Prior Treatment History Research Articles

BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population.

Pakistan is endemic to a diverse set of parasitic, mycobacterial and viral diseases. The recognition of BCG Trained Immunity (TI) led us to postulate that the continued presence of BCG-TI may play a protective role, previously reported for both infectious and noninfectious conditions. Most of the previous studies have addressed the issue of BCG-TI in the paediatric populations. This study addressed the key issue of maintenance of BCG-TI in a wider age range (adolescent and adults) to identify the strength and quality of the immune responses. To assess the BCG-induced recall responses in healthy individuals by cytokines secreted from the TI network and its potential role in providing cross-protection against COVID-19 and other viral infections. In this cross-sectional study, healthy young adults and adolescents (n = 20) were recruited from 16-40 years of age, with no prior history of TB treatment, autoimmune, or chronic inflammatory condition. BCG-induced cytokine responses were assessed using prototypic markers for cells of the TI network [macrophages [M1 (TNFα, IFNγ), M2 (IL10)], NK (IL2), Gamma delta (γδ) T (IL17, IL4)] and SARS CoV2 IgG antibodies against RBD using short-term (12 hrs.) cultures assay. Significant differences were observed in the magnitude of recall responses to BCG with macrophage cytokines showing the highest mean levels of TNFα (9148 pg/ml) followed by IL10 (488 pg/ml) and IFNγ (355 pg/ml). The ratio of unstimulated vs.BCG-stimulated cytokines was 132 fold higher for TNFα, 40 fold fo r IL10, and 27 fold for IFNγ. Furthermore, SARS-CoV-2 antibodies were also detected in unstimulated plasma which showed cross reactivity with BCG. The presence of cross reactive antibodies to SARS-CoV-2 and the relative ratio of pro- and anti-inflammatory cytokines secreted by activated TI cellular network may play a pivotal role in protection in the early stages of infection as observed during the COVID-19 pandemic in the younger age groups resulting in lower morbidity and mortality.

Undernutrition increases the risk of unsuccessful treatment outcomes of patients with tuberculosis in Ethiopia: A multicenter retrospective cohort study

While undernutrition has been identified as a common risk factor for tuberculosis (TB), its impact on treatment outcomes has yet to be investigated in high TB burden and low-income countries such as Ethiopia. Therefore, this study aimed to investigate the effect of undernutrition on treatment outcomes among patients with TB in northwest Ethiopia. A retrospective cohort study was conducted using data from different hospitals in northwest Ethiopia, for the period from July 2017 to August 2023. A Cox proportional hazard model was performed to determine the effect of undernutrition on TB treatment outcomes, which were defined as a composite of death, treatment failure, or loss to follow-up. A total of 602 patients with TB were included in the analysis. Of these, 367 (60.9%) were male, and 344 (57.1%) were undernourished. Upon completion of the follow-up period, 65 (10.8%) adults with TB had unsuccessful treatment outcomes. After adjusting for potential confounders, patients with undernutrition had a two times higher risk of experiencing unsuccessful treatment outcomes compared to well-nourished patients (AHR: 2.0, 95% CI: 1.2, 3.6). In addition, patients residing in rural areas (AHR: 3.1, 95% CI: 1.7, 5.4), having a history of prior TB treatment (AHR: 2.2, 95%CI: 1.1, 4.1), and the presence of diabetes comorbidity (AHR: 2.4, 95% CI: 1.1, 5.2) were at higher risk of unsuccessful treatment outcomes. Undernutrition increases the risk of unsuccessful treatment outcomes in Ethiopia. This finding suggests that nutritional support during TB treatment can improve successful treatment outcomes in high TB burden and low-income countries such as Ethiopia.

Real-world effectiveness of CDK4/6 inhibitors on patients with HR+/HER2– advanced breast cancer in South Korea, focusing on underrepresented patients

Objective We assessed the real-world effectiveness of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors as first-line treatments in postmenopausal patients with HR+/HER2− advanced breast cancer, focusing on younger (<45 years) and older (>78 years) populations not considered in clinical trials. Methods We analyzed nationwide claims data from the Health Insurance Review and Assessment Service between November 2016 and February 2021. In this retrospective cohort study, patients using CDK4/6 inhibitors and aromatase inhibitors were selected and grouped by age as follows: 45–78 years (trial-enrolled), <45 years (younger), and >78 years (older). We estimated the median real-world progression-free survival (rwPFS) and overall survival (OS) using the Kaplan-Meier method. We conducted Cox regression analysis using a sub-distribution hazard model to evaluate risk factors (age, history of prior systemic treatment, presence of metastasis, comorbidity index, and type of provider) and estimated hazard ratios (HR). Results Among the 2,830 patients who received CDK4/6 inhibitors as first-line therapy, we identified 358 (12.65%) younger and 148 (5.23%) older underrepresented patients. The younger patient group (50.84%) had the highest rate of prior systemic therapy, followed by the trial-enrolled (25.39%) and older patient groups (8.11%). The median rwPFS was shorter in the older group (19.30 months) than those in the younger and the trial-enrolled age groups (30.33 and 34.53 months, respectively; p = .002). The HR of older age for death was 1.59 (95% confidence interval (CI) = 1.24–2.03). For rwPFS, the HR of prior systemic therapy was 1.19 (95% CI = 1.04–1.37). Conclusions The younger age group, which was underrepresented in the trial, did not show a significant difference in risk compared with the enrolled age group. However, the older age group, which was also underrepresented in the trial, faces a risk of mortality but not progression. Patients who fall outside the specified age groups for the clinical trial can still expect the same level of effectiveness in terms of progression.

