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Abstract Systemic inflammation significantly increases the risk of short- and long-term mortality in geriatric hospitalized patients. To predict mortality in older patients with various age-related diseases and infections, including COVID-19, inflammatory biomarkers such as the C-reactive protein (CRP) to albumin ratio (CAR), and related scores and indexes, i.e. Glasgow Prognostic Score (GPS), modified GPS (mGPS), and high sensitivity (hs)-mGPS, have been increasingly utilized. Despite their easy affordability and widespread availability, these biomarkers are predominantly assessed for clinical purposes rather than predictive applications, leading to their underutilization in hospitalized older patients. In this study, we investigated the association of CAR, GPS, mGPS, and hs-mGPS with short-term mortality in 3,206 geriatric hospitalized patients admitted for acute conditions, irrespective of admission diagnosis. We observed that unit increases of CAR, and the highest classes of GPS, mGPS, and hs-mGPS were significantly associated with a two- to threefold increased risk of death, even adjusting the risk for different confounding variables. Interestingly, a hs-mGPS of 2 showed the highest effect size. Furthermore, gender analysis indicated a stronger association between all CRP-albumin based parameters and mortality in men, underscoring the gender-specific relevance of inflammation-based circulating parameters in mortality prediction. In conclusion, scores based on serum CRP and albumin levels offer additional guidance for the stratification of in-hospital mortality risk in older patients by providing additional information on the degree of systemic inflammation.

Sjogren’s Disease (SjD) is associated with an increased risk of lymphoma. We investigated the prevalence of lymphoma in a retrospective case series of patients with SjD and reported on the clinical presentation, treatment, response, and outcome. A retrospective review of 132 patients diagnosed with Sjogren’s Disease was conducted at our institution from June 2000 to November 2023, and 10 cases of malignant lymphoma were identified. Clinical and biological markers known to be predictors of lymphoma, as well as lymphoma characteristics, were examined. The most common predictive lab findings were hypergammaglobulinemia, the rheumatoid factor, and lymphopenia. Persistent parotid gland enlargement was also found in greater than 50% of patients. The majority of patients were Caucasian females, and the average time between the diagnosis of SjD and lymphoma was 14.3 years. The median age at lymphoma diagnosis was 59.5 years, with 9 out of 10 lymphomas identified as non-Hodgkin lymphoma, the majority of cases being mucosa-associated lymphoid tissue (MALT) lymphoma. We identified similarities in our series, such as laboratory markers and clinical symptoms, to those previously identified as possible predictors of lymphoma development. These factors may be useful in determining the risk of malignancy development and justify the need for long-term monitoring, as well as provider education and awareness.

Hydroxychloroquine (HCQ) induced cardiotoxicity is a rare diagnosis and is often associated with chronic use of the medication. It has been shown that chronic HCQ use is associated with a drug-induced cardiomyopathy mainly driven by acquired lysosomal storage defects leading to hypertrophy and conduction abnormalities. As the only proven treatment is the discontinuation of the offending agent, prompt recognition is required to avoid further exposure to the drug and potential progression of disease. History, physical examination and advanced imaging modalities are useful diagnostic tools, but more invasive testing with an endomyocardial biopsy is required for definitive diagnosis. We present a descriptive case series of ten patients that were diagnosed with biopsy proven HCQ cardiotoxicity.

This text explores the intricate relationship between personal autonomy and public health objectives, particularly accentuated during the recent pandemic. Emphasising the challenge of balancing individual autonomy with broader public health imperatives, the discussion delves into state interventions that may restrict individual freedom and the potential moral justifications behind such actions. Public health interventions, encompassing various policies from data collection to preventive legislation, are examined in light of their impact on individual freedom. Drawing on Holland’s analysis, the text illustrates how these policies may limit individual autonomy while serving the interests and welfare of society. It argues that, in a liberal society, restrictions on citizen choices are justified not only for individual health but also to safeguard collective interests. The recent COVID-19 response, including measures like lockdowns and vaccine passports, exemplifies this evolving balance. The text contends that, as the state places more emphasis on public health over personal autonomy, interventions like genome editing might cease to be considered mere options, potentially leading to mandatory genetic modifications for those desiring children. This shift raises ethical questions about protecting individual autonomy in a diverse society. The text highlights the absence of compelling justifications against restricting individuals from making autonomous decisions about their children’s genetic makeup or imposing legal obligations for genome editing.

