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1.
PLoS Comput Biol ; 19(4): e1011060, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37083820

RESUMEN

Mitochondria form a network in the cell that rapidly changes through fission, fusion, and motility. Dysregulation of this four-dimensional (4D: x,y,z,time) network is implicated in numerous diseases ranging from cancer to neurodegeneration. While lattice light-sheet microscopy has recently made it possible to image mitochondria in 4D, quantitative analysis methods for the resulting datasets have been lacking. Here we present MitoTNT, the first-in-class software for Mitochondrial Temporal Network Tracking in 4D live-cell fluorescence microscopy data. MitoTNT uses spatial proximity and network topology to compute an optimal tracking assignment. To validate the accuracy of tracking, we created a reaction-diffusion simulation to model mitochondrial network motion and remodeling events. We found that our tracking is >90% accurate for ground-truth simulations and agrees well with published motility results for experimental data. We used MitoTNT to quantify 4D mitochondrial networks from human induced pluripotent stem cells. First, we characterized sub-fragment motility and analyzed network branch motion patterns. We revealed that the skeleton node motion is correlated along branch nodes and is uncorrelated in time. Second, we identified fission and fusion events with high spatiotemporal resolution. We found that mitochondrial skeleton nodes near the fission/fusion sites move nearly twice as fast as random skeleton nodes and that microtubules play a role in mediating selective fission/fusion. Finally, we developed graph-based transport simulations that model how material would distribute on experimentally measured mitochondrial temporal networks. We showed that pharmacological perturbations increase network reachability but decrease network resilience through a combination of altered mitochondrial fission/fusion dynamics and motility. MitoTNT's easy-to-use tracking module, interactive 4D visualization capability, and powerful post-tracking analyses aim at making temporal network tracking accessible to the wider mitochondria research community.


Asunto(s)
Células Madre Pluripotentes Inducidas , Humanos , Programas Informáticos , Simulación por Computador , Microscopía Fluorescente , Mitocondrias/fisiología , Dinámicas Mitocondriales
2.
Harefuah ; 161(12): 757-762, 2022 Dec.
Artículo en Hebreo | MEDLINE | ID: mdl-36916115

RESUMEN

INTRODUCTION: Intra-cochlear hemorrhage is a rare cause of sudden sensorineural hearing loss (SSNHL) which may be accompanied by diverse labyrinthine symptoms. In these cases, we expect magnetic resonance imaging (MRI) to demonstrate a high signal intensity in the labyrinth on unenhanced T1-weighted images as well as in fluid-attenuated inversion recovery (FLAIR) images. AIMS: To describe an experience with a case of intra-cochlear hemorrhage in a patient treated with anticoagulation, causing SSNHL and vertigo. METHODS: Case report and literature review. RESULTS: An 85-year old patient treated with anticoagulation therapy presented with right SSNHL, tinnitus and vertigo. Physical examination revealed: bilateral normal otoscopic examination, lateralized left Weber tuning fork test and a spontaneous left horizontal nystagmus. MRI performed demonstrated a high signal intensity inside the cochlea on unenhanced T1-weighted images. CONCLUSIONS: Performing an MRI is necessary in order to rule out frequent causes of SSNHL including benign as well as malignant tumors, malformations, trauma and more. The finding of an intra-labyrinthine hemorrhage causing SSNHL is rare, and should be taken into consideration when treated by anticoagulation therapy.


Asunto(s)
Pérdida Auditiva Sensorineural , Pérdida Auditiva Súbita , Humanos , Anciano de 80 o más Años , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Sensorineural/patología , Cóclea/diagnóstico por imagen , Cóclea/patología , Vértigo/complicaciones , Vértigo/patología , Pérdida Auditiva Súbita/diagnóstico , Pérdida Auditiva Súbita/etiología , Pérdida Auditiva Súbita/patología , Hemorragia/etiología , Imagen por Resonancia Magnética/métodos , Anticoagulantes
3.
Mol Ther ; 28(1): 189-201, 2020 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-31628052

RESUMEN

Duchenne muscular dystrophy (DMD) is an X-linked muscle wasting disease that is caused by the loss of functional dystrophin protein in cardiac and skeletal muscles. DMD patient muscles become weakened, leading to eventual myofiber breakdown and replacement with fibrotic and adipose tissues. Inflammation drives the pathogenic processes through releasing inflammatory cytokines and other factors that promote skeletal muscle degeneration and contributing to the loss of motor function. Selective inhibitors of nuclear export (SINEs) are a class of compounds that function by inhibiting the nuclear export protein exportin 1 (XPO1). The XPO1 protein is an important regulator of key inflammatory and neurological factors that drive inflammation and neurotoxicity in various neurological and neuromuscular diseases. Here, we demonstrate that SINE compound KPT-350 can ameliorate dystrophic-associated pathologies in the muscles of DMD models of zebrafish and mice. Thus, SINE compounds are a promising novel strategy for blocking dystrophic symptoms and could be used in combinatorial treatments for DMD.


