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19 pages, 684 KiB  
Article
Does the Timing of Response Impact the Outcome of Relapsed/Refractory Acute Myeloid Leukemia Treated with Venetoclax in Combination with Hypomethylating Agents? A Proof of Concept from a Monocentric Observational Study
by Ermelinda Longo, Fanny Erika Palumbo, Andrea Duminuco, Laura Longo, Daniela Cristina Vitale, Serena Brancati, Cinzia Maugeri, Marina Silvia Parisi, Giuseppe Alberto Palumbo, Giovanni Luca Romano, Filippo Drago, Francesco Di Raimondo, Lucia Gozzo and Calogero Vetro
J. Clin. Med. 2025, 14(15), 5586; https://doi.org/10.3390/jcm14155586 (registering DOI) - 7 Aug 2025
Abstract
Background: Relapsed/refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge due to disease heterogeneity, resistance mechanisms, and poor tolerability to intensive regimens. Venetoclax (VEN), a BCL-2 inhibitor, has shown promise in combination with hypomethylating agents (HMAs), but data on response timing [...] Read more.
Background: Relapsed/refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge due to disease heterogeneity, resistance mechanisms, and poor tolerability to intensive regimens. Venetoclax (VEN), a BCL-2 inhibitor, has shown promise in combination with hypomethylating agents (HMAs), but data on response timing in the R/R setting are limited. The aim of this study was to assess the efficacy, safety, and kinetics of response to HMA-VEN therapy in a real-world cohort of R/R AML patients, with particular focus on early versus late responders. Methods: This prospective single-center study included 33 adult patients with R/R AML treated with VEN plus either azacitidine (AZA) or decitabine (DEC) from 2018 to 2021. The primary endpoint was the composite complete remission (cCR) rate and the rate of early and late response, respectively, occurring within two cycles of therapy or later; secondary endpoints included overall survival (OS), relapse-free survival (RFS), time to relapse (TTR), and safety. Results: The cCR was 58%, with complete remission (CR) or CR with incomplete recovery (CRi) achieved in 52% of patients. Median OS was 9 months. No significant differences in OS or TTR were observed between early (≤2 cycles) and late (>2 cycles) responders. Eight responders (42%) underwent allogeneic hematopoietic stem cell transplantation (HSCT), with comparable transplant rates in both groups of responders. Toxicity was manageable. Grade 3–4 neutropenia occurred in all patients, and febrile neutropenia occurred in 44% of patients. An Eastern Cooperative Oncology Group (ECOG) score >2 was associated with inferior response and shorter treatment duration. Conclusions: HMA-VEN therapy is effective and safe in R/R AML, including for patients with delayed responses. The absence of a prognostic disadvantage for late responders supports flexible treatment schedules and suggests that the continuation of therapy may be beneficial even without early blast clearance. Tailored approaches based on performance status and comorbidities are warranted, and future studies should incorporate minimal residual disease (MRD)-based monitoring to refine response assessment. Full article
(This article belongs to the Section Hematology)
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18 pages, 836 KiB  
Article
CAPOX vs. FOLFOX for Colorectal Cancer—Real World Outcomes in Ontario, Canada
by Deepro Chowdhury, Gregory R. Pond and John R. Goffin
Curr. Oncol. 2025, 32(8), 435; https://doi.org/10.3390/curroncol32080435 - 31 Jul 2025
Viewed by 226
Abstract
CAPOX and FOLFOX are widely used chemotherapy regimens for colorectal cancer (CRC). The superiority of one regimen over the other in a real-world setting (RWE) could have significant clinical implications given their common use, but such RWE is limited. This study analyzed provincial [...] Read more.
CAPOX and FOLFOX are widely used chemotherapy regimens for colorectal cancer (CRC). The superiority of one regimen over the other in a real-world setting (RWE) could have significant clinical implications given their common use, but such RWE is limited. This study analyzed provincial database records of 13,461 Canadian patients treated from 2005 to 2017. The primary outcomes were rates of Emergency Department visits and/or hospitalizations (ED/H) and overall survival (OS). CAPOX was used less frequently (8.4%) than FOLFOX (91.6%), often in older patients (p < 0.003 for Stage I–III; p < 0.001 for Stage IV). CAPOX recipients had shorter treatment durations (median 15 vs. 20 weeks, p = 0.002) and higher unadjusted ED/H rates (60.8% vs. 50.9%, p < 0.001), though this difference was nonsignificant on multivariate analysis (MVA) (HR 1.05 (0.92, 1.20), p = 0.466). Patients receiving CAPOX had worse OS than those on FOLFOX, (5-year OS 70.1% vs. 77.2% (p < 0.001) non-metastatic; 16.6% vs. 33.2% (p < 0.001) metastatic). MVA confirmed inferior OS with CAPOX (HR 1.42, p < 0.001). Other predictors of shorter OS included older age, male sex, comorbidities, rural residence, and lower income. This administrative data is at risk of bias but highlights the need for careful patient selection and informed treatment decision making. Full article
(This article belongs to the Section Gastrointestinal Oncology)
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14 pages, 480 KiB  
Article
Decoding Treatment Failures in Metastatic Renal Cell Carcinoma: Predictors Across Immunotherapy and Targeted Therapies from a Retrospective Real-World Analysis
by Sorin Saftescu, Vlad-Norin Vornicu, Dorel-Ionel Popovici, Radu-Dumitru Dragomir, Dana-Sonia Nagy, Daniela-Lidia Sandu, Ana Dulan, Șerban-Mircea Negru and Alina-Gabriela Negru
J. Clin. Med. 2025, 14(15), 5271; https://doi.org/10.3390/jcm14155271 - 25 Jul 2025
Viewed by 253
Abstract
Background: Despite recent advances in the management of metastatic renal cell carcinoma (mRCC), real-world outcomes remain heterogeneous, and early treatment failure is common. Predictive biomarkers for time to treatment failure (TTF) outside clinical trials are poorly characterized. Objective: To identify clinical [...] Read more.