ObjectiveDry eye disease (DED) is a condition associated with a myriad of systemic disorders. According to recent preliminary data, axial spondylarthritis (axial-SpA) could represent a new entity associated with DED. Therefore, this study aimed to assess DED in patients with axial SpA by performing quantitative and qualitative specific tests to investigate the potential association between DED and ocular surface damage in patients with axial-SpA and to identify potential variables associated with DED.MethodsA total of 71 patients with axial-SpA who fulfilled the Assessment of SpondyloArthritis International Society (ASAS) classification criteria and 19 healthy controls were enrolled in this study. Both the patients and the controls underwent a complete ocular assessment aimed at evaluating the tear film and ocular surface, which included the Schirmer test, tear break-up time (TBUT), fluorescein staining, and lissamine green staining. The Ocular Surface Disease Index (OSDI) questionnaire was administered to all patients.ResultsDED symptoms were reported in 46 (64.8%) patients and three (15.8%) healthy controls (p = 0.0004). The odds ratio for receiving a diagnosis of axial-SpA based on the presence of dry-eye-related symptoms was 9.2 (95% C.I. 2.72–42.52, p = 0.001). The Schirmer test values of < 6 mm/5 min were observed in 31 (43.7%) patients with axial-SpA and two (10.5%) healthy controls (p = 0.013); a TBUT of

Microvascular remodeling and capillary repopulation can occur after autologous hematopoietic stem cell transplant (HSCT) in patients with systemic sclerosis and systemic lupus erythematosus (SLE). We aim to report evidence for microvascular remodeling after autologous HSCT as observed by nailfold videocapillaroscopy (NVC). We describe a rare occurrence of features consistent with systemic sclerosis and SLE in a 33-year-old female with a complex clinical course refractory to conventional treatments, ultimately requiring autologous HSCT. We performed NVC before and after HSCT using optical video and light microscopy. At the microvascular level, morphologic changes in the capillary vascular bed were observed after HSCT. Pretransplant damage in capillary structure was noted as evidenced on NVC with architectural loss, ramifications, capillary drop, and decreased density. Posttransplant NVC revealed an increase in capillary density with evidence of microvascular remodeling. Further studies on the clinical use and impact of microvascular remodeling on disease progression are needed and looking into the application of NVC scoring to assess clinical response would be meaningful.

IntroductionNon-infectious inflammatory ocular diseases pose significant challenges in diagnosis and management, often requiring systemic immunosuppressive therapy. Since Janus kinase (JAK) inhibitors may represent a novel therapeutic option for these disorders, the present study aimed to expand current knowledge about their efficacy and safety in patients with these conditions.MethodsThis prospective cohort study included 12 adult patients from the international AutoInflammatory Disease Alliance (AIDA) Network registries dedicated to non-infectious ocular inflammatory conditions. We assessed ocular flares, visual acuity, disease course, and complications before and after initiating JAK inhibitor therapy.ResultsOcular inflammation was related to a systemic disease in 8 (66.7%) patients as follows: spondyloarthritis (n = 3), peripheral psoriatic arthritis (n = 1), rheumatoid arthritis (n = 1), antinuclear antibodies (ANA) positive juvenile idiopathic arthritis (n = 1), Behçet’s syndrome (n = 1), Vogt-Koyanagi-Harada syndrome (n = 1). In total, 4 patients received baricitinib, 1 patient received tofacitinib, and 7 patients underwent upadacitinib treatment. The overall average duration of JAK inhibitors treatment was 8.6 ± 5.5 months (ranging from 3 to 20 months). At the last assessment, ocular disease control was complete in 12/12 patients. One patient discontinued baricitinib due to poor compliance after a 12-month relapse-free period. The incidence of ocular flares was 125 episodes/1.000 person-months prior to the initiation of JAK inhibitors and 28.6 episodes/1.000 person-months thereafter. The incidence rate ratio for experiencing a relapse before starting a JAK inhibitor compared to the following period was 4.37 (95% CI 1.3–14.7, p-value: 0.02).ConclusionJAK inhibitors demonstrate efficacy and safety in controlling ocular inflammatory relapses, confirming that they represent a valuable treatment option for patients with non-infectious inflammatory ocular diseases resistant to conventional treatments.

