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Cancer immunotherapy is an increasingly common treatment option based on anti-tumor immune response. However, a challenge is arising regarding its potential, which is the poorly understood recognized immune-mediated adverse effects.
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Adenocarcinoma del Pulmón , Gastritis , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/inducido químicamente , Adenocarcinoma del Pulmón/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Gastritis/inducido químicamente , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patologíaRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic has affected the care of all patients around the world. The International League Against Epilepsy (ILAE) COVID-19 and Telemedicine Task Forces examined, through surveys to people with epilepsy (PWE), caregivers, and health care professionals, how the pandemic has affected the well-being, care, and services for PWE. The ILAE included a link on their website whereby PWE and/or their caregivers could fill out a survey (in 11 languages) about the impact of the COVID-19 pandemic, including access to health services and impact on mental health, including the 6-item Kessler Psychological Distress Scale. An anonymous link was also provided whereby health care providers could report cases of new-onset seizures or an exacerbation of seizures in the context of COVID-19. Finally, a separate questionnaire aimed at exploring the utilization of telehealth by health care professionals since the pandemic began was available on the ILAE website and also disseminated to its members. Seventeen case reports were received; data were limited and therefore no firm conclusions could be drawn. Of 590 respondents to the well-being survey (422 PWE, 166 caregivers), 22.8% PWE and 27.5% caregivers reported an increase in seizure frequency, with difficulty in accessing medication and health care professionals reported as barriers to care. Of all respondents, 57.1% PWE and 21.5% caregivers had severe psychological distress (k score >13), which was significantly higher among PWE than caregivers (p<0.01). An increase in telemedicine use during the COVID-19 pandemic was reported by health care professionals, with 40% of consultations conducted by this method. Although 74.9% of health care providers thought that this impacted positively, barriers to care were also identified. As we move forward, there is a need to ensure ongoing support and care for PWE to prevent a parallel pandemic of unmet health care needs.
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COVID-19 , Epilepsia/terapia , Pandemias , Cuidadores , Comunicación , Atención a la Salud/estadística & datos numéricos , Epilepsia/psicología , Accesibilidad a los Servicios de Salud , Humanos , Distrés Psicológico , Convulsiones/epidemiología , Estrés Psicológico/etiología , Estrés Psicológico/psicología , Encuestas y Cuestionarios , TelemedicinaRESUMEN
OBJECTIVE: This study was aimed to analyze the effectiveness of sodium channel blockers (SCBs) in CDKL5 deficiency disorder (CDD)-related epilepsy. METHODS: A retrospective, observational study was performed, including patients with CDD diagnosis evaluated between 2016 and 2019 at three tertiary Epilepsy Centers. Demographic, electroclinical and genetic features, as well as ASM treatments and their outcomes were analyzed, with special focus on SCBs. RESULTS: Twenty-one patients evaluated at three tertiary Epilepsy Centers were included, of which 19 presented with epilepsy (90.5%); all had pathogenic mutations of CDKL5. Six patients (31.6%) were classified as SCB responders (more than 50% reduction), four being currently seizure free (mean seizure-free period of 8â¯years). Most frequent SCB drugs were oxcarbazepine (OXC), carbamazepine (CBZ), and lacosamide (LCM). None of them presented relevant adverse events. In contrast, three patients showed seizure aggravation in the non-responder group. When comparing both groups, responders had statistically significant younger age at SCB treatment and epilepsy onset, higher proportion of focal epileptiform activity and less frequent history of West syndrome. CONCLUSIONS: The results of this study indicate that treatment with SCBs might be effective and safe in a subset of patients with CDD-related epilepsy.
