Sequential Treatment Approach Research Articles

Optimizing bacteriophage treatment of resistant Pseudomonas.

Phage therapy is increasing in relevance as an alternative treatment to combat antibiotic resistant bacteria. Phage cocktails are the state-of-the-art method of administering phages in clinical settings, preferred over monophage treatment because of their ability to eliminate multiple bacterial strains and reduce resistance formation. In our study, we compare monophage applications and phage cocktails to our chosen method of phage sequential treatments. To do so, we isolated four novel bacteriophages capable of infecting Pseudomonas alcaligenes T3, a close relative of P. aeruginosa, and characterized them using sequencing and transmission electron microscopy. While investigating monophage treatments, we observed that different phage concentrations had a strong impact on the timing and amount of resistance formation. When using phage cocktails, we observed that P. alcaligenes were capable of forming resistance in the same timespan it took them to become resistant to single phages. We isolated mutants resistant to each single phage as well as mutants exposed to phage cocktails, resulting in bacteria resistant to all four phages at once. Sequencing these mutants showed that different treatments yielded unique single nucleotide polymorphism mutation patterns. In order to combat resistance formation, we added phages one by one in intervals of 24 h, thus managing to delay resistance development and keeping bacterial growth significantly lower compared to phage cocktails.IMPORTANCEWHO declared antimicrobial resistance a top threat to global health; while antibiotics have stood at the forefront in the fight against bacterial infection, the increasing number of multidrug-resistant bacteria highlights a need to branch out in order to address the threat of antimicrobial resistance. Bacteriophages, viruses solely infecting bacteria, could present a solution due to their abundance, versatility, and adaptability. For this study, we isolated new phages infecting a fast-mutating Pseudomonas alcaligenes strain capable of forming resistance within 30 h. By using a sequential treatment approach of adding one phage after another, we were able to curb bacterial growth significantly more compared to state-of-the-art phage cocktails.

Comparison of the efficacy of immunotherapy at different time points during the perioperative period for stage II-III NSCLC.

e20009 Background: The application of immune checkpoint inhibitors (ICIs) in early-stage lung cancer is fraught with unresolved issues, and there are no clinical studies directly comparing the efficacy of ICIs used in neoadjuvant, adjuvant, and neoadjuvant followed by adjuvant therapy across different perioperative time points in non-small cell lung cancer (NSCLC). Consequently, the optimal timing for immunotherapy in surgically resectable NSCLC remains uncertain. Methods: This study encompassed 536 patients with stage II-III NSCLC, diagnosed and treated across multiple centers from January 2019 to December 2022. Clinical data for all patients ultimately included in the study were retrospectively collected. The primary endpoints evaluated were event-free survival (EFS)/disease-free survival (DFS) and overall survival (OS) . Secondary endpoints included pathological complete response (pCR) and major pathological response (MPR). Propensity score matching was utilized to mitigate confounding factors, comparing the efficacy of ICIs across different treatment modalities and time dimensions during the perioperative period of lung cancer. Results: The integration of neoadjuvant ICIs with chemotherapy was observed to significantly enhance pCR ( p < 0.001), MPR ( p < 0.001), EFS ( p = 0.002), and OS ( p < 0.001) in comparison to neoadjuvant chemotherapy alone. Similarly, the combination of adjuvant ICIs with chemotherapy markedly improved DFS ( p = 0.034) and OS ( p = 0.021) relative to adjuvant chemotherapy alone. Building on these insights, we further delineated the efficacy of ICIs across distinct temporal dimensions within the perioperative interval, categorizing patients into three groups: neoadjuvant ICIs plus chemotherapy, adjuvant ICIs plus chemotherapy, and a sequential regimen of neoadjuvant followed by adjuvant ICIs plus chemotherapy. The analysis revealed no significant differences in DFS and OS among the three patient groups for stage II NSCLC. In contrast, for stage III NSCLC, both neoadjuvant ( p = 0.015) and sequential treatment approaches ( p = 0.047) demonstrated significantly improved DFS outcomes compared to the adjuvant protocol, with no substantial statistical difference noted between the neoadjuvant and sequential treatments ( p = 0.274). Furthermore, the sequential regimen outperformed the adjuvant strategy in OS ( p = 0.020). However, when comparing the neoadjuvant strategy with either the adjuvant ( p = 0.054) or sequential approaches ( p = 0.717), there were no statistically significant variances detected. Conclusions: For individuals with resectable stage III NSCLC, perioperative administration of neoadjuvant and sequential adjuvant ICIs appears to confer enhanced survival advantages. Future efforts should focus on refining treatment strategies for early-stage NSCLC, aiming to deliver enhanced survival benefits to patients.

