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1.
World Neurosurg ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39098502

RESUMEN

OBJECTIVE: Postural abnormalities are a debilitating symptom of Parkinson's disease (PD) that may require spinal intervention. Camptocormia is a unique abnormality most seen in PD, defined by a severe forward-flexion of the trunk that completely resolves when supine. The condition presents a challenge due to an undefined pathophysiology and optimal therapeutic approach in a high-risk patient population. In this study, the authors systematically reviewed the literature regarding the use of spine surgery for the treatment of camptocormia in PD. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were systematically queried for studies involving spine surgery as treatment of PD-associated camptocormia. Studies involving nonsurgical management, deep brain stimulation (DBS), non-camptocormic PD patients undergoing surgery, or were out of scope were excluded. RESULTS: The search resulted in 5 studies, with a total of 19 PD patients with camptocormia who underwent spine surgery (73.7% female). The mean age was 69.5 years (range, 59 - 83), and mean PD duration was 69.5 months (range, 36 - 84). Out of 19 patients, 11 required surgical revision (57.9%), with an average of 0.68 revisions per patient (range, 0-2). Radiographic and patient-reported outcomes were inconsistently reported yet showed improvement. Ultimately, 18 patients were reported to have positive outcomes. CONCLUSION: Despite an increased risk of complication and revision that is inherent to PD patients, spine surgery has been proven as a reasonable alternative that should be prospectively studied further, as 18/19 patients had favorable outcomes.

2.
J Clin Oncol ; : JCO2302503, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39094065

RESUMEN

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.LIBRETTO-001 is a registrational phase I/II, single-arm, open-label study of selpercatinib in patients with RET (REarranged during Transfection)-activated cancers (ClinicalTrials.gov identifier: NCT03157128). We present long-term safety and efficacy from LIBRETTO-001 in patients with RET-mutant medullary thyroid cancer (MTC; n = 324) and RET fusion-positive thyroid cancer encompassing different histological subtypes (TC; n = 66). At the data cutoff of January 2023, the objective response rate was 82.5% among patients with cabozantinib/vandetanib-naïve MTC and 95.8% among patients with treatment-naïve TC. At a median follow-up time of 42.4 and 44.0 months in patients with cabozantinib/vandetanib-naïve and pretreated MTC, the median progression-free survival (PFS) was not reached and 41.4 months, respectively. At a median follow-up time of 24.9 and 30.4 months in patients with treatment-naïve and pretreated TC, the median PFS was not reached and 27.4 months, respectively. Three-year PFS rates were 75.2% and 87.3% among patients with cabozantinib/vandetanib-naïve MTC and treatment-naïve TC, respectively. Median PFS was similar to median duration of response for each patient group. The safety profile of selpercatinib was consistent with previous reports. With an additional follow-up of 37 months and 228 more patients from the last disclosure, selpercatinib continued to provide durable and robust responses in treatment-naïve and previously treated patients with RET-mutant MTC and RET fusion-positive TC.

3.
J Nat Prod ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39038492

RESUMEN

The Solanaceae plant family contains at least 98 genera and over 2700 species. The Duboisia genus stands out for its ability to produce pyridine and tropane alkaloids, which are relatively poorly characterized at the phytochemical level. In this study, we analyzed dried leaves of Duboisia spp. using supercritical CO2 extraction and ultra-high-pressure liquid chromatography coupled to high-resolution tandem mass spectrometry, followed by feature-based molecular networking. Thirty-one known tropane alkaloids were putatively annotated, and the identity of six (atropine, scopolamine, anisodamine, aposcopolamine, apoatropine, and noratropine) were identified using reference standards. Two new granatane alkaloids connected in the molecular network were highlighted from Duboisia myoporoides, and their α-granatane tropate and α-granatane isovalerate structures were unambiguously established by semisynthesis.

