Combined pathologic-genomic algorithm for early-stage breast cancer improves cost-effective use of the 21-gene recurrence score assay.

Background: The 21-gene recurrence score (RS) (Oncotype DX®; Genomic Health, Redwood City, CA) partitions hormone receptor positive, node negative breast cancers into three risk groups for recurrence. The Anne Arundel Medical Center (AAMC) model has previously been shown to accurately predict RS risk categories using standard pathology data. A pathologic-genomic (P-G) algorithm then is presented using the AAMC model and reserving the RS assay only for AAMC intermediate-risk patients. Patients and methods: A survival analysis was done using a prospectively collected institutional database of newly diagnosed invasive breast cancers that underwent RS assay testing from February 2005 to May 2015. Patients were assigned to risk categories based on the AAMC model. Using Kaplan-Meier methods, 5-year distant recurrence rates (DRR) were evaluated within each risk group and compared between AAMC and RS-defined risk groups. Five-year DRR were calculated for the P-G algorithm and compared with DRR for RS risk groups and the AAMC model's risk groups. Results: A total of 1268 cases were included. Five-year DRR were similar between the AAMC low-risk group (2.7%, n = 322) and the RS < 18 low-risk group (3.4%, n = 703), as well as between the AAMC high-risk group (22.8%, n = 230) and the RS > 30 high-risk group (23.0%, n = 141). Using the P-G algorithm, more patients were categorized as either low or high risk and the distant metastasis rate was 3.3% for the low-risk group (n = 739) and 24.2% for the high-risk group (n = 272). Using the P-G algorithm, 44% (552/1268) of patients would have avoided RS testing. Conclusions: AAMC model is capable of predicting 5-year recurrences in high- and low-risk groups similar to RS. Further, using the P-G algorithm, reserving RS for AAMC intermediate cases, results in larger low- and high-risk groups with similar prognostic accuracy. Thus, the P-G algorithm reliably identifies a significant portion of patients unlikely to benefit from RS assay and with improved ability to categorize risk.

Decreased dopaminergic treatment of hospitalized Parkinson's disease patients during infectious diseases is associated with poor outcomes.

A retrospective analysis of consecutive Parkinson's disease (PD) patients hospitalized in internal medicine wards during the years 2008 to 2013 due to infectious disease was performed. PD patients are prone to infections, often leading to hospitalization in internal medicine wards. We observed that during these hospitalizations, chronic anti-Parkinson's medications are frequently overlooked and withdrawn, their reintroduction is delayed and dosages are decreased. Only patients on chronic therapy with at least one anti-Parkinson's medication were included in this study. Multivariate analyses established the association between medication dose reductions on short-term clinical outcomes, including in-hospital mortality and change in discharge destination. Medical records from 528 PD patients were analyzed and 430 were excluded. Of the 98 included, 53 had pneumonia and 58 had urinary tract infections. The overall in-hospital mortality rate was 11.2%. 56.1% of patients' dopaminergic medications were decreased in dose upon admission (22.5% mean decrease in levodopa equivalent daily dose [LEDD]; p<0.001). Both absolute and relative LEDD reductions were associated with significantly increased in-hospital mortality (mean reduction of 394.5 mg versus 188.4 mg; p=0.035 by analysis of variance adjusted to age, sex and renal function) and was also associated with worse discharge destination relative to original place of arrival (mean reduction of 377.8 mg versus 150.7 mg; p=0.014). Decreased dopaminergic medication dosing upon admission of PD patients due to infection is widespread and potentially associated with worse clinical outcomes.

Review of key findings from the Singapore Malay Eye Study (SiMES-1).

