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BACKGROUND: Over the past two decades, our group has conducted five multicenter trials focusing on first-line systemic therapy for patients with advanced pancreatic cancer. The current pooled analysis was designed to evaluate prognosis over time and the impact of clinical characteristics on survival. PATIENTS AND METHODS: Individual patient data were derived from five prospective, controlled, multicenter trials conducted by the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO): 'Gem/Cis', 'Ro96', 'RC57', 'ACCEPT' and 'RASH', which recruited patients between December 1997 and January 2017. RESULTS: Overall, 912 patients were included. The median overall survival (OS) for all assessable patients was 7.1 months. OS significantly improved over time, with a median OS of 8.6 months for patients treated from 2012 to 2017 compared with 7.0 months from 1997 to 2006 [hazard ratio (HR) 1.06; P < 0.004]. Eastern Cooperative Oncology Group performance status (HR 1.48; P < 0.001), use of second-line treatment (HR 1.51; P < 0.001), and Union for International Cancer Control (UICC) stage (III versus IV) (HR 1.34, P = 0.002) had a significant impact on OS. By contrast, no influence of age and gender on OS was detectable. Comparing combination therapy with single-agent chemotherapy did not demonstrate a survival benefit, nor did regimens containing epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as afatinib or erlotinib, compared with chemotherapy-only arms. Patients with early-onset pancreatic cancer (age at study entry of ≤50 years, n = 102) had a similar OS compared with those >50 years (7.1 versus 7.0 months; HR 1.13; P = 0.273). The use of a platinum-containing regimen was not associated with better outcomes in patients with early-onset pancreatic cancer. CONCLUSIONS: Within this selected group of patients treated within prospective clinical trials, survival has shown improvement over two decades. This effect is likely attributable to the availability of more effective combination therapies and treatment lines, rather than to any specific regimen, such as those containing EGFR-TKIs. In addition, concerning age and sex subgroups, the dataset did not provide evidence for distinct clinical behavior.
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Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Alemania , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Adulto , Estudios Prospectivos , Anciano de 80 o más Años , PronósticoRESUMEN
BACKGROUND: Olfactory training (OT) is considered an effective intervention for most causes of smell loss and is recommended as a long-term treatment. However, the treatment adherence of OT remains unclear. This study aims to identify the frequency and causalities for lack of adherence to OT. METHODS: In this prospective study, 53 patients previously diagnosed with olfactory dysfunction (OD), who were recommended to perform OT, were enrolled. Patients underwent olfactory testing using Sniffin' Sticks for threshold, discrimination, and identification (TDI) and a subjective numeric rating scale (NRS) at a baseline and follow-up visit. In addition, patients answered a six-item treatment adherence questionnaire. The primary outcome measures were clinically relevant improvements according to the TDI (>=5.5) and NRS (>=5.5) scores. RESULTS: Out of 53 patients, 45 performed OT. Among patients who performed OT, 31% discontinued the use of OT on their own due to a self-perceived improvement, while 51% discontinued use due to lack of improvements in olfaction. In these patients, the average duration of OT use was five months. After controlling for baseline duration of OD, baseline TDI score and smell loss aetiologies, discontinuing OT due to a lack of self-perceived improvement remained significantly associated with worse TDI and NRS outcomes at follow-up. CONCLUSIONS: Our data show that therapeutical adherence to OT is low, regardless of patients' perception of olfactory function. Olfactory improvement leads to decreased training due to satisfaction, while lack of improvement leads to non-adherence based on disappointing subjective outcome. Patients should be advised to perform OT consistently.
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Trastornos del Olfato , Humanos , Trastornos del Olfato/diagnóstico , Anosmia/complicaciones , Estudios Prospectivos , Entrenamiento Olfativo , OlfatoRESUMEN
A 58-year-old patient was admitted to the emergency department due to severe respiratory insufficiency. Anamnesis revealed that the patient had experienced increasing stress dyspnea for a few months. Upon imaging, an acute pulmonary embolism was excluded, but peribronchial and hilar soft tissue proliferation with compression of central parts of the pulmonary circulation was found. The patient had a history of silicosis. The histology report showed tumor-free lymph node particles with prominent anthracotic pigment and dust depositions without evidence of IgG4-associated disease. The patient was administered steroid therapy and underwent simultaneous stenting of the left interlobular pulmonary artery and the upper right pulmonary vein. As a result, a significant improvement in symptoms and physical performance was achieved. The diagnosis of inflammatory or, in particular, fibrosing mediastinal processes can be challenging and important clinical symptoms must be taken into account, especially if the pulmonary vasculature is involved. In such cases, the possibility of interventional procedures should be examined in addition to drug therapy options.
