Elective neck dissection in patients with salivary gland carcinoma: A systematic review and meta-analysis.

OBJECTIVE: Elective neck dissection in patients with salivary gland carcinoma and clinically negative lymph nodes is controversial. Reported proportion of occult nodal metastases vary with histological subtype, tumour classification and preoperative diagnostic methods. This is a systematic review and meta-analysis on the role of END in salivary gland carcinoma. METHODS: A search in PubMed, Embase and Cochrane was performed. Original articles in English with data on tumour characteristics, clinical and pathological N-classification, and neck dissection were included. Reporting Items for Systematic Reviews and Meta-analyses were followed. Random effect modelling was performed to pool the data. Meta-analysis of proportions was performed for occult metastases overall, for T3/T4 versus T1/T2 tumours and for tumours with high-grade versus low-grade histology. Heterogeneity across studies was assessed with I-squared statistics. RESULTS: We included 22 articles in the qualitative synthesis and meta-analysis. The pooled proportion of occult metastases was 21%. In patients with T3/T4 tumour, the pooled proportion of occult metastases was 36%, and in patients with high-grade histology, it was 34%. Most studies concluded that END should be performed in patients with advanced T-classification and high-grade histology tumours. Nine studies assessed occult metastases per level. CONCLUSION: The overall occult metastases proportion does not require END in all patients with salivary gland carcinoma. We recommend END in patients with high-grade or unknown histology or T3/T4 tumours. END should involve level II and III, and level I should be included in tumours in the submandibular gland, sublingual gland and minor oral salivary glands.

Definition of locally recurrent head and neck squamous cell carcinoma: a systematic review and proposal for the Odense-Birmingham definition.

PURPOSE: The objectives of this study were (1) to systematically review current definitions of head and neck squamous cell carcinoma (HNSCC) recurrence and (2) to propose a definition of locally recurrent HNSCC. METHODS: A systematic literature review was performed according to the 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' statement in Medline, Embase, and Cochrane databases guided by the study question "What is the definition of local recurrence for patients with HN:SCC?". All retrieved studies were reviewed and qualitatively analyzed. RESULTS: The systematic literature search resulted in 3467 publications after removal of duplicates. Forty studies were examined as full text, and a total of five were found suitable for inclusion. All five included studies dealt with definitions of second primary HNSCC and were based on the Warren and Gates Criteria; (1) each of the tumors are malignant, (2) each must be distinct, and (3) the probability of one being a metastasis of the other must be excluded. Each of the included studies added specific anatomical and/or temporal separation measures to the criteria of second primary HNSCC. We propose the definition of locally recurrent HNSCC to be: (1) Same anatomical subsite or adjacent subsite within 3 cm of the primary lesion, (2) time-interval no more than 3 years (from completed treatment of the primary lesion), and (3) same p16-status for oropharyngeal carcinomas. CONCLUSIONS: No uniform definition of locally recurrent HNSCC currently exists. We propose the Odense-Birmingham definition based on the anatomical subsite combined with a specific measurable distance and a temporal separation of three years.

Therapeutic Use of the Human Papillomavirus Vaccine on Recurrent Respiratory Papillomatosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Recurrent respiratory papillomatosis is a benign condition caused by human papillomavirus (HPV). Surgery is the mainstay of treatment, but numerous adjuvant therapies have been applied to improve surgical outcome. Recently, HPV vaccination has been introduced, but only smaller studies of its effect have been published. The present meta-analysis is intended as a possible substitute for a proposed but not yet realized multicenter randomized controlled trial. METHODS: A systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. PubMed, Embase, and Cochrane were systematically searched. All retrieved studies (n = 593) were reviewed and qualitatively assessed. In addition, 2 previously unpublished data sets were included. The systematic review included 11 studies, comprising 133 patients, of whom 63 patients from 5 studies were eligible for meta-analysis. A random-effects meta-analysis was conducted for the mean difference in number of surgical procedures per month before and after vaccination. RESULTS: The number of surgical procedures per month was significantly reduced after HPV vaccination compared with before vaccination (estimated mean, 0.06 vs 0.35). The mean intersurgical interval increased from 7.02 months (range, 0.30-45 months) before to 34.45 months (2.71-82 months) after HPV vaccination. CONCLUSION: The present study supports the continued use of the HPV vaccine as an adjuvant treatment for recurrent respiratory papillomatosis.

Risk of Malignancy in FDG-Avid Thyroid Incidentalomas on PET/CT: A Prospective Study.

