Impact of the COVID-19 Pandemic on a Cancer Fast-Track Programme.

INTRODUCTION: The COVID-19 pandemic has disrupted many aspects of clinical practice in oncology, particularly regarding early cancer diagnosis, sparking public health concerns that possible delays could increase the proportion of patients diagnosed at advanced stages. In 2009, a cancer fast-track program (CFP) was implemented at the Clinico-Malvarrosa Health Department in Valencia, Spain with the aim of shortening waiting times between suspected cancer symptoms, diagnosis and therapy initiation. OBJECTIVES: The study aimed to explore the effects of the COVID-19 pandemic on our cancer diagnosis fast-track program. METHODS: The program workflow (patients included and time periods) was analysed from the beginning of the state of alarm on March 16th, 2020 until March 15th, 2021. Data was compared with data from the same period of time from the year before (2019). RESULTS: During the pandemic year, 975 suspected cancer cases were submitted to the CFP. The number of submissions only decreased during times of highest COVID-19 incidence and stricter lockdown, and overall, referrals were slightly higher than in the previous 2 years. Cancer diagnosis was confirmed in 197 (24.1%) cases, among which 33% were urological, 23% breast, 16% gastrointestinal and 9% lung cancer. The median time from referral to specialist appointment was 13 days and diagnosis was reached at a median of 18 days. In confirmed cancer cases, treatment was started at around 30 days from time of diagnosis. In total, 61% of cancer disease was detected at early stage, 20% at locally advanced stage, and 19% at advanced stage, displaying time frames and case proportions similar to pre-pandemic years. CONCLUSIONS: Our program has been able to maintain normal flow and efficacy despite the challenges of the current pandemic, and has proven a reliable tool to help primary care physicians referring suspected cancer patients.

The Relation of CFTR-Genotype and Associated Comorbidities to Development of Pulmonary Atelectasis in Cystic Fibrosis Patients

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Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER).

BACKGROUND: The potential benefit of adding palbociclib to fulvestrant as first-line treatment in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative endocrine-sensitive advanced breast cancer (ABC) patients remains uncharacterized. PATIENTS AND METHODS: In this randomized (1:1), double-blind, phase II study, postmenopausal women with HR-positive, HER2-negative ABC with de novo metastatic disease or those who relapsed after >12 months of adjuvant endocrine therapy received palbociclib/fulvestrant or placebo/fulvestrant. Stratification was based on recurrent versus de novo metastatic disease and visceral involvement. The primary objective was one-year progression-free survival (PFS-1y) rate. The sample size was 190 patients. The two-sided alpha of 0.2, 80% of power to detect a difference between the arms, assuming PFS rates of 0.695 and 0.545 for palbociclib/fulvestrant and placebo/fulvestrant, respectively. RESULTS: In total, 189 patients were randomized to palbociclib/fulvestrant ([n = 94] or placebo/fulvestrant [n = 95]). 45.5% and 60.3% of patients had de novo metastatic disease and visceral involvement, respectively. PFS-1y rates were 83.5% and 71.9% in the palbociclib/fulvestrant and placebo/fulvestrant arms, (HR 0.55, 80% CI 0.36-0.83, P = 0.064). The median PFS were 31.8 and 22.0 months for the palbociclib/fulvestrant and placebo/fulvestrant arms (aHR 0.48, 80% CI 0.37-0.64, P = 0.001). The most frequent grade 3-4 adverse events were neutropenia (68.1% vs. 0%), leucopenia (26.6% vs. 0%), anemia (3.2% vs. 0%), and lymphopenia (14.9% vs. 2.1%) for the palbociclib/fulvestrant and placebo/fulvestrant, respectively. The most frequent non-hematologic grade 3-4 adverse event was fatigue (4.3% vs. 0%). CONCLUSIONS: Palbociclib/fulvestrant demonstrated better PFS-1y rates and median PFS than placebo/fulvestrant in HR-positive/HER2-negative endocrine-sensitive ABC patients.

Ten-year assessment of a cancer fast-track programme to connect primary care with oncology: reducing time from initial symptoms to diagnosis and treatment initiation.

