Treatment Strategies Research Articles

Advances in Mechanism of HIV-1 Immune Reconstitution Failure: Understanding Lymphocyte Subpopulations and Interventions for Immunological Nonresponders.

In individuals diagnosed with AIDS, the primary method of sustained suppression of HIV-1 replication is antiretroviral therapy, which systematically increases CD4+ T cell levels and restores immune function. However, there is still a subset of 10-40% of people living with HIV who not only fail to reach normal CD4+ T cell counts but also experience severe immune dysfunction. These individuals are referred to as immunological nonresponders (INRs). INRs have a higher susceptibility to opportunistic infections and non-AIDS-related illnesses, resulting in increased morbidity and mortality rates. Therefore, it is crucial to gain new insights into the primary mechanisms of immune reconstitution failure to enable early and effective treatment for individuals at risk. This review provides an overview of the dynamics of key lymphocyte subpopulations, the main molecular mechanisms of INRs, clinical diagnosis, and intervention strategies during immune reconstitution failure, primarily from a multiomics perspective.

Research of active compounds from Allii Macrostemonis Bulbus and potential targets against Non-Hodgkin's Lymphoma based on Network pharmacology.

Non-Hodgkin's Lymphoma (NHL) is a series of lymphoid malignancies in some aggressive subtypes with unsatisfactory treatment effects. Allii Macrostemonis Bulbus (Xie Bai) is a traditional Chinese medicine with anti-cancer activities, which may potentially suppress aggressive NHL. This study tries to discover active components and targets of Xie Bai in treating NHL by network pharmacology-based approaches. Compounds and related targets of Xie Bai were collected from the Traditional Chinese Medicine Database and Analysis Platform. Target genes associated with NHL were searched by GeneCards and DisGeNET, then the overlapped targets were further analyzed by STRING tool, GO, and KEGG pathway enrichment analysis. Molecular docking was employed to verify the interaction between compounds and targets. 11 bioactive compounds were successfully identified, with 30 targets that were screened out for the treatment of NHL. Functional enrichment analysis suggested that Xie Bai exerted its potential effects against NHL via pathways in cancer, such as PI3K/ AKT, p53, and MAPK signaling pathways. Molecular docking results showed that 3 active compounds (quercetin, beta-sitosterol, and naringenin) had good affinity with selected 6 targets（TP53, AKT1, CASP3, CCND1, HPK1, and NLRP3). Identifying six potential genes could accurately be docked with Xie Bai and had close interactions with NHL, which may provide insight into further research and new treatment strategy.

Multimetal exposure: Challenges in diagnostics, prevention, and treatment.

Extensive use of heavy metals has posed a serious concern for ecosystem and human too. Heavy metals are toxic in nature and their accumulation in human body causes serious disorders such as neurological disease, cardiac disease, gastrointestinal problems, skin disorders, reproductive disease, lungs diseases, and so on. Furthermore, heavy metals not only affect the human health but also have a negative impact on the economy. In the current review, we have elaborated the impact of heavy metal exposure on human health and socioeconomics. We have discussed the molecular mechanism involved in the heavy metal-induced human disorders such as oxidative stress, neuroinflammation, and protein misfolding. Finally, we discussed the preventive measure and treatment strategy that could counter the negative effects of heavy metal intoxications. In conclusion, there is a substantial correlation between heavy metals and the onset and advancement of several health issues. Chelation treatment could be a useful tactic to lessen the toxic metal load and the difficulties that come with it.