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Epilepsia , Bloqueadores de los Canales de Sodio/uso terapéutico , Espasmos Infantiles , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Síndromes Epilépticos , Humanos , Lactante , Proteínas Serina-Treonina Quinasas/genética , Estudios Retrospectivos , Espasmos Infantiles/complicaciones , Espasmos Infantiles/tratamiento farmacológico , Espasmos Infantiles/genéticaRESUMEN
BACKGROUND: Series of patients with SARS-CoV-2 infection report headache in 6%-15% of cases, although some data suggest that the actual frequency is higher, and that headache is not associated with fever. No study published to date has analyzed the characteristics of headache in these patients. OBJECTIVE: To analyze the characteristics of COVID-19 related headaches. METHODS: We conducted a survey of Spaniard healthcare professionals who have been infected by SARS-CoV-2 and presented headache during the course of the disease. The survey addressed respondents' medical history and headache characteristics, and we analyzed the association between both. RESULTS: We analyzed the responses of a sample of 112 healthcare professionals. History of migraine was reported by 20/112 (17.9%) of respondents, history of tension-type headache by 8/112 (7.1%), and history of cluster headache was reported by a single respondent; 82/112(73.2%) of respondents had no history of headache. Headache presented independently of fever, around the third day after symptom onset. The previous history of migraine was associated with a higher frequency of pulsating headache (20% in patients with previous migraine vs 4.3% in those with no history of migraine, P = .013). CONCLUSION: Headache is often holocranial, hemicranial, or occipital, pressing, and worsens with physical activity or head movements. Because the characteristics of the headache and the associated symptoms are heterogeneous in our survey, we suggest that several patterns with specific pathophysiological mechanisms may underlie the headache associated with COVID-19.
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COVID-19/epidemiología , Cefalea/epidemiología , Personal de Salud , SARS-CoV-2 , Adulto , COVID-19/complicaciones , Comorbilidad , Estudios Transversales , Diabetes Mellitus/epidemiología , Dislipidemias/epidemiología , Femenino , Enfermedades Gastrointestinales/etiología , Cefalea/clasificación , Cefaleas Secundarias/diagnóstico , Cefaleas Secundarias/epidemiología , Cefaleas Secundarias/etiología , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/epidemiología , Enfermedades Profesionales/epidemiología , Pandemias , Equipo de Protección Personal , Prevalencia , Trastornos de la Sensación/etiología , España/epidemiología , Encuestas y Cuestionarios , Cefalea de Tipo Tensional/epidemiologíaRESUMEN
Mixed pyrazole-acetonitrile complexes, both neutral fac-[ReBr(CO)3(NCMe)(pz*H)] (pz*H = pzH, pyrazole; dmpzH, 3,5-dimethylpyrazole; or indzH, indazole) and cationic fac-[Re(CO)3(NCMe)(pz*H)2]A (A = BF4, ClO4, or OTf), are described. Their role as the only starting products to obtain final pyrazolylamidino complexes fac-[ReBr(CO)3(NHâC(Me)pz*-κ(2)N,N)] and fac-[Re(CO)3(pz*H)(NHâC(Me)pz*-κ(2)N,N)]A, respectively, is examined. Other products involved in the processes, such as fac-[ReBr(CO)3(pz*H)2], fac-[Re(CO)3(NCMe)(NHâC(Me)pz*-κ(2)N,N)]A, and fac-[Re(CO)3(pz*H)2(OTf)] are also described. Warming CD3CN solutions of fac-[Re(CO)3(NCMe)(pz*H)2]A at 40 °C gives cleanly the pyrazolylamidino complexes [Re(CO)3(pz*H)(NHâC(Me)pz*-κ(2)N,N)]A as the only products, pointing to an intramolecular process. This is confirmed by carrying out reactions in the presence of one equivalent of a pyrazole different from that coordinated, which affords complexes where the pyrazolylamidino ligand contains only the pyrazole previously coordinated. When the reactions lead to an equilibrium mixture of the final and starting products, the reverse reaction gives the same equilibrium mixture, which indicates that the coupling reaction of pyrazoles and nitriles to obtain pyrazolylamidino ligands is a reversible intramolecular process. A systematic study of the possible factors which may affect the reaction gives the following results: (a) the yields of the direct reactions are higher for lower temperatures; (b) the tendency of the pyrazoles to give pyrazolylamidino complexes follows the sequence indzH > pzH > dmpzH; and (c) the reaction rates do not depend on the nature of the anion even when a large excess is added. The presence of a small amount of aqueous solution of NaOH catalyzes the reaction. Thus, addition of 0.5-1% of NaOH (aq) to solutions of fac-[ReBr(CO)3(NCMe)(pz*H)] (in CD3CN) or fac-[Re(CO)3(NCMe)(pz*H)2]A (in CD3CN, CD3NO2 or (CD3)2CO) allowed the syntheses of the corresponding pyrazolylamidino complexes [ReBr(CO)3(NHâC(Me)pz*-κ(2)N,N)] or [Re(CO)3(pz*H)(NHâC(Me)pz*-κ(2)N,N)]A with better yields, more rapidly, and in milder conditions.