INTRODUCTION: This study highlights the key epidemiological findings from the Singapore Malay Eye Study (SiMES-1). METHODS: SiMES-1 was a cross-sectional, population-based epidemiological study on eye diseases. It was performed on 3,280 randomly selected Malay adults living in the south-western part of Singapore. All study participants underwent various validated questionnaires and detailed eye examinations. A review of all papers published from SiMES-1 was performed. RESULTS: A total of 24.6% of the study population had myopia, while 35.3% had hyperopia and 39.4% had astigmatism. 20.4% of the population had under-corrected refractive error. 1,338 (45.7%) participants were diagnosed to have cataracts in at least one eye. 8.6% of the study population had undergone cataract surgery in either eye, while 4.7% had bilateral cataract surgery. 150 (4.6%) participants were diagnosed to have glaucoma, of which primary open angle glaucoma was the most common type (3.2% of the study population), followed by secondary glaucoma (0.8%) and primary angle closure glaucoma (0.2%). Pterygium was diagnosed in 508 out of 3,266 study participants, giving a prevalence rate of 15.6%. The presence of diabetic retinopathy was observed in 421 (12.9%) out of 3,265 study participants. 183 (5.6%) study participants had some degree of age-related macular degeneration (AMD), of which 23 (0.7%) were classified as having late AMD. CONCLUSION: This paper provides a summary of the prevalence of common eye diseases among the Singaporean adult Malay population and provides data useful for public health education and disease prevention.

Impact of symptomatic dry eye on vision-related daily activities: the Singapore Malay Eye Study.

PURPOSE: To examine the impact of symptomatic dry eye on vision-related daily activities. METHODS: A population-based survey of eye diseases was conducted on 3280 (78.7% response rate) Malay persons aged >or=40 years, who were randomly selected from designated areas in southwestern Singapore. Participants were administered a standardized dry eye questionnaire consisting of six questions on symptoms, a questionnaire on vision-related daily activities, and underwent a comprehensive systemic and ocular examination. Symptomatic dry eye was defined as one or more self-reported symptoms that were frequently present (ranked as often or all the time). Logistic regression method was used to examine the relationship of symptomatic dry eye with difficulty in performing daily activities. RESULTS: In adults without visual impairment, symptomatic dry eye after adjusting for age, gender, and presenting visual acuity was significantly associated with difficulty in vision-related activities such as navigating stairs (odds ratio (OR)=1.96, 95% confidence interval (CI): 1.28-3.00), recognizing friends (OR=1.99, 95% CI: 1.45-2.73), reading road signs (OR=1.87, 95% CI: 1.36-2.57), reading newspaper (OR=1.50, 95% CI: 1.11-2.04), watching television (OR=1.90, 95% CI: 1.26-2.87), cooking (OR=1.94, 95% CI: 1.02-3.71), and driving at night (OR=2.06, 95% CI: 1.32-3.21). CONCLUSION: Symptomatic dry eye was associated with difficulty in performing vision-dependent tasks, independent of visual acuity and other factors. These findings have public health significance and suggest that the visual dysfunction in dry eye should be further characterized.

Knowledge and beliefs associated with refractive errors and undercorrection: the Singapore Malay Eye Study.

BACKGROUND/AIMS: Refractive errors, especially if undercorrected, are a common and important cause of poor vision, particularly in Asia. The knowledge and beliefs of refractive errors and possible impact of undercorrection in a population-based study in Singapore are described. METHODS: This study was a substudy on 503 subjects with refractive error from a population-based survey of 3280 adult Malays in Singapore aged 40 to 80 years. The Health Belief Model was used to develop a questionnaire, subjects with refractive errors were evaluated on their health beliefs towards adopting health-seeking behaviour for correction of refractive error, and the responses were compared between undercorrected subjects and subjects with corrected refractive errors. RESULTS: Of persons with myopia, 79.5% had heard of myopia, 79.2% of hyperopes had heard of hyperopia, while only 7.7% of those with astigmatism had heard of astigmatism. Adults who had never previously visited an eye-care specialist were less likely to have heard of astigmatism and to know that they have refractive error (p<0.01). Adults with undercorrected refractive error were more likely to be female (61.1% vs 49.3%) and not wear spectacles (41.7% vs 22.3%). Knowledge on astigmatism (1.4% vs 5.6%) and refractive errors (62.6% vs 77.5%) were significantly lower in the undercorrected group. CONCLUSIONS: The lack of knowledge and awareness of refractive errors are important risk factors for undercorrected refractive error in an urban Singapore population.

Retinal detachment in Chinese, Malay and Indian residents in Singapore: a comparative study on risk factors, clinical presentation and surgical outcomes.

