Ti/Ta-based composite polysaccharide scaffolds for guided bone regeneration in total hip arthroplasty.

Guided bone regeneration can play an important role in orthopedic applications. This work presents the synthesis and characterization of composite scaffolds based on polysaccharides loaded with microparticles of titanium or tantalum as novel materials proposed for composite systems with promising characteristics for guided bone regeneration. Ti/Ta composite scaffolds were synthesized using chitosan and gellan gum as organic substrates and crosslinked with oxidized dextran resulting in stable inorganic-organic composites. Physico-chemical characterization revealed a uniform distribution of metal nanoparticles within the scaffolds that showed a release of metals lower than 5 %. In vitro biological assays demonstrated that Ta composites exhibit a 2 times higher ALP activity than Ti and a higher capacity to support the full differentiation of human mesenchymal stem cells into osteoblasts. These results highlight their potential for bone regeneration applications.

Multidisciplinary expert consensus statements and recommendations for use of hypochlorous acid as a solution for negative pressure wound therapy with instillation.

BACKGROUND: HOCl (eg, pHAp) preserved solutions have antimicrobial properties and are considered safe and effective for wound management. NPWTi-d (or NPWTi) is an established adjunctive wound modality for a variety of wound etiologies in various anatomic locations in which an instillate solution dwells on the surface of the wound to assist in wound bed preparation. A variety of solutions have been used, including 0.9% normal saline wound cleansers and antiseptics. pHAp is growing in popularity as the solution of choice for NPWTi-d. OBJECTIVE: To evaluate consensus statements on the use of NPWTi-d with pHAp. METHODS: A 15-member multidisciplinary panel of expert clinicians in the United States, Canada, and France convened in person in April 2023 in Washington, D.C. and/or corresponded later to discuss 10 statements on the use of pHAp with NPWTi-d. The panelists then replied "agree" or "disagree" to each statement and had the option to provide comments. RESULTS: Ten consensus statements are presented, along with the proportion of agreement or disagreement and summary comments. Although agreement with the statements on NPWTi-d with pHAp varied, the statements appear to reflect individual preferences for use rather than concerns about safety or efficacy. CONCLUSION: The consensus indicates that NPWTi-d with pHAp can have a beneficial effect in wound care.

Synergistic clinical application of synthetic electrospun fiber wound matrix in the management of a complex traumatic wound: degloving left groin and thigh auger injury.

BACKGROUND: Managing complex traumatic soft tissue wounds involving a large surface area while attempting to optimize healing, avoid infection, and promote favorable cosmetic outcomes is challenging. Regenerative materials such as ECMs are typically used in wound care to enhance the wound healing response and proliferative phase of tissue formation. CASE REPORT: The case reported herein is an example of the efficacious use of an SEFM in the surgical management of a large complex traumatic wound involving the left lower extremity and lower abdominal region. The wound bed was successfully prepared for skin grafting over an area of 1200 cm2, making this among the largest applications of the SEFM reported in the literature. CONCLUSION: This case report demonstrates the clinical versatility of the SEFM and a synergistic approach to complex traumatic wound care. The SEFM was successfully used to achieve tissue granulation for a successful skin graft across a large surface in an anatomic region with complex topography.

Impact of Living Donor Liver Transplantation on the Improvement of Hepatocellular Carcinoma Treatment.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, with increasing incidence. There are different treatment options, but only 30%-40% of HCC cases are diagnosed at an early stage for curative treatment. With the implementation of Milan Criteria for liver transplantation (LT) in HCC cases and its use for organ allocation with successful outcomes, LT has become an optimal treatment. Seeking new criteria for LT and developing updated algorithms for HCC treatment has become a hot topic nowadays. With the experience in living donor liver transplantation (LDLT), especially in Asian countries, LDLT was established and adopted with different criteria for HCC treatment, especially including criteria beyond Milan's size and number of tumors. Living donor grafts are uniquely different than deceased donor grafts as they are not considered a public resource. A living donor graft is rather a private gift intended for a specific recipient. Living donor livers are not limited by organ allocation systems, and this significant advantage of LDLT has opened new frontiers in the treatment of HCC. Improvements in LDLT have had remarkable parallel effects in the successful treatment of HCC as supported by a growing body of literature in the past decade.

