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1.
J Laryngol Otol ; 137(8): 883-889, 2023 Aug.
Article En | MEDLINE | ID: mdl-36443933

OBJECTIVE: This study aimed to discuss the role of large cavity functional endoscopic sinus surgery in the management of chronic rhinosinusitis with nasal polyps in patients with non-steroidal anti-inflammatory drug exacerbated respiratory disease. METHODS: This was a retrospective review of patients undergoing large cavity functional endoscopic sinus surgery for non-steroidal anti-inflammatory drug exacerbated respiratory disease from January 2016 to March 2022. Population characteristics, pre- and post-operative number of functional endoscopic sinus surgical procedures, endoscopic polyp grade, Lund-Mackay score and nasal symptoms were recorded. RESULTS: Thirteen consecutive patients with a median age of 47 years were included. They all failed maximal medical treatment and/or conservative functional endoscopic sinus surgery and underwent large cavity sinus surgery followed by post-operative maximal medical therapy. All patients showed an improvement in nasal symptoms with improved Lund-Mackay scores post-operatively. The median length of follow up was 1.5 years. CONCLUSION: Large cavity functional endoscopic sinus surgery seems to halt the progression of chronic rhinosinusitis with nasal polyps in non-steroidal anti-inflammatory drug exacerbated respiratory disease. In this case series, large cavity functional endoscopic sinus surgery combined with optimal post-operative medical treatment appeared to switch off chronic rhinosinusitis with nasal polyps in patients with non-steroidal anti-inflammatory drug exacerbated respiratory disease.


Nasal Polyps , Paranasal Sinuses , Rhinitis , Sinusitis , Humans , Middle Aged , Nasal Polyps/surgery , Nasal Polyps/drug therapy , Rhinitis/drug therapy , Rhinitis/surgery , Sinusitis/drug therapy , Sinusitis/surgery , Paranasal Sinuses/surgery , Endoscopy/methods , Chronic Disease , Anti-Inflammatory Agents/therapeutic use
2.
J Laryngol Otol ; 136(12): 1177-1182, 2022 Dec.
Article En | MEDLINE | ID: mdl-34857063

OBJECTIVE: This study reviewed all rhinology clinical negligence claims in the National Health Service in England between 2013 and 2018. METHOD: All clinical negligence claims held by National Health Service Resolution relating to rhinology in England between 1 April 2013 and 1 April 2018 were reviewed. RESULTS: There were 171 rhinology related claims with a total estimated potential cost of £13.6 million. There were 119 closed claims (70 per cent) with a total cost of £2.3 million, of which 55 claims resulted in payment of damages. Over three quarters of all rhinology claims were associated with surgery (n = 132). Claims associated with endoscopic sinus surgery had the highest mean cost per claim (£172 978). Unnecessary pain (33.9 per cent) and unnecessary operation (28.1 per cent) were the most commonly cited patient injuries. CONCLUSION: Patient education and consent have been highlighted as key areas for improvement from this review of rhinology related clinical negligence claims. A shift in clinical practice towards shared decision making could reduce litigation in rhinology.


Malpractice , Surgery, Plastic , Humans , State Medicine , England , Endoscopy
3.
Eur Arch Otorhinolaryngol ; 275(11): 2739-2744, 2018 Nov.
Article En | MEDLINE | ID: mdl-30293091

PURPOSE: Nasal obstruction is a highly subjective and commonly reported symptom. The internal nasal valve (INV) is the rate limiting step to nasal airflow. A static INV grading score was devised with regard to visibility of the middle turbinate. METHODS: A prospective study of all patients who underwent primary external functional septorhinoplasty in 2017 for nasal obstruction. All patients' INV score was assessed pre- and postoperatively in a blinded and independent fashion by surgeons of varying seniority. RESULTS: Twenty-eight patients were studied, with mean age 30.9 years and follow-up 18.8 weeks. Inter-rater and test-retest reliability of INV grading were excellent, with Cronbach's alpha 0.936 and 0.920, respectively. There was also statistically significant improvement in both subjective and objective postoperative outcome measures including nasal inspiratory peak flows. CONCLUSIONS: We demonstrate a novel, easy to interpret, clinically valuable grading system of the static internal nasal valve that is reliable and reproducible.


