J. Clin. Med., Volume 11, Issue 13 (July-1 2022) – 360 articles

(1) Background: The aim of this study was to assess the effects of the COVID-19 pandemic on the use and outcomes of cardiac procedures among people with chronic obstructive pulmonary disease (COPD) in Spain. (2) Methods: We used national hospital discharge data to select patients admitted to hospital with a diagnosis of COPD from 1 January 2019 to 31 December 2020. (3) Results: The number of COPD patients hospitalized in 2019 who underwent a cardiac procedure was 4483, 16.2% higher than in 2020 (n = 3757). The length of hospital stay was significantly lower in 2020 than in 2019 (9.37 vs. 10.13 days; p = 0.004), and crude in-hospital mortality (IHM) was significantly higher (5.32% vs. 4.33%; p = 0.035). Multivariable logistic regression models to assess the differences in IHM from 2019 to 2020 showed Odds Ratio (OR) values over 1, suggesting a higher risk of dying in 2020 compared to in 2019. However, the ORs were only statistically significant for “any cardiac procedure” (1.18, 95% CI 1.03–1.47). The Charlson comorbidity index increased IHM for each of the procedures analyzed. The probability of IHM was higher for women and older patients who underwent coronary artery bypass graft or open valve replacement procedures. Suffering a COVID-19 infection was associated with significantly higher mortality after cardiac procedures. (4) Conclusions: The COVID-19 pandemic limited the access to healthcare for patients with COPD. Full article

Interest in palliative care has increased in recent times, particularly in its multidisciplinary approach developed to meet the needs of patients with a life-threatening disease and their families. Although the modern concept of palliative simultaneous care postulates the adoption of these qualitative treatments early on during the life-threatening disease (and potentially just after the diagnosis), palliative care is still reserved for patients at the end of their life in most of the clinical realities, and thus is consequently mistaken for hospice care. Patients with acute or chronic kidney disease (CKD) usually experience poor quality of life and decreased survival expectancy and thus may benefit from palliative care. Palliative care requires close collaboration among multiple health care providers, patients, and their families to share the diagnosis, prognosis, realistic treatment goals, and treatment decisions. Several approaches, such as conservative management, extracorporeal, and peritoneal palliative dialysis, can be attempted to globally meet the needs of patients with kidney disease (e.g., physical, social, psychological, or spiritual needs). Particularly for frail patients, pharmacologic management or peritoneal dialysis may be more appropriate than extracorporeal treatment. Extracorporeal dialysis treatment may be disproportionate in these patients and associated with a high burden of symptoms correlated with this invasive procedure. For those patients undergoing extracorporeal dialysis, individualized goal setting and a broader concept of adequacy should be considered as the foundations of extracorporeal palliative dialysis. Interestingly, little evidence is available on palliative and end of life care for acute kidney injury (AKI) patients. In this review, the main variables influencing medical decision-making about palliative care in patients with kidney disease are described, as well as the different approaches that can fulfill the needs of patients with CKD and AKI. Full article

(1) Background: Absent contractility (AC) is an esophageal motility disorder defined as a normal integrated relaxation pressure with 100% failed peristalsis. We sought to clarify the natural history of this disorder and its relationship with rheumatologic diseases, such as systemic sclerosis (scleroderma). (2) Methods: We retrospectively identified patients with AC based on high-resolution manometry findings at three referral institutions and then matched them with controls with esophageal complaints who had normal manometries. (3) Results: Seventy-four patients with AC were included (mean age 56 years; 69% female). Sixteen patients (21.6%) had a rheumatologic disease. Compared to controls, patients with AC were significantly more likely to present with heartburn, dysphagia, vomiting, and weight loss. During follow-up, they were also more likely to be seen by a gastroenterologist, be diagnosed with gastroesophageal reflux disease, take a proton pump inhibitor, and undergo repeat upper endoscopies. No AC patients developed a new rheumatologic disease during follow-up. No significant differences were noted in the clinical presentation or course of AC patients with rheumatologic disease compared to those without. (4) Conclusions: Patients with AC have more esophageal symptoms and require more intense gastrointestinal follow-up than controls. Only a minority of patients with AC have underlying rheumatologic disease. Those without rheumatologic disease at baseline did not subsequently develop one, suggesting that a rheumatologic evaluation is likely unnecessary. The clinical course of AC in patients with rheumatologic disease and those without appears to be similar. Full article