Overall Survival From the EORTC LCG-1613 APPLE Trial of Osimertinib Versus Gefitinib Followed by Osimertinib in Advanced EGFR-Mutant Non-Small-Cell Lung Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Osimertinib has been established as a standard of care for patients with common sensitizing EGFR-mutant advanced non-small-cell lung cancer (NSCLC) although the sequential approach (first-generation inhibitor gefitinib followed by osimertinib) has not been formally compared. The phase II APPLE trial (ClinicalTrials.gov identifier: NCT02856893) enrolled 156 treatment-naïve patients, and two treatment strategies were evaluated: osimertinib up front or the sequential treatment approach with gefitinib up front followed by osimertinib at the time of progression, either molecular progression (detection of plasma T790M resistance mutation) regardless of the radiologic status or just at the time of radiologic progression. Patients' characteristics were well balanced, except for the higher proportion of baseline brain metastases in the sequential approach (29% v 19%). Per protocol, 73% of patients switched to osimertinib in the sequential arm. Up-front treatment with osimertinib was associated with a lower risk of brain progression versus the sequential approach (hazard ratio [HR], 0.54 [90% CI, 0.34 to 0.86]), but a comparable overall survival was observed between both strategies (HR, 1.01 [90% CI, 0.61 to 1.68]), with the 18-month survival probability of 84% and 82.3%, respectively. The APPLE trial suggests that a sequential treatment approach is associated with more frequent progression in the brain but a similar survival in advanced EGFR-mutant NSCLC.

Efficacy of High-dose Liraglutide 3.0 mg in Patients with Poor Response to Bariatric Surgery: Real-world Experience and Updated Meta-analysis

PurposePoor response to bariatric surgery, characterized by insufficient weight loss (IWL) or weight regain (WR), poses a significant challenge in obesity treatment. This study aims to assess the effectiveness of liraglutide in addressing this issue.Materials and MethodsA retrospective, multicenter cohort study investigated the impact of liraglutide 3 mg on weight loss in adults with suboptimal responses or weight regain after bariatric surgery (BS). Additionally, a systematic review and meta-analysis were conducted for a comprehensive evaluation.ResultsA total of 119 patients (mean age 41.03 ± 11.2 years, 71.4% female) who experienced IWL or WR after BS received pharmacologic therapy with liraglutide 3 mg. Mean percent weight loss in the entire cohort was 5.6 ± 2.6% at 12 weeks and 9.3 ± 3.6% at 24 weeks with a significant reduction in waist circumference (p < 0.0001). No serious side effects were reported. A meta-analysis, utilizing the fixed effect model with the metafor package in R, included 6 and 5 papers for the change in body weight and BMI after liraglutide treatment, respectively. The analysis demonstrated a considerable reduction in body weight (7.9; CI − 10.4; − 5.4, p < 0.0001) and BMI (3.09; CI 3.89; − 2.28, p < 0.0001).ConclusionLiraglutide 3 mg emerges as a viable option for significant weight loss in patients experiencing IWL or WR after BS. Its inclusion in a multimodal, sequential obesity treatment approach proves promising.Graphical

Harnessing the potential of white rot fungi and ligninolytic enzymes for efficient textile dye degradation: A comprehensive review.