In the recent years, the development of so-called omics technologies has greatly contributed to the discovery of new biomarkers and targets, spanning different areas from diagnosis to therapy, and helping to accelerate the progress of precision and personalized medicine. In addition to classic omics, including genomics, transcriptomics, proteomics, and metabolomics, newer-generation omics technologies and related platforms, such as microbiomics and nutrigenomics, are emerging. At the same time, the use of liquid biopsies is becoming established as optimal biological samples, consisting in biological fluids (i.e. blood, saliva, and urine), that are easy to collect, and whose components (cells, nucleic acids, exosome) can be analysed using throughput techniques. In addition, it is becoming attractive, because it consents the extrapolation of big data via multi-omics technologies. Here, we report a brief description and discussion of such technologies, highlighting applications and possible limitations.

Abstract Introduction Since many biological drug patents have expired, biosimilar agents (BIOs) have been developed; however, there are still some reservations in their use, especially in childhood. The aim of the current study is to evaluate the efficacy and safety of tumor necrosis factor (TNF) inhibitors BIOs as treatment for pediatric non-infectious uveitis (NIU). Methods Data from pediatric patients with NIU treated with TNF inhibitors BIOs were drawn from the international AutoInflammatory Disease Alliance (AIDA) registries dedicated to uveitis and Behçet's disease. The effectiveness and safety of BIOs were assessed in terms of frequency of relapses, risk for developing ocular flares, best-corrected visual acuity (BCVA), glucocorticoids (GCs)-sparing effect, drug survival, frequency of ocular complications, and adverse drug event (AE). Results Forty-seven patients (77 affected eyes) were enrolled. The BIOs employed were adalimumab (ADA) (89.4%), etanercept (ETA) (5.3%), and infliximab (IFX) (5.3%). The number of relapses 12 months prior to BIOs and at last follow-up was 282.14 and 52.43 per 100 patients/year. The relative risk of developing ocular flares before BIOs introduction compared to the period following the start of BIOs was 4.49 (95% confidence interval [CI] 3.38–5.98, p = 0.004). The number needed to treat (NNT) for ocular flares was 3.53. Median BCVA was maintained during the whole BIOs treatment (p = 0.92). A significant GCs-sparing effect was observed throughout the treatment period (p = 0.002). The estimated drug retention rate (DRR) at 12-, 24-, and 36-month follow-up were 92.7, 83.3, and 70.8%, respectively. The risk rate for developing structural ocular complications was 89.9/100 patients/year before starting BIOs and 12.7/100 patients/year during BIOs treatment, with a risk ratio of new ocular complications without BIOs of 7.1 (CI 3.4–14.9, p = 0.0003). Three minor AEs were reported. Conclusions TNF inhibitors BIOs are effective in reducing the number of ocular uveitis relapses, preserving visual acuity, allowing a significant GCs-sparing effect, and preventing structural ocular complications. Trial Registration ClinicalTrials.gov ID NCT05200715.

