COVID‐19 in Spain: Transplantation in the midst of the pandemic

Spain has been one of the most affected countries by the COVID‐19 outbreak. As of April 28, 2020, the number of confirmed cases is 210 773, including 102 548 patients recovered, more than 10 300 admitted to the ICU, and 23 822 deaths, with a global case fatality rate of 11.3%. From the perspective of donation and transplantation, the Spanish system first focused on safety issues, providing recommendations for donor evaluation and testing, and to rule out SARS‐CoV‐2 infection in potential recipients prior to transplantation. Since the country entered into an epidemiological scenario of sustained community transmission and saturation of intensive care, developing donation and transplantation procedures has become highly complex. Since the national state of alarm was declared in Spain on March 13, 2020, the mean number of donors has declined from 7.2 to 1.2 per day, and the mean number of transplants from 16.1 to 2.1 per day. Increased mortality on the waiting list may become a collateral damage of this terrible pandemic.     

Tuftsin phosphorylcholine—a novel compound harnessing helminths to fight autoimmunity

The distinction that in areas where helminthic infections are common, autoimmune diseases are less prevalent, led to the investigation of immune modulatory properties of helminths and their derivatives. Such are phosphorylcholine (PC) moieties which are a component of secreted products of helminths. PC has been broadly studied for its attenuating effects on the human immune system. In an attempt to develop a novel therapeutic small molecule for the treatment of autoimmune conditions, we have conjugated PC with tuftsin, a natural immunomodulatory tetrapeptide, to create TPC. Herein, we review our findings regarding the effects of TPC in murine models of three autoimmune diseases—systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and rheumatic arthritis (RA), as well as ex-vivo samples from giant cell arteritis (GCA) patients. In all four disease models examined, TPC was shown to attenuate the inflammatory response by reducing expression of pro-inflammatory cytokines and altering the phenotype of T cell expression. In murine models, TPC has further produced a significant improvement in clinical disease scores with no significant side effects noted. Our findings suggest TPC presents promising potential as a novel therapeutic agent for the effective treatment of various autoimmune conditions.     

Functional characterization of five NR5A1 gene mutations found in patients with 46,XY disorders of sex development

Steroidogenic factor‐1 (SF1), encoded by the NR5A1 gene, is a key regulator of steroidogenesis and reproductive development. NR5A1 mutations described in 46,XY patients with disorders of sex development (DSD) can be associated with a range of conditions of phenotypes; however, the genotype–phenotype correlation remains elusive in many cases. In the present study, we describe the impact of five NR5A1 variants (three novel: p.Arg39Cys, p.Ser32Asn, and p.Lys396Argfs*34; and two previously described: p.Cys65Tyr and p.Cys247*) on protein function, identified in seven patients with 46,XY DSD. In vitro functional analyses demonstrate that NR5A1 mutations impair protein functions and result in the DSD phenotype observed in our patients. Missense mutations in the DNA binding domain and the frameshift mutation p.Lys396Argfs*34 lead to both, markedly affected transactivation assays, and loss of DNA binding, whereas the mutation p.Cys247* retained partial transactivation capacity and the ability to bind a consensus SF1 responsive element. SF1 acts in a dose‐dependent manner and regulates a cascade of genes involved in the sex determination and steroidogenesis, but in most cases reported so far, still lead to a sufficient adrenal steroidogenesis and function, just like in our cases, in which heterozygous mutations are associated to 46,XY DSD with intact adrenal steroid biosynthesis.     

Expression Pattern and Immunoregulatory Roles of Galectin-1 and Galectin-3 in Atopic Dermatitis and Psoriasis

Inflammation - The pathogenesis of atopic dermatitis (AD) and psoriasis (Ps) overlaps, particularly the activation of the immune response and tissue damage. Here, we evaluated galectin (Gal)-1 and...     

