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BackgroundDiffuse large B-cell lymphoma (DLBCL) involving the gastrointestinal (GI) organs is rare, and real-world outcomes after combined modality therapy (CMT) with systemic therapy (ST) and radiotherapy (RT) are not well-characterized, particularly in the contemporary era. We characterized outcomes in a large cohort of GI-DLBCL patients treated with ST alone or CMT.MethodsPatients with GI-DLBCL treated at a single institution were retrospectively reviewed. Kaplan-Meier and Cox regression models estimated survival. Multivariable analyses were conducted using the Cox proportional hazards model.ResultsOf 204 patients, gastric involvement was most common (63%). Most presented with early-stage disease (61%). All patients received ST and 65 patients (32%) received RT, 88% as part of first-line CMT. Median dose was 36 Gy (IQR 30.6–39.6) in 18 fractions (IQR 17–22). Median follow-up was 46 months. Five-year overall survival (OS) and progression-free survival (PFS) was 88% and 84%, respectively; complete response (CR) rate was 82%. Improved OS associated with low IPI (p=0.001), fewer chemotherapy lines (p0.25). Only early stage and CR correlated with improved OS on multivariable analysis. Stomach-directed RT vs. RT to other sites correlated with improved PFS and OS (p

Background: Undifferentiated pleomorphic sarcomas (UPSs) are amongst the most common subtypes of soft-tissue sarcomas. Few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and other high-grade pleomorphic STS patients are available. Purpose: The purpose of our study is to describe the efficacy and toxicity of ICB in patients with advanced UPSs and other high-grade pleomorphic sarcomas treated at our institution. Methods: This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center between 1 January 2015 and 1 January 2023. Patients included in trials for which results are not yet published were excluded. Results: Thirty-six patients with advanced/metastatic pleomorphic sarcomas were included. The median age was 52 years. A total of 26 patients (72%) had UPSs and 10 patients (28%) had other high-grade pleomorphic sarcomas. The median follow-up time was 8.8 months. The median PFS was 2.9 months. The 3-month PFS and 6-month PFS were 46% and 32%, respectively. The median OS was 12.9 months. The 12-month OS and 24-month OS were 53% and 29%, respectively. The best response, previous RT, and type of ICB treatment were significantly and independently associated with shorter PFS (p = 0.0012, p = 0.0019 and p = 0.036, respectively). No new safety signal was identified, and the toxicity was overall manageable with no toxic deaths and only four patients (11%) stopping treatment due to toxicity. Conclusions: Real-world retrospective data are consistent with the published literature, with a promising 6-month PFS of 32%. Partial or stable responders to ICB treatment have significantly improved PFS compared to progressors.

Abstract The effects of the curvature parameters on the energy eigenvalues and thermodynamic properties of quantum pseudoharmonic oscillator are investigated within the framework of nonrelativistic quantum mechanics. By employing Nikiforov-Uvarov method, the energy spectra are obtained and used to study the ordinary statistics and q-deformed superstatistics as a function of temperature in the presence and absence of the curvature parameters. It is shown that the q-deformed supertatistics properties of the quantum pseudoharmonic oscillator reduce to the ordinary statistical properties in the absence of the deformation parameter. Finally, our results are illustrated graphically to show the behaviour of the energy spectra and thermodynamic properties for the three curvature parameters: $$\kappa = - 1,\,\,\kappa = 1\,\,{\text{and}}\,\,\kappa = 0$$ κ = - 1 , κ = 1 and κ = 0 .