(1) Background: Intensive care unit (ICU) survivors from severe COVID-19 acute respiratory distress syndrome (CARDS) with chronic critical illness (CCI) may be considered vast resource consumers with a poor prognosis. We hypothesized that a holistic approach combining an early intensive rehabilitation with a protocol of difficult weaning would improve patient outcomes (2) Methods: A single-center retrospective study in a five-bed post-ICU weaning and intensive rehabilitation center with a dedicated fitness room specifically equipped to safely deliver physical activity sessions in frail patients with CCI. (3) Results: Among 502 CARDS patients admitted to the ICU from March 2020 to March 2022, 50 consecutive tracheostomized patients were included in the program. After a median of 39 ICU days, 25 days of rehabilitation were needed to restore patients’ autonomy (ADL, from 0 to 6; p < 0.001), to significantly improve their aerobic capacity (6-min walking test distance, from 0 to 253 m; p < 0.001) and to reduce patients’ vulnerability (frailty score, from 7 to 3; p < 0.001) and hospital anxiety and depression scale (HADS, from 18 to 10; p < 0.001). Forty-eight decannulated patients (96%) were discharged home. (4) Conclusions: A protocolized weaning strategy combined with early intensive rehabilitation in a dedicated specialized center boosted the physical and mental recovery. Full article

A recall for histological pseudocapsule (PS) and reappraisal of transsphenoidal surgery (TSS) as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas are getting vibrant. We hope to investigate the effectiveness and risks of extra-pseudocapsular transsphenoidal surgery (EPTSS) for young women with microprolactinoma, and to look into the factors that influenced remission and recurrence, and thus to figure out the possible indication shift for primary TSS. We proposed a new classification method of microprolactinoma based on the relationship between tumor and pituitary position, which can be divided into hypo-pituitary, para-pituitary and supra-pituitary groups. We retrospectively analyzed 133 patients of women (<50 yr) with microprolactinoma (≤10 mm) who underwent EPTSS in a tertiary center. PS were identified in 113 (84.96%) microadenomas intraoperatively. The long-term surgical cure rate was 88.2%, and the comprehensive remission rate was 95.8% in total. There was no severe or permanent complication, and the surgical morbidity rate was 4.5%. The recurrence rate with over 5 years of follow-up was 9.2%, and a lot lower for the tumors in the complete PS group (0) and hypo-pituitary group (2.1%). Use of the extra-pseudocapsule dissection in microprolactinoma resulted in a good chance of increasing the surgical remission without increasing the risk of CSF leakage or endocrine deficits. First-line EPTSS may offer a greater opportunity of long-term cure for young female patients with microprolactinoma of hypo-pituitary located and Knosp grade 0-II. Full article

Virtual reality enables the manipulation of a patient’s perception, providing additional motivation to real-time biofeedback exercises. We aimed to test the effect of manipulated virtual kinematic intervention on measures of active and passive range of motion (ROM), pain, and disability level in individuals with traumatic stiff shoulder. In a double-blinded study, patients with stiff shoulder following proximal humerus fracture and non-operative treatment were randomly divided into a non-manipulated feedback group (NM-group; n = 6) and a manipulated feedback group (M-group; n = 7). The shoulder ROM, pain, and disabilities of the arm, shoulder and hand (DASH) scores were tested at baseline and after 6 sessions, during which the subjects performed shoulder flexion and abduction in front of a graphic visualization of the shoulder angle. The biofeedback provided to the NM-group was the actual shoulder angle while the feedback provided to the M-group was manipulated so that 10° were constantly subtracted from the actual angle detected by the motion capture system. The M-group showed greater improvement in the active flexion ROM (p = 0.046) and DASH scores (p = 0.022). While both groups improved following the real-time virtual feedback intervention, the manipulated intervention provided to the M-group was more beneficial in individuals with traumatic stiff shoulder and should be further tested in other populations with orthopedic injuries. Full article

(1) Background: Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a long-established estimation methodology for medical diagnosis using image classification illustrating conditions in coronary artery disease. For these procedures, convolutional neural networks have proven to be very beneficial in achieving near-optimal accuracy for the automatic classification of SPECT images. (2) Methods: This research addresses the supervised learning-based ideal observer image classification utilizing an RGB-CNN model in heart images to diagnose CAD. For comparison purposes, we employ VGG-16 and DenseNet-121 pre-trained networks that are indulged in an image dataset representing stress and rest mode heart states acquired by SPECT. In experimentally evaluating the method, we explore a wide repertoire of deep learning network setups in conjunction with various robust evaluation and exploitation metrics. Additionally, to overcome the image dataset cardinality restrictions, we take advantage of the data augmentation technique expanding the set into an adequate number. Further evaluation of the model was performed via 10-fold cross-validation to ensure our model’s reliability. (3) Results: The proposed RGB-CNN model achieved an accuracy of 91.86%, while VGG-16 and DenseNet-121 reached 88.54% and 86.11%, respectively. (4) Conclusions: The abovementioned experiments verify that the newly developed deep learning models may be of great assistance in nuclear medicine and clinical decision-making. Full article

