RESUMEN
BACKGROUND: Identification of proinflammatory factors responding to Mycobacterium tuberculosis is important to reduce long-term sequelae of pulmonary tuberculosis (TB). METHODS: We examined the association between plasma biomarkers, the fraction of exhaled nitric oxide (FeNO), and lung function among a prospective cohort of 105 adults newly diagnosed with TB/human immunodeficiency virus (HIV) in South Africa. Participants were followed for 48 weeks from antiretroviral therapy (ART) initiation with serial assessments of plasma biomarkers, FeNO, lung function, and respiratory symptoms. Linear regression and generalized estimating equations were used to examine the associations at baseline and over the course of TB treatment, respectively. RESULTS: At baseline, higher FeNO levels were associated with preserved lung function, whereas greater respiratory symptoms and higher interleukin (IL)-6 plasma levels were associated with worse lung function. After ART and TB treatment initiation, improvements in lung function were associated with increases in FeNO (rate ratio [RR] = 86 mL, 95% confidence interval [CI] = 34-139) and decreases in IL-6 (RR = -118 mL, 95% CI = -193 to -43) and vascular endothelial growth factor ([VEGF] RR = -178 mL, 95% CI = -314 to -43). CONCLUSIONS: Circulating IL-6, VEGF, and FeNO are associated with lung function in adults being treated for TB/HIV. These biomarkers may help identify individuals at higher risk for post-TB lung disease and elucidate targetable pathways to modify the risk of chronic lung impairment among TB survivors.
Asunto(s)
Infecciones por VIH , Tuberculosis , Adulto , Humanos , Óxido Nítrico/metabolismo , Factor A de Crecimiento Endotelial Vascular , VIH , Interleucina-6 , Estudios Prospectivos , Tuberculosis/tratamiento farmacológico , Tuberculosis/complicaciones , Biomarcadores/metabolismo , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Pulmón/metabolismoRESUMEN
BACKGROUND: Patients with tuberculosis (TB) and HIV often present with impairments in lung function and exercise capacity after treatment. We evaluated clinical and immunologic variables associated with a minimum clinically important difference (MCID) in the change in the 6 min walk test distance during the first 24 weeks of antiretroviral (ART) and anti-tubercular therapy. METHODS: Adults initiating ART and anti-TB treatment in the setting of newly-diagnosed HIV and pulmonary TB were enrolled in a prospective cohort study in South Africa. Patients underwent 6 min walk tests and spirometry at weeks 0, 4, 12, and 24 and biomarker level measurements early during treatment, at weeks 0, 4, and 12, when inflammation levels are typically elevated. Biomarkers included matrix metalloproteinases-1 (MMP-1), tissue inhibitor of MMP (TIMP)-1, collagen 1a, IL-6, IL-8, vascular cell adhesion molecule 1 (VCAM-1), C-X-C motif chemokine 10 (CXCL-10), CXCL-11, macrophage colony-stimulating factor (M-CSF), plasminogen activator, vascular endothelial growth factor, and chemokine (C-C) motif-2 (CCL-2). An MCID was derived statistically, and achievement of an MCID was modeled as the outcome using logistic regression model. RESULTS: Eighty-nine patients walked an average of 393 (± standard deviation = 69) meters at baseline, which increased by an average of 9% (430 ± 70 m) at week 24. The MCID for change in walk distance was estimated as 41 m. Patients experiencing an MCID on treatment had worse lung function, lower 6 min walk test distance, higher levels of proinflammatory biomarkers including TIMP-1 and M-CSF, and lower levels of collagen 1a at baseline. Experiencing an MCID during treatment was associated with increases in forced expiratory volume in 1-s [odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.05-1.33] and increases in blood collagen 1a levels (OR = 1.31, 95%CI 1.06-1.62). CONCLUSIONS: ART and TB treatment are associated with substantial improvements in 6 min walk test distance over time. Achievement of an MCID in the 6 min walk test in this study was associated with more severe disease at baseline and increases in collagen 1a levels and lung function during therapy.
