AI Deployment on GBM Diagnosis: A Novel Approach to Analyze Histopathological Images Using Image Feature-Based Analysis.

BACKGROUND: Glioblastoma (GBM) is one of the most common malignant primary brain tumors, which accounts for 60-70% of all gliomas. Conventional diagnosis and the decision of post-operation treatment plan for glioblastoma is mainly based on the feature-based qualitative analysis of hematoxylin and eosin-stained (H&E) histopathological slides by both an experienced medical technologist and a pathologist. The recent development of digital whole slide scanners makes AI-based histopathological image analysis feasible and helps to diagnose cancer by accurately counting cell types and/or quantitative analysis. However, the technology available for digital slide image analysis is still very limited. This study aimed to build an image feature-based computer model using histopathology whole slide images to differentiate patients with glioblastoma (GBM) from healthy control (HC). METHOD: Two independent cohorts of patients were used. The first cohort was composed of 262 GBM patients of the Cancer Genome Atlas Glioblastoma Multiform Collection (TCGA-GBM) dataset from the cancer imaging archive (TCIA) database. The second cohort was composed of 60 GBM patients collected from a local hospital. Also, a group of 60 participants with no known brain disease were collected. All the H&E slides were collected. Thirty-three image features (22 GLCM and 11 GLRLM) were retrieved from the tumor volume delineated by medical technologist on H&E slides. Five machine-learning algorithms including decision-tree (DT), extreme-boost (EB), support vector machine (SVM), random forest (RF), and linear model (LM) were used to build five models using the image features extracted from the first cohort of patients. Models built were deployed using the selected key image features for GBM diagnosis from the second cohort (local patients) as model testing, to identify and verify key image features for GBM diagnosis. RESULTS: All five machine learning algorithms demonstrated excellent performance in GBM diagnosis and achieved an overall accuracy of 100% in the training and validation stage. A total of 12 GLCM and 3 GLRLM image features were identified and they showed a significant difference between the normal and the GBM image. However, only the SVM model maintained its excellent performance in the deployment of the models using the independent local cohort, with an accuracy of 93.5%, sensitivity of 86.95%, and specificity of 99.73%. CONCLUSION: In this study, we have identified 12 GLCM and 3 GLRLM image features which can aid the GBM diagnosis. Among the five models built, the SVM model proposed in this study demonstrated excellent accuracy with very good sensitivity and specificity. It could potentially be used for GBM diagnosis and future clinical application.

The Shoulder Trans-pectoralis Arthroscopic Portal Is a Safe Approach to the Arthroscopic Latarjet Procedure: A Cadaveric Analysis.

PURPOSE: To assess the proximity of neurovascular structures in a layered approach during medial portal placement and determine standardized measurements for establishing a portal medial to the coracoid used in arthroscopic Latarjet-type procedures. METHODS: Twelve shoulders (6 right and 6 left) in 6 fresh frozen cadaveric torsos were mounted in the modified beach-chair position. A standard posterior portal and 3 anterior portals-central, lateral, and medial-were used. A long spinal needle was placed along the path of the medial portal to the lateral tip of the coracoid, superficial to the conjoined tendon and pectoralis minor. A second long spinal needle was directed toward the medial base of the coracoid, penetrating the pectoralis minor. Superficial and deep plane dissections were performed, and distances to surrounding neurovascular structures were recorded. RESULTS: In the superficial plane, the cephalic vein and lateral pectoral nerve were located a mean distance (± standard deviation) of 4.6 ± 1.9 mm and 9.4 ± 2.6 mm from the spinal needle, respectively. In the deep plane, the axillary nerve was 24.9 ± 7.4 mm from the needle; the lateral cord of the brachial plexus, 25.5 ± 8.1 mm; the axillary artery, 34.1 ± 6.0 mm; and the musculocutaneous nerve, 42.2 ± 9.2 mm. The portal was consistently established 45.0 to 50.0 mm distal and 30.0 to 35.0 mm medial to the coracoid, which was a minimum distance of 10 mm to the lateral pectoral nerve. CONCLUSIONS: In a cadaveric model, the creation of a medial trans-pectoralis major portal used in the arthroscopic Bankart-Bristow-Latarjet procedure can avoid compromise of vital neurovascular structures, alleviating concerns of creating a portal medial to the coracoid. Portal placement 45.0 to 50.0 mm distal and 30.0 to 35.0 mm medial to the palpable tip of the coracoid process may be a safe approach to perform the arthroscopic Bankart-Bristow-Latarjet procedure. CLINICAL RELEVANCE: Creation of a portal medial to the level of the coracoid may pose a risk to neurovascular structures. This cadaveric study establishes a working zone for medial trans-pectoralis portal placement, which avoids vital neurovascular structures, and provides standardized measurements for establishing this portal for use in the arthroscopic Bankart-Bristow-Latarjet procedure.

