Randomized trial comparing three fixed combinations of prostaglandins/prostamide with timolol maleate

Jaime Pablo Kelly Rigollet, Joan Anton Ondategui, Angels Pasto, Laura Lop, Institut Català de la Salut, Centre de Atenció Primària MANSO, Eixample esquerra, Barcelona, Spain, The results of this were first presented in the World Glaucoma Congress, Boston (8–11 July 2009)Introduction: To evaluate the long-term efficacy and safety of 3 commercially available fixed combinations of prostaglandin analogs or a prostamide with timolol maleate in patients with primary open angle glaucoma or ocular hypertension.Methods: In this randomized, prospective, single-blind study, intraocular pressure (IOP) was measured after a 1-month washout period and pachymetry was performed before randomizing patients to latanoprost 50 µg/timolol 5 mg/1 mL (L/T), bimatoprost 300 µg/timolol 5 mg/1 mL (B/T), or travoprost 40 µg/timolol 5 mg/1 mL (T/T). IOP was measured monthly for 6 months and then at 12 months by an investigator blinded to the study drug. Adverse reactions were recorded.Results: 128 cases were included in the study. The 3 treatment groups had similar baseline characteristics and comparable IOP. All 3 combinations decreased IOP by at least 6 mmHg and IOP remained below 21 mmHg throughout the study. At 12 months L/T achieved greater reduction in IOP than the other 2 fixed combinations, but the difference between L/T and B/T was not statistically significant. At 6 months, more B/T-treated patients reported red eye (P < 0.05 vs L/T and T/T). At 12 months, fewer adverse reactions were reported, with no cases of red eye reported for L/T (P = 0.03 vs B/T).Conclusions: All 3 combinations are effective at lowering IOP but at 12 months L/T and B/T were found to be more effective than T/T. Treatments were well tolerated after 12 months but L/T showed less hyperemia than B/T throughout the study (P < 0.05).Keywords: bimatoprost/timolol, fixed combinations, intraocular pressure, latanoprost/timolol, ocular hypertension, primary open angle glaucoma, travoprost/timolol

Causes of long-term mortality in patients with head and neck squamous cell carcinomas

Altres ajuts: Acord transformatiu CRUE-CSICPurpose: After treatment of a head and neck squamous cell carcinoma (HNSCC), patients with an adequate control of the tumor have a decreased overall survival when compared to age- and gender-matched controls in the general population. The aim of our study was to analyze the causes of long-term mortality in patients with HNSCC. Methods: We carried out a retrospective study of 5122 patients with an index HNSCC treated at our center between 1985 and 2018. We analyzed the survival considering three causes of death: mortality associated with the HNSCC index tumor, mortality associated with a second or successive neoplasm, and mortality associated with a non-cancer cause. Results: After the diagnosis of an HNSCC the most frequent cause of death is the head and neck tumor itself during the first 3.5 years of follow-up. Thereafter, mortality is more frequently associated with competing causes of death, such as second malignancies and non-cancer causes. Mortality associated with second and successive neoplasms was 2.3% per year, a percentage that was maintained constant throughout the follow-up. Likewise, mortality attributable to non-cancer causes was 1.6% per year, which also remained constant. There were differences in the mortality patterns according to the characteristics of the patients. Conclusion: There are differences in the mortality patterns of patients with HNSCC depending on their characteristics. Knowledge of these patterns can help in the design of guidelines to improve the follow-up protocols of this group of patients to optimize the clinical cost-effectiveness

Correction: Dueñas et al. Assessing effectiveness of colonic and gynecological risk reducing surgery in Lynch syndrome individuals. Cancers 2020, 12, 3419.

