Confirming the presence of HTLV-1 infection and the absence of HTLV-2 in blood donors from Arequipa, Peru

Epidemiological studies conducted in Peru disclosed HTLV-1 to be prevalent in different ethnic groups, and found HTLV-2 in some Amazonian Indians and in men who have sex with men. No data concerning HTLV-1/2 infection in blood donors from Arequipa, a highlands region in southern Peru, is available. We searched for the presence of HTLV-1 and HTLV-2 antibodies in 2,732 serum samples obtained from blood donors from this geographic area. HTLV-1/2-specific antibodies were detected using an enzyme-linked immunosorbent assay (ELISA) and were confirmed by Western blot (WB). Reactive sera had their blood bags discarded from donation, and the demographic characteristics of the donors were analyzed. Thirty-five sera (1.2%) were HTLV seroreactive by ELISA, and 25 were confirmed HTLV-1-positive by WB. One serum disclosed HTLV-positivity, and the remaining nine serum samples showed indeterminate results by WB; three of which had an HTLV-1 indeterminate Gag profile. The median age of HTLV-positive individuals was 34.6 years; 27 were male and eight were female. All individuals were from southern Peru: 27 from Arequipa, five from Puno, and three from Cuzco. HTLV co-positivity with hepatitis B (five sera) and syphilis (one serum) were detected. Previous transfusion and tattooing were observed in two and one individuals, respectively. No serum was positive for HTLV/HIV co-infection. This study confirmed, for the first time, HTLV-1 infection and the absence of HTLV-2 infection in blood donors from Arequipa, Peru and suggests vertical transmission as the major route of HTLV-1 transmission and acquisition in this geographic region.Estudos epidemiológicos conduzidos no Peru apontam a infecção por HTLV-1 como prevalente em diferentes grupos étnicos e por HTLV-2 restrita a alguns índios da região Amazônica e a homens que fazem sexo com homens. Não existem dados sobre a infecção por HTLV-1/2 em doadores de sangue de Arequipa, região montanhosa do sul do Peru. Portanto, o presente estudo pesquisou anticorpos anti-HTLV-1 e HTLV-2 em 2.732 doadores de sangue desta região geográfica. Foram utilizados na triagem sorológica os testes imunoenzimáticos (ELISA) e para confirmação dos resultados o Western Blot (WB). Soros reagentes no ELISA tiveram suas bolsas de sangue descartadas. Os resultados obtidos foram analisados de acordo com características demográficas dos indivíduos. Trinta e cinco soros (1,2%) resultaram HTLV-1/2 reagentes no ELISA, 25 confirmaram infecção por HTLV-1 no WB. Um soro resultou HTLV positivo e os nove soros restantes resultaram em padrão indeterminado no WB: três com perfil HTLV-1 Gag indeterminado. A média de idade dos indivíduos HTLV positivos foi de 34,6 anos; 27 do gênero masculino e oito do gênero feminino. Todos eram da região sul do país: 27 de Arequipa, cinco de Puno e três de Cuzco. Foi detectada co-positividade HTLV com hepatite B (cinco soros) e sífilis (um soro). Nenhum soro resultou positivo para a co-infecção HIV/HTLV. Havia dois indivíduos com transfusão prévia e um com tatuagem. Este trabalho confirma pela primeira vez infecção por HTLV-1 e ausência de infecção por HTLV-2 em doadores de sangue de Arequipa, sul do Peru e sugere que a transmissão vertical seja a principal via de transmissão/aquisição de HTLV-1 nesta região geográfica

Desempenho de testes sorológicos para o diagnóstico de infecção por HTLV em população de alto-risco de São Paulo, Brasil

