Insights into the Window of Opportunity and Outcome Measures in Patients with Moderate to Severe Hidradenitis Suppurativa Treated with Secukinumab: A Real-World Study.

INTRODUCION: The concept of a window of opportunity in hidradenitis suppurativa (HS) management suggests that early initiation of biological therapy leads to better outcomes, though its timing remains uncertain. METHODS: We conducted a retrospective observational multicenter study, including consecutive patients with moderate to severe HS who initiated secukinumab treatment following prior failure with systemic antibiotics or adalimumab. Therapeutic burden was defined as the sum of previous systemic treatment cycles and previous major surgical interventions for HS. Patients were followed up for 24 weeks. Main outcomes were safety and effectiveness, assessed through the proportion of patients achieving HS Clinical Response (HiSCR) and a 55% reduction in International HS Severity Score System (IHS4-55). Additionally, potential predictors of response to secukinumab were studied. Analysis was performed on an intention-to-treat basis. RESULTS: A total of 67 patients (33 men, 34 women) were included, with a mean age of 41.55 (11.94) years and a mean baseline IHS4 of 17.88 (11.13). The mean therapeutic burden was 6.06 (3.49). At week 24, 10.45% (7/67) of patients experienced adverse events, with three leading to treatment discontinuation. At week 24, 41.79% (28/67) of patients achieved HiSCR, and 44.78% (30/67) of patients achieved IHS4-55. HiSCR could not be calculated in 12 patients with a baseline AN count < 3. A lower therapeutic burden was significantly associated with a higher likelihood of achieving HiSCR and IHS4-55 at week 24. CONCLUSIONS: Secukinumab showed safety and efficacy in real-world patients with HS, and the inverse correlation found between therapeutic burden and treatment response supports the concept of a window of opportunity, offering insights into its timing.

Preventive Intake of a Multiple Micronutrient Supplement during Mild, Acute SARS-CoV-2 Infection to Reduce the Post-Acute COVID-19 Condition: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

Patients hospitalized with COVID-19 have low levels of vitamins and trace elements. This could lead to a post-acute COVID-19 condition (PCC) that can worsen a patient's quality of life. We aimed to study the baseline micronutrient status of patients and assess whether a multiple micronutrient supplement (MMS) taken for 2 weeks at the first sign of COVID-19 symptoms would be able to reduce the incidence of PCC. This double-blind, placebo-controlled, randomized clinical trial was conducted in adult outpatients with acute COVID-19, recruited between 2021 and 2023 in Spain. Of the 285 patients assessed for eligibility, 267 were randomized and 246 were included in the intent-to-treat population. The mean age was 46.8 years, and 68% were female. Overall, 54.6% had micronutrient deficiencies in the acute phase of COVID-19 at baseline, and 26.2% had PCC after 180 days of follow-up (D180). The most frequently recorded PCC symptoms were neurological (14.1%), with 24% patients scoring worse in the cognitive tests compared to their baseline status. The rate of PCC at D180 was similar between the placebo (25.0%) and intervention (27.7%) groups, without significant differences (p = 0.785). Age over 50 years was the most relevant risk factor for developing PCC, followed by female sex. The most important protective factor against PCC was SARS-CoV-2 vaccination. In this population of predominantly middle-aged, white women with acute COVID-19 not requiring hospital admission, MMS intake for 14 days at symptom onset did not prevent PCC nor improve their micronutrient status at D180.

Clinical and Immunologic Characteristics of Colorectal Cancer Tumors Expressing LY6G6D.