Endoscopy , Nasal Cavity/pathology , Nasal Obstruction/surgery , Adult , Female , Humans , Inhalation , Male , Nasal Septum/surgery , Prospective Studies , Reproducibility of Results , Rhinoplasty , Turbinates/pathology
4.
Am J Transplant ; 18(2): 293-307, 2018 02.
Article En | MEDLINE | ID: mdl-29243394

The kidney sessions of the 2017 Banff Conference focused on 2 areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i-IFTA) and its relationship to T cell-mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody-mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by 2 groups that i-IFTA is associated with reduced graft survival. Furthermore, these groups presented that i-IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with underimmunosuppression. The classification was thus revised to include moderate i-IFTA plus moderate or severe tubulitis as diagnostic of chronic active TCMR. Other studies demonstrated that certain molecular classifiers improve diagnosis of ABMR beyond what is possible with histology, C4d, and detection of donor-specific antibodies (DSAs) and that both C4d and validated molecular assays can serve as potential alternatives and/or complements to DSAs in the diagnosis of ABMR. The Banff ABMR criteria are thus updated to include these alternatives. Finally, the present report paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next-generation clinical trials.


Graft Rejection/diagnosis , High-Throughput Nucleotide Sequencing/methods , Inflammation/diagnosis , Isoantibodies/immunology , Kidney Transplantation/adverse effects , Postoperative Complications , T-Lymphocytes/immunology , Graft Rejection/etiology , Graft Rejection/pathology , Humans , Inflammation/etiology , Inflammation/pathology , Prognosis , Research Report
5.
Clin Otolaryngol ; 42(6): 1187-1192, 2017 Dec.
Article En | MEDLINE | ID: mdl-28247540

OBJECTIVES: Whilst nasal function and airflow improve subjectively following functional endoscopic sinus surgery (FESS), a clinically useful and objective tool for quantifying such improvement is lacking. The peak nasal inspiratory flow (PNIF) metre offers convenient and objective measures of nasal patency. However, it has not yet been established whether changes in PNIF after surgery reflect changes in subjective disease burden. In this study we aimed to determine whether changes in PNIF correlate with commonly used subjective symptom and quality of life outcome measures following FESS for chronic rhinosinusitis (CRS). DESIGN: Prospective cohort. SETTING: Royal National Throat Nose and Ear Hospital. PARTICIPANTS: Thirty-seven patients undergoing FESS for CRS, with or without polyps (21 male, mean age 48.8). MAIN OUTCOME MEASURES: PNIF, "SNOT-22", "NOSE" and "VAS" questionnaires were performed before and after surgery. RESULTS: In all patients, there was a strong negative correlation between change in PNIF and change in "SNOT-22" score following surgery (Pearson r=-.64, P<.0001). Strong negative correlations were also seen during subgroup analysis of patients with and without polyps (r=-.57, P=.006 and r=-.67, P=.005, respectively). Change in PNIF correlated significantly with change in "NOSE" score following surgery in all patients and those without polyps (r=-.54, P=.0005 and r=-.68, P=.003). There were no significant correlations between PNIF and VAS (nasal obstruction). CONCLUSIONS: Changes in PNIF after FESS appear to best reflect improvements in quality of life in CRS as measured using the "SNOT-22" questionnaire.


Inhalation/physiology , Quality of Life , Rhinitis/physiopathology , Rhinitis/surgery , Sinusitis/physiopathology , Sinusitis/surgery , Adult , Chronic Disease , Cohort Studies , Endoscopy , Female , Humans , Male , Middle Aged , Nasal Polyps/complications , Nasal Polyps/physiopathology , Nasal Polyps/surgery , Reproducibility of Results , Respiratory Function Tests , Rhinitis/complications , Sinusitis/complications , Surveys and Questionnaires , Treatment Outcome
6.
Am J Transplant ; 17(1): 140-150, 2017 01.
Article En | MEDLINE | ID: mdl-27333454

