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Background: Wilms tumor (WT) is the most common malignant renal tumor in children. This study investigated the clinical features, pathological findings, and outcomes of children with malignant renal tumors in Southern Iran. Factors associated with recurrence and mortality were assessed. Methods: Electronic files of children with malignant renal tumors from 2009 to 2023 were reviewed. The 5-year overall survival (OS) and event-free survival (EFS) were reported. Results: Eighty-three patients (44 males) with a median age of 40 months (range: 3-122) were included. WT was the most common pathological variant (94%). Anaplasia was found in 17.3% of patients. Upfront chemotherapy followed by nephrectomy was performed in 54.2% of the patients. Ten patients (12%) experienced relapse, and five patients (6%) died during the 14-year follow-up. The 5-year OS and EFS were 90.75% (95% CI, 78.64–96.16%) and 81.9% (95% CI, 70.10-89.38%), respectively, and were comparable between the two treatment strategies (upfront chemotherapy vs. upfront nephrectomy). Metastasis and residual disease were associated with relapse, whereas tumor recurrence was the only predictive factor of survival. Conclusion: WT is a curable disease with excellent outcomes if diagnosed and treated promptly. The timing of nephrectomy does not affect OS and EFS. Patients with low-stage tumors and those with complete surgical excision are at a lower risk of tumor recurrence. Relapse is the primary risk factor for death. [ABSTRACT FROM AUTHOR]

Medical thoracoscopy has been extensively utilized in the diagnosis of pleural disease, yet its potential therapeutic applications remain underutilized. This article presents a comprehensive overview of the various uses of medical thoracoscopy in managing pleural diseases. It has been employed to facilitate thoracic drainage and reduce hospitalization duration of patients with complicated parapneumonic effusions and empyema. Additionally, medical thoracoscopic occlusion therapy can be used for bronchoscopic closure and refractory pneumothorax. However, there is currently a lack of standardized protocols for utilizing medical thoracoscopy to reduce the volume of giant emphysematous bullae. Furthermore, medical thoracoscopy allows for pleurodesis or photodynamic therapy in patients with malignant pleural effusion. Nevertheless, further high-quality clinical research is needed to validate these findings. [ABSTRACT FROM AUTHOR]

Objective Data sources Review methods Results Conclusion Neck metastases are a poor prognostic factor in olfactory neuroblastoma (ONB). Pathologic dural invasion (pathDI) may increase the risk of neck metastases due to invasion of dural lymphatics. We aim to evaluate the prognostic value of pathDI in predicting rates of neck metastases and recurrence using a large, multicenter database of ONB patients.Retrospective review of a prospective, multicenter database of electronic health records of all patients who presented with ONB between 2005 and 2021 at nine tertiary academic care centers within North America.Clinicopathologic features including modified Kadish staging systems, margin status, treatment modalities, Hyams grading, follow‐up time, and survival.Of 258 ONB patients, 189 patients met the inclusion criteria. The 10‐year neck recurrence‐free survival (neck‐RFS) rates were 85.7% (75.6‒97.3) and 61.8% (47.9‒79.8) for patients without and with pathDI, respectively (p = 0.018). Time‐to‐event multivariable regression analysis found pathDI to have an odds ratios of 9.7 (95% confidence interval [CI] 1.2–80.4, p = 0.04) for neck‐RFS and 9.5 for RFS at any site (95% CI 1.1–83.3, p = 0.04).In multivariable analysis, the presence of pathDI appears to be the strongest predictor of neck recurrence and recurrence at any site. Future studies exploring the benefit of elective neck dissection or radiation for patients with pathDI may impact disease management. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Method Results Discussion It is often stated that a higher body mass index (BMI) at the beginning of treatment predicts a better weight outcome at the end of treatment in persons with anorexia nervosa (AN). However, this interpretation is based on the between‐persons relationship of BMI at the two measurements, which primarily reflects the fact that the rank‐ordering of persons according to their BMI is quite stable over time. In contrast, a lower BMI at baseline is related to a larger BMI change, which primarily reflects the fact that the variance of BMI at the end of treatment is larger than that at baseline. This study aimed to demonstrate these relationships empirically and caution against interpreting BMI at baseline as a predictor of BMI at discharge or BMI change.Changes of BMI from admission to discharge were analyzed based on 4863 persons with AN (97% female) who received inpatient treatment between 2015 and 2024.BMI at admission was positively related to BMI at discharge (r = 0.55) but negatively related to BMI change from admission to discharge (r = −0.39).While it is true that a higher BMI at baseline is associated with a higher BMI at the end of treatment, a lower BMI at baseline is actually related to a larger weight gain during treatment. Yet, concluding that the treatment is more effective for patients with low or high BMI at baseline would be incorrect in either case, as the independent and dependent variables are the same variables measured at different time points. [ABSTRACT FROM AUTHOR]

• Comprehensively synthesize the functional features of OECs. • The function and mechanism of OECs in the repair of peripheral nerve injury were discussed. • Application of OECs in the treatment of pathological pain induced by peripheral nerve injury was discussed. Direct or indirect injury of peripheral nerve can lead to sensory and motor dysfunction, which can lead to pathological pain and seriously affect the quality of life and psychosomatic health of patients. While the internal repair function of the body after peripheral nerve injury is limited. Nerve regeneration is the key factor hindering the recovery of nerve function. At present, there is no effective treatment. Therefore, more and more attention have been paid to the development of foreground treatment to achieve functional recovery after peripheral nerve injury, including relief of pathological pain. Cell transplantation strategy is a therapeutic method with development potential in recent years, which can exert endogenous alternative repair by transplanting exogenous functional bioactive cells to the site of nerve injury. Olfactory ensheathing cells (OECs) are a special kind of glial cells, which have the characteristics of continuous renewal and survival. The mechanisms of promoting nerve regeneration and functional repair and relieving pathological pain by transplantation of OECs to peripheral nerve injury include secretion of a variety of neurotrophic factors, axonal regeneration and myelination, immune regulation, anti-inflammation, neuroprotection, promotion of vascular growth and improvement of inflammatory microenvironment around nerve injury. Different studies have shown that OECs combined with biomaterials have made some progress in the treatment of peripheral nerve injury and pathological pain. These biomaterials enhance the therapeutic effect of OECs. Therefore, the functional role of OECs in peripheral nerve injury and pathological pain was discussed in this paper. Although OECs are in the primary stage of exploration in the repair of peripheral nerve injury and the application of pain, but OECs transplantation may become a prospective therapeutic strategy for the treatment of peripheral nerve injury and pathological pain. [ABSTRACT FROM AUTHOR]

Immunotherapy stands as the frontrunner in treatment strategies imparting efficient remission in various types of cancer. In fact, emerging breakthroughs with immune checkpoint inhibitors (ICI) in a spectrum of cancers have evoked interest in research related to the potential effects of immunotherapy in breast cancer patients. A major challenge with breast cancer is the molecular heterogeneity that limits the efficacy of many therapeutic regimes. Clinical trials have shown favorable clinical outcomes with immunotherapeutic options in some subtypes of breast cancer. However, ICI monotherapy may not be sufficient for all breast cancer patients, emphasizing the need for combinatorial approaches. Ongoing research is focused on untangling the interplay of ICI with established as well as novel anticancer therapeutic regimens in preclinical models of breast cancer. Our review will analyze the existing research regarding the mechanisms and clinical impact of immunotherapy for the treatment of breast cancer. We shall evaluate the role of immune cell modulation for improved therapeutic response in breast cancer patients. This review will provide collated evidences about the current clinical trials that are testing out the implications of immunotherapy in conjunction with traditional treatment modalities in breast cancer and summarize the potential future research directions in the field. In addition, we shall underline the recent findings related to microbiota modulation as a key regulator of immune therapy response in cancer patients and its plausible applications in breast cancer. [ABSTRACT FROM AUTHOR]

Kidney disease is marked by complex pathological mechanisms and significant therapeutic hurdles, resulting in high morbidity and mortality rates globally. A deeper understanding of the fundamental processes involved can aid in identifying novel therapeutic targets and improving treatment efficacy. Current comprehensive data analyses indicate the involvement of methyltransferase-like 3 (METTL3) and its role in RNA N6-methyladenosine methylation in various renal pathologies, including acute kidney injury, renal fibrosis, and chronic kidney disease. However, there is a paucity of thorough reviews that clarify the functional mechanisms of METTL3 and evaluate its importance in enhancing therapeutic outcomes. This review seeks to systematically examine the roles, mechanisms, and potential clinical applications of METTL3 in renal diseases. The findings presented suggest that METTL3 is implicated in the etiology and exacerbation of kidney disorders, affecting their onset, progression, malignancy, and responsiveness to chemotherapeutic agents through the regulation of specific genetic pathways. In conclusion, this review underscores a detrimental correlation between METTL3 and kidney diseases, highlighting the therapeutic promise of targeting METTL3. Additionally, it offers critical insights for researchers concerning the diagnosis, prognosis, and treatment strategies for renal conditions. [ABSTRACT FROM AUTHOR]

Introduction: Raynaud's phenomenon (RP) is a quite common but often unrecognised vasospastic condition of the peripheral vessels. This may happen after exposure to the cold, stress, vibrations or a wide range of medical conditions. It causes episodic colour changes of the digits, firstly there is a pallor, followed by cyanosis and/or redness, usually with pain. Raynaud's phenomenon can be primary (i.e. Raynaud's disease) or secondary (i.e. Raynaud's syndrome) to underlying disease. Aim of the study: The aim of the study was to discuss the complex and incompletely understood pathophysiology of Raynaud's phenomenon and to evaluate treatment approaches of both 'uncomplicated' - mostly primary and 'complicated' - mostly secondary Raynaud's phenomenon. State of knowledge: Raynaud's phenomenon is a common disorder with an unclear pathophysiology. Although many treatment approaches have been reported, there is still no cure or gold standard therapy. Further investigations into treatment are required. Conclusions: Future research is needed to understand the complex pathogenesis of RP and to develop optimised approaches to management. [ABSTRACT FROM AUTHOR]