Injury to the Popliteal Artery and Vein During Open Fibular Collateral Ligament Reconstruction: A Case Report.

CASE: We present a case involving a 26-year-old male who sustained an iatrogenic injury to the right popliteal artery and vein during open fibular collateral ligament reconstruction. The lesions were repaired immediately and required subsequent procedures on postoperative day 1. CONCLUSIONS: Iatrogenic vascular injuries during knee surgery can be devastating for patients and may lead to increased medical costs, unexpected hospital admissions, and additional surgical procedures. Surgeons should scrutinize preoperative imaging to identify the anatomic location of the popliteal artery and vein, which may be at risk during posterolateral knee reconstruction.

Relevance of heat stress and dehydration to chronic kidney disease (CKDu) in Sri Lanka.

Chronic kidney disease in the absence of hypertension and diabetes is a growing problem among agricultural laborers in tropical and subtropical regions. It is unclear if heat stress and dehydration are risk factors for this form of chronic kidney disease (CKDu). To investigate this relationship, agricultural workers in four villages (n = 261) in North Central Province, Sri Lanka completed the US National Institute for Occupational Safety and Health (NIOSH) health hazard evaluation of heat stress, translated into Sinhalese (July 2017). We constructed a heat stress/dehydration index based on the frequency of 16 symptoms (range 0-32; reliability, 0.84). Workers provided a urine sample for dipstick assessment of urine albumin-creatinine ratio (ACR) and refractometer analysis of urine concentration. Of 261 respondents, 41 participants reported diabetes or chronic kidney disease. They scored higher on the heat stress-dehydration index (10.78 vs. 8.03, p < .01) and were more likely to have ACR > 30 (85.4% vs. 69.4%, p < .05). Among 216 non-pregnant agricultural workers without diabetes or kidney disease (mean age, 46.6; 37% male), villagers in the high-CKDu prevalence area were more likely to show signs of dehydration (for example, greater urine concentration, 1.015 vs. 1.012, p < .05, among males); however, the heat stress-dehydration index overall was not associated with ACR or urine concentration. Because an elevated ACR (proteinuria) is not a reliable marker of early CKDu, additional studies are needed to assess the association between heat stress-dehydration symptoms and risk of CKDu.

Effectiveness of statewide falls prevention efforts with and without group exercise.

Group-based falls prevention programs vary in use of exercise, education, home modification, and other program elements. Pennsylvania's Department of Aging offers two large-scale falls prevention programs that differ in these components, allowing a strong test of the effectiveness of exercise in reducing falls incidence relative to less intensive education-based programs. In 2016-2017, we followed three groups of older adults attending senior centers: (i) older adults who completed Healthy Steps in Motion (HSIM, n=560), an 8-week exercise program, (ii) older adults completing Healthy Steps for Older Adults (HSOA, n=651), a falls education workshop with assessment and referral; and (iii) older adults not completing falls prevention programs (n=787). Participants were followed for up to 6months with monthly ascertainment of falls. We estimated Poisson regression models to compare incidence rate ratios. The groups did not differ in falls risk at baseline or attrition over follow-up. HSIM participants reported 5.3 fall months per 100 person-months of follow-up. The group not completing falls prevention programming reported 7.3 (incidence rate ratio [IRR], 0.72 [0.59, 0.89]), and the group completing HSOA 6.5 (IRR, 0.82 [0.66, 1.02]). In stratified analyses, falls incidence was lower in HSIM for older adults reporting better balance and no falls in the prior 12months. Non-exercise-based falls prevention programs may also reduce falls, perhaps through indirect physical benefits such as greater social engagement and increased activity.

