Need For Treatment Research Articles

Minimal disease activity and associated factors in patients with psoriatic arthritis: cross-sectional study from a single center

IntroductionPsoriatic arthritis (PsA) is a heterogeneous disease with various manifestations such as dactylitis, enthesitis, spondylitis, and skin involvement. Minimal disease activity (MDA) has been successfully used in daily clinical practice and is considered a reasonable treatment target in patients with PsA. In this study, we aimed to evaluate the MDA status and associated factors in patients with PsA in our tertiary referral clinic.Material and methodsThis cross-sectional study included patients who met the CASPAR classification criteria and had at least 6 months of follow-up data between 2001 and 2021. Patients who met at least 5 of 7 criteria (tender joint count ≤ 1/68, swollen joint count ≤ 1/66, Psoriasis Area Severity Index [PASI] ≤ 1, Visual Analogue Scale [VAS] ≤ 15, patient global VAS ≤ 20, Health Assessment Questionnaire-Disability Index [HAQ-DI] ≤ 0.5, and enthesitis number ≤ 1) were considered to achieve MDA.ResultsData from 172 patients (61% female) were analyzed and included in the study. While most patients had polyarticular involvement (33.7%), mono-oligoarthritis was present in 30.2%, mixed type in 26.2%, isolated distal interphalangeal arthritis in 5.8%, isolated spondylitis in 2.9%, and arthritis mutilans in 1.2%. Overall, 95 (55.2%) of the patients were observed at MDA, which was lower in tumor necrosis factor inhibitor (TNFi) users compared to only conventional synthetic disease-modifying antirheumatic drug users. In univariate analysis, MDA was associated with higher patient age, longer psoriasis duration, late-onset PsA, and continued use of first TNFi. In multivariate analysis, higher patient age, late-onset PsA, and higher continuation rate of first TNFi were associated with MDA.ConclusionsIn the study, more than half of our patients achieved MDA status. A higher MDA rate was associated with a higher continuation rate at first-line TNFi treatment. The relatively large po­pulation who could not reach MDA status in our study indicates an unmet need for monitoring and treatment of PsA.

Clinical and Laboratory Characteristics of Pediatric Patients With ACKR1/DARC-Associated Neutropenia.

ACKR1/DARC-associated neutropenia (ADAN), resulting from homozygosity for a single nucleotide polymorphism (SNP) in the ACKR1/DARC gene (rs2814778), is a common cause of benign neutropenia that primarily affects individuals of African and Jewish Yemenite descent. We aimed to characterize ADAN in pediatric patients in Israel, given its ethnically diverse population. We assessed children with isolated neutropenia treated during 2018-2023 at one pediatric center, for the ACKR1/DARC polymorphism, using Sanger sequencing or targeted next-generation sequencing. Of 115 patients evaluated, 49 (42.6%) were diagnosed with ADAN; of these, 29 (59%) had absolute neutrophil counts in the severe range (0-0.5×109/L) at diagnosis. The allele distribution revealed 37% of Muslim Arab and 61% of Jewish origin. Yemenite, Ethiopian, Mediterranean, Asian, and European ancestry were included; 59% had a family history of neutropenia. The median age at the first neutropenia detection was 1.2years; 91.8% were identified during routine blood counts. The median absolute neutrophil count at diagnosis was 0.5×109/L (interquartile range: 0.3). An increased susceptibility to infections was not found either before or during the median follow-up period of 2.5years (interquartile range: 1.54) after the diagnosis of ADAN. In 34 patients (72.3%), neutrophil counts were in the normal range during febrile illnesses. We identified ADAN in individuals of variable ethnicities, almost half with severe neutropenia. We recommend testing for ADAN in all children with isolated neutropenia without severe infections. Homozygosity for the ACKR1/DARC rs2814778 SNP may obviate the need for further investigation, follow-up, or treatment in specific clinical scenarios.

Emerging strategies to overcome ovarian cancer: advances in immunotherapy

Ovarian cancer is the second most common malignant neoplasm of gynecological origin and the leading cause of death from cancer in the female reproductive system worldwide. This scenario is largely due to late diagnoses, often in advanced stages, and the development of chemoresistance by cancer cells. These challenges highlight the need for alternative treatments, with immunotherapy being a promising option. Cancer immunotherapy involves triggering an anti-tumor immune response and developing immunological memory to eliminate malignant cells, prevent recurrence, and inhibit metastasis. Some ongoing research investigate potentially immunological advancements in the field of cancer vaccines, immune checkpoint blockade, CAR-T cell, and other strategies.

