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BACKGROUND AND AIMS: During early phases of inflammation, activated neutrophils extrude neutrophil extracellular traps (NETs) in a PAD4-dependent manner, aggravating tissue injury and remodelling. In this study, we investigated the potential pro-fibrotic properties and signalling of NETs in Crohn's disease (CD). METHODS: NETs and activated fibroblasts were labelled on resected ileum from CD patients by multiplex immunofluorescence staining. NETs-treated human primary intestinal fibroblasts were analysed by bulk RNA-sequencing to uncover cell signalling pathways, and by high-throughput imaging to assess collagen production and migratory activity. Consequentially, TLR2/NF-kB pathway was evaluated by transfection of CCD-18Co fibroblasts with NF-kB-luciferase reporter plasmid, incorporating C29 to block TLR2 signalling. A chronic DSS mouse model was used to define the specific role of PAD4 deletion in neutrophils (MRP8-Cre, Pad4fl/fl). RESULTS: Immunofluorescence showed spatial co-localisation of NETs and activated fibroblasts in ileal ulcerations of CD patients. Transcriptomic analysis revealed upregulation of pro-fibrotic genes and activation of TLR-signalling pathways in NETs-treated fibroblasts. NETs treatment induced fibroblast proliferation, diminished migratory capability, and increased collagen release. Transfection experiments indicated a substantial increase in NF-kB expression with NETs, whereas C29 led to decreased expression and release of collagen. In line, a significantly reduction in collagen content was observed in the colon of MRP8-Cre, Pad4fl/fl mice subjected to chronic DSS colitis. CONCLUSIONS: NETs potentially serve as an initial stimulus for pathological activation of fibroblasts within the intestine via the TLR2/NF-kB pathway. Given their early involvement in inflammation, inhibition of PAD4 might offer a strategy to modulate both inflammation and fibrogenesis in CD.
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BACKGROUND: The interplay between cancer cells and the immune system is crucial in cancer progression and treatment. In this regard, the tumor immune microenvironment and macroenvironment, marked by systemic inflammation markers and TILs, could be considered key prognostic factors in tumors, including oral and lung squamous cell carcinoma. METHODS: We conducted a retrospective clinical study on patients with Oral Squamous Cell Carcinoma (OSCC) and Lung Squamous Cell Carcinoma (LUSCC), examining stages, comorbidities, treatments, and outcomes. We evaluated the prognostic significance of pre-surgical systemic inflammation markers and tumor microenvironment composition. RESULTS: Associations were found between systemic inflammation markers-NLR, MLR, and PLR-and tumor microenvironment factors, such as TILs and CD8+ cell prevalence-elevated inflammation markers correlated with advanced stages. Specifically, NLR was prognostic in OSCC, whereas PLR was prognostic in LUSCC. Using a cutoff value, we divided our tumor samples into two prognostic groups. Moreover, TILs levels >15% of tumor stroma correlated with prolonged overall survival in both OSCC and LUSCC, while increased CD8+ expression was linked to extended disease-free survival in LUSCC. DISCUSSION: Systemic inflammation markers and TILs can be valuable prognostic factors of survival, highlighting the immune response's role in OSCC and LUSCC. Despite limited clinical integration of the presented cohorts due to a lack of standardization, we concluded that analyzing tumor immune profiles may offer novel prognostic insights. CONCLUSIONS: Future integration into cancer classification could improve risk stratification and treatment guidance.
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BACKGROUND AND PURPOSE: Parapharyngeal space (PPS) neoplasms represent 1% of all head and neck tumors and are mostly benign. Surgery is the mainstay of treatment and the transcervical-transparotid (TC-TP) corridor still represents the workhorse for adequate PPS exposure. Our series investigates strengths and limits of this approach on a multi-institutional basis. METHODS: We reviewed consecutive patients submitted to PPS surgery via TC-TP route between 2010 and 2020. Hospital stay, early and long-term complications, and disease status were assessed. RESULTS: One hundred and twenty nine patients were enrolled. Most tumors were benign (79.8%) and involved the prestyloid space (83.7%); the median largest diameter was 4.0 cm. The TC-TP corridor was used in 70.5% of patients, while a pure TC route in about a quarter of cases. Early postoperative VII CN palsy was evident in 32.3% of patients, while X CN deficit in 9.4%. The long-term morbidity rate was 34.1%, with persistent CN impairment detectable in 26.4% of patients: carotid space location, lesion diameter and malignant histology were the main independent predictors of morbidity. A recurrence occurred in 12 patients (9.4%). CONCLUSIONS: The TC-TP corridor represents the benchmark for surgical management of most of PPS neoplasms, though substantial morbidity can still be expected.
