ABSTRACT
BACKGROUND SARS-CoV-2 infection can persist in immunocompromised patients with hematological malignancies, despite antiviral treatment. This report is of a 67-year-old man with chronic lymphocytic leukemia (CLL), secondary hypogammaglobulinemia, and thrombocytopenia on maintenance therapy with ibrutinib, with persistent SARS-CoV-2 infection unresponsive to antiviral treatment, including remdesivir, nirmatrelvir/ritonavir (Paxlovid), and tixagevimab/cilgavimab (Evusheld). CASE REPORT The patient was admitted to our hospital 3 times. During his first hospitalization, he was treated with 5-day course of remdesivir and intravenous steroids; however, antigen and molecular nasopharyngeal swabs were persistently positive, and he was discharged home. Due to respiratory worsening, he was rehospitalized, and despite being treated initially with tixagevimab/cilgavimab, and subsequently with a remdesivir course of 5 days, SARS-CoV-2 tests remained persistently positive. During his third hospital stay, our patient was subjected to combined therapy with remdesivir and nirmatrelvir/ritonavir for 5 days, obtaining a significant reduction of viral load at both antigen and molecular testing. As an ultimate attempt to achieve a negative status before discharge, a 10-day course of combined remdesivir and nirmatrelvir/ritonavir was administered, with a temporary reduction of viral load, followed by a sudden increase immediately after the discontinuation of Paxlovid. Due to worsening hematological disease and bacterial over-infections, the patient gradually worsened until death. CONCLUSIONS This is an emblematic case of correlation between persistent SARS-CoV-2 infection and immunosuppression status in hematological hosts. In these patients, the viral load remains high, favoring the evolution of the virus, and the immunodeficiency makes it difficult to identify the appropriate therapeutic approach.
Subject(s)
Adenine , COVID-19 , Leukemia, Lymphocytic, Chronic, B-Cell , Piperidines , Humans , Male , Aged , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Adenine/analogs & derivatives , Adenine/therapeutic use , COVID-19/diagnosis , Piperidines/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , SARS-CoV-2 , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Immunocompromised Host , Maintenance ChemotherapyABSTRACT
External ventricular drain-related cerebrospinal fluid infection represents a fearsome complication of neurosurgical interventions. Although vancomycin represents the standard of care for methicillin-resistant CoNS healthcare-associated ventriculitis, resistance phenomena have been described. We reported a case of a persistent external ventricular fluid drain infection after device removal by pandrug-resistant Staphylococcus epidermidis successfully treated with intravenous ceftaroline in combination with fosfomycin and vancomycin. No evidence regarding pandrug-resistant S. epidermidis therapy currently exists to our knowledge. In this case, the S. epidermidis phenotype emerged during the therapy course, possibly due to initial device retention, biofilm formation and the host immune impaired response. Despite being poorly studied in vivo, ceftaroline may be considered an option when other alternatives are unavailable, thanks to its described activity against CoNS in vitro. This case extends the experience with ceftaroline for central nervous system infections suggesting it could also be used in high antimicrobial resistance settings for immunocompromised people.
