Browsing by Author "Pérez, Rodrigo"
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Publication Increased respiratory dead space could associate with coagulation activation and poor outcomes in COVID-19 ARDS(2022) Graf, Jerónimo; Pérez, Rodrigo; López, RenéPurpose: To determine whether VDPhys/VT is associated with coagulation activation and outcomes. Materials and methods: We enrolled patients with COVID-19 pneumonia who were supported by invasive mechanical ventilation and were monitored using volumetric capnography. Measurements were performed during the first 24 h of mechanical ventilation. The primary endpoint was the likelihood of being discharge alive on day 28. Results: Sixty patients were enrolled, of which 25 (42%) had high VDPhys/VT (>57%). Patients with high vs. low VDPhys/VT had higher APACHE II (10[8-13] vs. 8[6-9] points, p = 0.002), lower static compliance of the respiratory system (35[24-46] mL/cmH2O vs. 42[37-45] mL/cmH2O, p = 0.005), and higher D-dimer levels (1246[1050-1594] ng FEU/mL vs. 792[538-1159] ng FEU/mL, p = 0.001), without differences in P/F ratio (157[112-226] vs. 168[136-226], p = 0.719). Additionally, D-dimer levels correlated with VDPhys/VT (r = 0.530, p < 0.001), but not with the P/F ratio (r = -0.103, p = 0.433). Patients with high VDPhys/VT were less likely to be discharged alive on day 28 (32% vs. 71%, aHR = 3.393[1.161-9.915], p = 0.026). Conclusions: In critically ill COVID-19 patients, increased VDPhys/VT was associated with high D-dimer levels and a lower likelihood of being discharged alive. Dichotomic VDPhys/VT could help identify a high-risk subgroup of patients neglected by the P/F ratio.Item Small molecules to perform big roles: The search for Parkinson's and Huntington's disease therapeutics(2023) Pérez, Rodrigo; Cisternas, Marisol; Sepúlveda, Denisse; Troncoso, Paulina; Vidal, ReneNeurological motor disorders (NMDs) such as Parkinson's disease and Huntington's disease are characterized by the accumulation and aggregation of misfolded proteins that trigger cell death of specific neuronal populations in the central nervous system. Differential neuronal loss initiates the impaired motor control and cognitive function in the affected patients. Although major advances have been carried out to understand the molecular basis of these diseases, to date there are no treatments that can prevent, cure, or significantly delay the progression of the disease. In this context, strategies such as gene editing, cellular therapy, among others, have gained attention as they effectively reduce the load of toxic protein aggregates in different models of neurodegeneration. Nevertheless, these strategies are expensive and difficult to deliver into the patients' nervous system. Thus, small molecules and natural products that reduce protein aggregation levels are highly sought after. Numerous drug discovery efforts have analyzed large libraries of synthetic compounds for the treatment of different NMDs, with a few candidates reaching clinical trials. Moreover, the recognition of new druggable targets for NMDs has allowed the discovery of new small molecules that have demonstrated their efficacy in pre-clinical studies. It is also important to recognize the contribution of natural products to the discovery of new candidates that can prevent or cure NMDs. Additionally, the repurposing of drugs for the treatment of NMDs has gained huge attention as they have already been through clinical trials confirming their safety in humans, which can accelerate the development of new treatment. In this review, we will focus on the new advances in the discovery of small molecules for the treatment of Parkinson's and Huntington's disease. We will begin by discussing the available pharmacological treatments to modulate the progression of neurodegeneration and to alleviate the motor symptoms in these diseases. Then, we will analyze those small molecules that have reached or are currently under clinical trials, including natural products and repurposed drugs.Item Survival of Critically Ill Oncologic Patients Requiring Invasive Ventilatory Support: A Prospective Comparative Cohort Study With Nononcologic Patients(2019) López, René; Pérez-Araos, Rodrigo; Samtani, Suraj; Montes, José Miguel; Pérez, Rodrigo; Martin, María José; Salazar, Álvaro; Graf, JeronimoPurpose: Cancer is in the process of changing to become a chronic disease; therefore, an increasing number of oncologic patients (OPs) are being admitted to intensive care units (ICUs) for supportive care of disease or therapy-related complications. We compare the short- and long-term outcomes of critically ill mechanically ventilated OPs with those of their nononcologic counterparts. Patients and methods: We performed a prospective study of patients admitted to our ICU between October 2017 and February 2019. Demographic, physiologic, laboratory, clinical, and treatment data were obtained. The primary outcome was survival at 28 days and at the end of the follow-up period. Secondary outcomes were survival according to acute severity scoring (Acute Physiology and Chronic Health Evaluation II score), Eastern Cooperative Oncology Group (ECOG) performance status, and Charlson comorbidity index. Results: A total of 1,490 patients were admitted during the study period; 358 patients (24%) were OPs, and 100 of these OPs were supported with mechanical ventilation. Seventy-three percent of OPs had an ECOG performances status of 0 or 1, and 90% had solid tumors. Reason for admission to the ICU was postoperative admission in 44 patients and neutropenic infection in 10 patients. The follow-up period was 148 days (range, 42 to 363 days). Survival at 28 days was similar between OPs and nononcologic patients and associated with the Acute Physiology and Chronic Health Evaluation II score. However, long-term survival was lower in OPs compared with nononcologic patients (52% v 76%, respectively; P < .001) and associated with poor ECOG performance status. Conclusion: Short-term survival of critically ill, mechanically ventilated OPs is similar to that of their nononcologic counterparts and is determined by the severity of the critical illness.