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1.
Curr Opin Otolaryngol Head Neck Surg ; 32(3): 188-192, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38363234

RESUMO

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.


Assuntos
Otolaringologia , Humanos , Otolaringologia/educação , África , Sexismo/estatística & dados numéricos , Feminino , Masculino , Procedimentos Cirúrgicos Otorrinolaringológicos/estatística & dados numéricos , Países em Desenvolvimento
2.
Int J Pediatr Otorhinolaryngol ; 176: 111836, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38154416

RESUMO

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.


Assuntos
Tonsila Faríngea , Criança , Masculino , Humanos , Lactente , Pré-Escolar , Feminino , Tonsila Faríngea/cirurgia , Estudos Retrospectivos , Sulfetos , Adenoidectomia , Sprays Nasais , Hipertrofia/tratamento farmacológico , Hipertrofia/cirurgia , Hipertrofia/complicações
3.
JAMA Otolaryngol Head Neck Surg ; 149(10): 904-911, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37651133

RESUMO

Importance: A core component of delivering care of head and neck diseases is an adequate workforce. The World Health Organization report, Multi-Country Assessment of National Capacity to Provide Hearing Care, captured primary workforce estimates from 68 member states in 2012, noting that response rates were a limitation and that updated more comprehensive data are needed. Objective: To establish comprehensive workforce metrics for global otolaryngology-head and neck surgery (OHNS) with updated data from more countries/territories. Design, Setting, and Participants: A cross-sectional electronic survey characterizing the OHNS workforce was disseminated from February 10 to June 22, 2022, to professional society leaders, medical licensing boards, public health officials, and practicing OHNS clinicians. Main Outcome: The OHNS workforce per capita, stratified by income and region. Results: Responses were collected from 121 of 195 countries/territories (62%). Survey responses specifically reported on OHNS workforce from 114 countries/territories representing 84% of the world's population. The global OHNS clinician density was 2.19 (range, 0-61.7) OHNS clinicians per 100 000 population. The OHNS clinician density varied by World Bank income group with higher-income countries associated with a higher density of clinicians. Regionally, Europe had the highest clinician density (5.70 clinicians per 100 000 population) whereas Africa (0.18 clinicians per 100 000 population) and Southeast Asia (1.12 clinicians per 100 000 population) had the lowest. The OHNS clinicians deliver most of the surgical management of ear diseases and hearing care, rhinologic and sinus diseases, laryngeal disorders, and upper aerodigestive mucosal cancer globally. Conclusion and Relevance: This cross-sectional survey study provides a comprehensive assessment of the global OHNS workforce. These results can guide focused investment in training and policy development to address disparities in the availability of OHNS clinicians.


Assuntos
Otolaringologia , Humanos , Estudos Transversais , Recursos Humanos , Otolaringologia/educação , Inquéritos e Questionários , Cabeça , Saúde Global
4.
PLoS Comput Biol ; 19(4): e1011060, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37083820

RESUMO

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.


Assuntos
Células-Tronco Pluripotentes Induzidas , Humanos , Software , Simulação por Computador , Microscopia de Fluorescência , Mitocôndrias/fisiologia , Dinâmica Mitocondrial
5.
Curr Opin Otolaryngol Head Neck Surg ; 31(3): 194-201, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36942853

RESUMO

PURPOSE OF REVIEW: To highlight the need for comprehensive resource lists to provide baseline care of otolaryngologic conditions; to present a proposed list of essential equipment and services that may be applied toward surgical systems research, policymaking, and charitable efforts in global otolaryngology-head and neck surgery. RECENT FINDINGS: To provide effective and high-quality surgical care across care settings, there must be a global standard for equipment and ancillary services necessary to provide baseline care. Though there have been efforts to devise resource standards via equipment lists and appraisal tools, these have been limited in scope to general surgery, emergency care, and a few other subspecialty surgical contexts. Recent efforts have brought attention to the significant burden imposed by otolaryngologic conditions such as hearing loss, otitis media, head and neck cancer, head and neck trauma, and upper airway foreign bodies. Yet, there has not been a comprehensive list of resources necessary to provide baseline care for common otolaryngologic conditions. SUMMARY: Through an internal survey of its members, the Global Otolaryngology-Head and Neck Surgery Initiative has compiled a list of essential equipment and services to provide baseline care of otolaryngologic conditions. Our efforts aimed to address common otolaryngologic conditions that have been previously identified as high-priority with respect to prevalence and burden of disease. This expert-driven list of essential resources functions as an initial framework to be adapted for internal quality assessment, implementation research, health policy development, and economic priority-setting.


