Accuracy of a multidisciplinary team-led discussion in predicting postmastectomy radiotherapy

Introduction

Immediate breast reconstruction (IBR) is performed increasingly following mastectomy for breast cancer. The literature suggests higher reconstructive failure and poorer cosmesis in the subgroup of patients receiving postmastectomy radiotherapy (PMRT) following IBR. We set out to determine the accuracy of a multidisciplinary team (MDT) discussion in predicting PMRT.

Methods

Preoperative MDT discussions were recorded prospectively over a 12-month period (from February 2011) in a symptomatic breast unit. The estimated need for PMRT was stratified into ‘PMRT not required’, ‘PMRT possibly required’, ‘PMRT probably required’ and ‘PMRT required’ groups.

Results

Of 156 referrals included in the study, 76 patients (49%) underwent mastectomy: 61 simple mastectomy, 10 skin sparing mastectomy (SSM) and delayed-immediate breast reconstruction, 3 SSM and implant-based IBR, and 2 mastectomy IBR with an autologous flap. The IBR rate was therefore 19.7%. The proportion of patients who received PMRT was 14% (3/21) in the ‘PMRT not required’, 30% (7/23) in the ‘PMRT possibly required’, 65% (9/14) in the ‘PMRT probably required’ and 94% (17/18) in the ‘PMRT required’ groups. Assigning a linear numerical score (1–4) to these groups (higher score representing greater likelihood of receiving PMRT), the predicted need for PMRT correlated with the proportion of patients who ultimately received PMRT (linear regression r²=0.98, p=0.01).

Conclusions

This study has examined the factors influencing MDT discussions regarding IBR, demonstrating that the MDT is reasonably accurate at predicting need for PMRT. Whether such accuracy is clinically adequate and/or reproducible across units is debatable.     

Monocytoid differentiation of freshly isolated human myeloid leukemia cells and HL-60 cells induced by the glutamine antagonist acivicin

Previously we showed that starvation of HL-60 promyelocytic leukemia cells for a single essential amino acid induced irreversible differentiation into more mature monocyte-like cells. Although not an essential amino acid, glutamine is important in the growth of normal and neoplastic cells. The glutamine analogue, alpha S,5S-alpha-amino-3- chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin) inhibits several glutamine-utilizing enzymes and therefore depletes cells of certain metabolic end products. The current study was designed to examine in vitro the effects of acivicin on growth and differentiation of several established human myeloid leukemia cell lines, including the HL-60 cell line, and of freshly isolated cells from patients with acute nonlymphocytic leukemia (ANLL). Four-day culture of HL-60 cells with acivicin at concentrations of 0.1 to 10.0 micrograms/mL (0.56 to 56 nmol/L) decreased cell growth by 33% to 88% as compared with untreated control cells. Viability of cells was greater than 92% for untreated cells and 93% to 41% for acivicin-treated cells. Cells treated with acivicin differentiated along a monocytic pathway as shown by increased H2O2 production and alpha-naphthyl butyrate esterase (NSE) content. Differentiation was time and dose dependent, and was irreversible. Changes in H2O2 production and NSE content were partially abrogated by co-culture with 10 mmol/L exogenous cytidine and guanosine but not by co-culture with other nucleosides or glutamine. At these concentrations of acivicin, differentiation was associated with expression of the N- formyl-methyl-leucyl-phenylalanine-receptor (FMLP-R) on 8% to 29% of cells as compared with 8% for control cells. Acivicin potentiated the differentiating effects of interferon-gamma, tumor necrosis factor, dihydroxyvitamin D3, dimethylsulfoxide, and retinoic acid. Culture of cells from the U937 (monoblastic), K562 (erythroleukemia), and KG-1 (myeloblastic) cell lines resulted in decreased growth and viability, but not consistently in differentiation. Acivicin decreased survival of freshly isolated ANLL cells and increased their H2O2 production and NSE content. These results suggest that the glutamine analogue acivicin may be useful as a differentiating agent with antileukemia activity in patients with ANLL.     

Combined treatment with enuresis alarm and desmopressin for nocturnal enuresis

Seventy-one children with nocturnal enuresis were enrolled in a controlled trial. The children were allocated to two matched groups. Children in both groups used an enuresis alarm until the end of treatment. Children in the first group were treated with 40/^g of intranasal desmopressin (Desmospray) for up to 6 weeks at the start of treatment with the alarm. During the observation period before treatment there were 2.3 dry nights per week in both groups. At the end of treatment there was a significant difference in the mean number of dry nights per week between the two groups (6.3 in the alarm and desmopressin group and 4.8 in the alarm group) and also in the number of children becoming reliably dry. The combination of desmopressin and alarm was particularly helpful for children with severe wetting and those with family and behavioural problems. Desmopressin, enuresis alarm, nocturnal enuresis
MG Bradbury, Department of Paediatrics and Child Health, St James's University Hospital, Leeds LS9 7TF, UK     

