Prior Treatment History Research Articles

Guselkumab Efficacy by Psoriasis Disease Severity and Treatment History: VOYAGE 1 and 2 Post Hoc Analyses.

The pivotal Phase 3 VOYAGE 1 and VOYAGE 2 studies established the robust efficacy and safety of guselkumab for up to 5 years in patients with moderate-to-severe psoriasis. Here, the long-term efficacy of guselkumab by baseline disease severity and treatment history was analyzed using pooled data from the VOYAGE studies. Patients were randomized to guselkumab 100 mg every 8 weeks, placebo with week 16 crossover to guselkumab, or adalimumab with week 52 crossover to guselkumab (VOYAGE 1) or week 28-76 randomized withdrawal/re-treatment (VOYAGE 2); all patients then received open-label guselkumab through week 252. These post hoc analyses evaluated the Investigator’s Global Assessment of cleared/minimal (IGA 0/1) and Psoriasis Area and Severity Index (PASI) 90 responses from week 100-252 by baseline PASI (<20/≥20), IGA (=3/=4), body surface area (BSA; <20%/≥20%), and prior psoriasis treatments. Analyses used observed data after applying treatment failure rules. At all assessment timepoints from weeks 100-252, response rates were similar by baseline PASI <20 vs ≥20 (IGA 0/1: 82.0%-85.4% vs 81.1%-81.4%; PASI 90: 78.6%-81.1% vs 81.4%-83.8%), IGA=3 vs =4 (IGA 0/1: 82.7%-85.4% vs 77.6%-79.0%; PASI 90: 79.1%-82.7% vs 79.7%-82.9%), BSA <20% vs ≥20% (IGA 0/1: 82.5%-86.2% vs 81.1%-82.6%; PASI 90: 80.4%-82.7% vs 79.1%-82.0%), prior phototherapy no vs yes (IGA 0/1: 81.7%-84.3% vs 81.5%-83.8%; PASI 90: 82.2%-84.0% vs 77.5%-81.1%), prior nonbiologic use no vs yes (IGA 0/1: 81.1%-84.5% vs 81.9%-84.1%; PASI 90: 80.9%-83.0% vs 79.0%-82.0%), and prior biologic use no vs yes (IGA 0/1: 83.2%-85.3% vs 75.3%-79.5%; PASI 90: 82.2%-83.8% vs 71.2%-76.3%). Durable guselkumab efficacy was sustained through 5 years of treatment among patient subpopulations irrespective of baseline disease severity or prior treatment history. J Drugs Dermatol. 2025;24(2):196-202. doi:10.36849/JDD.8344.

Association between ex vivo pharmacotyping of patient-derived tumor organoids and personalized therapeutic options for patients with biliary tract cancer.

618 Background: Biliary tract cancers (BTC), including cholangiocarcinomas and gallbladder adenocarcinomas, present significant therapeutic challenges due to limited treatment options and poor prognoses. We report findings from the CLIA-certified PARIS assay, evaluating drug sensitivities of patient-derived tumor organoids (PDTOs) to a panel of oncology drugs. Methods: PDTOs were successfully cultured from 27 out of 46 live tumor samples obtained from 43 BTC patients. The majority of patients presented with advanced metastatic disease (60% stage IV, 13% stage III, 10% stage II, 4.4% stage I, 10% unknown) and had exhausted standard therapeutic options. Each PDTO culture underwent testing against an average of 50 drugs, encompassing chemotherapeutic agents and targeted therapies. Results: Comparative analysis of PDTO drug sensitivities with patients' prior treatment histories revealed non-responsiveness to >80% of drugs associated with clinical progression, including gemcitabine, cisplatin, and targeted therapies for FGFR translocations. In contrast, 100% (26/26) of the samples demonstrated significant sensitivity to one or more targeted agents, particularly inhibitors of EGFR, MEK, ERK, mTOR, PI3K, MDM2, BCL2, and BET families. Despite these shared sensitivities, each individual PDTO culture exhibited unique responses to targeted therapies, highlighting the genetic and phenotypic diversity between BTC patients. Comparison of ex vivo drug sensitivities with tumor genomic profiles validated oncogenic drivers such as HER2 amplification, KRAS and PIK3CA pathogenic mutations, correlating with sensitivities to EGFR/HER2 inhibitors, MEK inhibitors, and PI3K inhibitors, respectively. While mutations in KRAS , BRAF , BRCA1 , BRCA2 , ERBB2 , ERBB3 , or MET are present in less than 8% of cases, their role as biomarkers in BTCs requires further validation. PDTOs offer a promising tool to expedite this validation process. The PARIS assay results guided treatment decisions for five patients with metastatic disease, two of whom maintained treatment for over 4 weeks. Notably, two patients showed clinical benefit with everolimus (5 weeks) and dasatinib (11 weeks), experiencing symptom relief and reduced ascites. Intriguingly, 5 out of 7 PDTOs with FGFR alterations exhibited exceptional PARIS test responses to dasatinib, suggesting potential efficacy linked to FGFR activation. Conclusions: In conclusion, our study demonstrates that ex vivo drug testing of PDTO cultures can inform treatment selection and potentially accelerate drug approvals for BTC, leveraging therapies approved for other cancers. Early integration of such assays in patient management, possibly at diagnosis, holds promise for improving outcomes in this challenging disease.