ANFIS Fuzzy convolutional neural network model for leaf disease detection

Leaf disease detection is critical in agriculture, as it directly impacts crop health, yield, and quality. Early and accurate detection of leaf diseases can prevent the spread of infections, reduce the need for chemical treatments, and minimize crop losses. This not only ensures food security but also supports sustainable farming practices. Effective leaf disease detection systems empower farmers with the knowledge to take timely actions, leading to healthier crops and more efficient resource management. In an era of increasing global food demand and environmental challenges, advanced leaf disease detection technologies are indispensable for modern agriculture. This study presents an innovative approach for detecting pepper bell leaf disease using an ANFIS Fuzzy convolutional neural network (CNN) integrated with local binary pattern (LBP) features. Experiments involve using the models without LBP, as well as, with LBP features. For both sets of experiments, the proposed ANFIS CNN model performs superbly. It shows an accuracy score of 0.8478 without using LBP features while its precision, recall, and F1 scores are 0.8959, 0.9045, and 0.8953, respectively. Incorporating LBP features, the proposed model achieved exceptional performance, with accuracy, precision, recall, and an F1 score of higher than 99%. Comprehensive comparisons with state-of-the-art techniques further highlight the superiority of the proposed method. Additionally, cross-validation was applied to ensure the robustness and reliability of the results. This approach demonstrates a significant advancement in agricultural disease detection, promising enhanced accuracy and efficiency in real-world applications.

Pediatric Hospital Utilization During Medical Stabilization for Patients With Eating Disorders.

Few studies have examined pediatric hospital utilization across the spectrum of eating disorder (ED) diagnoses among hospitalized patients. We describe sociodemographic and clinical characteristics, hospital utilization, and enteral tube feeding and examine factors associated with hospital utilization among patients with EDs. Using data from the Pediatric Health Information System, we included patients aged 4 to 20 years with primary ED diagnoses hospitalized from 2018 to 2022. We examined sociodemographic factors, length of stay, costs, and enteral tube feeding by ED diagnosis. Adjusted regression models compared hospital utilization by diagnosis, adjusting for sociodemographic and clinical factors. Among N = 10 279 hospitalizations from 49 hospitals, anorexia nervosa (AN) was most common (70.9%), followed by avoidant restrictive food intake disorder (ARFID) (15.6%). Mean age was 15.1 years (SD = 2.5), and most were female (86.6%), of white non-Hispanic race (70.9%), with private insurance (70.1%), with 63.9% occurring after the coronavirus disease 2019 pandemic onset. Median (interquartile range) length of stay was 8.0 days (7.0), and hospital costs were $18 099 ($15 592). A total of 18.8% received enteral tube feeding, with significant hospital variation. In adjusted models, compared with AN, ARFID, binge disorders, and unspecified feeding and ED had shorter stays, whereas hospital costs were lower for binge disorders, and enteral feeding was more likely for ARFID. Our findings indicate long and costly hospitalizations, especially for AN, with implications for hospital and treatment capacity, highlighting the need for earlier diagnosis and treatment to prevent the need for hospitalization.

Precision Cut Lung Slices: Emerging Tools for Preclinical and Translational Lung Research. An Official American Thoracic Society Workshop Report.

The urgent need for effective treatments for acute and chronic lung diseases underscores the significance of developing innovative preclinical human research tools. The 2023 ATS Workshop on Precision Cut Lung Slices (PCLS) brought together 35 experts to discuss and address the role of human tissue-derived PCLS as a unique tool for target and drug discovery and validation in pulmonary medicine. With increasing interest and usage, along with advancements in methods and technology, there is a growing need for consensus on PCLS methodology and readouts. The current document recommends standard reporting criteria and emphasizes the requirement for careful collection and integration of clinical metadata. We further discuss current clinically relevant readouts that can be applied to PCLS and highlight recent developments and future steps for implementing novel technologies for PCLS modeling and analysis. The collection and correlation of clinical metadata and multiomic analysis will further advent the integration of this preclinical platform into patient endotyping and the development of tailored therapies for lung disease patients.

The effects of professional expertise on perceptions of treatment need in patients with class II division 1 malocclusion: a comparison between orthodontists, general dentists, and lay people in Germany.