Microenvironment Responsive Hydrogel Exerting Inhibition of Cascade Immune Activation and Elimination of Synovial Fibroblasts for Rheumatoid Arthritis Therapy

Rheumatoid arthritis (RA) is a progressive autoimmune disease and drug therapy has been restricted due to poor therapeutic efficacy and adverse effects. In RA synovium, dendritic cells present self-antigens to activate cascade immune pathway. Furthermore, downstream macrophages secrete high levels of pro-inflammatory cytokines; Hyperplasia of activated synovial fibroblasts (FLS) is responsible for hypoxic synovium microenvironment, secretion of cytokines/chemokines and erosion of bone/cartilage tissues. Positive feedback loop of inflammation between macrophages and FLS independent of antigen-presentation is constructed. Herein, an injectable pH-sensitive peptide hydrogel encapsulating siRNA/Methotrexate-polyethyleneimine (siMP, including sip65MP, sip38MP, siCD86MP) and Bismuthene nanosheet/Methotrexate-polyethyleneimine (BiMP) is successfully developed. Among them, siCD86MP reduces protein level of co-stimulatory molecule CD86 while sip65MP and sip38MP separately inhibit NF-κB and MAPK-p38 pathways of macrophages and FLS to suppress secretion of cytokines and MMPs. Meanwhile, reduction in anti-apoptotic property of FLS induced by inhibition of NF-κB pathway has a synergistic effect with photodynamic therapy (PDT) and photothermal therapy (PTT) mediated by BiMP for FLS elimination, effectively ameliorating hypoxic synovium microenvironment. After being injected into synovium, hydrogel responds to acidic microenvironment and serves as a reservoir for sustained drug release and inherent retention capacity of which enables cationic nanoparticles to bypass tissue barrier for precise synovium targeting. This brand-new drug delivery system combines modulating cascade immune pathway from beginning to end by RNAi and eliminating FLS for improving synovium microenvironment by phototherapy together, providing a robust strategy for clinical RA treatment.

Efficient degradation of wastewater by ultra-low platinum doped ZnO lamellar nanoflowers via photoinduced formation of hydroxyl radicals

Photocatalytic degradation technology is a promising strategy for the water treatment, which has many advantages such as saving time, cleanliness and environmental friendliness. In this study, ultra-low amount (0.01wt.%) of nano platinum (Pt) obtained from one-pot reduction method, was doped onto zinc oxide (ZnO) to form a lamellar nanoflower (Pt-ZnO). The characterization of Pt-ZnO was put forwards via scanning electron microscopy, high-angle annular dark-field scanning transmission election microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, liquid chromatography-mass spectrometry, etc. The highest degradation efficiencies of methylene blue (MB), rhodamine B (Rh B), methylene orange (MO), and acid black ATT (ATT) after being treated by Pt-ZnO for about 60min reached 99.9%, 99.9%, 96.0%, and 97.8% respectively. While the MB and Rh B remained at a degradation efficiency of 99.9% even after being reused 5 times. Surprisingly, Pt-ZnO showed the removal rate of industrial effluent containing acid dyes was 93.9% and the chemical oxygen demand (COD) of wastewater was significantly reduced. Experimental results of LC-MS and free radical scavenging testing indicated MB was mainly split through the continuous open-ring cleavage of C-N bond in N, N-dimethylamine group by ·OH, and finally decomposed into H2O and CO2 achieving the decolorization.

Developing a remotely delivered intensive outpatient program adapted for hospitalized patients with opioid use disorder: A qualitative study

IntroductionIndividuals with opioid use disorder (OUD) who inject drugs have an elevated risk of experiencing serious injection-related infections. While such infections can be treated, treatment for the underlying OUD is often limited. One potential strategy for more intensive addiction treatment is to offer a remotely delivered intensive outpatient program (IOP), adapted from an existing remote IOP (“Smart IOP”). We aimed to conduct a qualitative study to gather feedback on Smart IOP and identify adaptations needed for hospitalized patients. MethodsIndividuals with OUD and a history of serious injection-related infections completed a semi-structured interview and were shown samples of the videos and program content. The interviews were transcribed verbatim and coded to conduct a thematic analysis. ResultsSeventeen individuals participated. The mean age was 40.8 years and 70.6% were men. Participants reported that IOP during the hospitalization would have been helpful to their recovery. The themes that emerged were the importance of medications for OUD, having a relapse prevention plan, engaging with a recovery coach, and ensuring treatment linkage post-discharge. Other themes included the recognition of the severity of one’s illness and the emotional experiences related to the hospitalization. ConclusionsParticipants expressed the value of an IOP during hospitalization and provided insights into the support needed while hospitalized. The tailored IOP is now being developed and will undergo a pilot feasibility trial.