Lung cancer leads in causing cancer-related mortality worldwide, continually posing a significant threat to human health. Current imaging diagnostic techniques, while offering non-invasive detection, suffer from issues such as insufficient sensitivity and the risks associated with radiation exposure. Pathological diagnosis, the gold standard for confirmation, also faces challenges like invasiveness and high costs. In treatment, surgery, radiotherapy, and chemotherapy are the main modalities, each encountering challenges related to precision, environmental adaptability, and side effects. Nanotechnology's advancement provides new solutions for the diagnosis and treatment of lung cancer, promising to enhance diagnostic accuracy and reduce side effects during treatment. This article introduces the main types of nanomaterials used in the field of lung cancer, offering a comprehensive overview of current research on the application of nanotechnology in early screening, diagnosis, treatment, and monitoring of lung cancer, and summarizing ongoing clinical research findings. [ABSTRACT FROM AUTHOR]

Background: Different countries, including Iran, have implemented various policies to address substance use disorder. This study aims to describe the policies related to substance use disorder treatment and identify challenges related to these policies in Iran since the beginning of the Iranian Revolution in 1979. Methods: This qualitative study utilized document analysis and interviews with policymakers and implementers. We reviewed a total of 22 documents related to substance use disorder treatment and harm reduction. The results from document analysis complemented and validated the interview data. The research population comprised policymakers and implementers, including individuals directly involved in formulating and implementing substance use disorder treatment policies. Purposive sampling was employed, with a snowball strategy utilized to maximize diversity. Data saturation was achieved after conducting 32 semi-structured interviews. Conventional content analysis was used for data analysis. Results: In general, the policy landscape for substance use disorder treatment in the Islamic Republic of Iran can be divided into two periods: the "Moral Model" era (1979–1993) and the "Disease Model" era (1993–present). Challenges within the content of substance use disorder treatment policies in Iran encompass the lack of law revisions, existence of contradictions in laws and nature of disease, the absence of evidence-based policymaking, and an inadequate comprehensive perspective on the phenomenon of substance use disorder. Conclusions: The presence of multiple authorities with different perspectives on substance use disorder and its treatment, coupled with the application of personal preferences in policymaking and the absence of evidence-based policymaking, have contributed to weaknesses in decision-making and policy formulation. The true philosophy of Disease Model appears not to have been fully grasped by health policymakers in Iran, as all Disease Model policies have been pursued with an emphasis on abstinence and quitting. Iran and other nations facing similar challenges should place more reliance on evidence-based approaches and shift away from the "Moral Model" paradigm to develop more effective substance use disorder treatment policies. [ABSTRACT FROM AUTHOR]

Introduction: Hyperacusis is common among the autistic population, with a lifetime prevalence estimated at up to 60% compared to 17.1% in those without autism. For autistic children, avoidance behaviors and distress associated with hyperacusis significantly disrupt participation in everyday routines including academic, social and leisure activities. Although hyperacusis is a significant problem for children with autism and their families, there is little research on effective interventions. This report describes the clinical case of an 11-year-old boy with autism who received a modified cognitive behavioral therapy (CBT) approach to address symptoms of hyperacusis. Case presentation: Patient A is an 11-year-old boy with autism and hyperacusis. He and his parents report difficulties tolerating loud or high-pitched sounds including whistling, fireworks, traffic and high-pitched musical instruments (e.g., the ocarina and flute). When hearing these sounds during everyday activities (e.g., celebrations and social events) he will often ask strangers to stop, cover his ears, or avoid/run away from the source of sound. A modified CBT approach was combined with exposure therapy, and sensory-based self-regulation strategies to improve tolerance and decrease distress when hearing whistling. Treatment outcomes include improved loudness discomfort levels in audiology evaluations, improved auditory domain scores on the Sensory Profile questionnaires, lower self-reported subjective units of distress scale (SUDS) ratings in response to bothersome sounds, and decreased use of noise canceling headphones during daily activities. The client and his parents also reported generalization of these improvements with other sounds (e.g., fireworks). Conclusion: The patient described in this case report showed measurable improvements in his ability to tolerate whistling, a bothersome sound encountered regularly in his daily life. Considering the high prevalence rate of hyperacusis in autism and its impact on children and family routines, stress and daily living, the development and testing of an effective treatment approach for hyperacusis is needed. The treatment plan for this case arose from the collaboration between professionals in occupational therapy, applied behavior analysis, audiology, and clinical psychology. Future studies are encouraged to determine the efficacy of this combined approach for other children with autism and hyperacusis. [ABSTRACT FROM AUTHOR]

Background: Eliminating hepatitis C virus (HCV) infections is a goal set by the World Health Organization. This has become possible with the introduction of highly effective and safe direct-acting antivirals (DAA) but limitations remain due to undiagnosed HCV infections and loss of patients from the cascade of care at various stages, including those lost to follow-up (LTFU) before the assessment of the effectiveness of the therapy. The aim of our study was to determine the extent of this loss and to establish the characteristics of patients experiencing it. Methods: Patients with chronic HCV infection from the Polish retrospective multicenter EpiTer-2 database who were treated with DAA therapies between 2015 and 2023 were included in the study. Results: In the study population of 18,968 patients, 106 had died by the end of the 12-week post-treatment follow-up period, and 509 patients did not report for evaluation of therapy effectiveness while alive and were considered LTFU. Among patients with available assessment of sustained virological response (SVR), the effectiveness of therapy was 97.5%. A significantly higher percentage of men (p<0.0001) and a lower median age (p=0.0001) were documented in LTFU compared to the group with available SVR assessment. In LTFU patients, comorbidities such as alcohol (p<0.0001) and drug addiction (p=0.0005), depression (p=0.0449) or other mental disorders (p<0.0001), and co-infection with human immunodeficiency virus (HIV) (p<0.0001) were significantly more common as compared to those with SVR assessment. They were also significantly more often infected with genotype (GT) 3, less likely to be treatment-experienced and more likely to discontinue DAA therapy. Conclusions: In a real-world population of nearly 19,000 HCV-infected patients, we documented a 2.7% loss to follow-up rate. Independent predictors of this phenomenon were male gender, GT3 infection, HIV co-infection, alcohol addiction, mental illnesses, lack of prior antiviral treatment and discontinuation of DAA therapy. [ABSTRACT FROM AUTHOR]

Herpes Simplex Virus-1 (HSV-1) Kaposi varicelliform eruption (KVE) is a rare and severe cutaneous manifestation, clinically characterized by the presence of widespread vesicles and pustules. A case report details a patient with a history of Atopic Dermatitis (AD) and recent SARS-CoV-2 infection who developed a severe KVE subsequent to the viral illness. The patient, a 35-year-old male, presented with severe atopic dermatitis (AD) subsequent to a SARS-CoV-2 infection. In a period of four months, the dermatological eruption underwent a rapid progression to a severe state, characterised by the presence of extensive vesicles and pustules, in addition to the emergence of symptoms. In conjunction with a chest CT scan, plasma and antigen testing, the patient was confirmed to be positive for HSV-1 positive. The patient exhibited elevated levels of IgE and a notable reduction in the absolute number of immune cells. The patient was treated with valaciclovir, piperacillin-tazobactam, IVIG at the same time. Within seven days of treatment, the blisters had dried up and the scabs had fallen off without any pain, pruritus, or fever. This case highlights the potential for severe viral eruptions, such as KVE in individuals with underlying dermatological conditions following viral infections. [ABSTRACT FROM AUTHOR]

Background: Complex Regional Pain Syndrome type 1 (CRPS-1) is severely debilitating and painful disease that is difficult to treat. Objective: The objective was to evaluate the long-term residual disability of patients with CRPS-1 following parenteral neridronate treatment. Design: This is real-life retrospective observational study. Methods: Patients affected by CRPS-1 of the upper limb were treated with neridronate infusions (400 mg over 10 days) between February 2017 and December 2021 for whom clinical and demographic information was collected. From November 2022, patients treated ⩾1 year previously were recalled for clinical evaluation. A dedicated instrument (DASH questionnaire, Disabilities of the Arm, Shoulder and Hand) was employed to assess residual disability. Multivariate logistic regression analysis was used to investigate predictors of disability. Results: Forty-nine patients aged 61.1 ± 11.5 years and 73.5% female with CRPS-1 of the upper limb were included. Disease duration before treatment was 9.9 ± 8.0 weeks, and the mean length of follow-up was 4 years (47.7 ± 22.0 months). The disease had fully resolved in 46 patients (93.9%) for whom the diagnostic criteria were no longer recognized. According to the DASH score, 38 patients (77.6%) resulted free of functional limitations, whereas 11 patients (22.4%) were still suffering from disability. The DASH score was positively correlated with residual visual analogue scale (VAS; Spearman's Rho = 0.61; P <.001). Predictors of residual disability were younger age (odds ratio [OR]: 0.77, 95% CI: 0.63-0.93; P =.012) and delay between disease onset and treatment (OR: 1.45, 95% CI: 1.13-1.96; P =.004). Conclusions: In this real-life study, neridronate parenteral treatment provided a full recovery of CRPS-1 in over 3 quarters of patients, provided they are treated early. [ABSTRACT FROM AUTHOR]

