Line Treatment Research Articles

Cost-Effectiveness of Capivasertib as a Second-Line Therapy for Advanced Breast Cancer.

Capivasertib, a first-in-class AKT inhibitor, was recently approved as a second-line treatment for advanced breast cancer. However, capivasertib is expensive, raising questions over its economic value. This study provides the first evidence on the cost effectiveness of adding capivasertib to endocrine therapy (fulvestrant) for patients with PIK3CA/AKT1/PTEN-altered, hormone receptor-positive (HR+) human epidermal growth factor receptor2-negative (HER2-) advanced breast cancer. A Markov model was built to compare the costs and effectiveness of three treatment strategies. The first strategy involved adding capivasertib to fulvestrant for all patients, while the second strategy involved adding it for only postmenopausal women. The third strategy involved treatment with fulvestrant alone. Analyses were conducted from a US payer perspective over a lifetime horizon. Costs were measured in 2023 US dollars, and effectiveness was measured in life years (LYs) and quality adjusted life years (QALYs), discounted at 3% per year. One-way sensitivity analyses, probabilistic sensitivity analyses, and scenario analyses were conducted to assess the robustness of results. The addition of capivasertib to fulvestrant for all patients was associated with $410,765 higher costs and 1.46 additional quality adjusted life years (QALYs) compared with fulvestrant alone, resulting in an incremental cost effectiveness ratio of $280,854/QALY. The strategy of adding capivasertib for only patients who are postmenopausal was extended dominated, i.e., yielded fewer QALYs at a higher cost per QALY than if capivasertib was added for all patients. These results were found to be robust in sensitivity and scenario analyses. At its current price, our analysis suggests that theaddition of capivasertib to fulvestrant as a second line treatment is not cost effective versus fulvestrant alone at a willingness-to-pay threshold of $100,000/QALY. The price of capivasertib will need to be reduced by nearly 70% (to $7000 per cycle) for it to become cost effective.

Elotuzumab in combination with pomalidomide, bortezomib, and dexamethasone in relapsed and refractory multiple myeloma.

Elotuzumab is an approved monoclonal antibody targeting SLAMF7 on plasma and NK cells that enhances the activity of lenalidomide, pomalidomide, and bortezomib in multiple myeloma (MM). The OPTIMISMM study showed improved outcomes with the combination of pomalidomide, bortezomib, and dexamethasone (PVd) in relapsed/refractory MM. We therefore studied adding elotuzumab to PVd (elo-PVd) in relapsed/refractory MM in a multicenter phase 2 trial. The primary objective was to determine the overall response rate (ORR). Patients with relapsed/refractory disease and ≥1 prior line of treatment (including lenalidomide and a proteasome inhibitor) were eligible. For each 28 day cycle, elotuzumab was weekly for the first 2 cycles and then every other week; pomalidomide was on days 1-21; bortezomib was on days 1, 8, 15; and dexamethasone was weekly. The trial completed accrual in September 2018 with 48 patients receiving treatment. The median age was 64 (range 40-80) and the median number of prior lines was 3 (range 1-9); 25% had high risk FISH. Prior therapies included: pomalidomide (33%), daratumumab (25%), and isatuximab (4%). Best ORR was 56.3% and median PFS was 10 months. In patients with 1 prior line of therapy, ORR was 73.7% and median PFS was 23.4 months. Common grade ≥3 adverse events were neutropenia (33%); infections, any (33%); lung infection (27%); hypophosphatemia (19%); and thrombocytopenia (15%). Elo-PVd is one of the first trials of a quadruplet regimen in relapsed/refractory MM incorporating a monoclonal antibody to show efficacy across diverse prior treatments, including triple class exposed with prior anti-CD38 monoclonal antibody.