BACKGROUND: Due to a substantial risk of malignancy, patients with focal FDG-avid thyroid incidentalomas (FFTIs) on PET/CT are in most of Denmark referred to Head and Neck Cancer (HNC) fast track programs. The aim of this study was to determine the risk of malignancy in FFTI managed in a HNC fast track program. METHODS: A prospective cohort study including all patients with FFTI referred to the HNC fast track program, Odense University Hospital between September 1, 2016 and August 31, 2017. Ultrasonography (US) and fine-needle aspiration biopsy (FNAB) were intended to be done in all patients. Nodules with cytology of Bethesda 1, 3, 4, 5, or 6 were planned for surgical removal. RESULTS: A total of 104 patients were included. All patients had US and 101 patients (97%) had FNAB. Forty-two patients had benign cytology classified as Bethesda 2. The remaining 62 patients underwent surgery except from 11 patients, mainly due to comorbidity. The overall risk of malignancy for patients with FFTI referred to our HNC fast track program was calculated to be 24% (23/95) based on patients with unequivocal cytology and/or histology. The only statistically significant US characteristic to predict malignancy was the appearance of irregular margins with a sensitivity of 47% and specificity of 96%. CONCLUSION: The risk of malignancy of FFTIs handled in our HNC fast track program is 24%.

Making decisions for follow-up chemotherapy based on digital patient reported outcomes data in patients with multiple myeloma and other M protein diseases - A mixed method study.

OBJECTIVES: To test if Patient Reported Outcomes (PRO) data can replace physical on-site consultation in determining if patients with multiple myeloma, AL amyloidosis, or plasma cell leukemia are ready for their next bortezomib treatment without dose reduction. METHODS: We developed an online questionnaire addressing common side effects to bortezomib and an algorithm stratifying patients according to their responses and asked them to complete the questionnaire the day before attending the clinic. Applying a mixed-method study design of PRO data, time registrations, and interviews with patients and healthcare professionals, we tested the usability of electronic PRO data forming the basis of decision-making on whether patients are physically fit for the next treatment with an unchanged dose. RESULTS: The questionnaire and the associated algorithm were able to identify patients who were physically fit for treatment without need for further consultation, with a positive predictive value of 98 %. The method proved to be feasible for all groups of patients regardless of age and educational level. Patients and healthcare professionals found the online questionnaire to be advantageous and flexible. CONCLUSION: The use of PRO data to evaluate patients prior to bortezomib treatment is safe and feasible. Patients prefer to report their side effects themselves as it provides them with more freedom during their treatment.

Home is best. Self-administration of subcutaneous Bortezomib at home in patients with multiple myeloma - A mixed method study.

OBJECTIVES: To examine the perspectives of patients and healthcare professionals of self-administration of subcutaneous (SC) injection of Bortezomib in the homes of patients with Multiple Myeloma (MM), and to assess organizational aspects. METHODS: A prospective, clinical, parallel mixed-method design with a qualitative core and a quantitative supplementary component was conducted at a single hematological centre in Denmark. Qualitative data were obtained from individual, semi-structured interviews with patients (n = 10) and a focus group interview with healthcare professionals (n = 5); data were analyzed using a hermeneutic approach. Quantitative data were acquired from time registrations performed by patients and nurses and descriptively analyzed applying a micro-costing approach, using cost data per individual. RESULTS: In general, patients and healthcare professionals were pleased with self-administration as patient empowerment increased. Qualitative findings yielded three themes: "Home is best", "Everyone is different", and "Safety first". Quantitative data were confirmative and revealed self-administration to be time saving for patients and nurses. In a Danish context, delivery of the medicine to the patient's home was slightly more expensive than administration at the hospital. CONCLUSIONS: Self-administration of SC Bortezomib in the homes of patients with MM is advantageous for patients and healthcare professionals. It is feasible, safe, and timesaving. These advantages come with a negligible increase in expenses.

Diagnostic accuracy of imaging modalities in detection of histopathological extranodal extension: A systematic review and meta-analysis.

