Delaying Surgery in Favorable-Risk Prostate Cancer Patients: An NCDB Analysis of Oncologic Outcomes.

INTRODUCTION: Concern for overtreatment in very low-, low-, and favorable intermediate-risk prostate cancer has promoted a more conservative approach through active surveillance (AS) with comparable survival outcomes. We analyzed the National Cancer Database (NCDB) to determine if delaying radical prostatectomy greater than 6 months is associated with an increase in the rate of adverse pathology or secondary treatment (adjuvant or salvage) at radical prostatectomy. METHODS: Utilizing the NCDB from 2004 to 2019, 40 to 75-year-old men with very low-, low-, and favorable-intermediate-risk prostate cancer, as defined by the National Comprehensive Cancer Network, were identified for this study. These individuals received radical prostatectomy either before or after 6 months following diagnosis. Clinical, demographic, and pathologic characteristics were obtained. Adverse pathologic outcomes were defined as pT3-4N0-1 and/or positive surgical margins. Multiple logistic regression models were used to predict delays in treatment, adverse pathologic outcomes, and receipt of secondary therapy. Survival analysis was performed using the Cox Proportional Hazards Model and the Kaplan-Meier Method. RESULTS: Of the 195,397 patients who met inclusion criteria, only 13,393 patients received surgery 6 months after diagnosis. The median time of delay was 7.5 months compared to 2.3 months in the immediate treatment group. Overall, delaying surgery had no statistically significant impact on adverse pathologic outcomes, regardless of risk category. However, when accounting for the interaction between race and delayed treatment, non-Hispanic black patients who received a delay in treatment were more likely to experience adverse features (OR 1.12, 95%CI 1.00-1.26, P = .041). Conversely, patients who had delayed surgery were less likely to receive additional therapy (either adjuvant or salvage) (OR 0.60, 95%CI 0.52-0.68, P < .001). Survival analysis showed that both groups fared well, with a 5-year survival of 97% for both groups. The treatment group was not predictive of survival. CONCLUSION: Overall, delaying surgery more than 6 months following diagnosis did not have a significant impact on adverse pathologic features or overall survival. However, when specifically looking at non-Hispanic black patients with a treatment delay, these patients were at increased risk for adverse features, suggesting that the negative impact of treatment delay depends on the patient's race. As race is a social construct, this finding likely points to the complex socioeconomic factors that contribute to overall health outcomes rather than any inherent disease characteristics. Lastly, delayed treatment patients were actually less likely to require secondary therapy, regardless of race, possibly reflecting high clinician acumen in selecting patients appropriate for treatment delay. The results suggest that patients who ultimately "fail" AS and require subsequent surgery have overall comparable survival outcomes. However, pathologic outcomes are dependent on the patient's underlying race, with non-Hispanic black patients experiencing an increased risk of adverse outcomes if treatment is delayed.

A mass balance approach for quantifying the role of natural decay and fate mechanisms on SARS-CoV-2 genetic marker removal during water reclamation.

The recent SARS-CoV-2 outbreak yielded substantial data regarding virus fate and prevalence at water reclamation facilities (WRFs), identifying influential factors as natural decay, adsorption, light, pH, salinity, and antagonistic microorganisms. However, no studies have quantified the impact of these factors in full scale WRFs. Utilizing a mass balance approach, we assessed the impact of natural decay and other fate mechanisms on genetic marker removal during water reclamation, through the use of sludge and wastewater genetic marker loading estimates. Results indicated negligible removal of genetic markers during P/PT (primary effluent (PE) p value: 0.267; preliminary and primary treatment (P/PT) accumulation p value: 0.904; and thickened primary sludge (TPS) p value: 0.076) indicating no contribution of natural decay and other fate mechanisms toward removal in P/PT. Comparably, adsorption and decomposition was found to be the dominant pathway for genetic marker removal (thickened waste activated sludge (TWAS) log loading 9.75 log10 GC/day); however, no estimation of log genetic marker accumulation could be carried out due to high detections in TWAS. PRACTITIONER POINTS: The mass balance approach suggested that the contribution of natural decay and other fate mechanisms to virus removal during wastewater treatment are negligible compared with adsorption and decomposition in P/PT (p value: 0.904). During (P/PT), a higher viral load remained in the (PE) (14.16 log10 GC/day) compared with TPS (13.83 log10 GC/day); however, no statistical difference was observed (p value: 0.280) indicting that adsorption/decomposition most probably did not occur. In secondary treatment (ST), viral genetic markers in TWAS were consistently detected (13.41 log10 GC/day) compared with secondary effluent (SE), indicating that longer HRT and the potential presence of extracellular polymeric substance-containing enriched biomass enabled adsorption/decomposition. Estimations of total solids and volatile solids for TPS and TWAS indicated that adsorption affinity was different between solids sampling locations (p value: <0.0001).

