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Chronic skin defects in the head, face and neck pose challenges for closure, especially after multiple surgeries or radiation therapy. We report the case of a woman in her 70s with a chronic occipital wound following squamous cell carcinoma resections, resulting in exposed skull bone. Despite various options, we successfully treated the 4 cm x 5 cm wound with a Kerecis fish skin graft (FSG), observing significant improvement within a week. The FSG promoted granulation tissue formation, enabling subsequent full-thickness skin grafting from the patient's groin. Complete wound closure was achieved within 2 weeks, indicating FSG's efficacy in complex wound management. Our experience highlights FSG's potential as a valuable tool in wound healing and reconstruction, particularly in challenging cases involving the head and neck.
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Carcinoma de Células Escamosas , Trasplante de Piel , Cicatrización de Heridas , Humanos , Femenino , Trasplante de Piel/métodos , Carcinoma de Células Escamosas/cirugía , Anciano , Animales , Peces , Neoplasias de Cabeza y Cuello/cirugía , Neoplasias Cutáneas/cirugía , Resultado del Tratamiento , Enfermedad Crónica , Hueso Occipital/cirugíaRESUMEN
BACKGROUND: The growing prominence of Artificial Intelligence (AI) in medicine introduces both transformative possibilities and potential challenges. Our study focuses on the current status and perceptions of AI in Head and Neck Surgery (HNS), examining its utilization, benefits, ethical concerns, and protective measures. OBJECTIVES: The study aims to illuminate the existing landscape of AI in HNS in Germany. MATERIALS AND METHODS: Conducted through a questionnaire, key aspects include its current usage, potential applications (e.g., diagnosis, surgical planning), anticipated benefits (e.g., improved patient care ), and significant ethical concerns (e.g., miscalculations by AI, data privacy). RESULTS: The survey reveals limited AI adoption in HNS, with substantial potential for improvement. Ethical considerations, especially miscalculations by AI and data privacy, emerge as central issues. The survey emphasizes the crucial role of physician control and the need for legal oversight to address concerns related to AI integration. While AI's presence in HNS is modest, the study identifies opportunities for enhancement. Ethical guidelines and practitioner-centric control are vital for discussions surrounding AI integration. CONCLUSIONS: This research underscores the significance of ethical considerations and practitioner control in the context of AI in surgical practices. It highlights the demand for targeted training to empower practitioners in navigating the complexities of AI technologies in healthcare, ensuring responsible and patient-centric implementation.
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OBJECTIVE: Successful outcomes in head and neck surgery rely on maintaining perfusion in pedicled skin flaps. Thermal imaging offers a noninvasive means to assess tissue perfusion, potentially aiding in predicting flap viability. This pilot study explores the utility of SBTI (smartphone-based thermal imaging) for predicting flap vitality and monitoring during surgery. METHODS: Thermal imaging was employed using the FLIR One System. An imaging protocol was established, defining points of interest (T1-T4) on pedicled skin flaps. Conducted over four months, the study integrated SBTI into reconstructive surgery for the face, head and neck defects post-tumor resections. SBTI's effectiveness was assessed with n = 11 pedicled flaps, capturing images at key stages and correlating them with clinical flap assessment. Thermal images were retrospectively graded by two surgeons, evaluating flap perfusion on a scale from 1 to 5, based on temperature differences (1 = ΔT < 2 °C, 2 = ΔT ≥ 2 °C, 3 = ΔT ≥ 4 °C, 4 = ΔT ≥ 6 °C, and 5 = ΔT ≥ 8 °C), with assessments averaged for consensus and compared with the clinical assessment control group. RESULTS: The study encountered challenges during implementation, leading to the exclusion of six patients. Patient data included 11 cases with n = 44 SBTI images. Intraoperative assessments consistently showed good perfusion. One postoperative dehiscence was noted, which retrospectively coincided with intraoperative SBTI grading, but not with clinical assessment. Statistical analysis indicated consistent outcomes following clinical and SBTI assessments. Thermal imaging accurately predicted flap viability, although it had limitations with small flaps. CONCLUSION: SBTI proved effective, inexpensive, and noninvasive for assessing tissue perfusion, showing promise for predicting flap viability and intraoperative monitoring in head and neck surgery.