P0880 Sphingosine 1-phosphate (S1P) Receptor Modulators for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract Background Ulcerative colitis (UC) is a chronic autoimmune inflammatory disease of the colon, classified as mild, moderate, or severe. Conventional treatments, including corticosteroids and thiopurines, are effective for mild to moderate disease, while biologics and small molecules are used for more severe cases. Previous studies have shown the benefits of Sphingosine-1-phosphate (S1P) receptor modulators in UC, but their efficacy in specific patient subgroups remains unclear. This meta-analysis aims to evaluate the efficacy of S1P receptor modulators in achieving clinical remission in UC patients, focusing on prior treatment history, including corticosteroid and TNF-alpha inhibitor use. Methods We searched PubMed, Embase, Cochrane, and ClinicalTrials.gov in August 2024 for clinical trials assessing the efficacy of S1P receptor modulators in UC patients, comparing them to placebo. A random-effects model was used for this meta-analysis and RStudio software was used for statistical analysis. Results Four clinical trials were included1,2,3, comprising 1,670 patients with UC. Two studies evaluated ozanimod, and three evaluated etrasimod. Compared to placebo, S1P inhibitors were effective in achieving clinical remission in patients with corticosteroid (CS) use at baseline (RD 0.1; 95% CI 0.04-0.17; Figure 1A), in those without CS use at baseline (RD 0.21; 95% CI 0.11-0.31; Figure 1B), and in those with no prior TNF-alpha inhibitor use (RD 0.19; 95% CI 0.12-0.26; Figure 2B). Data for patients with prior TNF-alpha inhibitor use were available in only two trials, showing a trend toward efficacy (RD 0.07; 95% CI -0.00 to 0.13; Figure 2A), but statistical significance was not reached. Conclusion S1P receptor modulators are effective in achieving clinical remission in UC patients, including those without prior TNF-alpha inhibitor use, as well as in patients with or without corticosteroid use at baseline.

Trends in screening and treatment of osteoporosis after periprosthetic fractures from 2010 to 2020.

Periprosthetic fractures (PPF) typically occur from low-energy mechanisms and are pathognomonic for osteoporosis. However, osteoporosis is often underrecognized and undertreated. The aim of this study was to examine trends in dual energy X-ray absorptiometry (DXA) scans and treatment of osteoporosis after PPF between 2010 and 2020. Patients older than 40 who experienced a lower extremity PPF between 2010 and 2020 and had no prior history of osteoporosis screening or treatment were identified utilizing a large national administrative database. Rates of bone mineral density (BMD) measurement using DXA and anti-osteoporotic treatment with pharmacotherapy, or either intervention within 1year following experiencing a PPF were determined. The rate of change for these interventions was calculated using the compounded annual growth rate (CAGR), with linear regression used to determine whether trends were statistically significant. In total, 5.7% and 3.6% of patients were screened and treated for osteoporosis, respectively. Between 2010 and 2020, there was no significant change in rates of osteoporosis screening (CAGR + 0.1%; p = 0.13), treatment (CAGR - 2.4%; p = 0.29), or either intervention (CAGR - 1.1%; p = 0.77) within 1year following PPF. Factors associated with intervention included older age, female sex, and increased comorbidities. Our study found that there has been no significant change in the rates of osteoporosis screening or treatment within 1year following PPF. Orthopedic surgeons and allied healthcare workers can play an integral role in helping to curtail the osteoporosis epidemic.

Phase Ib study of SCT200 combined with paclitaxel or docetaxel in patients with recurrent or metastatic head and neck squamous cell carcinoma following platinum-based chemotherapy and PD-1 antibody.