4.
Front Pharmacol ; 15: 1417945, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39045055

RESUMEN

Cyclophilins (Cyps), characterized as peptidyl-prolyl cis-trans isomerases (PPIases), are highly conserved and ubiquitous, playing a crucial role in protein folding and cellular signaling. This review summarizes the biochemical pathways mediated by Cyps, including their involvement in pathological states such as viral replication, inflammation, and cancer progression, to underscore the therapeutic potential of Cyp inhibition. The exploration of Cyp inhibitors (CypI) in this review, particularly non-immunosuppressive cyclosporine A (CsA) derivatives, highlights their significance as therapeutic agents. The structural and functional nuances of CsA derivatives are examined, including their efficacy, mechanism of action, and the balance between therapeutic benefits and off-target effects. The landscape of CypI is evaluated to emphasize the clinical need for targeted approaches to exploit the complex biology of Cyps and to propose future directions for research that may enhance the utility of non-immunosuppressive CsA derivatives in treating diseases where Cyps play a key pathological role.

5.
Sci Rep ; 14(1): 17566, 2024 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080362

RESUMEN

Associations between the fat mass and obesity-associated (FTO) gene and obesity are well-established. However, recent studies have linked FTO to addiction phenotypes and dopaminergic signaling, thus suggesting broader psychiatric implications. We explored this assumption by conducting a phenome-wide association study across 4756 genome-wide association studies, identifying 23-26 psychiatric traits associated with FTO at the multiple-corrected significance level. These traits clustered into four categories: substance use, chronotype/sleep, well-being, and neuroticism. To validate these findings, we analyzed a functionally suggestive FTO variant (rs1421085) in a separate cohort, examining its impact on (i) alcohol use based on the Alcohol Use Disorders Identification Test (AUDIT), (ii) subjective well-being based on the WHO (Ten) Well-Being Index, and (iii) neuroticism based on Schafer's Five Factor Model or the Karolinska Scales of Personality. Our results confirmed a direct association between rs1421085 and neuroticism that was independent of age, sex, alcohol use, body mass index (BMI), and childhood adversities. Interestingly, while no direct association with alcohol intake was observed, both cross-sectional and lagged longitudinal mediation analyses uncovered indirect relationships between rs1421085 and problematic alcohol use (AUDIT-P), with increased neuroticism acting as the intermediary. Mediation analyses also supported an indirect effect of rs1421085 on lower well-being through the pathways of increased neuroticism and BMI. Our study is the first to validate a direct association between FTO and neuroticism. However, additional studies are warranted to affirm the causal pathways linking FTO to well-being and alcohol use through neuroticism.


Asunto(s)
Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Estudio de Asociación del Genoma Completo , Neuroticismo , Humanos , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Masculino , Femenino , Adulto , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Alcoholismo/genética , Consumo de Bebidas Alcohólicas/genética , Índice de Masa Corporal , Predisposición Genética a la Enfermedad
6.
J Eur Acad Dermatol Venereol ; 38 Suppl 7: 12-20, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39051131

RESUMEN

BACKGROUND: Acne vulgaris is a common chronic inflammatory disorder of the pilosebaceous unit, characterized by papules, pustules and/or nodules manifesting primarily on the face and/or upper back that can leave scars, post-inflammatory hyperpigmentation (PIH) and erythema (PIE). OBJECTIVE: To evaluate the anti-inflammatory properties of a protein-free sap extruded from Rhealba® oat plantlets and a Garcinia mangostana extract on Cutibacterium acnes-induced inflammation in vitro and assess the tolerability and efficacy of a dermocosmetic product containing these actives in subjects with mild-to-moderate acne. METHODS: Monocyte-derived dendritic cells (Mo-DCs) from acne patients were stimulated with a planktonic culture of C. acnes and cytokine production was evaluated before and after addition of the test extracts by RT-PCR and ELISA. The clinical study was conducted in subjects with mild-to-moderate acne who applied the product to their face and upper back twice-daily for 2 months. RESULTS: Cutibacterium acnes-induced IL-6, IL-12p40, IL-10 and TNFα synthesis was reduced by the addition of the Garcinia mangostana extract and oat sap in vitro. The clinical study included 54 subjects. The 2-month, twice-daily application of the test product to the whole face and acne-affected areas on the upper back was well tolerated. It led to significant decreases in the number of retentional (-21% for 69% of subjects at D57) and inflammatory (-35% for 79% of subjects at D57) acne lesions, as well as a decrease in Global Acne Evaluation severity scores (2.5 at D1, 2.2 at D29 and 2.1 at D57). The dermatologist also rated the product as effective or very effective in most subjects with PIE (82%; n = 33/40) and PIH (70%; n = 8/11) at D57. CONCLUSION: The actives demonstrated anti-inflammatory effects in vitro, and the dermocosmetic product showed good clinical efficacy and tolerability in subjects with mild-to-moderate acne, supporting the use of this product in acne management.


