Clinicopathological implications of immunohistochemical expression of TBX21, CXCR3, GATA3, CCR4, and TCF1 in nodal follicular helper T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified.

BACKGROUND: The classification of nodal peripheral T-cell lymphoma (PTCL) has evolved according to histology, cell-of-origin, and genetic alterations. However, the comprehensive expression pattern of follicular helper T-cell (Tfh) markers, T-cell factor-1 (TCF1), and Th1- and Th2-like molecules in nodal PTCL is unclear. METHODS: Eighty-two cases of nodal PTCL were classified into 53 angioimmunoblastic T-cell lymphomas (AITLs)/nodal T-follicular helper cell lymphoma (nTFHL)-AI, 18 PTCLs-Tfh/nTFHL-not otherwise specified (NOS), and 11 PTCLs-NOS according to the revised 4th/5th World Health Organization classifications. Immunohistochemistry for TCF1, TBX21, CXCR3, GATA3, and CCR4 was performed. RESULTS: TCF1 was highly expressed in up to 68% of patients with nTFHL but also in 44% of patients with PTCL-NOS (p > .05). CXCR3 expression was higher in AITLs than in non-AITLs (p = .035), whereas GATA3 expression was higher in non-AITL than in AITL (p = .007) and in PTCL-Tfh compared to AITL (p = .010). Of the cases, 70% of AITL, 44% of PTCLTfh/ nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the TBX21 subtype; and 15% of AITL, 38% of PTCL-Tfh/nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the GATA3 subtype. The others were an unclassified subtype. CCR4 expression was associated with poor progression-free survival (PFS) in patients with PTCL-Tfh (p < .001) and nTFHL (p = .023). The GATA3 subtype showed poor overall survival in PTCL-NOS compared to TBX21 (p = .046) and tended to be associated with poor PFS in patients with non-AITL (p = .054). CONCLUSIONS: The TBX21 subtype was more prevalent than the GATA3 subtype in AITL. The GATA3 subtype was associated with poor prognosis in patients with non-AITL and PTCL-NOS.

Discrepancies in Hormone Receptor and HER2 Expression between Malignant Serous Effusions and Paired Tissues from Primary or Recurrent Breast Cancers.

OBJECTIVES: Immunohistochemistry (IHC) for the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) biomarkers has prognostic and therapeutic value in breast cancer, while it facilitates molecular subtyping. This study aimed to identify subtype discordance and its clinical significance among different phases of breast cancer evolution, focusing on effusion cytology samples diagnosed with malignancy. METHODS: Our electronic archive was searched for all effusion cases diagnosed as breast carcinomas within a pre-defined period (January 2018-October 2021), and their cell blocks (CBs) were subjected to ER, PR, and HER2 IHC or in situ hybridization. Furthermore, information regarding the same biomarkers from previously obtained tissue specimens of these patients was extracted. RESULTS: Only 2/76 (2.6%) of the breast cancer patients analyzed showed a malignant effusion at their initial presentation. The triple negative breast cancer (TNBC) phenotype was found significantly more often at effusion CBs, compared to their paired biopsies received during initial diagnosis (30/70 vs 16/70; p<0.001). In addition, the presence of TNBC subtype was significantly associated with an earlier development of a malignant effusion, more specifically at initial diagnosis (P<0.001; log-rank test), at first recurrence/metastasis (either solid or effusion) (P=0.012; log-rank test), at effusion (P=0.007; log-rank test), and at any tumor evolution phase (P=0.009; log-rank test). CONCLUSION: Serous effusion cytology provides high-quality material for ancillary techniques, especially when CBs are prepared, reflecting cancer heterogeneity.

Prognostic Impact of the Immunoscore Based on Whole-Slide Image Analysis of CD3+ Tumor-Infiltrating Lymphocytes in Diffuse Large B-Cell Lymphoma.

