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Chronic kidney disease and nutrition support.
No full textIndividuals with chronic kidney disease (CKD), particularly those undergoing maintenance dialysis, are prone to protein-energy wasting (PEW), the latter of which can be ameliorated with different methods of nutrition support. Dietary counseling guided by dietitians is the key for preventing and managing PEW in CKD. If dietary counseling per se fails to meet the recommended energy and protein requirements, the addition of oral nutrition supplements (ONSs) would be necessary. When these initial measures cannot attain the recommended energy and protein requirements, nutrition support, including enteral tube feeding or parenteral nutrition (PN), should be considered as a viable option to improve nutrition status. Partial PN, comprising intraperitoneal PN (IPPN) and intradialytic PN (IDPN) therapies, may be attempted as supplemental nutrition support in patients with PEW requiring peritoneal dialysis and hemodialysis, respectively. Despite the debatable effectiveness of IPPN for patients undergoing peritoneal dialysis, it remains a feasible means in these patients. The indications for IPPN in patients undergoing peritoneal dialysis include inadequate dietary intake of energy and protein, and barriers of oral intake and other forms of enteral supplementation such as issues with suitability, tolerance, and compliance. Nonetheless, in the case of spontaneous dietary consumption of energy and protein meeting the difference between the IDPN provision and the nutrition targets, the use of IDPN is rational. In patients with PEW and malfunctioning gastrointestinal tract, as well as those whose enteral intake (with or without partial PN) is below the recommended nutrient requirements, total PN becomes a relevant nutrition intervention
Clinical benefit of surveillance after resection of pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.
No full textBACKGROUND
The value of routine surveillance after resection of pancreatic ductal adenocarcinoma (PDAC) is unclear, and expert guidelines offer conflicting recommendations. This study is a systematic review of evidence for surveillance programs.
METHODS
A systematic review of studies evaluating different surveillance methods was undertaken. A meta-analysis was performed for those studies reporting rates of asymptomatic recurrence, treatment of recurrence and overall survival, according to different surveillance methods.
RESULTS
Ten studies were included in the literature review, with five studies appropriate for meta-analysis (1596 patients). Patients within active surveillance programs were more likely to have recurrence detected at an asymptomatic stage (Pooled Rate: 49.3% vs. 19.1%, p = 0.043). Within studies reporting these outcomes, patients with asymptomatic recurrence were more likely to receive treatment for recurrence (Odds Ratio 3.49; 95% CI: 1.73-7.07; p < 0.001) and had longer overall survival (Mean Difference: 9.5 months; 95% CI: 4.1-14.8; p < 0.001) than those with symptoms at time of recurrence.
DISCUSSION
Routine surveillance after surgery for PDAC appears to detect more patients at an asymptomatic stage. Data from these non-randomised trials also suggest that treatment rates and survival may be superior in patients were recurrence is detected when asymptomatic. As such, these data suggest that routine surveillance may improve patient outcomes, although an appropriately conducted trial would be required to address concerns that various sources of bias may be affecting these results
Oligosarcomas, IDH-mutant are distinct and aggressive.
No full textOligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 24 IDH-mutant oligosarcomas from 23 patients forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 12 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dense network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA and CALD1, loss of OLIG2 and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Copy number neutral LOH was determined as underlying mechanism. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional CNS WHO grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as first recurrence than for grade 3 oligodendrogliomas as first recurrence. These results establish oligosarcomas as a distinct group of IDH-mutant gliomas differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. The diagnosis can be based on the combined presence of (a) sarcomatous histology, (b) IDH-mutation and (c) TERT promoter mutation and/or 1p/19q codeletion, or, in unresolved cases, on its characteristic DNA methylation profile
Hypothalamic-Pituitary and Other Endocrine Surveillance Among Childhood Cancer Survivors.
