Three families of CD4-induced antibodies are associated with the capacity of plasma from people living with HIV to mediate ADCC in the presence of CD4-mimetics.

CD4-mimetics (CD4mcs) are small molecule compounds that mimic the interaction of the CD4 receptor with HIV-1 envelope glycoproteins (Env). Env from primary viruses normally samples a "closed" conformation that occludes epitopes recognized by CD4-induced (CD4i) non-neutralizing antibodies (nnAbs). CD4mcs induce conformational changes on Env resulting in the exposure of these otherwise inaccessible epitopes. Here, we evaluated the capacity of plasma from a cohort of 50 people living with HIV to recognize HIV-1-infected cells and eliminate them by antibody-dependent cellular cytotoxicity (ADCC) in the presence of a potent indoline CD4mc. We observed a marked heterogeneity among plasma samples. By measuring the levels of different families of CD4i Abs, we found that the levels of anti-cluster A, anti-coreceptor binding site, and anti-gp41 cluster I antibodies are responsible for plasma-mediated ADCC in the presence of CD4mc. IMPORTANCE: There are several reasons that make it difficult to target the HIV reservoir. One of them is the capacity of infected cells to prevent the recognition of HIV-1 envelope glycoproteins (Env) by commonly elicited antibodies in people living with HIV. Small CD4-mimetic compounds expose otherwise occluded Env epitopes, thus enabling their recognition by non-neutralizing antibodies (nnAbs). A better understanding of the contribution of these antibodies to eliminate infected cells in the presence of CD4mc could lead to the development of therapeutic cure strategies.

Usage of 3D prints with ceramic coating applied as neurological tools - preliminary research.

Purpose: The paper shows a preliminary study of the basic strength parameters of printed parts made of biocompatible polymers with ceramic layers applied to increase the strength of the tool cutting surface. Methods: The specimens were made from different materials and using different 3D printing technologies and the working surfaces that will eventually form the cutting element of the tool were coated with Al2O3. Gloss tests were conducted, properties of the coating, a scratch test of the coated surface, also evaluated surface to-pography. Results: Based on the conducted research, it was found that polymeric materials are characterized by sufficient strength and can be used for disposable tools, however, the use of thin layers of Al2O3 significantly increases the surface strength parameters, which may have a significant impact on the reliability and durability of the tools. The polymer surface covered with an Al2O3 layer is characterised by increased scratch resistance ranging from 24% to 75% depending on the core material and printing technology. The gloss of the surfaces is disproportionately low compared to currently used metal tools, which indicates that they can be used in endoscopic procedures. Conclusions: Based on the conducted research, it was found that the use of thin layers of Al2O3 covering polymer 3D prints is an excellent way to increase strength parameters such as scratch resistance, tribological parameters and light reflections arising on the surface as a result of endoscopic lighting are disproportionately small compared to metallic biomaterials. This gives great hope for using polymer 3D prints for personalised neurosurgical tools.

Cigarette Smoking Is Associated With Lower Chance of Hepatitis B Surface Antigen Seroclearance and Altered Host Immunity.

Cigarette smoking is associated with worse clinical outcomes in patients with chronic hepatitis B (CHB) infection, but the effects on hepatitis B surface antigen (HBsAg) seroclearance are unclear. This study aimed to investigate the effect of active smoking on HBsAg seroclearance (SC) and its impact on peripheral blood lymphocytes in patients with CHB infection. Longitudinal follow-up data was retrieved in 7833 antiviral-treated CHB subjects identified from a centralised electronic patient record database (Part 1). Phenotypic analysis of peripheral blood mononuclear cells (PBMCs) from 27 CHB-infected patients (6 active smokers; 13 with SC) was performed by flow cytometry to assess programmed death-1 (PD-1) expression and proportion of regulatory T cells (CD4+CD25+CD127lo). Effector function of HBV-specific T cells was examined by comparing granzyme B (GZMB) and transforming growth factor beta (TGFß) production in undepleted PBMCs and Treg-depleted PBMCs after 7 days in vitro stimulation with HBV envelope protein overlapping peptides (Part 2). Over a median follow-up of 5 years, smoking was associated with lower probability of SC (aHR 0.70, 95% CI 0.57-0.87). PD-1 expression was increased in CD4+T cells, CD8+T cells and CD20+B cells among smokers compared to non-smokers and positively correlated with pack years (all p < 0.05). Treg depletion led to partial functional recovery of HBV-specific T cells, with significantly bigger magnitude in smokers (p = 0.0451, mean difference = 4.68%) than non-smokers (p = 0.012, mean difference = 4.2%). Cigarette smoking is associated with lower chance of HBsAg seroclearance, higher PD-1 expression on lymphocytes, and impairment of effector functions of HBV-specific T cells in CHB.