Heel Pain After Landing in a Soccer Player: A Case of Abductor Hallucis Strain

BACKGROUND: Plantar heel pain is often attributed to the plantar fascia and calcaneal fat pad, both for athletes and sedentary individuals. Another potential cause of heel pain is Abductor Hallucis muscle (AbdH) strain. CASE PRESENTATION: The athlete jumped for a header during a league game, and after he landed on his left foot with a dorsiflexed ankle, he felt sudden pain and was not able to continue. The initial physical examination has overlapping features of AbdH and plantar fascia injury. Detailed physical examinations and radiological images revealed AbdH strain. OUTCOME AND FOLLOW-UP: Immobilization and cold therapy were started as the first line of treatment, then stretching and gradual loading were added. The patient was able to play after 3 weeks. DISCUSSION: AbdH strain is a rare cause of heel pain, but it should be kept in mind, especially when a suspected mechanism of injury occurs.

Neuropsychiatric Symptoms in Dementia

ABSTRACT OBJECTIVE This article discusses the prevalence, pathophysiology, assessment, and management of neuropsychiatric symptoms in patients with dementia. LATEST DEVELOPMENTS There is a growing body of evidence localizing neuropsychiatric symptoms in dementia to frontal circuits in the brain, as well as relating them to pathologic changes seen in different dementias. Although very few medications have been approved by the US Food and Drug Administration (FDA) for the treatment of neuropsychiatric symptoms in dementia, there are more clinical trials showing the benefit of antidepressants, stimulants, and antipsychotics. In line with that trend, in 2023, the FDA approved the use of brexpiprazole, an atypical antipsychotic, for the treatment of agitation in Alzheimer disease dementia. ESSENTIAL POINTS Neuropsychiatric symptoms are a core feature of all dementias and often emerge before cognitive symptoms manifest. They are highly clinically significant symptoms that disrupt the lives of patients and care partners and greatly influence the decision to place patients in long-term care facilities. The first line of treatment for neuropsychiatric symptoms in dementia is nonpharmacologic behavioral modification, but clinicians often must supplement this intervention with medications using an empiric approach.

Salvage Therapy with Second-Generation Inhibitors for FLT3 Mutated Acute Myeloid Leukemia: A Real-World Study by the CETLAM and PETHEMA Groups

Background/Objectives: Patients with relapsed/refractory (R/R) AML with FLT3 mutation (FLT3mut) have a dismal prognosis. FLT3mut offers a target for therapy in these patients. Gilteritinib (gilter) and quizartinib (quizar) have demonstrated efficacy as single agents in two phase 3 clinical trials. Methods: We retrospectively analyzed the characteristics, treatments, and outcomes of 50 patients with R/R FLT3mut AML who received gilter or quizar as monotherapy in 27 Spanish centers before their commercial availability. Forty-four patients were treated with gilter and six with quizar. Results: The median age was 62.5 years, and 52% were women. Most patients presented with FLT3-ITD mutations (80%); 46% had refractory disease and 54% had relapsed disease at treatment initiation. First-line treatment was chemotherapy in 80% of patients, with 40% of these also receiving midostaurin. Twenty-five patients (50%) had previously received FLT3 inhibitor, and twenty-eight (56%) had received more than one line treatment before starting gilter/quizar. The rates of complete remission (CR), CR without hematological recovery (CRi), and partial remission were 22%, 18%, and 16%, respectively. The median overall survival (OS) and disease-free survival were 4.74 months and 2.99 months, respectively. We observed a significant improvement in OS in patients who had received only one prior line of therapy compared to those who had received two or more therapies (10.77 months vs. 4.24 months, p = 0.016). Multivariate analysis identified failure to achieve CR/CRi, receiving more than one prior line of therapy, age, and white blood cells count as independent prognostic factors for OS. The most common toxicities were febrile neutropenia, liver function abnormalities, and QT interval prolongation. Conclusions: Gilter/quizar monotherapy are effective and tolerable options for patients with R/R FLT3mut AML in a real-world setting. Response and toxicity rates are similar to those reported in the phase 3 trials, despite the more heterogeneous nature of the study population.

