Interferon Alfa-2b Research Articles

The established of a machine learning model for predicting the efficacy of adjuvant interferon alpha1b in patients with advanced melanoma

BackgroundInterferon-alpha1b (IFN-α1b) has shown remarkable therapeutic potential as adjuvant therapy for melanoma. This study aimed to develop five machine learning models to evaluate the efficacy of postoperative IFN-α1b in patients with advanced melanoma.MethodsWe retrospectively analyzed 113 patients with the American Joint Committee on Cancer (AJCC) stage III-IV melanoma who received postoperative IFN-α1b therapy between July 2009 and February 2024. Recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan-Meier analysis. Five machine learning models (Decision Tree, Cox Proportional Hazards, Random Forest, Support Vector Machine, and LASSO regression) were developed and compared for their capacity to predict the outcomes of patients. Model performance was evaluated using concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, and decision curve analysis.ResultsThe 1-year, 2-year, and 3-year RFS rates were 71.10%, 43.10%, and 31.10%, respectively. For OS, the 1-year, 2-year, and 3-year OS rates were 99.10%, 82.30%, and 75.00%, respectively. The Decision Tree (DT) model demonstrated superior predictive performance with the highest C-index of 0.792. Time-dependent ROC analysis for predicting 1-, 2-, and 3-year RFS based on the DT model is 0.77, 0.79 and 0.76, respectively. Serum albumin emerged as the important predictor of RFS.ConclusionsOur study demonstrates the considerable efficacy DT model for predicting the efficacy of adjuvant IFN-α1b in patients with advanced melanoma. Serum albumin was identified as a key predictive factor of the treatment efficacy.

Topical 5-fluorouracil as monotherapy for ocular surface squamous neoplasia

Ocular surface squamous neoplasia (OSSN) comprises a gamut of diseases, which encompass conjunctival intraepithelial neoplasia, conjunctival carcinoma in situ, and squamous cell conjunctival neoplasia. Gold standard treatment for OSSN entails excision with cryotherapy. A lot of progress has been made recently that shows that chemotherapeutic drugs, such as mitomycin C, 5-fluorouracil (5-FU), and interferon alfa2b, can be just as effective. This is a case report that includes two cases: An 81-year-old Filipino female and a 65-year-old Filipino male who presented with a pinkish lesion on the bulbar conjunctiva. Documentation was done through clinical observation, slit-lamp examination, and the use of anterior segment optical coherence tomography (OCT). 1% topical 5-FU was given as chemotherapy administered at 1 drop 4×/day for 1 week with a 3-week drug holiday. During the course of treatment, we noted clinical resolution of the lesions grossly on slit-lamp examination. On anterior segment OCT, a decrease in diameter and thickness was noted, but with remaining areas of hyperreflectivity and thickened epithelium at the site of the lesion. No decrease in visual acuity was noted during the course of treatment, as well as any adverse effects such as eye pain or inflammation. Considering its safety and efficacy profile, 5-FU has great potential to be considered as a first-line therapy in the topical treatment of OSSN. Topical chemotherapy can target microscopic diseases that may be missed surgically and decrease adverse effects. As seen in this case report, 5-FU shows much promise as a possible alternative in the treatment of OSSN.

A Scoping Review of Arthropod-Borne Flavivirus Infections in Solid Organ Transplant Recipients.