The identification of targets that are expressed on the cell membrane is a main goal in cancer research. The Lymphocyte Antigen 6 Family Member G6D (LY6G6D) gene codes for a protein that is mainly present on the surface of colorectal cancer (CRC) cells. Therapeutic strategies against this protein like the development of T cell engagers (TCE) are currently in the early clinical stage. In the present work, we interrogated public genomic datasets including TCGA to evaluate the genomic and immunologic cell profile present in tumors with high expression of LY6G6D. We used data from TCGA, among others, and the Tumor Immune Estimation Resource (TIMER2.0) platform for immune cell estimations and Spearman correlation tests. LY6G6D expression was exclusively present in CRC, particularly in the microsatellite stable (MSS) subtype, and was associated with left-side tumors and the canonical genomic subgroup. Tumors with mutations of APC and p53 expressed elevated levels of LY6G6D. This protein was expressed in tumors with an inert immune microenvironment with an absence of immune cells and co-inhibitory molecules. In conclusion, we described clinical, genomic and immune-pathologic characteristics that can be used to optimize the clinical development of agents against this target. Future studies should be performed to confirm these findings and potentially explore the suggested clinical development options.

Characterization of Human B Cell Hematological Malignancies Using Protein-Based Approaches.

The maturation of B cells is a complex, multi-step process. During B cell differentiation, errors can occur, leading to the emergence of aberrant versions of B cells that, finally, constitute a malignant tumor. These B cell malignancies are classified into three main groups: leukemias, myelomas, and lymphomas, the latter being the most heterogeneous type. Since their discovery, multiple biological studies have been performed to characterize these diseases, aiming to define their specific features and determine potential biomarkers for diagnosis, stratification, and prognosis. The rise of advanced -omics approaches has significantly contributed to this end. Notably, proteomics strategies appear as promising tools to comprehensively profile the final molecular effector of these cells. In this narrative review, we first introduce the main B cell malignancies together with the most relevant proteomics approaches. Then, we describe the core studies conducted in the field and their main findings and, finally, we evaluate the advantages and drawbacks of flow cytometry, mass cytometry, and mass spectrometry for the profiling of human B cell disorders.

Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease.

Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.

Progress towards the elimination of trachoma in Nigeria.

Trachoma is targeted for elimination as a public health problem worldwide by 2030. In Nigeria, elimination activities are implemented at the local government area (LGA) level. They started in 2002 by conducting baseline population-based prevalence surveys (PBPSs), which continued in a systematic manner with engagement from the Global Trachoma Mapping Project in 2013, and subsequently Tropical Data. The results led to the development of Nigeria's first trachoma action plan and its subsequent revision with additional information. Following 449 baseline PBPSs, 122 LGAs had an active trachoma prevalence above the elimination threshold, requiring interventions, while 231 LGAs required community-based interventions for trichiasis management. By 2021, >34 million antibiotic treatments had been provided in 104 LGAs, with 89 LGAs eliminating active trachoma. Nationally, water and sanitation coverages increased by 3% and 18%, respectively, in 7 y. Systematic trichiasis case finding and management were carried out in 231 LGAs, resulting in the management of 102 527 people. Fifty-four LGAs decreased trichiasis prevalence unknown to the health system to <0.2% in persons ≥15 y of age. Where this elimination prevalence threshold was reached, trichiasis services were transitioned to routine eye/healthcare systems. Such progress relied on strong leadership and coordination from the national trachoma program and tremendous support provided by partners. Attaining elimination of trachoma as a public health problem in Nigeria by 2030 is feasible if funding support is sustained.

Chemically tailored graphite oxide nanoparticles for improving material properties of canola protein-based films.

Canola protein obtained from canola meal, a byproduct of the canola industry, is an economical biopolymer with promising film-forming properties. It has significant potential for use as a food packaging material, though it possesses some functional limitations that need improvement. Incorporating nanomaterials is an option to enhance functional properties. This study aims to produce canola protein films by integrating GO exfoliated at several oxidation times and weight ratios to optimize mechanical, thermal, and barrier properties. Oxidation alters the C/O ratio and adds functional groups that bond with the amino/carboxyl groups of protein, enhancing the film properties. Significant improvement was obtained in GO at 60 and 120 min oxidation time and 3% addition level. Tensile strength and elastic modulus increased 200% and 481.72%, respectively, compared to control. Control films showed a 37.57 × 10-3 cm3m/m2/day/Pa oxygen permeability, and it was significantly reduced to 5.65 × 10-3 cm3m/m2/day/Pa representing a 665% reduction.