Asunto(s)
Transporte Activo de Núcleo Celular/efectos de los fármacos , Carioferinas/antagonistas & inhibidores , Distrofia Muscular de Duchenne/tratamiento farmacológico , Receptores Citoplasmáticos y Nucleares/antagonistas & inhibidores , Pez Cebra/genética , Administración Oral , Animales , Biomarcadores/sangre , Citocinas/antagonistas & inhibidores , Citocinas/sangre , Modelos Animales de Enfermedad , Locomoción/efectos de los fármacos , Macrófagos/efectos de los fármacos , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos DBA , Ratones Endogámicos mdx , Proteínas Musculares/genética , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Mutación , Proteínas de Pez Cebra/genética , Proteína Exportina 1
4.
Isr Med Assoc J ; 23(7): 426-431, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34251125

RESUMEN

BACKGROUND: Decisions on medication treatment in children dying from cancer are often complex and may result in polypharmacy and increased medication burden. There is no information on medication burden in pediatric cancer patients at the end of life (EOL). OBJECTIVES: To characterize medication burden during the last hospitalization in children dying from cancer. METHODS: We performed a retrospective cohort study based on medical records of 90 children who died from cancer in hospital between 01 January 2010 and 30 December 2018. Demographic and clinical information were collected for the last hospitalization. We compared medication burden (number of medication orders) at hospitalization and at time of death and examined whether changes in medication burden were associated with clinical and demographic parameters. RESULTS: Median medication burden was higher in leukemia/lymphoma patients (6 orders) compared to solid (4 orders) or CNS tumor patients (4 orders, P = 0.006). Overall, the median number of prescriptions per patient did not change until death (P = 0.42), while there was a significant reduction for some medication subgroups (chemotherapy [P = 0.035], steroids [P = 0.010]).Patients dying in the ICU (n=15) had a higher medication burden at death (6 orders) than patients dying on wards (3 orders, P = 0.001). There was a trend for a reduction in medication burden in patients with "Do not resuscitate" (DNR) orders (P = 0.055). CONCLUSIONS: Polypharmacy is ubiquitous among pediatric oncology patients at EOL. Disease type and DNR status may affect medication burden and deprescribing during the last hospitalization.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias , Cuidados Paliativos , Polifarmacia , Esteroides/uso terapéutico , Cuidado Terminal , Niño , Vías Clínicas/estadística & datos numéricos , Demografía , Femenino , Investigación sobre Servicios de Salud , Hospitalización/estadística & datos numéricos , Humanos , Israel/epidemiología , Masculino , Estadificación de Neoplasias , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Neoplasias/patología , Cuidados Paliativos/métodos , Cuidados Paliativos/estadística & datos numéricos , Órdenes de Resucitación , Cuidado Terminal/métodos , Cuidado Terminal/estadística & datos numéricos
5.
J Virol ; 93(4)2019 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-30541831

RESUMEN

Respiratory syncytial virus (RSV) is a leading cause of hospitalization of infants and young children, causing considerable respiratory disease and repeat infections that may lead to chronic respiratory conditions such as asthma, wheezing, and bronchitis. RSV causes ∼34 million new episodes of lower respiratory tract illness (LRTI) in children younger than 5 years of age, with >3 million hospitalizations due to severe RSV-associated LRTI. The standard of care is limited to symptomatic relief as there are no approved vaccines and few effective antiviral drugs; thus, a safe and efficacious RSV therapeutic is needed. Therapeutic targeting of host proteins hijacked by RSV to facilitate replication is a promising antiviral strategy as targeting the host reduces the likelihood of developing drug resistance. The nuclear export of the RSV M protein, mediated by the nuclear export protein exportin 1 (XPO1), is crucial for RSV assembly and budding. Inhibition of RSV M protein export by leptomycin B correlated with reduced RSV replication in vitro In this study, we evaluated the anti-RSV efficacy of Verdinexor (KPT-335), a small molecule designed to reversibly inhibit XPO1-mediated nuclear export. KPT-335 inhibited XPO1-mediated transport and reduced RSV replication in vitro KPT-335 was effective against RSV A and B strains and reduced viral replication following prophylactic or therapeutic administration. Inhibition of RSV replication by KPT-335 was due to a combined effect of reduced XPO1 expression, disruption of the nuclear export of RSV M protein, and inactivation of the NF-κB signaling pathway.IMPORTANCE RSV is an important cause of LRTI in infants and young children for which there are no suitable antiviral drugs offered. We evaluated the efficacy of KPT-335 as an anti-RSV drug and show that KPT-335 inhibits XPO1-mediated nuclear export, leading to nuclear accumulation of RSV M protein and reduction in RSV levels. KPT-335 treatment also resulted in inhibition of proinflammatory pathways, which has important implications for its effectiveness in vivo.


