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In the recent mpox outbreak, people living with HIV (PLWH) were at high risk both for contracting infection and for suffering a more severe disease course. We studied cellular and humoral immune responses elicited by mpox infection (n = 5; n = 3 PLWH) or smallpox vaccination (n = 17; all PLWH) in a cohort of men who have sex with men. All PLWH were successfully treated, with stable CD4 counts and undetectable HIV viral loads. 11/17 vaccinated individuals had received childhood smallpox vaccination. In this group of individuals, both two-dose MVA-vaccination and natural infection evoked mpox-specific immune responses mediated by B cells as well as CD4 and CD8 T cells. This study improves our understanding of smallpox vaccination mediated cross-reactivity to other orthopox viruses, and the long-lasting durability of childhood smallpox vaccination mediated immune responses including in PLWH.
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BACKGROUND: Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear. METHODS: We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality. RESULTS: CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10-6.19] and 2.03 [95% CI 1.24-3.33], respectively). CD4 cell counts below 350 cells/µL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies. CONCLUSIONS: In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM.
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Síndrome da Imunodeficiência Adquirida , Fármacos Anti-HIV , Infecções por HIV , Neoplasias , Humanos , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/tratamento farmacológico , Relação CD4-CD8 , Carga Viral , Fármacos Anti-HIV/efeitos adversosRESUMO
Cognitive symptoms (CS) belong to the most common manifestations of the Post COVID-19 (PC) condition. We sought to objectify CS in PC patients using routine diagnostic assessments: neurocognitive testing (NCT) and brain imaging (BI). Further, we investigated possible associations of CS with patient reported outcomes (PROs), and risk factors for developing CS. Clinical data and PROs of 315 PC patients were assessed at a mean of 6 months after SARS-CoV-2 infection. 231 (73.3%) patients reported any sort of CS. Among them, 78 underwent NCT and 55 received BI. In NCT, the cognitive domains most affected were the working memory, attention, and concentration. Nonetheless, pathological thresholds were exceeded only in few cases. Neurocognitive performance did not differ significantly between patients complaining of severe (n = 26) versus non-severe (n = 52) CS. BI findings were abnormal in 8 (14.5%) cases with CS but were most likely not related to PC. Patients reporting high severity of CS scored worse in the PHQ-9, FSS, WHOQOL-BREF, were more likely to report impaired sleep, and had a higher prevalence of psychiatric diagnoses. Overall, NCT could confirm mild impairment in some but not all PC patients with CS, while BI studies were abnormal in only few cases. CS severity did not affect NCT results, but severe CS were associated with symptoms of depression (PHQ-9), fatigue (FSS), reduced quality of life (WHOQOL-BREF) and higher prevalence of psychiatric illnesses. These findings support the importance of NCT, BI, and neuro-psychological assessment in the work-up of PC patients reporting CS. TRIAL REGISTRATION: Trial registration number and date of registration: DRKS00030974, 22 Dec 2022, retrospectively registered.
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OBJECTIVES: Our objective was to determine whether antiretroviral drugs (ARVs) were used according to the European AIDS Clinical Society (EACS) guidelines for people with HIV/hepatitis C virus (HCV) coinfection treated with direct-acting antivirals (DAAs) between 30 November 2014 and 31 December 2019 in the pan-European EuroSIDA study. METHODS: At each publication date of the EACS guidelines, plus 3 and 6 months, we calculated the number of people receiving DAAs with potential and actual ARV contraindications ('red shading' in the EACS guidelines). We used logistic regression to investigate factors associated with using contraindicated ARVs. RESULTS: Among 1406 people starting DAAs, the median age was 51 years, 75% were male, 57% reported injected drug use as an HIV risk, and 76% were from western Europe. Of 1624 treatment episodes, 609 (37.5%) occurred while the patient was receiving ARVs with potential contraindications; among them, 38 (6.2%; 95% confidence interval [CI] 4.3-8.2) involved a contraindicated ARV (18 non-nucleoside reverse transcriptase inhibitors), 16 involved protease inhibitors, and four involved integrase strand transfer inhibitors. The adjusted odds of receiving a contraindicated ARV were higher (3.25; 95% CI 1.40-7.57) among participants from east/central east Europe (vs. south) and lower (0.22; 95% CI 0.08-0.65) for 2015-2018 guidelines (vs. 2014). In total, 29 of the 32 (90.6%) patients receiving a contraindicated ARV and 441 of the 461 (95.7%) with potential ARV contraindications experienced a sustained virological response ≥12 weeks after stopping treatment (SVR12; p = 0.55). CONCLUSION: In this large heterogenous European cohort, more than one-third of people with HIV/HCV coinfection received DAAs with potential ARV contraindications, but few received a contraindicated ARV. Use of contraindicated ARVs declined over time, corresponding to the increased availability of ARV therapy regimens without interactions with DAA across Europe. Participants who received a contraindicated DAA and ARV combination still had a high rate of SVR12.