Uptake and protective effects of ergothioneine in human endothelial cells.

Ergothioneine is a thiourea derivative of histidine found in food, especially mushrooms. Experiments in cell-free systems and chemical assays identified this compound as a powerful antioxidant. Experiments were designed to test the ability of endothelial cells to take up ergothioneine and hence benefit from protection against oxidative stress. Reverse-transcription polymerase chain reaction and Western blotting demonstrated transcription and translation of an ergothioneine transporter in human brain microvascular endothelial cells (HBMECs). Uptake of [(3)H]ergothioneine occurred by the organic cation transporter novel type-1 (OCTN-1), was sodium-dependent, and was reduced when expression of OCTN-1 was silenced by small interfering RNA (siRNA). The effect of ergothioneine on the production of reactive oxygen species (ROS) in HBMECs was measured using dichlorodihydrofluorescein and lucigenin, and the effect on cell viability was studied using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. ROS production and cell death induced by pyrogallol, xanthine oxidase plus xanthine, and high glucose were suppressed by ergothioneine. The antioxidant and cytoprotective effects of ergothioneine were abolished when OCTN-1 was silenced using siRNA. The expression of NADPH oxidase 1 was decreased, and those of glutathione reductase, catalase, and superoxide dismutase enhanced by the compound. In isolated rat basilar arteries, ergothioneine attenuated the reduction in acetylcholine-induced relaxation caused by pyrogallol, xanthine oxidase plus xanthine, or incubation in high glucose. Chronic treatment with the compound improved the response to acetylcholine in arteries of rats with streptozotocin-induced diabetes. In summary, ergothioneine is taken up by endothelial cells via OCTN-1, where the compound then protects against oxidative stress, curtailing endothelial dysfunction.

The anterior cruciate ligament-deficient knee and unicompartmental arthritis.

Treatment of medial and lateral compartment arthritis in the anterior cruciate ligament (ACL)-deficient knee remains a topic of debate among orthopedic surgeons. This article discusses the treatment options for the ACL-deficient knee with unicompartmental arthritis and provides a rationale for clinical decision making in this difficult group of patients. Unicondylar knee arthroplasty (UKA) is a viable option in a select group of patients to decrease pain and maintain an active lifestyle. When performing a UKA in an ACL-deficient knee, it is important to manage appropriate expectations for a successful outcome.

Unicondylar knee arthroplasty: intramedullary technique.

Unicondylar knee arthroplasty (UKA) is a challenging surgical procedure for many orthopedic surgeons when compared with total knee arthroplasty (TKA). Given the proven similarities in knee biomechanics between UKA and the native knee and recent evidence showing excellent survivorship and functionality, UKA is an excellent alternative to TKA in the appropriate patient. This article discusses the use of intramedullary guides for preparation in partial knee replacement surgery. The concerns of complications arising from cannulating the medullary canal and excessive bleeding have not been seen. The intramedullary UKA yields high levels of success and long-term outcomes, with excellent alignment.

Physiological and pharmacological roles of vascular nucleoside transporters.

Adenosine modulates various vascular functions such as vasodilatation and anti-inflammation. The local concentration of adenosine in the vicinity of adenosine receptors is fine tuned by 2 classes of nucleoside transporters: equilibrative nucleoside transporters (ENTs) and concentrative nucleoside transporters (CNTs). In vascular smooth muscle cells, 95% of adenosine transport is mediated by ENT-1 and the rest by ENT-2. In endothelial cells, 60%, 10%, and 30% of adenosine transport are mediated by ENT-1, ENT-2, and CNT-2, respectively. In vitro studies show that glucose per se increases the expression level of ENT-1 via mitogen-activating protein kinase-dependent pathways. Similar results have been demonstrated in diabetic animal models. Hypertension is associated with the increased expression of CNT-2. It has been speculated that the increase in the activities of ENT-1 and CNT-2 may reduce the availability of adenosine to adenosine receptors, thereby weakening the vascular functions of adenosine. This may explain why patients with diabetes and hypertension suffer greater morbidity from ischemia and atherosclerosis. No oral hypoglycemic agents can inhibit ENTs, but an exception is troglitazone (a thiazolidinedione that has been withdrawn from the market). ENTs are also sensitive to dihydropyridine-type calcium-channel blockers, particularly nimodipine, which can inhibit ENT-1 in the nanomolar range. Those calcium-channel blockers are noncompetitive inhibitors of ENTs, probably working through the reversible interactions with allosteric sites. The nonsteroidal anti-inflammatory drug sulindac sulfide is a competitive inhibitor of ENT-1. In addition to their original pharmacological actions, it is believed that the drugs mentioned above may regulate vascular functions through potentiation of the effects of adenosine.

