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Simple Summary: Many patients diagnosed with gastroenteropancreatic neuroendocrine tumors present with metastatic disease at the time of diagnosis. As many as 20% of patients with this diagnosis will present with metastasis to the peritoneal cavity which portends a significantly worse prognosis than solid organ metastasis alone. There is little to no evidence to guide treatment algorithms given the rarity of this disease. Surgical cytoreduction has been found to improve symptoms related to disease burden, though an understanding of the optimal cytoreductive strategies to offer the greatest benefit to most patients is lacking. While the current body of literature pertaining to the systemic treatment of the solid organ metastasis of this disease is more robust, it largely excludes patients with peritoneal metastasis. We provide a review of the current literature which is used to guide these management strategies and offer insight into the knowledge gaps that exist. Peritoneal metastasis in gastroenteropancreatic neuroendocrine tumors poses a significant clinical challenge, with limited data guiding management strategies. We review the existing literature on surgical and systemic treatment modalities for peritoneal metastasis from gastroenteropancreatic neuroendocrine tumors. Surgical interventions, including cytoreductive surgery, have shown promise in improving symptom control and overall survival—particularly in cases in which 70% cytoreduction can be achieved. Hyperthermic intraperitoneal chemotherapy remains controversial due to a paucity of high-level evidence and a lack of consensus for routine use. The use of systemic therapy in the setting of peritoneal metastasis from gastroenteropancreatic neuroendocrine tumors is extrapolated from high-quality evidence for its use in the setting of the solid organ metastasis of this disease. The use of somatostatin analogs for symptom control and some antiproliferative effects is supported by large clinical trials. Additional strong evidence exists for the use of interferon-alpha, everolimus, and sunitinib, particularly in pancreatic neuroendocrine tumors. Cytotoxic chemotherapy and peptide receptor radionuclide therapy may be used in select cases, though as an emerging treatment modality, the optimal sequence of peptide receptor radionuclide therapy within the existing algorithms is unknown. Significant gaps in understanding and standardized management exist, particularly for those patients presenting with peritoneal metastasis, and targeted research to optimize outcomes in this population is needed. [ABSTRACT FROM AUTHOR]

In recent decades, the prevalence of inborn errors of immunity has increased, necessitating the development of more effective treatment and care options for these highly morbid conditions. Due to these "experiments of nature," the complicated nature of the immune system is being revealed. Based on the functional and molecular tests, targeted therapies are now being developed which offer a more effective approach and reduce damage. This study aimed to investigate a key cytokine of the cellular immune response, interferon-gamma (IFN-γ), which is linked to Mendelian susceptibility to Mycobacterial disease, and its potential as a therapeutic option for IFN-γ deficiency. [ABSTRACT FROM AUTHOR]

Introduction: Chronic hepatitis B (CHB) is a significant public health issue worldwide, especially in the Middle East region. Around 8% to 20% of patients with CHB develop cirrhosis, which may progress to hepatocellular carcinoma. The significant morbidity and mortality associated with CHB denote the importance of high-quality treatment. Methods: We searched the PubMed, Medline, and Cochrane databases from inception to January 2024 to identify relevant studies. Search terms were generated using established treatment guidelines for CHB. We also manually searched the bibliographies of relevant literature to obtain additional papers. Results: In this narrative review, we evaluated the seven currently licensed antiviral therapies for chronic Hepatitis B treatment, including nucleos(t)ide analogs (NAs) and pegylated interferon-alpha (PEG-IFNα). NAs can be divided into two categories: high barrier to resistance and low barrier to resistance. Tenofovir disoproxil fumarate, tenofovir alafenamide, and entecavir are NAs with a high barrier to resistance. Telbivudine has shown promise in providing high efficacy with low viral resistance rates; however, it is not recommended because of insufficient evidence and lack of cost-effectiveness. Lamivudine and adefovir dipivoxil, despite being efficacious, have a low barrier to resistance, the primary reason they are no longer recommended. PEG-IFNα has high efficacy and can be completed in 48 weeks. It is not associated with resistance; however, it has been reported to have several systemic adverse effects. Conclusions: Current first-line NA treatments in the Middle East include entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide. These drugs are favored over other NAs because of their low rates of resistance. PEG-IFNα has superiority over NAs in inducing a more durable antiviral response and having a finite treatment duration. The main drawback of PEG-IFNα is an unfavorable safety profile. [ABSTRACT FROM AUTHOR]

Background: The current endpoints for therapeutic trials of hospitalized COVID-19 patients capture only part of the clinical course of a patient and have limited statistical power and robustness. Methods: We specify proportional odds models for repeated measures of clinical status, with a common odds ratio of lower severity over time. We also specify the proportional hazards model for time to each level of improvement or deterioration of clinical status, with a common hazard ratio for overall treatment benefit. We apply these methods to Adaptive COVID-19 Treatment Trials. Results: For remdesivir versus placebo, the common odds ratio was 1.48 (95% confidence interval (CI) = 1.23–1.79; p < 0.001), and the common hazard ratio was 1.27 (95% CI = 1.09–1.47; p = 0.002). For baricitinib plus remdesivir versus remdesivir alone, the common odds ratio was 1.32 (95% CI = 1.10–1.57; p = 0.002), and the common hazard ratio was 1.30 (95% CI = 1.13–1.49; p < 0.001). For interferon beta-1a plus remdesivir versus remdesivir alone, the common odds ratio was 0.95 (95% CI = 0.79–1.14; p = 0.56), and the common hazard ratio was 0.98 (95% CI = 0.85–1.12; p = 0.74). Conclusions: The proposed methods comprehensively characterize the treatment effects on the entire clinical course of a hospitalized COVID-19 patient. [ABSTRACT FROM AUTHOR]

Simple Summary: The introduction of direct-acting antivirals (DAAs) has significantly improved the treatment of Hepatitis C, achieving high success rates and reducing complications and deaths. Despite their success, there are concerns about the potential risk of developing liver tumors after DAA treatment. This study analyzed data from the Swiss Hepatitis C Cohort to compare the risk of liver tumors and death among patients treated with DAAs, those treated with interferon (IFN)-based therapy, and untreated patients. The findings suggest that, while DAAs reduce the risk of death and do not increase the risk of non-liver tumors, there is a higher risk of liver tumors in patients treated with DAAs compared with untreated patients. This highlights the importance of ongoing liver cancer screening for patients who have undergone DAA treatment. Introduction: The use of direct-acting antivirals (DAAs) has drastically changed the management of HCV-infected patients by achieving a 95–98% sustained virologic response (SVR) and reducing morbidity and mortality in this population. However, despite their effectiveness, controversy exists concerning the occurrence of oncologic events following DAA therapy. Aims and Methods: A retrospective analysis was conducted on data from the Swiss Hepatitis C Cohort Study, a prospective cohort involving patients with positive HCV viremia upon inclusion, enrolled in various Swiss centers from September 2000 to November 2021. To examine potential differences in the risk of intrahepatic tumor (IHT) occurrence and death among patients treated with direct-acting antivirals (DAAs), untreated patients, and those receiving interferon (IFN)-based therapy, a semiparametric competing risk proportional hazards regression model was used. Results: Among 4082 patients (63.1% male, median age 45 years; genotype 1: 54.1%; cirrhosis: 16.1%), 1026 received exclusive treatment with IFN-based regimens, and 1180 were treated solely with DAAs. Over a median follow-up of 7.8 years (range: 3.8–11.9), 179 patients (4.4%) developed intrahepatic tumors (IHT), and 168 (4.1%) experienced extrahepatic tumors (EHT). The 5-year cumulative incidence of IHT was 1.55% (95% CI 0.96–2.48) for IFN-based therapy, 4.27% (95% CI 2.93–6.2) for DAA and 0.89% (95% CI 0.4–1.99) for untreated patients. There was no statistically significant difference in the risk of developing IHT (HR = 1.34; 95% CI = [0.70; 2.58]; p = 0.380) or death (HR = 0.66; 95% CI = [0.43; 1.03]; p = 0.066) between patients treated with DAAs and those treated with IFN. Conclusions: The DAAs reduced the risk of death and were not associated with an increased risk of extrahepatic tumors (EHT). In the adjusted model, accounting for cirrhosis and high liver stiffness, the DAA treatment was associated with a higher risk of IHT occurrence compared with untreated patients, emphasizing the relevance of implementing standardized hepatocellular carcinoma (HCC) screening post-DAA treatment. [ABSTRACT FROM AUTHOR]