An Immunoscore based on tumor-infiltrating T-cell density was validated as a prognostic factor in patients with solid tumors. However, the potential utility of the Immunoscore in predicting the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) is unclear. Here, the prognostic value of an Immunoscore based on tumor-infiltrating CD3+ T-cell density was evaluated in 104 patients with DLBCL who underwent R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy. Digitally scanned whole-slide images were analyzed using Aperio ImageScope software. CD3+ cell densities in the whole tumor area were quantitated using 3 different methods, including number of CD3+ cells/area (mm2), ratio of CD3+ cells to total cells, and ratio of CD3+ cells to CD20+ cells. There was a high concordance among the 3 methods. Patients with low CD3+ cell density had an elevated serum lactate dehydrogenase level and a high Ki-67 proliferation index (all, P < .05). Patients with low CD3+ cell density, according to all 3 methods, had worse overall survival (OS) and worse progression-free survival (P < .05, all). They also had poor OS, independent of MYC/BCL2 double expression (DE) status, Eastern Cooperative Oncology Group performance status, or Ann Arbor stage (all, P < .05). These results were validated using 2 publicly available data sets. In both validation cohorts, patients with low CD3E mRNA expression had an elevated serum lactate dehydrogenase level, extranodal site involvement, and DE status (P < .05). They also had worse progression-free survival (P = .067 and P = .002, respectively) and OS (both P < .05). A low CD3E mRNA level was predictive of poor OS, independent of DE status. An Immunoscore based on whole-slide image analysis of CD3+ T-cell infiltration was sufficient to predict survival in patients with DLBCL. Low CD3+ cell density was a poor prognostic factor, independent of other prognostic parameters and DE status.

Declining life expectancy in the Great Lakes region: contributors to Black and white longevity change across educational attainment.

BACKGROUND: The East North Central Census division (aka the Great Lakes region) experienced a decrease in life expectancy of 0.3 years from 2014 to 2016 - one of the largest declines across the nine Census divisions. Disadvantaged groups that typically have below-average life expectancy, including Black individuals and those without a college education, may have been disproportionately affected by this longevity shift. This investigation examines life expectancy changes among different sex, race, and education groups in the Great Lakes region, and how specific causes of death contributed to within-group longevity changes over time and across age. METHODS: We used 2008 to 2017 death counts from the National Center for Health Statistics and American Community Survey population estimates to measure within-group change in life expectancy at age 25 among non-Hispanic Black and white males and females by educational attainment. We decomposed life expectancy change over time for each subgroup by 24 causes of death and measured their contribution to longevity change across 13 age groups. RESULTS: Among persons with ≤ 12 years of education, white males and females experienced 1.3- and 1.7-year longevity declines respectively, compared to a 0.6-year decline among Black males and a 0.3-year decline among Black females. Life expectancy declined among all groups with 13-15 years of education, but especially Black females, who experienced a 2.2-year loss. With the exception of Black males, all groups with 16 + years of education experienced longevity gains. Homicide contributed 0.34 years to longevity decline among Black males with ≤ 12 years of education. Drug poisoning made large contributions to longevity losses among Black females with ≤ 12 years of education (0.31 years), white males and females with 13-15 years of education (0.35 and 0.21 years, respectively), and white males and females with ≤ 12 years of education (0.92 and 0.65 years, respectively). CONCLUSIONS: Public health efforts to reduce the risks of homicide among Black males without a college education and drug poisoning among all groups could improve life expectancy and reduce racial and educational longevity disparities in the Great Lakes region.

Case report: Focal segmental glomerulosclerosis in a pediatric atypical progeroid syndrome.

Atypical progeroid syndrome (APS) is a rare type of progeroid syndrome mainly caused by heterozygous missense mutations in the LMNA (MIM 150330) gene. APS has heterogeneous clinical manifestations, and its kidney manifestations, particularly in children, are rarely documented. Here, we report the first pediatric case of APS with focal segmental glomerulosclerosis (FSGS). A 10-year-old boy with progeroid features was referred to the nephrology clinic because of hyperuricemia. He had dark skin, protruding eyes, and beaked nose and was very thin, suggesting lipodystrophy. He had been treated for recurrent urinary tract infection during infancy, and liver biopsy for persisting hepatitis showed steatohepatitis. He also had hypertrophic cardiomyopathy (HCMP) with mitral and tricuspid valve regurgitation. Genetic studies were performed considering his multisystem symptoms, and he was diagnosed as having APS according to exome sequencing findings (c.898G > C, p.Asp300His of LMNA). During the first visit to the nephrology clinic, he had minimal proteinuria (urine protein/creatinine ratio of 0.23 mg/mg), which worsened during follow-up. In three years, his urine protein/creatinine ratio and N-acetyl-b-D-glucosaminidase/creatinine ratio increased to 1.52 and 18.7, respectively. The kidney biopsy result was consistent with findings of FSGS, peri-hilar type, showing segmental sclerosis of 1 (5%) glomerulus out of 21 glomeruli. An angiotensin receptor blocker was added to manage his proteinuria. This is the first pediatric report of FSGS in an APS patient with confirmed LMNA defect, who manifested progeroid features, lipodystrophy, HCMP with heart valve dysfunction, and steatohepatitis. Our case suggests that screening for proteinuric nephropathy is essential for managing APS patients since childhood.