Background: Intervertebral disc degeneration (IDD) was the most common cause of low back pain. Platelet rich plasma (PRP) has the potential to repair IDD, however, there is still no conclusion on whether Leukocyte-poor platelet rich plasma (Lp-PRP) or Leukocyte-rich platelet rich plasma (Lr-PRP) is better for the treatment of IDD. Methods: First, we conducted an in vitro study to compare the effects of autologous Lp-PRP and Lr-PRP on human degenerated nucleus pulposus (NP) cells. Then we verified the in vivo effects of autologous Lp-PRP and Lr-PRP in treating disc degeneration through a rabbit IDD model. Results: The in vitro study showed both autologous Lp-PRP and Lr-PRP can promote the cell proliferation, the synthesis of COL II and Aggrecan of human degenerated NP cells, while Lp-PRP are better than Lr-PRP (P<0.05). In addition, only Lp-PRP can inhibit the apoptosis of human degenerated NP cells (P<0.05), whereas Lr-PRP activates the catabolism on the contrary (P<0.05). Further, the in vivo study through the rabbit IDD model verified that autologous Lp-PRP has better effects than autologous Lr-PRP in repairing IDD according to X-ray, MRI, histological, and immunohistochemical assessment (P<0.05, respectively). And the caspase-3 IHC results also showed that only autologous Lp-PRP treatment could inhibit apoptosis of NP cells in the rabbit IDD model (P<0.05). Conclusion: Combining in vivo and in vitro studies, the present study confirmed that autologous Lp-PRP has a better effect than autologous Lr-PRP in repairing IDD, which may be due to the inflammatory factors (TNFα, IL-1β, etc.) in Lr-PRP antagonizing part of the repair effects and promoting the catabolism additionally. Therefore, our findings suggest that Lp-PRP may provide better results than Lr-PRP for treating IDD. Further randomized clinical trials will provide evidence to guide practice. [ABSTRACT FROM AUTHOR]

Functional analyses are used to assess maintaining variables of behavior. Despite the large amount of research on functional analyses with humans, there are limited examples with nonhumans and even fewer studies incorporating modifications to standard methods of assessment with nonhumans. One modification that has yet to be evaluated with nonhuman animals is the trial‐based functional analysis in which control and test conditions are embedded in naturalistic environments. This study compared a standard functional analysis with a trial‐based functional analysis across different topographies of problem behavior with dogs. The results of the functional analyses corresponded for every dog. Individualized treatments were designed to reduce problem behavior. Implications of the trial‐based functional analysis include feasibility for privately owned dogs and dogs under the care of shelters. The trial‐based functional analysis offers a modification to established functional analyses that may allow increased access to the assessment of problem behavior. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Design Method Results Conclusion Implications Impact Reporting Method Patient or Public Contribution To explore trajectories of understanding and managing persistent chemosensory dysfunction after COVID‐19 in patients undergoing clinical treatment.A descriptive qualitative interview study with a realist approach.Data were collected in Sweden, from August 2022 to March 2023 through semi‐structured interviews with 30 patients undergoing treatment for long‐lasting smell and taste dysfunction resulting from COVID‐19. Thematic analysis was applied in a process that involved continuous discussions and refinement of codes into themes and subthemes.Three main themes were identified: (1) Understanding the sensory alterations, which includes subthemes of Searching for validation and Seeking remedies; (2) Practical coping strategies, encompassing Adapted eating and Managing olfactory training and (3) Navigating the emotional landscape, featuring Self‐persuasion and suppression and The ambivalence of acceptance. These themes highlight the cyclic and fluid nature of coping with the dysfunction, reflecting a dynamic process of adaptation. Despite treatment options like olfactory training, participants frequently experienced frustration due to limited perceived improvement and the psychological toll of managing their condition.The study highlights the complex and personal nature of coping with long‐term smell and taste dysfunction post‐COVID‐19. Coping strategies varied widely and evolved over time, reflecting a dynamic process of adaptation. The emotional and psychological impact was profound, underscoring the need for comprehensive treatment approaches that include both physiological and psychological support. There is a need for more effective interventions and support mechanisms to improve the quality of life for those affected by these persistent symptoms.This study contributes to the understanding of COVID‐19's long‐term effects on smell and taste, highlighting the need for ongoing support from health care, further research into effective interventions, and a comprehensive approach to care for individuals affected by these conditions.This study addresses trajectories and challenges of coping with persistent chemosensory dysfunction. Findings emphasise the complexity of managing persistent chemosensory dysfunction and the critical role of personalised care. The study contributes to knowledge for nurses in understanding patients with chemosensory dysfunction.This research adheres to the EQUATOR guidelines: Standards for reporting qualitative research (SRQR).No patient or public contribution. [ABSTRACT FROM AUTHOR]

ABSTRACT Chronic hepatitis C virus (HCV) infection can be associated with neuropsychiatric symptoms like fatigue and cognitive impairment, independent of the liver status. The present study aims to assess changes in the pattern and extent of neuropsychological symptoms after successful treatment with interferon (IFN)‐based and IFN‐free therapy. HCV‐infected patients who underwent neuropsychological assessment in previous studies were invited to a follow‐up examination. Patients were grouped according to the treatment status: Sustained virological response (SVR) after IFN treatment (IFN SVR, n = 14) or after therapy with direct acting antivirals (DAA SVR, n = 28) or ongoing HCV infection (HCV RNA+, n = 11). A group of 33 healthy controls served as reference. Patients completed self‐report questionnaires addressing health‐related quality of life (HRQoL), mood and sleep quality and a neuropsychological test battery including tests of memory and attention (Luria's list of words, PSE test, cancelling “d” test, Word–Figure–Memory Test and computer‐based test battery for the assessment of attention [TAP]). At baseline, all three patient groups had worse fatigue, depression, anxiety and HRQoL scores compared to healthy controls. Longitudinal analysis revealed that fatigue and mood slightly improved in all patient groups over time, while HRQoL improved in SVR patients but not in HCV RNA+ patients. Memory test results improved significantly in all patient groups, irrespective of their virological status. In contrast, the attention test results showed no clear change from baseline to follow‐up. Our data can be considered as a hint that HCV eradication—independent of therapy regimen—does not substantially ameliorate neuropsychiatric symptoms in HCV‐afflicted patients. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinomas (CCA) are a group of aggressive malignancies with poor prognosis. The distinct subtypes are related to different etiologies and genetic aberrations that are subject to targeted therapies. Mouse double minute 2 homolog (MDM2) is a potent inhibitor of tumor suppressor p53 and is proven to be altered in certain carcinomas. Novel targeted drugs, such as the MDM2-p53 antagonist Brigimadlin, have shown promising results for therapeutic efficacy in patients with MDM2 amplification and wild-type TP53. Objectives: This study therefore aimed to characterize CCAs regarding their MDM2 status, compare the concordance between fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methods, and elucidate the role of MDM2 amplification in prognosis and other clinicopathological characteristics. Design: Retrospective cohort study. Methods: All patients (n = 52) were diagnosed with CCA and received surgical resection with curative intention at the University Hospital of Cologne. Samples were analyzed retrospectively for MDM2 amplification with FISH and IHC. We correlated results with pre-existing molecular as well as clinical data. Results: We included 52 patients with primary CCA, three of which showed positive MDM2 amplification (5.8%). MDM2 amplification was present only in the intrahepatic CCA type and all patients with positive MDM2 amplification exhibited normal p53 status. Among the large-duct subtypes of intrahepatic CCAs, patients with positive MDM2 amplification demonstrated better survival than patients with negative MDM2 amplification (p = 0.041). Of the patients with MDM2 amplification, two underwent adjuvant therapy post-surgery (66.7%). There was a strong correlation between MDM2 amplification and positive protein expression in IHC. There were no identifiable molecular co-alterations of MDM2 with FGFR2 or SWI/SNF complex alterations. Conclusion: Real-world evidence in our Caucasian patient population confirmed that a significant number of intrahepatic CCAs showcase MDM2 amplification, qualifying for a personalized therapy option with Brigimadlin. MDM2 amplification must therefore be considered in the context of personalized molecular testing in CCA. [ABSTRACT FROM AUTHOR]

Mobile Phone Addiction represents an emergent addictive disorder that gravely jeopardizes the physical and mental health of adolescents worldwide, necessitating exhaustive research. Current reviews of MPA are in dire need of updates and enhancements. Therefore, this review aggregates the extant research spanning the past two decades on the prevalence, pathogenesis, comorbidities, assessment, and treatment of MPA, aiming to furnish a reference for future investigations into this condition. Pathogenesis, pathophysiology, assessment and treatment of MPA. [ABSTRACT FROM AUTHOR]

Background: We previously conducted a retrospective Japanese cohort study of patients who underwent radical prostatectomy (RP) between January 2010 and December 2020 in Ehime Prefecture. This study revealed an increase in the number of RP, but other treatment trends remained unclear. In the current study, we examined prostate cancer treatment in Ehime Prefecture using the hospital-based cancer registry of all designated cancer care hospitals and community cancer care hospitals belonging to the Council of Ehime Cancer Care Hospitals. Methods: Trends of prostate cancer were compared by year according to stage and treatment using data from the hospital-based cancer registry between 2011 and 2020. Results: The number of patients with stage 1 disease increased over time, but the proportion of patients with stage 1 disease among all patients decreased from 65.2% in 2012 to 56.9% in 2020. The number of patients with stage 2 disease also increased, but the proportion of such patients among all patients remained constant. Meanwhile, the proportions of patients with stage 3 or 4 disease increased significantly over time, while that of patients undergoing RP increased from 29.2% in 2011 to 45.7% in 2020 (P < 0.001). The proportion of patients receiving radiotherapy (RT) decreased from 25.8% in 2011 to 17.2% in 2020. The use of hormone therapy (HT) remained unchanged, and the proportion of patients undergoing observation fell from 11.0% in 2011 to 7.0% in 2020. A higher proportion of patients with stage 3 cancer received HT, and RT was more frequently used in stage 3 cancer than in stage 1–2 cancer. The use of HT increased with age. Conclusions: The data highlighted differences in prostate cancer stages and treatment over time. This information could be shared with both urologists and radiologists to improve treatment. [ABSTRACT FROM AUTHOR]

