Biological Treatment Options Research Articles

Enhancing Cartilage Repair: Surgical Approaches, Orthobiologics, and the Promise of Exosomes.

Treating cartilage damage is challenging as its ability for self-regeneration is limited. Left untreated, it can progress to osteoarthritis (OA), a joint disorder characterized by the deterioration of articular cartilage and other joint tissues. Surgical options, such as microfracture and cell/tissue transplantation, have shown promise as techniques to harness the body's endogenous regenerative capabilities to promote cartilage repair. Nonetheless, these techniques have been scrutinized due to reported inconsistencies in long-term outcomes and the tendency for the defects to regenerate as fibrocartilage instead of the smooth hyaline cartilage native to joint surfaces. Orthobiologics are medical therapies that utilize biologically derived substances to augment musculoskeletal healing. These treatments are rising in popularity because of their potential to enhance surgical standards of care. More recent developments in orthobiologics have focused on the role of exosomes in articular cartilage repair. Exosomes are nano-sized extracellular vesicles containing cargo such as proteins, lipids, and nucleic acids, and are known to facilitate intercellular communication, though their regenerative potential still needs to be fully understood. This review aims to demonstrate the advancements in cartilage regeneration, highlight surgical and biological treatment options, and discuss the recent strides in understanding the precise mechanisms of action involved.

Modern paradigms in biologic sequencing of inflammatory bowel disease in Aotearoa New Zealand.

The modern treatment of inflammatory bowel disease (IBD) has evolved significantly in recent years. This includes development of new pharmacologic therapies and their implementation in clinical practice. Moderate-to-severe IBD represents a group of patients at risk of poorer outcomes, and mounting evidence suggests biologic and small molecule medications, collectively termed advanced therapies, are the most effective tools clinicians possess. Even with biologic treatment, many patients do not respond or lose response over time. Until recently, most randomised trials demonstrating efficacy and safety of biologics have been placebo-controlled with a lack of head-to-head studies. Therefore, selecting the right medication for the appropriate clinical scenario can be difficult. In addition, there is evidence of differing clinical success when positioning biologic treatments in different sequences. This is important, as one-third of patients treated with biologics will require a switch to a second agent by 12 months, and a further 20% will require a third agent. Over the years, there have been widespread calls in Aotearoa New Zealand for increasing biologic treatment options. Ustekinumab and vedolizumab received public funding for the treatment of moderate-to-severe IBD in 2023, and this has presented long-awaited opportunities for patients, but also new challenges for clinicians in regard to treatment selection. The purpose of this document is to provide guidance to clinicians on biologic selection, sequencing and optimisation for IBD. These recommendations are specific to the domestic prescribing climate, supported by the best available evidence and endorsed by the New Zealand Society of Gastroenterology IBD Working Group.

Performance of salt‐bridge microbial fuel cell (SB‐MFC) with various microorganism cultures on the generation of electricity from tofu wastewater

A suitable wastewater treatment system is required due to the high organic compound content in tofu wastewater, which can harm the environment. Biological treatment methods are effective for treating tofu wastewater due to its characteristics. Microbial fuel cells (MFCs) represent one such biological treatment option, effectively removing organic contaminants while generating low‐power electricity through bioenergetic reactions. In MFCs, microorganisms are used as biocatalysts to degrade the organic compounds present in wastewater. This study aimed to assess the efficacy of Salt‐bridge microbial fuel cells (SB‐MFC) using various acclimatized microbe cultures for reducing organic compounds and generating energy from tofu wastewater. Tofu wastewater was sterilized prior to introduction into the reactor. Additional microbes, including the native microbe consortium from tofu wastewater, Escherichia coli, Saccharomycopsis fibuligera, and a mixed culture of E. coli and S. fibuligera, were then introduced as biocatalysts. Carbon electrodes were utilized as both the anode and cathode. The results indicate that the mixed culture of E. coli and S. fibuligera significantly reduced COD and BOD5 levels, with removal rates of 82.74% and 76.53%, respectively, after 48 h. Furthermore, the culture generated a voltage of 676 mV, a current of 2.53 mA, a power density of 428 mWatt/m2, and 4.789×10‐2 kWh of energy. This study contributes to the advancement of SB‐MFC by utilizing wastewater and a combination of bacteria and yeast as biocatalysts.