The contamination of wastewater with textile dyes has emerged as a pressing environmental concern due to its persistent nature and harmful effects on ecosystems. Conventional dye treatment methods have proven inadequate in effectively breaking down complex dye molecules. However, a promising alternative for textile dye degradation lies in the utilization of white rot fungi, renowned for their remarkable lignin-degrading capabilities. This review provides a comprehensive analysis of the potential of white rot fungi in degrading textile dyes, with a particular focus on their ligninolytic enzymes, specifically examining the roles of lignin peroxidase (LiP), manganese peroxidase (MnP), and laccase in the degradation of lignin and their applications in textile dye degradation. The primary objective of this paper is to elucidate the enzymatic mechanisms involved in dye degradation, with a spotlight on recent research advancements in this field. Additionally, the review explores factors influencing enzyme production, including culture conditions and genetic engineering approaches. The challenges associated with implementing white rot fungi and their ligninolytic enzymes in textile dye degradation processes are also thoroughly examined. Textile dye contamination poses a significant environmental threat due to its resistance to conventional treatment methods. White rot fungi, known for their ligninolytic capabilities, offer an innovative approach to address this issue. The review delves into the intricate mechanisms through which white rot fungi and their enzymes, including LiP, MnP, and laccase, break down complex dye molecules. These enzymes play a pivotal role in lignin degradation, a process that can be adapted for textile dye removal. The review also emphasizes recent developments in this field, shedding light on the latest findings and innovations. It discusses how culture conditions and genetic engineering techniques can influence the production of these crucial enzymes, potentially enhancing their efficiency in textile dye degradation. This highlights the potential for tailored enzyme production to address specific dye contaminants effectively. The paper also confronts the challenges associated with integrating white rot fungi and their ligninolytic enzymes into practical textile dye degradation processes. These challenges encompass issues like scalability, cost-effectiveness, and regulatory hurdles. By acknowledging these obstacles, the review aims to pave the way for practical and sustainable applications of white rot fungi in wastewater treatment. In conclusion, this comprehensive review offers valuable insights into how white rot fungi and their ligninolytic enzymes can provide a sustainable solution to the urgent problem of textile dye-contaminated wastewater. It underscores the enzymatic mechanisms at play, recent research breakthroughs, and the potential of genetic engineering to optimize enzyme production. By addressing the challenges of implementation, this review contributes to the ongoing efforts to mitigate the environmental impact of textile dye pollution. PRACTITIONER POINTS: Ligninolytic enzymes from white rot fungi, like LiP, MnP, and laccase, are crucial for degrading textile dyes. Different dyes and enzymatic mechanisms is vital for effective wastewater treatment. Combine white rot fungi-based strategies with mediator systems, co-culturing, or sequential treatment approaches to enhance overall degradation efficiency. Emphasize the broader environmental impact of textile dye pollution and position white rot fungi as a promising avenue for contributing to mitigation efforts. This aligns with the overarching goal of sustainable wastewater treatment practices and environmental conservation. Consider scalability, cost-effectiveness, and regulatory compliance to pave the way for sustainable applications that can effectively mitigate the environmental impact of textile dye pollution.

The Sequential Therapy in Osteoporosis.

Osteoporosis management often involves a sequential treatment approach to optimize patient outcomes and minimize fracture risks. This strategy is tailored to individual patient characteristics, treatment responses, and fracture risk profiles. A thorough literature review was systematically executed using prominent databases, including PubMed and EMBASE. The primary aim was to identify original articles and clinical trials evaluating the effectiveness of sequential therapy with anti-osteoporosis drugs, focusing on the period from 1995 to 2023. The analysis encompassed an in-depth examination of osteoporosis drugs, delineating their mechanisms of action, side effects, and current trends as elucidated in the literature. Our study yielded noteworthy insights into the optimal sequencing of pharmacologic agents for the long-term treatment of patients necessitating multiple drugs. Notably, the achievement of optimal improvements in bone mass is observed when commencing treatment with an anabolic medication, followed by the subsequent utilization of an antiresorptive drug. This stands in contrast to initiating therapy with a bisphosphonate, which may potentially diminish outcomes in the post-anabolic intervention period. Furthermore, it has been discerned that caution should be exercised against transitioning from denosumab to PTH homologs due to the adverse effects of heightened bone turnover and sustained weakening of bone structure. Despite the absence of fracture data substantiating the implementation of integrated anabolic/antiresorptive pharmacotherapy, the incorporation of denosumab and teriparatide presents a potential avenue worthy of consideration for individuals at a heightened vulnerability to fragility fractures. A judiciously implemented sequential treatment strategy in osteoporosis offers a flexible and tailored approach to address diverse clinical scenarios, optimizing fracture prevention and patient outcomes.

Comparative efficacy of sequential treatment and open abdomen approaches for corrosive abdominal hemorrhage due to inadequate drainage of duodenal leakage: a cohort study.