Background: The risk for behavioral addictions is rising among women within the general population and in clinical settings. However, few studies have assessed treatment effectiveness in females. The aim of this work was to explore latent empirical classes of women with gambling disorder (GD) and buying/shopping disorder (BSD) based on the treatment outcome, as well as to identify predictors of the different empirical groups considering the sociodemographic and clinical profiles at baseline. Method: A clinical sample of n = 318 women seeking treatment for GD (n = 221) or BSD (n = 97) participated. Age was between 21 to 77 years. Results: The four latent-classes solution was the optimal classification in the study. Latent class 1 (LT1, good progression to recovery) grouped patients with the best CBT outcomes (lowest risk of dropout and relapses), and it was characterized by the healthiest psychological state at baseline, the lowest scores in harm avoidance and self-transcendence, and the highest scores in reward dependence, persistence, self-directedness and cooperativeness. Latent classes 3 (LT3, bad progression to drop-out) and 4 (LT4, bad progression to relapse) grouped women with the youngest mean age, earliest onset of the addictive behaviors, and worst psychological functioning. Conclusions: GD and BSD are complex conditions with multiple interactive causes and impacts, which need wide and flexible treatment plans. Specific interventions should be designed according to the specific profiles of women for achieving early inclusion, retention and well-maintained long-term effects. Full article

This study aimed to evaluate the clinical utility of the subclinical hypothyroidism (SCH) marker, elevated thyroid-stimulating hormone (TSH) and thyroid antibodies in their ability to predict subsequent gestational diabetes mellitus (GDM). In a prospective clinical trial, 230 pregnant women were screened for thyroid function during the first trimester of pregnancy. Increased TSH levels with normal free thyroxine (fT4) were considered SCH. The titers of thyroid peroxidase antibody (anti TPO Ab) at >35 IU/mL and thyroglobulin antibody (anti Tg Ab) at >115 IU/mL were considered as antibodies present. According to the OGTT results, the number of pregnant women with GDM showed the expected growth trend, which was 19%. Two groups of pregnant women were compared, one with GDM and the other without. Increased TSH levels and the presence of thyroid antibodies showed a positive correlation with the risk of GDM. TSH levels were significantly higher in pregnant women with GDM, p = 0.027. In this study, 25.6% of pregnant women met the diagnostic criteria for autoimmune thyroiditis. Hashimoto’s thyroiditis was significantly more common in GDM patients, p < 0.001. Through multivariate logistic regression, it was demonstrated that patient age, TSH 4 IU/mL, and anti TPO Ab > 35 IU/mL are significant predictors of gestational diabetes mellitus that may improve first-trimester pregnancy screening performance, AUC: 0.711; 95% CI: 0.629–0.793. Full article

(1) Aims: Patients receiving antitumor necrosis factor (anti-TNF) therapy are at risk of developing tuberculosis (TB), usually due to the reactivation of a latent TB infection (LTBI). LTBI screening and treatment decreases the risk of TB. This study evaluated the diagnostic performance of different LTBI screening strategies in patients with inflammatory bowel disease (IBD). (2) Methods: Patients in the Spanish ENEIDA registry with IBD screened for LTBI between January 2003 and January 2018 were included. The diagnostic yield of different strategies (dual screening with tuberculin skin test [TST] and interferon-ץ-release assay [IGRA], two-step TST, and early screening performed at least 12 months before starting biological treatment) was analyzed. (3) Results: Out of 7594 screened patients, 1445 (19%; 95% CI 18–20%) had LTBI. Immunomodulator (IMM) treatment at screening decreased the probability of detecting LTBI (20% vs. 17%, p = 0.001). Regarding screening strategies, LTBI was more frequently diagnosed by dual screening than by a single screening strategy (IGRA, OR 0.60; 95% CI 0.50–0.73, p < 0.001; TST, OR 0.76; 95% CI 0.66–0.88, p < 0.001). Two-step TST increased the diagnostic yield of a single TST by 24%. More cases of LTBI were diagnosed by early screening than by routine screening before starting anti-TNF agents (21% [95% CI 20–22%] vs. 14% [95% CI 13–16%], p < 0.001). The highest diagnostic performance for LTBI (29%) was obtained by combining early and TST/IGRA dual screening strategies in patients without IMM. (4): Conclusions: Both early screening and TST/IGRA dual screening strategies significantly increased diagnostic performance for LTBI in patients with IBD, with optimal performance achieved when they are used together in the absence of IMM. Full article