Testing problems in diagnosing human T-lymphotropic virus (HTLV) infection, mostly HTLV-II, have been documented in HIV/AIDS patients. Since December 1998, the Immunology Department of Instituto Adolfo Lutz (IAL) offers HTLV-I/II serology to Public Health Units that attend HTLV high-risk individuals. Two thousand, three hundred and twelve serum samples: 1,393 from AIDS Reference Centers (Group I), and 919 from HTLV out-patient clinics (Group II) were sent to IAL for HTLV-I/II antibodies detection. The majority of them were screened by two enzyme immunoassays (EIAs), and confirmed by Western Blot (WB 2.4, Genelabs). Seven different EIA kits were employed during the period, and according to WB results, the best performance was obtained by EIAs that contain HTLV-I and HTLV-II viral lysates and rgp21 as antigens. Neither 1st and 2nd, nor 3rd generation EIA kits were 100% sensitive in detecting truly HTLV-I/II reactive samples. HTLV-I and HTLV-II prevalence rates of 3.3% and 2.5% were detected in Group I, and of 9.6% and 3.6% in Group II, respectively. High percentages of HTLV-seroindeterminate WB sera were detected in both Groups. The algorithm testing to be employed in HTLV high-risk population from São Paulo, Brazil, needs the use of two EIA kits of different formats and compounds as screening, and because of high seroindeterminate WB, may be another confirmatory assay.Problemas nos testes diagnósticos de infecção pelos vírus linfotrópicos de células T humanas (HTLV), principalmente HTLV-II, têm sido observados em pacientes com HIV/Aids. Desde Dezembro de 1998, a Seção de Imunologia do Instituto Adolfo Lutz (IAL) oferece a sorologia para HTLV-I/II para Serviços de Saúde Pública que atendem populações consideradas de risco para esta infecção. Duas mil trezentas e doze amostras de soro: 1.393 de Centros de Referência em Aids (Grupo I) e 919 de Clínicas de Especialidade em HTLV (Grupo II) foram encaminhadas para o IAL para a pesquisa de anticorpos anti-HTLV-I/II. A maioria delas foram testadas por dois ensaios imunoenzimáticos (EIAs) e confirmadas por Western Blot (WB 2.4, Genelabs). Sete kits diferentes de EIAs foram empregados durante o período e de acordo com os resultados do WB a melhor performance foi obtida com os EIAs que continham lisado viral dos HTLV-I e -II e a rgp21 como antígenos. Nenhum kit de EIA de 1ª, 2ª ou 3ª geração foi 100% sensível para detectar todas as amostras verdadeiramente HTLV-I/II reagentes. A prevalência de HTLV-I e HTLV-II, respectivamente, foi de 3,3% e 2,5% no Grupo I e de 9,6% e 3,6% no Grupo II. Em ambos os Grupos, foram detectadas altas percentagens de soros com padrão indeterminado no WB. O algoritmo de testes sorológicos para ser usado em população de alto risco para HTLV de São Paulo, Brasil, necessita de dois kits EIAs de princípios e composição diferentes para a triagem sorológica e, pelo elevado número de WB indeterminado, talvez de um outro teste confirmatório

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Human Herpesvirus type 8 (HHV-8): Study of target segments of the HHV-8 genoma in blood, saliva and urine of HIV/aids infected patients with or without Kaposi's Sarcoma