Antifungal activity of extracts from Justicia species against Fusarium graminearum.

Fusarium graminearum causes destructive ear rot diseases in maize and wheat. New antifungals are essential to combat this pathogen, and aerial parts of Justicia species (Acanthaceae) are a potential source. We investigated the antifungal activity of extracts from stems and leaves of five Justicia species native to Northwest Argentina. The aerial parts were subjected to sequential extractions with dichloromethane, ethyl acetate, and methanol. The resulting extracts were tested by the disc diffusion method against F. graminearum strains. Only the leaf and stem extracts from J. xylosteoides displayed inhibitory effects, with the dichloromethane leaf extract as the most active. The compounds involved were identified as the lignans hinokinin, savinin, and isohibalactone. Both the dichloromethane extract and hinokinin synergised with tebuconazole, and inhibited deoxynivalenol biosynthesis. The identified compounds warrant further research as additives to azole fungicides for F. graminearum control.

In Silico Transcriptomic Expression of MSR1 in Solid Tumors Is Associated with Responses to Anti-PD1 and Anti-CTLA4 Therapies.

Immuno-oncology has gained momentum with the approval of antibodies with clinical activities in different indications. Unfortunately, for anti-PD (L)1 agents in monotherapy, only half of the treated population achieves a clinical response. For other agents, such as anti-CTLA4 antibodies, no biomarkers exist, and tolerability can limit administration. In this study, using publicly available genomic datasets, we evaluated the expression of the macrophage scavenger receptor-A (SR-A) (MSR1) and its association with a response to check-point inhibitors (CPI). MSR1 was associated with the presence of macrophages, dendritic cells (DCs) and neutrophils in most of the studied indications. The presence of MSR1 was associated with macrophages with a pro-tumoral phenotype and correlated with TIM3 expression. MSR1 predicted favorable overall survival in patients treated with anti-PD1 (HR: 0.56, FDR: 1%, p = 2.6 × 10-5), anti PD-L1 (HR: 0.66, FDR: 20%, p = 0.00098) and anti-CTLA4 (HR: 0.37, FDR: 1%, p = 4.8 × 10-5). When specifically studying skin cutaneous melanoma (SKCM), we observed similar effects for anti-PD1 (HR: 0.65, FDR: 50%, p = 0.0072) and anti-CTLA4 (HR: 0.35, FDR: 1%, p = 4.1 × 10-5). In a different dataset of SKCM patients, the expression of MSR1 predicted a clinical response to anti-CTLA4 (AUC: 0.61, p = 2.9 × 10-2). Here, we describe the expression of MSR1 in some solid tumors and its association with innate cells and M2 phenotype macrophages. Of note, the presence of MSR1 predicted a response to CPI and, particularly, anti-CTLA4 therapies in different cohorts of patients. Future studies should prospectively explore the association of MSR1 expression and the response to anti-CTLA4 strategies in solid tumors.

Genomic and Immunologic Correlates in Prostate Cancer with High Expression of KLK2.

The identification of surfaceome proteins is a main goal in cancer research to design antibody-based therapeutic strategies. T cell engagers based on KLK2, a kallikrein specifically expressed in prostate cancer (PRAD), are currently in early clinical development. Using genomic information from different sources, we evaluated the immune microenvironment and genomic profile of prostate tumors with high expression of KLK2. KLK2 was specifically expressed in PRAD but it was not significant associated with Gleason score. Additionally, KLK2 expression did not associate with the presence of any immune cell population and T cell activating markers. A mild correlation between the high expression of KLK2 and the deletion of TMPRSS2 was identified. KLK2 expression associated with high levels of surface proteins linked with a detrimental response to immune checkpoint inhibitors (ICIs) including CHRNA2, FAM174B, OR51E2, TSPAN1, PTPRN2, and the non-surface protein TRPM4. However, no association of these genes with an outcome in PRAD was observed. Finally, the expression of these genes in PRAD did not associate with an outcome in PRAD and any immune populations. We describe the immunologic microenvironment on PRAD tumors with a high expression of KLK2, including a gene signature linked with an inert immune microenvironment, that predicts the response to ICIs in other tumor types. Strategies targeting KLK2 with T cell engagers or antibody-drug conjugates will define whether T cell mobilization or antigen release and stimulation of immune cell death are sufficient effects to induce clinical activity.