In the original article, there was a mistake in Figure 3 as published [1]. The image presented corresponded to endometrial cancer-specific mortality cumulative incidence, instead of the figure referred to in the title (all-cause mortality cumulative incidence)

P53 wild-type colorectal cancer cells that express a fetal gene signature are associated with metastasis and poor prognosis

Current therapy against colorectal cancer (CRC) is based on DNA-damaging agents that remain ineffective in a proportion of patients. Whether and how non-curative DNA damage-based treatment affects tumor cell behavior and patient outcome is primarily unstudied. Using CRC patient-derived organoids (PDO)s, we show that sublethal doses of chemotherapy (CT) does not select previously resistant tumor populations but induces a quiescent state specifically to TP53 wildtype (WT) cancer cells, which is linked to the acquisition of a YAP1-dependent fetal phenotype. Cells displaying this phenotype exhibit high tumor-initiating and metastatic activity. Nuclear YAP1 and fetal traits are present in a proportion of tumors at diagnosis and predict poor prognosis in patients carrying TP53 WT CRC tumors. We provide data indicating the higher efficacy of CT together with YAP1 inhibitors for eradication of therapy resistant TP53 WT cancer cells. Together these results identify fetal conversion as a useful biomarker for patient prognosis and therapy prescription. The failure of chemotherapy in colorectal cancer is currently unclear. Here, the authors show that upon sub-lethal dose of chemotherapy wild-type p53 colorectal cancers acquire a quiescence-like phenotype and a YAP-dependent fetal-like intestinal stem cell state associated with a higher metastatic activity and poor prognosis in patients

Análisis de la supervivencia competitiva en pacientes con carcinoma escamoso de cabeza y cuello

El paciente con carcinoma escamoso de cabeza y cuello cuenta con un riesgo importante de mortalidad competitiva derivado de los factores de riesgo (principalmente tabaco y alcohol) compartidos entre el tumor índice y la aparición de segundas neoplasias y enfermedades crónicas potencialmente letales. El análisis de la supervivencia mediante el método de riesgos competitivos permite el cálculo de la incidencia acumulada de múltiples eventos de desenlace simultáneamente, por lo que proporciona estimaciones de la probabilidad neta de mortalidad por distintas causas. Además, los pacientes que sobreviven cierto tiempo desde el diagnóstico del tumor precisan de un ajuste de la probabilidad de supervivencia, pues su pronóstico mejora transcurrido ese tiempo. Este ajuste es posible gracias al estudio de la supervivencia dinámica mediante el cálculo de la supervivencia condicional. En el presente estudio se realizó un análisis de la supervivencia competitiva en 4.823 pacientes de una base de datos oncológica del Hospital de Sant Pau con carcinoma escamoso de cabeza y cuello y con un seguimiento mínimo de un año. Se obtuvo una estimación de la incidencia acumulada de mortalidad relacionada con el tumor índice, con segundas neoplasias de cabeza y cuello, con segundas neoplasias no cabeza y cuello y no relacionada con el cáncer en función de las variables edad, sexo, estadio, Karnofsky, tratamiento, localización del tumor índice y consumo de tóxicos. El impacto de estas variables sobre los diferentes tipos de mortalidad se estudió mediante un análisis multivariante de Fine-Gray. De manera similar se estudió el impacto del estatus VPH sobre la mortalidad competitiva en pacientes con carcinoma de orofaringe. Adicionalmente se estimó la supervivencia condicional, global y específica, de los pacientes de la cohorte general. La mortalidad relacionada con el tumor siguió un patrón asintótico, con una incidencia acumulada a los 5 años del 30.6% y a los 25 años del 32.8%. La mortalidad relacionada con segundos cánceres de cabeza y cuello, con segundas neoplasias no cabeza y cuello, y no relacionada con el cáncer siguió un patrón lineal, incrementándose un 0.5% anual. Los resultados del estudio multivariante mostraron que la la mortalidad por el tumor índice se relacionó significativamente con todas las variables incluidas excepto el