Asunto(s)
Infecciones por VIH , Tuberculosis , Humanos , Adulto , Prueba de Paso , Factor Estimulante de Colonias de Macrófagos/uso terapéutico , Estudios Prospectivos , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Tuberculosis/complicaciones , Biomarcadores , Pulmón , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológicoRESUMEN
OBJECTIVE: Planar dosimetry is often performed in developing countries due to its simplicity during basic quantitative dosimetry. The geometric mean method is often used during planar dosimetry and imaging counts can be corrected for background, attenuation and scatter. The aim of our study was to develop computerized software called Masterdose that may be used for therapeutic isotope planar organ personalized dosimetry. MATERIALS AND METHODS: Masterdose software uses various methods to correct for background, scatter and attenuation.We also introduced a method to convert imaging counts to activity on the software,which is Java based and runs on Windows, Linux and Macintosh platforms. RESULTS: Three user interfaces named image processing, quantification and dosimetry were developed for the software. Masterdose could quantify kidney and liver doses of lutetium-177-DOTA-0-Tyr3-octreotate (177Lu-DOTATATE) patients. The software was validated throughcalculation of the kidney and liver doses of ten neuroendocrine tumour patients (NET) treated with 177Lu-DOTATATE. CONCLUSION: Masterdose presents an option for planar quantification that can be used as a quality control tool to verify imaging counts and perform dosimetry in particular organs.
Asunto(s)
Tumores Neuroendocrinos , Compuestos Organometálicos , Países en Desarrollo , Humanos , Compuestos Organometálicos/uso terapéutico , Tomografía de Emisión de Positrones , Radiometría/métodos , Cintigrafía , Radiofármacos/uso terapéutico , Programas InformáticosRESUMEN
BACKGROUND: Current tuberculosis treatments leave most patients with bronchiectasis and fibrosis, permanent conditions that impair lung function and increase all-cause post-TB mortality. Host-directed therapies (HDTs) may reduce lung inflammation and hasten eradication of infection. Biomarkers can accelerate tuberculosis regimen development, but no studies have yet examined early biomarkers of TB-HDTs. METHODS: Biomarkers of inflammation and microbicidal activity were evaluated as a part of a recent phase-2 randomized controlled trial of four HDTs in 200 patients with pulmonary tuberculosis and baseline predictors of poor outcome, including CC-11050 (PDE4i), everolimus (mTORi), auranofin (oral gold salt), and ergocalciferol (vitamin D). Two of the 4 arms (CC-11050 and everolimus) showed superior recovery of lung function at day 180 compared to control; none showed accelerated eradication of MTB infection. Patients underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) on entry and day 56. PET signals were analyzed according to total, maximal, and peak glycolytic activity; CT was analyzed according to total modified Hounsfield units to assess radiodensity. Mycobactericidal activity in ex vivo whole blood culture was measured on days 42, 84, and 140. C-reactive protein (CRP) was measured at multiple time points. RESULTS: All PET/CT parameters showed highly significant reductions from baseline to day 56; however, only maximal or peak glycolytic activity showed further experimental reduction compared to controls, and only in everolimus recipients. CRP dropped precipitously during early treatment, but did so equally in all arms; over the entire period of treatment, the rate of decline of CRP tended to be greater in CC-11050 recipients than in controls but this fell short of statistical significance. Whole blood mycobactericidal activity in ex-vivo culture was enhanced by auranofin compared to controls, but not by other HDTs. CONCLUSIONS: None of these early biomarkers correctly predicted HDT effects on inflammation or infection across all four experimental arms. Instead, they each appear to show highly specific responses related to HDT mechanisms of action.
Asunto(s)
Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
Nuclear medicine technologists (NMTs) are experts in the acquisition of myocardial perfusion (MP) images, in addition to the many other types of images acquired in nuclear medicine departments. NMTs are expected to ensure that images are of optimal quality in order to facilitate accurate interpretation by nuclear medicine physicians (NMPs). However, ensuring optimal image quality is a shared responsibility between NMTs and NMPs. The shared responsibilities have resulted in inconsistences in the assessment of MP image quality among NMTs in different departments. Little is known about the perceptions and experiences of NMTs on the assessment of MP image quality. Therefore, the focus of this research study was NMTs. The aim of this qualitative study was to explore and describe the perceptions and experiences of NMTs on the assessment of MP image quality. The research question was, "How do NMTs perform the responsibility of ensuring MP image quality?" Methods: The study followed a qualitative explorative approach using focus groups as a means of collecting data. Nineteen NMTs from 4 academic hospitals were purposefully selected to participate. A semistructured questionnaire was used to conduct the focus groups. The collected data were managed using a computer-aided qualitative data analysis software program to formulate codes, categories, and themes. Results: Two overarching themes emerged from the data: the management of MP images, and the resources required to support NMTs. NMTs differed in their management of MP images because of the prevailing circumstances in their respective departments. In addition, the results suggested that NMTs' level of involvement in the assessment of MP image quality was influenced by the availability of resources required for processing and assessing image quality. Conclusion: Despite the shared responsibility in the assessment of MP image quality with NMPs, NMTs considered themselves as playing a major role. However, resources to facilitate the assessment of image quality are considered necessary and should be available to support NMTs in submitting images of optimal quality for interpretation.