BACKGROUND: Cancer is the second leading cause of mortality worldwide. Integrating different levels of care by implementing screening programmes, extending diagnostic tools and applying therapeutic advances may increase survival. We implemented a cancer fast-track programme (CFP) to shorten the time between suspected cancer symptoms, diagnosis and therapy initiation. PATIENTS AND METHODS: Descriptive data were collected from the 10 years since the CFP was implemented (2009-2019) at the Clinico-Malvarrosa Health Department in Valencia, Spain. General practitioners (GPs), an oncology coordinator and 11 specialists designed guidelines for GP patient referral to the CFP, including criteria for breast, digestive, gynaecological, lung, urological, dermatological, head and neck, and soft tissue cancers. Patients with enlarged lymph nodes and constitutional symptoms were also considered. On identifying patients with suspected cancer, GPs sent a case proposal to the oncology coordinator. If criteria were met, an appointment was quickly made with the patient. We analysed the timeline of each stage of the process. RESULTS: A total of 4493 suspected cancer cases were submitted to the CFP, of whom 4019 were seen by the corresponding specialist. Cancer was confirmed in 1098 (27.3%) patients: breast cancer in 33%, urological cancers in 22%, gastrointestinal cancer in 19% and lung cancer in 15%. The median time from submission to cancer testing was 11 days, and diagnosis was reached in a median of 19 days. Treatment was started at a median of 34 days from diagnosis. CONCLUSIONS: The findings of this study show that the interval from GP patient referral to specialist testing, cancer diagnosis and start of therapy can be reduced. Implementation of the CFP enabled most patients to begin curative intended treatment, and required only minimal resources in our setting.

[Evaluation of the change in pneumococcal vaccination in 2018 in adults in the Community of Madrid]. / Evaluación del cambio de pauta de vacunación frente al neumococo de 2018 en la población adulta en la Comunidad de Madrid.

BACKGROUND: In the Community of Madrid since 2005 vaccination against pneumococcus in adults from 60 years of age has been carried out with pneumococcal polysaccharide vaccine (PPV23). In January 2018, the guideline changed in favor of pneumococcal conjugate vaccine (PCV13). The objective of this study was to analyze the data of pneumococcal vaccination and to evaluate the implementation of the new guideline of vaccination against pneumococcus in adults in the Community of Madrid. METHODS: Cross-sectional study to estimate vaccine coverage by a retrospective review of the record of vaccination history of people ≥60 years resident in the Community of Madrid. RESULTS: In the Community of Madrid until 2018, 83% of the population were vaccinated with PPV23, 6% with PCV13 and 11% with both vaccines. 96.5% came from Primary Care records. The doses administered of PCV13 surpassed those of PPV23 in ≥60 years in all age groups. 78,660 people ≥60 years were vaccinated with PCV13 (19.5% without risk factors, 67.3% with chronic diseases, 2.5% of the high-risk group and 10.7% belonging to both groups). CONCLUSIONS: In 2018, following Community of Madrid recommendations, 6,639 people were not properly vaccinated with PCV13 and 72,021 (91.6%) were properly vaccinated. The greatest confusion occurred in people ≥60 years without risk factors who had a previous PPV23 and did not require another vaccine but received a PCV13 without complying with the recommended schedule.

Interstitial nephritis with pembrolizumab: A case report and review.

INTRODUCTION: Pembrolizumab is a monoclonal antibody approved for adult patients with advanced non-small-cell lung cancer (NSCLC). Although immune related adverse events are considered to be well tolerated, complications may occur and discontinuation of the treatment could be required. CASE REPORT: A 62-year old patient diagnosed with advanced non-small cell lung cancer experienced a decline in the renal function after seven cycles with pembrolizumab.Management & outcome: After ruling out other common causes of interstitial nephritis, pembrolizumab was attributed as a cause of interstitial nephritis. At first, toxicity was managed with corticosteroids and closely monitoring the patient, but finally pembrolizumab had to be discontinued due to the kidney function did not recover. DISCUSSION: Renal and urinary disorders were reported in <3% of patients treated with pembrolizumab, being interstitial nephritis the most reported toxicity. The kidney damage can be a complication to consider in patients receiving pembrolizumab. Early identification of an increase in serum creatinine levels may help with prevention by establishing an effective treatment, although it may not mean a total recovery of kidney function.

