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1.
Int J Dermatol ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426359

RESUMO

A 60-year-old female with diabetes and hypothyroidism presented with a 2-year history of asymptomatic elevated lesions on the dorsum of her hands.

3.
Reg Anesth Pain Med ; 49(3): 192-199, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-37407277

RESUMO

INTRODUCTION: Spinal cord injury (SCI) is one of the most dreaded complications after spinal cord stimulation (SCS) implantation surgery. As a result, intraoperative neurophysiological monitoring (IONM) has been proposed to avoid accidental damage to nervous structures under anesthesia and confirm positioning for optimal stimulation. Our study uses a large administrative claims database to determine the 30-day risk of SCI after SCS implantation. METHODS: This retrospective cohort study used the IBM MarketScan Commercial and Medicare Supplemental Databases from 2016 to 2019. Adult patients undergoing SCS surgical procedures with at least 90 days of follow-up, IONM use, the type of sedation used during the procedure, and subsequent SCI were identified using administrative codes. In addition, logistic regression was used to examine the relationship between various risk factors and subsequent SCI. RESULTS: A total of 9676 patients underwent SCS surgery (64.7% percutaneous implants) during the study period. Nine hundred and forty-four (9.75%) patients underwent SCS implantation with IONM. Conscious sedation, Monitored Anesthesia Care anesthesia, and general anesthesia were used in patients with 0.9%, 60.2%, and 28.6%, respectively. Eighty-one (0.8%) patients developed SCI within 30 days after SCS implant surgery. The SCI rate was higher in the group that underwent IONM (2% vs 0.7%, p value <0.001) during the implantation procedure, reflecting the underlying risk. After adjustment for other factors, the OR of SCI is 2.39 (95% CI: 1.33 to 4.14, p value=0.002) times higher for those with IONM than those without IONM. CONCLUSIONS: Increased SCI risk among patients with IONM likely reflects higher baseline risk, and further research is needed for risk mitigation.


Assuntos
Monitorização Neurofisiológica Intraoperatória , Traumatismos da Medula Espinal , Estimulação da Medula Espinal , Adulto , Humanos , Idoso , Estados Unidos , Monitorização Neurofisiológica Intraoperatória/métodos , Estudos Retrospectivos , Medicare , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/etiologia , Estimulação da Medula Espinal/efeitos adversos , Estimulação da Medula Espinal/métodos , Anestesia Geral/efeitos adversos , Medula Espinal
5.
Infect Genet Evol ; 116: 105537, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38056703

RESUMO

BACKGROUND: Leprosy is caused by Mycobacterium leprae and Mycobacterium lepromatosis. Both organisms cannot be cultured in vitro. M. lepromatosis was found to be associated mainly with diffuse lepromatous leprosy and with Lucio's phenomena initially. Later, M. lepromatosis was observed in borderline leprosy cases (BL), lepromatous leprosy cases (LL) and leprosy reactional cases (T1R and ENL). Although many cases are being reported with similar clinical features like Lucio phenomenon in India but M. lepromatosis was not isolated from these cases. The aim of this study was to screen MB patients and patients with type 2 reaction for the presence of M. lepromatosis. METHODOLOGY: We recruited a total of 75 multibacillary leprosy cases (45 MB cases without reaction and 30 type 2 reaction (ENL) cases) from TLM hospitals Purulia (West Bengal), Barabanki (Uttar Pradesh), Shahdara (Delhi) and PGIMER (Chandigarh), India. Punch biopsies of 5 mm were collected in 70% ethanol from all the study subjects. DNA was extracted followed by Hemi-nested PCR targeting 16S rRNA gene specific for M. lepromatosis. Further, PCR products were processed for Sanger sequencing for an absolute confirmation of M. lepromatosis. Whole genome sequencing was done to confirm the presence of M. lepromatosis. RESULT: We observed presence of M. lepromatosis in 4 necrotic ENL patients by heminested PCR. There was 100% 16S rRNA sequence similarity with M. lepromatosis FJ924 in one case, 98.96% in two cases and in one case it was 90.9% similarity by nucleotide BLAST (BLASTn) by using the NCBI website. On the basis of Sanger sequencing, we noted presence of M. lepromatosis in 3 necrotic ENL patients as one sample only gave 90.9% similarity by BLASTn. On the basis of de novo assembly and genome obtained, only one sample S4 with a 2.9 mb genome size was qualified for downstream analysis. Sixteen M. lepromatosis- specific proteins were identified in this case and the closest species was M. lepromatosis strain FJ924 based on whole genome level phylogeny. CONCLUSION: These results provide valuable insights into the prevalence of M. lepromatosis in ENL patients in different regions of India and contribute to our understanding of the genetic characteristics of this pathogen in the context of leprosy.


