Exploring the Roles and Responsibilities of an Educational Supervisor in Medical Training Within the United Kingdom.

Medical trainees or junior doctors within the United Kingdom, regardless of their level of training or specialty, are assigned an educational supervisor (ES). The General Medical Council within the United Kingdom defines an ES as "a trainer who is selected and appropriately trained to be responsible for the overall supervision and management of a specified trainee's educational progress during a clinical placement or series of placements." This article critically evaluates the current literature to explore the roles of the ES in supporting and monitoring a trainee's progress while discussing challenges associated with the role. Through clearer delineation of the role of an ES, barriers to improving training can be identified and overcome, thus improving overall satisfaction with training.

Exploring the Role of Urocortin in Osteoporosis.

Osteoporosis is a debilitating disease that affects over 200 million people worldwide. Overactive osteoclast activity leads to micro-architectural defects and low bone mass. This culminates in fragility fractures, such as femoral neck fractures. Treatments currently available either are not completely effective or have considerable side effects; thus, there is a need for more effective treatments. The urocortin (Ucn) family, composed of urocortin 1 (Ucn1), urocortin 2 (Ucn2), urocortin 3 (Ucn3), corticotropin-releasing factor (CRF) and corticotropin-releasing factor-binding protein (CRF-BP), exerts a wide range of effects throughout the body. Ucn1 has been shown to inhibit murine osteoclast activity. This review article will aim to bridge the gap between existing knowledge of Ucn and whether it can affect human osteoclasts.

Value of Drains in Soft-Tissue Tumour Surgery: A Specialist Regional Centre Experience.

Background The mainstay of therapy in most soft-tissue tumours (STTs) is excision. However, this often results in blood/extracellular fluid collection within large dead spaces necessitating the use of surgical drains. Whether meticulous attention to haemostasis, careful closure of dead space, and use of compression bandage obviates the need for drains was investigated. This study aimed to compare postoperative outcomes in patients undergoing surgery for STTs with and without the use of drains. Methodology A retrospective analysis of patients undergoing STT surgery over five years was undertaken using a regional STT specialist service database. Patients were stratified into the following two groups: compression bandage alone (CB) versus compression bandage with drain (CBD). The chi-square test was used to examine associations with infection, seroma, and haematoma, while the unpaired t-test was used for associations with hospital stay and time to wound healing. The unpaired t-test with Bonferroni correction was used to account for tumour dimensions across both groups. Results A total of 81 CB and 25 CBD patients were included. The mean hospital stay was significantly lower in CB compared to CBD (4.9 days, SD = 8.574 vs. 9.8 days, SD = 7.647, p = 0.0125). None of the other variables was significantly different between the two groups, including infection (21.3% vs. 24.0%, p = 0.7804), seroma (25.0% vs. 36.0%, p = 0.2865), haematoma (0.026% vs. 2.0%, p = 0.2325), and time to wound healing (55.8 days, SD = 63.59 vs. 42.3 days, SD = 58.88, p = 0.3648). Conclusions Our findings suggest that the use of drains in patients undergoing STT tumour surgery lengthens hospital stay without reducing the incidence of postoperative complications/time to wound healing. A larger, prospective trial is needed.

Adult Stem Cells for Cartilage Regeneration.

As cartilage is an avascular, aneural structure, it has very low capabilities of self-repair. Osteoarthritis prevalence is increasing, and there are no clinically approved management techniques that can cure the degradation of cartilage. This report investigates the efficacy of different sources of cells to generate articular cartilage. Autologous chondrocyte implantation has been used to some extent in clinics; however it has not generated efficient, reliable results, and there is no evidence of long-term success. The usage of stem cells is more promising, particularly mesenchymal stem cells (MSCs). Human embryonic stem cells (hESCs) have also been trialed; however, it is important to note that the process of differentiation into chondrocytes is not fully understood, and the cartilage produced can often be of poor quality. MSCs seems to be the way forward, and hESCs will perhaps need further study with the usage of MSC differentiation methodology.

Surgical Fixation of Three- and Four-Part Proximal Humeral Fractures Using the Proximal Humeral Interlocking System Plate.