"Hg distribution and accumulation in soil and vegetation in areas impacted by artisanal gold mining in the Southern Amazonian region of Madre de Dios, Peru."

Artisanal and small-scale gold mining (ASGM) is the primary global source of anthropogenic mercury (Hg) emissions. It has impacted the Amazon rainforest in the Peruvian region of Madre de Dios. However, few studies have investigated Hg's distribution in terrestrial ecosystems in this region. We studied Hg's distribution and its predictors in soil and native plant species from artisanal mining sites. Total Hg concentrations were determined in soil samples collected at different depths (0-5 cm and 5-30 cm) and plant samples (roots, shoots, leaves) from 19 native plant species collected in different land cover categories: naked soil (L1), gravel piles (L2), natural regeneration (L3), reforestation (L4), and primary forest (L5) in the mining sites. Hg levels in air were also studied using passive air samplers. The highest Hg concentrations in soil (average 0.276 and 0.210 mg kg-1 dw.) were found in the intact primary forest (L5) at 0-5 cm depth and in the plant rooting zones at 5-30 cm depth, respectively. Moreover, the highest Hg levels in plants (average 0.64 mg kg-1 dw) were found in foliage of intact primary forest (L5). The results suggest that the forest in these sites receives Hg from the atmosphere through leaf deposition and that Hg accumulates in the soil surrounding the roots. The Hg levels found in the plant leaves of the primary forest are the highest ever recorded in this region, exceeding values found in forests impacted by Hg pollution worldwide and raising concerns about the extent of the ASGM impact in this ecosystem. Correlations between Hg concentrations in soil, bioaccumulation in plant roots, and soil physical-chemical characteristics were determined. Linear regression models showed that the soil organic matter content (SOM), pH, and electrical conductivity (EC) predict the Hg distribution and accumulation in soil and bioaccumulation in root plants.

Enhancing HIV positivity yield in southern Mozambique: The effect of a Ministry of Health training module in targeted provider-initiated testing and counselling.

In Mozambique, targeted provider-initiated HIV testing and counselling (PITC) is recommended where universal PITC is not feasible, but its effectiveness depends on healthcare providers' training. This study aimed to evaluate the effect of a Ministry of Health training module in targeted PITC on the HIV positivity yield, and identify factors associated with a positive HIV test. We conducted a single-group pre-post study between November 2018 and November 2019 in the triage and emergency departments of four healthcare facilities in Manhiça District, a resource-constrained semi-rural area. It consisted of two two-month phases split by a one-week targeted PITC training module ("observation phases"). The HIV positivity yield of targeted PITC was estimated as the proportion of HIV-positive individuals among those recommended for HIV testing by the provider. Additionally, we extracted aggregated health information system data over the four months preceding and following the observation phases to compare yield in real-world conditions ("routine phases"). Logistic regression analysis from observation phase data was conducted to identify factors associated with a positive HIV test. Among the 7,102 participants in the pre- and post-training observation phases (58.5% and 41.5% respectively), 68% were women, and 96% were recruited at triage. In the routine phases with 33,261 individuals (45.8% pre, 54.2% post), 64% were women, and 84% were seen at triage. While HIV positivity yield between pre- and post-training observation phases was similar (10.9% (269/2470) and 11.1% (207/1865), respectively), we observed an increase in yield in the post-training routine phase for women in triage, rising from 4.8% (74/1553) to 7.3% (61/831) (Yield ratio = 1.54; 95%CI: 1.11-2.14). Age (25-49 years) (OR = 2.43; 95%CI: 1.37-4.33), working in industry/mining (OR = 4.94; 95%CI: 2.17-11.23), unawareness of partner's HIV status (OR = 2.50; 95%CI: 1.91-3.27), and visiting a healer (OR = 1.74; 95%CI: 1.03-2.93) were factors associated with a positive HIV test. Including these factors in the targeted PITC algorithm could have increased new HIV diagnoses by 2.6%. In conclusion, providing refresher training and adapting the current targeted PITC algorithm through further research can help reach undiagnosed PLHIV, treat all, and ultimately eliminate HIV, especially in resource-limited rural areas.