Arthropod-borne flaviviruses (ABFs), transmitted by mosquitoes or ticks, are increasing due to climate change and globalization. This scoping review examines the epidemiology, clinical characteristics, diagnostics, treatment, and outcomes of ABF infection in solid organ transplant recipients (SOTRs). A database search up to January 25, 2024, focused on ABFs such as West Nile virus (WNV), dengue virus (DENV), Japanese encephalitis virus (JEV), Powassan virus (POWV), yellow fever virus (YFV), and Zika virus (ZIKV), limited to SOTRs. We identified 173 WNV cases from 84 studies, with 28 donor-derived infections (DDIs). Common clinical features included fever (78.5%), altered mental status (65.1%), and weakness or paralysis (45.6%). Treatment involved reducing immunosuppression (IS) in 93 cases, with intravenous immunoglobulin (IVIG), interferon alfa-2b, and ribavirin used in 75 cases. Seven cases involved graft loss or rejection post-infection. WNV infection had a 23.7% mortality rate, with severe neurological complications in 43.9% For DENV infection, 386 cases from 47 studies were identified, including 14 DDI cases. Symptoms included fever (85%), myalgias (56.4%), and headache or retro-orbital pain (34.6%). Severe dengue occurred in 50 cases (13.0%). IVIG was administered in six cases. Reduction in IS was reported in 116 patients. DENV mortality rate was 4.9%. Additionally, 26 cases of less common ABFs such as JEV, POWV, YFV, and ZIKV were described. In summary, ABF infections among SOTRs are associated with higher morbidity and mortality compared to the general population, emphasizing the need for improved preventive strategies, timely diagnosis, and optimized management protocols.

Highly selective split intein method for efficient separation and purification of recombinant therapeutic proteins from mammalian cell culture fluid

Biologics and vaccines have been successfully developed over the last few decades to treat many diseases. Each of these drugs must be highly purified for clinical use. Monoclonal antibodies (mAbs), the dominant therapeutic modality on the market, can be easily purified using the standard Protein A affinity platform. However, no generally applicable affinity platforms are available for the manufacture of other therapeutic proteins for clinical use. Thus, multicolumn chromatography processes for widely being used for product purification. These processes demand significant optimization to meet desired product quality attributes, where each step also decreases final yields. In this work, we demonstrate the novel self-removing iCapTagTM affinity tag, which provides a new platform for capturing, concentrating, and purifying recombinant proteins. Importantly, this system provides a tagless target protein, which is suitable for research and clinical use, where the only requirement for tag removal is a small change in buffer pH. No additional proteins, reagents or cofactors are required. We also present case studies demonstrating the use of iCapTagTM for highly efficient purification of untagged interferon alpha 2b, the ML39 single chain variable fragment (scFv), and the receptor binding domain (RBD) of SARS-CoV-2 spike protein. These proteins were expressed and secreted by Expi293 cells with the self-removing tag fused to their N-terminus. We were able to obtain highly pure (> 99%) tagless protein in a single purification step with high clearance of host cell DNA, tagged precursor, higher and lower molecular weight impurities. Based on these preliminary results, we propose the iCapTagTM as a universal capture platform for diverse classes of recombinant therapeutic proteins.

OSSN in South India: Clinical presentation, treatment outcomes, and histopathologic correlations.

This study aimed to analyze the clinical presentation, treatment outcomes, and histopathology features of ocular surface squamous neoplasia (OSSN) in a South Indian population and correlate the area of lesions to the histopathological grade/severity of carcinoma in situ (CIN) and squamous cell carcinoma (SqCC) invasive and noninvasive tumors. The study was a retrospective cross-sectional study. The study reviewed electronic medical records (EMRs) of 99 eyes of 99 South Indian patients who underwent en bloc excision and biopsy for tumors in the corneal and conjunctival epithelium with suspicion of OSSN over 1 year from January 2019 to December 2019. Postoperatively, patients were treated with three cycles of topical 0.04% mitomycin C eye drops. Sixty-three had requisite EMR data with a follow-up period of 1 year. Patients had equal gender distribution with an age range of 28-83 years. The most common clinical variant was leukoplakic lesion, and the area of the lesion was the only predicting factor for SqCC and CIN. Bigger (T2) lesions should be strongly suspected for OSSN and promptly excised. Histopathologic analysis should be performed, and post-op topical mitomycin C or interferon alpha 2b is administered to avoid recurrence. In this study, by correlating the area of the lesion, we introduce a new variable that may aid in clinical prognostication alongside the AJCC classification.