The discovery of interferon in the 1950s represents much more than the identification of the first cytokine and the key mediator of antiviral host defense. Defining the molecular nature and complexity of the type I interferon family, as well as its inducers and molecular mechanisms of action, was the work of investigators working at the highest level and producing insights of great consequence. Current knowledge of receptor–ligand interactions, cell signaling, and transcriptional regulation derives from studies of type I interferon. It is on the shoulders of the giants who produced that knowledge that others stand and have revealed critical mechanisms of the pathogenesis of systemic lupus erythematosus and other autoimmune diseases. The design of novel therapeutics is informed by the advances in investigation of type I interferon, with the potential for important impact on patient management. [ABSTRACT FROM AUTHOR]

Mosquito-borne diseases are a public health concern. Pharmacists are often a patient's first stop for health information and may be asked questions regarding transmission, symptoms, and treatment of mosquito borne viruses (MBVs). The objective of this paper is to review transmission, geographic location, symptoms, diagnosis and treatment of MBVs. We discuss the following viruses with cases in the US in recent years: Dengue, West Nile, Chikungunya, LaCrosse Encephalitis, Eastern Equine Encephalitis Virus, and Zika. Prevention, including vaccines, and the impact of climate change are also discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Sézary syndrome (SS) is a rare and aggressive form of cutaneous T-cell lymphoma. Despite various treatments, it remains incurable, with a median survival of only 2.1 years. This retrospective study of 17 SS patients in West Sweden from 2012 to 2024 aimed to understand demographic characteristics, treatment effectiveness, and disease progression. Only 35% of patients showed the classic symptoms at diagnosis, indicating the need for personalized diagnostic approaches. Different treatment modalities were used, but combination therapy showed advantages in median survival over monotherapies. Notably, triple therapy involving retinoids, interferon alpha, and extracorporeal photopheresis (ECP) exhibited the longest median time to the next treatment, at 14.1 months. However, early initiation of ECP did not improve outcomes. This study underscores the complexity of SS, emphasizes the urgent need for more effective treatments, and highlights the importance of future prospective research in optimizing treatment strategies. Sézary syndrome (SS) is a rare primary cutaneous T-cell lymphoma variant. Despite various treatment options, it remains incurable, with a poor prognosis. There is an urgent need for additional descriptive research to enhance our understanding and treatment of SS. The aim of this retrospective register-based study was to outline patients' demographic characteristics; investigate the clinical, histopathological, and molecular findings; and assess treatment effectiveness with a focus on time to next treatment (TTNT) and disease progression. Data on 17 patients with SS were obtained from the primary cutaneous lymphoma register in West Sweden between 2012 and 2024. The results revealed that not all patients exhibited the classical triad of symptoms at diagnosis, emphasizing the need for personalized diagnostic approaches. The median survival was only 2.1 years, which reflects the aggressive nature of SS. The longest median TTNT was observed in triple therapy involving retinoids, interferon alpha, and extracorporeal photopheresis (ECP). There was no significant difference in TTNT between various lines of treatment. Early initiation of ECP treatment did not result in improved outcomes. This study highlights the importance of combination therapy for improved outcomes and underscores the need for future studies to identify optimal treatment approaches. [ABSTRACT FROM AUTHOR]

Background: Human interferon-α1b (hIFN-α1b) is the first genetically engineered drug approved by the National Medical Product Administration for cancer therapy in China. hIFN-α1b is a relatively safe therapy and can improve survival in advanced melanoma and its long-term efficacy against resection of stage III melanoma is unknown. Objective: The objective of this study is to assess the safety and efficacy of hIFN-α1b in patients with resected stage III melanoma. Methods: The clinical data were collected from patients who underwent resection of stage IIIB or IIIC melanoma and received subcutaneous injection of hIFN-α1b every other day. The efficacy of hIFN-α1b was determined by rate of recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS). Safety data were acquired by review of adverse events at follow-ups. Results: The study included a total of 61 patients. The median follow-up duration was 45 months. The RFS at 12, 24, and 36 months were observed to be 75.4%, 47.4%, and 37.2% respectively, while the DMFS rates were found to be 83.6%, 65.5%, and 62.2%. Furthermore, the OS rates at these time points were recorded as being 100%, 81.9%, and 71.5%. The overall tolerability of hIFN-α1b was satisfactory, with only 8.2% of the patients experiencing grade 3/4 toxicity and no treatment-related deaths observed. Conclusion: Our findings suggest that adjuvant hIFN-α1b treatment is relatively safe and may potentially enhance the rate of RFS, DMFS and OS in patients who have undergone resection for stage IIIB or IIIC melanoma. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) are considered a promising therapeutic strategy for rheumatoid arthritis (RA), but the current clinical results are varied. This study is to analyze the therapeutic effect of cell-based strategies on RA. Materials and Methods: The searches were performed with public databases from inception to June 17, 2021. Randomized controlled trials researching cell-based therapies in RA patients were included. Results: Eight studies, including 480 patients, were included in the analysis. The results showed that compared to the control, MSC treatment significantly reduced the disease activity score (DAS) at the second standardized mean difference (SMD): -0.70; 95% confidence interval (CI): -1.25, -0.15; P = 0.01) and 3rd month (SMD: -1.47; 95% CI: -2.77, -0.18; P < 0.01) and significantly reduced the rheumatoid factor (RF) level at the first (SMD: -0.38; 95% CI: -0.72, -0.05; P = 0.03) and 6th months (SMD: -0.81; 95% CI: -1.32, -0.31; P < 0.01). In the network meta-analysis, MSCs combined with interferon-γ (MSC_IFN) had a significant effect on increasing the American college of rheumatology criteria (ACR) 20, ACR50, and DAS <3.2 populations, had a significant effect on reducing the DAS, and decreased the RF level for a long period. Conclusion: MSCs could relieve the DAS of RA patients in the short term and reduce the level of RF. MSC_IFN showed a more obvious effect, which could significantly improve the results of ACR20, ACR50, and DAS <3.2 and reduce the DAS and RF levels. [ABSTRACT FROM AUTHOR]

With the introduction of highly effective and safe therapies with next-generation direct-acting antivirals (DAAs), that act without interferon, hepatitis C virus (HCV) infection remains the only treatable chronic infectious disease. The review aims to provide an overview of the therapy revolution with a description of specific DAAs, their mechanisms of action, a summary of the safety and efficacy of specific regimens, and a discussion of populations requiring special therapeutic approaches. DAAs are highly effective, safe, and easy to use. However, challenges such as access to health services and loss of patients from the cascade of care, especially in groups disproportionately affected by HCV infection, such as substance abusers, make it difficult to achieve the WHO's goal of HCV elimination. The proposed strategy to combat these difficulties involves a one-step approach to diagnosing and treating the infection, the availability of long-lasting forms of medication, and the development of an effective vaccine. The aforementioned opportunities are all the more important as the world is facing an opioid epidemic that is translating into an increase in HCV prevalence. This phenomenon is of greatest concern in women of childbearing age and in those already pregnant due to treatment limitations. Hepatitis C virus (HCV) is an insidious pathogen. Most people infected with HCV will develop chronic infections that may not give any symptoms for years or decades but eventually lead to liver disease and liver cancer. It is essential to diagnose infected individuals as soon as possible and start the treatment to increase the elimination of the virus from the organism and prevent harmful long-term effects. Fortunately, these goals are possible nowadays, and this is due to a remarkable example of translational research at work. The discovery of the virus in 1989 (for which Harvey J. Alter, Michael Houghton, and Charles M. Rice received the Nobel Prize in 2020) was followed by the rapid development of diagnostic tests and later by the introduction of the first interferon therapies, which had numerous shortcomings. The revolution started in 2011 when the first oral drugs that act directly on HCV (direct-acting antivirals, DAAs) were registered. Another giant leap for HCV treatment was made in 2018 when the combinations of DAAs that act on different HCV genotypes were introduced. In this paper, we review in detail the DAAs used to treat HCV infection and explain different combinations in which they can be used while showing their favorable safety profile, short-term and convenient treatment regimen, and impressive effectiveness in clearing HCV infection. Although we believe eliminating HCV is eventually reachable, we also argue that there is room for improvement. HCV testing and DAAs availability must improve in selected groups, including people without health insurance, prisoners, and drug addicts. There are still people living with chronic HCV infection without knowing it. Their identification and start of effective treatment is equal to savings in future medical care related to liver disease and cancer, not to mention benefits from the individual health perspective. In addition, and in line with a popular phrase that prevention is better than cure, it is reasonable to pursue the development of the HCV vaccine, which is currently unavailable. The last word on managing the health burden caused by this pathogen is yet to be said. [ABSTRACT FROM AUTHOR]

The article presents the discussion on exploring senescence as a therapeutic target for osteoarthritis, emphasizing the importance of understanding the mechanisms underlying cellular senescence in joint tissues. Topics include complexity of the senescence phenotype, the role of DNA damage in senescence initiation, and the therapeutic implications of targeting IRF1 in osteoarthritis.