Assuntos
Hanseníase Virchowiana , Hanseníase , Humanos , Hanseníase Virchowiana/epidemiologia , Hanseníase Virchowiana/microbiologia , Hanseníase Virchowiana/patologia , RNA Ribossômico 16S/genética , Mycobacterium leprae/genética , Hanseníase/microbiologia , Genômica
6.
Semin Pediatr Neurol ; 48: 101087, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38065633

RESUMO

The relationship between sleep and epilepsy is both intimate and bidirectional. The molecular mechanisms which control circadian rhythm and the sleep/wake cycle are dysregulated in epileptogenic tissue and are themselves effected by molecular pathways for epilepsy. Sleep affects the frequency of interictal epileptiform discharges and recent research has raised new questions regarding the impact of discharges on sleep function and cognition. Epileptiform discharges themselves affect sleep architecture and increase the risk of sleep disorders. Several sleep-related epilepsy syndromes have undergone changes in their classification which highlights their intimate relationship to sleep and novel screening tools have been developed to help clinicians better differentiate epileptic seizures from sleep-related paroxysmal events. Improving sleep and addressing sleep disorders has been associated with improved seizure control and increased well-being in people with epilepsy. These interactions are discussed in detail in this review.


Assuntos
Epilepsia , Transtornos do Sono-Vigília , Humanos , Eletroencefalografia , Sono , Convulsões/complicações , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/diagnóstico
7.
Indian Dermatol Online J ; 14(6): 753-761, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38099011

RESUMO

Mycobacterium indicus pranii (MIP), previously called Mw vaccine, is a one-of-a-kind immunomodulatory vaccine. It was indigenously developed in India for use in leprosy. MIP is heat-killed Mycobacterium w, which is a non-pathogenic atypical mycobacterium belonging to Class IV of Runyon classification. It shares epitopes with Mycobacterium leprae and Mycobacterium tuberculosis, which forms the rationale behind its use in leprosy and tuberculosis. MIP activates both innate and acquired immunity. It induces a Th1 and Th17 immune response along with downregulation of Th2 pathway and activates macrophages and dendritic cells. MIP vaccine is safe with adverse effects such as local site erythema, swelling, and rarely fever and other systemic reactions. Apart from leprosy, MIP has been used in dermatological diseases such as warts and psoriasis. Clinical trials have evaluated the efficacy of MIP in a plenitude of non-dermatological conditions such as category II tuberculosis, Gram-negative sepsis, non-small cell lung cancer, human immunodeficiency virus (HIV), muscle-invasive bladder cancer, and very recently, coronavirus 2019 (COVID-19). In vitro and animal studies have also demonstrated its utility in leishmaniasis, melanoma, and as a vaccine for the prevention of pregnancy. The PubMed database was searched using "Mycobacterium indicus pranii, MIP, Mycobacterium w" as the keyword in title. This comprehensive review provides useful information for healthcare professionals about immunotherapeutic potential of MIP vaccine, its composition, dosing schedule, administration, and side effects besides its efficacy in various indications other than leprosy.