Approximate maximum likelihood estimation in cure models using aggregated data, with application to HPV vaccine completion.

Research into vaccine hesitancy is a critical component of the public health enterprise, as rates of communicable diseases preventable by routine childhood immunization have been increasing in recent years. It is therefore important to estimate proportions of "never-vaccinators" in various subgroups of the population in order to successfully target interventions to improve childhood vaccination rates. However, due to privacy issues, it may be difficult to obtain individual patient data (IPD) needed to perform the appropriate time-to-event analyses: state-level immunization information services may only be willing to share aggregated data with researchers. We propose statistical methodology for the analysis of aggregated survival data that can accommodate a cured fraction based on a polynomial approximation of the mixture cure model log-likelihood function relying only on summary statistics. We study the performance of the method through simulation studies and apply it to a real-world data set from a study examining reminder/recall approaches to improve human papillomavirus (HPV) vaccination uptake. The proposed methods may be generalized for use when there is interest in fitting complex likelihood-based models but IPD is unavailable due to data privacy or other concerns.

Outcome of Primary Hyperparathyroidism: Retrospective Tertiary Center Experience From Basrah, Iraq.

BACKGROUND: Primary hyperparathyroidism is regarded as a common endocrine disorder that is biochemically identified and could be symptomatic or asymptomatic. A detailed history and a thorough evaluation with regular follow-ups are required until a definite diagnosis is made. The study aims to evaluate the characteristics of patients and the performance of a tertiary endocrine center in managing the disease in Basrah, Iraq. MATERIAL AND METHODS: A retrospective study was conducted at the Faiha Specialized Diabetes, Endocrine, and Metabolism Center in Basrah, southern Iraq, on 106 patients diagnosed with primary hyperparathyroidism between 2012 and 2023. The patients' general characteristics were assessed, and those who underwent parathyroidectomy were evaluated post-surgery, and the cure rate was determined. RESULTS: The mean age of presentation was 47.5 ± 14.6 years, with a median of 50 years. The highest occurrence is in the sixth decade. Females comprised 79 (75%) of the patients, and the female-to-male ratio was 3:1. Symptomatic patients were 84 (90%), 30 (70%) of the patients had nephrolithiasis, and 52 (68%) had osteoporosis. The cure rate was 15 (83%). CONCLUSION: In our single-center study, the frequency of primary hyperparathyroidism has increased with time. The disease's highest occurrence was seen in the sixth decade. Females were substantially higher than males. Most patients were symptomatic. The cure rate was 83%.

Evaluation of Radiant Power of the Light Curing Units Used in Clinics at Governmental and Privates Dental Faculties.

Background:  To evaluate the radiant power of the light cure units (LCUs) in relation to their type, radiant exitance, number of years in clinical use, and condition of LCUs tips in governmental and public clinics in Dental Faculties in Sana'a City. Materials and Methods: LCUs were collected from different colleges at Sanaa City, Yemen, then LCU data as type, clinical age (<1 year, between 1-5 and ˃ 5-years), tip condition was visually inspected for damage and adhering debris, and the radiant exitance values of the tested LCUs. Radiant exitance values were subcategorized into three groups: <400, 400-850, and >850 mW/cm², labeled as inadequate, marginal, and adequate radiant exitances, respectively. A Woodpecker radiometer was used with a mode lasting of 20 seconds was used with each LCU. Descriptive statistics of the different parameters were evaluated with SPSS version 25. One-way ANOVA and Mann-Whitney tests were performed to determine the mean difference between the groups with a significance value of ˂ 0.05 was considered. Results: Two hundred twenty-three LCUs were surveyed, and the majority were Light-emitting diode (LED). Forty-nine (21.9%), 117 (52.4%), 57 (25.6%) recorded lesser than, 400-850, and more than 850 mW/cm², respectively. Radiant exitances of < year-old units were found to be higher than those of units used for ˃ 5 years with significant differences (p=0.001). The ANOVA test showed significant differences between the radiant exitance with clinical age and LCU tip conditions and a strong correlation p ˃ 0.050. Conclusion: LED curing lights were the most used in the tested Dental Faculties. More than half of the used LCU offered sufficient radiant exitance. Clinical age, the presence or absence of composite buildups, and damage to curing tips showed significantly affect radiant exitance values.

