 1.0 cm and 0.25 Hz, respectively. Results: The amplitude and frequency of motion agreed within the limits of uncertainty with the manually and RPM measured values. The length of target in the motion matched within 1.0 mm with TL. The 3D displacement of individual phase volume showed no target size dependence, and the degree of similarity between VFBand V4Dand VFBand ITVMIPdecreases with increase in the displacement between the two volumes. Conclusions: The mechanical and imaging performances of FDDP were found within the acceptable limits. Therefore, this phantom can be used for quality assurance of 4D imaging process in radiotherapy.

Multi-energy computed tomography breast imaging with Monte Carlo simulations: Contrast-to-noise-based image weighting Déte Van Eeden, Freek C. P Du Plessis Journal of Medical Physics 2019 44(2):106-112 Context: Photon-counting detectors and breast computed tomography imaging have been an active area of research. With these detectors, photons are assigned an equal weight and weighting schemes can be enabled. More weight can be assigned to lower energies, resulting in an increase in the contrast-to-noise ratio (CNR). Aims: The aim of this study is to develop and evaluate an energy weighting imaging technique to improve the CNR of simulated breast phantoms and to improve tumour detection. Materials and Methods: Breast phantoms consisting of adipose, glandular, malignant tissues and iodine contrast were constructed with BreastSimulator software. The phantoms were used in egs_cbct simulations for energies ranging between 20 and 65 keV from which multiple images were reconstructed. A new CNR-based image weighting method was proposed based on the CNR values obtained from the images. This method improves on previous methods and can be applied to complicated phantoms since no structural information is needed. Results: An increase in the CNR can be seen for lower energies. A sharp increase in the CNR is seen just above the K-edge for the phantoms with the iodine contrast. The CNR-based image weighting leads to a 68.47% (1.68-fold) increase in the CNR for the malignant tissue without iodine. For the malignant tissue with iodine contrast, the increase in the CNR was 96.14% (1.96-fold). Conclusions: The new proposed CNR-based image weighting scheme is easy to implement and can be used for complicated phantoms with varying structures. A large increase in the CNR is seen with or without the use of iodine contrast.

Probing the effects of ionizing radiation on young's modulus of human erythrocytes cytoskeleton using atomic force microscopy Ellas Spyratou, Maria Dilvoi, George Patatoukas, Kalliopi Platoni, Mersini Makropoulou, Efstathios Petros Efstathopoulos Journal of Medical Physics 2019 44(2):113-117 Purpose/Aim: In this work, we examined the possible effects of ionizing radiation (IR) on biomechanical properties of the membrane–cytoskeleton of human erythrocytes, after X-ray irradiation. Materials and Methods: Whole human blood from three healthy middle-aged volunteers was drawn by venipuncture and stored in tubes containing anticoagulant. Six blood samples were collected for each volunteer. Five of them were irradiated in the range of 0.1 Gy–2.0 Gy doses and one was used as control. The morphology and the elastic modulus of the erythrocytes were examined using atomic force microscopy and just few drops of whole blood. Results: No morphological changes appeared according to the shape and the morphology of the erythrocytes. The elastic modulus of the irradiated samples was reduced with the increase of radiation dose. The findings indicate that X-ray irradiation affects the biomechanical properties of erythrocyte cytoskeleton. The mean value of Young's modulus of all the irradiated blood samples was significant difference from the control at a level,P < 0.01. Conclusions: The elastic modulus of the erythrocytes could be an indicator of the adverse effect in the human blood generated by IR exposure through a radiotherapy treatment.