9.
J Glob Antimicrob Resist ; 35: 262-267, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37852372

RESUMO

OBJECTIVES: Drug resistance in leprosy is an emerging concern, leading to treatment failures, recurrences, and potential spread of resistant Mycobacterium leprae in the community. In this study, we aimed to assess drug resistance prevalence and patterns amongst leprosy patients at a tertiary care referral hospital in India. METHODS: Mutations in drug resistance determining regions for dapsone, rifampicin, and ofloxacin of the M. leprae genome in DNA extracted from skin biopsies of 136 leprosy patients (treatment-naive = 67, with persistent skin lesions = 35, with recurrence = 34) were analysed by polymerase chain reaction followed by Sanger sequencing. Wild-type strain (Thai-53) was used as a reference strain. RESULTS: Resistance mutations were identified in a total of 23 patients, constituting 16.9% of the cohort. Within this subset of 23 cases, resistance to ofloxacin was observed in 17 individuals (12.5%), while resistance to both dapsone and rifampicin was detected in three patients each (2.2% for both). The occurrence of ofloxacin resistance showed minimal disparity between recurrent and treatment-naive cases, at 17.6% and 16.4%, respectively. Dapsone resistance emerged in two treatment-naive cases and one case with persistent skin lesions. Notably, none of the treatment-naive cases or those with recurrence/relapse exhibited rifampicin resistance. Subsequently, no statistically significant correlation was identified between other clinical variables and the presence of antimicrobial resistance. CONCLUSIONS: The occurrence of resistance to the current multidrug therapy regimen (specifically dapsone and rifampicin) and to ofloxacin, a secondary antileprosy medication in M. leprae, represents a concerning scenario. This calls for an expansion towards bactericidal drug options and the establishment of robust surveillance for drug resistance in countries burdened with high leprosy rates. Moreover, the introduction of stringent antimicrobial stewardship initiatives is imperative. As a single centre study, it represents a limited, cross-sectional view of the real situation in the field.


Assuntos
Hanseníase , Mycobacterium leprae , Humanos , Mycobacterium leprae/genética , Rifampina/farmacologia , Rifampina/uso terapêutico , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Ofloxacino/farmacologia , Quimioterapia Combinada , Estudos Transversais , Farmacorresistência Bacteriana/genética , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Dapsona/farmacologia , Dapsona/uso terapêutico , Índia/epidemiologia
10.
Neuromodulation ; 26(5): 1095-1101, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35953425

RESUMO

OBJECTIVES: Lead migration (LM) after spinal cord stimulation (SCS) implantation surgery is the most common device-related complication. Our study of lead and implantable pulse generator (IPG) migration using a large administrative claims data base aims to understand rates, risk factors, and outcomes after SCS implantation. MATERIALS AND METHODS: This retrospective cohort study used the IBM® MarketScan® (Armonk, NY) Commercial and Medicare Supplemental Databases from 2016 to 2018. Adult patients who underwent SCS surgical procedures with at least 90 days of follow-up were identified using Current Procedural Terminology (CPT®) codes. Patients with LM and IPG migration after SCS surgery were identified using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10 CM) codes. Patients who underwent revision surgery after SCS implantation were identified using the CPT codes and ICD-10 CM codes. In addition, patient characteristics associated with LM or IPG migration, the temporal relationship of migration diagnosis, and revision surgery were evaluated in the cohort. Continuous outcomes were compared between groups using the two-sample Student t-test. The Fisher exact test was used to compare categorical outcomes between groups. RESULTS: A total of 7322 patients (64.4% percutaneous SCS) underwent SCS surgery during the study period. A total of 141 patients (1.9%) had LM or IPG migration. Of those, 116 patients (1.6%) had LM only; 18 patients (0.2%) had IPG migration; and seven patients (0.1%) had LM and IPG migration. The mean duration for migration diagnosis after initial SCS implantation was 168 (±163.1) days. The mean duration to revision surgery after the migration diagnosis was 12.3 (±35.2) days only. Most patients with migration (105, 74.5%) underwent revision surgery. Only younger age (p = 0.02) was associated with migration in this study. CONCLUSIONS: LM and pulse generator migration that required revision surgery occurred in a small proportion of patients who underwent SCS surgical procedures.