Asunto(s)
Acrilamidas/farmacología , Hidrazinas/farmacología , Virus Sincitiales Respiratorios/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Células A549 , Acrilamidas/metabolismo , Transporte Activo de Núcleo Celular/efectos de los fármacos , Animales , Antivirales/farmacología , Apoptosis/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Chlorocebus aethiops , Glicoproteínas/inmunología , Humanos , Hidrazinas/metabolismo , Carioferinas/efectos de los fármacos , Carioferinas/metabolismo , Receptores Citoplasmáticos y Nucleares/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/metabolismo , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Células Vero , Proteína Exportina 1
6.
Brain Inj ; 34(11): 1489-1496, 2020 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-32853051

RESUMEN

PRIMARY OBJECTIVE: We tested whether KPT-350, a novel selective inhibitor of nuclear export, could attenuate cortical network hyperexcitability, a major risk factor for developing post-traumatic epilepsy (PTE) following traumatic brain injury (TBI). RESEARCH DESIGN: All mice in this study underwent TBI and were subsequently treated with either KPT-350 or vehicle during the post-injury latent period. Half of the animal cohort was used for electrophysiology while the other half was used for immunohistochemical analysis. METHODS AND PROCEDURES: TBI was induced using the controlled cortical impact (CCI) model. Cortical network activity was recorded by evoking field potentials from deep layers of the cortex and analyzed using Matlab software. Immunohistochemistry coupled with fluorescence microscopy and Image J analysis detected changes in neuronal and glial markers. MAIN OUTCOMES AND RESULTS: KPT-350 attenuated TBI-associated epileptiform activity and restored disrupted input-output responses in cortical brain slices. In vivo KPT-350 treatment reduced the loss of parvalbumin-(+) GABAergic interneurons after CCI but did not significantly change CCI-induced loss of somatostatin-(+) GABAergic interneurons, nor did it reduce reactivity of GFAP and Iba1 glial markers. CONCLUSION: KPT-350 can prevent cortical hyperexcitability and reduce the loss of parvalbumin-(+) GABAergic inhibitory neurons, making it a potential therapeutic option for preventing PTE.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Animales , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Modelos Animales de Enfermedad , Neuronas GABAérgicas , Interneuronas , Ratones , Parvalbúminas
7.
Eur Arch Otorhinolaryngol ; 277(2): 641-643, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31853642
8.
J Pediatr Hematol Oncol ; 41(4): e201-e205, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30499908

RESUMEN

BACKGROUND: It is currently expected that about 20% of children with cancer will ultimately die. Writing advanced life directives sufficiently long before the actual death of a child ensues allows both parents and medical staff to develop optimal treatment plans in the best interests of the child. AIM OF THE STUDY: The aim of the study was to evaluate factors that may influence the process of decision-making regarding Do-Not-Resuscitate (DNR) status. METHODS: Retrospective single institution study. RESULTS: Totally, 79 patients died between September 01, 2011 and August 31, 2017. Median age of the children was 10.5 years (range, 1 to 24 y). Forty-five were males. There were 37 Muslims, 27 Jews, 9 Druze, and 6 Christians. Twenty-one patients had sarcomas, 20 had CNS tumors, 10 had neuroblastoma, 17 had leukemias/lymphomas, 11 had carcinomas, and other rare tumors as well as nonmalignant diseases. No statistically significant association between all evaluated factors and DNR order status was found. CONCLUSIONS: It is possible that, other than demographic, clinical-associated, or therapy-associated factors play an important role in the process of decision-making regarding DNR. We feel that sincere communication between parents, their child (when appropriate) and medical and psychosocial staff may have a more crucial role when such decisions have to be made.