Minimally invasive techniques in the management of muscular temporomandibular joint disorders: A five-year observational study.

To evaluate the effectiveness of three minimally invasive techniques for managing patients with myofascial pain dysfunction, determine their association with sociodemographic factors, habits, medication usage, comorbidities, treatment history, pain duration, complaint intensity, and diagnosis limitations. This five-year observational study scrutinized 1,000 medical records from individuals treated at the TMD Orofacial Dental Research Center. TMD treatments were organized into Group 1 (thermotherapy, exercises, and CBT), Group 2 (Group 1 plus intramuscular manual therapy), and Group 3 (Group 1 and Group 2 plus occlusal appliances) and correlated with sociodemographic factors, habits, prior medication usage, comorbidities, history of prior treatments, duration of pain, intensity of complaint, and diagnosis limitations or without limitations regarding the symptoms of muscular temporomandibular disorders (TMD). Treatment durability was proportionally higher in Groups II and III (p<0.05). Although no significant differences were found for habits (p= 0.051) and pain duration (p= 0.001), clenching was more prevalent in Groups II n= 77 (57.0%) and III n= 39 (63.9%) and among those with therapy duration equal to or greater than 6 months for n=102 (59.3%). Statistically significant correlations were noted between age and education (rho=-0.198; p<0.001) and between pain duration and treatment durability (rho=0.317; p<0.001). Intraoral devices do not constitute the primary treatment for myofascial pain. For cases of prolonged pain, comorbidities, limited mouth opening, and a history of prior medication or treatments, a splint combined with other therapies is recommended for effective management. Key words:Temporomandibular disorders, myofascial pain, occlusal appliances, clinical diagnosis, thermotherapy, exercise therapy, cognitive behavioral therapy.

The relative risk of immune checkpoint inhibitor pneumonitis in advanced non-small- cell lung cancer: Meta-analyses of controlled clinical trials.

Immune checkpoint inhibitor pneumonitis (CIP) is a prevalent form of immunotherapy-induced pulmonary toxicity, ranking among the leading causes of mortality associated with immune checkpoint inhibitors (ICIs). Despite its significance, the risk stratification of CIP in advanced non-small cell lung cancer (NSCLC) remains uncertain. In this study, we conducted a comprehensive analysis, comparing various factors such as histological types, treatment regimens, PD-L1 expression levels, and EGFR/ALK negativity in advanced NSCLC. Our investigation extends to evaluating the relative risk of developing CIP based on previous treatment history. This analysis aims to provide valuable insights for the identification of specific patient subgroups at higher risk, facilitating more effective risk management and precision therapy approaches. PubMed, Embase, and Cochrane databases were systematically searched up to February 16, 2023. We conducted a screening of randomized controlled trials (RCTs) that compared ICI monotherapy or its combination with chemotherapy in advanced NSCLC. The trials were categorized based on histological type, treatment regimen, PD-L1 expression level, EGFR/ALK-negative status, and prior treatment history. Subsequently, the data were stratified into five subgroups, and the occurrences of all-grades (1-5) and high-grades (3-5) pneumonia events were extracted. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were then calculated for further analysis. Twenty-two RCTs, encompassing 13,725 patients with advanced NSCLC, were included in this analysis. Regardless of histology (OR = 2.47, 95% CI 1.41-4.33, P = 0.002; OR = 1.84, 95% CI 1.10-3.09, P = 0.02), treatment regimen (OR = 3.27, 95% CI 2.00-5.35, P < 0.00001; OR = 2.91, 95% CI 1.98-4.27, P < 0.00001), PD-L1 expression level (OR = 5.11, 95% CI 2.58-10.12, P < 0.00001; OR = 5.15, 95% CI 2.48-10.70, P < 0.0001), negative EGFR/ALK expression (OR = 4.32, 95% CI 2.22-8.41, P < 0.0001; OR = 3.6, 95% CI 1.56-8.28, P = 0.003), whether there is a history of treatment (OR = 3.27, 95% CI 2.00-5.35, P < 0.00001; OR = 2.74, 95% CI 1.75-4.29, P < 0.0001), ICI use was associated with a higher risk of all-grade (1-5) and high-grade (3-5) pneumonia compared to chemotherapy. Subgroup analysis revealed that the squamous group, the ICI vs. combination chemotherapy (CT) group, the PD-L1 > 50% group, and the previously untreated group had a higher risk of developing all-grade and grade 3-5 CIP (P < 0.05). In advanced NSCLC, ICI treatment was linked to an elevated risk of pneumonitis across all grades (1-5) as well as high-grade occurrences (3-5) compared to chemotherapy. Notably, individuals with squamous histology and high PD-L1 expression, along with those lacking a history of prior treatment, demonstrated a heightened susceptibility to developing immune-related pneumonitis of all grades (1-5) and high grades (3-5). These observations provide valuable insights for clinicians seeking to enhance the management of pulmonary toxicity associated with immunotherapy.