This study aimed to compare the perception of practitioners with varying levels of expertise and laypeople regarding the orthodontic treatment need and facial harmony in patients with increased anterior overjet. Three groups of observers (orthodontists, general dentists, and laypeople, in total n = 48) were asked to rate on images-using a10-point visual analog scale (VAS)-the facial harmony and treatment need of asample of 8patients with classII division1 malocclusion and overjets of 2, 4, 6, and 8 mm. Statistically significant differences were observed between the three groups of observers regarding patients with an overjet of 4 mm and above (p < 0.001). Treatment need was perceived at an overjet of 4 mm by orthodontists and 6 mm by general dentists, whereas laypeople did not perceive aneed for treatment in any of the groups (p < 0.001). Regarding perception of facial harmony, orthodontists had the lowest threshold (4 mm overjet), while dentists followed at agreater overjet of 6 mm or more (p < 0.001). Astatistically significant correlation between the noticed facial harmony and the perceived orthodontic treatment need was found in all observers (p < 0.001). The perceived orthodontic treatment need for classII division1 malocclusion increased with increasing professional expertise.

Changes in insomnia and binge-eating symptom severity before and after treatment of eating disorders in individuals with non-low-weight binge-spectrum disorders.

Although emerging research suggests insomnia is a significant problem among people with eating disorders, little is known about how insomnia symptoms may serve as risk factors for eating disorder symptoms, treatment outcome, and relapse. University students with non-low-weight eating disorders (N = 89) completed a mobile guided self-help cognitive behavioural intervention for eating disorders. Insomnia and binge-eating symptoms were assessed at pre-treatment and end-of-treatment using the Insomnia Severity Index and Eating Pathology Symptoms Inventory. Multiply imputed datasets were used to test associations between insomnia and binge eating before, during and after treatment. Insomnia was positively associated with binge-eating symptoms prior to treatment (r = 0.47). Baseline insomnia symptoms were associated with binge-eating symptoms at end-of-treatment (est = 0.269). Eating disorder treatment modestly reduced insomnia (d = -0.38); however, about half of people with clinically significant insomnia prior to treatment remained symptomatic. Insomnia symptoms and binge-eating symptoms did not change concurrently during treatment. Overall, results support an association between insomnia and binge eating. Although eating disorder treatment may impact insomnia, many individuals remained symptomatic for sleep problems, suggesting the need for follow-up treatments, such as cognitive behavioural therapy for insomnia, or the development of integrated insomnia-eating disorder treatments. Future studies are needed to examine causal links between insomnia and eating disorder symptoms, and test if insomnia predicts relapse after eating disorder treatment.

Strong association between high burden of soil-transmitted helminthiasis and household transmission among Malaysian Negritos, urging anthelmintic treatment beyond children

The Orang Asli (OA), Malaysia’s indigenous minority, continue to experience ongoing soil-transmitted helminth (STH) infections despite efforts including the Resettlement Programme (RPS). This study explores STH epidemiology and associated risks of moderate-to-heavy infections among 259 indigenous Negritos across four states in Peninsular Malaysia. Stool samples, anthropometrics, haemoglobin levels (finger-prick) and sociodemographic and environmental-sanitation factors via pretested questionnaires were collected. Parasitological examinations (direct faecal smear, formol-ether concentration, and Kato-Katz techniques) were thoroughly performed. The study revealed a 63.3% overall STH prevalence, with Trichuris trichiura (57.9%) being the most common, followed by Ascaris lumbricoides (35.5%) and hookworm (8.9%). Moderate-to-heavy infections were observed in 39.3% for T. trichiura and 48.9% for A. lumbricoides, with mixed infections of these two species being the most prevalent (50.6%). The risk for moderate-to-heavy infection increased significantly if other household members were infected (P < 0.001). Adults and adolescents also showed high infection rates, with no significant differences with children’s groups. These findings emphasize the need for anthelmintic treatment across all age groups and strategize local policies targeting older groups of the OA community to control ongoing transmission and reduce the STH burden and protect the future well-being of OA children, who deserve a healthier future.

Faecal incontinence: investigation, treatment and management.

