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Background The development of direct-acting antivirals (DAA) for HCV has revolutionized the treatment of HCV, including its treatment in patients with HIV coinfection. The aim of this study was to compare the changes in liver function between coinfected and monoinfected patients with cirrhosis who achieved HCV eradication by DAA. Methods Patients with pre-treatment diagnosis of HCV liver cirrhosis, consecutively enrolled in the multicenter PITER cohort, who achieved a sustained virological response 12 weeks after treatment cessation (SVR12) were analysed. Changes in Child-Pugh (C-P) class and the occurrence of a decompensating event was prospectively evaluated after the end of DAA treatment. Cox regression analysis was used to evaluate factors independently associated with changes in liver function following viral eradication. Results We evaluated 1350 patients, of whom 1242 HCV monoinfected (median follow-up 24.7, range 6.8–47.5 months after viral eradication) and 108 (8%) HCV/HIV coinfected (median follow-up 27.1, range 6.0–44.6). After adjusting for age, sex, HCV-genotype, HBsAg positivity and alcohol use, HIV was independently associated with a more advanced liver disease before treatment (C-P class B/C vs A) (OR: 3.73, 95% CI:2.00–6.98). Following HCV eradication, C-P class improved in 17/20 (85%) coinfected patients (from B to A and from C to B) and in 53/82 (64.6%) monoinfected patients (from B to A) ( p  = 0.08). C-P class worsened in 3/56 coinfected (5.3%) (from A to B) and in 84/1024 (8.2%) monoinfected patients ( p  = 0.45) (from A to B or C and from B to C). Baseline factors independently associated with C-P class worsening were male sex (HR = 2.00; 95% CI = 1.18–3.36), platelet count < 100,000/μl (HR = 1.75; 95% CI 1.08–2.85) and increased INR (HR = 2.41; 95% CI 1.51–3.84). Following viral eradication, in 7 of 15 coinfected (46.6%) and in 61 of 133 (45.8%) monoinfected patients with previous history of decompensation, a new decompensating event occurred. A first decompensating event was recorded in 4 of 93 (4.3%) coinfected and in 53 of 1109 (4.8%) monoinfected patients ( p  = 0.83). Conclusions Improvement of liver function was observed following HCV eradication in the majority of patients with cirrhosis; however viral eradication did not always mean cure of liver disease in both monoinfected and coinfected patients with advanced liver disease.

Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure. To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage. Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers. Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve SVR. Genotype 3, bilirubin levels >1.5mg/dl, platelet count <120,000/mm3 and the sofosbuvir+ribavirin regimen were independent predictors of failure by logistic regression analysis. The failure rate was 7.6% for patients treated with regimens that are no longer recommended or considered suboptimal (sofosbuvir+ribavirin or simeprevir+sofosbuvir±ribavirin), whereas 1.4% for regimens containing sofosbuvir combined with daclatasvir or ledipasvir or other DAAs. Of the patients who failed to achieve SVR, 72 (51.8%) were retreated with a second DAA regimen, specifically 38 (52.7%) with sofosbuvir+daclatasvir, 27 (37.5%) with sofosbuvir+ledipasvir, and 7 (9.7%) with other DAAs ±ribavirin. Among these, 69 (96%) patients achieved SVR12 and 3 (4%) failed. During a median time of 6 months (range: 5-14 months) between failure and the second DAA therapy, the Child-Pugh class worsened in 12 (16.7%) patients: from A to B in 10 patients (19.6%) and from B to C in 2 patients (10.5%), whereas it did not change in the remaining 60 patients. Following the retreatment SVR12 (median time of 6 months; range: 3-12 months), the Child-Pugh class improved in 17 (23.6%) patients: from B to A in 14 (19.4%) patients, from C to A in 1 patient (1.4%) and from C to B in 2 (2.9%) patients; it remained unchanged in 53 patients (73.6%) and worsened in 2 (2.8%) patients. Of patients who were retreated, 3 (4%) had undergone OLT before retreatment (all reached SVR12 following retreatment) and 2 (2.8%) underwent OLT after having achieved retreatment SVR12. Two (70%) of the 3 patients who failed to achieve SVR12 after retreatment, and 2 (2.8%) of the 69 patients who achieved retreatment SVR12 died from liver failure (Child-Pugh class deteriorated from B to C) or HCC complications. Failure rate following the first DAA regimen in patients with advanced disease is similar to or lower than that reported in clinical trials, although the majority of patients were treated with suboptimal regimens. Interim findings showed that worsening of liver function after failure, in terms of Child Pugh class deterioration, was improved by successful retreatment in about one third of retreated patients within a short follow-up period; however, in some advanced liver disease patients, clinical outcomes (Child Pugh class, HCC development, liver failure and death) were independent of viral eradication.