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PURPOSE: For patients with cancer of unknown primary (CUP), treatment options are limited. Precision oncology, the interplay of comprehensive genomic profiling (CGP) and targeted therapies, aims to offer additional treatment options to patients with advanced and hard-to-treat cancers. We aimed to highlight the use of a molecular tumor board (MTB) in the therapeutic management of CUP patients. METHODS: In this single-center observational study, CUP patients, presented to the MTB of the Comprehensive Cancer Center Munich LMU, a tertiary care center, were analyzed retrospectively. Descriptive statistics were applied to describe relevant findings. RESULTS: Between June 2016 and February 2022, 61 patients with unfavorable CUP were presented to the MTB, detected clinically relevant variants in 74% (45/61) of patients, of which 64% (29/45) led to therapeutic recommendation. In four out of 29 patients (14%), the treatment recommendations were implemented, unfortunately without resulting in clinical benefit. Reasons for not following the therapeutic recommendation were mainly caused by the physicians' choice of another therapy (9/25, 36%), especially in the context of worsening of general condition, lost to follow-up (7/25, 28%) and death (6/25, 24%). CONCLUSION: CGP and subsequent presentation to a molecular tumor board led to a high rate of therapeutic recommendations in patients with CUP. Recommendations were only implemented at a low rate; however, late GCP diagnostic and, respectively, MTB referral were found more frequent for the patients with implemented treatment. This contrast underscores the need for early implementation of CGP into the management of CUP patients.
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Neoplasias Primarias Desconocidas , Humanos , Neoplasias Primarias Desconocidas/diagnóstico , Neoplasias Primarias Desconocidas/genética , Neoplasias Primarias Desconocidas/terapia , Estudios Retrospectivos , Medicina de Precisión/métodos , Oncología MédicaRESUMEN
BACKGROUND: Climate change has been associated with an increase in extreme weather conditions. The aim of this study was to identify environmental factors and the effect of extreme weather events (95th percentile) on the risk for epistaxis-related emergency room visits (EV). METHODS: A total of 2179 epistaxis-related EVs were identified between 2015 and 2018. A distributed lag non-linear model was fitted to investigate the relationship between extreme weather conditions and the total number of epistaxis-related EVs per day. Cumulative relative risk (cRR) is defined as the cumulated daily risk of EV for epistaxis within a stated period after an extreme weather condition compared to the risk of EV at the median value of that weather condition. RESULTS: At a mean daily temperature of 27°C (P95), cRR for epistaxis-related EV was 2.00. At a relative humidity of 39% (P5), cRR was highest on day 3 at 1.59, while extremely high humidity (92%, P99) led to a decreased cRR of 0.7 on day 1. Intense precipitation of 24mm (P99) reduced the cRR on day 3 to 0.38. For prolonged extreme conditions over three days, extremely low wind speed, as well as both high and low atmospheric pressure events, diminished cRR. CONCLUSIONS: Extreme temperatures, relative humidity, and precipitation, as well as extended periods of extreme wind speeds and atmospheric pressure, significantly impact cRR for epistaxis-related EVs.
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Clima Extremo , Humanos , Epistaxis/epidemiología , Epistaxis/etiología , Servicio de Urgencia en HospitalRESUMEN
Previous work has shown that event-based prospective memory (EBPM) predicted health-related quality of life (HrQoL). In the present study, we aimed to examine whether the relationship between EBPM and HrQoL extended to life satisfaction, and whether it persisted after controlling for other cognitive functions related to EBPM, namely executive functions and retrospective memory. We tested two models using structural equation modeling with latent variables in a sample of older adults. In the first model, we assessed whether EBPM predicted life satisfaction and HrQoL; in the second model, we controlled for retrospective memory and executive functions. The first model indicated that EBPM was related to HrQoL. However, in the second model, this relationship was eliminated by executive functions; life satisfaction was not related to any of the cognitive variables. Findings corroborated the link between HrQoL and EBPM, suggesting that such relationship stems from executive functions rather than retrospective memory.