Asunto(s)
Medicina Nuclear , Percepción , Perfusión , Encuestas y CuestionariosRESUMEN
BACKGROUND: Current tuberculosis treatments leave patients with clinically significant lung injury and increased all-cause mortality post-cure. Adjunctive host-directed therapies could protect the lungs, improve long-term survival, and shorten treatment duration; however, few have been tested clinically. Therefore, we aimed to assess the safety and preliminary efficacy of four host-directed therapies for tuberculosis. METHODS: In this prospective, open-label, phase 2, randomised controlled trial, patients with pulmonary tuberculosis were recruited at three clinical sites in South Africa. Eligible patients were aged 18-65 years, HIV-1-negative, and had rifampicin-susceptible Mycobacterium tuberculosis, a sputum Xpert cycle threshold of less than 20, and moderately advanced or far advanced disease on chest radiography. By use of numbers generated in blocks of ten and stratification by site, eligible patients were randomly assigned (1:1:1:1:1) to receive one of the four oral host-directed treatments plus standard tuberculosis treatment or standard treatment alone (the control group). Host-directed treatments were: CC-11050 (200 mg twice daily, taken with food; day 1-112); everolimus (0·5 mg/day; day 1-112); auranofin (3 mg/day for seven doses, then 6 mg/day; day 1-112); and ergocalciferol (5 mg on day 1, then 2·5 mg on day 28 and day 56). All study participants received oral rifabutin-substituted standard tuberculosis treatment for 180 days. Patients and clinicians were not masked to treatment assignment. Spirometry and sputum culture with solid and liquid media were done at baseline and up to 180 days at specified intervals throughout treatment. The primary endpoint was safety and tolerability up to day 210. Secondary preliminary efficacy endpoints were treatment effects on sputum microbiology (culture status at day 56 and the hazard ratio for stable culture conversion up to day 180) and lung function (FEV1 and forced vital capacity [FVC]) measured by spirometry at day 56, day 180, and day 540. Safety was analysed in the intention-to-treat population and preliminary efficacy primarily in the per-protocol population. The trial is registered at ClinicalTrials.gov, NCT02968927. Post-treatment follow-up was completed in 2020. FINDINGS: Between Nov 18, 2016, and Sept 27, 2018, 200 patients were screened and randomly assigned to different treatment groups (n=40 per group, apart from n=39 in the everolimus group after one patient withdrew consent). 11 treatment-emergent serious adverse events occurred either during treatment or within 30 days after treatment discontinuation, of which three were attributable to a host-directed treatment. Life-threatening thrombocytopenia occurred in an auranofin recipient; apparent intra-abdominal sepsis leading to death occurred in another auranofin recipient and was classified as a suspected unexpected serious adverse reaction. Tuberculous spondylitis occurred as an apparent paradoxical reaction in a patient receiving ergocalciferol. Two patients in the control group had life-threatening, treatment-attributable liver injury. No treatment-emergent, treatment-attributable serious adverse events occurred in patients receiving CC-11050 or everolimus. Mean FEV1 in the control group was 61·7% of predicted (95% CI 56·3-67·1) at baseline and 69·1% (62·3-75·8) at day 180. Patients treated with CC-11050 and everolimus had increased recovery of FEV1 at day 180 relative to the control group (mean difference from control group 6·30%, 95% CI 0·06-12·54; p=0·048; and 6·56%, 0·18-12·95; p=0·044, respectively), whereas auranofin and ergocalciferol recipients did not. None of the treatments had an effect on FVC during 180 days of follow-up or on measures of sputum culture status over the course of the study. INTERPRETATION: CC-11050 and everolimus were safe and reasonably well tolerated as adjunctive therapies for tuberculosis, and analysis of preliminary efficacy suggests they might also enhance the recovery of FEV1, a key measure of lung function and predictor of all-cause mortality. Further studies of these candidates are warranted. FUNDING: The Bill & Melinda Gates Foundation and the South African Medical Research Council.