Impact of silver nanoparticles on the ultraviolet radiation direct and bystander effects on TK6 cell line Zohreh Eftekhari-Kenzerki, Reza Fardid, Abbas Behzad-Behbahani Journal of Medical Physics 2019 44(2):118-125 Purpose/Aim: Ultraviolet C (UVC) radiation is harmful to cells and living organisms that cause direct and indirect DNA damage. UVC can also increase the inflammatory genes expression such as COX-2 that results in elevated oxidative stress that plays a role in radiation-induced bystander effect (BSE). Silver nanoparticles (AgNPs) have used widely in commercial and medical products and the toxicological risks of AgNPs must be determined. The aim of this study was to investigate the direct and BSEs of UVC radiation and AgNPs on TK6 cell line. Materials and Methods: TK6 cells were exposed to AgNPs (10 μg/ml, 1 h). Then, they were exposed to UVC and to determine the BSEs of radiation, the irradiated cells media were transferred to nonirradiated cells. Expression level of H2AX and COX-2 mRNAs were examined by quantitative real-time PCR and 8-OHdG formation was examined by ELISA. The cell viability examined by MTT assay. Results: P < 0.05 was considered as the level of significance. The results showed that the mean expression level of H2AX mRNA in the AgNPs + UVC group increased significantly in comparison with UVC group. 8-OHdG increased significantly in the BSE of UV group in comparison with sham control of BSE. COX-2 mRNA increased significantly in the BSE of AgNPs + UVC with sham control in BSE. Conclusions: Our findings showed the induced DNA damage in TK6 cell by AgNPs and UVC radiation and also were seen BSE.

Validation of the RapidArc delivery system using a volumetric phantom as per task group report 119 of the American association of physicists in medicine Lalit Kumar, Girigesh Yadav, Vimal Kishore, Manindra Bhushan, Munish Gairola, Deepak Tripathi Journal of Medical Physics 2019 44(2):126-134 Aim: This study validated the RapidArc (RA) delivery using a volumetric ArcCHECK phantom as per the guidelines proposed in Task Group Report 119 from the American Association of Physicists in Medicine Task group 119 (AAPM TG 119). This study also investigated the impact of the Acuros XB (AXB) algorithm in comparison to analytical anisotropic algorithm (AAA) on the RA dose calculations in the homogeneous medium of the ArcCHECK phantom. Materials and Methods: A volumetric ArcCHECK phantom along with AAPM TG 119 tests was used to evaluate the RA plans and verify the dose delivery for photon beam of 6 MV energy. Results: The RA planning results were comparable and satisfied the planning criteria stated in the TG 119 report for all test cases. The average percentage gamma passing rates for the AAA-calculated plans were 98.5 (standard deviation [SD]: 0.6), 98.5 (SD: 1.3), and 98.1 (SD: 2.0) and for the AXB-calculated plans were 95.1 (SD: 1.8), 96.1 (SD: 1.3), and 94.0 (SD: 0.9) for the Clinac-iX (6 MV) and TrueBeam (TB)-STx (6 MV_filtered beam [FB] and 6 MV_flattening filter-free beam [FFFB]), respectively. For ion chamber measurements, the average percentage dose differences for the AAA-calculated plans were 1.5 (SD: 2.5), 2.7 (SD: 1.4), and 1.4(SD: 2.7) and for AXB-calculated plans were 2.3 (SD: 1.6), 3.2 (SD: 1.5), and 2.3 (SD: 2.0) for Clinac-iX (6 MV) and TB-STx (6 MV_FB and 6 MV_FFFB), respectively. Conclusion: Thus, the ArcCHECK can successfully be utilized for the validation of the RA delivery. The AXB has potential to perform dose calculations comparable to those of the AAA for RA plans in the homogeneous medium of the ArcCHECK phantom.

External beam radiotherapy with telecobalt machine: Tissue deficiency compensation in head-and-neck region and effect on skin reactions Ramamoorthy Ravichandran, Bandana Barman, Gopal Datta, Ravi Kannan Journal of Medical Physics 2019 44(2):135-138

Clinical three-dimensional dosimetry in modern radiation therapy Tharmarnadar Ganesh Journal of Medical Physics 2019 44(2):139-141 \

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Anaesthesia

Continuous wound infiltration of local anaesthetics for acute postoperative pain – A revisit Vimi Rewari, Rashmi Ramachandran Indian Journal of Anaesthesia 2019 63(6):425-427

Focused review on management of the difficult paediatric airway Andrea S Huang, John Hajduk, Catherine Rim, Sarah Coffield, Narasimhan Jagannathan Indian Journal of Anaesthesia 2019 63(6):428-436 Management of the difficult paediatric airway management may be associated with a high rate of complications. It is important that clinicians understand the patient profiles associated with difficult airway management, and the equipment and techniques available to effectively manage these children. The goal of this focused review is to highlight key airway management concepts when managing the paediatric difficult airway. This includes understanding the advantages and limitations of various airway equipment designed for children and reviewing the difficult airway algorithm with its unique considerations for the paediatric patient. Early recognition of known risk factors and thorough preparation may be helpful in reducing the risk of complications during difficult airway management in children.