A New Mixture Model With Cure Rate Applied to Breast Cancer Data.

We introduce a new modelling for long-term survival models, assuming that the number of competing causes follows a mixture of Poisson and the Birnbaum-Saunders distribution. In this context, we present some statistical properties of our model and demonstrate that the promotion time model emerges as a limiting case. We delve into detailed discussions of specific models within this class. Notably, we examine the expected number of competing causes, which depends on covariates. This allows for direct modeling of the cure rate as a function of covariates. We present an Expectation-Maximization (EM) algorithm for parameter estimation, to discuss the estimation via maximum likelihood (ML) and provide insights into parameter inference for this model. Additionally, we outline sufficient conditions for ensuring the consistency and asymptotic normal distribution of ML estimators. To evaluate the performance of our estimation method, we conduct a Monte Carlo simulation to provide asymptotic properties and a power study of LR test by contrasting our methodology against the promotion time model. To demonstrate the practical applicability of our model, we apply it to a real medical dataset from a population-based study of incidence of breast cancer in São Paulo, Brazil. Our results illustrate that the proposed model can outperform traditional approaches in terms of model fitting, highlighting its potential utility in real-world scenarios.

Link workers' and clients' perspectives on how social prescribing offers a social cure for loneliness.

Social prescribing is a healthcare model designed to reduce loneliness and improve individuals' health by addressing unmet social needs. The present study adopted the Social Cure framework to provide an understanding of the psychosocial processes involved in helping participants to engage with social activities, from both the link workers' and clients' perspectives. Semi-structured interviews were conducted with 15 link workers (Mage = 40.12; 87% female) and 15 clients (Mage = 55.33; 73% female, 7% non-binary) of social prescribing programmes across Australia and the transcripts were analysed using reflexive thematic analysis. Three overarching themes were identified: (1) Breaking Down Barriers, (2) Finding Fit with Others, and (3) Rebuilding a Sense of Self. These findings communicate how social prescribing addressed the psychosocial barriers of clients, and how joining groups that fostered positive shared social identities resulted in meaningful improvements to clients' well-being.

Functional cure induced by tenofovir alafenamide plus peginterferon-alpha-2b in young children with chronic hepatitis B: a case series study.

BACKGROUND AND AIMS: Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α. METHODS: In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored. RESULTS: As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment. CONCLUSIONS: TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB.

Self-Correcting Method for Highly Effective Office-Based Helicobacter pylori Therapy Using Cumulative Test of Cure Data.

BACKGROUND AND AIM: Helicobacter pylori infections have become resistant to many previously highly effective antimicrobial regimens resulting in clarithromycin, metronidazole, or fluoroquinolone-containing therapies becoming unsuccessful. Pretreatment susceptibility testing is only widely available in the United States but is still rarely done. Here, we propose a framework to monitor H. pylori eradication in small clinical settings by routinely assessing the effectiveness of therapy. METHODS: Because of the small sample size in individual practice's, we assume an acceptable cure rate of ≥80% (preferred cure rate ≥85%) in adherent patients, with a dichotomous outcome (cured vs. failed) and consecutive patient enrollment. To obtain results (feedback) in a timely manner, for individual practices, cure rates can be estimated after 10 patients. Large practices which acquire patients more rapidly can delay analysis until a total of 104 H. pylori-infected patients, assuming a baseline cure rate of at least 85% with the preferred regimen. RESULTS: We show how data from individual practices can be utilized to improve the effectiveness of H. pylori treatment decisions. The method consists of recording and accumulating the confirmation of cure data for successive small groups of patients. These data are then analyzed as binary outcomes (pass-fail) and serve as the basis for studying and improving the effectiveness of H. pylori treatment decisions. CONCLUSION: A simple actuarial method can serve outpatient clinics to ensure a reliable test-to-cure method and avoid futile Hp regimens.