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The reactions of cis-[MoCl(η(3)-methallyl)(CO)(2)(NCMe)(2)] (methallyl = CH(2)C(CH(3))CH(2)) with Na(NCNCN) and pz*H (pzH, pyrazole, or dmpzH, 3,5-dimethylpyrazole) lead to cis-[Mo(η(3)-methallyl)(CO)(2)(pz*H)(µ-NCNCN-κ(2)N,N)](2) (pzH, 1a; dmpzH, 1b), where dicyanamide is coordinated as bridging ligand. Similar reactions with fac-[MnBr(CO)(3)(NCMe)(2)] lead to the pyrazolylamidino complexes fac-[Mn(pz*H)(CO)(3)(NHâC(pz*)NCN-κ(2)N,N)] (pzH, 2a; dmpzH, 2b), resulting from the coupling of pyrazol with one of the CN bonds of dicyanamide. The second CN bond of dicyanamide in 2a undergoes a second coupling with pyrazole after addition of 1 equiv of fac-[MnBr(CO)(3)(pzH)(2)], yielding the dinuclear doubly coupled complex [{fac-Mn(pzH)(CO)(3)}(2)(µ-NHâC(pz)NC(pz)=NH-κ(4)N,N,N,N)]Br (3). The crystal structure of 3 reveals the presence of two isomers, cis or trans, depending on whether the terminal pyrazoles are coordinated at the same or at different sides of the approximate plane defined by the bridging bis-amidine ligand. Only the cis isomer is detected in the crystal structure of the perchlorate salt of the same bimetallic cation (4), obtained by metathesis with AgClO(4). All the N-bound hydrogen atoms of the cations in 3 or 4 are involved in hydrogen bonds. Some of the C-N bonds of the pyrazolylamidino ligand have a character intermediate between single and double, and theoretical studies were carried out on 2a and 3 to confirm its electronic origin and discard packing effects. Calculations also show the essential role of bromide in the planarity of the tetradentate ligand in the bimetallic complex 3.
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Headache disorders are the most prevalent neurological conditions in the Sub-Saharan Africa and the second cause of disability. In this study, we analyze the knowledge about headache disorders and their management among Cameroonian healthcare providers. We conducted an interventional study with a prospective cohort design. Cameroonian health care providers from the whole country were invited. The evaluation was based on a questionnaire that was done before and after a 4-day educational course. The study included 42 participants, 52.4% female, aged 36.8 years. Participants treated a median of 240 monthly patients. Headache was reported as the most frequent neurological condition in their clinics (34%). Mean number of neurological patients seen per week was 69.3, among them 20 were headache patients. At baseline, only 35.8% correctly mentioned at least one primary headache, increasing to 78.6% after the course (p = 0.002). Secondary headaches were correctly identified by 19.0% at baseline and 40.5% after the course (p = 0.01). Clinical history was considered sufficient for headache diagnosis by 57.1% before and 78.6% after (p = 0.5). Correct red flags were mentioned at baseline by only 14.3% of participants, increasing to 40.5% after the course (p = 0.005). At baseline, the preferred symptomatic was paracetamol (47.6%) and Non-Steroidal Anti-Inflammatory Drugs (9.5%), changing to 23.8 and 66.7% after the course (p = 0.05 and < 0.001). Headache was reported as the most frequent neurological disorders. Knowledge about primary headache disorders and their etiology was scarce, and the clinical concept of red flags was limited. The acute drug of choice was paracetamol.