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This article provides a comprehensive analysis of modern techniques used in the assessment of cutaneous flaps in reconstructive surgery. It emphasizes the importance of preoperative planning and intra- and perioperative assessment of flap perfusion to ensure successful outcomes. Despite technological advancements, direct clinical assessment remains the gold standard. We categorized assessment techniques into non-invasive and invasive modalities, discussing their strengths and weaknesses. Non-invasive methods, such as acoustic Doppler sonography, near-infrared spectroscopy, hyperspectral imaging thermal imaging, and remote-photoplethysmography, offer accessibility and safety but may sacrifice specificity. Invasive techniques, including contrast-enhanced ultrasound, computed tomography angiography, near-infrared fluorescence angiography with indocyanine green, and implantable Doppler probe, provide high accuracy but introduce additional risks. We emphasize the need for a tailored decision-making process based on specific clinical scenarios, patient characteristics, procedural requirements, and surgeon expertise. It also discusses potential future advancements in flap assessment, including the integration of artificial intelligence and emerging technologies.
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Procedimientos de Cirugía Plástica , Piel , Humanos , Piel/diagnóstico por imagen , Piel/irrigación sanguínea , Colgajos Quirúrgicos/irrigación sanguíneaRESUMEN
Introduction: Frey's syndrome, described by Lucy Frey in 1923, is a unique condition characterized by sweating, flushing, and reddening as a direct response to mastication. This phenomenon results from the aberrant regeneration of postganglionic parasympathetic neurons originating from the auriculotemporal nerve and the subsequent acetylcholine secretion induced by masticatory stimuli. Although rare, this syndrome can have multiple underlying causes and is frequently observed, occurring in up to 65% of cases following lateral parotid resections. Additionally, it can less commonly manifest after neck dissection, facelift procedures, or be associated with diabetes mellitus. Method: This article outlines a comprehensive diagnostic algorithm for Frey's syndrome, which includes the utilization of the Minor-Starch-Iodine Test. This test is a key component in diagnosing the syndrome and is discussed in detail, providing insights into its procedure and interpretation. Additionally, the gold standard of treatment for established Frey's syndrome, botulinum toxin A, is thoroughly described, including its mechanism of action, administration, and potential side effects. Discussion: Finally, the article underscores the need for further research to enhance our understanding of Frey's syndrome, leading to better diagnostic methods and more tailored treatment options for patients.
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Estética , Neoplasias Nasales , Rinoplastia , Colgajos Quirúrgicos , Humanos , Colgajos Quirúrgicos/trasplante , Rinoplastia/métodos , Masculino , Femenino , Neoplasias Nasales/cirugía , Cartílago Auricular/trasplante , Cartílago Auricular/cirugía , Anciano , Persona de Mediana Edad , Carcinoma Basocelular/cirugía , Cirugía de Mohs , Neoplasias Cutáneas/cirugía , Resultado del Tratamiento , Nariz/cirugía , Anciano de 80 o más AñosRESUMEN
Thrombosis and thrombophlebitis of the facial vein represent exceptionally rare diagnoses, particularly when occurring as complications of acute sialadenitis of the submandibular gland. This case report details the experience of a middle-aged man initially presenting at a tertiary care ear, nose and throat department with right submandibular gland sialadenitis. Despite initiating outpatient treatment involving oral antibiotics and sialagogues, the patient returned after a week with persistent and worsening pain, accompanied by swelling of the right submandibular gland and cheek. Using ultrasound, the accurate diagnosis was promptly identified, revealing thrombosis in the facial vein.The patient underwent a comprehensive treatment regimen involving anticoagulation and intravenous antibiotics. With a subsequent reduction in pain and swelling, the patient was discharged, continuing oral anticoagulation and antibiotics. Outpatient follow-up revealed a complete recovery 3 weeks later. This case underscores the importance of timely and precise diagnostic measures in managing rare complications associated with sialadenitis.