Intra-abdominal bleeding resulting from inadequate drainage of duodenal leakage (DL) is typically caused by the corrosiveness of duodenal fluid. Open abdomen (OA) treatment addresses both the drainage and bleeding simultaneously. However, a sequential treatment (ST) approach involving hemostasis through transcatheter arterial embolization (TAE) followed by percutaneous drainage of source control has emerged as an alternative method. This study aimed to evaluate the prognosis of ST in cases of DL-induced intra-abdominal bleeding. This retrospective cohort study included 151 participants diagnosed with DL-induced intra-abdominal bleeding from January 2004 to December 2010, and January 2013 to December 2021. The ST and OA groups were established based on the treatment method applied. Propensity score-matching (PSM) matched patients in the ST group with those in the OA group. Among the 151 patients, 61 (40.4%) died within 90days after the bleeding episode. ST was associated with a lower mortality rate (28.2% vs. 51.3% adjusted odds ratio [OR] = 0.34; 95% confidence interval [CI] 0.17-0.68; P = 0.003) compared to OA. Following PSM, ST remained the only factor associated with reduced mortality (OR = 0.32; 95% CI 0.13-0.75; P = 0.009). Moreover, ST demonstrated a higher rate of initial hemostasis success before (90.1% [64/71] vs. 77.5% [62/80]; adjusted OR = 2.84; 95% CI 1.07-7.60; P = 0.04) and after PSM (94.4% [51/54] vs. 77.8% [42/54], adjusted OR = 3.85; 95% CI 2.15-16.82; P = 0.04). Additionally, ST was associated with a lower incidence of rebleeding within 90days after the initial bleeding, before (7 vs. 23; adjusted OR 0.41; 95% CI 0.18-0.92; P = 0.03) and after PSM (5 vs. 14; adjusted OR 0.37; 95% CI 0.15-0.93; P = 0.03). Applying ST involving TAE and subsequent percutaneous drainage might be superior to OA in lowering the mortality in DL-induced intra-abdominal hemorrhage.

Time-Limited Maintenance with Ibrutinib after First-Line Therapy and the Incremental Impact on Minimal Residual Disease (MRD) for Patients with Chronic Lymphocytic Leukemia (CLL)

Background: Inhibitors of Bruton's tyrosine kinase (BTKi) are approved and clinically used as indefinite treatments (until disease progression) irrespective of the depth of response in patients (pts) with CLL. Despite impressive, sustained efficacy, their ability (as single agent) to target residual disease clone post induction treatment in CLL is not well established. As indefinite treatment is associated not only with cumulative toxicity but also high cost and compromised quality of life, we investigated the benefit of time-limited maintenance treatment (3 years) with ibrutinib to assess the ability of a BTKi to further deepen antitumor response achieved post induction treatment. Methods: CLL pts (n=35) who had residual disease (by clinical or molecular assessment) after primary induction treatment were enrolled on a prospective phase 2 trial (NCT02649387). MRD assessed in blood (PB)/bone marrow (BM), was determined by 8-color flowcytometry (1x10-4) and defined as ≥1 CLL cell per 10,000 leukocytes or ≥0.01%. Patient were eligible if they had detectable residual (non-progressive) disease within 1 year of completing induction and no prior ibrutinib (or other BTKi) treatment. Ibrutinib 420mg PO QD was given on days 1-28 of a 28-day cycle for up to 36 cycles. Clinical (iwCLL 2008 response criteria) and molecule response MRD (on PB) was done at baseline and then every 3 cycles while on treatment. BM-MRD evaluation was conducted only if PB-MRD was negative (on two separate timepoints 3 months apart). Monitoring of the PB-MRD was continued for 24 months after completing time-limited maintenance with ibrutinib. Cumulative toxicity was assessed using the CTCAE v4.0 and iwCLL criteria. Results: Patient characteristics are summarized in Table 1. In 34 out of 35 (97%) patients, obinutuzumab alone was used as induction therapy. The median follow up is 38.6 months (range 0.9-73.2) and the median number of maintenance cycles completed is 34 (range 1-36). Of the 33 patients assessed for PB-MRD, 8 (24.2%) pts became MRD- on at one assessment. Five patients had BM-MRD assessment with 1 (2.8%) converting to MRD-. The median time to achievement of MRD- was 4.4 months (range 2.7-34.7). We noted that single agent ibrutinib was unable to deliver stringent MRD-negativity (defined as achievement of MRD- status both in PB and BM sustained over 2 consecutive evaluations at least 3 months apart).To assess if pre-maintenance response could impact MRD post-treatment; we note that out of the 8 pts that achieved MRD-, 2 (25%) started with CR and 6 (75%) with nPR/PR at registration. Deepening of response was noted in 5 pts (14.3%) after a median of 14 cycles [3 (8.6%) pts improved nPR to CR and 1(2.9%) went from nPR to CRi and 1 (2.9%) went from a CRi to a CR]. Nine patients proceeded to subsequent treatment with the median time to next treatment (mTTNT) of 32.5 m (range: 12.1 - 61.0). One patient died due to a failure to thrive and acute kidney injury on dialysis and six pts have progressed. The median PFS for the entire cohort was 41.1 m (95% CI: 39.8 - NE). The most commonly reported adverse events (AEs) (seen in >10% pts) regardless of attributions were thrombocytopenia (24 pts; 68.6%), anemia (12 pts; 34.3%), neutropenia (9 pts; 25.7%), lymphopenia (9 pts; 25.7%), hypertension (9 pts; 25.7%), leucopenia (6 pts; 17.1%), fatigue (5 pts; 14.3%), headache (4 pts; 11.4%), and skin infections (4 pts; 11.4%). Atrial fibrillation (AFib) was noted in 3 pts (8.6%). Conclusion: We conclude that BTK targeting with ibrutinib alone although able to clear PB-MRD (24.2%), had limited efficacy to eradicate BM-MRD (2.8%) demonstrating a differential impact in these two disease compartments. While the rate of complete MRD eradication was not necessarily high (when compared to recent data with BTKi/BCL2i combination regimens) MRD-kinetics over time demonstrated progressive decrease in disease burden and response improvement with maintenance treatment. The sequential single agent treatment approach was well tolerated, and the time-limited therapy aimed at minimizing cumulative toxicity seemed to be effective in lowering rate of Afib (compared to historical control ~16%). This data warrants further investigation of time-limited maintenance therapy with newer, more favorably tolerated BTKi and/or Bcl2i post induction treatment(s) to optimize response vs. cumulative toxicity. Further evaluation of sequential time-limited treatments in CLL is warranted. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Research on two-step advanced treatment of old landfill leachate by sequential electrochemical peroxidation-electro-Fenton process