The Banff working group on preimplantation biopsy was established to develop consensus criteria (best practice guidelines) for the interpretation of preimplantation kidney biopsies. Digitally scanned slides were used (i) to evaluate interobserver variability of histopathologic findings, comparing frozen sections with formalin-fixed, paraffin-embedded tissue of wedge and needle core biopsies, and (ii) to correlate consensus histopathologic findings with graft outcome in a cohort of biopsies from international medical centers. Intraclass correlations (ICCs) and univariable and multivariable statistical analyses were performed. Good to fair reproducibility was observed in semiquantitative scores for percentage of glomerulosclerosis, arterial intimal fibrosis and interstitial fibrosis on frozen wedge biopsies. Evaluation of frozen wedge and core biopsies was comparable for number of glomeruli, but needle biopsies showed worse ICCs for glomerulosclerosis, interstitial fibrosis and tubular atrophy. A consensus evaluation form is provided to help standardize the reporting of histopathologic lesions in donor biopsies. It should be recognized that histologic parameters may not correlate with graft outcome in studies based on organs deemed to be acceptable after careful clinical assessment. Significant limitations remain in the assessment of implantation biopsies.


Kidney Transplantation , Kidney/pathology , Kidney/surgery , Tissue Donors , Biopsy, Needle , Consensus , Humans
7.
Am J Transplant ; 17(1): 28-41, 2017 01.
Article En | MEDLINE | ID: mdl-27862883

The XIII Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d-negative antibody-mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor-specific antibody tests (anti-HLA and non-HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection requires further consensus agreement and validation in biopsies. Newly introduced concepts include the i-IFTA score, comprising inflammation within areas of fibrosis and atrophy and acceptance of transplant arteriolopathy within the descriptions of chronic active T cell-mediated rejection (TCMR) or chronic ABMR. The pattern of mixed TCMR and ABMR was increasingly recognized. This report also includes improved definitions of TCMR and ABMR in pancreas transplants with specification of vascular lesions and prospects for defining a vascularized composite allograft rejection classification. The goal of the Banff process is ongoing integration of advances in histologic, serologic, and molecular diagnostic techniques to produce a consensus-based reporting system that offers precise composite scores, accurate routine diagnostics, and applicability to next-generation clinical trials.


Arteritis/immunology , Complement C4b/immunology , Graft Rejection/classification , Graft Rejection/pathology , Isoantibodies/immunology , Kidney Transplantation/adverse effects , Peptide Fragments/immunology , Graft Rejection/etiology , Humans , Research Report
8.
Clin Otolaryngol ; 42(3): 508-513, 2017 Jun.
Article En | MEDLINE | ID: mdl-27627585

OBJECTIVE: Body dysmorphic disorder (BDD) is defined as having a preoccupation with a perceived flaw in one's appearance, which appears slight to others and significantly interferes with a person's functioning. When undetected in septorhinoplasty patients, it will often lead to poor outcomes. DESIGN: We performed a prospective cohort study to determine the prevalence of BDD in our patients and whether surgical correction could be considered. SETTING AND PARTICIPANTS: We recruited 34 patients being considered for septorhinoplasty in a tertiary referral rhinology clinic and a control group of 50 from the otology clinic giving a total of 84. MAIN OUTCOME MEASURES: Participants completed the Body Dysmorphic Disorder Questionnaire (BDDQ), the sino-nasal outcome test-23 (SNOT-23) and underwent nasal inspiratory peak flow (NIPF). Those found to be at high risk for BDD were referred to a clinical psychologist. RESULTS: Of the septorhinoplasty patients, 11 (32%) were high risk for BDD. Following psychological assessment, 7 (63%) patients were felt to be unsuitable for surgery and were offered psychological therapy. SNOT-23 scores were significantly higher in the BDD group indicating a negative impact on quality of life. NIPF readings were not significantly different in the BDD group compared to the control group. CONCLUSIONS: The BDDQ is a valid tool for identifying patients at risk of BDD. A close working relationship with clinical psychology has been advantageous to help the selection process of candidates for surgery when there is a high risk of BDD.