Simple Summary: Hepatitis B virus (HBV) affects around 300 million people worldwide and is a significant risk factor for the development of hepatocellular carcinoma (HCC). Nucleos(t)ide analog therapy has aided in decreasing mortality from HBV. However, no cure for HBV currently exists. Despite adequate treatment based on the undetectable viral load or absence of surface protein, there has been much research demonstrating persistent risk for HBV-associated HCC. The aim of this paper is to review the related factors, pathophysiology, and evidence for why this risk exists. Further clarification of the relationship and risk factors for HBV-related HCC is necessary for appropriate screening and the eventual development of a cure. Chronic hepatitis B virus (HBV) infection is the largest global cause of hepatocellular carcinoma (HCC). Current HBV treatment options include pegylated interferon-alpha and nucleos(t)ide analogues (NAs), which have been shown to be effective in reducing HBV DNA levels to become undetectable. However, the literature has shown that some patients have persistent risk of developing HCC. The mechanism in which this occurs has not been fully elucidated. However, it has been discovered that HBV's covalently closed circular DNA (cccDNA) integrates into the critical HCC driver genes in hepatocytes upon initial infection; additionally, these are not targets of current NA therapies. Some studies suggest that HBV undergoes compartmentalization in peripheral blood mononuclear cells that serve as a sanctuary for replication during antiviral therapy. The aim of this review is to expand on how patients with HBV may develop HCC despite years of HBV viral suppression and carry worse prognosis than treatment-naive HBV patients who develop HCC. Furthermore, HCC recurrence after initial surgical or locoregional treatment in this setting may cause carcinogenic cells to behave more aggressively during treatment. Curative novel therapies which target the life cycle of HBV, modulate host immune response, and inhibit HBV RNA translation are being investigated. [ABSTRACT FROM AUTHOR]

Purpose Multiple sclerosis (MS) and the evolution of disease-modifying therapies (DMTs) and their indications, mechanisms of action, efficacy, pregnancy class, and cost are discussed. Summary MS is an immune-mediated, demyelinating, and progressive neurological disorder that can cause both motor and cognitive deficits. Onset of MS typically occurs between the ages of 20 and 40 years, and the disease can result in significant disability over time. Since the introduction of the first DMT for the treatment of MS in 1993, significant progress has been made in the development of new classes of DMTs with different mechanisms of action, higher efficacy, and simpler administration schedules, offering patients better alternatives. However, drawbacks with the use of DMTs include their increasing cost and formulary restrictions. Conclusion The treatment landscape of MS has significantly changed over the past 2 decades, and the introduction of newer classes of DMTs provides an opportunity for pharmacists to play an important role in the management of this patient population. [ABSTRACT FROM AUTHOR]

Objectives: The management of metastatic renal cell carcinoma (RCC) in the third-line setting presents significant challenges due to limited data on treatment options beyond first-line and second-line therapies. Immunotherapy rechallenge with immune checkpoint inhibitors has emerged as a potential strategy for selected patients who previously responded to initial treatment but experienced disease progression. This study aimed to evaluate the effectiveness of nivolumab in patients previously treated with interferon alpha and anti-vascular endothelial growth factor therapies. Methods: A total of 54 adult patients with metastatic RCC were included. Demographic data, International Metastatic RCC Database Consortium (IMDC) risk scores, pre-treatment laboratory findings, and previous treatment lines were reviewed retrospectively. Overall and progression-free survival (OS and PFS) outcomes were analyzed by statistical tests. Results: The median OS and PFS were 25.3 (95% CI: 22.3-28.3) and 9.7 (95% CI: 4.8-14.6) months, respectively. No significant relationships were found between OS and sex (p=0.585), age (< vs. =65 years, p=0.98), IMDC risk groups (p=0.39), second-line treatment (pazopanib vs. sunitinib, p=0.425) or nivolumab line (III vs. IV, p=0.249). PFS was consistent with OS in this sense. Conclusion: The median PFS of 9.7 months surpassed previous data on immunotherapy rechallenge, suggesting a potential benefit of interferon alfa in enhancing immunotherapy response. [ABSTRACT FROM AUTHOR]

Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphomas. This article discusses the management of MF at our institute in view of the international guidelines with modifications according to the available facilities and suggested a stepwise algorithm for management of different stages of MF focusing mainly on early stages. [ABSTRACT FROM AUTHOR]

Background: Effective therapeutics given early to high-risk ambulatory patients with coronavirus disease 2019 (COVID-19) could improve outcomes and reduce overall healthcare burden. However, conducting site visits in non-hospitalised patients, who should remain isolated, is problematic. Aim: To evaluate the feasibility of a purely remote (virtual) study in non-hospitalised patients with COVID-19; and the efficacy and safety of nebulised recombinant interferon-β1a (SNG001) in this setting. Design & setting: Randomised, double-blind, parallel-group study, which was conducted remotely. Method: Eligible patients aged ≥65 years (or ≥50 years with risk factors) with COVID-19 and not requiring hospital admission were recruited remotely. They were randomised to SNG001 or placebo once-daily via nebuliser for 14 days. The main outcomes were assessments of feasibility and safety, which were all conducted remotely. Results: Of 114 patients treated, 111 (97.4%) completed 28 days of follow-up. Overall compliance to study medication was high, with ≥13 doses taken by 89.7% and 92.9% of treated patients in the placebo and SNG001 groups, respectively. Over the course of the study, only two patients were hospitalised, both in the placebo group; otherwise there were no notable differences between treatments for the efficacy parameters. No patients withdrew owing to an adverse event, and a similar proportion of patients experienced on-treatment adverse events in the two treatment groups (64.3% and 67.2% with SNG001 and placebo, respectively); most were mild or moderate and not treatment-related. Conclusion: This study demonstrated that it is feasible to conduct a purely virtual study in community-based patients with COVID-19, when the study included detailed daily assessments and with medication administered via nebuliser. [ABSTRACT FROM AUTHOR]

Simple Summary: Malignant melanoma spreads to other organs and is resistant in part due to the presence of cancer stem cell subpopulations (CSCs). To combat these aggressive subpopulations, different therapies are being studied. Our study aimed to evaluate the anti-tumor effect of interferon-alpha (IFN-α) treatments on melanoma CSCs and explore potential biomarkers. We found that even low doses of IFN-α reduced CSC formation and stemness properties, and led to a significant decrease in the ability to form tumors in mice xenotransplants. IFN-α also modulated the expression of genes and microRNAs involved in several cancer processes and the metabolomics of released exosomes. Our data suggest further investigations of new dose and combination approaches with IFN-α in malignant melanoma. Malignant melanoma (MM) can spread to other organs and is resistant in part due to the presence of cancer stem cell subpopulations (CSCs). While a controversial high dose of interferon-alpha (IFN-α) has been used to treat non-metastatic high-risk melanoma, it comes with undesirable side effects. In this study, we evaluated the effect of low and high doses of IFN-α on CSCs by analyzing ALDH activity, side population and specific surface markers in established and patient-derived primary cell lines. We also assessed the clonogenicity, migration and tumor initiation capacities of IFN-α treated CSCs. Additionally, we investigated genomic modulations related to stemness properties using microRNA sequencing and microarrays. The effect of IFN-α on CSCs-derived exosomes was also analyzed using NanoSight and liquid chromatography (LC-HRMS)-based metabolomic analysis, among others. Our results showed that even low doses of IFN-α reduced CSC formation and stemness properties, and led to a significant decrease in the ability to form tumors in mice xenotransplants. IFN-α also modulated the expression of genes and microRNAs involved in several cancer processes and metabolomics of released exosomes. Our work suggests the utility of low doses of interferon, combined with the analysis of metabolic biomarkers, as a potential clinical approach against the aggressiveness of CSCs in melanoma. [ABSTRACT FROM AUTHOR]