TRATAMENTO DA LEISHMANIOSE TEGUMENTAR NO BRASIL

Objective: To describe the efficacy of treatment for tegumentary leishmaniasis in Brazil, its CE and alternative treatments. Methods: This is a qualitative, retrospective and cross-sectional study carried out through an integrative literature review. The regional portal of the Virtual Health Library (VHL) and the National Library of Medicine of the United States (PubMed) were used. Articles published in the last 10 years (2014-2024); Controlled clinical trial type, free and full text. After reading the articles and using the criteria, a total of 20 articles were maintained. Results: It was observed that in Brazil they are used for the first line of treatment for TL, which are high-cost drugs that present limitations in patient management due to toxicity, need for parenteral administration and hospitalization. New treatment alternatives, such as miltefosine, pentoxifylline, liposomal amphotericin B, thermotherapy, and tamoxifen, have been used with similar cure rates and lower CE and could be recommended as a treatment option. Conclusion: The CE of the treatments interfere with the follow-up of the therapy, and it is necessary to use new drugs to bring comfort to the patients, increase efficacy and adherence.

Immunotherapy in Non-Small-Cell Lung Cancer: A Modified Delphi Survey Consensus on First Line Treatment, Special Populations and Rechallenge

Background: The treatment landscape for non-small cell lung cancer (NSCLC) has evolved significantly with the advent of immunotherapy. Nonetheless, uncertainty regarding optimal first-line treatments, special populations, and the feasibility of rechallenge remains. This study aims to investigate Italian oncologists’ opinions on these aspects through a Delphi Survey. Methods: A steering committee (SC) of six oncologists identified three topics of interest, namely NSCLC (first line) therapeutic choice, NSCLC special populations, and NSCLC immunotherapy rechallenge), and drafted several topic-related statements to be voted in the Delphi Survey by the 61 oncologists forming the Delphi Panel. The survey included two rounds, wherein the experts rated their agreement/disagreement with the statements on a 5-point Likert scale. Consensus was defined as agreement/disagreement by at least 75% of the panel. Results: The SC drafted 69 statements for the first round, of which 16 (23.2%) met the agreement threshold, 5 (7.2%) met the disagreement threshold, and 48 (69.6%) did not reach consensus. The SC revised the latter statements and drafted 37 for the second round. Overall, 5 (13.5%) statements met the agreement threshold, 1 (2.7%) met the disagreement threshold, and 31 (83.8%) did not reach consensus in the second round. Conclusions: The survey showed agreement on the necessity of molecular characterization, mutations, smoke, the role of steroid therapy, and immunotherapy rechallenge, and revealed several areas of uncertainty among Italian oncologists on the use of immunotherapy in NSCLC. Statements—where consensus was not met—can be used to guide future clinical research in resolving the issues.

Green-synthesized silver nanoparticles induced apoptotic cell death in CACO2 cancer cells by activating MLH1 gene expression

MLH1 (Mult homolog1) gene is the main element of Multlα heterodimer and plays a role in the repair of base-base mismatches and deletion and addition loops. When the MLH1 protein is not present, the number of errors that remain unrepaired increases, and this can lead to the formation of tumors in the body. Colorectal cancer is the third most common type of cancer in terms of incidence and the third type of cancer in terms of mortality worldwide. In this regard, the present study was conducted with the aim of investigating the effect of biological silver nanoparticles with anticancer properties and MLH1 gene expression on cancer cell samples of people with colorectal cancer. In this study, the green synthesis of silver nanoparticles was carried out by precipitation method with reduction of silver ions by leaf and flower extract of Moringa oleifera plant. Then, silver nanoparticles were confirmed using UV-visible spectroscopy, transmission and scanning electron microscopy. The cytotoxic effects of nanoparticles on cells were evaluated by MTT colorimetric method within 42 h. After RNA extraction of treated cells, cDNA synthesis and primers were designed by the Exon-Exon Junction method and the Real-time Polymerase test for MLH1 and Beta-actin genes was repeated three times. The final analysis of the results was done using Graphpad Prism and Rest 2009 software. The presence of a peak at the wavelength of 234 nm for the synthesized silver nanoparticles was confirmed by ultraviolet-visible spectroscopic analysis. The morphological study on the size and shape of the silver nanoparticles showed that the nanoparticles are spherical and have a size between 40 and 34 nanometers in diameter. The leaf extract typically produces smaller, more uniform particles than the flower extract. The Green-Synthesized Silver Nanoparticles of leaf extract were used to evaluation of induced Apoptotic Cell Death in CACO2 Cancer Cells by Activating MLH1 Gene Expression. MTT results showed that the anti-proliferative effect of nanoparticles depends on the concentration of synthesized silver nanoparticles. The treatment of MLH1 cancer cell line and normal with synthesized nanoparticles at a concentration of 0.44 micrograms per ml for 42 h showed the effects of cell toxicity. The percentage of cancer cell death under the influence of quercetin present in Moringa green bio-particles depends on the concentration and time, and this difference is statistically significant compared to the control group (P < 0.05). So that the lethal dose of the extract for 50% survival IC50 in a period of 48 h for intestinal cancer cells was equal to 21 μg/ml, and the expression ratio of the MLH1 gene in the tumor tissue to the adjacent healthy tissue has increased (P ≤ 0.05).