Body Dysmorphic Disorders/epidemiology , Mass Screening/methods , Nose Deformities, Acquired/complications , Rhinoplasty , Adult , Body Dysmorphic Disorders/diagnosis , Body Dysmorphic Disorders/etiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Nose Deformities, Acquired/diagnosis , Nose Deformities, Acquired/surgery , Preoperative Period , Prevalence , Prospective Studies , Quality of Life , Surveys and Questionnaires , United Kingdom/epidemiology
9.
Am J Transplant ; 16(10): 2816-2835, 2016 10.
Article En | MEDLINE | ID: mdl-27273869

The Banff Working Group on Liver Allograft Pathology reviewed and discussed literature evidence regarding antibody-mediated liver allograft rejection at the 11th (Paris, France, June 5-10, 2011), 12th (Comandatuba, Brazil, August 19-23, 2013), and 13th (Vancouver, British Columbia, Canada, October 5-10, 2015) meetings of the Banff Conference on Allograft Pathology. Discussion continued online. The primary goal was to introduce guidelines and consensus criteria for the diagnosis of liver allograft antibody-mediated rejection and provide a comprehensive update of all Banff Schema recommendations. Included are new recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization. In an effort to create a single reference document, previous unchanged criteria are also included.


Graft Rejection/etiology , Graft Rejection/pathology , Isoantibodies/immunology , Liver Transplantation/adverse effects , Allografts , Humans , Research Report
10.
Am J Transplant ; 16(11): 3131-3138, 2016 11.
Article En | MEDLINE | ID: mdl-27273900

This study interrogates the antigen-specificity of inflammatory infiltrates in renal biopsies with BK polyomavirus (BKPyV) viremia (BKPyVM) with or without allograft nephropathy (BKPyVN). Peripheral blood mononuclear cells (PBMC) from five healthy HLA-A0101 subjects were stimulated by peptides derived from the BKPYV proteome or polymorphic regions of HLA. Next generation sequencing of the T cell-receptor complementary DNA was performed on peptide-stimulated PBMC and 23 biopsies with T cell-mediated rejection (TCMR) or BKPyVN. Biopsies from patients with BKPyVM or BKVPyVN contained 7.7732 times more alloreactive than virus-reactive clones. Biopsies with TCMR also contained BKPyV-specific clones, presumably a manifestation of heterologous immunity. The mean cumulative T cell clonal frequency was 0.1378 for alloreactive clones and 0.0375 for BKPyV-reactive clones. Samples with BKPyVN and TCMR clustered separately in dendrograms of V-family and J-gene utilization patterns. Dendrograms also revealed that V-gene, J-gene, and D-gene usage patterns were a function of HLA type. In conclusion, biopsies with BKPyVN contain abundant allospecific clones that exceed the number of virus-reactive clones. The T cell component of tissue injury in viral nephropathy appears to be mediated primarily by an "innocent bystander" mechanism in which the principal element is secondary T cell influx triggered by both antiviral and anti-HLA immunity.


BK Virus/immunology , Graft Rejection/immunology , Kidney Diseases/immunology , Kidney Transplantation , Polyomavirus Infections/immunology , T-Lymphocytes/immunology , Tumor Virus Infections/immunology , Adult , Aged , Antibody Specificity , Female , High-Throughput Nucleotide Sequencing/methods , Humans , Kidney Diseases/genetics , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/virology , Male , Middle Aged , Polyomavirus Infections/virology , Receptors, Antigen, T-Cell/genetics , Tumor Virus Infections/virology , Young Adult
11.
Am J Transplant ; 16(9): 2654-60, 2016 09.
Article En | MEDLINE | ID: mdl-26988137