Biological treatment options for severe asthma in Poland

Intruduction and purpose: Patients with severe asthma account for approximately 3% to 10% of all asthma patients. They have higher hospital utilization rates and treatment costs than patients with non-severe asthma. Previously, treatment options for these patients were limited due to unacceptable side effects. However, the advent of biologic therapies has provided promising targeted therapy for these patients. State of knowledge: Biologic therapies target inflammatory modulators that play a key role in the pathogenesis of asthma, particularly in patients with high T2 cells. These therapies have shown promising results in reducing asthma symptoms, improving lung function, decreasing the use of oral corticosteroids, and enhancing patients' quality of life. Conclusions: This article reviews the mechanism of action, efficacy, and indications of currently approved biologic drugs available in Poland, as well as potential therapeutic targets for the future.

Advances in Hodgkin Lymphoma Treatment: From Molecular Biology to Clinical Practice.

Classical Hodgkin Lymphoma (cHL) is a highly curable disease, but around 20% of patients experience progression or relapse after standard frontline chemotherapy regimens. Salvage regimens followed by autologous stem cell transplants represent the historical treatment approach for these cases. In the last decade, with the increasing understanding of cHL biology and tumor microenvironment role in disease course, novel molecules have been introduced in clinical practice, improving outcomes in the relapsed/refractory setting. The anti-CD30 antibody-drug conjugated brentuximab vedotin and PD-1/PD-L1 checkpoint inhibitors represent nowadays curative options for chemorefractory patients, and randomized trials recently demonstrated their efficacy in frontline immune-chemo-combined modalities. Several drugs able to modulate the patients' T-lymphocytes and NK cell activity are under development, as well as many anti-CD30 chimeric antigen receptor T-cell products. Multiple tumor aberrant epigenetic mechanisms are being investigated as targets for antineoplastic compounds such as histone deacetylase inhibitors and hypomethylating agents. Moreover, JAK2 inhibition combined with anti-PD1 blockade revealed a potential complementary therapeutic pathway in cHL. In this review, we will summarize recent findings on cHL biology and novel treatment options clinically available, as well as promising future perspectives in the field.

The Genetics of Parkinson’s Disease

Parkinson's disease (PD) is one of the most common neurodegenerative diseases worldwide. Approximately 15% of PD patients have a family history of the disease in one or more first-degree relatives, and 5-10% of PD cases exhibit a classical Mendelian inheritance pattern. In 1997, the heritable transmission of PD was first documented. Recent studies have found 90 independent genome-wide signals at 78 loci that may be associated with PD. The identification of genes linked to PD and their functions has uncovered novel biological pathways and treatment options that play a role in the development of PD. In this article, it is aimed to review up-to-date information on the genetics of PD.

Exploring Perceptions of Biologic Therapies: A Qualitative Study Among Canadians Living with Severe Asthma.

Biologic therapies have demonstrated benefits for individuals with severe asthma, including reduced daily symptoms and severe exacerbations. However, data describing patient perspectives on these treatments are limited. This study sought to understand the preferences and priorities of Canadians with severe asthma in the context of novel biologic treatment options. Semi-structured, qualitative interviews were conducted among Canadians with severe asthma from July to August 2022. Purposeful sampling included individuals with and without biologic therapy experience. All participants described daily life with severe asthma, experiences and priorities related to asthma treatment and their impressions of biologics. Reflexive thematic analysis was used to explore patterns in the data. Among 18 individuals included, 10 were currently taking or had prior experience with biologic treatment for asthma. Those who had never been treated with biologics were unfamiliar with them, considering treatment, or believed that they may not be eligible. Four themes were developed to convey the perspectives of participants on biologics: (1) life-changing benefits, but not for all; (2) navigating barriers to being prescribed and remaining adherent to biologic treatments; (3) treatment administration preferences are not only about convenience; (4) concerns about safety and the unknown as a source of treatment hesitancy. Findings suggest that the clinical benefits of biologics align with patient perceptions of achieving good asthma control. However, treatment gaps persist among individuals who do not experience a meaningful improvement in their asthma symptoms and those who face barriers accessing biologics. People with severe asthma attributed importance to greater availability of at-home treatment options, improved access to financial support to cover treatment costs and support to address safety concerns. This research provides insight into patient-based treatment priorities and preferences for biologics, which may help inform decision-making related to emerging therapies for severe asthma.