Sulforaphane decreases oxidative stress and inhibits NLRP3 inflammasome activation in a mouse model of ulcerative colitis

Excessive oxidative stress and NLRP3 inflammasome activation are considered the main drivers of inflammatory bowel disease (IBD), and inhibition of inflammasomes ameliorates clinical symptoms and morphological manifestations of IBD. Herein, we examined the roles of NLRP3 activation in IBD and modulation of NLRP3 by sulforaphane (SFN), a compound with multiple pharmacological activities that is extracted from cruciferous plants. To simulate human IBD, we established a mouse colitis model by administering dextran sodium sulfate in the drinking water. SFN (25, 50 mg·kg−1·d−1, ig) or the positive control sulfasalazine (500 mg/kg, ig) was administered to colitis-affected mice for 7 days. Model mice displayed pathological alterations in colon tissue as well as classic symptoms of colitis beyond substantial tissue inflammation. Expression of NLRP3, ASC, and caspase-1 was significantly elevated in the colonic epithelium. The expression of NLRP3 inflammasomes led to activation of downstream proteins and increases in the cytokines IL-18 and IL-1β. SFN administration either fully or partially reversed these changes, thus restoring IL-18 and IL-1β, substantially inhibiting NLRP3 activation, and decreasing inflammation. SFN alleviated the inflammation induced by LPS and NLRP3 agonists in RAW264.7 cells by decreasing the levels of reactive oxygen species. In summary, our results revealed the pathological roles of oxidative stress and NLRP3 in colitis, and indicated that SFN might serve as a natural NLRP3 inhibitor, thereby providing a new strategy for alternative colitis treatment.

Economic assessment of an intervention strategy to reduce antimicrobial usage in small-scale chicken farms in Vietnam

Antimicrobials are a core aspect of most livestock production systems, especially in low-and middle-income countries. They underpin the efficient use of scarce feed resources and stabilize returns on capital and labor inputs. Antimicrobial use (AMU) contributes to the production of healthy animals, yet AMU in livestock is linked to antimicrobial resistance (AMR) in animals, humans and the environment.The Vietnamese Platform for Antimicrobial Reduction in Chicken Production was implemented during 2016–2019 and was one of Southeast Asia's first interventions focused on AMU reductions in livestock production. The project targeted small-scale commercial poultry farms in the Mekong Delta region of Vietnam using a “randomized before-and-after controlled” study design. It provided farmers with a locally adapted support service (farmer training plan, advisory visits, biosecurity, and antimicrobial replacement products) to help them reduce their reliance on antimicrobials. A partial budget analysis was performed comparing the control group (status-quo) and intervention group (alternative). The median net farm-level benefit of the intervention strategies with the project's support was VND 6.78 million (interquartile range (IR) VND -71.9–89 million) per farm. Without project support the benefit was reduced to VND 5.1 million (IR VND -69.1–87.2 million) to VND 5.3 million (IR -VND 68.9–87.5 million) depending on the antimicrobial alternative product used. At the project level with a focus on AMU and its reduction, subsequently influence on the resistance reduction, our results showed that achieving resistance reduction benefits with the current knowledge and technologies required investment of at least VND 9.1 million (US$ 395.10) per farm during the project's lifetime. The results highlight the positive net profit for the majority of enrolled farms and a reasonable investments from the project. The recommendation focuses on the implementation of policies on financial support, legislation, and information as potential solutions to facilitate the application of intervention strategies to reduce AMU in poultry production.