Asunto(s)
Acné Vulgar , Avena , Garcinia mangostana , Extractos Vegetales , Humanos , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/microbiología , Garcinia mangostana/química , Extractos Vegetales/farmacología , Femenino , Masculino , Adulto , Adulto Joven , Adolescente , Índice de Severidad de la Enfermedad , Propionibacterium acnes/efectos de los fármacos
7.
Eur Stroke J ; : 23969873241255867, 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38853524

RESUMEN

RATIONALE: Novel therapeutic approaches are needed in stroke recovery. Whether pharmacological therapies are beneficial for enhancing stroke recovery is unclear. Dopamine is a neurotransmitter involved in motor learning, reward, and brain plasticity. Its prodrug levodopa is a promising agent for stroke recovery. AIM AND HYPOTHESIS: To investigate the hypothesis that levodopa, in addition to standardized rehabilitation therapy based on active task training, results in an enhancement of functional recovery in acute ischemic or hemorrhagic stroke patients compared to placebo. DESIGN: ESTREL (Enhancement of Stroke REhabilitation with Levodopa) is a randomized (ratio 1:1), multicenter, placebo-controlled, double-blind, parallel-group superiority trial. PARTICIPANTS: 610 participants (according to sample size calculation) with a clinically meaningful hemiparesis will be enrolled ⩽7 days after stroke onset. Key eligibility criteria include (i) in-hospital-rehabilitation required, (ii) capability to participate in rehabilitation, (iii) previous independence in daily living. INTERVENTION: Levodopa 100 mg/carbidopa 25 mg three times daily, administered for 5 weeks in addition to standardized rehabilitation. The study intervention will be initiated within 7 days after stroke onset. COMPARISON: Matching placebo plus standardized rehabilitation. OUTCOMES: The primary outcome is the between-group difference of the Fugl-Meyer-Motor Assessment (FMMA) total score measured 3 months after randomization. Secondary outcomes include patient-reported health and wellbeing (PROMIS 10 and 29), patient-reported assessment of improvement, Rivermead Mobility Index, modified Rankin Scale, National Institutes of Health Stroke Scale (NIHSS), and as measures of harm: mortality, recurrent stroke, and serious adverse events. CONCLUSION: The ESTREL trial will provide evidence of whether the use of Levodopa in addition to standardized rehabilitation in stroke patients leads to better functional recovery compared to rehabilitation alone.

8.
Behav Res Methods ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834812

RESUMEN

Video recordings accurately capture facial expression movements; however, they are difficult for face perception researchers to standardise and manipulate. For this reason, dynamic morphs of photographs are often used, despite their lack of naturalistic facial motion. This study aimed to investigate how humans perceive emotions from faces using real videos and two different approaches to artificially generating dynamic expressions - dynamic morphs, and AI-synthesised deepfakes. Our participants perceived dynamic morphed expressions as less intense when compared with videos (all emotions) and deepfakes (fearful, happy, sad). Videos and deepfakes were perceived similarly. Additionally, they perceived morphed happiness and sadness, but not morphed anger or fear, as less genuine than other formats. Our findings support previous research indicating that social responses to morphed emotions are not representative of those to video recordings. The findings also suggest that deepfakes may offer a more suitable standardized stimulus type compared to morphs. Additionally, qualitative data were collected from participants and analysed using ChatGPT, a large language model. ChatGPT successfully identified themes in the data consistent with those identified by an independent human researcher. According to this analysis, our participants perceived dynamic morphs as less natural compared with videos and deepfakes. That participants perceived deepfakes and videos similarly suggests that deepfakes effectively replicate natural facial movements, making them a promising alternative for face perception research. The study contributes to the growing body of research exploring the usefulness of generative artificial intelligence for advancing the study of human perception.

