Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Σάββατο 19 Νοεμβρίου 2016

Elevated regulatory T cells, surface and intracellular CTLA-4 expression and interleukin-17 in the lung cancer microenvironment in humans

Abstract

Regulatory T cells (Tregs) play an important role in the suppression of the immune response in lung cancer. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) expressed on T lymphocytes is capable of downregulating cytotoxic T cells and is constitutively expressed on Tregs. Little is known about the population of Tregs with two forms of CTLA-4: surface (s) and intracellular (in) in the lung cancer environment. Th17 cells defined by production of IL-17 have pleiotropic functions in anticancer immune response. Our aim was to detect the elements of immune response regulation in lung cancer in three compartments: by analysis of bronchoalveolar lavage fluid (BALF) from the lung affected by cancer (clBALF), healthy symmetrical lung (hlBALF) and peripheral blood (PB) from the same patient. A total of 54 samples were collected. Tregs, (s)CTLA-4, (in)CTLA-4 were detected by flow cytometry with antibodies against CD4, CD25, Foxp3, CD127, CTLA-4, and concentration of IL-17 was estimated by ELISA. We observed a significantly higher proportion of Tregs in clBALF than in hlBALF or PB (8.5 vs. 5.0 vs. 5.1%, respectively, p < 0.05). The median proportion of (in)CTLA-4+ Tregs was higher in clBALF than in hlBALF or PB (89.0, 81.5, 56.0%, p < 0.05). IL-17 concentration was the highest in clBALF—6.6 pg/ml. We observed a significant correlation between the proportion of Tregs and (in)CTLA-4+ Tregs with IL-17A concentration in clBALF. We confirmed significant differences in the proportion of regulatory elements between cancerous lung and healthy lung and PB and the usefulness of BALF analysis in evaluation of immune response regulation in local lung cancer environment.



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Elevated systemic interleukin-7 in patients with colorectal cancer and individuals at high risk of cancer: association with lymph node involvement and tumor location in the right colon

Abstract

Interleukin (IL)-7 is a cytokine essential for protective immunity, and it is considered as a promising agent for cancer immunotherapy. Recent studies, however, appear to associate IL-7 with aggressiveness of solid tumors. The IL-7 has been less studied in colorectal cancer (CRC) and conditions associated with increased risk of CRC development. To explore IL-7 status in bowel diseases, it was measured immunofluorometrically in 431 individuals (110 with CRC) by using Luminex platform. A level of IL-7 in CRC patients was significantly higher than in controls, did not differ from those with adenomas, but was lower than in both active and inactive inflammatory bowel disease (IBD) cases. In CRC, IL-7 was higher in patients with lymph node and distant metastases and with tumors located in right colon. In adenomas, IL-7 elevation was associated exclusively with villous growth pattern, while in IBD, circulating IL-7 reflected clinical activity of Crohn's disease and ulcerative colitis. Systemic TNFα, IL-10, and PDGF-BB were independent predictors of circulating IL-7. In summary, our study is the first to demonstrate IL-7 elevation in CRC in association with metastatic disease and tumor location. Both associations should be considered when designing IL-7-based immunotherapies for CRC. Further studies on IL-7 functionality in CRC are necessary.



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Efficacy of the C-terminal telopeptide test in predicting the development of bisphosphonate-related osteonecrosis of the jaw: a systematic review

Publication date: Available online 19 November 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): K.J. Dal Prá, C.A.A. Lemos, R. Okamoto, A.M.P. Soubhia, E.P. Pellizzer
This systematic review evaluated the efficacy of the morning fasting serum C-terminal telopeptide (CTX) test in predicting the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). A comprehensive search of studies published up to March 2016, and listed in the PubMed/MEDLINE, Web of Science, and Cochrane Library databases, was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review has been registered in the PROSPERO international prospective register of systematic reviews (CRD42016036717). The search identified 542 publications; eight studies were finally deemed eligible for inclusion according to the study criteria. These studies included a total 1442 patients (mean age 66.7 years). The most prescribed drug was alendronate, with osteoporosis being the most frequent indication for the prescription of bisphosphonates. Tooth extraction was the most common trigger for BRONJ. Of all patients evaluated after bisphosphonate treatment, only 24 (1.7%) developed BRONJ. All eight of the selected studies found that CTX levels were not predictive of the development of BRONJ. In conclusion, this systematic review indicates that the CTX test has no predictive value in determining the risk of osteonecrosis in patients taking bisphosphonates.