Background: Obstructive sleep apnea (OSA) is characterized by repeated airway obstructions during sleep, causing hypopnea, apnea, intermittent hypoxia, and sleep fragmentation. The severity of OSA is measured using the apnea–hypopnea index (AHI), with AHI ≥ 5 indicating OSA. This study aims to assess the frequency and type of depressive disorder characteristics of OSA patients and to evaluate the impact on quality of life, also considering the presence of hyperactivity. Methods: A case-control study using OSA patients referred to Cagliari’s sleep disorder center. Controls were matched by age and sex from community databases. OSA diagnoses were made with AHI > 15. Depressive episodes were identified using BDI-SF, and H-QoL (Health related Quality of Life) was measured with the SF-12, focusing on item 10 for hyper-energy. Results: The clinical sample (n = 25) had a higher frequency of depressive episodes (36%) compared to controls (7% and 4%). Depressed OSA patients had worse H-QoL and higher hyper-energy scores, but the additional burden from depression was relatively low. Conclusions: The OSA sample has a higher frequency of depressive episodes compared to the general population. Depressive episodes in OSA patients are linked to higher scores on item 10 of the SF-12, indicating hyper-energy despite lower overall quality of life scores. While OSA significantly impacts quality of life, the additional burden from depression is less severe than in other chronic diseases. These findings suggest that depressive episodes in OSA may be related to rhythm dysregulation and hyperactivity (DYMERS).

Mitochondrial dysfunction represents a central hallmark of aging and a broad spectrum of chronic diseases, ranging from metabolic to neurodegenerative and ocular disorders. Nicotinamide riboside (NR), a vitamin B3 derivative and efficient precursor of NAD+ (nicotinamide adenine dinucleotide), and berberine (BBR), an isoquinoline alkaloid widely investigated in metabolic regulation, have independently emerged as promising mitochondrial modulators. NR enhances cellular NAD+ pools, thereby activating sirtuin-dependent pathways, stimulating PGC-1α–mediated mitochondrial biogenesis, and triggering the mitochondrial unfolded protein response (UPRmt). BBR, by contrast, primarily activates AMPK (AMP-activated protein kinase) and interacts with respiratory complex I, improving bioenergetics, reducing mitochondrial reactive oxygen species, and promoting mitophagy and organelle quality control. Importantly, despite distinct upstream mechanisms, NR and BBR converge on shared signaling pathways that support mitochondrial health, including redox balance, metabolic flexibility, and immunometabolic regulation. Unlike previous reviews addressing these compounds separately, this article integrates current preclinical and clinical findings to provide a unified perspective on their converging actions. We critically discuss translational opportunities as well as limitations, including heterogeneous clinical outcomes and the need for robust biomarkers of mitochondrial function. By outlining overlapping and complementary mechanisms, we highlight NR and BBR as rational combinatorial strategies to restore mitochondrial resilience. This integrative perspective may guide the design of next-generation clinical trials and advance precision approaches in mitochondrial medicine.