The clinical application of incisional negative pressure wound therapy in severe subcutaneous emphysema: A case series.

Severe subcutaneous emphysema (SSE) is the presence of a high-volume accumulation of air in the subcutaneous tissue caused by traumatic injuries, infections, iatrogenic causes, or can also manifest spontaneously. A variety of techniques have been reported, with varying levels of success. We present a multicenter case series detailing four patients who developed SSE and were treated with Incisional Negative Pressure Wound Therapy (INPWT). All patients significantly improved with the INPWT treatment within 6 to 48 h. Our experience suggests INPWT is a valuable procedure available for treating SSE and recommend prospective randomized studies be conducted to determine targeted patient selection and clinical application of INPWT among the SSE patient population.

Prevalence of extra-intestinal symptoms according to irritable bowel syndrome subtype.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional disorder commonly associated with extra-intestinal symptoms. However, the prevalence of these symptoms according to IBS subtype is not well established. AIM: To compare the prevalence of extra-intestinal symptoms among patients with different subtypes of IBS. METHODS: A descriptive cross-sectional study including patients with IBS according to Rome IV criteria was performed between July 2022 and April 2023. Patients were classified according their subtype of IBS: IBS-D (diarrhea-predominant), IBS-C (constipation-predominant), and IBS-M (mixed bowel habits). Patients completed the IBS severity scoring system questionnaire (IBS-SSS) to determine severity of IBS symptoms and patient health questionnaire- 9 (PHQ-9) to define presence and severity of depressive symptoms. The prevalence of reported extra-intestinal symptoms was also assessed and compared between groups. KEY RESULTS: A total of 4862 patients with IBS were included; 608 IBS-D (12.5%), 1978 IBS-C (40.7%), and 2276 IBS-M (46.8%). Patients with IBS-C had significantly lower IBS-symptoms severity (mean IBS-SSS 290 vs. 310 and 320 for IBS-D and IBS-M, respectively, p = 0.03). The prevalence of obesity was also significantly lower in these patients (17.1% vs. 30.9% IBS-D and 27.9% IBS-M, p = 0.0001). Patients with IBS-D showed a significantly higher prevalence of food intolerance perception (9.5%, p = 0.03), history of cholecystectomy (17.8%, p = 0.03), and fecal incontinence (36.2%, p = 0.0001) as compared to the other groups. Patients with IBS-M had significantly higher mean PHQ-9 score (12.7 vs. 11.1 IBS-D and 10.5 IBS-C, p = 0.001) and prevalence of depressive symptoms (80.0%, p = 0.01). Patients with IBS-M also had higher prevalence of extra-intestinal symptoms such as arthralgia (62.4%, p = 0.0001), extremity numbness (64.5%, p = 0.0001), atopic dermatitis (28.2%, p = 0.02), and chronic cervicalgia (81.0%, p = 0.01). CONCLUSIONS & INFERENCES: The prevalence of most extra-intestinal symptoms is higher among patients with IBS-M. Further research is needed to better characterize IBS subtypes, which could potentially help refining tailored therapeutic strategies.

Long-term effectiveness and safety of tolvaptan in autosomal dominant polycystic kidney disease.

