Epidermolysis Bullosa in Spain: A Qualitative Analysis of Its Social Impact on Families With Diagnosed Minors.

BACKGROUND: Epidermolysis bullosa (EB) comprises a group of rare types of genodermatoses characterized by extreme mucocutaneous fragility, leading to blistering and/or erosions, even with minimal trauma. Continuous care through wound management is an integral part of daily life for the families and individuals affected. The aim of this study was to assess the social reality and impacts on families of having minor members diagnosed with EB in Spain. METHODS: A qualitative methodology was employed, utilizing four focus groups entailing participation by 24 parents (19 mothers and five fathers) of minors diagnosed with EB in Spain. RESULTS: Negative impacts on the family nucleus were evident in four priority areas of analysis: sociorelational, economic-labour, physical and psychoemotional, with significant differences observed based on the severity of the symptoms. CONCLUSION: Impacts on the family nucleus are noticeable from birth, influencing all other daily life routines and complicating family planning and organization. There is an imperative need to enhance the availability of sociohealth resources and to adopt an interdisciplinary approach to address their biopsychosocial needs. PATIENT OR PUBLIC CONTRIBUTION: The active participation of relatives of minors diagnosed with Epidermolysis Bullosa (EB) is invaluable to sociohealth professionals, legislators and researchers. A team member conducts their professional activities at DEBRA España (national patient association dedicated to enhancing the quality of life for individuals with EB and their families), actively engaging in all study phases.

Outpatient treatment with concomitant vaccine-boosted convalescent plasma for patients with immunosuppression and COVID-19.

Although severe coronavirus disease 2019 (COVID-19) and hospitalization associated with COVID-19 are generally preventable among healthy vaccine recipients, patients with immunosuppression have poor immunogenic responses to COVID-19 vaccines and remain at high risk of infection with SARS-CoV-2 and hospitalization. In addition, monoclonal antibody therapy is limited by the emergence of novel SARS-CoV-2 variants that have serially escaped neutralization. In this context, there is interest in understanding the clinical benefit associated with COVID-19 convalescent plasma collected from persons who have been both naturally infected with SARS-CoV-2 and vaccinated against SARS-CoV-2 ("vax-plasma"). Thus, we report the clinical outcome of 386 immunocompromised outpatients who were diagnosed with COVID-19 and who received contemporary COVID-19-specific therapeutics (standard-of-care group) and a subgroup who also received concomitant treatment with very high titer COVID-19 convalescent plasma (vax-plasma group) with a specific focus on hospitalization rates. The overall hospitalization rate was 2.2% (5 of 225 patients) in the vax-plasma group and 6.2% (10 of 161 patients) in the standard-of-care group, which corresponded to a relative risk reduction of 65% (P = 0.046). Evidence of efficacy in nonvaccinated patients cannot be inferred from these data because 94% (361 of 386 patients) of patients were vaccinated. In vaccinated patients with immunosuppression and COVID-19, the addition of vax-plasma or very high titer COVID-19 convalescent plasma to COVID-19-specific therapies reduced the risk of disease progression leading to hospitalization.IMPORTANCEAs SARS-CoV-2 evolves, new variants of concern (VOCs) have emerged that evade available anti-spike monoclonal antibodies, particularly among immunosuppressed patients. However, high-titer COVID-19 convalescent plasma continues to be effective against VOCs because of its broad-spectrum immunomodulatory properties. Thus, we report clinical outcomes of 386 immunocompromised outpatients who were treated with COVID-19-specific therapeutics and a subgroup also treated with vaccine-boosted convalescent plasma. We found that the administration of vaccine-boosted convalescent plasma was associated with a significantly decreased incidence of hospitalization among immunocompromised COVID-19 outpatients. Our data add to the contemporary data providing evidence to support the clinical utility of high-titer convalescent plasma as antibody replacement therapy in immunocompromised patients.

Outcomes of Vasopressin-Receptor Agonists Versus Norepinephrine in Adults With Perioperative Hypotension: A Systematic Review.