Subject(s)
Fosfomycin , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Ceftaroline , Vancomycin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Staphylococcus epidermidis/genetics , Fosfomycin/therapeutic use , Cephalosporins/therapeutic use , Staphylococcal Infections/drug therapy , Drainage , Microbial Sensitivity TestsSubject(s)
HIV Infections , Humans , Rome/epidemiology , Italy/epidemiology , Hospitals, University , HIV Infections/drug therapyABSTRACT
Background: cytomegalovirus (CMV) retinitis, cerebral and ocular toxoplasmosis are common infections in patients with acquired immunodeficiency syndrome (AIDS). Material and methods: this is a case of a 46-year-old female with previous Kaposi's sarcoma, diagnosed with an HIV infection two weeks prior to hospitalization. Blood test at diagnosis showed a CD4+ count of 77 cell/µL and HIV-RNA 3.758.745 copies/mL. Therapy with bictegravir/emtricitabine/tenofovir alafenamide fumarate was started and clinical, viroimmunological and microbiological investigations were performed. Results: the patient went to our hospital for the onset of left occipito-parietal headache and blurred vision. Brain CT and MRI were performed which did not show focal lesions or vascular alterations. Syphilis serology was negative, Toxoplasma gondii serology showed positive IgG and negative IgM, serum CMV-DNA was 31.184 IU/mL. Eye fundus evidenced intraretinal hemorrhages, fluorescein angiography and computed optical tomography documented cottony exudates, retinal hemorrhages and vitreous involvement. Therapy with valganciclovir was initiated for suspicion of CMV retinitis. About a month later, the patient reported blurred vision for which she was re-admitted. Ocular fundus showed a cottony lesion near the macula. Molecular test on vitreous body was positive for Toxoplasma gondii, while on cerebrospinal fluid it was negative; in addition, an MRI of the brain with contrast medium was performed which showed an area of altered hyperintense signal compatible with a diagnosis of Toxoplasma gondii uveitis and neurotoxoplasmosis. Therapy with pyrimethamine and clindamycin (allergy for sulfonamide reported by the patient) was started. Allergy counseling was performed with the execution of allergy tests (patch test) with negative result; therefore the administration of clindamycin was replaced with sulfadiazine. A month following the start of anti-toxoplasma therapy, there was a clinical and radiological improvement. Conclusions: despite progressive developments in the management of PLWH, in this case two different kind of opportunistic infection are found in a late-presenter patient. In particular, two aspects can be highlighted. The first one is that, in the setting of an highly impaired immune system, clinical presentation can be deceptive and more than one opportunistic infection can be observed together in the same patient. The second aspect is that after starting antiretroviral therapy, a rapid improvement of viro-immunologic parameters has been documented, probably leading to an immune reconstitution inflammatory syndrome (IRIS).
ABSTRACT
BackgroundGraves' disease occurrence during pregnancy is not a frequent event, showing an incidence of 0.2-0.4% in unselected pregnant women. Depending on their functional properties, TSH-receptor antibodies can induce hypothyroidism or hyperthyroidism. Recognizing the signs of altered thyroid function is essential to prevent possible complications on the fetus.Materials and methodsThe case of a pregnant woman without previous history of thyroid disease presenting with severe overt hypothyroidism during the first trimester is reported. Levothyroxine therapy was started and 6 weeks later overt hyperthyroidism was observed. TRAb were detected at high titers. Levothyroxine was withdrawn and low dose methimazole was started. Serial obstetric ultrasound scans were negative for indirect signs of fetal thyroid dysfunctions and no fetal goiter was visualized throughout pregnancy. Spontaneous delivery occurred without complications at 39 weeks of gestation. In the post-partum, severe overt hypothyroidism recurred, thus methimazole was discontinued and levothyroxine was restarted. TRAb persisted at high levels. The infant experienced a transient thyrotoxicosis, which fully resolved in three months with normalization of thyroid function and negativization of TRAb levels.ResultsThe present case report allows us to overview the challenges related to the management of hypo and hyperthyroidism in patients with high TRAb levels, requiring strict monitoring aimed at early detection of both maternal and fetal consequences.ConclusionsThis case underlines the importance of close follow-up and the need of collaboration in a multidisciplinary team when Graves's disease is diagnosed in a pregnant woman to prevent adverse neonatal outcomes.
Subject(s)
Graves Disease , Hyperthyroidism , Hypothyroidism , Pregnancy Complications , Thyroid Diseases , Female , Graves Disease/complications , Graves Disease/diagnosis , Graves Disease/drug therapy , Humans , Hypothyroidism/complications , Hypothyroidism/diagnosis , Hypothyroidism/drug therapy , Infant, Newborn , Methimazole/therapeutic use , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Complications/drug therapy , Pregnant Women , Thyroid Diseases/diagnosis , Thyroxine/therapeutic useABSTRACT
All the figures [...].
ABSTRACT
The dissemination of severe acute respiratory syndrome linked to the novel coronavirus, SARS-CoV-2, prompted all health services to provide adequate measures to limit new cases that could affect healthcare professionals. Due to the large number of suspected patients subjected to CT scans and the proximity of radiologists to the patient during exams, radiologists as well as the entire staff of the radiology department are particularly exposed to SARS-CoV-2. This article includes the emergency management procedures, the use of personal protective devices, and the rearrangement of exam rooms and of human resources in the department of radiology at "Policlinico Tor Vergata" in Rome performed during the SARS-CoV-2 pandemic. We introduce the management measures that our department has taken to cope with the influx of patients while still ensuring the proper management of other emergencies and time-sensitive exams.