557 - Tralokinumab real-world use in adults with atopic dermatitis: baseline characteristics of the first 100 patients recruited to the TRACE study in the United States

Abstract Introduction/Background Tralokinumab is a fully human, high-affinity, monoclonal antibody that specifically neutralizes interleukin-13, a key driver of atopic dermatitis (AD) pathogenesis. Numerous clinical studies have established that tralokinumab is an efficacious treatment for patients with moderate-to-severe AD, along with having a favorable safety profile. However, there is a lack of evidence on tralokinumab use in routine clinical practice, where patient management may differ from that defined by clinical trial protocols. Objectives TRACE is a global, real-world study that aims to better understand the effectiveness, safety, and clinical use of tralokinumab in patients with AD in daily practice. Methods TRACE is a global, observational, prospective, single-cohort study of tralokinumab-treated adults with moderate-to-severe AD. Overall, 11 countries across Europe, North America and the Middle East are participating. The primary objective of TRACE is to assess changes in clinical signs and symptoms of AD in patients treated with tralokinumab according to the nationally approved labels. Secondary objectives include safety, quality of life, patient-reported outcomes and treatment adherence. For this interim analysis, the objective was to report the baseline characteristics of the first 100 US patients. Results Overall, 55% of the first 100 US patients initiated on tralokinumab in the TRACE study were female; the majority (54%) were White, followed by 18% Black or African American and 12% Asian. Mean (standard deviation [SD]) age was 46.4 years (18.2) and body mass index was 28.6 kg/m2 (7.7). Patients had a mean disease duration of 13.9 years (SD 16.5), with 46% being biologic-naïve and 54% biologic-experienced. Most patients (88%) had moderate-to-severe AD, with a mean Investigator’s Global Assessment score of 3.2 (SD 0.8); mean Eczema Area and Severity Index was 15.4 (SD 7.9). A heavy symptomatic burden of disease was evident, with a mean eczema-related sleep numerical rating scale (NRS) of 4.2 (SD 3.3) and mean worst daily pruritus NRS of 6.1 (SD 2.6). Patients also reported a substantial impact of AD on quality of life; mean Dermatology Life Quality Index was 13.2 (SD 8.5). Almost one quarter (24%) of patients reported ≥1 atopic comorbidity, with asthma (12%), cardiovascular disease (8%) and autoimmune disease (6%) being the most frequent; 3% of patients had psychiatric illness. Conclusions Initial findings showed that tralokinumab is being prescribed as a first-line biologic treatment option in the US in accordance with the label. Treated patients had a heavy burden of disease with considerable impact on quality of life.

Abstract B019: Deciphering the role of homologous recombination deficiency mutations in the response to combined immune checkpoint and PARP inhibitors