Continuous wound infiltration of bupivacaine at two different anatomical planes for caesarean analgesia – A randomised clinical trial Diana Thomas, Sakthirajan Panneerselvam, Pankaj Kundra, Priya Rudingwa, Ranjith K Sivakumar, Gowri Dorairajan Indian Journal of Anaesthesia 2019 63(6):437-443 Background and Aims: Continuous wound infiltration of local anaesthetics provide postoperative analgesia by peripheral nociceptors blockade. The placement of wound infiltration catheter in the optimal anatomical plane of surgical wound may play a significant role in reducing postoperative pain depends on the surgical procedure. We hypothesised that preperitoneal infusion of local anaesthetics will reduce the postoperative opioid consumption as compared to subcutaneous infusion following cesarean section. Methods: This was a randomised, double-blinded clinical trial. Fifty-two pregnant women who underwent lower segment caesarean section by Pfannensteil incision, under spinal anaesthesia, were randomised to group 'subcutaneous' and group 'preperitoneal'. A wound infiltration catheter was placed in the subcutaneous or preperitoneal plane, depending on their randomisation at the end of the surgery. Bupivacaine of 0.25% at 5 mL/h was infused for the next 48 h. Pain was assessed using numerical rating scale at 1, 2, 3, 4, 5, 6, 12, 24, 36 and 48 h after surgery. Cumulative postoperative consumption and adverse effects of morphine and complications of the procedure were looked for. Results: Cumulative 48-h morphine consumption showed no statistical significance between the preperitoneal group (15.96 ± 7.69 mg) and subcutaneous group (21.26 ± 11.03 mg); P = 0.058. Pain score was comparable. Independent T-test and Mann–Whitney test were the statistical tests used for continuous and categorical data, respectively. Conclusion: Postoperative cumulative morphine consumption and pain scores are comparable when bupivacaine is infused continuously through wound infiltration catheter either in the preperitoneal or subcutaneous layer following Caesarean delivery.

Derivation and validation of a formula for paediatric tracheal tube size using bootstrap resampling procedure M Ganesh Kumar, Meenakshi Atteri, Yatindra K Batra, Lakshminarayana Yaddanapudi, Sandhya Yaddanapudi Indian Journal of Anaesthesia 2019 63(6):444-449 Background and Aims: The accuracy of age-, length- and weight-based formulae to predict optimal size of uncuffed tracheal tubes (TTs) in children varies widely. We determined the accuracy of age, length and weight in predicting the size of TT in Indian children, and derived and validated a formula using the best predictor. Methods: In the derivation phase, 100 children aged 1-8 years undergoing general anaesthesia and tracheal intubation with an uncuffed tube were prospectively studied. The correct size of the TT used was confirmed using the leak test. A bootstrap resampling procedure was used to estimate the accuracy of the predictors (age, weight, or length alone; length and age; length and weight; and length, weight and age). The best predictor was used to derive a formula (Paediatric Tube Size Predictor, PTSP) to calculate the size of TT. The accuracy of PTSP was tested in 150 children of the same age group in the validation phase. Results: Length (L (in meters), R2 = 0.61) was the best single predictor of the size of TT and was used to derive the PTSP as internal diameter = 3L + 2.5. In the validation phase, the PTSP predicted the size of TT correctly in 75% of children. Re-intubation was associated with a higher incidence of respiratory morbidity than one-time tracheal intubation. Conclusion: Length of the child predicts the size of an uncuffed TT better than age and weight. The PTSP formula based on length correctly predicts the size of uncuffed TT in 75% of children.