Subject(s)
COVID-19 , Radiology , Hospitals , Humans , Pandemics , Rome/epidemiology , SARS-CoV-2ABSTRACT
IgG4-related disease (IgG4-RD) is fibro-inflammatory, immune-mediated, systemic disease recognized as a defined clinical condition only in 2001. The prevalence of IgG4-RD is 6/100 000, but it is likely to be underestimated due to insufficient awareness of the disease. The diagnostic approach is complex because of the heterogeneity of clinical presentation and because of rather variable diagnostic criteria. Indeed, high concentrations of IgG4 in tissue and serum are not a reliable diagnostic marker. The spectrum of IgG4-RD also includes well-known thyroid diseases including Riedel's thyroiditis, Hashimoto's thyroiditis and its fibrotic variant, Graves' disease and Graves' orbitopathy. Results from clinical studies indicate that a small subset of patients with the above-mentioned thyroid conditions present some features suggestive for IgG4-RD. However, according to more recent views, the use of the term thyroid disease with an elevation of IgG4 rather than IgG4-related thyroid diseases would appear more appropriate. Nevertheless, the occurrence of high IgG4 levels in patients with thyroid disease is relevant due to peculiarities of their clinical course.
Subject(s)
Graves Disease/diagnosis , Immunoglobulin G4-Related Disease/diagnosis , Immunoglobulin G/blood , Thyroid Gland/pathology , Thyroiditis, Autoimmune/diagnosis , Graves Disease/blood , Humans , Immunoglobulin G4-Related Disease/blood , Thyroiditis, Autoimmune/bloodABSTRACT
OBJECTIVE: The objectives of the study were: a) to identify osteoporotic proximal humerus fractures in a large consecutive series of patients; b) to identify radiographic fracture patterns among osteoporotic and non-osteoporotic proximal humerus fractures; and c) to calculate intra- and inter-observer reliability of assessment of osteoporosis and of radiographic fracture patterns. METHODS: This was a prospective observational study of patients admitted to the emergency department affected by a proximal humerus fracture between June 2014 and June 2016. Three researchers evaluated demographic data and comorbidities, x-rays and CT-scans. A new evaluation method for assessment of osteoporosis was proposed; 7 radiographic fracture patterns were studied. Reliabilities between intra- and inter-tester evaluations, and correlations between the presence of osteoporosis and the 7 radiologic fracture patterns were calculated. RESULTS: Two hundred twenty-five patients with a humeral fracture were recruited. Their mean (26-95, 32) age was 58. Of those, 163 (72.4%) were identified as osteoporotic. Among the three raters, the intra- and inter-observer agreement using the proposed methods were high or excellent. Significant correlations with diagnosis of osteoporosis were found with Codman-Lego type 12(pâ¯=â¯0.041), metaphyseal comminution(pâ¯<â¯0.001), impaction of fragments(pâ¯=â¯0.023), comminution of tuberosities(pâ¯=â¯0.037), inferior subluxation(pâ¯=â¯0.029). Intra- and inter-tester reliability of evaluation of these osteoporotic fracture patterns were high. CONCLUSIONS: Osteoporosis of the proximal humerus was identified in 72% of patients during a two year period; most of these patients were elderly females sustaining low energy trauma. These fractures showed to have specific radiographic patterns, as comminution of metaphysis and tuberosities, impaction of fragments, and inferior subluxation of the humeral head. These patterns can be assessed with the simple observation of a 2-plan view of a radiograph, without the use of specific software.