Human allogeneic umbilical cord blood serum stands out as a potent adjunct to conventional therapies for ocular surface disorders related to severe Dry Eye Disease. By expediting ocular surface regeneration and fostering epithelial integrity, umbilical cord blood serum not only enhances subjective patient experiences but also improves objective clinical indicators. This makes it particularly useful in patients with corneal ulcers through ocular surface regeneration and anti-inflammatory activity. This retrospective, interventional, non-randomized clinical study aims to explore the efficacy of allogenic umbilical cord blood serum in patients who had previously received other treatments unsuccessfully. This study was a retrospective, non-comparative, interventional clinical study involving 55 patients (35 females and 20 males) aged 18–82 years with severe Dry Eye Disease who were unresponsive to standard treatments. The study was conducted at Eye Center “G.B. Morgagni-DSV”, Catania, Italy. Patients were categorized based on the etiology of severe Dry Eye Disease into four groups: group I consisted of 26 patients with filamentary keratitis and corneal ulcers associated with rheumatologic diseases such as Sjogren’s syndrome and systemic sclerosis; group II comprised 15 patients with graft-versus-host disease; group III consisted of 10 patients with corneal neurotrophic ulcers; group IV included four patients with Steven–Johnson syndrome. Outcomes evaluated before and after treatment were OSDI (Ocular Surface Disease Index) and SANDE (Symptom Assessment in Dry Eye) Questionnaires, VAS (Visual Analog Scale), Slit-Lamp Examination, Esthesiometry, Lissamine Green Staining, NIBUT (Non-Invasive Break-Up Time) and BUT, Fluorescein Staining with Photography and Oxford Classification, Schirmer Test, Best-Corrected Visual Acuity (BCVA), Meibography. We observed a significant improvement in SANDE, VAS and OSDI questionnaires, Schirmer Test, BUT, BCVA, and Oxford classification after treatment with allogeneic cord blood serum eyedrops. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, or pain, were also considered individually. Nevertheless, pain and inflammation reduced markedly over time until completely healed in all cases. Our study highlights the remarkable efficacy of allogeneic cord blood serum eyedrops in patients with severe Dry Eye Disease who have shown absent or inadequate response to usual treatments for dry eye. This underscores the need for further comprehensive investigations in this field.

Background: Glaucoma is a chronic neurodegenerative disorder characterized by the selective vulnerability of retinal ganglion cells (RGCs), in which mitochondrial dysfunction, redox imbalance, and impaired bioenergetic signaling play central pathogenetic roles. Mitochondrial homeostasis in RGCs critically depends on maintaining intracellular NAD+ pools, which support oxidative phosphorylation, sirtuin-mediated deacetylation, and antioxidant gene expression. Nicotinamide riboside (NR), a potent NAD+ precursor, and berberine (BBR), an AMPK activator derived from Berberis aristata, have recently emerged as synergistic modulators of mitochondrial metabolism and oxidative stress resistance. Methods: This study retrospectively assessed clinical outcomes associated with combined nutraceutical supplementation of nicotinamide riboside (NR) and berberine (BBR) in patients with primary open-angle glaucoma undergoing stable topical hypotensive therapy. We have included a narrative review in the current literature regarding NAD+ biology, AMPK–sirtuin signaling, and oxidative stress responses in retinal ganglion cell (RGC) degeneration. Due to the absence of comparator groups receiving only NR or only berberine in this retrospective cohort, the combined supplementation has been regarded as a biologically complementary strategy, and the potential for synergistic efficacy remains a subject for further investigation. Results: Translationally, a retrospective clinical cohort receiving combined NR and BBR supplementation showed functional stabilization of the visual field and structural preservation of the retinal nerve fiber layer over a six-month follow-up, in line with the proposed mitochondrial protective mechanisms. Conclusions: The clinical trends identified in this retrospective cohort have substantiated the translational significance of NR + BBR supplementation as a potential adjunctive approach in glaucoma management. NAD+ repletion and engagement of the AMPK–SIRT–NRF2 pathway may enhance mitochondrial resilience in RGCs. Collectively, these findings offer initial clinical evidence advocating for additional controlled studies on NR + berberine supplementation, while mechanistic interpretations have been derived from the existing literature and are hypothesis-generating.

Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95-positive elements. Further analysis indicates that “long thin” but not “mushroom” spines are selectively affected. In addition, patch-clamp experiments from Nacc slices reveal that long-term depression (LTD) formation is hampered, with parallel changes in field potential recordings and reductions in NMDA-mediated synaptic currents. These changes are restricted to the withdrawal phase of ethanol dependence, suggesting their relevance in the genesis of signs and/or symptoms affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these results highlight the key role of dynamic alterations in dendritic spines and their presynaptic afferents in the evolution of alcohol dependence. Furthermore, they suggest that the selective loss of long thin spines together with a reduced NMDA receptor function may affect learning. Disruption of this LTD could contribute to the rigid emotional and motivational state observed in alcohol dependence.

