It is unknown whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have a positive, neutral, or negative effect on clinical outcomes in patients with ...coronavirus disease 2019 (COVID-19).
To determine whether discontinuation compared with continuation of ACEIs or ARBs changed the number of days alive and out of the hospital through 30 days.
A randomized clinical trial of 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization (enrolled: April 9-June 26, 2020; final follow-up: July 26, 2020).
Discontinuation (n = 334) or continuation (n = 325) of ACEIs or ARBs.
The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression.
Among 659 patients, the median age was 55.1 years (interquartile range IQR, 46.1-65.0 years), 14.7% were aged 70 years or older, 40.4% were women, and 100% completed the trial. The median time from symptom onset to hospital admission was 6 days (IQR, 4-9 days) and 27.2% of patients had an oxygen saturation of less than 94% of room air at baseline. In terms of clinical severity, 57.1% of patients were considered mild at hospital admission and 42.9% were considered moderate. There was no significant difference in the number of days alive and out of the hospital in patients in the discontinuation group (mean, 21.9 days SD, 8 days) vs patients in the continuation group (mean, 22.9 days SD, 7.1 days) and the mean ratio was 0.95 (95% CI, 0.90-1.01). There also was no statistically significant difference in death (2.7% for the discontinuation group vs 2.8% for the continuation group; odds ratio OR, 0.97 95% CI, 0.38-2.52), cardiovascular death (0.6% vs 0.3%, respectively; OR, 1.95 95% CI, 0.19-42.12), or COVID-19 progression (38.3% vs 32.3%; OR, 1.30 95% CI, 0.95-1.80). The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs 7.7% in the continuation group), shock requiring vasopressors (8.4% vs 7.1%, respectively), acute myocardial infarction (7.5% vs 4.6%), new or worsening heart failure (4.2% vs 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs 2.8%).
Among patients hospitalized with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue vs continue these medications. These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment.
ClinicalTrials.gov Identifier: NCT04364893.
Timely localization of a bleeding source can improve the efficacy of trauma management, and improvements in the technology of computed tomography (CT) have expedited the work-up of the traumatized ...patient. The classic pattern of active extravasation (ie, administered contrast agent that has escaped from injured arteries, veins, or urinary tract) at dual phase CT is a jet or focal area of hyperattenuation within a hematoma that fades into an enlarged, enhanced hematoma on delayed images. This finding indicates significant bleeding and must be quickly communicated to the clinician, since potentially lifesaving surgical or endovascular repair may be necessary. Active extravasation can be associated with other injuries to arteries, such as a hematoma or a pseudoaneurysm. Both active extravasation and pseudoaneurysm (unlike bone fragments and dense foreign bodies) change in appearance on delayed images, compared with their characteristics on arterial images. Other clues to the location of vessel injury include lack of vascular enhancement (caused by occlusion or spasm), vessel irregularity, size change (such as occurs with pseudoaneurysm), and an intimal flap (which signifies dissection). The sentinel clot sign is an important clue for locating the bleeding source when other more localizing findings of vessel injury are not present. Timely diagnosis, differentiation of vascular injuries from other findings of trauma, signs of depleted intravascular volume, and localization of vascular injury are important to convey to interventional radiologists or surgeons to improve trauma management.
Background The school journey is often studied in relation to health outcomes in children and adolescents. Self-report is the most common measurement tool. Purpose To investigate the error on ...self-reported journey duration in adolescents, using a wearable digital camera (Microsoft SenseCam). Methods During March–May 2011, participants ( n =17; aged 13–15 years) from four schools wore wearable cameras to and from school for 1 week. The device automatically records time-stamped, first-person point-of-view images, without any action from the wearer. Participants also completed a researcher-administered self-report travel survey over the same period. Analysis took place in November 2011. Within- and between-subjects correlation coefficients and Bland-Altman 95% limits of agreement were derived, accounting for the multiple observations per individual. Results Self-report data were collected for 150 journey stages and SenseCam data for 135 (90%) of these. The within-subjects correlation coefficient for journey duration was 0.89 (95% CI=0.84, 0.93). The between-subjects correlation coefficient was 0.92 (95% CI=0.79, 0.97). The mean difference (bias) between methods at the whole sample level was small (10 seconds per journey, 95% CI= −33, 53). The wide limits of agreement (±501 seconds, 95% CI= −491, 511) reveal large random error. Conclusions Compared to direct observation from images, self-reported journey duration is accurate at the mean group level but imprecise at the level of the individual participant.
To evaluate the effect on donor rim cultures and postoperative infections of doubling the povidone-iodine exposure time during corneal tissue recovery before its use in keratoplasty.
Consecutive ...donor cornea recoveries were evaluated for positive donor corneal rim cultures and postoperative infections before and after a protocol change of doubling the exposure time of povidone-iodine during donor preparation.