Subject(s)
Head and Neck Neoplasms , Pharyngeal Neoplasms , Humans , Parapharyngeal Space , Retrospective Studies , Head and Neck Neoplasms/surgery , Pharyngeal Neoplasms/surgery , Pharyngeal Neoplasms/pathologyABSTRACT
OBJECTIVES: Squamous cell carcinoma of the nasal vestibule (NV-SCC) is a rare but challenging entity, due to the complex anatomy of the region. Consensus on the best treatment strategy is still lacking, as well as a dedicated staging system. Our aim was to analyze oncological outcomes of surgically treated patients and to investigate possible prognostic factors. METHODS: We performed a retrospective multi-centric observational study including six Academic Hospitals over a 10-year period, including only patients who underwent upfront surgery for primary NV-SCC. Patients were staged according to all currently available staging systems. The Kaplan-Meier method was used to compute overall, disease-free, and disease-specific survival. Logistic regression models were used to correlate between survival outcomes and clinical and pathological variables. RESULTS: Seventy-one patients with a median follow-up of 38 months were included in the study. Partial and total rhinectomy were the most commonly performed procedures, respectively, in 49.3% and 25.4% of cases. Neck dissection was performed on 31% of patients, and 45.1% of them underwent adjuvant radiotherapy. Three years overall, disease-specific and disease-free survival were, respectively, 86.5%, 90.3%, and 74.2%. None of the currently available staging systems were able to effectively stratify survival outcomes. Factors predicting lower overall survival on multivariate analysis were age (p = 0.021) and perineural invasion (p = 0.059), whereas disease-free survival was negatively affected by age (p = 0.033) and lymphovascular invasion (p = 0.019). CONCLUSION: Currently available staging systems cannot stratify prognosis for patients who underwent surgery for NV-SCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2634-2645, 2024.
Subject(s)
Carcinoma, Squamous Cell , Neoplasm Staging , Nose Neoplasms , Humans , Male , Female , Retrospective Studies , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/mortality , Aged , Nose Neoplasms/pathology , Nose Neoplasms/mortality , Nose Neoplasms/surgery , Middle Aged , Nasal Cavity/pathology , Nasal Cavity/surgery , Aged, 80 and over , Prognosis , Adult , Disease-Free Survival , Treatment OutcomeABSTRACT
Introduction: Pancreatic adenocarcinoma (PC) is one of the most lethal malignancies; even after resection the patients' 5-year disease-free survival (DFS) is lower than 26%. The genetic mutational landscape of PC is dominated by activating KRAS mutations, that have been reported in approximately 90% of cases; however, beyond KRAS - direct mutations, several KRAS-targeting miRNAs appear to be downregulated, strengthening the already activated RAS signaling. In addition, the interplay between miRNAs and RAS includes poorly investigated downstream miRNAs. The aim of this study was to determine the prognostic value of some of these candidate KRAS-related miRNAs. Patients and methods: Between 2015 and 2022, 44 patients with pathologically confirmed PC, who received surgery and were enrolled by the Clinical Oncology Unit, Careggi University Hospital, Florence (Italy). PC Total RNA was extracted from FFPE sections, retro-transcribed and the resulting cDNA was then used for qPCR analysis. A panel of KRAS-related miRNA (miR-155, miR-206 and miR-143) was analyzed. Results: In this observational study patients sex distribution was unequal with 34.1% being male and 65.9% female. The most frequent tumor localization was the head of the pancreas (65.9%) and the pathological stages were pT1-2 (45.5%), pT3 (54.5%), pN0 (22.7%), pN+ (77.3%). Adjuvant therapy was administered to 63.6% of patients; disease recurrence was observed in 69% of cases. Twenty-three patients, whose RNA was of adequate quality, were used in the mRNAs expression studies. When comparing the miRNA expression between PC and a pool of healthy tissues, miR-155 was overexpressed and miR-206 downregulated in PC, while miR-143 expression was unchanged. However, when categorized in low- and high- miR-143 expressing PC (according to the median value), high miR-143 was associated with nodal involvement (pN+) (p=0.029), who in turn was linked with shorter DFS (p=0.009) and overall survival (OS) (p=0.021) compared to pN0. A trend toward inferior DFS was observed for higher expression of miR-206 (p=0.095) and miR-143 (p=0.092). Finally, responders to a first-line treatment for advanced disease had miR-155 overexpressed (p=0.048). Conclusions: miRNAs are involved in PC tumorigenesis and metastatic spread. In light of miR-143 association with lymphatic spread and poor prognosis, a comprehensive analysis of miRNA interplay with KRAS deserves further investigation.