Background: Despite recent advances in the management of metastatic renal cell carcinoma (mRCC), real-world outcomes remain heterogeneous, and early treatment failure is common. Predictive biomarkers for time to treatment failure (TTF) outside clinical trials are poorly characterized. Objective: To identify clinical and laboratory predictors associated with early treatment failure in a real-world cohort of mRCC patients treated with immune checkpoint inhibitors (ICIs), tyrosine kinase inhibitors (TKIs), or combination regimens. Methods: We conducted a retrospective, single-center analysis of patients with metastatic non-urothelial RCC treated between 2018 and 2023. Cox proportional hazards regression was used to evaluate the association between baseline biological parameters and TTF for each treatment regimen. Results: Among 137 patients receiving first-line therapy, 50 received Ipilimumab + Nivolumab, 49 Sunitinib, and 17 Avelumab + Axitinib. For Ipilimumab + Nivolumab, elevated AST was significantly associated with shorter TTF. For Avelumab + Axitinib, shorter TTF was associated with lymph node metastases, low lymphocyte count, low creatinine, low BMI, and low hemoglobin. For Cabozantinib in subsequent lines, a higher platelet count, ALT, and presence of liver metastases were associated with shorter TTF. No statistically significant predictors were found for Nivolumab used in the second-line setting. Conclusions: Routine, accessible biomarkers such as AST, hemoglobin, lymphocyte count, and creatinine may serve as predictors of treatment failure in specific therapeutic contexts. These findings support risk-adapted strategies and individualized monitoring in real-world clinical practice, though further validation in larger cohorts is warranted. Full article
(This article belongs to the Special Issue Advances and Perspectives in Cancer Diagnostics and Treatment)
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14 pages, 662 KiB  
Article
Weekly Cisplatin and 5-Fluorouracil in Neoadjuvant Chemoradiotherapy for Esophageal Cancer: A Pandemic-Era Evaluation
by Yi-Ting Hwang, Cheng-Yen Chuang and Chien-Chih Chen
Medicina 2025, 61(8), 1326; https://doi.org/10.3390/medicina61081326 - 23 Jul 2025
Viewed by 194
Abstract
Background and Objectives: The COVID-19 pandemic disrupted cancer care, prompting adaptations to reduce patient exposure while preserving treatment efficacy. This retrospective observational study compared a weekly cisplatin and 5-fluorouracil (5-FU) regimen to the standard monthly regimen for neoadjuvant chemoradiotherapy in patients with [...] Read more.
Background and Objectives: The COVID-19 pandemic disrupted cancer care, prompting adaptations to reduce patient exposure while preserving treatment efficacy. This retrospective observational study compared a weekly cisplatin and 5-fluorouracil (5-FU) regimen to the standard monthly regimen for neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. Materials and Methods: This single-center retrospective study included 91 patients, divided into two cohorts: weekly chemotherapy (n = 30) and standard chemotherapy (n = 61). Treatment assignment was based on hospital policy changes during the pandemic, with weekly outpatient chemotherapy implemented after November 2022 to conserve inpatient resources. All patients received radiotherapy at 50 Gy in 25 fractions. The weekly regimen consisted of cisplatin 20 mg/m2 and 5-FU 800 mg/m2, administered over 1–2 h weekly, while the standard regimen administered the same doses over four consecutive days on weeks 1 and 5. Primary endpoints were pathologic complete response (pCR), progression-free survival (PFS), and overall survival (OS). Results: The response rates were similar between groups (weekly: 86.7% vs. standard: 90.2%; p = 0.724). The weekly regimen group showed a higher pCR (40.0% vs. 26.2%; p = 0.181) and significantly lower recurrence (26.7% vs. 52.5%; p = 0.020). Mortality was also reduced in the weekly group (6.7% vs. 34.4%; p = 0.004), though the follow-up duration was shorter (10.6 vs. 22.8 months; p < 0.001). Conclusions: In this retrospective observational study, weekly cisplatin and 5-FU demonstrated comparable efficacy to the standard regimen, with potential advantages in reducing recurrence and mortality. This modified approach may be a viable alternative for maintaining oncologic outcomes while minimizing the burden on healthcare systems during pandemic conditions, although prospective validation is needed. Full article
(This article belongs to the Section Oncology)
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10 pages, 232 KiB  
Article
Symptom-Triggered Alcohol Detoxification Compared to Fixed-Dose Regimen of Benzodiazepines: A Retrospective Case–Control Study
by Laurent Becciolini, Fabienne Wehrli, Jens Kronschnabel, Carolina Wiesendanger, Norbert Scherbaum and Patrik Roser
Brain Sci. 2025, 15(7), 758; https://doi.org/10.3390/brainsci15070758 - 17 Jul 2025
Viewed by 333
Abstract
Background: Alcohol withdrawal syndrome is a common clinical challenge that may lead to significant complications if not properly managed. Symptom-triggered therapy (STT) represents a promising alternative to fixed-dose regimens (FDRs) providing benzodiazepine prescriptions based on objectively quantified withdrawal symptoms. This study aimed to [...] Read more.