Background and Aims The question of when and how to treat truly asymptomatic patients with severe aortic stenosis (AS) and normal left ventricular (LV) systolic function is still subject to debate and ongoing research. Here, the results of extended follow-up of the AVATAR trial are reported (NCT02436655, ClinicalTrials.gov). Methods The AVATAR trial randomly assigned patients with severe, asymptomatic AS and LV ejection fraction ≥ 50% to undergo either early surgical aortic valve replacement (AVR) or conservative treatment with watchful waiting strategy. All patients had negative exercise stress testing. The primary hypothesis was that early AVR will reduce a primary composite endpoint comprising all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure (HF), as compared with conservative treatment strategy. Results A total of 157 low-risk patients (mean age 67 years, 57% men, mean Society of Thoracic Surgeons score 1.7%) were randomly allocated to either the early AVR group (n = 78) or the conservative treatment group (n = 79). In an intention-to-treat analysis, after a median follow-up of 63 months, the primary composite endpoint outcome event occurred in 18/78 patients (23.1%) in the early surgery group and in 37/79 patients (46.8%) in the conservative treatment group [hazard ratio (HR) early surgery vs. conservative treatment 0.42; 95% confidence interval (CI) 0.24–0.73, P =.002]. The Kaplan–Meier estimates for individual endpoints of all-cause death and HF hospitalization were significantly lower in the early surgery compared with the conservative group (HR 0.44; 95% CI 0.23–0.85, P =.012, for all-cause death and HR 0.21; 95% CI 0.06–0.73, P =.007, for HF hospitalizations). Conclusions The extended follow-up of the AVATAR trial demonstrates better clinical outcomes with early surgical AVR in truly asymptomatic patients with severe AS and normal LV ejection fraction compared with patients treated with conservative management on watchful waiting. [ABSTRACT FROM AUTHOR]

Total knee arthroplasty (TKA) is an efficacious treatment for end-stage knee osteoarthritis, often accompanied by severe postoperative pain. In certain patients, this pain can persist for over 3 months and is referred to as chronic post-surgical pain (CPSP). Postoperative persistent pain has emerged as a significant and noteworthy issue impacting patient quality of life following TKA. The etiology of CPSP after TKA is multifaceted. Peripheral or central sensitizations resulting from inflammatory reactions, nerve injury, and neurobiological mechanisms are the primary mechanisms contributing to chronic persistent pain after TKA. Preoperative, intraoperative, and postoperative factors can induce pain sensitization. Once CPSP occurs after TKA, it significantly hampers patient recovery with challenging treatment options. Currently, among the preventive and therapeutic strategies for chronic pain after TKA, it is widely believed that early comprehensive preventive treatment to prevent acute to chronic pain transition can substantially reduce the incidence of CPSP following TKA. In recent years, studies have investigated perioperative strategies aimed at reducing the occurrence of persistent pain after TKA. This article provides an overview of advancements in understanding the pathogenesis, high-risk factors, and preventive measures for chronic pain following TKA. We hope that this review will guide future research directions on CPSP after TKA while contributing to clinical perioperative pain management. Key points: What do we know about CPSP after TKA: CPSP after TKA is a key factor affecting the long-term quality of life and satisfaction of patients, and has always been a clinical concern. At present, the etiology and pathogenesis of CPSP after TKA are still not completely clear. Existing evidence shows that there are great clinical differences in the prevention and treatment of CPSP, and the results of researches are also quite heterogeneous. What this review article can provide further: We hope that by summarizing the latest research progress, we can provide some references for perioperative analgesia of TKA, and point out the direction for the research of CPSP after TKA. [ABSTRACT FROM AUTHOR]

To elucidate the clinicopathological characteristics and oncological outcomes of a special group of patients with gestational trophoblastic neoplasia (GTN) initially presenting with isolated lung lesions, elevated human chorionic gonadotropin (hCG) levels, and unobserved pelvic lesions. Overall, 2358 patients with GTN treated at our hospital between 2000 and 2023 were retrospectively reviewed, and 40 patients were evaluated. The demographic characteristics, clinicopathological features, treatment data, and follow-up information of each patient were collected. The primary outcome was progression free survival. Kaplan-Meier analysis and univariate and multivariate Cox proportional hazard analyses were used to identify the risk factors. Among the 40 patients, 95.0 % had solitary lung lesions, with a median size of 1.9 cm. Moreover, 72.5 % of patients were pathologically confirmed as epithelioid trophoblastic tumors (ETT). During a median follow-up period of 53.5 months (range, 2–143), 11 patients experienced recurrence, including all patients who received chemotherapy alone as the initial treatment, and no death was observed. Relapse treatment involved lung segmentectomy and lobectomy combined with chemotherapy and immunotherapy. Univariate and multivariate Cox analyses identified comparing with surgery±chemotherapy, chemotherapy alone as the initial treatment (hazard ratio [HR] =7.738, 95 % confidence interval [CI] 1.698–35.269, P = 0.008) as independent risk factor for recurrence. In patients with a history of pregnancy exhibiting isolated pulmonary lesions, elevated hCG levels (mostly <1000 mIU/mL), and unobserved pelvic lesions, ETT should be considered first. Surgical resection of lung lesion is crucial for optimal management. When chemotherapy is considered, multidrug regimen is recommended. • Gestational trophoblastic neoplasia (GTN) comprises a group of pregnancy-associated malignancies. • Most patients with isolated GTN of the lung had a pathological diagnosis of epithelial trophoblastic tumors (ETT). • Surgical resection of lung lesions is crucial, adjuvant and multidrug chemotherapy is recommended when needed. [ABSTRACT FROM AUTHOR]

Background: Attention Deficit Hyperactivity Disorder (ADHD) is the most prevalent childhood psychiatric condition with profound public health, personal, and family consequences. ADHD requires comprehensive treatment; however, lack of communication and integration across multiple points of care is a substantial barrier to progress. Given the chronic and pervasive challenges associated with ADHD, innovative approaches are crucial. We developed the digital health intervention (DHI)—CoolTaCo [Cool Technology Assisting Co-regulation] to address these critical barriers. CoolTaCo uses Patient-Centered Digital Healthcare Technologies (PC-DHT) to promote co-regulation (child/parent), capture patient data, support efficient healthcare delivery, enhance patient engagement, and facilitate shared decision-making, thereby improving access to timely and targeted mental health intervention for children at significant risk for poor outcomes. The present paper will describe our planned protocol to evaluate the efficacy of CoolTaCo via randomized control trial (RCT). Methods/design: We will recruit 60 children (ages 8–12) with ADHD who will be randomized to either immediate (n = 30) or delayed (n = 30) treatment (i.e., a waitlist control group). Among those randomized to immediate treatment, half will be assigned to DHI (delivered via a smartwatch and smartphone application), the other half to an active control treatment as usual (TAU). Unlike the DHI group, the TAU group will receive the smartwatch with no assigned activities, applications, or interventions on the devices. The intervention period will last 16 weeks; after a participant has been in the delayed treatment group for 16 weeks and has completed the post-waiting period assessment, they will be randomly assigned to either the intervention or active control group. Thus, 30 participants will complete the intervention, and 30 will complete the active control, with half of the total sample completing a waitlist period. Discussion: Individuals with ADHD have complex needs. Despite improvement in outcomes following cognitive behavioral therapies (CBT) and pharmaceutical treatment, long-term maintenance is a challenge often not addressed by traditional medical approaches, and, as we described, ineffective approaches to information sharing across points of care create further barriers to progress. Our research will fill a significant gap in translating early treatment investments and gains into long-term, sustainable outcomes. This study was registered as a clinic trial at ClinicalTrials.gov (Digital Health Intervention for Children With ADHD, ID# NCT06456372) on 06/13/2024. [ABSTRACT FROM AUTHOR]