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Síndrome da Imunodeficiência Adquirida , Coinfecção , Infecções por HIV , Hepatite C Crônica , Hepatite C , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Antivirais/uso terapêutico , Hepacivirus , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Coinfecção/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Antirretrovirais/uso terapêutico , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológicoRESUMO
Patient-reported outcome measures (PROMs) such as the Numeric Pain Rating Scale (NPRS) or Likert scales addressing various domains of health are important tools to assess disease severity in Post COVID-19 (PC) patients. By design, they are subjective in nature and prone to bias. Our findings reveal substantial differences in the perception of disease severity between patients (PAT), their attending internists (INT) and psychiatrists/psychologists (PSY). Patients rated almost all aspects of their health worse than INT or PSY. Most of the differences were statistically highly significant. The presence of fatigue and mood disorders correlated negatively with health perception. The physical health section of the WHO Quality of Life Assessment (WHOQoL-BREF) and Karnofsky index correlated positively with overall and mental health ratings by PAT and INT. Health ratings by neither PAT, PSY nor INT were associated with the number of abnormal findings in diagnostic procedures. This study highlights how strongly perceptions of disease severity diverge between PC patients and attending medical staff. Imprecise communication, different experiences regarding health and disease, and confounding psychological factors may explain these observations. Discrepancies in disease perception threaten patient-physician relationships and pose strong confounders in clinical studies. Established scores (e.g., WHOQoL-BREF, Karnofsky index) may represent an approach to overcome these discrepancies. Physicians and psychologists noting harsh differences between a patient's and their own perception of the patient's health should apply screening tools for mood disorders (i.e., PHQ-9, WHOQoL-BREF), psychosomatic symptom burden (SSD-12, FCV-19) and consider further psychological evaluation. An interdisciplinary approach to PC patients remains imperative. Trial Registration Number & Date of Registration: DRKS00030974, 22 Dec 2022, retrospectively registered.
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BACKGROUND: A hepatitis C (HCV) cure is associated with changes in lipids and inflammatory biomarkers, but its impact on clinical endpoints among treated human immunodeficiency virus (HIV)/HCV coinfected persons is unclear. METHODS: People living with HIV from EuroSIDA with a known HCV status after January 2001 were classified into strata based on time-updated HCV RNA measurements and HCV treatment, as either HCV antibody-negative; spontaneously resolved HCV; chronic, untreated HCV; cured HCV (HCV RNA-negative); or HCV treatment failures (HCV RNA-positive). Poisson regression was used to compare incidence rates between HCV groups for end-stage liver disease (ESLD; including hepatocellular carcinoma [HCC]), non-acquired immunodeficiency virus defining malignancy (NADM; excluding HCC), and cardiovascular disease (CVD). RESULTS: There were 16 618 persons included (median follow-up 8.3 years, interquartile range 3.1-13.7). There were 887 CVD, 902 NADM, and 436 ESLD events; crude incidence rates/1000 person-years follow-up were 6.4 (95% confidence interval [CI] 6.0-6.9) for CVD, 6.5 (95% CI 6.1-6.9) for NADM, and 3.1 (95% CI 2.8-3.4) for ESLD. After adjustment, there were no differences in incidence rates of NADM or CVD across the 5 groups. HCV-negative individuals (adjusted incidence rate ratio [aIRR] 0.22, 95% CI 0.14-0.34) and those with spontaneous clearance (aIRR 0.61, 95% CI 0.36-1.02) had reduced rates of ESLD compared to cured individuals. Persons with chronic, untreated HCV infections (aIRR 1.47, 95% CI 1.02-2.13) or treatment failure (aIRR 1.80, 95% CI 1.22-2.66) had significantly raised rates of ESLD, compared to those who were cured. CONCLUSIONS: Incidences of NADM or CVD were independent of HCV group, whereas those cured had substantially lower incidences of ESLD, underlining the importance of successful HCV treatment for reducing ESLD.