No full textEndocrine disorders in survivors of childhood, adolescent, and young adult (CAYA) cancers are associated with substantial adverse physical and psychosocial effects. To improve appropriate and timely endocrine screening and referral to a specialist, the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) aims to develop evidence and expert consensus-based guidelines for healthcare providers that harmonize recommendations for surveillance of endocrine disorders in CAYA cancer survivors. Existing IGHG surveillance recommendations for premature ovarian insufficiency, gonadotoxicity in males, fertility preservation, and thyroid cancer are summarized. For hypothalamic-pituitary (HP) dysfunction, new surveillance recommendations were formulated by a guideline panel consisting of 42 interdisciplinary international experts. A systematic literature search was performed in MEDLINE (through PubMed) for clinically relevant questions concerning HP dysfunction. Literature was screened for eligibility. Recommendations were formulated by drawing conclusions from quality assessment of all evidence, considering the potential benefits of early detection and appropriate management. Healthcare providers should be aware that CAYA cancer survivors have an increased risk for endocrine disorders, including HP dysfunction. Regular surveillance with clinical history, anthropomorphic measures, physical examination, and laboratory measurements is recommended in at-risk survivors. When endocrine disorders are suspected, healthcare providers should proceed with timely referrals to specialized services. These international evidence-based recommendations for surveillance of endocrine disorders in CAYA cancer survivors inform healthcare providers and highlight the need for long-term endocrine follow-up care in subgroups of survivors and elucidate opportunities for further research
Recurrent miscarriage: evidence to accelerate action.
No full textWomen who have had repeated miscarriages often have uncertainties about the cause, the likelihood of recurrence, the investigations they need, and the treatments that might help. Health-care policy makers and providers have uncertainties about the optimal ways to organise and provide care. For this Series paper, we have developed recommendations for practice from literature reviews, appraisal of guidelines, and a UK-wide consensus conference that was held in December, 2019. Caregivers should individualise care according to the clinical needs and preferences of women and their partners. We define a minimum set of investigations and treatments to be offered to couples who have had recurrent miscarriages, and urge health-care policy makers and providers to make them universally available. The essential investigations include measurements of lupus anticoagulant, anticardiolipin antibodies, thyroid function, and a transvaginal pelvic ultrasound scan. The key treatments to consider are first trimester progesterone administration, levothyroxine in women with subclinical hypothyroidism, and the combination of aspirin and heparin in women with antiphospholipid antibodies. Appropriate screening and care for mental health issues and future obstetric risks, particularly preterm birth, fetal growth restriction, and stillbirth, will need to be incorporated into the care pathway for couples with a history of recurrent miscarriage. We suggest health-care services structure care using a graded model in which women are offered online health-care advice and support, care in a nurse or midwifery-led clinic, and care in a medical consultant-led clinic, according to clinical needs
Effects of Negation and Uncertainty Stratification on Text-Derived Patient Profile Similarity.
No full textSemantic similarity is a useful approach for comparing patient phenotypes, and holds the potential of an effective method for exploiting text-derived phenotypes for differential diagnosis, text and document classification, and outcome prediction. While approaches for context disambiguation are commonly used in text mining applications, forming a standard component of information extraction pipelines, their effects on semantic similarity calculations have not been widely explored. In this work, we evaluate how inclusion and disclusion of negated and uncertain mentions of concepts from text-derived phenotypes affects similarity of patients, and the use of those profiles to predict diagnosis. We report on the effectiveness of these approaches and report a very small, yet significant, improvement in performance when classifying primary diagnosis over MIMIC-III patient visits
Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial.
No full textBACKGROUND
Sjögren's syndrome is an autoimmune disease characterised by dry eyes and mouth, systemic features, and reduced quality of life. There are no disease-modifying treatments. A new biologic, ianalumab (VAY736), with two modes of suppressing B cells, has previously shown preliminary efficacy. This dose-finding trial aimed to assess the safety and efficacy of different subcutaneous doses of ianalumab in patients with moderate to severe primary Sjögren's syndrome.