Contrast-enhanced Ultrasound Using Intradermal Microbubble Sulfur Hexafluoride in Non-invasive Axillary Staging in Breast Cancer: Are we Missing a Chance?

In the context of surgical de-escalation in early breast cancer (EBC), this study aimed to evaluate the contrast enhancement ultrasound (CEUS) sentinel lymph node (SLN) procedure as a non-invasive axillary staging procedure in EBC in comparison with standard SLN biopsy (SLNB). A subanalysis of the AX-CES study, a prospective single-arm, monocentric phase 3 study was performed (EudraCT: 2020-000393-20). The study included patients with EBC undergoing upfront surgery and SLN resection, with no prior history of locoregional treatment, and weighing between 40-85 kg. All patients underwent the CEUS SLN procedure as a non-invasive axillary staging procedure, with CEUS SLN accumulation marked using blue dye. After the CEUS SLN procedure, all patients underwent the standard mapping procedure. Data on success rate, systemic reactions, mean procedure time, mean surgical procedure, mean procedure without axillary staging, CEUS SLN appearance (normal/pathological), SLN number, and concordance with standard mapping procedure were collected. After the CEUS SLN procedure, 29 LNs among 16 patients were identified and marked. In all cases, CEUS SLN revealed at least one LN enhancement. Six (37.50%) LNs were defined as pathological after the CEUS SLN procedure. Definitive staining of CEUS SLN pathology revealed metastatic involvement in four (66.67%) of the cases. Two SLNs were identified during the CEUS SLN procedure; however, owing to the low disease burden, no change in the surgical plan was reported. The CEUS SLN procedure shows promise as a technique for non-invasive assessment of the axilla, potentially enabling safe axillary de-escalation in EBC by estimating the axillary disease burden.

TFE3 -Rearranged PEComa/PEComa-like Neoplasms : Report of 25 New Cases Expanding the Clinicopathologic Spectrum and Highlighting its Association With Prior Exposure to Chemotherapy.

Since their original description as a distinctive neoplastic entity, ~50 TFE3 -rearranged perivascular epithelioid cell tumors (PEComas) have been reported. We herein report 25 new TFE3 -rearranged PEComas and review the published literature to further investigate their clinicopathologic spectrum. Notably, 5 of the 25 cases were associated with a prior history of chemotherapy treatment for cancer. This is in keeping with prior reports, based mainly on small case series, with overall 11% of TFE3 -rearranged PEComas being diagnosed postchemotherapy. The median age of our cohort was 38 years. Most neoplasms demonstrated characteristic features such as nested architecture, epithelioid cytology, HMB45 positive, and muscle marker negative immunophenotype. SFPQ was the most common TFE3 fusion partner present in half of the cases, followed by ASPSCR1 and NONO genes. Four of 7 cases in our cohort with meaningful follow-up presented with or developed systemic metastasis, while over half of the reported cases either recurred locally, metastasized, or caused patient death. Follow-up for the remaining cases was limited (median 18.5 months), suggesting that the prognosis may be worse. Size, mitotic activity, and necrosis were correlated with aggressive behavior. There is little evidence that treatment with MTOR inhibitors, which are beneficial against TSC -mutated PEComas, is effective against TFE3 -rearranged PEComas: only one of 6 reported cases demonstrated disease stabilization. As co-expression of melanocytic and muscle markers, a hallmark of conventional TSC -mutated PEComa is uncommon in the spectrum of TFE3 -rearranged PEComa, an alternative terminology may be more appropriate, such as " TFE3 -rearranged PEComa-like neoplasms," highlighting their distinctive morphologic features and therapeutic implications.

