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1.
J Neurosurg ; : 1-11, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39303312

RESUMEN

OBJECTIVE: The overall benefit of employing a sitting/semisitting position for neurosurgical procedures remains under criticism due to concerns for additional risk, especially the risk of intraoperative venous air embolism (VAE). The aim of this single-center cohort study was to evaluate the frequency and severity of VAEs and associated complications in patients undergoing neurosurgery in the lounging position. METHODS: From 2010 to 2020, 1000 patients, including 172 patients with a patent foramen ovale, underwent surgery in the lounging position for different neurosurgical pathologies. All patients were monitored intraoperatively using continuous transesophageal echocardiography (TEE). The anesthesia team documented any observed incidences of VAEs and scored their severity according to the Tuebingen classification system (TCS) for VAE (TCS-VAE). The patients' clinical condition, radiological findings, and hospital course were subsequently analyzed to assess complications in a retrospective analysis of prospectively collected data. RESULTS: In the cohort of 1000 patients, 5 underwent cervical spine surgery and 995 underwent suboccipital craniotomy. VAE was detected by TEE in 51.4% (95% CI 48.4%-54.5%) of patients, with synchronous changes in end-tidal CO2 (grade 2-5 TCS-VAE) noted in 10.2% (95% CI 8.3%-12.3%). None of the patients presented with hemodynamic instability (grade 5 TCS-VAE). Patients with high-grade VAEs were significantly older (p = 0.02) and had lower BMIs (p = 0.001) than the respective mean value of the cohort. VAE grade was not associated with any of the outcome measures such as Karnofsky Performance Scale score, duration of ventilation, length of intensive care unit stay, and length of hospital stay. Postoperative acute respiratory distress syndrome (ARDS) was diagnosed in 0.3% (95% CI 0.0%-0.7%, n = 3) of all cases, and ARDS was associated with perioperative VAE grade (p = 0.001). No patient suffered a new permanent neurological deficit due to a paradoxical VAE. CONCLUSIONS: In this large cohort, the risk of an intraoperative VAE during neurosurgery in the lounging position was assessed, and contrary to the general perception in the field, no permanent sequelae or fatal adverse events attributable to VAEs were observed. Furthermore, the overall incidence of ARDS was very low. This study clearly establishes that experienced interdisciplinary teams can safely use the lounging position for neurosurgical procedures.

2.
Commun Biol ; 7(1): 1125, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39266696

RESUMEN

During continuous tasks, humans show spontaneous fluctuations in performance, putatively caused by varying attentional resources allocated to process external information. If neural resources are used to process other, presumably "internal" information, sensory input can be missed and explain an apparent dichotomy of "internal" versus "external" attention. In the current study, we extract presumed neural signatures of these attentional modes in human electroencephalography (EEG): neural entrainment and α-oscillations (~10-Hz), linked to the processing and suppression of sensory information, respectively. We test whether they exhibit structured fluctuations over time, while listeners attend to an ecologically relevant stimulus, like speech, and complete a task that requires full and continuous attention. Results show an antagonistic relation between neural entrainment to speech and spontaneous α-oscillations in two distinct brain networks-one specialized in the processing of external information, the other reminiscent of the dorsal attention network. These opposing neural modes undergo slow, periodic fluctuations around ~0.07 Hz and are related to the detection of auditory targets. Our study might have tapped into a general attentional mechanism that is conserved across species and has important implications for situations in which sustained attention to sensory information is critical.


Asunto(s)
Atención , Percepción Auditiva , Electroencefalografía , Humanos , Atención/fisiología , Femenino , Masculino , Adulto , Percepción Auditiva/fisiología , Adulto Joven , Estimulación Acústica , Encéfalo/fisiología
3.
J Neuroophthalmol ; 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39148181