Kinematic parameters related to functional capacity, fatigue, and breathlessness during the 6-min walk test in older adults with heart failure with preserved ejection fraction.

AIMS: This paper aims to assess kinematic parameters related to functional capacity, fatigue, and breathlessness during the 6-min walk test (6MWT) in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: A cross-sectional study was conducted in which adults 70 years or older with HFpEF were voluntarily recruited between April 2019 and March 2020. An inertial sensor was placed at the L3-L4 level and another on the sternum to assess kinematic parameters. The 6MWT was divided into two 3-min phases. Leg fatigue and breathlessness, assessed by the Borg scale, the heart rate (HR), and the oxygen saturation (SpO2), were measured at the beginning and the end of the 6MWT. The difference in kinematic parameters between the 6MWT two 3-min phases was also calculated. Bivariate Pearson correlations and subsequent multivariate linear regression analysis were performed. Seventy older adults with HFpEF (mean = 80.74 years old) were included. Kinematic parameters explained 81.00% of the functional capacity, 45.50% of the leg fatigue and 66.10% of the breathlessness variance. Moreover, kinematic parameters could explain 30.90% of the SpO2 variance at the end of the 6MWT. Kinematic parameters also explained 33.10% of the SpO2 difference between the beginning and end of 6MWT. Kinematic parameters explained neither the HR variance at the end of 6MWT nor the HR difference between the beginning and end. CONCLUSION: Gait kinematics from L3-L4 and sternum explain a part of the variance in subjective outcomes, assessed by the Borg scale, and objective outcomes such as functional capacity and SpO2. The kinematic assessment allows clinicians to quantify fatigue and breathlessness through objective parameters related to the patient's functional capacity. REGISTRATION: ClinicalTrials.gov NCT03909919.

Tropical Data: Approach and Methodology as Applied to Trachoma Prevalence Surveys.

PURPOSE: Population-based prevalence surveys are essential for decision-making on interventions to achieve trachoma elimination as a public health problem. This paper outlines the methodologies of Tropical Data, which supports work to undertake those surveys. METHODS: Tropical Data is a consortium of partners that supports health ministries worldwide to conduct globally standardised prevalence surveys that conform to World Health Organization recommendations. Founding principles are health ministry ownership, partnership and collaboration, and quality assurance and quality control at every step of the survey process. Support covers survey planning, survey design, training, electronic data collection and fieldwork, and data management, analysis and dissemination. Methods are adapted to meet local context and needs. Customisations, operational research and integration of other diseases into routine trachoma surveys have also been supported. RESULTS: Between 29th February 2016 and 24th April 2023, 3373 trachoma surveys across 50 countries have been supported, resulting in 10,818,502 people being examined for trachoma. CONCLUSION: This health ministry-led, standardised approach, with support from the start to the end of the survey process, has helped all trachoma elimination stakeholders to know where interventions are needed, where interventions can be stopped, and when elimination as a public health problem has been achieved. Flexibility to meet specific country contexts, adaptation to changes in global guidance and adjustments in response to user feedback have facilitated innovation in evidence-based methodologies, and supported health ministries to strive for global disease control targets.

Considerations for the design of antibody drug conjugates (ADCs) for clinical development: lessons learned.