Treatment options for recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) are limited, especially for patients who progress after immune checkpoint inhibitor (ICI) therapy. This phase Ib study investigates the efficacy and safety of SCT200, an epidermal growth factor receptor (EGFR) antibody, combined with paclitaxel or docetaxel in R/M HNSCC patients who have failed both platinum-based chemotherapy and programmed cell death protein 1 (PD-1) inhibitors. This was a multicenter, open-label study enrolling patients with resistance or intolerance to platinum-based chemotherapy and PD-1 inhibitors. Patients received intravenous SCT200 (6mg/kg weekly for 12 weeks, followed by 8mg/kg every two weeks). Paclitaxel (80mg/m2 weekly) or docetaxel (75mg/m2 every three weeks) was administered according to the patient's prior paclitaxel treatment history. The primary endpoint was objective response rate (ORR). Thirty patients were included in the efficacy and safety analyses. The ORR was 26.7% (95% confidence interval [CI]: 12.3-45.9). The median progression-free survival (PFS) was 4.1 months (95% CI: 2.7-5.7), and the median overall survival (OS) was 8.7 months (95% CI: 5.0-11.9). For patients receiving SCT200 with docetaxel, median PFS was 5.7 months, and OS was 9.5 months. Common adverse events (AEs) included hypomagnesemia, acneiform dermatitis, and rash. No unexpected safety signals were observed. SCT200 in combination with paclitaxel or docetaxel shows promising efficacy in patients with R/M HNSCC following platinum-based chemotherapy and PD-1 inhibitors, warranting further investigation. ClinicalTrials.gov identifier: NCT05552807.

Comparing Level of Happiness and Depression Between Turkish and International Medical Students

This cross-sectional study was aimed to compare happiness and depression levels among group Turkish and international medical students in Istanbul, Turkey. Data were collected through an online survey that included demographic inquiries, the Oxford Happiness Scale, and Beck’s Depression Inventory II. Significant contrasts emerged in demographic and lifestyle factors between Turkish and international students. Turkish medical students displayed a higher prevalence of unhappiness, although this difference was not statistically significant (66.3% for Turkish students vs. 59.1% for international students; χ² = 2.472, p = 0.116). Conversely, no marked differences were observed in the severity of depression between the two groups (χ² = 0.028, p = 0.986). Conversely, no marked differences were observed in the severity of depression between the two groups (χ2 = 0.028, p = 0.986). Logistic regression analyses revealed noteworthy associations. Factors such as age, academic phase, family history of psychiatric illness, and prior psychiatry treatment were linked to heightened odds of experiencing unhappiness among students. Similarly, significant predictors of depression included a family history of depression and prior psychiatry treatment. However; gender, age, relationship status, accommodation, alcohol consumption, smoking habits, and repeated academic years did not exhibit significant associations with unhappiness among the sampled medical students. While the models demonstrated modest explanatory power, these findings emphasize the urgent need to address mental health issues among medical students. Tailored interventions targeting specific vulnerable subgroups are crucial and further research is needed to identify additional factors contributing to psychological distress in this demographic.

LATE PRESENTATION OF STROKE PATIENTS TO TERTIARY CARE HOSPITALS THE UNDERLYING REASONS

Background: Stroke is a major neurological emergency and a leading cause of morbidity and mortality worldwide. Timely hospital presentation is crucial for effective treatment, including intravenous thrombolysis and endovascular therapy, both of which significantly improve outcomes. However, delays in hospital presentation remain prevalent, especially in resource-limited settings, due to socioeconomic, logistical, and awareness-related factors. Understanding these barriers is essential for implementing effective interventions to reduce prehospital delays and improve stroke care outcomes. Objective: To evaluate the awareness and knowledge of stroke patients and their companions presenting to a tertiary care hospital and to identify the common causes of prehospital delays. Methods: This cross-sectional retrospective study was conducted at Sheikh Zayed Hospital, Lahore, over six months, including 200 patients with ischemic or hemorrhagic stroke who met the inclusion criteria. Data were collected on variables such as age, sex, time since last known well (LKW), education level, knowledge of stroke symptoms, availability of transportation, lifestyle (urban or rural), and history of prior treatment. Patients younger than 18 or with non-stroke neurological conditions were excluded. Data were analyzed using SPSS version 25, with descriptive and inferential statistics calculated. The Chi-square test was applied to identify statistically significant associations. Results: The mean age of participants was 60.1 ± 18.5 years, with ischemic stroke comprising 76% (n = 152) of cases and hemorrhagic stroke 24% (n = 48). Among the cohort, 55% (n = 110) presented early (within 4 hours), while 45% (n = 90) presented late. A total of 70% (n = 140) of patients did not recognize stroke symptoms, and 75.3% (n = 151) reported lack of transportation as a barrier. Distance from the hospital affected 40.1% (n = 80) of rural patients, requiring over 45 minutes of travel. A statistically significant association was found between stroke knowledge and timing of hospital presentation (p = 0.013). Conclusion: A considerable proportion of stroke patients presented late to the hospital due to factors such as low literacy, reliance on public transportation, misinterpretation of symptoms, and low perceived severity of their condition. Addressing these barriers through targeted educational programs and systemic healthcare improvements is critical for enhancing timely access to stroke care.