Sample size calculation for mixture cure model with restricted mean survival time as a primary endpoint.

It is not uncommon for a substantial proportion of patients to be cured (or survive long-term) in clinical trials with time-to-event endpoints, such as the endometrial cancer trial. When designing a clinical trial, a mixture cure model should be used to fully consider the cure fraction. Previously, mixture cure model sample size calculations were based on the proportional hazards assumption of latency distribution between groups, and the log-rank test was used for deriving sample size formulas. In real studies, the latency distributions of the two groups often do not satisfy the proportional hazards assumptions. This article has derived a sample size calculation formula for a mixture cure model with restricted mean survival time as the primary endpoint, and did simulation and example studies. The restricted mean survival time test is not subject to proportional hazards assumptions, and the difference in treatment effect obtained can be quantified as the number of years (or months) increased or decreased in survival time, making it very convenient for clinical patient-physician communication. The simulation results showed that the sample sizes estimated by the restricted mean survival time test for the mixture cure model were accurate regardless of whether the proportional hazards assumptions were satisfied and were smaller than the sample sizes estimated by the log-rank test in most cases for the scenarios in which the proportional hazards assumptions were violated.

A New Approach to Modeling the Cure Rate in the Presence of Interval Censored Data.

We consider interval censored data with a cured subgroup that arises from longitudinal followup studies with a heterogeneous population where a certain proportion of subjects is not susceptible to the event of interest. We propose a two component mixture cure model, where the first component describing the probability of cure is modeled by a support vector machine-based approach and the second component describing the survival distribution of the uncured group is modeled by a proportional hazard structure. Our proposed model provides flexibility in capturing complex effects of covariates on the probability of cure unlike the traditional models that rely on modeling the cure probability using a generalized linear model with a known link function. For the estimation of model parameters, we develop an expectation maximization-based estimation algorithm. We conduct simulation studies and show that our proposed model performs better in capturing complex effects of covariates on the cure probability when compared to the traditional logit link-based two component mixture cure model. This results in more accurate (smaller bias) and precise (smaller mean square error) estimates of the cure probabilities, which in-turn improves the predictive accuracy of the latent cured status. We further show that our model's ability to capture complex covariate effects also improves the estimation results corresponding to the survival distribution of the uncured. Finally, we apply the proposed model and estimation procedure to an interval censored data on smoking cessation.

Regression of liver fibrosis after HBsAg loss: A prospective matched case-control evaluation using transient elastography and serum enhanced liver fibrosis test.

BACKGROUND AND AIM: We assessed the effect of hepatitis B surface antigen (HBsAg) seroclearance (HBsAg-loss) on liver fibrosis regression in patients with chronic hepatitis B (CHB) infection. METHOD: CHB patients with recent documented HBsAg-loss were age- and gender-matched with treatment-naïve HBeAg-negative CHB infection. Paired assessment with transient elastography and enhanced liver fibrosis (ELF) measurements were performed and repeated at 3 years. Fibrosis regression was arbitrarily defined as decrease in ≥ 1 fibrosis stage by ELF, or combining with reduction > 30% in liver stiffness. RESULTS: A total of 142 HBsAg-loss and 142 CHB subjects were recruited (median age 58.1 years, 51.4% male). A total of 1.8% (1.4% HBsAg-loss vs 2.1% CHB) achieved combined endpoint of fibrosis regression at 3 years. When ELF-only definition of fibrosis regression was used, 14.5% HBsAg-loss and 16.9% CHB subjects achieved this endpoint, which was significantly associated with baseline ELF (hazard ratio (HR) 1.827, 95% confidence interval (CI) 1.085-3.075) and time since HBsAg-loss (HR 2.688, 95% CI 1.257-5.748). While increasing time since HBsAg-loss increased the proportion of ELF-defined fibrosis regression, increasing age was also associated with significant fibrosis. Age of achieving HBsAg-loss (ageSC) was independently associated with high baseline ELF values. Up to 52.3% and 63.8% subjects with ageSC > 50 had advanced fibrosis/cirrhosis at baseline and 3 years, respectively, compared with 5.9% and 20.6% in subjects with ageSC < 50. CONCLUSION: Fibrosis regression occurred in a minority of subjects achieving HBsAg-loss, which was not significantly different compared with subjects with persistent overt CHB. Subjects after achieving HBsAg-loss, especially among those with ageSC > 50, should receive ongoing surveillance for liver-related complications.

