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  1. Tao S, Kichula KM, Harrison GF, Farias TDJ, Palmer WH, Leaton LA, et al.
    Immunology, 2021 Apr;162(4):389-404.
    PMID: 33283280 DOI: 10.1111/imm.13289
    Killer cell immunoglobulin-like receptors (KIRs) interact with polymorphic human leucocyte antigen (HLA) class I molecules, modulating natural killer (NK) cell functions and affecting both the susceptibility and outcome of immune-mediated diseases. The KIR locus is highly diverse in gene content, copy number and allelic polymorphism within individuals and across geographical populations. To analyse currently under-represented Asian and Pacific populations, we investigated the combinatorial diversity of KIR and HLA class I in 92 unrelated Malay and 75 Malaysian Chinese individuals from the Malay Peninsula. We identified substantial allelic and structural diversity of the KIR locus in both populations and characterized novel variations at each analysis level. The Malay population is more diverse than Malay Chinese, likely representing a unique history including admixture with immigrating populations spanning several thousand years. Characterizing the Malay population are KIR haplotypes with large structural variants present in 10% individuals, and KIR and HLA alleles previously identified in Austronesian populations. Despite the differences in ancestries, the proportion of HLA allotypes that serve as KIR ligands is similar in each population. The exception is a significantly reduced frequency of interactions of KIR2DL1 with C2+ HLA-C in the Malaysian Chinese group, caused by the low frequency of C2+ HLA. One likely implication is a greater protection from preeclampsia, a pregnancy disorder associated with KIR2DL1, which shows higher incidence in the Malay than in the Malaysian Chinese. This first complete, high-resolution, characterization of combinatorial diversity of KIR and HLA in Malaysians will form a valuable reference for future clinical and population studies.
  2. Podda M, Pacella D, Pellino G, Coccolini F, Giordano A, Di Saverio S, et al.
    Pancreatology, 2022 Nov;22(7):902-916.
    PMID: 35963665 DOI: 10.1016/j.pan.2022.07.007
    BACKGROUND/OBJECTIVES: Reports about the implementation of recommendations from acute pancreatitis guidelines are scant. This study aimed to evaluate, on a patient-data basis, the contemporary practice patterns of management of biliary acute pancreatitis and to compare these practices with the recommendations by the most updated guidelines.

    METHODS: All consecutive patients admitted to any of the 150 participating general surgery (GS), hepatopancreatobiliary surgery (HPB), internal medicine (IM) and gastroenterology (GA) departments with a diagnosis of biliary acute pancreatitis between 01/01/2019 and 31/12/2020 were included in the study. Categorical data were reported as percentages representing the proportion of all study patients or different and well-defined cohorts for each variable. Continuous data were expressed as mean and standard deviation. Differences between the compliance obtained in the four different subgroups were compared using the Mann-Whitney U, Student's t, ANOVA or Kruskal-Wallis tests for continuous data, and the Chi-square test or the Fisher's exact test for categorical data.

    RESULTS: Complete data were available for 5275 patients. The most commonly discordant gaps between daily clinical practice and recommendations included the optimal timing for the index CT scan (6.1%, χ2 6.71, P = 0.081), use of prophylactic antibiotics (44.2%, χ2 221.05, P 

  3. Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C, Heuton KR, et al.
    Lancet, 2014 Sep 13;384(9947):980-1004.
    PMID: 24797575 DOI: 10.1016/S0140-6736(14)60696-6
    BACKGROUND: The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.

    METHODS: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.

    FINDINGS: 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland.

    INTERPRETATION: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.

    FUNDING: Bill & Melinda Gates Foundation.

  4. Murray CJ, Ortblad KF, Guinovart C, Lim SS, Wolock TM, Roberts DA, et al.
    Lancet, 2014 Sep 13;384(9947):1005-70.
    PMID: 25059949 DOI: 10.1016/S0140-6736(14)60844-8
    BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.

    METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets.

    FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.

    INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.

    FUNDING: Bill & Melinda Gates Foundation.

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