BACKGROUND AND OBJECTIVES: Evidence on the long-term use of tolvaptan in autosomal dominant polycystic kidney disease (ADPKD) is limited. The aim was to evaluate the tolvaptan effectiveness and safety in real clinical setting. MATERIAL AND METHODS: A single-center observational study (2016-2022) involving ADPKD patients treated with tolvaptan was conducted. Annual change in serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) before and after treatment initiation were evaluated. Change in total kidney volume (TKV), blood pressure (BP) and urinary albuminuria at 12, 24 and 36 months after initiation were also determined. Adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 were analyzed. RESULTS: A total of 22 patients were included. No significant differences pre- vs post tolvaptan treatment in annual rate of change in eGFR (-3.52ml/min/1.73m2 [-4.98%] vs -3.98ml/min/1.73m2 [-8.48%], p=0.121) and sCr (+0.06mg/dL [4.22%] vs +0.15mg/dL [7.77%], p=0.429) were observed. Tolvaptan improved urinary osmolality at 12 (p=0.019) and 24 months (p=0.008), but not at 36 months (p=0.11). There were no changes in TKV, BP control and urinary albuminuria at 12, 24 or 36 months. A worse response was shown in patients with rapid kidney function decline (p=0.042). A 36.4% of the patients developed grade III/IV AEs. A 22.7% discontinued treatment due to unacceptable toxicity. CONCLUSIONS: This study shows a modest benefit of tolvaptan in ADPKD patients, as well as safety concerns.

Global mercury concentrations in biota: their use as a basis for a global biomonitoring framework.

An important provision of the Minamata Convention on Mercury is to monitor and evaluate the effectiveness of the adopted measures and its implementation. Here, we describe for the first time currently available biotic mercury (Hg) data on a global scale to improve the understanding of global efforts to reduce the impact of Hg pollution on people and the environment. Data from the peer-reviewed literature were compiled in the Global Biotic Mercury Synthesis (GBMS) database (>550,000 data points). These data provide a foundation for establishing a biomonitoring framework needed to track Hg concentrations in biota globally. We describe Hg exposure in the taxa identified by the Minamata Convention: fish, sea turtles, birds, and marine mammals. Based on the GBMS database, Hg concentrations are presented at relevant geographic scales for continents and oceanic basins. We identify some effective regional templates for monitoring methylmercury (MeHg) availability in the environment, but overall illustrate that there is a general lack of regional biomonitoring initiatives around the world, especially in Africa, Australia, Indo-Pacific, Middle East, and South Atlantic and Pacific Oceans. Temporal trend data for Hg in biota are generally limited. Ecologically sensitive sites (where biota have above average MeHg tissue concentrations) have been identified throughout the world. Efforts to model and quantify ecosystem sensitivity locally, regionally, and globally could help establish effective and efficient biomonitoring programs. We present a framework for a global Hg biomonitoring network that includes a three-step continental and oceanic approach to integrate existing biomonitoring efforts and prioritize filling regional data gaps linked with key Hg sources. We describe a standardized approach that builds on an evidence-based evaluation to assess the Minamata Convention's progress to reduce the impact of global Hg pollution on people and the environment.

Predictors of salvage therapy for parasagittal meningiomas treated with primary surgery, radiosurgery, or surgery plus adjuvant radiotherapy.