9.
Nat Comput Sci ; 4(6): 412-422, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38877120

RESUMEN

Apparent parallels between natural language and antibody sequences have led to a surge in deep language models applied to antibody sequences for predicting cognate antigen recognition. However, a linguistic formal definition of antibody language does not exist, and insight into how antibody language models capture antibody-specific binding features remains largely uninterpretable. Here we describe how a linguistic formalization of the antibody language, by characterizing its tokens and grammar, could address current challenges in antibody language model rule mining.


Asunto(s)
Anticuerpos , Lingüística , Humanos , Anticuerpos/inmunología
10.
Future Oncol ; : 1-12, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38884254

RESUMEN

WHAT IS THIS SUMMARY ABOUT?: This summary describes the results from a phase 2 study called FOENIXCCA2. The study evaluated treatment with futibatinib in people with a rare form of advanced bile duct cancer called intrahepatic cholangiocarcinoma (or iCCA), where the tumors have changes in the structure of a gene called FGFR2. These changes include FGFR2 gene fusions. Bile duct cancer often returns after surgery or cannot be treated by surgery because the tumor has spread, so it requires treatment with chemotherapy. People live for a median of 1 year after their first chemotherapy treatment and 6 months after their second treatment. This study included people whose cancer had grown/spread after one or more chemotherapy treatments. The aims of the study were to see if futibatinib could shrink the size of tumors and stop the cancer from growing/spreading and to see how long people lived when treated with futibatinib. Clinicians also looked at side effects from taking futibatinib and at how it affected people's quality of life. WHAT WERE THE RESULTS?: Futibatinib treatment shrank tumors in over 80% of people who received treatment. Tumors shrank by at least 30% in 42% of people. Futibatinib stopped tumors from growing/spreading for a median of 9.7 months. People who took the medicine lived for a median of 21.7 months, and 72% of people were still alive after 1 year. Side effects from taking futibatinib were like those reported for similar medicines, and clinicians considered the side effects to be manageable by adjusting the dose of futibatinib or treating the side effects. Most people reported that their quality of life stayed the same or improved during the first 9 months of taking futibatinib. WHAT DO THE RESULTS MEAN?: The results support the use of futibatinib for treating people with advanced bile duct cancer. Based on the results of this study, futibatinib is now approved in the US, Europe, and Japan. Futibatinib is approved for treating adults with advanced bile duct cancer who have received previous treatment for their cancer, and whose tumors have a gene fusion or other change in the FGFR2 gene.Clinical Trial Registration: NCT02052778 (FOENIX-CCA2).

12.
Clin Nutr ESPEN ; 63: 74-83, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38923468

RESUMEN

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by recurrent inflammation of the gastrointestinal tract and has been linked to an imbalance in gut bacteria. Synbiotics, which combine probiotics and prebiotics, are emerging as potential IBD treatments. AIM: To examine the effects of four synbiotic formulations on intestinal inflammation and peripheral biomarkers in a rodent IBD model of both sexes. METHODS: Colitis was induced in male and female C57BL/6 mice using 1% dextran sulfate sodium (DSS). Concurrently, a non-exposed control group was maintained. Starting on day 4 post-induction, DSS-exposed mice received one of four synbiotic preparations (Synbio1-4 composed of lactic acid bacteria, Bifidobacterium and dietary fibres), an anti-inflammatory drug used to treat IBD (mesalazine), or placebo (water) until day 14. Clinical symptoms and body weight were monitored daily. Blood samples (taken on days -3, 4, and 14, relative to DSS introduction), were used to analyze plasma biomarkers. At the end of the study, intestinal tissues underwent histological and morphological evaluation. RESULTS: Compared to placebo, the Synbio1-, 2- and 3-treated groups had improved clinical scores by day 14. Synbio1 was the only preparation that led to clinical improvements to scores comparable to those of controls. The Synbio1-and 3-treated groups also demonstrated histological improvements in the colon. Plasma biomarker analyses revealed significant Synbio1-induced changes in plasma IL17A, VEGFD, and TNFRSF11B levels that correlated with improved clinical or histological scores. Sex-stratified analyses revealed that most therapeutic-like effects were more pronounced in females. CONCLUSION: Our findings underscore the potential therapeutic benefits of specific synbiotics for IBD management. However, further research is needed to validate these outcomes in human subjects.