Treatment Outcomes of Second-Line Systemic Therapy for Neuroendocrine Prostate Cancer: A Report of Four Cases.

Neuroendocrine prostate cancer (NEPC) is a histological variant of prostate cancer and is characterized by aggressiveness and poor clinical outcomes. NEPC usually develops as a mechanism of treatment resistance in patients receiving hormone therapy for advanced prostate cancer. NEPC is sensitive to primary platinum-based chemotherapy, and has a short response duration. Second-line therapy is required in many cases, but clinical data on subsequent treatment after progression to first-line chemotherapy is limited. Here we report our experience of four cases of NEPC treated with second-line chemotherapy. Progression-free and overall survival rates were very low in three of the patients. One patient received multidisciplinary therapy using systemic and local chemotherapy and radiation therapy and survived for 24 months after initiation of second-line chemotherapy. Multidisciplinary therapy with chemotherapy and radiation is a promising option for improving the survival of patients with NEPC.

Complexing Protein-Free Botulinum Neurotoxin A Formulations: Implications of Excipients for Immunogenicity.

The formation of neutralizing antibodies is a growing concern in the use of botulinum neurotoxin A (BoNT/A) as it may result in secondary treatment failure. Differences in the immunogenicity of BoNT/A formulations have been attributed to the presence of pharmacologically unnecessary bacterial components. Reportedly, the rate of antibody-mediated secondary non-response is lowest in complexing protein-free (CF) IncobotulinumtoxinA (INCO). Here, the published data and literature on the composition and properties of the three commercially available CF-BoNT/A formulations, namely, INCO, Coretox® (CORE), and DaxibotulinumtoxinA (DAXI), are reviewed to elucidate the implications for their potential immunogenicity. While all three BoNT/A formulations are free of complexing proteins and contain the core BoNT/A molecule as the active pharmaceutical ingredient, they differ in their production protocols and excipients, which may affect their immunogenicity. INCO contains only two immunologically inconspicuous excipients, namely, human serum albumin and sucrose, and has demonstrated low immunogenicity in daily practice and clinical studies for more than ten years. DAXI contains four excipients, namely, L-histidine, trehalosedihydrate, polysorbate 20, and the highly charged RTP004 peptide, of which the latter two may increase the immunogenicity of BoNT/A by introducing neo-epitopes. In early clinical studies with DAXI, antibodies against BoNT/A and RTP004 were found at low frequencies; however, the follow-up period was critically short, with a maximum of three injections. CORE contains four excipients: L-methionine, sucrose, NaCl, and polysorbate 20. Presently, no data are available on the immunogenicity of CORE in human beings. It remains to be seen whether all three CF BoNT/A formulations demonstrate the same low immunogenicity in patients over a long period of time.

Anaerobic Wastewater Treatment and Potable Reuse: Energy and Life Cycle Considerations.