Differential properties and effects of fluorescent carbon nanoparticles towards intestinal theranostics.

Given the potential applications of fluorescent carbon nanoparticles in biomedicine, the relationship between their chemical structure, optical properties and biocompatibility has to be investigated in detail. In this work, different types of fluorescent carbon nanoparticles are synthesized by acid treatment, sonochemical treatment, electrochemical cleavage and polycondensation. The particle size ranges from 1 to 6 nm, depending on the synthesis method. Nanoparticles that were prepared by acid or sonochemical treatments from graphite keep a crystalline core and can be classified as graphene quantum dots. The electrochemically produced nanoparticles do not clearly show the graphene core, but it is made of heterogeneous aromatic structures with limited size. The polycondensation nanoparticles do not have CC double bonds. The type of functional groups on the carbon backbone and the optical properties, both absorbance and photoluminescence, strongly depend on the nanoparticle origin. The selected types of nanoparticles are compatible with human intestinal cells, while three of them also show activity against colon cancer cells. The widely different properties of the nanoparticle types need to be considered for their use as diagnosis markers and therapeutic vehicles, specifically in the digestive system.

Septo-optic dysplasia caused by a novel FLNA splice site mutation: a case report.

BACKGROUND: Septo-optic dysplasia (SOD), also known as de-Morsier syndrome, is a rare disorder characterized by any combination of optic nerve hypoplasia, pituitary gland hypoplasia, and midline abnormalities of the brain including absence of the septum pellucidum and corpus callosum dysgenesis. The variable presentation of SOD includes visual, neurologic, and/or hypothalamic-pituitary endocrine defects. The unclear aetiology of a large proportion of SOD cases underscores the importance of identifying novel SOD-associated genes. CASE PRESENTATION: To identify the disease-causing gene in a male infant with neonatal hypoglycaemia, dysmorphic features, and hypoplasia of the optic nerve and corpus callosum, we designed a targeted next-generation sequencing panel for brain morphogenesis defects. We identified a novel hemizygous deletion, c.6355 + 4_6355 + 5delAG, in intron 38 of the FLNA gene that the patient had inherited from his mother. cDNA studies showed that this variant results in the production of 3 aberrant FLNA transcripts, the most abundant of which results in retention of intron 38 of FLNA. CONCLUSIONS: We report for the first time a case of early-onset SOD associated with a mutation in the FLNA gene. This finding broadens the spectrum of genetic causes of this rare disorder and expands the phenotypic spectrum of the FLNA gene.

Effect of respiratory Achromobacter spp. infection on pulmonary function in patients with cystic fibrosis.

PURPOSE: Cystic fibrosis (CF) patients are susceptible to infection with Achromobacter spp., although its clinical significance remains controversial. The aim of this study was to investigate the clinical impact of infection with Achromobacter spp. in CF patients. METHODS: CF outpatients with multiple sputum cultures and follow-up lung function tests were assigned to the case group (infected with Achromobacter spp.) or the control group (never infected with Achromobacter spp.) according to the isolation of Achromobacter spp. The Achromobacter spp. group included two subgroups, taking into consideration whether the isolation of Achromobacter spp. was intermittent or chronic. Baseline lung function tests and longitudinal behaviour were examined in relation to Achromobacter spp. status. RESULTS: A total of 190 CF patients were treated from January 2003 to December 2015 in the CF unit and 21 (11 %) had at least one positive culture for Achromobacter spp. Of these, 11/21 (52.4 %) patients were chronically infected with Achromobacter spp. An analysis of changes during follow-up showed the annual rate of FEV1 decline: -2.3±1.6 % in the Achromobacter spp. group compared to -1.1±0.9 % (P=0.02) in the control group. The chronically infected group also had a significantly greater decline in FEV1 compared to the control group (-2.9±1.9 vs -1.1±0.9; P=0.04). The mean number of annual pulmonary exacerbations during the study period was significantly higher in the case group (1.9±0.9 vs 1.1±0.8; P=0.03). CONCLUSIONS: The Achromobacter spp. status in CF shows a trend towards more severe airflow obstruction and an association with accelerated decline in lung function parameters.