Outcomes with loncastuximab tesirine following CAR T-cell therapy in patients with relapsed or refractory diffuse large B-cell lymphoma

The efficacy of loncastuximab tesirine (lonca) following chimeric antigen receptor T-cell therapy (CAR-T) progression/failure is unknown. Hence, we sought to examine real-world use and outcomes of lonca following CAR-T in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in the USA. In this retrospective study, we included adults (age ≥ 18 years) with R/R DLBCL who received lonca monotherapy as third- (3 L) or fourth line (4 L) treatment after progressing on second line (2 L) or 3 L CAR-T, respectively. Post-CAR-T lonca outcomes included response rates (overall response rate [ORR] and complete response [CR] rate), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). A total of 118 patients were included in the analysis with 95 receiving lonca following 2 L CAR-T (median age:66 years; 61% male) and 23 following 3 L CAR-T (median age:57 years; 43% male). Patients with 2 L CAR-T/3 L lonca had an ORR of 73% (CR rate of 34%). With a median follow-up of 8.5 months following lonca initiation, median DOR, PFS, and OS were not reached. The DOR, PFS, and OS at 12 months were 68%, 77%, and 84%, respectively. Patients with 3 L CAR-T/4 L lonca had an ORR of 78% (CR rate of 17%). With a median follow-up of 13 months following lonca initiation, the median DOR and PFS were 7.6 and 12.0 months, while median OS was not reached. OS at 12 months was 95%. In this study, we found that lonca monotherapy was an effective treatment option in R/R DLBCL in 3 L and 4 L settings including those who were resistant to or progressed after CAR-T.

Chaturvimshati Upkrama: General Treatment Principles For Poisoning Cases- A Review

Poisoning is a very common cause of death. Intentional poisoning cases account for 68.42% and 31.58% cases due to accidental poisoning. Ancient ayurvedic treatises have mentioned 24 treatment modalities for cases of poisoning termed as “Chaturvimshati Upkrama” i.e. 24 types of treatment principles as a general line of treatment in the cases of poisoning. Acharya Charak mentioned it in his chikitsasthan 23, vishachikitsa adhyay. These 24 treatment modalities include the shodhan, shaman, shastra etc. karma to overcome poison.

Antecedent viral immunization and efficacy of immune checkpoint blockade: an extensive serum antibody profile to predict outcomes in non-small cell lung cancer

IntroductionImmune checkpoint blockers (ICBs) revolutionized the treatment of patients with advanced non-small cell lung cancer (NSCLC) but only a fraction of them obtain a response, and clinical benefit from these...

Prognostic factors associated with worse outcomes following chemoradiation therapy in patients with anal carcinoma.

