Electron flow of biological H2 production by sludge under simple thermal treatment: Kinetic study

Mixed culture sludge has been widely used as a microbial consortium for biohydrogen production. Simple thermal treatment of sludge is usually required in order to eliminate any H2-consuming bacteria that would reduce H2 production. In this study, thermal treatment of sludge was carried out at various temperatures. Electron flow model was then applied in order to assess community structure in the sludge upon thermal treatment for biohydrogen production. Results show that the dominant electron sink was acetate (150–217 eˉ meq/mol glucose). The electron equivalent (eˉ eq) balances were within 0.8–18% for all experiments. Treatment at 100 °C attained the highest H2 yield of 3.44 mol H2/mol glucose from the stoichiometric reaction. As the treatment temperature increased from 80 to 100 °C, the computed acetyl-CoA and reduced form of ferredoxin (Fdred) concentrations increased from 13.01 to 17.34 eˉ eq (1.63–2.17 mol) and 1.34 to 4.18 eˉ eq (0.67–2.09 mol), respectively. The NADH2 balance error varied from 3 to 10% and the term eˉ(Fd↔NADH2) (m) in the NADH2 balance was NADH2 consumption (m = −1). The H2 production was mainly via the Fd:hydrogenase system and this is supported with a good NADH2 balance. Using the modified Gompertz model, the highest maximum H2 production potential was 1194 mL whereas the maximum rate of H2 production was 357 mL/h recorded at 100 °C of treatment

Survival outcomes of patients with muscle-invasive bladder cancer according to pathological response at radical cystectomy with or without neo-adjuvant chemotherapy: a case-control matching study

Objectives To assess survival of patients with muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy (RC) with or without neo-adjuvant chemotherapy (NAC) according to the pathological response at RC. Methods 965 patients with MIBC (cT2-4aN0M0) who underwent RC with or without NAC were analyzed. Among the collected data were comorbidity, clinical and pathological tumor stage, tumor grade, nodal status (y)pN, and OS. Case–control matching of 412 patients was performed to compare oncological outcomes. Kaplan–Meier curves were created to estimate OS for patients who underwent RC with or without NAC, and for those with complete response (pCR), partial response (pPR), or residual or progressive disease (PD). Results Patients with a pCR or pPR at RC, with or without NAC, had better OS than patients who had PD (both p val- ues < 0.001). Moreover, the incidence of pCR was significantly higher in patients receiving NAC prior to RC than in patients undergoing RC only (31% versus 15%, respectively; p < 0.001). Case–control matching displayed better OS of patients who underwent RC with NAC, median survival not reached, than of those who underwent RC only, median 4.5 years (p = 0.023). Conclusions This study showed that patients with MIBC who underwent NAC with RC had a significant better OS than those who underwent RC only. The proportion of patients with a pCR was higher in those who received NAC and RC than in those who were treated by RC only. The favorable OS rate in the NAC and RC cohort was probably attributed to the higher observed pCR rate

Staging fluorodeoxyglucose positron emission tomography/computed tomography for muscle-invasive bladder cancer: a nationwide population-based study

Objective: To provide insight into the use and staging information on lymph-node involvement added by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with muscle-invasive bladder cancer (MIBC), based on a nationwide population-based cohort study. Patients and methods: We analysed a nationwide cohort of patients with MIBC without signs of distant metastases, newly diagnosed in the Netherlands between November 2017 and October 2019. From this cohort, we selected patients who underwent pre-treatment staging with CT only or CT and FDG-PET/CT. The distribution of patients, disease characteristics, imaging findings, nodal status (clinical nodal stage cN0 vs cN+) and treatment were described for each imaging modality group (CT only vs CT and FDG-PET/CT). Results: We identified 2731 patients with MIBC: 1888 (69.1%) underwent CT only; 606 (22.2%) underwent CT and FDG-PET/CT, 237 (8.6%) underwent no CT. Of the patients who underwent CT only, 200/1888 (10.6%) were staged as cN+, vs 217/606 (35.8%) who underwent CT and FDG-PET/CT. Stratified analysis showed that this difference was found in patients with clinical tumour stage (cT)2 as well as cT3/4 MIBC. Of patients who underwent both imaging modalities and were staged with CT as cN0, 109/498 (21.9%) were upstaged to cN+ based on FDG-PET/CT. Radical cystectomy (RC) was the most common treatment within both imaging groups. Preoperative chemotherapy was more frequently applied in cN+ disease and in FDG-PET/CT-staged patients. Concordance of pathological N stage after upfront RC was higher among patients staged as cN+ with CT and FDG-PET/CT (50.0% pN+) than those staged as cN+ with only CT (39.3%). Conclusion: Patients with MIBC who underwent pre-treatment staging with FDG-PET/CT were more often staged as lymph node positive, regardless of cT stage. In patients with MIBC who underwent CT and FDG-PET/CT, FDG-PET/CT led to clinical nodal upstaging in approximately one-fifth. Additional imaging findings may influence subsequent treatment strategies