Assuntos
Estimulação da Medula Espinal , Adulto , Humanos , Idoso , Estados Unidos/epidemiologia , Estimulação da Medula Espinal/efeitos adversos , Estimulação da Medula Espinal/métodos , Estudos Retrospectivos , Medicare , Próteses e Implantes , Reoperação , Medula Espinal/cirurgia
11.
EBioMedicine ; 86: 104344, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36370635

RESUMO

BACKGROUND: Large lung nodules (≥15 mm) have the highest risk of malignancy, and may exhibit important differences in phenotypic or clinical characteristics to their smaller counterparts. Existing risk models do not stratify large nodules well. We aimed to develop and validate an integrated segmentation and classification pipeline, incorporating deep-learning and traditional radiomics, to classify large lung nodules according to cancer risk. METHODS: 502 patients from five U.K. centres were recruited to the large-nodule arm of the retrospective LIBRA study between July 2020 and April 2022. 838 CT scans were used for model development, split into training and test sets (70% and 30% respectively). An nnUNet model was trained to automate lung nodule segmentation. A radiomics signature was developed to classify nodules according to malignancy risk. Performance of the radiomics model, termed the large-nodule radiomics predictive vector (LN-RPV), was compared to three radiologists and the Brock and Herder scores. FINDINGS: 499 patients had technically evaluable scans (mean age 69 ± 11, 257 men, 242 women). In the test set of 252 scans, the nnUNet achieved a DICE score of 0.86, and the LN-RPV achieved an AUC of 0.83 (95% CI 0.77-0.88) for malignancy classification. Performance was higher than the median radiologist (AUC 0.75 [95% CI 0.70-0.81], DeLong p = 0.03). LN-RPV was robust to auto-segmentation (ICC 0.94). For baseline solid nodules in the test set (117 patients), LN-RPV had an AUC of 0.87 (95% CI 0.80-0.93) compared to 0.67 (95% CI 0.55-0.76, DeLong p = 0.002) for the Brock score and 0.83 (95% CI 0.75-0.90, DeLong p = 0.4) for the Herder score. In the international external test set (n = 151), LN-RPV maintained an AUC of 0.75 (95% CI 0.63-0.85). 18 out of 22 (82%) malignant nodules in the Herder 10-70% category in the test set were identified as high risk by the decision-support tool, and may have been referred for earlier intervention. INTERPRETATION: The model accurately segments and classifies large lung nodules, and may improve upon existing clinical models. FUNDING: This project represents independent research funded by: 1) Royal Marsden Partners Cancer Alliance, 2) the Royal Marsden Cancer Charity, 3) the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, 4) the National Institute for Health Research (NIHR) Biomedical Research Centre at Imperial College London, 5) Cancer Research UK (C309/A31316).


Assuntos
Neoplasias Pulmonares , Lesões Pré-Cancerosas , Masculino , Humanos , Feminino , Estudos Retrospectivos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia Computadorizada por Raios X , Pulmão/patologia
12.
Sleep ; 45(9)2022 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-35695235

RESUMO

This study was aimed to evaluate the yearly incidence of pediatric narcolepsy prior to and following the 2009 H1N1 pandemic and to evaluate seasonal patterns of narcolepsy onset and associations with H1N1 influenza infection in the United States. This was a multicenter retrospective study with prospective follow-up. Participants were recruited from members of the Pediatric Working Group of the Sleep Research Network including 22 sites across the United States. The main outcomes were monthly and yearly incident cases of childhood narcolepsy in the United States, and its relationship to historical H1N1 influenza data. A total of 950 participants were included in the analysis; 487 participants were male (51.3%). The mean age at onset of excessive daytime sleepiness (EDS) was 9.6  ±â€… 3.9 years. Significant trend changes in pediatric narcolepsy incidence based on EDS onset (p  <  .0001) occurred over the 1998-2016 period, peaking in 2010, reflecting a 1.6-fold increase in narcolepsy incidence. In addition, there was significant seasonal variation in narcolepsy incident cases, with increased cases in spring (p  <  .05). Cross-correlation analysis demonstrated a significant correlation between monthly H1N1 infection and monthly narcolepsy incident cases (p  =  .397, p  <  .0001) with a lag time of 8 months. We conclude that there is a significant increase in pediatric narcolepsy incidence after the 2009 H1N1 pandemic in the United States. However, the magnitude of increase is lower than reported in European countries and in China. The temporal correlation between monthly H1N1 infection and monthly narcolepsy incidence, suggests that H1N1 infection may be a contributing factor to the increased pediatric narcolepsy incidence after the 2009 H1N1 pandemics.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Narcolepsia , Criança , Distúrbios do Sono por Sonolência Excessiva/complicações , Feminino , Humanos , Incidência , Influenza Humana/complicações , Influenza Humana/epidemiologia , Masculino , Narcolepsia/epidemiologia , Narcolepsia/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Sono , Vacinação/efeitos adversos
14.
BMC Infect Dis ; 21(1): 580, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134647

