On the evolution of the COVID-19 epidemiological parameters using only the series of deceased. A study of the Spanish outbreak using Genetic Algorithms.

We propose a methodology for estimating the evolution of the epidemiological parameters of a SIRD model (acronym of Susceptible, Infected, Recovered and Deceased individuals) which allows to evaluate the sanitary measures taken by the government, for the COVID-19 in the Spanish outbreak. In our methodology the only information required for estimating these parameters is the time series of deceased people; due to the number of asymptomatic people produced by the COVID-19, it is not possible to know the actual number of infected people at any given time. Therefore, among the different time series that quantify the pandemic we consider just the number of deceased people to minimize the square sum of errors. The time series of deaths considered runs from March to the end of September and is divided into four sub-periods reflecting the different isolation measures taken by the Spanish government. The parameters that we can estimate are the time from the beginning of the disease, the transmission rate, and the recovery rate; these last two ratios are estimated in each of the different sub-periods. In this way the model considered has 2x4+1=9 parameters that are estimated jointly over the whole period from the data of deceased. Given the complexity of the model, to estimate the parameters that minimize the square sum of errors, a Genetic Algorithm is used. Our methodology confirms the effectiveness of the sanitary measures taken by the Spanish government showing a dramatic reduction in the basic reproductive number R 0 during confinement; also, a further increase in R 0 after the end of the alarm state decreed by the government on June 21 was detected. Our results also point out that the Patient Zero in the COVID-19 Spanish outbreak emerged between the end of December and early January, at least four weeks before January 31st, that was the moment when the Spanish authorities reported the first positive case.

Wound Infusion of 0.35% Levobupivacaine Reduces Mechanical Secondary Hyperalgesia and Opioid Consumption After Cesarean Delivery: A Prospective, Randomized, Triple-Blind, Placebo-Controlled Trial.

BACKGROUND: Some patients still report moderate-to-severe postoperative pain after cesarean delivery. Local anesthetic wound infusion improves acute pain and might act on peripheral and central sensitization mechanisms; however, no studies have proved this hypothesis. We evaluated the potential benefits of continuous wound infusion of levobupivacaine after cesarean delivery on secondary hyperalgesia (primary end point) and primary hyperalgesia, pain relief, persistent pain, and inflammatory and metabolic stress response. METHODS: Healthy women scheduled for elective cesarean delivery participated in this prospective, randomized, triple-blind, placebo-controlled trial (NCT01458431). All patients received spinal anesthesia with 0.5% hyperbaric bupivacaine with fentanyl and a multiholed wound catheter placed under the fascia. Women were randomized to receive continuous wound infusion (0.35% levobupivacaine 7 mL/h for 48 hours; group L) or an equal volume of saline (group S). Secondary hyperalgesia to punctate mechanical stimuli was evaluated using dynamic tests, and primary hyperalgesia was evaluated using an electronic von Frey anesthesiometer; both were assessed at 24, 48, and 72 hours. The following variables were collected: intensity of postoperative parietal and visceral pain at rest and on movement rated on a visual analog scale >72 hours, time to first bolus of patient-controlled analgesia (PCA), cumulative dose of rescue morphine (PCA) and acetaminophen, ability to sleep and sleep quality, and patient satisfaction. Persistent postoperative pain was evaluated during a telephone interview at 1, 3, 6, and 12 months after surgery. C-reactive protein, acid glycoprotein, preprandial glucose, insulin, cortisol, prolactin, growth hormone, and interleukin-6 were measured before cesarean delivery and at 8, 24, and 48 hours. Adverse events and patient outcomes were recorded. RESULTS: Seventy women were included. In group L, the area of secondary hyperalgesia was significantly reduced (43.4 [18.5-80] vs 68.4 [39.0-136] cm2 and 45.1 [0.9-89.8] vs 67.3 [31.3-175] cm2 at 24 and 48 hours, respectively; group:time interaction P value < .001), the mechanical pain threshold was significantly higher at 24 hours (633 [441-802] vs 417 [300-572] g.mm-2; P = .001), and morphine consumption was significantly lower at 24 hours (4 [2-11] vs 11[6-23]; P = .003) compared with group S. Levobupivacaine had no effect on persistent postoperative pain at 1, 3, 6, and 12 months. Plasma insulin levels in the immediate postoperative period and at 8, 24, and 48 hours were significantly lower in group L (P < .001). There were no significant differences in other biochemical parameters of inflammatory and endocrine-metabolic response. CONCLUSIONS: Levobupivacaine wound infusion provides adequate analgesia and might be an effective antihyperalgesic adjunct.