The definition of Banff Borderline became ambiguous when the Banff 2005 consensus modified the lower threshold from i1t1 (10-25% interstitial inflammation with mild tubulitis) to i0t1 (0-10% interstitial inflammation with mild tubulitis). We conducted a worldwide survey among members of the Renal Pathology Society about their approach to this diagnostic category. A web-based survey was sent out to all 503 current members (153 respondents). A database search yielded which threshold for Banff i was applied in the most influential manuscripts about Borderline. Among the 139 nephropathologists using the Borderline category, 67% use the Banff 1997 definition, requiring Banff i1. Thirty-seven percent admitted to sometimes exaggerating Banff i in the presence of tubulitis, to reach a diagnosis of Borderline. Forty-eight percent were dissatisfied with the definition of Borderline. The majority of the most influential manuscripts used the 1997 definition, contrary to the current one. There is considerable dissatisfaction with Borderline, and practice in Banff i thresholds is variable. Until additional studies inform a revision, we suggest leaving it to each pathologist's discretion whether to use i0 or i1 as the minimal threshold. In order to avoid future ambiguity, a web-based synopsis of all scattered current Banff definitions and rules should be created.


Graft Rejection/diagnosis , Graft Rejection/etiology , Graft Survival/immunology , Kidney Failure, Chronic/pathology , Kidney Transplantation/adverse effects , T-Lymphocytes/immunology , Glomerular Filtration Rate , Humans , Kidney Failure, Chronic/surgery , Kidney Function Tests , Prognosis , Risk Factors
12.
Am J Transplant ; 16(2): 398-406, 2016 Feb.
Article En | MEDLINE | ID: mdl-26731714

BK polyomavirus (BKPyV) infection represents a major problem in transplantation, particularly for renal recipients developing polyomavirus-associated nephropathy (PyVAN). The possibility that BKPyV may also be oncogenic is not routinely considered. Twenty high-grade renourinary tumors expressing polyomavirus large T antigen in the entirety of the neoplasm in 19 cases, including the metastases in six, have been reported in transplant recipients with a history of PyVAN or evidence of BKPyV infection. Morphological and phenotypical features consistent with inactivation of the tumor suppressors pRB and p53 were found in the bladder tumors, suggesting a carcinogenesis mechanism involving the BKPyV large tumor oncoprotein/antigen. The pathogenesis of these tumors is unclear, but given the generally long interval between transplantation and tumor development, the risk for neoplasms after BKPyV infections may well be multifactorial. Other elements potentially implicated include exposure to additional exogenous carcinogens, further viral mutations, and cell genomic instability secondary to viral integration, as occurs with the Merkel cell PyV-associated carcinoma. The still scarce but increasingly reported association between longstanding PyVAN and renourinary neoplasms requires a concerted effort from the transplant community to better understand, diagnose, and treat the putative association between the BKPyV and these neoplasms.


BK Virus/pathogenicity , Carcinogenesis/pathology , Kidney Diseases/etiology , Polyomavirus Infections/complications , Tumor Virus Infections/complications , Urinary Bladder Neoplasms/etiology , Humans , Kidney Diseases/pathology , Polyomavirus Infections/virology , Prognosis , Tumor Virus Infections/virology , Urinary Bladder Neoplasms/pathology
13.
Clin Otolaryngol ; 41(1): 15-20, 2016 Feb.
Article En | MEDLINE | ID: mdl-25974245

OBJECTIVES: To assess olfactory outcomes in patients undergoing septorhinoplasty surgery in our unit. DESIGN: Prospective cohort study. SETTING: The Royal National Throat Nose and Ear Hospital, London. PARTICIPANTS: Forty-three patients undergoing functional septorhinoplasty (Males = 26; mean age = 34.1 ± 12.2) were recruited into the study. MAIN OUTCOME MEASURES: The primary outcome of olfactory function was assessed using 'Sniffin sticks'. Our secondary outcomes were assessment of patient quality of life using the disease specific Sino-nasal Outcome Test-23 questionnaire (SNOT-23) and a visual analogue scale for sense of smell. These measures were repeated at 12 weeks post operatively. RESULTS: There was a significant change in the Sniffin' sticks score post-operatively (8.3 versus 9.6; P < 0.001). The SNOT-23 score also showed a significant improvement post-operatively (53.5 versus 40.4; P < 0.001). A significant improvement was not found in the smell/taste question (question 21) of the SNOT-23 questionnaire as well as the visual analogue scale for sense of smell. A difference in olfactory outcome was not found between open versus closed approaches, primary versus revision surgery and traumatic versus non traumatic cases. CONCLUSIONS: The results show a measured significant improvement in olfaction following functional Septorhinoplasty but not a subjective improvement in the patients perception of their sense of smell and hence not a clinically significant difference. The reasons for the measured improvement are not clear and are likely to be multifactorial.