Comparative efficacy of postoperative analgesia between ultrasound-guided dual transversus abdominis plane and Ilioinguinal/Iliohypogastric nerve blocks for open inguinal hernia repair: An open label prospective randomised comparative clinical trial Vinod Hosalli, Basavaraja Ayyanagouda, Preetika Hiremath, Uday Ambi, SY Hulkund Indian Journal of Anaesthesia 2019 63(6):450-455 Background and Aims: Transversus abdominis plane (TAP) and Ilioinguinal/Iliohypogastric (IL/IH) nerve blocks have been advocated in reducing postoperative pain and additional analgesic requirement following lower abdominal surgeries with varied effect. The aim of this study was to determine post-operative analgesic efficacy by comparing dual TAP [combining TAP and IL/IH nerve blocks] and IL/IH nerve block alone for open inguinal hernia repair. Methods: Two hundred patients undergoing elective primary unilateral open inguinal hernia repair with a mesh were included in to this trial. Ultrasound-guided dual TAP (D-TAP Group) or IL/IH (IL/IH Group) nerve block were administered to patients following subarachnoid block according to their group allocation, with 0.5% ropivacaine. Post operatively patients were monitored for visual analogue scale (VAS) scores at rest (at 4, 12, 24 and 48h) and during movement (at 24, 48 h, 3 and 6 months). Pain scores at 3 and 6 months were assessed by telephonic interview, using the DN4 questionnaire for neuropathic pain. The statistics was obtained using Chi-square test for proportions in qualitative data and student's unpaired t test for quantitative data. P value <0.05 was considered significant. Results: The pain scores at rest (VAS-R) were significantly lower at 12 hours and 24 hours (P < 0.001) in D-TAP group, while pain scores at movement were significantly lower (P < 0.001) in D-TAP group at 24 and 48 hours compared to IL/IH group. The mean time required for first rescue analgesic was longer in D-TAP group (5.590 ± 2.386 hr) in comparison to IL/IH group (3.1053 ± 1.1822h). Conclusion: Ultrasound-guided dual TAP block provides more effective post-operative analgesia in open inguinal hernia repair.

McGrath MAC video laryngoscope versus direct laryngoscopy for the placement of double-lumen tubes: A randomised control trial Sumitra G Bakshi, Ajay Gawri, Jigeeshu V Divatia Indian Journal of Anaesthesia 2019 63(6):456-461 Background and Aims: Role of video laryngoscopes (VLs) in the management of difficult airway with single-lumen tubes (SLTs) is established. VLs provide improved glottis view but are associated with longer time to intubate (TTI). We aimed to compare the TTI for double-lumen tube (DLT) insertion using the McGrath® MAC VL versus direct Macintosh laryngoscope (DL). Methods: Eleven senior anaesthesiologists experienced in SLT insertion, but not DLT insertion with VL participated. Seventy-four adults belonging to American Society of Anesthesiologists physical status I–II posted for elective surgery needing lung isolation were randomised to both intubator and laryngoscope (VL/DL). Primary endpoint was TTI; secondary endpoints included glottic view assessed by the Cormack and Lehane (CL) grade, need for external laryngeal manipulation, ease of intubation [scored using Numeric Rating Scale (1 – easiest, 10 – most difficult)] and associated complications. TTI was compared using Student's t-test. Results: No difference was found in TTI with DL and VL [(56.6 ± 14) s vs (64.4 ± 24) s, P = 0.104] as well as ease of use of laryngoscope [median score of 2 (1–3) in both]. Use of VL resulted in more patients with CL I glottic view – 86.0% versus 58.0% (P = 0.007). Fewer patients required external laryngeal manipulations (19% vs 47%, P = 0.013), and complications were fewer in the VL group (5% vs 24%, P = 0.023). Conclusion: TTI for DLT insertion was similar with VL and DL. However, VL was associated with better glottis visualisation, reduced need of external laryngeal manipulation and fewer complications.

