The role of Vesalius and his contemporaries in the transfiguration of human anatomical science.

The understanding of human anatomy has been an endeavour spanning thousands of years from the Egyptians and Greeks in antiquity to the present day. Scholars and scientists have overcome great barriers to discover the inner workings and complexities of the human body, from personal challenges and prejudices to obstacles placed by society. Our present understanding of anatomy has accumulated over centuries, and progressive generations of physicians have contributed to the ever-growing evidence-based knowledge. This article explores the contributions made by Vesalius and his contemporaries in the first half of the sixteenth century. These enlightened scholars advanced anatomical knowledge and, perhaps more importantly, the scientific method, directly impacting the mindset and methodologies of future anatomists. Individuals such as Berengario da Carpi and Gabriele Falloppio produced bodies of work during their lifetime that were not only important in disputing the teachings of Galen of Pergamon, which had been accepted as almost unquestionable truths for a thousand years, but also instrumental in developing a new generation of scientists. The anatomists of the late renaissance were unable to resolve many of the factual inaccuracies of Galenic teaching but provided the groundwork for scientific thinking which future generations of anatomists benefited greatly from. The principles of documenting what is observed and establishing a methodical approach to question discrepancies in experiments would go on to influence physicians such as Harvey and Malpighi to investigate and draw correct conclusions in their research and ultimately advance our understanding of human anatomy to what it is today.

Regular endoscopic surveillance and polypectomy is effective in managing rectal adenoma progression following colectomy and ileorectal anastomosis in patients with familial adenomatous polyposis.

AIM: Total colectomy with ileorectal anastomosis (TC-IRA) is a surgical option for patients with familial adenomatous polyposis (FAP). Regular endoscopic surveillance of the rectum is recommended to prevent rectal cancer. We aimed to document polyp progression in the rectum following TC-IRA and evaluate the role of polypectomy during surveillance. METHOD: Patients with FAP who underwent TC-IRA between 1990 and 2017 were identified. Demographic, endoscopic and genetic data were retrieved. Cumulative rectal adenoma (polyp) counts were obtained, whilst accounting for any polypectomies during the study period. The rate of polyp progression and factors influencing secondary proctectomy were evaluated. RESULTS: One hundred and ninety-nine patients fulfilled our inclusion criteria, of which 44% were male. The median age at colectomy was 19 (range 11-70) years and median preoperative rectal polyp count was 7 (range 0-50). All patients had an APC pathogenic variant, of which 151 (79%) were 5' of the mutation cluster region (MCR), 19 (10%) in the MCR, six (3%) were 3' of the MCR and 15 (8%) had a gross deletion. After a median follow-up of 8.6 (range1-27) years and a median of 11 (range 2-37) flexible sigmoidoscopies per patient, the median rate of polyp progression was 5.5 polyps/year (range 0-70.2). There was no evidence of polyp regression. Eight (4%) patients underwent secondary proctectomy for neoplasia, of which one (0.5%) had rectal adenocarcinoma. A total of 13,527 polyps were removed, a median of 35 polyps/patient (range 0-829). The rate of polyp progression was not significantly associated with genotypic or phenotypic factors. CONCLUSION: Progression of rectal adenoma burden following TC-IRA appears to be slow and dependent on the length of follow-up. In the modern era of stringent endoscopic surveillance and therapeutic procedures such as cold snare polypectomy, the rate of secondary proctectomy and the risk of rectal cancer after TC-IRA are very low. These findings are important when counselling patients with regard to the choice of surgery for FAP and implementing endoscopic surveillance.

Polyp Progression in Paediatric Patients With Familial Adenomatous Polyposis: A Single-centre Experience.