RESUMEN

BACKGROUND: Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in individuals over the age of 50 years. It is associated with conventional vascular risk factors and structural vulnerabilities including "disc-at-risk." We aim to ascertain if a correlation exists between optic nerve head size and the onset of NAION. METHODS: We performed a retrospective chart review of patients with an ICD-10 diagnosis of unilateral or bilateral NAION who underwent optical coherence tomography (OCT) and visual field testing. The primary outcome measure was the disc area as measured on OCT at a follow-up (minimum 6 months after acute vision loss) of the involved (or first involved for bilateral cases) vs fellow eye. The secondary outcome was the cup-to-disc ratio (CDR) of the first vs fellow eye. RESULTS: Seventy-three patients were included, of which 58 (79%) had unilateral and 15 (21%) had bilateral NAION, with a median follow-up of 23 months. Between the first eye involved and the fellow eye, there were no statistically significant differences in the mean disc area (1.69 ± 0.29 vs 1.71 ± 0.29, P = 0.7). However, average CDR (0.41 ± 0.20 vs 0.28 ± 0.18, P < 0.001) and vertical CDR (0.42 ± 0.20 vs 0.28 ± 0.19, P < 0.0001) were significantly larger in the involved eye. CONCLUSIONS: Despite no statistically significant differences in the disc area between the affected eye and the fellow eye, CDR was larger in eyes with a history of NAION compared with fellow eyes. Further research is required to elucidate local factors that may increase the risk of NAION in one eye relative to the other.

4.
Front Psychol ; 15: 1378843, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39171219

RESUMEN

Based on self-determination theory, this study examined the extent to which the satisfaction of the basic psychological needs for autonomy, competence, and social relatedness in instrumental lessons explain the quality and quantity of motivation, which are responsible for persistence and dropout in music schools. This study also investigated whether parental involvement contributes to dropout. A total of 140 music students from Austria (37.16% male, 62.1% female, 0.8% diverse) were surveyed using a quantitative questionnaire. The central variables are the tendency to dropout (dependent variable) and, as predictors, the motivational regulation styles, the satisfaction of basic psychological needs in the classroom and parental involvement. The results of a structural equation model indicated that satisfaction of basic needs in class and parental involvement, mediated by motivation, predicted dropout tendencies. Autonomous motivation in lessons is negatively associated and controlled motivation is positively associated with the tendency to drop out of music schools. Satisfaction of basic psychological needs during lessons and parental involvement predicts autonomous motivation. However, basic psychological needs cannot predict controlled motivation but parental involvement can predict controlled motivation to a limited extent. Finally, this study emphasizes the practical importance of need satisfaction and parental involvement in motivation and continuing to play a musical instrument.

6.
Ann Hematol ; 103(8): 2775-2785, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38967662

RESUMEN

Development of Janus-kinase (JAK) inhibitors has revolutionized the therapeutic landscape for patients with myeloproliferative neoplasia (MPN). Following approval of the first JAK1/2-inhibitor Ruxolitinib, symptoms of this inflammatory disease, characterized by splenomegaly, release of inflammatory cytokines and appearance of thrombosis, could be effectively reduced for the first time. However, JAK-inhibitor treatment is limited in several aspects: 1) duration of response: 3 years after initiation of therapy more than 50% of patients have discontinued JAK-inhibitor treatment due to lack of efficacy or resistance; 2) reduction of disease burden: while effective in reducing inflammation and constitutional symptoms, JAK-inhibitors fail to reduce the malignant clone in the majority of patients and therefore lack long-term efficacy. Early clinical trials for patients with myelofibrosis (MF) have tried to address these issues for patients with suboptimal response to Ruxolitinib therapy while combination therapies with Fedratinib are rare. Recent reports provided first evidence on how the JAK2-V617F mutated myeloid cells may influence T-cell responses. JAK2-V617F promoted the synthesis of PD-L1 in MPN cells leading to limited anti-neoplastic T-cell responses, metabolic changes in T-cells and eventually JAK2-V617F-driven immune-escape of MPN cells. These findings may facilitate the use of immunotherapeutic approaches for JAK-mutated clones. Immune checkpoints refer to a variety of inhibitory pathways that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. The FRACTION study is a single arm, open label Phase II trial investigating the combination of Fedratinib with the PD-1 inhibitor Nivolumab in patients with myelofibrosis and suboptimal or lack of response to JAK-inhibitor therapy. Over a 12 months period the trial assesses longer term outcomes, particularly the effects on clinical outcomes, such as induction of clinical remissions, quality of life and improvement of anemia. No prospective clinical trial data exist for combinations of JAK- and immune-checkpoint-inhibitors in the planned MF study population and this study will provide new findings that may contribute to advancing the treatment landscape for MF patients with suboptimal responses and limited alternatives.