Abstract Introduction Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples. Methods Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated. Results Overall, a median DNA concentration of 3.3 ng/µL (range 0.1–10.0 ng/µL) and 13.4 ng/µL (range 2.0–45.8 ng/µL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/µL (range 0.2–11.9 ng/µL) and 9.3 ng/µL (range 0.5–18.0 ng/µL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation. Conclusions Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice.

The sexual needs of astronauts have long been overlooked in space missions. Only recently has the scientific community begun to show interest in the sexual lives of astronauts and pay attention to the issues surrounding sex in space. However, sex remains a central concern for astronauts involved in space missions. We would argue that in the initial phase of space exploration and colonization of new planets, astronauts should have the opportunity for sexual activity but should not have children. Furthermore, we assert that a program for the colonization of new planets should consider the possibility of providing intelligent machines to accompany astronauts, capable not only of assisting them operationally in their mission but also of satisfying their sexual needs. So far, the debate on sex robots has primarily focused on their use on our planet. However, sex robots could prove to be a valuable resource for space missions aimed at establishing new space stations or colonizing new territories.

Abstract Background The neurological effects of the coronavirus disease of 2019 (COVID-19) raise concerns about potential long-term consequences, such as an increased risk of Alzheimer's disease (AD). Neuroinflammation and other AD-associated pathologies are also suggested to increase the risk of serious SARS-CoV-2 infection. Anosmia is a common neurological symptom reported in COVID-19 and in early AD. The olfactory mucosa (OM) is important for the perception of smell and a proposed site of viral entry to the brain. However, little is known about SARS-CoV-2 infection at the OM of individuals with AD. Methods To address this gap, we established a 3D in vitro model of the OM from primary cells derived from cognitively healthy and AD individuals. We cultured the cells at the air–liquid interface (ALI) to study SARS-CoV-2 infection under controlled experimental conditions. Primary OM cells in ALI expressed angiotensin-converting enzyme 2 (ACE-2), neuropilin-1 (NRP-1), and several other known SARS-CoV-2 receptor and were highly vulnerable to infection. Infection was determined by secreted viral RNA content and confirmed with SARS-CoV-2 nucleocapsid protein (NP) in the infected cells by immunocytochemistry. Differential responses of healthy and AD individuals-derived OM cells to SARS-CoV-2 were determined by RNA sequencing. Results Results indicate that cells derived from cognitively healthy donors and individuals with AD do not differ in susceptibility to infection with the wild-type SARS-CoV-2 virus. However, transcriptomic signatures in cells from individuals with AD are highly distinct. Specifically, the cells from AD patients that were infected with the virus showed increased levels of oxidative stress, desensitized inflammation and immune responses, and alterations to genes associated with olfaction. These results imply that individuals with AD may be at a greater risk of experiencing severe outcomes from the infection, potentially driven by pre-existing neuroinflammation. Conclusions The study sheds light on the interplay between AD pathology and SARS-CoV-2 infection. Altered transcriptomic signatures in AD cells may contribute to unique symptoms and a more severe disease course, with a notable involvement of neuroinflammation. Furthermore, the research emphasizes the need for targeted interventions to enhance outcomes for AD patients with viral infection. The study is crucial to better comprehend the relationship between AD, COVID-19, and anosmia. It highlights the importance of ongoing research to develop more effective treatments for those at high risk of severe SARS-CoV-2 infection. Graphical Abstract