PURPOSE: To evaluate the risk factors, clinical presentation and surgical outcomes of retinal detachment (RD) among Chinese, Malay and Indian residents in Singapore. METHODS: A retrospective descriptive study from January 1995 to December 1998. All RD operations performed at a tertiary ophthalmic center in Singapore were initially identified from a computerized audit database. Case records data of all Malay and Indian patients as well as a 10% randomized sample of Chinese patients were retrieved and analyzed. Tractional and exudative RD's were excluded. RESULTS: Of the Singapore residents who had a RD operation over the 4-year period, 597 (89.6%) were Chinese, 47 (7.1%) were Malays and 22 (3.3%) were Indians. The age (mean: 46.1 +/- 15.5 years), gender distribution (70.5% males) and presenting visual acuities were similar in the 3 races. The most common site of the retinal break(s) was the superotemporal retina (44.9%), followed by the inferotemporal retina (15.3%). Chinese patients were more likely to have multiple or indeterminate breaks (p = 0.09) and macula-on RD (p = 0.04), compared to Malays and Indians. The distribution of known risk factors (myopia, lattice degeneration, prior cataract surgery and prior ocular trauma) was similar between the three races. The majority of patients required a scleral buckling operation either in isolation (71.3%), or in combination with vitrectomy (19.4%), and only 10 (7.8%) had vitrectomies without buckles. At 6 months postoperatively, anatomical success (defined as an attached retina on ocular examination) and functional success (defined as visual acuities of 6/60 or better) were achieved in 108 (94.7%) and 62 patients (54.4%), respectively, with no significant racial variation seen. The overall rate of redetachment after the initial operation was low (9.3%). CONCLUSION: Variation in risk factors, clinical presentations and postoperative outcomes of retinal detachment appears to be minimal among Chinese, Malays and Indians in Singapore.

Genotype-phenotype correlations in families with deletions in the von Hippel-Lindau (VHL) gene.

Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome characterized by predisposition for bilateral and multi-centric hemangioblastoma in the retina and central nervous system, pheochromocytoma, renal cell carcinoma, and cysts in the kidney, pancreas, and epididymis. We describe five families for which direct sequencing of the coding region of the VHL gene had failed to identify the family-specific mutation. Further molecular analysis revealed deletions involving the VHL gene in each of these families. In four families, partial deletions of one or more exons were detected by Southern blot analysis. In the fifth family, FISH analysis demonstrated the deletion of the entire VHL gene. Our results show that (quantitative) Southern blot analysis is a sensitive method for detecting germline deletions of the VHL gene and should be implemented in routine DNA diagnosis for VHL disease. Our data support the previously established observation that families with a germline deletion have a low risk for pheochromocytoma. Further unraveling of genotype-phenotype correlations in VHL disease has revealed that families with a full or partial deletion of the VHL gene exhibit a phenotype with a preponderance of central nervous system hemangioblastoma.

Involutional lower eyelid entropion: results of a combined approach.

BACKGROUND AND OBJECTIVE: To evaluate the effect of adding horizontal eyelid tightening and the removal of orbital fat to reinsertion of the lower eyelid retractors to correct involutional entropion. PATIENTS AND METHODS: During 6 consecutive years, 266 cases (229 patients) were treated. Of these, 240 cases (207 patients) showed horizontal laxity, in which reinsertion of the lower eyelid retractors was combined with lower eyelid tightening in the lateral canthal angle. In 60 of these cases (47 patients), prolapsing orbital fat was removed during the operation. In 26 cases (22 patients), no horizontal laxity was found. Their treatment consisted of reinserting the lower eyelid retractors without eyelid tightening. Follow-up of 28 weeks postoperatively was available in all cases. In 213 cases (178 patients), follow-up of 5 months or longer (range 5 to 80 months, average 42 months) was available. RESULTS: The most common complication of surgery was persistent ectropion, which occurred in 12 cases (5.6%). It occurred significantly more often after reinsertion without horizontal eyelid tightening than after combined reinsertion and horizontal tightening (P = .04). Adding the excision of orbital fat to the latter procedure did not significantly influence the results. Transient ectropion also occurred significantly more often after retractor reinsertion alone than after combined retractor reinsertion and horizontal tightening (P = .01). The entropion recurred in 9 cases (3.3%), 5 of which within 24 months (2.4%). The authors found no difference in recurrence rate between the three groups. A disadvantage of eyelid tightening is tenderness, which was reported by 42 (29%) of the patients. In 9 patients this had persisted longer than 4 months. CONCLUSION: Horizontal eyelid laxity is common in involutional entropion. Tightening of the lower eyelid in the lateral canthus, added to reinsertion of the lower eyelid retractors, significantly lowers the incidence of surgical overcorrection, but has no effect on the recurrence rate. A disadvantage of eyelid tightening in the lateral canthus is that it may lead to mostly transient eyelid tenderness.