Correlates and Comparability of Two Devices for Measuring Bite Force in Dentate Health Volunteers.

This study aimed to correlate the bite/occlusal force measurements obtained through two methods: a hydraulic pressure gauge with a biting transducer (GM-10), and a computer-assisted device that records occlusal force on a pressure-sensitive film (Prescale II). Healthy, dentate volunteers were recruited. Participants' demographic data included age, sex, number of teeth present, presence of oral pain, history of prior orthodontic treatment and presence of parafunction. Bite/occlusal force measurements were recorded for each participant using the GM-10 and the Prescale II devices. Linear Mixed-effect model regression was performed with the significance set at p < 0.05. Forty-six volunteers (women = 25, men = 21; mean-age = 30.9 ± 9.3 years) participated. 54.3% and 34.8% presented with 28 and 29-32 teeth, respectively. 60.9% and 26.1% of the participants reported previous orthodontic treatment and oral parafunction. The overall mean GM-10 measurements recorded were 333.0 ± 192, 276 ± 167, 208 ± 134, 142 ± 103 Newtons, for the 2nd and 1st molars, 2nd and 1st premolars, respectively. GM-10 measurements were associated with the tooth position (p < 0.001) and the number of teeth (p < 0.001). The mean Prescale II measurements obtained with and without filter were 826 ± 594 and 1049 ± 595 Newtons, respectively, which were positively correlated with the occlusal contact area (r = 0.765; p < 0.001) and GM-10 (r = 0.245; p = 0.019). The regression analysis for dependent repeated data confirmed the significant effect of the GM-10 measurements (bite force) and the occlusal contact area on the Prescale II measurements. Within the limitations of this study, it can be concluded that the correlation between bite force measurements carried out by GM-10 and Dental Prescale II was low and may not be considered interchangeable methods. The maximum bite force measured in isolated point contacts was a predictive factor of the occlusal force distributed over the entire arch. Further studies are warranted to explore this influence in the clinical implications of these findings.

Predictors for choosing doravirine‐based versus INSTI‐based regimen in ART‐naïve and ART‐experienced people with HIV in real‐world setting: Data from the Icona cohort

AbstractRationaleDoravirine (DOR) is an attractive new option both for ART‐naïve people with HIV (PWH) and those with suppressed HIV‐RNA who seek treatment simplification. We used real‐world data to examine the pattern of use of DOR‐containing regimens in these settings.MethodsAll PWH enrolled in the Icona cohort after January 2020 who initiated a three‐drug regimen (3‐DR) with DOR or an integrase inhibitor (INSTI)‐based regimen as first antiretroviral therapy (ART) or when switching ART, with HIV‐RNA ≤50 copies/mL, were included. We used univariate and multivariable logistic regression models to identify demographic factors, immuno‐virological and laboratory markers associated with the prescription of 3‐DR DOR instead of INSTI‐based regimens.ResultsA total of 5803 PWH were included; 1958 were in the first regimen (80 DOR, 1,878 INSTI) and 3854 (387 DOR, 3,458 INSTI) were ART‐experienced virologically suppressed. In the first line, 3‐DR DOR was more frequently started in people who inject drugs, and its use was also associated with higher body mass index, higher low‐density lipoprotein levels, and less advanced HIV disease compared with PWH initiating an INSTI‐based regimen. In the switch setting, older age, Italian origin, higher estimated glomerular filtration rate and aspartate aminotransferase levels were all strongly associated with 3‐DR DOR use, as well as higher a CD4/CD8 ratio (only vs. 3‐DR INSTI), while the association with lipid abnormalities was attenuated.ConclusionsOur analysis shows that among PWH in care in Italy, those with less advanced HIV disease but with other fragilities and potential risk factors for comorbidities are more likely to use DOR‐ than INSTI‐based regimens, regardless of prior treatment history.

