Emerging gene-based prognostic tools in early breast cancer: First steps to personalised medicine

Breast cancer remains a major cause of neoplastic disease in much of the developed world. The majority of cases are diagnosed with oestrogen receptor(ER)-positive and human epidermal growth factor receptor-2 negative invasive ductal carcinoma and are treated predominantly by surgery which includes sentinel node biopsy and adjuvant endocrine therapy ± adjuvant radiotherapy. It is believed that an indeterminate subset of the patient population is needlessly incurring chemotherapy related morbidity without attaining any increase in survival due to therapy. Furthermore in the era of extended adjuvant endocrine therapy it is important to identify those patients who can be safely treated with 5 years rather than 10 years of endocrine therapy thus optimising the benefit-risk balance. This perception has propelled the development of more personalised prognostic tools for newly diagnosed cases of ER-positive breast cancer. In this article, we shall review the evidence regarding the currently available gene assays for human breast cancer.

Management of critically ill patients with type 2 diabetes:The need for personalised therapy

Critical illness in patients with pre-existing diabetes frequently causes deterioration in glycaemic control.Despite the prevalence of diabetes in patients admitted to hospital and intensive care units,the ideal management of hyperglycaemia in these groups is uncertain.There are data that suggest that acute hyperglycaemia in critically ill patients without diabetes is associated with increased mortality and morbidity.Exogenous insulin to keep blood glucose concentrations < 10 mmol/L is accepted as standard of care in this group.However,preliminary data have recently been reported that suggest that chronic hyperglycaemia may result in conditioning,which protects these patients against damage mediated by acute hyperglycaemia.Furthermore,acute glucose-lowering to < 10 mmol/L in patients with diabetes with inadequate glycaemic control prior to their critical illness appears to have the capacity to cause harm.This review focuses on glycaemic control in critically ill patients with type 2 diabetes,the potential for harm from glucose-lowering and the rationale for personalised therapy.

An intensive and personalised care planning programme improves clinical outcomes in patients with diabetic retinopathy:a pilot randomised controlled trial

Background:Using a pilot randomised controlled trial(RCT),to assess the short-term effectiveness of a structured diabetic retinopathy(DR)-specific,intensive,and personalised care planning(DR-IPCP)intervention on diabetes control outcomes in Singaporeans with poorly controlled type 2 diabetes.Methods:Eighteen individuals with mild-moderate DR and poor glycemic control[HbA1c≥64 mmol/mol(≥8.0%)over two consecutive 6-month readings]were randomized to DR-IPCP(n=9)or usual care(UC,n=9).The intervention included a physician consultation,an initial personalised eye consultation with a experienced diabetes nurse educator,and three behaviour change follow-up calls.HbA1c(primary outcome),lipids and blood pressure were assessed at baseline and three months post-intervention.Participant feedback regarding the DR-IPCP program was collected at three months via a semi-structured telephone interview.Results:While no significant between-group differences were observed,DR-IPCP participants experienced significant within-group reductions in HbA1c,total cholesterol,and low density lipoprotein at follow-up compared to baseline[7 mmol/mol(−0.8%),−0.64 mmol/L,and−0.66 mmol/L,respectively].No significant within-group changes in these parameters were observed in the UC group.Following the DR-IPCP intervention,participants reported a clearer understanding of the link between diabetes management;the development and progression of DR.Conclusions:DR-IPCP provides an effective short-term improvement in diabetes control parameters in DR patients with poor diabetes control.An adequately powered and longitudinal RCT is warranted to assess the clinical,patient-centred and economic potential of this programme in this population.

Selective internal radiation therapy segmentectomy:A new minimally invasive curative option for primary liver malignancies?

Transarterial radioembolization or selective internal radiation therapy(SIRT)has emerged as a minimally invasive approach for the treatment of tumors.This percutaneous technique involves the local,intra-arterial delivery of radioactive microspheres directly into the tumor.Historically employed as a palliative measure for liver malignancies,SIRT has gained traction over the past decade as a potential curative option,mirroring the increasing role of radiation segmentectomy.The latest update of the BCLC hepatocellular carcinoma guidelines recognizes SIRT as an effective treatment modality comparable to other local ablative methods,particularly well-suited for patients where surgical resection or ablation is not feasible.Radiation segmentectomy is a more selective approach,aiming to deliver high-dose radiation to one to three specific hepatic segments,while minimizing damage to surrounding healthy tissue.Future research efforts in radiation segmentectomy should prioritize optimizing radiation dosimetry and refining the technique for super-selective administration of radiospheres within the designated hepatic segments.

Association of KRAS Gene and microRNA-124-3p in Sporadic Colorectal Tumours

Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.