Asunto(s)
Inhibidores de las Cinasas Janus , Nivolumab , Mielofibrosis Primaria , Pirrolidinas , Humanos , Mielofibrosis Primaria/tratamiento farmacológico , Inhibidores de las Cinasas Janus/uso terapéutico , Pirrolidinas/uso terapéutico , Nivolumab/uso terapéutico , Nivolumab/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Alemania , Trastornos Mieloproliferativos/tratamiento farmacológico , Nitrilos/uso terapéutico , Janus Quinasa 2/antagonistas & inhibidores , Janus Quinasa 2/genética , Pirimidinas/uso terapéutico , Pirazoles/uso terapéutico , Bencenosulfonamidas
7.
Cogn Affect Behav Neurosci ; 24(5): 894-911, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39085585

RESUMEN

Theta oscillations support memory formation, but their exact contribution to the communication between prefrontal cortex (PFC) and the hippocampus is unknown. We tested the functional relevance of theta oscillations as a communication link between both areas for memory formation using transcranial alternating current stimulation (tACS). Healthy, young participants learned two lists of Dutch-German word pairs and retrieved them immediately and with a 30-min delay. In the encoding group (N = 30), tACS was applied during the encoding of list 1. List 2 was used to test stimulation aftereffects. In the retrieval group (N = 23), we stimulated during the delayed recall. In both groups, we applied tACS bilaterally at prefrontal and tempo-parietal sites, using either individualized theta frequency or 15 Hz (as control), according to a within-subject design. Stimulation with theta-tACS did not alter overall learning performance. An exploratory analysis revealed that immediate recall improved when word-pairs were learned after theta-tACS (list 2). Applying theta-tACS during retrieval had detrimental effects on memory. No changes in the power of the respective frequency bands were observed. Our results do not support the notion that impacting the communication between PFC and the hippocampus during a task by bilateral tACS improves memory. However, we do find evidence that direct stimulation had a trend for negatively interfering effects during immediate and delayed recall. Hints for beneficial effects on memory only occurred with aftereffects of the stimulation. Future studies need to further examine the effects during and after stimulation on memory formation.


Asunto(s)
Hipocampo , Recuerdo Mental , Corteza Prefrontal , Ritmo Teta , Estimulación Transcraneal de Corriente Directa , Humanos , Masculino , Femenino , Ritmo Teta/fisiología , Adulto Joven , Recuerdo Mental/fisiología , Corteza Prefrontal/fisiología , Adulto , Hipocampo/fisiología
8.
Cancer ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39078647

RESUMEN

BACKGROUND: Ruxolitinib (RUX) is a JAK1/2 inhibitor approved for the therapy of myelofibrosis (MF) based on clinical trials including only intermediate2-high risk (INT2/HIGH) patients. However, RUX is commonly used in intermediate-1 (INT1) patients, with scarce information on responses and outcome. METHODS: The authors investigated the benefit of RUX in 1055 MF patients, included in the "RUX-MF" retrospective study. RESULTS: At baseline (BL), 595 (56.2%) patients were at INT1-risk according to DIPSS (PMF) or MYSEC-PM (SMF). The spleen was palpable at <5 cm, between 5 and 10 cm, and >10 cm below costal margin in 5.9%, 47.4%, and 39.7% of patients, respectively; 300 (54.1%) were highly symptomatic (total symptom score ≥20). High-molecular-risk (HMR) mutations (IDH1/2, ASXL-1, SRSF2, EZH2, U2AF1Q157) were detected in 77/167 patients. A total of 101 (19.2%) patients had ≥1 cytopenia (Hb < 10 g/dL: n.36; PLT <100 x 109/L: n = 43; white blood cells <4 x 109/L: n = 40). After 6 months on RUX, IWG-MRT-defined spleen and symptoms response rates were 26.8% and 67.9%, respectively. In univariate analysis, predictors of SR at 6 months were no HMR mutations odds ratio [OR], 2.0, p = .05], no cytopenia (OR, 2.10; p = .01), and blasts <1% (OR, 1.91; p = .01). In multivariate analysis, absence of HMR maintained a significant association (OR, 2.1 [1.12-3.76]; p = .01). CONCLUSIONS: In INT1 patients, responses were more frequent and durable, whereas toxicity rates were lower compared to INT2/high-risk patients. Presence of HMR mutations, cytopenia, and peripheral blasts identified less-responsive INT1 patients, who may benefit for alternative therapeutic strategies.