Historical heritage – MultiCriteria Decision Method (H-MCDM) to prioritize intervention strategies for the adaptive reuse of valuable architectural assets

Identifying the most suitable strategy for the adaptive reuse of historic architectural heritage is a complex challenge. This is because each rehabilitation project of an abandoned historic building must not only ensure the simultaneous pursuit of social, cultural and financial goals, but also the transmission of tangible and intangible values to future generations.In this context, the use of multi-criteria approaches helps to synthesise stakeholders' preferences based on multiple and conflicting criteria, with the aim of promoting sustainable solutions for the restoration and valorisation of valuable architectural assets. To this end, we characterise the Historical heritage - MultiCriteria Decision Method (H-MCDM), an analysis and evaluation tool aimed at identifying the best adaptive reuse of historic buildings considering the principles of architectural conservation and both economic and socio-cultural values. It is a model based on the Analytic Hierarchy Process (AHP), which employs 7 evaluation indicators, chosen after a critical and interpretative analysis of both the sustainability principles promoted by the United Nations and UNESCO, and the ICOMOS quality principles.The H-MCDM is structured on the following five logical-operational steps: (i) identification of strategies for adaptive reuse of the historic building; (ii) construction of the matrices of the pairwise comparisons of the criteria and estimation of the vector of the weights of the criteria; (iii) construction of the matrices of the pairwise comparisons of the alternatives against each evaluation criterion and estimation of the local scores of the alternatives; (iv) consistency checks of the decision matrices; (v) calculation of the total priority and ranking of the HBU strategies for historic assets.The application to a case study demonstrates that, due to its adaptability and versatility, the H-MCDM can be a valid and consistent decision support in public resource allocation processes for the rehabilitation of architectural heritage.

Internet of things-based digital scale to detect stunting symptoms in babies under two years of age

Given the ongoing global challenge of stunting, characterized primarily by chronic underweight in infants under two years of age, a new approach leveraging digital scale and the internet of things (IoT) has been developed. This innovative system was designed to facilitate the early detection and continual monitoring of stunting symptoms caused by malnourishment. Key features include an IoT-enabled digital scale for precise weight measurement, a robust cloud platform for reliable data storage and comprehensive analysis, and an easy-to-use mobile app for user engagement. This system demonstrates its potential to simplify tracking fluctuations in baby weight and development progress related to stunting over time. Early trials demonstrated an impressive accuracy rate of 99.4% in body weight measurements and provided excellent conclusions in determining the body weight status of the infants. Overall, this IoT-based solution catalyzes the improvement of stunting detection methodologies and early intervention strategies, thus promising a better solution and a significant positive impact on global child health.

Mg alloys with antitumor and anticorrosion properties for orthopedic oncology: A review from mechanisms to application strategies.

As a primary malignant bone cancer, osteosarcoma (OS) poses a great threat to human health and is still a huge challenge for clinicians. At present, surgical resection is the main treatment strategy for OS. However, surgical intervention will result in a large bone defect, and some tumor cells remaining around the excised bone tissue often lead to the recurrence and metastasis of OS. Biomedical Mg-based materials have been widely employed as orthopedic implants in bone defect reconstruction, and, especially, they can eradicate the residual OS cells due to the antitumor activities of their degradation products. Nevertheless, the fast corrosion rate of Mg alloys has greatly limited their application scope in the biomedical field, and the improvement of the corrosion resistance will impair the antitumor effects, which mainly arise from their rapid corrosion. Hence, it is vital to balance the corrosion resistance and the antitumor activities of Mg alloys. The presented review systematically discussed the potential antitumor mechanisms of three corrosion products of Mg alloys. Moreover, several strategies to simultaneously enhance the anticorrosion properties and antitumor effects of Mg alloys were also proposed.