Abstract Background: Over 2 million women develop breast cancer globally every year despite immense advances in disease biology, diagnostic strategies and novel treatment options. The deeper knowledge of disease biology and genomic landscape has fostered a broader mechanistic approach to patients and their therapeutic choices. Many preclinical and clinical studies suggest a benefit of combining PARP inhibitors (PARPi) and immune checkpoint inhibitors (ICPi) in patients with homologous recombination deficiency (HRD) intact and mutated cancers. However, similar to the varied benefits of either drug class based on tissue and mutational context, the benefits of such combination are strongly variable based on tumor type, tissue and mutation context. Methods: To study how select HRD mutations respond to a combination of a PARPi inhibitor with an ICPi, we used CRISPR engineering to functionally impair or repress BRCA1, BRCA2, ATM, CHEK2, PALB2 in different mouse breast cancer cell lines. EMT6 and 4T1 cells were engineered to expressed deactivated cas9 nuclease (dcas9) fused to the repressor domain Kruppel-associated- box (KRAB) and mcherry florescent protein. The dcas9-KRAB-mcherry breast cancer cells were further engineered to express BFP-tagged guide RNAs targeting selected genes under a doxycycline inducible tet-on system. After establishing functional loss/repression of the targeted HRD mutations, cells were then implanted in the mammary fat pad of balb/cJ mice and treated with PARPi and ICPi to determine the ICPi, PARPi and their combination induced changes in inflammatory signals and their association with therapy response. Results: Induced suppression of BRCA1 and PALB2 in these breast cancer cells showed exquisite sensitivity to PARPi (IC50 0.01 uM and 0.098 uM) and diminishing sensitivity to PARPi in BRCA2 and ATM (IC50 0.16 uM and IC50 0.28 uM). In contrast, inducible suppression of CHEK2 showed resistance to PARPi versus parental EMT6 cells (IC50 13.9 uM versus 5.3 uM). Evaluation of changes in expression levels of PDL1 and select chemokines including CCL2, CCL5, CXCL9, CXCL10 and CXCL11 suggest a differential response to PARPi depending on specific HRD mutations. HRD mutations and tissue-context will be further characterized in combination therapy of ICPi and PARPi. Conclusion: Using inducible suppression of HRD function in an immune competent mouse breast cancer model helps to understand the differential role of individual HRD mutations (BRCA1, BRCA2, ATM, CHEK2, PALB2) in altering inflammatory signals in response to PARPi and ICI. This data may guide the clinical development of such combination in breast cancer and other cancers. Citation Format: Sibapriya Chaudhuri, Scott Thomas, Luika Timmerman, Pamela Munster. Deciphering the role of homologous recombination deficiency mutations in the response to combined immune checkpoint and PARP inhibitors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B019.

Evaluation of on-site biological treatment options for hydrothermal liquefaction aqueous phase derived from sludge in municipal wastewater treatment plants

Aerobic treatment, mesophilic anaerobic digestion, thermophilic anaerobic digestion, and dark fermentation were evaluated for on-site biological treatment of municipal sludge derived HTL aqueous. For all four described batch test scenarios, municipal sludge-derived HTL aqueous samples obtained under 290–360 °C and 0–30 min retention time were used. In the aerobic respirometric tests, HTL aqueous samples resulted in a five-day biochemical oxygen demand range of 40.75 g/L (350 °C-25.6 min) to 54 g/L (325 °C-0 min). The calculated aerobic biodegradability index showed that approximately 50 % of the organics in HTL aqueous were easily biodegradable. Mesophilic and thermophilic biochemical methane potential tests resulted in specific yields of 151–179 mL CH4/g chemical oxygen demand (COD) and 103–122 mL CH4/g COD, respectively. HTL aqueous obtained under 360 °C-15 min condition caused total inhibition in both mesophilic and thermophilic anaerobic digestion. Possible causes for this inhibition were pyridine, pyrrolidinone, piperidinone, pyridinol, and phenolic compounds, which were higher in abundance in the 360 °C-15 min sample. HTL aqueous was found unfit for hydrogen production in dark fermentation due to inhibitory composition. In summary, on-site biological treatment of HTL aqueous was found to be most suitable under aerobic and mesophilic anaerobic conditions.

Diagnostics and treatment of large vessel vasculitis

Giant cell arteritis (GCA) and Takayasu arteritis (TAK), as the main representatives of large vessel vasculitis, are rheumatological autoimmune disorders associated with inflammatory vessel wall changes in the arterial system that can lead to many types of organ damage. In this review the current scientific evidence on the diagnostics and treatment of large vessel vasculitis is evaluated and discussed. In addition to the medical history and clinical presentation, imaging techniques nowadays represent the core of large vessel vasculitis diagnostics and have largely replaced the histological confirmation of GCA. After the diagnosis, acute treatment with glucocorticoids should be initiated as rapidly as possible but in the long term this should be tapered out or replaced by asteroid-sparing basic treatment. In contrast to GCA with already available options and other biologic disease-modifying antirheumatic drugs (DMARDs) about to be approved, there are still no approved biologic DMARD treatment options available for the less common TAK. In contrast to the substantial progress in imaging diagnostics of large vessel vasculitis and with respect to the treatment of GCA, the much rarer TAK still requires intensive research efforts, especially to improve the treatment situation.