Guía clínica española del acceso vascular para hemodiálisis / Spanish clinical guidelines on vascular access for haemodialysis

El acceso vascular para hemodiálisis es esencial para el enfermo renal tanto por su morbimortalidad asociada como por su repercusión en la calidad de vida. El proceso que va desde la creación y mantenimiento del acceso vascular hasta el tratamiento de sus complicaciones constituye un reto para la toma de decisiones debido a la complejidad de la patología existente y a la diversidad de especialidades involucradas. Con el fin de conseguir un abordaje consensuado, el Grupo Español Multidisciplinar del Acceso Vascular (GEMAV), que incluye expertos de las cinco sociedades científicas implicadas (nefrología [S.E.N.], cirugía vascular [SEACV], radiología vascular e intervencionista [SERAM-SERVEI], enfermedades infecciosas [SEIMC] y enfermería nefrológica [SEDEN]), con el soporte metodológico del Centro Cochrane Iberoamericano, ha realizado una actualización de la Guía del Acceso Vascular para Hemodiálisis publicada en 2005. Esta guía mantiene una estructura similar, revisando la evidencia sin renunciar a la vertiente docente, pero se aportan como novedades, por un lado, la metodología en su elaboración, siguiendo las directrices del sistema GRADE con el objetivo de traducir esta revisión sistemática de la evidencia en recomendaciones que faciliten la toma de decisiones en la práctica clínica habitual y, por otro, el establecimiento de indicadores de calidad que permitan monitorizar la calidad asistencial.

Vascular access for haemodialysis is key in renal patients both due to its associated morbidity and mortality and due to its impact on quality of life. The process, from the creation and maintenance of vascular access to the treatment of its complications, represents a challenge when it comes to decision-making, due to the complexity of the existing disease and the diversity of the specialities involved. With a view to finding a common approach, the Spanish Multidisciplinary Group on Vascular Access (GEMAV), which includes experts from the five scientific societies involved (nephrology [S.E.N.], vascular surgery [SEACV], vascular and interventional radiology [SERAM-SERVEI], infectious diseases [SEIMC] and nephrology nursing [SEDEN]), along with the methodological support.

Lens density measurement with Scheimpflug camera in vitrectomised eyes. / Densidad critaliniana medida con cámara de Scheimpfug en ojos vitrectomizados.

OBJETIVE: To determine whether vitrectomised eyes have a higher lens optical density, when measured with a Scheimpflug camera, compared to non-vitrectomised eyes. METHOD: The peak and linear Scheimpflug optical density (DOS), and area of both eyes were measured in a sample size of 81 vitrectomised phakic patients. A comparison was made between the DOS of the vitrectomised eye lens and the contralateral non-vitrectomised eye using the Student-t test. RESULTS: A significantly higher linear DOS and area was obtained in the 81 vitrectomised phakic eyes when compared to the non-vitrectomised eyes (P<.001). The peak DOS is not significantly increased in respect to non-vitrectomised eyes (P=.59). CONCLUSIONS: The lens DOS in vitrectomised eyes is higher than in non-vitrectomised eyes. The importance of the vitreous in the maintenance of lens transparency is emphasised.

Peptide-based biomaterials. Linking l-tyrosine and poly l-tyrosine to graphene oxide nanoribbons.