13.
Pediatr Allergy Immunol ; 35(6): e14140, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38822743

RESUMEN

Basophil activation test (BAT) or the mast cell activation test (MAT) are two in vitro tests that are currently being studied in food allergy as diagnostic tools as an alternative to oral food challenges (OFCs). We conducted a meta-analysis on BAT and MAT, assessing their specificity and sensitivity in diagnosing peanut allergy. Six databases were searched for studies on patients suspected of having peanut allergy. Studies using BAT or MAT to peanut extract and/or component as diagnostic tools with results given in percentage of CD63 activation were included in this meta-analysis. Study quality was evaluated with the QUADAS-2 tool. On the 11 studies identified, eight focused exclusively on children, while three included a mixed population of adults and children. Only one study provided data on MAT, precluding us from conducting a statistical analysis. The diagnostic accuracy of BAT was higher when stimulated with peanut extract rather than Ara h 2 with a pooled specificity of 96% (95% CI: 0.89-0.98) and sensitivity of 0.86 (95% CI: 0.74-0.93). The sensitivity and specificity of BATs in discriminating between allergic and sensitized patients were studied as well, with pooled analysis revealing a sensitivity of 0.86 (95% CI: 0.74; 0.93) and a specificity of 0.97 (95% CI: 0.94, 0.98). BATs, when stimulated with peanut extracts, exhibit a satisfactory sensitivity and specificity for the diagnosis of peanut allergy and can help to discriminate between allergic individuals and those only sensitized to peanuts. More investigations on the potential for MATs diagnostic methods are warranted.


Asunto(s)
Hipersensibilidad al Cacahuete , Sensibilidad y Especificidad , Hipersensibilidad al Cacahuete/diagnóstico , Hipersensibilidad al Cacahuete/inmunología , Humanos , Basófilos/inmunología , Arachis/inmunología , Niño , Mastocitos/inmunología , Prueba de Desgranulación de los Basófilos/métodos , Alérgenos/inmunología , Adulto
14.
Endocr Connect ; 13(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38934378

RESUMEN

Background: Prednisolone and prednisone are recommended treatment options for adults with congenital adrenal hyperplasia (CAH); however, there is no randomised comparison of prednis(ol)one with hydrocortisone. Design: Six-month open-label randomised phase 3 study and interim analysis of a single-arm extension study was the design of the study. Methods: The method of the study was hydrocortisone dose equivalent and 09:00-h 17-hydroxyprogesterone (17OHP) from 48 patients taking prednis(ol)one at baseline. Results: At baseline, the median hydrocortisone dose equivalent was 30 mg/day and 17OHP was < 36 nmol/L (3× upper limit of normal) in 56% of patients. Patients were randomised to continue prednis(ol)one or switch to modified-release hydrocortisone capsule (MRHC) at the same hydrocortisone-equivalent dose. At 4 weeks, 94% on MRHC and 71% on prednis(ol)one had 17OHP < 36 nmol/L. At 18 months in the extension study of MRHC, the median MRHC dose was 20 mg/day and 82% had 17OHP < 36 nmol/L. The per cent of patients with 17OHP < 36 nmol/L on a hydrocortisone dose equivalent ≤ 25 mg/day was greater at 18 months in the extension study on MRHC than while on prednis(ol)one at baseline: 57% vs 27%, P = 0.04. In the randomised study, no patients had an adrenal crisis on MRHC and one on prednisolone. In the extension study (221 patient years), there were 12 adrenal crises in 5 patients (5.4/100 patient years). Conclusion: MRHC reduces 17OHP at 09:00 h compared to prednis(ol)one and the dose of MRHC can be down-titrated over time in the majority of patients.