A high functional cure rate was induced by pegylated interferon alpha-2b treatment in postpartum hepatitis B e antigen-negative women with chronic hepatitis B virus infection: an exploratory study.

Background and aims: Limited data have been reported on achieving functional cure using pegylated interferon (Peg-IFN) alpha-2b treatment for postpartum hepatitis B e antigen (HBeAg)-negative women with chronic hepatitis B virus (HBV) infection. This study was to assess the effectiveness and safety of Peg-IFN alpha-2b in HBV postpartum women without HBeAg and identify factors linked to the functional cure. Methods: A total of 150 HBeAg-negative postpartum women were retrospectively recruited.47 patients received Peg-IFN alpha-2b [Peg-IFN(+) group] and 103 patients did not [Peg-IFN(-) group]. Propensity score matching (PSM) was used to adjust the baseline imbalance between the two groups. The patients were followed for at least 48 weeks. The primary endpoints were hepatitis B surface antigen(HBsAg) loss and HBsAg seroconversion at 48 weeks. Logistic regression analysis was used to assess factors associated with HBsAg loss at 48 weeks. Results: At week 48,the HBsAg loss and seroconversion rate in Peg-IFN(+) group were 51.06%(24/47) and 40.43%(19/47), respectively. Even after PSM, Peg-IFN(+) group still showed higher HBsAg loss rate (50.00% vs 7.14%,p<0.001) and higher HBsAg seroconversion rate (38.10% vs 2.38%,p<0.001). Baseline HBsAg levels (Odds Ratio [OR]: 0.051, 95% Confidence Interval [CI]: 0.003-0.273, P=0.010), HBsAg at week 24 (OR:0.214, 95%CI:0.033-0.616, P=0.022), HBsAg decline at week 24 (OR:4.682, 95%CI: 1.624-30.198, P=0.022) and postpartum flare (OR:21.181, 95%CI:1.872-633.801, P=0.030) were significantly associated with HBsAg loss at week 48 after Peg-IFN alpha-2b therapy. Furthermore, the receiver operating characteristic curve (ROC) showed that the use of baseline HBsAg<182 IU/mL, HBsAg at week24 < 4 IU/mL and HBsAg decline at week24>12IU/mL were good predictors of HBsAg loss. No serious adverse events were reported. Conclusion: Peg-IFN alpha-2b treatment could achieve a high rate of HBsAg loss and seroconversion in HBeAg-negative postpartum women with reliable safety, particularly for patients experience postpartum flare and have low baseline HBsAg levels.

Near-cure in patients with Gadolinium deposition disease undergoing intravenous DTPA chelation.

Purpose: To demonstrate and evaluate factors contributing to near-cures in patients with Gadolinium Deposition Disease (GDD) undergoing intravenous (IV) DTPA chelation. Methods: Patients who had undergone or are currently undergoing DTPA chelation for GDD were included in this report based on their medical records that showed their perceived improvement was at least 80% back to normal. A survey was developed that included factors commonly reported by patients treated in one clinic to determine if these 'near-cured' (pre-MRI baseline health) individuals possessed certain factors and lacked others. The anonymized survey was emailed to these individuals by the principal treating physician, the only investigator not blinded to the subjects. This report describes clinical documentation of patient status and their underlying factors in individuals treated by the primary author, and no research was performed. The survey was sent to sixteen individuals; Fourteen patients completed it (10 females; 41.1 ± 11.2 y/o). Results: The most common factor was the administration of ≤5 lifetime doses of a Gadolinium-Based Contrast Agents (GBCA) (12/14). Unconfounded agents triggering GDD were seen in nine subjects. Most subjects (12/14) initiated chelation in the first year after the causative GBCA, and most (11/14) underwent ≤10 chelations with DTPA. Good healthcare status prior to MRI was observed in 5 subjects. The majority (11/14) described their immune status as strong. Severe physical disability prior to chelation was seen in 1. Conclusion: Subjects with GDD can experience near-cure with IV DTPA chelation. Factors surveyed that predict near-cure include the start of chelation in the first year, few GBCA administrations, and good health status before MRI with GBCA injection. Nonetheless, a few patients with predictors of less successful outcomes still experienced near-cure.