Modern etiotropic therapy of chronic viral hepatitis B

Chronic viral hepatitis B (CHB) is a significant global health problem. The biological characteristics of the hepatitis B virus, which causes this disease, significantly impede the achievement of complete virus elimination in most patients. In this regard, the rational choice of drugs and antiviral therapy regimens is crucial for increasing life expectancy and improving the quality of life in patients with CHB. The purpose of this literature review is to identify current approaches and trends in etiotropic therapy for CHB.Materials and methods. The review uses data published in domestic and foreign scientific journals, clinical guidelines, regulatory documents, and Internet resources.Results. Currently, the most effective means of etiotropic therapy for CHB are interferons (standard interferon alpha, pegylated interferons alpha-2a and alpha-2b), as well as first-line nucleoside/nucleotide analogs (entecavir, tenofovir) and second-line analogs (lamivudine, telbivudine, adefovir). The choice of a specific drug is determined by the patient's clinical condition, preferences, availability, and cost of treatment. Despite certain limitations of current etiotropic therapies for CHB, their use can significantly increase patients' life expectancy and improve their quality of life.

Chemoimmunotherapy-Resistant Ocular Surface Squamous Neoplasia Managed With I-125 Brachytherapy

Purpose: The purpose of this study was to report the management of chemoimmunotherapy-resistant ocular surface squamous neoplasia (OSSN) with iodine-125 (I-125) brachytherapy. Methods: A 36-year-old man presented to the clinic with biopsy-proven OSSN that covered ∼70% of the corneal surface and extended to the 6 o'clock position of the inferior limbus of the OS. The visual acuity was 20/20 in the OD and 20/40 in the affected OS. He was treated with topical interferon alpha-2b 1 MIU/mL (4 times daily [QID] for 6 weeks) and then 4 cycles of topical 5-fluorouracil 1% (QID, 1 week on, 3 weeks off) with an incomplete response. He switched to topical mitomycin C 0.04% (QID, 1 week on, 2 weeks off) for 2 cycles and received a subconjunctival injection 25 mg (0.5 mL of a 50-mg/mL solution) of 5-fluorouracil. The tumor persisted. The patient was ultimately cured with placement of an 18-mm I-125 brachytherapy plaque for 97 hours (50 Gy). Results: Because of extensive corneal involvement and risks associated with surgery, an 18-mm I-125 brachytherapy plaque was placed over the cornea and limbus. The treatment led to full resolution of the tumor within 1 month of treatment and recovery of 20/20 vision in the affected eye. Thirty-two months after treatment, the patient developed a visually significant posterior subcapsular cataract OS and underwent successful phacoemulsification surgery, returning to 20/20 vision. He has remained tumor-free for over 55 months. Conclusions: This case highlights the efficacy and safety of I-125 brachytherapy as an alternative for intraepithelial OSSN unresponsive to conventional chemoimmunotherapy, particularly when extensive surgical excision poses significant risks.

Aeromonas veronii-associated bacteremia in the course of treatment of acute myeloid leukemia: a case report and review of the literature

PurposeThis study aimed to report a case of acute myeloid leukemia (AML) complicated by Aeromonas veronii infection-induced bacteremia and to review relevant literature on the etiology, prevention, treatment, and prognosis of bacteremia in immunocompromised populations, aiming to reduce mortality in individuals with hematologic and other end-stage diseases and improve patient outcomes.Methods and resultsWe reported the case of a 23-year-old male patient with relapsed AML characterized by AML1:ETO and ASXL positivity, classified as a high-risk group. The patient presented with fever, abdominal pain, diarrhea, nausea, and vomiting after consuming partially cooked fish. The patient was admitted with high leucocytes, C-reactive protein, procalcitonin, and interleukin-6 levels. Peripheral blood high-throughput sequencing (Next-Generation Sequencing NGS) confirmed infection with Aeromonas veronii, while an abdominal CT scan indicated a liver abscess with gas formation. Culture of the drainage fluid from the ultrasound-guided liver abscess puncture demonstrated growth of Aeromonas veronii. Based on the sensitivity results, the patient was treated with intravenous ciprofloxacin and cefoperazone-sulbactam. After treatment with antibiotics, blood transfusion, liver protection, and azacitidine 100 mg ih, combined with dry white sand(interferon alpha-1B, interleukin-2, and thalidomide), the critical condition of the patient improved, and he was discharged. This study was approved by the Ethics Committee of Medical Research in the Second Affiliated Hospital of Henan University of Science and Technology. Informed consent was obtained from this patient and we have obscured the patient's identifying information. All methods were carried out in accordance with relevant guidelines and regulations.ConclusionWhen patients with a recurrence of AML have a history of consuming or contacting aquatic products, clinicians should be vigilant about Aeromonas veronii infection. The presence of Aeromonas veronii in peripheral blood must alert clinicians to the possibility of severe sepsis and septic shock. Early diagnosis and prompt treatment are crucial to reducing patient mortality.

