Grading Scheme Research Articles

Impact of New Grading System and New Hemodynamic Classification on Long-Term Outcome in Patients With Severe Tricuspid Regurgitation.

A new grading of tricuspid regurgitation (TR) beyond severe has been proposed. However, few studies assessing the validity of such a new grading scheme of TR have been conducted. Therefore, we evaluated associations of TR grades beyond severe with patient outcome and hemodynamics. We retrospectively studied patients who underwent 2-dimensional echocardiography and were diagnosed with severe TR between January 2014 and December 2015. According to the vena contracta width of TR (VC), the patients were classified into 2 groups: VC under 14 mm (VC<14 mm) and VC 14 mm or greater (VC≥14 mm). Hemodynamic parameters were estimated by echocardiography and were obtained by right heart catheterization. Cardiovascular events were defined as cardiovascular death or admission for heart failure. A total of 679 patients (mean 72±17 years, 56% women) were included. During follow-up (median, 158 days; range, 29-891), 210 patients experienced cardiovascular events. By multivariate analysis, VC≥14 mm and left ventricular ejection fraction were independent predictors of cardiovascular events (hazard ratio, 1.57 [1.06-2.33]; hazard ratio, 0.99 [0.98-0.99], respectively). Patients with VC≥14 mm had significantly lower cardiac index (median, 1.8 versus 2.1 L/min per m2, P=0.001) and a higher prevalence of right atrial pressure 15 mm Hg (74% versus 60%, P<0.001) on echocardiography. Also, right heart catheterization confirmed higher right atrial pressure in patients with VC≥14 mm than those with VC<14 mm (16±8 versus 12±6 mm Hg, P=0.004). The new subset classification developed by cardiac index and right atrial pressure both on echocardiography predicted cardiovascular events (Log-rank P<0.001). The relationship of VC≥14 mm to adverse outcome and poor hemodynamics showed the clinical relevance and need of a new grading system beyond severe. The new hemodynamic subset classification provides additional prognostic value for cardiovascular events in patients with severe TR.

Application of circular anti slide pile with plum blossom arrangement in Expressway Engineering

By using the finite element numerical simulation method, the simplified Bishop method and strength reduction method are used to analyze the stability of a high slope which is protected and treated by anti slide pile combined with prestressed anchor cable grading scheme in Guangdong Province, and the similarities and differences between rectangular pile and plum shaped circular pile in slope treatment effect are compared. Through calculation and analysis of field measured data, it is proved that the circular anti slide pile with plum shaped layout has similar effect with the traditional rectangular anti slide pile, and has the advantages of high degree of mechanization construction and low construction safety risk, so it can be used as the alternative scheme of rectangular pile

Neuroendocrine neoplasms of the digestive tract : incorporating the 2019 WHO grading schema in the South African context

Background The classification of gastrointestinal (GI) neuroendocrine neoplasms (NENs) has been updated in the WHO classification of tumours of the digestive tract. Mitotic rate and Ki-67 proliferation index are central to the histopathological grading of these tumours. Assessing these variables is not standardised in local practice. This study addresses this deficit in the South African context. Methods This is a retrospective audit of archival material of resection specimens of GI NENs (excluding appendix) at Groote Schuur Hospital from 2004 to 2017. We performed a mitotic count and immunohistochemistry for Ki-67 to reclassify tumours according to the 2019 WHO criteria. Results Thirty-five resection specimens were examined. These represented stomach (n = 5), jejunoileum (n = 17), colon (n = 7) and rectum (n = 6). The mean age at the time of resection was 56 years (range 32-72). Twenty-one cases (60%) were women and 14 (40%) were men. The majority (24/35) of tumours were classified as grade 1 well-differentiated neuroendocrine tumours (WD NETs), 8/35 were classified as grade 2 WD NETs and 3/35 were classified as small cell poorly differentiated neuroendocrine carcinomas (PD NECs). Re-classification resulted in 7/35 (20%) changes in tumour grade (4 upgraded, 3 downgraded). In most instances (7/8), the Ki-67 proliferation index was the determining factor in assigning tumour grade. Conclusion This study has increased awareness of the recently updated WHO classification system. We conclude that an objective and systematic approach to counting of mitoses and determination of the Ki-67 proliferation index is recommended in routine practice.