Correlation between Dental Composite Filler Percentage and Strength, Modulus, Shrinkage Stress, Translucency, Depth of Cure and Radiopacity.

Filler content in dental composites is credited for affecting its physical and mechanical properties. This study evaluated the correlation between the filler percentage and strength, modulus, shrinkage stress, depth of cure, translucency and radiopacity of commercially available high- and low-viscosity dental composites. Filler weight percentage (wt%) was determined through the burned ash technique (800 °C for 15 min). Three-point bend flexural strength and modulus were measured according to ISO 4049 with 2 mm × 2 mm × 25 mm bars. Shrinkage stress was evaluated using a universal testing machine in which composite was polymerized through two transparent acrylic rods 2 mm apart. Shrinkage was measured from the maximum force following 500 s. The translucency parameter (TP) was measured as the difference in color (ΔE00) of 1 mm thick specimens against white and black tiles. The depth of cure was measured according to ISO 4049 in a cylindrical metal mold (4 mm diameter) with a 10 s cure. Radiopacity was measured by taking a digital X-ray (70 kVp for 0.32 s at 400 mm distance) of 1 mm thick specimens and comparing the radiopacity to an aluminum step wedge using image analysis software. The correlation between the filler wt% and properties was measured by Pearson's correlation coefficient using SPSS. There was a positive linear correlation between the filler wt% and modulus (r = 0.78, p < 0.01), flexural strength (r = 0.46, p < 0.01) and radiopacity (r = 0.36, p < 0.01) and negative correlation with translucency (r = -0.29, p < 0.01). Filler wt% best predicts the modulus and strength and, to a lesser extent, the radiopacity and translucency. All but two of the high- and low-viscosity composites from the same manufacturer had statistically equivalent strengths as each other; however, the high-viscosity materials almost always had a statistically higher modulus. For two of the flowable composites measured from the same manufacturer (3M and Dentsply), there was a lower shrinkage stress in the bulk-fill version of the material but not for the other two manufacturers (Ivoclar and Tokuyama). All flowable bulk-fill composites achieved a deeper depth of cure than the flowable composite from the same manufacturer other than Omnichroma Flow Bulk.

Predictors of functional cure of chronic hepatitis B virus infection - A long-term follow-up study.

BACKGROUND & AIMS: Functional cure is an essential endpoint in the management of patients with chronic hepatitis B virus (HBV) infection. We evaluated the cumulative probability and predictors of functional cure in patients with chronic HBV infection after hepatitis B e antigen (HBeAg)-seroconversion. METHODS: We retrospectively analyzed 413 (249 males and 164 females) initially HBeAg-positive chronic HBV-infected patients, who were followed up for a mean of 26.36 ± 0.53 years. All underwent HBeAg-seroconversion during follow-up. A functional cure was defined as durable HBsAg and HBV DNA loss without antiviral treatment for more than 24 weeks. RESULTS: After 10,888 person-years of follow-up, the cumulative probability of functional cure was 14.53% (n = 60). There were 24 (40%) subjects with functional cure after antiviral therapy. The annual functional cure rate was 0.55% per perperson-year, and increased to 0.96% per person-year after HBeAg-seroconversion. In subjects with functional cure, the HBsAg and HBV DNA titers after HBeAg-seroconversion were positively correlated with the time to functional cure (P < .001 and < .001, respectively). Multivariate Cox proportional hazard analysis of the cohort revealed that HBeAg-seroconversion at < 18 years of age, high genetic barrier nucleos(t)ide analogue(s) therapy before HBeAg-seroconversion, and a serum HBsAg titer < 1,000 IU/mL at 18 months after HBeAg-seroconversion were significant predictors of functional cure (P < .001, .001, and .001, respectively). CONCLUSIONS: In a cohort of chronic HBV-infected patients with long-term follow-up, HBeAg-seroconversion in childhood, high genetic barrier nucleos(t)ide analogue(s) therapy, and low HBsAg titers after HBeAg-seroconversion were significant predictors of functional cure.