Subject(s)
Osteoporosis/complications , Osteoporotic Fractures/diagnostic imaging , Radiography/methods , Shoulder Fractures/diagnostic imaging , Adult , Aged , Aged, 80 and over , Female , Humans , Humerus/diagnostic imaging , Male , Middle Aged , Observer Variation , Osteoporosis/diagnostic imaging , Osteoporotic Fractures/etiology , Prospective Studies , Reproducibility of Results , Shoulder Fractures/etiologyABSTRACT
PURPOSE: The objectives of this study are to propose a reliable radiologic method for detecting static inferior subluxation of humeral head, to calculate the relative intra- and inter-observer reliability, and to evaluate its presence pre- and post-surgery. METHODS: This is a retrospective observational study of patients surgically treated for a fracture of the proximal humerus. Fractures were classified using Codman-Lego criteria (radiographic, CT images), osteoporosis was assessed. To identify inferior subluxation, an original method is proposed. This measurement was done pre-operatively, at three and 12 month post-operatively. Clinical evaluation was recorded at final follow-up using Constant Score. RESULTS: One hundred fifty fractures surgically treated were studied. Intra- and inter-observer reliabilities were excellent and high, respectively. In pre-operative x-rays, a significant inferior subluxation was noted in 17/150 cases (11.3%), with significant correlation with fracture pattern (p=0.045), female sex (p=0.038), age older than 70 (p=0.003), obesity (BMI>30, p=0.03), and local osteoporosis (p=0.002). At three month of follow-up, 22 cases (14.6%) had inferior subluxation, with significant correlation with female sex (p=0.04), age older than 70 (p=0.002), obesity (p=0.02), pin or screw articular surface perforation (p<0.001). At 12 month of follow-up, seven cases showed persistent inferior subluxation, with significant correlation with age older than 70 (p=0.032), obesity (p=0.041), screw joint perforation and lower Constant Score (p<0.001). DISCUSSION: Inferior subluxation was mostly found in osteoporotic fractures of the elderly, obese, and of female sex both pre- and post-operatively. The intra- and inter-observer reliabilities of proposed radiographic measurement were high and excellent, respectively. CONCLUSIONS: In the early postoperative months, we found a high correlation between inferior subluxation and articular surface perforation; when persisting at later follow-ups, we might speculate that it could represent an early phase of avascular necrosis of the humeral head. LEVEL OF EVIDENCE: Level III, observational study.
Subject(s)
Humeral Head/diagnostic imaging , Joint Dislocations/diagnostic imaging , Shoulder Fractures/diagnostic imaging , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Fracture Fixation, Internal/adverse effects , Fracture Fixation, Internal/methods , Humans , Humeral Head/injuries , Joint Dislocations/etiology , Joint Dislocations/surgery , Male , Middle Aged , Observer Variation , Reproducibility of Results , Retrospective Studies , Risk Factors , Shoulder Fractures/complications , Shoulder Fractures/surgery , Tomography, X-Ray Computed/methodsABSTRACT
INTRODUÇÃO: Estudos anteriores relataram maior prevalência de Tuberculose e HIV entre os prisioneiros do que na população geral no Brasil, mas existem dados limitados disponíveis para facilitar o desenvolvimento de intervenções efetivas neste cenário de alta transmissão. O objetivo deste estudo foi avaliar a prevalência e os fatores de risco associados à Tuberculose e ao HIV. METODOLOGIA: Realizado questionário para a amostra de detentos de 12 prisões em Mato Grosso do Sul (Brasil), prova tuberculínica, coletado sangue para teste de HIVe duas amostras de escarro para baciloscopia e cultura de participantes que relataram tosse de qualquer duração, de Janeiro a Dezembro de2013. RESUILTADOS: Foram recrutados 3.380 detentos, dos quais 2.861(84,6%) eram homens de 8 prisões e 519 (15,4%) eram mulheres de4 prisões. Entre os 1.020 (30%) indivíduos que relataram tosse, 691(68%) coletaram escarro e foram identificados 31 casos de tuberculose ativa, com uma prevalência de 917 por 100.000 detentos. A prevalência de tuberculose latente foi de 22,5% e 11,7% para homens e mulheres,respectivamente. Dos participantes, 55 (1,63%) são soropositivos: 45(1,58%) homens e 10 mulheres (1,93%). CONCLUSÕES: Observou-se que a prevalência de tuberculose ativa e HIV são mais elevadas entre detentos do que na população geral, o que indica um alto risco de infecção e transmissão dentro dessas configurações. Para melhorar o controle da tuberculose nas prisões é necessária a detecção de casos de TB ativa em presídios através da triagem frequente e detecção de casos passiva e ativa.
