OncotypeDX Recurrence Score Does Not Predict Nodal Burden in Clinically Node Negative Breast Cancer Patients.

BACKGROUND: OncotypeDX recurrence score (RS)® has been found to predict recurrence and disease-free survival in patients with node negative breast cancer. Whether RS is useful in guiding locoregional therapy decisions is unclear. We sought to evaluate the relationship between RS and lymph node burden. METHODS: Patients with invasive breast cancer who underwent sentinel lymph node dissection from 2010 to 2015 were identified from a prospectively maintained database. Patients were excluded if they were clinically node positive or if they received neoadjuvant chemotherapy. RS was classified as low (< 18), intermediate (18-30), or high (> 30). The association between RS, lymph node burden, and disease recurrence was evaluated. Statistical analyses were performed in R version 3.4.0; p < 0.05 was considered significant. RESULTS: A positive SLN was found in 168 (15%) of 1121 patients. Completion axillary lymph node dissection was performed in 84 (50%) of SLN-positive patients. The remaining 84 (50%) patients had one to two positive SLNs and did not undergo further axillary surgery. RS was low in 58.5%, intermediate in 32.6%, and high in 8.9%. RS was not associated with a positive SLN, number of positive nodes, maximum node metastasis size, or extranodal extension. The median follow-up was 23 months. High RS was not associated with locoregional recurrence (p = 0.07) but was significantly associated with distant recurrence (p = 0.0015). CONCLUSIONS: OncotypeDX RS is not associated with nodal burden in women with clinically node-negative breast cancer, suggesting that RS is not useful to guide decisions regarding extent of axillary surgery for these patients.

Medical education in difficult circumstances: analysis of the experience of clinical medical students following the new innovative medical curriculum in Aksum, rural Ethiopia.

BACKGROUND: In 2012, 12 medical schools were opened in Ethiopia to tackle the significant shortage of doctors. This included Aksum School of Medicine situated in Aksum, a rural town in Northern Ethiopia. The new Innovative Medical Curriculum (NIMC) is a four-year programme designed by the Ethiopian Federal Ministries of Health and Education. The curriculum is designed to train biomedical science graduates to become doctors in 4 years, with a focus on the healthcare needs of rural people living in poverty. METHODS: This research was conducted at Aksum School of Medicine and included two hospitals (Aksum Referral Hospital and St Mary's District Hospital). This study focused on medical students during their clinical years across multiple specialities (61 Clerkship 1 students and 13 Clerkship 2 students). We used primarily qualitative research methods supplemented with quantitative measures. There were 3 stages of data collection over a 1 month period, this included qualitative group interviews, direct observation of students in a clinical setting and direct observation of skills sessions followed by a questionnaire on the sessions. We analysed the data by reconstructing the student experience and comparing it with the NIMC. RESULTS: The proposed typical week set out in the NIMC tended to differ from the real clinical experience of these students. Through qualitative group interview and direct observation of teaching, the main theme that was consistent throughout was the lack of doctors with specialist postgraduate training. Clinical need often took priority over education. However, students enjoyed taking early responsibility and gaining practical experience. Through direct observation of skills sessions and short questionnaires, these sessions were highly valuable to the students and they felt confident in carrying out the taught procedures in the future. CONCLUSIONS: The combination of poorly resourced hospitals and lack of specialist doctors provides a challenging environment for medical students to learn. However, it is a unique clinical experience that is rarely seen in developed countries and facilitates the acquirement of skills from an early stage. Supervision and specialist input is fundamental in enabling students to learn and this is a key area that was lacking in the students' clinical experience.

Breast conserving surgery and locoregional control after neoadjuvant chemotherapy.

The management of breast malignancy and the role of neoadjuvant systemic therapy has continued to evolve over the past 50 years. Survival equivalence with adjuvant systemic therapy is well accepted and demonstrated in several clinical trials. However, strong association with survival outcome and pathologic complete response emerged. Assessment of tumor response, as a surrogate for outcome, continues to be a driver for neoadjuvant therapy with increased applicability in the setting of sophisticated understanding and implications of breast tumor biology and molecular subtype. Furthermore, tumor response to neoadjuvant therapy can significantly impact local regional therapy decision-making by down-staging disease without compromising local regional control. This includes facilitation of breast conserving surgery and increased eligibility for limited axillary surgery in selected patients. Furthermore, the omission of surgery in the setting of exceptional response to neoadjuvant chemotherapy, the ultimate breast conserving strategy, is being actively studied. With further refinement of systemic and targeted therapies, neoadjuvant systemic therapy continues to provide a robust mechanism for innovation in local regional management paradigms with increased attention to individualized breast oncologic care.

Cognitively unimpaired HIV-positive subjects do not have increased 11C-PiB: a case-control study.