Aims: Virtual reality hypnosis (VRH) has been used successfully in various clinical settings to decrease anxiety and the sensation of pain. We aimed to investigate the feasibility and safety of VRH in patients undergoing electrophysiology and pacing procedures under conscious sedation. Methods: During a two-month period, VRH support was proposed and accepted by 25 patients undergoing electrophysiological procedures. Data were compared with a control group (n = 61) enrolled during the following three-month period. Both groups underwent the measurement of the duration of intervention, the consumption of analgesics and hypnotics, and their pain and comfort using a validated visual analogue scale (VAS 0−10). Results: The baseline characteristics were comparable in both groups, including age. There were no differences in procedure duration (46 (±29) vs. 56 (±32) min, p = 0.18) or in hypnotic/antalgic consumption (midazolam 1.95 (±1.44) vs. 2.00 (±1.22) mg, p = 0.83; sufentanyl 3.78 (±2.87) vs. 3.58 (±2.48) μg, p = 0.9) between the control and VRH groups. In a multivariate analysis, the use of VRH was independently associated with lower comfort during the procedure assessed by postoperative visual analogue scale (OR 15.00 [95% CI 4.77−47.16], p < 0.01). There was no influence of VRH use on pain or drug consumption. Conclusions: In our experience, compared with VRH, human care is preferable during procedures in electrophysiology lab to improve the comfort of the patient. VRH has no influence on pain or drug consumption. Full article

Since endometrial cancers (ECs) are frequently TMB-H and MSI-H/dMMR tumors, this element has provided the rationale for testing immune checkpoint inhibitors (ICIs), which have recently emerged as a potential game-changer. However, several questions remain to be addressed, including the identification of patients who may benefit from the addition of ICIs as well as those who do not need immunotherapy. In the current paper, we provide an overview of the clinical development of immunotherapy in advanced or recurrent EC, discussing the role of MMR and the “elective affinities” between ICIs and this predictive biomarker in this setting. Full article

Physical exercise has been recognized as an important strategy in the promotion of healthy aging. Positive effects on older adults’ motor ability are brought about by engaging their motor skills and promoting sensorimotor learning and cortical plasticity. These processes could be increased with the use of immersive virtual reality (IVR) technology, since the multisensory stimulation is greater. The aim of this study was to explore the usability and balance effects of an IVR exercise program in community-dwelling nonagenarian people. A sample of 12 women were allocated to an experimental group (EG n = 6; 91.67 ± 1.63 years) and a control group (CG n = 6; 90.83 ± 2.64 years). For 10 weeks, the EG used a commercial IVR exergame three times a week. All the sample completed the program without adverse effects (without Simulator Sickness Questionnaire symptoms). Post-gaming usability was good (System Usability Scale 78.33). The EG improved some balance parameters significantly (Tinetti test: balance (10.97 %; Sig = 0.017), gait (9.23%; Sig = 0.047) and total score (10.20%; Sig = 0.014) and maintained total TUG test times (−0.45%)). There were significant differences between groups (Tinetti test: balance (Sig = 0.004) and total score (Sig = 0.0032)). We successfully demonstrated that IVR training is feasible and is an effective and personalized method to enhance balance and to reduce the risk of falls in community-dwelling nonagenarian women. Full article

Artificial intelligence (AI) is an integral part of clinical decision support systems (CDSS), offering methods to approximate human reasoning and computationally infer decisions. Such methods are generally based on medical knowledge, either directly encoded with rules or automatically extracted from medical data using machine learning (ML). ML techniques, such as Artificial Neural Networks (ANNs) and support vector machines (SVMs), are based on mathematical models with parameters that can be optimally tuned using appropriate algorithms. The ever-increasing computational capacity of today’s computer systems enables more complex ML systems with millions of parameters, bringing AI closer to human intelligence. With this objective, the term deep learning (DL) has been introduced to characterize ML based on deep ANN (DNN) architectures with multiple layers of artificial neurons. Despite all of these promises, the impact of AI in current clinical practice is still limited. However, this could change shortly, as the significantly increased papers in AI, machine learning and deep learning in cardiology show. We highlight the significant achievements of recent years in nearly all areas of cardiology and underscore the mounting evidence suggesting how AI will take a central stage in the field. Full article

