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Routine serum biomarkers, but not dual-energy X-ray absorptiometry, correlate with cortical bone mineral density in children and young adults with chronic kidney disease.
No full textBACKGROUND
Biomarkers and dual-energy X-ray absorptiometry (DXA) are thought to be poor predictors of bone mineral density (BMD). The Kidney Disease: Improving Global Outcomes guidelines suggest using DXA if the results will affect patient management, but this has not been studied in children or young adults in whom bone mineral accretion continues to 30 years of age. We studied the clinical utility of DXA and serum biomarkers against tibial cortical BMD (CortBMD) measured by peripheral quantitative computed tomography, expressed as Z-score CortBMD, which predicts fracture risk.
METHODS
This was a cross-sectional multicentre study in 26 patients with CKD4 and 5 and 77 on dialysis.
RESULTS
Significant bone pain that hindered activities of daily living was present in 58%, and 10% had at least one low-trauma fracture. CortBMD and cortical mineral content Z-scores were lower in dialysis compared with CKD patients (P = 0.004 and P = 0.02). DXA BMD hip and lumbar spine Z-scores did not correlate with CortBMD or biomarkers. CortBMD was negatively associated with parathyroid hormone (PTH; r = -0.44, P < 0.0001) and alkaline phosphatase (ALP; r = -0.22, P = 0.03) and positively with calcium (Ca; r = 0.33, P = 0.001). At PTH <3 times upper limit of normal, none of the patients had a CortBMD below -2 SD (odds ratio 95% confidence interval 7.331 to infinity). On multivariable linear regression PTH (β = -0.43 , P < 0.0001), ALP (β = -0.36, P < 0.0001) and Ca (β = 0.21, P = 0.005) together predicted 57% of variability in CortBMD. DXA measures did not improve this model.
CONCLUSIONS
Taken together, routinely used biomarkers, PTH, ALP and Ca, but not DXA, are moderate predictors of cortical BMD. DXA is not clinically useful and should not be routinely performed in children and young adults with CKD 4-5D
The risk of later surgery at the anastomotic site following right hemicolectomy for Crohn's disease in a national cohort of 12 230 patients.
No full textBACKGROUND
Crohn's disease (CD) has a high-risk of bowel resection and later surgery for recurrent disease. Recent guidelines recommend colonoscopy 6-12 months following surgery to reduce further surgical intervention through medical therapy intensification.
AIMS
To investigate the risk of further surgery at the anastomosis following right hemicolectomy for CD.
METHODS
Hospital Episode Statistics were used to identify patients with CD and a right hemicolectomy between 2007 and 2016. Adherence to post-resection colonoscopy guidance timing and risk of further surgery at the anastomosis were examined. Cox proportional hazards models assessed risk factors for further surgery.
RESULTS
12 230 patients were identified: 45% male; median age 36 (IQR 26-49) years. Median follow-up was 5.9 (IQR 3.6-8.6) years: totalling 74 960 person-years. Median time to further surgery was 2.9 (IQR 1.2-5.3) years. By 5 years 9% and by 10 years 16.9% of those with sufficient follow-up had at least one further surgery involving the anastomotic site. Older, less deprived patients and those whose index surgery took place on an elective admission had a reduced risk of further surgery. The annual number of right hemicolectomies increased over the study from 1063 to 1317, driven by the increasing prevalence of CD. Overall, 78% of patients did not have a colonoscopy, as recommended, within 6-12 months following index resection.
CONCLUSIONS
Further surgery involving the anastomotic site remains common following index right hemicolectomy for CD. Post-surgical colonoscopy was only undertaken in 22% of patients within suggested timeframes. Increased colonoscopy may lead to a reduced need for surgery if early optimisation of medical therapy is undertaken for recurrence
Improving management of diabetic kidney disease: will GLP-1 receptor agonists have a role?
No full textVariation of radiation dose with distance from radiotherapy linac bunker maze entrances.
No full textInstantaneous dose rate (IDR) measurements were made at the entrances of a number of linac bunkers for a range of beam energies and gantry angles in a large radiotherapy department. The results demonstrate that the IDR does not decrease with distance from the maze entrances according to the inverse square law (ISL), which is commonly used in the design of such bunkers. No simple relationship exists, but a useful guiding principle was found that the IDR at 1 m back from the maze entrance is approximately 50% of that at the entrance itself. This was found to hold with a standard error within 5% across the full extent of the maze entrance by measuring in a grid pattern. The ISL should therefore be used with caution in the design of radiotherapy bunker mazes as it may not provide accurate estimates of the dose in surrounding areas. The results of the grid pattern measurements also indicate that the centre of the maze entrance is the best position to affix passive dosemeters for the purpose of environmental monitoring. This may not always be practical (e.g. if the bunker does not have a door), but factors have been found to correct readings taken elsewhere to the central reading. For instance, if the dosemeter is placed on the wall, the measured dose rate will be equal to 94% ± 8% of the value at the centre of the bunker
Improving management of diabetic kidney disease: will GLP-1 receptor agonists have a role?
No full textReal-world Outcomes With Rituximab-based Therapy for Posttransplant Lymphoproliferative Disease Arising After Solid Organ Transplant.
No full textBACKGROUND
Optimal upfront therapy for posttransplant lymphoproliferative disease (PTLD) arising after solid organ transplant remains contentious. Rituximab monotherapy (R-Mono) in unselected patients has shown a lack of durable remissions. CHOP-based chemotherapy confers improved response rates, although concerns exist about toxicity.
