Experience with the use of baricitinib and tocilizumab monotherapy or combined, in patients with interstitial pneumonia secondary to coronavirus COVID19: a real-world study / Experiencia con el uso de baricitinib y tocilizumab en monoterapia o combinados, en pacientes con neumonía intersticial secundaria al coronavirus COVID-19: un estudio del mundo real

OBJECTIVE: To describe the experience of treatment with baricitinib (BARI) and/or tocilizumab (TCZ), in monotherapy or combined, in patients admitted for interstitial pneumonia secondary to COVID19, and for 30 days after discharge. METHODS: Medical records of patients admitted with COVID19 and IP with PaO2/FiO2<300, treated with BARI and/or TCZ, and compared with patients who did not, were retrospectively reviewed. RESULTS: Sixty patients were included; 43 (72%) are males, mean age 67 (SD: 14) years (<50 years: 17%; 51-70: 30%; >70: 53%), with 8.5 (SD: 1) days of symptoms. Sixteen (27%) patients required ICU (94% in <70 years). Fifteen (25%) patients died, 67% in >70 years; 11 (18%) patients died in the first 15 days of admission and 4 (7%) between days 16 to 30. Twenty-three (38%) patients received BARI, 12 (52%) monotherapy (Group 1), during 6 (SD: 2.6) days on average, none required ICU and 2 (17%) died. Thirty-one (52%) patients received TCZ, 20 (33%) as monotherapy (Group 2), 16 (52%) patients required ICU and 4 (20%) died. In the 11 (18%) patients who received BARI (2.8 [SD: 2.5] days average) and TCZ combined (Group 3), 3 (27%) required ICU and died. There were no severe side effects in BARI or TCZ patients. In the 17 (28%) patients who received neither BARI nor TCZ (Group 4), none required ICU and 6 (35%) died. Mean (SD) PaO2/FiO2 at admission between groups was respectively: 167 (82.3), 221 (114.9), 236 (82.3), 276 (83.2). CONCLUSION: Treatment with BARI and TCZ did not cause serious side effects. They could be considered early in patients with NI secondary to COVID19 and impaired PaO2/PaFi

OBJETIVO: Describir la experiencia con baricitinib (BARI) y/o tocilizumab (TCZ), en monoterapia o combinados en pacientes ingresados por neumonía intersticial (NI) por COVID-19 y durante los 30 días después del alta. MÉTODO: Se revisaron retrospectivamente las historias clínicas de los pacientes ingresados por COVID-19 y NI, con PaO2/FiO2<300, tratados con BARI y/o TCZ y se compararon con pacientes que no los recibieron. RESULTADOS: Se incluyeron 60 pacientes; 43 (72%) varones, edad media 67 (DE: 14) años (< 50 años: 17%; 51-70: 30%; > 70: 53%), y 8,5 (DE: 1) días de síntomas. Dieciséis (27%) ingresaron en la unidad de cuidados intensivos (UCI) (94% < 70 años). Quince (25%) fallecieron (67% > 70 años); 11 (18%) de ellos en los primeros 15 días del ingreso y cuatro (7%) entre los días 16 y 30. Veintitrés (38%) pacientes recibieron BARI, 12 (52%) en monoterapia (Grupo 1), durante seis (DE: 2.6) días de promedio, ninguno de ellos ingresó en UCI y dos (17%) fallecieron. Treinta y un (52%) pacientes recibieron una dosis de TCZ, 20 (33%) en monoterapia (Grupo 2), 16 (52%) ingresaron en UCI y cuatro (20%) fallecieron. Entre los 11 (18%) pacientes que recibieron BARI (2,8 [DE: 2,5] días de promedio) y TCZ combinados (Grupo 3), tres (27%) ingresaron en UCI y fallecieron. No hubo efectos secundarios graves entre los que recibieron BARI y/o TCZ. Entre los 17 (28%) pacientes que no recibieron ni BARI ni TCZ (Grupo 4), ninguno ingresó en UCI y seis (35%) fallecieron. La PaO2/FiO2 media (DE) al ingreso entre los grupos fue respectivamente: 167 (82,3), 221 (114,9), 236 (82,3), 276 (83,2). CONCLUSIÓN: El tratamiento con BARI y TCZ no provocó efectos secundarios graves. Podrían considerarse precozmente en pacientes con NI secundaria a COVID-19 y deterioro de PaO2/PaFi

ß2­adrenergic receptor functionality and genotype in two different models of chronic inflammatory disease: Liver cirrhosis and osteoarthritis.

The present study was designed to investigate the functional status of ß2 adrenoceptors (ß2AR) in two models of chronic inflammatory disease: liver cirrhosis (LC) and osteoarthritis (OA). The ß2AR gene contains three single nucleotide polymorphisms at amino acid positions 16, 27 and 164. The aim of the present study was to investigate the potential influence of lymphocyte ß2AR receptor functionality and genotype in LC and OA patients. Blood samples from cirrhotic patients (n=52, hepatic venous pressure gradient 13±4 mmHg, CHILD 7±2 and MELD 11±4 scores), OA patients (n=30, 84% Kellgren­Lawrence severity 4 grade, 14% knee replacement joint) and healthy volunteers as control group (n=26) were analyzed. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood and basal and isoproterenol induced adenylate cyclase activity (isoproterenol stimulus from 10­9 to 10­4 mM), and ß2AR allelic variants (rs1042713, rs1042714, rs1800888) were determined. ß2AR functionality was decreased in the two different models of chronic inflammatory disease studied, OA (50% vs. control) and LC (85% vs. control). In these patients, the strength of the ß2AR response to adrenergic stimulation was very limited. Adrenergic modulation of PBMC function through the ß2AR stimulus is decreased in chronic inflammatory processes including LC and OA, suggesting that the adrenergic system may be important in the development of these processes.

Influence of fluid therapy on the prognosis of acute pancreatitis: a prospective cohort study.

OBJECTIVES: Although aggressive fluid therapy during the first days of hospitalization is recommended by most guidelines and reviews on acute pancreatitis (AP), this recommendation is not supported by any direct evidence. We aimed to evaluate the association between the amount of fluid administered during the initial 24 h of hospitalization and the incidence of organ failure (OF), local complications, and mortality. METHODS: This was a prospective cohort study. We included consecutive adult patients admitted with AP. Local complications and OF were defined according to the Atlanta Classification. Persistent OF was defined as OF of >48-h duration. Patients were divided into three groups according to the amount of fluid administered during the initial 24 h: group A: <3.1 l (less than the first quartile), group B: 3.1-4.1 l (between the first and third quartiles), and group C: >4.1 l (more than the third quartile). RESULTS: A total of 247 patients were analyzed. Administration of >4.1 l during the initial 24 h was significantly and independently associated with persistent OF, acute collections, respiratory insufficiency, and renal insufficiency. Administration of <3.1 l during the initial 24 h was not associated with OF, local complications, or mortality. Patients who received between 3.1 and 4.1 l during the initial 24 h had an excellent outcome. CONCLUSIONS: In our study, administration of a small amount of fluid during the initial 24 h was not associated with a poor outcome. The need for a great amount of fluid during the initial 24 h was associated with a poor outcome; therefore, this group of patients must be carefully monitored.