Asunto(s)
Directivas Anticipadas , Órdenes de Resucitación , Adolescente , Directivas Anticipadas/etnología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Adulto Joven
9.
ORL J Otorhinolaryngol Relat Spec ; 81(5-6): 304-308, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31499507

RESUMEN

OBJECTIVE: To compare the level of the inflammatory markers (IM) neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) among healthy subjects and those presenting with vestibular neuritis (VN). METHODS: A cross-sectional retrospective study was conducted in a tertiary hospital setting. The medical records of patients (20-60 years old) who were hospitalized between the years 2005 and 2014 with the diagnosis of VN were retrieved. Inclusion criteria were: (1) acute vertigo lasting for at least 24 h, (2) absence of auditory complaints, (3) presence of horizontal unidirectional nystagmus during physical examination, (4) absence of neurological symptoms or signs. The levels of the IM were compared with levels reported among two large cohorts of healthy subjects, within the same age range. RESULTS: A statistically significant difference was found between the levels of NLR in VN subjects compared with controls, with higher levels of NLR in VN subjects (p < 0.001), while no significant difference was found between both groups concerning the levels of PLR. CONCLUSION: Higher levels of IM were found among VN patients, with significantly higher levels of NLR, but not PLR. This may suggest a possible inflammatory etiology of VN.


Asunto(s)
Neuronitis Vestibular/sangre , Adulto , Estudios Transversales , Femenino , Humanos , Recuento de Leucocitos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Neutrófilos , Recuento de Plaquetas , Estudios Retrospectivos , Neuronitis Vestibular/tratamiento farmacológico
10.
J Craniofac Surg ; 30(6): e508-e511, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30921074

RESUMEN

Waldeyer's lymphatic ring granulomas in children are infrequent, and may represent an underlying systemic disease, often nondiagnosed before adenotonsillectomy is performed. The authors report on a 5-year-old otherwise healthy girl presented with remarkable tonsillar asymmetry as well as adenoid hypertrophy, with no systemic signs or complaints. Adenotonsillectomy was performed to rule out malignancy. Blood workup was normal. Microscopy of both adenoidectomy and tonsillectomy specimens showed multiple foci of epithelioid, noncaseating granulomas with giant multinucleated cells surrounded by nonspecific chronic inflammation. Immunostainings for B-cell markers, Ki-67, and Ziehl-Neelson were negative. This unusual pathology raised a differential diagnosis which included inflammatory diseases (sarcoidosis, Crohn's disease), foreign body reaction, lymphoma and infections (tuberculosis, fungi). However, none of these entities could be attributed to the girl's condition, and the reason for her pathologic findings remained unknown.


Asunto(s)
Células Gigantes/patología , Granuloma/patología , Adenoidectomía , Tonsila Faríngea/patología , Preescolar , Diagnóstico Diferencial , Femenino , Granuloma/cirugía , Humanos , Tonsila Palatina/patología , Tonsilectomía
11.
Pediatr Emerg Care ; 35(8): 544-547, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27977506

RESUMEN

INTRODUCTION: Acute mastoiditis (AM) is a medical emergency that mandates prompt diagnosis and treatment. Nevertheless, its management often differs between otorhinolaryngologists (ORLs) and pediatricians (PEDs) working in emergency departments. We sought to characterize the similarities and differences between management protocols of these 2 disciplines. METHODS: A voluntary electronic questionnaire, including 17 items pertaining to pediatric AM management, was sent to all the 20 otorhinolaryngology and their corresponding pediatric emergency departments nationwide. Each department sent 1 filled out questionnaire. The response rate was 100%. RESULTS: Eighteen (90%) ORLs are notified when a child with suspected AM arrives. Medical history collected by both disciplines was similar-previous otologic history (100%), previous antibiotic use (100%), and pneumococcal conjugate vaccination status (60%)-whereas acute otitis media risk factors were more important to PEDs (13 [65%] PEDs, 10 [50%] ORLs). According to 85% to 90% of ORLs and PEDs, imaging was not mandatory upon admission. According to 14 (70%) PEDs and 16 (80%) ORLs, imaging was overall performed in less than 50% of patients during hospitalization. Intravenous ceftriaxone and cefuroxime were the most common first-line antibiotic treatments (8 [40%] ORLs, 10 [50%] PEDs), with a mean treatment duration of 7 to 10 days. Eighteen (90%) of the ORLs, compared with 15 (75%) PEDs, reported that myringotomy (with or without ventilating tube insertion) was performed upon diagnosis (P = 0.05). CONCLUSIONS: The management of pediatric AM is generally similar by both disciplines. The use of imaging studies is mild-moderate. We call for a national registry and encourage the publication of guidelines.