Antibody-drug conjugates (ADCs) have emerged as a novel therapeutic strategy that has successfully reached patient treatment in different clinical scenarios. ADCs are formed by an antibody against a specific tumor-associated antigen (TAA), a cytotoxic payload, and a chemical linker that binds both. To this regard, most efforts have been focused on target identification, antibody design and linker optimization, but other relevant aspects for clinical development have not received the necessary attention. In this article using data from approved ADCs, we evaluated all characteristics of these agents, including payload physicochemical properties, in vitro potency, drug antibody ratio (DAR), exposure-response relationships, and clinical development strategies. We suggest that compounds with best options for clinical development include those with optimal payload physicochemical properties and cleavable linkers that would lead to a bystander effect. These modalities can facilitate the development of ADCs in indications with low expression of the TAA. Early clinical development strategies including changes in the schedule of administration with more frequent doses are also discussed in the context of an efficient strategy. In conclusion, we highlight relevant aspects that are needed for the optimal development of ADCs in cancer, proposing options for improvement.

Accuracy, acceptability and feasibility of photography for use in trachoma surveys: a mixed methods study in Tanzania.

BACKGROUND: Photography could be used to train individuals to diagnose trachomatous inflammation-follicular (TF) as trachoma prevalence decreases and to ensure accurate field TF grading in trachoma prevalence surveys. We compared photograph and field TF grading and determined the acceptability and feasibility of eyelid photography to community members and trachoma survey trainers. METHODS: A total of 100 children ages 1-9 y were examined for TF in two Maasai villages in Tanzania. Two images of the right everted superior tarsal conjunctiva of each child were taken with a smartphone and a digital single-lens reflex (DSLR) camera. Two graders independently graded all photos. Focus group discussions (FGDs) were conducted with community members and Tropical Data trainers. RESULTS: Of 391 photos, one-fifth were discarded as ungradable. Compared with field grading, photo grading consistently underdiagnosed TF. Compared with field grading, DSLR photo grading resulted in a higher prevalence and sensitivity than smartphone photo grading. FGDs indicated that communities and trainers found photography acceptable and preferred smartphones to DSLR in terms of practicalities, but image quality was of paramount importance for trainers. CONCLUSIONS: Photography is acceptable and feasible, but further work is needed to ensure high-quality images that enable accurate and consistent grading before being routinely implemented in trachoma surveys.

Partial characterization of canola (Brassica napus L.) protein isolates as affected by extraction and purification methods.

Canola (Brassica napus L.) meal represents a prominent alternative plant-based source for protein isolation. This work aimed to investigate the combined effect of extraction and purification methods for the production of canola protein isolates (CPIs). CPIs were characterized in terms of process yield, protein recovery, basic composition, amino acid profile, in vitro protein digestibility, techno-functional properties, structural properties, and molecular features. The results showed that the Alk-Uf method enhanced yield (16.23 %) and protein recovery (34.88 %). Meanwhile, the Et-Alk-Uf method exhibited the highest crude protein (89.71 %) and free amino nitrogen (4.34 mg g protein-1) contents. Furthermore, protein digestibility (95.5 %) and protein digestibility corrected amino acid score (1.0) were improved using the Et-Alk-Ac method. Conversely, the amino acid composition, secondary structure, and electrophoretic profiles were generally similar for all CPIs. The Alk-Uf and Et-Alk-Uf methods produced isolates with the highest water solubility (∼39.18 %), water absorption capacity (∼3.86 g water g protein-1), oil absorption capacity (∼2.77 g oil g protein-1), and foaming capacity (∼505.26 %). Finally, the foaming stability (93.75 %) and foaming density (34.38 %) were increased when employing the Alk-Ac method. These findings suggest that, in general, the Alk-Uf and Et-Alk-Uf methods can be used to obtain CPIs with high added value for use in food formulations.