RESUMO

BACKGROUND: COVID-19 has resulted in significant morbidity and mortality worldwide. Lateral flow assays can detect anti-Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies to monitor transmission. However, standardized evaluation of their accuracy and tools to aid in interpreting results are needed. METHODS: We evaluated 20 IgG and IgM assays selected from available tests in April 2020. We evaluated the assays' performance using 56 pre-pandemic negative and 56 SARS-CoV-2-positive plasma samples, collected 10-40 days after symptom onset, confirmed by a molecular test and analyzed by an ultra-sensitive immunoassay. Finally, we developed a user-friendly web app to extrapolate the positive predictive values based on their accuracy and local prevalence. RESULTS: Combined IgG + IgM sensitivities ranged from 33.9 to 94.6%, while combined specificities ranged from 92.6 to 100%. The highest sensitivities were detected in Lumiquick for IgG (98.2%), BioHit for both IgM (96.4%), and combined IgG + IgM sensitivity (94.6%). Furthermore, 11 LFAs and 8 LFAs showed perfect specificity for IgG and IgM, respectively, with 15 LFAs showing perfect combined IgG + IgM specificity. Lumiquick had the lowest estimated limit-of-detection (LOD) (0.1 µg/mL), followed by a similar LOD of 1.5 µg/mL for CareHealth, Cellex, KHB, and Vivachek. CONCLUSION: We provide a public resource of the accuracy of select lateral flow assays with potential for home testing. The cost-effectiveness, scalable manufacturing process, and suitability for self-testing makes LFAs an attractive option for monitoring disease prevalence and assessing vaccine responsiveness. Our web tool provides an easy-to-use interface to demonstrate the impact of prevalence and test accuracy on the positive predictive values.


Assuntos
Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Imunoglobulina G/sangue , Imunoglobulina M/sangue , SARS-CoV-2/imunologia , Adulto , Idoso , COVID-19/sangue , Feminino , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Sensibilidade e Especificidade , Design Centrado no Usuário , Interface Usuário-Computador
15.
Cephalalgia ; 41(2): 135-147, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32903062