Comparison of analgesic efficacy of continuous bilateral transversus abdominis plane catheter infusion with that of lumbar epidural for postoperative analgesia in patients undergoing lower abdominal surgeries Sabina Regmi, S Srinivasan, Ashok S Badhe, M V S Satyaprakash, S Adinarayanan, VK Mohan Indian Journal of Anaesthesia 2019 63(6):462-468 Background and Aims: Epidural analgesia (EA) and transversus abdominal plane (TAP) block have been part of multimodal analgesia techniques for postoperative pain relief in abdominal surgeries though EA has been established as gold standard. This study assesses and compares the analgesic efficacy of continuous bilateral TAP catheter infusion and lumbar epidural infusion. Methods: In this randomised, single-blind, prospective, non-inferiority trial, 75 patients were randomised to receive a bolus dose of 15 ml, 0.25% bupivacaine followed by an infusion of 5–12 ml/h of 0.125% bupivacaine via lumbar epidural in EA group and a bolus dose of 0.4 ml/kg of 0.25% bupivacaine bilaterally via TAP catheter followed by continuous infusion at 5ml/h of 0.125% bupivacaine in TAP group postoperatively. VAS scores (primary objective) and sensory dermatome blockade were recorded at 1, 4, 8, 12 and 24 h. Total morphine consumption, PONV, incidence of hypotension and patient satisfaction scales were recorded at the end of 24 hours. Results: The median VAS scores were comparable between the groups at 1, 4, 8, 12 and 24 hours both at rest (P = 0.11, 0.649, 0.615, 0.280 and 0.191, respectively) and on coughing (p = 0.171, 0.224, 0.207, 0.142 and 0.158, respectively). Total morphine consumption in 24 h between TAP and EA group was comparable (p = 0.366). There was no statistical difference in the incidence of hypotension, PONV and patient satisfaction scale. Conclusion: Continuous bilateral TAP block is as efficacious as the continuous lumbar epidural infusion in relieving postoperative pain in patients undergoing lower abdominal surgeries.

Effect of dexamethasone as an adjuvant to ropivacaine on duration and quality of analgesia in ultrasound-guided transversus abdominis plane block in patients undergoing lower segment cesarean section - A prospective, randomised, single-blinded study Anie Gupta, Alok Gupta, Neeraj Yadav Indian Journal of Anaesthesia 2019 63(6):469-474 Background and Aims: Ultrasound guided transversus abdominis plane block is an efficacious abdominal field block. The aim was to determine the effect of dexamethasone to 0.375% ropivacaine on the analgesic duration of TAP block in patients undergoing lower segment cesarean section (LSCS). Methods: A single-blinded randomised control study was conducted on 90 patients, who were divided in two groups of 45 each. Group R received 0.375% ropivacaine (25 ml) with normal saline (1 ml) each side and group D received 0.375% ropivacaine (25 ml) with dexamethasone 4 mg (1 ml) each side in transversus abdominis plane block after lower segment cesarean section. Primary objective was to compare time to first rescue analgesia and secondary objectives to compare the total amount of analgesia required in first 24 h postoperatively, visual analog scale scores for somatic and visceral pain and incidence of nausea and vomiting, between the two groups. Student's t test, Chi-square, or Fisher's exact test were performed using SPSS 17.0. Results: Time to first rescue analgesia was significantly less in group R (11.62 ± 3.80 h) compared to group D (19.04 ± 4.13 h) (P < 0.001). Total tramadol consumed in 24 h was significantly higher in group R (86.67 ± 30.55 mg) than group D (35.56 ± 39.54 mg) (P < 0.001). Visual analog scale scores for both somatic and visceral pain were significantly higher in group R than group D at 8 h, 12 h, and 24 h postoperatively. Conclusion: Addition of dexamethasone to ropivacaine in transversus abdominis plane block significantly prolongs the duration of postoperative analgesia.

Influence of time interval between coronary angiography to off-pump coronary artery bypass surgery on incidence of cardiac surgery associated acute kidney injury Deepak Prakash Borde, Balaji Asegaonkar, Pramod Apsingekar, Sujeet Khade, Bapu Khodve, Shreedhar Joshi, Antony George, Amey Pujari, Anand Deodhar Indian Journal of Anaesthesia 2019 63(6):475-484 Background and Aims: Cardiac surgery associated acute kidney injury (CSA-AKI) is serious complication after cardiac surgery. The time interval between coronary angiography (CAG) to coronary artery bypass surgery (CABG) is proposed as modifiable risk factor for reduction of CSA-AKI. The aim of this study was to assess influence of time interval between CAG to off-pump CABG (OPCABG) on incidence of CSA-AKI. Methods: This was a retrospective observational study of 900 consecutive OPCABG patients who were classified into 2 groups based on time interval between CAG and OPCABG: ≤7 days or longer. Results: The incidence of CSA-AKI was 24% (214/900) by Kidney Disease: Improving Global Outcomes (KDIGO) definition. The incidence of CSA-AKI was not significantly different in two groups (22% in >7 days groupvs. 28% in ≤7 days group, P = 0.31). The factors independently associated with CSA-AKI were: Age (OR 1.04; P = 0.002), baseline creatinine (OR 1.99,; P = 0.03), moderate LV dysfunction (OR 1.64,; P = 0.007) and blood transfusion (OR 3.3,; P < 0.001), but not the time interval between CAG and OPCABG. The incidence of CSA-AKI was highest in patients with creatinine clearance (CC) <50 mL/min when OPCABG was performed ≤7 days of CAG (16/38; 42%, OR 2.7, 1.4-5.4; P = 0.005) compared to lowest incidence of CSA-AKI in patients with CC >50 mL/min and OPCABG performed >7 days of CAG (114/543; 21%). Conclusion: This study demonstrated that there is no increased incidence of CSA-AKI if OPCABG is performed ≤7 days of CAG; but we recommend to postpone OPCABG for seven days if CC is <50 mL/min and there is no urgent indication for OPCABG in order to reduce incidence of CSA-AKI.