This systematic review aimed to evaluate interventions individually and compare the clinical outcome of young, immature teeth treated with regenerative endodontic therapy (RET) and apexification procedure. The protocol was registered with PROSPERO (International Prospective Register of Systematic Reviews), bearing the registration number CRD42021230284. A bibliographic search in the biomedical databases was conducted in four databases—PubMed, CENTRAL, EMBASE and ProQuest—using searching keywords and was limited to studies published between January 2000 and April 2022 in English. The search was supplemented by manual searching, citation screening and scanning of all reference lists of selected paper. The study selection criteria were randomized clinical trial, prospective clinical studies and observational studies. The search found 32 eligible articles, which were included in the study. The quality assessment of the studies was performed using the Cochrane risk of bias tool for randomized control trials and non-randomized clinical studies. The meta-analysis was performed using Review Manager software (REVMAN, version 5). The results indicated that a clinicians’ MTA apexification procedure was more successful compared to calcium hydroxide. In RET, apical closure and overall success rate is statistically same for both apical platelet concentrates (APCs) and blood clots (BC). Both interventions have similar survival rates; however, RET should be preferred in cases where the root development is severely deficient, there is insufficient dentine and the tooth’s prognosis is hopeless even with an apexification procedure. Full article

Background: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is associated with poor prognosis in cardiovascular diseases. However, the predictive value of TRAIL for the short-term outcome and risk stratification of acute pulmonary embolism (PE) remains unknown. Methods: This study prospectively included 151 normotensive patients with acute PE. The study outcome was a composite of 30-day adverse events, defined as PE-related death, shock, mechanical ventilation, cardiopulmonary resuscitation, and major bleeding. Results: Overall, nine of 151 (6.0%) patients experienced 30-day adverse composite events. Multivariable logistic regression showed that TRAIL was an independent predictor of study outcome (OR 0.19 per SD; 95% CI 0.04–0.90). An ROC curve revealed that TRAIL’s area under the curve (AUC) was 0.83 (95% CI 0.76–0.88). The optimal cut-off value for TRAIL was 18 pg/mL, with a sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, and negative likelihood ratio of 89%, 69%, 99%, 15%, 2.87, and 0.16, respectively. Compared with the risk stratification algorithm outlined in the 2019 ESC guidelines, our biomarker-based risk stratification strategy (combining TRAIL and hs-cTnI) has a similar risk classification effect. Conclusion: Reduced plasma TRAIL levels predict short-term adverse events in normotensive patients with acute PE. The combination of the 2019 ESC algorithm and TRAIL aids risk stratification in normotensive patients with acute PE. Full article

(1) Background: Alzheimer’s disease is an irreversible brain disease, and current treatments are aimed at fighting cognitive decline. We have explored the feasibility of a game-based intervention for people with moderate Alzheimer’s disease; (2) Methods: Six participants, five women and one man, were recruited from a day center to participate in a five-week study, which included a re- and post-evaluation with the Montreal Cognitive Assessment (MoCA) and INECO Frontal Screening (IFS) tests. Three participants were assigned to the control group and three others to the experimental one. Both groups performed a play activity consisting of assembling a pie toy. Participants in the experimental group were asked to make a pie matching a sample after a time interval. Control group participants were asked to freely assemble a pie without the matching component; (3) Results: Patients were shown to be motivated during such an activity during the nine sessions. The experimental group showed a significant increase in IFS scores when comparing the post- and pre-intervention assessments. No significant differences were observed in MoCA scores; (4) The intervention created a social and emotional climate suitable to maintaining participants’ satisfaction and motivation, as well as to developing executive function while promoting positive emotions. Full article

This study compared the absorption of subretinal fluid (SRF) in patients with rhegmatogenous retinal detachment (RRD) with and without high myopia after scleral buckling (SB) and investigated the effect of high myopia on SRF absorption. This retrospective study included patients with primary macula-off RRD grouped according to myopia and age. The optical coherence tomography (OCT) and OCT angiography indicators included subretinal fluid height (SRFH), subfoveal choroidal thickness (SFCT), and choroidal capillary blood flow density (CCFD) measured regularly. The presence of SRF 3 months after surgery was defined as delayed absorption. Overall, 90 eyes of 89 patients were enrolled, and 46 eyes (51.11%) had high myopia. In 43 eyes (47.78%), SRF absorption was delayed. There was no significant difference in SRF absorption after SB between the high and non-high myopia groups; younger patients (<35 years) had a higher probability of delayed absorption (p < 0.05). The SFCT in high myopia was significantly thinner than that in the non-high myopia group (p < 0.05); SFCT and SRFH were positively correlated (r_s = 0.275, p = 0.002), and there was a significant difference between the average CCFD with and without SRF (p < 0.05). High myopia had no significant effect on SRF absorption after SB. Full article