RESUMO

BACKGROUND: Pharmacological management of migraine can be ineffective for some patients. We previously demonstrated that exposure to green light resulted in antinociception and reversal of thermal and mechanical hypersensitivity in rodent pain models. Given the safety of green light emitting diodes, we evaluated green light as a potential therapy in patients with episodic or chronic migraine. MATERIAL AND METHODS: We recruited (29 total) patients, of whom seven had episodic migraine and 22 had chronic migraine. We used a one-way cross-over design consisting of exposure for 1-2 hours daily to white light emitting diodes for 10 weeks, followed by a 2-week washout period followed by exposure for 1-2 hours daily to green light emitting diodes for 10 weeks. Patients were allowed to continue current therapies and to initiate new treatments as directed by their physicians. Outcomes consisted of patient-reported surveys. The primary outcome measure was the number of headache days per month. Secondary outcome measures included patient-reported changes in the intensity and frequency of the headaches over a two-week period and other quality of life measures including ability to fall and stay asleep, and ability to perform work. Changes in pain medications were obtained to assess potential reduction. RESULTS: When seven episodic migraine and 22 chronic migraine patients were analyzed as separate cohorts, white light emitting diodes produced no significant change in headache days in either episodic migraine or chronic migraine patients. Combining data from the episodic migraine and chronic migraine groups showed that white light emitting diodes produced a small, but statistically significant reduction in headache days from (days ± SEM) 18.2 ± 1.8 to 16.5 ± 2.01 days. Green light emitting diodes resulted in a significant decrease in headache days from 7.9 ± 1.6 to 2.4 ± 1.1 and from 22.3 ± 1.2 to 9.4 ± 1.6 in episodic migraine and chronic migraine patients, respectively. While some improvement in secondary outcomes was observed with white light emitting diodes, more secondary outcomes with significantly greater magnitude including assessments of quality of life, Short-Form McGill Pain Questionnaire, Headache Impact Test-6, and Five-level version of the EuroQol five-dimensional survey without reported side effects were observed with green light emitting diodes. Conclusions regarding pain medications reduction with green light emitting diode exposure were not possible. No side effects of light therapy were reported. None of the patients in the study reported initiation of new therapies. DISCUSSION: Green light emitting diodes significantly reduced the number of headache days in people with episodic migraine or chronic migraine. Additionally, green light emitting diodes significantly improved multiple secondary outcome measures including quality of life and intensity and duration of the headache attacks. As no adverse events were reported, green light emitting diodes may provide a treatment option for those patients who prefer non-pharmacological therapies or may be considered in complementing other treatment strategies. Limitations of this study are the small number of patients evaluated. The positive data obtained support implementation of larger clinical trials to determine possible effects of green light emitting diode therapy.This study is registered with clinicaltrials.gov under NCT03677206.


Assuntos
Transtornos de Enxaqueca , Qualidade de Vida , Estudos Cross-Over , Cefaleia , Humanos , Luz , Transtornos de Enxaqueca/terapia , Dor , Resultado do Tratamento
16.
Pain Med ; 22(1): 118-130, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33155057

RESUMO

OBJECTIVE: Fibromyalgia is a functional pain disorder in which patients suffer from widespread pain and poor quality of life. Fibromyalgia pain and its impact on quality of life are not effectively managed with current therapeutics. Previously, in a preclinical rat study, we demonstrated that exposure to green light-emitting diodes (GLED) for 8 hours/day for 5 days resulted in antinociception and reversal of thermal and mechanical hypersensitivity associated with models of injury-related pain. Given the safety of GLED and the ease of its use, our objective is to administer GLED as a potential therapy to patients with fibromyalgia. DESIGN: One-way crossover clinical trial. SETTING: United States. METHOD: We enrolled 21 adult patients with fibromyalgia recruited from the University of Arizona chronic pain clinic who were initially exposed to white light-emitting diodes and then were crossed over to GLED for 1 to 2 hours daily for 10 weeks. Data were collected by using paper surveys. RESULTS: When patients were exposed to GLED, but not white light-emitting diodes, they reported a significant reduction in average pain intensity on the 10-point numeric pain scale. Secondary outcomes were assessed by using the EQ-5D-5L survey, Short-Form McGill Pain Questionnaire, and Fibromyalgia Impact Questionnaire and were also significantly improved in patients exposed to GLED. GLED therapy was not associated with any measured side effects in these patients. CONCLUSION: Although the mechanism by which GLED elicits pain reduction is currently being studied, these results supporting its efficacy and safety merit a larger clinical trial.


Assuntos
Fibromialgia , Adulto , Animais , Fibromialgia/terapia , Humanos , Dor , Medição da Dor , Qualidade de Vida , Ratos , Inquéritos e Questionários , Resultado do Tratamento
17.
Nat Commun ; 10(1): 3991, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488816

RESUMO

Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a need for personalised medicine. Here, we report lung cancer organoids and normal bronchial organoids established from patient tissues comprising five histological subtypes of lung cancer and non-neoplastic bronchial mucosa as in vitro models representing individual patient. The lung cancer organoids recapitulate the tissue architecture of the primary lung tumours and maintain the genomic alterations of the original tumours during long-term expansion in vitro. The normal bronchial organoids maintain cellular components of normal bronchial mucosa. Lung cancer organoids respond to drugs based on their genomic alterations: a BRCA2-mutant organoid to olaparib, an EGFR-mutant organoid to erlotinib, and an EGFR-mutant/MET-amplified organoid to crizotinib. Considering the short length of time from organoid establishment to drug testing, our newly developed model may prove useful for predicting patient-specific drug responses through in vitro patient-specific drug trials.