Asunto(s)
Mastoiditis/tratamiento farmacológico , Mastoiditis/cirugía , Otorrinolaringólogos/estadística & datos numéricos , Pediatras/estadística & datos numéricos , Enfermedad Aguda , Antibacterianos/uso terapéutico , Niño , Preescolar , Estudios Transversales , Diagnóstico por Imagen/métodos , Diagnóstico por Imagen/estadística & datos numéricos , Manejo de la Enfermedad , Servicio de Urgencia en Hospital/estadística & datos numéricos , Humanos , Israel/epidemiología , Mastoiditis/diagnóstico por imagen , Mastoiditis/epidemiología , Ventilación del Oído Medio/métodos , Ventilación del Oído Medio/estadística & datos numéricos , Factores de Riesgo , Encuestas y Cuestionarios
12.
J Virol ; 88(17): 10228-43, 2014 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-24965445

RESUMEN

UNLABELLED: Influenza is a global health concern, causing death, morbidity, and economic losses. Chemotherapeutics that target influenza virus are available; however, rapid emergence of drug-resistant strains is common. Therapeutic targeting of host proteins hijacked by influenza virus to facilitate replication is an antiviral strategy to reduce the development of drug resistance. Nuclear export of influenza virus ribonucleoprotein (vRNP) from infected cells has been shown to be mediated by exportin 1 (XPO1) interaction with viral nuclear export protein tethered to vRNP. RNA interference screening has identified XPO1 as a host proinfluenza factor where XPO1 silencing results in reduced influenza virus replication. The Streptomyces metabolite XPO1 inhibitor leptomycin B (LMB) has been shown to limit influenza virus replication in vitro; however, LMB is toxic in vivo, which makes it unsuitable for therapeutic use. In this study, we tested the anti-influenza virus activity of a new class of orally available small-molecule selective inhibitors of nuclear export, specifically, the XPO1 antagonist KPT-335 (verdinexor). Verdinexor was shown to potently and selectively inhibit vRNP export and effectively inhibited the replication of various influenza virus A and B strains in vitro, including pandemic H1N1 virus, highly pathogenic H5N1 avian influenza virus, and the recently emerged H7N9 strain. In vivo, prophylactic and therapeutic administration of verdinexor protected mice against disease pathology following a challenge with influenza virus A/California/04/09 or A/Philippines/2/82-X79, as well as reduced lung viral loads and proinflammatory cytokine expression, while having minimal toxicity. These studies show that verdinexor acts as a novel anti-influenza virus therapeutic agent. IMPORTANCE: Antiviral drugs represent important means of influenza virus control. However, substantial resistance to currently approved influenza therapeutic drugs has developed. New antiviral approaches are required to address drug resistance and reduce the burden of influenza virus-related disease. This study addressed critical preclinical studies for the development of verdinexor (KPT-335) as a novel antiviral drug. Verdinexor blocks progeny influenza virus genome nuclear export, thus effectively inhibiting virus replication. Verdinexor was found to limit the replication of various strains of influenza A and B viruses, including a pandemic H1N1 influenza virus strain, a highly pathogenic H5N1 avian influenza virus strain, and a recently emerging H7N9 influenza virus strain. Importantly, oral verdinexor treatments, given prophylactically or therapeutically, were efficacious in limiting lung virus burdens in influenza virus-infected mice, in addition to limiting lung proinflammatory cytokine expression, pathology, and death. Thus, this study demonstrated that verdinexor is efficacious against influenza virus infection in vitro and in vivo.


Asunto(s)
Transporte Activo de Núcleo Celular/efectos de los fármacos , Antivirales/metabolismo , Inhibidores Enzimáticos/metabolismo , Virus de la Influenza A/fisiología , Virus de la Influenza B/fisiología , Carioferinas/antagonistas & inhibidores , Receptores Citoplasmáticos y Nucleares/antagonistas & inhibidores , Replicación Viral/efectos de los fármacos , Animales , Antivirales/uso terapéutico , Línea Celular , Quimioprevención/métodos , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/uso terapéutico , Femenino , Humanos , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza B/efectos de los fármacos , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/prevención & control , Proteína Exportina 1
13.
Eur Arch Otorhinolaryngol ; 272(4): 929-935, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25528553