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Speech restoration after total laryngectomy may be achieved in different ways, the gold standard being tracheoesophageal puncture (TPE) with the positioning of a speech prosthesis. TPE is not immune to complications, the most common of which being leakage through or around the prosthesis. When dealing with an enlarged tracheoesophageal fistula, the management can be either conservative or surgical. In the following case report, we present a particularly challenging case, in which every conservative strategies failed and a major surgery was required to close the fistula.
Subject(s)
Laryngeal Neoplasms , Larynx, Artificial , Tracheoesophageal Fistula , Humans , Tracheoesophageal Fistula/surgery , Tracheoesophageal Fistula/complications , Trachea/diagnostic imaging , Trachea/surgery , Laryngeal Neoplasms/surgery , Laryngectomy , Retrospective StudiesABSTRACT
BACKGROUND AND PURPOSE: Parotid gland lymphoma (PGL) is a rare and challenging diagnosis. Different lymphomas can develop in the parotid gland, with the most common being the mucosa-associated lymphoid tissue (MALT) lymphoma, which originates directly from the glandular parenchyma. Other histologic subtypes arise from both intraglandular and extraglandular parotid lymph nodes. A consensus on diagnosis and treatment of PGL is still lacking, and published data is scarce and heterogeneous. METHODS: We performed a systematic review of the literature, including studies published after 2001, when the WHO classification of lymphoid tumours was introduced. RESULTS: Twenty retrospective studies were included in the analyses, eight of which focused exclusively on MALT lymphomas. Final analysis included 612 cases of PGL, with a 1.68:1 F/M ratio. MALT lymphoma was the most common histology, followed by follicular and diffuse large B-cell lymphoma. Most cases were low stages (IE/IIE acc. Ann Arbour, 76.5%) and only 10% of patients presented with symptoms, most commonly pain (4.8%) and B symptoms (2.2%). A high prevalence of associated autoimmune diseases was found, particularly Sjögren's syndrome, that affected up to 70% of patients with MALT lymphoma. In most cases diagnosis was achieved through parotidectomy (57.5%), or open biopsy (31.2%). Treatment strategies were either surgical, non-surgical or a combination of modalities. Surgery as a single-modality treatment was reported in about 20% of patients, supposing it might be a valuable option for selected patients. CONCLUSIONS: Our review showed that the diagnosis and treatment of PGLs is far from being standardized and needs further, more homogeneous reports to reach consensus.