sexo y consumo de tóxicos. La mortalidad por segundo cánceres primarios de cabeza y cuello se relacionó con el estadio, localización del tumor índice, edad y consumo de tóxicos. La mortalidad por segundos cánceres primarios no cabeza y cuello se relacionó con la localización del tumor índice, edad, sexo y consumo de tóxicos. La mortalidad no relacionada con el cáncer se relacionó con todas las variables incluidas en el análisis excepto con el estadio. En pacientes con carcinoma de orofaringe se demostró una fuerte influencia del estatus VPH sobre la mortalidad relacionada con el tumor índice y con segundos cánceres primarios, pero no sobre la mortalidad no relacionada con el cáncer. El análisis de supervivencia condicional, global y específica, mostró una mejoría del pronóstico durante los 3 primeros años sobrevividos. El cáncer escamoso de cabeza y cuello es especialmente sensible al padecimiento de mortalidad por causas competitivas; en la presente serie casi la mitad de los fallecimientos fueron por causas no relacionadas con el tumor índice. El incremento de la supervivencia específica que proporcionan los nuevos tratamientos multimodales en el cáncer de cabeza y cuello, junto con el envejecimiento y subsecuente aumento de las morbilidades de la población, condicionan un escenario dónde el estudio de la mortalidad competitiva y condicional es cada vez más relevante.Head and neck cancer patients are at high risk of competing mortality because of shared risk factors (alcohol and tobacco) between the index tumor, second primary cancers and other comorbidities. Competing risks survival analysis allows simultaneous estimation of the cumulative incidence of different final events, providing net estimation of mortality by different causes. Patients that survive a number of years after tumor diagnosis experience an improvement in the chance of survival. Such an improvement may be estimated by dynamic survival study using conditional survival analysis. A competing survival analysis was performed on 4,283 patients with head and neck squamous cell carcinoma selected from a tertiary center oncologic database with a minimum follow-up of one year. Index tumor related mortality, second primary cancer mortality and non-cancer related mortality cumulative incidences were estimated depending on covariates sex, age, stage, Karnofsky, treatment modality, index tumor location and substance abuse. A Fine-Gray multivariate analysis was used to assess the impact of these covariates on each group of mortality. VPH status impact on competing survival on patients with oropharynx carcinomas was assessed as well. Finally, conditional global and specific survival on the whole cohort was estimated. Index tumor related mortality followed an asymptotic pattern, with a 5 and 25 year cumulative incidence of 30.6% and 32.8% respectively. Second primary head neck and non-head and neck cancer mortality and non-cancer related mortality followed a linear pattern, increasing 0.5% per year. Multivariate analysis showed that index tumor mortality was significantly related with all the covariates included except for sex and substance abuse. Second primary head and neck cancer mortality was related with stage, location, age and substance abuse. Second primary non-head and neck cancer mortality was related with index tumor location, age, stage and substance abuse. Non-cancer related mortality was related with all covariates included in the study except for the index tumor stage. A strong impact of VPH-status on index tumor related mortality and second cancer mortality was found in oropharynx carcinoma patients, but not for non-cancer related mortality. Conditional specific and global survival analysis showed an improvement on prognosis over the first 3 years after diagnosis. Head and neck cancer patients are at high risk for competing mortality; in this cohort almost half of the deaths were not related with the index tumor. Improvement in specific survival due to new multimodal treatments in head and neck cancer, as well as the increase in morbidity prevalence secondary to population ageing, is leading to a new scenario where competing and conditional mortality assessment is becoming much more relevant