Schneiderian papillomas and carcinomas: a retrospective study with special reference to p53 and p16 tumor suppressor gene expression and association with HPV.

Schneiderian papillomas are uncommon benign tumors of the sinonasal area. They are prone to local aggressiveness and recurrence, and some undergo malignant progression. We analyzed specimens obtained from 67 Chinese patients who had presented to the ENT department of a regional hospital with biopsy-proven schneiderian papilloma. Seven of these patients had either synchronous or metachronous carcinoma, 1 of whom had pure carcinoma in situ. For each case, we documented the morphology, immunohistochemical expression of tumor suppressor genes p53 and p16, and any association with human papillomavirus (HPV) infection as detected by either polymerase chain reaction or in situ hybridization techniques. We found that severe dysplasia and p53 positivity were strongly associated with malignant progression. Association with HPV was demonstrated in 22 of the 67 patients (33%); the association was strongest among patients with exophytic papillomas and carcinomas. The effect of HPV in papilloma oncogenesis probably begins during the early phase, while other factors are responsible for progression to carcinoma. We conclude that p53-positive, dysplastic schneiderian papillomas warrant aggressive surgical treatment.

Hypermethylation of SOX2 gene in hydatidiform mole and choriocarcinoma.

This study investigated the expression and methylation profiles of SOX2, a stem cell-related transcription factor, in placentas and gestational trophoblastic disease. The methylation status of SOX2 promoter region in 55 hydatidiform moles, 4 choriocarcinoma, 23 first trimester, and 15 term placentas was evaluated by methylation-specific polymerase chain reaction. The methylated allele was found in 4.4% (1/23) of first trimester placentas, 26.7% (4/15) term placentas, and 56.4% (31/55) of hydatidiform moles and all choriocarcinoma samples and cell lines. A significant reduction in SOX2 messenger RNA expression was found in the hydatidiform moles (P = .027) when compared with that in the placentas. SOX2 messenger RNA expression was significantly correlated with SOX2 hypermethylation (P < .001). SOX2 expression was restored in choriocarcinoma cell lines following treatment to 5-Aza-2(')-deoxycytidine and/or Trichostatin A, demethylation and histone deacetylase inhibitors, respectively, and the response was synergistic. Epigenetic mechanisms may play important role on the transcriptional regulation of SOX2 and contribute to pathogenesis of gestational trophoblastic disease.

Cross-cultural variation in mental health at end of life in patients with ALS.

OBJECTIVE: To examine mental health at the end of life among patients with ALS in three countries: Israel, Germany, and the United States. METHODS: Patients met criteria for definite or probable ALS and had forced vital capacity (FVC) <60% of predicted. Patients completed nonsomatic items from the Beck Depression Inventory and visual analogue scale ratings. RESULTS: The three sites contributed a total of 92 patients; 60 died during follow-up. Patients at the three sites did not differ significantly in sociodemographic features or ALS Functional Rating Scale-Revised summary disability score; sites differed in use of nasal ventilation but not percutaneous esophageal gastrostomy (PEG) tube placement. In analyses that adjusted for disability and use of nasal ventilation, patients at the three sites differed in reports of pessimism and suffering; American patients reported the least distress and Israeli patients the most. In analyses limited to people who died, similar patterns emerged, with wish to live greatest in Americans and least among Israelis. These models adjusted for disability and days until death. CONCLUSIONS: Cultural factors may affect mental health at the end of life in patients with ALS.