Anaerobic secondary treatment has the potential to facilitate energy-positive operations at wastewater treatment plants, but post-treatment of the anaerobic effluent is needed to recover dissolved methane and nutrients and remove sulfide. In this study, a life cycle assessment was conducted to compare hypothetical full-scale wastewater treatment trains and direct potable reuse trains that combine the staged anaerobic fluidized membrane bioreactor (SAF-MBR) with appropriate post-treatment. We found that anaerobic wastewater treatment trains typically consumed less energy than conventional aerobic treatment, but overall global warming potentials were not significantly different. Generally, recovery of dissolved methane for energy production resulted in lower life cycle impacts than microbial transformation of methane, and microbial oxidation of sulfide resulted in lower environmental impacts than chemical precipitation. Use of reverse osmosis to produce potable water was also found to be a sustainable method for nutrient removal because direct potable reuse trains with the SAF-MBR consumed less energy and had lower life cycle impacts than activated sludge. Moving forward, dissolved methane recovery, reduced chemical usage, and investments that enable direct potable reuse have been flagged as key research areas for further investigation of anaerobic secondary treatment options.

"Pseudo"-Secondary Treatment Failure Explained via Disease Progression and Effective Botulinum Toxin Therapy: A Pilot Simulation Study.

BACKGROUND: The objective of this study was to provide evidence from a simple simulation. In patients with focal dystonia, an initial good response to botulinum neurotoxin (BoNT) injections followed by a secondary worsening does not necessarily arise from an antibody-induced secondary treatment failure (NAB-STF), but may stem from a "pseudo"-secondary treatment failure (PSEUDO-STF). METHODS: The simulation of the outcome after BoNT long-term treatment was performed in four steps: 1. The effect of the first single BoNT injection (SI curve) was displayed as a 12-point graph, corresponding to the mean improvement from weeks 1 to 12. 2. The remaining severity of the dystonia during the nth injection cycle was calculated by subtracting the SI curve (weighted by the outcome after n - 1 cycles) from the outcome after week 12 of the (n - 1)th cycle. 3. A graph was chosen (the PRO curve), which represents the progression of the severity of the underlying disease during BoNT therapy. 4. The interaction between the outcome during the nth BoNT cycle and the PRO curve was determined. RESULTS: When the long-term outcome after n cycles of BoNT injections (applied every 3 months) was simulated as an interactive process, subtracting the effect of the first cycle (weighted by the outcome after n - 1 cycles) and adding the progression of the disease, an initial good improvement followed by secondary worsening results. This long-term outcome depends on the steepness of the progression and the duration of action of the first injection cycle. We termed this response behavior a "pseudo"-secondary treatment failure, as it can be compensated via a dose increase. CONCLUSION: A secondary worsening following an initial good response in BoNT therapy of focal dystonia might not necessarily indicate neutralizing antibody induction but could stem from a "PSEUDO"-STF (a combination of good response behavior and progression of the underlying disease). Thus, an adequate dose adaptation must be conducted before diagnosing a secondary treatment failure in the strict sense.

Abundance, characterization, and removal of microplastics in different technology-based sewage treatment plants discharging into the middle stretch of the Ganga River, India.

Sewage treatment plants (STPs) are considered as a prominent source for releasing microplastics (MPs) into the riverine systems. Though MPs abundance and removal efficacy in different secondary treatment technique-based STPs have been extensively studied worldwide, such studies are scarce in Indian conditions. Herein, this study comprehensively assesses MPs abundance, characterization, and their removal in the selected secondary treatment technique-based STPs discharging into the middle stretch of the Ganga River in India. MPs concentration (n/L) in influent and effluent of the STPs varied between 42 ± 10 to 150 ± 19 and 3 ± 1 to 22 ± 5, respectively. Overall, the primary treatment stage was observed to remove MPs by 23-42 %, while the secondary treatment stage removed MPs by 67-90 %. Selected technique-based STPs exhibited varying MPs removal efficacies as follows: SBR (94 %), TF (90 %), AL (88 %), UASB (87 %), ASP (85 %), FAB (84 %), and Bio-tower (77 %). MPs ranging from 50 to 250 µm were the dominant sizes, with PP, PE, and PS being the prevalent polymers. The Ganga River receives about 3 × 108 MPs/day from STP effluents, and an estimated 4.5 × 107 MPs/day are released via the sludge. This comprehensive assessment of MPs abundance and removal from different technology-based Indian STPs will allow the comparison of the generated dataset with similar studies worldwide.

