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In this article the author shares her experience of being trained to perform percutaneous dialysis (PD) catheter insertions under local anaesthetic. She discusses about her training, criteria for PD catheter insertion and complications associated with it. She mentions that Nurse-performed peritoneal dialysis (PD) catheter insertion allows a complete nurse-led service and reduces the need for in-patient stay promoting more responsive and timely access. She also states that the patient feedback has been delighting since the patients enjoy the continuity of having the same practitioner from assessment to discharge and have complete confidence in them.

When a patient on peritoneal dialysis (PD) presents with suspected PD-related peritonitis (e.g. cloudy PD fluid and abdominal pain), one of the most important initial aspects of management is for the nephrology nurse/home dialysis nurse to collect PD effluent specimens for white blood cells count, Gram stain, culture and sensitivity for inspection and to send for laboratory testing before antibiotics are started. A review by seven members of the International Society for Peritoneal Dialysis (ISPD) Nursing Committee of all 133 questions posted to the ISPD website 'Questions about PD' over the last 4 years (January 2018-December 2021), revealed 97 posted by nephrology nurses from around the world. Of these 97 questions, 10 were noted to be related to best practices for PD effluent specimen collection. For our review, we focused on these 10 questions along with their responses by the members of the ISPD 'Ask The Experts Team', whereby existing best practice recommendations were considered, if available, relevant literature was cited and differences in international practice discussed. We revised the original responses for clarity and updated the references. We found that these 10 questions were quite varied but could be organised into four categories: how to collect PD effluent safely; how to proceed with PD effluent collection; how to collect PD effluent for assessment; and how to proceed with follow-up PD effluent collection after intraperitoneal antibiotics have been started. In general, we found that there was limited evidence in the PD literature to answer several of these 10 questions posted to the ISPD website 'Questions about PD' by nephrology nurses from around the world on this important clinical topic of best practices for PD effluent specimen collection. Some of these questions were also not addressed in the latest ISPD Peritonitis Guidelines. Moreover, when polling members of our ISPD Nursing Committee we found when answering a few of these questions, nursing practice varied within and among countries. We encourage PD nurses to conduct their own research on this important topic, focusing on areas where research evidence is lacking., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Precision medicine can significantly improve outcomes for patients with cancer, but implementation requires comprehensive characterization of tumor cells to identify therapeutically exploitable vulnerabilities. Here, we describe somatic biallelic TET2 mutations in an elderly patient with acute myeloid leukemia (AML) that was chemoresistant to anthracycline and cytarabine but acutely sensitive to 5'-azacitidine (5'-Aza) hypomethylating monotherapy, resulting in long-term morphological remission. Given the role of TET2 as a regulator of genomic methylation, we hypothesized that mutant TET2 allele dosage affects response to 5'-Aza. Using an isogenic cell model system and an orthotopic mouse xenograft, we demonstrate that biallelic TET2 mutations confer sensitivity to 5'-Aza compared with cells with monoallelic mutations. Our data argue in favor of using hypomethylating agents for chemoresistant disease or as first-line therapy in patients with biallelic TET2-mutated AML and demonstrate the importance of considering mutant allele dosage in the implementation of precision medicine for patients with cancer.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic in 2020, high rates of acute kidney injury (AKI) in critically unwell patients are being reported, leading to an increased demand for renal replacement therapy (RRT). Providing RRT for this large number of patients is proving challenging, and so alternatives to continuous renal replacement therapies (CRRT) in the intensive care unit (ICU) are needed. Peritoneal dialysis (PD) can be initiated immediately after percutaneous insertion of the catheter, but there are concerns about impact on ventilation and RRT efficacy. We sought to describe our recent experience with percutaneous catheter insertion and peritoneal dialysis in patients in the ICU with COVID-19 infection., Method: Patients were selected according to local protocol, and catheters were inserted percutaneously by experienced operators using a Seldinger technique. Sequential Organ Failure Assessment (SOFA) score and ventilation requirements were recorded at the time of insertion and 24 hours later. Procedural complications, proportion of RRT provided by PD, renal recovery, and RRT parameters (serum potassium and maximum base excess) during PD were assessed., Results: Percutaneous PD catheters were successfully inserted in 37 of 44 patients (84.1%) after a median of 13.5 days (interquartile range [IQR] = 10.0, 20.3 days) in the ICU. No adverse events were reported; SOFA scores and ventilation requirements were comparable before and after insertion; and adequate RRT parameters were achieved. The median proportion of RRT provided by PD following catheter insertion was 94.6% (IQR = 75.0, 100%)., Conclusion: Peritoneal dialysis provides a safe and effective alternative to CRRT in selected patients with AKI and COVID-19 infection requiring ventilation on intensive care., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Prostate cancer is a significant global health issue, and limitations to current patient management pathways often result in overtreatment or undertreatment. New ways to stratify patients are urgently needed. We conducted a feasibility study of such novel assessments, looking for associations between genomic changes and lymphocyte infiltration. An innovative workflow using an in-house targeted sequencing panel, immune cell profiling using an image analysis pipeline, RNA sequencing, and exome sequencing in select cases was tested. Gene fusions were profiled by RNA sequencing in 27 of 27 cases, and a significantly higher tumor-infiltrating lymphocyte (TIL) count was noted in tumors without a TMPRSS2:ERG fusion compared with those with the fusion (P = 0.01). Although this finding was not replicated in a larger validation set (n = 436) of The Cancer Genome Atlas images, there was a trend in the same direction. Differential expression analysis of TIL-high and TIL-low tumors revealed the enrichment of both innate and adaptive immune response pathways. Mutations in mismatch repair genes (MLH1 and MSH6 mutations in 1 of 27 cases) were identified. We describe a potential immune escape mechanism in TMPRSS2:ERG fusion-positive tumors. Detailed profiling, as shown herein, can provide novel insights into tumor biology. Likely differences with findings with other cohorts are related to methods used to define region of interest, but this warrants further study in a larger cohort., (Copyright © 2020 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Enrichment of CD103 + tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103 + cytotoxic CD8 + T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103 + CTLs by assessing T-cell receptor (TCR)-matched CD103 + and CD103 - cancer-specific CTL immunity in vitro and its immunophenotype ex vivo Interestingly, we found that differentiated CD103 + cancer-specific CTLs expressed the active form of TGFβ1 to continually self-regulate CD103 expression, without relying on external TGFβ1-producing cells. The presence of CD103 on CTLs improved TCR antigen sensitivity, which enabled faster cancer recognition and rapid antitumor cytotoxicity. These CD103 + CTLs had elevated energetic potential and faster migration capacity. However, they had increased inhibitory receptor coexpression and elevated T-cell apoptosis following prolonged cancer exposure. Our data provide fundamental insights into the properties of matured human CD103 + cancer-specific CTLs, which could have important implications for future designs of tissue-localized cancer immunotherapy strategies., (©2019 American Association for Cancer Research.)