Consensus statements recommend the use of norepinephrine and/or vasopressin for hypotension in cardiac surgery. However, there is a paucity of data among other surgical subgroups and vasopressin analogs. Therefore, the authors conducted a systematic review of randomized controlled trials (RCTs) to compare vasopressin-receptor agonists with norepinephrine for hypotension among those undergoing surgery with general anesthesia. This review was registered prospectively (CRD42022316328). Literature searches were conducted by a medical librarian to November 28, 2023, across MEDLINE, EMBASE, CENTRAL, and Web of Science. The authors included RCTs enrolling adults (≥18 years of age) undergoing any surgery under general anesthesia who developed perioperative hypotension and comparing vasopressin receptor agonists with norepinephrine. The risk of bias was assessed by the Cochrane risk of bias tool for randomized trials (RoB-2). Thirteen (N = 719) RCTs were included, of which 8 (n = 585) enrolled patients undergoing cardiac surgery. Five trials compared norepinephrine with vasopressin, 4 trials with terlipressin, 1 trial with ornipressin, and the other 3 trials used vasopressin as adjuvant therapy. There was no significant difference in all-cause mortality. Among patients with vasoplegic shock after cardiac surgery, vasopressin was associated with significantly lower intensive care unit (N = 385; 2 trials; mean 100.8 v 175.2 hours, p < 0.005; median 120 [IQR 96-168] v 144 [96-216] hours, p = 0.007) and hospital lengths of stay, as well as fewer cases of acute kidney injury and atrial fibrillation compared with norepinephrine. One trial also found that terlipressin was associated with a significantly lower incidence of acute kidney injury versus norepinephrine overall. Vasopressin and norepinephrine restored mean arterial blood pressure with no significant differences; however, the use of vasopressin with norepinephrine was associated with significantly higher mean arterial blood pressure versus norepinephrine alone. Further high-quality trials are needed to determine pooled treatment effects, especially among noncardiac surgical patients and those treated with vasopressin analogs.

Obesity and Extracorporeal Membrane Oxygenation (ECMO): Analysis of Outcomes.

Traditionally, patients with obesity have been deemed ineligible for extracorporeal life support (ELS) therapies such as extracorporeal membrane oxygenation (ECMO), given the association of obesity with chronic health conditions that contribute to increased morbidity and mortality. Nevertheless, a growing body of literature suggests the feasibility, efficacy, and safety of ECMO in the obese population. This review provides an in-depth analysis of the current literature assessing the effects of obesity on outcomes among patients supported with ECMO (venovenous [VV] ECMO in noncoronavirus disease 2019 and coronavirus disease 2019 acute respiratory distress syndrome, venoarterial [VA] ECMO, and combined VV and VA ECMO), offer a possible explanation of the current findings on the basis of the obesity paradox phenomenon, provides a framework for future studies addressing the use of ELS therapies in the obese patient population, and provides guidance from the literature for many of the challenges related to initiating, maintaining, and weaning ELS therapy in patients with obesity.

Should Obesity Be an Exclusion Criterion for Extracorporeal Membrane Oxygenation Support? A Scoping Review.

Obesity is often considered a contraindication to extracorporeal membrane oxygenation (ECMO) candidacy due to technical challenges with vascular access, higher cardiac output requirements, and known associations between obesity and overall increased morbidity and mortality due to chronic health conditions. However, a growing body of literature suggests that ECMO may be as safe and efficacious in both obese and nonobese patients. This scoping review provides a synthesis of the available literature on the outcomes of obese patients supported with (1) venovenous (VV)-ECMO in acute respiratory distress syndrome (ARDS) not due to coronavirus disease 2019 (COVID-19), (2) VV-ECMO in ARDS due to COVID-19, (3) venoarterial (VA)-ECMO for all indications, and (4) studies combining data of patients supported with VA- and VV-ECMO. A librarian-assisted search was performed using 4 primary electronic medical databases (PubMed, Web of Science, Excerpta Medica database [Embase], and Cochrane Library) from January 2003 to March 2023. Articles that reported outcomes of obese patients requiring ECMO support were included. Two reviewers independently screened titles, abstracts, and full text of articles to determine eligibility. Data extraction was performed using customized fields established a priori within a systematic review software system. A total of 354 publications were imported for screening on titles and abstracts, and 30 studies were selected for full-text review. A total of 26 publications met the inclusion criteria: 7 on VV-ECMO support in non-COVID-19 ARDS patients, 6 on ECMO in COVID-19 ARDS patients, 8 in patients supported with VA-ECMO, and 5 combining both VA- and VV-ECMO data. Although the included studies are limited to retrospective analyses and display a heterogeneity in definitions of obesity and comparison groups, the currently available literature suggests that outcomes and complications of ECMO therapy are equivalent in obese patients as compared to nonobese patients. Hence, obesity as measured by body mass index alone should not be considered an exclusion criterion in the decision to initiate ECMO.