A Comprehensive Literature Review on the Architecture of the Upper Labial Frena

Over the past few years, various surgical procedures have evolved that focus on releasing the taut superior labial frena in infants, yet little is known about their normal or variant morphology despite the growing incidence of severe upper labial frenar tie. Apart from this, the role played by distorted upper labial frena in uncomfortable latching or problems in breast feeding has been a major concern among mothers thereby significantly affecting public health. Hence, the purpose of this literature review is to lucidly highlight the various existing grading schemes and classification systems in literature for superior labial frena and also to understand their precise morphology and developmental origins that will be of great help to oral surgeons and plastic surgeons in performing release repair or reconstructions for the upper lip tie.

The Crucial Role of Eosinophils in the Life Cycle, Radiographical Architecture, and Risk of Recurrence of Chronic Subdural Hematomas.

Chronic subdural hematomas (CSDHs) are a common neurological condition, whose incidence is expected to increase with an aging population. Although surgical evacuation is the mainstay of treatment, it results in a recurrence requiring reoperation (RrR) in 3–30% of cases. Recurrence is thought to be driven by a combination of inflammatory and angiogenic processes occurring within the CSDH outer membrane. Pathological specimens of 72 primary CSDHs were examined for eosinophilic infiltrate. For each case, the pre-operative computed tomography (CT) scan was graded according to the Nakaguchi grading scheme as homogeneous, laminar, separated, or trabecular. Rate of RrR was compared based on eosinophilic infiltrate and CT grade. A dense eosinophilic infiltrate was observed in 22% of specimens. The rate of RrR among specimens with a dense eosinophilic infiltrate was 0%, whereas it was 14.3% among specimens without a dense eosinophilic infiltrate. Incidence among homogeneous, laminar, separated, and trabecular CT subtypes was 4%, 27%, 58%, and 24%, respectively. A dense eosinophilic infiltrate found within the outer membrane of a CSDH may be a marker of hematoma maturation, signaling a transition toward healing and fibrosis, and a lower risk of RrR.

Machine learning approaches to predict rehabilitation success based on clinical and patient-reported outcome measures

Abstract A common way to treat hip, knee or foot injuries is by conducting a corresponding physician-guided rehab over several weeks or even months. While health professionals are often able to estimate the treatment success beforehand to a certain extent based on their experience, it is scientifically still not clear to what extent relevant factors and circumstances explain or predict rehab outcomes. To this end, we apply modern machine learning techniques to a real-life dataset consisting of data from more than a thousand rehab patients (N = 1,047) and build models that are able to predict the rehab success for a patient upon treatment start. By utilizing clinical and patient-reported outcome measures (PROMs) from questionnaires, we compute patient-related clinical measurements (CROMs) for different targets like the range of motion of a knee, and subsequently use those indicators to learn prediction models. While we at first apply regression algorithms to estimate the rehab success in terms of percental admission and discharge value differences, we finally also utilize classification models to make predictions based on a three-classed grading scheme. Extensive evaluations for different treatment groups and targets show promising results with F-scores exceeding 65% that are able to substantially outperform baselines (by up to 40%) and thus show that machine learning can indeed be applied for better medical controlling and optimized treatment paths in rehab praxis. Future developments should include further relevant critical success criteria in the rehabilitation routine to further optimize the prognosis models for clinical practice.

Shifting Participation Grade Policies to Value More Kinds of Student Engagement

This is a story about discovering a bias that affected participation grades in my Introductory Physics for Life Sciences class. My expectation, that actively engaged students tended to talk frequently in my presence as their teaching assistant, would have erased two students’ outstanding performances if not for the participation grade policies described here. The two students, Diana and Alice (pseudonyms), both appeared to be Asian American women, which prompted a quick check for possible course-wide bias in participation grades by students’ gender and ethnicity. The quick check—a quantitative analysis—suggested that in-class participation by multiple different groups of Asian American women may have been undervalued on average by graduate physics teaching assistants, though this requires further analysis. My perspective of Diana’s and Alice’s top performances along with the informal check connects to published research on Asian American student experiences. I also present practical suggestions for physics educators, who could benefit from critically reflecting on what values and biases may be baked into their grading schemes.