Subject(s)
Lymphoma, B-Cell, Marginal Zone , Parotid Neoplasms , Sjogren's Syndrome , Humans , Parotid Gland/pathology , Lymphoma, B-Cell, Marginal Zone/diagnosis , Lymphoma, B-Cell, Marginal Zone/therapy , Lymphoma, B-Cell, Marginal Zone/complications , Retrospective Studies , Salivary Glands/pathology , Sjogren's Syndrome/complications , Sjogren's Syndrome/diagnosis , Parotid Neoplasms/diagnosis , Parotid Neoplasms/surgeryABSTRACT
BACKGROUND: Rectal cancer is a major mortality cause in the United States (US), and its treatment is based on individual risk factors for recurrence in each patient. In patients with rectal cancer, accurate assessment of response to chemoradiotherapy has increased in importance as the variety of treatment options has grown. In this scenario, a controversial non-operative approach may be considered in some patients for whom complete tumor regression is believed to have occurred. The recommended treatment for locally advanced rectal cancer (LARC, T3-4 ± N+) is total mesorectal excision (TME) after neoadjuvant chemoradiotherapy (nCRT). Magnetic resonance imaging (MRI) has become a standard technique for local staging of rectal cancer (tumor, lymph node, and circumferential resection margin [CRM] staging), in both the US and Europe, and it is getting widely used for restaging purposes. AIM: In our study, we aimed to use an MRI radiomic model to identify features linked to the different responses of chemoradiotherapy of rectal cancer before surgery, and whether these features are helpful to understand the effectiveness of the treatments. METHODS: We retrospectively evaluated adult patients diagnosed with LARC who were subjected to at least 2 MRI examinations in 10-12 weeks at our hospital, before and after nCRT. The MRI acquisition protocol for the 2 exams included T2 sequence and apparent diffusion coefficient (ADC) map. The patients were divided into 2 groups according to the treatment response: complete or good responders (Group 1) and incomplete or poor responders (Group 2). MRI images were segmented, and quantitative features were extracted and compared between the two groups. Features that showed significant differences (SF) were then included in a LASSO regression method to build a radiomic-based predictive model. RESULTS: We included 38 patients (26 males and 12 females), who are classified from T2 and T4 stages in the rectal cancer TNM. After the nCRT, the patients were divided into Group 1 (13 patients), complete or good responders, and Group 2 (25 patients), incomplete or poor responders. Analysis at baseline generated the following significant features for the Mann-Whitney test (out of a total of 107) for each sequence. Also, the analysis at the end of the follow-up yielded a high number of significant features for the Mann-Whitney test (out of a total of 107) for each image. Features selected by the LASSO regression method for each image analyzed; ROC curves relative to each model are represented. CONCLUSION: We developed an MRI-based radiomic model that is able to differentiate and predict between responders and non-responders who went through nCRT for rectal cancer. This approach might identify early lesions with high surgical potential from lesions potentially resolving after medical treatment.
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INTRODUCTION: The aim of this study is to assess the impact of lymph node ratio (LNR) and number of positive lymph nodes (NPLN) on mortality and recurrence rates in patients with laryngeal squamous cell carcinoma. MATERIALS AND METHODS: We conducted a retrospective multicenter international study involving 24 Otorhinolaryngology-Head and Neck Surgery divisions. Disease-specific survival (DSS) and disease-free survival (DFS) were evaluated as the main outcomes. The curves for DSS and DFS according to NPLN and LNR were analyzed to identify significant variations and establish specific cut-off values. RESULTS: 2507 patients met the inclusion criteria. DSS and DFS were significantly different in the groups of patients stratified according to LNR and NPLN. The 5-year DSS and DFS based on LNR and NPLN demonstrated an improved ability to stratify patients when compared to pN staging. CONCLUSION: Our data demonstrate the potential prognostic value of NPLN and LNR in laryngeal squamous cell carcinoma.
Subject(s)
Head and Neck Neoplasms , Lymph Nodes , Humans , Lymph Nodes/pathology , Squamous Cell Carcinoma of Head and Neck/pathology , Neoplasm Staging , Lymphatic Metastasis/pathology , Lymph Node Ratio , Prognosis , Retrospective Studies , Head and Neck Neoplasms/pathology , Lymph Node ExcisionABSTRACT
Eating disorders (EDs) are syndromes with a multifactorial etiopathogenesis, involving childhood traumatic experiences, as well as biological factors. Human microbiome has been hypothesised to play a fundamental role, impacting on emotion regulation, as well as with eating behaviours through its metabolites such as short chain fatty acids (SCFAs). The present study investigated the interactions between psychopathology of EDs, the gut microbiome and SCFAs resulting from bacterial community metabolic activities in a population of 47 patients with Anorexia Nervosa, Bulimia Nervosa, and Binge Eating Disorder and in healthy controls (HCs). Bacterial gut microbiota composition differences were found between subjects with EDs and HCs, especially in association with different pathological behaviours (binge-purge vs restricting). A mediation model of early trauma and ED-specific psychopathology linked reduction of microbial diversity to a typical microbiota-derived metabolite such as butyric acid. A possible interpretation for this model might be that childhood trauma represents a risk factor for gut dysbiosis and for a stable modification of mechanisms responsible for SCFAs production, and that this dysfunctional community is inherited in the passage from childhood to adulthood. These findings might open the way to novel interventions of butyric acid-like compounds as well as faecal transplant.