RESUMEN

There is no clinical dynamic staging system which scores according to severity all the anatomical regions in adult supraglottitis. The objective of the study was to describe the demographics, clinical presentation, interventions and outcomes of adult patients diagnosed with acute supraglottitis (AS), and to study the correlation of a new AS classification with the need for airway intervention, in comparison with the current classification. This was a retrospective, cohort study conducted at a secondary medical care center. Adults diagnosed with AS from the years 1990-2013 were identified. Data were extracted for demographic and clinical information and there was no intervention. The main outcome and measures were the need for airway intervention. 288 eligible patients were enrolled. AS incidence rate was 4.3/100,000 patients/year. The mean age was 50 ± 16 years. Sore throat (94 %) and dysphagia (88 %) were the most common presenting symptoms. Patients were hospitalized either in the Otolaryngology Department (n = 255, 89 %) or in the Intensive Care Unit (n = 33, 11 %). Of the latter, 19 (58 %) had an airway securing intervention procedure. Our suggested classification was more sensitive than the current one for predicting the need for intubation (p = 0.03). Signs and symptoms of AS in adults are different from those in children. Adult patients presenting with oropharyngeal complaints should be suspected for AS and treated appropriately.


Asunto(s)
Obstrucción de las Vías Aéreas , Trastornos de Deglución/etiología , Intubación Intratraqueal , Faringitis/etiología , Supraglotitis , Enfermedad Aguda , Adulto , Obstrucción de las Vías Aéreas/epidemiología , Obstrucción de las Vías Aéreas/etiología , Obstrucción de las Vías Aéreas/terapia , Estudios de Cohortes , Comorbilidad , Demografía , Femenino , Humanos , Intubación Intratraqueal/métodos , Intubación Intratraqueal/estadística & datos numéricos , Israel/epidemiología , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Supraglotitis/diagnóstico , Supraglotitis/epidemiología , Supraglotitis/fisiopatología , Supraglotitis/terapia
14.
Pediatr Hematol Oncol ; 32(4): 284-9, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25551199

RESUMEN

OBJECTIVES: The goal of this study was to identify second opinion consultations by physicians and to determine patient and family factors that appeared to contribute to a second opinion being sought. METHODS: One hundred and fifty consecutive parents of children with cancer recently treated in our Department of Pediatric Hematology Oncology were interviewed by telephone. The questionnaire included epidemiological data, details about the disease, timing of the second opinion consultation, reasons for seeking a second opinion, and the outcome of the consultation. RESULTS: Thirty-seven (24.7%) parents sought a second opinion. Advice was sought from other physicians in the hospital or at other clinics. There was a correlation to a higher socioeconomic status (P = .003) and to the number of educational years (P = .001). Most of the parents sought a second opinion because they wanted confirmation about the treatment protocol and the professional level of the hematologist oncologist/surgeon and the institution. CONCLUSIONS: Second opinion consultations were not uncommon and were mainly secondary to the desire for reassurance. Pediatric oncologists should ensure that patients and their families feel comfortable requesting a second opinion consultation.


Asunto(s)
Neoplasias , Derivación y Consulta , Encuestas y Cuestionarios , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad
15.
Curr Opin Otolaryngol Head Neck Surg ; 32(3): 188-192, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38363234

RESUMEN

PURPOSE OF REVIEW: Various factors affect otolaryngology - head and neck surgery (OHNS) services in low- and middle-income countries (LMICs); including inadequate infrastructure, limited academic positions, unfavorable hospital research policies, and traditional misconceptions about gender and surgery, among others. Although gender inequalities exist globally, they are particularly pronounced in LMICs, especially in Africa. RECENT FINDINGS: A comparative narrative literature review for relevant manuscripts from January 1, 2017 to through January 10th, 2024, using PubMed, Embase and Google Scholar for articles from the United States/Canada and Africa was done. 195 relevant articles were from the United States/Canada, while only 5 were from Africa and only 1 manuscript was relevant to OHNS. The reviewed articles reported that gender disparities exist in medical training, authorship, and career advancement. We highlight possible solutions to some of these disparities to promote a more gender-diversified workforce in OHNS in Africa as well as all over the world. SUMMARY: Additional studies on gender disparities in Africa, are needed. These studies will highlight need for inclusive policies, structured and accessible mentorship programs; through which these disparities can be highlighted and addressed. This will in the long run ensure sustainability of OHNS care in LMICs.