Differential efficacy of medical therapies for ulcerative colitis according to disease extent: patient-level analysis from multiple randomized controlled trials

Disease extent in Ulcerative Colitis (UC) has prognostic implications for disease course. It is unclear whether the efficacy of medical therapies for moderate to severely active UC vary according to disease extent at enrollment. We analyzed patient level data from 11 Phase 2 and 3 clinical trials of advanced therapies in patients with moderate-to-severe UC to assess modifications of advanced therapy effects by disease extent. Primary outcome was clinical response and secondary outcomes were clinical remission, endoscopic response/remission and endoscopic improvement, and Mayo clinic subscore for both induction and maintenance studies. Binary and continuous outcomes were analyzed using the modified Poisson regression model and the mixed-effects model, respectively, adjusting for age, sex, disease duration, concomitant steroid use and prior anti-TNF use. Effect modifications with binary outcomes were quantified by ratios of risk ratio for left-sided to that for extensive colitis while effect modifications with the Mayo subscores were quantified by differences of the differences between mean scores of the left-sided and extensive colitis. Results were presented with point estimates and 95% confidence intervals as well as p-values. Eleven clinical trials enrolling 5450 UC patients (infliximab=2, adalimumab=2, golimumab=2, vedolizumab=2, tofacitinib=3) were included. In induction trials, there was evidence to suggest effect modification by disease extent for clinical response with tofacitinib (the ratio of RRs 0.67, 95% CI [0.45, 0.99], p=0.049) and clinical remission with infliximab (ratio of RRs 0.33, 95% CI [0.13, 0.85], p=0.020) favoring patients with extensive colitis. There was no evidence to suggest effect modification for endoscopic improvement and clinical outcomes. There was evidence to suggest effect modification by disease extent for clinical remission with tofacitinib (ratio of RRs 0.44, 95% CI [0.22, 0.89], p=0.020) favoring patients with extensive colitis. For symptom subscores from the Mayo Clinic score, tofacitinib was associated with a greater reduction in both stool frequency (difference of differences 0.37, 95% CI [0.08, 0.65], p=0.012) and rectal bleeding scores (difference of differences 0.25, 95% CI [0.03, 0.47], p=0.026) in patients with extensive colitis compared to left sided. These findings underscore the possibility of differential efficacy of medical therapies according to disease distribution. These results warrant further exploration in forthcoming trials to better inform treatment strategies and consideration of disease distribution as a baseline stratification factor in clinical trials. This study did not receive any financial support.

Outcomes of Multiple Treatment Strategies for Iatrogenic Trauma From Femoral Artery Access

Outcomes of Multiple Treatment Strategies for Iatrogenic Trauma From Femoral Artery Access

Diagnosis and Management of Desmoid Fibromatosis of the Breast.

Desmoid fibromatosis of the breast (also known as desmoid tumor of the breast) is a rare entity infrequently encountered by oncologists and surgeons caring for patients with breast disease. The current body of literature is highly reliant on case series and extrapolations from other sites of desmoid tumor-related disease. Much remains unclear regarding the pathological origins, natural history, and response to treatment of this condition. Traditional treatment strategies have centered on surgical resection, which may result in significantly disfiguring cosmetic and functional outcomes, frequent need for re-operation, and associated morbidity. There are limited data to support the superiority of upfront surgical resection when compared to medical therapy or watchful waiting strategies. Current treatment guidelines for desmoid tumors do not focus on the breast as a site of disease and are purposefully ambiguous due to the paucity of evidence available. We aim to review the literature concerning desmoid fibromatosis of the breast and propose an algorithm for current evidence-based management of this rare disease in the context of our experience with this pathology at a high-volume quaternary referral center.

Non-Small Cell Lung Cancer Metastatic Without Oncogenic Alterations.