Real-Life Use of Filgotinib in Rheumatoid Arthritis: A Retrospective Cohort Study.

Background: Janus kinase inhibitors (JAKis) are a novel class of drugs interfering with intracellular signaling of type I and type II cytokines, which play a crucial role in immune dysregulation associated with several chronic inflammatory diseases. Filgotinib (FIL), in particular, is the newest member of the JAKi class and exerts its therapeutic effects by selectively targeting and inhibiting the kinase activity of JAK1. While the efficacy of FIL in rheumatoid arthritis (RA) has been confirmed in clinical trials, real-world evidence may provide better insights into its effectiveness and safety in routine clinical practice. Methods: We performed a multicenter, retrospective cohort study investigating the real-life effectiveness and safety of FIL in adult patients with RA. Demographic information, disease characteristics, prior treatment history, and comorbid conditions were retrieved from clinical records at baseline (M0) and after 3 (M3) and 6 months (M6) of treatment. Results: A total of 82 patients (63 women) agreed to participate in the study, of whom 39 (47.6%) were older than 65 years. The average RA duration was 13 ± 9 years; 19 patients (23.1%) were current or former smokers, and 4 patients (4.9%) had a history of cardiovascular events. Most patients had previously received at least one biologic disease-modifying antirheumatic drug (range: 1-6+); in addition, 11 patients (13.4%) had been already exposed to another JAKi. During the follow-up, 7 patients discontinued treatment due to primary failure (n = 3) or adverse events (n = 4). Significant reductions in pain and number of tender and swollen joints were observed at M3 and M6. A relevant proportion of patients achieved DAS28-CRP remission at M3 and M6 (46.3% and 66.2%, respectively). Conclusions: Our data provide additional insight into the effectiveness of filgotinib in a real-world setting, even among patients with difficult-to-treat RA and a high prevalence of cardiovascular risk factors.

Evaluation of efficacy of Hemoporfin-PDT in the treatment of PWS birthmarks of young children previously received PDL treatment

Hemoporfin-mediated photodynamic therapy (Hemoporfin-PDT) is considered a safe and effective treatment for port-wine stains (PWS). This study aims to investigate the influence of prior pulse dye laser (PDL) treatments history on the effectiveness of Hemoporfin-PDT in young children aged 1-3 years with PWS. Data was gathered for individuals with PWS aged 1-3 years who received two or more Hemoporfin-PDT treatments. The study population was stratified into two groups: Cohort 1 (No PDL) comprised patients without a history of PDL treatment, while Cohort 2 (Prior PDL) consisted of patients with a history of PDL treatment. An analysis was conducted to investigate the relationship between treatment efficacy and variables including gender, age, location, and type of PWS. There were a total of 220 cases in the No PDL group and 53 cases in the Prior PDL group. It was observed that prior PDL treatment history did not impact the efficacy of Hemoporfin-PDT in treating PWS among young children. Both the type and location of PWS significantly influence the clinical effectiveness of Hemoporfin-PDT for PWS (P = 0.040, P < 0.001), while gender and age show no association with treatment outcomes (P > 0.05). Notably, the peripheral face might be an independent influencing factor for high efficacy of Hemoporfin-PDT of the facial regions (P < 0.05). Previous PDL treatment history does not impact the effectiveness of Hemoporfin-PDT therapy in young children with PWS.

Current treatment approach and future perspectives in B cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) represent the two major subtypes of mature B cell lymphoma. A deeper understanding of tumor biology, as well as molecular classification characterized by targetable gene alterations, and the introduction of novel treatment options, including targeted drugs (e.g., antibody-drug conjugates and small molecules [e.g., Bruton tyrosine kinase inhibitor]) and immune therapies (e.g., chimeric antigen receptor [CAR] T cell therapy and bispecific antibody [BsAb]), has changed the treatment paradigms for DLBCL and FL. In clinical practice, however, treatment regimens are determined mainly based on prior treatment history, duration of response after previous treatment, patient age, and patient frailty because there have been few randomized trials to inform treatment selection for patients with relapsed or refractory disease and because there is no single prognostic index that guides suitable treatment for each patient. In this review, we summarize the treatment options for DLBCL and FL and discuss the treatment strategies for these two subtypes. We also discuss future perspectives for the treatment of these subtypes.

Hepatitis B surface antigen loss in chronic hepatitis B patients with low-viral-load.