(1) Background: The development of effective COVID-19 vaccines has reduced the impact of COVID-19 on the general population. Our study aims to analyze how vaccination modifies the likelihood of death and length of stay in hospitalized patients with COVID-19; (2) Methods: A retrospective cohort study of 1927 hospitalized patients infected with COVID-19 was conducted. Information was gathered on vaccination status, hospitalization episode, and clinical profile of the patients. The effect of vaccination on mortality was analyzed using a multiple logistic regression model, and length of stay was analyzed using linear regression. The performance and fit of the models were evaluated; (3) Results: In hospitalized patients with COVID-19, the risk of dying during admission in vaccinated patients was half that of non-vaccinated (OR: 0.45; CI 95%: 0.25 to 0.84). In patients who were discharged due to improvement, the reduction in hospital stay in vaccinated patients was 3.17 days (CI 95%: 5.88 to 0.47); (4) Conclusions: Patients who, despite having been vaccinated, acquire the infection by SARS-CoV-2, have a significant reduction of the risk of death during admission and a reduction of hospital stay compared with unvaccinated patients. Full article

This editorial of the Special Issue “Clinical and Physiological Consequences of Hypoxia/Hypoxemia in Healthy Subjects and Patients” aims to draw more attention to the broad and diverse field of hypoxia research and serves as an invitation for research groups to share their most recent findings with the medical community [...] Full article

This study’s goal is to determine the accuracy of a linear classifier that predicts the prognosis of patients with macular edema (ME) due to a branch retinal vein occlusion during the maintenance phase of antivascular endothelial growth factor (anti-VEGF) therapy. The classifier was created using the clinical information and optical coherence tomographic (OCT) findings obtained up to the time of the first resolution of ME. In total, 66 eyes of 66 patients received an initial intravitreal injection of anti-VEGF followed by repeated injections with the pro re nata (PRN) regimen for 12 months. The patients were divided into two groups: those with and those without good vision during the PRN phase. The mean AUC of the classifier was 0.93, and the coefficients of the explanatory variables were: best-corrected visual acuity (BCVA) at baseline was 0.66, BCVA at first resolution of ME was 0.51, age was 0.21, the average brightness of the ellipsoid zone (EZ) was −0.12, the intactness of the external limiting membrane (ELM) was −0.14, the average brightness of the ELM was −0.17, the brightness value of EZ was −0.17, the area of the outer segments of the photoreceptors was −0.20, and the intactness of the EZ was −0.24. This algorithm predicted the prognosis over time for individual patients during the PRN phase. Full article

Background: Cerebrovascular events (CVE) are feared complications following transcatheter aortic valve replacement (TAVR). We aimed to develop a new risk model for CVE prediction with the application of multimodal imaging. Methods: From May 2011 to August 2019, a total of 2015 patients underwent TAVR at our institution. The study cohort was subdivided into a derivation cohort (n = 1365) and a validation cohort (n = 650) for risk model development. Results: Of 2015 patients, 72 (3.6%) developed TAVR-related CVE. Pre-procedural factors of our risk model were history of prior CVE, a larger aortic valve area (≥0.55 cm²), a large aortic angulation (≥48.5°), and enhanced calcification of the right coronary cusp (≥447.2 AU), left ventricular outflow tract (≥262.4 AU), and ascending thoracic aorta (≥116.4 AU). Our risk model was superior for in-hospital CVE prediction following TAVR in the establishment cohort (AUC 0.73, 95% CI 0.66–0.80; p < 0.001) compared to other risk scores, such as the EuroSCORE II or the CHA₂DS₂-VASc score. Conclusions: Although CVE prediction in patients undergoing TAVR is challenging due to the complex nature of the TAVR procedure, our study highlights that multimodal imaging is a promising approach to generate a more accurate risk model for CVE prediction. Full article

Background: Long bone fractures display significant non-union rates, but the exact biological mechanisms implicated in this devastating complication remain unclear. The combination of osteogenetic and angiogenetic factors at the fracture site is an essential prerequisite for successful bone regeneration. The aim of this study is to investigate the results of the clinical implantation of growth factors for intraoperative enhancement of osteogenesis for the treatment of long bone fractures and non-unions. Methods: A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed and Web of Science databases from the date of inception of each database through to 10 January 2022. Specific inclusion and exclusion criteria were applied in order to identify relevant studies reporting on the treatment of upper and lower limb long bone non-unions treated with osteoinductive or cellular factors. Results: Overall, 18 studies met the inclusion criteria and examined the effectiveness of the application of Bone Morphogenetic Proteins-2 and -7 (BMPs), platelet rich plasma (PRP) and mesenchymal stem cells (MSCs). Despite the existence of limitations in the studies analysed (containing mixed groups of open and close fractures, different types of fractures, variability of treatment protocols, different selection criteria and follow-up periods amongst others), their overall effectiveness was found significantly increased in patients who received them compared with the controls (I² = 60%, 95% CI = 1.59 [0.99–2.54], Z =1.93, p = 0.05). Conclusion: Administration of BMP-2 and -7, PRP and MSCs were considered effective and safe methods in fracture treatment, increasing bone consolidation, reducing time to repair and being linked to satisfactory postoperative functional scores. Full article