Lessons about Botulinum Toxin A Therapy from Cervical Dystonia Patients Drawing the Course of Disease: A Pilot Study.

AIM OF THE STUDY: To compare the course of severity of cervical dystonia (CD) before and after long-term botulinum toxin (BoNT) therapy to detect indicators for a good or poor clinical outcome. PATIENTS AND METHODS: A total of 74 outpatients with idiopathic CD who were continuously treated with BoNT and who had received at least three injections were consecutively recruited. Patients had to draw the course of severity of CD from the onset of symptoms until the onset of BoNT therapy (CoDB graph), and from the onset of BoNT therapy until the day of recruitment (CoDA graph) when they received their last BoNT injection. Mean duration of treatment was 9.6 years. Three main types of CoDB and four main types of CoDA graphs could be distinguished. The demographic and treatment-related data of the patients were extracted from the patients' charts. RESULTS: The best outcome was observed in those patients who had experienced a clear, rapid response in the beginning. These patients had been treated with the lowest doses and with a low number of BoNT preparation switches. The worst outcome was observed in those 17 patients who had drawn a good initial improvement, followed by a secondary worsening. These secondary nonresponders had been treated with the highest initial and actual doses and with frequent BoNT preparation switches. A total of 12 patients were primary nonresponders and did not experience any improvement at all. No relation between the CoDB and CoDA graphs could be detected. Primary and secondary nonresponses were observed for all three CoDB types. The use of initial high doses as a relevant risk factor for the later development of a secondary nonresponse was confirmed. CONCLUSIONS: Patients' drawings of their course of disease severity helps to easily detect "difficult to treat" primary and secondary nonresponders to BoNT on the one hand, but also to detect "golden responders" on the other hand.

No Secondary Treatment Failure during Incobotulinumtoxin-A Long-Term Treatment Demonstrated by the Drawing of Disease Severity.

The aim of this study was to detect clinical hints regarding the development of secondary treatment failure (STF) in patients with focal dystonia who were exclusively treated with incobotulinumtoxin/A (incoBoNT/A). In total, 33 outpatients (26 with idiopathic cervical dystonia, 4 with Meige syndrome and 3 with other cranial dystonia) who were treated with repeated injections of incoBoNT/A for a mean period of 6.4 years without interruptions were recruited to draw the course of their disease severity (CoD) from the onset of symptoms to the onset of BoNT therapy (CoDB graph) and from the onset of BoNT therapy to recruitment (CoDA graph). At the time of recruitment, the patients assessed the change in severity as a percentage of the severity at the onset of BoNT therapy. Blood samples were taken to test the presence of neutralizing antibodies (NABs) using the mouse hemidiaphragm assay (MHDA). Patients reported an improvement of about 70% with respect to the mean. None of the patients tested positive for MHDA. Three different types of CoDB and three different types of CoDA graphs could be distinguished. The patients with different CoDB graphs reported different long-term outcomes, but there was no significant difference in long-term outcomes between patients with different CoDA graphs. None of the patients produced a CoDA graph with an initial improvement and a secondary worsening as a hint for the development of STF. A primary non-response was not observed in any of the patients. During long-term treatment with BoNT/A, NABs and/or STF may develop. However, in the present study on patients with incoBoNT/A long-term monotherapy, no hints for the development of NABs or STF could be detected, underlining the low antigenicity of incoBoNT/A.