Mitotic Figures-Normal, Atypical, and Imposters: A Guide to Identification.

Counting mitotic figures (MF) in hematoxylin and eosin-stained histologic sections is an integral part of the diagnostic pathologist's tumor evaluation. The mitotic count (MC) is used alone or as part of a grading scheme for assessment of prognosis and clinical decisions. Determining MCs is subjective, somewhat laborious, and has interobserver variation. Proposals for standardizing this parameter in the veterinary field are limited to terminology (use of the term MC) and area (MC is counted in an area measuring 2.37 mm2). Digital imaging techniques are now commonplace and widely used among veterinary pathologists, and field of view area can be easily calculated with digital imaging software. In addition to standardizing the methods of counting MF, the morphologic characteristics of MF and distinguishing atypical mitotic figures (AMF) versus mitotic-like figures (MLF) need to be defined. This article provides morphologic criteria for MF identification and for distinguishing normal phases of MF from AMF and MLF. Pertinent features of digital microscopy and application of computational pathology (CPATH) methods are discussed. Correct identification of MF will improve MC consistency, reproducibility, and accuracy obtained from manual (glass slide or whole-slide imaging) and CPATH approaches.

Fingerprick Autologous Blood in the Treatment of Severe Dry Eyes and Ocular Surface Disease

To evaluate the efficacy of autologous blood eye drops in patients diagnosed with severe ocular surface disease and dry eye who were unresponsive to conventional therapy and who would otherwise be considered for autologous serum eye drops. A total of 38 eyes of 19 patients (15 women and 4 men) with ocular surface disease and severe dry eye refractory to conventional treatment were treated with fingerprick autologous blood 4 times daily for 6 months. Follow-up visits occurred at 1-, 3-, and 6-month intervals. At each visit, visual acuity, Oxford Grading Scheme score, tear film break-up time, Schirmer test, and ocular surface disease index were measured. There was a significant improvement in the ocular surface staining score at all time gates. The mean score at presentation was 2.13, and this improved to 1.50 at 1 month (P < 0.001), 1.29 at 3 months (P < 0.01), and 1.42 at 6 months (P < 0.01). There was an improvement in tear film break-up time from 4.75 seconds at baseline to 6.79 seconds at 3 months (P < 0.01) and 7.0 seconds at 6 months (P < 0.001). An improvement in the Schirmer test was only found at 6 months with an improvement from 3.67 mm to 13.33 mm (P < 0.05). There was no statistical change in visual acuity at any time gate or ocular surface disease index score, although 83% of patients reported an improvement in their symptoms at 6 months. There were no adverse events reported. Fingerprick autologous blood is an effective, readily accessible, and safe therapy for the treatment of recalcitrant cases of severe ocular surface disease and dry eye unresponsive to conventional therapy.

Four-dimensional CT excretory urography is an accurate technique for diagnosis of canine ureteral ectopia.