OBJECTIVES: Prophylactic colectomy at a premalignant stage is the cornerstone of management of familial adenomatous polyposis (FAP). Before surgery, colonoscopy surveillance is recommended in children with FAP. This study aimed to examine the natural history of FAP in children by evaluating adenoma progression and factors influencing timing of colectomy. METHOD: Patients with FAP younger than 18 years at first surveillance colonoscopy and who had undergone more than 1 colonoscopy were identified. Demographic, endoscopic, genetic, and surgical data were retrieved. Cumulative adenoma (polyp) counts were obtained while accounting for any polypectomies during the study period. The rate of polyp progression and factors influencing the timing of colectomy were evaluated. RESULTS: Eighty-four patients (50% boys; mean age at first colonoscopy 13 years [standard deviation 1.97]) were identified, of which 83 had a family history of FAP. At first colonoscopy, 67 (79%) had <100 adenomas and 29 (35%) had colonic polyps identified despite rectal sparing. The median rate of polyp progression per patient was 12.5 polyps/year (range 0-145). Of the 45 (54%) patients who had undergone surgery, 41 (91%) underwent colectomy with ileorectal or ileodistal sigmoid anastomosis. Polyp progression did not alter the choice of surgical intervention in any patient. CONCLUSION: Our results suggest that adenoma number remains relatively stable in the majority of children under surveillance. Tailored surveillance intervals according to phenotype are a more appropriate strategy as recommended by recently published guidelines.

Gene Mutations in Cushing's Syndrome.

Background: Prolonged exposure to glucocorticoids can result in the development of Cushing's syndrome. Excess serum cortisol can occur due to several factors including exogenous steroids, pituitary and adrenal adenoma, and ectopic ACTH secretion. Summary: The last 2 decades have seen significant progress in identifying new genetic and molecular mechanisms underlying hypercortisolemia. This has implicated mutations seen in a multitude of aberrant pathways that underpin the pathophysiology of Cushing's syndrome. Key Messages: There is much overlap between the different, with mutations affecting well-understood molecular pathways such as the cAMP/PKA/MAPK and Wnt signalling systems. Further work should delineate the exact involvement of specific mutations in Cushing's syndrome and the effect of epigenetic/microenvironmental interactions. This could have implications for screening, as the identification of specific mutations may lead to earlier identification and subsequently improved prognosis.

Renal transplantation in gigantism: A case report.

BACKGROUND: Gigantism, characterized by excessive growth and height is due to increased secretion of growth hormone, most commonly from a pituitary adenoma. In addition to the surgical and anesthetic complexity, the extreme stature of these patients presents a unique challenge for kidney transplantation in deciding whether to proceed with a single or dual kidney transplantation. The lack of relevant literature further adds to the dilemma. CASE SUMMARY: A 45-year-old patient with untreated gigantism and end stage renal failure on renal replacement therapy was waitlisted for a deceased donor dual kidney transplantation due to the extreme physical stature (Height-247 cm and weight-200 kg). He was offered 2 kidneys from a 1-0-1 HLA mismatched 24-year-old DCD donor (Height-179 cm and weight-75 kg), and was planned for a bilateral retroperitoneal implantation into the recipient external iliac vessels. The immunosuppression consisted of alemtuzumab induction (50 mg) and steroid-free maintenance with tacrolimus. The donor's right kidney was uneventfully implanted extra-peritoneally into the right external iliac vessels. On contralateral exposure, the left common and external iliac arteries were ectatic and frail. A complex vascular reconstruction was not preferred in order to preserve the arterial supply to the left lower limb, to minimise the cold ischemia time and prevent additional warm ischemic insult to the second kidney. Hence, it was decided not to proceed with dual transplantation. Amidst concerns of nephron mass insufficiency, the graft function was remarkable with a serum creatinine of 120 µmol/L within a month from transplantation and 94 µmol/L at 1-year post transplantation, and without proteinuria. CONCLUSION: To our knowledge, this is the first case report on kidney transplantation in gigantism. Although it is believed that dual kidney transplantation is ideal, a single kidney transplantation from an appropriately selected donor can provide sufficient functioning nephron mass in patients with gigantism.