Hepatitis D virus (HDV), also referred to as hepatitis delta virus, is the smallest virus capable of causing human disease. It is unable to replicate on its own and can only propagate in the presence of hepatitis B virus (HBV). Infection with both HBV and HDV frequently results in more severe disease than HBV alone, with higher instances of cirrhosis, liver failure and hepatocellular carcinoma (HCC). Thus, there is a need for effective treatment for HDV; however, currently approved treatment options are very limited both in terms of their efficacy and availability. This makes the management of HDV a challenge for physicians. In this review, we look at the background, diagnosis and treatment of HDV, informed by our hospital data, to set out the optimal management of HDV; we also explore novel treatment options for this disease. [ABSTRACT FROM AUTHOR]

Purpose: To report the efficacy and safety of 5-fluorouracil as the second line of treatment for two cases of conjunctival intraepithelial neoplasia refractive to topical interferon alpha-2b. Case report: In the first case, a 77-year-old woman was evaluated because of a fleshy vascularized lesion in the temporal conjunctiva on her right eye with leukoplakia of the corneal epithelium from 10- to 5-o'clock limbus. In the second case, an 81-year-old man, a nodular lesion in the temporal conjunctiva on his RE, with corneal adjacent opalescence, one millimeter in extent, was observed. Both patients were initially treated with excisional surgery, the samples being reported as conjunctival intraepithelial neoplasia with high-grade dysplasia. Co-adjuvant treatment with topical interferon alpha-2b 1 mIU/mL was indicated 4 times/day uninterruptedly. In the first case, there was no response despite 8 months of treatment, while in the second, the corneal lesion progressed in an arboriform pattern after 4 months of topical chemotherapy. Management & outcome: In the absence of efficacy, the treatment was then changed to topical 5-fluorouracil (1%), 4 times/day for 7 days with a time-lapse of 21 days off, which constitutes a course. Two and four courses of treatment with 5-fluorouracil 1% were completed in both cases in the absence of important side effects. After the first course, both patients showed complete remission of the lesions. No clinical signs of relapse were noted after 1 year of follow-up. Discussion: The treatment with 5-fluorouracil is a good option as the second line of treatment for conjunctival intraepithelial neoplasia who are low-responders to interferon alpha-2b, with fewer side effects than other currently available alternatives. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate whether early ocular findings can be demonstrated with optical coherence tomography angiography in patients with Behçet's disease. Patients and methods: Thirty-seven eyes of 22 patients with Behçet's disease with ocular involvement, 48 eyes of 26 Behçet patients without any ocular involvement, and 44 eyes of 22 healthy controls were included, for a total of 70 patients (39 males, 31 females; mean age: 42.3±11.7 years; range, 18 to 65 years), in the cross-sectional study conducted between September 2019 and April 2020. The parameters analyzed were the foveal avascular zone (FAZ), central macular thickness, total deep capillary plexus vessel density (DCPVD), parafoveal deep capillary plexus vessel density (PaDCPVD), total superficial capillary plexus vessel density (SCPVD), and parafoveal superficial capillary plexus vessel density (PaSCPVD). Results: Total DCPVD, total SCPVD, PaDCPVD, and PaSCPVD were found to be low in the ocular involvement group compared to the others, and the FAZ area was larger compared to the control group. Capillary plexus densities were positively correlated with the best-corrected visual acuity and negatively correlated with disease duration. No statistically significant difference was found between patients with Behçet without ocular involvement and the control group in terms of the FAZ area, DCPVD, PaDCPVD, SCPVD, and PaSCPVD. Conclusion: Optical coherence tomography angiography demonstrated decreased vascularity in Behçet patients with ocular involvement; however, it revealed no microvascular differences between patients with Behçet's disease who do not have ocular involvement and the control group. [ABSTRACT FROM AUTHOR]

Simple Summary: This was a phase III randomized controlled trial investigating the outcomes of low-dose interleukin-2 (IL-2) plus interferon alfa (IFNα) versus sunitinib as the first line and axitinib as the second line in patients with low- and intermediate-risk metastatic renal cell carcinoma (mRCC). There was a trend toward better total progression-free survival up to the end of the second line for IL-2 + IFNα but no significant advantage in terms of overall survival. The study was underpowered to draw any definitive conclusions. The results showed no clear advantage of IL-2 + IFNα over sunitinib in the first line; however, it may be an option in some relatively low-risk mRCC cases due to the difference in the adverse events profile. This trial was registered with the University Hospital Medical Information Network (UMIN), center identifier UMIN 000012522. Background: The sequence of first-line cytokine and second-line molecular targeted therapies may be suitable for some patients with metastatic renal cell carcinoma (mRCC) because of the expectation of complete remission and durable response achieved with cytokine therapy. Methods: This was a phase III randomized controlled trial investigating the outcomes of low-dose interleukin-2 (IL-2) plus interferon alfa (IFNα) versus sunitinib as the first line and axitinib as the second line in patients with low- and intermediate-risk mRCC. Results: Thirty-five patients were randomly assigned. The total progression-free survival (PFS) to the end of the second line was 29.0 months (95% CI, 11.7–46.3) in the IL-2 + IFNα group and 16.3 months (95% CI, 6.3–26.4) in the sunitinib group. The PFS hazard ratio for the IL-2 + IFNα group relative to the sunitinib group was 0.401 (95% CI, 0.121–1.328; p = 0.135). The hazard ratio for overall survival (OS) was 1.675 (95% CI, 0.418–6.705; p = 0.466), which was better in the sunitinib group than in the IL-2 + IFNα group but not statistically significant. The types of adverse events (AEs) differed significantly, although there was no significant difference in the incidence of AEs. Conclusions: There was a trend toward better total PFS for IL-2 + IFNα, but it was not significant. There was also no advantage of IL-2 + IFNα in terms of OS. The study was underpowered to draw any definitive conclusions. The results showed no clear advantage of IL-2 + IFNα over sunitinib in the first-line setting; however, it may be an option in some relatively low-risk mRCC cases due to the difference in the AE profile. This trial was registered with the University Hospital Medical Information Network (UMIN), center identifier UMIN 000012522. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has caused havoc in the health sector. Inflammatory cytokines play an important role in the disease condition. Existing evidence has provided certain insights into the repurposing of the drugs. This meta-analysis and systematic review aimed to explore the efficacy of the administration of interferon beta-1b (IFN β-1b) and standard care versus only standard care as the therapeutic agent for managing COVID-19 patients who are severely ill. The search was conducted in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Scopus, and Google Scholar, which were published during the period January 1, 2020, to February 16, 2023. All the included three studies were independently assessed for eligibility. The modified data extraction form of Cochrane were used. The quality of the three included studies was assessed using the Cochrane risk of bias tool. GradePro software was used to summarize the quality grading of the primary outcome measures. The time taken for clinical improvement was (MD: - 3.28 days; 95% CI: - 5.65, - 0.91; P value = 0.007) when treated with IFN β-1b. The duration of hospital stays (MD: - 2.43 days; 95% CI: - 4.45, - 0.30; P value = 0.03), and need for intensive care unit (ICU) admission (RR: 0.71; 95% CI: 0.52, 0.97; P value = 0.03) was statistically significant. Interferon beta-1b is proven to reduce the duration of hospital stay, and the improved clinical status may become a cornerstone of COVID-19 treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICIs) can cause granulomatous and sarcoid-like lesions (GSLs) in several organs, and limited data existing that adequately inform the incidence and severity. This study examined GSL incidence in patients with high-risk melanoma treated with CTLA4 or PD1 blocking adjuvant therapy in two randomized clinical trials, the ECOG-ACRIN E1609 and SWOG S1404. The investigation identified 11 GSL cases among 2878 patients treated with ICIs or high-dose IFNα-2b. Grade III events were dominantly reported. Lung, mediastinal lymph nodes, skin, subcutaneous tissue, and eye were implicated in the reported GSLs. In addition, 62 literature reports were summarized. In conclusion, GSLs following anti-CTLA4 or anti-PD1 adjuvant treatment were uncommonly reported. Background: Treatment with immune checkpoint inhibitors (ICIs) has been linked to granulomatous and sarcoid-like lesions (GSLs) affecting different organs. This study sought to evaluate GSL incidence in patients with high-risk melanoma treated with cytotoxic T-lymphocyte antigen 4 (CTLA4) or programmed cell death 1 (PD1) blockade adjuvant therapy in two clinical trials: ECOG-ACRIN E1609 and SWOG S1404. Descriptions and GSL severity ratings were recorded. Methods: Data were collected from ECOG-ACRIN E1609 and SWOG S1404. Descriptive statistics along with GSL severity grades were reported. Additionally, a literature review for such cases was summarized. Results: A total of 11 GSL cases were reported among 2878 patients treated with either ICI or with High-Dose Interferon Alfa-2b (HDI) in ECOG-ACRIN E1609 and SWOG S1404 trials. Cases were numerically more commonly reported with ipi10, followed by pembrolizumab, ipi3, and HDI, respectively. Most of the cases were grade III. Further, organs involved included lung, mediastinal lymph nodes, skin and subcutaneous tissue, and eye. Furthermore, a summary of 62 reports in the literature was described. Conclusions: GSLs following anti-CTLA4 and anti-PD1 antibody therapy in patients with melanoma were reported unusually. Reported cases ranged in grade from I to III and appeared manageable. Careful attention to these events and their reporting will be essential to better guide practice and management guidelines. [ABSTRACT FROM AUTHOR]

