Correction to: Understanding and using AlloSure donor derived cell-free DNA.

An erratum to this paper has been published: https://doi.org/10.1007/s12551-020-00763-9 .

Understanding and using AlloSure donor derived cell-free DNA.

Renal transplant is a lifesaving and cost-effective intervention for patients with End Stage Renal Failure. Yet it is often regarded as replacement therapy rather than a cure given the overall failure rate over time. With a shortage of organs, this global issue has been further compounded by increased incidences of obesity, hypertension and diabetes, such that the disease burden and need for transplantation continues to increase. Considering the lifetime of immunosupression in transplant patients, there will also be significant associated co-morbidities By leveraging the advances in innovation in Next Generation Sequencing, the field of transplant can now monitor patients with an optimized surveillance schedule, and change the care paradigm in the post-transplant landscape. Notably, low grade inflammation is an independent risk for mortality across different disease states. In transplantation, sub-clinical inflammation enhances acute and chronic rejection, as well as accelerates pathologies that leads to graft loss. Cell free DNA has been shown to be increased in inflammatory processes as we all as provide an independent predictor of all-cause mortality. This review considers the utility of AlloSure, a donor derived cell free DNA molecular surveillance tool, which has shown new clinical insights on how best to manage renal transplant patients, and how to improve patient outcomes.

The rise and potential fall of pancreas transplantation.

BACKGROUND: The aim of this review is to bring pancreatic transplantation out of the specialist realm, informing practitioners about this important procedure, so that they feel better equipped to refer suitable patients for transplantation and manage, counsel and support when encountering them within their own speciality. SOURCES OF DATA: Narrative review conducted in May 2017. OVID interface searching EMBASE and MEDLINE databases, using Timeframe: Inception to June 1, 2017. Articles were assessed for clinical relevance and most up to date content with articles written in english as the only inclusion criteria. Other sources, used included conference proceedings/presentations, unpublished data from our institution (Oxford Transplant Centre). AREAS OF AGREEMENT: Pancreas transplantation has evolved from an experimental procedure to the gold standard of care for patients with type 1 diabetes and uraemia. Currently, it remains the most effective method of establishing and maintaining euglycemia over the longer term, halting and potentially reversing many of the secondary complications associated with diabetes. Significant improvements to quality of life and better life expectancy make it in the longer term, a lifesaving procedure compared to waiting candidates. AREAS OF CONTROVERSY: The future of solid organ pancreas transplantation remains uncertain, with extensive comorbidity and advances in alternative therapies makes the long-term growth of the procedure questionable. GROWING POINTS AND AREAS TIMELY FOR DEVELOPING RESEARCH: Therapies to alleviate problems associated with ischaemia reperfusion injury, graft pancreatitis and more effective monitoring methods for detecting and treating organ rejection are the key areas of growth.

Significance of steatosis in pancreatic transplantation.

The on-going success of whole organ pancreatic transplantation is dependent on overcoming the imbalance between demand and supply of optimal organs as well as tackling the vast comorbidity associated with the procedure. Pancreas steatosis is a common contributing factor to the problem and with obesity pandemics affecting the global population; the size and type of organs received from donors will only make steatosis more of an issue. The aim of this review is to highlight what is known about steatosis in the context of pancreas transplantation identifying potential methods to help its evaluation. Narrative review of literature from inception to June 2017, using OVID interface searching EMBASE and MEDLINE databases as well recent transplant conference data. All studies related to pancreas steatosis examined for clinical relevance with no exclusion criteria. Key ideas extracted and referenced. Pancreatic steatosis is not innocuous and is precariously regarded by transplant surgeons, however its associations with obesity, metabolic syndrome and long list of associated complications clearly show it needs more careful consideration. Radiologic and surgical advances now allow assessment of the fat content of organs, which could be used to quantify organs allowing better optimisation, but there is still much work to be done to refine the optimal method to achieve this.

The use of kinase inhibitors in solid organ transplantation.

INTRODUCTION: Despite the efficacy of current immunosuppression regimes used in solid organ transplantation, graft dysfunction, graft lost and antibody-mediated rejection continue to be problematic. As a result, clear attraction in exploiting key potential targets controlled by kinase phosphorylation has led to a number of studies exploring the use of these drugs in transplantation. Aim In this review, we consider the role of tyrosine kinase as a target in transplantation and summarize the relevant studies on kinase inhibitors that have been reported to date. METHODS: Narrative review of literature from inception to December 2016, using OVID interface searching EMBASE and MEDLINE databases. All studies related to kinase based immunosuppression were examined for clinical relevance with no exclusion criteria. Key ideas were extracted and referenced. CONCLUSION: The higher incidence of infections when using kinase inhibitors is an important consideration, however the number and range inhibitors and their clinical indications are likely to expand, but their exact role in transplantation is yet to be determined.