Purpose/Objectives: This study evaluated the effects of the COVID-19 pandemic on children within the U.S. by assessing how parents' perceptions of children's nutritional patterns changed in relationship to school nutrition assistance program participation. Methods: A cross-sectional survey of American parents was used to evaluate changes to their children's nutritional patterns during the pandemic. Participants were recruited through Facebook advertisements and snowball sampling. Data was collected through an electronic survey. Descriptive statistics and Pearson correlation were calculated. Qualitative data was organized by question stem. Once organized, responses were summarized by topics and sub-topics. Results: There was not a significant change in the perceived intake of foods from the major food groups, however parents reported increased snacking behavior, including processed foods. Participation in school nutrition assistance programs, including free or reduced price meals did increase during the pandemic and parents perceived these programs as more important. Applications To Child Nutrition Professionals: School nutrition programs were perceived as increasingly important as families navigated the fallout of the pandemic which was complicated by financial strain and food insecurity. The increase in snacking behavior raises concerns about the long term consequences of the pandemic. It is possible the change in snacking behavior was the product of food access concerns and children being at home during the pandemic. Administrators and policymakers should build upon what was learned during the pandemic to improve community infrastructure and capacity to support school nutrition assistance program participation.

ObjectiveInflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF.MethodsThe risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still’s disease patients and Behçet’s disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression.Results580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet’s disease patients and 497 Still’s disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still’s disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet’s disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (β1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (β1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (β1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (β1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (β1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (β1 = 2.089, 95% CI. 0.7-3.5, p=0.002).ConclusionsThe risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

Drug residues that contaminate food and water represent a serious concern for human health. The major concerns regard the possible irrational use of these contaminants, since this might increase the amplitude of exposure. Multiple sources contribute to the overall exposure to contaminants, including agriculture, domestic use, personal, public and veterinary healthcare, increasing the possible origin of contamination. In this review, we focus on crop pesticides and veterinary drug residues because of their extensive use in modern agriculture and farming, which ensures food production and security for the ever-growing population around the world. We discuss crop pesticides and veterinary drug residues with respect to their worldwide distribution and impacts, with special attention on their harmful effects on human reproduction and embryo development, as well as their link to epigenetic alterations, leading to intergenerational and transgenerational diseases. Among the contaminants, the most commonly implicated in causing such disorders are organophosphates, glyphosate and antibiotics, with tetracyclines being the most frequently reported. This review highlights the importance of finding new management strategies for pesticides and veterinary drugs. Moreover, due to the still limited knowledge on inter- and transgenerational effects of these contaminants, we underlie the need to strengthen research in this field, so as to better clarify the specific effects of each contaminant and their long-term impact.

Thoracic aortic aneurysms (TAAs) represent a serious health concern, as they are associated with early aortic dissection and rupture. TAA formation is triggered by genetic conditions, in particular Marfan syndrome (MFS) and bicuspid aortic valve (BAV). During the aneurysmatic process, aortic endothelial cells can undergo endothelial-to-mesenchymal transition (End–MT) with consequent phenotypic and functional alterations. We previously documented that MFS TAA is characterized by miR-632–driven End–MT exacerbation, whereas in BAV aortopathy, the occurrence of this process remains still controversial. We investigated the End–MT process and the underlined regulatory mechanisms in BAV, TAV and MFS TAA tissues. Gene expression and immunohistochemical analysis were performed in order to analyze some important miRNAs and genes characterizing End–MT. We documented that BAV endothelium maintains the expression of the endothelial homeostasis markers, such as ERG, CD31 and miR-126-5p, while it shows lower levels of miR-632 and mesenchymal markers compared with MFS. Interestingly, we also found higher levels of miR-632 in MFS patients’ blood. Our findings definitively demonstrate that the End–MT process does not characterize BAV that, among the other TAAs, better maintains the endothelial features. In addition, our results suggest miR-632 as a promising diagnostic/prognostic factor in MFS aortopathy.

Increasing evidence shows that epigenetics also plays a key role in regulating the pathogenetic mechanism of all types of aortic aneurysms. It is well-known that epigenetic factors modulate gene expression. This mechanism appears to be of interest especially knowing the relevance of genetic susceptibility and genetic factors in the complex pathophysiology of aortic aneurysms, and of sporadic forms; in fact, the latter are the result of a close interaction between genetic and modifiable lifestyle factors (i.e., nutrition, smoking, infections, use of drugs, alcohol, sedentary lifestyle, etc.). Epigenetic factors include DNA methylation, post-translational histone modifications, and non-coding RNA. Here, our attention is focused on the role of miRNA in syndromic and sporadic forms of thoracic aortic aneurysms. They could be both biomarkers and targets of novel therapeutic strategies.