In 631 consecutive cornea donor recoveries, 18 (2.9%) had positive fungal rim cultures and 41 (6.5%) had positive bacterial rim cultures. Three (0.48%) developed postoperative fungal infections, and no bacterial infections occurred. After doubling the povidone-iodine exposure time during the recovery process, 725 consecutive corneas were reviewed. Four (0.6%) had positive fungal rim cultures, and 29 (4.0%) had positive bacterial rim cultures. No postoperative fungal or bacterial infections occurred. No noticeable increase in epithelial toxicity developed between the 2 groups.
Increasing the povidone-iodine exposure time during the donor cornea recovery process decreased the rate of positive donor corneal rim fungal cultures (P = 0.001), positive donor corneal rim bacterial cultures (P = 0.04), and postoperative fungal infections (P = 0.06).
We examined diatom assemblages from 18 stream and pond samples in the Franz Josef Land Archipelago (FJL), the most northern land of Eurasia. More than 216 taxa were observed, revealing a rich ...circumpolar diatom flora, including many undescribed taxa. Widely distributed taxa were the most abundant by cell densities, while circumpolar taxa were the most species rich. Stream and pond habitats hosted different assemblages, and varied along a pH gradient. Diatoma tenuis was the most abundant and ubiquitous taxon. However, several circumpolar taxa such as Chamaepinnularia gandrupii, Cymbella botellus, Psammothidium sp. and Humidophila laevissima were also found in relatively high abundances. Aerophilic taxa were an important component of FJL diatom assemblages (Humidophila spp., Caloneis spp. and Pinnularia spp.), reflecting the large and extreme seasonal changes in Arctic conditions. We predict a decrease in the abundance of circumpolar taxa, an increase in local (α-) freshwater diatom diversity, but a decrease in regional diversity (circumpolar homogenization) as a result of current warming trends and to a lesser extent the increasing human footprint in the region.
The G12/13 class of heterotrimeric G proteins, comprising the α-subunits Gα12 and Gα13, regulates multiple aspects of cellular behavior, including proliferation and cytoskeletal rearrangements. ...Although guanine nucleotide exchange factors for the monomeric G protein Rho (RhoGEFs) are well characterized as effectors of this G protein class, a variety of other downstream targets has been reported. To identify Gα12 determinants that mediate specific protein interactions, we used a structural and evolutionary comparison between the G12/13, Gs, Gi, and Gq classes to identify "class-distinctive" residues in Gα12 and Gα13. Mutation of these residues in Gα12 to their deduced ancestral forms revealed a subset necessary for activation of serum response element (SRE)-mediated transcription, a G12/13-stimulated pathway implicated in cell proliferative signaling. Unexpectedly, this subset of Gα12 mutants showed impaired binding to heat-shock protein 90 (Hsp90) while retaining binding to RhoGEFs. Corresponding mutants of Gα13 exhibited robust SRE activation, suggesting a Gα12-specific mechanism, and inhibition of Hsp90 by geldanamycin or small interfering RNA-mediated lowering of Hsp90 levels resulted in greater downregulation of Gα12 than Gα13 signaling in SRE activation experiments. Furthermore, the Drosophila G12/13 homolog Concertina was unable to signal to SRE in mammalian cells, and Gα12:Concertina chimeras revealed Gα12-specific determinants of SRE activation within the switch regions and a C-terminal region. These findings identify Gα12 determinants of SRE activation, implicate Gα12:Hsp90 interaction in this signaling mechanism, and illuminate structural features that arose during evolution of Gα12 and Gα13 to allow bifurcated mechanisms of signaling to a common cell proliferative pathway.
To develop a system prognostic of outcome in those undergoing allogeneic hematopoietic cell transplantation (allo HCT) for myelodysplastic syndrome (MDS).
We examined 2,133 patients with MDS ...undergoing HLA-matched (n = 1,728) or -mismatched (n = 405) allo HCT from 2000 to 2012. We used a Cox multivariable model to identify factors prognostic of mortality in a training subset (n = 1,151) of the HLA-matched cohort. A weighted score using these factors was assigned to the remaining patients undergoing HLA-matched allo HCT (validation cohort; n = 577) as well as to patients undergoing HLA-mismatched allo HCT.
Blood blasts greater than 3% (hazard ratio HR, 1.41; 95% CI, 1.08 to 1.85), platelets 50 × 10(9)/L or less at transplantation (HR, 1.37; 95% CI, 1.18 to 1.61), Karnofsky performance status less than 90% (HR, 1.25; 95% CI, 1.06 to 1.28), comprehensive cytogenetic risk score of poor or very poor (HR, 1.43; 95% CI, 1.14 to 1.80), and age 30 to 49 years (HR, 1.60; 95% CI, 1.09 to 2.35) were associated with increased hazard of death and assigned 1 point in the scoring system. Monosomal karyotype (HR, 2.01; 95% CI, 1.65 to 2.45) and age 50 years or older (HR, 1.93; 95% CI, 1.36 to 2.83) were assigned 2 points. The 3-year overall survival after transplantation in patients with low (0 to 1 points), intermediate (2 to 3), high (4 to 5) and very high (≥ 6) scores was 71% (95% CI, 58% to 85%), 49% (95% CI, 42% to 56%), 41% (95% CI, 31% to 51%), and 25% (95% CI, 4% to 46%), respectively (P < .001). Increasing score was predictive of increased relapse (P < .001) and treatment-related mortality (P < .001) in the HLA-matched set and relapse (P < .001) in the HLA-mismatched cohort.