Effect of entropy-guided low-flow desflurane anaesthesia on laryngeal mask airway removal time in children undergoing elective ophthalmic surgery – A prospective, randomised, comparative study Shivangi Mishra, Renu Sinha, Bikash Ranjan Ray, Ravinder Kumar Pandey, Vanlal Darlong, Jyotsna Punj Indian Journal of Anaesthesia 2019 63(6):485-490 Background and Aims: In children, entropy-guided titration of isoflurane and sevoflurane leads to faster recovery after anaesthesia. However, role of entropy in recovery following desflurane anaesthesia is not known. Hence, we compared laryngeal mask airway (LMA) removal time and desflurane consumption with entropy and minimal alveolar concentration–guided titration in children given low-flow desflurane anaesthesia. Methods: After ethics committee approval and parental consent, 80 American Society of Anesthesiologists grade I–II children, age 2–14 years, undergoing elective ophthalmic surgery were randomised into entropy and minimal alveolar concentration–guided groups. After LMA insertion, anaesthesia was maintained using oxygen, air (FiO2 0.5) and desflurane using low fresh gas flow of 0.75 L/min. In the entropy-guided group, desflurane was titrated to maintain state entropy between 40 and 60. In the minimal alveolar concentration–guided group, desflurane was titrated to maintain a minimal alveolar concentration between 1 and 1.3. We recorded LMA removal time (from switching off desflurane at the end of surgery till removal of LMA), haemodynamic parameters, uptake and consumption of desflurane between the groups. Results: LMA removal time was significantly decreased in the entropy-guided group in comparison to the minimal alveolar concentration–guided group (4.34 ± 2.03 vs 8.8 ± 2.33 min) (P < 0.0001). Consumption of desflurane was significantly less in the entropy-guided group compared with the minimal alveolar concentration–guided group (18.7 ± 5.07 vs 25.3 ± 8.11 mL) (P < 0.0001). Conclusion: Entropy-guided low-flow desflurane anaesthesia is associated with faster LMA removal and reduced consumption of desflurane in children undergoing ophthalmic surgery.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Physical and Rehabilitation Medicine

Defining physical and rehabilitation medicine Gerard E Francisco The Journal of the International Society of Physical and Rehabilitation Medicine 2019 2(2):1-1

Foreword The Journal of the International Society of Physical and Rehabilitation Medicine 2019 2(2):2-2

Contributing Authors The Journal of the International Society of Physical and Rehabilitation Medicine 2019 2(2):3-5

Executive Summary Walter R Frontera, Christoph Gutenbrunner, Boya Nugraha The Journal of the International Society of Physical and Rehabilitation Medicine 2019 2(2):6-6

Introduction Walter R Frontera, Christoph Gutenbrunner, Boya Nugraha The Journal of the International Society of Physical and Rehabilitation Medicine 2019 2(2):7-7

1.1 Basic Concepts, Definitions and Models Gerold Stucki, Jerome Bickenbach The Journal of the International Society of Physical and Rehabilitation Medicine 2019 2(2):8-12

1.2 Epidemiology of Disability Gerold Stucki, Jerome Bickenbach The Journal of the International Society of Physical and Rehabilitation Medicine 2019 2(2):13-14