Renal donors with prostate cancer, no longer a reason to decline.

OBJECTIVE: To fully assess the true risk of prostate cancer transmission in during renal transplantation. METHODS: A full review of all existing literature relevant to the topic. RESULTS: There has not been a single documented case of transmission of prostate cancer during renal transplant. Prostate cancer in deceased organ donors has an incidence estimated between 3% and 18.5% and over 100 transplants have been performed using organs from donor with proven prostate cancer without issue. CONCLUSION: Transmission of prostate cancer through kidney transplantation seems very unlikely. The risks of remaining on the waiting list are outweighed by a transmission risk and the potential benefit makes the case to have clear guidelines about donor prostate malignancy when accepting potential organs.

The role of laparoscopic surgery in the management of a malfunctioning peritoneal catheter.

INTRODUCTION: Peritoneal catheter malfunction is a common complication of peritoneal dialysis (PD). It has a high failure rate with conservative management. Catheter replacement was historically the standard surgical treatment of choice. Nowadays, laparoscopy has been introduced as an alternative surgical modality to rescue the malfunctioning peritoneal catheter and also offers the possibility of replacement if indicated. The aim of this study was to compare the outcomes of these two surgical modalities. METHODS: The medical records of consecutive patients who underwent surgical treatment for malfunctioning PD catheters (between January 2010 and April 2013) were analysed. The primary outcome included successful return to adequate PD. The secondary endpoint was length of catheter patency and the cause of catheter failure. RESULTS: A total of 32 cases were identified, of which 8 had open catheter replacement and 24 had a laparoscopic intervention. The overall median follow-up duration was 12.5 months. The success rate for laparoscopic surgery in terms of functioning catheter at 12 months was 62.5% but only 37.5% for open surgery. The mean length of catheter patency after laparoscopic intervention was 31.6 months compared with only 13.6 months for the open surgery group. The most common cause of catheter failure diagnosed during laparoscopic intervention was catheter migration (33.0%), followed by omental wrap and catheter blockage by fibrin/blood plug (25.0% each). Open surgery did not have any diagnostic potential. CONCLUSIONS: Laparoscopy is the treatment of choice for malfunctioning PD. Its proven benefit includes simultaneous identification of the aetiological cause of malfunction together with direct correction of this problem, thereby maximising outcome. It also allows for rapid recommencement of PD and avoidance of haemodialysis, saving cost and resources.

Recurrent limb pain and migraine: case reports and a clinical review.

Recurrent limb pain (RLP) is a well-known entity in childhood. It is considered a precursor of migraine. The temporal relationship of RLP with headache in childhood is lacking in the literature. However, there are many cases with limb pain in a close temporal relationship with migraine headache in adults. We report six female patients with RLP and migraine and delineate the temporal relationship between the two. Three patients had a history of RLP in childhood and developed migraine headache after many years. Conversely, two patients had a long history of migraine headache and later developed RLP. One patient developed RLP and migraine headache at the same age. Isolated limb pain was frequent in all six patients. It was mild to severe, for a few minutes to a few days, and predominantly located in the upper extremities. Only one patient reported allodynia. The patients showed response to preventive measures (all six patients) and abortive therapies (four patients), even in those attacks of RLP that were not associated with headache episodes. We also review the clinical profiles of the patients in whom RLP and migraine were related to each other, and speculate on the possible mechanisms for RLP in the patients with migraine.

Proteolysis in the myelopathy of acquired immunodeficiency syndrome: preferential loss of the C-8 component of myelin basic protein.

Many patients with AIDS have a myelopathy characterized by vacuolization of spinal cord white matter. The biochemical and molecular changes underlying this myelin disturbance have not yet been characterized. Myelin basic protein (MBP) is potentially important because it is a key structural protein of myelin with roles in compaction and stabilization. In the present study, we describe the steady-state protein concentration of MBP in 46 patients with AIDS and 12 control subjects at autopsy. Patients with myelopathy exhibited no change in the abundance of the predominant 18.5- and 17.2-kd isoforms, but a 14-kd MBP-immunoreactive degradation fragment was increased significantly. MBP degradation correlated significantly with the severity of histopathologic changes, including neutral lipid deposition, the density of vacuolated fibers, and the number of ferritin-stained activated microglia. Alkaline gel electrophoresis of isolated MBP showed preferential loss of the least cationic isomer (C-8). The concentration of MBP RNA in slot blots was normal in cords exhibiting myelopathy, and the ratio of mRNA corresponding to the 18.5- and 17.2-kd MBP isoforms, measured using reverse transcriptase-PCR, was not altered. This study suggests that mononuclear phagocyte-mediated degradation of MBP may play a role in AIDS myelopathy, and the preferential loss of the C-8 component of MBP may have mechanistic implications.

