Liquid biopsy in breast carcinoma: Are we there yet?

Breast carcinoma is the most common malignancy among women worldwide. Liquid biopsy is a method of obtaining tumour-derived material from blood and body fluid. This includes the assessment of circulating tumour cells (CTCs), circulating tumour deoxyribose nucleic acid (ctDNA), tumour educated platelets (TEPs) and exosomes. Detection of CTCs and ctDNA in liquid biopsy has been shown to have prognostic and predictive value in both early and metastatic breast carcinoma. The study of CTCs could also advance our understanding of aspects of tumour biology, including epithelial mesenchymal transition. ctDNA can be used to assess and monitor the molecular profile of breast carcinoma. It may help detect new genetic alterations in tumours and predict disease progression before the onset of clinical features or radiological evidence. TEPs and exosomes are also emerging as diagnostic, prognostic and predictive markers of breast carcinoma. Thus, liquid biopsy provides a non-invasive, repeatable method for the dynamic assessment of the tumour. Many methods have been used for the detection of CTCs and ctDNA. Most of these are still in the research stage and only the CellSearch method for the detection of CTCs and Therascreen PIK3CA RGQ polymerase chain reaction (PCR) assay for the detection of PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha) mutations in liquid biopsy have approval of the United States, Food and Drug Administration. However, their high costs, lack of standardized procedures, and a long and complicated detection process have limited their use. Despite its limitations, liquid biopsy is a useful tool in clinical decision making and has the potential to play an increasingly important role in the management of breast carcinoma in the future as we move toward more personalized cancer care.

Hydrodynamic Interactions, Hidden Order, and Emergent Collective Behavior in an Active Bacterial Suspension.

Spontaneous self-organization (clustering) in magnetically oriented bacteria arises from attractive pairwise hydrodynamics, which are directly determined through experiment and corroborated by a simple analytical model. Lossless compression algorithms are used to identify the onset of many-body self-organization as a function of experimental tuning parameters. Cluster growth is governed by the interplay between hydrodynamic attraction and magnetic dipole repulsion, leading to logarithmic time dependence of the cluster size. The dynamics of these complex, far-from-equilibrium structures are relevant to broader phenomena in condensed matter, statistical mechanics, and biology.

Impact of diabetes on inpatient mortality and length of stay for elderly patients presenting with fracture of the proximal femur.

INTRODUCTION: Osteoporosis-related fractures of the proximal femur cause significant morbidity and result in an economic burden on societies. It remains debatable whether diabetic patients with proximal fracture of the femur demonstrate poorer outcomes in terms of hospital stay and mortality compared to non-diabetic controls. METHODS: All patients over 65years old admitted to the University Hospital Birmingham during 2007-2010 with a diagnosis of a fracture of the proximal femur (total 1468 including 197 patients with diabetes) were analysed. Eligibility and case definitions were ascertained using electronic records. Multivariate analyses were conducted to control for the confounding effect of covariates, which may be associated with the outcomes of interest on the basis of biological plausibility and known risks. RESULTS: In-patient mortality was estimated at 14.2% and 12% for the diabetic and non-diabetic patients respectively. Diabetes was not found to be a significant predictor of in-patient mortality, before and after adjustment for the covariates [Adjusted odds ratio 1.01 (95% CI 0.62-1.65)], in contrast to advancing age, male gender, co-morbidity score, low albumin and high creatinine concentrations. Similarly, median length of stay was greater in the diabetes patients, yet only by a day (20 versus 19 days). This was not statistically significant in either the unadjusted (p=0.17) or in the multivariate analysis (p=0.06). CONCLUSIONS: Diabetic patients admitted with fracture of the proximal femur did not demonstrate significantly poorer outcomes in terms of in-patient mortality and length of stay compared to non-diabetic patients.

Trans rectal ultra sound guided prostate biopsies: a single centre experience in Sri Lanka.