BACKGROUND: Prior studies have reported higher Tuberculosis and HIVprevalence among prisoners than the general population in Brazil, yet there are limited data available to facilitate the development of effectiveinterventions in this high-transmission setting. The aim of this study wasto evaluate the prevalence and risk factors associated with TB and HIV. METHODS: We administered a questionnaire and tuberculin skin test (TST)to a population-based sample of inmates from 12 prisons in Mato Grasso do Sul (Brazil) and collected sera for HIV testing and two sputum samplesfor smear microscopy and culture from participants reporting a cough ofany duration, from January to December 2013. RESULTS: We recruited 3,380inmates, of which 2,861 (84.6%) were males from 8 prisons, and 519(15.4%) were females from 4 prisons. Among the 1,020 (30%) subjectswho reported a cough, we obtained sputum from 691 (68%) and identified31 cases of active TB for a prevalence of 917 per 100,000 prisoners. The prevalences of LTBI were 22.5% and 11.7% for male and female prisoners, respectively. Of these participants, 55 (1.63%) tested HIV-positive: 45(1.58%) men and 10 women (1.93%). It is observed that the prevalence ofTB and HIV are higher in prisons than in urban populations, indicating ahigh risk of infection and transmission within these settings. CONCLUSIONS: It is observed that the prevalence of Tuberculose and HIV are higher inprisons than in urban populations, indicating a high risk of infection andtransmission within these settings. For enhancing TB control in prisons is necessary case detection for active TB in prison facilities through frequent screening and passive and active case-finding of inmates.
Subject(s)
Male , Female , Humans , Tuberculosis , HIV , Prisoners , Cross-Sectional Studies , Epidemiology , Communicable Disease Control , Sexually Transmitted DiseasesABSTRACT
Fournier's gangrene is a life-threatening acute necrotizing fasciitis of perianal,genitourinary and perineal areas. Nowadays, is well known that Fournier gangrene is almost never an idiopathic disease. In this article we report a case of a 70-year-old patient that initially was not treated properly. The gold standard therapy of the Fournier's gangrene remains today a complete, early and extended surgical debridement.
Subject(s)
Debridement/methods , Fournier Gangrene/surgery , Plastic Surgery Procedures/methods , Aged , Fournier Gangrene/pathology , Humans , MaleABSTRACT
BACKGROUND: Globally, prison inmates are a high-risk population for tuberculosis (TB), but the specific drivers of disease and impact of mass screening interventions are poorly understood. METHODS: We performed a prospective cohort study to characterize the incidence and risk factors for tuberculosis infection and disease in 12 Brazilian prisons, and to investigate the effect of mass screening on subsequent disease risk. After recruiting a stratified random sample of inmates, we administered a questionnaire to ascertain symptoms and potential risk factors for tuberculosis; performed tuberculin skin testing (TST); collected sera for HIV testing; and obtained two sputum samples for smear microscopy and culture, from participants reporting a cough of any duration. We repeated the questionnaire and all tests for inmates who remained incarcerated after 1 year. TST conversion was defined as TST ≥10 mm and an induration increase of at least 6 mm in an individual with a baseline TST <10 mm. Cox proportional hazard models were performed to identify risk factors associated with active TB. To evaluate the impact of screening on subsequent risk of disease, we compared TB notifications over one year among individuals randomized to screening for active TB with those not randomized to screening. RESULTS: Among 3,771 inmates recruited, 3,380 (89.6 %) were enrolled in the study, and 1,422 remained incarcerated after one year. Among 1,350 inmates (94.9 %) with paired TSTs at baseline and one-year follow-up, 25.7 % (272/1060) converted to positive. Among those incarcerated for the year, 10 (0.7 %) had TB at baseline and 25 (1.8 %) were diagnosed with TB over the subsequent year. Cases identified through active screening were less likely to be smear-positive than passively detected cases (10.0 % vs 50.9 %; p < 0.01), suggesting early case detection. However, there was no reduction in subsequent disease among individuals actively screened versus those not screened (1.3 % vs 1.7 %; p = 0.88). Drug use during the year (AHR 3.22; 95 % CI 1.05-9.89) and knows somebody with TB were (AHR 2.86; 95 % CI 1.01-8.10) associated with active TB during one year of follow up CONCLUSIONS: Mass screening in twelve Brazilian prisons did not reduce risk of subsequent disease in twelve Brazilian prisons, likely due to an extremely high force of infection. New approaches are needed to control TB in this high-transmission setting.