Background: Alcohol withdrawal syndrome is a common clinical challenge that may lead to significant complications if not properly managed. Symptom-triggered therapy (STT) represents a promising alternative to fixed-dose regimens (FDRs) providing benzodiazepine prescriptions based on objectively quantified withdrawal symptoms. This study aimed to evaluate the effectiveness and safety of STT using the Hamburg Alcohol Withdrawal Scale (HAES) compared to FDRs in the management of inpatient alcohol detoxification. Methods: In a retrospective case–control study, alcohol detoxification treatment in STT was compared with FDRs. During a twelve-month observation period, a total of 123 patients in the STT group were recruited and compared with 123 controls in the FDR group (matched according to sex, age, and current amount of alcohol consumption) treated in the same hospital before the implementation of STT. The study outcomes included the total benzodiazepine dosage, duration of acute detoxification phase, length of inpatient stay, and occurrence of complications such as epileptic seizures and delirium tremens. Results: STT showed a significantly lower total benzodiazepine dosage (22.50 mg vs. 115.00 mg, p < 0.001), a shorter duration of the detoxification phase (48.00 h vs. 201.75 h, p < 0.001), and a reduced length of inpatient stay (23.00 days vs. 28.00 days, p = 0.003) compared to FDRs. There were no significant differences in the rates of complications between the two settings. Linear mixed model analysis revealed that the differences remained highly significant even after adjusting for various explanatory variables (i.e., age, sex, standard units of alcohol, psychiatric comorbidities, treatment discontinuation, and occurrence of any complication). Conclusions: STT appears to be as effective and safe as traditional fixed-dose regimens of benzodiazepines for the management of inpatient alcohol detoxification. This approach may thereby minimize unnecessary pharmacological exposure, facilitate the earlier integration of patients into psychoeducational and psychosocial interventions, and reduce healthcare costs. Full article
(This article belongs to the Special Issue Psychiatry and Addiction: A Multi-Faceted Issue)
16 pages, 876 KiB  
Article
The Real-World Efficacy and Side Effects of Different Nivolumab Regimens in Japanese Patients with Advanced Melanoma: A Single-Center Retrospective Study
by Ken Horisaki, Shusuke Yoshikawa, Wataru Omata, Arata Tsutsumida and Yoshio Kiyohara
Cancers 2025, 17(14), 2299; https://doi.org/10.3390/cancers17142299 - 10 Jul 2025
Viewed by 407
Abstract
Background/Objectives: Nivolumab is a key therapy for advanced-stage melanoma; however, limited data are available from Asian populations comparing the efficacy and side effects of four dosing regimens: 3 mg/kg every 2 weeks (3mg/kgQ2W), 2 mg/kg every 3 weeks (2mg/kgQ3W), 240 mg every [...] Read more.
Background/Objectives: Nivolumab is a key therapy for advanced-stage melanoma; however, limited data are available from Asian populations comparing the efficacy and side effects of four dosing regimens: 3 mg/kg every 2 weeks (3mg/kgQ2W), 2 mg/kg every 3 weeks (2mg/kgQ3W), 240 mg every 2 weeks (240mgQ2W), and 480 mg every 4 weeks (480mgQ4W). This retrospective study evaluated Japanese patients with advanced melanoma treated with various nivolumab regimens to assess the impact of dosing interval and dosage on treatment efficacy and immune-related adverse events (irAEs). Methods: We reviewed the records of 153 participants with stage IV melanoma who received nivolumab monotherapy between February 2012 and December 2024 at Shizuoka Cancer Center. Patients were categorized by nivolumab regimen, dosing interval, and dose per body weight. We then compared treatment efficacy and incidence of irAEs across groups. Results: No significant differences were observed in objective response rate (ORR), progression-free survival (PFS), overall survival (OS), or irAE incidence between the 240mgQ2W and 480mgQ4W groups. Similar results were observed in the 3mg/kgQ2W and 2mg/kgQ3W groups. However, participants who received nivolumab within 3 weeks exhibited a significantly higher ORR than those who received nivolumab more than 3 weeks. No significant differences were found in PFS or OS. Conclusions: The administration of nivolumab at shorter intervals may provide short-term benefits in Japanese patients with advanced melanoma. However, long-term efficacy and side effects did not differ significantly across the studied nivolumab regimens. Full article
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15 pages, 1715 KiB  
Article
High Levels of Community Support for Mansonellosis Interventions in an Endemic Area of the Brazilian Amazon
by Uziel Ferreira Suwa, Carla Letícia Gomes Simão, Ulysses Carvalho Barbosa, Patrícia Moura Sousa, Cláudia Patrícia Mendes de Araújo, Marilaine Martins and James Lee Crainey
Trop. Med. Infect. Dis. 2025, 10(7), 186; https://doi.org/10.3390/tropicalmed10070186 - 2 Jul 2025
Viewed by 310
Abstract
Mansonellosis is a chronic infectious tropical disease that affects hundreds of millions of people worldwide but is not currently targeted for control. In this study, we interviewed 320 residents from Sao Gabriel do Cachoeira (SGC) about their support for soil transmitted helminth (STH) [...] Read more.