Olfactory and gustatory disorders associated with SARS-CoV-2 infection in children and adults: a topic review.

This paper is aimed at comprehensively reviewing olfactory and gustatory disorders caused by SARS-CoV-2 in children and adults. An electronic and manual search was done on three databases: MEDLINE, Embase, and Web of Science. Inclusion criteria included publications written in English, involving humans in the age range of 0 to 99 years that were captured by a controlled vocabulary of thesaurus terms. Olfactory and gustatory disorders rates in COVID-19 ranged from 22% to 71.9% in adults and 16.6% to 25.8% in children. Olfactory and gustatory disorders might appear as the first symptom, and in adults might even be the only symptom (4.8% to 10%). Anosmia is the most common olfactory disorder and hypogeusia is the most common gustatory disorder. In 33% to 89% of cases, olfactory and gustatory disorders resolve spontaneously within a few weeks, coinciding with the resolution of other COVID-19 symptoms, both in adults and children. However, in some patients, olfactory and gustatory disorders persist beyond the resolution of other symptoms. Notably, children generally experience a swifter and more favorable recovery compared to adults. The precise pathogenesis underlying olfactory and gustatory disorders in the context of COVID-19 remains unclear and is likely multifactorial. Presently, no established treatment protocol exists for olfactory and gustatory disorders and current treatments reviewed lack robust evidence and are not readily available for clinical use. Olfactory training represents the only therapy currently recommended by international authorities. Pediatric practitioners and general dental practitioners should be aware of olfactory and gustatory disorders in both pediatric and adult populations, including their biologic mechanisms, treatment options, and recovery rates.

Has the Survival in Patients with Multiple Myeloma Changed with the Advent of Latest Treatments?

Introduction: Multiple Myeloma (MM) is a hematologic malignancy of plasma cells. Over the last couple of decades, there have been groundbreaking advances in its treatment, emergence of chimeric antigen receptor T-cell (CAR-T) therapies and bispecific antibodies (bsAbs). As per National Comprehensive Cancer Network's (NCCN) current guidelines, the current standard of treatment is a 3-drug regimen bortezomib/lenalidomide/dexamethasone. The year 2003, marked the beginning of the revolution in the MM biological treatment. The aim of this retrospective study is to analyze the trends of multiple myeloma, particularly to assess the difference in survival, with the innovation in its novel treatment options. Methods: The data was collected from Surveillance, Epidemiology and End Result database Research. We extracted Multiple Myeloma cases diagnosed between 01-85+ years of age, using Incidence- SEER Research Date 17 Registries, Nov 2022 Sub (2000-2020), with ICD 0-3 Hist/behavior, malignant, code 9732/3 for plasma cell myeloma. The analysis was stratified based on age, sex, race, & survival curves based were compared, using the Log-rank test (GraphPad Prism). Results: A total of 109222 cases of multiple myeloma were identified between 2000-2020. Of these, ~55.18% were males and ~44.81% were females. Median age at the time of diagnosis is 69 years. The incidence rate overall has been increasing and was noted to be 62.38 per 1,000,000 population vs 56.38 in the year 2000. When stratified further on gender, incidence rates for males were noted to be up-trending from 69.32 in 2000 to 75.87 in the year 2020. Whereas for females the incidence rates in females in 2000 was at 47.02 and at 51.51 in 2020. The survival was compared for the general population before and after the emergence of newer treatment in the year 2003. There was a statistical difference found in the median of survival (mOS) before the introduction of the biologicals in 2003, was 25 months, and after the year 2003, was 46 months (P Value <0.0001, Hazard Ratio 1.451 95% Confidence Interval 1.421 to 1.481). Conclusion: Multiple Myeloma is a relatively rare malignancy, with a slightly stronger male predilection. Its overall incidence has been noted to be up-trending within the last 20 years, in the United States. The median age for diagnosis is 69 years. In the year 2003, FDA approved Bortezomib for the treatment of MM, which primarily targeted the proteasome and the ubiquitin proteasome system (UPS). This established the role of UPS in MM, and further led to the invention of newer biological treatment options for MM. When survival months were compared in the pre-and-post biological treatment era, it was noted that the mOS was only 25 months, whereas a significant increase in mOS to 46 months was noted, after the introduction of biological therapy in 2003. With newer groundbreaking research and approval of CAR-T therapies, we are on our way to making MM, a curable malignancy.