Education and rates of cognitive decline in incident Alzheimer's disease.

BACKGROUND: Some (but not all) epidemiological studies have noted faster rates of progression in high education patients with Alzheimer's disease (AD), which has been attributed to harbouring/tolerating a higher pathological burden at the time of clinical dementia for subjects with higher education. We wanted to assess the relationship between education and rates of decline in AD. METHODS: During the course of a community based multiethnic prospective cohort study of individuals aged > or = 65 years living in New York, 312 patients were diagnosed with incident AD and were followed overall for 5.6 (up to 13.3) years. The subjects received an average of 3.7 (up to 9) neuropsychological assessments consisting of 12 individual tests. With the aid of a normative sample, a standardised composite cognitive score as well as individual cognitive domain scores were calculated. Generalised estimating equation models were used to examine the association between education and rates of cognitive decline. RESULTS: Composite cognitive performance declined by 9% of a standard deviation per year. Rates of decline before and after AD incidence were similar. For each additional year of education there was 0.3% standard deviation lower composite cognitive performance for each year of follow up. The association between higher education and faster decline was noted primarily in the executive speed (0.6%) and memory (0.5%) cognitive domains and was present over and above age, gender, ethnicity, differential baseline cognitive performance, depression, and vascular comorbidity. CONCLUSIONS: We conclude that higher education AD patients experience faster cognitive decline.

Decline in cognitive and functional skills increases mortality risk in nondemented elderly.

OBJECTIVE: To investigate the relation between rate of decline in cognitive and functional/physical abilities and risk of death in nondemented elderly. METHODS: Data were included from individuals participating in a prospective study of aging and dementia in Medicare recipients, 65 years and older, residing in northern Manhattan. The authors included 878 members of the cohort who had measures of memory, cognitive, language, or functional scores over three study intervals, excluding all participants who were demented or had more than one problem in activity of daily living (ADL) skills at baseline. Participants were classified as showing no decline, slow, medium, or rapid rate of decline, based on the slope of change in cognitive and functional/physical factors. The authors used survival methods to examine the relation of rate of decline in cognitive and functional performance to subsequent mortality in younger and older nondemented elderly and across three ethnic groups, adjusting for potential confounders. RESULTS: Nondemented elderly with preserved ADL skills who showed rapid rates of decline on measures of visuospatial reasoning/cognitive, language, ADL, and instrumental ADL functions were approximately twice as likely to die as nondemented elderly who showed no decline or slower rates of decline, while rate of decline in memory or in measures of extremity mobility was not related to risk of death. The association of the rate of decline to risk of death was stronger in relatively young (< or =75 years) than in older participants. CONCLUSIONS: Rate of decline in cognitive and functional skills predicts mortality in nondemented elderly.

Prevalence of depressive disorders and change over time in late-stage ALS.

OBJECTIVE: To determine the prevalence of depressive disorders and symptoms in patients with late-stage ALS, to identify possible risk and protective factors associated with depression, and to determine whether depression increases as death approaches. METHODS: Semistructured interviews were conducted monthly with hospice-eligible patients with ALS and caregivers until the study endpoints of death or tracheostomy. Standardized measures were administered to assess depressive disorders and symptoms, hopelessness, spiritual beliefs, attitudes toward hastened death, quality of life, and related constructs. RESULTS: Sixty-three percent of eligible patients were enrolled. Of the 80 participants, 17 were seen only once; the number of monthly assessments for the others ranged from 2 to 18. For the 53 patients who died, median interval between last assessment and death was 30 days. At study baseline, 81% had no depressive disorder, 10% had minor depression, and 9% had symptoms consistent with major depression. Diagnoses of depression were made on 16% of 369 monthly assessments. Fifty-seven percent of patients never had a depression diagnosis at any visit, and 8% were depressed at all visits. There was no trend toward increasing depression as death approached. Presumed protective factors including spiritual beliefs, spouse as care partner, financial situation, depression in caregiver, and hospice participation did not distinguish between those who were depressed and those who were not. CONCLUSIONS: Results of multiple measures of depression and distress converged to indicate that major depression in people with late-stage ALS is rare, although transient depressive symptoms may occur, and depression does not generally increase as death approaches.