Electrochemical technology is an alternative method for the removal of high concentration ammonium-N (NH4+-N) and refractory organics from old landfill leachate (OLL). However, the limited performance of a single electrochemical process and the subsequent long tertiary treatment time to meet the water quality standards are the key technical problems that hinder its practical application. This study demonstrates that the sequential ECP-EF process can realize two-step advanced treatment of OLL. Under the optimal conditions (ECP: j = 30 mA cm−2, initial pH = 9.0; EF: j = 30 mA cm−2, initial pH = 3.5), the removals of COD, TOC, NH4+-N, and TN can be achieved 95.9 ± 0.4 %, 85.1 ± 0.8 %, 99.4 ± 0.1 %, and 99.2 ± 0.1 %, respectively, to meet the first-class standard of integrated wastewater discharge standard of China. The organics in OLL are mainly removed by ECP process and further mineralized or converted to small molecular hydrophobic components in EF process. The sequential ECP-EF process can reduce the aromaticity and complexity of organics, as well as can decrease the acute cytotoxicity (ACT) and hydrophilicity. A proper electrolysis time can effectively avoid the rise of ACT, energy consumption, and cost. The treatment cost ($0.0134 L−1) is approximately 32 % less than the previously reported electrochemical processes of electrocoagulation/electro-Fenton. These findings obtained with real OLL provide a basis for scaling up this new sequential electrochemical treatment approach.

Submental fat reduction using sequential treatment approach with cryolipolysis and ATX-101.