Design and Application of 3D Printing Based Personalised Pelvic Prostheses

In this paper,we describe the design and surgical process of personalised pelvic prostheses fixation through 3D printing according to different Enneking pelvic tumour zones:the ilium(Zone I),acetabulum(Zone II),and pubis and ischium(Zone III).A 3D model of the pelvis was reconstructed using imaging data,and the parameters on the planes of the acetabulum and pelvic incisal margin were measured.The main body of the pelvic prosthesis was constructed,a porous structure was designed on the bone-prosthesis interface,and the movement paths,lengths,and diameters of screws were planned.By combining the pathological model and osteotomy guide,limb salvage reconstruction was performed in patients with pelvic tumours.Preoperative and postoperative data were compared to verify the prosthesis stability.Our investigation revealed that the long-term survival of pelvic reconstruction prostheses depends on accurate matching with the bone defect area,good initial stability,and a porous structure to allow bone ingrowth.

A mechanical study of personalised Ti6Al4V tibial fracture fixation plates with grooved surface by finite element analysis

Low shape matching and high stress shielding rates between bone plate and human bone are not conducive to the primary healing of fracture.In this study,taking the fracture site of the lower one‐third of human tibia as an application case,six types of personalised Ti6Al4V tibial plates with grooved surface were designed and evaluated by reverse en-gineering and finite element analysis.The results showed that the grooved design can reduce the stress shielding rate of bone plate and promote the facture healing.Among the six types of bone plates,the‘OUT-MI’bone plate has the lowest stress shielding rate and the most uniform stress distribution.Meanwhile,with the increasing tibial load during the convalescence,the average stress and maximum axial displacement of the tibial fracture surface increased,which can effectively improve the bone regeneration in the tibial fracture area.Moreover,there was no significant difference in four-point bending performance between the‘OUT-MI’bone plate and the‘STR-BE’bone plate,indicating that the mechanical properties of this bone plate were reliable.The results provide a theoretical basis for the design of fracture fixation plates on clinical treatment.

Biomechanical Analysis of Personalised 3D-Printed Clavicle Plates of Different Materials to Treat Midshaft Clavicle Fractures

This study was aimed at comparing the biomechanical performance of personalised 3D-printed clavicle plates of different materials to treat midshaft clavicle fractures with the finite element(FE)method.The FE model of a fractured clavicle with a personalised 3D-printed clavicle plate and screws was constructed.Three types of materials were simulated,including stainless steel,titanium alloy,and magnesium alloy.Two loading conditions(axial compression and inferior bending)were applied at the distal end of the clavicle to simulate arm abduction.Plate stiffness,peak stress,and bone strain at the clavicle fracture site were measured and compared.The stiffness of the stainless steel clavicle plate was significantly greater than that of the titanium alloy clavicle plate.The stiffness of the magnesium alloy clavicle plate was similar to that of the intact clavicle;peak stress of the magnesium alloy clavicle plate was the lowest;thus,it had less stress-shielding effects on bone formation.The magnesium alloy clavicle plate was more likely to form bone by distributing proper strain at the clavicle fracture site.According to the influence of different materials on the tensile strength,magnesium alloy clavicle plates might be preferred owing to their bionic stiffness in the treatment of patients with a low risk of falling.For patients who engage in contact sports,a titanium alloy clavicle plate might be more suitable.

Panoramic and Personalised Intelligent Healthcare Mode

Although the development of national conditions and the increase in health risk factors undoubtedly pose a huge challenge to China’s medical health and labour security system,these simultaneously promote the elevation and transformation of national healthcare consciousness.Given that the current disease diagnosis and treatment models hardly satisfy the growing demand for medical and health care in China,based on the theory of healthcare and basic laws of human physiological activities,and combined with the characteristics of the information society,this paper presents a panoramic and personalised intelligent healthcare mode that is aimed at improving and promoting individual health.The basic definition and conceptual model are provided,and its basic characteristics and specific connotations are elaborated in detail.Subsequently,an intelligent coordination model of daily time allocation and a dynamic optimisation model for healthcare programmes are proposed.The implementation of this mode is explicitly illustrated with a practical application case.It is expected that this study will provide new ideas for further healthcare research and development.

Challenges of bone tissue engineering in orthopaedic patients

Bone defects may impede normal biomechanics and the structural stability of bone as an organ. In many cases, the correction of bone defects requires extensive surgical intervention involving the use of bone-grafting techniques and other procedures in which healing is slow, there is a high risk of infection and considerable pain is provoked- with no guarantee of complete correction of the defect. Therefore, the search for surgical alternatives continues to present a major challenge in orthopaedic traumatology. The reamer-irrigator-aspirator(RIA) system, which was devised to avoid the problems that can arise with autograft harvesting from the iliac crest, consists of collecting the product of the femoral canal after reaming. The RIA technique improves osteogenic differentiation of mesenchymal stem cells, compared to bone marrow aspiration or cancellous bone harvesting from the iliac crest using a spoon. Another approach, the Masquelet technique, consists of reconstructing a long bone defect by means of an induced membrane grown onto an acrylic cement rod inserted to fill the defect; in a second surgical step, once the membrane is constituted, the cement rod is removed and cancellous autograft is used to fill the defect. Both in RIA and in the Masquelet technique, osteosynthesis is usually needed. Bone transportation by compression-distraction lengthening principles is commonly implemented for the treatment of large bone loss. However, complications are frequently encountered with these techniques. Among new techniques that have been proposed to address the problem of large bone loss, the application of stem cells in conjunction with tissue engineering techniques is very promising, as is the creation of personalised medicine(or precision medicine), in which molecular profiling technologies are used to tailor the therapeutic strategy, to ensure the right method is applied for the right person at the right time, after determining the predisposition to disease among the general population. All of the above techniques for addressing bone defects are discussed in this paper.

