Clinical characteristics and outcomes of 1,331 patients with COVID-19: HM Spanish Cohort.

OBJECTIVE: Spain is one of the European countries most affected by the COVID-19 pandemic. Epidemiologic studies are warranted to improve the disease understanding, evaluate the care procedure and prepare for futures waves. The aim of the study was to describe epidemiologic characteristics associated with hospitalized patients with COVID-19. METHODS: This real-world, observational, multicenter and retrospective study screened all consecutive patients admitted to 8 Spanish private hospitals. Inclusion criteria: hospitalized adults (age≥18 years old) with clinically and radiologically findings compatible with COVID-19 disease from March 1st to April 5th, 2020. Exclusion criteria: patients presenting negative PCR for SARS-CoV-2 during the first 7 days from hospital admission, transfer to a hospital not belonging to the HM consortium, lack of data and discharge against medical advice in emergency departments. RESULTS: One thousand and three hundred thirty-one COVID-19 patients (medium age 66.9 years old; males n= 841, medium length of hospital stayed 8 days, non-survivors n=233) were analyzed. One hundred and fifteen were admitted to intensive care unit (medium length of stay 16 days, invasive mechanical ventilation n= 95, septic shock n= 37 and renal replacement therapy n= 17). Age, male gender, leukocytes, platelets, oxygen saturation, chronic therapy with steroids and treatment with hydroxychloroquine/azithromycin were independent factors associated with mortality. The proportion of patients that survive and received tocilizumab and steroids were lesser and higher respectively than those that die, but their association was not significant. CONCLUSIONS: Overall crude mortality rate was 17.5%, rising up to 36.5% in the subgroup of patients that were admitted to the intensive care unit. Seven factors impact in hospital mortality. No immunomodulatory intervention were associated with in-hospital mortality.

Stromal disrupting effects of nab-paclitaxel in pancreatic cancer.

BACKGROUND: Nab-paclitaxel and gemcitabine have demonstrated a survival benefit over gemcitabine alone in advanced pancreatic cancer (PDA). This study aimed to investigate the clinical, biological, and imaging effects of the regimen in patients with operable PDA. METHODS: Patients with operable PDA received two cycles of nab-paclitaxel and gemcitabine before surgical resection. FDG-PET and CA19.9 tumour marker levels were used to measure clinical activity. Effects on tumour stroma were determined by endoscopic ultrasound (EUS) elastography. The collagen content and architecture as well as density of cancer-associated fibroblasts (CAFs) were determined in the resected surgical specimen and compared with a group of untreated and treated with conventional chemoradiation therapy controls. A co-clinical study in a mouse model of PDA was conducted to differentiate between the effects of nab-paclitaxel and gemcitabine. RESULTS: A total of 16 patients were enrolled. Treatment resulted in significant antitumour effects with 50% of patients achieving a >75% decrease in circulating CA19.9 tumour marker and a response by FDG-PET. There was also a significant decrement in tumour stiffness as measured by EUS elastography. Seven of 12 patients who completed treatment and were operated had major pathological regressions. Analysis of residual tumours showed a marked disorganised collagen with a very low density of CAF, which was not observed in the untreated or conventionally treated control groups. The preclinical co-clinical study showed that these effects were specific of nab-paclitaxel and not gemcitabine. CONCLUSION: These data suggest that nab-paclitaxel and gemcitabine decreases CAF content inducing a marked alteration in cancer stroma that results in tumour softening. This regimen should be studied in patients with operable PDA.

A preclinical and clinical study of mycophenolate mofetil in pancreatic cancer.

A high throughput screening for anticancer activity of FDA approved drugs identified mycophenolic acid (MPA), an inhibitor of inositol monophosphate dehydrogenase (IMPDH) as an active agent with an antiangiogenesis mode of action. Exposure of pancreatic cancer cell lines to MPA resulted in growth inhibition and reduced the expression of VEGF that was reversed by supplementing the media with guanosine supporting and IMPDH-dependant mechanism. In preclinical in vivo study, MPA showed a moderate inhibition of tumor growth in a panel of 6 human derived pancreatic cancer xenografts but reduced the expression of VEGF. To investigate the effects of MPA in human pancreatic cancer, a total of 12 patients with resectable pancreatic cancer (PDA) received increasing doses of mycophenolate mofetil (MMF) in cohorts of 6 patients each from 5-15 days prior to surgical resection. Treatment was well tolerated with one episode of grade 1 muscle pain, one episode of grade 2 lymphopenia (2 gr/day dose) and one episode of grade 2 elevantion in LFT (all in the 2 gr./day dose). Patients recovered from surgery uneventfully with no increased post-operative complications. Assessment of CD31, VEGF, and TUNEL in resected specimens compared to a non treated control of 6 patients showed no significant variations in any of the study endpoints. In conclusion, this study shows the feasibility of translating a preclinical observation to the clinical setting and to explore a drug mechanism of action in patients. MPA, however, did not show any hints of antiangiogenesis of anticancer clinical activity questioning if this agent should be further developed in PDA.