Six elderly suicides in a 1-year period in a rural midwestern community.

In a 1-year period, 6 of 11 suicides in a rural Wisconsin county were committed by people over the age of 60. At the request of the local coroner, the American Medical Association sent a team of investigators to perform psychological autopsies. Family member survivors, friends, and attending physicians were interviewed. The majority of suicide victims had evidence of major depressive episodes, delusions that they had a terminal physical illness, and knowledge of family/friends who had committed suicide. Most had seen their physician within 48 hours before their death. Continuing education efforts focused on increasing a physician's abilities to recognize depression and suicidal ideation have ensued, based on this experience.

Prognostic indicators for poor risk epithelial ovarian carcinoma.

BACKGROUND: The objective of this study was to identify factors that categorize patients with epithelial ovarian carcinoma into favorable and unfavorable prognostic groups at the time of initial treatment. METHODS: Data were analyzed from 51 women who were treated at Yale University, had an evaluable CA 125 half-life (t1/2), and were followed for disease recurrence for at least 2 years. RESULTS: Grade, maximum level of CA 125, and histology did not provide useful prognostic information. Stage, residual disease, minimum CA 125, and CA 125 t1/2 individually were predictive of persistent disease or recurrence within 3 years of diagnosis with sensitivities of 97, 70, 34, and 49%, respectively, and specificities of 33, 83, 100, and 83%, respectively. When these factors are combined, defining an unfavorable prognostic group as those patients having residual disease greater than 1 cm, CA 125 t1/2 greater than 12 days, or minimum CA 125 never falling below 35 U/ml, sensitivity and specificity were 96 and 65%, respectively, at 1 year of follow-up and 91 and 75%, respectively, at 3 years of follow-up. 75%, respectively, at 3 years of follow-up. CONCLUSIONS: In those patients in whom residual small volume disease after primary surgery indicates a good prognosis, minimum CA 125 and CA 125 t1/2 during chemotherapy can further categorize patients into favorable and unfavorable prognostic groups.

Peritalar dislocations in children.

Five patients with peritalar dislocations were identified in a search for injuries of the talus. We report the mechanism, management, and outcome of their injuries and compare and contrast the injuries with the same injury in adults. To our knowledge, our series is the only small series of this rare injury in children. Four of our 5 patients had acceptable results with respect to pain and gait. In two patients, the peritalar dislocation was missed, necessitating a delay in management because more attention is focused on obvious fractures, when they exist.

Diagnostic efficiency of carcinoembryonic antigen and CA125 in the cytological evaluation of effusions.