Efficacy and safety of PD-1 monoclonal antibody combined with interferon-alpha 1b and anlotinib hydrochloride as the second-line therapy in patients with unresectable advanced melanoma: A retrospective study.

Immune-checkpoint inhibitors are now used more commonly in combination than monotherapy as the first-line choice in patients with unresectable advanced melanoma. Nevertheless, for cases that progressed after the initial combination therapy, the subsequent regimen option can be very difficult. Herein, we reported the efficacy and safety of a triple combination regimen in Chinese unresectable advanced melanoma patients who had poor responses to the first-line immune therapy. We reviewed the clinical profiles of patients diagnosed with stage IIIC-IV melanoma between June 1, 2020, and September 30, 2023. The patients who failed the prior immune therapies and received anti-PD-1 mono antibody plus interferon(IFN)-alpha 1b and anlotinib hydrochloride as the second-line therapy were enrolled in the retrospective analysis. Additionally, we examined the exhaustion of T-cells using mIHC staining in available tumor samples. Fifty-five patients were included in this study. The median follow-up period was 13.6 months. The objective response rate evaluated by the investigators was 9.1%(1CR, 4PR). The disease control rate was 47.3%. The median overall survival was 17.6 months, and the median progression-free survival was 2.8 months. The adverse events rate of any grade was 100%. Grade 3 or 4 irAEs were observed in 29.1% of cases. Multiplex immunohistochemical staining revealed an increased trend of TIM3 expression on tumor-infiltrating T cells in patients without objective response. PD-1 monoclonal antibody plus interferon-alpha 1b plus anlotinib showed acceptable tolerability and anticancer benefits in Chinese metastatic melanoma patients as a second-line therapy.

Integrated analysis reveals the immunotoxicity mechanism of BPs on human lymphocytes

Bisphenol A (BPA) is a well-documented endocrine-disrupting chemical widely used in plastic products. In addition to its endocrine-disrupting effects, BPA exhibits immunotoxicity. Many countries have banned BPA because of its adverse effects on human health. In recent years, many chemicals such as bisphenol B (BPB), bisphenol E (BPE), bisphenol S (BPS), and bisphenol fluorene (BHPF) have been used to replace BPA. Because these replacement chemicals have chemical structures similar to that of BPA, they may also harm human health. However, their immunotoxicity and the molecular mechanisms underlying their toxicity remain largely unknown. The aim of this study was to investigate the immunotoxicity of BPA and its replacement chemicals, as well as the underlying mechanisms by exposing primary human lymphocytes to BPA and its replacement chemicals. Our results showed that exposure to BPA and its replacement chemicals altered the interleukin (IL) and cytokine production, such as IL-1b, IL-5, IL-6, IL-8, interferon alfa-2b (IFN-a2B), and tumor necrosis factor alpha (TNF-α), in the lymphocytes. Among these, BPA and BHPF caused a greater inhibition. Using comparative transcriptomic analysis, we further investigated the biological processes and signaling pathways altered by BHPF exposure. Our data highlighted alterations in the immune response, T cell function, and cytokine-cytokine receptor interactions in human lymphocytes through the deregulation of gene clusters. In addition, the results of ingenuity pathway analysis demonstrated the inhibition of T lymphocyte function, including differentiation, movement, and infiltration. Our results, for the first time, delineate the mechanisms underlying the immunotoxicity of BHPF in human lymphocytes.

Feasibility, tolerability, and first experience of intracystic treatment with peginterferon alfa-2a in patients with cystic craniopharyngioma.