Faecal incontinence is a hidden problem that is often under-reported, under-diagnosed, under-investigated and under-treated. Faecal incontinence is more common in women and older people. Its prevalence also increases with age. Faecal incontinence occurs because of a complex interplay of contributing factors, some of which can be reversed in primary care without the need for specialist investigations and treatment. This article explores the reasons why adults develop faecal incontinence and how to identify and treat reversible causes in primary care. It also provides information on specialist treatment and the management of intractable faecal incontinence. A structured approach to assessment and management is key in identifying problems and offering primary care for timely treatment.

High-resolution cryo-EM analysis of a Streptococcus pyogenes M-protein/human plasminogen complex.

The importance of human plasminogen (hPg)/plasmin (hPm)/cell receptor complexes in invasiveness of cells has been amply established. The objective of this investigation was to determine a high-resolution structure of a major Group A Streptococcus (GAS) bacterial receptor (PAM) for hPg/hPm when bound on a cell surface to its major ligand, hPg. As a model cell surface with endogenous PAM, we employed engineered PAM-expressing lentivirus (LV) particles. We show that the ectodomain of a PAM-type M-Protein (M-Prt), in complex with hPg, is folded through distinct intra- and inter-domain interactions to a more compact form on the cell surface, thus establishing a new paradigm for membrane-bound M-Prt/ligand structures. These studies provide a framework for addressing the need for treatments of GAS disease by providing a molecular platform to solve structures of virulence-determining membrane proteins.

OA24 Extended oligoarthritis with proximal muscle weakness and antinuclear antibody positivity associated with a novel genetic variant of uncertain significance in lipopolysaccharide-responsive and beige-like anchor protein (LRBA) gene

Abstract Introduction LRBA deficiency is associated with recurrent infections and immune dysregulation, particularly autoimmune cytopenias, enteropathy and intestitial lung disease, and in a few cases chronic polyarthritis and uveitis. Case description A girl presented at three years old with history of not walking for two months with no history of trauma or fever. Examination revealed arthritis in her ankles and knees. Ultrasound showed synovial thickening in both knees and small effusion to hips. There was no evidence of uveitis at presentation. Her bloods showed raised C-Reactive Protein (CRP) 33 mg/L and Erythrocyte Sedimentation rate (ESR) 45 mm/h. Anti-nuclear and anti-centromere antibodies were positive. Diagnosis was made of oligoarticular JIA and she was treated with intra-articular steroids in both knees and ankles and was started on oral prednisolone, weekly oral methotrexate. On subsequent clinic review, she had started to walk with mild restriction to internal rotation of hips and difficulty in getting up from sitting. She was started on regular hydrotherapy, physiotherapy and occupational therapy. From five to 11 years old, she had four flares of uveitis, treated with prednisolone eye drops; and two flares of arthritis, treated with steroids. Her methotrexate was changed to subcutaneous and at eight years of age she was also started on subcutaneous adalimumab fortnightly. Due to prolonged proximal muscle weakness, abnormal gait and chronic pain in leg joints without clinical or radiological evidence of synovitis during clinic reviews, she underwent thorough neurological work up which was inconclusive for myopathies. Her creatinine kinase levels, thyroid profile, MRI brain and spine were normal. Genetic work up showed two variants in the LRBA gene, one pathogenic and the other was variant of uncertain significance (VUS). Her CTLA4 expression was normal by flow cytometry. Discussion Three case reports have previously associated homozygous LRBA deficiency with polyarthritis. Compound heterozygous LRBA deficiency may present with various phenotypes including autoimmune disease affecting multiple organs, immune cytopenia and immune dysregulations including CTLA-4 expression. This report potentially widens the clinical spectrum of LRBA deficiency and given that it is a novel variant, prompts us to screen for this gene mutation in patients with JIA where remission is challenging and there is a need for continuous immunosuppressive or immune-modulatory therapy. Three case reports have previously associated homozygous LRBA deficiency with polyarthritis. Compound heterozygous LRBA deficiency may present with various phenotypes including autoimmune disease affecting multiple organs, immune cytopenia and immune dysregulations including CTLA-4 expression. This report potentially widens the clinical spectrum of LRBA deficiency and given that it is a novel variant, prompts us to screen for this gene mutation in patients with JIA where remission is challenging and there is a need for continuous immunosuppressive or immune-modulatory therapy. Three case reports have previously associated homozygous LRBA deficiency with polyarthritis. Compound heterozygous LRBA deficiency may present with various phenotypes including autoimmune disease affecting multiple organs, immune cytopenia and immune dysregulations including CTLA-4 expression. This report potentially widens the clinical spectrum of LRBA deficiency and given that it is a novel variant, prompts us to screen for this gene mutation in patients with JIA where remission is challenging and there is a need for continuous immunosuppressive or immune-modulatory therapy. Key learning points • There is no single diagnostic investigation for JIA as the aetiology is complex and there are currently no specific clinical guidelines of when to consider genetic testing in patients with JIA. With the mainstreaming of genetic services and improved access to cheaper, advanced next-generation sequencing, we should consider looking into monogenic conditions that mimic JIA. • The case illustrates the challenges of determining whether VUS are pathogenic in causing arthritis, or just incidental findings. Compound heterozygous LRBA may present within a spectrum of clinical features, further analysis with CTLA4 expression by flow cytometry and genetic analysis of siblings and parents will be helpful. • Compound heterozygous LRBA variation has different clinical manifestation which needs personalised treatment. Treatment with abatacept (a soluble CTLA4 immunoglobulin fusion protein) which is reported in a case series of LRBA deficiency. Risks of continuous immunosuppressive treatment need to be balanced with more definitive hematopoietic stem cell transplantation (HSCT) previously used to achieved complete remission in LRBA deficiency.