OBJECTIVE: To present an up to date systematic review and meta-analysis evaluating the diagnostic accuracy of the most used imaging modalities in detection of histopathological extra nodal extension (ENE) in head and neck squamous cell carcinoma. MATERIALS AND METHODS: Medline, Embase, and Cochrane databases were systematically searched on March 27th 2020. Screening, inclusion, quality assessment, and data extraction were done by two reviewers. Meta-analysis was conducted using the bivariate model approach after pooling the studies according to imaging modality. Heterogeneity was explored by meta-regression. Comparison was done by meta-regression and sub-group analyses. RESULTS: Out of 476 initial hits, 25 studies were included for analysis. Of these, 14 dealt with CT, nine with PET/CT, four with MRI, two with ultrasound, and none with PET/MRI. Meta-analysis based on a total sample size of 3391 showed that CT had a sensitivity of 76% [67-82%] and specificity of 77% [69-83%], MRI a sensitivity of 72% [64-79%] and specificity of 78% [57-90%], and PET/CT a sensitivity of 80% [76-84%] and specificity of 83% [74-90%] in the ability to predict ENE. No meta-analysis could be done on ultrasound. There were no significant differences between modalities in overall accuracy; however, PET/CT had significantly higher sensitivity than CT and MRI. CONCLUSION: There was no significant difference in the ability of CT, MRI, and PET/CT to diagnose histopathological ENE, except that PET/CT had a significantly higher sensitivity than CT and MRI.

Histopathological Definitions of Extranodal Extension: A Systematic Review.

Extranodal extension (ENE) is a very strong prognostic factor in head and neck squamous cell carcinoma. However, significant variance in reported incidence of ENE suggests discordance in perception of ENE among pathologists. This study aims to map the different definitions of histopathological ENE used in the literature. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. Guided by the research question: "How is histopathological ENE defined?" the databases Medline, Embase, and Cochrane were systematically searched. All retrieved studies were reviewed and qualitatively analyzed. Three categories of existing definitions were formed. The systematic literature search yielded 1786 studies after removal of duplicates. Nine hundred and thirty-four full text articles were assessed for inclusion and 44 unique ENE definitions were identified and categorized 1-3; (1) simple definitions only describing a breach in the capsule (48%), (2) definitions also including a description of the perinodal tissue (43%), and (3) definitions adding a description of a specific reaction in the perinodal structure (9%). No consensus definition of ENE exists, but based on the level of details in the identified definitions, three overall categories of ENE definitions were established.

Surgical treatment of patulous Eustachian tube - a systematic review.

INTRODUCTION: Patulous Eustachian tube (PET) seems to be caused by a defect in the mucosal valve of the Eustachian tube. It causes troublesome autophony occasionally leading to an impaired quality of life. In the present study, we aimed to evaluate the effect of surgical treatment of PET through a systematic review of published studies. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis statement. Medline, Embase and Cochrane were searched systematically for publications about PET. METHODS: Fourteen publications counting a total of 510 ears from 390 patients who had been treated surgically for PET were included. Complete relief of symptoms ranged from 7% to 77%, improvement from 7% to 86% and 0% to 41% had no response. No studies reported aggravation of symptoms. CONCLUSIONS: A number of suggested treatments appear to be promising for PET, but it is difficult to propose a specific surgical treatment due to low numbers of patients, lack of clinical trials and cohort studies without control groups.

Reproducibility of Automated Voice Range Profiles, a Systematic Literature Review.

OBJECTIVE: Reliable voice range profiles are of great importance when measuring effects and side effects from surgery affecting voice capacity. Automated recording systems are increasingly used, but the reproducibility of results is uncertain. Our objective was to identify and review the existing literature on test-retest accuracy of the automated voice range profile assessment. STUDY DESIGN: Systematic review. DATA SOURCES: PubMed, Scopus, Cochrane Library, ComDisDome, Embase, and CINAHL (EBSCO). METHODS: We conducted a systematic literature search of six databases from 1983 to 2016. The following keywords were used: phonetogram, voice range profile, and acoustic voice analysis. Inclusion criteria were automated recording procedure, healthy voices, and no intervention between test and retest. Test-retest values concerning fundamental frequency and voice intensity were reviewed. RESULTS: Of 483 abstracts, 231 full-text articles were read, resulting in six articles included in the final results. The studies found high reliability, but data are few and heterogeneous. CONCLUSION: The reviewed articles generally reported high reliability of the voice range profile, and thus clinical usefulness, but uncertainty remains because of low sample sizes and different procedures for selecting, collecting, and analyzing data. More data are needed, and clinical conclusions must be drawn with caution.

Heterogenic expression of stem cell markers in patient-derived glioblastoma spheroid cultures exposed to long-term hypoxia.