Single-shot 2-dimensional optical imaging of transient phenomena is indispensable for numerous areas of study. Among existing techniques, compressed ultrafast photography (CUP) using a chirped ultrashort pulse as active illumination can acquire nonrepetitive time-evolving events at hundreds of trillions of frames per second. However, the bulky size and conventional configurations limit its reliability and application scopes. Superdispersive metalenses offer a promising solution for an ultracompact design with a stable performance by integrating the functions of a focusing lens and dispersive optical components into a single device. Nevertheless, existing metalens designs, typically optimized for the full visible spectrum with a relatively low spectral resolution, cannot be readily applied to active-illumination CUP. To address these limitations, here, we propose single-shot compressed ultracompact femtophotography (CUF) that synergically combines the fields of nanophotonics, optical imaging, compressed sensing, and deep learning. We develop the theory of CUF’s data acquisition composed of temporal–spectral mapping, spatial encoding, temporal shearing, and spatiotemporal integration. We also develop CUF’s image reconstruction via deep learning. Moreover, we design and evaluate CUF’s crucial components—a static binary transmissive mask, a superdispersive metalens, and a 2-dimensional sensor. Finally, using numerical simulations, CUF’s feasibility is verified using 2 synthetic scenes: an ultrafast beam sweeping across a surface and the propagation of a terahertz Cherenkov wave.

IntroductionThe effectiveness of canakinumab may change according to the different times it is used after Still’s disease onset. This study aimed to investigate whether canakinumab (CAN) shows differences in short- and long-term therapeutic outcomes, according to its use as different lines of biologic treatment.MethodsPatients included in this study were retrospectively enrolled from the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to Still’s disease. Seventy-seven (51 females and 26 males) patients with Still’s disease were included in the present study. In total, 39 (50.6%) patients underwent CAN as a first-line biologic agent, and the remaining 38 (49.4%) patients were treated with CAN as a second-line biologic agent or subsequent biologic agent.ResultsNo statistically significant differences were found between patients treated with CAN as a first-line biologic agent and those previously treated with other biologic agents in terms of the frequency of complete response (p =0.62), partial response (p =0.61), treatment failure (p >0.99), and frequency of patients discontinuing CAN due to lack or loss of efficacy (p =0.2). Of all the patients, 18 (23.4%) patients experienced disease relapse during canakinumab treatment, 9 patients were treated with canakinumab as a first-line biologic agent, and nine patients were treated with a second-line or subsequent biologic agent. No differences were found in the frequency of glucocorticoid use (p =0.34), daily glucocorticoid dosage (p =0.47), or concomitant methotrexate dosage (p =0.43) at the last assessment during CAN treatment.ConclusionCanakinumab has proved to be effective in patients with Still’s disease, regardless of its line of biologic treatment.