Empowering municipal wastewater treatment: Enhancing particulate organic carbon removal via chemical advanced primary treatment

The present study aimed to determine the physical and chemical parameters in the primary treatment process of municipal wastewater by flocculation processes using natural and synthetic polymers as chemically advanced primary treatment (CAPT). Flocculants like chitosan-based, starch-based, and polyacrylamide were chosen, and their feasibility for preliminary treated (PSTin) and pre-treated WASTEWATER (PSTout) underwent precise investigations applying the batch test setup. Since TSS concentration varies hourly in wastewater treatment plants (WWTP) and significantly affects the required dosage of the flocculants, various samples with TSS concentrations ranging from extremely low (<100 mg L−1) to incredibly high (> 700 mg L−1) were gathered to account for all TSS ranges. Several tests were then performed on the samples to establish the efficacy, optimum dosage, settleability, and filterability of the flocs generated by the polymers. The flocs' morphological characteristics were also analyzed by two-dimensional image analysis (2D-IA). The results showed that PSTin or PSTout can be purified solely with synthetic and environmentally confirmed natural-based polymers readily and efficiently. This concept introduces one-stage flocculation for the primary treatment of municipal wastewater rather than the conventional two stages of coagulation-flocculation, which has been used so far while applying harmful aluminum or ferric salts. The results also revealed that the CAPT system can be enhanced by coupling with a microstrain (MS) to remove nearly all particulate organic carbon in the form of COD or TSS. Exploring a range of biological treatment options in conjunction with the CAPT system revealed a significant reduction in external energy reliance for municipal WWTPs, transferring from roughly 75 % to complete independence. This evolution also enables the efficient production of valuable byproducts such as Hydrogen, Polyhydroxyalkanoates, and Ammonium chloride fertilizers, ultimately empowering municipal WWTPs from energy-dependent facilities into self-sustaining energy sources.

Real-world effectiveness and safety of ustekinumab in bio-naive patients with moderate-to-severe Crohn's disease: A Canadian multi-center study

BackgroundClinical practice guidelines recommend ustekinumab as a first-line biological treatment option for moderately-to-severely active Crohn's disease (CD). However, there is limited real-world effectiveness and safety data in bio-naïve patients. AimsTo assess ustekinumab effectiveness and safety in bio-naïve CD patients. MethodsMedical charts were reviewed retrospectively at seven Canadian centers. The primary outcome was the proportion of patients achieving clinical remission at Month 6 following ustekinumab initiation. Secondary outcomes included clinical, biochemical, and endoscopic response, and remission at Months 4, 6 and 12. Ustekinumab safety was assessed over the one-year follow-up period. Results158 charts were reviewed. Clinical remission was achieved by 50.0% (36/72), 67.7% (105/155), and 73.7% (84/114) of patients at Months 4, 6, and 12, respectively. At these study timepoints, biochemical remission was observed in 65.2% (43/66), 71.6% (63/88), and 73.9% (68/92) of patients. At Months 6 and 12, endoscopic remission was observed in 40.5% (15/37) and 56.3% (27/48) of patients, respectively. Most participants (93.5%; 145/155) persisted on ustekinumab through Month 12. No serious adverse drug reactions were reported. ConclusionIn this real-world study, ustekinumab presents as an effective first-line biologic for induction and maintenance of remission among bio-naïve Canadian patients with moderately-to-severely active CD.