OBJECTIVE: Parasagittal meningiomas (PM) are treated with primary microsurgery, radiosurgery (SRS), or surgery with adjuvant radiation. We investigated predictors of tumor progression requiring salvage surgery or radiation treatment. We sought to determine whether primary treatment modality, or radiologic, histologic, and clinical variables were associated with tumor progression requiring salvage treatment. METHODS: Retrospective study of 109 consecutive patients with PMs treated with primary surgery, radiation (RT), or surgery plus adjuvant RT (2000-2017) and minimum 5 years follow-up. Patient, radiologic, histologic, and treatment data were analyzed using standard statistical methods. RESULTS: Median follow up was 8.5 years. Primary treatment for PM was surgery in 76 patients, radiation in 16 patients, and surgery plus adjuvant radiation in 17 patients. Forty percent of parasagittal meningiomas in our cohort required some form of salvage treatment. On univariate analysis, brain invasion (OR: 6.93, p < 0.01), WHO grade 2/3 (OR: 4.54, p < 0.01), peritumoral edema (OR: 2.81, p = 0.01), sagittal sinus invasion (OR: 6.36, p < 0.01), sagittal sinus occlusion (OR: 4.86, p < 0.01), and non-spherical shape (OR: 3.89, p < 0.01) were significantly associated with receiving salvage treatment. On multivariate analysis, superior sagittal sinus invasion (OR: 8.22, p = 0.01) and WHO grade 2&3 (OR: 7.58, p < 0.01) were independently associated with receiving salvage treatment. There was no difference in time to salvage therapy (p = 0.11) or time to progression (p = 0.43) between patients receiving primary surgery alone, RT alone, or surgery plus adjuvant RT. Patients who had initial surgery were more likely to have peritumoral edema on preoperative imaging (p = 0.01). Median tumor volume was 19.0 cm3 in patients receiving primary surgery, 5.3 cm3 for RT, and 24.4 cm3 for surgery plus adjuvant RT (p < 0.01). CONCLUSION: Superior sagittal sinus invasion and WHO grade 2/3 are independently associated with PM progression requiring salvage therapy regardless of extent of resection or primary treatment modality. Parasagittal meningiomas have a high rate of recurrence with 80.0% of patients with WHO grade 2/3 tumors with sinus invasion requiring salvage treatment whereas only 13.6% of the WHO grade 1 tumors without sinus invasion required salvage treatment. This information is useful when counseling patients about disease management and setting expectations.

HIV Care Retention in Three Multi-Month ART Dispensing: a Retrospective Cohort Study in Mozambique.

OBJECTIVE: Evaluate the effect of three multi-month dispensing (3MMD) of antiretroviral therapy (ART) on HIV care retention in southern Mozambique. DESIGN: Retrospective cohort study. METHODS: We analysed routine health data from people living with HIV (PLHIV) ≥10 years old who started ART between January 2018 and March 2021. Individuals were followed until December 2021. Cox proportional-hazards models were used to compare attrition (lost to follow-up, death, and transfer out) between 3MMD and monthly ART dispensing. Results were stratified by time on ART before 3MMD enrolment: "early enrollers" (<6 months on ART) and "established enrollers" (≥6 months on ART), and age groups: adolescents and youth (AYLHIV) (10-24 years) and adults (≥25 years). RESULTS: We included 7,378 PLHIV (25% AYLHIV, 75% adults), with 59% and 62% enrolled in 3MMD, respectively. Median follow-up time was 11.3 (IQR: 5.7-21.6) months for AYLHIV and 10.2 (IQR: 4.8-20.9) for adults. Attrition was lower in PLHIV enrolled in 3MMD compared to monthly ART dispensing, in both established (aHR AYLHIV = 0.65; 95%CI: 0.54-0.78 and aHR adults = 0.50; 95%CI: 0.44-0.56) and early enrollers (aHR AYLHIV = 0.70; 95%CI: 0.58-0.85 and aHR adults = 0.63; 95%CI: 0.57-0.70). Among individuals in 3MMD, male gender (aHR = 1.30; 95%CI: 1.18-1.44) and receiving care in a medium/low-volume healthcare facility (aHR = 1.18; 95%CI: 1.03-1.34) increased attrition risk. Conversely, longer ART time before 3MMD enrolment (aHR = 0.93; 95% CI: 0.92-0.94 per one-month increase) and age ≥45 years (aHR = 0.77, 95%CI: 0.67-0.89) reduced risk of attrition. CONCLUSIONS: 3MMD improves retention in care compared to monthly dispensing among established and early enrollers, although to a lesser extent among the latter.

The Effect of Polymorphisms and Other Biomarkers on Infliximab Exposure in Paediatric Inflammatory Bowel Disease: Development of a Population Pharmacokinetic Model.