Microwave ablation as a primary versus secondary treatment for hepatocellular carcinoma

PURPOSE: The purpose of this study was to analyze and compare the outcomes of percutaneous microwave ablation (MWA) when used as a primary vs. secondary treatment for hepatocellular carcinoma (HCC). METHODS: The clinical data of 192 patients with HCC treated with MWA between January 2012 and July 2021 were reviewed retrospectively, with 152 patients being treatment naïve (primary treatment) vs. 40 who had residual or recurrent disease following previous trans-arterial chemoembolization or trans-arterial radioembolization (secondary treatment). The primary outcomes were primary technical efficacy, 1- and 3-year local recurrence-free survival (RFS) and overall survival (OS), local recurrence rates, and adverse events. Pre- and post-intervention liver function tests were compared using a Wilcoxon signed rank test. Univariate and multivariate analyses were also performed, looking at prognostic factors associated with OS and local RFS. RESULTS: There was no significant difference in 1-year local RFS (primary 93.6% vs. secondary 93.7; P = 0.97) and 3-year local RFS (primary 80.6% vs. secondary 86.5%; P = 0.37) rates. There was no significant difference in 1-year OS (primary 82.4% vs. secondary 86.6%; P = 0.51) and 3-year OS (primary 68.3% vs. secondary 77.4%; P = 0.25) between the two groups. The local recurrence rate (primary 9.8% vs. secondary 14.6%; P = 0.37), primary technical efficacy (primary 96.2% vs. secondary 95%; P = 0.73), and adverse events (primary 8.0% vs. secondary 11.6%; P = 0.45) were also similar between the two groups. CONCLUSION: Microwave ablation is safe and effective as a secondary treatment for patients with HCC in a clinical salvage scenario and should be utilized more frequently.

Performance assessment of a modified trickling filter and conventional activated sludge process along with tertiary treatment in removing emerging pollutants from urban sewage.

The absence of effective wastewater treatment technology to eliminate emerging pollutants from municipal sewage has become a pressing issue. In this study, the efficacy of a novel modified trickling filter (MTF), conventional activated sludge process (ASP) and two tertiary systems (UV and ozonation) were compared in eliminating antibiotic-resistant bacteria (ARB), antibiotic resistance genes (ARGs) and pharmaceuticals and personal care products (PPCPs) from urban sewage. MTF and ASP resulted in >1 log unit reduction in the abundance of ARB, while for ARGs, the removal was observed in the range of 0.1 to 1.7 log units. In MTF, ARGs were substantially removed in the aerobic zone compared to the anoxic zone. The relative abundance of most of the ARGs either decreased or remained unchanged during MTF and ASP operations. However, the relative abundance of most of the ARGs increased in the secondary sludge generated from ASP. The concentration of PPCPs such as atenolol, sulfamethazine, triclosan, and ranitidine was reduced by MTF by >80 %. Overall, the results indicated that MTF followed by ozonation is the most effective combination for removing emerging contaminants from municipal sewage.

Outcome and characteristics of patients with adult grade 4 diffuse gliomas changing sites of treatment.

PURPOSE: With increasing patient self-empowerment and participation in decision making, we hypothesized that patients with adult-type diffuse gliomas, CNS WHO grade 4 who change sites of treatment differ from patients being entirely treated in one neuro-oncological center. METHODS: Prospectively collected data from all diffuse glioma grade 4 patients who underwent treatment in our neuro-oncological center between 2012 and 2018 were retrospectively examined for differences between patients having initially been diagnosed and/or treated elsewhere (External Group) and patients having entirely been treated in our neuro-oncological center (Internal Group). Additionally, a matched-pair analysis was performed to adjust for possible confounders. RESULTS: A total of 616 patients was analyzed. Patients from the External Group (n = 78) were significantly younger, more frequently suffered from IDH-mutant astrocytoma grade 4, had a greater extent of tumor resection, more frequently underwent adjuvant therapy and experienced longer overall survival (all p < 0.001). However, after matching these patients to patients of the Internal Group considering IDH mutations, extent of resection, adjuvant therapy, age and gender, no difference in patients' overall survival was observed anymore. CONCLUSION: The present study demonstrates that mobile diffuse glioma grade 4 patients stand out from a comprehensive diffuse glioma grade 4 patient cohort due to their favorable prognostic characteristics. However, changing treatment sites did not result in survival benefit over similar patients being entirely taken care of within one neuro-oncological institution. These results underline the importance of treatment and molecular markers in glioma disease for patients' self-empowerment, including changing treatment sites according to patients' needs and wishes.