Background: Exit-site infection (ESI) and tunnel infection (TI) of the peritoneal dialysis (PD) catheter are significant causes of catheter or even method loss as well as patient morbidity. Among the methods that have been in use thus far, the removal and replacement of the catheter often needs to be followed by switching temporarily to hemodialysis, whereas catheter splicing or unroofing of the tunnel tract and shaving/removal of the superficial catheter cuff have not gained universal acceptance thus far. Methods: We treat chronic ESI with exit-site relocation under local anesthetic with removal of the external cuff. For the purposes of this study, we conducted a retrospective cohort analysis of all exit-site relocations performed using that technique over a 5-year period. Results: Twenty-seven patients (16 male, mean age 58 years, range 23 - 81 years) with chronic ESI underwent exit-site relocation under local anesthetic as a day-case procedure. Follow-up was 47.5 ± 22.4 months (range 10.8 - 79.4 months). No dialysate leaks occurred following the procedure. Peritoneal dialysis was resumed immediately. The procedure resulted in long-term resolution of the infection in 20 of the 27 patients (74%). In 7 patients (26%), the catheter had to be removed eventually, either because of ESI recurrence (5 patients) or TI (2 patients), which in 2 cases was subsequently complicated by PD peritonitis, and the patients were switched to hemodialysis. Conclusion: The technique described herein is a safe, straightforward, and effective method for the treatment of chronic ESI while the patient remains on PD and avoids switching to hemodialysis., (Copyright © 2019 International Society for Peritoneal Dialysis.)