Nasal Septum/surgery , Rhinoplasty , Smell/physiology , Adult , Female , Humans , Male , Quality of Life , Surveys and Questionnaires , Taste/physiology , Treatment Outcome , Visual Analog Scale
15.
Clin Otolaryngol ; 40(6): 698-703, 2015 Dec.
Article En | MEDLINE | ID: mdl-25943502

OBJECTIVES: To assess the reliability of nasal inspiratory peak flow (NIPF) in providing a clinically accurate objective measure following functional septorhinoplasty by comparing it to the validated disease-specific quality-of-life questionnaire, SNOT-22. Studies so far have demonstrated poor correlation between bilateral NIPF and symptom-specific nasal questionnaires following septorhinoplasty. DESIGN: To perform a prospective comparative analysis between NIPF and the validated disease-specific quality-of-life questionnaire SNOT-22 and to determine whether a correlation exists following septorhinoplasty surgery. SETTING: The Royal National Throat Nose and Ear Hospital, London. PARTICIPANTS: A total of 122 patients (78 males, 44 females; mean age 33.5 ± 12.2 years) were recruited from the senior authors rhinology clinic and underwent functional septorhinoplasty surgery. MAIN OUTCOME MEASURES: Preoperative and postoperative nasal inspiratory peak flow (NIPF) measurements were performed in addition to the completion of three subjective quality-of-life and symptom assessment tool questionnaires; Sinonasal Outcome Test 22 (SNOT-22), Nasal Obstruction Symptom Evaluation (NOSE) and Visual Analogue Scale (VAS: 0-10). RESULTS: The mean preoperative NIPF was 88.2 L/min, and the postoperative value was 101.6 L/min and showed a significant improvement following surgery (P = 0.0064). The mean total SNOT-22 score improved significantly from 48.6 to 26.6 (P < 0.0001); the NOSE score from 14.1 to 6.6 (P < 0.0001); and the Visual Analogue Scale (VAS) blockage score from 6.9 to 3.2 (P < 0.0001). All individual domains assessed showed improvements postoperatively, but no correlation was found between the NIPF and SNOT-22 score. Equally, we did not find a correlation between NIPF and the symptom-specific NOSE questionnaire and the nasal blockage domain on the Visual Analogue Scale (VAS) scale. CONCLUSION: We have demonstrated that NIPF does not correlate with the SNOT-22 disease-specific questionnaire, although both outcomes significantly improve postoperatively. At present, we are still lacking a clinically accurate objective measure of nasal function for the evaluation of patients undergoing septorhinoplasty surgery.


Nasal Obstruction/surgery , Nasal Septum/surgery , Outcome Assessment, Health Care/methods , Quality of Life , Rhinoplasty/methods , Adolescent , Adult , Female , Follow-Up Studies , Humans , Male , Nasal Obstruction/psychology , Postoperative Period , Prospective Studies , Surveys and Questionnaires , Young Adult
16.
Am J Transplant ; 15(4): 1014-20, 2015 Apr.
Article En | MEDLINE | ID: mdl-25736704