Mansonellosis is a chronic infectious tropical disease that affects hundreds of millions of people worldwide but is not currently targeted for control. In this study, we interviewed 320 residents from Sao Gabriel do Cachoeira (SGC) about their support for soil transmitted helminth (STH) and mansonellosis interventions. Our survey found no significant difference between community support for mansonellosis and STH disease treatment when comparing any equivalent treatment regimen or program, although support for STH treatments was always higher than for mansonellosis treatments. No significant differences were detected when comparing community members’ willingness to participate in treatment programs and their willingness to allow family members to participate in an equivalent program. Our survey did, however, almost always find that significantly more community members were willing to participate in a proposed treatment program if the treatment regimen of that program was shorter than an otherwise equivalent regimen. Although significantly fewer people said they would participate in a curative four-week treatment course for mansonellosis than in a mansonellosis mass drug administration (MDA) program, significantly more community members said they would take a curative mansonellosis treatment course that lasted seven days or less than they would participate in any type of anthelminthic MDA proposed to them. The number of community members who said they would participate in any helminthic treatment program if they knew there was a ≥50% chance that they were infected was significantly higher than the number who said that they would without knowing the regional prevalence rate. Full article
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13 pages, 816 KiB  
Article
“Pre-Treatment“ and “Post-Treatment” Systemic Inflammatory Markers: Is There Any Prognostic Role for Metastatic Cervical Cancer on Bevacizumab Containing Treatment?
by Serkan Yaşar, Ahmet Kadıoğlu, Arif Akyildiz, Nadiye Sever, Mehmet Emin Büyükbayram, Mehmet Bilici, Elanur Karaman, Mehmet Uzun, Murat Bardakcı, Caglar Koseoglu, Irem Bilgetekin, Mehmet Cihan İçli, Alper Türkel, Zafer Arık, Murat Sarı, Tugba Yavuzsen, Mehmet Ali Nahit Sendur, İsmail Erturk and Mutlu Dogan
Medicina 2025, 61(6), 1100; https://doi.org/10.3390/medicina61061100 - 17 Jun 2025
Viewed by 515
Abstract
Background and Objectives: Despite developments in cervical cancer (CC) treatment, an advanced stage is a poor prognostic factor. Cervical cancer is an immunogenic tumor in which viruses, like HPV, play a role in carcinogenesis. Therefore, systemic inflammatory markers (SIMs) may have prognostic [...] Read more.
Background and Objectives: Despite developments in cervical cancer (CC) treatment, an advanced stage is a poor prognostic factor. Cervical cancer is an immunogenic tumor in which viruses, like HPV, play a role in carcinogenesis. Therefore, systemic inflammatory markers (SIMs) may have prognostic value. Most studies on SIMs focus on the early stage by evaluating pretreatment levels. This study aims to evaluate the prognostic and predictive values of both pretreatment and post-treatment parameters at the advanced stage, as well as treatment efficacy after progression with first-line treatment. Materials and Methods: A total of 133 advanced-stage CC patients with progression on first-line platin–paclitaxel and bevacizumab were evaluated retrospectively. Demographic and histopathological characteristics were recorded along with treatment details. Pre-treatment baseline blood parameters and post-treatment follow-up values were recorded to calculate SIMs as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammatory response index (SIRI). Results: Median values for SIMs were accepted as cut-off values. Post-treatment values demonstrated stronger predictive power, with pre-treatment SIRI and NLR being significant only in univariate analysis, but not in multivariate analysis. High post-treatment SIRI (>2.1) was correlated with shorter overall survival (OS) and considered a poor prognostic factor. High post-treatment SIRI (>2.1), -SII (>746), and -PLR (>197) emerged as independent prognostic factors for progression-free survival (PFS). Their prognostic values were clearer in the whole population and the metachronous metastatic subgroup. Rechallenge of platinum-based chemotherapy was an option for those who had at least 6 months of PFS with first-line platinum-based chemotherapy. Bevacizumab addition to single-agent or combination regimens led to improved ORR as well. Conclusions: Post-treatment SIRI is a promising prognostic factor for OS, while post-treatment SIRI, SII, and PLR may serve as convenient SIMs for PFS. Platinum-based combination chemotherapy reinduction is a feasible second-line treatment strategy, especially with the addition of bevacizumab. Full article