Increasing value and reducing waste by optimizing the development of complex interventions : Enriching the development phase of the Medical Research Council (MRC) Framework

BACKGROUND: In recent years there has been much emphasis on 'research waste' caused by poor question selection, insufficient attention to previous research results, and avoidable weakness in research design, conduct and analysis. Little attention has been paid to the effect of inadequate development of interventions before proceeding to a full clinical trial. OBJECTIVE: We therefore propose to enrich the development phase of the MRC Framework by adding crucial elements to improve the likelihood of success and enhance the fit with clinical practice METHODS: Based on existing intervention development guidance and synthesis, a comprehensive iterative intervention development approach is proposed. Examples from published reports are presented to illustrate the methodology that can be applied within each element to enhance the intervention design. RESULTS: A comprehensive iterative approach is presented by combining the elements of the MRC Framework development phase with essential elements from existing guidance including: problem identification, the systematic identification of evidence, identification or development of theory, determination of needs, the examination of current practice and context, modelling the process and expected outcomes leading to final element: the intervention design. All elements are drawn from existing models to provide intervention developers with a greater chance of producing an intervention that is well adopted, effective and fitted to the context. CONCLUSION: This comprehensive approach of developing interventions will strengthen the internal and external validity, minimize research waste and add value to health care research. In complex interventions in health care research, flaws in the development process immediately impact the chances of success. Knowledge regarding the causal mechanisms and interactions within the intended clinical context is needed to develop interventions that fit daily practice and are beneficial for the end-user

Impact of the Extent of Lymph Node Dissection on Survival Outcomes in Clinically Lymph Node-Positive Bladder Cancer.

OBJECTIVE To determine the oncologic impact of extended pelvic lymph node dissection (ePLND) over standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). PATIENTS AND METHODS In this retrospective, multicenter study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based perioperative chemotherapy for cTany N1-3 M0 BCa between 1991-2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity score matching using covariates associated with the extent of PLND on univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. RESULTS Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. Median time to recurrence was 8 months (IQR 4-16), and median follow-up of alive patients was 30 months (IQR 13-51). Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 patients (27%), 47 patients (9.2%), and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (p>0.05). ePLND improved neither RFS (HR: 0.91; 95%CI 0.70-1.19; p=0.5) nor OS (HR: 0.78; 95%CI: 0.60-1.01; p=0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. CONCLUSION Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of the induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach

Intermediate term survival following open versus robot-assisted radical cystectomy in the Netherlands:results of the Cystectomie SNAPSHOT study

There is insufficient knowledge on intermediate-term survival of non-metastatic muscle-invasive bladder cancer (MIBC) after open (ORC) versus robot-assisted (RARC) cystectomy, with or without neo-adjuvant chemotherapy (NAC). This retrospective study was performed in 19 Dutch hospitals between 2012 and 2015 to assess the five-year survival after both interventions and the influence of NAC. Out of 1,534 cT1-4N0-1-patients, 1,086 patients were treated with ORC and 389 with RARC. The 5-year survival rate after ORC was 51% (95% CI 47–53) versus 58% after RARC (95% CI 52–63), hazard ratio 1.00 (95% CI 0.84–1.20) after multivariable analysis. 226 of 965 cT2-4aN0 patients were treated with NAC. More patients had ypT0 after NAC than after no NAC (31% vs 15%; p?&lt; 0.01). The best five-year survival was in patients with ypT0 after NAC (89%; 95% CI 81–97). This study shows similar five-year survival of MIBC patients treated with ORC or RARC and shows that the best survival was after NAC

Survival outcomes of patients with muscle-invasive bladder cancer according to pathological response at radical cystectomy with or without neo-adjuvant chemotherapy: a case–control matching study

Objectives: To assess survival of patients with muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy (RC) with or without neo-adjuvant chemotherapy (NAC) according to the pathological response at RC. Methods: 965 patients with MIBC (cT2-4aN0M0) who underwent RC with or without NAC were analyzed. Among the collected data were comorbidity, clinical and pathological tumor stage, tumor grade, nodal status (y)pN, and OS. Case–control matching of 412 patients was performed to compare oncological outcomes. Kaplan–Meier curves were created to estimate OS for patients who underwent RC with or without NAC, and for those with complete response (pCR), partial response (pPR), or residual or progressive disease (PD). Results: Patients with a pCR or pPR at RC, with or without NAC, had better OS than patients who had PD (both p values < 0.001). Moreover, the incidence of pCR was significantly higher in patients receiving NAC prior to RC than in patients undergoing RC only (31% versus 15%, respectively; p < 0.001). Case–control matching displayed better OS of patients who underwent RC with NAC, median survival not reached, than of those who underwent RC only, median 4.5 years (p = 0.023). Conclusions: This study showed that patients with MIBC who underwent NAC with RC had a significant better OS than those who underwent RC only. The proportion of patients with a pCR was higher in those who received NAC and RC than in those who were treated by RC only. The favorable OS rate in the NAC and RC cohort was probably attributed to the higher observed pCR rate