Etheno adducts in spleen DNA of SJL mice stimulated to overproduce nitric oxide

In order to investigate specific DNA damage caused by nitric oxide (NO) induced lipid peroxidation, levels of promutagenic etheno adducts 1,N6- ethenodeoxyadenosine (epsilondA) and 3,N4-ethenodeoxycytidine (epsilondC) were measured in spleen DNA of SJL mice induced to produce high levels of NO by injection of RcsX (pre-B-cell lymphoma) cells. epsilondA and epsilondC levels were quantified by an ultrasensitive immunoaffinity-32P-post-labeling method. Spleen DNA of control mice (n = 5) had background levels of 9.2+/-5.4 epsilondA adducts per 10(9) dA and 13.1+/-5.7 epsilondC adducts per 10(9) dC. In RcsX cell-injected mice (n = 7), levels of these adducts were elevated approximately 6- fold, i.e. 53.9+/-39.4 epsilondA per 10(9) dA and 83.5+/-57.8 epsilondC per 10(9) dC (P < 0.05). Mice injected with RcsX cells and also treated with NG-methyl-L-arginine (NMA), an inhibitor of inducible nitric oxide synthase (n = 6), had significantly reduced levels (P < 0.05) of both epsilondA and epsilondC (13.5+/-5.7 epsilondA per 10(9) dA and 28.2+/- 15.7 epsilondC per 10(9) dC). These findings constitute the first available evidence of formation of etheno adducts associated with NO overproduction in vivo. The adducts were presumably formed from lipid peroxidation products such as trans-4-hydroxy-2-nonenal (HNE), generated via oxidation of lipids by peroxynitrite. The results suggest that etheno-DNA adducts, among other types of damage, may contribute to the etiology of cancers associated with chronic infection/inflammation in which NO is overproduced.      

Precipitants and aetiology of cyclic vomiting syndrome

Thirty-two patients aged 2-22 y with cyclic vomiting syndrome (CVS), and 64 age- and gender-matched controls were assessed to determine the nature, severity, precipitants and associated features of attacks and the incidence of potential aetiological factors. The mean age of onset was 3.5 y. Patients experienced a mean of nine attacks per year, of average duration 2.4 d, and two-thirds missed more than 10 d of school per year. Patients were more likely to have migraine and co-ordination difficulties, a past history of forceps delivery and gastroesophageal reflux than controls. Compared with controls, subjects had a higher incidence of psychological symptoms (38% compared with 19%) and migraine (37% compared with 9%). CVS is a chronic, disabling condition and is a migraine variant, with attacks usually precipitated by stress and intercurrent infections.     

Early child health in Lahore, Pakistan: IX. Perinatal events

In Pakistan there are a number of acute problems related to maternal and infant health in the perinatal period. There is also lack of reliable data needed for the formulation of action strategies. To provide a database 1490 women have been followed from the 5th month of pregnancy in four different areas at various levels of urbanization and socio-economic development. After adjusting for gestational age, the proportion of newborns with weight for length < -2SDS in relation to the Swedish National Standard was 12–31% for boys and 12–25% for girls, the figure being highest in the most deprived area. Preterm birth was infrequent compared with IUGR. The overall prevalence rate of birth defects was 21% out of which 8% were severe defects. The overall perinatal mortality rate was 56/1000 births, with rates of 60, 75, 36 and 33/1000 births for the village, periurban slum, urban slum and the upper middle class. Two thirds of the deaths were related to either a continuation of intrauterine disturbances or severe congenital defects incompatible with life. One third of the deaths were due to infection; mostly diarrhoea, clinical sepsis and ARI. Neonatal mortality was significantly related to birth length (<-2SDS, odds ratio 5.5) and length of gestation (<37 weeks, odds ratio 5.6) and was to a lesser extent related to weight (<-2SDS, odds ratio 2.0) and weight for length (<-2SDS, odds ratio 1.3). Forty percent of the mothers had weight for height below -2SDS, 23–35% had height <-2SDS. Forty percent of mothers from a subset within the cohort had a hemoglobin < 10 gm/dl and 20% showed signs of pre-eclampsia. This presentation raises the issue of expanding the current Child Survival Programs into the perinatal period as well.     

The physiology of falling: assessment and prevention strategies for older people

Balance calls upon contributions from vision, peripheral sensation, vestibular sense, muscle strength, neuromuscular control and reaction time. With increased age, there is a progressive loss of functioning of these systems and an increased likelihood of falls. Falls can mark the beginning of a decline in function and independence and are the leading cause of injury-related hospitalisation in older people. By using simple tests of vision, leg sensation, muscle strength, reaction time and standing balance, it is possible to identify accurately older people at risk of falls and assess intervention outcomes. This approach overcomes the limitations associated with traditional methods of assessing falls risk via medical diagnoses, including varied severity between individuals. Using a physiological approach provides information at the impairment and functional capacity levels to assist in understanding falls and developing and evaluating optimal falls prevention strategies for older people.