Computed tomographic (CT) excretory urography is commonly used to investigate canine ureteral ectopia (UE). Modern technology allows time-resolved CT imaging (four-dimensional CT excretory urography [4D-CTEU]) over a distance exceeding the detector collimation. Objectives of this prospective, observational, diagnostic accuracy study were to evaluate the diagnostic accuracy of CT excretory urography (CTEU) and 4D-CTEU for UE in dogs with lower urinary tract signs, assess the influence of pelvis positioning, and to determine the significance of the ureterovesical junction (UVJ) angle for UE diagnosis. Thirty-six dogs, with a total of 42 normotopic ureters, 27 intramural ectopic ureters, and three extramural ectopic ureters, underwent CTEU and 4D-CTEU with randomized pelvis positioning. Randomized CTEU and 4D-CTEU studies were scored by two observers for ureteral papilla location and murality on a grading scheme. Interobserver agreement, sensitivity, and specificity for ureter topia status and diagnosis were calculated. Computed tomographic excretory urography showed moderate interobserver agreement for the left ureter and perfect for the right ureter, whereas 4D-CTEU showed bilateral nearly perfect agreement between both observers. When comparing CTEU versus confirmed diagnosis, there was a sensitivity and specificity of 73% and 90.2%, respectively, whereas 4D-CTEU showed a sensitivity and specificity of 97% and 94.6%, respectively. An obtuse UVJ angle is significantly more commonly observed in ectopic intramural than normotopic ureters and is significantly associated with increased diagnostic confidence of UE. The use of a wedge to angle the pelvis did not increase the diagnostic confidence in determining ureteral opening position. Four-dimensional CT excretory urography is an accurate and reliable diagnostic technique to investigate UE as cause of urinary incontinence in dogs that is slightly superior to CTEU.

Inflammatory cytokines in horses with cervical articular process joint osteoarthritis on standing cone beam computed tomography.

Standing cone beam computed tomography (CT) provides cross-sectional imaging of the caudal cervical articular process joints (CAPJs) in the sedated horse, though the clinical implications of osteoarthritis (OA) identified on CT in this location are unknown. Increases in concentrations of intra-synovial cytokines could lend support to the clinical significance of CAPJ OA identified on this imaging modality. Investigate the presence and concentration of intra-synovial inflammatory cytokines in CAPJs with and without standing cone beam CT evidence of OA using an equine specific multiplex assay. Prospective clinical study. Standing cone beam CT of C5-6 and C6-7 was performed on horses with CAPJ OA and control horses. Synovial fluid samples of the CAPJs of C5-6 and C6-7 were obtained bilaterally using ultrasound guidance and analysed for concentrations of IFN-γ, IL-1β, IL-6, IL-10, IL-17 and TNFα with the Milliplex® multi-analyte profiling kit. CT Images were retrospectively graded using a novel grading scheme. Significant differences between concentrations of inflammatory cytokines between joints with different categories of osteoarthritis severity were explored using a Wilcoxon rank-sum test or Kruskal-Wallis test. Concentrations of intra-synovial cytokines were higher in joints with moderate to severe OA when compared to joints with no or mild OA, with differences in concentrations of IL-17 reaching statistical significance (P=.007). Limitations include discrepancy in number, age, and breed between control and OA populations, use of a novel grading scheme, and lack of a histologic gold-standard to confirm the presence and severity of CAPJ OA. Differences in inflammatory cytokines between caudal CAPJs with and without evidence of moderate to severe osteoarthritis on standing cone beam CT exist. This finding lends support to the clinical relevance of a diagnosis of moderate to severe CAPJ OA in the caudal cervical vertebral column as identified with this imaging modality.

Independent Observational Analysis of Ulcer Outcomes for SINBAD and University of Texas Ulcer Scoring Systems.

The aim of this study was to compare the University of Texas (UT) and Site, Ischemia, Neuropathy, Bacterial Infection, and Depth (SINBAD) foot ulcer scores in predicting ulcer outcome within a routine diabetes foot clinic. From 2006 to 2018, data were collected from all patients attending an outpatient diabetes foot clinic with an active ulcer not healed within 4 weeks. UT and SINBAD were compared in predicting ulcer outcome. A unified numerical score for UT was constructed and compared with UT grade (depth) and stage scores. Outcomes included death, a healed ulcer, or a nonhealed ulcer, which included major or minor amputation and nonhealing chronic ulcers. Outcomes were available from 1,645 ulcer outcomes in 1,068 patients (mean [SD] age 65.4 [4] years, 72% male), of which 1,108 (67%) healed. With exclusion of death as an adverse outcome, the c-statistic (area under operator curve) was 0.67 (95% CI 0.65-0.71) for UT grade/depth and 0.64 (0.61-0.67) for UT stage. The new unified UT score had an improved c-statistic of 0.71 (0.68-0.74). The c-statistic was 0.72 (0.69-0.75) for SINBAD. There was a stepwise decrease in the proportion of ulcers healed for each increased score on ulcer grading for both grading schemes. This large and independent observational comparison, in a real-world clinical setting, demonstrated that the UT and SINBAD diabetes foot ulcer grading schemes had similar prognostic ability for predicting foot ulcer outcomes. We have devised and validated a unified numerical scoring system for UT.