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Sialadenitis , Tromboflebitis , Trombosis de la Vena , Masculino , Persona de Mediana Edad , Humanos , Trombosis de la Vena/complicaciones , Tromboflebitis/diagnóstico , Tromboflebitis/tratamiento farmacológico , Tromboflebitis/etiología , Glándula Submandibular/diagnóstico por imagen , Sialadenitis/diagnóstico , Sialadenitis/etiología , Dolor/complicaciones , Antibacterianos/uso terapéutico , Anticoagulantes/uso terapéuticoRESUMEN
With the onset of the coronavirus pandemic, it has become clear that patients with diabetes are at risk for more severe and fatal COVID-19. Type 2 diabetes mellitus (T2D) is a major risk factor for adverse COVID-19 outcomes. The goal of study was to assess the characteristics and outcomes of hospitalized patients with COVID-19 with or without T2D in the hospital and at 10-month follow-up (FU). METHODS: A total of 2486 hospitalized patients in the first wave of COVID-19 were analyzed according to the absence/presence of T2D, with 2082 (84.1%) patients in the control COVID-19 group and 381 (15.5%) in the T2D group. Twenty-three patients had other types of diabetes and were therefore excluded from the study. In-hospital mortality and cardiovascular endpoints (myocardial infarction, stroke, cardiovascular deaths and hospitalizations and composite endpoints) at the 10-month follow-up were analyzed. To remove bias in patients' characteristics disproportion, Propensity Score Matching (PSM) was used for hospital and follow-up endpoints. RESULTS: Hospital mortality was considerably greater in T2D than in the control COVID-19 group (13.89% vs. 4.89%, p < 0.0001), and the difference remained after PSM (p < 0.0001). Higher glucose-level T2D patients had a higher mortality rate (p = 0.018). The most significant predictors of hospital death in T2D patients were a high CRP, glucose, neutrophils count, and Charlson Comorbidity Index. The follow-up of patients over 10 months showed a non-significant increase for all endpoints in the T2D group (p > 0.05), and significant increase in stroke (p < 0.042). After the PSM, the difference decreased in stroke (p = 0.090), but became significant in cardiovascular hospitalizations (p = 0.023). CONCLUSION: In T2D patients with COVID-19, an increase in hospital mortality, stroke and cardiovascular hospitalizations rates in the follow-up was observed.
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PURPOSE: Patients at risk for sudden cardiac death may temporarily need a wearable cardioverter-defibrillator (WCD). Exercise-based cardiac rehabilitation (CR) has a class I recommendation in patients with cardiac disease. The aim of this study was to evaluate the safety and feasibility of undergoing CR with a WCD. METHODS: We performed a retrospective analysis of all patients with a WCD who completed a CR in Austria (2010-2020). RESULTS: Patients (n = 55, 60 ± 11 yr, 16% female) with a median baseline left ventricular ejection fraction (LVEF) of 36 (30, 41)% at the start of CR showed a daily WCD wearing duration of 23.4 (22, 24) hr. There were 2848 (8 [1, 26]/patient) automatic alarms and 340 (3 [1, 7]/patient) manual alarms generated. No shocks were delivered by the WCD during the CR period. One patient had recurrent hemodynamically tolerated ventricular tachycardias that were controlled with antiarrhythmic drugs.No severe WCD-associated adverse events occurred during the CR stay of a median 28 (28, 28) d. The fabric garment and the device setting needed to be adjusted in two patients to diminish inappropriate automatic alarms. Left ventricular ejection fraction after CR increased significantly to 42 (30, 44)% ( P < .001). Wearable cardioverter-defibrillator therapy was stopped due to LVEF restitution in 53% of patients. In 36% of patients an implantable cardioverter-defibrillator was implanted, 6% had LVEF improvement after coronary revascularization, one patient received a heart transplantation (2%), two patients discontinued WCD treatment at their own request (4%). CONCLUSION: Completing CR is feasible and safe for WCD patients and may contribute positively to the restitution of cardiac function.