Interrater Reliability and Validity of the Stair Ascend/Descend Test in Subjects With Total Knee Arthroplasty

Almeida GJ, Schroeder CA, Gil AB, Fitzgerald GK, Piva SR. Interrater reliability and validity of the stair ascend/descend test in subjects with total knee arthroplasty.

Objective

(1) To determine the interrater reliability and measurement error of an 11-step stair ascend/descend test (STTotal-11) and stair up (ascend) test (STUp-11); (2) to seek evidence for the STTotal-11 and STUp-11 as valid measures of physical function by determining if they relate to measures of physical function and do not relate to measures not of physical function; and (3) to explore if the STTotal-11 and STUp-11 scores relate to lower-extremity muscle weakness and knee range of motion (ROM) in subjects with total knee arthroplasty (TKA).

Design

Cross-sectional study.

Setting

Academic center.

Participants

Subjects (N=43, 30 women; mean age, 68±8y) with unilateral TKA.

Interventions

Not applicable.

Main Outcome Measures

STTotal-11 and STUp-11 were performed twice, and scores were compared with scores on 4 lower extremity performance-based tasks, 2 patient-reported questionnaires of physical function, 3 psychologic factors, knee ROM, and strength of quadriceps, hip extensors, and abductors.

Results

Intraclass correlation coefficient was .94 for both the STTotal-11 and STUp-11, standard error of measurements were 1.14 seconds and .82 seconds, and minimum detectable change associated with 90% confidence interval was 2.6 seconds and 1.9 seconds, respectively. Correlations between stair tests and performance-based measures and knee and hip muscle strength ranged from Pearson correlation coefficient (r)=.40 to .78. STTotal-11 and STUp-11 had a small correlation with one of the patient-reported measures of physical function. Stair tests were not associated with psychologic factors and knee extension ROM and were associated with knee flexion ROM.

Conclusions

STTotal-11 and STUp-11 have good interrater reliability and minimum detectable changes adequate for clinical use. The pattern of associations supports the validity of the stair tests in TKA.     

Role of endogenous adenosine as a predictive marker of vasoplegia during cardiopulmonary bypass and postoperative severe systemic inflammatory response

OBJECTIVE: Systemic inflammatory response (SIRS) and severe SIRS (SIRS with organ dysfunction) occurring after cardiopulmonary bypass (CPB) are common causes of morbidity and mortality among cardiac surgical patients. These syndromes are often preceded by a profound vasodilation, characterized by vasoplegia occurring during surgery. Many substances have been implicated in their pathophysiology. Adenosine is a strong endogenous vasodilating agent released by endothelial cells and myocytes under metabolic stress and may be involved in blood pressure failure during CPB induced by severe SIRS. DESIGN: A prospective comparative observational study. SETTING: The operating room and intensive care unit of a tertiary care university hospital. PATIENTS: Adenosine plasma levels (mean+/-sd; APLs) were measured before (baseline), during, and immediately after surgery in 35 patients who underwent aortic valve replacement involving CPB. APLs were correlated to operative and postoperative clinical courses. MEASUREMENTS AND MAIN RESULTS: APLs were significantly higher in seven patients with vasoplegia and postoperative severe SIRS (1.6 micromol.L [0.2-2.6] vs. 0.4 micromol.L [0.1-1.0]) at baseline and during surgery. The duration of mechanical ventilation and stay in the intensive care unit were significantly longer for patients with higher APLs. Mean arterial pressure was inversely correlated with mean arterial APLs (Pearson's correlation coefficient: R=-0.66; p<.001). CONCLUSIONS: High APLs were found in patients with operative vasoplegia and postoperative severe SIRS occurring after cardiopulmonary bypass. This suggests that adenosine release is involved in vasoplegia that occurs during the systemic inflammatory response to cardiac surgery. Further studies are needed to clarify the association between cytokine production and adenosine release in severe SIRS following cardiac surgery.     

Amélioration de la perfusion des organes vitaux par la valve d’impédance inspiratoire et le concept de pompe respiratoire : rationnel physiologique et application clinique

Objective

In this article, we review the effects of the respiratory pump to improve vital organ perfusion by the use of an inspiratory threshold device.