AIM: To investigate the time profile of hypoxia and stem cell markers in glioblastoma spheroids of known molecular subtype. MATERIALS & METHODS: Patient-derived glioblastoma spheroids were cultured up to 7 days in either 2% or 21% oxygen. Levels of proliferation (Ki-67), hypoxia (HIF-1α, CA9 and VEGF) and stem cell markers (CD133, nestin and musashi-1) were investigated by immunohistochemistry. RESULTS: Hypoxia markers as well as CD133 and partially nestin increased in long-term hypoxia. The proliferation rate and spheroid size were highest in normoxia. CONCLUSION: We found differences in hypoxia and stem cell marker profiles between the patient-derived glioblastoma cultures. This heterogeneity should be taken into consideration in development of future therapeutic strategies.

The Danish Head and Neck Cancer fast-track program: a tertiary cancer centre experience.

INTRODUCTION: During the 1990s, all Nordic countries except for Denmark experienced a general increase in 5-year survival rates for cancer patients. In 2007, the Danish National Board of Health in collaboration with national multidisciplinary cancer groups and the Danish regions initiated fast-track clinical pathway solutions. OBJECTIVES: The objectives of this study were 1) to present the setup of the head and neck cancer (HNC) fast-track program at Odense University Hospital (OUH) as an example of the Danish model and 2) to present patient characteristics, diagnostic outcome, cancer detection rate, and duration of the fast-track patient courses. MATERIALS AND METHODS: From 1st July 2012 to 1st September 2015, all patients referred to the HNC fast-track program at OUH for diagnostics and treatment were consecutively included in the study resulting in 3165 patient courses. RESULTS: The overall malignancy detection rate was 40.6% and for HNC it was 29.2%. The overall median fast-track course duration was 12 days (range 0-74). Overall 2990 (94.5%) of 3165 patients completed their fast-track course within the maximally permitted course duration. DISCUSSION AND CONCLUSION: Based on our findings, it was concluded that: 1) a HNC fast-track program build on pre-booked slots for diagnostics and treatment is feasible and can secure acceptable course durations for more than 90% of patient courses, 2) by using private ENT specialists as a 'filter-function', an acceptable detection rate can be achieved.

Can the Ni classification of vessels predict neoplasia? A systematic review and meta-analysis.

OBJECTIVES: The Ni classification of vascular change from 2011 is well documented for evaluating pharyngeal and laryngeal lesions, primarily focusing on cancer. In the planning of surgery it may be more relevant to differentiate neoplasia from non-neoplasia. We aimed to evaluate the ability of the Ni classification to predict laryngeal or hypopharyngeal neoplasia and to investigate if a changed cutoff value would support the recent European Laryngological Society (ELS) proposal of perpendicular vascular changes as indicative of neoplasia. DATA SOURCES: PubMed, Embase, Cochrane, and Scopus databases. REVIEW METHODS: A systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. We systematically searched for publications from 2011 until 2016. All retrieved studies were reviewed and qualitatively assessed. The pooled sensitivity and specificity of the Ni classification with two different cutoffs were calculated, and bubble and summary receiver operating characteristics plots were created. RESULTS: The combined sensitivity of five studies (n = 687) with Ni type IV-V defined as test-positive was 0.89 (95% confidence interval [CI]: 0.76-0.95), and specificity was 0.82 (95% CI: 0.72-0.89). The equivalent combined sensitivity of four studies (n = 624) with Ni type V defined as test-positive was 0.82 (95% CI: 0.75-0.87), and specificity was 0.93 (95% CI: 0.82-0.97). CONCLUSIONS: The diagnostic accuracy of the Ni classification in predicting neoplasia was high, without significant difference between the two analyzed cutoff values. Implementation of the proposed ELS classification of vascular changes seems reasonable from a clinical perspective, with comparable accuracy. Attention must be drawn to the accompanying risk of exposing patients to unnecessary surgery. Laryngoscope, 128:168-176, 2018.

Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells.

Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson's disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting in both protection and generation of reactive oxygen species. The present study investigated the effect of CO produced by a novel CO-releasing molecule on dopaminergic differentiation of human neural stem cells. Short-term exposure to 25 ppm CO at days 0 and 4 significantly increased the relative content of ß-tubulin III-immunoreactive immature neurons and tyrosine hydroxylase expressing catecholaminergic neurons, as assessed 6 days after differentiation. Also the number of microtubule associated protein 2-positive mature neurons had increased significantly. Moreover, the content of apoptotic cells (Caspase3) was reduced, whereas the expression of a cell proliferation marker (Ki67) was left unchanged. Increased expression of hypoxia inducible factor-1α and production of reactive oxygen species (ROS) in cultures exposed to CO may suggest a mechanism involving mitochondrial alterations and generation of ROS. In conclusion, the present procedure using controlled, short-term CO exposure allows efficient dopaminergic differentiation of human neural stem cells at low cost and may as such be useful for derivation of cells for experimental studies and future development of donor cells for transplantation in Parkinson's disease.