Trabeculectomy remains gold-standard surgical approach for intraocular pressure (IOP) control in glaucoma, yet its impact on optic nerve head (ONH) morphology and retinal microvasculature has not been fully clarified. This study aimed to investigate structural and vascular changes of the ONH and macula after trabeculectomy using spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA). In this retrospective study, data from 22 patients with primary open-angle glaucoma who underwent uncomplicated trabeculectomy were reviewed. The fellow eye served as control. Structural parameters, including Bruch's membrane opening (BMO), maximum cup depth (MCD), and cup area, were measured with SD-OCT. Vessel density (VD) of the optic disc, peripapillary retina, and macular superficial (SCP) and deep (DCP) capillary plexuses were analyzed with OCTA. Preoperative and two-month postoperative data were compared using paired statistical tests. Mean IOP decreased from 23.1 ± 3.9 mmHg to 13.2 ± 3.2 mmHg ( < 0.001). Significant postoperative reductions were observed in BMO (-5 ± 6%, = 0.004), MCD (-31 ± 8%, < 0.001), and cup area (-44 ± 18%, < 0.001). RNFL thickness and ONH vascular parameters remained stable. In contrast, DCP vessel density increased in the foveal ( = 0.002) and parafoveal ( = 0.023) regions, while SCP density showed no significant change. Trabeculectomy was associated with measurable reversal of optic disc cupping, indicating partial structural recovery of the ONH following IOP reduction. The selective improvement in deep retinal vessel density suggests a layer-specific microvascular response. These findings provide further insight into the interplay between mechanical and vascular mechanisms in glaucoma and may inform postoperative monitoring strategies.

Background: Vernal keratoconjunctivitis (VKC) is a chronic, recurrent, and frequently severe allergic ocular condition predominantly impacting children and adolescents in tropical and subtropical areas. It profoundly affects patients’ quality of life owing to its chronic symptoms and possible vision-threatening effects. Notwithstanding progress in comprehending VKC, its ocular symptoms and therapeutic approaches necessitate ongoing assessment. Aims: This review summarizes the main factors to consider when diagnosing, treating, and managing patients with VKC based on the current literature in this field. Methods: This comprehensive review examined peer-reviewed literature from 2010 to 2024 obtained from PubMed. The selection criteria encompassed research addressing the clinical presentation, diagnostic difficulties, and therapy of visual symptoms in pediatric patients with VKC. The publications chosen were those focusing on those that elucidate the pathophysiology, consequences, and innovations in treatment methodologies. Results: The ocular manifestations of VKC are varied and characterized by prominent symptoms such as severe itching, photophobia, lacrimation, and a viscous mucoid discharge. Clinical manifestations range from conjunctival hyperemia and limbal thickening to severe consequences that jeopardize vision, including shield ulcers and keratoconus. Improvements in imaging techniques such as anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy have enhanced diagnostic accuracy. The pharmacological approach has transitioned to steroid-sparing techniques, prioritizing mast cell stabilizers, antihistamines, and immunomodulators such as cyclosporine. Novel therapies, including biologics that target interleukin pathways, demonstrate potential in refractory instances. Nonetheless, access to modern medicines is restricted in resource-limited environments. Conclusions: VKC poses considerable diagnostic and treatment difficulties due to its chronic nature and possible consequences. This review emphasizes the necessity for prompt diagnosis and customized management approaches to avert vision impairment. Despite considerable advancements in comprehending VKC’s etiology and therapy, inequalities in access to sophisticated care highlight the necessity for global activities to guarantee equitable treatment alternatives.

Esophageal barrier has been investigated until now on the epithelial side only. Gut vascular barrier dysfunction has been recently implicated in a number of immune-mediated gastrointestinal disorders. We here characterized the esophageal vascular barrier (EVB) in eosinophilic esophagitis (EoE). Probe-based confocal laser endomicroscopy (pCLE) was performed in two EoE and two reflux esophagitis (RE) patients. The vascular barrier marker plasmalemma vesicle-1 (PV-1) was investigated as a measure of barrier disruption, by both immunohistochemistry and qPCR, in esophageal biopsies of 16 patients with EoE, 15 with RE, and 15 healthy controls (HC). In EoE, but not RE, pCLE revealed leakage of the EVB, which was restored in one patient after dupilumab treatment. PV-1 was significantly increased in EoE in comparison to RE and HC, both in terms of protein and transcript levels, supporting vascular leakage. EVB is disrupted in active EoE. Further studies are needed to understand the diagnostic and pathogenic implications of this finding.