2.1 Rehabilitation: Rehabilitation as a health strategy Christoph Gutenbrunner, Boya Nugraha The Journal of the International Society of Physical and Rehabilitation Medicine 2019 2(2):15-18

2.2 Rehabilitation: Rehabilitation as an intervention John L Melvin The Journal of the International Society of Physical and Rehabilitation Medicine 2019 2(2):19-24

3.1 Physical and rehabilitation medicine: Clinical scope – Definition and basic competencies Christoph Gutenbrunner, Anthony B Ward, Boya Nugraha The Journal of the International Society of Physical and Rehabilitation Medicine 2019 2(2):25-28

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Medicine

A study on the assessment of haller cells in panoramic radiograph KS Prem Kumar, R Sudarshan, G Sree Vijayabala, Samuel Raj Srinivasan, Prajna V Kini Nigerian Medical Journal 2018 59(3):25-27 Context: Haller cells are extensions of ethmoid cells which can be seen in several imaging modalities. Literature search has shown that idiopathic orofacial pain is associated with the presence of Haller cells. Hence, a simple cost-effective imaging modality for displaying the presence of Haller cells is desirable. Aims: This study aims to determine the prevalence of Haller cells in panoramic radiography. Subjects and Methods: The retrospective study comprised of 403 individuals of both genders. Panoramic radiograph was taken for every individual and interpreted for the presence of Haller cells. Factors incorporated in the interpretation were prevalence of Haller cells, distribution of Haller cells among genders, site predilection, unilocular or multilocular variant, and most common shape prevalent among the individuals. Statistical Analysis Used: Chi-square test with SPSS software. Results: Among 403 individuals, the Haller cells were present in 92 (22.8%) individuals. Of 92 (22.8%) individuals with Haller cells, 40 (18.5%) were males and 52 (27.8%) were females. Seventy-four individuals (80.4%) were unilocular and 18 (19.6%) were multilocular. Forty-five individuals had (48.9%) tear-shaped Haller cells, 27 (29.3%) had round-shaped Haller cells, and 20 (21.8%) had oval-shaped Haller cells. Forty (43.5%) were on the right side, 29 (31.5%) were on the left side, and 23 (25%) were on both sides. Conclusions: The present study assessed the prevalence of Haller cells as 22.8%, and this was done in a cost-effective way using panoramic radiographs.

Patterns and Impact of Consultations to an Endocrinology Unit in a Tertiary Hospital in Southwestern Nigeria Akolade O Idowu, Oluwaseyitan Andrew Adesegun, Ayokunle Osonuga, Bamikole Osibowale, Theophilus Ajiro, Taamaka Davis Ngubor, Oyindamola Falade, Olumide Abiodun Nigerian Medical Journal 2018 59(3):28-32 Background: The dearth of endocrinologists in Nigeria, coupled with a paucity of data on patterns of endocrine consultations pose a challenge in evaluating the impact of consultations on patients' management and eventual outcomes. The objectives of this study were to determine the frequency, sources of referrals, the common cases referred, the reasons for consultation requests, and the outcome of patients who benefitted from endocrine consultations. Materials and Methods: This study was carried out in the Endocrinology unit of Babcock University Teaching Hospital, over 9 months. All patients referred to the unit were sampled (total sampling). Their sociodemographic parameters, sources, and reasons for consultations were documented. The patients' case notes were then retrospectively reviewed, to determine the impact of the consultation on their management and outcome. Results: A total of 108 consults were received throughout the study. Most consultations were requested by the general outpatient clinic (37%) followed by cardiology clinic (12%). The most common reason was to take over management of the patients. Diabetes mellitus accounted for 68.7% of the cases seen. Diagnosis made by the referring physician was confirmed in most cases, new diagnoses or change in diagnosis was reached in 9.3% and 3.7%, respectively. About 39.8% of the patients were lost to follow-up, while 53.8% were in good and fair clinical condition. Conclusion: Most of the cases referred for specialist care were from the general outpatient clinic, had diabetes mellitus, and benefitted from specialist care by the way of advanced investigations and treatments, though about a third were lost to follow-up. It is imperative that a good referral system is maintained among physicians, to ensure that patients get the best care available. Attention must be paid to common causes of patient attrition such as lack of widespread health insurance coverage, to ensure continuity of care.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com