Postoperative Plasma Mitochondrial DNA and Cytokine Profiles of Elderly Patients Undergoing Minimally Invasive Aortic Valve Replacement.

INTRODUCTION: Mitochondrial DNA (mtDNA) is gaining increasing interest as a marker of cellular damage and could also act as an inflammatory mediator in cardiopulmonary bypass induced postoperative inflammatory response. Although minimally invasive heart valve surgery reportedly reduces inflammation, the mtDNA and cytokine profile in this context remains unclear. MATERIALS AND METHODS: Here, we report a prospective series of 40 elderly patients with aortic stenosis who underwent bioprosthetic aortic valve replacement (AVR) through upper ministernotomy with either a sutureless (n = 20) or a conventional (n = 20) valve. Primary end points included serial plasma levels of mtDNA (T1: at baseline; T2: 4 hours after surgery; and T3: 24s hour after surgery), cytokines (interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α]), and myocardial necrosis biomarkers (MNBs), whereas secondary end points included clinical and echocardiographic data. RESULTS: Significant increases in the postoperative plasma levels (T2) of mtDNA, cytokines, and MNBs were observed in all patients. The postoperative plasma levels of mtDNA, TNF-α, and MNBs showed no significant differences between the treatment groups, although there was a trend toward lower levels in the sutureless group. The decreases in aortic cross-clamp and cardiopulmonary bypass times seen in the sutureless group were associated with significant lower postoperative levels (T2 and T3) of IL-6. CONCLUSION: AVR through upper ministernotomy was associated with a significant increase in postoperative plasma levels of mtDNA and cytokines. There was no difference in the mtDNA levels between the sutureless and conventional valve groups, suggesting a similar level of inflammation in both groups. However, the shorter operation time observed in the sutureless valve group was associated with significantly lower postoperative levels of IL-6, indicating potential clinical benefits.

Age-related reference values for plasma amino acids in a Spanish population measured by gas chromatography-mass spectrometry.

OBJECTIVES: Reference ranges of blood plasma amino acids are required for the diagnosis and management of inherited metabolic disorders affecting one or more amino acids and can significantly impact the clinical decision-making and the quality of patient care. Our objective was to establish the reference values for plasma amino acids in a Spanish population measured by gas chromatography-mass spectrometry (GC-MS). METHODS: Amino acids were extracted, derivatized to N(O)-tert-butyldimethylsilyl, and analyzed by GC-MS. RESULTS: Significant differences in the concentrations of several amino acids have been determined between age groups. Such differences might be due to a combination of several factors, including age, genetic factors, nutritional status, and dietary habits. CONCLUSIONS: The amino acid values are not evidently affected by sex, but they do vary with age. Such data help to provide a basis for diagnosing metabolic abnormalities. To our knowledge, this is the first published article showing the age-related reference ranges for plasma amino acids analyzed by GC-MS.

Patient with double bence jones proteinuria after hematopoietic cell transplantation.

About two thirds of patients with multiple myeloma and M-component in serum also have light chains in urine. However, the simultaneous presence of 2 Bence Jones proteins of different immunologic types in the same patient is rare. We describe the case of a 58-year-old woman with multiple myeloma, having 2 monoclonal light chains of both types (kappa and lambda) and an immunoglobulin G-lambda monoclonal protein in urine. The quantitative determination of light chains in urine was carried out using nephelometry, and Bence Jones proteinuria was confirmed by agarose gel immunofixation. To the best of our knowledge, this is the first reported case of double Bence Jones proteinuria after hematopoietic cell transplantation.