Patients' experiences of a suppoRted self-manAGeMent pAThway In breast Cancer (PRAGMATIC): quality of life and service use results.

PURPOSE: To describe trends and explore factors associated with quality of life (QoL) and psychological morbidity and assess breast cancer (BC) health service use over a 12-month period for patients joining the supported self-management (SSM)/patient-initiated follow-up (PIFU) pathway. METHODS: Participants completed questionnaires at baseline, 3, 6, 9 and 12 months that measured QoL (FACT-B, EQ 5D-5L), self-efficacy (GSE), psychological morbidity (GHQ-12), roles and responsibilities (PRRS) and service use (cost diary). RESULTS: 99/110 patients completed all timepoints; 32% (35/110) had received chemotherapy. The chemotherapy group had poorer QoL; FACT-B total score mean differences were 8.53 (95% CI: 3.42 to 13.64), 5.38 (95% CI: 0.17 to 10.58) and 8.00 (95% CI: 2.76 to 13.24) at 6, 9 and 12 months, respectively. The odds of psychological morbidity (GHQ12 >4) were 5.5-fold greater for those treated with chemotherapy. Financial and caring burdens (PRRS) were worse for this group (mean difference in change at 9 months 3.25 (95% CI: 0.42 to 6.07)). GSE and GHQ-12 scores impacted FACT-B total scores, indicating QoL decline for those with high baseline psychological morbidity. Chemotherapy patients or those with high psychological morbidity or were unable to carry out normal activities had the highest service costs. Over the 12 months, 68.2% participants phoned/emailed breast care nurses, and 53.3% visited a hospital breast clinician. CONCLUSION: The data suggest that chemotherapy patients and/or those with heightened psychological morbidity might benefit from closer monitoring and/or supportive interventions whilst on the SSM/PIFU pathway. Reduced access due to COVID-19 could have affected service use.

A robust experimental and computational analysis framework at multiple resolutions, modalities and coverages.

The ability to study cancer-immune cell communication across the whole tumor section without tissue dissociation is needed, especially for cancer immunotherapy development, which requires understanding of molecular mechanisms and discovery of more druggable targets. In this work, we assembled and evaluated an integrated experimental framework and analytical process to enable genome-wide scale discovery of ligand-receptors potentially used for cellular crosstalks, followed by targeted validation. We assessed the complementarity of four different technologies: single-cell RNA sequencing and Spatial transcriptomic (measuring over >20,000 genes), RNA In Situ Hybridization (RNAscope, measuring 4-12 genes) and Opal Polaris multiplex protein staining (4-9 proteins). To utilize the multimodal data, we implemented existing methods and also developed STRISH (Spatial TRanscriptomic In Situ Hybridization), a computational method that can automatically scan across the whole tissue section for local expression of gene (e.g. RNAscope data) and/or protein markers (e.g. Polaris data) to recapitulate an interaction landscape across the whole tissue. We evaluated the approach to discover and validate cell-cell interaction in situ through in-depth analysis of two types of cancer, basal cell carcinoma and squamous cell carcinoma, which account for over 70% of cancer cases. We showed that inference of cell-cell interactions using scRNA-seq data can misdetect or detect false positive interactions. Spatial transcriptomics still suffers from misdetecting lowly expressed ligand-receptor interactions, but reduces false discovery. RNAscope and Polaris are sensitive methods for defining the location of potential ligand receptor interactions, and the STRISH program can determine the probability that local gene co-expression reflects true cell-cell interaction. We expect that the approach described here will be widely applied to discover and validate ligand receptor interaction in different types of solid cancer tumors.

Prenatal sonographic diagnosis of a congenital oral fibrovascular hamartoma.

We report the diagnosis of a congenital oral fibrovascular hamartoma with two- and three-dimensional ultrasound. The distinctive sonographic features including the fibrovascular stalk and a single vascular pedicle are described. Prenatal magnetic resonance imaging and postnatal computed tomography confirmed the ultrasound findings. Despite concerns about impaired swallowing, the prenatal and perinatal courses were straightforward. The lesion was removed soon after birth. Histopathology of the removed lesion provided the definitive diagnosis of a fibrovascular hamartoma and reported a cellular composition that differentiates it from similar lesions. To our knowledge, such a lesion has not been reported pre- or postnatally and provides an alternative differential diagnosis for a fetus presenting with a mouth mass.

HPLC determination of imatinib in plasma and tissues after multiple oral dose administration to mice.