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Cochlear implantation in autistic children with profound sensorineural hearing loss

Publication date: Available online 19 November 2016
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Magdalena Lachowska, Agnieszka Pastuszka, Zuzanna Łukaszewicz-Moszyńska, Lidia Mikołajewska, Kazimierz Niemczyk
IntroductionCochlear implants have become the method of choice for the treatment of severe-to-profound hearing loss in both children and adults. Its benefits are well documented in the pediatric and adult population. Also deaf children with additional needs, including autism, have been covered by this treatment.ObjectiveThe aim of this study was to assess the benefits from cochlear implantation in deafened children with autism as the only additional disability.MethodsThis study analyzes data of six children. The follow-up time was at least 43 months. The following data were analyzed: medical history, reaction to music and sound, Ling's six sounds test, onomatopoeic word test, reaction to spoken child's name, response to requests, questionnaire given to parents, sound processor fitting sessions and data.ResultsAfter cochlear implantation each child presented other communication skills. In some children, the symptoms of speech understanding were observed. No increased hyperactivity associated with daily use cochlear implant was observed. The study showed that in autistic children the perception is very important for a child's sense of security and makes contact with parents easier.ConclusionOur study showed that oral communication is not likely to be a realistic goal in children with cochlear implants and autism. The implantation results showed benefits that varied among those children. The traditional methods of evaluating the results of cochlear implantation in children with autism are usually insufficient to fully assess the functional benefits. These benefits should be assessed in a more comprehensive manner taking into account the limitations of communication resulting from the essence of autism. It is important that we share knowledge about these complex children with cochlear implants.



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Hearing Preservation After Penetrating Cochlear Injury

Objectives:

To share results and recommendations for management of penetrating cochlear injury.

Methods:

A patient underwent repair of a penetrating cochlear injury after a projectile led to a traumatic cochleostomy with a narrow miss of the facial nerve and intracranial carotid artery.

Results:

Postoperatively, the patient's audiogram demonstrated a pure tone average of 47.5 dB for air conduction and 35 dB for bone conduction, worse in the high frequencies, with a Word Recognition Score of 76%.

Conclusions:

Hearing loss from a penetrating cochlear injury can be mitigated with early repair, minimizing inner ear trauma, and steroid use to treat posttraumatic labyrinthitis.



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Localization and expression patterns of TRP channels in submandibular gland development

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Publication date: February 2017
Source:Archives of Oral Biology, Volume 74
Author(s): Motoya Fujiseki, Masahito Yamamoto, Sobhan Ubaidus, Takashi Shinomiya, Shinichi Abe, Masakazu Tazaki, Hitoshi Yamamoto
ObjectiveExpression of Transient receptor potential (TRP) channels: TRP canonical (TRPC)1, TRP vanilloid (TRPV)3, TRPV4 and TRP melastatin (TRPM)8 in adult rat salivary gland has recently been reported. The authors investigated expression of these TRP channels in the submandibular gland during early developmental stage in which the cell constitution is different, and discussed the function of TRP in the submandibular gland in early development.DesignUsing rat submandibular gland at embryonic days (E)18 and E20 and postnatal days (PN)0 and PN5 and PN28, expression of TRPV3, TRPV4, TRPC1 and TRPM8 was investigated using real-time polymerase chain reaction (RT-PCR) and immunohistochemistry.ResultsAll TRP channels were expressed in cells constituting the submandibular gland in early developmental stage, but an increase in the expression level at PN5 on RT-PCR was significant compared with those at E18, PN0 and PN28 in TRPC1 and TRPV4 channels, whereas an increase was observed but not significant in the others. On immunohistochemical staining at PN5, whereas strong reactions of anti-TRPM8 antibody, anti-TRPV3 and anti-TRPV4 antibodies were observed in cells which proliferated from a terminal portion of cells arranged tubular structure which previously constituted mostly the submandibular gland.ConclusionIt was clarified that TRP channels are expressed in the rat submandibular gland in early developmental stage although cells constituting the submandibular gland are different from those in adult animals, suggesting that these TRP channels are involved in cell differentiation in at PN5 into the adult submandibular gland during early development.