Objective: As research into preclinical rheumatoid arthritis (pre-RA) has advanced, a growing body of evidence suggests that abnormalities in RA-affected joint cartilage precede the onset of arthritis. Thus, early prevention and treatment strategies are imperative. In this study, we aimed to explore the protective effects of mesenchymal stem cell (MSC)-derived microvesicles (MVs) on cartilage degradation in a collagen-induced arthritis (CIA) mouse model. Methods: A CIA mouse model was established to observe early pathological changes in cartilage (days 21-25) through histological and radiological examinations. On day 22, MSCs-MVs were intravenously injected into the mice with CIA. Radiological, histological, and flow cytometric examinations were conducted to observe inflammation and cartilage changes in these mice compared to the mice with CIA and the control mice. In vitro, chondrocytes were cultured with inflammatory factors such as IL-1β and TNFα to simulate inflammatory damage to cartilage. After the addition of MVs, changes in inflammatory levels and collagen expression were measured via Western blotting, immunofluorescence, enzyme-linked immunosorbent assays (ELISAs), and quantitative PCR to determine the role of MVs in maintaining chondrocytes. Results: MSC–MVs expressed vesicular membrane proteins (CD63 and Annexin V) and surface markers characteristic of MSCs (CD44, CD73, CD90, and CD105). In the early stages of CIA in mice, a notable decrease in collagen content was observed in the joint cartilage. In mice with CIA, injection of MSCs-MVs resulted in a significant reduction in the peripheral blood levels of IL-1β, TNFα, and IL-6, along with a decrease in the ratio of proinflammatory T and B cells. Additionally, MSC-MVs downregulated the expression of IL-1β, TNFα, MMP-13, and ADAMTS-5 in cartilage while maintaining the stability of type I and type II collagen. These MVs also attenuated the destruction of cartilage, which was evident on imaging. In vitro experiments demonstrated that MSC-MVs effectively suppressed the secretion of the inflammatory factors IL-1β, TNFα, and IL-6 in stimulated peripheral blood mononuclear cells (PBMCs). Conclusions: MSCs-MVs can inhibit the decomposition of the inflammation-induced cartilage matrix by regulating immune cell inflammatory factors to attenuate cartilage destruction. MSC-MVs are promising effective treatments for the early stages of RA. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Few data are available on the course of myasthenia gravis (MG) regarding disease severity and stability over time in real‐world settings. This study used the French National Health Insurance Database (SNDS) to assess markers of disease severity in patients with MG longitudinally.All patients with MG‐related claims in the SNDS between 2013 and 2020 were identified. Patients were followed for up to 8 years after the first claim. Intensive care unit (ICU) stays, treatment with intravenous immunoglobulin (IVIg) or plasma exchange (PE), and death were documented throughout the follow‐up period. Standardized mortality rates were estimated, and mortality‐related variables were identified using a Cox model.In all, 14,459 individuals constituted the full study population, including 6354 incident patients. In the incident population, 2199 (34.6%) were admitted to ICUs at least once, principally during the first year after the index date (N = 1477; 23.3%). This proportion decreased progressively to reach 3.0% in the seventh year. A total of 2817 patients received IVIg and 432 PE, again principally in the first year. In the full study population, the standardized mortality rate was 1.08 (95% confidence interval [CI] 1.03–1.13), being lower in men (0.95, 95% CI 0.89–1.02) than in women (1.15, 95% CI 1.07–1.23) and in patients aged >65 years (1.06, 95% CI 1.01–1.11) than in younger patients (1.50, 95% CI 1.24–1.76). Male gender, older age and higher comorbidity were independently associated with mortality.A subgroup of patients with MG require ICU admission and rescue therapy with IVIg or PE, indicative of poor disease control. New therapies are needed to improve disease control and reduce disease burden. [ABSTRACT FROM AUTHOR]

Extensive research has been conducted on postpartum depression (PPD) over the past century, and yet no definitive answer regarding its etiopathogenesis, risk factors, genetic predilection, and treatment has been found. The few preclinical and clinical studies propose that maternal brain adaptations to the endocrinological, immunological, and behavioral changes and external sociodemographic risk factors in the perinatal period make women more vulnerable to anxiety and depression. Irrespective of the cause, a dilemma exists regarding the type of help to provide postpartum mothers. With very few treatment options at our disposal, deciding between psychotherapy, pharmacological, and non‐pharmacological therapy on a case‐by‐case basis is unproductive because in developing countries infrastructure is limited and the availability of medications, especially for psychiatric illnesses, is still evolving. Hence, regardless of psychotherapy, antidepressants remain the first line of treatment with selective serotonin reuptake inhibitors (SSRIs); sertraline has the best efficacy and safety profile in breastfeeding women. As endocrine factors play a significant role in etiopathogenesis, hormonal therapy with oxytocin has been shown to be efficacious, and studies investigating the role of testosterone in treating PPD are also under way. In 2019, the US Food and Drug Administration (FDA) approved the first and only drug for the sole purpose of treating PPD, brexanolone. Zuranolone, a drug recently approved by the FDA, has a similar mechanism of action to brexanolone. For breastfeeding mothers reluctant to use pharmacotherapy, somatic therapy has been studied, including bright light therapy, vagal nerve stimulation, and newer noninvasive interventions. This article encompasses a short note on PPD, including its etiopathogenesis and clinical characteristics, and recapitulates the various available and evolving pharmacological and nonpharmacological therapies. [ABSTRACT FROM AUTHOR]

Inflammation is a physiological response of the body to harmful stimuli such as pathogens, damaged cells, or irritants, involving a series of cellular and molecular events. It is associated with various diseases including neurodegenerative disorders, cancer, and atherosclerosis, and is a leading cause of global mortality. Key inflammatory factors, such as Tumor Necrosis Factor‐alpha (TNF‐α), Interleukin‐1 (IL‐1), Interleukin‐6 (IL‐6), Monocyte Chemoattractant Protein‐1 (MCP‐1/CCL2), RANTES (CCL5), and prostaglandins, play central roles in inflammation and disease progression. Traditional treatments such as NSAIDs, steroids, biologic agents, and antioxidants have limitations. Recent advancements in nanomaterials present promising solutions for treating inflammation‐related diseases. Unlike nanomaterials that rely on passive targeting and face challenges in precise drug delivery, nanomotors, driven by chemical or optical stimuli, offer a more dynamic approach by actively navigating to inflammation sites, thereby enhancing drug delivery efficiency and therapeutic outcomes. Nanomotors allow for controlled drug release in response to specific environmental changes, such as pH and inflammatory factors, ensuring effective drug concentrations at disease sites. This active targeting capability enables the use of smaller drug doses, which reduces overall drug usage, costs, and potential side effects compared to traditional treatments. By improving precision and efficiency, nanomotors address the limitations of conventional therapies and represent a significant advancement in the treatment of inflammation‐related diseases. This review summarizes the latest research on nanomotor‐mediated treatment of inflammation‐related diseases and discusses the challenges and future directions for optimizing their clinical translation. [ABSTRACT FROM AUTHOR]

Summary Although emerging research suggests insomnia is a significant problem among people with eating disorders, little is known about how insomnia symptoms may serve as risk factors for eating disorder symptoms, treatment outcome, and relapse. University students with non‐low‐weight eating disorders (N = 89) completed a mobile guided self‐help cognitive behavioural intervention for eating disorders. Insomnia and binge‐eating symptoms were assessed at pre‐treatment and end‐of‐treatment using the Insomnia Severity Index and Eating Pathology Symptoms Inventory. Multiply imputed datasets were used to test associations between insomnia and binge eating before, during and after treatment. Insomnia was positively associated with binge‐eating symptoms prior to treatment (r = 0.47). Baseline insomnia symptoms were associated with binge‐eating symptoms at end‐of‐treatment (est = 0.269). Eating disorder treatment modestly reduced insomnia (d = −0.38); however, about half of people with clinically significant insomnia prior to treatment remained symptomatic. Insomnia symptoms and binge‐eating symptoms did not change concurrently during treatment. Overall, results support an association between insomnia and binge eating. Although eating disorder treatment may impact insomnia, many individuals remained symptomatic for sleep problems, suggesting the need for follow‐up treatments, such as cognitive behavioural therapy for insomnia, or the development of integrated insomnia–eating disorder treatments. Future studies are needed to examine causal links between insomnia and eating disorder symptoms, and test if insomnia predicts relapse after eating disorder treatment. [ABSTRACT FROM AUTHOR]

Background: Luspatercept, an inhibitor of the transforming growth factor beta (TGF-β) pathway, is a novel treatment for anemic patients with lower-risk myelodysplastic syndromes (MDS) with transfusion dependence (TD) who do not respond to erythropoiesis-stimulating agents (ESA) therapy or are not suitable candidates for this treatment. We present real-world experience with luspatercept therapy from two hematology centers in the Czech Republic. Methods: By January 2024, 54 MDS patients (33 men, 21 women) with a median age of 74 years (range, 55–95) were treated with luspatercept ± ESA at two Charles University hematology centers in Prague and Hradec Králové. According to the WHO 2016 classification, the cohort included 32 MDS-RS-MLD, seven MDS-MLD, two patients with 5q- + ring sideroblasts (RS), 12 RARS-T, and 1 patient with CMML-0 + RS. SF3B1 mutation data were available for 45 patients. All patients were in the IPSS-R and IPSS-M lower-risk groups (except four IPSS-M high). The median follow-up was 17 months (range, 1–54). All patients were transfusion-dependent. Thirty-five (64.8%) patients had a high transfusion burden (HTB) with ≥ 4 transfusion units (TU)/8 weeks, and 19 (35.2%) had a low transfusion burden (LTB) (< 4 TU/8 weeks). The median time between diagnosis and initiation of luspatercept was 27 months (range, 4–156). ESA were used prior to luspatercept in 45 patients, and luspatercept was used as first-line treatment in nine patients. Thirty-one (61%) patients were treated simultaneously with ESA. Results: Only patients who received luspatercept for ≥ 8 weeks (51 patients) were assessed. We evaluated the achievement of transfusion independence (TI) lasting 8, 12, 16, and 24 weeks. Thirty-two (62.7%) patients achieved TI for ≥ 8 weeks, 31 (60.7%) for ≥ 12 weeks, 29 (56.8%) for ≥ 16 weeks, and 25 (49%) for ≥ 24 weeks. Hematologic improvement (HI) without TI was achieved in six patients (11.7%). Overall, HI + TI was achieved in 38 patients (74.5%). Epoetin alfa was used simultaneously in 31 patients (60.7%). In 21 (55.2%) of all responding patients, concomitant therapy with epoetin alfa led to an improved response, with 16 reaching TI. Thirteen (25.5%) patients were nonresponders. Eight (21%) patients experienced therapy failure and became transfusion-dependent again. Optimal response required a gradual increase in the luspatercept dose to 1.75 mg/kg in up to 35 patients, with 23 responders (TI + HI). Response rates varied by transfusion burden: 79% in LTB and 50% in HTB reached TI. Of RS+ patients, 70% reached TI, while only one out of five RS− patients achieved TI. Among 39 SF3B1 -positive patients, 61.6% achieved TI. In the low and very low IPSS-M groups, 86% of patients responded (TI + HI), compared to 62% in the moderate-low group. Luspatercept was well-tolerated, with no adverse events higher than grade II toxicity. Conclusion: We have demonstrated in real-world clinical practice that luspatercept is a very effective agent, even in an unselected, pretreated, significantly TD MDS population. The effect was particularly high in the IPSS-M low and very low groups. We believe that the relatively high response rate in our patients was influenced by the frequent use of a higher dose (1.75 mg/kg) and especially by adding ESA to luspatercept in poorly responding patients. [ABSTRACT FROM AUTHOR]