Asunto(s)
Antituberculosos/administración & dosificación , Auranofina/administración & dosificación , Ergocalciferoles/administración & dosificación , Everolimus/administración & dosificación , Indoles/administración & dosificación , Inhibidores de Fosfodiesterasa 4/administración & dosificación , Sulfonas/administración & dosificación , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto , Antituberculosos/efectos adversos , Auranofina/efectos adversos , Auranofina/farmacología , Método Doble Ciego , Quimioterapia Combinada , Ergocalciferoles/efectos adversos , Ergocalciferoles/farmacología , Everolimus/efectos adversos , Everolimus/farmacología , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Indoles/efectos adversos , Indoles/farmacología , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis , Inhibidores de Fosfodiesterasa 4/efectos adversos , Inhibidores de Fosfodiesterasa 4/farmacología , Estudios Prospectivos , Sudáfrica , Esputo/efectos de los fármacos , Esputo/microbiología , Sulfonas/efectos adversos , Sulfonas/farmacologíaRESUMEN
BACKGROUND: While tuberculosis is considered a risk factor for chronic obstructive pulmonary disease, a restrictive pattern of pulmonary impairment may actually be more common among tuberculosis survivors. We aimed to determine the nature of pulmonary impairment before and after treatment among people with HIV and tuberculosis and identify risk factors for long-term impairment. METHODS: In this prospective cohort study conducted in South Africa, we enrolled adults newly diagnosed with HIV and tuberculosis who were initiating antiretroviral therapy and tuberculosis treatment. We measured lung function and symptoms at baseline, 6, and 12 months. We compared participants with and without pulmonary impairment and constructed logistic regression models to identify characteristics associated with pulmonary impairment. RESULTS: Among 134 participants with a median CD4 count of 110 cells/µl, 112 (83%) completed baseline spirometry at which time 32 (29%) had restriction, 13 (12%) had obstruction, and 9 (7%) had a mixed pattern. Lung function was dynamic over time and 30 (33%) participants had impaired lung function at 12 months. Baseline restriction was associated with greater symptoms and with long-term pulmonary impairment (adjusted odds ratio 5.44, 95% confidence interval 1.16-25.45), while baseline obstruction was not (adjusted odds ratio 1.95, 95% confidence interval 0.28-13.78). CONCLUSIONS: In this cohort of people with HIV and tuberculosis, restriction was the most common, symptomatic, and persistent pattern of pulmonary impairment. These data can help to raise awareness among clinicians about the heterogeneity of post-tuberculosis pulmonary impairment, and highlight the need for further research into mediators of lung injury in this vulnerable population.
Asunto(s)
Infecciones por VIH/fisiopatología , Pulmón/fisiopatología , Tuberculosis Pulmonar/fisiopatología , Adulto , Fármacos Anti-VIH/uso terapéutico , Antituberculosos/uso terapéutico , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Volumen Espiratorio Forzado/fisiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Enfermedades Pulmonares Obstructivas/fisiopatología , Masculino , Estudios Prospectivos , Sudáfrica , Espirometría , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológico , Capacidad Vital/fisiologíaRESUMEN
Background: A Phase III randomized controlled trial investigating the addition of modulated electro-hyperthermia (mEHT) to chemoradiotherapy for locally advanced cervical cancer patients is being conducted in South Africa (Human Research Ethics Committee approval: M1704133; ClincialTrials.gov ID: NCT03332069). Two hundred and ten participants were randomized and 202 participants were eligible for six month local disease control evaluation. Screening 18F-FDG PET/CT scans were conducted and repeated at six months post-treatment. Significant improvement in local control was reported in the mEHT group and complete metabolic resolution (CMR) of extra-pelvic disease was noted in some participants. We report on an analysis of the participants with CMR of disease inside and outside the radiation field. Method: Participants were included in this analysis if nodes outside the treatment field (FDG-uptake SUV>2.5) were visualized on pre-treatment scans and if participants were evaluated by 18F-FDG PET/CT scans at six months post-treatment. Results: One hundred and eight participants (mEHT: HIV-positive n = 25, HIV-negative n = 29; Control Group: HIV-positive n = 26, HIV-negative n = 28) were eligible for analysis. There was a higher CMR of all disease inside and outside the radiation field in the mEHT Group: n = 13 [24.1%] than the control group: n = 3 [5.6%] (Chi squared, Fisher's exact: p = 0.013) with no significant difference in the extra-pelvic response to treatment between the HIV-positive and -negative participants of each group. Conclusion: The CMR of disease outside the radiation field at six months post-treatment provides evidence of an abscopal effect which was significantly associated with the addition of mEHT to treatment protocols. This finding is important as the combined synergistic use of radiotherapy with mEHT could broaden the scope of radiotherapy to include systemic disease.