Asunto(s)
Otolaringología , Humanos , Otolaringología/educación , África , Sexismo/estadística & datos numéricos , Femenino , Masculino , Procedimientos Quirúrgicos Otorrinolaringológicos/estadística & datos numéricos , Países en Desarrollo
16.
Breastfeed Med ; 19(2): 73-80, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38386988

RESUMEN

Introduction: Human breast milk (HBM) contains a complex and dynamically changing variety of factors that contribute to the infant's developing immune system's ability to fight upper respiratory tract infections, including otitis media (OM). We sought to summarize the current evidence on the protective characteristics of HBM, through direct or donated feeding, toward early childhood OM. Methods: For this narrative review, we performed a literature search on OM in the context of HBM feeding in the PubMed, Embase, and Google Scholar databases, between January 1, 2008, and July 1, 2023. Results: Immunoglobulin A (IgA) provides a short-term immunity of 2-3 days against otopathogens causing OM. IgA-mediated immunity is effective against OM up to 7 months of age if breastfeeding continues. The role of transferred IgM and IgG in HBM is unclear. Although there is a potential protective value of microRNA, hormones, oligosaccharides, stem cells, and interleukins present in HBM, their role is unclear. Any duration of breastfeeding is superior to no breastfeeding in OM risk reduction, with a big variability among studies (odds ratio 0.23-0.81, depending on the duration). Duration of breastfeeding ≥6 months was found to be the most effective in OM risk reduction, but there was no evidence of continued benefits after 2 years of age. Expressed breastfeeding was not shown to be more beneficial. The protective values of donor HBM against OM are still undetermined. Conclusion: HBM has numerous components that contribute to protection against early childhood OM.


Asunto(s)
MicroARNs , Otitis Media , Femenino , Lactante , Humanos , Preescolar , Lactancia Materna , Leche Humana , Inmunoglobulina A , Otitis Media/prevención & control
17.
Int J Pediatr Otorhinolaryngol ; 176: 111836, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38154416

RESUMEN

OBJECTIVE: We sought to study adenoidectomy rates in children with adenoid hypertrophy (AH) who were either treated with medical therapy or not during a 2-year follow-up period in a longitudinal population-based study. METHODS: We retrospectively identified healthy children aged 1-18 years between 2014 and 2020 with AH diagnosis from the Clalit Health Services database, the largest healthcare maintenance organization in Israel. The main outcome was adenoidectomy alone or in combination with other procedures performed within 2 years after diagnosis. The treatment group consisted of children who received medical therapy, defined as a pharmacy purchase of montelukast, nasal steroid sprays and/or antihistamines (medical therapy aimed to reduce AH) for ≥2 consecutive months, while the control group consisted of untreated children. RESULTS: We identified 68,356 unique children with AH, of them 56 % were boys, with a mean age of 4.9 ± 3.3 years. Of them, 5310 (7.7 %) received medical therapy. Overall, 6633 (9.7 %) underwent adenoidectomy within 2 years following diagnosis. There was no significant difference in surgery referral rates between the treatment and the control groups, 10 % vs. 9.7 %, respectively (p = 0.3). When adjusted for age and sex, the likelihood of undergoing adenoidectomy was similar in both groups (HR = 0.98, 95 % CI = 0.90-1.07, p = 0.6). Among operated children, the average time from diagnosis to surgery was statistically significantly longer in the treatment group than in the control group, 346 ± 180 vs 311 ± 175 days (p < 0.001). CONCLUSION: Prescribing montelukast, nasal steroids and/or oral antihistamines was not associated with a reduction in adenoidectomy rates and was associated with an average surgery delay of 35 days.


Asunto(s)
Tonsila Faríngea , Niño , Masculino , Humanos , Lactante , Preescolar , Femenino , Tonsila Faríngea/cirugía , Estudios Retrospectivos , Sulfuros , Adenoidectomía , Rociadores Nasales , Hipertrofia/tratamiento farmacológico , Hipertrofia/cirugía , Hipertrofia/complicaciones
18.
Semin Pediatr Neurol ; 48: 101090, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38065637

RESUMEN

Sleep problems are highly prevalent in those with neurodevelopmental disorders (NDDs). We propose this is secondary to multiple factors that directly and indirectly negatively impact sleep and circadian processes in those with NDDs, which in turn, further perturbs development, resulting in a "developmental and sleep/circadian-related encephalopathy." In this review, we discuss select NDDs with known or suspected sleep and circadian phenotypes. We also highlight important considerations when evaluating and treating sleep and circadian disorders in these populations.