This overview provides a thorough review of current treatment approaches for first-line management of nononcogenic addicted non-small cell lung cancer. We also address pertinent clinical decision-making queries encountered in everyday practice, such as the optimal treatment strategy for PD-L1-high patients, predictive factors for response to immune checkpoint inhibitors (ICI) both in terms of patient and cancer characteristics, the potential benefits of dual checkpoint blockade, and the unresolved issue of safe discontinuation strategies for long-term responders. Around one in five patients falls into this latter category while the majority develop either primary or acquired resistance to ICI-based first-line therapy, necessitating effective subsequent lines of treatment. Docetaxel, with or without combination of antiangiogenic agents, serves as the backbone of treatment, although evidence in the post-ICI setting is limited. Given that an inflamed tumor microenvironment (TME) is crucial for ICI responses, targeting the TME in cases of acquired resistance alongside continued ICI administration appears rational, although clinical trials so far have failed to confirm this hypothesis. Antibody-drug conjugates have emerged as a promising treatment modality, offering the potential for reduced toxicity and improved efficacy by targeting specific cancer antigens. Moreover, several chemotherapy-free approaches are currently under investigation for treatment-naïve patients, including alternative ICI and drugs targeting epitopes on both cancer and immune cells.

Effect of loading direction and anatomical location on the ultimate tensile stress, fracture toughness, and failure patterns of knee meniscus

BackgroundRupture of the knee menisci is a common injury that can have implications for other conditions, such as osteoarthritis. The fracture toughness of soft tissue (Jc) is a mechanical property that characterizes its resistance to tear extension. To date, Jc of the meniscus has not been quantified. MethodsCyclic tensile tests were conducted on meniscus samples to determine Jc and explore its characteristics. Initially, the study investigated the impact of an initial notch on the ultimate tensile stress. This allowed for an understanding of how the presence of a notch affects its structural integrity. Subsequently, Jc was measured in both the radial and circumferential directions to assess its loading direction dependency. Furthermore, the study assessed the effect of anatomical location by comparing samples collected from the femoral and tibial layers. ResultsDefect tolerance of the meniscus is influenced by the loading direction. In the circumferential direction, the presence of an initial notch did not affect the ultimate stress, and no crack expansion was observed. In radial samples with a notch length of 40% or more of the total width, crack propagation occurred, leading to a decrease in the ultimate stress (p< 0.01). Additionally, Jc was found to be higher in the femoral layer compared to the tibial layer (p= 0.017). ConclusionThe study also examined the failure patterns of the meniscus to enhance our understanding of its pathology. These insights contribute to a better comprehension of meniscus injuries and can aid in the development of more effective treatment strategies.

Therapeutic Outcome of Multidisciplinary Treatment in Unresectable Biliary Tract Cancer: A Multicenter Retrospective Analysis.

There is little established evidence regarding treatment strategies for unresectable biliary tract cancer (BTC). This study aimed to clarify the situation of multidisciplinary treatment for unresectable BTC in the 2000s when there was no international standard first-line therapy. We retrospectively reviewed 315 consecutive patients with unresectable BTC who had been treated at seven tertiary institutions in Kanagawa Prefecture, Japan between 1999 and 2008. The unresectable factors were as follows: locally advanced, 101 cases (32.1%); hematogenous metastases, 80 cases (25.4%); and peritoneal dissemination, 30 cases (9.5%). Chemotherapy or radiation therapy was administered to 218 patients (69.2%). The best supportive care was provided in 97 cases (30.8%). The most common regimen was gemcitabine monotherapy, followed by gemcitabine combination therapy and S-1 monotherapy. The 1- and 2-year survival rates of all patients were 34.6% and 12.2%, respectively. The median survival time (MST) was 8 months in all patients. The 1-year survival rate was 65%, and the MST was 12 months among the locally advanced patients, whereas patients with peritoneal dissemination had the worst outcome; the 1-year survival rate was 7%, and the MST was 5 months. Among treated 90 cases of perihilar cholangiocarcinoma, patients who received chemoradiotherapy (n = 24) had a significantly better outcome than those who received chemotherapy alone (MST: 20 vs. 11 months, P < 0.001). Unresectable BTC has heterogeneous treatment outcomes depending on the mode of tumor extension and location. Multidisciplinary treatment seems useful for patients with locally advanced BTC, whereas patients with metastatic disease still have a poor prognosis.