Children with craniopharyngiomas (CPs) typically suffer from a life-long chronic disease. The younger the child, the more vulnerable the maturing brain is to invasive therapies such as surgery or radiotherapy. Therefore, treatment modalities facilitating avoidance or delay of invasive therapies are beneficial for these patients. In the last decade, intracystic injection of interferon alfa-2a or alfa-2b evolved as a treatment of choice based on efficacy and minor toxicity. However, the drug is no longer available internationally. After an extensive pharmacological review, peginterferon alfa-2a was identified as the agent with closest similarity. A retrospective case series is described, including five patients treated with intracystic peginterferon alfa-2a for cystic CP according to an innovative care protocol. After initial CP cyst aspiration, peginterferon alfa-2a was injected once per week via an Ommaya reservoir for 6 weeks followed by response assessment with MRI. Patients' age ranged from 4 to 54 years (four patients <12 years, one adult patient). Intracystic therapy with peginterferon alfa-2a was tolerated well by all five individuals without any major toxicities and resulted in cyst shrinkage in all of the five patients. The importance of a permeability study prior to commencing intracystic therapy became apparent in one patient who suffered from cyst leakage. Intracystic treatment with peginterferon alfa-2a was found to be a tolerable and efficacious treatment modality in patients with cystic CP. This experience warrants further research with a larger number of patients with measurement of long-term efficacy and safety outcomes.

Efficacy of topical 5-Fluorouracil in the management of ocular surface squamous neoplasia: a study of 101 eyes.

To study the efficacy and side-effect profile of topical 5-Fluorouracil (5-FU) in the treatment of ocular surface squamous neoplasia (OSSN). Retrospective study of 101 eyes of 100 patients treated with 5-FU with one week on and 3weeks off regimen. Of the 100 patients (101 eyes), the mean age at diagnosis of OSSN was 49 (median, 52years; range, 11-87years). History of prior intervention was noted in 6 (6%) eyes. Tumor epicenter included bulbar conjunctiva (n = 54; 53%), limbus (n = 27; 27%), and cornea (n = 20;20%). Mean number of cycles of topical 5-FU administered was 3 (median, 3; range, 1-8). Complete tumor regression was achieved with topical 5-FU in 89 (88%) eyes with a mean number of 2 cycles (median, 2; range, 1-6) of 5-FU. The remaining 12 (12%) lesions underwent additional treatment including excisional biopsy (n = 7), extended enucleation (n = 3), and topical Interferon alpha 2b (n = 2) for complete tumor control. Over a mean follow-up period of 6months (median, 5months; range, 1-36months) following treatment, tumor recurrence was noted in 2 (2%) patients, and side-effects were noted in 7 (7%) eyes including conjunctival hyperemia (n = 1), punctal stenosis (n = 1), sterile keratitis (n = 4), and limbal stem cell deficiency (n = 1). Topical 5-FU is an effective non-invasive therapy for OSSN with a minimal side-effect profile.

The Topical Novel Formulations of Interferon α-2в Effectively Inhibit HSV-1 Keratitis in the Rabbit Eye Model and HSV-2 Genital Herpes in Mice.

Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are widespread human pathogens that establish chronic latent infections leading to recurrent episodes. Current treatments are limited, necessitating the development of novel antiviral strategies. This study aimed to assess the antiviral efficacy of novel topical formulations containing interferon alpha-2b (IFN α-2b) against HSV-1 and HSV-2. The formulations, Oftalmoferon® forte (eye drops) and Interferon Vaginal Tablets, demonstrated potent antiviral effects against HSV-1 and HSV-2 in Vero cells, respectively, with concentration-dependent inhibition of viral replication. Subsequently, their efficacy was tested in animal models: HSV-1 keratitis in the rabbit eye model and HSV-2 genital herpes in mice. Oftalmoferon® forte effectively treated HSV-1 keratitis, reducing clinical symptoms and ulcerations compared to virus control. Interferon Vaginal Tablets showed promising results in controlling HSV-2 genital herpes in mice, improving survival rates, reducing clinical signs, weight loss and viral replication. The novel IFN α-2b formulations exhibited significant antiviral activity against HSV infections in cell culture and animal models. These findings suggest the potential of these formulations as alternative treatments for HSV infections, particularly in cases resistant to current therapies. Further studies are warranted to optimize treatment regimens and assess clinical efficacy in humans.