A standardized pathological proposal for evaluating microvascular invasion of hepatocellular carcinoma: a multicenter study by LCPGC.

Microvascular invasion (MVI) is a key pathological factor that severely affects the postoperative prognosis of patients with hepatocellular carcinoma (HCC). However, no MVI classification schemes based on standardized gross sampling protocols of HCC are available at present. 119 HCC specimens were sampled at multiple sites (3-, 7-, and 13 points) for the optimum MVI detection rate. 16,144 resected HCCs were graded as M0, M1 or M2 by adopting three-tiered MVI grading (MVI-TTG) scheme based on the seven-point sampling protocol (SPSP). Survival analyses were performed on 2573 patients to explore the advantages of MVI-TTG. The MVI detection rate determined by SPSP was significantly higher than that determined by the 3-point sampling method (34.5% vs. 47.1%, p = 0.048), but was similar to that determined by the 13-point sampling method (47.1% vs. 51.3%, p = 0.517). Among 16,144 resected HCCs, the proportions of M0, M1 and M2 specimens according to SPSP were 53.4%, 26.2% and 20.4%, respectively. Postoperative survival analysis in 2573 HCC patients showed that the 3-year recurrence rates in M0, M1 and M2 MVI groups were 62.5%, 71.6% and 86.1%, respectively (p < 0.001), and the corresponding 3-year overall survival (OS) rates were 94.1%, 87.5% and 67.0%, respectively (p < 0.001). M1 grade was associated with early recurrence, while M2 grade was associated with both early and late recurrence. MVI-TTG had a larger area under the curve and net benefit rate than the two-tiered MVI grading scheme for predicting time to recurrence and OS. SPSP is a practical method to balance the efficacy of sampling numbers and MVI detection rates. MVI-TTG based on SPSP is a better prognostic predictor than the two-tiered MVI scheme. The combined use of SPSP and MVI-TTG is recommended for the routine pathological diagnosis of HCC.

A completely annotated whole slide image dataset of canine breast cancer to aid human breast cancer research

Canine mammary carcinoma (CMC) has been used as a model to investigate the pathogenesis of human breast cancer and the same grading scheme is commonly used to assess tumor malignancy in both. One key component of this grading scheme is the density of mitotic figures (MF). Current publicly available datasets on human breast cancer only provide annotations for small subsets of whole slide images (WSIs). We present a novel dataset of 21 WSIs of CMC completely annotated for MF. For this, a pathologist screened all WSIs for potential MF and structures with a similar appearance. A second expert blindly assigned labels, and for non-matching labels, a third expert assigned the final labels. Additionally, we used machine learning to identify previously undetected MF. Finally, we performed representation learning and two-dimensional projection to further increase the consistency of the annotations. Our dataset consists of 13,907 MF and 36,379 hard negatives. We achieved a mean F1-score of 0.791 on the test set and of up to 0.696 on a human breast cancer dataset.

Guidelines for the use and statistical analysis of the Home Office fingermark grading scheme for comparing fingermark development techniques

This paper provides guidance on how to properly analyse data generated from the Home Office fingermark grading scheme. The core of the issue is that it creates ordinal data and should therefore not be analysed using averages. To reduce confusion, it is recommended to label the different degrees of fingermark development as classes rather than numerical scores. Appropriate statistical tests are provided to properly analyse Home Office fingermark grading scheme data, however, not using statistical tests is perfectly acceptable so long as conclusions are worded appropriately and do not exaggerate the significance of the findings. Some guidance is provided on estimating sample size and optimal methods for presenting results.

