Long-Term Patient-Reported Dyspareunia After Definitive Chemoradiation for Anal Cancer: Using the Anterior Vaginal Wall as an Organ-at-Risk to Define an Actionable Dosimetric Goal.

Purpose: Chemoradiation therapy (CRT) is the standard treatment for squamous cell carcinoma of the anus (SCCA). This study aimed to investigate the relationship between vaginal dosimetry and long-term patient-reported dyspareunia after treatment. We further aimed to use the anterior vaginal wall (AVW) as an organ at risk to define an actionable dosimetric clinical goal to decrease the risk of patient-reported dyspareunia. Methods and Materials: Women with SCCA treated with intensity modulated radiation therapy-based CRT were surveyed at least 2 years after successfully completing therapy. A Female Sexual Function Index (FSFI) pain subscore ≤4 was used to define dyspareunia. Dosimetric parameters were calculated for both the full vaginal canal and AVW. Multivariable linear regression models were created to identify predictors of FSFI pain subscore using backward selection to identify final variables include in the models. An actionable dosimetric predictor for dyspareunia was established using the Youden index method for cutoff optimization. Results: Of 184 women who were contacted, 90 (49%) returned completed surveys. Of those who completed surveys, 51 (56.7%) reported being sexually active, and 47 had dosimetric data available for review. Of sexually active respondents, 32 (68%) had an FSFI pain subscore ≤4. Multiple regression models were generated using the full vaginal canal and AVW as organs at risk, and both models showed similar predictive relationships with volumetric dose parameters emerging as the best dosimetric predictors for dysparenuia. Age over 65 years was also associated with higher FSFI pain subscores (eg, less pain with intercourse) in both models. AVW V35 Gy < 60% was identified as the optimal cutoff to reduce the risk of patient-reported dyspareunia. Conclusions: Increased dose to the vaginal canal is significantly associated with worse patient-reported dyspareunia following CRT for SCCA. Minimizing dose to the AVW to V35 Gy < 60% may reduce the risk of this quality of life-limiting toxicity. Further prospective evaluation is needed to validate these findings.

Analyzing the Relationship between Dose and Geometric Agreement Metrics for Auto-Contouring in Head and Neck Normal Tissues.

This study aimed to determine the relationship between geometric and dosimetric agreement metrics in head and neck (H&N) cancer radiotherapy plans. A total 287 plans were retrospectively analyzed, comparing auto-contoured and clinically used contours using a Dice similarity coefficient (DSC), surface DSC (sDSC), and Hausdorff distance (HD). Organs-at-risk (OARs) with ≥200 cGy dose differences from the clinical contour in terms of Dmax (D0.01cc) and Dmean were further examined against proximity to the planning target volume (PTV). A secondary set of 91 plans from multiple institutions validated these findings. For 4995 contour pairs across 19 OARs, 90% had a DSC, sDSC, and HD of at least 0.75, 0.86, and less than 7.65 mm, respectively. Dosimetrically, the absolute difference between the two contour sets was <200 cGy for 95% of OARs in terms of Dmax and 96% in terms of Dmean. In total, 97% of OARs exhibiting significant dose differences between the clinically edited contour and auto-contour were within 2.5 cm PTV regardless of geometric agreement. There was an approximately linear trend between geometric agreement and identifying at least 200 cGy dose differences, with higher geometric agreement corresponding to a lower fraction of cases being identified. Analysis of the secondary dataset validated these findings. Geometric indices are approximate indicators of contour quality and identify contours exhibiting significant dosimetric discordance. For a small subset of OARs within 2.5 cm of the PTV, geometric agreement metrics can be misleading in terms of contour quality.

Impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in patients with soft tissue sarcoma: an analysis from the OnCovid registry.