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Carcinoma Hepatocelular , Coinfecção , Infecções por HIV , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hepacivirus , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , HumanosRESUMO
We analyzed 1,397 HIV-1 pol sequences of antiretroviral therapy-naive patients in a total of 7 university hospitals in Bonn, Cologne, Frankfurt, Hamburg, Hannover, and Munich, Germany. Phylogenetic and network analysis elucidated numerous cases of shared drug resistance mutations among genetically linked patients; K103N was the most frequently shared mutation.
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Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Genótipo , Alemanha/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Mutação , FilogeniaRESUMO
BACKGROUND: The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships. METHODS: The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and env sequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods. FINDINGS: Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1-3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33-46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4-2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76â088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up). INTERPRETATION: Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV. FUNDING: National Institute for Health Research.
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Fármacos Anti-HIV/uso terapêutico , Soropositividade para HIV/transmissão , Homossexualidade Masculina , Sexo sem Proteção , Adulto , Terapia Antirretroviral de Alta Atividade , Preservativos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Parceiros Sexuais , Carga ViralRESUMO
OBJECTIVE: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving. METHODS: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan-Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data. RESULTS: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59-66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39-0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011-2017), being on a multi-tablet regimen (MTR). CONCLUSIONS: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Carga Viral , Adulto , Estudos de Coortes , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Due to the excellent efficacy of antiretroviral treatment increasingly more people with human immunodeficiency virus (HIV) infections survive to old age. The national and international definition of older people with HIV infections comprises those aged 50 years and older. Practitioners caring for these patients have to take age-related comorbidities and polypharmacy into account. Cooperation between HIV caregivers and general practitioners as well as geriatric specialists should provide a network that covers topics such as vaccinations, early detection of malignancies and psychosocial aspects, such as loneliness and organization of nursing care. A schedule for preventive measures is presented in this article as well as practical approaches including access to drug interaction databases and HIV treatment guidelines.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Polimedicação , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Terapia Antirretroviral de Alta Atividade , Comorbidade , Interações Medicamentosas , Geriatras , Infecções por HIV/diagnóstico , Humanos , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Medicamentos sob Prescrição/uso terapêuticoRESUMO
The original version of this article unfortunately contained mistakes.
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PURPOSE: To determine whether changing from a tenofovir disoproxil fumarate (TDF)- to a tenofovir alafenamide fumarate (TAF)-containing regimen is correlated with weight changes in a human immunodeficiency virus (HIV)-positive adult cohort. METHODS: Retrospective analysis was conducted of data gathered from routine care in a university hospital in Munich, Germany, between July 2015 and June 2017. Data from patients' charts were extracted and a two-step approach was applied. First, weight/BMI progression within 1 year after initiation of either TDF or TAF was compared. Subsequently, weight measurements within subjects changing from a TDF- to a TAF-containing antiretroviral regimen were analyzed by means of a repeated measurements general linear model. RESULTS: After 360 days of initiating TAF, patients showed a mean (± standard deviation) percentual weight increase of 3.17 ± 0.21, whereas after 360 days of initiating TDF, patients only showed a mean (± standard deviation) percentual weight increase of 0.55 ± 0.17. The repeated measurements general linear model for within-subjects design showed a statistically significant correlation in weight after changing from a TDF to a TAF containing antiretroviral regimen. The weight difference between the two measurements while on TDF was not statistically significant, but every measure after switching to TAF was significantly higher than the previous. CONCLUSION: Changing from a TDF- to a TAF-containing regimen is correlated with weight gain in this retrospectively analyzed real-world cohort in Munich, Germany.