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Función Ejecutiva , Memoria Episódica , Humanos , Anciano , Estudios Retrospectivos , Calidad de Vida/psicología , Pruebas NeuropsicológicasRESUMEN
INTRODUCTION: The aim of the study was to evaluate the quality of ICU 'end-of-life care' as well as the current bereavement support strategies in a large tertiary hospital, reported by bereaved family members of patients who were admitted to ICU who received bereavement support. METHODS: A cross-sectional single site study was conducted, in which two (online) questionnaires (euroQ2 and a customized version of the ARREVE questionnaire) were sent to relatives of deceased ICU patients at one timepoint, ranging from 1 week to ± 16 months after a follow-up phone call, which is part of the standard care procedure. RESULTS: We sent 139 questionnaires and 95 questionnaires were returned (response rate 68.3%). Overall, the quality of care was rated as good, with excellence in 'concern and caring by ICU staff' towards the patient, consideration of the needs of the family members, ease of getting information and the completeness of information about what is done. Points for improvement include the presence at bedside, consistency of information and the overall quality of information given by the physicians. The follow-up call 2-3 months after the loss was appreciated and beneficial for the family members. Point of improvement was asking if they wanted to have a scheduled phone call or a spontaneous one at the beginning of the follow-up call, since participants can have a preference for a planned (22.4%) or unplanned (28.2%) call. However, 49.4% of the participants had no preference. CONCLUSION: In general, the quality of care, and 'end-of-life care' in the ICU was good, as assessed by relatives of deceased ICU patients. To optimize the 'quality of end-of-life care' in the ICU, improvements in terms of information provision and possibilities to visit the patient can be made.
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Aflicción , Cuidados Paliativos al Final de la Vida , Estudios Transversales , Muerte , Familia , Cuidados Paliativos al Final de la Vida/métodos , Humanos , Unidades de Cuidados Intensivos , Encuestas y CuestionariosRESUMEN
P is a high-prevalence antigen present in 99.9 percent of the population and is fully developed at birth. P- individuals form naturally occurring antibodies against P, which are often of immunoglobulin (Ig)M and/or IgG type, very potent in complement activation, and able to cause serious intravascular hemolytic transfusion reactions. Some people with anti-P have the rare P1 k phenotype, which lacks P in the presence of P1 and Pk. Blood transfusion in patients with anti-P is challenging, as is described here. A male patient without a history of blood transfusion was admitted for a planned cardiac surgery. The preoperative ABO blood group could not be determined because of unexpected reactions in the reverse grouping, and all red blood cells (RBCs) in the antibody detection test were positive, except for the autocontrol. Further analysis of the patient's sample confirmed the presence of the P1 k phenotype, and anti-P was identified. If transfusion was needed, P- blood would be required, and the only P- RBCs available were at the national Sanquin Bank of Frozen Blood. These units are limited, expensive, and only available for 48 hours after thawing. In the case of massive blood loss, first ABO and Rh-compatible units should be transfused, followed by P- units after the bleeding stops. In our case, the surgery was conducted without transfusion. This case illustrates the importance of preoperative ABO blood group testing and antibody screening in cases where blood loss can be expected. In recent years, more focus has been put on patient blood management. A good collaboration between the local laboratory, surgery department, and dedicated blood transfusion laboratory is critical to prevent unnecessary incompatible blood transfusions with potentially serious outcomes.
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Procedimientos Quirúrgicos Cardíacos , Reacción a la Transfusión , Sistema del Grupo Sanguíneo ABO , Anticuerpos , Incompatibilidad de Grupos Sanguíneos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Humanos , Masculino , PrevalenciaRESUMEN
BACKGROUND: Colorectal cancer (CRC) in the indigenous African population of South Africa is uncommon (age standardised incidence rates of 11.29 for males and 7.27/100 000 for females) and tends to occur at a young age. Lynch syndrome (LS), an inherited mismatch repair (MMR) gene abnormality, accounts for 3-4% of newly diagnosed CRCs in high incidence areas. There is some evidence that the contribution of an MMR abnormality to the overall CRC burden may be increased in low incidence areas. We aimed to determine the prevalence of MMR deficiency in an indigenous African population. METHODS: A cohort of 66 self-declared indigenous African patients, less than 50 years of age at diagnosis with CRC was identified from clinical and pathological records. The original histopathology was reviewed to confirm the diagnosis and features suggestive of MMR abnormality determined (pushing edge, mucinous, lymphocytic infiltration, Crohn's like reaction). Where sufficient tissue was available, samples were sectioned and stained for the four MMR proteins. RESULTS: Histopathological examination confirmed adenocarcinoma in 31 individuals. At least one feature suggestive of MMR was identified in 22 of these specimens. Twenty-seven cases were stained for all four MMR proteins using standard immunohistochemistry (IHC). MMR deficiency was found in 37% (n = 10/27) of cases. Median age of diagnosis was 35 years in the MMR-proficient group and 44 years in the MMR-deficient group, p < 0.008. No other significant differences between the groups were noted. CONCLUSION: MMR deficiency was common in colorectal carcinomas in the older patients in this cohort, but very young indigenous Africans CRCs do not appear to result from mismatch repair gene mutations.