Background: To date, limited evidence exists on the impact of COVID-19 in patients with soft tissue sarcoma (STS), nor about the impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in this specific population. Methods: We described COVID-19 morbidity and mortality among patients with STS across 'Omicron' (15 December 2021-31 January 2022), 'Pre-vaccination' (27 February 2020-30 November 2020), and 'Alpha-Delta' phase (01 December 2020-14 December 2021) using OnCovid registry participants (NCT04393974). Case fatality rate at 28 days (CFR28) and COVID-19 severity were also described according to the SARS-CoV-2 vaccination status, while the impact of the receipt of cytotoxic chemotherapy within 4 weeks prior to COVID-19 on clinical outcomes was assessed with Inverse Probability of Treatment Weighting (IPTW) models adjusted for possible confounders. Results: Out of 3820 patients, 97 patients with STS were included. The median age at COVID-19 diagnosis was 56 years (range: 18-92), with 65 patients (67%) aged < 65 years and most patients had a low comorbidity burden (65, 67.0%). The most frequent primary tumor sites were the abdomen (56.7%) and the gynecological tract (12.4%). In total, 36 (37.1%) patients were on cytotoxic chemotherapy within 4 weeks prior to COVID-19. The overall CFR28 was 25.8%, with 38% oxygen therapy requirement, 34% rate of complications, and 32.3% of hospitalizations due to COVID-19. CFR28 (29.5%, 21.4%, and 12.5%) and all indicators of COVID-19 severity demonstrated a trend toward a numerical improvement across the pandemic phases. Similarly, vaccinated patients demonstrated numerically improved CFR28 (16.7% versus 27.7%) and COVID-19 morbidity compared with unvaccinated patients. Patients who were on chemotherapy experienced comparable CFR28 (19.4% versus 26.0%, p = 0.4803), hospitalizations (50.0% versus 44.4%, p = 0.6883), complication rates (30.6% versus 34.0%, p = 0.7381), and oxygen therapy requirement (28.1% versus 40.0%, p = 0.2755) compared to those who were not on anticancer therapy at COVID-19, findings further confirmed by the IPTW-fitted multivariable analysis. Conclusion: In this study, we demonstrate an improvement in COVID-19 outcomes in patients with STS over time. Recent exposure to chemotherapy does not impact COVID-19 morbidity and mortality and SARS-CoV-2 vaccination confers protection against adverse outcomes from COVID-19 in this patient population.

An analysis from the OnCovid registry on the impact of chemotherapy and SARS-CoV-2 vaccines on clinical outcomes of patients with soft tissue sarcoma and COVID-19 Soft tissue sarcomas (STS) are a group of rare and aggressive tumours, usually treated with high dose cytotoxic chemotherapy. To date no clear evidence exists on the impact of COVID-19 in patients with STS, nor on the potential impact of recent chemotherapy and prior SARS-CoV-2 vaccination in this specific patient population. This is the 1st study to show COVID-19 outcomes in patients with STS, highlighting a substantial vaccine efficacy with no negative impact of recent chemotherapy on COVID-19 outcomes.

Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy.

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity of such aberrant signaling. Although inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of protein phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor-suppressive resistance. Significance: A therapy consisting of deliberate hyperactivation of oncogenic signaling combined with perturbation of the stress responses that result from this is very effective in animal models of colon cancer. Resistance to this therapy is associated with loss of oncogenic signaling and reduced oncogenic capacity, indicative of tumor-suppressive drug resistance.

Ventajas del método problémico en la enseñanza de la bioquímica en la licenciatura en enfermería / Advantages of the problem-based learning method in the teaching of Biochemistry in Bachelor of Nursing curricula

Para precisar las ventajas del método problémico de enseñanza en la Bioquímica en relación con el tradicional se realizó el presente estudio en una muestra constituida por 17 estudiantes del último grupo que recibió la asignatura por el programa convencional y 27 estudiantes a los que les fue impartido el programa por solución de problemas. En el acápite que midió la opinión de los estudiantes sobre la vinculación con la práctica de los temas impartidos, la puntuación obtenida indicó mayor interrelación básico-clínica. La valoración de los educandos acerca de la calidad de las actividades docentes fue superior en los que estaban involucrados con el método activo y los resultados en la prueba diagnóstico no mostraron relación con el programa de estudio recibido. Se corroboraron los aciertos de la utilización del método problémico en el desarrollo de hábitos y actitudes hacia el estudio, así como en la independencia cognoscitiva de los educandos.

To specify the advantages of the problem-based learning method in Biochemistry over the traditional one, the present study was carried out with a sample made up of 17 students from the last group that had been taught this subject by the traditional program and of 27 students who were given the same subject by the problem-based learning program. In the section dealing with the students´opinions about the linking of the received topics to practice, the highest score indicated a higher basic-clinical interrelation in this type of learning. The assessment made by the students about the quality of the teaching activities was higher in those involved in the active learning method; the results of the diagnostic test did not show any relation with the type of curriculum. The study confirmed the advantages of the use of the problem-based learning method for the development of habits and attitudes toward studying as well as the cognitive independence of the students.