Expectations of Patients Receiving Orthodontic Treatment from Saidu College of Dentistry Swat: A Cross Sectional Study

OBJECTIVE: The aim of this study was to assess the anticipations of orthodontic treatment held by both patients and parents. This would enable the provision of optimal services for expectations that are rational, while also facilitating discussions or guidance for expectations that are impractical. One of the key goals of healthcare systems today is to meet patient expectations. The declaration of a patient’s desires is significant because healthcare providers frequently undervalue their need for treatment. When a clinician is aware of patient demands, they are better equipped to meet the patient’s realistic expectations while explaining the least possibility to fulfil arbitrary expectations, thus results in more rewarding therapeutic interventions. METHODOLOGY: The data collection process involved the utilization of a non-randomized sampling technique, specifically selecting 300 participants as determined through Epi info using a structured form. The study focused on recruiting new patients who exhibited internal motivation, along with anatomical or morphological issues related to their teeth or jaws. A prior history of orthodontic treatment was an exclusion criterion. Participants with craniofacial syndromes or malformations, as well as those dealing with mental or psychological health conditions, were excluded from the research. RESULTS: In total, 300 individuals were examined, with 170 females and 130 males. Improvement in facial appearance was the most popular reason for seeking orthodontic treatment (180 patients out of 300), although other functions like mastication, better oral health and communication were mentioned by 120 patients. 70% (210) had a thought, since they would receive treatment, they would be more accepted by society and thus improve their social standing, while the remaining 30% (90) thought that it would have no difference. CONCLUSION: Essentially, expectations from orthodontic interventions among patients are quite uniform, although males generally display more practical perceptions regarding treatment duration and the initial appointment. However, when it comes to dietary and beverage restrictions during orthodontic treatment, patient expectations differ from those held by their parents. KEYWORDS: Patient expectations, orthodontics, Evaluate.

Influence factors of metagenomic next-generation sequencing negative results in diagnosed patients with spinal infection

The aim of this study was to evaluate the influence factors of metagenomic next-generation sequencing (mNGS) negative results in the diagnosed patients with spinal infection. mNGS test was applied in a cohort of 114 patients with suspected spinal infection, among which 56 patients had a final diagnosis of spinal infection. mNGS achieved a sensitivity of 75.0% (95% CI, 61.6% to 85.6%) and a specificity of 84.5% (95% CI, 72.6% to 92.7%), using histopathology and culture results as reference. Diagnosed patients with a negative culture result had lower white blood cell account, percentage of neutrophilic granulocyte, C-reactive protein (all P<0.05) and relatively higher rate of prior antimicrobial treatment history (P=0.059). However, diagnosed patients with a negative mNGS result did not have such difference with mNGS-positive patients, suggesting that mNGS was not strictly limited by the above indicators, which presented the advantages of this technique from another point of view.

"There is nothing that can prevent me from supporting her:" men's perspectives on their involvement and support of women's use of topical therapy for cervical precancer treatment in Kenya.

Cervical cancer disproportionately impacts women in low- and middle-income countries (LMICs). The World Health Organization's (WHO) 90/70/90 strategy aims to eliminate cervical cancer by 2030 by increasing HPV vaccination coverage to 90%, screening 70% of eligible women, and effectively treating 90% of those with abnormal results by 2030, potentially preventing 62 million deaths in LMICs. LMICs, however, struggle with limited access to cervical precancer treatment, in part due to a lack of trained professionals and weak health systems. Effective non-surgical, self-administered, which have demonstrated efficacy in high-income countries, could bridge the treatment gap in LMICs and may be more scalable and cost-effective than provider-administered therapies. To inform feasibility studies in LMICs, data are needed on the role of male partners in influencing the acceptability and uptake of self-administered topical therapies, including their support of recommended abstinence and contraception guidelines associated with these therapies. Between November 2022 and April 2023, we conducted five focus group discussions (FGDs) with men aged 25 to 65 years in Kenya to explore their perspective and perceived support regarding their female partners using topical self-administered therapies for cervical precancer treatment. The FGDs were moderated by local qualitative research assistants and conducted in local languages, transcribed, coded, and analyzed using qualitative description. Thirty-nine male participants meeting the eligibility criteria participated in five FGDs. The mean age of participants was 42.5 years. Most participants, 79.5%, had a female partner with a history of cervical precancer treatment, 5.1% did not, and 15.4% were unsure of their female partner's prior precancer treatment history. The study aimed to assess men's support of their female partners' use of topical therapies for treating cervical precancer. We find that male participants strongly express acceptance and willingness to support their wives or partners in using such therapies, if available. Reported supportive behavior included permitting the use of the therapies and support of maintaining abstinence during the recommended times. Additionally, participants desired male involvement in clinic and community-based education about topical therapies to facilitate widespread support. The use of self-administered topical therapies for cervical precancer treatment, if supported by efficacy studies in LMICs, may support achieving the WHO's 2030 goal of 90% treatment access. We find that with adequate education, men express overwhelming support of their female partner's use of topical therapies, including adherence to abstinence and contraception guidelines.