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Rehabilitación Cardiaca , Desfibriladores Implantables , Humanos , Femenino , Masculino , Estudios Retrospectivos , Volumen Sistólico , Función Ventricular Izquierda , Cardioversión EléctricaRESUMEN
To respond to auxin, the chief orchestrator of their multicellularity, plants evolved multiple receptor systems and signal transduction cascades. Despite decades of research, however, we are still lacking a satisfactory synthesis of various auxin signaling mechanisms. The chief discrepancy and historical controversy of the field is that of rapid and slow auxin effects on plant physiology and development. How is it possible that ions begin to trickle across the plasma membrane as soon as auxin enters the cell, even though the best-characterized transcriptional auxin pathway can take effect only after tens of minutes? Recently, unexpected progress has been made in understanding this and other unknowns of auxin signaling. We provide a perspective on these exciting developments and concepts whose general applicability might have ramifications beyond auxin signaling.
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Ácidos Indolacéticos , Tetranitrato de Pentaeritritol , Membrana Celular , Transducción de SeñalRESUMEN
Backround: Branchial cleft anomalies (BCA) can occur as sinuses, fistulas or cysts. They arise from the first, second, third or fourth pharyngeal cleft due to non-fusion or subinvolution. Mostly, located in Robbin's neck-level II, BCA clinically present as a painless compressible swelling, cutaneous draining sinus, or fistula. Aims: Surgical treatment is the gold standard to prevent recurrence in BCA, though the necessity of ipsilateral tonsillectomy is discussed and was being examined within this work. Methods: In retrospect, data was collected from patients, that were admitted with the diagnosis BCA between 2006 and 2020 in an academic tertiary care center. 160 patients met inclusion criteria, the data was further evaluated, the focus was set on the occurrence of recurrence. Results: Recurrence of BCA was observed in 2 out of 160 surgically treated patients (1,25%), one of them with simultaneous tonsillectomy, the other without. Conclusion: A statistically significant difference in the recurrence-rate between these two groups (with/without tonsillectomy) could not be shown. The performance of an ipsilateral simultaneous tonsillectomy in the surgical workup of BCA cannot be recommended at the basis of our data. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03543-5.
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BACKGROUND: After acute myocardial infarction (AMI), patients are at risk of sudden cardiac death. The VEST trial failed to show a reduction in arrhythmic mortality in AMI patients with an LVEF ≤ 35% prescribed with a WCD, having a lower-than-expected WCD wearing compliance. OBJECTIVES: The aim was to investigate on outcomes of patients in a real-world Austrian cohort with good compliance. METHODS: A retrospective analysis of all eligible Austrian WCD patients according to the VEST trial inclusion and exclusion criteria between 2010 and 2020 was performed. RESULTS: In total, 105 Austrian patients (64 ± 11 years, 12% female; LVEF 28 ± 6%) received a WCD for a median of 69 (1; 277) days after AMI (wearing duration 23.5 (0; 24) hours/day). Within the first 90 days, 4/105 (3.8%) patients received 9 appropriate shocks (2 (1; 5) shocks). No inappropriate shocks were delivered, and 3/105 (2.9%) patients died during follow-up. Arrhythmic mortality (1.9% Austria vs. 1.6% VEST, p = 0.52), as well as all-cause mortality (2.9% vs. 3.1%, p = 0.42) was comparable in both cohorts. CONCLUSIONS: The WCD is a safe treatment option in a highly selected cohort of patients with LVEF ≤ 35% after AMI. However, despite excellent WCD wearing duration in our cohort, the arrhythmic mortality rate was not significantly different.