Morphologic changes associated with neoadjuvant-treated pancreatic ductal adenocarcinoma and comparison of two tumor regression grading systems

Pancreatic ductal adenocarcinoma (PDAC) is aggressive, with an overall five-year survival rate of 9%, and few patients are candidates for pancreatectomy at presentation. The role of neoadjuvant therapy (NAT) is evolving, especially for high-risk potentially resectable tumors. Owing to the increasing number of NAT resection specimens, we aim to characterize the histologic changes associated with NAT and to compare two tumor regression grading schemes. One hundred eighteen resections for PDAC were selected from the cases between 2011 and 2018, 59 not treated and 59 treated with NAT. All H&E stained tumor slides were reviewed for histologic changes and graded using the four-tier modified Ryan score (recommended by College of American Pathologists) and the three-tier MD Anderson (MDA) score. The histologic changes evaluated included blue/grey fibrosis, islet cell hyperplasia, dystrophic calcification, amyloid deposition, cholesterol clefts, nerve hypertrophy, elastotic stromal/vascular change, abscess formation, and eosinophilic tumor cell changes. There were statistically significant differences for dystrophic calcification, eosinophilic tumor cell changes, elastotic stromal/vascular change, islet cell hyperplasia, and nerve hypertrophy between the two groups, with these features seen more frequently in NAT cases. Blue/grey stromal fibrosis was present in all cases regardless of NAT, except few complete regression cases and one treated case with intraneural invasion only. Blue/grey fibrosis is a useful histologic visual clue to suggest the possibility of adjacent tumor in the majority of PDAC cases regardless of NAT. By Kaplan-Meier analysis, neither grading scheme correlated with overall survival in our cohort. However, the MDA score was significantly correlated with both time to primary tumor recurrence (p=0.002) and time to distant recurrence (p=0.04), whereas the modified Ryan score was not.

Validation through a comparison of physical examination and DNA test results: OLFML3 case study

ObjectiveTo investigate the usefulness of predicting the presence of a genetic mutation in a population based on data arising from physical examinations and its use as a validator of grading schemes. MethodsWe employ an inference algorithm adjusted for large scale application and apply it to the particular case of Olfactomedin Like 3 (OLFML3) gene in the Border Collie, where essentially independent results of DNA test and physical exam exist, to find out to what extent the two predictions agree and highlight systematic discrepancies. ResultsLarge scale inference over a population of 243,752 Border Collie dogs is combined with statistical data mining techniques on available DNA test and physical exam results corresponding to the OLFML3 gene and physical gonioscopy. Aside from validating the inference technique, the results are two fold: (1) sources of possible errors are identified indicating potential revisions of the physical examination grading scheme, and (2) the inference is found to approach close values within a short distance (1 or 2 steps away from a tested animal) based on physical examinations alone, supporting the usefulness of predictions based solely on the results of a physical exam. ConclusionA systematic comparison of the inference results based on a physical examination and on DNA tests highlights any problems with the grading scheme used for the physical examinations. The proximity of physical examination and DNA based inference suggests that the method could be employed to select the most informative subjects to explore when a method of inheritance of a condition is suspected but only a physical examination is possible.

Study of texture segmentation and classification for grading small hepatocellular carcinoma based on CT images

To grade Small Hepatocellular CarCinoma (SHCC) using texture analysis of CT images, we retrospectively analysed 68 cases of Grade II (medium-differentiation) and 37 cases of Grades III and IV (high-differentiation). The grading scheme follows 4 stages: (1) training a Super Resolution Generative Adversarial Network (SRGAN) migration learning model on the Lung Nodule Analysis 2016 Dataset, and employing this model to reconstruct Super Resolution Images of the SHCC Dataset (SR-SHCC) images; (2) designing a texture clustering method based on Gray-Level Co-occurrence Matrix (GLCM) to segment tumour regions, which are Regions Of Interest (ROIs), from the original and SR-SHCC images, respectively; (3) extracting texture features on the ROIs; (4) performing statistical analysis and classifications. The segmentation achieved accuracies of 0.9049 and 0.8590 in the original SHCC images and the SR-SHCC images, respectively. The classification achieved an accuracy of 0.838 and an Area Under the ROC Curve (AUC) of 0.84. The grading scheme can effectively reduce poor impacts on the texture analysis of SHCC ROIs. It may play a guiding role for physicians in early diagnoses of medium-differentiation and high-differentiation in SHCC.