In our previous study, the combination of the concentrations of carcinoembryonic antigen (CEA) and CA125 and the findings from cytological examination in 189 benign and malignant pleural and peritoneal effusions was useful in the diagnosis/classification of malignant effusions. Sensitivity of CEA (level, greater than 5 ng/mL) was 68%; specificity was 99% for the diagnosis of malignant effusions secondary to carcinoma of the lung, breast, gastrointestinal tract, and mucinous carcinoma of the ovary. Sensitivity of CA125 (level, greater than 5000 U/mL) was 85%; specificity was 96% for the diagnosis of malignant effusions in carcinoma of the ovary, fallopian tube, and endometrium. We now expanded the study to include 840 pleural and peritoneal effusions (benign, n = 520; malignant, n = 320) and analyzed the data by the statistical method of Rudolph and colleagues. Based on new cutoff values, ie, CEA level at 6.3 ng/mL and CA125 level at 3652 U/mL, the sensitivities for detection of malignant effusions secondary to carcinomas of the lung, breast, and gastrointestinal tract and mucinous carcinoma of the ovary varied between 75% and 100%; specificity was 98%. Sensitivity of CA125 for detection of malignant effusions from müllerian epithelial carcinoma was 71%; specificity was 99%. The elevated CEA fluid level alone helped to diagnose malignant effusions of the gastrointestinal tract in 54%, breast in 19%, and lung in 16%. The high CA125 fluid level was predictive of müllerian epithelial carcinoma. Adjunctive use of CEA and CA125 levels in fluid enhances the sensitivity of cytological diagnosis and may be predictive of the primary site in patients who present with carcinoma of an unknown primary source.

Preoperative Ilizarov frame construction for correction of ankle and foot deformities.

The Ilizarov method is being used increasingly to correct many orthopedic deformities. The frames required for ankle and foot deformity correction are among the most difficult to construct owing to the complexity of the deformities which must be corrected. A technique using a rubberized material (Pedilen) to create an exact replica of a preoperative ankle and foot deformity is described. This exact model, both in size and shape, may then be used on a workbench to preconstruct an Ilizarov frame that resembles the patient's deformity exactly in three dimensions with respect to size and shape. This allows thoughtful frame construction before operation reducing operating time and minimizing frustrations that may arise with complex deformities.

Central fracture-dislocation of the hip in a child.

A case report of a 10-year-old child with a central fracture-dislocation of the hip, managed by open reduction is presented, with a long-term result. The rarity of this injury in children is discussed, with the possible complications of inadequate joint congruity and potential growth injury.

Congenital "high-arched (cavus) forefoot"--a newly described deformity and surgical correction.

A previously unreported forefoot deformity (cavus) is described, clinically and radiologically, and a surgical operation for successful correction is detailed.

The role of chemotherapy in non-small cell lung cancer: the community perspective.

In the past decade, several drugs have been identified that possess activity in treating non-small cell lung cancer (NSCLC). The combination of mitomycin C, vinblastine, and cisplatin (MVP) was studied in 56 previously untreated patients with advanced NSCLC in Bridgeport Hospital from 1981 to 1984. In a selected patient population, 73% of 52 evaluable patients had complete (four patients) or partial (34 patients) responses. Response rate was 88% in epidermoid carcinoma, 70% in adenocarcinoma, and 50% in undifferentiated carcinoma. Median survival was 10 months in responding patients v 4 months in nonresponders. Performance status was the most important factor predictive of prolonged survival. MVP cannot be recommended for patients with poor performance status but may offer worthwhile palliation to patients with advanced NSCLC. Active drug combinations must now be studied as part of a multidisciplinary approach to the primary management of patients with clinically localized NSCLC.

Medial osteochondritis of the talus in children: review and new surgical management.

Review of the management of medial osteochondritis of the talus in the young patient has revealed the poor results of casting and the equivocal results of past surgical options. A new surgical technique of bone grafting is described. The results in six patients treated with bone grafting are compared with the results in 10 patients treated by excision. Because of the more favorable results following bone grafting, we recommend it as primary treatment of this condition in children and adolescents.

Acute hematogenous osteomyelitis in children.

We reviewed the cases of 60 children with acute osteomyelitis with an average follow-up of 34 months. All patients were treated initially with high-dose intravenous (i.v.) antibiotics. Eight patients did not respond to this treatment within 48 h and had surgical drainage. The remaining 52 patients were divided into two subgroups: (a) 35 patients received i.v. antibiotics for an average of 21 days; (b) 17 patients received i.v. antibiotics for an average of 8 days followed by 4 weeks of oral therapy with monitoring of serum bactericidal levels. The incidence of chronic infection (12% for the operatively treated group and 4% for the nonoperatively treated group) depended more on the time interval between the presentation of symptoms and the onset of treatment than it did on the route of antibiotic administration.