Peptide-based biomaterials are being studied actively in a variety of applications in materials science and biointerface engineering. Likewise, there has been ongoing exploration over the last few decades into the potential biological applications of carbon nanomaterials, motivated by their size, shape, structure and their unique physical and chemical properties. In recent years, the functionalization of carbon nanotubes and graphene has led to the preparation of bioactive carbon nanomaterials that are being used in biomedicine as structural elements and in gene therapy and biosensing. The present study proposes different strategies for the bonding of l-tyrosine and the homopolypeptide poly-l-tyrosine to graphene oxide nanoribbons (GONRs). The covalent attachment of l-tyrosine was undertaken by amidation of the α-amine group of tyrosine with the existing carboxylic groups in GONR and by means of esterification through phenol nucleophiles contained in their side chains. In both cases use was made of protective groups to address the functionalization with the desired reactive groups. The linking of GONRs to the PTyr was attempted according to two different strategies: either by ester bonding of commercial PTyr through its phenol side groups or by in situ ring-opening polymerization of an N-carboxyanhydride tyrosine derivative (NCA-Tyr) with Tyr-functionalized GONRs. These biofunctionalized nanomaterials were characterized by Raman and infrared spectroscopies, X-ray photoelectron spectroscopy, thermogravimetric analysis, transmission electron microscopy, fluorescence and electrochemical techniques. On the basis of their properties, prospects for the potential utilization of the prepared hybrid nanomaterials in different applications are also given.

Implementation and assessment of a fast-track programme to improve communication between primary and specialized care in patients with suspected cancer: how to shorten time between initial symptoms of cancer, diagnosis and initiation of treatment.

PURPOSE: This study aims to asses a cancer fast-track programme (CFP) to shorten the time since a patient with suspicion of cancer is referred by the primary care (PC) physician to the specialized medical team. METHODS: Guidelines for main suspected tumours were designed to help PC physicians to detect and rapidly refer cases to the CFP oncology coordinator, who sent them to the appropriate department to accelerate diagnosis, staging and therapy. All patients analysed in this report were referred from June 2009 to July 2012. RESULTS: A total of 897 suspected cancer cases were submitted and finally 705 were studied. In 205 (29 %) a cancer diagnosis was confirmed within 23 days (median). Therapy was initiated within 46 days after referral (median). Early diagnoses with a potential curative approach were made in 166 (82 %). CONCLUSIONS: This CFP decreased the waiting time for cancer diagnosis, by improving communication between PC physician and specialized care teams. Most patients included in this program could get therapy with curative intent.

Fibrosis quística diagnosticada en edad adulta / Cystic fibrosis in adult age

Objetivo. Precisar la prevalencia de enfermos con fibrosis quística (FQ) diagnosticados en edades superiores a los 18 años y analizar sus características clínicas, genéticas y microbiológicas. Pacientes y métodos. Estudio observacional, transversal y descriptivo de todos los pacientes diagnosticados de FQ a edad igual o superior a los 18 años. Las variables analizadas fueron: edad actual, edad al diagnóstico, sexo, nacionalidad, parámetros de función pulmonar, patologías presentes al momento del diagnóstico, características microbiológicas y hallazgos genéticos. Resultados. Se incluyeron 89 pacientes (14,8%, del total de 600 pacientes en seguimiento en las unidades participantes), 45 mujeres (50,6%) y 44 varones (49,4%), con una edad media al diagnóstico de 36,4 años. Ochenta y un pacientes (91%) eran de nacionalidad española. La prueba del sudor fue diagnóstica en 77 de los 89 estudiados (86,5%). Las mutaciones detectadas con mayor frecuencia fueron la F508del/otra y la G542X/otra y los hallazgos clínicos más frecuentes en el momento del diagnóstico fueron las bronquiectasias en 33 pacientes (37,1%) y la esterilidad en 12 (13,5%). Los microorganismos colonizadores más frecuentes fueron Staphylococcus aureus (S.aureus) sensible a meticilina (23,6%) y Pseudomonas aeruginosa (P. aeruginosa) (13,5%). La mayoría de los pacientes presentaban una alteración ventilatoria obstructiva leve y no tenía afectación pancreática. La prueba del sudor con frecuencia ofreció resultados no concluyentes. Conclusiones. La FQ es también una enfermedad de diagnóstico en la edad adulta. Los pacientes diagnosticados en edad adulta presentan una función pulmonar levemente alterada y una baja incidencia de afectación pancreática, por lo que su pronóstico tiende a ser favorable (AU)