Effectiveness of a cardiac rehabilitation program on biomechanical, imaging, and physiological biomarkers in elderly patients with heart failure with preserved ejection fraction (HFpEF): FUNNEL + study protocol.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) have a low functional status, which in turn is a risk factor for hospital admission and an important predictor of survival in HFpEF. HFpFE is a heterogeneous syndrome and recent studies have suggested an important role for careful, pathophysiological-based phenotyping to improve patient characterization. Cardiac rehabilitation has proven to be a useful tool in the framework of secondary prevention in patients with HFpEF. Facilitating decision-making and implementing cardiac rehabilitation programs is a challenge in public health systems for HFpEF management. The FUNNEL + study proposes to evaluate the efficacy of an exercise and education-based cardiac rehabilitation program on biomechanical, physiological, and imaging biomarkers in patients with HFpEF. METHODS: A randomised crossover clinical trial is presented among people older than 70 years with a diagnosis of HFpEF. The experimental group will receive a cardiac rehabilitation intervention for 12 weeks. Participants in the control group will receive one educational session per week for 12 weeks on HFpEF complications, functional decline, and healthy lifestyle habits. VO2peak is the primary outcome. Biomechanical, imaging and physiological biomarkers will be assessed as secondary outcomes. Outcomes will be assessed at baseline, 12 weeks, and 24 weeks. DISCUSSION: Identifying objective functional parameters indicative of HFpEF and the subsequent development of functional level stratification based on functional impairment ("biomechanical phenotypes") may help clinicians identify cardiac rehabilitation responders and non-responders and make future clinical decisions. In this way, future pharmacological and non-pharmacological interventions, such as exercise, could be improved and tailored to improve quality of life and prognosis and reducing patients' hospital readmissions, thereby reducing healthcare costs. TRIAL REGISTRATION: NCT05393362 (Clinicaltrials.gov).

Safety and effectiveness of bDMARDs during pregnancy in patients with rheumatic diseases: Real-world data from the BIOBADASER registry.

INTRODUCTION: Inflammatory rheumatic diseases usually affect women of childbearing age treated with biologic drugs. However, there is a lack of literature on the efficacy and toxicity of biologic disease-modifying drugs during pregnancy. The aim of this study was to determine the presence of pregnant patients treated with bDMARDs in a real-world dataset and to examine the impact of pregnancy and lactation on the evolution of rheumatic disease in a registry of Spanish patients. METHOD: This was a multicentre prospective study with a real-world setting. Information was obtained from BIOBADASER registry. Patients included are women who got pregnant until November 2020 from 19 rheumatology units. We conducted proportions, means, and standard deviations (SD) to describe the study population and the use of treatments. T-test and Chi-square test were applied to assess differences between groups. RESULT: Ninety cases of pregnancy were registered (n=68 full-term pregnancies; n=22 spontaneous miscarriages). Most of the cases discontinued bDMARDs during pregnancy (78.9%) but 13 cases continued treatment during pregnancy, mainly using certolizumab pegol. These cases were obtaining better management of rheumatic disease, although the differences were not statistically significant [DAS28-CRP, 2.9 (SD: 1.6) vs. 2.0 (1.2), p=.255; DAS28-ESR, 2.2 (1.0) vs. 1.7 (.5), p=.266]. No serious adverse events were reported during pregnancy and lactation. CONCLUSION: Being pregnant is still an uncommon condition in patients with rheumatic diseases and using bDMARDs. Our results show that rheumatic disease tended to progress better during pregnancy in patients who continued to take bDMARDs.

Twenty-Three Population-Based Trachoma Prevalence Surveys in the Central and Northern Regions of Benin, 2018-2022.