Análisis de la supervivencia competitiva en pacientes con carcinoma escamoso de cabeza y cuello /

El paciente con carcinoma escamoso de cabeza y cuello cuenta con un riesgo importante de mortalidad competitiva derivado de los factores de riesgo (principalmente tabaco y alcohol) compartidos entre el tumor índice y la aparición de segundas neoplasias y enfermedades crónicas potencialmente letales. El análisis de la supervivencia mediante el método de riesgos competitivos permite el cálculo de la incidencia acumulada de múltiples eventos de desenlace simultáneamente, por lo que proporciona estimaciones de la probabilidad neta de mortalidad por distintas causas. Además, los pacientes que sobreviven cierto tiempo desde el diagnóstico del tumor precisan de un ajuste de la probabilidad de supervivencia, pues su pronóstico mejora transcurrido ese tiempo. Este ajuste es posible gracias al estudio de la supervivencia dinámica mediante el cálculo de la supervivencia condicional. En el presente estudio se realizó un análisis de la supervivencia competitiva en 4.823 pacientes de una base de datos oncológica del Hospital de Sant Pau con carcinoma escamoso de cabeza y cuello y con un seguimiento mínimo de un año. Se obtuvo una estimación de la incidencia acumulada de mortalidad relacionada con el tumor índice, con segundas neoplasias de cabeza y cuello, con segundas neoplasias no cabeza y cuello y no relacionada con el cáncer en función de las variables edad, sexo, estadio, Karnofsky, tratamiento, localización del tumor índice y consumo de tóxicos. El impacto de estas variables sobre los diferentes tipos de mortalidad se estudió mediante un análisis multivariante de Fine-Gray. De manera similar se estudió el impacto del estatus VPH sobre la mortalidad competitiva en pacientes con carcinoma de orofaringe. Adicionalmente se estimó la supervivencia condicional, global y específica, de los pacientes de la cohorte general. La mortalidad relacionada con el tumor siguió un patrón asintótico, con una incidencia acumulada a los 5 años del 30.6% y a los 25 años del 32.8%. La mortalidad relacionada con segundos cánceres de cabeza y cuello, con segundas neoplasias no cabeza y cuello, y no relacionada con el cáncer siguió un patrón lineal, incrementándose un 0.5% anual. Los resultados del estudio multivariante mostraron que la la mortalidad por el tumor índice se relacionó significativamente con todas las variables incluidas excepto el sexo y consumo de tóxicos. La mortalidad por segundo cánceres primarios de cabeza y cuello se relacionó con el estadio, localización del tumor índice, edad y consumo de tóxicos. La mortalidad por segundos cánceres primarios no cabeza y cuello se relacionó con la localización del tumor índice, edad, sexo y consumo de tóxicos. La mortalidad no relacionada con el cáncer se relacionó con todas las variables incluidas en el análisis excepto con el estadio. En pacientes con carcinoma de orofaringe se demostró una fuerte influencia del estatus VPH sobre la mortalidad relacionada con el tumor índice y con segundos cánceres primarios, pero no sobre la mortalidad no relacionada con el cáncer. El análisis de supervivencia condicional, global y específica, mostró una mejoría del pronóstico durante los 3 primeros años sobrevividos. El cáncer escamoso de cabeza y cuello es especialmente sensible al padecimiento de mortalidad por causas competitivas; en la presente serie casi la mitad de los fallecimientos fueron por causas no relacionadas con el tumor índice. El incremento de la supervivencia específica que proporcionan los nuevos tratamientos multimodales en el cáncer de cabeza y cuello, junto con el envejecimiento y subsecuente aumento de las morbilidades de la población, condicionan un escenario dónde el estudio de la mortalidad competitiva y condicional es cada vez más relevante.Head and neck cancer patients are at high risk of competing mortality because of shared risk factors (alcohol and tobacco) between the index tumor, second primary cancers and other comorbidities. Competing risks survival analysis allows simultaneous estimation of the cumulative incidence of different final events, providing net estimation of mortality by different causes. Patients that survive a number of years after tumor diagnosis experience an improvement in the chance of survival. Such an improvement may be estimated by dynamic survival study using conditional survival analysis. A competing survival analysis was performed on 4,283 patients with head and neck squamous cell carcinoma selected from a tertiary center oncologic database with a minimum follow-up of one year. Index tumor related mortality, second primary cancer mortality and non-cancer related mortality cumulative incidences were estimated depending on covariates sex, age, stage, Karnofsky, treatment modality, index tumor location and substance abuse. A Fine-Gray multivariate analysis was used to assess the impact of these covariates on each group of mortality. VPH status impact on competing survival on patients with oropharynx carcinomas was assessed as well. Finally, conditional global and specific survival on the whole cohort was estimated. Index tumor related mortality followed an asymptotic pattern, with a 5 and 25 year cumulative incidence of 30.6% and 32.8% respectively. Second primary head neck and non-head and neck cancer mortality and non-cancer related mortality followed a linear pattern, increasing 0.5% per year. Multivariate analysis showed that index tumor mortality was significantly related with all the covariates included except for sex and substance abuse. Second primary head and neck cancer mortality was related with stage, location, age and substance abuse. Second primary non-head and neck cancer mortality was related with index tumor location, age, stage and substance abuse. Non-cancer related mortality was related with all covariates included in the study except for the index tumor stage. A strong impact of VPH-status on index tumor related mortality and second cancer mortality was found in oropharynx carcinoma patients, but not for non-cancer related mortality. Conditional specific and global survival analysis showed an improvement on prognosis over the first 3 years after diagnosis. Head and neck cancer patients are at high risk for competing mortality; in this cohort almost half of the deaths were not related with the index tumor. Improvement in specific survival due to new multimodal treatments in head and neck cancer, as well as the increase in morbidity prevalence secondary to population ageing, is leading to a new scenario where competing and conditional mortality assessment is becoming much more relevant