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Introduction: While acute Coronavirus disease 2019 (COVID-19) affects the cardiovascular (CV) system according to recent data, an increased CV risk has been reported also during long-term follow-up (FU). In addition to other CV pathologies in COVID-19 survivors, an enhanced risk for arrhythmic events and sudden cardiac death (SCD) has been observed. While recommendations on post-discharge thromboprophylaxis are conflicting in this population, prophylactic short-term rivaroxaban therapy after hospital discharge showed promising results. However, the impact of this regimen on the incidence of cardiac arrhythmias has not been evaluated to date. Methods: To investigate the efficacy of this therapy, we conducted a single center, retrospective analysis of 1804 consecutive, hospitalized COVID-19 survivors between April and December 2020. Patients received either a 30-day post-discharge thromboprophylaxis treatment regimen using rivaroxaban 10 mg every day (QD) (Rivaroxaban group (Riva); n = 996) or no thromboprophylaxis (Control group (Ctrl); n = 808). Hospitalization for new atrial fibrillation (AF), new higher-degree Atrioventricular-block (AVB) as well as incidence of SCD were investigated in 12-month FU [FU: 347 (310/449) days]. Results: No differences in baseline characteristics (Ctrl vs Riva: age: 59.0 (48.9/66.8) vs 57 (46.5/64.9) years, p = n.s.; male: 41.5% vs 43.7%, p = n.s.) and in the history of relevant CV-disease were observed between the two groups. While hospitalizations for AVB were not reported in either group, relevant rates of hospitalizations for new AF (0.99%, n = 8/808) as well as a high rate of SCD events (2.35%, n = 19/808) were seen in the Ctrl. These cardiac events were attenuated by early post-discharge prophylactic rivaroxaban therapy (AF: n = 2/996, 0.20%, p = 0.026 and SCD: n = 3/996, 0.30%, p < 0.001) which was also observed after applying a logistic regression model for propensity score matching (AF: χ 2-statistics = 6.45, p = 0.013 and SCD: χ 2-statistics = 9.33, p = 0.002). Of note, no major bleeding complications were observed in either group. Conclusion: Atrial arrhythmic and SCD events are present during the first 12 months after hospitalization for COVID-19. Extended prophylactic Rivaroxaban therapy after hospital discharge could reduce new onset of AF and SCD in hospitalized COVID-19 survivors.
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(1) Background: Heart failure with reduced ejection fraction (HFrEF) remains a major health burden. Angiotensin-Receptor-Neprilysin-Inhibitors (ARNIs) are an established HFrEF therapy which increases natriuretic peptide levels by inhibiting neprilysin. Leptin is a lipid metabolism parameter, which is also involved in glucose metabolism and is suggested to correlate with HF burden. While the hormone also seems to interact with neprilysin, potential associations with ARNI therapy have not been investigated yet. (2) Methods: To study this issue, we measured levels of leptin and fructosamine in consecutive 72 HFrEF patients before initiation of ARNI therapy and 3-6 months after initiation of therapy in two European centers. Biomarker levels were correlated with clinical parameters including ejection fraction, LVEF, and NYHA class. (3) Results: During a follow-up of up to 6 months, clinical parameters improved significantly (LVEF: 30.2 ± 7.8% to 37.6 ± 10.0%, (p < 0.001) and a significant improvement of the mean NYHA class with initial 32 patients in NYHA III or IV and 8 patients in NYHA class III/IV during the follow up (p < 0.001). The initial NT-proBNP levels of 2251.5 ± 2566.8 pg/mL significantly improved to 1416.7 ± 2145 pg/mL, p = 0.008) during follow up. ARNI therapy was also associated with an increase in leptin levels (17.5 ± 23.4 µg/L to 22.9 ± 29.3, p < 0.001) and furthermore, affected glucose metabolism indicated by elevation of fructosamine values (333.9 ± 156.8 µmol/L to 454.8 ± 197.8 µmol/L, p = 0.013). (4) Conclusion: while in the early phase of therapy, ARNI promotes clinical improvement of HFrEF, and it also seems to affect fat and glucose parameters, indicating significant metabolic implications of this therapy regime.