Assuntos
Surdez , Corpos Estranhos , Perda Auditiva , Otolaringologia , Humanos
6.
Int. arch. otorhinolaryngol. (Impr.) ; 26(3): 414-421, July-Sept. 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1405134

RESUMO

Abstract Introduction High-resolution computed tomography (HRCT) scans of the temporal bone are used to assess the bony erosion of the middle-ear structures whenever cholesteatoma is suspected. Objective To study the differences in HRCT Hounsfield unit (HU) index measurements of middle-ear bony structures between an ears with and without cholesteatoma. Methods A retrospective study of 59 patients who underwent surgery due to unilateral cholesteatoma. The HRCT HU index of the scutum, of three middle-ear ossicles, of the lateral semicircular canal (LSCC), and of the fallopian canal was measured in both ears. A comparison was made between the cholesteatoma and the non-cholesteatomatous ear (control). All measurements were conducted by an otolaryngologist. To assess the interobserver bias, 10% of the samples were randomly and independently assessed by another otolaryngologist and a neuroradiologist who were blinded. Results The average HU index was lower in the ear with cholesteatoma when compared with the non-cholesteatomatous ear. While the differences were statistically significant regarding the measurements of the scutum (516.02 ± 311.693 versus 855.64 ± 389.999; p = 0.001), the malleus (1049.44 ± 481.765 versus 1413.47 ± 313.376; p = 0.01), and the incus (498.03 ± 264.184 versus 714.25 ± 405.631; p = 0.001), the differences in the measurements of the LSCC (1042.34 ± 301.066 versus 1154.53 ± 359.609; p = 0.69) and of the fallopian canal (467.19 ± 221.556 versus 543.51 ± 263.573; p = 0.108) were not significantly different between both groups. The stapes was immeasurable in both groups due to its small size. Conclusion Hounsfield unit index measurements are a useful tool that may aid in the diagnosis of early-stage cholesteatoma.

7.
Int Arch Otorhinolaryngol ; 26(3): e414-e421, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35846805

RESUMO

Introduction High-resolution computed tomography (HRCT) scans of the temporal bone are used to assess the bony erosion of the middle-ear structures whenever cholesteatoma is suspected. Objective To study the differences in HRCT Hounsfield unit (HU) index measurements of middle-ear bony structures between an ears with and without cholesteatoma. Methods A retrospective study of 59 patients who underwent surgery due to unilateral cholesteatoma. The HRCT HU index of the scutum, of three middle-ear ossicles, of the lateral semicircular canal (LSCC), and of the fallopian canal was measured in both ears. A comparison was made between the cholesteatoma and the non-cholesteatomatous ear (control). All measurements were conducted by an otolaryngologist. To assess the interobserver bias, 10% of the samples were randomly and independently assessed by another otolaryngologist and a neuroradiologist who were blinded. Results The average HU index was lower in the ear with cholesteatoma when compared with the non-cholesteatomatous ear. While the differences were statistically significant regarding the measurements of the scutum (516.02 ± 311.693 versus 855.64 ± 389.999; p = 0.001), the malleus (1049.44 ± 481.765 versus 1413.47 ± 313.376; p = 0.01), and the incus (498.03 ± 264.184 versus 714.25 ± 405.631; p = 0.001), the differences in the measurements of the LSCC (1042.34 ± 301.066 versus 1154.53 ± 359.609; p = 0.69) and of the fallopian canal (467.19 ± 221.556 versus 543.51 ± 263.573; p = 0.108) were not significantly different between both groups. The stapes was immeasurable in both groups due to its small size. Conclusion Hounsfield unit index measurements are a useful tool that may aid in the diagnosis of early-stage cholesteatoma.