BackgroundSubmental fat (SMF) detracts from facial aesthetics and negatively impacts self‐image.AimsTo evaluate safety, effectiveness, and satisfaction of cryolipolysis and ATX‐101 used sequentially to reduce SMF.MethodsA prospective, open‐label, interventional, single‐site study enrolling 22‐ to 65‐year‐old participants rated as Grade 4 (extreme) on the Clinician‐Rated SMF Rating Scale (CR‐SMFRS). Co‐primary effectiveness endpoints were proportions of participants with ≥1‐grade and ≥2‐grade improvement on CR‐SMFRS at 12 weeks post final treatment. Additional assessments included ultrasound measurement of fat thickness and Subject Self‐Rating Scale (SSRS) scores at 12 weeks post final treatment. Safety was assessed throughout the study.ResultsOf 16 enrolled participants, 62.5% were female, mean age of 43, and mean body mass index of 31.8 kg/m2. 100% of participants achieved ≥1‐grade improvement, and 71.4% achieved ≥2‐grade CR‐SMFRS improvement. Mean (SD) reduction in SMF thickness was 0.2 mm (1.3), and SSRS scores ≥4 (slightly to extremely satisfied) were reported by 71.4% of participants. Adverse events (AEs) were mild and resolved by study end. No unanticipated adverse device effects or serious or unexpected AEs occurred.ConclusionSequential treatment with cryolipolysis and ATX‐101 was found safe and effective for reducing extreme SMF, resulting in approximately a 2‐grade improvement.

From sequential to combination and personalised therapy in lupus nephritis: moving towards a paradigm shift?

The current treatment paradigm in lupus nephritis consists of an initial phase aimed at inducing remission and a subsequent remission maintenance phase. With this so-called sequential treatment approach, complete renal...

Risk-Stratified Sequential Treatment with Ibrutinib and Rituximab (IR) and IR-CHOP for De-Novo Post-Transplant Lymphoproliferative Disorder: Results of the Tidal Trial

Risk-Stratified Sequential Treatment with Ibrutinib and Rituximab (IR) and IR-CHOP for De-Novo Post-Transplant Lymphoproliferative Disorder: Results of the Tidal Trial

Patient-derived lung cancer organoids for the selection of therapeutic options in an ALK-rearranged tumor.

e21014 Background: ALK rearrangements are key targets in non-small-cell lung cancer (NSCLC). Unfortunately, the optimal sequential strategy of ALK-tyrosine kinase inhibitors (TKI) remains to be defined. Testing drug sensitivity in patient derived organoids (PDOs) could support a rational drug selection in this setting. Methods: We designed an observational study assessing the correlation between drug sensitivity of PDOs established in Invitrocue and the clinical outcome in our institution. To date, forty cases have been included, of which nine were lung cancers. Results: PDO was sucessfully established in 7/9 cases (77%). Three patients did not receive any of the drugs tested in vitro due to clinical deterioration. One patient was deemed as sensitive to carboplatin but tumor showed to be resistant. A meaningful correlation was observed in an oncogenic addicted tumor. A 54-year-old never-smoker man who had been diagnosed with lung adenocarcinoma stage IVa (T3N1M1a). He received standard first-line therapy with platinum-based chemotherapy, immunotherapy and antiangiogenics achieving tumor progression. A next-generation sequencing (NGS) panel revealed the presence of the EML4-ALK fusion variant 3a/b. The patient started alectinib but showed progression after 12 months. A second NGS panel did not identify any new ALK resistance mutation but acquiring TP53. Treatment was switched to brigatinib with no response. Finally, fresh tumor tissue was obtained from a liver biopsy to establish PDOs and drug sensitivity to 8 compounds was tested. The In vitro results demonstrated no activity of lorlatinib but a strong response to crizotinib. The patient started Crizotinib 250mg BID achieving partial response after 8 weeks and treatment duration of 6 months. A third liver biopsy for PDOs and NGS revealed acquired ALK C1156Y and I1171T mutations that confer resistance to crizotinib but sensitive to ceritinib, respectively. Conclusions: We present clinical evidence that PDOs are an alternative tool in oncogenic addicted tumors helping to guide treatment decisions and increasing a more personalized sequential treatment approach.

Society for Vascular Surgery implementation of clinical practice guidelines for patients with an abdominal aortic aneurysm: Endoleak management

Society for Vascular Surgery implementation of clinical practice guidelines for patients with an abdominal aortic aneurysm: Endoleak management

Biodegradation of Lindane (γ-Hexachlorocyclohexane) To Nontoxic End Products by Sequential Treatment with Three Mixed Anaerobic Microbial Cultures.