Long-Term Observation of Prognostic Factors and Clinical Outcome of Vernal Keratoconjunctivitis in Childhood.

Purpose: Vernal keratoconjunctivitis (VKC) is a refractory ocular allergic disorder that mainly affects boys. Long-term follow-up has been rarely reported for VKC. We investigated the long-term clinical outcome of VKC to identify relevant clinical features of prognostic value based on follow-up for a median of 70 months. Methods: In total, 45 consecutive patients clinically diagnosed with VKC aged 4 to 12 years at onset at the Department of Ophthalmology of Fukuoka University Hospital were included. Patients were treated with immunosuppressive eye drops without simultaneous corticosteroid eye drops, except for the occurrence of exacerbations. Collated variables were gender, age at onset, clinical score of ocular lesions (conjunctival giant papillae, limbal edema and corneal epithelial lesions) at the first visit, and clinical score of atopic dermatitis (AD) at baseline. Cumulative cure rate was estimated using Kaplan-Meier method. A binomial logistic predictive model was used to determine the most reliable clinical predictors of VKC outcome. Results: The observation period ranged from 24 to 188 months, with median of 70 months. Among the 45 cases enrolled, all non-cured cases (14 cases) observed clinically were complicated by AD. Cumulative cure rate was 74.5% and 84.9% at eight- and ten-year follow-up, respectively. Ten-year cumulative cure rates of cases with and without AD were 50.5% and 100%, respectively, and a significant difference was found between these cumulative cure curves. Binomial regression analysis revealed that AD and gender were significantly related to worse outcome, and this binomial regression model had high sensitivity and specificity. Conclusion: This study demonstrated that th eclinical outcomeof VKC might be predicted by several factors that can beobtained in the early clinical phase. Information on the long-term prognosis of VKC patients might play an important role for precision medicine for VKC in childhood.

Radiobiological analysis of VMAT treatment plan with flattened and flattening filter free photon beam: an EUD and TCP based comparative study.

Background: This study aimed to evaluate the dosimetric and radiobiological differences between 6MV flattened filter (FF) and flattening filter free (FFF) using volumetric modulated arc (VMAT) technique for head and neck (H&N) cancer patients. Materials and methods: Fifteen patients with H&N carcinoma were selected and treated with VMAT with FF (VMATFF) treatment plan. Retrospectively, additional VMAT treatment plans were developed using FFF beams (VMATFFF). Radiobiological parameters, such as equivalent uniform dose (EUD), tumor cure probability (TCP), and normal tissue complication probability (NTCP), were calculated using Niemierko's model for both VMATFF and VMATFFF. Correlation between dosimetric and radiobiological data were analyzed and compared. Results: The conformity index (CI) was 0.975 ± 0.014 (VMATFF) and 0.964 ± 0. 019 (VMATFFF) with p ≥ 0.05. Statistically, there was an insignificant difference in the planning target volume (PTV) results for TCP (%) values, with values of 81.20 ± 0.88% (VMATFF) and 81.01 ± 0.92 (%) (VMATFF). Similarly, there was an insignificant difference in the EUD (Gy) values, which were 71.53 ± 0.33 Gy (VMATFF) and 71.46 ± 0.34 Gy (VMATFFF). The NTCP values for the spinal cord, left parotid, and right parotid were 6.54 × 10-07%, 8.04%, and 7.69%, respectively, in the case of VMATFF. For VMATFFF, the corresponding NTCP values for the spinal cord, parotids left, and parotid right were 3.09 × 10-07%, 6.57%, and 6.73%, respectively. Conclusion: The EUD and Mean Dose to PTV were strongly correlated for VMATFFF. An increased mean dose to the PTV and greater TCP were reported for the VMATFF, which can enhance the delivery of the therapeutic dose to the target.