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Rate of Kidney Function Decline and Factors Predicting Progression of Kidney Disease in Type 2 Diabetes Mellitus Patients with Reduced Kidney Function: A Nationwide Retrospective Cohort Study.
No full textOBJECTIVES
Currently, the data on independent risk factors for the progression of kidney disease in type 2 diabetes mellitus (T2DM) patients with CKD were limited. This study aimed to investigate CKD progression in T2DM patients who have reduced kidney function with baseline eGFRs between 15 and 59 mL/min/1.73 m .
METHODS
This study was composed of a nationwide retrospective cohort of adult T2DM patients from 831 public hospitals in Thailand during the year 2015. T2DM patients with CKD stage 3-4 were followed up until development of CKD stage 5, requirement of chronic dialysis, loss to follow-up, death, or May 31st, 2018, whichever came first. Cox proportional hazard regression was utilized to analysis.
RESULTS
A total of 8464 participants were included. 30.4% were male. The mean age was 69 ± 10 years. The mean eGFR was 45 ± 11 mL/min/1.73 m . The incidence of CKD stage 5 or need for chronic dialysis was 16.4 per 1000 person-years. The annual rate of eGFR decline during a mean follow-up of 29 months was -2.3 mL/min/1.73 m . 14.4% had a rapid decline in eGFR. The risk factors associated with progression to CKD stage 5 or need for chronic dialysis were diabetes duration, systolic blood pressure, serum uric acid, albuminuria, and baseline eGFR. Conversely, older age and the use of renin-angiotensin aldosterone system blockades were associated with decreased risks for rapid CKD progression and incidence CKD stage 5 or dialysis.
CONCLUSION
This study identifies multiple predictive risk factors that support a multifaceted approach to prevent progression of advanced CKD
Machine learning to predict early recurrence after oesophageal cancer surgery.
No full textBACKGROUND
Early cancer recurrence after oesophagectomy is a common problem, with an incidence of 20-30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches.
METHODS
Consecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in one Dutch and six UK oesophagogastric units were analysed. Using clinical characteristics and postoperative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and extreme gradient boosting (XGB). Finally, a combined (ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model.
RESULTS
A total of 812 patients were included. The recurrence rate at less than 1 year was 29·1 per cent. All of the models demonstrated good discrimination. Internally validated areas under the receiver operating characteristic (ROC) curve (AUCs) were similar, with the ensemble model performing best (AUC 0·791 for ELR, 0·801 for RF, 0·804 for XGB, 0·805 for ensemble). Performance was similar when internal-external validation was used (validation across sites, AUC 0·804 for ensemble). In the final model, the most important variables were number of positive lymph nodes (25·7 per cent) and lymphovascular invasion (16·9 per cent).
CONCLUSION
The model derived using machine learning approaches and an international data set provided excellent performance in quantifying the risk of early recurrence after surgery, and will be useful in prognostication for clinicians and patients
Prevention of adrenal crisis: cortisol responses to major stress compared to stress dose hydrocortisone delivery.
No full textCONTEXT
Patients with adrenal insufficiency require increased hydrocortisone cover during major stress to avoid life-threatening adrenal crisis. However, current treatment recommendations are not evidence-based.
OBJECTIVE
To identify the most appropriate mode of hydrocortisone delivery in patients with adrenal insufficiency exposed to major stress.
DESIGN AND PARTICIPANTS
Cross-sectional study: 122 unstressed healthy subjects and 288 subjects exposed to different stressors (major trauma [N=83], sepsis [N=100], and combat stress [N=105]). Longitudinal study: 22 patients with preserved adrenal function undergoing elective surgery. Pharmacokinetic study: 10 patients with primary adrenal insufficiency undergoing administration of 200mg hydrocortisone over 24 hours in four different delivery modes (continuous intravenous infusion; six-hourly oral, intramuscular or intravenous bolus administration).
MAIN OUTCOME MEASURE
We measured total serum cortisol and cortisone, free serum cortisol and urinary glucocorticoid metabolite excretion by mass spectrometry. Linear pharmacokinetic modelling was used to determine the most appropriate mode and dose of hydrocortisone administration in patients with adrenal insufficiency exposed to major stress.
RESULTS
Serum cortisol was increased in all stress conditions, with the highest values observed in surgery and sepsis. Continuous intravenous hydrocortisone was the only administration mode persistently achieving median cortisol concentrations in the range observed during major stress. Linear pharmacokinetic modelling identified continuous intravenous infusion of 200mg hydrocortisone over 24 hours, preceded by an initial bolus of 50-100mg hydrocortisone, as best suited for maintaining cortisol concentrations in the required range.
CONCLUSIONS
Continuous intravenous hydrocortisone infusion should be favored over intermittent bolus administration in the prevention and treatment of adrenal crisis during major stress
Reply to Wei Liu, Xiaoping Liu, Sheng Li's Letter to the Editor, re: Robert A. Huddart, Emma Hall, Rebecca Lewis, et al. Patient-reported Quality of Life Outcomes in Patients Treated for Muscle-invasive Bladder Cancer with Radiotherapy ± Chemotherapy in the BC2001 Phase III Randomised Controlled Trial. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2019.11.001.