Subject(s)
Anorexia Nervosa , Child Abuse , Feeding and Eating Disorders , Gastrointestinal Microbiome , Humans , Child , Adolescent , Young Adult , Anorexia Nervosa/psychology , ButyratesABSTRACT
Background: Globalisation and international trade, in particular, are the major drivers of introduction and the spread of non-native species. To date, more than 30 species of non-native Hemiptera Auchenorrhyncha have been accidentally introduced into Europe. Some species are invasive with important repercussions primarily for agricultural activities, while almost no information exists on their impacts within natural ecosystems. Therefore, early detection of non-native species and their subsequent monitoring are extremely important actions to undertake. New information: The North American Osbornellusauronitens (Provancher, 1889), firstly recorded for the Palearctic and Europe in Switzerland in 2016, is recorded in Italy for the first time on the basis of 77 specimens collected between August 2015 and October 2022.
Subject(s)
Communicable Diseases , Gastroenterology , Gynecology , Schistosomiasis , Tropical Medicine , Urology , Female , Pregnancy , Humans , Child , Colposcopy , Global Health , Consensus , Endoscopy, Gastrointestinal , Schistosomiasis/diagnosis , Schistosomiasis/drug therapy , Schistosomiasis/epidemiology , Primary Health Care , Italy/epidemiologyABSTRACT
The round goby (Neogobius melanostomus) is a fish native to the Ponto-Caspian region that is highly invasive through freshwater and brackish habitats in northern Europe and North America. Individual behavioural variation appears to be an important factor in their spread, for example a round goby's personality traits can influence their dispersal tendency, which may also produce variation in the behavioral composition of populations at different points along their invasion fronts. To further analyze the drivers of behavioral variation within invasive round goby populations, we focused on two populations along the Baltic Sea invasion front with closely comparable physical and community characteristics. Specifically, this study measured personality within a novel environment and predator response context (i.e., boldness), and directly analyzed links between individuals' personality traits and their physiological characteristics and stress responses (i.e., blood cortisol and lactate, brain neurotransmitters). In contrast to previous findings, the more recently established population had similar activity levels but were less bold in response to a predator cue than the older population, which suggests that behavioral compositions within our study populations may be more driven by local environmental conditions rather than being a result of personality-biased dispersal. Furthermore, we found that both populations showed similar physiological stress responses, and there also appeared to be no detectable relationship between physiological parameters and behavioral responses to predator cues. Instead, body size and body condition were important factors influencing individual behavioral responses. Overall, our results reinforce the importance of boldness traits as a form of phenotypic variation in round goby populations in the Baltic Sea. We also highlight the importance of these traits for future studies specifically testing for effects of invasion processes on phenotypic variation in the species. Nonetheless, our results also highlight that the physiological mechanisms underpinning behavioural variation in these populations remain unclear.
Subject(s)
Body Size , Oceans and Seas , Perciformes , Predatory Behavior , Stress, Physiological , Perciformes/anatomy & histology , Perciformes/blood , Perciformes/physiology , Predatory Behavior/physiology , Body Size/physiology , Stress, Physiological/physiology , Denmark , Risk-Taking , Male , Female , Animals , Reproducibility of Results , Brain ChemistryABSTRACT
With no approved antiviral therapies, the continuous emergence and re-emergence of tick-borne encephalitis virus (TBEV) and yellow fever virus (YFV) is a rising concern. We performed head-to-head comparisons of the antiviral activity of available nucleos(t)ide analogs (nucs) using relevant human cell lines. Eight existing nucs inhibited TBEV and/or YFV with differential activity between cell lines and viruses. Remdesivir, uprifosbuvir and sofosbuvir were the most potent drugs against TBEV and YFV in liver cells, but they had reduced activity in neural cells, whereas galidesivir retained uniform activity across cell lines and viruses. Ribavirin, valopicitabine, molnupiravir and GS-6620 exhibited only moderate antiviral activity. We found antiviral activity for drugs previously reported as inactive, demonstrating the importance of using human cell lines and comparative experimental assays when screening the activity of nucs. The relatively high antiviral activity of remdesivir, sofosbuvir and uprifosbuvir against TBEV and YFV merits further investigation in clinical studies.