The γ isomer of hexachlorocyclohexane (HCH), also known as lindane, is a carcinogenic persistent organic pollutant. Lindane was used worldwide as an agricultural insecticide. Legacy soil and groundwater contamination with lindane and other HCH isomers is still a big concern. The biotic reductive dechlorination of HCH to nondesirable and toxic lower chlorinated compounds such as monochlorobenzene (MCB) and benzene, among others, has been broadly documented. Here, we demonstrate that complete biodegradation of lindane to nontoxic end products is attainable using a sequential treatment approach with three mixed anaerobic microbial cultures referred to as culture I, II, and III. Biaugmentation with culture I achieved dechlorination of lindane to MCB and benzene. Culture II was able to dechlorinate MCB to benzene, and finally, culture III carried out methanogenic benzene degradation. Distinct Dehalobacter populations, corresponding to different 16S rRNA amplicon sequence variants in culture I and culture II, were responsible for lindane and MCB dechlorination, respectively. This study continues to highlight key roles of Dehalobacter as chlorobenzene- and HCH -respiring bacteria and demonstrates that sequential treatment with specialized anaerobic cultures may be explored at field sites in order to address legacy soil and groundwater contamination with HCH.

Sustainable biological system for the removal of high strength ammoniacal nitrogen and organic pollutants in poultry waste processing industrial effluent

ABSTRACT The effluent generated from poultry waste processing industries contains several organic compounds such as collagen, gelatin, bovine serum albumin, carbohydrates, essential fatty acids, and so forth. This enabled the establishment of poultry waste processing industries to produce value-added products such as animal feed and organic fertilizers. During poultry waste processing, huge amounts of ammoniacal nitrogen and organic pollutants such as proteins, various carbohydrates, and fatty materials are discharged into the effluent stream which contributes to several environmental issues. Because of the shortcomings of the current conventional treatment, the present study is about with the development of a sequential bioreactor system for the effective treatment of poultry waste processing industrial effluent. Facultative anaerobe Paracoccus pantotrophus FMR19 along with the indigenous isolate Bacillus albus MN527241 obtained from clarifying sludge was used as mixed consortia for the treatment of poultry waste processing industrial effluent. The mixed microbial consortia resulted in the maximum activity of enzymes such as protease (247 U/mL) and lipase (28.266 U/mL) thereby achieving 90% of ammoniacal nitrogen reduction and 98% of COD removal within five days. Further, the confirmatory analysis of poultry effluent treatment was carried out using gas chromatography-mass spectroscopy (GC-MS), High-Performance Liquid Chromatography (HPLC), Fourier Transform Infrared Spectroscopy (FT-IR), and SDS-PAGE. Hence, the sequential bioreactor-based treatment approach has proved to be highly effective in removal of organic pollutants in the poultry waste processing industrial effluent.Implications: The poultry waste processing industrial (PWPI) effluent contains huge ammoniacal nitrogen and COD and affects the environment. Aerobic moving bed biofilm reactor and up-flow anaerobic sludge blanket reactor are in current practice and shows considerable reduction in the ammoniacal nitrogen and COD in long retention time. Therefore, there is a need of sustainable treatment process that could effectively remove the organic pollutants from the effluent in short duration. Our study focused on the application of sequential bioreactor approach for the treatment of PWPI using aerobic followed by anaerobic treatment process and observed efficient organic pollutants removal in short duration.

Comorbid posttraumatic stress disorder and major depressive disorder: The usefulness of a sequential treatment approach within a randomised design

Cognitive Processing Therapy (CPT) and Behavioural Activation Therapy (BA) were used to treat individuals with comorbid posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Fifty-two individuals (48 women, 4 men) were randomized to CPT alone (n = 18), CPT then BA for MDD (n = 17), or BA then CPT (n = 17). Presenting trauma was primarily interpersonal (87 %). Participants were assessed at pre-, posttreatment, and 6-month follow-up. PTSD and MDD symptoms were the main outcome of interest; trauma cognitions, rumination, and emotional numbing were secondary outcomes. All groups showed sizeable reductions in PTSD and depression (effect sizes at follow-up ranging between 1.02–2.54). A pattern of findings indicated CPT/BA showed better outcomes in terms of larger effect sizes and loss of diagnoses relative to CPT alone and BA/CPT. At follow-up greater numbers of the CPT/BA group were estimated to have achieved good end-state for remission of both PTSD and depression (49 %, CI95 [.26, .73]) relative to CPT alone (18 %, CI95 [.03, .38]) and BA/CPT (11 %, CI95 [.01, .29]). Although tempered by the modest sample size, the findings suggest that individuals with comorbid PTSD and MDD may benefit from having PTSD targeted first before remaining MDD symptoms are addressed.