Treatment Patterns and Negative Health Outcomes in Palmoplantar Pustulosis Patients in Germany and the US.

Limited information exists on the epidemiology, treatment, and burden of palmoplantar pustulosis (PPP) and defining the optimal course of treatment remains challenging without approved targeted treatments in most countries. Here, we describe the clinical and demographic characteristics, treatments received, and negative health outcomes experienced among patients with PPP in the United States (US) and Germany. Retrospective cohort study between 2016 and 2021 using data from the US Merative™ MarketScan® Research Database and IQVIA™ German Disease Analyzer. Adult patients with PPP (ICD-10-CM L40.3) were followed from the date of their first qualifying PPP diagnosis and continued until the earlier of disenrollment or end date of database, during which treatment patterns and incidence rates of negative health outcomes were assessed. Treatment patterns included adherence, non-persistence, discontinuation, re-initiation, switching, and combination therapy. The prevalence of PPP was 0.005% and 0.065% in the MarketScan database and German Disease Analyzer, respectively, with 1629 and 3866 patients meeting the inclusion criteria. Most patients were female (71.3%, 67.8%), with mean (SD) age of 54.1 (11.7) and 56.9 (14.3) years, respectively. One year post index, most patients received topical treatment (77.4%, 65.3%), but non-persistence and discontinuation were high. Oral and biologic treatments displayed higher levels of adherence, particularly apremilast and tofacitinib among oral treatments and TNF inhibitors and IL-23 inhibitors among biologics. Rates of negative health outcomes were higher among patients not receiving treatment post-index compared with those receiving treatment post-index across both databases, regardless of prior treatment history. Establishing treatment guidelines remains an unmet need for patients with PPP and could improve quality of life by reducing the occurrence of negative health outcomes. The findings from this study may provide insight into the effectiveness of current treatment options for patients with PPP and can be leveraged to support the development of treatment guidelines.

A Systematic Review and Classification of Factors Influencing Diabetic Foot Ulcer Treatment Adherence, in Accordance With the WHO Dimensions of Adherence to Long-Term Therapies.

Effective treatment of diabetic foot ulcers (DFUs) involves a multidisciplinary treatment plan to promote wound healing and prevent complications. Given the lack of consensus data on the factors affecting patient adherence, a systematic review was performed to identify and classify factors according to the WHO Dimensions of Adherence to Long-Term Therapies. Six hundred and forty-three articles from PubMed, Embase, and Scopus were reviewed. The inclusion criteria included qualitative and quantitative studies which discussed factors affecting patient adherence to DFU treatment, had study populations that comprised patients with either prior history of or existing DFU, and had either prior history of DFU treatment or were currently receiving treatment. Factors, and associated measures of adherence, were extracted and organized according to the WHO Dimensions of Adherence to Long-Term Therapies. Seven quantitative and eight qualitative studies were included. Eleven patient-related factors, seven condition-related factors, three therapy-related factors, five socioeconomic factors, and five health system-related factors were investigated by the included studies. The largest proportion of factors studied was patient-related, such as patient insight on DFU treatment, patient motivation, and patient perception of DFU treatment. There was notable overlap in the range of discussed factors across various domains, in the socioeconomic (including social support, income, social and cultural acceptability of DFU therapy, cost) and therapy-related domains (including duration of treatment, offloading footwear, and reminder devices). Different studies found that specific factors, such as gender and patients having a low internal locus of control, had differing effects on adherence on different cohorts. Current literature presents heterogeneous findings regarding factors affecting patient adherence. It would be useful for future studies to categorize factors as such to provide more comprehensive understanding and personalized care to patients. Further research can be done to explore how significant factors can be addressed universally across different cohort populations in different cultural and socioeconomic contexts.

Treatment of Helicobacter Pylori İnfection and the Colonization of the Gastrointestinal System by Resistant Bacteria.