Neutralizing antibodies (NAbs) form the basis of immunotherapeutic strategies against many important human viral infections. Accordingly, we studied the prevalence, titer, genotype-specificity, and mechanism of action of anti-polyomavirus BK (BKV) NAbs in commercially available human immune globulin (IG) preparations designed for intravenous (IV) use. Pseudovirions (PsV) of genotypes Ia, Ib2, Ic, II, III, and IV were generated by co-transfecting a reporter plasmid encoding luciferase and expression plasmids containing synthetic codon-modified VP1, VP2, and VP3 capsid protein genes into 293TT cells. NAbs were measured using luminometry. All IG preparations neutralized all BKV genotypes, with mean EC50 titers as high as 254 899 for genotype Ia and 6,666 for genotype IV. Neutralizing titers against genotypes II and III were higher than expected, adding to growing evidence that infections with these genotypes are more common than currently appreciated. Batch to batch variation in different lots of IG was within the limits of experimental error. Antibody mediated virus neutralizing was dose dependent, modestly enhanced by complement, genotype-specific, and achieved without effect on viral aggregation, capsid morphology, elution, or host cell release. IG contains potent NAbs capable of neutralizing all major BKV genotypes. Clinical trials based on sound pharmacokinetic principles are needed to explore prophylactic and therapeutic applications of these anti-viral effects, until effective small molecule inhibitors of BKV replication can be developed.


Antibodies, Neutralizing/immunology , BK Virus/genetics , Genes, Viral , Genotype , Immunoglobulins/immunology , Cell Line , Humans
17.
Rhinology ; 52(4): 301-304, 2014 12.
Article En | MEDLINE | ID: mdl-25479209

BACKGROUND: There has been a great expansion in patient-based outcome measures to face the ever-increasing demand to demonstrate surgical efficacy. However, surgeons have not adopted until now any systematic outcome instrument. The 22-item Sino-Nasal Outcome Test (SNOT-22) is a validated sinonasal outcome score in sinonasal and septorhinoplasty surgery but does not measure aesthetic outcome. The aim of this paper is to validate a modification to the Sino-Nasal Outcomes Test-22 (SNOT-22) with a new question regarding the shape of the nose (SNOT-23). METHODOLOGY: We conducted a prospective cohort study on 69 consecutive patients undergoing septorhinoplasty and a control group of healthy volunteers. Reproducibility, responsiveness to treatment, known group differences and validity of the SNOT-23 were analysed. Scores were compared to visual analogue scales, nasal obstruction symptoms evaluation (NOSE) score and nasal inspiratory peak flow. RESULTS: SNOT-23 has good test-retest reliability and is a valid outcome measure for assessing response to surgery especially with regards to shape of the nose and nasal obstruction when compared to other patient reported measures. CONCLUSION: SNOT-23 is a valid and reliable tool that can be easily used in routine clinical practice to assess the functional and aesthetic outcomes from septorhinoplasty surgery. The SNOT-23 could be adopted as a universal, easy to use tool in rhinology clinics for the assessment of response to septorhinoplasty and sinus surgery.


Nasal Obstruction/surgery , Nasal Septum/surgery , Nasal Surgical Procedures/methods , Rhinoplasty/instrumentation , Humans , Nasal Surgical Procedures/standards , Outcome Assessment, Health Care , Prospective Studies , Quality of Life , Rhinoplasty/standards , Surveys and Questionnaires
18.
Am J Transplant ; 14(9): 2137-47, 2014 Sep.
Article En | MEDLINE | ID: mdl-25091177

Immunohistochemistry (IHC) is the gold standard for diagnosing (positive vs. negative) polyomavirus BK (BKV) nephropathy and has the potential for disease staging based on staining intensity and quantification of infected cells. This multicenter trial evaluated the reproducibility of BKV IHC among 81 pathologists at 60 institutions. Participants stained tissue microarray slides and scored them for staining intensity and percentage of positive nuclei. Staining protocol details and evaluation scores were collected online. Slides were returned for centralized panel re-evaluation and kappa statistics were calculated. Individual assessment of staining intensity and percentage was more reproducible than combined scoring. Inter-institutional reproducibility was moderate for staining intensity (κ = 0.49) and percentage (κ = 0.42), fair for combined (κ = 0.25) and best for simple positive/negative scoring (κ = 0.78). Inter-observer reproducibility was substantial for intensity (κ = 0.74), percentage (κ = 0.66), positive/negative (κ = 0.78) and moderate for combined scoring (κ = 0.43). Inter-laboratory reproducibility was fair for intensity (κ = 0.37), percentage (κ = 0.40) and combined (κ = 0.24), but substantial for positive/negative scoring (κ = 0.67). BKV RNA copies/cell correlated with staining intensity (r = 0.56) and percentage (r = 0.62). These results indicate that BKV IHC is reproducible between observers but scoring should be simplified to a single-feature schema. Standardization of tissue processing and staining protocols would further improve inter-laboratory reproducibility.