Grading Chromophobe Renal Cell Carcinoma: Evidence for a Four-tiered Classification Incorporating Coagulative Tumor Necrosis

BackgroundAlthough grading systems have been proposed for chromophobe renal cell carcinoma (ChRCC), including a three-tiered system by Paner et al (Paner GP, Amin MB, Alvarado-Cabrero I, et al. A novel tumor grading scheme for chromophobe renal cell carcinoma: prognostic utility and comparison with Fuhrman nuclear grade. Am J Surg Pathol 2010;34:1233–40), none have gained clinical acceptance, and the World Health Organization (WHO) currently recommends against grading ChRCC. ObjectiveTo validate a previously published grading scheme and propose a scheme that includes tumor necrosis. Design, setting, and participantsA total of 266 patients who underwent nephrectomy for nonmetastatic ChRCC between 1970 and 2012 were reviewed for ChRCC grade according to the Paner system and coagulative tumor necrosis. Outcome measurements and statistical analysisAssociations with cancer-specific survival (CSS) were evaluated using Cox proportional hazard regression models and summarized with hazard ratios (HRs). Results and limitationsTwenty-nine patients died from RCC; the median follow-up was 11.0 (interquartile range 7.9–15.9) yr. ChRCC grade according to the Paner system was significantly associated with CSS, including the difference in outcome between grade 1 and 2 tumors. Among patients with grade 2 tumors, the presence of tumor necrosis helped delineate patients with worse CSS. As such, the Paner system was expanded to four tiers separating grade 2 into those with and without tumor necrosis. HRs for associations of the proposed grade 2, 3, and 4 tumors with CSS were 4.63 (p=0.007), 17.8 (p<0.001), and 20.9 (p<0.001), respectively. The study is limited by the lack of multivariable analysis including additional pathologic features. ConclusionsThe expansion of a previously reported ChRCC grading system from three to four tiers by the inclusion of tumor necrosis helps further delineate patient outcome and can, therefore, enhance patient counseling following surgery. It also aligns the number of ChRCC grades with the WHO/International Society of Urologic Pathology four-tiered grading systems for clear cell and papillary RCC. Patient summaryChromophobe renal cell carcinoma is the third most common type of renal cancer, and unlike other renal cancers, there is no accepted prognostic grading system. In this study, we found that a grading system that included a pathologic feature of tumor necrosis could better define outcomes for patients with chromophobe renal cell carcinoma.

Understanding the Dual Dilemma of Dry Eye and Glaucoma: An International Review.

Glaucoma-related ocular surface disease (G-OSD) is a significant, yet often underdiagnosed, ocular co-morbidity affecting 40% to 59% of glaucoma patients worldwide. Although the use of topical glaucoma medications represents a proven strategy to control the untoward effects of high intraocular pressure, this treatment can profoundly disrupt the homeostasis of the tear film. The cumulative effect of medications, preservatives, and excipients alter underlying cellular structures which results in tear film abnormalities and instability of the ocular surface. Furthermore, these chronic inflammatory changes have been shown to impact efficacy of glaucoma treatment, patient compliance with therapy and overall quality of life. The pathogenesis of G-OSD is multifactorial and involves a vicious self-perpetuating cycle of inflammatory cytokines and proteins. The diagnosis of such disease is based on similar tests used in assessing traditional dry eye, taking into consideration findings specific to this patient population. The hallmark of treatment for these patients is to minimize the ocular surface inflammatory response by choosing glaucoma therapies that spare the ocular surface such as preservative free formulations and initiating dry eye treatment early in the course of care. In summary, glaucoma affects millions of patients around the world and chronic use of topical glaucoma medications may negatively impact the patient's ocular surface, symptoms, and vision. Understanding the pathogenesis of G-OSD, recognizing its risk factors and incorporating diagnostic and therapeutic strategies that restore and maintain ocular surface homeostasis will result in improved care for our patients.