Aim. To know the prevalence of the patients diagnosed of cystic fibrosis (CF) older than 18 years old of five specific Spanish Units and to analyze their clinical, genetic and microbiological characteristics. Patients and methods. Observational, cross-sectional, descriptive study of patients diagnosed with CF at age or older than 18 years. The variables analyzed were: current age, age at diagnosis, sex, nationality, lung function parameters, pathologies presented at diagnosis, microbiological features and genetic findings. Results. Eigthy nine patients (14.8% of the total of 600 CF patients followed at the participating units), of which 45 patients were female (50.6%) and 44 were males (49.4%), were included with a mean age at diagnosis of 36.4 years. Eigthy one patients (91%) were Spaniards. The sweat test was diagnostic in 77 (86.5%) of the patients studied. The sweat test was diagnostic in 77 of the 89 patients studied (86.5%). The most frequently detected mutations were F508del/other and G542X/other, and the most frequent clinical findings at diagnosis were the presence of bronchiectasis in 33 patients (37.1%) followed by sterility in 12 patients (13.5%). The most common colonizing organisms were meticillin-sensitive Staphylococcus aureus (S.aureus) (23.6%) and Pseudomonas aeruginosa (P. aeruginosa) (13.5%). Most patients presented a mild obstructive ventilatory defect and had no pancreatic involvement. The sweat test used to be indeterminate. Conclusions. CF is also a disease which diagnosis can be in adulthood. CF patients diagnosed in adulthood have a mild lung function and lower incidence of pancreatic involvement, so their prognosis tends to be favorable (AU)

Cystic fibrosis in adult age. / Fibrosis quística diagnosticada en edad adulta.

AIM: To know the prevalence of the patients diagnosed of cystic fibrosis (CF) older than 18 years old of five specific Spanish Units and to analyze their clinical, genetic and microbiological characteristics. PATIENTS AND METHODS: Observational, cross-sectional, descriptive study of patients diagnosed with CF at age or older than 18 years. The variables analyzed were: current age, age at diagnosis, sex, nationality, lung function parameters, pathologies presented at diagnosis, microbiological features and genetic findings. RESULTS: Eigthy nine patients (14.8% of the total of 600 CF patients followed at the participating units), of which 45 patients were female (50.6%) and 44 were males (49.4%), were included with a mean age at diagnosis of 36.4 years. Eigthy one patients (91%) were Spaniards. The sweat test was diagnostic in 77 (86.5%) of the patients studied. The sweat test was diagnostic in 77 of the 89 patients studied (86.5%). The most frequently detected mutations were F508del/other and G542X/other, and the most frequent clinical findings at diagnosis were the presence of bronchiectasis in 33 patients (37.1%) followed by sterility in 12 patients (13.5%). The most common colonizing organisms were meticillin-sensitive Staphylococcus aureus (S.aureus) (23.6%) and Pseudomonas aeruginosa (P. aeruginosa) (13.5%). Most patients presented a mild obstructive ventilatory defect and had no pancreatic involvement. The sweat test used to be indeterminate. CONCLUSIONS: CF is also a disease which diagnosis can be in adulthood. CF patients diagnosed in adulthood have a mild lung function and lower incidence of pancreatic involvement, so their prognosis tends to be favorable.

Retrospective analysis of the use of G-CSF and its impact on dose response for anthracycline plus taxane-based schedules in early breast cancer.

PURPOSE: To evaluate the impact on survival of the relative dose intensity (RDI) achieved in patients with early breast cancer receiving anthracycline plus taxane-based chemotherapy in the adjuvant setting. PATIENTS AND METHODS: Patients with early breast cancer diagnosed from January 1999 through December 2006 were included. Dose intensity was evaluated according to the number of delayed cycles and days and the percentage of RDI. RESULTS: A total of 231 breast cancer patients were included. Granulocyte colony-stimulating factor (G-CSF) was given to 39 % of patients. Few patients delayed chemotherapy administration ≥2 cycles (6 %) and ≥15 days (2 %), and the majority of them received ≥85 % of the RDI (98 %). Overall survival was statistically lower at 5 years in patients who received <85 % of RDI in comparison with those who received ≥85 % of RDI (80 vs. 97 %; p = 0.026). CONCLUSIONS: With a wide use of G-CSF in patients treated with adjuvant anthracyclines plus taxane-based schedules, 98 % of patients received a RDI ≥85 %. A significant although inconsistent impairment of survival was found in those patients with lower RDI.