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Neoplasias Encefálicas , Neoplasias Colorrectales , Síndromes Neoplásicos Hereditarios , Adulto , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Reparación de la Incompatibilidad de ADN/genética , Femenino , Humanos , Masculino , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/genéticaRESUMEN
OBJECTIVE: To evaluate which risk factors for RhD immunisation remain, despite adequate routine antenatal and postnatal RhIg prophylaxis (1000 IU RhIg) and additional administration of RhIg. The second objective was assessment of the current prevalence of RhD immunisations. DESIGN: Prospective cohort study. SETTING: The Netherlands. POPULATION: Two-year nationwide cohort of alloimmunised RhD-negative women. METHODS: RhD-negative women in their first RhD immunised pregnancy were included for risk factor analysis. We compared risk factors for RhD immunisation, occurring either in the previous non-immunised pregnancy or in the index pregnancy, with national population data derived from the Dutch perinatal registration (Perined). RESULTS: In the 2-year cohort, data from 193 women were eligible for analysis. Significant risk factors in women previously experiencing a pregnancy of an RhD-positive child (n = 113) were: caesarean section (CS) (OR 1.7, 95% CI 1.1-2.6), perinatal death (OR 3.5, 95% CI 1.1-10.9), gestational age >42 weeks (OR 6.1, 95% CI 2.2-16.6), postnatal bleeding (>1000 ml) (OR 2.0, 95% CI 1.1-3.6), manual removal of the placenta (MRP) (OR 4.3, 95% CI 2.0-9.3); these factors often occurred in combination. The miscarriage rate was significantly higher than in the Dutch population (35% versus 12.-5%, P < 0.001). CONCLUSION: Complicated deliveries, including cases of major bleeding and surgical interventions (CS, MRP), must be recognised as a risk factor, requiring estimation of fetomaternal haemorrhage volume and adjustment of RhIg dosing. The higher miscarriage rate suggests that existing RhIg protocols need adjustment or better compliance. TWEETABLE ABSTRACT: Complicated delivery (caesarean section, manual removal placenta, major bleeding) is the most valid risk factor for RhD immunization despite antenatal and postnatal RhIg.
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Aborto Espontáneo , Isoinmunización Rh , Cesárea , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Inmunización , Lactante , Embarazo , Estudios Prospectivos , Isoinmunización Rh/epidemiología , Isoinmunización Rh/etiología , Isoinmunización Rh/prevención & control , Sistema del Grupo Sanguíneo Rh-Hr , Globulina Inmune rho(D)/uso terapéutico , Factores de RiesgoRESUMEN
BACKGROUND: Pulmonary metastasis (M1-PUL) as first site of dissemination in pancreatic ductal adenocarcinoma (PDAC) is a rare event and may define a distinct biological subgroup. PATIENTS AND METHODS: Arbeitsgemeinschaft Internistische Onkologie-Young Medical Oncologists-Pankreas-0515 study (AIO-YMO-PAK-0515) was a retrospective German multicenter study investigating clinical and molecular characteristics of M1-PUL PDAC patients; 115 M1-PUL PDAC patients from 7 participating centers were included. Clinical characteristics and potential prognostic factors were defined within the M1-PUL cohort. Archival tumor samples were analyzed for Her2/neu, HNF1A and KRT81 expression. Additionally, messenger RNA (mRNA) expression analysis (using a 770-gene immune profiling panel) was carried out in the M1-PUL and in a control cohort (M1-ANY). RESULTS: Median overall survival in the entire M1-PUL cohort was 20 months; the most favorable prognosis (median survival: 28 months) was observed in the subgroup of 66 PDAC patients with metachronous lung metastases after previous curative-intent surgery. The number of metastatic lesions, uni- or bilateral lung involvement as well as metastasectomy were identified as potential prognostic factors. Her2/neu expression and PDAC subtyping (by HNF1A and KRT81) did not differ between the M1-PUL and the M1-ANY cohort. mRNA expression analysis revealed significant differentially expressed genes between both cohorts: CD63 and LAMP1 were among the top 20 differentially expressed genes and were identified as potential mediators of organotropism and favorable survival outcome of M1-PUL patients. CONCLUSION: M1-PUL represents a clinically favorable cohort in PDAC patients. Site of relapse might already be predetermined at the time of surgery and could potentially be predicted by gene expression profiling.