Introduction The management of proximal humeral fractures ranges greatly from conservative management to surgical treatment. For those fractures requiring surgical treatment, internal fixation is the primary method. The aim of internal fixation is to achieve rigid fracture fixation until union occurs, return of shoulder range of motion, and minimise intra-and postoperative complications. The aim of this study was to evaluate the results of the Proximal Humeral Interlocking System Plate (PHILOS) used for the treatment of three-and four-part proximal humeral fractures. Materials and methods This study included 30 patients with a mean age of 54 years (range 20-80 years). Results were checked post-operatively with standard radiographs and clinical evaluation according to the Constant-Murley shoulder score. All patients were followed up for 12 months. Results Union was achieved in all patients with a mean neck/shaft angle of 130° (range 108°-150°). The mean Constant-Murley score at the final follow-up was 82.28 (range 67-96) correlating with good results. No patients developed an intraoperative or postoperative vascular injury, wound complications, or avascular necrosis of the humeral head. Conclusion Our study has shown that the surgical treatment of three- and four-part proximal humeral fractures with the use of the PHILOS plate leads to a good functional outcome. It has also demonstrated the PHILOS plate and is an effective system for fracture stabilisation provided the correct surgical technique is used with awareness of potential hardware complications.

Is skipped nodal metastasis a phenomenon of cutaneous melanoma?

BACKGROUND AND METHODS: Skipped nodal metastasis (SNM) is a recognized phenomenon of visceral cancers when metastases bypass the regional basin and skip to a distant nodal basin without evidence of distant metastases. Its occurrence is undocumented in cutaneous melanoma patients but of potential prognostic significance. We therefore assessed the frequency of SNM in a large series of patients with limb melanomas. PATIENTS AND METHODS: We studied melanoma patients attending a tertiary oncology hospital in northwest England using two approaches. First, we systematically searched medical records of an unselected patient sample treated 2002-2015, and second, we studied lymphoscintigrams of all patients with limb melanoma who underwent sentinel node biopsy 2008-2019. RESULTS: Of 672 melanoma patients whose clinical records were examined, 16 had regional nodal metastases without apparent visceral spread and one appeared to have SNM but further scans were uncovered that showed concurrent pulmonary metastases. Of 667 limb melanoma patients with lymphoscintigrams, 7 showed dual lymphatic drainage patterns to distal as well as regional nodal basins, but none had micro-metastases solely in the distant basin. CONCLUSION: Occurrence of SNM in cutaneous melanoma is highly unlikely.

Multi-omics analyses identify HSD17B4 methylation-silencing as a predictive and response marker of HER2-positive breast cancer to HER2-directed therapy.

HER2-positive breast cancers that achieve pathological complete response (pCR) after HER2-directed therapy consistently have good survival. We previously identified HSD17B4 methylation as a marker for pCR by methylation screening. Here, we aimed to identify a new marker by conducting a multi-omics analysis of materials prepared by laser capture microdissection, and adding 71 new samples. In the screening set (n = 36), mutations, methylation, and expression were analyzed by targeted sequencing, Infinium 450 K, and expression microarray, respectively, and 15 genes were identified as differentially expressed and eight genomic regions as differentially methylated between cancer samples with and without pCR. In a validation set (n = 47), one gene showed differential expression, and one region had differential methylation. Further, in the re-validation set (n = 55), all new samples, only HSD17B4 methylation was significantly different. The HSD17B4 methylation was at the transcriptional start site of its major variant, and was associated with its silencing. HSD17B4 was highly expressed in the vast majority of human cancers, and its methylation was present only in breast cancers and one lymphoblastic leukemia cell line. A combination of estrogen receptor-negative status and HSD17B4 methylation showed a positive predictive value of 80.0%. During HER2-directed neoadjuvant therapy, HSD17B4 methylation was the most reliable marker to monitor response to the therapy. These results showed that HSD17B4 methylation is a candidate predictive and response marker of HER2-positive breast cancer to HER2-directed therapy.

Genetic and epigenetic profiling indicates the proximal tubule origin of renal cancers in end-stage renal disease.