No full textA comprehensive evaluation of the long-term clinical and economic impact of minor bile duct injury.
No full textBACKGROUND
Outcomes after Strasberg grade E bile duct injury have been widely reported. However, there are comparatively few reports of outcomes after Strasberg A to D bile duct injury. Therefore, the aim of this study was to comprehensively evaluate the long-term clinical and economic impact of Strasberg A to D bile duct injury.
METHODS
Patients with Strasberg A to D bile duct injury were identified from a prospectively collected and maintained database. Long-term biliary complication rates, as well as treatment costs were then estimated, and compared across Strasberg injury grades.
RESULTS
A total of N = 120 patients were identified, of whom N = 49, 13, 20, and 38 had Strasberg grade A, B, C, and D bile duct injury, respectively. Surgical repair was most commonly performed in Strasberg grade D injuries (74% vs 8%-20% in lower grades, P < .001). By 5 years post bile duct injury, the estimated long-term biliary complication rate was 40% in Strasberg grade D injuries, compared with 15% in Strasberg grade A (P = .022). A significant difference in total treatment and follow-up costs was also detected (P < .001), being highest in Strasberg grade D injuries (mean £11,048/US13,689 per patient).
DISCUSSION
Strasberg grade A to D injuries lead to considerable long-term morbidity and cost. Strasberg grade D injuries are typically managed surgically and result in the highest complication rate and treatment costs. Strasberg grade B injuries lead to a similar complication rate and treatment cost but are often managed without surgery
A pilot integrative analysis of colonic gene expression, gut microbiota and immune infiltration in primary sclerosing cholangitis-inflammatory bowel disease: association of disease with bile acid pathways.
No full textBACKGROUND
Although majority of patients with PSC have colitis (PSC-IBD) this is phenotypically different from UC. We sought to define further the pathophysiologic differences in PSC-IBD and UC, by applying a comparative and integrative approach in this pilot study.
METHODS
Colonic biopsies were collected from patients with PSC-IBD (n=10), UC (n=10) and healthy controls (HC; n=10). Shotgun RNA-sequencing for differentially expressed colonic mucosal genes (DEGs), 16S rRNA analysis for microbial profiling and immunophenotyping were performed followed by multi-omic integration.
RESULTS
The colonic transcriptome differed significantly between groups (P=0.01). Colonic transcriptomes from HC were different from both UC (1343 DEGs) and PSC-IBD (4312 DEGs). Of these genes, only 939 had shared differential gene expression in both UC and PSC-IBD compared to HC. Imputed pathways were predominantly associated with upregulation of immune response and microbial defence in both disease cohorts compared to HC. There were 1692 DEGs between PSC-IBD and UC. Bile acid signalling pathways were upregulated in PSC-IBD compared to UC (P=0.02). Microbiota profiles were different between the three groups (P=0.01); with inferred function in PSC-IBD also being consistent with dysregulation of bile acid metabolism. Th17 cells and IL17 producing CD4 cells were increased in both PSC-IBD and UC when compared to HC (P<0.05). Multi-omic integration revealed networks involved in bile acid homeostasis and cancer regulation in PSC-IBD.
CONCLUSIONS
Colonic transcriptomic and microbiota analysis in PSC-IBD points toward dysregulation of colonic bile acid homeostasis compared to UC. This highlights important mechanisms and suggests the possibility of novel approaches in treating PSC-IBD
Clinical and surgical outcomes of patients with peritoneal mesothelioma discussed at a monthly national multidisciplinary team video-conference meeting.
No full textBACKGROUND
Peritoneal mesothelioma (PM) is a rare primary neoplasm of the peritoneum with an increasing incidence worldwide. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promise as a treatment strategy. A national PM multidisciplinary team (national PM MDT) video-conference meeting was established in the UK and Ireland in March 2016, aiming to plan optimal treatment, record outcomes and provide evidence for the benefits of centralization. This article reports on the activities and outcomes of the first 2·5 years.
METHODS
Between March 2016 and December 2018, patients with PM, referred to peritoneal malignancy centres in Basingstoke, Birmingham, Manchester and Dublin, were discussed by the national PM MDT via video-conference. The MDT was composed of surgeons, radiologists, specialist nurses and pathologists. Patients were considered for CRS and HIPEC if considered fit for surgery and if radiological imaging suggested that complete surgical cytoreduction could be achieved. Morbidity and mortality following surgery were analysed. Survival analysis following MDT discussion was conducted.
RESULTS
A total of 155 patients (M : F ratio 0·96) with a mean(s.d.) age of 57(17) years were discussed. To date, 22 (14·2 per cent) have had CRS and HIPEC; the median Peritoneal Cancer Index for the surgical group was 17·0. Complete cytoreduction was achieved in 19 patients. Clavien-Dindo grade I-II complications occurred in 16 patients; there was no grade III-IV morbidity or 30-day in-hospital mortality. The median follow-up for the whole cohort was 18·7 months, and the 2-year survival rate from time of first review at the national PM MDT was 68·3 per cent.
CONCLUSION
The centralized national PM MDT was effective at selecting patients suitable for CRS and HIPEC, reporting a good outcome from patient selection