PURPOSE: Trachoma is an infectious eye disease caused by Chlamydia trachomatis. Infection causes conjunctival inflammation, which can be manifested by the sign known as trachomatous inflammation-follicular (TF). Repeated inflammation leads to eyelid scarring, which in susceptible individuals can cause in-turning of the eyelashes, referred to as trachomatous trichiasis (TT). This article describes 23 population-based surveys conducted in northern and central Benin to determine TF and/or TT prevalence for trachoma elimination purposes. METHODS: A total of 18 surveys estimated the prevalence of both TF and TT: two baseline surveys, eight impact surveys after implementation of interventions against trachoma, and eight surveillance surveys. Five other evaluation units (EUs) were surveyed for TT only. To estimate the TF prevalence, a target sample size of 1701 (baseline) and 1164 1-9-year-olds (impact and surveillance) was required, whereas 2818 ≥ 15-year-olds were required to estimate the less prevalent TT. In each EU, individuals were selected by two-stage cluster sampling and examined by certified graders for TF and/or TT. RESULTS: A total of 68,613 people were examined. TF prevalence estimates were under the 5% elimination threshold in all surveys. TT prevalence estimates were above the 0.2% elimination threshold in all five TT-only surveys and in four impact surveys, ranging from 0.2-0.57. CONCLUSION: TF prevalence in Benin is low, but TT was above 0.2% in nine districts. Increased case-finding and continuing efforts to improve surgery accessibility will be needed to reduce the burden of TT in Benin.

Prevalence of Trachoma After Three Rounds of Antibiotic Mass Drug Administration in 13 Woredas of Gambella Region, Ethiopia.

BACKGROUND: Following baseline surveys in 2013 and 2014, trachoma elimination interventions, including three rounds of azithromycin mass drug administration (MDA), were implemented in 13 woredas (administrative districts) of Gambella Regional State, Ethiopia. We conducted impact surveys to determine if elimination thresholds have been met or if additional interventions are required. METHODS: Cross-sectional population-based surveys were conducted in 13 woredas of Gambella Regional State, combined into five evaluation units (EUs), 6─12 months after their last MDA round. A two-stage systematic (first stage) and random (second stage) sampling technique was used. WHO-recommended protocols were implemented with the support of Tropical Data. Household water, sanitation and hygiene (WASH) access was assessed. RESULTS: The age-adjusted prevalence of trachomatous inflammation - follicular (TF) in 1-9-year-olds in the five EUs ranged from 0.3-19.2%, representing a general decline in TF prevalence compared to baseline estimates. The age- and gender-adjusted prevalence of trachomatous trichiasis (TT) unknown to the health system in those aged ≥ 15 years ranged from 0.47-3.08%. Of households surveyed, 44% had access to an improved drinking water source within a 30-minute return journey of the house, but only 3% had access to an improved latrine. CONCLUSION: In two EUs, no further MDA should be delivered, and a surveillance survey should be conducted after two years without MDA. In one EU, one further round of MDA should be conducted followed by another impact survey. In two EUs, three further MDA rounds are required. Surgery, facial cleanliness and environmental improvement interventions are needed throughout the region.

Uncovering therapeutic opportunities in the clinical development of antibody-drug conjugates.

INTRODUCTION: Antibody-drug conjugates (ADCs) are a family of therapeutic agents that have demonstrated clinical activity in several indications. MATERIAL AND METHODS: In this article, we performed a deep analysis of their clinical landscape matched with public genomic human datasets from tumour antigen targets (TATs), to identify empty areas for clinical development. RESULTS: We observed that TATs used in haematological malignancies were more specific than the ones developed in solid cancers. Those included CD19, CD22, CD30, CD33 and CD79b. In solid tumours, we identified TATs, with approved ADCs, widely expressed in non-explored niche indications like Enfortumab vedotin (anti-Nectin4) in lung or cervical cancer; Tisotumab vedotin (anti-TF) in glioblastoma or pancreatic cancer; and Sacituzumab govitecan (anti-TROP2) in pancreatic, gastric, thyroid or endometrial cancer, among others. Similarly, niche indications for ADCs in clinical development included targets for CD71, PSMA, PTK7 or CD74, in tumours like breast, lung, stomach or colon. Some of these TATs were essential for the survival of tumour cells like CD71, PSMA and PTK7. CONCLUSIONS: In summary, our study opens the door for further evaluation of ADCs in several indications not explored before.