(This article belongs to the Section Oncology)
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25 pages, 4785 KiB  
Article
TGFB2 Gene Methylation in Tumors with Low CD8+ T-Cell Infiltration Drives Positive Prognostic Overall Survival Responses in Pancreatic Ductal Adenocarcinoma
by Vuong Trieu, Michael Potts, Scott Myers, Stephen Richardson and Sanjive Qazi
Int. J. Mol. Sci. 2025, 26(12), 5567; https://doi.org/10.3390/ijms26125567 - 10 Jun 2025
Cited by 1 | Viewed by 747
Abstract
Pancreatic ductal adenocarcinoma (PDAC) typically exhibits asymptomatic clinical features, with most patients diagnosed at an advanced metastatic stage. Current treatment options are limited to cytotoxic standard therapies, primarily FOLFIRINOX or modified FOLFIRINOX regimens. This highlights a critical need for targeted therapies to improve [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) typically exhibits asymptomatic clinical features, with most patients diagnosed at an advanced metastatic stage. Current treatment options are limited to cytotoxic standard therapies, primarily FOLFIRINOX or modified FOLFIRINOX regimens. This highlights a critical need for targeted therapies to improve efficacy and reduce toxicity. We have sought to identify potential biomarkers based on DNA methylation profiles to identify patient groupings with improved overall survival (OS) based on the Transforming Growth Factor Beta (TGFB) gene complex, and the interferon-related pathway gene, IFI27, using the TCGA dataset for PDAC patients. We employed a multivariate Cox proportional hazards model to directly compare hazard ratios for TGFB1/2/3 and IFI27 methylation impacting OS. We also controlled for age at diagnosis, sex, and TGFB2 gene methylation by examining the statistical interactions between the marker gene mRNA expression and the TGFB2 gene. Genes were filtered based on the tumor-specific expression patterns and Cox models with highly significant interaction terms to identify mRNA expression of genes that amplified the impact of TGFB2 methylation. The effect of the TGFB2 gene methylation in the context of marker gene mRNA expression was analyzed using Kaplan–Meier (KM) analysis. Marker genes were correlated to T-cell enrichment patterns using the deconvolution algorithms provided by the TIMER 2.0 database. Methylation of TGFB2, TGFB3 and IFI27 genes using median cut-off values for KM plots showed significant improvements in median overall survival of 5.7 (p = 0.044), 5.2 (p = 0.036), and 3.7 (p = 0.028) months for high methylation levels for TGFB2, IFI27, and TGFB3 genes, respectively. In contrast, high levels of TGFB1 methylation exhibited a shorter 4.7 (p = 0.016) month median OS time. The impact of TGFB2 methylation was amplified at low expressions of marker genes that were highly correlated with CD8+ T-cell infiltration. Patients with high levels of TGFB2 methylation when compared to low levels of TGFB2 methylation showed median overall survival (OS) improvements at low mRNA expression levels: 54.2 months for CD3D (p < 0.0001); 54 months for LCK (p = 0.0009); 54.9 months for HLA-DRA (p = 0.0001); and 9 months for RAC2 mRNA expression (p = 0.0057). TGFB2 gene methylation drives TGFB2 mRNA expression to achieve clinical impact, as high levels of TGFB2 mRNA, at low levels of the marker genes, resulted in worse median OS times. TGFB2 methylation is a prognostic marker for PDAC patients within an immunosuppressed tumor microenvironment characterized by low CD8+ T-cell infiltration. This correlation is functionally associated with TGFB2 mRNA production, suggesting that targeting TGFB2 mRNA through knockdown can potentially enhance PDAC prognosis. Full article
(This article belongs to the Special Issue Targeted Treatments in Cancer: 2nd Edition)
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18 pages, 3183 KiB  
Article
Optimizing Drug-Resistant Tuberculosis Treatment Outcomes in a High HIV-Burden Setting: A Study of Sputum Conversion and Regimen Efficacy in Rural South Africa
by Mojisola Clara Hosu, Lindiwe Modest Faye and Teke Apalata
Pathogens 2025, 14(5), 441; https://doi.org/10.3390/pathogens14050441 - 30 Apr 2025
Cited by 1 | Viewed by 709
Abstract
Background: Sputum culture and smear conversion are key indicators of treatment response in drug-resistant tuberculosis (DR-TB). This study aimed to assess sputum conversion and regimen efficacy among DR-TB patients and identify factors influencing conversion rates. Methods: This retrospective cohort study analyzed medical records [...] Read more.