Chemoradiation therapy (CRT) is considered as the first line of treatment for patients with squamous cell carcinoma of the anal canal. Following initial CRT, patients who present with either persistent or locally recurrent disease are treated by surgical intervention. The aim of our study is to determine the prognostic factors associated with failure of CRT and overall mortality in patients with anal squamous cell carcinoma (SCC). We performed a 14-year analysis (2004-2017) of the National Cancer Database and included patients diagnosed with non-metastatic SCC of the anal canal who underwent CRT. Baseline patient characteristics including demographics, comorbidities and tumour characteristics were analysed. Outcome measures were needed for operative intervention after 4 months of initiation of CRT (failure of CRT) and 5-year overall mortality. Multivariate logistic regression analysis identified prognostic factors independently associated with failure of CRT. We included a total of 37 615 patients with anal SCC who received CRT. Predictors of operative intervention included male sex, higher Deyo-Charlson Comorbidity Index (DCCI) and higher primary tumour stage. The 5-year overall survival rate was 77.6%, and 2.4% of patients failed CRT, defined as requiring and undergoing surgical intervention within 4 months post-initiation of CRT. Median follow-up time was 47 (95% CI 24-84) months. Independent predictors of overall mortality within the first 5 years of diagnosis were increased age, male sex, Black race, non-insured status, higher DCCI, higher primary tumour grade, and higher primary tumour and lymph node stage. The 5-year survival rate was significantly lower in patients who underwent operative intervention compared to those who received CRT alone (57.4% vs. 78.1%; P < 0.01). Our study showed that male sex, younger age, DCCI of 1 and 3, and increased tumour size were predictive of CRT failure among patients with anal SCC. Increased age, male sex, Black race, non-insured status, increased DCCI, and more aggressive tumour characteristics were associated with increased 5-year overall mortality. More importantly, patients who failed CRT had worse 5-year overall survival. Our findings support increased emphasis on intensive surveillance for these high-risk patient cohorts.

NivobotulinumtoxinA in the Treatment of Glabellar Lines With or Without Concurrent Treatment of Lateral Canthal Lines in Two Phase 3 Clinical Trials.

Botulinum neurotoxins used in aesthetic medicine require reconstitution before administration, which may be inconvenient and present errors among injectors. Evaluate the efficacy and safety of ready-to-use nivobotulinumtoxinA liquid formulation for the treatment of glabellar lines (GL) with/without treatment of lateral canthal lines (LCL). Two multicenter, phase 3, double-blind, randomized trials enrolled participants with moderate-to-severe GL (Study 001) or moderate-to-severe GL+LCL (Study 005). Participants received double-blind nivobotulinumtoxinA (20U) or placebo (Period 1) then ≤2 open-label nivobotulinumtoxinA GL treatments (Period 2) in Study 001 or double-blind nivobotulinumtoxinA 20U (GL), nivobotulinumtoxinA 44U (GL+LCL), or placebo (Period 1) then ≤2 double-blind injections of the same treatment (Period 2) in Study 005. The composite primary endpoint was the proportion of participants achieving ≥2-grade improvement in Facial Wrinkle Scale (FWS) at maximum frown on investigator and participant assessment; co-primary endpoints were investigator- and participant-assessed FWS "none or mild" rating. At Day 30, significantly higher responder rates were observed for the composite primary endpoint with GL treatment alone (Study 001, 46.1%; Study 005, 45.1%) and GL+LCL (Study 005, 41.3%) versus placebo (0%; all P < 0.001). Responder rates of "none or mild" by investigator and participant assessment, respectively, were significantly higher for GL treatment alone (Study 001, 77.2% and 65.0%; Study 005, 74.3% and 68.8%) and GL+LCL (Study 005, 74.0% and 61.2%) versus placebo (all P < 0.001). Adverse events were similar between treatment groups and placebo. Liquid nivobotulinumtoxinA was effective and well tolerated for treating moderate-to-severe GL alone or with LCL.

A case of delayed initial response to combination ipilimumab and nivolumab in malignant pleural mesothelioma

Malignant pleural mesothelioma has a poor prognosis with limited therapeutic options Although numerous trials have shown that combination immunotherapy with nivolumab and ipilimumab is one of the first line treatments for patients with unresectable MPM, there is limited data on delayed responses over a long follow up period. We report a case of a delayed response 7 months after the cessation of immunotherapy in a patient who initially had progressive malignant pleural mesothelioma with metastases.