METHODS
This multicenter retrospective study reports outcomes for adults with biopsy-proven B-cell PTLD treated initially with R-Mono or R-CHOP. Selection of therapy was made according to physician preference.
RESULTS
Amongst 101 patients, 41 received R-Mono and 60 had R-CHOP. Most (93%) had undergone renal or liver transplantation. R-CHOP showed a trend toward improved complete (53% vs. 71%; P=0.066) and overall (75% vs. 90%; P=0.054) response rates. In the R-Mono group 13/41 (32%) subsequently received chemotherapy, whilst 25/41 (61%) remained progression-free without further therapy. With median follow-up of 47 months, overall survival (OS) was similar for R-Mono and R-CHOP, with 3-year OS of 71% and 63% respectively (P=0.722). Non-PTLD mortality was 3/41 (7%) and 4/60 (7%) within 12 months of R-Mono or R-CHOP respectively. The international prognostic index was statistically significant, with low- (0-2 points) and high-risk (≥3 points) groups exhibiting 3-year OS of 78% and 54% respectively (P=0.0003). In low-risk PTLD, outcomes were similar between therapies. However, in high-risk disease R-Mono conferred an inferior complete response rate (21% vs. 68%; P=0.006), albeit with no impact on survival.
CONCLUSION
Our data support R-Mono as initial therapy for PTLD arising after renal or liver transplantation. However, upfront R-CHOP may benefit selected high-risk cases in whom rapid attainment of response is desirable
Treatment Strategies for the Optimal Management of Locally Advanced Pancreatic Adenocarcinoma With Curative Intent: A Systematic Review.
No full textHistorically, locally advanced pancreatic adenocarcinoma (LAPDAC) was considered a palliative condition. Advances in treatment have resulted in studies reporting survival after neoadjuvant treatment and surgery similar to earlier disease stages. However, there is no consensus on optimal LAPDAC management. Our aim was a systematic review of published evidence on LAPDAC treatment strategies with curative intent. Twenty-eight studies defining LAPDAC as per established criteria and reporting outcomes after neoadjuvant treatment with a view to resection were included. Primary outcomes were resection rate and proportion of curative resections. Secondary outcomes were postoperative mortality, progression-free survival, and overall survival. Neoadjuvant treatment varied significantly, most common being the combination of folinic acid, fluorouracil, irontecan, and oxaliplatin. Median percentage of patients proceeding to surgery after completion of neoadjuvant pathway was 33.5%. Median resection rate was 25%. Median R0 resection was 80% of resected patients. These outcomes ranged 0% to 100% across studies. Ninety-day postoperative mortality ranged from 0% to 5%. Median progression-free and overall survival for resected patients were 12.9 and 30 months, respectively, versus 13.2 months overall survival for unresected patients. In conclusion, although there is wide variability in reported LAPDAC resection rates post-neoadjuvant chemotherapy, retrospective data suggest that neoadjuvant treatment followed by surgery results in improved survival
Outcomes of Cochlear Implantation in Patients with Pendred syndrome: A Systematic Review and Narrative Synthesis.
No full textEstablish outcomes following cochlear implantation (CI) in patients with Pendred syndrome. Systematic review and narrative synthesis. Databases searched: Medline, Pubmed, Embase, Web of Science, Cochrane Collection and ClinicalTrials.gov. No limits placed on language or year of publication. Review conducted in accordance with the PRISMA statement. Searches identified 251 abstracts and 242 full texts. Of these, 22 studies met inclusion criteria reporting outcomes in 231 patients with at least 234 implants. Hearing outcomes were generally good with patients experiencing useful functional improvement. A total of 46 minor complications were reported in 78 cases. The methodological quality of included studies was modest, predominantly consisting of case reports and non-controlled case series with small numbers of patients. All studies were OCEBM grade III-IV. Hearing outcomes following CI in Pendred syndrome are generally good with useful functional improvement. However, outcomes reported in published studies lack long term follow up
Systematic review and meta-analysis of factors associated with post-operative pancreatic fistula following pancreatoduodenectomy.
No full textBACKGROUND
Many studies have explored factors relating to post-operative pancreatic fistula (POPF); however, the original definition (All-POPF) was revised to include only 'clinically relevant' (CR) POPF. This study identified variables associated with the two International Study Group on Pancreatic Surgery definitions to identify which variables are more strongly associated with CR-POPF.
METHODS
A systematic review identified all studies reporting risk factors for POPF (using both International Study Group on Pancreatic Fistula definitions) following pancreatoduodenectomy. The primary outcome was factors associated with CR-POPF. Meta-analyses (random effects models) of pre-, intra- and post-operative factors associated with POPF in more than two studies were included.
RESULTS
Among 52 774 patients All-POPF (n = 69 studies) and CR-POPF (n = 53 studies) affected 27% (95% confidence interval (CI ) 23-30) and 19% (CI 17-22), respectively. Of the 176 factors, 24 and 17 were associated with All- and CR-POPF, respectively. Absence of pre-operative pancreatitis, presence of renal disease, no pre-operative neoadjuvant therapy, use of post-operative somatostatin analogues, absence of associated venous or arterial resection were associated with CR-POPF but not All-POPF.
CONCLUSION
In conclusion this study demonstrates wide variation in reported rates of POPF and that several risk factors associated with CR-POPF are not used within risk prediction models. Data from this study can be used to shape future studies, research and audit across ethnic and geographic boundaries in POPF following pancreatoduodenectomy