The Evolution of Nadofaragene Firadenovec: A Review and the Path Forward.

The intravesical gene therapy nadofaragene firadenovec (rAd-IFNα/Syn3) was FDA approved in 2022 for non-muscle invasive bladder cancer (NMIBC) unresponsive to frontline treatment with BCG, and the first gene therapy developed for bladder cancer. This non-replicating recombinant adenovirus vector delivers a copy of the human interferon alpha-2b gene into urothelial and tumor cells, causing them to express this pleotropic cytokine with potent antitumor effects. To provide a historical overview describing how several decades of preclinical and clinical studies investigating the role of interferon in the treatment of bladder cancer ultimately led to the development of gene therapy with nadofaragene for NMIBC. We conducted a review of the literature using PubMed, Google Scholar, and ClinicalTrials.gov to summarize our knowledge of the evolution of interferon-based therapy in NMIBC. The FDA approval of this therapy represents an important landmark in urologic oncology and several decades of research dedicated to the study of interferon's direct and indirect antitumor properties in NMIBC. The data gathered from the phase 1, 2, and 3 clinical trials continue to provide additional insights into the precise mechanisms underlying both the efficacy of and resistance to nadofaragene. Nadofaragene leverages the cytotoxic, anti-angiogenic, and immune-modulatory roles of interferon to effectively treat NMIBC that is resistant to BCG. Ongoing studies of resistance mechanisms and prognostic biomarkers have been promising; these will ultimately improve patient selection and allow for the modulation of factors in the tumor or immune microenvironment to further increase therapeutic response.

Comparison of postoperative topical interferon-α2b versus intraoperative mitomycin C for pterygium recurrence prevention: a randomized clinical trial.

To evaluate the effect of postoperative interferon-alpha 2b (IFN-α2b) ophthalmic drops versus intraoperative mitomycin-c (MMC) on preventing pterygium recurrence. This prospective randomized clinical trial was conducted on patients who were candidates for pterygium surgery. A total of 75 patients were included in the study from December 2021 to December 2022, of which 64 patients (one eye each) were examined and analyzed based on the inclusion criteria. Then the patients were randomly assigned to control groups, intra-operative MMC (32 patients) and the intervention group, IFN-α2b drops after the operation (32 patients). All patients underwent pterygium surgery using the rotational conjunctival flap method. In terms of pterygium grading, 8 (12.5%), 25 (39.06%), and 31 (48.44%) eyes were in grades 1, 2, and 3, respectively. The average size of the pterygium was 3.6 ± 0.7mm. The grade and size of pterygium had the same distribution in the two groups. There was no statistically significant difference between the two groups in the level of post-operative clinical inflammation. The present study showed no significant difference in complications between the two groups (p = 0.999). The recurrence rate in the control group was 9.4% (3 eyes), and 0% (no recurrence) in the intervention group (p = 0.119). interferon-alpha 2b group did not show a statistically significant difference in preventing pterygium recurrence compared to the mitomycin C group. The post-surgery administration of IFN-α 2b drops can effectively prevent pterygium recurrence with a comparable and even more compelling effect than MMC during surgery.

Association between circulating tumor DNA (ctDNA) and recurrence-free survival (RFS) in patients (pts) with resected stage III melanoma: An exploratory analysis of SWOG S1404.