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Investigation of CD40 gene rs4810485 and rs1883832 mutations in patients with recurrent aphthous stomatitis

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Publication date: February 2017
Source:Archives of Oral Biology, Volume 74
Author(s): Serbulent Yigit, Akin Tekcan, Aydin Rustemoglu, Mehmet Kemal Tumer, Goknur Kalkan, Kaan Yerliyurt
ObjectivesRecurrent aphthous stomatitis (RAS) is a common painful disorder affecting oral health, mucosa and overall quality of life. The etiopathogenesis of RAS remains unclear. RAS shows a large genetic diversity among the patients. In present study, we investigated whether CD40 gene rs4810485 and rs1883832 are associated with RAS and its clinical findings in Turkish patients.Materials and methodsGenomic DNA obtained from 387 individuals (160 patients with RAS and 227 healthy controls) were used in the study. CD40 gene rs4810485 and rs1883832 mutations were determined by using polymerase chain reaction with the specific primers.ResultsThere was no statistically significant difference between the groups with respect to genotype and allele distribution (p>0.05, OR 0.94, 95% CI 0.70–1.28, OR 1.01 95% CI 0.75–1.37, respectively). Additionally, there was no statistically significant difference in the combined genotype analysis of CD40 gene rs4810485 and rs1883832 mutations (p>0.05).ConclusionsAccording to our results, we found that CD40 gene mutations are not associated with RAS. We are convinced that CD40 gene mutations do not predispose to develop RAS in Turkish population. To our knowledge, this is the first study regarding CD40 gene rs4810485 and rs1883832 mutations investigated in RAS patients.



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Detection and quantification of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Streptococcus oralis in blood samples with different microbiological identification methods: An in vitro study

S00039969.gif

Publication date: February 2017
Source:Archives of Oral Biology, Volume 74
Author(s): María José Marin, Nagore Ambrosio, Leire Virto, Pedro Diz, Maximiliano Álvarez, David Herrera, Mariano Sanz, Elena Figuero
BackgroundCulture-based methods (culture broth bottles or lysis methods) have been the standard for detecting bacteremia. More recently, quantitative polymerase chain reaction (qPCR) was proposed as a more sensitive and specific test although none of them has been validated for the identification of periodontal pathogens (fastidious growing bacteria) in blood samples.ObjectiveTo compare the ability to detect and quantify Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Streptococcus oralis (alone or in combination) in blood samples with three culture techniques [direct anaerobic culturing (DAC), haemo-culture (BACTEC), and lysis-centrifugation (LC)] and a non-culture dependent approach (qPCR) in an in vitro study.Material and methodsBlood samples from 12 periodontally healthy volunteers were contaminated with three concentrations [104,102 and 101 colony forming units (CFU)/mL] of A. actinomycetemcomitans, P. gingivalis and S. oralis, alone or in combination. Samples were analysed by DAC, BACTEC, LC and qPCR. Sensitivity, specificity, predictive values, kappa index and Lińs correlation coefficients were calculated.ResultsDAC, LC and qPCR were able to detect the three target species at all concentrations. An excellent concordance (correlation coefficient r: 0.92–1) was observed between DAC and the reference standard (sensitivity raging 93.33–100% and specificity 88.89–100%) values. BACTEC was not able to identify P. gingivalis in any of the performed experiments. qPCR provided false negative results for S.oralis.ConclusionsDAC showed the best results for the proper identification and quantification of A. actinomycetemcomitans, P. gingivalis and S. oralis, alone or in combination, in blood samples.