Rates Among Hospitalized Patients With COVID-19 Treated With Convalescent Plasma: A Systematic Review and Meta-Analysis.

Objective: To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19. Patients and Methods: On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to October 26, 2022. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of 5 reviewers. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using an inverse-variance random effects model. The prespecified end point was all-cause mortality during hospitalization. Results: Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses reported that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio [OR], 0.87; 95% CI, 0.76-1.00) and matched cohort studies (OR, 0.76; 95% CI, 0.66-0.88). The meta-analysis of subgroups revealed 2 important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared with convalescent plasma containing low antibody levels (OR, 0.85; 95% CI, 0.73 to 0.99). Second, earlier treatment with COVID-19 convalescent plasma was associated with a decrease in mortality compared with the later treatment cohort (OR, 0.63; 95% CI, 0.48 to 0.82). Conclusion: During COVID-19 convalescent plasma use was associated with a 13% reduced risk of mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course.

Coagulation Tests and Bleeding Classification After Cardiopulmonary Bypass: A Prospective Study.

OBJECTIVE: No recent prospective studies have analyzed the accuracy of standard coagulation tests and thromboelastography (TEG) to identify patients with excessive microvascular bleeding following cardiopulmonary bypass (CPB). The aim of this study was to assess the value of coagulation profile tests, as well as TEG, for the classification of microvascular bleeding after CPB. DESIGN: A prospective observational study. SETTING: At a single-center academic hospital. PARTICIPANTS: Patients ≥18 years of age undergoing elective cardiac surgery. INTERVENTIONS: Qualitative assessment of microvascular bleeding post-CPB (surgeon and anesthesiologist consensus) and the association with coagulation profile tests and TEG values. MEASUREMENTS AND MAIN RESULTS: A total of 816 patients were included in the study-358 (44%) bleeders and 458 (56%) nonbleeders. Accuracy, sensitivity, and specificity for the coagulation profile tests and TEG values ranged from 45% to 72%. The predictive utility was similar across tests, with prothrombin time (PT) (62% accuracy, 51% sensitivity, 70% specificity), international normalized ratio (INR) (62% accuracy, 48% sensitivity, 72% specificity), and platelet count (62% accuracy, 62% sensitivity, 61% specificity) displaying the highest performance. Secondary outcomes were worse in bleeders versus nonbleeders, including higher chest tube drainage, total blood loss, transfusion of red blood cells, reoperation rates (p < 0.001, respectively), readmission within 30 days (p = 0.007), and hospital mortality (p = 0.021). CONCLUSIONS: Standard coagulation tests and individual components of TEG in isolation agree poorly with the visual classification of microvascular bleeding after CPB. The PT-INR and platelet count performed best but had low accuracy. Further work is warranted to identify better testing strategies to guide perioperative transfusion decisions in cardiac surgical patients.

Universal Time-Dependent Control Scheme for Realizing Arbitrary Linear Bosonic Transformations.