BackgroundEvaluating the effectiveness of Chagas disease treatment poses challenges due to the lack of biomarkers for disease progression and therapeutic response. In this study, we aimed to assess the clearance of Trypanosoma cruzi (T. cruzi) parasites in a group of benznidazole (BNZ)-treated chronic Chagas disease patients using high-sensitivity quantitative PCR (qPCR) and track T. cruzi antibody levels through a semiquantitative chemiluminescent assay.MethodsA total of 102 T. cruzi seropositive patients with previous PCR-positive results were enrolled in the study. We collected samples 30 days before treatment (T-30d), on the day before initiating BNZ treatment (T0d), and at follow-up visits 60 days (T60d), 6 months (T6M), 12 months (T12M), and 36 months (T36M) after treatment initiation. Treatment efficacy was assessed by testing of serial samples using a target-capture qPCR assay specific to satellite T. cruzi DNA and the ORTHO T. cruzi ELISA Test System for antibody quantitation.ResultsOf the enrolled individuals, 87 completed at least 50% of the treatment course, and 86 had PCR results at follow-up visits T6M, T12M, and T36M. PCR results exhibited fluctuations before and after treatment, but levels were significantly lower post-treatment. Only 15 cases consistently tested PCR-negative across all post-treatment visits. Notably, nearly all participants demonstrated a declining antibody trajectory, with patients who tested PCR-negative at T36M exhibiting an earlier and more pronounced decline compared to PCR-positive cases at the same visit.ConclusionOur study suggests that serial PCR results pose challenges in interpretation. In contrast, serial antibody levels may serve as an ancillary, or even a more reliable indicator of parasite decline following BNZ treatment. Monitoring antibody levels can provide valuable insights into the efficacy of treatment and the persistence of parasites in Chagas disease patients.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma (P.1) variant emerged in November 2020 and drove the second wave of coronavirus disease (COVID-19) in Brazil. Emergence of this [...]

Background: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country. Methods: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil’s most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning. Results: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5–21.2%) in Curitiba to 75.0% (95% CrI 70.8–80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system’s collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43–3.53). Conclusions: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread. Funding: This work was supported by Itaú Unibanco ‘Todos pela Saude’ program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Medicina; Programa Inova Fiocruz-CE/Funcap - Edital 01/2020 Number: FIO-0167-00065.01.00/20 SPU N°06531047/2020; JBS – Fazer o bem faz bem.

Background The epidemiology of childhood SARS-CoV-2 infection and COVID-19-related illness remains little studied in high-transmission tropical settings, partly due to the less severe clinical manifestations typically developed by children and the limited availability of diagnostic tests. To address this knowledge gap, we investigate the prevalence and predictors of SARS-CoV-2 infection (either symptomatic or not) and disease in 5 years-old Amazonian children. Methodology/Principal findings We retrospectively estimated SARS-CoV-2 attack rates and the proportion of infections leading to COVID-19-related illness among 660 participants in a population-based birth cohort study in the Juruá Valley, Amazonian Brazil. Children were physically examined, tested for SARS-CoV-2 IgG and IgM antibodies, and had a comprehensive health questionnaire administered during a follow-up visit at the age of 5 years carried out in January or June-July 2021. We found serological evidence of past SARS-CoV-2 infection in 297 (45.0%; 95% confidence interval [CI], 41.2–48.9%) of 660 cohort participants, but only 15 (5.1%; 95% CI, 2.9–8.2%) seropositive children had a prior medical diagnosis of COVID-19 reported by their mothers or guardians. The period prevalence of clinically apparent COVID-19, defined as the presence of specific antibodies plus one or more clinical symptoms suggestive of COVID-19 (cough, shortness of breath, and loss of taste or smell) reported by their mothers or guardians since the pandemic onset, was estimated at 7.3% (95% CI, 5.4–9.5%). Importantly, children from the poorest households and those with less educated mothers were significantly more likely to be seropositive, after controlling for potential confounders by mixed-effects multiple Poisson regression analysis. Likewise, the period prevalence of COVID-19 was 1.8-fold (95%, CI 1.2–2.6-fold) higher among cohort participants exposed to food insecurity and 3.0-fold (95% CI, 2.8–3.5-fold) higher among those born to non-White mothers. Finally, children exposed to household and family contacts who had COVID-19 were at an increased risk of being SARS-CoV-2 seropositive and–even more markedly–of having had clinically apparent COVID-19 by the age of 5 years. Conclusions/Significance Childhood SARS-CoV-2 infection and COVID-19-associated illness are substantially underdiagnosed and underreported in the Amazon. Children in the most socioeconomically vulnerable households are disproportionately affected by SARS-CoV-2 infection and disease. Author summary The epidemiology of childhood COVID-19 in the tropics remains a relatively neglected research topic, in part because SARS-CoV-2 typically causes fewer severe illnesses, hospitalizations, and deaths in children than in adults. Here we show that 45% of 660 participants in a birth cohort study in the Brazilian Amazon had SARS-CoV-2 antibodies at the age of 5 years, although only 5% of them reported previously diagnosed COVID-19 episodes–implying that as many as 8 in 9 SARS-CoV-2 infections had remained undiagnosed in these young children. Only 16% of the seropositive children had reportedly experienced cough, shortness of breath, and/or loss of taste or smell. The most socioeconomically vulnerable participants were more likely to have experienced SARS-CoV-2 infection and overt COVID-19 by the age of 5 years. Importantly, children exposed to household food insecurity, which affects 54% of our study participants, had their COVID-19 risk increased by 76%.