Objective Assessment in Continual Medical Education (CME) Medical Objective Assessment in System Control

Existing examinations in postgraduate education and continuing medical education (CME) are not perfect. Modern assessment does not reflect disadvantages of older responders, for whom more time for reply is needed. Specialists with wide clinical experience may choose more than one correct answer in alternative questions. Reduced ability to remember in older people restricts examination without additional sources of information. We offer an individualised system for testing doctors. It provides personalised choice of examination questions using multiple choice questions with weight characteristics and absence of distractors, interactive cooperation in case of negative answers and the final decision of an expert in relation to the person tested. A special algorithm is proposed for typical questions that combines the advantages of known approaches to testing. The questioning system is complex for the creators of tests, but is more convenient and objective than existing ones for medical doctors.

Antimicrobial stewardship and targeted therapies in the changing landscape of maternal sepsis

Pregnant and postnatal women are a high-risk population particularly prone to rapid progression to sepsis with significant morbidity and mortality worldwide.Moreover,severe maternal infections can have a serious detrimental impact on neonates with almost 1 million neonatal deaths annually attributed to maternal infection or sepsis.In this review we discuss the susceptibility of pregnant women and their specific physiological and immunological adaptations that contribute to their vulnerability to sepsis,the implications for the neonate,as well as the issues with antimicrobial stewardship and the challenges this poses when attempting to reach a balance between clinical care and urgent treatment.Finally,we review advancements in the development of pregnancy-specific diagnostic and therapeutic approaches and how these can be used to optimize the care of pregnant women and neonates.

Treatment recommendation and parameter estimation under single-index contrast function

In this article, we consider a semiparametric model for contrast function which is defined asthe conditional expected outcome difference under comparative treatments. The contrast function can be used to recommend treatment for better average outcomes. Existing approachesmodel the contrast function either parametrically or nonparametrically. We believe our approachimproves interpretability over the non-parametric approach while enhancing robustness overthe parametric approach. Without explicit estimation of the nonparametric part of our model,we show that a kernel-based method can identify the parametric part up to a multiplying constant. Such identification suffices for treatment recommendation. Our method is also extendedto high-dimensional settings. We study the asymptotics of the resulting estimation procedure inboth low- and high-dimensional cases. We also evaluate our method in simulation studies andreal data analyses.

Total Talar Replacement Using a Novel 3D-Printed Prosthesis for Recurrent Giant Cell Tumour of the Talus

In our case,3D printing was used to fabricate a custom-made titanium alloy total talar prosthesis as a mirror image of the contralateral healthy talus for a 16-year-old girl who underwent right talar resection for a recurrent giant cell tumour(GCT)of the talus.A porous surface was used over the neck and tail of the talus prosthesis to promote soft tissue attachment and improve the stability of the prosthesis.Pre-drilled medial and lateral holes were prepared for ligament repair and attachment.Eighteen months after the operation,there was no tumour recurrence,and the patient walked without symptoms.The Musculoskeletal Tumour Society score was 22/30,the American Orthopaedic Foot and Ankle Society score was 88/100,and the prosthesis was well positioned on radiographs.The short-and medium-term outcomes indicated that 3D-printed modular talar prostheses could be an effective treatment option.

Interpreting map usage patterns using geovisual analytics and spatiotemporal clustering

Extracting meaningful information from the growing quantity of spatial data is a challenge.The issues are particularly evident with spatio-temporal data describing movement.Such data typically corresponds to movement of humans,animals and machines in the physical environment.This article considers a special form of movement data generated through human–computer interactions with online web maps.As a user interacts with a web map using a mouse as a pointing tool,invisible trajectories are generated.By examining the spatial features on the map where the mouse cursor visits,a user’s interests and experience can be detected.To analyse this valuable information,we have developed a geovisual analysis tool which provides a rich insight into such user behaviour.The focus of this paper is on a clustering technique which we apply to mouse trajectories to group trajectories with similar behavioural properties.Our experiments reveal that it is possible to identify experienced and novice users of web mapping environments using an incremental clustering approach.The results can be used to provide personalised map interfaces to users and provide appropriate interventions for completing spatial tasks.