9564 Background: Our exploratory study aimed to understand the association between the presence of ctDNA after definitive surgical resection and RFS in pts with stage III melanoma treated with adjuvant immunotherapy. Methods: This study included 92 pts with resected stage III melanoma enrolled in a phase 3 trial (NCT02506153) that evaluated the efficacy of adjuvant pembrolizumab compared to interferon alfa-2b or ipilimumab in pts with stage IIIA(N2a)-IV resected melanoma. Personalized, tumor-informed ctDNA assays (Signatera) were run on banked plasma samples (median: 3.8 mL) collected at up to 5 time points after resection: pre-adjuvant treatment (pre-Tx), 1, 3, 6, or 12 months after Tx initiation and at recurrence. RFS was measured from randomization (pre-Tx) to first recurrence or death. A case-control design was used: 50% with recurrence within 2 yrs of randomization and 50% alive without recurrence for &gt; 2 yrs. Conditional logistic regression compared the presence of ctDNA at pre-Tx between case-control groups. Results: Of the 92 pts, samples from 10 did not pass quality control. This study analyzed a total of 245 plasma samples from 82 pts. No significant differences in demographics, including stage, number of + lymph nodes, and BRAF status, existed between pts who were ctDNA+ or ctDNA- pre-Tx. 7 of 10 pts (70.0%) who were ctDNA+ pre-Tx had disease recurrence within 2 yrs compared to 33 of 72 pts (45.8%) who were ctDNA- (p = 0.19). 2-yr RFS was 30% in pts who were ctDNA+ pre-Tx and 54% in pts who were ctDNA- (HR 1.75; 95% CI: 0.78, 3.94; p = 0.18). Of the 7 pts who were ctDNA+ pre-Tx and had disease recurrence within 2 yrs, 5 were ctDNA+ at all time points assessed. The other 2 pts transiently cleared ctDNA during Tx, turning back ctDNA+ prior to recurrence. Of the 3 pts who were ctDNA+ pre-Tx and did not recur within 2 yrs, 2 cleared ctDNA during immunotherapy and remained ctDNA- at later time points. All 39 pts who were ctDNA- pre-Tx and did not recur within 2 yrs remained ctDNA- at later time points. Among 29 pts having ctDNA timepoints available for analysis near the time of recurrence (end-of-Tx or on-progression timepoints), 22 (75.9%) were ctDNA+. Conclusions: In this study, pre-Tx incidence of ctDNA+ after surgical resection was low, potentially related to limited plasma yield. However, the ctDNA positivity rate increased in subsequent serial testing. ctDNA might help identify early disease recurrence in patients with melanoma in the adjuvant setting, but further studies of larger cohorts accounting for treatment effect with more uniform pre-analytic collection are needed.

On the Possibility of Using the Topical form of the Recombinant Interferon alpha-2b Drug in the Prevention of Acute Respiratory Viral Infections in Organized Groups

Relevance. Respiratory infections are an urgent problem for organized groups, including military ones, since the transmission of pathogens by airborne droplets and household contact routes, physical and psychological stress on adaptive mechanisms contribute to the development of the epidemic process. There is no doubt that vaccination makes a significant contribution to the prevention of respiratory infections, but the contingent remains vulnerable to other pathogens against which there are no vaccines. Therefore, the search for new methods of non-specific prevention is necessary in maintaining the health of persons permanently residing in collectives. Aim. Evaluation of the possibility of using the topical form of the recombinant interferon α-2b drug for the prevention of acute respiratory viral infections in organized groups. Materials and methods. The work was carried out according to the methodology of a multicenter (3 Centers) double-blind controlled trial involving 3,235 people aged 18 to 22 years, who were divided into three groups: 1 gy. - received a recombinant interferon α-2b (Grippferon) drug 3 drops in each nasal passage 2 times a day in for two weeks; 2 g. - saline solution intranasally according to the same scheme; 3 g. - the volunteers did not receive anything. The frequency of respiratory infections was studied. Results and discussion. Medical monitoring of the study participants, which was carried out for 2 months, showed that in the groups from the Center 1, the incidence of acute respiratory diseases for 2 months in the main group (gr. 1) was 2.3 times lower than in the control (gr. 2) and the comparison group (gr. 3). In the Center 2 The data corresponded to the dynamics of Center 1: the incidence values were 2.4-2.5 times lower in Group 1. In Center 3, the values were 2.0-2.1, respectively. The epidemic effect of intranasal administration of the topical form of the drug recombinant interferon α-2b is due to its effect on the factors of mucosal immunity, which contributes to non-specific protection and increased body resistance against respiratory infections. Conclusions. The presented advantages of the recombinant interferon α-2b drug make it possible to draw attention to the clinical feasibility of its use for preventive purposes in organized groups, including military ones, from the position of high epidemiological effectiveness, both pre-exposure and post-exposure prevention of acute respiratory viral infections.