A cluster-randomized trial comparing home-based primary health care and usual clinic care for epilepsy in a resource-limited country.

OBJECTIVE: To ascertain whether home-based care with community and primary healthcare workers' support improves adherence to antiseizure medications, seizure control, and quality of life over routine clinic-based care in community samples of people with epilepsy in a resource-poor country. METHODS: Participants included consenting individuals with active epilepsy identified in a population survey in impoverished communities. The intervention included antiseizure medication provision, adherence reinforcement and epilepsy self- and stigma management guidance provided by a primary health care-equivalent worker. We compared the intervention group to a routine clinic-based care group in a cluster-randomized trial lasting 24 months. The primary outcome was antiseizure medication adherence, appraised from monthly pill counts. Seizure outcomes were assessed by monthly seizure aggregates and time to first seizure and impact by the Personal Impact of Epilepsy scale. RESULTS: Enrolment began on September 25, 2017 and was complete by July 24, 2018. Twenty-four clusters, each comprising ten people with epilepsy, were randomized to either home- or clinic-care. Home-care recipients were more likely to have used up their monthly-dispensed epilepsy medicine stock (regression coefficient: 0.585; 95% confidence intervals, 0.289-0.881; P = 0.001) and had fewer seizures (regression coefficient: -2.060; 95%CI, -3.335 to -0.785; P = 0.002). More people from clinic-care (n = 44; 37%) than home-care (n = 23; 19%) exited the trial (P = 0.003). The time to first seizure, adverse effects and the personal impact of epilepsy were similar in the two arms. SIGNIFICANCE: Home care for epilepsy compared to clinic care in resource-limited communities improves medication adherence and seizure outcomes and reduces the secondary epilepsy treatment gap.

The complex relationship between antibody titers and clinical outcome in botulinum toxin type A long-term treated patients with cervical dystonia.

BACKGROUND: Repeated injections with abo- or onabotulinumtoxin type A (aboBoNT/A, onaBoNT/A) may lead to induction of neutralizing antibodies (NABs) and/or a secondary treatment failure (STF). The relation between NABs and STF is still unclear. AIM OF THE STUDY: To demonstrate that a significant improvement can be observed in patients with STF after abo- or onaBoNT/A-treatment when switched to incobotulinumtoxin type A (incoBoNT/A) and that in NAB-positive patients without STF abo- or onaBoNT/A-treatment can be continued without significant worsening. METHODS: Paralysis times (PT) of the mouse hemidiaphragm assay (MHDA) and clinical outcome (TSUI-score) was analyzed in 60 patients with cervical dystonia (CD) and STF after abo- or onaBoNT/A-treatment (STF-group) who were switched to incobotulinumtoxin type A (incoBoNT/A). These data were compared to those of 34 patients who were exclusively treated with incoBoNT/A (INCO-group). Furthermore, PTs and TSUI-scores were followed up over 7 years in 9 patients with NABs but without STF who were switched to inco-BoNT/A (SWI-group) and 9 other patients with NABs who remained on their previous BoNT/A preparation (NO-SWI-group). RESULTS: In the STF-group, a significant improvement of TSUI-scores could be detected after switch to incoBoNT/A. This improvement was less pronounced than in the INCO-group. There was no significant difference in long-term outcome between the SWI- and NO-SWI-group. CONCLUSION: The best strategy is to avoid the induction of NABs. A switch to incoBoNT/A may lead to improvement in patients with STF. However, in some patients with NABs without STF, BoNT/A-treatment can be continued without significant worsening.

The Use of High Initial Doses of Botulinum Toxin Therapy for Cervical Dystonia Is a Risk Factor for Neutralizing Antibody Formation-A Monocentric Cross-Sectional Pilot Study.