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Trastornos de Cefalalgia/terapia , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud/psicología , Adulto , Camerún , Competencia Clínica , Estudios de Cohortes , Femenino , Cefalea , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/terapia , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
The COVID-19 pandemic has changed the face of many practices throughout the world. Through necessity to minimize spread and provide clinical care to those with severe disease, focus has been on limiting face-to-face contact. Research in many areas has been put on hold. We sought to determine the impact of the COVID-19 pandemic on epilepsy research from international basic science and clinical researchers. Responses to five questions were solicited through a convenience sample by direct email and through postings on the ILAE social media accounts and an ILAE online platform (utilizing Slack). Information was collected from 15 respondents in 11 countries by email or via Zoom interviews between May 19, 2020, and June 4, 2020. Several themes emerged including a move to virtual working, project delays with laboratory work halted and clinical work reduced, funding concerns, a worry about false data with regard to COVID research and concern about research time lost. However, a number of positive outcomes were highlighted, not least the efficiency of online working and other adaptations that could be sustained in the future.
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Investigación Biomédica , COVID-19 , Epilepsia/terapia , Telemedicina , Investigación Biomédica/métodos , Investigación Biomédica/tendencias , COVID-19/epidemiología , COVID-19/prevención & control , Humanos , SARS-CoV-2RESUMEN
Introduction: Since the beginning of the Covid-19 epidemic produced by SARS2-Cov virus, olfactory alterations have been observed at a greater frequency than in other coronavirus epidemics. While olfactory alterations may be observed in patients with rhinovirus, influenza virus, or parainfluenza virus infection, they are typically explained by nasal obstruction with mucus or direct epithelial damage; in the case of SARS-CoV-2, olfactory alterations may present without nasal congestion with mucus. We performed a study of patients presenting olfactory/gustatory alterations in the context of SARS-CoV-2 infection in order to contribute to the understanding of this phenomenon. Material and Methods: We performed a descriptive, cross-sectional, observational study of the clinical characteristics of olfactory/gustatory alterations using a self-administered, anonymous online questionnaire. Results: A total of 909 patients with SARS-CoV-2 infection and olfactory/gustatory alterations responded to the questionnaire in the 4-day data collection period; 824 cases (90.65%) reported simultaneous olfactory and gustatory involvement. Patients' responses to the questionnaire revealed ageusia (581, 64.1% of respondents), hypogeusia (256, 28.2%), dysgeusia (22, 2.4%), anosmia (752 82.8%), hyposmia (142, 15.6%), and dysosmia (8, 0.9%). Fifty-four percent (489) did not report concomitant nasal congestion or mucus. Conclusion: Olfactory alterations are frequent in patients with SARS-CoV-2 infection and is only associated with nasal congestion in half of the cases.
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COVID-19/complicaciones , Trastornos del Olfato/etiología , Trastornos del Gusto/etiología , Adulto , COVID-19/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , SARS-CoV-2/aislamiento & purificación , Encuestas y CuestionariosRESUMEN
Six azobenzene derivatives bearing polyaromatic fragments have been prepared and their reversible photoisomerization has been assessed. Corannulene-functionalized molecules have demonstrated excellent switchable hosting abilities towards fullerenes in which an interesting range of affinities has been found. The success of this design relies upon the reversible formation and destruction of tweezer-like structures.
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The formation of an amidino chelating ligand from the coupling reaction of 1-methylcytosine and nitrile is a new method herein reported for the incorporation of biologically relevant substrates into rhenium(i) tricarbonyl complexes. The reactions are carried out thermally or are microwave assisted.
