Neoadjuvant chemotherapy in patients with breast cancer: Does response in the breast predict axillary node response?

INTRODUCTION: Determining the extent of residual disease in the breast and axilla following neoadjuvant chemotherapy (NACT) is vital for surgical planning. Traditionally patients with incomplete radiological response in the breast after NACT undergo axillary node clearance, regardless of axillary clinical and radiological response. The aim of this study was to determine whether radiological and/or pathological response in the breast to NACT were predictive of axillary response. MATERIALS AND METHODS: A retrospective cohort study of patients with operable breast cancer with histologically proven axillary lymph node involvement who received NACT and underwent definitive surgical treatment between 1/1/2016 and 31/12/2018 were included. All had MRI and/or US of the breast and axilla before, mid-treatment and at the end of NACT. RESULTS: The 83 patients had a median age of 50 years (range 25-77). MRI had a positive predictive value (PPV) of 52.6% and negative predictive value (NPV) of 81.8% for breast pathological complete response (pCR). For axillary pCR, US had a PPV of 60.0% and NPV of 89.6%. Only 71% of patients had radiological concordance; 15.9% had radiological complete response (rCR) in breast and axilla whilst 55.1% had neither breast nor axillary rCR. 85.6% of patients had pathological concordance (20.5% with breast and axillary pCR: 65.1% with residual disease in both). CONCLUSION: Radiological and pathological response in the breast to NACT does not accurately predict axillary response. The axilla and the breast should be viewed and assessed as two separate entities for treatment plans.

Core outcome sets in women's and newborn health: a systematic review.

BACKGROUND: Variation in outcome collection and reporting is a serious hindrance to progress in our specialty; therefore, over 80 journals have come together to support the development, dissemination, and implementation of core outcome sets. OBJECTIVE: This study systematically reviewed and characterised registered, progressing, or completed core outcome sets relevant to women's and newborn health. SEARCH STRATEGY: Systematic search using the Core Outcome Measures in Effectiveness Trial initiative and the Core Outcomes in Women's and Newborn Health initiative databases. SELECTION CRITERIA: Registry entries, protocols, systematic reviews, and core outcome sets. DATA COLLECTION AND ANALYSIS: Descriptive statistics to describe characteristics and results. RESULTS: There were 49 core outcome sets registered in maternal and newborn health, with the majority registered in 2015 (n = 22; 48%) or 2016 (n = 16; 32%). Benign gynaecology (n = 8; 16%) and newborn health (n = 3; 6%) are currently under-represented. Twenty-four (52%) core outcome sets were funded by international (n = 1; <1%), national (n = 18; 38%), and regional (n = 4; 8%) bodies. Seven protocols were published. Twenty systematic reviews have characterised the inconsistency in outcome reporting across a broad range of relevant healthcare conditions. Four core outcome sets were completed: reconstructive breast surgery (11 outcomes), preterm birth (13 outcomes), epilepsy in pregnancy (29 outcomes), and maternity care (48 outcomes). The quantitative, qualitative, and consensus methods used to develop core outcome sets varied considerably. CONCLUSIONS: Core outcome sets are currently being developed across women's and newborn health, although coverage of topics is variable. Development of further infrastructure to develop, disseminate, and implement core outcome sets is urgently required. TWEETABLE ABSTRACT: Forty-nine women's and newborn core outcome sets registered. 50% funded. 7 protocols, 20 systematic reviews, and 4 core outcome sets published. @coreoutcomes @jamesmnduffy.

Biallelic Mutations in TBCD, Encoding the Tubulin Folding Cofactor D, Perturb Microtubule Dynamics and Cause Early-Onset Encephalopathy.

Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause neurodevelopmental and neurodegenerative disorders. Growing evidence suggests that altered microtubule dynamics may also underlie or contribute to neurodevelopmental disorders and neurodegeneration. We report that biallelic mutations in TBCD, encoding one of the five co-chaperones required for assembly and disassembly of the αß-tubulin heterodimer, the structural unit of microtubules, cause a disease with neurodevelopmental and neurodegenerative features characterized by early-onset cortical atrophy, secondary hypomyelination, microcephaly, thin corpus callosum, developmental delay, intellectual disability, seizures, optic atrophy, and spastic quadriplegia. Molecular dynamics simulations predicted long-range and/or local structural perturbations associated with the disease-causing mutations. Biochemical analyses documented variably reduced levels of TBCD, indicating relative instability of mutant proteins, and defective ß-tubulin binding in a subset of the tested mutants. Reduced or defective TBCD function resulted in decreased soluble α/ß-tubulin levels and accelerated microtubule polymerization in fibroblasts from affected subjects, demonstrating an overall shift toward a more rapidly growing and stable microtubule population. These cells displayed an aberrant mitotic spindle with disorganized, tangle-shaped microtubules and reduced aster formation, which however did not alter appreciably the rate of cell proliferation. Our findings establish that defective TBCD function underlies a recognizable encephalopathy and drives accelerated microtubule polymerization and enhanced microtubule stability, underscoring an additional cause of altered microtubule dynamics with impact on neuronal function and survival in the developing brain.

Breast reconstruction: options post-mastectomy.

Breast cancer is the most common cancer affecting women in the UK. Breast reconstruction after resection of breast cancers increases patients' quality of life and psychosocial functioning. This article introduces this field and explores the options available to patients with breast cancer.