The proposed system is prognostic of outcome in patients undergoing HLA-matched and -mismatched allo HCT for MDS.
The Peutz-Jeghers syndrome is an autosomal dominant hereditary disease characterized by hamartomatous polyps of the gastrointestinal tract and by mucocutaneous melanin deposits. The frequency of ...cancer in this syndrome has not been studied extensively. Therefore, we investigated 31 patients with the Peutz-Jeghers syndrome who were followed from 1973 to 1985. All cases of cancer were verified by histopathological review. Cancer developed in 15 of the 31 patients (48 percent)--gastrointestinal carcinomas in 4, nongastrointestinal carcinomas in 10, and multiple myeloma in 1. In addition, adenomatous polyps of the stomach and colon occurred in three other patients. The cancers were diagnosed when the patients were relatively young, but after the Peutz-Jeghers syndrome had been diagnosed (interval between diagnoses, 25 +/- 20 years; range, 1 to 64). According to relative-risk analysis, the observed development of cancer in the patients with the syndrome was 18 times greater than expected in the general population (P less than 0.0001). Our results suggest that patients with the Peutz-Jeghers syndrome have an increased risk for the development of cancer at gastrointestinal and nongastrointestinal sites.
The aims of the echocardiographic substudy of this multicenter trial were to evaluate the use of quantitative assessment of mitral regurgitation (MR) severity using serial echocardiography and to ...assess the efficacy of percutaneous mitral valve repair. Previous surgical repair studies did not use quantitative echocardiographic methods. Results of a percutaneous mitral valve repair clip device in a core echocardiographic laboratory were evaluated. Published parameters for quantifying MR were used in a systematic protocol to qualify patients for study entry and evaluate treatment efficacy at discharge and 6 months after clip repair. Baseline results were presented for 55 patients, and follow-up results, for 49. Ninety-eight percent of required echocardiographic studies were submitted to the core laboratory, and >85% of required measurements were possible. At baseline, mean regurgitant volume was 54.8 ± 24 ml, regurgitant fraction was 46.9 ±16.2%, effective regurgitant orifice area was 0.71 ± 0.40 cm2 , and vena contracta width was 0.66 ± 0.20 cm. Based on a severity scale of 1 to 4, mean color flow grade was 3.4 ± 0.7, and mean pulmonary vein flow was 2.8 ± 1.2. In patients with a clip at 6 months, all measurements of MR severity were significantly decreased versus baseline, with mean regurgitant volume decreased from 50.3 to 27.5 ml (change −22.8 ml; p <0.0001), regurgitant fraction from 44.6% to 28.9% (change −15.7%; p <0.0001), color flow grade from an average of 3.4 to 1.8 (change −1.6; p <0.0001), and pulmonary vein flow from 2.8 to 1.8 (change −1.0; p <0.0018). In conclusion, quantitative assessment of MR is feasible in a multicenter trial, and percutaneous mitral repair with the MitraClip produces a sustained decrease in MR severity to moderate or less for ≥6 months.
Percutaneous mitral repair is rapidly developing as an alternative to cardiac surgery in select patients. The Evalve percutaneous E2E system uses the MitraClip to replicate the surgical suture-based ...approach. This procedure requires real-time echocardiographic guidance in a unique and significant collaboration between echocardiographer and interventionalist. transesophageal echocardiography (TEE) is used as the primary imaging modality to guide this procedure and is essential to its success.
In EVEREST I, the US multicenter phase I safety and feasibility trial, 47 patients with 3 or 4+ mitral regurgitation (MR) were enrolled. The trial involved a standardized echocardiographic imaging protocol with a standardized anatomic-based vocabulary, predetermined standard TEE views, preprocedural strategy meetings, and display of echocardiographic aids to optimize communication and procedural efficiency during placement of the clip.
TEE guidance facilitated the creation of a double-orifice mitral valve in all 47 patients enrolled (100%), and 40 patients were discharged with 1 or more clips (85%). At discharge, successful placement of a clip and <or= 2+ MR was present in 34 patients (74%). The standardized approach contributed to a reduction in the time to perform the procedure over the course of the trial at both initial and new sites.
TEE is essential to the guidance of percutaneous MitraClip E2E repair. A streamlined approach to echocardiographic guidance, using predetermined standardized views, a common anatomic-based vocabulary, preprocedural strategy meetings, and a display of echocardiographic aids in the catheterization laboratory shortens the procedure time and allows for efficient percutaneous repair.
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