9.
Cancer Res ; 84(18): 2985-3003, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-38885318

RESUMEN

Increasing evidence supports the interplay between oncogenic mutations and immune escape mechanisms. Strategies to counteract the immune escape mediated by oncogenic signaling could provide improved therapeutic options for patients with various malignancies. As mutant calreticulin (CALR) is a common driver of myeloproliferative neoplasms (MPN), we analyzed the impact of oncogenic CALRdel52 on the bone marrow (BM) microenvironment in MPN. Single-cell RNA sequencing revealed that CALRdel52 led to the expansion of TGFß1-producing erythroid progenitor cells and promoted the expansion of FoxP3+ regulatory T cells (Treg) in a murine MPN model. Treatment with an anti-TGFß antibody improved mouse survival and increased the glycolytic activity in CD4+ and CD8+ T cells in vivo, whereas T-cell depletion abrogated the protective effects conferred by neutralizing TGFß. TGFß1 reduced perforin and TNFα production by T cells in vitro. TGFß1 production by CALRdel52 cells was dependent on JAK1/2, PI3K, and ERK activity, which activated the transcription factor Sp1 to induce TGFß1 expression. In four independent patient cohorts, TGFß1 expression was increased in the BM of patients with MPN compared with healthy individuals, and the BM of patients with MPN contained a higher frequency of Treg compared with healthy individuals. Together, this study identified an ERK/Sp1/TGFß1 axis in CALRdel52 MPNs as a mechanism of immunosuppression that can be targeted to elicit T-cell-mediated cytotoxicity. Significance: Targeting the mutant calreticulin/TGFß1 axis increases T-cell activity and glycolytic capacity, providing the rationale for conducting clinical trials on TGFß antagonists as an immunotherapeutic strategy in patients with myeloproliferative neoplasms.


Asunto(s)
Calreticulina , Trastornos Mieloproliferativos , Linfocitos T Reguladores , Microambiente Tumoral , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Calreticulina/metabolismo , Animales , Humanos , Ratones , Trastornos Mieloproliferativos/inmunología , Trastornos Mieloproliferativos/metabolismo , Trastornos Mieloproliferativos/patología , Microambiente Tumoral/inmunología , Factor de Crecimiento Transformador beta/metabolismo , Médula Ósea/inmunología , Médula Ósea/metabolismo , Escape del Tumor/inmunología , Ratones Endogámicos C57BL , Factor de Crecimiento Transformador beta1/metabolismo , Mutación
10.
Neurosurg Rev ; 47(1): 291, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38914785

RESUMEN

Some vestibular schwannoma (VS) show cystic morphology. It is known that these cystic VS bear different risk profiles compared to solid VS in surgical treatment. Still, there has not been a direct comparative study comparing both SRS and SURGERY effectiveness in cystic VS. This retrospective bi-center cohort study aims to analyze the management of cystic VS compared to solid VS in a dual center study with both microsurgery (SURGERY) and stereotactic radiosurgery (SRS). Cystic morphology was defined as presence of any T2-hyperintense and Gadolinium-contrast-negative cyst of any size in the pre-interventional MRI. A matched subgroup analysis was carried out by determining a subgroup of matched SURGERY-treated solid VS and SRS-treated solid VS. Functional status, and post-interventional tumor volume size was then compared. From 2005 to 2011, N = 901 patients with primary and solitary VS were treated in both study sites. Of these, 6% showed cystic morphology. The incidence of cystic VS increased with tumor size: 1.75% in Koos I, 4.07% in Koos II, 4.84% in Koos III, and the highest incidence with 15.43% in Koos IV. Shunt-Dependency was significantly more often in cystic VS compared to solid VS (p = 0.024) and patients with cystic VS presented with significantly worse Charlson Comorbidity Index (CCI) compared to solid VS (p < 0.001). The rate of GTR was 87% in cystic VS and therefore significantly lower, compared to 96% in solid VS (p = 0.037). The incidence of dynamic volume change (decrease and increase) after SRS was significantly more common in cystic VS compared to the matched solid VS (p = 0.042). The incidence of tumor progression with SRS in cystic VS was 25%. When comparing EOR in the SURGERY-treated cystic to solid VS, the rate for tumor recurrence was significantly lower in GTR with 4% compared to STR with 50% (p = 0.042). Tumor control in cystic VS is superior in SURGERY, when treated with a high extent of resection grade, compared to SRS. Therapeutic response of SRS was worse in cystic compared to solid VS. However, when cystic VS was treated surgically, the rate of GTR is lower compared to the overall, and solid VS cohort. The significantly higher number of patients with relevant post-operative facial palsy in cystic VS is accredited to the increased tumor size not its sole cystic morphology. Cystic VS should be surgically treated in specialized centers.