Resistance to Tyrosine Kinase Inhibitors in Hepatocellular Carcinoma (HCC): Clinical Implications and Potential Strategies to Overcome the Resistance

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, and the development of effective treatment strategies remains a significant challenge in the management of advanced HCC patients. The emergence of tyrosine kinase inhibitors (TKIs) has been a significant advancement in the treatment of HCC, as these targeted therapies have shown promise in prolonging the survival of patients with advanced disease. Although immunotherapy is currently considered as the first line of treatment for advanced HCC patients, many such patients do not meet the clinical criteria to be eligible for immunotherapy, and in many parts of the world there is still lack of accessibility to immunotherapy. As such, TKIs still serve as the first line of treatment and play a major role in the treatment repertoire for advanced HCC patients. However, the development of resistance to these agents is a major obstacle that must be overcome. In this review, we explore the underlying mechanisms of resistance to TKIs in HCC, the clinical implications of this resistance, and the potential strategies to overcome or prevent the emergence of resistance.

Phase I Trial to Assess the Safety, Tolerability, and Preliminary Efficacy of OBI-858 for Treatment of Glabellar Lines.

OBI-858 is a brand-new botulinum Type A complex toxin with a specific molecular weight of 760kDa intended for development for both aesthetic and therapeutic applications.This is a phase I, dose-escalation study to evaluate the safety and preliminary efficacy of OBI-858 in subjects with moderate to severe glabellar lines. Each subject received OBI-858 by intramuscular injections with an assigned dose (10 U, 20 U, and 30 U). The safety and preliminary efficacy were evaluated at each of the in-person visits. A total of 36 subjects (12 subjects per cohort) were enrolled. The response rates (≥ 1 point) for all groups at maximum frown were assessed at week 4 were 100%. The initial improvement for 30 U occurred at day 3. Response rates revealed benefits lasting 4-6months or longer. Subject satisfaction at week 4 was high in all groups. Adverse effects were mild and infrequent. Among them, one subject had drug-related AE, and one subject had grade ≥ 3 unrelated AE. This study demonstrated that OBI-858 is well tolerated and showed preliminary efficacy. Overall, the OBI-858 has a clinically favorable profile of safety and efficacy that warrants proceeding to the next studies.

Novel Self-Expandable Laser-Cut Device for Effective Thrombus Retrieval: Overcoming Limitations in Thrombectomy for Deep Vein Thrombosis, Peripheral Artery Disease and Pulmonary Embolism

Pulmonary embolism (PE) is a serious complication of deep vein thrombosis (DVT) and peripheral artery disease, often leading to fatal outcomes. The first line of treatment for DVT and PAD is anticoagulation: preventing the thrombus, occlusion of blood vessels, and propagation of PE especially in the case of DVT where limb or life-threatening complications are at risk. Clots retrieved from vessels include mechanical and manual interventions such as catheter-directed thrombolysis and thrombectomy. Yet the risks involved with thrombotic and embolic vascular occlusions are high because they cause occlusion of blood flow in crucial vessels; this may lead to tissue damage, organ failure, and death. Most of the existing thrombectomy devices do not remove the organized thrombus completely while prevention of clot fragmentation is also lacking. The study presents a new, self-expanding laser-cut clot retrieval device specifically designed to remove both hard and soft thrombi with no trauma at all to the vessel wall. This is one of the promising advancements in thrombectomy that overcomes the disadvantages of other existing technologies and offers a stronger approach for the removal of occlusions in the vascular system associated with DVT, PAD, and PE. The simulation test in vitro and a trackability test have been conducted with the developed device together with its delivery system for validation. These tests were envisaged to demonstrate how the device can operate, for example, navigate through the vasculature, and retrieve thrombi safely and accurately.