Wish to die in end-stage ALS.

BACKGROUND: In retrospective studies, estimates of hastened dying among seriously ill patients range from <2% in one national survey to as much as 20% in end-stage disease cohorts. OBJECTIVE: To examine, in prospective studies, dying patients in the months before death, in order to understand the wish to die. METHODS: Patients with advanced ALS with a high likelihood of death or need for tracheostomy within 6 months were identified. Patients were assessed monthly with an extensive psychosocial interview, including a diagnostic interview for depression. Family caregivers were interviewed on the same schedule and also after patient deaths. RESULTS: Eighty patients with ALS were enrolled, 63% of eligible patients; 53 died over follow-up. Ten (18.9%) of the 53 expressed the wish to die, and 3 (5.7%) hastened dying. Patients expressing the wish to die did not differ in sociodemographic features, ALS severity, or perceived burden of family caregivers. They were more likely to meet criteria for depression, but differences were smaller when suicidality was excluded from the depression interview. Patients who expressed the wish to die reported less optimism, less comfort in religion, and greater hopelessness. Compared with patients unable to act on the wish to die, patients who hastened dying reported reduction in suffering and increased perception of control over the disease in the final weeks of life. CONCLUSION: These findings suggest caution in concluding that the desire to hasten dying in end-stage disease is simply a feature of depression.

Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated dementia.

OBJECTIVE: To evaluate whether baseline levels of plasma and CSF HIV RNA, tumor necrosis factor alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), or macrophage colony stimulating factor (M-CSF) are predictors of incident HIV-associated dementia (HIVD) in a cohort with advanced HIV infection. METHODS: A total of 203 nondemented subjects with CD4 lymphocyte counts less than 200/muL, or <300/microL but with cognitive impairment, underwent semiannual neurologic, cognitive, functional, and laboratory assessments. HIVD and minor cognitive motor disorder (MCMD) were defined using American Academy of Neurology criteria. The cumulative incidence of HIVD was estimated using Kaplan-Meier curves. Cox proportional hazards regression models were used to examine the associations between biologic variables and time to HIVD, adjusting for age, sex, years of education, duration of HIV infection, type of antiretroviral use, premorbid IQ score, and presence of MCMD. RESULTS: After a median follow-up time of 20.7 months, 74 (36%) subjects reached the HIVD endpoint. The dementia was mild in 70% of cases. The cumulative incidence of HIVD was 20% at 1 year and 33% at 2 years. Highly active antiretroviral therapy (HAART) was used by 73% of subjects at baseline. A plasma HIV RNA level was undetectable in 23% of subjects and a CSF HIV RNA level was undetectable in 48% of subjects. In adjusted analyses, neither plasma nor CSF HIV RNA levels (log10) were associated with time to HIVD; log10 levels of plasma TNFalpha (HR 3.07, p = 0.03) and CSF MCP-1 (HR = 3.36, p = 0.06) tended to be associated with time to HIVD. CONCLUSION: The lack of association between baseline plasma and CSF HIV RNA levels and incident dementia suggests highly active antiretroviral therapy may be affecting CNS viral dynamics, leading to lower HIV RNA levels, and therefore weakening the utility of baseline HIV RNA levels as predictors of HIV-associated dementia.

Disparities in perceptions of distress and burden in ALS patients and family caregivers.

OBJECTIVES: To examine agreement between end-stage ALS patients and their family caregivers on indicators of physical and psychological status at the end of life. METHODS: Patient-caregiver pairs completed monthly interviews in patient homes. Patients were asked to rate their current pain, energy, suffering, depression, control over ALS, optimism, interest in hastened death, weariness from ALS, will to live, and how burdened they thought caregivers were on Visual Analogue Scales. Caregivers completed identical ratings of patients as well as a measure of their own burden. Both independently completed the ALS Functional Rating Scale-Rev. (ALSFRS-R), a measure of patient disability and physical function. RESULTS: A total of 69 patient-caregiver pairs participated. For measures of physical function, kappa ranged from 0.49 to 0.83, indicating moderate to excellent agreement. Patient and caregiver composite ALSFRS-R scores were highly correlated (r = 0.92, p < 0.001). Agreement between patients and caregivers was high for ratings of patient pain, control over ALS, optimism, and will to live, and this level of agreement remained high over multiple assessments. In pairwise analyses, caregivers rated patients as having less energy, greater suffering, and greater weariness than patients indicated for themselves, whereas patients rated caregivers as more burdened than caregivers reported for themselves. CONCLUSIONS: Caregivers can accurately report information about a patient's physical function at the end of life. However, patients and caregivers each overestimated the psychosocial impact of the disease on the other.