Can videostroboscopy predict early glottic cancer? A systematic review and meta-analysis.

OBJECTIVE: Correct assessment of patients with a glottic lesion is crucial for ensuring proper treatment in cases of cancer or premalignancy and for avoiding unnecessary surgery. For years, videostroboscopy (VS) has been the gold standard for assessing such lesions, but diagnostic difficulties have been described. We aim to estimate the diagnostic accuracy of VS in differentiating early glottic cancer from noninvasive lesions by conducting a systematic review and meta-analysis of published studies. DATA SOURCES: PubMed and Embase databases were searched without restrictions on publication date. REVIEW METHODS: A systematic review and subsequent meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. We systematically searched the literature for publications on stroboscopic diagnosis of cancer or premalignant lesions on the vocal cords. All retrieved studies were reviewed and qualitatively assessed. The pooled sensitivity and specificity of VS were calculated, and bubble and summary receiver operating characteristics plots were created. RESULTS: A meta-analysis was conducted on five studies with a total of 307 patients. The sensitivities of VS within the single studies ranged from 86% to 100% and specificities ranged from 7% to 93%. The meta-analysis showed that the sensitivity of the combined results was 0.96 (95% confidence interval [CI]: 0.89-0.98), and the specificity was 0.65 (95% CI: 0.21-0.93). CONCLUSION: VS is able to identify almost all patients with cancer, but only approximately two-thirds of patients with noninvasive lesions are correctly identified as not having cancer. Further research concerning assessment of patients with vocal cord lesions is needed. LEVEL OF EVIDENCE: NA Laryngoscope, 126:2079-2084, 2016.

Effect of gender on results of percutaneous edge-to-edge mitral valve repair with MitraClip system.

Knowledge regarding gender-specific results of percutaneous edge-to-edge mitral valve repair is scarce. The aim of this study was to investigate gender differences in outcomes in a cohort of patients treated with MitraClip implantation. A multicenter registry of 173 patients treated with MitraClip prostheses from 2009 to 2012 at 3 experienced centers was performed. One hundred nine patients (63%) were men. Men were younger (mean age 73 ± 10 vs 79 ± 9 years, p = 0.001) and had a higher prevalence of previous coronary bypass graft surgery (34% vs 13%, p = 0.002), previous myocardial infarction (46% vs 20%, p = 0.001), and diabetes mellitus (26% vs 11%, p = 0.020). There were no differences regarding New York Heart Association (NYHA) functional class before the intervention (NYHA class III or IV in 95% of men vs 97% of women, p = 0.472) or the cause of mitral regurgitation (MR) (functional in 58% of men vs 48% of women, p = 0.233). Men exhibited significantly larger ventricles (mean indexed left ventricular end-systolic diameter 2.4 ± 0.8 vs 2.0 ± 1.6 cm/m(2), p = 0.002, and mean indexed left ventricular end-diastolic volume 92.7 ± 46.1 vs 59.9 ± 24.6 ml/m(2), p <0.001). At 1 month, there were no differences between groups in the reduction of MR or NYHA functional class (MR grade ≤2+ in 98.2% of men vs 96.8% of women, p = 0.586, and NYHA class ≤II in 78.3% of men vs 77% of women, p = 0.851). At 6 months, results were maintained (MR grade ≤2+ in 89.5% of men vs 96.8% of women, p = 0.414, and NYHA class ≤II in 73.1% of men vs 74.2% of women, p = 0.912). After a mean follow-up period of 16.1 ± 11.1 months, no difference was found between groups in the incidence of death or admission for heart failure (log-rank p = 0.798). In conclusion, MitraClip implantation seems to be an equally safe and effective treatment of MR in men and women.

Effect of advanced chronic kidney disease in clinical and echocardiographic outcomes of patients treated with MitraClip system.