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Introduction: While in the CASTLE-AF trial, in patients with atrial fibrillation and heart failure with reduced ejection fraction, interventional therapy using pulmonary vein isolation was associated with outcome improvement, data on cavotricuspid isthmus ablation (CTIA) in atrial flutter (AFL) in the elderly is rare. Methods: We included 96 patients between 60 and 85 years with typical AFL and heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) treated in two medical centers. 48 patients underwent an electrophysiological study with CTIA, whereas 48 patients received rate or rhythm control and guideline-compliant heart failure therapy. Patients were followed up for 2 years, with emphasis on left ventricular ejection fraction (LVEF) over time. Primary endpoints were cardiovascular mortality and hospitalization for cardiac causes. Results: Patients with CTIA showed a significant increase in LVEF after 1 (p < 0.001) and 2 years (p < 0.001) in contrast to baseline LVEF. Improvement of LVEF in the CTIA group was associated with significantly lower 2-year mortality (p = 0.003). In the multivariate regression analysis, CTIA remained the relevant factor associated with LVEF improvement (HR: 2.845 CI:95% 1.044-7.755; p = 0.041). Elderly patients (≥ 70 years) further benefited from CTIA, since they showed a significantly reduced rehospitalization (p = 0.042) and mortality rate after 2 years (p = 0.013). Conclusions: CTIA in patients with typical AFL and HFrEF/HFmrEF was associated with significant improvement of LVEF and reduced mortality rates after 2 years. Patient age should not be a primary exclusion criterion for CTIA, since patients ≥70 years also seem to benefit from intervention in terms of mortality and hospitalization.
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BACKGROUND: We quantified and characterized the outcomes of ablation in persistent atrial fibrillation (PersAF) subjects, and the utility of electroanatomical mapping with a market-released high-density (HD) mapping catheter. METHODS: PersAF subjects received electroanatomical mapping with the Advisor™ HD Grid mapping catheter, Sensor Enabled™ (HD Grid) and radiofrequency (RF) ablation to gather data regarding ablation strategies, mapping efficiency, quality, and outcomes. Subjects were enrolled from January 2019 to April 2020 across 25 international sites and followed for 12 months after the procedure. RESULTS: Three hundred thirty-four PersAF subjects (average age 64.2 years; 76% male; 25.4% previous AF ablation) were enrolled. Multiple map types were generated in a variety of rhythms using HD Grid. Significant differences in low voltage areas were identified in maps generated with the HD Wave Solution™ electrode configuration when compared to the standard configuration, which in some cases, influenced physicians' ablation strategies. PV-only ablation strategy was used in 59.0% of subjects and 34.1% of subjects received PV ablation and additional lesions. Of the subjects, 82.0% were free from recurrent atrial arrhythmias at 12 months and new or increased dose of class I/III antiarrhythmic drugs. About 6.0% of subjects experienced a serious adverse event or serious adverse device effect through 12 months including 1 event deemed related to HD Grid and the index procedure by the investigator and 1 death unrelated to study devices. CONCLUSIONS: The results of this study (NCT03733392) support the safety and utility of electroanatomical mapping with HD Grid in subjects with complex arrhythmias, such as PersAF in the real-world setting.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Ablación por Radiofrecuencia , Humanos , Masculino , Persona de Mediana Edad , Femenino , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Catéteres , Ablación por Catéter/métodos , Resultado del Tratamiento , Venas Pulmonares/cirugíaRESUMEN
Background: As a preventive procedure, minimizing periprocedural risk is crucially important during left atrial appendage closure (LAAC). Methods: We included consecutive patients receiving LAAC at nine centres and assessed the relationship between baseline characteristics and the acute procedural outcome. Major procedural complications were defined as all complications requiring immediate invasive intervention or causing irreversible damage. Logistic regression was performed and included age and left-ventricular function. Furthermore, the association between acute complications and long-term outcomes was evaluated. Results: A total of 405 consecutive patients with a median age of 75 years (37% female) were included. 47% had a history of stroke. Median CHA2DS2-VASc score was 4 (interquartile range, 3−5) and the median HAS-BLED score was 3 (2−4). Major procedural complications occurred in 7% of cases. Low haemoglobin (OR 0.8, 95% CI 0.65−0.99 per g/dL, p = 0.040) and end-stage kidney disease (OR 13.0, CI 2.5−68.5, p = 0.002) remained significant in multivariate analysis. Anaemia (haemoglobin < 12 and < 13 g/dL in female and male patients) increased the risk of complications 2.2-fold. Conclusions: The major complication rate was low in this high-risk patient population undergoing LAAC. End-stage kidney disease and low baseline haemoglobin were independently associated with a higher major complication rate.