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Neoplasias Pulmonares , Neoplasias Pancreáticas , Biología , Humanos , Neoplasias Pulmonares/genética , Recurrencia Local de Neoplasia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Pronóstico , Estudios RetrospectivosRESUMEN
As the population ages, risks for cognitive decline threaten independence and quality of life of older adults. Classically, psychological assessment tools that evaluate cognitive functioning are administered in face-to-face laboratory sessions, which are time- and resource-consuming. The present study set out to examine whether the eCOGTEL-an online adaptation of the Cognitive Telephone Screening Instrument (COGTEL; Kliegel et al. in J Psychol 141(2):147-170, 2007)-represents a reliable measure of cognitive performance in adulthood. Therefore, an age-stratified adult lifespan sample of 253 participants (aged 19-86 years) completed a face-to-face assessment in the laboratory and a self-administered online version, at their homes. A second, independent sample of 176 younger adults (aged 19-30 years) performed a test-retest assessment of the eCOGTEL. Results showed strong correlations between overall cognitive scores assessed online and in the laboratory, as well as a high test-retest reliability. Further, comparable data distributions between both assessment modes underline the feasibility of the eCOGTEL across the adult lifespan and particularly in older age. Our findings thereby indicate that the eCOGTEL can reliably measure cognitive performance across the lifespan at reduced costs, which may help detecting individuals at risk of developing age-related cognitive decline. Due to these strengths, the eCOGTEL represents a valuable contemporary approach for the resource-efficient online assessment of cognition, which may benefit a broad array of fundamental and applied research fields, such as clinical and organizational psychology. Supplementary Information: The online version contains supplementary material available at 10.1007/s10433-021-00667-x.
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The current study aimed to examine whether the Geneva Space Cruiser - a new online adaptation of the Cruiser - represents a valid, reliable and useful tool to assess prospective memory (PM) across the adult lifespan via fully self-administered online testing. Therefore, an adult lifespan sample of 252 adults (19-86 years old) performed the Geneva Space Cruiser in the laboratory and online, at home, and also performed a more traditional laboratory PM task. A second sample of 224 young adults (19-35 years old) participated in a test-retest online assessment of the Geneva Space Cruiser. Bayesian analyses showed that the Geneva Space Cruiser yielded similar results when administered in the laboratory versus online, both in terms of data distribution as well as of key outcome measures (i.e., PM performance and monitoring). Results further showed very good test-retest reliability and acceptable construct validity. Finally, the online tool was sensitive for detecting age-differences similar to those typically observed in laboratory studies. Together, our findings suggest that the Geneva Space Cruiser represents a rather valid, moderately to highly reliable, and generally useful tool to assess PM in online testing across wide ranges of the adult lifespan, with certain limitations for the oldest participants and for women.