Helicobacter pylori (H. pylori) infections are widely treated with antibiotic regimens such as "Amoxicillin 1 gr 2 × 1 tablet, Clarithromycin 500 mg 2 × 1 tablet, and Lansoprazole 30 mg 2 × 1 tablet" for 14 days. We conducted a prospective observational study to explore whether this treatment protocol serves as a predisposing factor for the colonization of resistant gastrointestinal microflora, namely vancomycin-resistant enterococci (VRE), extended-spectrum beta-lactamase Enterobacterales (ESBL-E), and carbapenem-resistant Enterobacterales (CRE). Pre- and post-treatment stool samples from 75 patients diagnosed with H. pylori, without a prior treatment history, were cultured and evaluated based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Of the 75 evaluated patients, a pronounced surge in ESBL-E positivity was observed. Before initiating antibiotic treatment, 12 patients (16%) had ESBL-E-positive strains in their gastrointestinal tract. Notably, this number surged to 24 patients (32%) after the conclusion of the 14-day treatment regimen. The change was statistically significant, with a P value of less than 0.002, indicating a clear association between treatment for H. pylori and heightened ESBL-E colonization. Notably, VRE and CRE remained undetected in patients throughout the study, suggesting that the treatment regimen may specifically amplify the risk of ESBL-E colonization without affecting VRE and CRE prevalence. As the inaugural report from Turkey on this issue, our study suggests that antibiotic regimens for H. pylori eradication contribute to the increased risk of ESBL-positive bacterial colonization in the gastrointestinal tract.

Surgical and oncological results after rectal resections with or without previous treatment for prostate cancer.

Previous treatment for prostate cancer (PC) may potentially affect the surgical and oncological outcomes of subsequent rectal cancer surgery, but there are only a few studies regarding this particular group. In this study, we present the 3-year surgical and oncological results of rectal cancer patients who had received previous treatment for PC at a single Finnish tertiary referral centre. Data regarding all male patients diagnosed with rectal cancer and treated at Tampere University Hospital (TAUH) between 1997 and 2016 were gathered from medical records. In total, this study included 553 rectal cancer patients who underwent curative surgery, and 54 of them (9.8%) had a prior history of treatment for prostate cancer. Patients in the PC group were older and had more comorbidities compared with those in the non-PC group. The PC patients had a significantly higher risk of permanent stoma compared with the non-PC patients (61.5% vs. 45.2%, respectively, p = 0.025). The PC patients seemed to have lower tumours than the non-PC patients (87% vs. 75%, respectively, p = 0.05). Overall, the 3-year overall survival (OS) for the PC and non-PC patients was 74.1% and 80.6%, respectively. No significant differences were observed between the study groups even in the age-adjusted comparison [hazard ratio (HR): 1.07, confidence interval (CI) 95%: 0.60-1.89]. In the univariable analysis, radically operated patients without a history of PC exhibited an improved overall survival, (HR: 2.46, 95% CI: 1.34-4.53, p = 0.004). However, only a higher age-adjusted Charlson comorbidity index (CCI) and a low tumour location (<10 cm) were found to have an independent prognostic impact on worse OS in the multivariable analysis (HR: 1.57, 95% CI: 1.36-1.82, p < 0.001 and HR: 2.74, 95% CI: 1.32-5.70, p = 0.007, respectively). No significant differences were observed between the groups in terms of disease-free or local recurrence-free survival. Rectal cancer is more frequently found in the middle or lower part of the rectum in patients who have previously received treatment for prostate cancer. These patients also have a higher likelihood of requiring a permanent stoma. In radically operated rectal cancer, the PC group had a worse OS rate, according to the univariable analysis. However, the only independent prognostic factors for a worse OS that were highlighted in the multivariable analysis included a higher CCI and a low tumour location.

Real-world effectiveness and safety of trifluridine-tipiracil (FTD/TPI) and bevacizumab (BEV) in refractory metastatic colorectal cancer (mCRC): The BeTAS trial.

51 Background: In the Sunlight Trial, the combination of FTD/TPI + BEV demonstrated significantly extended Overall Survival (OS) and Progression-Free Survival (PFS), along with an improved Disease Control Rate (DCR), compared to FTD/TPI alone in patients with refractory mCRC. The BeTAS trial aimed to evaluate the real-world effectiveness and safety of the FTD/TPI + BEV combination in patients with refractory mCRC. Methods: We conducted a multicenter, retrospective, observational study involving patients with mCRC who were refractory or intolerant to standard therapies (including oxaliplatin, irinotecan, fluoropyrimidines, anti-VEGF, and anti-EGFR if RAS/BRAF wild-type) and were treated with FTD/TPI + BEV at six university hospitals affiliated with the Galician Research Group on Digestive Tumors (GiTUD) in Northwest Spain. Results: A total of 110 patients were enrolled in the BeTAS trial between July 2019 and August 2023. The median age was 66 years (range 33-88 years), with 62.7% being male. Notably, 18.2% of patients had an ECOG performance status of 2, 50.9% had RAS mutations, 27.3% had three or more metastatic locations, and 72.7% had liver metastases. Additionally, 26.4% had a time since the diagnosis of the first metastases of less than 18 months, and 46.4% were categorized as the poor prognostic Tabernero´s Subgroup. Most patients (77.3%) received FTD/TPI + BEV as a third-line treatment, with 88.9% having received previous anti-VEGF therapy. Notably, 13.6% received FTD/TPI at a dose of 30 mg/m2, and 6.4% received prophylactic GCSF. The median number of cycles received was 4 (range 1-21 cycles). Among 97 evaluable patients, the overall response rate (ORR) was 2.1%, and the disease control rate (DCR) was 46.4%. With a median follow-up of 15.5 months, the median PFS was 4.2 months (95% CI, 3.5-4.9 months), and the median OS was 9.9 months (95% CI, 7.3 - 12.5 months). The most common grade 3-4 toxicities included neutropenia (41.8%), asthenia (7.3%), and hepatic toxicity (5.5%). No treatment-related deaths were reported. Conclusions: The BeTAS trial findings affirm the real-world effectiveness and safety of FTD/TPI + BEV in the context of routine clinical practice, even in a population with a poor prognosis and extensive prior treatment history.