Subject(s)
Tuberculosis/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Brazil/epidemiology , Cohort Studies , Cough , Female , Humans , Male , Mass Screening , Middle Aged , Prisoners/statistics & numerical data , Prisons/statistics & numerical data , Prospective Studies , Risk Factors , Substance-Related Disorders/epidemiology , Surveys and Questionnaires , Tuberculin Test , Young AdultABSTRACT
CXCL8 is secreted by both normal human thyrocytes (NHT) and thyroid cancer cell lines. CXCL8 displays several tumor-promoting effects and recent evidences indicate that its concentrations within the tumor microenvironment can impact the clinical course of the malignancy. Aim of this study was to compare the basal secretion of CXCL8 among NHT and thyroid cancer cell lines (TPC-1 and BCPAP), and to assess the specific cell response to TNF-α in terms of CXCL8 secretion. NHT primary cultures, TPC-1 and BCPAP cell lines were cultured with or without TNF-α (0, 0.1, 1, 10, and 100 ng/ml). CXCL8 levels were measured in the cell supernatants after 24 h. In basal condition, significant differences in the mean levels of CXCL8 were observed among the three cell types: NHT (110.5 ± 56.2 pg/ml), TPC1 (467.4 ± 43.2 pg/ml), and BCPAP (1731.8 ± 493.3 pg/ml), (F = 35.06; p < 0.0001). TNF-α significantly and in a dose-response manner induced CXCL8 secretion in NHT (F = 25.53; p < 0.00001), TPC-1 (F = 13.38; p < 0.0001), and BCPAP (F = 9.88; p < 0.001) cells. The magnitude of the TNF-α effect (fold-increase vs. basal level of CXCL8) differed significantly among the three cell types (F = 10.47; p < 0.0001). BCPAP were identified as the cells showing the highest basal secretion of CXCL8 and the less responsive to TNF-α. NHT, TPC-1, and BCPAP display significant differences in the secretion of both basal and TNF-α-induced CXCL8 secretion. These results indicate that the mechanisms regulating the secretion of CXCL8 differ in tumor cells harboring different genetic alterations suggesting that specific strategies aimed at inhibiting CXCL8 secretion will be required.
Subject(s)
Interleukin-8/metabolism , Thyroid Epithelial Cells/metabolism , Thyroid Gland/metabolism , Thyroid Neoplasms/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Cell Line , Cell Line, Tumor , Humans , Thyroid Epithelial Cells/drug effects , Thyroid Gland/cytology , Thyroid Gland/drug effects , Thyroid Neoplasms/pathologyABSTRACT
The chemokine receptor CCR6, selectively bound by CCL20, is involved in the metastatic spread of cancer cells. Tumor necrosis factor-α (TNF-α) displays a complex pro-tumorigenic actions, but it is unknown whether this cytokine could modulate the expression of chemokine receptors in thyroid tumors. The membrane expression of CCR6 was assessed by flow cytometry and immunofluorescence, in primary cultures of normal human thyroid (NHT) cells and in thyroid cancer cell lines (TPC-1 and BCPAP), both in basal conditions and after stimulation with TNF-α. In basal conditions, CCR6+ cells were virtually absent in NHT cells (0.4 ± 0.4 %), while they were detected in TPC-1 (23.6 ± 6.6 %) and in BCPAP (12.9 ± 9.4 %) tumor cells (ANOVA F: 10.534; p < 0.005). The incubation with TNF-α significantly increased the percentage of CCR6+ cells in TPC-1 (23.6 ± 6.6 % vs. 33.1 ± 8.7; p < 0.033) and in BCPAP (12.9 ± 9.4 % vs. 18.1 ± 11.5; p < 0.030), but not in NHT (0.4 ± 0.4 % vs. 0.2 ± 0.3; NS) cells. The magnitude of the TNF-α effect was similar for TPC-1 and BCPAP (â¼40 % vs. baseline) cells. TPC-1 cells were characterized by a greater amount of CCR6 per cell as compared with BCPAP cells, both in basal conditions (148.3 ± 33.7 fluorescence intensity vs. 102.5 ± 22.1 p < 0.016) and after TNF-α stimulation (147.8 ± 46.3 fluorescence intensity vs. 95.3 ± 18.5; p < 0.025). Cell migration assays showed that TNF-α treatment significantly increased the rate of migrated cells in those cells in which it also increased the membrane expression of CCR6 (TPC-1 and BCPAP) as compared to basal condition (p < 0.05 for both TPC-1 and BCPAP cells). No effect was observed in NHT cells in which TNF-α stimulation had no effect in terms of CCR6 expression. We first report that TNF-α enhances the expression of CCR6 in thyroid tumor cells, thus providing evidence that TNF-α increases the metastatic potential of thyroid tumors.