BACKGROUND: Trans rectal ultrasound guided prostate biopsy (TRUS) was introduced to Sri Lanka in 2002. OBJECTIVES: 1. To study clinicopathological features of males subjected to TRUS biopsy 2. To compare estimation of tumour burden by two methods in carcinoma prostate (CaP). METHODS: 749 symptomatic males subjected to TRUS biopsy over 64 months at a single centre. Information was retrieved from case records. Tumour burden in CaP was calculated as: 1. Calculated tumour burden (CTB)--total percentage tumour in each core/total number of cores 2. Percentage positive biopsy cores (PPBC)--number of positive cores/total number of cores X 100. SPSS 15.0, student's t test and Spearman's rank correlation coefficients were used for statistical analysis. RESULTS: 35.2% had CaP, microacinar in type. 34.88% were poorly differentiated. CaP was frequent among older patients (P<0.00001). The prostate volume in CaP was significantly lower than in the benign group (P<0.05). Prostate specific antigen (PSA) level was significantly higher in CaP (P<0.00001). A 99.6% sensitivity and 4.7% specificity was observed at PSA of 4 ng/ml for detecting CaP. Specificity was 98% at 25.5 ng/ml, with a sensitivity of 44.4%. CTB and PPBC had similar correlations with biochemical/histological parameters of CaP and were strongly correlated (0.786). INTERPRETATION: Males with CaP were older, had higher PSA levels and smaller prostates. A cut off level of PSA >4 ng/ml could be used for directing symptomatic patients for TRUS biopsy to detect CaP, keeping in mind that specificity is 98% only at 25.5 ng/ml. Both CTB and PPBC could be used to calculate tumour burden in TRUS with CaP.

Complications of a retrograde intubation in a trauma patient.

The authors report the case of an elder woman involved in a motor vehicle collision (MVC) requiring emergent intubation using the technique of retrograde intubation (RI). Since RI is a blind technique, potential complications arising from its use are numerous and may result in increased morbidity and mortality. Such was the case of this RI that involved incorrect placement of the endotracheal tube (ETT), resulting in suboptimal ventilation and increased morbidity. Additionally, this case illustrates how the failure to detect this error in multiple settings (ambulance, helicopter, emergency department) led to unnecessary and potentially deleterious procedures and significant delay in providing the basics of trauma care, oxygenation and ventilation. Although theoretical complications of RI have been addressed in the past, there have been very few published reports of actual complications. The emergency physician must be aware of difficult airways, options available to establish alternative airways, and methods to confirm appropriate placement of the ETT. The authors also discuss the indications, procedures, and complications involved in performing an RI.

Use of methylprednisolone as an adjunct in the management of patients with penetrating spinal cord injury: outcome analysis.

OBJECTIVE: Since the results of the Second National Acute Spinal Cord Injury Study were published in 1990, methylprednisolone has become a mainstay in the treatment of nonpenetrating spinal cord injury. Although potential significant relationships between the prompt administration of high-dose methylprednisolone after blunt spinal cord injury and outcome have recently been addressed, the relationship between the prompt administration of high-dose methylprednisolone after penetrating spinal cord injury and outcome remain unanswered. METHODS: To explore this relationship, we performed a retrospective nonrandomized study on a series of 252 patients with penetrating missile injuries to the spine who presented to our institution from March 1980 to July 1993. One hundred eighty-one patients (71%) were treated conventionally without adjunctive steroid therapy before 1990. Sixteen patients followed up during the 13-year study period received steroid protocols that were not consistent with the Second National Acute Spinal Cord Injury Study protocol and were excluded from the study. Since 1990, 55 patients (21%) were treated with intravenous methylprednisolone according to the Second National Acute Spinal Cord Injury Study protocol. All patients were subsequently transferred for rehabilitative care, and prospective evaluations of their neurological status were performed at admission and discharge. RESULTS: The study included 236 men and 16 women (mean age, 25.6 yr). The mean duration of stay for initial hospitalization was 94.6 days, and the mean duration of stay in rehabilitation was 78.6 days. Frankel scores were used to assess outcome (P < 0.05) and were assessed at admission and at the time of definitive discharge from the Spinal Cord Injury Care System. The hypothesis that methylprednisolone therapy significantly improves functional outcomes in patients with gunshot wound injuries to the spine was rejected. Only the total number of days in rehabilitation and the degree of neurological injury at admission contributed significantly to explaining outcome at discharge. CONCLUSION: The administration of methylprednisolone did not significantly improve functional outcomes in patients with gunshot wound injuries to the spine or increase the number of complications experienced by patients during their hospitalizations.