[Spinal leptomeningeal metastasis from cerebral glioblastoma: case report]. / Metástasis leptomeníngeas espinales y glioblastoma multiforme: caso clínico.

INTRODUCTION: Glioblastoma multiforme (GBM) is the most common primary malignant tumor of the central nervous system. Its tendency to infiltrate and recur locally is well known. Spinal leptomeningeal metastasis (SLM) due to a GBM are well documented at autopsy in patients previously diagnosed of GBM, however, systemic dissemination with symptomatic leptomeningeal metastasis is quite rare. Most of the time it is diagnosed late and misdiagnosis is a common problem. CASE REPORT: We present a case of a 65-year-old man with a right temporal GBM treated by surgical resection, radiotherapy and chemotherapy, who is readmitted 10 months later as he developed an ataxic gait. A new cerebral magnetic resonance imaging (MRI) showed multiple cerebellar metastasis. He also reported intense lumbar pain on the new admission, increasing in intensity and that was followed by flaccid paraparesis two weeks later. Multiple spinal metastasis deposits were documented by a contrast enhanced spinal MRI. CONCLUSIONS: SLM need to be suspected in patients with a past history of intracranial GBM, who present with clinical features that can not been explained by the primary lesion. Awareness of this complication might facilitate more rapid diagnosis and treatment. A discussion is made regarding SLM in patients with GBM with reference to the medical literature.

Metástasis leptomeníngeas espinales y glioblastoma multiforme: caso clínico / Spinal leptomeningeal metástasis fromcerebral glioblastoma: case report

Introducción. El glioblastoma multiforme (GBM) es el tumor cerebral primario más frecuente en adultos. Presenta una gran capacidad de invasión y recidiva local. Se han documentado metástasis leptomeníngeas espinales (MLE) en las autopsias de pacientes con GBM; no obstante, la diseminación sistémica con afectación leptomeníngea espinal sintomática es rara, diagnosticándose en muchas ocasiones de forma errónea o tardíamente. Caso clínico. Presentamos el caso de un paciente de 65 años diagnosticado de un GBM temporal derecho, que es tratado quirúrgicamente con radioterapia y quimioterapia adyuvante y que 10 meses después vuelve a ingresar tras desarrollar una alteración de la marcha. Se realizó una nueva resonancia magnética cerebral, objetivándose múltiples metástasis en el cerebelo. Posteriormente el paciente presentó dolor lumbar intenso y 2 semanas después una paraparesia flácida. Se realizó una resonancia magnética espinal en la que aparecieron múltiples depósitos metastásicos. Conclusiones. Las MLE se deben sospechar en todos los pacientes con antecedentes de GBM cerebral que presentan clínica no justificable por la lesión primaria. El conocimiento de esta complicación puede facilitar un diagnóstico y tratamiento más precoz. Realizamos una revisión bibliográfica en relación con las MLE en los pacientes con GBM (AU)

Introduction: Glioblastoma multiforme (GBM) is the most common primary malignant tumor of the central nervous system. Its tendency to infiltrate and recur locally is well known. Spinal leptomeningeal metastasis (SLM) due to a GBM are well documented at autopsy in patients previously diagnosed of GBM, however, systemic dissemination with symptomatic leptomeningeal metastasis is quite rare. Most of the time it is diagnosed late and misdiagnosis is a common problem. Case report: We present a case of a 65-year-old man with a right temporal GBM treated by surgical resection, radiotherapy and chemotherapy, who is readmitted 10 months later as he developed an ataxic gait. A new cerebral magnetic resonance imaging (MRI) showed multiple cerebellar metastasis. He also reported intense lumbar pain on the new admission, increasing in intensity and that was followed by flaccid paraparesis two weeks later. Multiple spinal metastasis deposits were documented by a contrast enhanced spinal MRI. Conclusions: SLM need to be suspected in patients with a past history of intracranial GBM, who present with clinical features that can not been explained by the primary lesion. Awareness of this complication might facilitate more rapid diagnosis and treatment. A discussion is made regarding SLM in patients with GBM with reference to the medical literatura (AU)

Actitud diagnóstica y terapéutica ante el paciente que acude con hemoptisis / Diagnostic and therapeutic attitude in patient with hemoptysis

La hemoptisis es un síntoma que requiere un estudio exhaustivo ya que puede ser secundaria a una enfermedad grave y/o dar lugar a una hemorragia fatal o incluso a un síndrome asfíctico. Por ello debemos confirmar el diagnóstico en el menor tiempo posible, así como evaluar la gravedad del cuadro, localizar la lesión responsable y tratarla adecuadamente porque la evolución clínica es impredecible. El objeto de este trabajo es repasar el manejo de esta entidad, así como establecer un modelo que coordine los Servicios de Atención Primaria y Neumología (AU)