Aims: While it is common practice to use intravenous (IV) iron in patients with left ventricular assist devices (LVADs) and iron deficiency, there is insufficient evidence regarding outcomes in this patient population. We evaluated the safety and effectiveness of IV iron therapy in patients supported by LVADs with iron deficiency. Methods: We performed a retrospective analysis of iron deficient patients on continuous LVAD support at a large academic center between 2008 and 2019. Patients were divided into two cohorts based on IV iron sucrose treatment. The primary endpoint was hemoglobin at 12 weeks. Secondary endpoints were mean corpuscular volume (MCV) and New York Heart Association (NYHA) class at 12 weeks. Safety endpoints included hospitalization, infection, pump thrombosis, arrhythmia, and gastrointestinal bleed. Models were weighted by the inverse probability of receiving IV iron using a propensity score, and endpoints were adjusted for their corresponding baseline values. Results: Among 213 patients, 70 patients received IV iron and 143 patients did not. Hemoglobin at 12 weeks was significantly greater among those treated (intergroup difference: 0.6 g/dL; 95% CI, 0.1 to 1.1; p = 0.01), while MCV was similar in both groups (intergroup difference: 0.7 μm³; 95% CI, −1.3 to 2.7; p = 0.50). NYHA class distribution at 12 weeks was significantly different (odds ratio for improvement: 2.84; 95% CI, 1.42 to 4.68; p = 0.003). The hazards of adverse events in each group were similar. Conclusions: In patients with LVADs and iron deficiency, treatment with IV iron sucrose was safe and associated with improvements in functional status and hemoglobin. Full article

In liver transplantation, older donor age is a well-known risk factor for dismal outcomes, especially due to the high susceptibility of older grafts to ischemia-reperfusion injury. However, whether the factors correlating with impaired graft and patient survival following the transplantation of older grafts follow a linear trend among elderly donors remains elusive. In this study, liver transplantations between January 2006 and May 2018 were analyzed retrospectively. Ninety-two recipients of grafts from donors ≥65 years were identified and divided into two groups: (1) ≥65–69 and (2) ≥ 70 years. One-year patient survival was comparable between recipients of grafts from donors ≥65–69 and ≥70 years (78.9% and 70.0%). One-year graft survival was 73.1% (donor ≥65–69) and 62.5% (donor ≥ 70), while multivariate analysis revealed superior one-year graft survival to be associated with a donor age of ≥65–69. No statistically significant differences were found for rates of primary non-function. The influence of donor age on graft and patient survival appears not to have a distinct impact on dismal outcomes in the range of 65–70 years. The impact of old donor age needs to be balanced with other risk factors, as these donors provide grafts that offer a lifesaving graft function. Full article

Obstructive hypertrophic cardiomyopathy (oHCM) has been studied primarily in comprehensive centers of excellence. Broadening the understanding of patients with oHCM in the general population may improve identification and treatment in other settings. This retrospective cohort study identified adults with oHCM from a large electronic medical record database comprising data from 39 integrated delivery networks (IBM Explorys; observational period: January 2009–July 2019). Clinical characteristics, healthcare resource utilization (HCRU), and outcomes were reported. Of 8791 patients, 53.0% were female and the mean index age was 61.8 years. Cardiovascular drugs prescribed included beta-blockers (80.5%), calcium channel blockers (46.0%), and disopyramide (2.4%). Over time, heart failure, atrial fibrillation, and ventricular arrhythmias increased. Surgical procedures included septal myectomy (22.0%), alcohol septal ablation (0.6%), and heart transplantation (0.3%). Implantable cardioverter defibrillators were present in 11.2% of patients. After initial septal reduction therapy (SRT), HCRU increased and 550 patients (27.7%) required a reintervention. Of the overall group, 2.7% experienced sudden cardiac arrest by end of study. In conclusion, this cohort of patients with oHCM had guideline-recommended drug therapy and procedures. Despite this, heart failure, atrial fibrillation, and ventricular arrhythmias increased, and more than a quarter of patients undergoing SRT required reintervention. These unresolved issues emphasize the unmet need for new, effective therapies for patients with oHCM. Full article