Evaluating the effectiveness of anti-Nogo treatment in spinal cord injuries.

As humans, we cannot regenerate axons within the central nervous system (CNS), therefore, making any damage to it permanent. This leads to the loss of sensory and motor function below the site of injury and can be crippling to a person's health. Spontaneous recovery can occur from plastic changes, but it is minimal. The absence of regeneration is due to the inhibitory environment of the CNS as well as the inherent inability of CNS axons to form growth cones. Amongst many factors, one of the major inhibitory signals of the CNS environment is the myelin-associated Nogo pathway. Nogo-A, Nogo-B and Nogo-C (Nogo), stimulate the Nogo receptor, inhibiting neurite outgrowth by causing growth cones to collapse through activation of Rho Kinase (ROCK). Antibodies can be used to target this signalling pathway by binding to Nogo and thus promote the outgrowth of neuronal axons in the CNS. This use of anti-Nogo antibodies has been shown to upregulate CNS regeneration as well as drastically improve sensory and motor function in both rats and primates when coupled with adequate training. Here, we evaluate whether the experimental success of anti-Nogo at improving CNS regeneration can be carried over into the clinical setting to treat spinal cord injuries (SCI) and their symptoms successfully. Furthermore, we also discuss potential methods to improve the current treatment and any developmental obstacles.

Why Have Immunization Efforts in Pakistan Failed to Achieve Global Standards of Vaccination Uptake and Infectious Disease Control?

Immunization is one of the most successful public health initiatives in recent times. It is, therefore, worrying to learn the level of under-vaccination in Pakistan. Diseases that have been successfully eliminated through the aid of vaccination in other countries have not been eliminated in Pakistan. The reasons for this vary and show the uniqueness of the economic, healthcare and environmental landscape of Pakistan, through which public health programmes need to be implemented. The "Expanded Programme of Immunization" (EPI) is the main programme through which routine immunization is provided to the public. Within Pakistan, it has encountered many problems since its inception. This includes logistical obstacles, inefficient health worker attitudes, parental and female awareness, and education, the influence of religious community leaders and the complications that accompany conflict. When compared to globally standardised targets for immunization, Pakistan is trailing behind. Not achieving these targets is worrying from both a global perspective and within the national healthcare landscape of Pakistan. Research is necessary to bring together findings on the failings of routine immunization and polio campaigns; there are many intersecting factors that global health bodies and the Department of Health in Pakistan must address in order to relieve the burden of vaccine-preventable diseases (VPDs).

Challenges In Widening Participation Outreach: Is Enough Being Done To Tackle The Under-Representation Of Low-Income Students In Medicine?

Widening Participation (WP) in medicine refers to all theory, activities and policy concerned with removing barriers to entering medical school for students from lower income and under-represented backgrounds. Medical schools and other institutions including; the Medical Schools Council, the Office for Fair Access, the Higher Education Funding Council for England, have been committed to improving Widening Participation for more than a decade. As senior medical students and academics, we have been actively involved with WP work at our respective medical schools and in conjunction with the British Medical Association (BMA) and the Medical Schools Council (MSC). Yet, we have observed over the years that the pace of change seems sometimes stuttering and stagnated. Here, we have investigated the reasons why there is still such a significant under-representation of students from lower income backgrounds in medicine. In order to make the medical student intake representative of the general population, the number of applications from lower income students would need to increase five-fold. This would require a great scaling up of WP outreach work. Critical analysis demonstrates that medical schools and the other key institutions in medical education have made many nominal commitments to WP, but have yet to make any commitments that are truly binding. This may be due to the institutions lack of belief in their own capacity to scale up WP Outreach sufficiently to achieve success. Ultimately binding commitments will be needed to secure a representative intake of medical students. In order for institutions to be willing to move towards such commitments, evidence-based success in WP must first be demonstrated through collaboration on specific projects that are scalable, sustainable and impactful.