The Effectiveness of Risankizumab Following Guselkumab Failure in Moderate-to-Severe Psoriasis Patients: A Retrospective Study.

Psoriasis is a chronic inflammatory skin disease with a strong genetic predisposition and autoimmune component that is often treated with immunomodulators such as biologic therapy. Guselkumab is a biologic treatment option that selectively targets the p19 subunit of interleukin (IL)-23; risankizumab is a more recently developed monoclonal antibody of the same class that targets IL-23p19. There is limited research around effective treatment response with intra class switching within IL-23-targeted therapies for the treatment of moderate-to-severe plaque psoriasis. The purpose is to assess patient response to risankizumab after guselkumab failure for the treatment of plaque psoriasis. A retrospective chart review was conducted for 13 patients meeting inclusion criteria. Physical examination findings were converted to a 5-point static physicians' global assessment (sPGA) score. Baseline, 4-month, and 12-month sPGA scores were assigned from visits immediately prior to and during their course of risankizumab treatment. sPGA scores were analyzed to compare changes between baseline and 4 months and 12 months of therapy. Patients treated with risankizumab had lower sPGA scores after both 4 and 12 months compared to their baseline sPGA score. 46% of patients met the primary outcome of an sPGA score of 0 or 1 at 4 months of risankizumab, increasing to 90% of patients at 12 months. Our findings reflect an improvement in sPGA scores when patients are treated with risankizumab following guselkumab failure. This highlights the benefit of in-class switch to risankizumab when patients with moderate-to-severe plaque psoriasis have failed multiple treatments including guselkumab.

Definitions, Biology, and Current Therapeutic Landscape of Myelodysplastic/Myeloproliferative Neoplasms.

Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are hematological disorders characterized by both proliferative and dysplastic features. According to the 2022 International Consensus Classification (ICC), MDS/MPN consists of clonal monocytosis of undetermined significance (CMUS), chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), MDS/MPN with SF3B1 mutation (MDS/MPN-T-SF3B1), MDS/MPN with ring sideroblasts and thrombocytosis not otherwise specified (MDS/MPN-RS-T-NOS), and MDS/MPN-NOS. These disorders exhibit a diverse range of genetic alterations involving various transcription factors (e.g., RUNX1), signaling molecules (e.g., NRAS, JAK2), splicing factors (e.g., SF3B, SRSF2), and epigenetic regulators (e.g., TET2, ASXL1, DNMT3A), as well as specific cytogenetic abnormalities (e.g., 8 trisomies, 7 deletions/monosomies). Clinical studies exploring therapeutic options for higher-risk MDS/MPN overlap syndromes mostly involve hypomethylating agents, but other treatments such as lenalidomide and targeted agents such as JAK inhibitors and inhibitors targeting PARP, histone deacetylases, and the Ras pathway are under investigation. While these treatment modalities can provide partial disease control, allogeneic bone marrow transplantation (allo-BMT) is the only potentially curative option for patients. Important prognostic factors correlating with outcomes after allo-BMT include comorbidities, splenomegaly, karyotype alterations, and the bone marrow blasts percentage at the time of transplantation. Future research is imperative to optimizing therapeutic strategies and enhancing patient outcomes in MDS/MPN neoplasms. In this review, we summarize MDS/MPN diagnostic criteria, biology, and current and future treatment options, including bone marrow transplantation.