Uveal melanoma (UM) is the most common primary intraocular tumour in adults. Local resection, radiation therapy, and enucleation are the current first-line, primary UM treatments. However, regardless of the treatment received, around 50% of UM patients will develop metastatic disease within five to 7 years. In the largest published series of unselected patients with metastatic UM (mUM), the median survival time after diagnosis of metastasis was 3.6 months, with less than 1% of patients surviving beyond 5 years. Approved drugs for treatment of mUM include systemic treatment with tebentafusp-tebn or isolated hepatic perfusion (IHP) with melphalan. However, these drugs are only available to a subset of patients and improve survival by only a few months, highlighting the urgent need for new mUM treatments. Accurately predicting which patients are at high risk for metastases is also crucial. Researchers are developing gene expression signatures in primary UM to create reliable prognostic models aimed at improving patient follow-up and treatment strategies. In this review we discuss the evidence supporting ferroptosis, a non-apoptotic form of cell death, as a potential novel treatment target and prognosticator for UM. [ABSTRACT FROM AUTHOR]

The rising incidence of fibrosis poses a major threat to global public health, and the continuous exploration of natural products for the effective treatment of fibrotic diseases is crucial. Berberine (BBR), an isoquinoline alkaloid, is widely used clinically for its anti-inflammatory, anti-tumor and anti-fibrotic pharmacological effects. Until now, researchers have worked to explore the mechanisms of BBR for the treatment of fibrosis, and multiple studies have found that BBR attenuates fibrosis through different pathways such as TGF-β/Smad, AMPK, Nrf2, PPAR-γ, NF-κB, and Notch/snail axis. This review describes the anti-fibrotic mechanism of BBR and its derivatives, and the safety evaluation and toxicity studies of BBR. This provides important therapeutic clues and strategies for exploring new drugs for the treatment of fibrosis. Nevertheless, more studies, especially clinical studies, are still needed. We believe that with the continuous implementation of high-quality studies, significant progress will be made in the treatment of fibrosis. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is the most common type of rhinitis, the treatment of which relies on relieving symptoms. Therefore, we aimed to assess the criteria that influence doctors' decision-making in the process of drug selection for the treatment of allergic rhinitis based on quantitative, qualitative, and cost analyses. Methods: We conducted a survey study with the participation of 300 allergologists. A self-developed questionnaire was presented during a computer-assisted telephone interview (CATI) according to standard procedures. The contingency table underwent statistical analysis using the chi-square test with Cramer's V. Results were considered statistically significant at p < 0.05. Results: Our analyses showed that doctors most often prescribe intranasal glucocorticoids and oral antihistamines to treat allergic rhinitis in patients of all ages. The most common factor that affects the decision-making related to AR treatment was the efficiency of the drug. We found a significant relationship between factors and the main workplace (X-squared = 122.81, df = 90, p -value = 0.0123, Cramer's V = 0.1787216), as well as voivodeship of the main workplace (X-squared = 440.75, df = 270, p -value = 2.378e-10, Cramer's V = 0.1954731). In our study, respondents claimed that patients are willing to pay 31–50 PLN (∼€7- €11) monthly for the treatment of mild and moderate forms of AR, while they were willing to pay 51–100 PLN (∼€11–€22) for treatment of the severe AR form. Conclusion: Our study confirms that the management of AR should be focused on the patient. One of the most important factors in choosing a drug is its effectiveness. Moreover, an important factor in the effective treatment of AR is the financial issue; as shown in our analysis, AR treatment costs can be a significant burden, especially for less wealthy citizens in Poland. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament (ACL) injury is a common sports injury, and ACL reconstruction is an effective surgery for this trauma. Most cases gain good recovery after surgery, while some patients may experience knee stiffness, which is characterized by joint fibrosis, leading to reduced joint mobility, pain, and dysfunction. Currently, various research studies have been conducted to unveil the mechanisms underlying this condition, identifying pre-, intra-, and post-operative risk factors, and testify the efficacy of different therapeutic methods against it. In this review, we summarize the current progress regarding the advancements in knee fibrosis after ACL reconstruction. The risk factors associated with knee fibrosis are systematically delineated, accompanied by an evaluation of the efficacy of various treatment modalities for both the prevention and mitigation of fibrosis. Furthermore, recommendations for future research directions are proposed, offering a foundational basis for subsequent investigations. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to compare the safety and efficacy of drug-eluting bead (DEB) transarterial chemoembolization combined with lenvatinib and camrelizumab (DEB-TACE-Len-C) and DEB-TACE-Len for the treatment of unresectable hepatocellular carcinoma (uHCC). Methods: This retrospective study consecutively included uHCC patients who underwent DEB-TACE-Len-C or DEB-TACE-Len treatment at our hospital and Qujing Second People's Hospital from April 2020 to April 2022. In total, 85 patients were enrolled. There were 42 patients in the DEB-TACE-Len-C group and 43 patients in the DEB-TACE-Len group. The disease control rate (DCR), objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared between the two groups, and the factors influencing OS and PFS were analysed. Results: The ORR, DCR, PFS and OS were significantly greater in the DEB-TACE-Len-C group than in the DEB-TACE-Len group (ORR: 76.2% vs. 46.5%, P = 0.005; DCR: 88.1% vs. 67.8%, P = 0.039; PFS: 10 months vs. 6 months, P < 0.0001; OS: 24 months vs. 16 months, P = 0.0038). Multivariate Cox proportional hazard regression analysis revealed that portal tumour thrombus (PVTT) and therapeutic approach were independent factors affecting PFS and OS. There were no statistically significant differences in the incidence of AEs between the two groups (P > 0.05). Conclusion: Compared with DEB-TACE-Len, DEB-TACE-Len-C is an effective treatment option that can improve the tumour therapeutic response and prolong the OS and PFS in uHCC patients. [ABSTRACT FROM AUTHOR]

Purpose: Medication overuse headache (MOH) is a chronic headache caused by regular overuse of medications. OnabotulinumtoxinA (BoNTA) is used for preventive treatment of MOH. However, its efficacy and safety remain controversial. Methods: Seven online databases (Cochrane Library, Embase, Medline, PubMed, China National Knowledge Infrastructure, Wanfang data, and Chinese BioMedical Literature Database) were searched for relevant articles published between January 2002 and March 2024. We included randomized controlled trials (RCTs) and cohort studies on the treatment of MOH using BoNTA versus a placebo or other active treatments. Results: We retrieved 487 articles in the database search. Of these, four eligible RCTs were identified after detailed screening. A total of 1,259 patients with MOH (622 patients treated with BoNTA, 607 with placebo, and 30 with topiramate) were included in the four RCTs. We found that BoNTA significantly reduced headache frequency compared with placebo (mean difference, 1.89; 95% confidence interval (CI), 1.11–2.67; I 2 = 0%; p < 0.001). There was no significant difference between BoNTA and the placebo in terms of secondary outcomes, which included reductions in acute medication intake (MD, 1.30; 95% CI, −1.18–3.78; I 2 = 0%; p = 0.30), Migraine Disability Assessment questionnaire scores (MIDAS, MD, −4.04; 95% CI, −29.36–21.28; I 2 = 0%; p = 0.75), and Headache Impact Test scores (HIT-6, MD, 0.03; 95% CI, −1.77–1.83; I 2 = 0%; p = 0.97). BoNTA was more likely to cause adverse events (OR, 1.87; 95% CI, 1.45–2.42; I 2 = 0%; p < 0.001) than placebo. Conclusion: The results of this study show that BoNTA reduces headache frequency and is effective for the treatment of MOH. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022315845. [ABSTRACT FROM AUTHOR]

Background: Digital innovations can reduce the global burden of depression by facilitating timely and scalable interventions. In recent years, the number of commercial Digital Health Interventions for Depression (DHIDs) has been on the rise. However, there is limited knowledge on their content and underpinning scientific evidence. This study aimed to: (i) identify the top-funded companies offering DHIDs and (ii) provide an overview of their interventions, including scientific evidence, psychotherapeutic approaches and use of novel technologies. Methods: A systematic search was conducted using two venture capital databases to identify the top-30 funded companies offering DHIDs. In addition, studies related to the DHIDs' were identified via academic databases and hand-searching. The methodological quality of the publications was evaluated using the Mixed Methods Appraisal Tool. Results: The top-30 funded companies offering DHIDs received a total funding of 2,592 million USD. Less than half of the companies produced any scientific research associated with their DHIDs, with a total of 83 publications identified. Twenty-five publications were randomised control trials, of which 15 reported moderate-to-large effects in reducing depression symptoms. Regarding novel technologies, few DHIDs incorporated the use of conversational agents or low-burden sensing technologies. Conclusions: Funding received by top-funded companies was not related to the amount of scientific evidence provided on their DHIDs. There was a strong variation in the quantity of evidence produced and an overall need for more rigorous effectiveness trials. Few DHIDs used automated approaches such as conversational agents, limiting their scalability. [ABSTRACT FROM AUTHOR]