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Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Soropositividade para HIV/tratamento farmacológico , Tenofovir/uso terapêutico , Aumento de Peso/efeitos dos fármacos , Redução de Peso/efeitos dos fármacos , Adenina/administração & dosagem , Adenina/uso terapêutico , Adulto , Alanina , Fármacos Anti-HIV/administração & dosagem , Estudos de Coortes , Feminino , Fumaratos/administração & dosagem , Fumaratos/uso terapêutico , Alemanha , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tenofovir/administração & dosagemRESUMO
BACKGROUND: To evaluate clinical outcomes after either immediate or deferred initiation of antiretroviral therapy in HIV-1-infected patients, presenting late with pneumocystis pneumonia (PCP) or toxoplasma encephalitis (TE). METHODS: Phase IV, multicenter, prospective, randomized open-label clinical trial. Patients were randomized into an immediate therapy arm (starting antiretroviral therapy (ART) within 7 days after initiation of OI treatment) versus a deferred arm (starting ART after completing the OI-therapy). All patients were followed for 24 weeks. The rates of clinical progression (death, new or relapsing opportunistic infections (OI) and other grade 4 clinical endpoints) were compared, using a combined primary endpoint. Secondary endpoints were hospitalization rates after completion of OI treatment, incidence of immune reconstitution inflammatory syndrome (IRIS), virologic and immunological outcome, adherence to proteinase-inhibitor based antiretroviral therapy (ART) protocol and quality of life. RESULTS: 61 patients (11 patients suffering TE, 50 with PCP) were enrolled. No differences between the two therapy groups in all examined primary and secondary endpoints could be identified: immunological and virologic outcome was similar in both groups, there was no significant difference in the incidence of IRIS (11 and 10 cases), furthermore 9 events (combined endpoint of death, new/relapsing OI and grade 4 events) occurred in each group. CONCLUSIONS: In summary, this study supports the notion that immediate initiation of ART with a ritonavir-boosted proteinase-inhibitor and two nucleoside reverse transcriptase inhibitors is safe and has no negative effects on incidence of disease progression or IRIS, nor on immunological and virologic outcomes or on quality of life.
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Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Pneumonia por Pneumocystis/virologia , Toxoplasmose/virologia , Infecções Oportunistas Relacionadas com a AIDS , Síndrome da Imunodeficiência Adquirida/complicações , Adulto , Progressão da Doença , Esquema de Medicação , Feminino , Alemanha , Infecções por HIV/complicações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de VidaRESUMO
Outcome of HIV-infected patients with AIDS-related lymphomas has improved during recent years. However, data on incidence, risk factors, and outcome of relapses in AIDS-related lymphomas after achieving complete remission are still limited. This prospective observational multicenter study includes HIV-infected patients with biopsy- or cytology-proven malignant lymphomas since 2005. Data on HIV infection and lymphoma characteristics, treatment and outcome were recorded. For this analysis, AIDS-related lymphomas patients in complete remission were analyzed in terms of their relapse- free survival and potential risk factors for relapses. In total, 254 of 399 (63.7%) patients with AIDS-related lymphomas reached a complete remission with their first-line chemotherapy. After a median follow up of 4.6 years, 5-year overall survival of the 254 patients was 87.8% (Standard Error 3.1%). Twenty-nine patients relapsed (11.4%). Several factors were independently associated with a higher relapse rate, including an unclassifiable histology, a stage III or IV according to the Ann Arbor Staging System, no concomitant combined antiretroviral therapy during chemotherapy and R-CHOP-based compared to more intensive chemotherapy regimens in Burkitt lymphomas. In conclusion, complete remission and relapse rates observed in our study are similar to those reported in HIV-negative non-Hodgkin lymphomas. These data provide further evidence for the use of concomitant combined antiretroviral therapy during chemotherapy and a benefit from more intensive chemotherapy regimens in Burkitt lymphomas. Modifications to the chemotherapy regimen appear to have only a limited impact on relapse rate.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/epidemiologia , Adulto , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Incidência , Linfoma Relacionado a AIDS/patologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Indução de Remissão , Fatores de Risco , Taxa de SobrevidaRESUMO
OBJECTIVE: "Choosing Wisely" is a growing international campaign aiming at practice changes to improve patient health and safety by both, conduct of essential and avoidance of unnecessary diagnostic, preventive and therapeutic procedures. The goal is to create an easily recognizable and distributable list ("Choosing Wisely items") that addresses common over- and underuse in the management of infectious diseases. METHODS: The German Society of Infectious Diseases (DGI) participates in the campaign "Klug Entscheiden" by the German Society of Internal Medicine. Committee members of the (DGI) listed potential 'Choosing Wisely items'. Topics were subjected to systematic evidence review and top ten items were selected for appropriateness. Five positive and negative recommendations were approved via individual member vote. RESULTS: The final recommendations are: (1) Imperatively start antimicrobial treatment and remove the focus in Staphylococcus aureus bloodstream infection. (2) Critically ill patients with signs of infection need early appropriate antibiotic therapy. (3) Annual influenza vaccination should be given to individuals with age >60 years, patients with specific co-morbidities and to contact persons who may spread influenza to others. (4) All children should receive measles vaccine. (5) Prefer oral formulations of highly bioavailable antimicrobials whenever possible. (6) Avoid prescribing antibiotics for uncomplicated upper respiratory tract infections. (7) Do not treat asymptomatic bacteriuria with antibiotics. (8) Do not treat Candida detected in respiratory or gastrointestinal tract specimens. (9) Do not prolong prophylactic administration of antibiotics in patients after they have left the operating room. (10) Do not treat an elevated C-reactive protein (CRP) or procalcitonin with antibiotics for patients without signs of infection. CONCLUSIONS: Physicians will reduce potential harm to patients and increase the value of health care when implementing these recommendations.