Subject(s)
Neoplasm Invasiveness/genetics , Receptors, CCR6/biosynthesis , Thyroid Neoplasms/genetics , Tumor Necrosis Factor-alpha/genetics , Cell Line, Tumor , Cell Movement/genetics , Chemokine CCL20/genetics , Chemokine CCL20/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Humans , Neoplasm Metastasis , Receptors, CCR6/genetics , Thyroid Epithelial Cells/metabolism , Thyroid Epithelial Cells/pathology , Thyroid Gland/cytology , Thyroid Gland/drug effects , Thyroid Gland/metabolism , Thyroid Neoplasms/pathology , Tumor Necrosis Factor-alpha/administration & dosageABSTRACT
BACKGROUND: Prior studies have reported higher HIV prevalence among prisoners than the general population in Brazil, but data have been derived from single prisons. The aim of this study was to evaluate HIV testing practices, prevalence and linkage to care among inmates in a network of 12 prisons. METHODS: We administered a questionnaire to a population-based sample of inmates from 12 prisons in Central-West Brazil and collected sera for HIV and syphilis testing from January to December 2013. We evaluated factors associated with HIV testing and infection using multivariable logistic regression models. Six months after HIV testing, we assessed whether each HIV-infected prisoner was engaged in clinical care and whether they had started antiretroviral therapy. RESULTS: We recruited 3,362 inmates, of whom 2,843 (85%) were men from 8 prisons, and 519 (15%) were women from 4 prisons. Forty-five percent of participants reported never having been tested for HIV previously. In multivariable analysis, the variables associated with previous HIV testing were lack of a stable partner (adjusted odds ratio [AOR]: 1.38; 95% CI: 1.18-1.60), completed more than four years of schooling (AOR 1.40; 95% CI: 1.20-1.64), history of previous incarceration (AOR: 1.68; 95% CI: 1.43-1.98), history of mental illness (AOR 1.52; 95% CI: 1.31-1.78) and previous surgery (AOR 1.31; 95% CI: 1.12-1.52). Fifty-four (1.6%) of all participants tested positive for HIV; this included 44 (1.54%) men and 10 (1.92%) women. Among male inmates, HIV infection was associated with homosexuality (AOR 6.20, 95% CI: 1.73-22.22), self-report of mental illness (AOR 2.18, 95% CI: 1.13-4.18), history of sexually transmitted infections (AOR 3.28, 95% CI: 1.64-6.56), and syphilis sero-positivity (AOR 2.54, 95% CI: 1.20-5.39). Among HIV-infected individuals, 34 (63%) were unaware of their HIV status; only 23 of these 34 (68%) newly diagnosed participants could be reached at six month follow-up, and 21 of 23 (91%) were engaged in HIV care. CONCLUSIONS: HIV testing rates among prison inmates are low, and the majority of HIV-infected inmates were unaware of their HIV diagnosis. Incarceration can be an opportunity for diagnosis and treatment of HIV among vulnerable populations who have poor access to health services, but further work is needed on transitional HIV care for released inmates.
Subject(s)
HIV Infections/diagnosis , HIV Infections/epidemiology , Mass Screening/methods , Prisoners , Prisons , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Retroviral Agents/chemistry , Brazil , Cross-Sectional Studies , Female , HIV Infections/complications , Health Services Accessibility , Humans , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Prevalence , Surveys and Questionnaires , Syphilis/complications , Syphilis/diagnosis , Syphilis/epidemiology , Vulnerable Populations , Young AdultABSTRACT
Prisoners have among the highest incidence of tuberculosis (TB) globally. However, the contribution of the prison environment on transmission is not well understood and structural characteristics have received little attention as effective epidemiological interventions in TB control. We evaluated architectural characteristics and estimated ventilation rates in 141 cells in three prisons in central west Brazil using steady-state exhaled carbon dioxide (CO2) levels. We used a modified Wells-Riley equation to estimate the probability of infection for inmates sharing a cell with an infectious case and projected the impact of interventions, including early diagnosis and improved ventilation. Overall, prison cells were densely populated (mean 2.1 m(2) per occupant) and poorly ventilated, with only three cells meeting World Health Organization (WHO) standards for per-person ventilation (60 L/s) applied in infection control settings. In the absence of interventions, projected mean risk of infection was 78.0% during a 6-month period. Decreasing time-to-diagnosis by 25% reduced transmission risk by 8.3%. Improving ventilation to WHO standards decreased transmission by 38.2%, whereas optimizing cross-ventilation reduced transmission by 64.4%. Prison environments promote high infection risk over short-time intervals. In this context, enhanced diagnostics have a limited impact on reducing transmission. Improving natural ventilation may be required to effectively control TB in prisons.