8.
Int J Pediatr Otorhinolaryngol ; 158: 111158, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35509139

RESUMO

OBJECTIVE: To identify risk factors associated with acute otitis media treatment failure (AOMTF) among 13-valent pneumococcal conjugate vaccine (PCV) immunized children. METHODS: In this retrospective study, we identified children <12 years who were admitted to our hospital November 2017-October 2020. Children were categorized either as acute otitis media treatment failure (AOMTF), if they received adequate pre-admission antibiotics, or as AOM without treatment failure (AOMwTF), if they did not receive any pre-admission antibiotics. We collected demographics, clinical behavior, laboratory results, length and hospitalization course. Hospitalization was justified if previously treated properly. RESULTS: The AOMTF group included 84 children (43 boys, mean age: 1.30 ± 0.83 years), whereas the AOMwTF group included 251 children (132 boys, mean age: 1.20 ± 0.89 years). AOMTF accounted for 25% of all AOM admissions. Among the AOMTF group, 46 (54.8%) were treated with amoxicillin and 24 (28.6%) with amoxicillin/clavulanic acid. Risk factors for AOMTF included recurrent AOM episodes history (30.9% vs 5.5%, OR 7.6, 95%CI 3.5-15.4, p < 0.001), otorrhea (29.4% vs 9.5%, OR 4, 95%CI 2.1-7.5, p < 0.001), tympanic membrane perforation (14.2% vs 4.3%, OR 3.6, 95%CI 1.5-8.6, p < 0.0019). Children with AOMTF were treated more with 2nd- or 3rd-line antibiotics (90.2% vs 65.9%, OR 4, 95%CI 2.2-10.4, p < 0.001), and underwent more myringotomy/ventilation tube insertions (14.4% vs 6.9%, OR 2.3, 95%CI 1.0-5.0, p = 0.037). Mean admission durations were similar: 3.83 ± 1.6 days in the AOMTF group vs 3.37 ± 2.77 days in the AOMwTF group (p = 0.15). CONCLUSION: Risk factors associated with AOMTF should be identified early during the AOM course to reduce complication rates and surgery referral.


Assuntos
Antibacterianos , Otite Média , Doença Aguda , Amoxicilina/uso terapêutico , Criança , Pré-Escolar , Humanos , Lactente , Masculino , Otite Média/tratamento farmacológico , Vacinas Pneumocócicas , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento
9.
Arthritis Rheumatol ; 74(8): 1363-1375, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35333447

RESUMO

OBJECTIVE: To investigate the hypothesis that selective inhibitors of nuclear export (SINE compounds), recently approved for treatment of refractory plasma cell (PC) malignancy, may have potential in the treatment of lupus. METHODS: Female NZB/NZW mice were treated with the SINE compound KPT-350 or vehicle control. Tissue specimens were harvested and analyzed by flow cytometry, using standard markers. Nephritis was monitored by determining the proteinuria score and by histologic analysis of kidney specimens. Serum anti-double-stranded DNA (anti-dsDNA) levels were measured by enzyme-linked immunosorbent assay, and total numbers of IgG-secreting and dsDNA-specific antibody-secreting cells were assessed by enzyme-linked immunospot assay. RESULTS: KPT-350 abrogated murine lupus nephritis at both early and late stages of the disease and rapidly impaired generation of autoreactive PCs in germinal centers (GCs). SINE compounds inhibited the production of NF-κB-driven homeostatic chemokines by stromal cells, altering splenic B and T cell strategic positioning and significantly reducing follicular helper T cell, GC B cell, and autoreactive PC counts. KPT-350 also decreased levels of cytokines and chemokines involved in PC survival and recruitment in the kidney of lupus-prone mice. Exportin 1, the target of SINE compounds, was detected in GCs of human tonsils, splenic B cells of lupus patients, and multiple B cell subsets in the kidneys of patients with lupus nephritis. CONCLUSION: Collectively, our results provide support for the therapeutic potential of SINE compounds, via their targeting of several molecular and cellular pathways critical in lupus pathogenesis, including autoantibody production by plasma cells.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Transporte Ativo do Núcleo Celular , Animais , Autoanticorpos , Modelos Animais de Doenças , ELISPOT , Feminino , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Camundongos , Camundongos Endogâmicos NZB , Plasmócitos
10.
Harefuah ; 161(12): 757-762, 2022 Dec.
Artigo em Hebraico | MEDLINE | ID: mdl-36916115