Significance of atypical repair in liquid-based gynecologic cytology: a follow-up study with molecular analysis for human papillomavirus.

BACKGROUND: "Atypical repair" is a controversial topic in gynecologic cytology. Although some cases do represent reparative change of dysplastic epithelium, the overall significance of identifying atypical reparative cells, especially in liquid-based cytology specimens, has not been investigated thoroughly. METHODS: All the liquid-based cytology cases with the diagnostic connotation of atypical repair were retrieved from the files of Pamela Youde Nethersole Eastern Hospital, Hong Kong, during a 4.5-year period from early 1998 to mid 2002. The clinical data and follow-up cytology/surgical biopsy findings were analyzed to explain the atypical cytologic change. Retrospective molecular analysis for human papillomavirus (HPV) using polymerase chain reaction and restriction fragment length polymorphism was also carried out on the liquid-based cytology samples. RESULTS: During the study period, the authors identified 21 patients with a cytologic diagnosis of atypical repair, for which follow-up information was available. The liquid-based cytology samples revealed scattered atypical squamoid cells demonstrating reparative change, including the presence of prominent nucleoli. In addition to typical repair, these cells showed more obvious nuclear pleomorphism, anisonucleosis, irregularities of nuclear outline, slight coarsening of the chromatin, and focal loss of nuclear polarity. Of the 21 patients, 4 did not have a significant history of cervical/vaginal pathology before or after the cytologic examination, whereas the 17 remaining patients had squamous intraepithelial lesions (SIL; n = 9), genital prolapse (n = 3), endocervical polyps (n = 2), SIL/cervical carcinoma with local radiotherapy (n = 2), or uterine malignancy with cervical extension (n = 1). These associations could not be delineated solely on the basis of morphologic assessment of the liquid-based cytology preparations. However, HPV DNA was detected frequently in cases of atypical repair associated with subsequent development of SIL (positive predictive value = 71.4%; negative predictive value = 77.8%). CONCLUSIONS: The presence of atypical reparative cells in liquid-based cytology is associated with a variety of conditions ranging from reactive to neoplastic conditions. Close follow-up with clinical correlation and further investigations (if indicated) are necessary for this group of high-risk patients. Reflex molecular analysis for HPV performed on liquid-based cytology samples is also helpful in predicting the possible association with an underlying SIL.

Inter-rater reliability of a clinical staging of HIV-associated cognitive impairment.

OBJECTIVE: To determine the inter-rater reliability of a modification of the Memorial Sloan-Kettering (MSK) Staging for HIV-associated cognitive impairment. METHODS: Data were abstracted on neurologic, neuropsychological, and functional status on 100 individuals participating at four sites in the Northeast AIDS Dementia (NEAD) Consortium cohort study, a longitudinal study of predictors of cognitive impairment in HIV-infected individuals. Neuropsychological performance was defined 1) based on the neuropsychologist's global impression and 2) solely based on neuropsychological test scores. Raters at each site used the abstracted data to assign an MSK stage to each subject blind to any identifying information. Inter-rater reliability was assessed using kappa statistics. Agreement between computer-generated ratings and site-generated ratings was also assessed. RESULTS: Kappa statistics for pair-wise agreement among the sites regarding MSK stage ranged from 0.70-0.91, representing good to excellent agreement between sites. Agreement between computer-generated ratings and site-generated ratings was in the good to excellent range (0.62-0.79). CONCLUSIONS: The authors have modified the MSK rating scale and developed a reliable instrument that can be used in multicenter studies. This instrument will be useful in staging HIV-dementia in future longitudinal studies and will be valuable in increasing accuracy of clinicopathologic studies.