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Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/terapia , Saúde Global , Promoção da Saúde , Procedimentos Desnecessários/estatística & dados numéricos , Atenção à Saúde , Alemanha , Humanos , Saúde PúblicaAssuntos
Linfoma Relacionado a AIDS/terapia , Linfoma de Efusão Primária/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gerenciamento Clínico , Feminino , Alemanha/epidemiologia , HIV-1/isolamento & purificação , Humanos , Linfoma Relacionado a AIDS/epidemiologia , Linfoma Relacionado a AIDS/virologia , Linfoma de Efusão Primária/epidemiologia , Linfoma de Efusão Primária/virologia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Human myeloid-derived suppressor cells (MDSC) have been described as a group of immature myeloid cells which exert immunosuppressive action by inhibiting function of T lymphocytes. While there is a huge scientific interest to study these cells in multiple human diseases, the methodological approach varies substantially between published studies. This is problematic as human MDSC seem to be a sensible cell type concerning not only cryopreservation but also time point after blood draw. To date data on delayed blood processing influencing cell numbers and phenotype is missing. We therefore evaluated the kinetics of granulocytic MDSC (gMDSC) and monocytic MDSC (mMDSC) frequencies after blood draw in order to determine the best time point for analysis of this recently defined cell type. METHODS: In this study, we isolated peripheral blood mononuclear cells (PBMC) of patients with HIV infection or solid tumors directly after blood draw. We then analyzed the frequencies of gMDSC and mMDSC 2, 4 and 6 h after blood draw and after an overnight rest by FACS analysis using the standard phenotypic markers. In addition, part of the cells was frozen directly after PBMC preparation and was measured after thawing. RESULTS: gMDSC levels showed no significant difference using fresh PBMC over time with a limitation for the overnight sample. However they were massively diminished after freezing (p = 0.0001 for all subjects). In contrast, frequencies of fresh mMDSC varied over time with no difference between time point 2 and 4 h but a significantly reduction after 6 h and overnight rest (p = 0.0005 and p = 0.005 respectively). Freezing of PBMC decreased the yield of mMDSC reaching statistical significance (p = 0.04). For both MDSC subgroups, FACS analysis became more difficult over time due to less sharp divisions between populations. CONCLUSIONS: According to our data human MDSC need to be studied on fresh PBMC. gMDSC can be studied with delay, mMDSC however should be studied no later than 4 h after blood draw. These results are crucial as an increasing number of clinical trials aim at analyzing MDSC nowadays and the logistics of blood processing implies delayed sample processing in some cases.
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Coleta de Amostras Sanguíneas/métodos , Células Mieloides/citologia , Contagem de Células , Humanos , Cinética , Fenótipo , DescansoRESUMO
Overall survival (OS) of patients with acquired immunodeficiency syndrome (AIDS)-related Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and plasmablastic lymphoma (PBL) was analysed in the German AIDS-related-Lymphoma-Cohort-Study. Of 291 patients prospectively included between January 2005 and December 2012, 154 had DLBCL, 103 BL and 34 PBL. Two-year OS rates were similar between BL (69%) and DLBCL patients (63%) but lower for PBL patients (43%). Intermediate (Hazard ratio [HR] 4·1 95% confidence interval [CI] 1·98-8·49) or high (HR 4·92 95% CI 2·1-11·61) International Prognostic Index, bone marrow involvement (HR 1·69 95% CI 1·00-2·84) and PBL histology (HR 2·24 95% CI 1·24-4·03) were independent predictors of mortality.