P50 Systemic lupus erythematous presenting as Kikuchi-Fujimoto disease complicated with haemophagocytic lymphohistiocytosis: a case report and review of the literature

Abstract Introduction Kikuchi-Fujimoto disease (KFD) or histiocytic necrotising lymphadenitis is a rare, self-limiting inflammatory condition that can be associated with autoimmune connective tissue disorders (CTD) especially systemic lupus erythematosus (SLE). The aetiopathogenesis remains unclear but it is thought to be triggered by an infection in individuals with autoimmune predisposition leading to T-cells mediated apoptosis and inflammatory cascade. This condition most commonly affects children and young adults of Asian descent with a slight female preponderance although it can affect any age and ethnic groups. Cervical lymphadenopathy and fever are the salient manifestations, and it can be fatal if complicated with haemophagocytic lymphohistiocytosis (HLH). Case description A 16 year old girl presented with a 2-month history of persistent fever, progressive bilateral cervical lymphadenopathy, generalised maculopapular rash, angioedema-like facial swelling, oral ulcers and B symptoms. Laboratory investigations revealed pancytopaenia, profound acute phase response and abnormalities consistent with HLH with an HScore of 200 points. A thorough infectious workup was unrevealing apart from serological evidence of past Epstein-Barr virus (EBV) infection. ANA, anti-Sm, anti-RNP and anti-B2GP1 IgG were positive. An ultrasound of her neck showed bilateral multilevel cervical lymphadenopathy and the excision biopsy of her lymph node confirmed features of histiocytic necrotising lymphadenitis and ruled out lymphoma. Notably, there were scattered EBV-positive blasts and the special staining for mycobacteria was negative. A CT scan has also demonstrated bilateral axillary and abdominal lymphadenopathy with no hepatosplenomegaly. There was thrombosis in her right internal jugular vein with no intracranial or cardiac extension of the thrombus. The patient was admitted to ITU for close monitoring due to concerns about possible airway compromise but she did not require any respiratory support. She received intravenous (IV) methylprednisolone pulses for three consecutive days, mycophenolate mofetil, hydroxychloroquine and treatment dose of enoxaparin with good response and did not require IV immunoglobulins (IVIG) and/or interleukin-1 receptor antagonists. However, she subsequently developed an abscess in her neck which was complicated by Staphylococcus aureus bacteraemia and underwent an emergency incision and drainage of the abscess. She recovered well with IV antibiotics and was followed up in the CTD clinic with continuous psychological support from the rheumatology clinical nurse specialists. Discussion KFD most commonly presents with acute to subacute tender cervical lymphadenopathy and fevers which can be associated with other systemic features such as arthralgia, various cutaneous manifestations with great histologic heterogeneity, and neurological manifestations including aseptic meningitis, meningoencephalitis, acute cerebellar syndrome and optic neuritis. Generalised lymphadenopathy has been reported in 22% of cases but hepato- and/or splenomegaly is uncommon (3-5% of cases). Various infectious agents including the EBV have been implicated as the potential trigger of this condition but the evidence remains inconclusive. Our patient’s lymph node biopsy has demonstrated EBV-positive blasts with serological evidence of past EBV infection but a causal relationship between these findings and KFD cannot be established with certainty. It remains a diagnostic challenge to differentiate KFD from the other more sinister pathologies such as lymphoma, various infectious lymphadenitis and autoimmune conditions such as sarcoidosis and Kawasaki disease. Therefore, early excisional biopsy of the affected lymph nodes is essential for establishing the correct diagnosis and may obviate the need for inappropriate treatments. Both KFD and SLE share a complex clinicopathological relationship as SLE may precede, occur concurrently as in this case or develop later following the diagnosis of KFD. Moreover, lupus lymphadenitis can mimic KFD clinically and these two entities can only be distinguished histologically by the demonstration of haematoxylin bodies in lupus lymphadenitis. Our patient developed thrombosis in her right internal jugular vein which was thought to be secondary to the compressive effect from her cervical lymphadenopathy rather than due the antiphospholipid syndrome as her repeat antiphospholipid screen was negative. Key learning points • Clinicians should be aware of this rare clinical entity to make an early diagnosis and avoid unnecessary investigations. Differentiating KFD from the other sinister conditions such as lymphoma remains a diagnostic challenge therefore an early excisional biopsy of the affected lymph nodes would avoid delayed diagnosis and obviate the need for potentially risky treatments. Patients with KFD should be carefully screened and monitored for SLE as it can precede, occur in conjunction with or follow the diagnosis of SLE. Most cases of KFD resolve within 1-6 months although recurrence has been reported in 3-4% and the mortality rate is estimated to be 2.1%. It is crucial to follow up these patients given the increased risk of recurrence which can continue for many years. Despite having a good response to treatments, our patient suffered from significant alopecia and post-inflammatory hyperpigmentation in her skin which has had a great impact on her self-esteem and mental well-being. We would like to highlight in this case the biopsychosocial ramifications of this condition and demonstrate the importance of a multidisciplinary approach in the management of young people with CTD.