Background and Objectives: The present study aims to analyze the complex patient/treating physician interaction at onset of botulinum toxin (BoNT) therapy in patients with idiopathic cervical dystonia (CD) and the influence of high initial doses on long-term outcomes. Materials and Methods: A total of 74 CD patients with well-documented courses of BoNT treatment were consecutively recruited after written informed consent. Patients had to rate the amount of improvement of CD in percent of severity of CD at onset of BoNT therapy. They had to draw the course of disease severity (CoD) of CD from the onset of symptoms until the onset of BoNT therapy and from the onset of BoNT therapy until recruitment. The remaining severity of CD was estimated by the treating physician using the TSUI score. Demographic- and treatment-related data were extracted from the charts of the patients. Seventeen patients with suspected secondary treatment failure (STF) were tested for the presence of antibodies. Results: Depending on the CoD before BoNT therapy, three patient subgroups could be distinguished: rapid onset, continuous onset and delayed onset groups. Time to BoNT therapy, increase in dose and improvement were significantly different between these three groups. In the rapid onset group, with the highest initial doses, the best improvement was reported, but the highest number of patients with an STF and with neutralizing antibodies was also observed. Conclusion: The use of high initial doses in the BoNT therapy of CD is associated with a rapid response and quick success; however, it leads to an elevated risk for the development of a secondary treatment failure and induction of neutralizing antibodies.

Significant Long-Lasting Improvement after Switch to Incobotulinum Toxin in Cervical Dystonia Patients with Secondary Treatment Failure.

Under continuous long-term treatment with abo- or onabotulinum toxin type A (BoNT/A), ~10 to 15% of patients with cervical dystonia (CD) will develop neutralizing antibodies and reduced responsiveness over an ~10-year treatment period. Among the botulinum neurotoxin type A preparations so far licensed for CD, incobotulinum toxin A (incoBoNT/A; Xeomin®) is the only one without complex proteins. Whether CD patients with treatment failure under abo- or onaBoNT/A may still respond to incoBoNT/A is unknown. In this cross-sectional, retrospective study, 64 CD patients with secondary treatment failure after abo- or onaBoNT/A therapy who were switched to incoBoNT/A were compared to 34 CD patients exclusively treated with incoBoNT/A. The initial clinical severity of CD, best outcome during abo- or onaBoNT/A therapy, severity at the time of switching to incoBoNT/A and severity at recruitment, as well as all corresponding doses, were analyzed. Furthermore, the impact of neutralizing antibodies (NABs) on the long-term outcome of incoBoNT/A therapy was evaluated. Patients significantly improved after the switch to incoBoNT/A (p < 0.001) but did not reach the improvement level obtained before the development of partial secondary treatment failure or that of patients who were exclusively treated with incoBoNT/A. No difference between abo- and onaBoNT/A pretreatments or between the long-term outcomes of NAB-positive and NAB-negative patients was found. The present study demonstrates significant long-term improvement after a switch to incoBoNT/A in patients with preceding secondary treatment failure after abo- or onaBoNT/A therapy and confirms the low antigenicity of incoBoNT/A.

Removal efficiency of organic micropollutants in successive wastewater treatment steps in a full-scale wastewater treatment plant: Bench-scale application of tertiary treatment processes to improve removal of organic micropollutants persisting after secondary treatment.

The goal of this study was to investigate the occurrence and removal of 52 organic micropollutants (OMPs) during each wastewater treatment step in a full-scale wastewater treatment plant (WWTP). Pharmaceuticals such as metformin, acetaminophen, caffeine, ibuprofen, cimetidine and naproxen were found with high average concentrations in the influent. Most OMPs were not affected by the primary treatment (removal <10%), while secondary biological treatment contributed the most to overall removal of the OMPs. Among the three lanes of the secondary treatment of the WWTP, a combined anaerobic-anoxic-oxic process followed by a membrane bioreactor (A2O-MBR) process effectively facilitated removal of the OMPs (96%) using a different redox: a conventional activated sludge (CAS) process exhibited removal of approximately 85% of total concentrations of the OMPs, while a Modified Ludzack-Ettinger (MLE) process achieved approximately 92.1% removal. Removal of more than 50% of the concentrations of 13 targeted OMPs was observed in the secondary effluent (except for metformin showing only 3.8% removal) via adsorption with powdered activated carbon (PAC) as additional tertiary treatment. Metformin, inadequately removed by additional tertiary treatments, was effectively removed by a biological activated carbon (BAC) process, reaching a removal efficiency of 90.5%. To increase the removal of the amounts and types of OMPs with various physico-chemical properties, hybrid processes through a combination of diverse advanced treatment should be tailored to WWTPs.