Imatinib inhibits Bcr-Abl, c-KIT and PDGFR kinases. It is approved for the treatment of chronic myeloid leukemia (CML), gastrointestinal stromal tumors (GIST) and has further therapeutic potential. Male ICR mice were given imatinib PO (50 or 25 mg/kg, 5 doses every 2 h); euthanized 2 h after the last dose administration; plasma, liver, brain, spleen and kidney were collected and imatinib concentration measured by an optimized HPLC method for quantification in tissues. Methanol (1:1 v/v plasma) and pH 4, 40:30:30 (v/v/v) water-methanol-acetonitrile at 5 ml/g (brain) and 10 ml/g (spleen, kidney, liver) ratio was added to the samples, homogenized, sonicated, centrifuged (15,000 rpm, 5 min, 2 degrees C) and the supernatant injected into an Inertsil CN-3 column (4.6 mm x 150 mm, 5 microm) using 64:35:1 (v/v/v) water-methanol-triethylamine (pH 4.8), flow rate 1 ml/min, 25 degrees C. Imatinib eluted at 7.5 min (268 nm). Linearity: 0.1-50 microg/ml; precision, accuracy, inter- and intra-day variability was within 15%. Recovery was above 95% (plasma), 80% (brain) and 90% (kidney, liver, spleen). Imatinib tissue concentrations were 6-8 folds higher than plasma except brain, where the ratio decreased from 0.24 to 0.08 suggesting limited brain penetration, likely due to blood brain barrier efflux transporters. The extensive distribution supports the expansion of therapeutic applications.

Evaluation of somnolence in Parkinson's disease: comparison with age- and sex-matched controls.

The authors found a significantly higher prevalence of daytime somnolence in 201 patients with PD compared with 214 age- and sex-matched healthy control subjects (Epworth Sleepiness Scale score 5.6 vs 4.6). The prevalence of "sleep attacks" (SA) was about seven times higher in patients with PD than in control subjects (13.9% vs 1.9%; p < 0.0005). Multivariate analysis demonstrated that a higher dose of levodopa and longer duration of disease significantly predicted for SA in patients with PD. Epworth Sleepiness Scale scores of > or =10 had 71.4% sensitivity and 88.4% specificity for SA.

Dose-dependent protective effect of coffee, tea, and smoking in Parkinson's disease: a study in ethnic Chinese.

INTRODUCTION: Few studies have examined the relationship of coffee and tea in Parkinson's disease (PD). The potential protective effect of coffee intake and risk of PD has not been studied in a Chinese population. There is a high prevalence of caffeine takers among Chinese in our population. OBJECTIVE: We undertook a case control study to examine the relationship between coffee and tea drinking, cigarette smoking, and other enviromental factors and risk of PD among ethnic Chinese in our population. METHODS AND RESULTS: 300 PD and 500 population controls were initially screened. Two hundred case control pairs matched for age, gender, and race were finally included in the analysis. Univariate analysis revealed significant association of PD with coffee drinking (p<0.0005), tea drinking (p=0.019), alcohol drinking (p=0.001), cigarette smoking (p<0.0005), and exposure to heavy metals (p=0.006). Conditional logistic regression analysis demonstrated that amount of coffee drunk (OR 0.787, 95%CI 0.664-0.932, p=0.006), amount of tea drunk (OR 0.724, 95%CI 0.559-0.937, p=0.014), number of cigarettes smoked (OR 0.384, 95%CI 0.204-0.722, p=0.003), history of heavy metal and toxin exposure (OR 11.837, 95%CI 1.075-130.366, p=0.044), and heart disease (OR 5.518, 95%CI 1.377-22.116, p=0.016) to be significant factors associated with PD. One unit of coffee and tea (3 cups/day for 10 years) would lead to a 22% and 28% risk reduction of PD. One unit of cigarette smoke (3 packs/day for 10 years) reduced the risk of PD by 62%. CONCLUSIONS: We demonstrated a dose-dependent protective effect of PD in coffee and tea drinkers and smokers in an ethnic Chinese population. A history of exposure to heavy metals increased the risk of PD, supporting the multifactorial etiologies of the disease.

Restless legs symptoms in thyroid disorders.