Phenotypes of patients with lupus-associated pulmonary hypertension in the Chinese Han population: a cluster analysis.

Pulmonary hypertension (PH) is a severe complication of systemic lupus erythematosus (SLE). This study investigated the clinical features of patients with SLE-PH in China based on disease manifestations and organ involvement to define precise treatment of SLE and early prevention of complications. In total, 205 SLE-PH patients were included in this study. A cluster analysis was applied according to six clinical and serological variables to define different subgroups of patients. The survival rates of SLE-PH patients and risk factors that influenced prognosis were also compared and a clinical prediction model was developed for the diagnosis of associated lupus nephritis (LN). Patients were clustered in five groups. Patients in cluster 1 had severe renal damage (all patients had LN and had the highest creatinine and urea nitrogen and the lowest eGFR levels). Patients in cluster 2 had mild renal damage (more than half of the patients had associated LN and 87.5% had increased urinary protein levels but presented a lower degree of renal damage than those in the first group. Patients in cluster 3 had low-grade proteinuria (all patients had 24h urinary protein < 0.5g). Patients in cluster 4 had hematuria or urinary tubular damage (26% of patients had associated LN, but none of the patients had proteinuria. In cluster 5, patients barely had any major organ involvement. The clinical prediction model for a diagnosis of SLE-PH-LN was anti-dsDNA antibodies > 364.64IU/mL and neutrophil-to-leukocyte ratio (NLR) > 5.55. Our findings provide evidence indicating that SLE-PH presents varying clinical phenotypes and the treatment varies accordingly, suggesting the need for individualized treatment. Key Points • Clustered grouping of patients with SLE-PH is associated with renal injury. • This may be because PH and LN share a common pathogenesis. • The clinical prediction model for a diagnosis of SLE-PH-LN was anti-dsDNA antibodies >364.64 IU/mL and NLR >5.55.