BACKGROUND: Data regarding the influence of different levels of renal dysfunction on clinical and echocardiographic results of MitraClip therapy are scarce. We aimed to evaluate the impact of baseline advance renal failure in the outcomes of a cohort of patients treated with MitraClip. METHODS AND RESULTS: We analyzed data from a multicenter registry of 173 patients treated with MitraClip between 2009 and 2012. Patients were classified as advanced chronic kidney disease (CKD, creatinine clearance [CrCl] <30 ml/min, group 1, n=20), moderate CKD (CrCl 30-60 ml/min, group 2, n=78) and normal renal function (CrCl >60 ml/min, group 3, n=75). Twenty patients (11.5%) presented advanced CKD. Procedural success was equal in the 3 groups (95.0% group 1, 100% in group 2 and 96.0% in group 3, p=0.180). Post-procedural MR and NYHA class at 1 month (MR ≥ 3+5.0% vs. 0% vs. 4.0% p=0.190 and NYHA>II 40.0% vs. 21.0% vs. 18.3%, p=0.101) and 6 months (MR ≥ 3+0% vs. 13.0% vs. 2.7%, p=0.330; and NYHA class>II 54.5% vs. 26.9% vs. 25.6%, p=0.298) did not differ between groups. However, patients in group 1 experienced higher frequency of the composite end-point of mortality or readmission at 16.2 ± 11.1 months of follow-up (HR 4.8, CI 95% 1.1-21.3). CONCLUSION: Advanced CKD is linked to an excess of cardiac adverse events. This should be judiciously taken into account when selecting patients for MitraClip.

[Percutaneous closure of the left atrial appendage for stroke prevention].

In patients with atrial fibrillation (AF) and increased risk of stroke, oral anticoagulation (OAC) is the standard treatment for stroke prevention - however, this therapy also carries a high risk of bleeding. Percutaneous closure of the left atrial appendage (LAA) has been suggested to be an alternative option for stroke prevention in AF patients with contraindication(s) for OAC treatment. In this paper, we discuss the rationale for LAA closure, the importance of a proper patient selection, as well as some pre- and post-procedural issues.

Novel approaches for quantifying protein biomarkers in gliomas: benefits and pitfalls.

The therapeutic paradigm of gliomas is changing from a general approach towards an individualized and targeted approach. Accordingly, the search for prognostic and predictive biomarkers, as well as the demand for quantitative, feasible and robust methods for biomarker analysis increases. We find that software classifiers can identify and quantify the expression of a given biomarker within different subcellular compartments and that such classifiers can exclude frequently occurring nontumor cells, thereby avoiding potential bias. The use of a quantitative approach provides a continuous measurement of the expression, allowing establishment of new cut-points and identification of patients with specific prognoses. However, some pitfalls must be noted. This article focuses on benefits and pitfalls of novel approaches for quantifying protein biomarkers in gliomas.

Echocardiographic and clinical outcomes of central versus noncentral percutaneous edge-to-edge repair of degenerative mitral regurgitation.

OBJECTIVES: This study aimed to assess the clinical and echocardiographic results of MitraClip implantation in noncentral degenerative mitral regurgitation (dMR) compared with central dMR. BACKGROUND: It is unknown whether the use of MitraClip therapy in noncentral dMR is as safe and effective as in central dMR. METHODS: We analyzed a multicenter registry of 173 patients treated with the MitraClip and compared results of central and noncentral dMR. RESULTS: Seventy-nine patients (age 79.2 ± 8.0 years, 58.2% men) had dMR. Forty-nine patients (62%) had central dMR, with the remainder classified as noncentral dMR (n = 30, 38%). Patients with noncentral dMR had a wider pre-procedural vena contracta (8.5 ± 2.0 mm vs. 6.9 ± 2.2 mm, p = 0.039) and higher systolic pulmonary pressure (57.9 ± 18.0 vs. 47.3 ± 13.0 mm Hg, p = 0.019). Procedural success was the same in both groups (95.5% central vs. 96.7% noncentral, p = 0.866). Post-procedural MR and New York Heart Association (NYHA) functional class at 1 month (MR ≤2, 96.0% vs. 96.6%, p = 0.866, and NYHA functional class ≤II, 81.6% vs. 90.0%, p = 0.335) and 6 months (95.2% central vs. 91.7% noncentral, p = 0.679; and NYHA functional class >II, 21.1% vs. 0%, p = 0.128) did not differ between groups. There were also no differences in serious post-procedural adverse events: partial clip detachment (central n = 1 [2.0%] vs. noncentral n = 1 [3.3%], p = 1.000), death (5.4% central vs. 13.0% noncentral, p = 0.298), or heart failure admission (10.8% central vs. 8.7% noncentral, p = 0.791). CONCLUSIONS: In experienced centers, MitraClip treatment can be performed safely and effectively in both central and noncentral dMR.