RESUMEN
Introduction: HIV infection is associated with increased treatment-related toxicity and worse outcomes in locally advanced cervical cancer patients (LACC), especially in resource-constrained settings. Local control (LC) in a phase III randomized, controlled trial investigating modulated electro-hyperthermia (mEHT) on LACC patients in South Africa (ethics registration: M120477/M190295), was significantly higher in participants randomized to receive chemoradiotherapy (CRT) with mEHT compared to CRT alone (stratum: HIV status, accounting for age and stage). This analysis investigates whether mEHT adds to the toxicity profile of CRT in HIV-positive LACC participants.Methods: Inclusion criteria: signed informed consent; International Federation of Gynecology and Obstetrics stages IIB to IIIB squamous cell carcinoma of the cervix; HIV-positive patients: CD4 count >200 cell/µL/on antiretroviral treatment for >6 months; eligible for CRT with radical intent. Recruitment: January 2014 to November 2017 (ClinicalTrials.gov: NCT03332069). Acute toxicity (evaluated using CTCAE v4 criteria) and quality of life (according to EORTC forms) in 206 participants randomized for treatment were evaluated alongside the LC results to determine safety and efficacy in HIV-positive participants.Results: Compliance to mEHT treatment was high (97% completed ≥8 treatments) with no significant differences in CRT-related toxicity between treatment groups or between HIV-positive and -negative participants. Adverse events attributed to mEHT were minor, even in obese patients, and did not affect CRT compliance. Participants treated with mEHT reported improved fatigue, pain, emotional and cognitive functioning.Conclusion: mEHT did not cause unexpected CRT-related toxicities and is a safe treatment modality for HIV-positive patients, with minor limitations regarding body weight, even in a low-resource setting.
Asunto(s)
Infecciones por VIH/terapia , Hipertermia Inducida/métodos , Calidad de Vida/psicología , Neoplasias del Cuello Uterino/terapia , Adulto , Femenino , Humanos , Persona de Mediana EdadRESUMEN
The role of fluorodeoxyglucose (FDG)-PET/computed tomography (CT) in tuberculosis (TB) continues to expand in disease detection, assessment of the extent of the disease, and treatment response monitoring. This article reviews available data regarding the use of FDG-PET/CT in patients with TB. A new method of quantification for patients with TB is introduced. This method produces robust parameters that represent the total disease burden.
Asunto(s)
Tomografía Computarizada por Tomografía de Emisión de Positrones , Tuberculosis/diagnóstico por imagen , Diagnóstico Diferencial , Fluorodesoxiglucosa F18 , Humanos , Radiofármacos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Inflammasomes mediate inflammation in adults living with both human immunodeficiency virus (HIV) and tuberculosis (TB), but the relevance of inflammasome gene polymorphisms in TB-associated pulmonary damage is unknown. We hypothesized that functional single-nucleotide polymorphisms (SNPs) in inflammasome pathway genes modify systemic and pulmonary inflammation, contributing to respiratory impairment in adults living with HIV/pulmonary TB. METHODS: This was a prospective cohort study set in South Africa following individuals living with HIV/TB up to 48 weeks post-antiretroviral therapy (ART) initiation. Ten functional SNPs in 5 inflammasome pathway genes were related to circulating inflammatory biomarkers and lung function assessed by spirometry pre- and post-ART initiation. Analyses used 2-sided t tests, Wilcoxon rank sum tests, Spearman correlation coefficients, linear regression, and generalized estimating equation models. RESULTS: Among 102 patients with baseline samples, the minor allele (T) in NLRC4 rs385076 was independently associated with lower levels of interleukin (IL)-18 and IL-6 before and up to 12 weeks post-ART initiation (Benjamini-Hochberg corrected P values < .02). Patients with the CT/TT genotypes also had improved lung function vs CC patients up to 48 weeks post-ART initiation (forced vital capacity, 206 mL higher; 95% confidence interval [CI], 67-345 mL; P = .004 and forced expiratory volume in 1 second, 143 mL higher; 95% CI, 11-274 mL; P = .034). CONCLUSIONS: A common SNP in the NLRC4 inflammasome may modify TB-associated inflammation in clinically relevant ways. This SNP may identify high-risk groups for lung damage in TB. Inhibition of NLRC4 activity may be an important approach for TB host-directed therapy.