Unlocking the Protective Potential of Upper Respiratory Infection Treatment Histories against Alzheimer's Disease: A Korean Adult Population Study.

With increasing interest in the inflammation-pathogen infection hypothesis and its potential links to Alzheimer's disease (AD) development, there is growing consideration of using upper respiratory infection (URI) treatments as interventions for AD. This nested case-control study explored the potential association between prior URI histories and AD development in a Korean adult population using the national health screening cohort data (2002-2019). The study included 26,920 AD patients and 107,680 matched control individuals, focusing on those seeking respiratory treatment. Logistic regression analyses assessed the impact of URI histories and treatment on AD risk while adjusting for covariates. Our results revealed that over a 1-year period, individuals with URI histories (≥1, ≥2, or ≥3 instances) exhibited decreasing probabilities of developing AD, with risk reductions of 19%, 15%, and 12%, respectively. Expanding our investigation to a 2-year period consistently showed a 17% reduction in AD risk. This effect remained robust across diverse demographic groups and after adjusting for covariates, encompassing comorbidities, hypertension, hyperlipidemia, blood glucose levels, and lifestyle factors. Subgroup analyses further substantiated this association. In conclusion, our findings cautiously suggest a potential protective role of prior URI treatment histories in mitigating the risk of AD development.

Efficacy and Safety of Carbon Dioxide Laser Ablation Combined with Manual Dermabrasion and Intralesional 5-Fluorouracil Injection in Bowen's Disease.

Bowen's disease (BD) is a precancerous in-situ squamous cell carcinoma and has a high recurrence rate with any single treatment modality, necessitating combination therapy for a successful outcome. This study aimed to the efficacy and safety of carbon dioxide (CO2) laser ablation followed by manual dermabrasion and intralesional 5-fluorouracil (IL 5-FU) injection as combination therapy for BD. This was a retrospective, observational study comprising 29 clinically and histopathologically diagnosed BD patients with no history of prior treatment. Demographic characteristics and clinical examination of the lesions and regional lymph nodes were retrieved. All patients were subjected to CO2 laser ablation followed by manual dermabrasion and IL 5-FU injection. Mean age was 61.93 ± 9.31 years with male preponderance (62.1%). Trunk (48.3%) was the most frequently involved site. Mean tumor size was 40.8 ± 16.4 mm (range: 15-86 mm). All lesions healed with a cure rate of 96.6%. Complications seen in patients included atrophic scarring with persistent post-inflammatory hyperpigmentation in three patients (10.3%), secondary infection in two cases (6.9%), and hypertrophic scar with early keloid in one patient (3.4%). Recurrence was reported in one patient (3.4%). The study was limited by retrospective study design, small sample size, and no comparison with standard therapy. Combination approach using carbon dioxide laser ablation followed by manual dermabrasion and IL 5-FU injection has been proved to be effective, efficient and safe with good functional, oncological and aesthetic outcomes in treating BD.

Factors predicting access to medications for opioid use disorder for housed and unhoused patients: A machine learning approach.