RESUMO

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.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Humanos , Idoso de 80 Anos ou mais , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/patologia , Cóclea/diagnóstico por imagem , Cóclea/patologia , Vertigem/complicações , Vertigem/patologia , Perda Auditiva Súbita/diagnóstico , Perda Auditiva Súbita/etiologia , Perda Auditiva Súbita/patologia , Hemorragia/etiologia , Imageamento por Ressonância Magnética/métodos , Anticoagulantes
11.
Clin Cancer Res ; 28(3): 452-460, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34728525

RESUMO

PURPOSE: Selinexor is an oral selective inhibitor of exportin-1 (XPO1) with efficacy in various solid and hematologic tumors. We assessed intratumoral penetration, safety, and efficacy of selinexor monotherapy for recurrent glioblastoma. PATIENTS AND METHODS: Seventy-six adults with Karnofsky Performance Status ≥ 60 were enrolled. Patients undergoing cytoreductive surgery received up to three selinexor doses (twice weekly) preoperatively (Arm A; n = 8 patients). Patients not undergoing surgery received 50 mg/m2 (Arm B, n = 24), or 60 mg (Arm C, n = 14) twice weekly, or 80 mg once weekly (Arm D; n = 30). Primary endpoint was 6-month progression-free survival rate (PFS6). RESULTS: Median selinexor concentrations in resected tumors from patients receiving presurgical selinexor was 105.4 nmol/L (range 39.7-291 nmol/L). In Arms B, C, and D, respectively, the PFS6 was 10% [95% confidence interval (CI), 2.79-35.9], 7.7% (95% CI, 1.17-50.6), and 17% (95% CI, 7.78-38.3). Measurable reduction in tumor size was observed in 19 (28%) and RANO-response rate overall was 8.8% [Arm B, 8.3% (95% CI, 1.0-27.0); C: 7.7% (95% CI, 0.2-36.0); D: 10% (95% CI, 2.1-26.5)], with one complete and two durable partial responses in Arm D. Serious adverse events (AEs) occurred in 26 (34%) patients; 1 (1.3%) was fatal. The most common treatment-related AEs were fatigue (61%), nausea (59%), decreased appetite (43%), and thrombocytopenia (43%), and were manageable by supportive care and dose modification. Molecular studies identified a signature predictive of response (AUC = 0.88). CONCLUSIONS: At 80 mg weekly, single-agent selinexor induced responses and clinically relevant PFS6 with manageable side effects requiring dose reductions. Ongoing trials are evaluating safety and efficacy of selinexor in combination with other therapies for newly diagnosed or recurrent glioblastoma.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Hidrazinas/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Triazóis/administração & dosagem , Administração Oral , Adulto , Idoso , Encéfalo/metabolismo , Neoplasias Encefálicas/cirurgia , Procedimentos Cirúrgicos de Citorredução , Feminino , Glioblastoma/cirurgia , Humanos , Hidrazinas/efeitos adversos , Hidrazinas/metabolismo , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Triazóis/efeitos adversos , Triazóis/metabolismo , Adulto Jovem
13.
OTO Open ; 5(2): 2473974X211024145, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34212124

RESUMO

Equitable research collaborations benefit the quality and relevance of global otolaryngology-head and neck surgery research. However, analyses of existing global health literature have shown disproportionate representation by foreign authors. To avert this inequity and improve global otolaryngology-head and neck surgery research, we propose a framework that emphasizes local representation and capacity building in research.

14.
Isr Med Assoc J ; 23(7): 426-431, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34251125

RESUMO

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.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias , Cuidados Paliativos , Polimedicação , Esteroides/uso terapêutico , Assistência Terminal , Criança , Procedimentos Clínicos/estatística & dados numéricos , Demografia , Feminino , Pesquisa sobre Serviços de Saúde , Hospitalização/estatística & dados numéricos , Humanos , Israel/epidemiologia , Masculino , Estadiamento de Neoplasias , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Neoplasias/patologia , Cuidados Paliativos/métodos , Cuidados Paliativos/estatística & dados numéricos , Ordens quanto à Conduta (Ética Médica) , Assistência Terminal/métodos , Assistência Terminal/estatística & dados numéricos
15.
Antiviral Res ; 192: 105115, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34157321