Aims Multiple sclerosis is a chronic demyelinating disease that is considered an autoimmune disorder affecting the central nervous system. This study aimed to investigate the pathogenic changes in the natural flora of the mouth in MS patient during different treatment modalities and compare them with healthy individuals. Materials & Methods: 120 patients were volunteered and divided into four groups of 30 people: 1) patients with MS taking Natalizumab or Tysabri, 2) patients with MS taking Betaferon, 3) naive MS patients without medications, 4] healthy individuals (control). The changes in oral bacteria (Staphylococcus aureus, Porphyromonas gingivalis, and Bacteroides frag ills) were investigate using real time-PCR. Finding: The prevalence of S. aureus was significantly higher in the Naive MS group (p-0.016), Betaferon group (p=0.001), and Tysabri group (p=0.0001) compared to the healthy group, as well as in Tysabri group compared to the Naive MS group (p=0.005). The prevalence of P.gingivaliswas significantly higher in the Betaferon group (p=0.002) and Tysabri group (p=0.0001) compared to the healthy group, as well as in Tysabri group compared to the Naive MS group (p= 0.020). The prevalence of B. fragilis was significantly higher in the Naive MS group (p=0.008), Betaferon group (p=0.015), and Tysabri group (p=0.008) compared to the healthy group. Conclusion: Oral bacteria are involved in MS development. Furthermore, MS patients are more susceptible to periodontal disease due to high P. gingivalis presence, and these patients need to receive extra care to prevent periodontal disease. [ABSTRACT FROM AUTHOR]

Aim: Multiple sclerosis is a chronic demyelinating disease, which is considered an autoimmune disease impacting the central nervous system. Patients with MS may have certain orofacial manifestations and oral microbiological changes as a result of different treatment modalities. This study aimed to investigate the changes of Candida albicans in normal oral flora during different modalities of treatment and compare them with healthy individuals. Materials & Methods: 120 Patients were volunteered and divided into four groups of 30 people: 1) patients with MS taking Natalizumab or Tysabri, 2) patients with MS taking Betaferon, 3] patients who were recently diagnosed with MS and were in a variety of progressive stages, 4) healthy individuals (control). The swap samples were taken from the participants, particularly from the oral cavity. PCR real-time program investigated the presence of Candida albicans. All patients were examined under standardized conditions by a single examiner, and the oral cavity was examined in an artificial light using a mouth mirror. Findings: Regarding the presence of Candida albicans, there was a significant difference between the naive MS patient group and healthy individuals (p=0.036). However, the difference between the Tysabri group and the healthy group was not significant (p>0.0 5), while in the Betaferon group, the presence of Candida albicans significantly increased (p=0.0001). Conclusic: Oral Candida albicans increase in naive MS patients compared to healthy individuals. This increase indicates that oral Candida albicans may involve in MS development On the other hand, orofacial manifestations decrease in all MS treatment groups. [ABSTRACT FROM AUTHOR]

Ropeginterferon alfa-2b (RopegIFN) enables effective cytoreduction in polycythemia vera (PV). Recent analyses suggest that long-term RopegIFN therapy fulfills treatment goals important to patients with PV including good quality of life, the slowing of disease progression, and long event-free survival. Data support the use of RopegIFN in both early PV therapy and second-line and beyond. [ABSTRACT FROM AUTHOR]

We report a case of interdigital acral nodular melanoma on the right fourth toe cleft of a 56-year-old Caucasian man that was initially misdiagnosed and mistreated as tinea pedis for over one year. Despite undergoing complete tumor resection and therapeutic lymphadenectomy, as well as adjuvant immunotherapy, the patient died of metastatic disease 18 months after his first visit. This case emphasizes that refractory interdigital dermatophytoses should raise suspicion for the possibility of concomitant malignant neoplasms. Histopathological assessment is indispensable for definite diagnosis of acral interdigital lesions not responding to treatment. [ABSTRACT FROM AUTHOR]

Mycosis fungoides is the most common primary cutaneous T-cell lymphoma, characterized by skin-homing CD4+ T cells derivation, indolent course, and low-grade of malignancy. Mycosis fungoides's classic type typically onsets with cutaneous erythematous patches, plaque, and tumor. In WHO-EORTC classification, folliculotropic mycosis fungoides, pagetoid reticulosis, and granulomatous slack skin are recognized as distinct variants of mycosis fungoides, because of their clinical and histological features, behavior, and /or prognosis. Mycosis fungoides often shows diagnostic difficulties, due to its absence of specific features and lesional polymorphism. A patient's treatment requires staging. In about 10% of cases, mycosis fungoides can progress to lymph nodes and internal organs. Prognosis is poor at advanced stage and management needs a multidisciplinary team approach. Advanced stage disease including tumors, erythroderma, and nodal, visceral, or blood involvement needs skin directed therapy associated with systemic drugs. Skin directed therapy includes steroids, nitrogen mustard, bexarotene gel, phototherapy UVB, and photochemiotherapy, i.e., total skin electron radiotherapy. Systemic therapies include retinoids, bexarotene, interferon, histone deacetylase inhibitors, photopheresis, targeted immunotherapy, and cytotoxic chemotherapy. Complexity of mycosis fungoides associated with long-term chronic evolution and multiple therapy based on disease stage need a multidisciplinary team approach to be treated. [ABSTRACT FROM AUTHOR]

Background Early antiviral therapy was effective in the treatment of coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients. Methods We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200 mg loading on day 1 followed by 100 mg daily on day 2 to 5 (combination group), or to remdesivir only of similar regimen (control group) (1:1). The primary endpoint was the time to complete alleviation of symptoms (NEWS2 = 0). Results Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom onset was 3 days. The median age was 65 years, and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary endpoint, the combination group was significantly quicker to NEWS2 = 0 (4 vs 6.5 days; hazard ratio [HR], 6.59; 95% confidence interval [CI], 6.1–7.09; P <.0001) when compared to the control group. For the secondary endpoints, the combination group was quicker to negative nasopharyngeal swab (NPS) viral load (VL) (6 vs 8 days; HR, 8.16; 95% CI, 7.79–8.52; P <.0001) and to develop seropositive immunoglobulin G (IgG) (8 vs 10 days; HR, 10.78; 95% CI, 9.98–11.58; P <.0001). All adverse events resolved upon follow-up. Combination group (HR, 4.1 95% CI, 1.9–8.6, P <.0001) was the most significant independent factor associated with NEWS2 = 0 on day 4. Conclusions Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, and in shortening viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients. Clinical Trials Registration NCT04647695. [ABSTRACT FROM AUTHOR]