OBJECTIVES: Diagnostic challenges exist for differentiating HIV dementia from Alzheimer disease (AD) in older HIV-infected (HIV+) individuals. Similar abnormalities in brain amyloid-beta42 (Alphabeta42) metabolism may be involved in HIV-associated neuropathology and AD. We evaluated the amyloid-binding agent (11)C-Pittsburgh compound B ((11)C-PiB), a biomarker for Alphabeta42 deposition, in cognitively unimpaired HIV+ (n = 10) participants and matched community controls without dementia (n = 20). METHODS: In this case-control study, all participants had an (11)C-PiB scan within 2 years of concomitant CSF studies and neuropsychometric testing. Statistical differences between HIV+ and community controls for demographic and clinical values were assessed by chi(2) tests. Participants were further divided into either low (<500 pg/mL) or normal (>or=500 pg/mL) CSF Alphabeta42 groups with Student t tests performed to determine if regional differences in fibrillar amyloid plaque deposition varied with CSF Alphabeta42. RESULTS: Regardless of CSF Alphabeta42 level, none of the HIV+ participants had fibrillar amyloid plaques as assessed by increased (11)C-PiB mean cortical binding potential (MCBP) or binding potential within 4 cortical regions. In contrast, some community controls with low CSF Alphabeta42 (<500 pg/mL) had high (11)C-PiB MCBP with elevated binding potentials (>0.18 arbitrary units) within cortical regions. CONCLUSIONS: Cognitively unimpaired HIV+ participants, even with low CSF Alphabeta42 (<500 pg/mL), do not have (11)C-PiB parameters suggesting brain fibrillar amyloid deposition. The dissimilarity between unimpaired HIV+ and preclinical AD may reflect differences in Abeta42 production and/or formation of diffuse plaques. Future longitudinal studies of HIV+ participants with low CSF Abeta42 and normal (11)C-PiB are required.

CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease.

BACKGROUND: HIV-associated neurologic disorders (HAND) continue to develop in many patients with HIV. CSF amyloid measurements in HAND have been reported to be similar to those in dementia of the Alzheimer type (DAT). Confirmatory evaluation of this finding in carefully evaluated subjects is needed. METHODS: CSF specimens were obtained from subjects clinically categorized with normal cognition from the general population, HIV+ subjects with normal cognition, HIV+ subjects with impaired cognition, or presumed HIV- subjects with mild DAT. CSF measurements of beta-amyloid((1-42)) (Abeta42), beta-amyloid((1-40)) (Abeta40), total tau (t-tau), and phosphorylated tau (p-tau181) were performed. RESULTS: CSF Abeta42 measured in 49 HAND subjects had a median level of 501 pg/mL, which was lower than that of 50 controls of similar age who had median of 686 pg/mL (p < 0.0001) or 21 HIV+ subjects without cognitive impairment who had median of 716 pg/mL (p < 0.003). HAND subjects had similar CSF Abeta42 to 68 subjects with mild DAT. There was no difference of CSF Abeta40 between the groups. Tau and p-tau181 was elevated in DAT, but slightly lower than control in both HIV+ groups. CONCLUSIONS: beta-Amyloid((1-42)) (Abeta42) measurements in CSF of cognitively impaired patients with HIV are similar to those in patients with mild dementia of the Alzheimer type (DAT). Normal or slightly depressed CSF tau and p-tau181 measurements distinguish these patients with HIV-associated neurologic disorders (HAND) from patients with DAT. Further evaluation of amyloid metabolism in patients with HIV cognitive disorder is needed to understand the implications of depressed CSF Abeta42 in the setting of HAND.

Pulmonary hypertension in children and adolescents with sickle cell disease.

The prevalence of pulmonary hypertension (PHTN) in the pediatric sickle cell disease (SCD) population is not known despite its high prevalence in adult patients. Our hypothesis was that increased pulmonary artery pressures (PAPs) would be found in SCD children and adolescents, especially those with a history of pulmonary complications: acute chest syndrome, obstructive sleep apnea, asthma, and reactive airway disease. Fifty-two SCD children, 23 of whom had underlying pulmonary disease, were screened for PHTN, which was defined as a tricuspid regurgitant jet velocity (TRV) of at least 2.5 m/s. Twenty-four (46.15%) SCD patients had increased PAP (i.e., TRV > or =2.5 m/s), and 6 (11.5%) had significant PHTN (i.e., TRV > or =3.0 m/s). Pulmonary disease was marginally associated with PHTN (odds ratio 2.80 and confidence interval 0.88 to 8.86; p = 0.0795). As in adult SCD patients with PHTN, this complication was correlated with the degree of hemolysis as manifested by significantly higher lactate dehydrogenase and bilirubin, lower hemoglobin and hematocrit levels, and a strong association with Hb-SS phenotype. However, after statistical adjustment for age and sex, increased serum LDH was not associated with the development of PHTN. Further studies are needed to clarify the prevalence and mechanisms of PHTN in pediatric and adolescent patients with SCD.