Simple Summary: Undifferentiated pleomorphic sarcomas (UPSs) represent 10–20% of all soft tissue sarcomas (STSs) and have quickly emerged as one of the more immune-sensitive types. There are few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and those with other high-grade pleomorphic STSs. This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center intended to describe the efficacy and toxicity of ICB in this particular group of patients. We find that our outcomes are comparable to those in the published literature and pose a question regarding the need to further evaluate the optimal sequencing of radiotherapy and prior lines of systemic therapy. Background: Undifferentiated pleomorphic sarcomas (UPSs) are amongst the most common subtypes of soft-tissue sarcomas. Few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and other high-grade pleomorphic STS patients are available. Purpose: The purpose of our study is to describe the efficacy and toxicity of ICB in patients with advanced UPSs and other high-grade pleomorphic sarcomas treated at our institution. Methods: This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center between 1 January 2015 and 1 January 2023. Patients included in trials for which results are not yet published were excluded. Results: Thirty-six patients with advanced/metastatic pleomorphic sarcomas were included. The median age was 52 years. A total of 26 patients (72%) had UPSs and 10 patients (28%) had other high-grade pleomorphic sarcomas. The median follow-up time was 8.8 months. The median PFS was 2.9 months. The 3-month PFS and 6-month PFS were 46% and 32%, respectively. The median OS was 12.9 months. The 12-month OS and 24-month OS were 53% and 29%, respectively. The best response, previous RT, and type of ICB treatment were significantly and independently associated with shorter PFS (p = 0.0012, p = 0.0019 and p = 0.036, respectively). No new safety signal was identified, and the toxicity was overall manageable with no toxic deaths and only four patients (11%) stopping treatment due to toxicity. Conclusions: Real-world retrospective data are consistent with the published literature, with a promising 6-month PFS of 32%. Partial or stable responders to ICB treatment have significantly improved PFS compared to progressors. [ABSTRACT FROM AUTHOR]

Swift J1357.2-0933 is a black hole transient that is of particular interest due to the optical recurrent dips found during its first two outbursts (in 2011 and 2017), which lack an obvious X-ray equivalent. We present a study based on fast optical photometry during its two most recent outbursts, in 2019 and 2021. Our observations reveal that the optical dips were present in every observed outburst of the source, although they were shallower and showed longer recurrence periods in the two most recent and fainter events. We performed a global study of the dips properties in the four outbursts and found that they do not follow a common temporal evolution. In addition, we discovered a correlation with the X-ray and optical fluxes, with the dips being more profound and showing shorter recurrence periods for brighter stages. This trend seems to extend even to the faintest, quiescent states of the source. We discuss these results in the context of the possible connection between optical dips and outflows found in previous works. [ABSTRACT FROM AUTHOR]