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Simple Summary: The myeloproliferative neoplasms (MPNs) are chronic blood cancers characterized by elevated blood cell counts and, after decades, the development of bone marrow failure. Blood clots are common and contribute massively to the symptom burden. Treatment with interferon (IFN) alpha-2 normalizes elevated blood cell counts within weeks to months. This treatment has been used off-label over the last 30 years. Today, a novel interferon alpha-2b formulation (Besremi) is marketed for treatment of the MPN disease polycythemia vera. Another IFN formulation is interferon beta (IFN-β), which has been used for decades in the treatment of multiple sclerosis. Several studies have shown IFN-β to possess stronger anticancer capabilities than IFN alpha-2. However, only a few cancer trials have been conducted, none in patients with MPNs. In this paper, the rationales and perspectives for using IFN-β in patients with MPNs are described, and future research directions are outlined for investigating the safety and efficacy of IFN-β in MPNs. About 30 years ago, the first clinical trials of the safety and efficacy of recombinant interferon-α2 (rIFN-α2) were performed. Since then, several single-arm studies have shown rIFN-α2 to be a highly potent anticancer agent against several cancer types. Unfortunately, however, a high toxicity profile in early studies with rIFN-α2 -among other reasons likely due to the high dosages being used-disqualified rIFN-α2, which was accordingly replaced with competitive drugs that might at first glance look more attractive to clinicians. Later, pegylated IFN-α2a (Pegasys) and pegylated IFN-α2b (PegIntron) were introduced, which have since been reported to be better tolerated due to reduced toxicity. Today, treatment with rIFN-α2 is virtually outdated in non-hematological cancers, where other immunotherapies—e.g., immune-checkpoint inhibitors—are routinely used in several cancer types and are being intensively investigated in others, either as monotherapy or in combination with immunomodulatory agents, although only rarely in combination with rIFN-α2. Within the hematological malignancies, rIFN-α2 has been used off-label for decades in patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPNs)—i.e., essential thrombocythemia, polycythemia vera, and myelofibrosis—and in recent years rIFN-α2 has been revived with the marketing of ropeginterferon-α2b (Besremi) for the treatment of polycythemia vera patients. Additionally, rIFN-α2 has been revived for the treatment of chronic myelogenous leukemia in combination with tyrosine kinase inhibitors. Another rIFN formulation-recombinant interferon-β (rIFN-β)—has been used for decades in the treatment of multiple sclerosis but has never been studied as a potential agent to be used in patients with MPNs, although several studies and reviews have repeatedly described rIFN-β as an effective anticancer agent as well. In this paper, we describe the rationales and perspectives for launching studies on the safety and efficacy of rIFN-β in patients with MPNs. [ABSTRACT FROM AUTHOR]

Simple Summary: Bladder cancers are frequently treated by instilling BCG vaccine into the bladder. By provoking inflammation, BCG can lead to the production of a factor called "interferon gamma" and an immune response that can eliminate the cancer. Here, we used normal human uro-epithelial cells that line the urinary tract to establish a specific "signature" of genes activated in response to interferon gamma. When assessed in bladder cancers, the interferon gamma signature was associated with a subset of patients who showed significantly better survival. In normal tissues, immune responses are subject to stop signals called "checkpoints" that prevent runaway inflammation, and this process may prevent immune cells from killing cancer cells. New treatments aimed at tackling immune checkpoints have met with limited success in bladder cancer. In this study, we have identified immune checkpoint genes expressed by normal human uro-epithelial cells that were increased by interferon gamma. This research suggests new targets for use in combination treatments aimed at overcoming immune checkpoints. Interferon gamma (IFNγ) is central to the inflammatory immune response, such as that entrained by BCG immunotherapy for bladder cancer. However, immune-mediated tumour cell killing is subject to modulation by immunoinhibitory "checkpoint" receptors such as PD-L1. We investigated the effects of IFNγ on barrier-forming in vitro-differentiated normal human urothelium using mRNA-sequencing, and showed canonical upregulation of MHC class I/II and de novo expression of the T cell tropic CXCL9-11 chemokines. Normal urothelium constitutively expressed immunoinhibitory B7 family member VSIR (VISTA), while CD274 (PD-L1) expression was induced/upregulated by IFNγ. We generated a urothelial IFNγ response gene signature. When applied to the unsupervised clustering of non-muscle-invasive bladder cancers, the IFNγ-signature predicted longer recurrence-free survival. In muscle-invasive cancers, the IFNγ-signature split the basal/squamous consensus subtype, with significantly worse overall survival when weak or absent. This study offers novel insights into strategies to enhance immunotherapy via the IFNγ and VISTA/PD-L1 nexus. [ABSTRACT FROM AUTHOR]

Elite athletes who participate in contact sports are at risk of bleeding injuries, leading to transmission of blood-borne viruses including hepatitis type B, C and D (HBV, HCV and HDV) capable of causing chronic liver disease, liver failure and liver cancer. In view of the significant advances in the viral hepatitis field over the past decade, more structured approaches should be in place to screen for and manage viral hepatitis in elite athletes. HBV status should be assessed in all elite athletes, and those infected should receive nucleos(t)ide analogues for viral suppression, while uninfected individuals should receive HBV vaccination. The all-oral direct acting antivirals for HCV are highly effective and safe, thus the remaining challenge with hepatitis C is case identification and linkage to care. HDV is only found in HBV-infected individuals, which is characterized by rapid disease progression and higher rates of cirrhosis and liver cancer in infected subjects. Pegylated interferon was the mainstay of treatment for HDV infection until bulevirtide, a viral entry inhibitor, was recently approved by the European Union (EMA) and FDA in America, while multiple novel therapies are already in clinical trials as part of the HBV cure program. Overall, awareness of chronic viral hepatitis in athletes should be improved. Prevention remains the cornerstone of the management of viral hepatitis in sport coupled with rigorous disease assessment in infected individuals, and antiviral therapy where indicated. [ABSTRACT FROM AUTHOR]

Background • The aim of this study was to determine the efficacy of interferon (IFN)-based therapy for coronavirus disease 2019 (COVID-19) based on relevant qualified studies. We searched for pertinent studies using keywords via PubMed, Cochrane and Embase databases. Studies from other pertinent sources and that were published before September 2021 were also reviewed. Methods • For each study, we assessed and synthesized the outcomes by relative risk (RR) or weighted mean difference (WMD) combined with a 95% confidence interval (CI). A total of 8 studies involving 2442 patients with COVID-19 were evaluated in this meta-analysis. Results • The IFN group had a significant decrease in ICU admissions (RR: 0.705; 95% CI, 0.515-0.964) and death (RR: 0.416; 95% CI, 0.217-0.797), and increased duration of ICU stay (WMD: 0.996; 95% CI, 0.834-1.158) compared with the control group in the randomized clinical trial (RCT) subgroup analysis. In non-RCT subgroup analysis, the IFN group showed a significant increase in discharge rate (RR: 1.052; 95% CI, 1.004-1.101) compared with the control group. Conclusion • IFN therapy appears to have better efficacy than non-IFN therapy as sedatives in patients with COVID-19 in terms of decreasing ICU admissions and death and increasing discharge. However, more highquality RCTs are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Guidelines for tyrosine kinase inhibitor (TKI)-treated chronic phase-chronic myeloid leukemia (CML) management are essentially based on data from clinical research trials; however, real-world data should be valuable for optimizing such recommendations. Here, we analyzed the data collected in the French CML Observatory database, a multicenter real-world cohort (n = 646), using a first-line "intention-to-treat" analysis strategy. This cohort included patients treated with first-line imatinib (n = 484), nilotinib (n = 103), dasatinib (n = 17), imatinib and interferon (n = 9), or second-generation (2G)-TKIs and interferon (n = 29). The cumulative incidence of major molecular response (MMR), MR4, MR4.5 and MR5 confirmed the faster response kinetics with 2G-TKIs. Multivariate analysis identified being a woman and residual disease at month 6 as the main predictive factors of deep molecular response (DMR). Moreover, 30% of patients met the criteria for treatment discontinuation (5 years of treatment and ≥ 2 years of DMR), but only 38% of them stopped treatment. Among the 92 patients who actually discontinued treatment due to optimal response, 31.5% relapsed (48% of them after > 6 months of TKI discontinuation). Multivariate analysis identified age and TKI duration as factors positively correlated with treatment-free remission maintenance. Late (> 6 months) relapses were more frequent in patients with the e14a2 BCR::ABL transcript. Relapse rate was higher in patients who stopped TKI before than after 5 years of treatment (52.6% vs 26%; p = 0.040). These results advocate caution concerning early treatment withdrawal, including in patients receiving 2G-TKIs. This still recruiting database is a valuable source of information for the real-world follow-up of patients with CML. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to evaluate hepatocellular carcinoma (HCC) risk in patients who achieved an sustained virological response (SVR) with interferon (IFN)-based treatments at long-term follow-up. Methods: In this retrospective study, we reviewed the data of patients with Chronic hepatitis C who received IFN-based treatments between January 2004 and July 2015 and had achieved SVR. Eighty-two patients who met the inclusion criteria were included in the study. Laboratory test results, liver biopsy results, and imaging findings at the start of treatment were recorded. Serum HCV RNA results at the start, the end and the 24th week after completion of treatment, and HCV genotype were also recorded. Follow-up was the time interval between the end of therapy and HCC diagnosis or the date of last available imaging in the absence of HCC. When any new lesion has appeared on USG, then patients underwent triphasic computed tomography or dynamic magnetic resonance imaging. HCC was diagnosis according to guidelines. Results: In our cohort, 10 (12%) patients had advanced fibrosis or cirrhosis. After 88 months of mean follow-up duration, 3 of 82 (3.7%) patients developed HCC. The mean time between the end of treatment and HCC development was 91 months. Two patients who developed HCC had cirrhosis, while 1 had F1 fibrosis at the start of treatment. However, the noncirrhotic patient had concomitant nonalcoholic liver disease and developed cirrhosis during follow-up, and had cirrhosis at the time of HCC diagnosis. One patient had genotype 1 and one had genotype 2 HCV, while genotype was not determined in 1 patient. Two of these patients had diabetes mellitus. Discussion and Conclusion: HCC can be developed even in patients who achieved an SVR after years of IFN-based treatments. Particularly, patients with advanced fibrosis or cirrhosis must be under surveillance for HCC indefinitely. Patients with no-mild fibrosis should also be under surveillance for HCC if they had another risk factors for cirrhosis. [ABSTRACT FROM AUTHOR]