METHODS
VAY736A2201 was a randomised, parallel, double-blind, placebo-controlled, phase 2b dose-finding study done in 56 centres in 19 countries. Patients aged 18-75 years with primary Sjögren's syndrome with moderate to severe disease activity (European Alliance of Associations for Rheumatology [EULAR] Sjögren's Syndrome Disease Activity Index [ESSDAI] score ≥6) and symptom severity (EULAR Sjögren's Syndrome Patient Reported Index score ≥5) were eligible. Participants were randomly assigned (1:1:1:1) to receive subcutaneous placebo or ianalumab (5 mg, 50 mg, or 300 mg) every 4 weeks for 24 weeks using a secure, online randomisation system. Randomisation was stratified by the ESSDAI score at baseline (≥10 or <10). Study personnel and patients were masked to treatment assignment. The primary outcome was the change in ESSDAI score from baseline to 24 weeks in all randomly assigned patients. Dose-related change in disease activity (ESSDAI) from baseline at week 24 was assessed by multiple comparison procedure with modelling analysis. Safety was measured in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT02962895.
FINDINGS
Between June 27, 2017, and Dec 06, 2018, 293 patients were screened, 190 of whom were randomly assigned (placebo n=49, ianalumab 5 mg n=47, ianalumab 50 mg n=47, ianalumab 300 mg n=47). Statistically significant dose-responses were seen for overall disease activity (ESSDAI score) in four of the five dose-response models tested (p<0·025 in four models, p=0·060 in one model). The ESSDAI score decreased from baseline in all ianalumab groups, with the maximal ESSDAI score change from baseline observed in the ianalumab 300 mg group: placebo-adjusted least-squares mean change from baseline -1·92 points (95% CI -4·15 to 0·32; p=0·092). There were four serious adverse events in three patients considered treatment-related (pneumonia [n=1] and gastroenteritis [n=1] in the placebo group; appendicitis plus tubo-ovarian abscess in the same patient in the ianalumab 50 mg group).
INTERPRETATION
The study met its primary objective, showing a dose-related decrease in disease activity as measured by ESSDAI at week 24. Overall, ianalumab was well tolerated and safe, with no increase in infections. To our knowledge, this is the first large, randomised, controlled trial in primary Sjögren's syndrome that met its primary endpoint, and its results mean there is potential for more studies of this mechanism in the future.
FUNDING
Novartis
Stevens-Johnson syndrome and toxic epidermal necrolysis: a comparison with practice in a large UK burns unit.
No full textIncreased Amylase and Lipase in Patients With COVID-19 Pneumonia: Don't Blame the Pancreas Just Yet!
No full textOpen Partial Nephrectomy with Zero Ischaemia Using a Supra 12th Rib Miniflank Incision: A Minimally Invasive Open Approach for Small Renal Masses.
No full textIntroduction
To assess a minimally invasive open technique for partial nephrectomy with zero ischaemia time.
Methods
A review was performed in a prospectively maintained database of a single surgeon series of all patients undergoing partial nephrectomy using a supra 12 rib miniflank incision with zero ischaemia. Data of seventy one patients who underwent a partial nephrectomy over an 82-month period were analyzed. Data analyzed included operative time, estimated blood loss, pre and postoperative renal function, complications, final pathological characteristics, and tumour size.
Results
Seventy one partial nephrectomies were performed from February 2009 to October 2015. None were converted to radical nephrectomy. Mean operative time was 72 minutes (range 30-250), and mean estimated blood loss was 608 mls (range 100-2500) with one patient receiving blood transfusion. The mean pre and postoperative haemoglobin levels were 144 and 112 g/l. The mean pre and postoperative creatinine levels were 82 and 103 Umol/L. There were 8 Clavian-Dindo Grade 2 complications and 1 major complication (Clavian IIIa). Histology confirmed 24 benign lesions and 47 malignant lesions, 46 cT1a lesions, 24 cT1b lesions, and 1 cT2 lesion. Median follow-up was 38 months with no local recurrence or progression of disease with 5 patients having a positive margin (7%).
Conclusion
Our results demonstrate that a supra 12th miniflank incision open partial nephrectomy with zero ischaemic time for SRMs has satisfactory outcomes with preservation of renal function. A minimally invasive open partial nephrectomy remains an important option for units that cannot offer patients a laparoscopic or a robotic procedure