Expansion of the cerebral ventricles and correlation with acquired immunodeficiency syndrome neuropathology in 232 patients.

BACKGROUND: Expansion of the cerebral ventricles is highly prevalent in patients with the acquired immunodeficiency syndrome (AIDS). The mechanism remains unclear. The purpose of this study was to correlate the volume of the cerebral ventricles with histopathologic abnormalities in the brain. METHODS: At autopsy, the volume of the cerebral ventricles in brain slices was estimated planimetrically in 232 patients with AIDS and 77 age-appropriate controls. Estimated volumes were compared with the neuropathologic results using multiple regression analysis. RESULTS: Multiple regression analysis demonstrated a significant relationship between ventricular volume and cerebral cytomegalovirus infection (P < .0004). When human immunodeficiency virus (HIV) encephalitis with multinucleated cells was present, median volume did not differ significantly from other subjects with AIDS. In 11 patients who had HIV-1 proviral DNA detected using the polymerase chain reaction, average volume was not different from 22 patients who tested negatively using polymerase chain reaction. Ventricular expansion did not have a clear-cut neuropathologic substrate in many instances. CONCLUSIONS: In some subjects with AIDS, cytomegalovirus encephalitis was the underlying neuropathologic lesion associated with ventricular expansion. Key indicators of brain HIV-1 infection were related either weakly or not at all, and the role of HIV-1 remains uncertain in most cases.

The solitary pulmonary nodule. Is it malignant or benign?

Solitary pulmonary nodules are usually identified on routine chest radiographs in asymptomatic patients. Most nodules have a benign cause, but bronchogenic carcinoma, metastases, and other malignant processes are important causes as well and must be excluded in differential diagnosis. Plain chest radiography, computed tomography, and fine-needle aspiration biopsy are useful diagnostic tools. When a malignant cause cannot be ruled out, the patient's age, smoking history, and nodule size must be considered. Observation by serial radiographs may be the appropriate course for patients who are at low risk for malignancy. For moderate- and high-risk patients, an immediate and more invasive workup is indicated.

The application of a comprehensive visual screening programme to children aged 3-5 years. Can a modified procedure be devised for visual screening by ancillary staff?

Current commercially available tests to examine visual performance in children are discussed and adapted for a visual screening programme applied to 249 children aged 3-5 years at school or playgroup premises. Correlation of refractive and ocular muscle findings with the remaining tests is evaluated. A simplified screening procedure is thereby recommended which may be undertaken by ancillary staff, without any need for sophisticated equipment. This would enable identification, for further examination, of most children whose refraction and eye coordination are outside normal limits.

Stereoscopic threshold in children and adults.

The threshold of stereoacuity is reported as measured on 369 normal children aged 3 to 7 years, and on 51 normal adults. Four standard clinical stereotests were used and two different testing procedures adopted. The results show that both threshold and variability decrease with age, and performance becomes adult-like at different ages for different tests. Interest correlations are poor, and in cases where the correlation is significant, no identifiable pattern emerges between testing procedures, age, and stereotests. The procedures themselves gave no significant difference in stereoacuity values between all four tests.

Ureteral seminal vesicle anomaly. Gross hematuria as presenting symptom.

An ectopic ureter ending in a seminal vesicle and associated with renal agenesis is a rare occurrence. There are no reports of this anomaly occurring with gross, total, painless hematuria as presenting symptom. Sonography and catheterization of the ejaculatory duct were the most helpful diagnostic studies used to demonstrate the abnormality. Surprisingly, on pathologic examination, the cystic area was not seminal vesicle but a dilated hemorrhagic ureter.

Surgical management of infected Thomas shunts.

Infected Thomas shunts pose a problem for the surgeon treating end-stage renal failure patients. Complete removal of the prosthesis with ligation of the femoral vessels may jeopardize the limb. Removal of the shunt without the Dacron patch usually will not eradicate the infection. The present article describes a two-stage approach in six patients with arterial bypass of the infected area and complete removal of the prosthesis. There were no postoperative complications. Arterial circulation was maintained, and all operative sites healed completely.