RESUMO

The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the recent global pandemic. The nuclear export protein (XPO1) has a direct role in the export of SARS-CoV proteins including ORF3b, ORF9b, and nucleocapsid. Inhibition of XPO1 induces anti-inflammatory, anti-viral, and antioxidant pathways. Selinexor is an FDA-approved XPO1 inhibitor. Through bioinformatics analysis, we predicted nuclear export sequences in the ACE-2 protein and confirmed by in vitro testing that inhibition of XPO1 with selinexor induces nuclear localization of ACE-2. Administration of selinexor inhibited viral infection prophylactically as well as therapeutically in vitro. In a ferret model of COVID-19, selinexor treatment reduced viral load in the lungs and protected against tissue damage in the nasal turbinates and lungs in vivo. Our studies demonstrated that selinexor downregulated the pro-inflammatory cytokines IL-1ß, IL-6, IL-10, IFN-γ, TNF-α, and GMCSF, commonly associated with the cytokine storm observed in COVID-19 patients. Our findings indicate that nuclear export is critical for SARS-CoV-2 infection and for COVID-19 pathology and suggest that inhibition of XPO1 by selinexor could be a viable anti-viral treatment option.


Assuntos
Tratamento Farmacológico da COVID-19 , Hidrazinas/farmacologia , SARS-CoV-2/efeitos dos fármacos , Triazóis/farmacologia , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Antivirais/farmacologia , COVID-19/virologia , Chlorocebus aethiops , Citocinas , Furões , Humanos , Carioferinas/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/virologia , SARS-CoV-2/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Células Vero , Replicação Viral , Proteína Exportina 1
16.
Neuro Oncol ; 23(8): 1252-1260, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-33822177

RESUMO

On July 24, 2020, a workshop sponsored by the National Brain Tumor Society was held on innovating brain tumor clinical trials based on lessons learned from the COVID-19 experience. Various stakeholders from the brain tumor community participated including the US Food and Drug Administration (FDA), academic and community clinicians, researchers, industry, clinical research organizations, patients and patient advocates, and representatives from the Society for Neuro-Oncology and the National Cancer Institute. This report summarizes the workshop and proposes ways to incorporate lessons learned from COVID-19 to brain tumor clinical trials including the increased use of telemedicine and decentralized trial models as opportunities for practical innovation with potential long-term impact on clinical trial design and implementation.


Assuntos
Neoplasias Encefálicas , COVID-19 , Neoplasias Encefálicas/terapia , Humanos , National Cancer Institute (U.S.) , SARS-CoV-2 , Estados Unidos , United States Food and Drug Administration
18.
Front Cell Infect Microbiol ; 11: 749911, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35071032

RESUMO

The global coronavirus disease-2019 (COVID-19) pandemic has changed the prevalence and management of many pediatric infectious diseases, including acute otitis media (AOM). Coronaviruses are a group of RNA viruses that cause respiratory tract infections in humans. Before the COVID-19 pandemic, coronavirus serotypes OC43, 229E, HKU1, and NL63 were infrequently detected in middle ear fluid (MEF) specimens and nasopharyngeal aspirates in children with AOM during the 1990s and 2000s and were associated with a mild course of the disease. At times when CoV was detected in OM cases, the overall viral load was relatively low. The new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen responsible for the eruption of the COVID-19 global pandemic. Following the pandemic declaration in many countries and by the World Health Organization in March 2020, preventive proactive measures were imposed to limit COVID-19. These included social distancing; lockdowns; closure of workplaces; kindergartens and schools; increased hygiene; use of antiseptics and alcohol-based gels; frequent temperature measurements and wearing masks. These measures were not the only ones taken, as hospitals and clinics tried to minimize treating non-urgent medical referrals such as OM, and elective surgical procedures were canceled, such as ventilating tube insertion (VTI). These changes and regulations altered the way OM is practiced during the COVID-19 pandemic. Advents in technology allowed a vast use of telemedicine technologies for OM, however, the accuracy of AOM diagnosis in those encounters was in doubt, and antibiotic prescription rates were still reported to be high. There was an overall decrease in AOM episodes and admissions rates and with high spontaneous resolution rates of MEF in children, and a reduction in VTI surgeries. Despite an initial fear regarding viral shedding during myringotomy, the procedure was shown to be safe. Special draping techniques for otologic surgery were suggested. Other aspects of OM practice included the presentation of adult patients with AOM who tested positive for SARS-2-CoV and its detection in MEF samples in living patients and in the mucosa of the middle ear and mastoid in post-mortem specimens.