BACKGROUND: Therapeutic drug monitoring (TDM) of infliximab has been shown to be a effective strategy for inflammatory bowel disease (IBD). Population pharmacokinetic (PopPK) modeling can predict trough concentrations for individualized dosing. OBJECTIVE: The aim of this study was to develop a PopPK model of infliximab in a paediatric population with IBD, assessing the effect of single nucleotide polymorphisms (SNPs) and other biomarkers on infliximab clearance. METHODS: This observational and ambispective single-centre study was conducted in paediatric patients with IBD treated with infliximab between July 2016 and July 2022 in the Paediatric Gastroenterology Service of the Hospital Universitari Vall d'Hebron (HUVH) (Spain). Demographic, clinical, and analytical variables were collected. Twenty SNPs potentially associated with variations in the response to infliximab plasma concentrations were analysed. infliximab serum concentrations and antibodies to infliximab (ATI) were determined by ELISA. PopPK modelling was performed using nonlinear mixed-effects analysis (NONMEM). RESULTS: Thirty patients (21 males) were included. The median age (range) at the start of infliximab treatment was 13 years (16 months to 16 years). A total of 190 samples were obtained for model development (49 [25.8%] during the induction phase). The pharmacokinetics (PK) of infliximab were described using a two-compartment model. Weight, erythrocyte sedimentation rate (ESR), faecal calprotectin (FC), and the SNP rs1048610 (ADAM17) showed statistical significance for clearance (CL), and albumin for inter-compartmental clearance (Q). Estimates of CL1 (genotype 1-AA), CL2 (genotype 2-AG), CL3 (genotype 3-GG), Q, Vc, and Vp (central and peripheral distribution volumes) were 0.0066 L/h/46.4 kg, 0.0055 L/h/46.4 kg, 0.0081 L/h/46.4 kg, 0.0029 L/h/46.4 kg, 0.6750 L/46.4 kg, and 1.19 L/46.4 kg, respectively. The interindividual variability (IIV) estimates for clearance, Vc, and Vp were 19.33, 16.42, and 36.02%, respectively. CONCLUSIONS: A popPK model utilising weight, albumin, FC, ESR, and the SNP rs1048610 accurately predicted infliximab trough concentrations in children with IBD.

Dispersal history of SARS-CoV-2 in Galicia, Spain.

The dynamics of SARS-CoV-2 transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the USA became increasingly significant. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.

Uncovering HIV and malaria interactions: the latest evidence and knowledge gaps.

The geographical distribution of malaria and HIV infections widely overlap in sub-Saharan Africa, constituting a complex global health challenge. The interplay between both infections raises concerns about potential immunological, clinical, and therapeutic interactions. Both diseases have been reported to exacerbate the transmission of the other, including the possible vertical transmission of HIV in pregnant individuals with malaria. Co-infection also increases the risk of adverse outcomes such as severe malaria and death. In addition, interactions between antiretroviral and antimalarial drugs have been reported, potentially reducing the efficacy of these drugs. We review the current knowledge of the epidemiological, clinical, immunological, and therapeutic interactions of both infections. We focus on the latest available data and identify key knowledge gaps that should be addressed to guide policy makers in providing optimal HIV and malaria prevention, care, and treatment in vulnerable populations.

The global challenge of reducing mercury contamination from artisanal and small-scale gold mining (ASGM): evaluating solutions using generic theories of change.

Mercury contamination from artisanal and small-scale gold mining (ASGM) currently accounts for 37% of the global total, often affecting tropical regions where regulations, if they exist, are often poorly enforced. Ingestion by people and other animals damages the nervous, reproductive, and cognitive systems. Despite the efforts of many organizations and governments to curb mercury releases from ASGM, it is increasing globally. There are many possible interventions, all with significant complexity and cost. Therefore, we recommend taking an established systematic approach to articulate the current situation and construct theories of change (ToC) for different possible interventions for any government or organization trying to solve this problem. Here we present a high-level situation analysis and generic ToC to support a more coordinated approach that explicitly builds upon previous experience to identify organization- and situation-appropriate engagement on this issue. We then illustrate the use of these generic models to construct a specific ToC with a policy-focused entry point. This includes interventions through (1) engagement with the global Minamata Convention on Mercury; (2) support for existing national laws and policies connected to ASGM and mercury contamination; and (3) engagement of indigenous people and local communities with governments to meet the governments' legal obligations. By methodically articulating assumptions about interventions, connections among actions, and desired outcomes, it is possible to create a more effective approach that will encourage more coordination and cooperation among governments and other practitioners to maximize their investments and support broad environmental and socio-political outcomes necessary to address this pernicious problem.