Background: Sputum culture and smear conversion are key indicators of treatment response in drug-resistant tuberculosis (DR-TB). This study aimed to assess sputum conversion and regimen efficacy among DR-TB patients and identify factors influencing conversion rates. Methods: This retrospective cohort study analyzed medical records of DR-TB patients treated between 2018 and 2020 in the Eastern Cape Province, South Africa. Kaplan–Meier curves, Spearman correlation, and logistic regression models were used to assess time-to-sputum conversion and its predictors. Results: Among the 88% of patients who achieved sputum conversion, the median time ranged from 29 to 59 days. Patients on short treatment regimens converted significantly faster than those on long regimens (p = 7.55 × 10−15), with 90% of short-regimen patients achieving favorable outcomes compared to 52% in the long regimen group (p = 0.0000040). Spearman correlation revealed a weak but significant positive association between comorbidities and conversion time (r = 0.041, p = 0.041). HIV-positive patients had a slower conversion rate than HIV-negative patients, but this association was not statistically significant (χ2 = 0.426, p = 0.514). Logistic regression identified older age as a predictor of favorable outcomes (coefficient = 0.039, p = 0.045), while regimen type and HIV status did not show significant predictive power. Conclusions: Shorter treatment regimens significantly improve sputum conversion rates and treatment outcomes. The findings support optimizing DR-TB treatment through personalized regimens based on patient health status and drug resistance patterns. This study provides evidence to enhance TB control efforts in high-burden regions, with implications for global treatment strategies. Full article
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14 pages, 2937 KiB  
Article
Impact of the Addition of Daratumumab to the Frontline Treatment of Patients with Immunoglobulin Light-Chain Amyloidosis: A Single-Centre Experience
by Elena Alejo, Cristina Agulló, Borja Puertas, Rocío Eiros, Beatriz Rey-Búa, Carmen Barnés, Marta Rodríguez-González, Lucía López-Corral, Ángel Santos-Briz, Fernando Escalante, María-Luisa Pérez-García, Silvia Jiménez-Cabrera, Norma C. Gutiérrez, Noemi Puig, María-Victoria Mateos and Verónica González-Calle
Cancers 2025, 17(9), 1440; https://doi.org/10.3390/cancers17091440 - 25 Apr 2025
Viewed by 460
Abstract
Background: Daratumumab-based regimens represent the gold-standard therapy for newly diagnosed AL amyloidosis patients. However, there are few studies about the efficacy of this treatment in real life. Methods: This study included 99 patients: 27 (27.3%) received daratumumab and proteasome inhibitor-based schemes, [...] Read more.
Background: Daratumumab-based regimens represent the gold-standard therapy for newly diagnosed AL amyloidosis patients. However, there are few studies about the efficacy of this treatment in real life. Methods: This study included 99 patients: 27 (27.3%) received daratumumab and proteasome inhibitor-based schemes, 46 (46.4%) were treated with proteasome inhibitors and/or immunomodulator-based regimens, and 26 (26.3%) were treated with chemotherapy. Results: Patients receiving daratumumab and proteasome inhibitor-based regimens achieved higher rates of partial haematological responses or better (100.0% vs. 78.3% vs. 58.3%; p = 0.009 and p < 0.001) and complete responses (74.1% vs. 37.0% vs. 12.5%; p = 0.003 and p < 0.001) than the proteasome inhibitors and/or immunomodulators and chemotherapy groups, respectively. Daratumumab and proteasome inhibitor-based schemes resulted in a shorter time to haematological response (1 month to partial response or better and 4 months to complete response). Moreover, in the group treated with daratumumab and proteasome inhibitor-based regimens, there was a trend of obtaining better and faster organ responses. The benefit of daratumumab and proteasome inhibitor-based regimens was that they resulted in an improvement in progression-free survival (not reached) compared to the proteasome inhibitor and chemotherapy groups (18 months; p = 0.022 and 6 months; p = 0.002). In addition, the clinical benefit was consistent in patients with Mayo Clinic stages III–IV. Conclusions: This study supports the efficacy and superiority of adding daratumumab to the frontline treatment over proteasome inhibitor-based regimens and chemotherapy in AL amyloidosis, including in advanced cardiac disease. Full article
(This article belongs to the Section Clinical Research of Cancer)
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21 pages, 1220 KiB  
Article
Long-Term Outcomes of Patients Undergoing Conversion Surgery After Induction Chemotherapy: Turkish Oncology Group Study
by Furkan Ceylan, Selin Aktürk Esen, Olçun Ümit Ünal, Ferit Aslan, İlknur Deliktaş Onur, Öztürk Ateş, Erkut Demirciler, İlkay Tuğba Ünek, Ahmet Gülmez, Esra Özen Engin, Semra Taş, Gamze Gököz Doğu, Melih Şimşek, Hacı Mehmet Türk, Ali İnal, Gökhan Şahin, Haydar Çağatay Yüksel, Ateş Kutay Tenekeci, Mutlu Hızal, Mehmet Ali Nahit Şendur and Doğan Uncuadd Show full author list remove Hide full author list
Medicina 2025, 61(5), 776; https://doi.org/10.3390/medicina61050776 - 22 Apr 2025
Viewed by 621
Abstract
Background and Objectives: Conversion surgery for liver metastatic colorectal cancer (mCRC) has been associated with prolonged survival. This study aimed to evaluate the efficacy and safety of integrating biological therapies with fluorouracil-based induction chemotherapy in patients with isolated liver mCRC who subsequently [...] Read more.