Assuntos
Ensaios de Seleção de Medicamentos Antitumorais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Organoides/patologia , Animais , Antígeno B7-H1/genética , Detecção Precoce de Câncer , Genômica , Humanos , Neoplasias Pulmonares/genética , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Medicina de Precisão , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Clin Sleep Med ; 15(5): 743-748, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31053208

RESUMO

STUDY OBJECTIVES: Previous studies have shown that non-rapid eye movement (NREM) sleep parasomnias commonly coexist with restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) in children, leading to speculation that RLS/PLMD may precipitate or worsen parasomnias. However, there are limited data about the effect of the treatment of RLS/PLMD on parasomnias in children. Hence, we performed this study to determine whether the treatment of RLS/PLMD with oral iron therapy is associated with improvement of parasomnias in children. METHODS: A retrospective database was created for children with RLS/PLMD who were treated with iron therapy. These participants were followed for at least 1 year at Cincinnati Children's Hospital Medical Center. All participants had ferritin level testing and were treated with iron therapy. In addition, all participants underwent polysomnography before starting iron therapy for RLS/PLMD except for one participant who was already on iron but required a higher dose. Most participants underwent polysomnography after iron therapy. RESULTS: A total of 226 participants were identified with the diagnosis of RLS/PLMD. Of these, 50 had parasomnias and 30 of them were treated with iron therapy. Of the 30 participants, RLS symptoms improved in 15 participants (50%) and resolution of parasomnias was noted in 12 participants (40%) participants after iron therapy. Repeat polysomnography after iron therapy was performed in 21 participants (70%). After iron therapy, there was a significant decrease in periodic limb movement index (17.2 ± 8.8 [before] versus 6.7 ± 7.3 [after] events/h, P < .001). In addition, there were significant decreases in PLMS (24.52 ± 9.42 [before] versus 7.50 ± 7.18 [after] events/h, P < .0001), PLMS-related arousals (4.71 ± 1.81 [before] versus 1.35 ± 1.43 [after] events/h, P < .0001), and total arousals (11.65 ± 5.49 [before] versus 8.94 ± 3.65 [after] events/h, P < .01) after iron therapy. CONCLUSIONS: Parasomnias are common in our cohort of children with RLS/PLMD. Iron therapy was associated with a significant improvement in periodic limb movement index, RLS symptoms, and resolution of a significant proportion of NREM sleep parasomnias, suggesting that RLS/PLMD may precipitate NREM sleep parasomnia.


Assuntos
Ferro/uso terapêutico , Síndrome da Mioclonia Noturna/complicações , Síndrome da Mioclonia Noturna/tratamento farmacológico , Síndrome das Pernas Inquietas/complicações , Síndrome das Pernas Inquietas/tratamento farmacológico , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Síndrome da Mioclonia Noturna/fisiopatologia , Parassonias/complicações , Parassonias/tratamento farmacológico , Parassonias/fisiopatologia , Polissonografia/métodos , Síndrome das Pernas Inquietas/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento
19.
Seizure ; 65: 1-5, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30590283