Subject(s)
Prisons/statistics & numerical data , Tuberculosis, Pulmonary/transmission , Ventilation/statistics & numerical data , Brazil/epidemiology , Early Diagnosis , Facility Design and Construction , Humans , Models, Theoretical , Prisons/standards , Risk Factors , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Ventilation/standardsABSTRACT
OBJECTIVE: The aim of the study was to evaluate the diagnostic performance of a new ultrasound elastography (USE) parameter based on the measurement of the percentage of maximal stiffness within a nodule as compared with the already established elastographic strain index (SI) and to investigate their diagnostic performance according to nodule size. METHODS: The study included 218 nodules. Each nodule underwent conventional ultrasound (US), USE evaluation, and fine-needle aspiration cytology (FNAC). Thyroid nodules were further stratified into 4 subgroups (G) according to their size (G1, <1 cm; G2, 1-2 cm; G3, >3 cm). USE evaluation comprised the measurement of the percentage of the areas included in the region of interest corresponding to the maximal stiffness (% Index) and of the SI. RESULTS: The % Index and of the SI were significantly higher in malignant than in benign thyroid nodules, and both measurements displayed a good diagnostic performance (SI sensitivity and specificity, 0.66 and 0.90, respectively; % Index sensitivity and specificity, 0.76 and 0.89, respectively). Compared with SI, the % Index was more informative, both in the whole group of thyroid nodules (odds ratio [OR], 18.68; 95% confidence interval [CI], 6.06 to 63.49; P<.0001 versus OR, 26.15; 95% CI, 8.01 to 102.87; P<.0001, respectively) and in the G1 and G2 subgroups. CONCLUSION: The % Index is a stronger predictor of nodule malignancy than both the SI and the conventional US signs. This is particularly true in nodules smaller than 1 cm, which are more difficult to explore both by conventional US and FNAC.
Subject(s)
Elasticity Imaging Techniques/methods , Thyroid Nodule/diagnostic imaging , Ultrasonography/methods , Adult , Biomechanical Phenomena , Biopsy, Fine-Needle , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Odds Ratio , Sensitivity and Specificity , Thyroid Nodule/pathologyABSTRACT
BACKGROUND: Tuberculosis (TB) rates among prisoners are more than 20 times that of the general population in Brazil, yet there are limited data available to facilitate the development of effective interventions in this high-transmission setting. We aimed to assess risk factors for TB infection and evaluate the yield of mass screening for active disease among inmates. METHODS: We administered a questionnaire and tuberculin skin test (TST) to a population-based sample of inmates from 12 prisons in Central-West Brazil and collected sera for HIV testing and two sputum samples for smear microscopy and culture from participants reporting a cough of any duration. Hierarchical Poisson regression models were used to evaluate factors associated with latent tuberculosis infection (LTBI). RESULTS: We recruited 3,380 inmates, of which 2,861 (84.6%) were males from 8 prisons, and 519 (15.4%) were females from 4 prisons. Among the 1,020 (30%) subjects who reported a cough, we obtained sputum from 691 (68%) and identified 31 cases of active TB for a point prevalence of 917 (95% CI, 623-1302) per 100,000 prisoners. Evaluation of the two sputum smear samples failed to identify 74% of the TB cases, and 29% of the cases reported less than 2 weeks of symptoms. Obtaining a second culture identified an additional 7 (24%) cases. The prevalences of LTBI were 22.5% and 11.7% for male and female prisoners, respectively and duration of incarceration (in years) was associated with LTBI in male and female in the multivariable model (1.04, 95% CI, 1.01-1.07 and 1.34, 95% CI, 1.06-1.70, respectively). The prevalence of LTBI is 8.6% among newly incarcerated inmates, among whom LTBI prevalence significantly increased by 5% with each year of incarceration. CONCLUSIONS: Although the overall LTBI prevalence among inmates in Central-West Brazil is low, tuberculosis incidence is high (>1,800/100,00), likely due to the high force of infection among a largely susceptible inmate population. Efforts to reduce transmission in prisons may require mass screening for active TB, utilizing sputum culture in case-detection protocols.