Dopaminergic dysfunction is associated with thyroid disorders and restless legs syndrome (RLS). In a 'face-to-face' interview, we evaluated for RLS using the diagnostic criteria of the International Restless Legs Syndrome Study Group (IRLSSG) in patients diagnosed biochemically with either hyper- or hypothyroidism, and in controls without thyroid disorders. Amongst 146 consecutive patients with biochemically confirmed thyroid disorders, none satisfied all the IRLSSG criteria of RLS, similar to the control population (0.2%, 1/434). However, we found 8.2% (12/146) with RLS-like symptoms (satisfied the first 3 IRLSSG criteria) compared to 0.9% (4/434) in the controls (p < 0.0001). Four (33.3%) of these patients reported complete resolution of these symptoms after treatment for their thyroid condition. In conclusion, while RLS-like symptoms were observed in some patients with thyroid disorders, our study demonstrates no significant difference of RLS prevalence between patients with thyroid disorders and euthyroid controls.

Removal of skin staples in an emergency.

We have highlighted this problem as there are situations where skin staples have to be removed rapidly, for example where bleeding and subsequent respiratory distress develop following neck surgery. A survey of junior hospital staff showed that many doctors had never removed skin staples nor were aware how best to remove them in the event of an emergency. Using skin simulation we compared the time to remove sutures and staples, and found it takes 55% longer to remove skin staples. Where the standard staple remover is not immediately available, an artery forceps, correctly applied, is just as quick.

Surgical reconstruction for mesenteric angina in a patient with infra-renal aortic occlusive disease--a case report and review.

Mesenteric angina is an uncommon condition which is underdiagnosed, or diagnosed too late when the patient has a mesenteric infarct. The preferred treatment is by surgical reconstruction. A case presented here illustrates the condition and the modifications necessary to reconstruct a completely occluded lower abdominal aorta in treating both mesenteric angina and claudication.

Early experience of limb salvage in critical leg ischaemia.

BACKGROUND: We report the retrospective review of 82 leg bypass grafts done in 79 patients who had critical leg ischaemia between May 1993 and November 1996. The mean age of the patients was 68 years (range 50 to 82). PATIENTS: There were 49 male and 35 female patients. Fifty-nine percent of the study population presented with gangrene, 33% had ischaemic ulceration and 58% had rest pain. Seventy-five percent of them were diabetics. Thirty-eight femoro-popliteal, 28 femoro-distal, 6 popliteal-distal, 5 pedal, 1 aorto-bifemoral, 3 axillo-bifemoral and 1 cross-over bypass grafts were done. RESULTS: The peri-operative mortality rate was 11.3% and 71% of patients were discharged with salvaged feet. Ninety percent of these legs were still viable 12 months after the operation.

Chronic haemodialysis with PTFE arterio-venous grafts.

BACKGROUND/AIM OF STUDY: End-stage renal failure (ESRF) patients requiring long-term haemodialysis need a durable vascular access. The arterio-venous fistula (AVF) with its long patency rate and low complication profile is usually the first choice procedure for vascular access creation. However when superficial veins are not suitable for AVF creation or have all been exhausted as a result of repeated AVF procedures, arterio-venous grafts (AVG) using polytetraflouroethylene (PTFE) to bridge arteries and veins is an alternative for provision of continued vascular access for haemodialysis. This study is a review of our experience in using PTFE AVGs for vascular access in patients requiring chronic haemodialysis. METHODS AND MATERIALS: A retrospective review was done on 92 grafts in 77 patients placed by 3 vascular access surgeons at the Singapore General Hospital from January 1989 to December 1994. RESULTS: There were 58 female and 19 male patients with a median age of 43 years (range 15-76 years). Twelve patients (16%) were diabetic and 6 patients (8%) had systemic lupus erythematosis requiring long-term steroids. Seventy-three percent of patients had up to 2 previous AVF creations before placement of AVG over the forearm (64%), upper arm (23%) or thigh (6.5%). Complications include graft infection (19), pseudoaneurysm formation (10), graft thrombosis (24), steal syndrome (1), venous congestion (1) and venous end stenosis (1). Diabetic status and long-term steroid therapy did not significantly increase the incidence of graft infection. The patency rates at 24 months and 36 months were 77% and 58% respectively. However serviceability rates were 61% at 2 years and 38% at 3 years mainly due to infective complications. CONCLUSION: PTFE AVGs offer reasonable patency and serviceability rates as a vascular access modality but in view of their complication profile, the native vein arteriovenous fistula should continue to be the first choice procedure for vascular access in patients requiring chronic haemodialysis.

Surgical management and outcome of carotid body tumours.