RESUMO

PURPOSE: Sleep disorders are common in epilepsy. Additionally, events of staring, jerking, or nocturnal behaviors are common presentations in neurology or sleep practice. Moreover, sleepiness and nocturnal awakenings are common symptoms in children with epilepsy and differentiation form ongoing seizures and sleep disorders is needed. However, limited data exist for the best evaluation methods. This study evaluated the usefulness of combined video electroencephalography (EEG) and polysomnography (PSG) studies (vEEG/PSG). METHODS: Polysomnography custom database was searched for combined vEEG/PSG studies, performed from July 2010 to April 2014, which identified 240 studies. From chart review, data were collected for presenting symptoms, sleep disorder and epilepsy/neurology diagnoses, and EEG and PSG results. RESULTS: Most common indications for performing combined vEEG/PSG were correlating sleep events with seizure occurrence, evaluating sleepiness, nocturnal awakenings and nocturnal events. Sleep physician evaluation and/or PSG were abnormal in 94% of the studies. The EEG was abnormal in 53% and events or seizures were recorded in 40% of the studies. Hence, vEEG/PSG addressed the diagnostic questions. Additionally, as compared to children with epilepsy, a significantly larger number of children with spells/parasomnia had a normal sleep evaluation including a normal PSG (9 Vs 37%, p = 0.00003). CONCLUSIONS: This study demonstrates that combined video EEG and polysomnography is useful in addressing the common management questions in children with epilepsy and suspicious nocturnal events. Additionally, sleep disorders are more common in children with epilepsy than parasomnia. Hence sleep evaluation is important in children with epilepsy. Further prospective studies are needed.


Assuntos
Gerenciamento Clínico , Eletroencefalografia , Epilepsia , Polissonografia , Transtornos do Sono-Vigília , Gravação em Vídeo , Adolescente , Criança , Pré-Escolar , Epilepsia/complicações , Epilepsia/diagnóstico , Epilepsia/terapia , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Sono , Transtornos do Sono-Vigília/classificação , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/terapia , Vigília
20.
Sleep Med ; 32: 213-219, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27282843

RESUMO

OBJECTIVES: Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) are thought to center around a genetically mediated sensitivity to iron insufficiency. Previous studies have shown the effectiveness of short-term iron therapy in children with low iron storage. Little is known, however, about long-term iron treatment in children with RLS and PLMD. Therefore, we performed this study to assess the long-term effect of iron therapy in children with RLS and PLMD. METHODS: A retrospective chart review was performed for children who met the following criteria: A) diagnosed as having either RLS or PLMD, B) started on iron supplementation, C) followed up for >2 years in a sleep clinic. Baseline values for iron, ferritin, and periodic limb movement of sleep index (PLMS index) were defined in the three months leading up to the initiation of iron therapy. Values were also computed for follow-up periods of 3-6 months, 1-2 years, and >2 years. Serum iron and ferritin levels and PLMS index were compared between baseline and all subsequent follow-ups. RESULTS: In total, 105 patients met inclusion criteria, of whom 64 were diagnosed with PLMD alone, seven with RLS alone, and 35 with both RLS and PLMD. The average age was 10.2 ± 5.3 years. Compared to the baseline (27.4 ± 12.1 ng/ml), the average ferritin values at 3-6 months (45.62 ± 21.2 ng/ml, p < 0.001, n = 34), 1-2 years (52.0 ± 48.3 ng/ml, p <0.001, n = 63), and >2 years (54.7 ± 40.5 ng/ml, p <0.001, n = 67) were all significantly increased. Inversely, compared to baseline (21 ± 27.0/h, n = 66), PLMS index values at 3-6 months (7.5 ± 9.5/h p < 0.05, n = 11), 1-2 years (6.9 ± 8.9/h, p <0.001, n = 29), and >2 years (10 ± 14.5/h, p <0.001, n = 31) were all significantly decreased. No significant change in serum iron levels was noted at any time point. CONCLUSION: While retrospective in nature, this study demonstrates a sustained improvement in PLMS index and maintenance of adequate ferritin levels >2 years after iron therapy initiation in our RLS/PLMD cohort with a long-term follow-up. Iron therapy appears to lead to long-lasting improvements in children with RLS/PLMD.


Assuntos
Ferro/uso terapêutico , Síndrome da Mioclonia Noturna/tratamento farmacológico , Síndrome das Pernas Inquietas/tratamento farmacológico , Criança , Suplementos Nutricionais , Feminino , Humanos , Masculino , Estudos Retrospectivos
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