Asunto(s)
Microcirugia , Neuroma Acústico , Radiocirugia , Humanos , Radiocirugia/métodos , Microcirugia/métodos , Neuroma Acústico/cirugía , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Anciano , Resultado del Tratamiento , Imagen por Resonancia Magnética , Quistes/cirugía , Adulto Joven
11.
Sci Rep ; 14(1): 14373, 2024 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-38909151

RESUMEN

Continued spread of chronic wasting disease (CWD) through wild cervid herds negatively impacts populations, erodes wildlife conservation, drains resource dollars, and challenges wildlife management agencies. Risk factors for CWD have been investigated at state scales, but a regional model to predict locations of new infections can guide increasingly efficient surveillance efforts. We predicted CWD incidence by county using CWD surveillance data depicting white-tailed deer (Odocoileus virginianus) in 16 eastern and midwestern US states. We predicted the binary outcome of CWD-status using four machine learning models, utilized five-fold cross-validation and grid search to pinpoint the best model, then compared model predictions against the subsequent year of surveillance data. Cross validation revealed that the Light Boosting Gradient model was the most reliable predictor given the regional data. The predictive model could be helpful for surveillance planning. Predictions of false positives emphasize areas that warrant targeted CWD surveillance because of similar conditions with counties known to harbor CWD. However, disagreements in positives and negatives between the CWD Prediction Web App predictions and the on-the-ground surveillance data one year later underscore the need for state wildlife agency professionals to use a layered modeling approach to ensure robust surveillance planning. The CWD Prediction Web App is at https://cwd-predict.streamlit.app/ .


Asunto(s)
Ciervos , Aprendizaje Automático , Enfermedad Debilitante Crónica , Animales , Enfermedad Debilitante Crónica/epidemiología , Enfermedad Debilitante Crónica/diagnóstico , Animales Salvajes , Estados Unidos/epidemiología , Incidencia
13.
GMS Hyg Infect Control ; 19: Doc16, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38766638

RESUMEN

In addition to emissions harmful to the environment, a significant amount of waste is generated in hospitals. In recognition of the fact that medical devices (MDs) contain valuable raw materials, such as rare earth elements, other metals, and high-quality plastics, a recycling concept has been developed. The project was examined for safety and feasibility from a hygiene point of view with sustainability in mind in order to create a reference solution for other areas as applicable. The recycling process begins when the MDs accumulate in the surgical facility and are separated into recyclable and disposable parts. The recyclable parts are subjected to wipe disinfection and collected in closed boxes until they are taken away, while the non-recyclable parts are sent for disposal. The recyclable waste, including the transport boxes, is steam-disinfected in a fractionated vacuum process before recycling. The waste is then recycled, and the emptied transport boxes are made available for re-collection by the surgical facility. The analysis of the overall recycling process shows that infectious risks both for the employees who collect, transport, and recycle the MDs and for the environment are neglectable.

14.
EcoSal Plus ; : eesp00252022, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767346

RESUMEN

Toxin-antitoxin systems are ubiquitous in the prokaryotic world and widely distributed among chromosomes and mobile genetic elements. Several different toxin-antitoxin system types exist, but what they all have in common is that toxin activity is prevented by the cognate antitoxin. In type I toxin-antitoxin systems, toxin production is controlled by an RNA antitoxin and by structural features inherent to the toxin messenger RNA. Most type I toxins are small membrane proteins that display a variety of cellular effects. While originally discovered as modules that stabilize plasmids, chromosomal type I toxin-antitoxin systems may also stabilize prophages, or serve important functions upon certain stress conditions and contribute to population-wide survival strategies. Here, we will describe the intricate RNA-based regulation of type I toxin-antitoxin systems and discuss their potential biological functions.