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Memoria Episódica , Adulto , Anciano , Anciano de 80 o más Años , Teorema de Bayes , Cognición , Femenino , Humanos , Longevidad , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Purpose This pilot study aimed on generating insight on alterations in circulating immune cells during the use of FOLFIRINOX and gemcitabine/nab-paclitaxel in pancreatic ductal adenocarcinoma (PDAC). Patients and methods Peripheral blood mononuclear cells were isolated before and 30 days after initiation of chemotherapy from 20 patients with advanced PDAC. Regulatory T cells (FoxP3+) and immune checkpoints (PD-1 and TIM-3) were analyzed by flow cytometry and immunological changes were correlated with clinical outcome. Results Heterogeneous changes during chemotherapy were observed in circulating T-cell subpopulations with a pronounced effect on PD-1+ CD4+/CD8+ T cells. An increase in FoxP3+ or PD-1+ T cells had no significant effect on survival. An increase in TIM3+/CD8+ (but not TIM3+/CD4+) T cells was associated with a significant inferior outcome: median progression-free survival in the subgroup with an increase of TIM-3+/CD8+ T cells was 6.0 compared to 14.0 months in patients with a decrease/no change (p = 0.026); corresponding median overall survival was 13.0 and 20.0 months (p = 0.011), respectively. Conclusions Chemotherapy with FOLFIRNOX or gemcitabine/nab-paclitaxel induces variable changes in circulating T-cell populations that may provide prognostic information in PDAC (AU)
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Humanos , Masculino , Femenino , Anciano , Linfocitos T Reguladores , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Estudios Prospectivos , Proyectos Piloto , Análisis de SupervivenciaRESUMEN
The complement system is an important defense mechanism against pathogens; however, in certain pathologies, the system also attacks human cells, such as red blood cells (RBCs). In paroxysmal nocturnal hemoglobinuria (PNH), RBCs lack certain complement regulators which sensitize them to complement-mediated lysis, while in autoimmune hemolytic anemia (AIHA), antibodies against RBCs may initiate complement-mediated hemolysis. In recent years, complement inhibition has improved treatment prospects for these patients, with eculizumab now the standard of care for PNH patients. Current complement inhibitors are however not sufficient for all patients, and they come with high costs, patient burden, and increased infection risk. This review gives an overview of the underlying pathophysiology of complement-mediated hemolysis in PNH and AIHA, the role of therapeutic complement inhibition nowadays, and the high number of complement inhibitors currently under investigation, as for almost every complement protein, an inhibitor is being developed. The focus lies with novel therapeutics that inhibit complement activity specifically in the pathway that causes pathology or those that reduce costs or patient burden through novel administration routes.
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Hemoglobinuria Paroxística , Inactivadores del Complemento/metabolismo , Inactivadores del Complemento/farmacología , Inactivadores del Complemento/uso terapéutico , Proteínas del Sistema Complemento/metabolismo , Eritrocitos/metabolismo , Eritrocitos/patología , Hemoglobinuria Paroxística/tratamiento farmacológico , Hemoglobinuria Paroxística/etiología , Hemólisis , HumanosRESUMEN
AIM: To investigate the school performance and behavioral difficulties in children with hemolytic disease of the fetus and newborn (HDFN) treated with intrauterine transfusion (IUT) compared to Dutch norm data. STUDY DESIGN: Cros-sectional cohort study. SUBJECTS: Children who received one or multiple IUTs for severe Rh- or K (Kell)-mediated HDFN between January 2008 and January 2015 at the LUMC. OUTCOME MEASURES: School performance reports were assessed as well as behavioral difficulties as assessed with the Dutch child behavioral checklist (CBCL) by parents and caregivers and the Teacher Report Form (TRF) completed by teachers. RESULTS: A response rate of 56% (70 children, aged 5-12 years) was obtained. Grade repetition occurred in 13 cases (19%), 16 children (23%) received some form of additional help, most often support by a speech therapist (n = 8), but also support for dyslexia (n = 4), physical therapy (n = 2) and social-emotional support (n = 2). None of the children in our study group attended special-needs education. School performance levels for reading comprehension, spelling and mathematics according to the Dutch National Pupil Monitoring System were similar for the study population and Dutch norm data. The incidence of behavioral problems as reported by parents was similar to the Dutch norm data, teachers reported less behavioral difficulties in the study group. CONCLUSION: This study shows favorable and reassuring school development in children treated with IUT in an experienced fetal-therapy center. A normal distribution in school and behavioral development is to be expected for children with HDFN treated with IUTs.