A CNS demyelination event in a person aged ≤ 18 years could signify the initial clinical presentation of multiple sclerosis (MS), a chronic, neuroinflammatory and neurodegenerative CNS disorder. The disease course of paediatric-onset MS (POMS) is typically more inflammatorily active than that of adult-onset MS, resulting in more frequent relapses but slower disability accumulation. Such early and frequent neuroinflammatory attacks can lead to impaired brain development and poor cognitive performance. Patients with POMS should be promptly diagnosed and treated with immunomodulators to delay physical worsening and cognitive decline. However, the use of disease-modifying therapies (DMTs) is mostly off-label and data are limited. [ABSTRACT FROM AUTHOR]

Background. Human papillomavirus (HPV) is a self-limiting disease, and there is no specific antiviral drug at present. Purpose. Here, we analyzed the influence of lacidophilin vaginal capsules plus recombinant human interferon α-2b (rh-IFN-α2b) on efficacy, vaginal microecology, and safety of patients with HPV infection. Two hundred cases of HPV infection admitted between January 2019 and December 2020 were retrospectively collected. Of them, 90 cases receiving rh-IFN-α2b intervention were assigned to the control group (CG), and 110 cases given lacidophilin vaginal capsules in addition to rh-IFN-α2b were included in the research group (RG). Baseline data, efficacy, vaginal microecology, microecological restoration recovery, and incidence of adverse events (AEs) were compared between the two groups. Results. The analyses revealed nonsignificant difference in baseline data between RG and CG, indicating comparability. In terms of efficacy, RG showed a statistically higher negative conversion ratio (NCR) than CG (57.27% vs. 47.78%), as well as an obviously higher overall response rate (ORR) (90.90% vs. 72.22%). As far as the vaginal microecology was concerned, the incidence rates of catalase-positive, sialidase-positive, abnormal microbial density, and abnormal microbial diversity of RG were significantly lower compared with CG, but no evident differences were determined in Trichomonas vaginalis-positive and Candida-positive. As for microecological restoration, RG had an obviously higher vaginal microecological recovery rate than CG (90.00% vs. 65.56%), as well as notably lower vaginal secretion pH and Nugent score. On the other hand, RG and CG showed no statistical significance in the incidence of AEs (12.73% vs. 13.33%). Conclusions. The main contributions of this study are as follows: first, it is confirmed that lacidophilin vaginal capsules plus rh-IFN-α2b has better clinical effects than rh-IFN-α2b alone in HPV-infected patients; second, it demonstrates that the combination therapy can significantly improve NCR and ORR, without increasing the incidence of AEs, and is beneficial to improve patients' vaginal microecology and promote its restoration from the multidimensional aspects of efficacy, safety, and vaginal microecology and its recovery. Our findings provide valuable clinical evidence for the drug treatment of HPV-infected patients. [ABSTRACT FROM AUTHOR]

In December 2019, the coronavirus disease-2019 (COVID-19) outbreak emerged in Wuhan, China. The World Health Organization officially declared it a pandemic on March 11, 2020. Reports indicated that the associated mortality of the infection is quite higher in the elderly, individuals with specific comorbidities (such as diabetes mellitus), and generally the ones with a compromised immune system. A cohort study in Wuhan, China, reported a dysregulated immune response in 452 patients with laboratory-confirmed COVID-19. As a result of this suppressed immune response, an increase in neutrophil to lymphocyte ratio, T lymphopenia, and a decrease in CD4+ T cells were all common laboratory findings, especially in severe cases. On the other hand, there is substantial evidence of T cell exhaustion in critically ill patients. Accordingly, the immune system seems to play an important role in the prognosis and pathogenesis of the disease. Therefore, this study aims to review the evidence on the immune response dysregulation in COVID-19 infection and the potential role of immunoregulatory treatments such as immune checkpoint inhibitors, interferons, and CD200 inhibitors in altering disease prognosis, especially in critically ill patients. [ABSTRACT FROM AUTHOR]

A case study of a 54‑year‑old immunocompetent man was admitted to the emergency unit due to shortness of breath, cough, and fever for a few days as a neurologist. Topics include chest computed tomography was performed for COVID‑19 infection, which showed bilaterally ground‑ glass and alveolar opacities; and Acute longitudinal extensive transverse myelitis (LETM) with necrotizing changes is a rare neurological complication of COVID‑19.

Hepatitis C virus infection among kidney transplant recipients (KTRs) is an important public health concern worldwide. Evidence on available treatments given shows a greater variability for safety and efficacy, thus we performed this large analysis to present the pooled findings. PubMed/Medline, ScienceDirect, and Google Scholar were searched to identify observational studies of both interferon‑based conventional treatment (CT) and recently approved direct‑acting antivirals (DAAs), published before November 2020. Meta‑analysis of effectiveness outcome (sustained virological response [SVR12]) and safety data (adverse events and discontinuation rate) was performed using a random‑effect model. Subgroup analysis based on ± ribavirin with both treatments was performed to assess its relevance in clinical practice. Chi‑square and I2 tests were used to assess heterogeneity between the studies. Twenty‑five and 9 observational records reporting on treatment with DAAs (n = 943) and CT (n = 125), respectively, are analyzed. The overall pooled estimate of SVR12 rate was found as 95.3%, (range: 92.6%–97%) with DAAs in comparison to 46.4% (range: 33.7%–59.6%) with CT. The pooled prevalence of adverse drug reactions (ADRs) in CT was higher as 47.8% than in DAAs as 23.8%, consequently showing a high discontinuation rate of 31.7% in CT as compared to 6.5% with DAAs. Subgroup analyses of both DAAs and interferon‑based treatment ± ribavirin showed decreased effectiveness and increased ADR rates on adding ribavirin. The effectiveness of DDAs was found significantly higher than CT with a better safety profile in KTRs. Ribavirin did not provide any additional benefits while given in combination with either of the treatments available. [ABSTRACT FROM AUTHOR]