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Novel technique for harvesting the sternoclavicular graft

Originally introduced for mandibular reconstruction more than 40 years ago, the sternoclavicular graft has gained widespread popularity for the reconstruction of the ramus-condyle unit owing to its anatomic and histological likeness to the normal mandibular condyle. The technique for its harvest has evolved from a full thickness clavicular graft to a split thickness sternoclavicular composite graft including the fibrocartilaginous articular disk at the sternal end of the bone. Conventional longitudinal osteotomy design for its harvest has been fraught with considerable complications at the donor site including fracture clavicle and major neurovascular injury.

http://ift.tt/2fsF4OB

Recurrence probability for keratocystic odontogenic tumors: An analysis of 6,427 cases

To investigate and compare the probability of recurrence of keratocystic odontogenic tumors (KCOTs) for different variables and treatment protocols.

http://ift.tt/2eSjmYo

Comparison of skeletal stability after sagittal split ramus osteotomy among mono-cortical plate fixation, bi-cortical plate fixation, and hybrid fixation using absorbable plates and screws

The purpose of this study was to examine skeletal stability and plate breakage after sagittal split ramus osteotomy (SSRO) with the mono-cortical plate fixation, bi-cortical plate fixation, and hybrid fixation techniques using absorbable plates and screws.

http://ift.tt/2fsGGIr

Craniofacial structure variations in patients with palatal anomalies and velopharyngeal dysfunction

Cephalometric evaluation of craniofacial and craniopharyngeal morphology is important for understanding the factors affecting velopharyngeal dysfunction (VPD) in patients with palatal anomalies.

http://ift.tt/2eSjuXI

Localization and expression patterns of TRP channels in submandibular gland development

S00039969.gif

Publication date: February 2017
Source:Archives of Oral Biology, Volume 74
Author(s): Motoya Fujiseki, Masahito Yamamoto, Sobhan Ubaidus, Takashi Shinomiya, Shinichi Abe, Masakazu Tazaki, Hitoshi Yamamoto
ObjectiveExpression of Transient receptor potential (TRP) channels: TRP canonical (TRPC)1, TRP vanilloid (TRPV)3, TRPV4 and TRP melastatin (TRPM)8 in adult rat salivary gland has recently been reported. The authors investigated expression of these TRP channels in the submandibular gland during early developmental stage in which the cell constitution is different, and discussed the function of TRP in the submandibular gland in early development.DesignUsing rat submandibular gland at embryonic days (E)18 and E20 and postnatal days (PN)0 and PN5 and PN28, expression of TRPV3, TRPV4, TRPC1 and TRPM8 was investigated using real-time polymerase chain reaction (RT-PCR) and immunohistochemistry.ResultsAll TRP channels were expressed in cells constituting the submandibular gland in early developmental stage, but an increase in the expression level at PN5 on RT-PCR was significant compared with those at E18, PN0 and PN28 in TRPC1 and TRPV4 channels, whereas an increase was observed but not significant in the others. On immunohistochemical staining at PN5, whereas strong reactions of anti-TRPM8 antibody, anti-TRPV3 and anti-TRPV4 antibodies were observed in cells which proliferated from a terminal portion of cells arranged tubular structure which previously constituted mostly the submandibular gland.ConclusionIt was clarified that TRP channels are expressed in the rat submandibular gland in early developmental stage although cells constituting the submandibular gland are different from those in adult animals, suggesting that these TRP channels are involved in cell differentiation in at PN5 into the adult submandibular gland during early development.



http://ift.tt/2grdDJs

Investigation of CD40 gene rs4810485 and rs1883832 mutations in patients with recurrent aphthous stomatitis