Severe Uncontrolled Asthma: A Longitudinal Retrospective Study Illustrating the Experience of the Pulmonology Clinic of Târgu-Mureș, Romania

Introduction: Severe uncontrolled asthma (SUA) affects approximately 5% of asthma patients, leading to frequent exacerbations, reduced lung function, and lower quality of life. Recent biologic therapies target specific inflammatory pathways, offering new options for SUA. Objective: This study aimed to evaluate clinical characteristics, treatment outcomes, and biomarkers in patients with SUA treated with biologics (Omalizumab, Benralizumab, and Dupilumab) at our clinic. Material and Methods: A six-month retrospective longitudinal study was conducted on 28 patients aged 36–83 years with SUA. Patients were divided into three groups: Omalizumab (n = 4), Benralizumab (n = 18), and Dupilumab (n = 6). Lung function tests and biomarkers such as eosinophil and IgE levels were measured over 3-month periods (T0, T1, and T2). Asthma control was assessed using asthma control tests (ACT), and non-parametric statistical methods were applied. Results: The median patient age was 64 years, with 75% showing elevated eosinophil counts (&gt;300 cells/µL). Benralizumab significantly improved lung function (p &lt; 0.05) and ACT scores (p &lt; 0.001), reducing eosinophil counts to zero (p &lt; 0.001). Patients on Dupilumab and Omalizumab showed improved asthma control (p &lt; 0.05) and reduced exacerbations, albeit to a lesser extent (p &gt; 0.05). Conclusions: Biologics, particularly Benralizumab and Dupilumab, improved asthma control, lung function, and quality of life in SUA patients, with improved ACT scores and spirometry values. Some patients remained poorly controlled, emphasizing the need for personalized treatment and regular biomarker monitoring. Multidisciplinary management and lifestyle changes are critical for better outcomes in SUA.

Deciphering the inhibitory mechanism of antimicrobial peptide pexiganan conjugated with sodium-alginate chitosan-cholesterol nanoparticle against the opportunistic pathogen Acinetobacter baumannii

The emergence of antibiotic resistance is one of the most challenging problems of modern times as the armory of conventional antibiotics is quickly exhausting due to the rapid rise of resistance in pathogenic microorganisms. Acinetobacter baumannii, a potential member of ESKAPE group of bacteria, has a great deal of clinical importance causing severe nosocomial infections which often become life-threatening. According to the World Health Organization (WHO), antimicrobial resistance accounts for 2-3 million deaths every year across the world. Since the pathogen has the remarkable ability to acquire or upregulate various resistant determinants in the form of secreting of β-lactamase, aminoglycoside modifying enzymes, uplifting the function of efflux pumps or altering the target sites of different antibiotics; conventional antibiotic therapy often falls short to eradicate the infection. As a possible solution, the application of alternative therapy is therefore the need of the hour. Here we emphasize potentiating the antimicrobial efficacy of pexiganan, a well-known antimicrobial peptide against Gram-negative bacteria. Conjugation with nanoparticles composed of sodium-alginate and chitosan-cholesterol has increased the antimicrobial effect of the peptide on this opportunist pathogen. The evaluation of the bactericidal analysis and minimum inhibitory concentration indicates this nanocomposite can kill the bacteria at a very low concentration (3 μg/ml). When applied to the bacterial biofilm, the key factor for producing recalcitrant infection; our synthesized complex could effectively reduce the biomass in a dose-dependent manner. Later we enfold the mechanism of killing by measuring oxidative stress, cell membrane perforation by biochemical analysis. Our analysis indicates this unique nanocomposite can bypass the need of antibiotic treatment by its pore-forming ability on bacterial membrane. The nominal in-vivo toxicity and non-specific mode of action make it an interesting candidate for future therapeutics.

Impact on Survival with Immunotherapy and Evaluation of Biomarkers in Peruvian Patients with Advanced Melanoma.

Advanced malignant melanoma is a very aggressive disease, historically with poor prognosis before the new advances with immunotherapy and targeted therapies that have changed the standard of care, especially in cutaneous melanoma. Peru has aggressive features such as higher rates of acral lentiginous melanoma (ALM) subtype with historically shorter survival. This study describes Peruvian patients with advanced melanoma treated with immunotherapy (nivolumab) in two oncological institutions (public and private), including the discussion of the impact on overall survival (OS) divided by subtype (with incidence in ALM histology) and potential biomarkers that could be related to prognosis. We found that immunotherapy is safe, and improves progression-free survival (PFS), OS and objective response rate (ORR) in our patients, with lower benefit in ALM histology. No prognostic blood inflammatory biomarkers were detected. There is very limited data of Peruvian patients with metastatic melanoma treated with immunotherapy, especially the outcomes in ALM histology. Our goal is to share an example of the impact of immunotherapy in a Latin American (LATAM) population considered as an unsatisfied group with an enormous need of novel treatments and biomarkers.