Background and Objectives: Conversion surgery for liver metastatic colorectal cancer (mCRC) has been associated with prolonged survival. This study aimed to evaluate the efficacy and safety of integrating biological therapies with fluorouracil-based induction chemotherapy in patients with isolated liver mCRC who subsequently underwent curative resection of both the primary tumor and liver metastases. Materials and Methods: This multicenter, retrospective study, conducted by the Turkish Oncology Group (TOG), included 116 patients from 11 tertiary centers who underwent conversion surgery following induction chemotherapy between 2009 and 2024. Results: The median age was 57 years, with 62% male patients. The median follow-up period was 55.3 months. The median progression-free survival (PFS) and overall survival (OS) were 21.1 and 53.7 months, respectively. No significant differences in PFS or OS were observed based on biological therapy use or tumor localization. Among patients with RAS/RAF wild-type tumors, PFS and OS were comparable between those receiving Anti-EGFR and Anti-VEGF therapy. In RAS/RAF mutant tumors, the addition of Anti-VEGF therapy did not confer a survival benefit. Factors associated with shorter PFS included advanced tumor stage (ypT3-T4), lymph node metastasis, and multiple metastases, while shorter OS was linked to advanced tumor stage and lack of objective response. Conclusions: Surgical resection plays a pivotal role in improving survival outcomes in patients with potentially resectable liver mCRC. Optimizing induction chemotherapy regimens may enhance conversion rates and prolong long-term survival. Further studies are needed to refine treatment selection based on tumor localization, mutation status, and molecular biomarkers. Full article
(This article belongs to the Section Oncology)
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18 pages, 1451 KiB  
Article
The Mesothelioma Systemic Inflammation Score Is Independently Associated with Overall Survival and Predicts Benefit of Multimodality Treatment in Pleural Mesothelioma
by Berta Mosleh, Katharina Sinn, Anna Cho, Anton Reiner, Ariane Steindl, Christian Lang, Sabine Zöchbauer-Müller, Karin Dieckmann, Joachim Widder, Helmut Prosch, Balazs Dome, Karin Schelch, Clemens Aigner, Thomas Klikovits, Michal Benej, Stefan Watzka, Martin Filipits, Servet Bölükbas, Pavla Sarova, Daniela Gompelmann, Michael Grusch and Mir Alireza Hodaadd Show full author list remove Hide full author list
Cancers 2025, 17(8), 1371; https://doi.org/10.3390/cancers17081371 - 20 Apr 2025
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Abstract
Background/Objectives: Malignant pleural mesothelioma (MPM) remains challenging to treat, with a poor prognosis. As controversy about clinical management continues, predictive biomarkers for patient selection to indicate the benefit of treatment modalities are urgently needed. Methods: In a retrospective analysis of 195 patients between [...] Read more.
Background/Objectives: Malignant pleural mesothelioma (MPM) remains challenging to treat, with a poor prognosis. As controversy about clinical management continues, predictive biomarkers for patient selection to indicate the benefit of treatment modalities are urgently needed. Methods: In a retrospective analysis of 195 patients between 1994 and 2020 at the Department of Thoracic Surgery, Medical University of Vienna, Austria, the Mesothelioma Systemic Inflammation Score (MSIS)—consisting of pretreatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), and fibrinogen—was tested for its prognostic and predictive significance. The prognostic impact of MSIS was subsequently validated in an independent cohort of 80 patients treated at the Department of Thoracic Surgery, Karl Landsteiner Institute for Clinical and Translational Thoracic Surgery Research, Clinic Floridsdorf, Vienna, Austria. Results: Median overall survival (OS) was 14 months for the entire cohort (95% CI: 11.4–16.6). Patients undergoing multimodality treatment including macroscopic complete resection had a longer OS (22.3 months, 95% CI: 18.6–26.0; p < 0.001). In multivariable analysis, MSIS (p < 0.001), disease stage (p = 0.001), and the type of treatment (p = 0.004) were confirmed as independent predictors for OS. Higher MSIS was associated with shorter OS (p < 0.001). Significant survival benefit of multimodality regimens including surgery was limited to patients with low MSIS. Among patients with low (≤ 2) MSIS, multimodality therapy was associated with significantly prolonged OS when compared with chemo- and/or radiotherapy alone (25.8 months [95% CI: 16.4–35.3] vs. 14.4 months [95% CI: 10.4–18.4], p < 0.001). In contrast, among patients with elevated MSIS, no survival benefit was achieved by surgery over conservative treatment (11.8 months [95% CI: 8.3–15.3] vs. 8.2 months [95% CI: 5.2–11.3], p = 0.233). The ability of MSIS to predict survival was equivalent between the baseline and the independent validation cohort (p < 0.001). Conclusions: The Mesothelioma Systemic Inflammation Score was found to be an independent prognostic score in pleural mesothelioma, predicting benefit from macroscopic complete resection as part of multimodality treatment in distinct patients. Full article
(This article belongs to the Section Cancer Therapy)
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19 pages, 3836 KiB  
Article
Impact of Infection on Survival Outcomes in High-Grade Gliomas: A Retrospective Analysis of 26 Cases in Our Fifteen-Year Experience—Janus Faced Phenomenon
by György Berényi, Dóra Szabó, Gergely Agócs, Blanka Andrássy, Imre Fedorcsák, Loránd Erőss and László Sipos
Cancers 2025, 17(8), 1348; https://doi.org/10.3390/cancers17081348 - 17 Apr 2025
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Abstract
Background/Objectives: Glioblastoma IDH-wildtype CNS WHO grade 4 and astrocytoma IDH-mutant WHO grade 4 (together, high-grade gliomas: HGGs) are the most prevalent malignant brain tumors, carrying a poor prognosis despite multimodal treatment. Surgical site infections (SSIs) represent a relative frequent postoperative complication in HGG [...] Read more.