Asunto(s)
Infecciones por VIH , Tuberculosis , Adulto , Proteínas Adaptadoras de Señalización CARD , Proteínas de Unión al Calcio/genética , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Inflamación/genética , Pulmón , Estudios Prospectivos , Sudáfrica , Tuberculosis/genéticaRESUMEN
End-organ impairment has received relatively little research attention as a possible manifestation of tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS). In this prospective cohort study, one-half of adults with human immunodeficiency virus and pulmonary tuberculosis experienced meaningful declines in lung function on antiretroviral therapy, suggesting a role for lung function in TB-IRIS definitions.
Asunto(s)
Infecciones por VIH , Síndrome Inflamatorio de Reconstitución Inmune , Tuberculosis , Adulto , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Pulmón , Estudios ProspectivosRESUMEN
BACKGROUND: Immune restoration on antiretroviral therapy (ART) can drive inflammation in people living with human immunodeficiency virus (HIV) who have pulmonary tuberculosis (TB), but its effects on the lungs have not been assessed. We evaluated associations between pulmonary inflammation, recovery of pathogen-specific CD4 T-cell function, and lung injury prior to and after ART initiation in adults with HIV and pulmonary TB. METHODS: This was a prospective cohort study in South Africa, following adults with HIV and pulmonary TB prior to and up to 48 weeks after ART initiation. Pulmonary-specific inflammation was defined as total glycolytic activity (TGA) on [18]F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) at baseline and 4 weeks after ART initiation. Spirometry, respiratory symptom tests, and flow cytometry were performed at the same times to assess lung involvement and the frequency of mycobacteria-specific CD4 T-cells. In addition, we evaluated lung function longitudinally up to 48 weeks after ART initiation. RESULTS: Greater lung TGA on FDG PET-CT was associated with worse lung function and respiratory symptoms prior to ART initiation, and nearly half of subjects experienced worsening lung inflammation and lung function at Week 4 of ART. Worsening Week 4 lung inflammation and pulmonary function were both associated with greater increases in pathogen-specific functional CD4 T-cell responses on ART, and early decreases in lung function were independently associated with persistently lower lung function months after TB treatment completion. CONCLUSIONS: Increases in pulmonary inflammation and decreases in lung function are common on ART, relate to greater ART-mediated CD4 T-cell restoration, and are associated with the persistent impairment of lung function in individuals with HIV/TB.
Asunto(s)
Infecciones por VIH , Lesión Pulmonar , Tuberculosis , Adulto , Recuento de Linfocito CD4 , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Prospectivos , SudáfricaRESUMEN
BACKGROUND: The global burden of cervical cancer remains high with the highest morbidity and mortality rates reported in developing countries. Hyperthermia as a chemo- and radiosensitiser has shown to improve treatment outcomes. This is an analysis of the local control results at six months post-treatment of patients enrolled in an ongoing study investigating the effects of the addition of modulated electro-hyperthermia (mEHT) to chemoradiotherapy for the treatment of HIV-positive and -negative cervical cancer patients in a low-resource setting. METHODS: This ongoing Phase III randomised controlled trial, conducted at a state hospital in Johannesburg, South Africa, was registered with the appropriate ethics committee. After signing an informed consent, participants with FIGO stages IIB to IIIB squamous cell carcinoma of the cervix were randomised to receive chemoradiotherapy with/without mEHT using a secure online random-sampling tool (stratum: HIV status) accounting for age and stage. Reporting physicians were blind to treatment allocation. HIV-positive participants on antiretroviral treatment, or with a CD4 count >200cell/µL were included. mEHT was administered 2/weekly immediately before external beam radiation. The primary end point is local disease control (LDC) and secondary endpoints are toxicity; quality of life analysis; and two year survival. We report on six month LDC, including nodes visualised in the radiation field on 18F-FDG PET/CT (censored for six month survival), and six month local disease free survival (LDFS) (based on intention to treat). Trial status: Recruitment closed (ClinicalTrials.gov: NCT03332069). RESULTS: 271 participants were recruited between January 2014 and November 2017, of which 210 were randomised for trial and 202 were available for analysis at six months post-treatment (mEHT: n = 101; Control: n = 101). Six month LDFS was higher in the mEHT Group (n = 39[38.6%]), than in the Control Group (n = 20[19.8%]); p = 0.003). LDC was also higher in the mEHT Group (n = 40[45.5%]) than the Control Group (n = 20[24.1%]); (p = 0.003). CONCLUSION: Our results show that mEHT is effective as a chemo-radiosensitiser for cervical cancer, even in high risk a patients and resource-constrained settings.