Introduction: Amphetamine-type stimulants (ATSs) are related to significant harm worldwide, with limited effective pharmacological treatments for ATS use disorder (ATSUD). Modafinil has been explored as a potential treatment for ATSUD. This systematic review and meta-analysis (PROSPERO ID: CRD42023388487) aimed to evaluate the efficacy and safety of modafinil for the treatment of ATSUD. Methods: A comprehensive search of major indexing sources and trial registries, from inception to search date, was conducted on February 15, 2023, and updated on October 31, 2023. Eligible studies were randomized placebo-controlled trials (RCTs) of modafinil in individuals meeting the criteria for the Diagnostic and Statistical Manual of Mental Disorders, fourth and fifth editions, diagnoses of ATSUD. Eligible studies were assessed for risk of bias, using the Cochrane Risk of Bias tool. The primary outcome included the effect of modafinil on ATS use. Secondary outcomes included retention in treatment, ATS craving, treatment discontinuation due to adverse events (AEs), and serious AEs. Subgroup analysis by modafinil dose was conducted where appropriate. Risk ratio (RR) or Peto's odds ratio (OR) was calculated for the meta-analysis of dichotomous variables and standardized mean difference (SMD) was calculated for the random-effect meta-analysis of continuous variables. Results: Five RCTs (N = 451 participants) were included. Modafinil did not significantly impact ATS use (RR = 0.99; 95% CI, 0.97 to 1.02; p = 0.655), retention in treatment (RR = 1.02; 95% CI, 0.91 to 1.14; p = 0.799), ATS craving (SMD = −0.36; 95% CI, −1.19 to 0.47; p = 0.398), or treatment discontinuation due to AEs (Peto's OR = 0.48; 95% CI, 0.20 to 1.14; p = 0.100). These results were consistent across subgroup analyses. More episodes of serious AEs were reported in the modafinil group than in the placebo group, at higher doses (Peto's OR = 4.80; 95% CI, 1.18 to 19.56, p = 0.029). Conclusion: There is currently no evidence suggesting that modafinil has a statistically significant effect on efficacy outcomes in populations with ATSUD. Continued research into effective treatments and harm reduction strategies for ATSUD is essential. [ABSTRACT FROM AUTHOR]

Purpose: Community care replaced institutional care for people with psychosis without guidance about what constituted effective treatment. In a Swedish birth cohort, many of those who developed schizophrenia or bipolar disorder as community care was being implemented were subsequently convicted of violent and non-violent crimes. Studies from other countries that were implementing community care at this time also reported elevated proportions of patients acquiring criminal convictions. Since community care was first implemented, much has been learned about factors that promote and treatments that limit aggressive/antisocial behaviour/criminality (AABC) among people with psychosis. Without the benefit of this knowledge, did mental health policy and practices that were in place as the asylums were closed inadvertently contribute to criminality? Material and methods: This article provides a narrative review of current evidence of effective treatments and management strategies to reduce AABC among patients with psychosis. Results: Reductions in AABC are associated with stable contact with psychiatric services, second-generation antipsychotic medication, clozapine for patients with schizophrenia and elevated levels of hostility and/or a history of childhood conduct disorder, abstinence from substances, avoidance of trauma, and constant monitoring of both illness symptoms and AABC. Conclusions: Failure to adopt evidence-based practices allows the problem of AABC to persist, prevents patients from experiencing independent, safe, community tenure, and puts those around them at risk. Many challenges remain, including implementing effective assessment and interventions at first-episode and convincing patients with antisocial attitudes and behaviours to participate in treatment programs to reduce AABC and to learn prosocial behaviours. [ABSTRACT FROM AUTHOR]

This study investigates the effect of agmatine on reducing mortality, neurobehavioral alterations, infarct size, and expression of pro‐inflammatory cytokines in mice subjected to bilateral carotid thrombosis. Under pentobarbital anesthesia, the left common carotid artery was exposed to 6% FeCl3. Thirty‐two days later, the same procedure was performed on the right common carotid artery. Subsequently, Agmatine (100 mg/kg) was administered 15 min after the second procedure, and in another experimental group, the dose of Agmatine was repeated at 72 h. Administration of agmatine extended survival in ischemic animals up to 72 h for the single‐dose group and up to 96 h for the repeated‐dose group, without significant increases in neurological deficits or infarct area size. This neurobehavioral effect was also observed in sham animals treated with agmatine. In ischemic animals, agmatine administration improved digging behavior and reduced recovery times, consistently shorter in those animals treated with repeated doses. RT‐PCR analyses revealed a positive regulation of the cytokine IL‐1β in agmatine‐treated animals, which has been associated with recovery stages. The results suggest that the observed effect may be attributed to the multiple interactions of agmatine with ischemic cascade events, highlighting its anti‐inflammatory role. [ABSTRACT FROM AUTHOR]

Background: Dysphagia services have only recently been formalised within Chinese health services. There has been no comprehensive evaluation of all aspects of dysphagia services practice in China. Aims: To provide a profile for the dysphagia practice in China by assessing various facets of dysphagia services. Methods and Procedures: This is a survey study carried out from December 2022 to May 2023 online in China. One hundred fifty‐nine respondents comprising doctors, nurses or therapists involved in the field of dysphagia rehabilitation completed a questionnaire via Sojump. The questionnaire included dichotomous (e.g., yes/no) and multiple‐choice questions related to participants' general information and their provision of dysphagia management services. Results were analysed descriptively and the differences among different levels of hospitals were analysed. Outcomes and Results: Approximately two‐thirds of hospitals (67.9%) started dysphagia services within the last 5 years. A significant difference in the initiation of dysphagia rehabilitation was observed across different hospital levels (χ2 = 32.70;p < 0.001). Routine dysphagia screening was a standard practice in most hospitals (71.7%), with the most frequently employed screening method being the water swallow test (95.6%). Clinical swallowing evaluation emerged as the preferred initial assessment method (80.5%) and the most utilised assessment method (91.8%). Video fluoroscopic swallow study and flexible endoscopic evaluation swallowing were used by 22.7% and 12.6% of respondents. A significant difference was observed in the choice of assessment methods across hospitals of different levels (χ2 = 43.397; p < 0.001). The majority of respondents (53.5%) primarily employed rehabilitation as the main intervention method (76%–100%). Most respondents indicated that they would reevaluate patients after treatment (74.8%) and reported routine follow‐up with patients (60.4%). Conclusions and Implications: Despite the relatively recent development of dysphagia management in China, the practice patterns uncovered in this study are broadly consistent with Chinese guidelines and consensus. However, the use of instrumental assessments remains low, resulting in a lack of objective evaluation of patient conditions and outcomes. There is a need for policy and resource support in the field of dysphagia rehabilitation in China. WHAT THIS PAPER ADDS: What is already known on this subject: Assessment and treatment methods for dysphagia are various across different patients, medical facilities and settings. There has been no comprehensive evaluation of all aspects of dysphagia rehabilitation practice in China. What this study adds to existing knowledge: The study assessed various facets of dysphagia rehabilitation in China through an online survey. We found that the relatively recent development of dysphagia management in China, but the practice patterns uncovered in this study are broadly consistent with Chinese guidelines and consensus. Variations in practice patterns between hospitals of different levels may be attributed to resource constraints and patient needs. Besides, while rehabilitation exercises are the primary intervention method for dysphagia in China, the assessment largely centres on clinical swallowing evaluation. The use of instrumental assessments remains low, resulting in a lack of objective evaluation of patient conditions and outcomes. What are the clinical implications of this work?: The study assessed various facets of dysphagia rehabilitation in China, and the results indicate that the use of instrumental assessments needs to be improved and there is a need for policy and resource support in the field of dysphagia rehabilitation in China. [ABSTRACT FROM AUTHOR]

Background: This study aimed to describe treatment patterns in patients with myasthenia gravis (MG) in France. Methods: A retrospective cohort analysis was performed using the French National Health Data System (SNDS) database between 2008 and 2019. MG patients were identified using ICD-10 codes during hospitalization and/or long-term disease. We defined two adult subpopulations: a prevalent MG population of patients alive on 31/12/2019 and an incident population of newly identified patients with MG in 2012 and 2013. Results: Among the 22,079 prevalent patients, 53.1% (n = 11,498) received at least one chronic MG treatment in 2019. Among these treated patients, 52.5% received Acetylcholinesterase inhibitors (AChEIs) only, 10.2% were treated with corticosteroids (CS) ± AChEIs, 7.3% with non-steroidal immunosuppressive treatments (NSIST) and CS, 24.2% with NSIST w/o CS, and 5.8% received immunoglobulin and/or plasma exchange. Among the 2,661 incident patients, 84.6% received at least one chronic MG treatment over the 6-year follow-up period, and among them, 79.0% had at least one treatment category change. During the first semester of follow-up, 28.1% of patients were treated with an immunomodulator (CS, NSIST). Among patients starting treatment with immunomodulator, the proportion of those treated with CS decreased from 35.3% at initiation to 10.9% at 6 years. Conclusion: This study illustrates the complexity of MG management. Significant CS sparing was observed over time. The frequent treatment changes especially in patients with an immunomodulator treatment reflect the high variability of the disease severity. The need for personalised treatment approaches in the management of MG to reduce the burden of disease remains. [ABSTRACT FROM AUTHOR]