We study the implementation of arbitrary excitation-conserving linear transformations between two sets of N stationary bosonic modes, which are connected through a photonic quantum channel. By controlling the individual couplings between the modes and the channel, an initial N-partite quantum state in register A can be released as a multiphoton wave packet and, successively, be reabsorbed in register B. Here we prove that there exists a set of control pulses that implement this transfer with arbitrarily high fidelity and, simultaneously, realize a prespecified N×N unitary transformation between the two sets of modes. Moreover, we provide a numerical algorithm for constructing these control pulses and discuss the scaling and robustness of this protocol in terms of several illustrative examples. By being purely control-based and not relying on any adaptations of the underlying hardware, the presented scheme is extremely flexible and can find widespread applications, for example, for boson-sampling experiments, multiqubit state transfer protocols, or in continuous-variable quantum computing architectures.

Quantum Approximate Optimization Algorithm Pseudo-Boltzmann States.

In this Letter, we provide analytical and numerical evidence that the single-layer quantum approximate optimization algorithm on universal Ising spin models produces thermal-like states. We find that these pseudo-Boltzmann states can not be efficiently simulated on classical computers according to the general state-of-the-art condition that ensures rapid mixing for Ising models. Moreover, we observe that the temperature depends on a hidden universal correlation between the energy of a state and the covariance of other energy levels and the Hamming distances of the state to those energies.

Environmental implications of reprocessing agricultural waste into animal food: An experience with rice straw and citrus pruning waste.

The aim of this study is to conduct an environmental comparison, by applying the life cycle assessment (LCA) methodology, of two different compositions for animal foods each with two different nutritional contents ('high' for the lactation period, and 'low' for the rest of the year). Thus, for each nutritional content, the environmental performance of producing animal feed with a traditional composition mainly based on cereals is compared with a composition based on a mixture of biomass obtained from rice straw and citrus pruning waste. It was observed that the reprocessing of rice straw and citrus pruning waste into animal feed offered environmental potential compared to the current alternative of being burned in the fields. The environmental impact category global warming is especially improved, with impact reductions of up to 50% and 95%, respectively, for high and low nutritional content compositions. In addition, the alternatives proposed herein make it possible to avoid all the inconvenience and impacts on the health of the population living near the fields.

Contemporary Perioperative Management of Direct Oral Anticoagulants.

Direct oral anticoagulants (DOACs) have rapidly emerged as popular alternatives to warfarin in the setting of nonvalvular atrial fibrillation, prevention and treatment of venous thromboembolism, and secondary prevention of arterial thrombosis. It is now estimated that more patients in the United States take DOACs than warfarin for approved indications. Studies to date have shown that these drugs are similarly efficacious with perhaps a lower bleeding risk than warfarin. The purpose of this review is to provide insight into the currently available DOACs and discuss the management and reversal strategies for patients in the perioperative period.

Greater central airway luminal area in people with COVID-19: a case-control series.

Respiratory epithelium in the conducting airways of the human body is one of the primary targets of SARS-CoV-2 infection, however, there is a paucity of studies describing the association between COVID-19 and physical characteristics of the conducting airways. To better understand the pathophysiology of COVID-19 on the size of larger conducting airways, we determined the luminal area of the central airways in patients with a history of COVID-19 compared to a height-matched cohort of controls using a case-control study design. Using three-dimensional reconstruction from low-dose high-resolution computed tomography, we retrospectively assessed airway luminal cross-sectional area in 114 patients with COVID-19 (66 females, 48 males) and 114 healthy, sex- and height-matched controls (66 females, 48 males). People with a history of smoking, cardiopulmonary disease, or a body mass index greater than 40 kg·m-2 were excluded. Luminal areas of seven conducting airways were analyzed, including trachea, left and right main bronchus, intermediate bronchus, left and right upper lobe, and left lower lobe. For the central conducting airways, luminal area was ~ 15% greater patients with COVID-19 compared to matched controls (p < 0.05). Among patients with COVID-19, there were generally no differences in the luminal areas of the conducting airways between hospitalized patients compared to patients who did not require COVID-19-related hospitalization. Our findings suggest that males and females with COVID-19 have pathologically larger conducting airway luminal areas than healthy, sex- and height-matched controls.

McConnell's Sign Is Not Always Pulmonary Embolism: The Importance of Right Ventricular Ischemia.