Asunto(s)
Quimioradioterapia , Hipertermia Inducida/métodos , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , VIH/patogenicidad , Seropositividad para VIH/virología , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Resultado del Tratamiento , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virologíaRESUMEN
BACKGROUND: Positron emission tomography detects patients with myocardial contractile dysfunction secondary to ischaemic heart disease who may benefit from coronary revascularisation. METHODS: We reviewed technetium-99m sestamibi singlephoton emission computed tomography (SPECT) and fluorine-18 fluorodeoxyglucose (F18-FDG) positron emission tomography (PET) data from 236 patients imaged between January 2009 and June 2015. The patients were grouped into three groups: no evidence of viability, viability 1-10% and viability > 10%. RESULTS: Viability exceeding 10% was evident in 55% of the patients. On multivariate analysis, aspirin intake [OR: 1.92; 95% CI: 1.08-3.41; p = 0.026] and hypertension [OR: 1.89; 95% CI: 1.07-3.33; p = 0.029] were clinical factors associated with the presence of myocardial viability. CONCLUSION: Our study demonstrated that F18-FDG PET was able to identify 55% of patients with ischaemic heart disease with viability in more than 10% of the total myocardium when using a 17-segment model.
RESUMEN
Literature reports increased FDG nodal uptake in HIV-positive patients. Our aim is to identify differences in presentation and characteristics of FDG-avid lymph nodes between HIV-positive and HIV-negative locally advanced cervical cancer (LACC) patients in our clinical setting. We evaluated 250 pre-treatment 18F-FDG PET/CT imaging studies from women screened for a phase III randomised controlled trial investigating modulated electro-hyperthermia as a radiosensitiser (Ethics approval: M120477). The number of nodes; size; maximum standardised uptake value (SUVmax); symmetry; and relationship between nodal size and SUVmax uptake, were assessed by region and by HIV status. In total, 1314 nodes with a SUVmax ≥ 2.5 were visualised. Of 128(51%) HIV-positive participants, 82% were on antiretroviral therapy (ART) and 10 had a CD4 count <200 cells/µL. Overall pattern of presentation and nodal characteristics were similar between HIV-positive and -negative groups and the uniformity in presentation of the nodes draining the cervix strongly suggests these nodes may be attributed to malignancy rather than HIV infection. Novel findings: HIV infection is associated with: >four nodes visualised in the neck, symmetrical inguinal lymph nodes, increased rates of supraclavicular node visualisation; FDG-avid axillary nodes were more common, but not exclusive, in HIV-positive participants. 18F-FDG PET/CT is a reliable staging method for LACC in HIV-positive patients who are not in acute stages of HIV infection, have a CD4 count >200 cells/µL, and/or are on ART and there is a potential risk of underestimating metastatic spread by attributing increased nodal metabolic activity to HIV infection in these patients.
Asunto(s)
Seropositividad para VIH/complicaciones , Ganglios Linfáticos/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Estadificación de Neoplasias/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/diagnóstico por imagen , Adulto , Anciano , Quimioradioterapia , Femenino , Humanos , Hipertermia Inducida , Ganglios Linfáticos/patología , Persona de Mediana Edad , Sudáfrica , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/terapiaRESUMEN
OBJECTIVE: The aim of this study was to determine whether technetium-99m (Tc) nanocolloid was a suitable alternative tracer for carrying out milk scan studies in pediatric patients. PARTICIPANTS AND METHODS: Twenty-seven milk scans performed with Tc nanocolloid were retrospectively assessed for identification of significant esophageal hold-up, gastroesophageal reflux, pulmonary aspiration, and gastric emptying (GE). Scans were also assessed for liver, spleen, and bone marrow uptake. GE results were compared with those of 27 randomly selected normal GE studies carried out using Tc tin colloid. RESULTS: None of the studies had liver, spleen, or bone marrow uptake, and all studies were interpretable. Significant esophageal hold-up and gastroesophageal reflux was observed in 11 and 48% of the patients, respectively. Only one patient had evidence of pulmonary aspiration, and all patients had normal GE at 2 h after radiolabeled milk ingestion. The average rate of GE at 2 h was faster in the Tc nanocolloid group compared with the Tc tin colloid group (8.85% retained±8.96% vs. 15.48% retained±10.52%, P=0.016). CONCLUSION: Our findings show that Tc nanocolloid is technically a suitable alternative to Tc sulfur colloid for performing milk scans. However, we could not conclude with certainty on the comparison of the GE rates of Tc nanocolloid and Tc tin colloid. This was because of the variability in the two population groups as well as the fact that the milk that was used in each patient was individualized to the patient and was not standardized.