Among low viral load (DNA of hepatitis B virus (HBV) was <2000IU/mL), the factor of the loss of hepatitis B surface antigen (HBsAg) remained elusive. The retrospective study recruited patients with chronic hepatitis B (CHB) who were negative low for hepatitis B e-antigen (HBeAg), had a low viral load, and experienced HBsAg loss during follow-up. CHB patients with low-viral load but without consequent HBsAg loss were also enrolled at the ratio of 1:4. The factors contributing to HBsAg loss were analyzed. A total of 80 patients were recruited for the current study, with a mean age of 63.9years and 61.3% being male. Among them, 62.5% patients (50/80) were treated with potent nucleoside/nucleotide analogues (NAs) during the follow-up period. Additionally, 12.5% patients (10/80) had a prior history of NAs treatment before enrolment. During the follow-up, HBsAg loss occurred in 17 patients (21.3%). Compared with patients without HBsAg loss, those with HBsAg loss were younger (57.9years vs 65.5years; P=0.01), had lower HBV DNA levels (1.3 log10 IU/mL vs 2.3 log10 IU/mL; P=0.003), and higher proportion of prior NAs-treated history. Logistic regression analysis revealed that the factors associated with factors associated with HBsAg loss were age <60years (OR/CI: 3.95/1.15-13.60, P=0.03), prior NAs-treated history (OR/CI: 7.59/1.42-40.51, P=0.01) and current NAs-treated (OR/CI: 0.19/0.05-0.71, P=0.01). In the study, older age and prior NAs were positively associated with HBsAg loss, and current NAs was negatively associated with HBsAg loss. Additionally, some patients experienced HBsAg loss during the NAs therapy.

Preliminary investigation of the significance of cavitary lesions in recurrent hemoptysis following bronchial artery embolization for nontuberculous mycobacterial pulmonary disease

Nontuberculous mycobacterial pulmonary disease (NTM-PD) varies widely in clinical presentation, and some patients experience hemoptysis. Bronchial artery embolization (BAE) is a treatment option for hemoptysis caused by NTM-PD. However, the association between post-BAE rebleeding risk and the presence of cavitary lesions has not been fully elucidated. A retrospective observational study was conducted on patients with NTM-PD who had undergone BAE at our institution. Patients were classified into Cavitary and Non-cavitary groups, and baseline characteristics and clinical outcomes were compared. Among the 155 BAE cases between 2013 and 2023, 18 were included in the analysis, and four experienced rebleeding. The Cavitary group tended to have a higher rebleeding rate 24 months after BAE (37.5% vs. 10.0%, p=0.27). Furthermore, the Cavitary group showed a significantly higher number of non-bronchial arteries involved (median number: 1.5 vs. 0.0, p=0.02), a higher proportion of patients with a prior antibiotic treatment history (100% vs. 20%, p=0.001), and longer duration from diagnosis to BAE (median year: 9.0 vs. 0.6, p=0.02). The Kaplan-Meier curves showed a tendency for shorter rebleeding-free survival in the Cavitary group (p=0.10). Cavitary lesions in patients with NTM-PD may predict higher rebleeding rates after BAE. Further research with larger cohorts is needed to better understand rebleeding risk factors in BAE for NTM-PD.

Prime Factors Influencing the Reluctance Expressed Toward Orthodontic Treatment Among a Tribal Population with No Prior History of Orthodontic Treatments in the Community: A Cross-sectional Study

Background Perceiving a need for orthodontic treatment is a heuristic process usually conditioned by the interplay between motivational factors and influencing factors in a community with orthodontic awareness and a history of already ongoing or completed orthodontic treatments. Using a verbally assigned index to elicit candid responses, the current study aimed at assessing reluctance toward orthodontic treatment in adolescents with clinically ascertained malocclusion in a community with no prior history of orthodontic treatment. Objectives Tribal adolescents from two regions with clinically ascertained malocclusion but no previous access to orthodontic treatment were evaluated for willingness or reluctance to undergo orthodontic treatment using a verbally assigned Simplified Malocclusion Index for Layperson Evaluation (SMILE index). Methods 2,835 tribal adolescents belonging to the tribal regions of Paderu and Parvathipuram in Andhra Pradesh were questioned to analyze factors related to reluctance toward orthodontic treatment in those with malocclusion. Necessary permission and consent were obtained from the institutional ethical clearance committee, tribal authorities, school authorities, and parents or guardians. Clinical screening employing appropriate infection prevention protocol under natural daylight was used to determine the presence of malocclusion. A verbally assigned SMILE index in the vernacular language of the students with malocclusion was used to record candid responses to analyze possible reluctance toward treatment. Specific reasons for reluctance to undergo treatment were documented and tabulated separately. Pearson chi-square statistical analysis of the data was performed to determine if there was any gender bias. Results At Paderu, of the 68% of the tribal adolescents presenting with malocclusion, the verbally assigned SMILE index revealed that 84.03% of the adolescents were reluctant. The chi-square statistical analysis of the data indicated a gender bias ( X 2 (1, N = 2,016) = 35.99, p &lt; .0001). At Parvathipuram, of the 93% of the tribal adolescents presenting with malocclusion, the SMILE index assigned revealed that 93.05% of the adolescents were reluctant. The chi-square statistical analysis of the data indicated a gender bias ( X 2 (1, N = 819) = 6.42, p = .11). Conclusion The use of the SMILE index allows for a qualitative analysis of reluctance based on the candid subjective inputs from each individual. The study reveals a high degree of orthodontic awareness among the tribal adolescents, and any reluctance toward orthodontic treatment is mainly related to difficulty in access to treatment.