We present radial velocity measurements of the very bright (V ∼ 5.7) nearby F star, DMPP-4 (HD 184960). The anomalously low Ca ii H&K emission suggests mass-loss from planets orbiting a low activity host star. Periodic radial velocity variability with ∼10 m s−1 amplitude is found to persist over a >4 yr time-scale. Although the non-simultaneous photometric variability in four TESS sectors supports the view of an inactive star, we identify periodic photometric signals and also find spectroscopic evidence for stellar activity. We used a posterior sampling algorithm that includes the number of Keplerian signals, N p, as a free parameter to test and compare (1) purely Keplerian models (2) a Keplerian model with linear activity correlation and (3) Keplerian models with Gaussian processes. A preferred model, with one Keplerian and quasi-periodic Gaussian process indicates a planet with a period of |$P_\textrm {b} = 3.4982^{+0.0015}_{-0.0027}$| d and corresponding minimum mass of |$m_\textrm {b}\, \textrm {sin}\, i = 12.2^{+1.8}_{-1.9}$| M⊕. Without further high-time resolution observations over a longer time-scale, we cannot definitively rule out the purely Keplerian model with two candidates planets with |$P_\textrm {b} = 2.4570^{+0.0026}_{-0.0462}$| d, minimum mass |$m_\textrm {b}\, \textrm {sin}\, i = 8.0^{+1.1}_{-1.5}$| M⊕ and |$P_\textrm {c} = 5.4196^{+0.6766}_{-0.0030}$| d and corresponding minimum mass of |$m_\textrm {b}\, \textrm {sin}\, i = 12.2^{+1.4}_{-1.6}$| M⊕. The candidate planets lie in the region below the lower-envelope of the Neptune Desert. Continued mass-loss may originate from the highly irradiated planets or from an as yet undetected body in the system. [ABSTRACT FROM AUTHOR]

Background: The COVID- 19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS- CoV- 2 or other respiratory pathogens in the country. Methods: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil's most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex- specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning. Results: The inferred attack rate of SARS- CoV- 2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5--21.2%) in Curitiba to 75.0% (95% CrI 70.8--80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age- specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma- dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43--3.53). Conclusions: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS- CoV- 2 spread. Funding: This work was supported by Itaú Unibanco 'Todos pela Saude' program; FAPESP (grants 18/14389- 0, 2019/21585- 0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV- 034652); REDS- IV- P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018- 6); Fundação Faculdade de Medicina; Programa Inova Fiocruz- CE/Funcap - Edital 01/2020 Number: FIO- 0167- 00065.01.00/20 SPU N°06531047/2020; JBS -- Fazer o bem faz bem. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: The objective is to develop a low-risk, cost-effective method to teach procedures that require learning by feel and high-volume pattern recognition, starting with the midurethral sling. Methods: This video describes the creation of a virtual reality model utilizing de-identified patient data, artificial intelligence algorithms and haptics; and demonstrates the use of the training system for trocar passage of the retropubic midurethral sling procedure. Results: This innovative system overcomes the lack of visualization and "blind" nature of sling surgery. Novel artificial intelligence provides high accuracy of anatomical landmarks and a realistic 3D environment. The trainee benefits from haptic and visual alerts for real-time feedback on the trocar insertion pathway and scoring to develop competency. Conclusion: This is one of the first noncadaveric, nonstatic models available in the field. It allows for multiple low-risk exercises and provides more surgeons with training outside the operating room, at their own institution, and avoids the need for patient subjects. Training can be disseminated at a significantly lower cost and greater convenience than remote cadaver laboratories or intraoperative observation and has a higher fidelity than available static models, particularly after multiple passes. This has implications not only for retropubic midurethral slings but also for urogynecological and "blind" surgery as a whole. [ABSTRACT FROM AUTHOR]