Asunto(s)
Reflujo Gastroesofágico/diagnóstico por imagen , Cintigrafía/métodos , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Animales , Niño , Vaciamiento Gástrico , Reflujo Gastroesofágico/fisiopatología , Humanos , LactanteRESUMEN
OBJECTIVE: The aim of the study was to assess the efficacy of technetium 99m-methyl diphosphonate (Tc-MDP) and technetium 99m-methoxyisobutylisonitrile (Tc-MIBI) as radioaerosol alternatives to technetium 99m-diethylenetriaminepentacetate (Tc-DTPA) in the evaluation of pulmonary thromboembolism, as the direct consequence of the possible outcome could be cost saving. PATIENTS AND METHODS: Patients referred to our institution from August 2015 to July 2017 for a ventilation-perfusion scan who fulfilled the inclusion criteria were enrolled into the study as participants. Each ventilation agent was used to ventilate 43 participants, making a total of 129 participants in the study. Images were assessed for quality and alveolar clearance qualitatively and semiquantitatively correspondingly by a nuclear medicine physician blinded to the agent used. RESULTS: Tc-MIBI had higher count rates than Tc-DTPA and Tc-MDP, with a statistically significant difference when compared with Tc-DTPA (P=0.021). Tc-MIBI clearly showed slower alveolar clearance when compared with the clearance of Tc-DTPA (P≤0.0001) and Tc-MDP (P≤0.001). In terms of image quality, Tc-MIBI generally had better quality images as compared with the other two radioaerosols, with a statistically significant difference when compared with Tc-DTPA (P=0.001). CONCLUSION: Tc-MIBI had superior image quality and slower alveolar clearance when compared with Tc-DTPA. Alongside Tc-MDP, these agents can replace Tc-DTPA whenever clinically and economically applicable.
Asunto(s)
Pulmón/diagnóstico por imagen , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/fisiopatología , Ventilación Pulmonar , Cintigrafía/métodos , Medronato de Tecnecio Tc 99m , Tecnecio Tc 99m Sestamibi , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenAsunto(s)
Radioisótopos de Yodo , Litio , Terapia Combinada , Enfermedad de Graves , Humanos , HipertiroidismoRESUMEN
OBJECTIVE: While nuclear myocardial perfusion imaging (MPI) offers many benefits to patients with known or suspected cardiovascular disease, concerns exist regarding radiation-associated health effects. Little is known regarding MPI practice in Africa. We sought to characterise radiation doses and the use of MPI best practices that could minimise radiation in African nuclear cardiology laboratories, and compare these to practice worldwide. METHODS: Demographics and clinical characteristics were collected for a consecutive sample of 348 patients from 12 laboratories in six African countries over a one-week period from March to April 2013. Radiation effective dose (ED) was estimated for each patient. A quality index (QI) enumerating adherence to eight best practices, identified a priori by an IAEA expert panel, was calculated for each laboratory. We compared these metrics with those from 7 563 patients from 296 laboratories outside Africa. RESULTS: Median (interquartile range) patient ED in Africa was similar to that of the rest of the world [9.1 (5.1-15.6) vs 10.3 mSv (6.8-12.6), p = 0.14], although a larger proportion of African patients received a low ED, ≤ 9 mSv targeted in societal recommendations (49.7 vs 38.2%, p < 0.001). Bestpractice adherence was higher among African laboratories (QI score: 6.3 ± 1.2 vs 5.4 ± 1.3, p = 0.013). However, median ED varied significantly among African laboratories (range: 2.0-16.3 mSv; p < 0.0001) and QI range was 4-8. CONCLUSION: Patient radiation dose from MPI in Africa was similar to that in the rest of the world, and adherence to best practices was relatively high in African laboratories. Nevertheless there remain opportunities to further reduce radiation exposure to African patients from MPI.