Osteopenia, sarcopenia, and increased vascular stiffness are common in patients with chronic kidney disease-mineral bone disorder (CKD-MBD) with protein energy wasting and can lead to worse clinical outcomes. We investigated the potential moderating role of the lean tissue index (LTI) in the relationship between bone microarchitecture and vascular stiffness in dialysis naïve patients with stage 5 CKD. Bioimpedance spectroscopy for evaluating LTI, lumbar spine dual energy X-ray absorptiometry for determining the trabecular bone score (TBS), and arterial applanation tonometry measurements for the central augmentation index, at a heart rate of 75 beats/minute (cAIx75), were simultaneously performed in 117 consecutive patients. A hierarchical regression analysis was conducted to assess the moderating effect of LTI on the relationship between TBS and cAIx75 after adjusting for age and sex. The effect of the interaction between LTI and TBS on cAIx75 was statistically significant (p = 0.030), demonstrating that the cAIx75 tends to decrease more, with the joint effect of LTI and TBS. In the separate analyses, the interaction effect was significant only in women (p = 0.048) and the group of diabetes (p = 0.042). Our study suggests that the evaluation of changes in body composition, bone health, and vascular stiffness needs to be performed simultaneously in patients with advanced-stage CKD. Further research in patients with different stages of CKD warranted to generalize and apply our results to patients in other stages. Full article

Postprocedural cardiac troponin I (cTnI) elevation commonly occurs in patients undergoing percutaneous coronary intervention (PCI); however, its prognostic value remains controversial. This study aimed to investigate the prognostic value of peak postprocedural cTnI in cardiac patients with or without three-vessel disease (TVD) undergoing complete PCI. A total of 1237 consecutive patients (77% males, mean age 58 ± 10 years) with normal baseline cTnI levels were enrolled, 439 patients (77% males, 59 ± 10 years) with TVD, and 798 patients (77% males, 57 ± 10 years) with single- or double-vessel disease (non-TVD). The primary outcome was the occurrence of major adverse cardiovascular events (MACE), defined as a composite of non-fatal MI, non-fatal stroke, unplanned revascularization, re-hospitalization due to heart failure or severe arrhythmias, and all-cause death. During the median follow-up of 5.3 years, a total of 169 patients (13.7%) developed MACE, including 73 (16.6%) in the TVD group and 96 (12.0%) in the non-TVD group (p = 0.024). After adjustment, the multivariate Cox analysis showed that hypertension (HR 1.50; 95% CI: 1.01–2.20; p = 0.042), TVD (HR 1.44; 95% CI: 1.03–2.02; p = 0.033), and cTnI ≥ 70× URL (HR 2.47; 95% CI: 1.28–4.78, p = 0.007) were independently associated with increased MACE during long-term follow-up. Further subgroup analyses showed that cTnI ≥ 70× URL was an independent predictor of MACE in TVD patients (HR 3.32, 95% CI: 1.51–7.34, p = 0.003), but not in non-TVD patients (HR 1.01, 95%CI: 0.24–4.32, p = 0.991). In conclusion, elevation of post-PCI cTnI ≥ 70× URL is independently associated with a high risk of MACE during long-term follow-up in patients with TVD, but not in those with non-TVD. Full article

The aim of this study was to evaluate the ability of second trimester plasma glycated CD59 (pGCD59), a novel biomarker, to predict the results of the 2 h 75 g oral glucose tolerance test at 24–28 weeks of gestation, employing the 2013 World Health Organisation criteria. This was a prospective study of 378 pregnant women. The ability of pGCD59 to predict gestational diabetes (GDM) was assessed using adjusted ROC curves for maternal age, BMI, maternal ethnicity, parity, previous GDM, and family history of diabetes. The pGCD59 levels were significantly higher in women with GDM compared to women with normal glucose tolerance (p = 0.003). The pGCD59 generated an adjusted AUC for identifying GDM cases of 0.65 (95%CI: 0.58–0.71, p < 0.001). The pGCD59 predicted GDM status diagnosed by a fasting glucose value of 5.1 mmol/L with an adjusted AUC of 0.74 (95%CI: 0.65–0.81, p < 0.001). Analysis of BMI subgroups determined that pGCD59 generated the highest AUC in the 35 kg/m² ≤ BMI < 40 kg/m² (AUC: 0.84 95%CI: 0.69–0.98) and BMI ≥ 40 kg/m² (AUC: 0.96 95%CI: 0.86–0.99) categories. This study found that second trimester pGCD59 is a fair predictor of GDM status diagnosed by elevated fasting glucose independent of BMI and an excellent predictor of GDM in subjects with a very high BMI. Full article