Visual outcomes after treatment of craniopharyngioma in children: A systematic review.

OBJECTIVE: Craniopharyngiomas (CP) are rare brain tumors that often result in visual impairment due to their proximity to the optic pathway. The optimal management approach to preserve visual function in these patients remains controversial. We sought to investigate visual outcomes of children with craniopharyngiomas based on treatment modality. METHODS: A systematic review was performed according to PRISMA guidelines. PubMed, Embase, and Scopus databases were searched in December 2022 for relevant articles. Articles were screened by title/abstract for relevance, then by full-text. Relevant demographic, intervention, and outcome data were extracted from included studies. RESULTS: A total of 59 studies were included, representing 2655 patients. The overall visual status (OVS) of patients receiving surgery alone was improved in 27.6% of reported outcomes, unchanged in 50.3%, and deteriorated in 22.1%. The OVS for patients receiving radiation alone was improved in 21.1%, unchanged in 42.1%, and deteriorated in 36.8%. Patients receiving surgery plus adjuvant radiotherapy had OVS improvement in 27.4%, unchanged in 63.2%, and deteriorated in 9.4%. Of those receiving intracystic bleomycin, 23.1% had improvement in OVS, 46.2% remained unchanged, and 30.8% deteriorated. Of patients receiving interferon-α, 34.8% improved, 54.5% remained unchanged, and 10.6% deteriorated. CONCLUSION: OVS most frequently remained unchanged regardless of intervention. The greatest improvement in OVS was seen in those receiving interferon-α or surgery alone. The greatest OVS deterioration was noted with radiation alone. Future standardized, randomized, large-scale studies with focused assessment of ophthalmologic findings are key to further understanding the impact different interventions have on visual outcomes in these children.

Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment.

BACKGROUND/AIMS: Changes in gene expression profiles among individuals with inflammatory bowel diseases (IBDs) could potentially influence the responsiveness to anti-TNF treatment. The aim of this study was to identify genes that could serve as predictors of early response to anti-TNF therapies in pediatric IBD patients prior to the initiation of treatment. METHODS: We conducted a prospective, longitudinal, and multicenter study, enrolling 24 pediatric IBD patients aged less than 18 years who were initiating treatment with either infliximab or adalimumab. RNA-seq from blood samples was analyzed using the DESeq2 library by comparing responders and non-responders to anti-TNF drugs. RESULTS: Bioinformatic analyses unveiled 102 differentially expressed genes, with 99 genes exhibiting higher expression in responders compared to non-responders prior to the initiation of anti-TNF therapy. Functional enrichment analyses highlighted defense response to Gram-negative bacteria (FDR = 2.3 ×10-7) as the most significant biological processes, and hemoglobin binding (FDR = 0.002), as the most significant molecular function. Gene Set Enrichment Analysis (GSEA) revealed notable enrichment in transcriptional misregulation in cancer (FDR = 0.016). Notably, 13 genes (CEACAM8, CEACAM6, CILP2, COL17A1, OLFM4, INHBA, LCN2, LTF, MMP8, DEFA4, PRTN3, AZU1, and ELANE) were selected for validation, and a consistent trend of increased expression in responders prior to drug administration was observed for most of these genes, with findings for 4 of them being statistically significant (CEACAM8, LCN2, LTF2, and PRTN3). CONCLUSIONS: We identified 102 differentially expressed genes involved in the response to anti-TNF drugs in children with IBDs and validated CEACAM8, LCN2, LTF2, and PRTN3. Genes participating in defense response to Gram-negative bacterium, serine-type endopeptidase activity, and transcriptional misregulation in cancer are good candidates for anticipating the response to anti-TNF drugs in children with IBDs.