Alteraciones del olfato en la COVID-19, revisión de la evidencia e implicaciones en el manejo de la pandèmia

Existe debate sobre si las alteraciones en el olfato deberían considerarse un síntoma de la COVID-19. Se realizó una revisión sistemática bibliográfica de los artículos indexados en PubMed sobre alteraciones del olfato en cuadros virales de vías respiratorias, con especial énfasis en la COVID-19. El objetivo principal fue encontrar evidencia de interés clínico que apoye la relación entre ansomia y COVID-19. Las alteraciones del olfato en procesos infecciosos de vías altas son frecuentes y en su mayoría responden a una causa obstructiva por edema de la mucosa nasal. Ocasionalmente aparece una disfunción olfatoria posviral de tipo neurosensorial, de pronóstico variable. La evidencia acerca de la anosmia en pacientes con COVID-19 es muy limitada, correspondiente a un grado 5 o D del Centre for Evidence-Based Medicine. De acuerdo con la evidencia disponible, parece razonable aplicar medidas de aislamiento, higiene y distanciamiento social a los pacientes con alteraciones del olfato de reciente aparición como único síntoma, aunque se debería estudiar la utilidad de la realización de pruebas diagnósticas a este tipo de sujetos

Parotid Incidentaloma Identified by Positron Emission/Computed Tomography: When to Consider Diagnoses Other than Warthin Tumor

Introduction Parotid gland incidentalomas (PGIs) are unexpected hypermetabolic foci in the parotid region that can be found when scanning with whole-body positron emission/computed tomography (PET/CT). These deposits are most commonly due to benign lesions such as Warthin tumor. Objective The aim of this study was to determine the prevalence of PGIs identified in PET/CT scans and to assess the role of smoking in their etiology. Methods We retrospectively reviewed all PET/CT scans performed at our center in search of PGIs and identified smoking status and standardized uptake value (SUVmax) in each case. We also analyzed the database of parotidectomies performed in our department in the previous 10 years and focused on the pathologic diagnosis and the presence or absence of smoking in each case. Results Sixteen cases of PGIs were found in 4,250 PET/CT scans, accounting for 0.4%. The average SUVmax was 6.5 (range 2.8 to 16). Cytology was performed in five patients; it was benign in four cases and inconclusive in one case. Thirteen patients had a history of smoking. Of the parotidectomies performed in our center with a diagnosis of Warthin tumor, we identified a history of smoking in 93.8% of those patients. Conclusions The prevalence of PGIs on PET/CT was similar to that reported by other authors. Warthin tumor is frequently diagnosed among PGIs on PET/CT, and it has a strong relationship with smoking. We suggest that a diagnosis other than Warthin tumor should be considered for PGIs in nonsmokers

Causes of long-term mortality in patients with head and neck squamous cell carcinomas

Purpose: after treatment of a head and neck squamous cell carcinoma (HNSCC), patients with an adequate control of the tumor have a decreased overall survival when compared to age- and gender-matched controls in the general population. The aim of our study was to analyze the causes of long-term mortality in patients with HNSCC. Methods: we carried out a retrospective study of 5122 patients with an index HNSCC treated at our center between 1985 and 2018. We analyzed the survival considering three causes of death: mortality associated with the HNSCC index tumor, mortality associated with a second or successive neoplasm, and mortality associated with a non-cancer cause. Results: after the diagnosis of an HNSCC the most frequent cause of death is the head and neck tumor itself during the first 3.5 years of follow-up. Thereafter, mortality is more frequently associated with competing causes of death, such as second malignancies and non-cancer causes. Mortality associated with second and successive neoplasms was 2.3% per year, a percentage that was maintained constant throughout the follow-up. Likewise, mortality attributable to non-cancer causes was 1.6% per year, which also remained constant. There were differences in the mortality patterns according to the characteristics of the patients. Conclusion: there are differences in the mortality patterns of patients with HNSCC depending on their characteristics. Knowledge of these patterns can help in the design of guidelines to improve the follow-up protocols of this group of patients to optimize the clinical cost-effectiveness