ONYCHOMATRICOMA, A RARE NAIL TUMOR

Abstract Introduction/Objective Nail apparatus tumors are rare and can pose diagnostic challenges. Onychomatricoma (also called onychomatrixoma) is a rare tumor first described in 1992. It is a benign biphasic fibroepithelial tumor of the nail. It has been reported in Caucasians, often in females with a peak incidence in the fifth decade of life. Rare cases are also reported in children. The common location is in the fingernail (75%), presenting with yellowing of the nail plate (xanthonychia) and thick longitudinal band. Cutaneous horn, melanonychia, nail bleeding, and nail deformity with or without bony extension can also be seen. Histologic findings show increased nail thickness surrounded by a layer of Malpighian epithelium. The fibroepithelial tumor shows hyperplasia of two components including onychogenic epithelium and mesenchymal stroma. Methods/Case Report A 65-year-old Vietnamese female presented with longstanding dark yellowish ridging discoloration, thickening and nail plate deformity of the left fourth fingernail with appearance of onychomycosis. However, KOH mount and fungal cultures of the nail plate were negative for fungal microorganisms. There was no history of pain, trauma, or prior treatment. Microscopic analysis of transverse and longitudinal sections of the nail shows a biphasic neoplasm that penetrates the nail plate with multiple digitations. There was deep finger-like epithelial cell strands that form anastomosis as well as invaginations into the dermis. Characteristic filiform projections are lined by onychogenic epithelium composed mostly of basal and supra-basal cells that lack granular and corneum layers. The stroma was hypercellular and fibrillary with spindle-shaped fibroblastic cells, and a deep layer with dense collagen. Immunohistochemical stains of the lesion show diffuse expression for CD10 and CD34 in the stroma and negativity for Periodic Acid Schiff staining. Results (if a Case Study enter NA) N/A Conclusion While most of the literature on onychomatricoma has been reported in Caucasian population, little is known about this tumor in non-Caucasians. This case report of onychomatricoma in a Vietnamese woman contributes to the emerging literature of this rare nail apparatus tumor in non-Caucasian population. Clinical and histopathologic correlation is important to achieve prompt and correct diagnosis since delay would result in nail dystrophy and deformity.

In Silico Investigation of Molecular Properties and Molecular Docking of Darunavir: An Anti‐HIV Drug

AbstractA second‐generation HIV protease enzyme inhibitor, darunavir is used in combination therapy for patients with history of prior antiretroviral treatments. It inhibits the cleavage of HIV encoded gag‐pol polyprotein in cells contaminated by a virus and thereby hinders the development of mature and infectious new virions. In this paper, optimization of molecular geometry of darunavir has been obtained by Density Functional Theory based B3LYP and ωB97XD methods with 6–311+G(d,p) basis set. The electro‐optical, global reactivity descriptors, and UV–visible spectrum of the drug have been examined using both the functionals. Further, binding affinity of darunavir at different sites of protein receptor (PDB ID: 5b18) has been analyzed using molecular docking technique. Results have been used to discuss electro‐optical and electronic properties of the drug along with its binding affinities with protein receptors.

Pyrazinamide Resistance: A Major Cause of Switching Shorter to Longer Bedaquiline-based Regimens in Multidrug-resistant Tuberculosis Patients.