Subject(s)
Encephalitis Viruses, Tick-Borne , Encephalitis, Tick-Borne , Yellow Fever , Humans , Sofosbuvir/pharmacology , Sofosbuvir/therapeutic use , Yellow Fever/drug therapy , Cell Line , Yellow fever virus , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic useABSTRACT
Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.
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BACKGROUND AND AIMS: Intestinal ultrasound [IUS] is widely accepted as a reliable tool to monitor Crohn's disease [CD]. Several IUS scores have been proposed, but none has been formally accepted by international organizations. Our aim here was to compare the available scores regarding their correlation with endoscopic activity. METHODS: Consenting CD patients undergoing ileocolonoscopy at our Unit between September 2021 and February 2023 were included. Endoscopic activity was defined as SES-CDâ ≥â 3 or Rutgeerts scoreâ ≥â i2b for operated patients. IUS was performed within 6 weeks of endoscopy and scored with IBUS-SAS, BUSS, Simple-US and SUS-CD scores. All correlations were performed using Spearman's rank coefficient [rho = ρ]. Receiver operating characteristic [ROC] curves were compared with the Hanley and McNeil method. RESULTS: Of 73 CD patients, 45 [61.6%] presented endoscopic activity, of whom 22 were severe [30.1%]. All IUS scores showed a significant positive correlation with endoscopy [pâ <â 0.0001], with IBUS-SAS ranking the highest [ρâ =â 0.87]. Similarly, IBUS-SAS was the most highly correlated with clinical activity [ρâ =â 0.58]. ROC analysis of IBUS-SAS for any endoscopic activity showed the highest area under the curve (0.95 [95% confidence interval 0.87-0.99]), with sensitivity of 82.2% and specificity of 100% for a cut-off value of 25.2. IBUS-SAS was statistically superior to all the other scores in detecting severe endoscopic activity [SES-CDâ ≥â 9 or Rutgeerts i4]. CONCLUSIONS: All IUS scores provided solid correlation with endoscopy and clinical symptoms. IBUS-SAS outperformed the others due to a more granular description that might help in stratifying different levels of disease activity. Therefore, the use of IBUS-SAS in centres with well-founded expertise in IUS can be suggested.
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PURPOSE: To compare visual performance and quality of life in patients who received either monofocal intraocular lenses (IOLs) or an enhanced monofocal IOL in a mini-monovision target approach. BACKGROUND: Monofocal lenses are the most common intraocular IOLs employed during cataract surgery because of their relatively low cost and good performance for distance sight. However, these lenses, generally, do not exonerate patients from spectacle use for near or intermediate tasks. On the other hand, enhanced monofocal IOLs (e.g., Tecnis Eyhance®) feature optical properties providing patients with good intermediate visual outcomes. Satisfactory near visual acuity results, regardless of IOL type, may be achieved through mini-monovision. We assessed visual performance outcomes between these IOLs, in a mini-monovision approach. METHODS: Retrospective case series of patients who underwent bilateral cataract surgery at our institution with implantation of Alcon SN60WF, J&J Tecnis DCB00 or J&J Tecnis Eyhance® DIB00 with a pre-operative mini-monovision target. The postoperative spherical equivalent was measured by a Nidek® auto-refractometer. Best-uncorrected binocular visual acuity (BUBVA) at far (3 m), intermediate (66 cm), and near (40 cm) distance and binocular contrast sensitivity (100%, 25%, and 5%, all at 1 m) were measured using Snellen and Pelli-Robson charts, respectively. Visual performance in daily life was evaluated with the Cataract VF-14 quality of life survey. RESULTS: 71 patients (35 in the monofocal IOL and 37 enhanced IOL group) were enrolled. Patients implanted with enhanced IOL exhibited statistically significant better BUBVA results at 66 cm and 40 cm distances compared to patients in the monofocal group. Additionally, patients in the enhanced IOL group presented a better contrast sensitivity in lower contrast conditions (5%) than patients with monofocal IOL. The quality of life survey showed statistically significant higher scores in daily activities without spectacles for patients with enhanced IOL. CONCLUSION: Enhanced monofocal IOLs, combined with a mini-monovision approach, provided patients with good visual performance at all tested distances, with superiority of enhanced monofocal IOLs at near and intermediate distances.