Corneal ocular surface squamous neoplasia: Case series and review of literature.

The authors present a retrospective analysis of three cases of isolated corneal ocular surface squamous neoplasia (C-OSSN) without limbal or conjunctival involvement and review the clinical and anterior segment optical coherence tomography (AS-OCT) features, along with treatment outcomes. The mean age at presentation was 51 years (range: 32-64 years). The mean tumor diameter was 5 mm (range: 3-6.5 mm). All lesions were placoid with <1 mm thickness. One case had surface keratin. AS-OCT revealed hyperreflective epithelium with abrupt transition in all cases, with mean thickness of 118 μm (range: 60-162 μm). One patient underwent alcohol-assisted keratoepitheliectomy (AKE) and two patients received topical Interferon alpha-2B followed by AKE. Histopathology revealed mild squamous dysplasia in all. No tumor residue or recurrence was noted at a mean follow-up period of 2 years (range: 1-4 years). Isolated C-OSSN is rare. AS-OCT serves as a useful noninvasive tool for supporting the diagnosis of AKE yielding long-term favorable outcomes.

Production of Recombinant Human Interferon alpha 2b (rhIFN?-2b) in genetically engineered strain of Bacillus subtilis

Interferon alpha 2b (IFN?-2b) is a critical therapeutic protein with immunomodulatory properties, widely used in the treatment of various diseases, including viral infections and cancer. This study presents a comprehensive methodology for the cloning and characterization of the IFN?-2b gene, including the identification of point mutations, followed by expression in Bacillus subtilis. The research begins with gene isolation, primer design, RNA extraction, cDNA synthesis, and PCR amplification. Cloning into a T/A vector and subsequent sequencing reveal point mutations within the gene. The transformed construct is expressed in Bacillus subtilis, and the resulting protein is analyzed using SDS-PAGE. The identification of point mutations and successful protein expression in Bacillus subtilis. This study provides valuable insights into the IFN?-2b gene and its potential applications.

Quantitative HBeAg is a strong predictor of HBeAg loss among patients receiving pegylated interferon

BackgroundHBeAg loss is an important endpoint for antiviral therapy in chronic hepatitis B (CHB), however there are no reliable biomarkers to identify patients who will respond to the addition of pegylated interferon to nucleos(t)ide analogue (NA) therapy. AimTo evaluate the use of serum biomarkers to predict HBeAg loss. MethodsHBeAg positive CHB participants on NAs who switched-to or added-on 48 weeks pegylated interferon alpha2b (clinicaltrial.gov NCT01928511) were evaluated at week 72 for HBeAg loss. The predictive ability of qHBeAg, qHBsAg, HBV RNA and clinical variables for HBeAg loss were investigated. ResultsHBeAg loss occurred in 15/55 (27.3%) participants who completed 48 weeks of pegylated interferon. There was a lower baseline qHBeAg (1.18 IU/mL [2.27] versus 10.04 IU/mL [24.87], P = 0.007) among participants who lost HBeAg. Baseline qHBeAg (OR = 0.15, 95% CI 0.03–0.66, P = 0.01) and detectable HBV DNA at baseline (OR = 25.00, 95% CI 1.67–374.70, P = 0.02) were independent predictors of HBeAg loss. In addition, on-treatment qHBeAg was also a strong predictor of HBeAg loss (OR = 0.39, 95% CI 0.18–0.81, P = 0.012). The models combining detectable baseline HBV DNA with baseline (C-statistic 0.82) and on-treatment (C-statistic 0.83) had good accuracy for predicting HBeAg loss. A rise in qHBeAg ≥ 10 IU/ml was a predictor of flare (ALT ≥ 120 U/ml) on univariable analysis but not after adjustment for treatment arm. ConclusionsBaseline and on-treatment qHBeAg is a useful biomarker that can identify participants on NA therapy who may benefit from adding or switching to pegylated interferon.