INTRODUCTION: Carotid body tumours are rare but are interesting in their manner of presentation and challenging with respect to surgical extirpation. They may present as a neck mass from which a bloody aspirate is obtained on fine needle aspiration. They are occasionally diagnosed only at the time of surgery, when one encounters the vascular tumour mass. METHODS: We reviewed the results of 8 cases operated in our department over a 10-year period from 1989 to 1999. We evaluated in-hospital mortality and morbidity, as well as the long-term outcome especially with regards to functional disability. RESULTS: Preoperative evaluation included angiography, computed tomography (CT) or magnetic resonance angiography. Operative technique involves good exposure, vascular control, identification and preservation of neurovascular structures and subadventitial tumour dissection. In all cases the vagus nerve was preserved, except in 1 case who had a malignant tumour and resection of the vagus nerve together with the accessory nerve and sympathetic chain. Two patients had unexpected hoarseness of voice postoperatively, 1 was due to permanent vagus nerve palsy and the other to transient vagus nerve palsy. One of them needed vocal cord medialisation and long-term tube feeding. One patient had bilateral tumours and developed a stroke after an operation on the second tumour. No patients exhibited local or metastatic disease during follow-up. There was no mortality in all cases. CONCLUSION: Although resection of the carotid body tumour is safe in experienced hands, long-term morbidity is still a significant problem and can be debilitating to the patient.

Protection by tocotrienols against hypercholesterolaemia and atheroma.

Antioxidants such as tocotrienols may protect against atherosclerosis since tissue injury from free radicals is a final common pathway of damage in arterial disease. In this study, the effects of tocotrienols on serum cholesterol, lipid peroxides, and aorta atheroma were assessed in rabbits fed an atherogenic diet for 12 weeks. Tocotrienols were more effective than tocopherols in preventing increases in serum LDL (p = 0.03) and total cholesterol (p = 0.008) levels in the cholesterol-fed rabbits. Elevation of serum lipid peroxides was effectively suppressed by tocotrienols (p = 0.01). Both tocopherols and tocotrienols offered significant protection against atheroma in the rabbit aorta, but tocotrienols had a stronger hypolipidaemic effect.

Volumetric modulated arc therapy: a review of current literature and clinical use in practice.

Volumetric modulated arc therapy (VMAT) is a novel radiation technique, which can achieve highly conformal dose distributions with improved target volume coverage and sparing of normal tissues compared with conventional radiotherapy techniques. VMAT also has the potential to offer additional advantages, such as reduced treatment delivery time compared with conventional static field intensity modulated radiotherapy (IMRT). The clinical worldwide use of VMAT is increasing significantly. Currently the majority of published data on VMAT are limited to planning and feasibility studies, although there is emerging clinical outcome data in several tumour sites. This article aims to discuss the current use of VMAT techniques in practice and review the available data from planning and clinical outcome studies in various tumour sites including prostate, pelvis (lower gastrointestinal, gynaecological), head and neck, thoracic, central nervous system, breast and other tumour sites.

The effect of image size on screen-positive rates for nuchal translucency screening.

It has been shown previously that the absolute measurement of nuchal translucency (NT) thickness, one of the most effective screening tests for fetal Down syndrome, significantly decreases with increasing image size. We undertook a prospective study to assess whether this effect materially alters the NT-derived risk estimation for fetal Down syndrome. In 350 women, NT was measured at both 100 and 200% image sizes. The median NT measurement at 200% was 8% smaller than at 100%. The screen-positive rates at 100 and 200% image sizes were 5.1% (18/350) and 2.3% (8/350), respectively (P= 0.048). Altering the image magnification settings is likely to decrease the sensitivity of NT-derived Down syndrome risk estimation. Further study is required to test the effect of our finding on the sensitivity of NT screening and to assess whether adjustments in gain settings mitigate the effect.

Takayasu's arteritis with renovascular hypertension: results of surgical treatment.

Renal artery stenosis caused by Takayasu's arteritis is an important cause of hypertension in young patients in the Far East. The role of surgery in Takayasu's arteritis is not as well-defined as in atherosclerosis or fibromuscular dysplasia. In this retrospective review, the author reports the results of 19 renal artery reconstructions in 12 young patients (median age 23.5 years, range 10-46 years) presenting with renovascular hypertension and Takayasu's arteritis, and discusses the different surgical options. The procedures performed included aortorenal bypass using vein (five), aortorenal bypass using polytetrafluoroethylene (PTFE) (eight), iliorenal bypass using vein (four), reimplantation of renal artery (one) and aortic replacement graft-renal bypass (one). Postoperatively, all 12 patients had a successful outcome with improved hypertension. There was no perioperative mortality, and complications included two early graft thrombosis and one late graft occlusion. These results support the view that surgical treatment for renovascular hypertension in Takaysu's disease is safe and effective.