Objective. To systematically evaluate the clinical value of tenofovir combined with recombinant human interferon α-2b in the treatment of chronic hepatitis B and to provide evidence-based medicine for its popularization and use. Methods. The randomized controlled trials (RCTs) of tenofovir combined with recombinant human interferon α-2b in the online database of PubMed, EMBASE, ScienceDirect, Cochrane Library, China knowledge Network (CNKI), China VIP database, Wanfang database, and China Biomedical Literature Database (CBM) were searched. The data included in this study were extracted by two independent researchers. After extracting the data of the study, the Cochrane manual 5.1.0 standard was used to evaluate the bias risk of all the literature included in this study. RevMan5.4 statistical software was used to analyze the collected data by meta. Results. Entecavir combined with recombinant human interferon α-2b can inhibit the activity of HBV polymerase and improve the inflammatory response of the liver. Recombinant human interferon α-2b can regulate immune function by inducing T cell differentiation and maturation and enhancing the production of cytokines. The systematic evaluation showed that entecavir combined with recombinant human interferon α-2b had higher serum HBeAg negative conversion rate, higher drug safety compared with entecavir alone, and improved liver function and immune status. Conclusion. Tenofovir combined with recombinant human interferon alpha-2b has a high serum HBeAg negative rate and safety profile for the treatment of chronic hepatitis B. The combination treatment can improve liver function and immune status in patients, but more studies with higher methodological quality and longer duration of intervention are needed for further validation. [ABSTRACT FROM AUTHOR]

Purpose. To observe the clinical efficacy of Reduning injection combined with recombinant human interferon α-2b spray in the treatment of children with viral pneumonia. Methods. A total of 200 children with viral pneumonia over 2 years old who were admitted to the Pediatrics Department of the Cangzhou Central Hospital from September 2018 to November 2020 were recruited and randomized into the control group and observation group at a ratio of 1 : 1, with 100 cases in each group. The children in the control group were given recombinant human interferon α-2b spray, and the children in the observation group were given Reduning injection on the basis of the control group. The clinical symptoms and signs, clinical efficacy, levels of inflammatory mediators, and drug safety were compared between the two groups. Results. The t-test results showed that the disappearance time of body temperature, respiratory rate, pulmonary rales, and cough in the observation group was significantly shorter than that in the control group. The chi-square revealed a significantly higher total effective rate in the observation group vs. the control group. After treatment, the levels of IL-1, IL-6, TNF-α, and CRP in the two groups were lower than the corresponding values before treatment, and greater reduction was observed in the observation group in relative to the control group (both p < 0.05). The two groups have a similar safety profile. Conclusion. Reduning combined with recombinant human interferon α-2b produces a remarkable effect in the treatment of children with viral pneumonia, and it ameliorates clinical symptoms and reduces inflammatory response with a good safety profile. [ABSTRACT FROM AUTHOR]

Background: As one kind of disease-modifying therapies, sphingosine-1-phosphate receptor (S1PR) modulators such as fingolimod, ozanimod, and siponimod have been approved or are being developed to treat multiple sclerosis (MS). Several randomized controlled trials (RCT) have been implemented to compare the efficacy and safety of S1PR modulators versus interferon beta in the treatment of people with relapsing-remitting multiple sclerosis (RRMS).Method: We searched RCTs which were implemented from January 2010 to June 2020 by searching PubMed, Embase, Cochrane Library databases, and the Central Register of Controlled Trials. Finally, five RCTs were included in our study after carefully choosing.Result: We pooled 4304 patients from 5 RCTs. The primary outcome was the annualized relapse rate. We found that the annualized relapse rate in the S1PR modulator group is 20% less than that in the interferon beta group (95%CI, - 0.32 to - 0.07, P = 0.002). S1PR modulators led to a significant reduction in number of new or enlarging T2 lesions per scan and number of gadolinium-enhancing lesions compared with interferon beta. Moreover, S1PR modulators can also improve 54-item multiple sclerosis quality of life (MSQOL-54) physical health composite score (P = 0.0005).Conclusion: S1PR modulators exhibited good efficacy and safety for the treatment of RRMS compared with interferon beta. According to follow-up trials, S1PR modulators can improve MSQOL-54 physical health composite score so that it may be beneficial to neurological recovery which need more research to confirm. [ABSTRACT FROM AUTHOR]

Bushen Formula (BSF) is the effective traditional Chinese medicine (TCM) for chronic hepatitis B (CHB) according to our previous researches. However, the special effectiveness of BSF treating CHB patients in different stages and the immunoregulatory mechanisms remain to be explored. To compare the therapeutic effects of BSF in both treatment-naive patients and Peg-IFN-α-treated patients, and explore the potential mechanism of immunomodulation. Ultra-high performance liquid chromatography-quadrupole electrostatic field-orbital trap high resolution mass spectrometry and the TCMSP database were used to determine the main components of BSF. Two hundred and sixty-six patients were enrolled in the retrospective study, and they were divided into the treatment group (T-Group, BSF plus Peg-IFN-α) and the control group (C-Group, Peg-IFN-α monotherapy). Within each group, patients were further grouped into subgroups, namely T1/C1 groups (treatment-naive patients, T1 = 34, C1 = 94) and T2/C2 groups (Peg-IFN-α-treated patients, T2 = 56, C2 = 82). Serum HBV markers, serum HBV DNA levels, serum ALT/AST and TCM symptoms were obtained from the record. Bioinformatics analysis was employed to obtain the potential immunoregulatory mechanisms of BSF treating CHB patients. Among patients in T2 and C2 group, peripheral mononuclear cells from 36 patients were used to analyze the characteristics of peripheral follicular helper T (Tfh) cells and B-cell subtypes by flow cytometry. Preparation of BSF-containing serum in rats. In vitro, the co-culture system of CXCR5+ cells and HepG2.2.15 cells was built to investigate the immunoregulatory effects of BSF. A total of 14 main active compounds were detected in BSF, which were deemed critical for the treatment of CHB. Our findings indicated that the T2-Group exhibited the higher percentage of HBsAg decline ≥ 1-log 10 IU/ml and rate of HBeAg seroclearance compared to the C2-Group (35.7% vs. 15.9%, P = 0.033; 33.9% vs. 11.0%, P = 0.002). Additionally, the T2-Group demonstrated the higher percentage of HBsAg decline ≥ 1-log 10 IU/ml and rate of HBeAg seroclearance compared to the T1-Group (35.7% vs. 14.7%, P = 0.031; 33.9% vs. 2.9%, P = 0.000). The total effective rate based on TCM clinical syndrome in T1-Group and T2-Group were significantly greater than those in C1-Group and C2-Group (85.3% vs. 61.7%, P = 0.012; 89.1% vs. 63.4%, P = 0.000). Bioinformatics analysis indicated that the immunoregulatory mechanisms of BSF treating CHB patients were mainly linked to the growth and stimulation of B-cell, T-cell differentiation, and the signaling pathway of the B-cell receptor. Furthermore, the frequencies of Tfh cells and its IL-21 level, and the IL-21R expressed by B-cell were all increased after BSF treatment. Additionally, in the co-culture system of CXCR5+ cells and HepG2.2.15 cells, HBsAg and HBeAg levels were decreased after BSF-containing serum treatment，as well as the up-regulating of Tfh cell frequencies and down-regulating of B-cell frequencies. BSF have the higher percentage of HBsAg decline and HBeAg seroclearance in Peg-IFN-α-treated patients compared with treatment-naive patients. The potential immunoregulatory mechanism may correlate with promoting the interaction between Tfh cells and B-cell through IL-21/IL-21R signaling pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Patients with chronic granulomatous disease, a primary immunodeficiency, experience granulomatous complications and recurrent life-threatening opportunistic bacterial and fungal infections. In this article, we report on a case of invasive aspergillosis in an eight-year-old boy with chronic granulomatous disease, who presented with pleural effusion and pneumonia, cerebral venous sinus thrombosis, and unusual skin lesions caused by Aspergillus fumigatus. Antifungal treatment with itraconazole and other antifungal agents, along with interferon-γ, was ineffective and the patient eventually died from cerebral venous sinus thrombosis, and intracerebral haemorrhage following increased intracranial pressure after one month. The diagnosis of invasive aspergillosis should be considered early in children presenting with invasive fungal infections, particularly those involving the central nervous system. [ABSTRACT FROM AUTHOR]