Kidney Transplantation , Polyomavirus/isolation & purification , Quality Assurance, Health Care , Alberta , Humans , Immunohistochemistry , Polymerase Chain Reaction , Polyomavirus/genetics , Reproducibility of Results , Transplantation, Homologous
19.
Clin Microbiol Infect ; 20 Suppl 7: 74-88, 2014 Sep.
Article En | MEDLINE | ID: mdl-24476010

Human polyomaviruses (HPyVs) are a growing challenge in immunocompromised patients in view of the increasing number of now 12 HPyV species and their diverse disease potential. Currently, histological evidence of disease is available for BKPyV causing nephropathy and haemorrhagic cystitis, JCPyV causing progressive multifocal leukoencephalopathy and occasionally nephropathy, MCPyV causing Merkel cell carcinoma and TSPyV causing trichodysplasia spinulosa, the last two being proliferative skin diseases. Here, the current role of HPyV in solid organ transplantation (SOT) was reviewed and recommendations regarding screening, monitoring and intervention were made. Pre-transplant screening of SOT donor or recipient for serostatus or active replication is currently not recommended for any HPyV. Post-transplant, however, regular clinical search for skin lesions, including those associated with MCPyV or TSPyV, is recommended in all SOT recipients. Also, regular screening for BKPyV replication (e.g. by plasma viral load) is recommended in kidney transplant recipients. For SOT patients with probable or proven HPyV disease, reducing immunosuppression should be considered to permit regaining of immune control. Antivirals would be desirable for treating proven HPyV disease, but are solely considered as adjunct local treatment of trichodysplasia spinulosa, whereas surgical resection and chemotherapy are key in Merkel cell carcinoma. Overall, the quality of the clinical evidence and the strength of most recommendations are presently limited, but are expected to improve in the coming years.


Organ Transplantation , Polyomavirus Infections/epidemiology , Polyomavirus Infections/prevention & control , Transplant Recipients , Epidemiological Monitoring , Europe/epidemiology , Humans , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Infection Control/methods , Mass Screening , Polyomavirus Infections/diagnosis
20.
Am J Transplant ; 14(2): 272-83, 2014 Feb.
Article En | MEDLINE | ID: mdl-24472190

The 12th Banff Conference on Allograft Pathology was held in Comandatuba, Brazil, from August 19-23, 2013, and was preceded by a 2-day Latin American Symposium on Transplant Immunobiology and Immunopathology. The meeting was highlighted by the presentation of the findings of several working groups formed at the 2009 and 2011 Banff meetings to: (1) establish consensus criteria for diagnosing antibody-mediated rejection (ABMR) in the presence and absence of detectable C4d deposition; (2) develop consensus definitions and thresholds for glomerulitis (g score) and chronic glomerulopathy (cg score), associated with improved inter-observer agreement and correlation with clinical, molecular and serological data; (3) determine whether isolated lesions of intimal arteritis ("isolated v") represent acute rejection similar to intimal arteritis in the presence of tubulointerstitial inflammation; (4) compare different methodologies for evaluating interstitial fibrosis and for performing/evaluating implantation biopsies of renal allografts with regard to reproducibility and prediction of subsequent graft function; and (5) define clinically and prognostically significant morphologic criteria for subclassifying polyoma virus nephropathy. The key outcome of the 2013 conference is defining criteria for diagnosis of C4d-negative ABMR and respective modification of the Banff classification. In addition, three new Banff Working Groups were initiated.


Arteritis/etiology , Complement C4b/metabolism , Graft Rejection/etiology , Isoantibodies/immunology , Organ Transplantation/adverse effects , Peptide Fragments/metabolism , Arteritis/metabolism , Graft Rejection/metabolism , Humans , Research Report
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