Abstract Introduction Scientific evidence of the effectiveness of the tumor necrosis factor inhibitor adalimumab (ADA) in pediatric patients with non-infectious non-anterior uveitis is still limited. The aim of this study is to investigate the therapeutic role of ADA in a cohort of pediatric patients with non-anterior uveitis. Methods This is an international multicenter study analyzing real-life data referred to pediatric patients treated with ADA for intermediate uveitis/pars planitis, posterior uveitis and panuveitis. Data were drawn from the AutoInflammatory Disease Alliance (AIDA) registry for patients with uveitis. Results Twenty-one patients (36 affected eyes) were enrolled, and all patients benefited from ADA administration. In detail, 11 patients (19 affected eyes) did not experience further ocular inflammation after ADA introduction; 10 cases (17 affected eyes) showed a significant clinical improvement consisting of a decrease in severity and/or frequency of ocular relapses. The number of ocular flares dropped from 3.91 to 1.1 events/patient/year after ADA introduction (p = 0.0009); macular edema and retinal vasculitis were respectively observed in 18 eyes and 20 eyes at the start of ADA and in 4 eyes and 2 eyes at the last assessment. The mean daily glucocorticoid dosage significantly decreased from 26.8 ± 16.8 mg/day at the start of ADA to 6.25 ± 6.35 mg/day at the last assessment (p = 0.002). Intermediate uveitis/pars planitis (p = 0.01) and posterior uveitis (p = 0.03) were more frequently observed in patients with full response to ADA; panuveitis (p = 0.001) was significantly more frequent among patients continuing to experience uveitic flares. This could be related to a higher use of systemic glucocorticoids (p = 0.002) and conventional immunosuppressants (p = 0.007) at the start of ADA when treating intermediate uveitis/pars planitis. Regarding the safety profile, only one adverse event was reported during ADA treatment, consisting of the development of generalized adenopathy. Conclusions ADA proved to have an effective therapeutic role in all pediatric patients with non-anterior uveitis enrolled in the study. An overall glucocorticoid-sparing effect was observed despite the severity of cases enrolled. A more aggressive treatment of panuveitis and posterior uveitis at start of ADA could increase the likelihood of full response to therapy.

The tropical seagrass Halophila stipulacea (Forsskål) Ascherson, 1867 entered in the Mediterranean Sea through the Suez Canal more than 100 years ago. In coastal-marine ecosystems the spatial niche of H. stipulacea is often overlapped with that of native Mediterranean Sea seagrasses and therefore it might out-compete them. Aiming to better understand its invasiveness potential, we monitored a Southern Mediterranean shallow coastal-marine water habitat from August 2010 to August 2011, where H. stipulacea co-occurred with the native seagrass Cymodocea nodosa (Ucria) Ascherson, 1870. Besides, the year-round dynamics of H. stipulacea was also monitored in four periods. To test the hypothesis that the presence/absence of H. stipulacea may have an effect on C. nodosa density, we analyzed the shoot density of C. nodosa in 8 sites, 4 sites where H. stipulacea was present (impacted sites) and 4 where H. stipulacea was absent (control sites). The results showed significant differences in C. nodosa shoot density according to the presence/absence of H. stipulacea, with the lowest values observed in sites where it co-occurred with H. stipulacea. We hypothesize that the dense rhizome-sediment net created by H. stipulacea can interfere with C. nodosa density, pushing down its rhizomes in the anoxic layer. The leaf features of H. stipulacea were generally comparable to those of other Mediterranean populations. In January 2011 a significant decline of H. stipulacea was observed, maybe related to changes in the environmental conditions that have become unfavorable (e.g. hydrodynamics, turbidity) and, unexpectedly, the seagrass disappeared in April 2011. In January, we also observed the occurrence of the green alien alga Caulerpa cylindracea Sonder, 1945 which rapidly invaded the bare substrate left by H. stipulacea.

Myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by fluctuating weakness of the skeletal muscles. Although antibodies against the neuromuscular junction components are recognized, the MG pathogenesis remains unclear, even if with a well-known multifactorial character. However, the perturbations of human microbiota have been recently suggested to contribute to MG pathogenesis and clinical course. Accordingly, some products derived from commensal flora have been demonstrated to have anti-inflammatory effects, while other have been shown to possess pro-inflammatory properties. In addition, patients with MG when compared with age-matched controls showed a distinctive composition in the oral and gut microbiota, with a typical increase in Streptococcus and Bacteroides and a reduction in Clostridia as well as short-chain fatty acid reduction. Moreover, restoring the gut microbiota perturbation has been evidenced after the administration of probiotics followed by an improvement of symptoms in MG cases. To highlight the role of the oral and gut microbiota in MG pathogenesis and clinical course, here, the current evidence has been summarized and reviewed.