Procederes de regresión lineal como soluciones al problema de la comparación de métodos. II / Procedures of linear regression as solutions to the problem of the methods to the problem of the methods comparison II Constant analythical errors but differents

En este trabajo se discute el desempeño de cuatro soluciones del problema de comparación de métodos: regresión de mínimos cuadrados ordinarios (P1), regresión de Passing-Bablok (P2), regresión de Deming con coeficiente l estimado a partir de las varianzas intrarreplicados (P3) y regresión de Deming con coeficiente l estimado a partir de las varianzas de las series (P4), cuando los errores analíticos correspondientes pueden asumirse constantes, en el rango de concentraciones de interés, pero diferentes. El caso de los errores analíticos constantes e iguales se presentó en otro trabajo [Delgado Ramos A, Ramos Salazar R, Martínez Canalejo H, Santana Porbén S. Procederes de regresión lineal como soluciones al problema de la comparación de métodos. I. Errores analíticos constantes e iguales. LABORAT-Acta (Archivos Mexicanos de Laboratorio Clínico). 2000]. Se evaluó también el desempeño de la regresión de Deming con valores prefijados del coeficiente l: 2.25 (caso del sodio), 4 (caso de la albúmina) y 2.25 (caso de la glucosa). El modelo teórico, los escenarios analíticos simulados, el algoritmo de simulación estadístico-matemático y las especificaciones de calidad del estudio se expusieron en la parte I. La regresión de mínimos cuadrados ordinarios y la regresión de Passing-Bablok dieron estimados sesgados de la pendiente y resultaron en una elevada tasa de rechazos de la hipótesis nula Ho: b = 1; por lo tanto, no constituyeron soluciones satisfactorias del problema de comparación de métodos. En el caso de la regresión de mínimos cuadrados, el error de estimación de la pendiente estaba alterado por un componente sistemático. No se pudo explicar el pobre desempeño de la regresión de Passing-Bablok, aunque se sospecha que este proceder sea sensible a diferencias entre los errores analíticos de los métodos en comparación. La implementación de la regresión de Deming con el coeficiente l, construido a partir de las varianzas de las series, tampoco fue una solución satisfactoria del problema de comparación de métodos, al obtener también estimados sesgados de la pendiente. Las restantes implementaciones de la regresión de Deming (valores prefijados del coeficiente l y coeficiente l construido a partir de las varianzas intrarreplicados, respectivamente) dieron estimados insesgados de la pendiente de la recta de comparación de métodos, pero a costa de una elevada tasa de rechazos de hipótesis nula Ho: b = 1

The cost of treating acute asthma at the Queen Elizabeth Hospital, Barbados

OBJECTIVES: To determine the cost of treating acute asthma at the Queen Elizabeth Hospital (QEH) and to identify ways of reducing these costs. DESIGN AND METHODS: Case notes of all patients presenting to the Asthma Bay of the QEH during a two-week period in March 1999, were reviewed. Data, extracted included gender, arrival time, number of nebulizations, dosage of oral prednisolone and inhalers prescribed. A questionnaire was completed by a sample of these patients regarding use of inhalers, follow-up care and time lost from work and school. RESULTS: A total of 303 cases were reviewed and 75 patients completed questionnaires. The majority of asthmatics received oral prednisolone (74 percent) and/or three nebulizations (42 percent). The cost of treating each patient was determined to be approximately US $22.00, including medical and nursing salary costs. The annual cost to the QEH was estimated to be US $214,000 including the costs of admitting patients. Indirect costs included the time lost from work or school in 86 percent of patients and in 56 percent of parents taking time off to look after their sick children. The questionnaire survey revealed that 63 percent of patients with "preventer" medications were not using them and only 38 percent received follow-up care. Seventy-four percent of these patients had repeated asthmatic attacks during the preceding 3 months with 11 percent having more than six attacks. CONCLUSIONS: A significant amount of money is spent on asthma care at the QEH. However, improper understanding and use of medication coupled with lack of continuity of care lead to poor control and frequent attacks. These findings justify the need for an asthma clinic for these patients.(Au)

Angiostrongiliasis abdominal en el Ecuador: identificación de huéspedes definitivos e intermediarios, casos humanos y su prevalencia / Abdominal Angiostrongiliasis in Ecuador: human identification of definitive and intermediary guests, cases and their prevalence

Contiene un estudio detallado sobre la angiostrongiliasis, presentando agente etiológico, morfología, ciclo evolutivo o desarrollo del parásito, formas de transmisión, patología clínica, diagnóstico y tratamiento de la enfermedad...