15.
Support Care Cancer ; 32(6): 353, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38748187

RESUMEN

PURPOSE: The integration of palliative care (PC) into oncological management is recommended well before the end of life. It improves quality of life and symptom control and reduces the aggressiveness of end-of-life care. However, its appropriate timing is still debated. Entry into an early-phase clinical trial (ECT) represents hopes for the patient when standard treatments have failed. It is an opportune moment to integrate PC to preserve the patient's general health status. The objective of this study was to evaluate the motives for acceptance or refusal of early PC management in patients included in an ECT. METHODS: Patients eligible to enter an ECT were identified and concomitant PC was proposed. All patients received exploratory interviews conducted by a researcher. Their contents were analyzed in a double-blind thematic analysis with a self-determination model. RESULTS: Motives for acceptance (PC acceptors: n = 27) were both intrinsic (e.g., pain relief, psychological support, anticipation of the future) and extrinsic (e.g., trust in the medical profession, for a relative, to support the advance of research). Motives for refusal (PC refusers: n = 3) were solely intrinsic (e.g., PC associated with death, negative representation of psychological support, no need for additional care, claim of independence). CONCLUSIONS: The motives of acceptors and refusers are not internalized in the same way and call for different autonomy needs. Acceptors and refusers are influenced by opposite representations of PC and a different perception of mixed management.


Asunto(s)
Motivación , Neoplasias , Cuidados Paliativos , Humanos , Cuidados Paliativos/psicología , Cuidados Paliativos/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Francia , Neoplasias/psicología , Neoplasias/terapia , Aceptación de la Atención de Salud/psicología , Anciano de 80 o más Años , Adulto , Negativa del Paciente al Tratamiento/psicología , Ensayos Clínicos como Asunto/psicología , Calidad de Vida , Método Doble Ciego , Investigación Cualitativa
16.
Exp Brain Res ; 242(7): 1623-1643, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38780803

RESUMEN

The size-weight illusion is a phenomenon where a smaller object is perceived heavier than an equally weighted larger object. The sensorimotor mismatch theory proposed that this illusion occurs because of a mismatch between efferent motor commands and afferent sensory feedback received when lifting large and small objects (i.e., the application of too little and too much lifting force, respectively). This explanation has been undermined by studies demonstrating a separation between the perceived weight of objects and the lifting forces that are applied on them. However, this research suffers from inconsistencies in the choice of lifting force measures reported. Therefore, we examined the contribution of sensorimotor mismatch in the perception of weight in the size-weight illusion and in non-size-weight illusion stimuli and evaluated the use of a lifting force aggregate measure comprising the four most common lifting force measures used in previous research. In doing so, the sensorimotor mismatch theory was mostly supported. In a size-weight illusion experiment, the lifting forces correlated with weight perception and, contrary to some earlier research, did not adapt over time. In a non-size-weight illusion experiment, switches between lifting light and heavy objects resulted in perceiving the weight of these objects differently compared to no switch trials, which mirrored differences in the manner participants applied forces on the objects. Additionally, we reveal that our force aggregate measure can allow for a more sensitive and objective examination of the effects of lifting forces on objects.


Asunto(s)
Ilusiones , Percepción del Tamaño , Percepción del Peso , Humanos , Percepción del Peso/fisiología , Ilusiones/fisiología , Masculino , Femenino , Adulto Joven , Adulto , Percepción del Tamaño/fisiología , Retroalimentación Sensorial/fisiología
18.
Gynecol Oncol ; 186: 182-190, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38718741