Sustainability assessment of wastewater treatment systems using cardinal weights and PROMETHEE method: case study of Morocco.

To cope with water scarcity, Morocco needs to integrate the reuse of treated wastewater fully into its water management strategies. However, this option imposes several concerns about the appropriate wastewater treatment system (WWTS) whose performance is balanced by technical, environmental, financial, and societal sustainability. To deal with these challenges, the present study aims to assess the sustainability of five WWTS using the cardinal (CAR) and PROMETHEE methods. After hierarchizing the criteria and identifying the WWTS, two separate surveys were performed in order to rank criteria and alternatives by preference strength. The delivered rankings were converted, then, respectively into cardinal weights (criteria) and cardinal scores (alternatives). The PROMETHEE rankings showed that the membrane systems are the most sustainable followed by trickling filters, while the infiltration-percolation is the least sustainable WWTS. The activated sludge and lagoon systems were incomparable using PROMETHEE I partial ranking, and they were both ranked in the third position of sustainability. In contrast, PROMETHEE II complete ranking favored the activated sludge than lagoon systems due to its slightly high net outranking flow. The stability intervals indicated that the weights of all criteria could not affect the two first actions, which is mainly due to the high precision and robustness of the CAR method in eliciting weights. Finally, each criterion affected variably the sustainability of WWTS according to their characteristics, but overall, the process efficiency is the key factor (21.07% of weight) to reaching higher sustainability levels in addition to gaseous emissions (12.41% of weight), flexibility (8.32% of weight), and energy requirement (7.50% of weight).

Outcomes of Bone Marrow Stimulation for Secondary Osteochondral Lesions of the Talus Equal Outcomes for Primary Lesions.

OBJECTIVE: To compare clinical, sports, work, and radiological outcomes between primary and secondary osteochondral lesions of the talus (OLTs; <15 mm) treated with arthroscopic bone marrow stimulation (BMS). DESIGN: Secondary OLTs were matched to primary OLTs in a 1:2 ratio to assess the primary outcome measure-the Numeric Rating Scale (NRS) during activities. Secondary outcomes included the pre- and 1-year postoperative NRS at rest, American Orthopaedic Foot and Ankle Society score, Foot and Ankle Outcome Score subscales, and the EQ-5D general health questionnaire. The rates and time to return to work and sports were collected. Radiological examinations were performed preoperatively and at final follow-up using computed tomography (CT). RESULTS: After matching, 22 and 12 patients with small (<15 mm) OLTs were included in the primary and secondary groups, respectively. The NRS during activities was not different between primary cases (median: 2, interquartile range [IQR]: 1-4.5) and secondary cases (median: 3, IQR: 1-4), P = 0.5. Both groups showed a significant difference between all pre- and postoperative clinical outcome scores, but no significant difference between BMS groups postoperatively. The return to sport rate was 90% for primary cases and 83% for secondary cases (P = 0.6). All patients returned to work. Lesion filling on CT was complete (67% to 100%) in 59% of primary cases and 67% of secondary cases (P = 0.6). CONCLUSION: No differences in outcomes were observed between arthroscopic bone marrow stimulation in primary and secondary OLTs at 1-year follow-up. Repeat BMS may therefore be a viable treatment option for failed OLTs in the short term.

The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis.

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank p = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633-1.799, p = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.