Partial purification and characterization of neutral proteases in lymph nodes of rats with experimental allergic encephalomyelitis.

Two kinds of neutral protease activities in lymph nodes from Lewis rats with acute experimental allergic encephalomyelits (EAE) have been separated and partially purified and characterized. A soluble enzyme preparation enriched by gel filtration and ion-exchange chromatography hydrolyzes myelin basic protein, polylysine, and other basic proteins with an optimum pH at 6.0-6.5. It is inhibited by p-chloromercuribenzoate, and thus appears to be a mixture of thiol proteases. Another fraction containing proteolytic enzyme activity is strongly bound to the insoluble lymph node residue, and it also hydrolyzes myelin basic protein and histone, but not polylysine. It has a pH optimum above 7.5, is inhibited by phenylmethylsulfonyl fluoride, thus resembling elastase, but does not hydrolyze elastin-Congo red. The insoluble enzyme preparation hydrolyzes basic protein to 4-5 peptides in a pattern on polyacrylamide gels resembling that of the hydrolysis of basis protein by whole lymphocytes; the soluble enzyme mixture produces small fragments not retained on gels. Lymphocytes are a major component of the cells infiltrating the nervous system in experimental allergic encephalomyelitis, and neutral proteases contained in these cells may contribute to the degradation of myelin, especially of the basic protein.

Comparison of human subjective and oculomotor responses to sinusoidal vertical linear acceleration.

Human subjects were vertically oscillated in the dark over a frequency range of 1-0.02 HZ at peak-to-peak acceleration amplitudes of 0.2-0.6 g, using both a vertical movement simulator and real flight. Subjective tracking of the movement was unreliable and showed no systematic dependence of phase upon frequency. In contrast, reflex oculomotor response, although weak, clearly demonstrated progressive and substantial phase lag with increasing frequency. The similarity of this characteristic to that previously obtained from brainstem neural responses in cat suggests the oculomotor response was primarily of a vestibular origin. The in-flight studies demonstrated that head movement in a changing linear accelerative field, especially at 0.1 Ha, is highly provocative of motion sickness despite subthreshold angular movement of the aircraft.

Serum testosterone, body composition, and strength of young adults.

The relationship between serum testosterone (ST), body composition, and static strength was studied in 26 college females and 16 male college football players. In addition, the transient effect of weight training on ST was studied in 10 college males (5 skilled and 5 unskilled weight trainers), 12 male high school students, and 5 female college students. ST, measured by radioimmunoassay, ranged from 333.7 to 848.1 ng/100 ml in males, and from 32.8 to 121.5 n/100 ml in females. The high school subjects had significantly lower levels of ST. Correlations between serum testosterone, body composition (measured by densitometry), and static strength (grip and backlift) were nonsignificant in males and females. Comparisons of subjects with the highest and lowest levels of testosterone within each sex showed no significant differences in strength or body composition. Serum testosterone increased 111.4 +/- 96.l ng/100 ml (X +/- SX) following a weight training session in the male college group, but failed to increase in the college females or high school males. There were no significant differences in testosterone increases between the skilled and unskilled male weight trainers. Maximal exertion may be necessary for an increase in serum testosterone to occur. Lack of an increase in testosterone by high school males or college females may have been due to a submaximal effort during the weight training exercise.

Body composition and Vo2max of exceptional weight-trained athletes.

The maximal oxygen uptake and body composition of 30 exceptional athletes who have trained extensively with weights was measured. The sample included 3 world record holders, 8 other world class athletes, and 19 national class competitors. The sports represented were shot-putting, discus throwing, body building, power lifting, wrestling, and olympic lifting. Vo2max as determined on a bicycle ergometer by the open-circuit method was 4.6 +/- 0.7 1-min-1 (mean +/- SD) (48.8 +/- 7 ml-kg-1., 56.4 +/- 8.6 ml-(kg LBW)-1). The mean maximal heart rate was 185.3 +/- 11.6 beats-min-1. The subjects attained a work rate of 1,728.2 +/- 223 kpm-min-1 on a continuous progressive bicycle ergometer test and had mean maximal ventilations of 152.5 +/- 27.7 1-min-1 BTPS. Body composition was determined by densitometry. Body weight averaged 96.0 +/- 14.9 kg, with mean percent fat of 13.8 +/- 4.5. The results of this study indicate that exceptional weight-trained athletes are within the normal college-age population range in body fat and of somewhat higher physical working capacity.

Venous and capillary blood hematocrit at rest and following submaximal exercise.

The purpose of this study was to determine if finger tip capillary blood hematocrit is a valid estimate of anticubital venous blood hematocrit at rest and after submaximal exercise. Simultaneous samples of finger tip cpaillary and venous blood were drawn from thirty-one subjects (15 males, 16 females) before and after a 15 min submaximal exercise on a bicycle ergometer. Venous and capillary blood hcts. were 42.0% +/- 3.9 and 42.0% +/- 3.5 respectively before exercise and 43.3% +/- 3.5 and 42% +/- 3.8 after exercise (X +/- s). The regression equation for predicting venous hct. from finger tip capillary blood after exercise was: Hctv = 0.87 Hctc + 6.44 with r = 0.95 (P less than 0.05). The results indicate that the finger tip capillary microhematocrit method is a valid indicator of venous blood hct. following exercise.