RESUMEN

OBJECTIVES: The phase 2, multicohort, open-label LEAP-005 study evaluated lenvatinib plus pembrolizumab in patients with previously treated advanced solid tumors. We report outcomes from the ovarian cancer cohort. METHODS: Eligible patients had metastatic/unresectable ovarian cancer and had received 3 previous lines of therapy. Patients received lenvatinib 20 mg/day plus pembrolizumab 200 mg every 3 weeks. Treatment continued until progression, unacceptable toxicity, or (for pembrolizumab) completion of 35 cycles. Primary endpoints were objective response rate (ORR) per RECIST version 1.1 and safety. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS: Thirty-one patients were enrolled. 39% had high grade serous ovarian cancer, 23% were platinum-sensitive, 55% were platinum-resistant, 23% were platinum-refractory, and 84% had tumors that had a PD-L1 combined positive (CPS) score ≥1. ORR (95% CI) was 26% (12%-45%) by investigator assessment and 35% (19%-55%) by blinded independent central review (BICR). Per BICR, median DOR was 9.2 (1.5+ to 37.8+) months. ORRs (95% CI) by BICR were 35% (9/26 patients; 17%-56%) for PD-L1 CPS ≥ 1 disease and 50% (2/4 patients; 7%-93%) for PD-L1 CPS < 1 disease. Median (95% CI) PFS by BICR and OS were 6.2 (4.0-8.5) months and 21.3 (11.7-32.3) months, respectively. Treatment-related AEs occurred in 94% of patients (grade 3-4, 77%). One patient died from treatment-related hypovolemic shock. CONCLUSIONS: Lenvatinib plus pembrolizumab demonstrated antitumor activity as fourth line therapy in patients with advanced ovarian cancer, and no unanticipated safety signals were identified. Responses were observed regardless of PD-L1 status.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Ováricas , Compuestos de Fenilurea , Quinolinas , Humanos , Femenino , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Quinolinas/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Persona de Mediana Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Adulto , Supervivencia sin Progresión , Anciano de 80 o más Años , Estudios de Cohortes
19.
Res Pract Thromb Haemost ; 8(3): 102396, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38694839

RESUMEN

Background: Plantar vein thrombosis (PVT) is a rare condition. Less than 50 cases have been described in the literature. Evidence from interventional and observational studies is sparse or lacking. Objectives: To describe a consecutive cohort of patients diagnosed with PVT at a single academic institution over the past 17 years. Methods: We searched medical charts from patients managed at the University Hospital Zurich between 2005 and 2022. PVT was detected through sonography (eg, in the presence of a noncompressible deep vein) and/or magnetic resonance (eg, a vein with a filling defect on non-contrast-enhanced or contrast-enhanced imaging). The study was approved by the local ethics commission. Results: We identified 45 patients who had been assessed for PVT. After manual check of these cases, we selected 16 patients with a confirmed, objective diagnosis. Median age was 62 (25th-75th percentiles, 46-73) years, and 9 (56%) patients were women. All patients were symptomatic, usually reporting local pain in the foot (100%) and swelling (67%). The most frequent risk factors were cancer (n = 6; 38%) and prior deep vein thrombosis (n = 4; 25%). Overall, 80% of patients received oral anticoagulation and 20% received parenteral anticoagulation for a median of 90 days. Over a median follow-up of 17 months, 2 (12.5%) recurrent venous thromboembolism events were recorded following the discontinuation of anticoagulation. Index vein recanalization occurred in all 15 survivors. One patient died from cancer 2 years after PVT diagnosis. Conclusion: We provided initial information on the clinical characteristics, treatment, and course of PVT, which partly resembles that of distal deep vein thrombosis.

20.
J Immunol ; 212(10): 1523-1529, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38709994

RESUMEN

The study of S100A9 in viral infections has seen increased interest since the COVID-19 pandemic. S100A8/A9 levels were found to be correlated with the severity of COVID-19 disease, cytokine storm, and changes in myeloid cell subsets. These data led to the hypothesis that S100A8/A9 proteins might play an active role in COVID-19 pathogenesis. This review explores the structures and functions of S100A8/9 and the current knowledge on the involvement of S100A8/A9 and its constituents in viral infections. The potential roles of S100A9 in SARS-CoV-2 infections are also discussed.


Asunto(s)
COVID-19 , Calgranulina A , Calgranulina B , Inflamación , SARS-CoV-2 , Humanos , COVID-19/inmunología , SARS-CoV-2/inmunología , Inflamación/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Virosis/inmunología
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