S00039969.gif

Publication date: February 2017
Source:Archives of Oral Biology, Volume 74
Author(s): Serbulent Yigit, Akin Tekcan, Aydin Rustemoglu, Mehmet Kemal Tumer, Goknur Kalkan, Kaan Yerliyurt
ObjectivesRecurrent aphthous stomatitis (RAS) is a common painful disorder affecting oral health, mucosa and overall quality of life. The etiopathogenesis of RAS remains unclear. RAS shows a large genetic diversity among the patients. In present study, we investigated whether CD40 gene rs4810485 and rs1883832 are associated with RAS and its clinical findings in Turkish patients.Materials and methodsGenomic DNA obtained from 387 individuals (160 patients with RAS and 227 healthy controls) were used in the study. CD40 gene rs4810485 and rs1883832 mutations were determined by using polymerase chain reaction with the specific primers.ResultsThere was no statistically significant difference between the groups with respect to genotype and allele distribution (p>0.05, OR 0.94, 95% CI 0.70–1.28, OR 1.01 95% CI 0.75–1.37, respectively). Additionally, there was no statistically significant difference in the combined genotype analysis of CD40 gene rs4810485 and rs1883832 mutations (p>0.05).ConclusionsAccording to our results, we found that CD40 gene mutations are not associated with RAS. We are convinced that CD40 gene mutations do not predispose to develop RAS in Turkish population. To our knowledge, this is the first study regarding CD40 gene rs4810485 and rs1883832 mutations investigated in RAS patients.



http://ift.tt/2fbTHou

Detection and quantification of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Streptococcus oralis in blood samples with different microbiological identification methods: An in vitro study

S00039969.gif

Publication date: February 2017
Source:Archives of Oral Biology, Volume 74
Author(s): María José Marin, Nagore Ambrosio, Leire Virto, Pedro Diz, Maximiliano Álvarez, David Herrera, Mariano Sanz, Elena Figuero
BackgroundCulture-based methods (culture broth bottles or lysis methods) have been the standard for detecting bacteremia. More recently, quantitative polymerase chain reaction (qPCR) was proposed as a more sensitive and specific test although none of them has been validated for the identification of periodontal pathogens (fastidious growing bacteria) in blood samples.ObjectiveTo compare the ability to detect and quantify Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Streptococcus oralis (alone or in combination) in blood samples with three culture techniques [direct anaerobic culturing (DAC), haemo-culture (BACTEC), and lysis-centrifugation (LC)] and a non-culture dependent approach (qPCR) in an in vitro study.Material and methodsBlood samples from 12 periodontally healthy volunteers were contaminated with three concentrations [104,102 and 101 colony forming units (CFU)/mL] of A. actinomycetemcomitans, P. gingivalis and S. oralis, alone or in combination. Samples were analysed by DAC, BACTEC, LC and qPCR. Sensitivity, specificity, predictive values, kappa index and Lińs correlation coefficients were calculated.ResultsDAC, LC and qPCR were able to detect the three target species at all concentrations. An excellent concordance (correlation coefficient r: 0.92–1) was observed between DAC and the reference standard (sensitivity raging 93.33–100% and specificity 88.89–100%) values. BACTEC was not able to identify P. gingivalis in any of the performed experiments. qPCR provided false negative results for S.oralis.ConclusionsDAC showed the best results for the proper identification and quantification of A. actinomycetemcomitans, P. gingivalis and S. oralis, alone or in combination, in blood samples.



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The risk of melanoma and hematologic cancers in patients with psoriasis

The risk of melanoma and hematologic cancers in patients with psoriasis is controversial.

http://ift.tt/2g8DYc3

Rapid visualization of nonmelanoma skin cancer

Mohs micrographic surgery examines all margins of the resected sample and has a 99% cure rate. However, many nonmelanoma skin cancers (NMSCs) are not readily amenable to Mohs micrographic surgery. This defines an unmet clinical need to assess the completeness of non-Mohs micrographic surgery resections during surgery to prevent re-excision/recurrence.

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Occupational exposure to bodily fluids in oral and maxillofacial surgery: an evaluation of reporting practices and attitudes among staff at a major teaching hospital in the UK

Our aim was to evaluate experience, practice, and beliefs about reporting of occupational exposures to blood and other body fluids among a sample of 88 healthcare providers working in oral and maxillofacial surgery at Sheffield Teaching Hospitals. We used a cross-sectional survey to evaluate awareness of the Trust's policy for reporting occupational exposure, recent incidence of exposure, and current reporting practices. Beliefs were measured using questions derived from the theory of planned behaviour.

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Scheduling terminology for oral and maxillofacial surgery. Are we speaking a universal language?