Asunto(s)
Encefalopatías , Trastornos del Neurodesarrollo , Trastornos del Sueño-Vigilia , Niño , Humanos , Trastornos del Neurodesarrollo/complicaciones , Sueño , Fenotipo , Trastornos del Sueño-Vigilia/complicaciones
19.
Otol Neurotol ; 44(2): e68-e72, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36624589

RESUMEN

OBJECTIVE: To compare sudden sensorineural hearing loss (SSNHL) incidence rates over the coronavirus disease 2019 (COVID-19) outbreak and the COVID-19 vaccination campaign periods to pre-COVID-19 periods. STUDY DESIGN: Retrospective cohort. SETTING: Secondary hospital. PATIENTS: Patients >12 years with auditory-confirmed SSNHL were enrolled. COVID-19 status and BNT162 inoculation records ≤28 days before SSNHL diagnosis were retrieved. Patients were categorized according to their date of presentation over four equal periods: 1) July 2018-April 2019 (first prepandemic period), 2) May 2019-February 2020 (second prepandemic period), 3) March 2020-December 2020 (COVID-19 outbreak), and 4) January 2021-October 2021 (BNT162b2 vaccinations campaign). INTERVENTIONS: Pre- and post-COVID-19 emergence; BNT162b2 vaccine. MAIN OUTCOME MEASURES: Incidence rate ratios (IRRs) were calculated to compare SSNHL cases during the COVID-19 and vaccination periods with pre-COVID-19 periods. RESULTS: Of the 100 patients with SSNHL over the four periods, 1 had COVID-19 and 8 were vaccinated. The annual SSNHL incidence was 12.87, 12.28, 13.45, and 19.89 per 100,000 over periods 1 to 4, respectively. SSNHL incidence over the third period was not significantly different than the first/second periods (IRR = 1.045, 95% confidence interval [CI] = 0.629-1.85, ρ = 0.788, and IRR = 1.095, 95% CI = 0.651-1.936, ρ = 0.683, respectively), whereas SSNHL incidence rate over the fourth period was higher (IRR = 1.545, 95% CI = 0.967-2.607, ρ = 0.068, and IRR = 1.619, 95% CI = 1-2.73, ρ = 0.05, respectively). SSNHL incidence in vaccine recipients was lower than prepandemic unvaccinated patients (IRR = 0.584, 95% CI =0.464-1.67, ρ = 0.984, and IRR = 0.612, 95% CI =0.48-1.744, ρ = 0.92, respectively). CONCLUSION: There were fewer SSNHL cases during the first COVID-19 months. Although the SSNHL rate over the COVID-19 vaccination campaign increased, it was not higher for patients who received the BNT162b2 vaccine.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Pérdida Auditiva Sensorineural , Pérdida Auditiva Súbita , Humanos , Vacuna BNT162 , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Pérdida Auditiva Sensorineural/epidemiología , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Súbita/epidemiología , Pérdida Auditiva Súbita/etiología , Incidencia , Estudios Retrospectivos , Vacunas
20.
J Int Adv Otol ; 19(5): 402-406, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37789627

RESUMEN

BACKGROUND: Temporary conductive hearing loss due to vernix accumulation in the external ear canal may lead to a false-positive result in newborn hearing screening tests. The aim of this study was to evaluate whether ear examination and intervention may reduce the false-positive rate prior to hospital discharge. METHODS: A case series of 42 newborns who failed initial otoacoustic emissions screening were studied in our institution between May and December 2020. RESULTS: During the study period, a total of 735 neonates (1470 ears) were screened by otoacoustic emissions in our hospital. Forty-two newborns who failed otoacoustic emissions were included in our study. They constituted 3.9% (n=58 ears) of the total number of ears screened. Forty-four ears (75.9%) passed and 14 ears (24.1%) failed otoacoustic emissions rescreening performed shortly following vernix cleaning. Twelve of the remaining 14 ears passed at 10-day rescreening. The remaining 2 ears presented true bilateral hearing loss. During the study period, the general false-positive rate decreased from 56/735 (7.61%) to 12/735(1.63%) (P < .00001). CONCLUSION: Cleaning the vernix of infants who failed otoacoustic emissions prior to hospital discharge lowers the false-positive rate of universal neonatal hearing screening. We may assume that vernix cleaning will reduce significant healthcare workload, costs of unnecessary investigations, as well as parental anxiety.


Asunto(s)
Pérdida Auditiva Conductiva , Examen Físico , Lactante , Humanos , Recién Nacido , Pérdida Auditiva Conductiva/diagnóstico , Conducto Auditivo Externo , Emisiones Otoacústicas Espontáneas , Tamizaje Neonatal
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