Oral health statuses of individuals diagnosed with gastroparesis: A Cross-Section study.

Gastroparesis (GP) is a debilitating gastric motility disorder associated with digestive dysfunction, reduced quality of life (QoL), and increased mortality rates. There is no known cure for GP and treatment options are limited. The oral cavity is responsible for initiating digestion, yet the impact of GP symptom frequency on oral health status and oral healthcare utilization is not well understood. A 21-item electronic survey was developed and disseminated to a private GP social media forum. Survey questions explored GP symptom frequency, oral health status, dental care utilization, and oral health education post GP diagnosis. Descriptive and inferential statistics analysed data. There were 434 study participants. An overwhelming 83% reported GP negatively influenced their oral health and oral function. Significance was observed between GP symptom frequency and oral health status (p = <0.0001). The majority (81%) reported receiving dental care post GP diagnosis, yet (63%) reported current untreated dental concerns. Interestingly, (74%) of participants reported that they have never been educated about oral health risks associated with GP by any healthcare professionals. GP negatively affects oral health. Study participants reported a need for extensive dental treatments and high levels of untreated dental concerns. Results strongly support that preventive oral healthcare and education must be provided for individuals with a GP diagnosis. As leading oral disease prevention specialists, dental hygienists must be aware of the effects of GP on the oral cavity to help provide person-centred evidence-based care, improve digestive processes, and increase QoL for GP sufferers.

The Unmet Treatment Need for Eating Disorders: What Has Changed in More Than 10 Years? An Updated Systematic Review and Meta-Analysis.

A minority of individuals with eating disorders seek help from health professionals qualified to provide eating disorder care. This review assessed the proportion of individuals with eating disorders who had sought help or received treatment, as an update to an earlier review conducted more than a decade ago. Three databases were searched for studies that: (1) included a community sample of help-seekers and non-help seekers, (2) used a standardized eating disorder screening instrument, and (3) assessed the percentage of participants who had sought help specifically for eating disorder concerns. Of 972 articles, 21 studies met inclusion criteria, representing 37,423 participants. The pooled proportion reporting help-seeking from any source (e.g., helpline, support groups, chat rooms as well as health professionals) was 30% and the pooled proportion reporting formal treatment seeking from health professionals (e.g., psychologist) specifically for eating disorder concerns was 32%. However, there was evidence of publication bias across studies. These rates suggest little to no improvement in the unmet need for treatment since the last review with studies continuing to focus on white adult women. Help-seeking rates among other populations remain unclear and there is an urgent need to understand reasons for overall low help-seeking rates. Clear definitions and measures of help-seeking with appropriate distinctions between sources of help are needed to improve our understanding of help-seeking pathways and identify solutions to facilitate help-seeking. Better visibility of health professionals qualified to provide safe and effective eating disorder care could help reduce the substantial treatment gap.

Continuous peripheral nerve blocks for burn management: a retrospective study of outcomes and complications in 281 burn patients.

There is scarce literature regarding the use of continuous peripheral nerve blocks in acute burn patients, who may be at higher risk for catheter-related complications, including infection. We sought to describe our center's experience and infection rate with continuous perineural catheters in the setting of pain management for patients suffering from burns. A retrospective observational study was performed including all patients admitted to an American Burn Association-verified regional burn center between January 2018 and July 2023 who received a continuous peripheral nerve block for an acute burn injury. There were 281 patients in the study cohort who received 484 perineural catheters. The cohort was 52% men with a median age of 39 years (IQR 30-55). A catheter-associated infection, defined as a clinical diagnosis by the treating physicians requiring the need for treatment with antibiotics or surgical debridement, was identified in six perineural catheters (1.2%, 95% CI 0% to 2.2%) involving six different patients (2.1%, 95% CI 0% to 3.8%). The median total body surface area burned was 5% (IQR 2-9%) and 20% of patients had full-thickness burns. The most commonly used catheters were infraclavicular (49%), popliteal sciatic (29%), femoral (19%), and adductor canal (17%). One-third (33%) of patients did not require operating room debridement as the block provided sufficient analgesia for bedside debridement. The median duration of catheter use was 6 days (IQR 4-8). There were no documented cases of nerve injury or toxicity, vascular injury, or local anesthetic systemic toxicity. In our practice, continuous perineural catheters in the setting of acute burns are associated with an infection rate comparable to other surgical populations.