Long-term effectiveness and safety of anti-TNF in pediatric-onset inflammatory bowel diseases: A population-based study

BackgroundAnti-TNF agents are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD. MethodsAll patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in the EPIMAD population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNF, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response (LOR) or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model. ResultsAmong a total of 1,007 patients with CD and 337 patients with UC, respectively 481 (48%) and 81 (24%) were treated with anti-TNF. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1–20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0–59.9). In CD, the probability of failure of 1st line anti-TNF at 1, 3 and 5 years was respectively 30.7%, 51.3% and 61.9% for infliximab and 25.9%, 49.3% and 57.7% for adalimumab (p = 0.740). In UC, the probability of failure of 1st line anti-TNF therapy was respectively 38.4%, 52.3% and 72.7% for infliximab and 12.5% for these 3 timepoints for adalimumab (p = 0.091). The risk of failure was maximal in the first year of treatment and LOR was the main reason for discontinuation. Female gender was associated with LOR (HR, 1.48; 95%CI 1.02–2.14) and with anti-TNF withdrawal for intolerance in CD (HR, 2.31; 95%CI 1.30–4.11) and disease duration (≥ 2 y vs. < 2 y) was associated with LOR in UC (HR, 0.37; 95%CI 0.15–0.94) in multivariate analysis. Sixty-three (13.5%) patients observed adverse events leading to termination of treatment (p = 0.57). No death, cancer or tuberculosis was observed while the patients were under anti-TNF treatment. ConclusionIn a population-based study of pediatric-onset IBD, about 60% in CD and 70% in UC experienced anti-TNF failure within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC.

Long-Term Effects of Severe Burns on the Kidneys: Research Advances and Potential Therapeutic Approaches.

Burns are a seriously underestimated form of trauma that not only damage the skin system but also cause various complications, such as acute kidney injury (AKI). Recent clinical studies have shown that the proportion of chronic kidney diseases (CKD) in burn patients after discharge is significantly higher than that in the general population, but the mechanism behind this is controversial. The traditional view is that CKD is associated with hypoperfusion, AKI, sepsis, and drugs administered in the early stages of burns. However, recent studies have shown that burns can cause long-term immune dysfunction, which is a high-risk factor for CKD. This suggests that burns affect the kidneys more than previously recognized. In other words, severe burns are not only an acute injury but also a chronic disease. Neglecting to study long-term kidney function in burn patients also results in a lack of preventive and therapeutic methods being developed. Furthermore, stem cells and their exosomes have shown excellent comprehensive therapeutic properties in the prevention and treatment of CKD, making them increasingly the focus of research attention. Their engineering strategy further improved the therapeutic performance. This review will focus on the research advances in burns on the development of CKD, illustrating the possible mechanism of burn-induced CKD and introducing potential biological treatment options and their engineering strategies.

Degradation of Dimethylacetamide from Membrane Production through Constructed Wetlands—Pathways, Ecotoxicological Effects and Consequences for Chemical Analysis

Wastewater from factories producing polysulfone-based membranes mainly contains the used organic solvent, i.e., dimethylacetamide (DMAc). Due to the environmental impact of DMAc, wastewater treatment is mandatory. Several biological treatment options based on the activated sludge process are described in the literature. Due to artificial aeration, these techniques have high energy requirements. Near-nature processes such as vertical flow constructed wetlands (VF wetlands) have a low energy demand, high tolerance to load fluctuations, and low maintenance requirements. Therefore, high-loaded, two-stage VF wetlands are an efficient option for treating wastewater. However, constructed wetlands have so far only been used to a limited extent for the treatment of industrial wastewater. In the present study, the ability of laboratory-scale, high-load, two-stage VF wetlands to treat DMAc was investigated. This included their DMAc degradation efficiency and corresponding pathways, removal of the total organic carbon (TOC), nitrification and denitrification of the nitrogen, as well as the ecotoxicological effects (mutagenicity, genotoxicity, reactive oxygen species) of untreated and treated wastewater. The focus was to determine the effect of different grain size distributions on removal rates, the maximum inflow loading, and the effect of high inflow concentrations on effluent concentrations. In general, DMAc was completely degraded using VF wetlands, with dimethylamine (DMA) identified as the main intermediate. TOC removal rates reached more than 99%. The nitrogen bound to DMAc was completely nitrified. However, the start-up of the VF wetlands without seeded filter material temporarily leads to high nitrite accumulation. This may affect the mutagenicity of the treated wastewater. The results show that high-loaded, two-stage VF wetlands are an effective option for treating wastewater containing DMAc with higher efficiency than comparable biological processes.