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Introduction: COVID-19 survivors reveal an increased long-term risk for cardiovascular disease. Biomarkers like troponins and sST-2 improve stratification of cardiovascular risk. Nevertheless, their prognostic value for identifying long-term cardiovascular risk after having survived COVID-19 has yet to be evaluated. Methods: In this single-center study, admission serum biomarkers of sST-2 and hs-TnI in a single cohort of 251 hospitalized COVID-19 survivors were evaluated. Concentrations were correlated with major cardiovascular events (MACE) defined as cardiovascular death and/or need for cardiovascular hospitalization during follow-up after hospital discharge [FU: 415 days (403; 422)]. Results: MACE was a frequent finding during FU with an incidence of 8.4% (cardiovascular death: 2.8% and/or need for cardiovascular hospitalization: 7.2%). Both biomarkers were reliable indicators of MACE (hs-TnI: sensitivity = 66.7% & specificity = 65.7%; sST-2: sensitivity = 33.3% & specificity = 97.4%). This was confirmed in a multivariate proportional-hazards analysis: besides age (HR = 1.047, 95% CI = 1.012−1.084, p = 0.009), hs-TnI (HR = 4.940, 95% CI = 1.904−12.816, p = 0.001) and sST-2 (HR = 10.901, 95% CI = 4.509−29.271, p < 0.001) were strong predictors of MACE. The predictive value of the model was further improved by combining both biomarkers with the factor age (concordance index hs-TnI + sST2 + age = 0.812). Conclusion: During long-term FU, hospitalized COVID-19 survivors, hs-TnI and sST-2 at admission, were strong predictors of MACE, indicating both proteins to be involved in post-acute sequelae of COVID-19.
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BACKGROUND: The early embryonic divisions of many organisms, including fish, flies, and frogs, are characterized by a very rapid S-phase caused by high rates of replication initiation. In somatic cells, S-phase is much longer due to both a reduction in the total number of initiation events and the imposition of a temporal order of origin activation. The physiological importance of changes in the rate and timing of replication initiation in S-phase remains unclear. RESULTS: Here we assess the importance of the temporal control of replication initiation using a conditional system in budding yeast to drive the early replication of the majority of origins in a single cell cycle. We show that global early replication disrupts the expression of over a quarter of all genes. By deleting individual origins, we show that delaying replication is sufficient to restore normal gene expression, directly implicating origin firing control in this regulation. Global early replication disrupts nucleosome positioning and transcription factor binding during S-phase, suggesting that the rate of S-phase is important to regulate the chromatin landscape. CONCLUSIONS: Together, these data provide new insight into the role of the temporal control of origin firing during S-phase for coordinating replication, gene expression, and chromatin establishment as occurs in the early embryo.
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Cromatina , Proteínas de Saccharomyces cerevisiae , Ciclo Celular/genética , Cromatina/metabolismo , Replicación del ADN , Expresión Génica , Nucleosomas/metabolismo , Origen de Réplica , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Factores de Transcripción/metabolismoRESUMEN
The phytohormone auxin triggers transcriptional reprogramming through a well-characterized perception machinery in the nucleus. By contrast, mechanisms that underlie fast effects of auxin, such as the regulation of ion fluxes, rapid phosphorylation of proteins or auxin feedback on its transport, remain unclear1-3. Whether auxin-binding protein 1 (ABP1) is an auxin receptor has been a source of debate for decades1,4. Here we show that a fraction of Arabidopsis thaliana ABP1 is secreted and binds auxin specifically at an acidic pH that is typical of the apoplast. ABP1 and its plasma-membrane-localized partner, transmembrane kinase 1 (TMK1), are required for the auxin-induced ultrafast global phospho-response and for downstream processes that include the activation of H+-ATPase and accelerated cytoplasmic streaming. abp1 and tmk mutants cannot establish auxin-transporting channels and show defective auxin-induced vasculature formation and regeneration. An ABP1(M2X) variant that lacks the capacity to bind auxin is unable to complement these defects in abp1 mutants. These data indicate that ABP1 is the auxin receptor for TMK1-based cell-surface signalling, which mediates the global phospho-response and auxin canalization.