Use of a universal vocabulary to assist with the scheduling of operations has been shown to considerably reduce delays and improve the use of theatre resources. Within the UK the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) has established a classification to assist with the triage of both emergency and non-emergency operating lists. We completed a survey to assess the uptake and understanding of this classification when scheduling maxillofacial operations. From a list of eight scheduling terms, respondents had to choose one each for 20 different clinical situations (that represented equally) immediate, urgent, expedited, and elective operations as defined by them.

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Submental island flap reconstruction in oral cavity cancer patients with level I lymph node metastasis

The submental island flap is useful as an alternative to microvascular free tissue transfer for the reconstruction of defects after resection of oral cancer because it is simple to harvest, reliable, and is associated with good oral function and low morbidity. However, because cancer of the oral cavity carries a risk of level I nodal metastases, the oncological safety of the flap remains controversial. Between April 2012 and September 2016, we studied patients with squamous cell carcinoma of the oral cavity who underwent surgical resection with submental island flap reconstruction for viability of the flap, signs of recurrence, and complications.

http://ift.tt/2fsxcN3

Follow up of surgically-assisted rapid maxillary expansion after 6.5 years: skeletal and dental effects

Surgically-assisted rapid maxillary expansion (SARME) is a technique used to widen the maxilla, and we present the results of our long-term follow up (6.5 years). Seventeen patients who had been treated with SARME and prospectively followed were invited for long-term follow up by dental casts and posteroanterior cephalograms. The following measurements were made on the dental casts: transverse distances at canine, premolar, and molar level, length of the arch, and width and depth of the palate at premolar and molar level.

http://ift.tt/2eSbt4U

Efficacy of the C-terminal telopeptide test in predicting the development of bisphosphonate-related osteonecrosis of the jaw: a systematic review

This systematic review evaluated the efficacy of the morning fasting serum C-terminal telopeptide (CTX) test in predicting the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). A comprehensive search of studies published up to March 2016, and listed in the PubMed/MEDLINE, Web of Science, and Cochrane Library databases, was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review has been registered in the PROSPERO international prospective register of systematic reviews (CRD42016036717).

http://ift.tt/2g95FSq

Optimizing the outcome of transnasal endoscopic sphenopalatine artery ligation in managing refractory posterior epistaxis: A case–control analysis

Publication date: Available online 19 November 2016
Source:Auris Nasus Larynx
Author(s): Mainak Dutta, Dibakar Haldar
ObjectiveTo optimize the outcome of transnasal endoscopic sphenopalatine artery ligation (TESPAL) by determining the key surgical steps and applying them accordingly.MethodsThis is a case–control study carried out in a tertiary care teaching institution on subjects who underwent TESPAL during the period of October 2010 to September 2015. Their surgical and clinical records were reviewed, and success (no re-bleed) and failure (return with re-bleed) were considered the main outcome measures of TESPAL. Accordingly, depending on whether the subjects returned with re-bleed or not, they were classified as "failure" and "success" groups. After appropriate matching in terms of age, gender and a given set of exclusion criteria that could influence per-operative decision-making or contribute to post-operative epistaxis, the groups were considered as cases (subjects undergoing TESPAL and returned with re-bleed; part of the "failure" group following matching) and controls (subjects undergoing TESPAL and did not return with re-bleed; part of the "success" group following matching). Per-operative/surgical factors executed or followed in varied combinations in each group that influenced the outcome of TESPAL were then identified from the surgical notes and were subsequently analyzed statistically.ResultsIn 89% of cases, the sphenopalatine artery (SPA) pedicle was either clipped or cauterized, whereas in 90% of the controls, it was both clipped and cauterized. The posterior nasal artery (PNA), when found, was cauterized in 25% of the cases, compared to 85% in the controls. Also, the septal artery region was cauterized in only 33% of cases. Both cauterization/clipping of the SPA along with cauterization of PNA was done in 69% of the controls, whereas in 59% the septal artery region was also cauterized. However, there were no cases when all these steps were combined. The results were statistically significant.ConclusionWhen only the per-operative/surgical factors were considered, the outcome of TESPAL was most favorable when the procedure could be done combining both clipping and cauterization of the SPA, along with cauterization of the PNA and the septal artery region.



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