Data sources

Medline and MeSH database.

Study selection

All papers with a level of proof of I to III have been used.

Data extraction

The analysis of the papers has focused on the physiological modifications induced by intrathoracic pressure regulation.

Data synthesis

Primary function of breathing is to provide gas exchange. Studies of the mechanisms involved in animals and humans provide the physiological underpinnings for “the other side of breathing”: to increase circulation to the heart and brain. We describe studies that focus on the fundamental relationship between the generation of negative intrathoracic pressure during inspiration through a low-level of resistance created by an impedance threshold device and the physiologic effects of a respiratory pump. A decrease in intrathoracic pressure during inspiration through a fixed resistance resulting in an intrathoracic pressure of −7 cmH₂O has multiple physiological benefits including: enhanced venous return, cardiac stroke volume and aortic blood pressure; lower intracranial pressure; resetting of the cardiac baroreflex; elevated cerebral blood flow oscillations and increased tissue blood flow/pressure gradient.

Conclusion

The clinical and animal studies support the use of the intrathoracic pump to treat different clinical conditions: hemorrhagic shock, orthostatic hypotension, septic shock, and cardiac arrest.     

Pharmacological characterization of a novel antiglaucoma agent,Bimatoprost (AGN 192024)

Replacement of the carboxylic acid group of prostaglandin (PG) F(2alpha) with a nonacidic moiety, such as hydroxyl, methoxy, or amido, results in compounds with unique pharmacology. Bimatoprost (AGN 192024) is also a pharmacologically novel PGF(2alpha) analog, where the carboxylic acid is replaced by a neutral ethylamide substituent. Bimatoprost potently contracted the feline lung parenchymal preparation (EC(50) value of 35-55 nM) but exhibited no meaningful activity in a variety of PG-sensitive tissue and cell preparations. Its activity seemed unrelated to FP receptor stimulation according to the following evidence. 1) Bimatoprost exhibited no meaningful activity in tissues and cells containing functional FP receptors. 2) Bimatoprost activity in the cat lung parenchyma is not species-specific because its potent activity in this preparation could not be reproduced in cells stably expressing the feline FP receptor. 3) Radioligand binding studies using feline and human recombinant FP receptors exhibited minimal competition versus [(3)H]17-phenyl PGF(2a) for Bimatoprost. 4) Bimatoprost pretreatment did not attenuate PGF(2alpha)-induced Ca(2+) signals in Swiss 3T3 cells. 5) Regional differences were apparent for Bimatoprost but not FP agonist effects in the cat lung. Bimatoprost reduced intraocular pressure in ocular normotensive and hypertensive monkeys over a 0.001 to 0.1% dose range. A single-dose and multiple-dose ocular distribution/metabolism studies using [(3)H]Bimatoprost (0.1%) were performed. Within the globe, bimatoprost concentrations were 10- to 100-fold higher in anterior segment tissues compared with the aqueous humor. Bimatoprost was overwhelmingly the predominant molecular species identified at all time points in ocular tissues, indicating that the intact molecule reduces intraocular pressure.     

Quality of life of adults with spinal cord injury: a study using the WHOQOL-bref

The objective of this study was to evaluate the quality of life (QOL) of adults with spinal cord injury and to identify the domains that may influence QOL. Data was collected using the WHOQOL-bref and a questionnaire with sociodemographic variables. Participants were 47 subjects, with a mean age of 42.95 years, 91.5% males and 8.5% females. The domains obtained the following scores: physical (58.59), psychological (63.82), social (68.79), and environmental (55.20). Through multiple linear regression, it was verified the correlation between domain scores and the perception of QOL: physical (p <0.187), psychological (p <0.399), social (p <0.000), and environmental (p <0.008). In conclusion, most participants (55.3%) are unsatisfied with their QOL, and the social and environmental domains showed a higher correlation with QOL.