All-oral regimens, including bedaquiline, are now standard in shorter treatment regimens (STRs) for multidrug-resistant tuberculosis (MDR-TB). Resistance or intolerance to drugs in STR often necessitates a switch to longer treatment regimens (LTRs). This study aims to identify the factors associated with this transition in MDR-TB patients. We conducted a retrospective analysis of medical records from MDR-TB patients treated with STR at Haji Hospital, Surabaya, between January 2022 and January 2023. Data on drug-resistance profiles, determined by drug-susceptibility testing (DST), and line probe assay, as well as adverse effects, were collected. Among 20 eligible patients, 8 (40.0%) switched from STR to LTR within the first 4 months. Resistance was observed in 62.5% of these patients for pyrazinamide, 25.0% for high-dose isoniazid, and 12.5% for levofloxacin. The overall prevalence of pyrazinamide resistance was 25.0%. A history of prior antitubercular treatment was significantly associated with pyrazinamide resistance (P = 0.015; RR - 16.000; confidence interval 95% 1.274-200.917). Pyrazinamide resistance is a major factor for switching from STR to LTR in MDR-TB patients, particularly among those with previous TB treatment. Rapid DST for pyrazinamide is essential for the early identification of resistance and timely adjustments to treatment regimens.

DXA In People Living With HIV

Abstract Background As people with HIV now live a near normal life-span, prevention of fractures is increasingly important. Alongside conventional risk factors for fractures, antiretrovirals and chronic inflammation are believed to contribute to their increased fracture risk compared to the general population. Methods We audited a 1-year series of consecutive DXA scans conducted on people living with HIV vs the European AIDS Clinical Society guidelines on bone health. These guidelines specify indications for DXA, for repeat DXA and for osteoporosis treatment. We recorded DXA results, any prior DXA, fracture history, fracture risks and drug treatment history. We assessed frequency of scanning and pharmacological management of low bone mass vs. guidelines. Results N=90 referred for DXA, of whom 18% did not attend, leaving n=74; 58% female, 42% male, median age 52 years [36-64] and 56 years [49-69] respectively. Of the 18% (n=14) who were aged under 50, 43% had no clear indication (fracture risk factor) for DXA. Of those aged &amp;gt;50 years (n=60), all scans were indicated as the guidelines advises this in those aged &amp;gt;50 years. Bone density was normal in n=32 (43%), osteopenic in 36 (49%) and osteoporotic in 7 (9%). Fifteen percent overall had a fragility fracture history, none of whom were taking osteoporosis treatment though it was indicated in at least 4 based on their DXA result. N=12 (16%) had a DXA in preceding years, and just 2 of the repeat scans were indicated according to guidelines. For the 12 with serial scans, there was no significant change in T score after a median three-year period. Conclusion Through an audit of consecutive DXA referrals, rather than consecutive individuals, low bone mass and fragility fractures are prevalent in people living with HIV. With advancing age, fracture incidence may rise sizeable in this group therefore due attention to bone health guidelines in required.

Impact of Previous Alopecia Areata Treatment on Efficacy Responses up to Week 48 Following Ritlecitinib Treatment: A Post Hoc Analysis.

Patients with alopecia areata (AA) may have received several therapies for management of AA during their lives. In the ALLEGRO phase 2b/3 (NCT03732807) study, the oral JAK3/TEC family kinase inhibitor ritlecitinib demonstrated efficacy and an acceptable safety profile in patients aged ≥ 12years with AA and ≥ 50% scalp hair loss. This post hoc analysis investigated associations between prior use of AA therapies and Severity of Alopecia Tool (SALT) responses in patients receiving ritlecitinib for AA. Patients receiving ritlecitinib 30mg or 50mg once daily with or without an initial 4-week 200-mg daily loading dose were grouped by previous exposure to AA treatments, including topicals, intralesional corticosteroids (ILCS), topical immunotherapy, and systemic immunosuppressants or any prior AA treatment. Multivariable logistic regression analyses evaluated the association between response based on a SALT score of ≤ 20 and any prior treatment for AA at weeks 24 and 48. Of 522 patients, 360 (69.0%) had previous exposure to any AA treatment. At Week 24, SALT ≤ 20 response was positively associated with prior use of ILCS (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.23-3.65; P < 0.05) and negatively associated with prior use of systemic immunosuppressants (OR 0.50; 95% CI 0.28-0.88; P < 0.05). Prior use of topicals or topical immunotherapy was not associated with SALT ≤ 20 response at Week 24. By Week 48, no association was identified between SALT ≤ 20 response and prior use of topicals, ILCS, topical immunosuppressants, or systemic immunosuppressants (all P > 0.05). Previous exposure to any AA therapy was not associated with SALT ≤ 20 response at weeks 24 or 48 (all P > 0.05). Prior AA treatment history had no effect on longer-term treatment response to ritlecitinib. NCT03732807.