McConnell's sign is a well-established, specific echocardiographic sign for acute pulmonary embolism. Multiple theories have been proposed regarding the mechanism of McConnell's sign in the context of acute pulmonary embolism. Here, we present 2 patient cases in which McConnell's sign was seen with right ventricular ischemia without pulmonary embolism. (Level of Difficulty: Beginner.).

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360.

Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors.

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.

Diversification of the CRISPR Toolbox: Applications of CRISPR-Cas Systems Beyond Genome Editing.

The discovery of CRISPR has revolutionized the field of genome engineering, but the potential of this technology is far from reaching its limits. In this review, we explore the broad range of applications of CRISPR technology to highlight the rapid expansion of the field beyond gene editing alone. It has been demonstrated that CRISPR technology can control gene expression, spatiotemporally image the genome in vivo, and detect specific nucleic acid sequences for diagnostics. In addition, new technologies are under development to improve CRISPR quality controls for gene editing, thereby improving the reliability of these technologies for therapeutics and beyond. These are just some of the many CRISPR tools that have been developed in recent years, and the toolbox continues to diversify.

Getting the First Thousand-Optimizing Instagram Residency Content to Increase Followers During the COVID-19 Pandemic.

BACKGROUND: Social media remains a growing platform for physicians to facilitate learning, network, and disseminate information. The Coronavirus Disease 2019 (COVID-19) pandemic has challenged traditional medical student recruitment and outreach. Instagram is a platform that can be used by residency programs to increase engagement and as a potential recruitment tool. The authors present social media failed and successful strategies used to increase engagement and gain new followers. METHODS: In June 2020, an initiative began to use Instagram on a more frequent and intentional basis. Three different strategies were implemented during the pandemic: mirroring Twitter posts, increasing multimedia, and leveraging Instagram Stories. The outcomes of interest included number of followers and engagement on posts. Data were collected October 2020. RESULTS: After June 1, 2020, the @mayoanesthesia account gained 1000 followers through 127 days, an average of 4.26 new followers each day. Before June 1, there were 24 total posts over 3.3 years with a total of 458 followers. Three different strategies were implemented at different times during the pandemic. During the mirroring Twitter posts period, the mean number of interactions per post was 14.5. During the second phase after separating the Twitter and Instagram strategy, the mean number of interactions per post increased to 57.8. CONCLUSION: Residency programs can creatively, yet methodically, use Instagram posts to increase social media engagement during resident recruitment season during the COVID-19 pandemic and likely beyond.

Evaluation of the primary stability in dental implants placed in low density bone with a new drilling technique, Osseodensification: an in vitro study / Evaluación de la estabilidad primaria en implantes dentales colocados en baja densidad hueso con una nueva técnica de perforación, Osteodensificación: un estudio in vitro

Background: Primary stability is an important key determinant of implant osseointegration. We investigated ap-proaches to improve primary implant stability using a new drilling technique termed osseodensification (OD),which was compared with the conventional under-drilling (UD) method utilized for low-density bones.Material and Methods: We placed 55 conical internal connection implants in each group, in 30 low-density sec-tions of pig tibia. The implants were placed using twist drill bits in both groups; groups Under Drilling (UD)and Osseodensification (OD) included bone sections subjected to conventional UD and OD drilling, respectively.Before placing the implants, we randomized the bone sections that were to receive these implants to avoid samplebias. We evaluated various primary stability parameters, such as implant insertion torque and resonance fre-quency analysis (RFA) measurements.Results: The results showed that compared with implants placed using the UD technique, those placed using theOD technique were associated with significantly higher primary stability. The mean insertion torque of the im-plants was 8.87±6.17 Ncm in group 1 (UD) and 21.72±17.14 Ncm in group 2 (OD). The mean RFA was 65.16±7.45ISQ in group 1 (UD) and 69.75±6.79 ISQ in group 2 (OD).Conclusions: The implant insertion torque and RFA values were significantly higher in OD group than in UD.Therefore, compared with UD, OD improves primary stability in low-density bones (based on torque and RFAmeasurements).(AU)