15.
Clocks Sleep ; 6(2): 211-233, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38651390

RESUMEN

Targeted memory reactivation (TMR) is an effective technique to enhance sleep-associated memory consolidation. The successful reactivation of memories by external reminder cues is typically accompanied by an event-related increase in theta oscillations, preceding better memory recall after sleep. However, it remains unclear whether the increase in theta oscillations is a causal factor or an epiphenomenon of successful TMR. Here, we used transcranial alternating current stimulation (tACS) to examine the causal role of theta oscillations for TMR during non-rapid eye movement (non-REM) sleep. Thirty-seven healthy participants learned Dutch-German word pairs before sleep. During non-REM sleep, we applied either theta-tACS or control-tACS (23 Hz) in blocks (9 min) in a randomised order, according to a within-subject design. One group of participants received tACS coupled with TMR time-locked two seconds after the reminder cue (time-locked group). Another group received tACS in a continuous manner while TMR cues were presented (continuous group). Contrary to our predictions, we observed no frequency-specific benefit of theta-tACS coupled with TMR during sleep on memory performance, neither for continuous nor time-locked stimulation. In fact, both stimulation protocols blocked the TMR-induced memory benefits during sleep, resulting in no memory enhancement by TMR in both the theta and control conditions. No frequency-specific effect was found on the power analyses of the electroencephalogram. We conclude that tACS might have an unspecific blocking effect on memory benefits typically observed after TMR during non-REM sleep.

16.
Ann Hematol ; 103(7): 2299-2310, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38438627

RESUMEN

Interferon-based therapies, such as ropeginterferon alfa-2b have emerged as promising disease-modifying agents for myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET). Current ET treatments aim to normalize hematological parameters and reduce the thrombotic risk, but they do not modify the natural history of the disease and hence, have no impact on disease progression. Ropeginterferon alfa-2b (trade name BESREMi®), a novel, monopegylated interferon alfa-2b with an extended administration interval, has demonstrated a robust and sustained efficacy in polycythemia vera (PV) patients. Given the similarities in disease pathophysiology and treatment goals, ropeginterferon alfa-2b holds promise as a treatment option for ET. The ROP-ET trial is a prospective, multicenter, single-arm phase III study that includes patients with ET who are intolerant or resistant to, and/or are ineligible for current therapies, such as hydroxyurea (HU), anagrelide (ANA), busulfan (BUS) and pipobroman, leaving these patients with limited treatment options. The primary endpoint is a composite response of hematologic parameters and disease-related symptoms, according to modified European LeukemiaNet (ELN) criteria. Secondary endpoints include improvements in symptoms and quality of life, molecular response and the safety profile of ropeginterferon alfa-2b. Over a 3-year period the trial assesses longer term outcomes, particularly the effects on allele burden and clinical outcomes, such as disease-related symptoms, vascular events and disease progression. No prospective clinical trial data exist for ropeginterferon alfa-2b in the planned ET study population and this study will provide new findings that may contribute to advancing the treatment landscape for ET patients with limited alternatives. TRIAL REGISTRATION: EU Clinical Trials Register; EudraCT, 2023-505160-12-00; Registered on October 30, 2023.


Asunto(s)
Interferón alfa-2 , Interferón-alfa , Polietilenglicoles , Proteínas Recombinantes , Trombocitemia Esencial , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Interferón alfa-2/uso terapéutico , Interferón alfa-2/efectos adversos , Interferón-alfa/uso terapéutico , Interferón-alfa/efectos adversos , Polietilenglicoles/uso terapéutico , Polietilenglicoles/efectos adversos , Polietilenglicoles/administración & dosificación , Estudios Prospectivos , Proteínas Recombinantes/uso terapéutico , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/administración & dosificación , Trombocitemia Esencial/tratamiento farmacológico , Resultado del Tratamiento , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase III como Asunto
17.
Int Wound J ; 21(3): e14811, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38477866

RESUMEN

To investigate the effectiveness of antimicrobial agents against wound infections, experiments using either 2D cultures with planktonic microorganisms or animal infection models are frequently carried out. However, the transferability of the results to human skin is limited by the lack of complexity of the 2D models or by the poor translation of the results from animal models. Hence, there is a need for wound infection models capable of assessing antimicrobial agents. In this study, an easily standardized wound infection model was established. This model consists of a mechanically wounded human skin model on a collagen matrix infected with various clinically relevant bacteria. Infection of the model led to recognition of the pathogens and induction of an inflammatory response. The untreated infection spread over time, causing significant tissue damage. By applying an antimicrobial-releasing wound dressing, the bacterial load could be reduced and the success of the treatment could be further measured by a decrease in the inflammatory reaction. In conclusion, this wound infection model can be used to evaluate new antimicrobial therapeutics as well as to study host-pathogen interactions.