Being aware of controversies and lack of evidence in peritoneal dialysis (PD) training, the Nursing Liaison Committee of the International Society for Peritoneal Dialysis (ISPD) has undertaken a review of PD training programs around the world in order to develop a syllabus for PD training. This syllabus has been developed to help PD nurses train patients and caregivers based on a consensus of training program reviews, utilizing current theories and principles of adult education. It is designed as a 5-day program of about 3 hours per day, but both duration and content may be adjusted based on the learner. After completion of our proposed PD training syllabus, the PD nurse will have provided education to a patient and/or caregiver such that the patient/caregiver has the required knowledge, skills and abilities to perform PD at home safely and effectively. The course may also be modified to move some topics to additional training times in the early weeks after the initial sessions. Extra time may be needed to introduce other concepts, such as the renal diet or healthy lifestyle, or to arrange meetings with other healthcare professionals. The syllabus includes a checklist for PD patient assessment and another for PD training. Further research will be needed to evaluate the effect of training using this syllabus, based on patient and nurse satisfaction as well as on infection rates and longevity of PD as a treatment., (Copyright © 2016 International Society for Peritoneal Dialysis.)

Objective: To present the diagnosis course and sequelae of a case of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, drawing attention to early psychiatric symptoms., Method: The literature on anti-NMDA encephalitis is reviewed and possible psychopathological mechanisms discussed., Result: New onset psychoses, presenting with the combination of hallucinations, dyskinesias and seizures and progressing to catatonia should be referred to neurology for consideration of anti-NMDA receptor encephalitis., Conclusion: Early diagnosis is important for a favourable prognosis., (© The Royal Australian and New Zealand College of Psychiatrists 2015.)

Controversy persists regarding the mechanism underlying the lactate threshold. It has recently been argued that there is in fact no "threshold" and that blood lactate increases as a continuous function during exercise (Hughson J. Appl. Physiol. 62:1975-1981, 1987). In comparing continuous and threshold models, questions have been raised regarding the ramp rate, data sampling, and the mathematical models employed (Morton J. Appl. Physiol. 67:885-888, 1989). To address some of these concerns, we evaluated 61 subjects (mean age 45 +/- 15), who underwent maximal ramp treadmill tests with the ramp rate individualized such that test duration was approximately 10 min for each subject. The relationship between changes in blood lactate and oxygen uptake were evaluated using a modification of the log-log transformation model described by Beaver (J. Appl. Physiol. 59:1936-1940, 1985) and a continuous exponential plus constant model described by Hughson et al. (J. Appl. Physiol. 62:1975-1981, 1987). Model fitting, using mean squared error (MSE) and coefficient of determination (CD) for each method were as follows: [table: see text] The modified log-log model had a better fit as indicated by the lower MSE and higher CD, suggesting the change in lactate was better described by this model. However, the differences were so slight as to suggest: 1) a meaningful difference does not exist between the two; or 2) these methods may not be capable of detecting a difference, if one exists.

Mechanisms that have been suggested to underlie the abnormal ventilatory response to exercise in patients with chronic congestive heart failure (CHF) include high pulmonary pressures, ventilation-perfusion mismatching, early metabolic acidosis, and abnormal respiratory control. To evaluate the role that ventilation and gas exchange play in limiting exercise capacity in patients with CHF, data from 33 patients with CHF and 34 normal subjects of similar age who underwent maximal exercise testing were analyzed. Maximal oxygen uptake was higher among normal subjects (31.7 +/- 6 ml/kg/min) than among patients with CHF (17.7 +/- 4 ml/kg/min; p less than 0.001). The ventilatory equivalent for oxygen, expressed as a percentage of maximal oxygen uptake, was 25% to 35% higher among patients with CHF compared with normal subjects throughout exercise (p less than 0.01). A steeper component effect of ventilation on maximal oxygen uptake was observed among normal subjects compared with patients with CHF, which suggests that a significant portion of ventilation in CHF is wasted. Maximal oxygen uptake was inversely related to the ratio of maximal estimated ventilatory dead space to maximal tidal volume (VD/VT) in both groups (r = -0.73, p less than 0.001). Any given oxygen uptake at high levels of exercise among patients with CHF was accompanied by a higher VD/VT, lower tidal volume, and higher respiratory rate compared with normal subjects (p less than 0.01). Relative hyperventilation in patients with CHF started at the beginning of exercise and was observed both below and above the ventilatory threshold, which suggests that the excess ventilation was not directly related to earlier than normal metabolic acidosis. Thus abnormal ventilatory mechanisms contribute to exercise intolerance in CHF, and excess ventilation is associated with both a higher physiologic dead space and an abnormal breathing pattern. The high dead space is most likely due to ventilation-perfusion mismatching in the lungs, which is related to poor cardiac output, and the abnormal breathing pattern appears to be an effort to reduce the elevated work of breathing that is caused by high pulmonary pressures and poor lung compliance.