Phytochemical, Cytoprotective Profiling, and Anti-Inflammatory Potential of Colchicum luteum in Rheumatoid Arthritis: An Experimental and Simulation Study

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by severe pain, inflammation, and joint deformity. Currently, it affects 1% of the population, with a projection to exceed 23 million cases by 2030. Despite significant advancements, non-steroidal anti-inflammatory drugs (NSAIDs), the first line of treatment, are associated with a range of adverse effects. Consequently, plant-based derivatives are being utilized as an effective alternative. This study evaluates the anti-inflammatory and safety profile of Colchicum luteum hydroethanolic extract (CLHE) in comparison to NSAIDs, with a focus on COX-2 and TNFα inhibition. Methods: CLHE potential was evaluated by phytochemical screening and in vitro bioactivity assays. Toxicity profile was conducted in Human Colon Epithelial Cells (HCEC) and Balb/c mice. Anti-inflammatory potential was explored in a collagen-induced arthritic (CIA) mice model. Bioactive compounds were identified computationally from GCMS data and subjected to docking and simulation studies against COX2 and TNFα. Results: CLHE demonstrated significant antioxidant (IC-50 = 6.78 µg/mL) and anti-inflammatory (IC-50 = 97.39 µg/mL) activity. It maintained 50% cell viability at 78.5 μg/µL in HCEC cells and exhibited no toxicity at a dose of 5000 mg/kg in mice. In the CIA model, CLHE significantly reduced paw swelling, arthritic scoring, C-reactive protein levels, and spleen indices, outperforming ibuprofen. Expression analysis confirmed the downregulation of COX-2, TNFα, and MMP-9. Histopathological analysis indicated the superior efficacy of CLHE compared to ibuprofen in reducing inflammation, synovial hyperplasia, and bone erosion. Computational studies identified compound-15 (CL15), (4-(4,7-dimethoxy-1,3-benzodioxol-5-yl)-2-oxo pyrrolidine-3-carboxylic acid), a non-toxic compound with strong binding affinities to COX-2 (−12.9 KJ/mol), and TNF-α (−5.8 KJ/mol). Conclusions: The findings suggest the potential of Colchicum luteum as a safer, anti-inflammatory, and multi-targeted alternative to NSAIDs for RA treatment.

Alternatives to Injectable Adrenaline for Treating Anaphylaxis.

Adrenaline is the first line treatment for anaphylaxis and adrenaline auto-injectors (AAI) allow reliable, safe and ergonomic administration in the community. However, AAIs have significant limitations and adrenaline is often not used in anaphylaxis. Innovations to administer adrenaline via alternative routes may potentially improve usage rates and treatment effectiveness. Here, we describe the known limitations and barriers to AAI use in anaphylaxis. We then summarise current data for adrenaline devices which use alternative routes of administration for treating anaphylaxis. Several novel devices are in development, which deliver adrenaline via nasal, sublingual or transcutaneous routes. Pharmacokinetic, pharmacodynamic and safety studies have compared these treatments with AAI or intramuscular adrenaline via needle and syringe. The first non-injectable adrenaline delivery device for emergency treatment of anaphylaxis was approved in Europe and the United States. Neffy, an adrenaline nasal spray, is licensed for use in adult and paediatric patients who weigh at least 30 kg. In the near future, multiple alternatives to injectable adrenaline may be available for managing anaphylaxis, overcoming some, but not all of the limitations of AAIs.

SNMMI PIC case competition finalist: Subcutaneous Panniculitis-Like T-Cell Lymphoma on 18F-FDG PET/CT

Abstract A 9-month-old girl was evaluated for recurrent fevers, rash, and indurated plaques, with laboratories demonstrating hyperferritinemia, hypertriglyceridemia, and pancytopenia, concerning for hemophagocytic lymphohistiocytosis. Biopsy of thigh lesion ultimately demonstrated subcutaneous panniculitis-like T-cell lymphoma. In a rare neoplasm of cytotoxic T-cells, subcutaneous panniculitis-like T-cell lymphoma presents with subcutaneous nodules in all age groups including children. Prognosis is generally good with immunosuppressive drugs being first line of treatment. 18F-FDG PET/CT demonstrates hypermetabolic lesions and is used to determine the extent of disease burden, identify sites of occult disease, and assess response to treatment.