Asunto(s)
Antiinfecciosos , Infección de Heridas , Animales , Humanos , Carga Bacteriana , Vendajes , Interacciones Huésped-Patógeno
19.
Bone Joint J ; 106-B(4): 344-351, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38555949

RESUMEN

Aims: Revision total hip arthroplasty in patients with Vancouver type B3 fractures with Paprosky type IIIA, IIIB, and IV femoral defects are difficult to treat. One option for Paprovsky type IIIB and IV defects involves modular cementless, tapered, revision femoral components in conjunction with distal interlocking screws. The aim of this study was to analyze the rate of reoperations and complications and union of the fracture, subsidence of the stem, mortality, and the clinical outcomes in these patients. Methods: A total of 46 femoral components in patients with Vancouver B3 fractures (23 with Paprosky type IIIA, 19 with type IIIB, and four with type IV defects) in 46 patients were revised with a transfemoral approach using a modular, tapered, cementless revision Revitan curved femoral component with distal cone-in-cone fixation and prospectively followed for a mean of 48.8 months (SD 23.9; 24 to 112). The mean age of the patients was 80.4 years (66 to 100). Additional distal interlocking was also used in 23 fractures in which distal cone-in-cone fixation in the isthmus was < 3 cm. Results: One patient (2.2%) died during the first postoperative year. After six months, 43 patients (93.5%) had osseous, and three had fibrous consolidation of the fracture and the bony flap, 42 (91.3%) had bony ingrowth and four had stable fibrous fixation of the stem. No patient had radiolucency around the interlocking screws and no screw broke. One patient had non-progressive subsidence and two had a dislocation. The mean Harris Hip Score increased from of 57.8 points (SD 7.9) three months postoperatively to 76.1 points (SD 10.7) 24 months postoperatively. Conclusion: The 2° tapered, fluted revision femoral component with distal cone-in-cone-fixation, combined with additional distal interlocking in patients with bony deficiency at the isthmus, led to reproducibly good results in patients with a Vancouver B3 fracture and Paprosky type IIIA, IIIB, and IV defects with regard to union of the fracture, subsidence or loosening of the stem, and clinical outcomes.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Fracturas del Fémur , Prótesis de Cadera , Fracturas Periprotésicas , Humanos , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/métodos , Fracturas Periprotésicas/cirugía , Fracturas Periprotésicas/etiología , Prótesis de Cadera/efectos adversos , Resultado del Tratamiento , Diseño de Prótesis , Reoperación/métodos , Fracturas del Fémur/cirugía , Estudios Retrospectivos
20.
J Appl Microbiol ; 135(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38439676

RESUMEN

AIMS: We aimed to develop a method to assess the virucidal performance of domestic laundry in a lab-scale washing machine (Rotawash) based on EN 17658. METHODS AND RESULTS: For method development, virus recovery was investigated after drying on cotton carriers for three test viruses murine norovirus (MNV), modified vaccinia virus Ankara (MVA), and bovine coronavirus (BCoV), followed by washing simulations in flasks and Rotawash. MNV and MVA demonstrated sufficient recovery from carriers after drying and washing (up to 40°C and 60 min). BCoV exhibited lower recovery, indicating less relevance as a test virus. Rotawash efficacy tests conducted with MNV, a resistant, non-enveloped virus, showed limited efficacy of a bleach-free detergent, aligning with results from a domestic washing machine. Rotawash washes achieved higher reductions in infectious virus titers than suspension tests, indicating the role of washing mechanics in virus removal. CONCLUSIONS: This study established a practical method to test the virucidal efficacy of laundry detergents in Rotawash, simulating domestic washing.


Asunto(s)
Detergentes , Norovirus , Bovinos , Animales , Ratones , Detergentes/farmacología , Textiles
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