Objective: Research on treatments for children with avoidant restrictive food intake disorder (ARFID) is needed. This pilot case series describes outcome data for 20 children ages 6–12 years old with a diagnosis of ARFID and who are low‐weight. Method: Participants were recruited nationwide as part of an ongoing randomized clinical trial. All participants in this study received a 14‐session psychoeducational and motivational treatment (PMT) protocol. Parents completed measures of ARFID severity (the Pica, ARFID, Rumination Disorder Interview) and parental self‐efficacy (Parents vs. ARFID scale). Height and weight were self‐reported by parents and percent of estimated body weight (%EBW) was calculated. Assessments occurred at baseline, 1‐month within treatment, 2‐months within treatment, end‐of‐treatment (EOT), and 6‐month follow‐up. Results: Twenty children (10.34 ± 1.76 years; 85% Non‐Hispanic; 75% White; 70% female; 84.16 ± 4.66% EBW) with low‐weight ARFID and their parents received PMT‐ARFID with a clinician specializing in eating disorders. By EOT, PARDI severity scores decreased (large effect size) parental self‐efficacy increased (medium effect size), but %EBW remained unchanged. Discussion: Additional research evaluating PMT in adequately powered clinical trials for youth with ARFID is needed. [ABSTRACT FROM AUTHOR]

Objective: Accessible treatment options for avoidant/restrictive food intake disorder (ARFID) in children are limited. The current study sought to assess acceptability, feasibility, and preliminary efficacy of a brief, virtual intervention for ARFID in children ("ARFID‐PTP"). Method: Families of children ages 5–12 with ARFID (n = 30) were randomized to immediate or waitlist treatment groups, with both groups ultimately receiving ARFID‐PTP. ARFID‐PTP consists of two, 2‐h individual treatment sessions with an optional booster session at 4‐week follow‐up. Families completed acceptability and feasibility measures at end‐of‐treatment, as well as preliminary efficacy measures at 4‐week, 3‐month, and 6‐month follow‐up. Results: Of 30 families who completed an intake session, 27 (90%) completed treatment. Families rated acceptability as high (MCEQ‐C = 7.75). Treatment was feasible by participant retention. Exposure adherence was lower than expected, and booster session requests were higher than expected, indicating that achieving feasibility across measures may require treatment modifications. Regarding preliminary efficacy, children in the immediate treatment group had a decrease in ARFID symptoms compared to those on the waitlist. Overall, at 6‐month follow‐up linear mixed models showed participants had significantly reduced ARFID symptoms by presentation (p < 0.05) and in follow‐up completers, children incorporated eight new foods on average. Discussion: ARFID‐PTP is acceptable and preliminarily efficacious. The protocol may benefit from modifications to increase feasibility; however, booster session content and treatment outcomes suggest a priori feasibility markers may not accurately capture the utility of ARFID‐PTP. Further work should continue to examine the efficacy ARFID‐PTP, particularly in diverse samples where treatment accessibility is urgently needed. Trial Registration: ClinicalTrials.gov identifier: NCT04913194 [ABSTRACT FROM AUTHOR]

Epilepsy and psychiatric illness have been long studied and today are better accepted as co-occurring than as discrete illnesses that are independent even if associated. Common pathophysiology may not be easily explained, but clearly exists given the significant overrepresentation of psychiatric illness among individuals with epilepsy. Conditions like autism spectrum disorder, anxiety, depression, and attention deficit hyperactivity disorder are prevalent in pediatric epilepsy much more than expected, even in the context of chronic neurologic disease. The interplay between pediatric epilepsy and neuropsychiatric symptoms represents a complex clinical circumstance that is not well subtended by the chasm-like division of labor between psychiatrists and neurologists. The unfortunate result is that children and families often experience care that is fractured and at worst, counterproductive for their quality of life. A neuropsychiatric paradigm is essential to address epilepsy and its intrinsic psychiatric symptoms. Practical strategies will be discussed to address this challenge. [ABSTRACT FROM AUTHOR]

Long coronavirus disease 2019 (COVID-19) is linked to an increased risk of post-acute sequelae affecting the pulmonary and extrapulmonary organ systems. Up to 20% of COVID-19 patients may proceed to a more serious form, such as severe pneumonia, acute respiratory distress syndrome (ARDS), or pulmonary fibrosis. Still, the majority of patients may only have mild, self-limiting sickness. Of particular concern is the possibility of parenchymal fibrosis and lung dysfunction in long-term COVID-19 patients. Furthermore, it has been observed that up to 43% of individuals hospitalized with COVID-19 also had acute renal injury (AKI). Care for kidney, brain, lung, cardiovascular, liver, ocular, and tissue injuries should be included in post-acute COVID-19 treatment. As a powerful immunomodulatory tool in regenerative medicine, dental stem cells (DSCs) have drawn much interest. Numerous immune cells and cytokines are involved in the excessive inflammatory response, which also has a significant effect on tissue regeneration. A unique reservoir of stem cells (SCs) for treating acute lung injury (ALI), liver damage, neurological diseases, cardiovascular issues, and renal damage may be found in tooth tissue, according to much research. Moreover, a growing corpus of in vivo research is connecting DSC-derived extracellular vesicles (DSC-EVs), which are essential paracrine effectors, to the beneficial effects of DSCs. DSC-EVs, which contain bioactive components and therapeutic potential in certain disorders, have been shown as potentially effective therapies for tissue damage after COVID-19. Consequently, we explore the properties of DSCs in this work. Next, we'll look at how SARS-CoV-2 affects tissue damage. Lastly, we have looked at the use of DSCs and DSC-EVs in managing COVID-19 and chronic tissue damage, such as injury to the heart, brain, lung, and other tissues. Stem cells obtained from various dental tissues, including dental pulp stem cells, dental follicle stem cells, periodontal ligament stem cells, and exfoliated deciduous teeth stem cells, along with extracellular vesicles derived from dental stem cells, possess distinct capabilities such as immunomodulation, regeneration, and potent anti-inflammatory effects. These properties make them suitable for treating different types of tissue injuries resulting from COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: The skin is the largest and most visible organ of the human body. As such, skin infections can have a significant impact on overall health, social wellbeing and self‐image. In 2019, we published a systematic review of the treatment, prevention and public health control of skin infections including impetigo, scabies, crusted scabies and tinea in resource‐limited settings where skin infections are endemic. This current review serves as an update to assess the evidence for treatment of these conditions as well as atopic dermatitis, molluscum contagiosum and head lice in endemic settings. The data from this systematic review have supported an update to the Australian National Healthy Skin guidelines. Methods: A systematic review was conducted using two separate searches in MEDLINE, PubMed, Embase, CINAHL, Cochrane and Web of Science. The first search was an update of the 2018 systematic review using the same search strategy for the same skin conditions to identify emerging literature from 2018 to 2022. The second search strategy used the same key terms but with the addition of atopic dermatitis, head lice and molluscum contagiosum from 1960 to 2022. Eligible studies included Indigenous peoples and populations in resource‐limited settings with a diagnosis of impetigo, scabies, crusted scabies, tinea capitis, atopic dermatitis, molluscum contagiosum or who presented with head lice. Studies conducted in high‐income countries were excluded. Articles were screened for inclusion independently by one author with a second group of reviewers independently double screening. Data extraction and an in‐depth quality assessment conducted by one author and checked by two others. Results: Of 1466 original articles identified, 68 studies were included and key findings outlined for impetigo, scabies, crusted scabies, atopic dermatitis, head lice and molluscum contagiosum. Recommendations for each condition based on the available evidence are provided. Conclusion: The importance of assessing literature relevant to the populations with heavy burden of skin infections is outlined in this systematic review. We have summarised updates to this literature, which may benefit in developing guidelines for skin infection management similar to the National Healthy Skin Guidelines for Australia. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal lung disease most commonly encountered in older individuals. Several decades of research have contributed to a better understanding of its pathogenesis, though only two drugs thus far have shown treatment efficacy, i.e., by slowing the decline of lung function. The pathogenesis of IPF remains incompletely understood and involves multiple complex interactions and mechanisms working in tandem or separately to result in unchecked deposition of extracellular matrix components and collagen characteristic of the disease. These mechanisms include aberrant response to injury in the alveolar epithelium, inappropriate communication between epithelial cells and mesenchymal cells, imbalances between oxidative injury and tissue repair, recruitment of inflammatory pathways that induce fibrosis, and cell senescence leading to sustained activation and proliferation of fibroblasts and myofibroblasts. Targeted approaches to each of these mechanistic pathways have led to recent clinical studies evaluating the safety and efficacy of several agents. This review highlights selected concepts in the pathogenesis of IPF as a rationale for understanding current or future therapeutic approaches, followed by a review of several selected agents and their recent or active clinical studies. Current novel therapies include approaches to attenuating or modifying specific cellular or signaling processes in the fibrotic pathway, modifying inflammatory and metabolic derangements, and minimizing inappropriate cell senescence. [ABSTRACT FROM AUTHOR]

Background: Malignant epithelial nail unit tumors pose significant diagnostic and therapeutic challenges due to their clinical presentation often mimicking benign conditions and due to the need to preserve as much nail unit function as possible during surgery. Early detection is crucial, even if none of these tumors represent a life-threatening disease. Objectives: This review focus on squamous cell carcinoma, verrucous carcinoma, eccrine porocarcinoma, onychocytic carcinoma, basal cell carcinoma, malignant onychopapilloma, malignant onycholemmal cyst and onycholemmal carcinoma. Methods: Existing literature on the aforementioned tumors has been revised and synthesized. Results: Clinical presentation, pathology, diagnostic procedures, risk factors and the challenges associated with surgical management have been described in detail. Conclusions: Malignant epithelial tumors of the nail unit require careful evaluation and management due to their complex presentation. Early detection and an informed surgical approach are essential to improve patient outcomes and minimize complications. [ABSTRACT FROM AUTHOR]