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Amidinas/química , Citosina/análogos & derivados , Sustancias Luminiscentes/química , Nitrilos/química , Compuestos de Organotecnecio/química , Renio/química , Citosina/química , Ligandos , Modelos Moleculares , Conformación MolecularRESUMEN
New pyrazolylamidino complexes fac-[ReCl(CO)3(NH[double bond, length as m-dash]C(Me)pz*-κ(2)N,N)] (pz*H = pyrazole, pzH; 3,5-dimethylpyrazole, dmpzH; indazole, indzH) and fac-[ReBr(CO)3(NH[double bond, length as m-dash]C(Ph)pz*-κ(2)N,N)] are synthesized via base-catalyzed coupling of the appropriate nitrile with pyrazole, or via metathesis by halide abstraction with AgBF4 from a bromido pyrazolylamidino complex and the subsequent addition of LiCl. In order to study both the influence of the substituents present at the pyrazolylamidino ligand, and that of the "sixth" ligand in the complex, photophysical, electrochemical, and computational studies have been carried out on this series and other complexes previously described by us, of the general formula fac-[ReL(CO)3(NH[double bond, length as m-dash]C(R')pz*-κ(2)N,N)](n+) (L = Cl, Br; R' = Me, Ph, n = 0; or L = NCMe, dmpzH, indzH, R' = Me, n = 1). All complexes exhibit phosphorescent decays from a prevalently (3)MLCT excited state with quantum yields (Φ) in the range between 0.007 and 0.039, and long lifetimes (τâ¼ 8-1900 ns). The electrochemical study reveals irreversible reduction for all complexes. The oxidation of the neutral complexes was found to be irreversible due to halido-dissociation, whereas the cationic species display a reversible process implying the ReI/ReII couple. Density functional and time-dependent density functional theory (TD-DFT) calculations provide a reasonable trend for the values of emission energies in line with the experimental photophysical data, supporting the (3)MLCT based character of the emissions.
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fac-[MBr(CO)3(pypzH)] (M = Mn, Re; pypzH = (3-(2-pyridyl)pyrazole) complexes are prepared from fac-[MBr(CO)3(NCMe)2] and pypzH. The result of their deprotonation depends on the metallic substrate: the rhenium complex affords cleanly the bimetallic compound [fac-{Re(CO)3(µ(2)-pypz)}]2 (µ(2)-pypz = µ(2)-3-(2-pyridyl-κ(1)N)pyrazolate-2κ(1)N), which was crystallographically characterized, whereas a similar manganese complex was not detected. When two equivalents of pyridylpyrazolate are used, polymetallic species [fac-M(CO)3(µ(2)-pypz)(µ(3)-pypz)M'] (µ(3)-pypz = µ(3)-3-(2-pyridyl-κ(1)N)pyrazolate-1κ(2)N,N:2κ(1)N:; M = Mn, M' = Li, Na, K; M = Re, M' = Na) are obtained. The crystal structures of the manganese carbonylate complexes were determined. The lithium complex is a monomer containing one manganese and one lithium atom, whereas the sodium and potassium complexes are dimers and reveal an unprecedented coordination mode for the bridging 3-(2-pyridyl)pyrazolate ligand, where the nitrogen of the pyridyl fragment and the nitrogen-1 of pyrazolate are chelated to manganese atoms, and each nitrogen-2 of pyrazolate is coordinated to two alkaline atoms. The polymetallic carbonylate complexes are unstable in solution and evolve spontaneously to [fac-{Re(CO)3(µ(2)-pypz)}]2 or to the trimetallic paramagnetic species [Mn(II)(µ(2)-pypz)2{fac-{Mn(I)(CO)3(µ(2)-pypz)}2}]. The related complex cis-[MnCl2(pypzH)2] was also synthesized and structurally characterized. The electrochemical behavior of the new homo- and heteropolymetallic 3-(2-pyridyl)pyrazolate complexes has been studied and details of their redox properties are reported.