Initial report of a phase II study with R-FND followed by ibritumomab tiuxetan radioimmunotherapy and rituximab maintenance in patients with untreated high-risk follicular lymphoma

R-FND (rituximab, fludarabine, mitoxantrone, and dexamethasone) can induce molecular remissions in indolent lymphoma. The addition of 90yttrium ibritumomab tiuxetan (90YIT) radioimmunotherapy following first-line induction treatment in patients with advanced follicular lymphoma (FL) may improve remission rates. We now report 10-year follow-up results from our sequential treatment approach with an abbreviated regimen of R-FND followed by 90YIT consolidation and rituximab maintenance. Forty-nine patients were enrolled; 47 received treatment. Patients had high-risk (FLIPI score ≥3) FL of grade 1–3A and stage III/IV with adequate hematologic function. Following R-FND, the complete and partial response rates were 91% and 8.5%, respectively. After 90YIT consolidation, the CR rate increased to 97%. The 10-year PFS rate was 49%. The most common non-hematologic, grade 3 or 4 adverse events were fatigue, dyspnea, and myalgia. Five developed myelodysplastic syndrome (MDS). This treatment approach is most appropriate in FLIPI-based high-risk patients whose outlook with standard therapy is inadequate.

Simultaneous treatment of toluene-containing gas waste and industrial wastewater by the Fenton process

This study reports a new perspective for the simultaneous oxidation of a volatile organic compound (VOC) – a toluene gas stream – and a real industrial liquid effluent by the Fenton's process; for that, a lab-scale bubbling reactor, operating in semi-continuous mode, was used. A parametric study was carried out to evaluate the effect of the aqueous matrix (water vs. real effluent), catalyst species nature (Fe2+ vs. Fe3+), concentration of organic matter in the liquid, and inlet toluene concentration in the gas phase. Their effects in the simultaneous gas-liquid treatment were assessed in terms of the toluene removal (from the gas stream) and wastewater mineralization (removal of dissolved organic carbon - DOC). The presence of organic matter in the liquid phase decreased toluene absorption. However, the simultaneous oxidation in the liquid phase extended the period of absorption until its saturation (and inherently the amount of toluene transferred) while still oxidizing 25% of the organic matter present in the industrial effluent. The application of the Fenton-like (H2O2 + Fe3+) process yielded a slightly reduced toluene transfer as compared to the Fenton one (H2O2 + Fe2+) – ca. 10%, although the overall mineralization has been similar. As expected, increasing the inlet toluene concentration reduces the process duration until liquid saturation, at the same time that a higher accumulation of by-products in the liquid due to oxidation was observed. Finally, a sequential treatment approach was performed, wherein liquid oxidation follows the previous simultaneous gas-liquid treatment, representing a strategy for long term operation, providing an opportunity for further VOC abatement in subsequent cycles. The main compounds resulting from oxidation remaining in the liquid phase after each stage were identified, allowing to close the carbon balance by ca. 80%.

Treatment of Sleep Comorbidities in Posttraumatic Stress Disorder.

Sleep disturbances, insomnia and recurrent nightmares in particular, are among the most frequently endorsed symptoms of posttraumatic stress disorder (PTSD). The present review provides a summary of the prevalence estimates and methodological challenges presented by sleep disturbances in PTSD, highlights the recent evidence for empirically supported psychotherapeutic and pharmacological interventions for comorbid sleep disturbances implicated in PTSD, and provides a summary of recent findings on integrated and sequential treatment approaches to ameliorate comorbid sleep disturbances in PTSD. Insomnia, recurrent nightmares, and other sleep disorders are commonly endorsed among individuals with PTSD; however, several methodological challenges contribute to the varying prevalence estimates. Targeted sleep-focused therapeutic interventions can improve sleep symptoms and mitigate daytime PTSD symptoms. Recently, attention has focused on the role of integrated and sequential approaches, suggesting that comprehensively treating sleep disturbances in PTSD is likely to require novel treatment modalities. Evidence is growing on the development, course, and treatment of comorbid sleep disturbances in PTSD. Further, interventions targeting sleep disturbances in PTSD show promise in reducing symptoms. However, longitudinal investigations and additional rigorous controlled trials with diverse populations are needed to identify key features associated with treatment response in order to alleviate symptoms.