Subject(s)
Cataract , Lenses, Intraocular , Phacoemulsification , Humans , Lens Implantation, Intraocular , Vision, Monocular , Quality of Life , Retrospective Studies , Prosthesis Design , Patient SatisfactionABSTRACT
OBJECTIVES: Four-class drug-resistant (4DR) people living with HIV (PLWH) are a fragile population with a high burden of disease. No data on their inflammation and T-cell exhaustion markers are currently available. METHODS: Inflammation, immune activation and microbial translocation biomarkers were measured through ELISA in 30 4DR-PLWH with HIV-1 RNA ≥ 50 copies/mL, 30 non-viremic 4DR-PLWH and 20 non-viremic non-4DR-PLWH. Groups were matched by age, gender and smoking habit. T-cell activation and exhaustion markers were assessed by flow cytometry in 4DR-PLWH. An inflammation burden score (IBS) was calculated from soluble marker levels and associated factors were estimated through multivariate regression. RESULTS: The highest plasma biomarker concentrations were observed in viremic 4DR-PLWH, the lowest ones in non-4DR-PLWH. Endotoxin core immunoglobulin G showed an opposite trend. Among 4DR-PLWH, CD38/HLA-DR and PD-1 were more expressed on CD4+ (p = 0.019 and 0.034, respectively) and CD8+ (p = 0.002 and 0.032, respectively) cells of viremic compared to non-viremic subjects. An increased IBS was significantly associated with 4DR condition, higher values of viral load and a previous cancer diagnosis. CONCLUSIONS: Multidrug-resistant HIV infection is associated with a higher IBS, even when viremia is undetectable. Therapeutic approaches aimed to reduce inflammation and T-cell exhaustion in 4DR-PLWH need to be investigated.
Subject(s)
Drug Resistance, Multiple, Viral , HIV Infections , Inflammation , Humans , HIV Infections/complications , HIV-1 , Inflammation/complications , Lymphocyte Activation , Viral Load , ViremiaABSTRACT
Metabolic disorders characterized by elevated blood glucose levels are a recognized risk factor for hepatocellular carcinoma (HCC). Lipid dysregulation is critically involved in the HCC progression, regulating energy storage, metabolism, and cell signaling. There is a clear link between de novo lipogenesis in the liver and activation of the NF-κB pathway, which is involved in cancer metastasis via regulation of metalloproteinases MMP-2/9. As conventional therapies for HCC reach their limits, new effective and safe drugs need to be found for the prevention and/or adjuvant therapy of HCC. The marine plant Posidonia oceanica (L.) Delile is endemic to the Mediterranean and has traditionally been used to treat diabetes and other health disorders. The phenol-rich leaf extract of Posidonia oceanica (POE) is known to have cell-safe bioactivities. Here, high glucose (HG) conditions were used to study lipid accumulation and fatty acid synthase (FASN) expression in human HepG2 hepatoma cells using Oil Red O and Western blot assays. Under HG conditions, the activation status of MAPKs/NF-κB axis and MMP-2/9 activity were determined by Western blot and gelatin zymography assays. The potential ameliorative role of POE against HG-related stress in HepG2 cells was then investigated. POE reduced lipid accumulation and FASN expression with an impact on de novo lipogenesis. Moreover, POE inhibited the MAPKs/NF-κB axis and, consequently, MMP-2/9 activity. Overall, these results suggest that P. oceanica may be a potential weapon in the HCC additional treatment.