Opioid use disorder (OUD) is a growing public health crisis, with opioids involved in an overwhelming majority of drug overdose deaths in the United States in recent years. While medications for opioid use disorder (MOUD) effectively reduce overdose mortality, only a minority of patients are able to access MOUD; additionally, those with unstable housing receive MOUD at even lower rates. Because MOUD access is a multifactorial issue, we leverage machine learning techniques to assess and rank the variables most important in predicting whether any individual receives MOUD. We also seek to explain why persons experiencing homelessness have lower MOUD access and identify potential targets for action. We utilize a gradient boosted decision tree algorithm (specifically, XGBoost) to train our model on SAMHSA's Treatment Episode Data Set-Admissions, using anonymized demographic and clinical information for over half a million opioid admissions to treatment facilities across the United States. We use Shapley values to quantify and interpret the predictive power and influencing direction of individual features (i.e., variables). Our model is effective in predicting access to MOUD with an accuracy of 85.97% and area under the ROC curve of 0.9411. Notably, roughly half of the model's predictive power emerges from facility type (23.34%) and geographic location (18.71%); other influential factors include referral source (6.74%), history of prior treatment (4.41%), and frequency of opioid use (3.44%). We also find that unhoused patients go to facilities that overall have lower MOUD treatment rates; furthermore, relative to housed (i.e., independent living) patients at these facilities, unhoused patients receive MOUD at even lower rates. However, we hypothesize that if unhoused patients instead went to the facilities that housed patients enter at an equal percent (but still received MOUD at the lower unhoused rates), 89.50% of the disparity in MOUD access would be eliminated. This study demonstrates the utility of a model that predicts MOUD access and both ranks the influencing variables and compares their individual positive or negative contribution to access. Furthermore, we examine the lack of MOUD treatment among persons with unstable housing and consider approaches for improving access.

Burden of leprosy and associated risk factors for disabilities in Tanzania from 2017 to 2020.

Leprosy is caused by Mycobacterium leprae which affects skin, nerves, eyes, and nasal mucosa. Despite global elimination efforts, Tanzania remains among 13 countries reporting more than 1000 leprosy cases annually. In 2021, Tanzania identified 1,511 new cases, with 10% having grade II disability. Moreover, 14 councils recorded leprosy rates exceeding 10 cases per 100,000 population. This study aimed to assess the burden of leprosy and associated risk factors for disabilities in Tanzania from 2017 to 2020. A retrospective cross-sectional study was conducted to investigate all registered treated leprosy patients from January 2017 to December 2020. The Leprosy Burden Score (LBS) was used to assess the disease burden, while binary logistic regression was employed to evaluate the risk factors for disability. A total of 6,963 leprosy cases were identified from 2017 to 2020. During this period, the point prevalence of leprosy declined from 0.32 to 0.25 per 10,000 people, and the new case detection rate decreased from 3.1 to 2.4 per 100,000 people; however, these changes were not statistically significant (p > 0.05). Independent risk factors for leprosy-related disabilities included male sex (Adjusted Odds Ratio (AOR) = 1.38, 95% Confidence Interval (CI) 1.22-1.57), age 15 years and above (AOR = 2.42, 95% CI 1.60-3.67), previous treatment history (AOR = 2.18, 95% CI 1.69-2.82), and positive Human Immunodeficiency Virus (HIV) status (AOR = 1.60, 95% CI 1.11-2.30). This study identified male sex, older age, positive HIV status, and prior treatment history as independent risk factors for leprosy-related disabilities. Additionally, despite the observed decline in point prevalence and new case detection rates, these changes were not statistically significant. To address leprosy-related disabilities, it is crucial to implement specific prevention strategies that focus on high-risk groups. This can be accomplished by enhancing screening and contact tracing efforts for early patient identification to prevent delays in intervention. Further research is warranted to analyze the burden of leprosy over a more extended period and to explore additional risk factors not covered in this study.

Factors Influencing Continued Usage of Intracavernosal injections for Erectile Dysfunction: A Retrospective Analysis.

Intracavernosal injections are used to treat erectile dysfunction. Patient compliance with intracavernosal injections is required for success, though factors influencing compliance are unknown. This study aimed to identify factors that influence compliance with intracavernosal injections among men with erectile dysfunction. A retrospective analysis was conducted using men who were prescribed intracavernosal injections between 2017 and 2022 at an academic medical center in a cosmopolitan area. Custom Python code was used to capture the first and last prescription refill events, and the duration of intracavernosal injection use was calculated. Additional patientrelated data, including demographics and comorbidities, were gathered through chart reviews. Cox Proportional Hazards Regression models were used to evaluate the effects of predictor variables on the duration of intracavernosal injection use. A total of 4,072 patients were included in the analysis. The study revealed that age significantly predicted discontinuation of intracavernosal injection therapy, showing an elevated hazard ratio of 1.007 for each additional year of age (p<0.001). Men who preferred to speak Spanish as their primary language was a significant predictor of discontinuation of injection therapy, showing a hazard ratio of 1.163 compared to those who preferred English (p=0.004). Men with a history of prostate cancer treatment stayed on treatment for 80 days fewer on average than those without (p=0.002). Older age, prior history of prostate cancer treatment, and men who preferred to speak Spanish were all identified as factors potentially associated with reduced continuation of intracavernosal injection therapy for erectile dysfunction. Understanding these factors can help healthcare providers in both patient selection and counseling when discussing treatment options for erectile dysfunction.