End-stage renal disease (ESRD) patients on dialysis therapy have a higher incidence of renal cell carcinomas (RCCs), which consist of 2 major histopathological types: clear-cell RCCs (ESRD-ccRCCs) and acquired cystic disease (ACD)-associated RCCs. However, their genetic and epigenetic alterations are still poorly understood. Here, we investigated somatic mutations, copy number alterations (CNAs), and DNA methylation profiles in 9 ESRD-ccRCCs and 7 ACD-associated RCCs to identify their molecular alterations and cellular origins. Targeted sequencing of 409 cancer-related genes, including VHL, PBRM1, SETD2, BAP1, KDM5C, MET, KMT2C (MLL3), and TP53, showed ESRD-ccRCCs harbored frequent VHL mutations, while ACD-associated RCCs did not. CNA analysis showed that ESRD-ccRCCs had a frequent loss of chromosome 3p while ACD-associated RCCs had a gain of chromosome 16. Beadarray methylation analysis showed that ESRD-ccRCCs had methylation profiles similar to those of sporadic ccRCCs, while ACD-associated RCCs had profiles similar to those of papillary RCCs. Expression analysis of genes whose expression levels are characteristic to individual segments of a nephron showed that ESRD-ccRCCs and ACD-associated RCCs had high expression of proximal tubule cell marker genes, while chromophobe RCCs had high expression of distal tubule cell/collecting duct cell marker genes. In conclusion, ESRD-ccRCCs and ACD-associated RCCs had mutation and methylation profiles similar to those of sporadic ccRCCs and papillary RCCs, respectively, and these 2 histopathological types of RCCs were indicated to have originated from proximal tubule cells of the nephron.

Effect of Concomitant Atrial Fibrillation on In-Hospital Outcomes of Non-ST-Elevation-Acute Coronary Syndrome-Related Hospitalizations in the United States.

Atrial fibrillation (AF) is the most common arrhythmia in patients presenting with acute coronary syndrome (ACS). The present study examined the rates and trends of clinical outcomes and management strategies of non-ST-elevation ACS (NSTE-ACS) related hospitalizations in the United States, in patients with concomitant AF compared with those in sinus rhythm (SR). We analyzed the "Nationwide Inpatient Sample" database (2004 to 2014) for patients with a primary discharge diagnosis of NSTE-ACS, and further stratified the cohort on the basis of diagnoses into SR and AF groups. Multivariate analysis was performed to examine the association between AF and major adverse cardiovascular and cerebrovascular events (composite of mortality, stroke, and cardiac complications) and its components. Of 4,668,737 NSTE-ACS hospitalizations, the proportions of SR and AF groups were 82.4% (3,848,202) and 17.6% (820,535), respectively. The incidence of AF increased significantly over time from 16.5% (2004) to 19.3% (2014). The AF group was at a greater risk of adverse outcomes with higher rates and adjusted relative risk (RR) of major adverse cardiovascular and cerebrovascular events (12.9% vs 5.3%; RR 1.74 [1.72, 1.75]), mortality (6.5% vs 3.3%; RR 1.12 [1.11, 1.13]), stroke (2.7% vs 1.5%; RR 1.32 [1.30, 1.34]), and bleeding (14.7% vs 8.8%; RR 1.42 [1.41, 1.43]). Furthermore, the AF group was less likely to receive coronary angiography (47.1% vs 58%) and percutaneous coronary intervention (18.7% vs 32.6%) in comparison to SR (p <0.001 for all outcomes). In conclusion, patients with concomitant AF and NSTE-ACS are less likely to be offered an invasive management strategy for their ACS and are associated with worse complications and higher mortality.

Clinic and ambulatory heart rates in patients with ischaemic heart disease and/or chronic heart failure taking rate-limiting medications: are they interchangeable?

BACKGROUND: The prognostic benefit from heart rate (HR) reduction in patients with ischaemic heart disease (IHD) and/or chronic heart failure (CHF) is now firmly established. Most decisions regarding initiation and/or dose adjustment of HR-limiting medications in such patients are based on clinic HR. Yet, this is a highly variable parameter that may not necessarily reflect HR control over the 24 h period. OBJECTIVE: To examine the level of agreement between mean clinic and mean ambulatory HRs in patients with IHD and/or CHF taking rate-limiting medications. METHODS: Prospective, observational study. Fifty patients with IHD and/or CHF who attended cardiology outpatient clinics at the Manchester Heart Centre and underwent same-day 24 h continuous ECG recording between March and October 2013 were included in the study. Mean clinic HR was compared with mean 24 h, daytime and night-time HRs. Limits-of-agreement plots were constructed to examine the relationship between the two HR measures in more detail. RESULTS: The mean clinic HR was numerically similar to the mean HRs of all ambulatory time periods examined. However, on Bland-Altman plots, the limits of agreement between clinic and ambulatory HR means were quite wide, with the mean clinic HR ranging between 10.93 and 13.58 bpm below and 8.4 and 18.15 bpm above the mean ambulatory HR. CONCLUSIONS: Although numerically similar, the means of clinic and ambulatory HRs in patients with IHD and/or CHF display wide limits of agreement. As such, the two measures cannot be regarded as interchangeable.