Prevalence and Antibiogram of Escherichia coli Isolated from Children Under Five Years of Age Presented with Acute Diarrhoea: Cross Sectional Study from a Tertiary Care Centre in South India

Aim: The study aimed to analyze the prevalence and antibiogram of E. coli isolated from stool sample cultures collected from children below five years of age who were presented with acute diarrhoea in a tertiary care centre. Background: Multidrug-resistant strains of diarrheagenic E. coliremain a major public health concern for greater morbidity and mortality. Antibiotic resistance and susceptibility patterns of E. coli were found to vary with geographical location. Objective: To determine the prevalence and antibiogram of E. coli isolated from cultures of diarrhoea stool samples collected from children below five years of age from laboratory records. Methods: A cross-sectional study was designed to analyze the report on stool culture of children (aged below five years) presented with acute diarrhea during the period between 2017 and 2020. The prevalence of E. coli and its antibiogram were analyzed. The data were subjected to statis-tical analysis. Results: A total of 245 diarrhoea stool samples results were analyzed. E. coli was confirmed in 176 samples (72%). More number of isolates (51/176, 28.9%) were found in children below one year of age with male dominance. Amoxicillin resistance was found in all the E. coli strains isolated with no significant difference (p=0.2233) between genders and age groups below and above one year. A significant difference (p=0.0001) was found between male and female chil-dren of age below and above one year for cefotaxime and ciprofloxacin resistance. Polymyxin B (72%) followed by imipenem (69%) sensitivity was exhibited by the isolated E. coli strains. Conclusion: E. coli isolates were more sensitive to polymyxin B and imipenem while they were most resistant to amoxicillin. Effective antibiotic treatment strategies should be developed to control E. coli infections in children.

Breaking the Mold: Trailblazing Melanoma Therapy Beyond Checkpoint Through Innovative Approaches.

Melanoma has long been a difficult malignancy to treat with low response rates to standard chemotherapies. In recent years, the use of immune checkpoint inhibitors have demonstrated promising results, paving the way for the use of the rapidly developing novel immune targeting therapies. In this review, we look beyond immune checkpoint inhibitor treatments and summarize several emerging treatment strategies for melanoma, including neoantigen vaccines, conventional antibody drug-conjugates, and bispecific T-cell engager therapies.

Parathyroidectomy: still the best choice for the management of severe secondary hyperparathyroidism.

Management of secondary hyperparathyroidism (SHPT) is a challenging endeavor with several factors contruibuting to treatment failure. Calcimimetic therapy has revolutionized the management of SHPT, leading to changes in indications and appropriate timing of parathyroidectomy (PTX) around the world. We compared response rates to clinical vs. surgical approaches to SHPT in patients on maintenance dialysis (CKD 5D) and in kidney transplant patients (Ktx). A retrospective analysis of the one-year follow-up findings was carried out. CKD 5D patients were divided into 3 groups according to treatment strategy: parathyroidectomy, clinical management without cinacalcet (named standard - STD) and with cinacalcet (STD + CIN). Ktx patients were divided into 3 groups: PTX, CIN (cinacalcet use), and observation (OBS). In CKD 5D we found a significant parathormone (PTH) decrease in all groups. Despite all groups had a higher PTH at baseline, we identified a more pronounced reduction in the PTX group. Regarding severe SHPT, the difference among groups was evidently wider: 31%, 14% and 80% of STD, STD + CIN, and PTX groups reached adequate PTH levels, respectively (p<0.0001). Concerning the Ktx population, although the difference was not so impressive, a higher rate of success in the PTX group was also observed. PTX still seems to be the best treatment choice for SHPT, especially in patients with prolonged diseases in unresourceful scenarios.