Background/Objectives: Glioblastoma IDH-wildtype CNS WHO grade 4 and astrocytoma IDH-mutant WHO grade 4 (together, high-grade gliomas: HGGs) are the most prevalent malignant brain tumors, carrying a poor prognosis despite multimodal treatment. Surgical site infections (SSIs) represent a relative frequent postoperative complication in HGG patients. Despite multimodal treatment protocols combining surgery, radiotherapy, and temozolomide chemotherapy, HGGs remain associated with a dismal prognosis, underscoring the need to evaluate how SSIs impact disease progression and survival outcomes. This study’s aim was to investigate the influence of SSIs on the clinical course of patients with HGGs. Methods: A comprehensive review of medical records for HGG patients treated at our institution between 2010 and 2024 identified 26 patients with SSIs. These patients were compared to an age-matched control group with the same histological diagnosis and treatment regimen. This study analyzed overall survival (OS), microbiological data, and pathological parameters to assess the impact of SSIs on patient outcomes. Survival differences between the infected and non-infected groups were evaluated using Kaplan–Meier survival curves. Remarkably, three patients with exceptionally long overall survival were highlighted in this study. Results: Among the cohort of 2008 patients with HGG surgery, 26 patients developed SSIs. An age-matched control group of 26 patients was identified, none of whom experienced SSIs. Comparing the OS between the infected and uninfected groups, a statistically significant improvement in OS was observed in the infected group (p = 0.049). The median OS in the infected group was 388 days, slightly shorter than the median OS of 422 days in the control group. However, the mean OS was markedly higher in the infected group (674 days) compared to the control group (442 days). The standard deviation of OS in the infected group was notably expansive, indicating substantial variability in survival outcomes. A cluster of infected patients with SSIs near the time of diagnosis had shorter OS, while other infected cases demonstrated significantly longer survival, exceeding both median and mean OS values. In contrast, the uninfected group showed limited standard deviation values, with uniformly distributed individual OS data around the median and mean values. Expectedly, IDH mutation status significantly influenced the survival in cohort patients. However, when stratified by infection status, no association between IDH mutation and improved infection-related survival was identified. The microbiological profile of SSIs was diverse, encompassing Gram-positive and Gram-negative bacteria as well as aerobic and anaerobic organisms. Conclusions: These findings underscore the heterogeneity of infection-related outcomes and their potential impact on survival in HGG patients. According to our knowledge, our study is one of the largest retrospective studies to date investigating and confirming the significant relationship between SSIs and HGG patients’ survival. Our results confirm the Janus Face phenomenon of infections, having both negative and positive effects depending on the context. Full article
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13 pages, 476 KiB  
Article
Post-Surgical Central Nervous System Infections in the Era of Multidrug Antibiotic Resistance in Greece—A Single-Center Experience of a Decade
by Konstantinos Markakis, Konstantina Kapiki, Angela Ava Arbelle Edric, Asimina Aphrodite Pappas, Georgios Feretos, Sideris Nanoudis, Dimitrios Pilalas, Theodoros Michailidis, Efthymia Protonotariou, Lemonia Skoura, Nikolaos Foroglou, Symeon Metallidis and Olga Tsachouridou
Pathogens 2025, 14(4), 390; https://doi.org/10.3390/pathogens14040390 - 16 Apr 2025
Cited by 1 | Viewed by 792
Abstract
Post-surgical central nervous system infections (PCNSIs) are a major cause of morbidity, poor functional outcomes and mortality in neurosurgical patients. These infections complicate operations of the CNS or are related to the use of neurosurgical devices or drainage catheters. Gram-negative bacteria, with multiple [...] Read more.
Post-surgical central nervous system infections (PCNSIs) are a major cause of morbidity, poor functional outcomes and mortality in neurosurgical patients. These infections complicate operations of the CNS or are related to the use of neurosurgical devices or drainage catheters. Gram-negative bacteria, with multiple resistance patterns, are often isolated and these infections are difficult to treat, due to suboptimal antibiotic therapeutic levels in the cerebrospinal fluid (CSF). This is a retrospective study of PCNSIs between 2014 and 2024 in a single center of a tertiary hospital in Thessaloniki, Greece. Out of 2401 neurosurgical procedures, forty-one were complicated by PCNSIs, yielding a total PCNSI prevalence of 1.7%. Thirty-five involved cases with positive CSF culture. The most common interventions were craniotomies for the resection of tumors or other lesions (30.1%). Most cases referred to an EVD infection. Acinetobacter baumannii was the most commonly isolated pathogen (34.1%), followed by coagulase-negative Staphylococcus (22%) and Pseudomonas spp. (14.6%). Colistin and tigecycline were the most prescribed combination regimens. The median time to the first positive CSF culture postoperatively was 11 days (IQR 18 days). Empirical antibiotic treatment was adequate in 26 (63.4%) cases. The mortality rate among these patients was 65.7%. Survivors were significantly younger than non-survivors (p < 0.01) and had a shorter ICU length of stay (p < 0.01). The type of infection, time to infection onset, isolated pathogen, susceptibility to the empirical treatment and Charlson Comorbidity Index did not differ between the two groups. The mortality rate remains high in patients with PCNSIs. An integrated approach including surgical source control, supportive care, combination antimicrobial therapy and subsequent rehabilitation are mandatory to achieve treatment success and neurological convalescence. Full article
(This article belongs to the Special Issue Hospital-Acquired Infections and Multidrug-Resistant (MDR) Pathogens)
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