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Transfusión de Sangre Intrauterina , Eritroblastosis Fetal , Niño , Estudios de Cohortes , Femenino , Feto , Humanos , Recién Nacido , Embarazo , Instituciones AcadémicasRESUMEN
Cisplatin-based chemotherapy regimens represent the standard of care in patients with locally advanced or metastatic urothelial carcinoma of the bladder. However, many patients are ineligible for cisplatin due to comorbidities or performance status. Immunotherapy with checkpoint inhibitors (CPI) has become a well-established treatment alternative in metastatic bladder cancer. The following review discusses current literature and guideline recommendations based on two case studies, in order to provide practical know-how about therapy sequences and treatment processes.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Cisplatino , Humanos , Inmunoterapia , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
PURPOSE: This pilot study aimed on generating insight on alterations in circulating immune cells during the use of FOLFIRINOX and gemcitabine/nab-paclitaxel in pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Peripheral blood mononuclear cells were isolated before and 30 days after initiation of chemotherapy from 20 patients with advanced PDAC. Regulatory T cells (FoxP3+) and immune checkpoints (PD-1 and TIM-3) were analyzed by flow cytometry and immunological changes were correlated with clinical outcome. RESULTS: Heterogeneous changes during chemotherapy were observed in circulating T-cell subpopulations with a pronounced effect on PD-1+ CD4+/CD8+ T cells. An increase in FoxP3+ or PD-1+ T cells had no significant effect on survival. An increase in TIM3+/CD8+ (but not TIM3+/CD4+) T cells was associated with a significant inferior outcome: median progression-free survival in the subgroup with an increase of TIM-3+/CD8+ T cells was 6.0 compared to 14.0 months in patients with a decrease/no change (p = 0.026); corresponding median overall survival was 13.0 and 20.0 months (p = 0.011), respectively. CONCLUSIONS: Chemotherapy with FOLFIRNOX or gemcitabine/nab-paclitaxel induces variable changes in circulating T-cell populations that may provide prognostic information in PDAC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Proteínas de Punto de Control Inmunitario/efectos de los fármacos , Neoplasias Pancreáticas/tratamiento farmacológico , Linfocitos T Reguladores/efectos de los fármacos , Anciano , Albúminas/uso terapéutico , Linfocitos T CD4-Positivos/química , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD8-positivos/química , Linfocitos T CD8-positivos/efectos de los fármacos , Carcinoma Ductal Pancreático/inmunología , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Factores de Transcripción Forkhead , Receptor 2 Celular del Virus de la Hepatitis A/análisis , Humanos , Proteínas de Punto de Control Inmunitario/análisis , Irinotecán/uso terapéutico , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Oxaliplatino/uso terapéutico , Paclitaxel/uso terapéutico , Neoplasias Pancreáticas/inmunología , Proyectos Piloto , Receptor de Muerte Celular Programada 1/análisis , Receptor de Muerte Celular Programada 1/efectos de los fármacos , Supervivencia sin Progresión , Estudios Prospectivos , Linfocitos T Reguladores/química , GemcitabinaRESUMEN
BACKGROUND: Targeting the epidermal growth factor receptor pathway remains controversial in pancreatic cancer. Afatinib is an oral irreversible ErbB family blocker approved in non-small-cell lung cancer. This open-label, multicenter, randomised phase II trial evaluated gemcitabine plus afatinib (Gem/afatinib) versus gemcitabine (Gem) alone as first-line treatment for metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomised in a 2:1 ratio to either Gem (1000 mg/m2 weekly for three weeks followed by one week of rest, repeated every four weeks) and afatinib (40 mg orally once daily) or Gem alone. Overall survival (OS) was the primary study end-point. The novel BOTh©™ methodology was implemented to derive a quantitative estimate for the 'Burden of Therapy/Toxicity' (BOTh) for each patient on every day during the clinical study. RESULTS: One hundred nineteen patients from 25 centres were randomised, 79 patients for Gem/afatinib and 40 for Gem. Median OS was 7.3 months in the Gem/afatinib arm versus 7.4 months in the Gem-alone arm (hazard ratio [HR]: 1.06, p = 0.80). Median progression-free survival was identical in both arms (3.9 months versus 3.9 months, HR: 0.85, p = 0.43). Adverse events were more frequent in the Gem/afatinib arm, especially diarrhoea (71% vs. 13%) and skin rash (65% vs. 5%). The BOTh©™ analysis revealed a significantly higher burden of toxicity in the combination arm (p = 0.0005). CONCLUSION: The addition of afatinib to Gem did not improve treatment efficacy and was more toxic. The BOTh©™ methodology allowed a detailed insight into the course of treatment-related adverse events over the study period. The trial was registered at clinicaltrials.gov (NCT01728818) and Eudra-CT (2011-004063-77).