Desde a descoberta do herpes vírus humano tipo 8 (HHV-8) como o agente etiológico do sarcoma de Kaposi (SK) nas suas diferentes formas clínico-epidemiológicas, vários estudos vêm sendo conduzidos com o intuito de determinar as vias de transmissão desse vírus em populações endêmicas e de risco epidemiológico. Em regiões endêmicas, a transmissão viral foi relacionada à transmissão horizontal de mães para filhos e entre irmãos e a sexual principalmente, nos casos de SK/aids. Com o objetivo de determinar segmentos do genoma viral em fluídos biológicos e consequentemente seu potencial infectante foi conduzido o presente trabalho. Foram avaliados quanto à presença de segmentos localizados em posições estratégicas do genoma do HHV-8 em sangue, saliva e urina de 76 pacientes com SK/aids, 19 pacientes com HIV/aids, 4 casos de SK clássico e 11 indivíduos sadios (HIV-soronegativos, sem SK). Foram utilizadas as técnicas de PCR "nested" para as ORF K1, ORF 25, ORF 26, ORF K8.1 e ORF 73 em DNA extraído de material de biópsia de lesão de SK (controle positivo), células do sangue periférico, saliva e urina. Os resultados de PCR positivo para o HHV-8 foram analisados quanto a variáveis epidemiológicas, clínicas e laboratoriais. Foram consideradas como variáveis: sexo, cor, origem étnica, tempo de infecção por HIV e de acompanhamento do SK, terapia ARV e para SK, contagem de células CD4+ e sorologia para o HHV-8 (IFI-LANA e IFI-Lítico). Os testes estatísticos de regressão logística e de razão de chances foram usados para detectar as associações estatisticamente significantes entre as PCRs positivas e as variáveis estudadas nos grupos SK/aids e HIV/aids. Os subtipos do HHV-8 foram também determinados pela técnica de PCR-RFLP da ORF K1 (VR1). Os resultados obtidos mostraram a detecção de DNA/HHV-8 em 80,2% do material de biópsia, 69,7% no sangue, 59,2% na saliva e 21,0% na urina de pacientes com SK/aids. No grupo HIV/aids, a PCR para o HHV-8 resultou positiva em 47,4% dos casos no sangue e em 26,3% na saliva e urina. Já no grupo SK clássico 100% das biópsias e salivas resultaram PCR positiva, 67% do sangue e 33% das urinas. A avaliação sorológica revelou 73,3% de reatividade para IFI-LANA e 85,3% para a IFI-Lítico no grupo SK/aids, enquanto o grupo HIV/aids mostrou reatividade de 15,8% para IFI-LANA e 47,4% para IFI-Lítico; todos os pacientes apresentaram resultados reagentes nas duas sorologias para o HHV-8 no grupo de SK clássico. No grupo controle sadio não houve reatividade na sorologia para o HHV-8, com exceção de um caso, que mostrou ser reagente na IFI-LANA. Foi possível realizar a subtipagem do HHV-8 em amostras de 69 pacientes, sendo detectadas 27 cepas do subtipo A, 13 do subtipo B, 28 do subtipo C e 1 do subtipo E. Após as análises estatísticas foi verificado que as PCRs que identificam as regiões ORF 26, ORF K8.1 e ORF 73 foram as que apresentaram melhor desempenho na identificação de DNA/HHV-8. Houve associação entre a reatividade de IFI-Lítico e a presença do vírus no sangue periférico, assim como a reatividade para IFI-LANA e a detecção de DNA/HHV-8 na saliva. Houve uma tendência dos subtipos B e C de HHV-8 serem detectados em pacientes com infecção profunda ou disseminada de SK. Estes resultados sugerem que a boca pode ser um sítio de latência da infecção por HHV-8 e confirmam a atuação de sangue, saliva e urina como fluídos potencialmente infectantes.Since the discovery of the human herpesvirus 8 (HHV-8) as the etiological agent of Kaposis sarcoma (KS), several studies have been conducted in order to determine routes of virus transmission, mostly in endemic and at risk populations. The main of the present study was to determine target segments of the HHV-8 genoma and consequently infected bodily fluids. DNA sequences of ORF K1, ORF 25, ORF 26, ORF K8.1 and ORF 73 strategically localized in viral genoma were searched using nested PCR techniques in KS lesions (positive control), blood, saliva, and urine from 76 KS/aids patients, 19 HIV/aids patients, 4 classic KS patients, and among 11 healthy individuals (HIV-1 seronegative, without KS). HHV-8 subtypes were determined by PCR-RFLP of the ORF K1 (VR1), and HHV-8 antibodies by IFA-LANA and IFA-Lytic assays. The results obtained were analyzed according to epidemiological, clinical and laboratorial data, and the c2 test, logistic regression and odds ratio were applied to identify statistical association among variables in KS/aids and HIV/aids groups. The results obtained showed HHV-8 DNA in 80.2% of biopsies, 69.7% of blood, 59.2% of saliva, and 21% of urines from KS/aids group. Among HIV/aids patients, 47.4% resulted PCR positive in blood, 26.3% in saliva and urine. In classic KS cases, all biopsies and saliva resulted PCR positive, 67% in blood, and 33% in urine. The serology in KS/aids group showed 73.3% frequency of anti-latent antibodies, and 85.3% frequency of anti-lytic antibodies, while in HIV/aids group the frequencies were 15.8% and 47.4%, respectively. All classic KS cases resulted HHV-8 seroposite, while all individuals from control group resulted HHV-8 seronegative. Molecular characterization of 69 HHV-8 strains disclosed: 27 of subtype A, 13 of subtype B, 28 of subtype C, and 1 of subtype E. The ORF 26, ORF K8.1 and ORF 73 were the best segments for identifying HHV-8 DNA in bodily fluids. It was observed an association between antibodies to lytic antigens and the presence of HHV-8 in blood, and antibodies to latent antigens and the detection of HHV8 DNA in saliva of KS/aids patients. Indeed, HHV-8 subtypes B and C were detected mostly in disseminated KS cases. Taken together, the results obtained suggest that the mouth could be one site of HHV-8 latency, and confirm that blood, saliva and urine were potentially infectious bodily fluids