Assuntos
COVID-19 , Otite Média , Criança , Controle de Doenças Transmissíveis , Humanos , Otite Média/epidemiologia , Otite Média/prevenção & controle , Pandemias/prevenção & controle , SARS-CoV-2
19.
Int J Pediatr Otorhinolaryngol ; 138: 110350, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32911240

RESUMO

BACKGROUND: Tympanostomy tube (TT) insertion is a common procedure in children with otitis media with effusion. Post-TT otorrhea (PTTO) is a frequent post-operative complication. Biofilms are involved in chronic PTTO cases. OBJECTIVE: To describe and qualitatively analyze the geometry and sites prone to biofilms on removed TTs, relatively to their position in the ear, past medical/surgical history and PTTO presence. METHODS: Biofilms presence and topographic distribution on TTs were ex vivo evaluated by using scanning electron microscope, confocal microscope and stereo-microscope. RESULTS: Forty-eight TTs from 30 children were analyzed. Indications for removal were: 71% due to retained TTs (average time from insertion: 24.4 ± 15.1 months), 23% due to chronic PTTO, and 6% due to TT obstruction/dysfunction. Different types of bacterial biofilms were detected on all TTs, regardless the time from their insertion nor their types. Biofilms were observed more on the perpendicular junction and on the internal lumen, and more biofilm colonies were detected on the medial part, facing the middle ear mucosa. TTs removed from children with PTTO exhibited more biofilm colonies when compared to their peers. Of the 16 children who underwent adenoidectomy concomitantly with TT insertion, 10 (62%) children were sent for TT removal due to retained TTs, and 6 (38%) children due to chronic PTTO (p = 0.03). CONCLUSION: Descriptive analysis of biofilm topographic distribution demonstrated adhesions on specific TT areas: perpendicular junctions and the internal lumen. Such "prone zones" may be the future target areas for changes in TT geometry or can be specifically coated with anti-biofilm materials.


Assuntos
Biofilmes , Ventilação da Orelha Média/efeitos adversos , Ventilação da Orelha Média/instrumentação , Otite Média com Derrame/cirurgia , Complicações Pós-Operatórias/microbiologia , Próteses e Implantes/microbiologia , Bactérias , Pré-Escolar , Humanos , Masculino
20.
Int. arch. otorhinolaryngol. (Impr.) ; 24(2): 181-187, Apr.-June 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1134126

RESUMO

Abstract Introduction Streptococcus pneumoniae is a major pathogen of otogenic meningitis (OgM), the most commonly reported intra-cranial complication of otitis media (OM). Objectives To study the changes in adult OgM patients in the pneumococcal conjugated vaccines (PCVs) era. Methods Retrospective cohort of adults presenting with concurrent OM and meningitis in a secondary medical care center between 2005 and 2015. Data collected included demographics, OM-related symptoms, cerebrospinal fluid (CSF) and ear culture results, pre- and during hospitalization antibiotic treatment, imaging findings, and complications. We compared the pre-PCV years (2005-2009) with the post-PCV years (2010-2015). Outcomes were 1) incidence of all-cause adult OgM from the total meningitis cases; 2) impact of PCVs on the clinical presentation of OgM and bacteriology. Results Otogenic meningitis was diagnosed in 26 out of 45 (58%) cases of all-cause meningitis admissions. Of those, 10 (38%) were male, with a mean age of 62.4 years old. Ear-related signs and symptoms were documented in 70% of the patients, and OgM was diagnosed following imaging studies in 6 out of 26 (23%) patients. All of the patients received intravenous antibiotic therapy, and 7 (27%) patients required surgical interventions: 6 required myringotomy and 1 required mastoidectomy. There were 12 (46%) patients in the pre-PCV years and 14 (56%) in the post-PCV years. The positive pneumococcal CSF and ear culture rates remained high and unchanged (~ 75%). There were no significant changes in the clinical presentation or mortality rates. Conclusion Micro-otoscopy should be included in the routine work-up of any suspected adult meningitis, because OgM is underdiagnosed. Unlike their impact on pediatric otitismedia, PCVs did not change the epidemiology and bacteriology of OgM.

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