TCF1+PD-1+ tumour-infiltrating lymphocytes predict a favorable response and prolonged survival after immune checkpoint inhibitor therapy for non-small-cell lung cancer.

BACKGROUND: T-cell factor 1 (TCF1)+Programmed cell death-1 (PD-1)+ tumour-infiltrating lymphocytes (TILs) are a recently defined subset of exhausted T-cells (Texh-cells) that exhibit a progenitor phenotype. They have been associated with a response to immune checkpoint inhibitor (ICI) therapy in murine tumour models and in patients with malignant melanoma. We investigated the significance of TCF1+PD-1+ TILs as a predictive biomarker for ICI therapy response in non-small-cell lung cancer (NSCLC). METHODS: Two different cohorts of NSCLC patients treated with ICI targeting the PD-1/PD-L1 pathway were included. RNA-seq was performed using NSCLC tissues obtained from 234 patients prior to immunotherapy (RNA-seq cohort). Double immunostaining of TCF1 and PD-1 and single immunostaining of other immunologic markers were performed in resected tumour tissues from another 116 patients (immunohistochemistry cohort). RESULTS: In the RNA-seq cohort, both Texh-cell and progenitor Texh-cell gene sets were enriched in responders compared with non-responders. Larger Texh-cell fractions and increased progenitor Texh-cell gene sets were significantly associated with better progression-free survival (PFS). In the immunohistochemistry cohort, the TCF1+PD-1+ TIL number and PD-L1 tumour proportion score were significantly higher in responders than in non-responders. A high number of TCF1+PD-1+ TILs was significantly associated with both PFS and overall survival (OS) after ICI therapy, and it independently predicted a better PFS and OS according to multivariate analysis. CONCLUSION: TCF1+PD-1+ TILs, representing progenitor Texh-cells, predict both better response and survival in NSCLC patients after ICI therapy. Thus, they may be a useful predictive biomarker for ICI therapy in NSCLC.

Pediatric-Type Indolent B-Cell Lymphomas With Overlapping Clinical, Pathologic, and Genetic Features.

Pediatric-type follicular lymphoma (PTFL) and pediatric nodal marginal zone lymphoma (PNMZL) are rare pediatric-type indolent B-cell lymphomas (PedIBCL) that differ clinicopathologically from their adult counterparts. Accurate diagnosis is important to avoid overtreatment but is often challenging. The mutational landscape of PTFL is known and may aid diagnosis, but the genetic features of PNMZL are not well understood. We analyzed 21 cases of PedIBCL according to their clinicopathologic findings and classified them into PTFL (n=11), PNMZL (n=2), and "mixed type" tumors (n=8) showing ambiguous histology. We also analyzed 2 cases of adult B-cell lymphomas showing features of PedIBCL. Targeted sequencing of 121 lymphoma-related genes was performed. The median age of PedIBCL patients was 16 years (range: 3 to 47), and all but 1 PTFL patient were male. All patients presented with limited-stage disease, and only 1 relapsed. There were no significant differences in clinical features among the 3 PedIBCL groups. The most frequently mutated genes were MAP2K1 , TNFRSF14 , KMT2C , IRF8 , and NOTCH2 . The genetic features of all groups were similar to the established mutational landscape of PTFL. The 2 adult B-cell lymphomas cases also had MAP2K1 , TNFRSF14 , and IRF8 mutations, but the clinical features were not typical of PedIBCL. In summary, this study demonstrated that PTFL and PNMZL are similar diseases with overlapping clinical, pathologic, and genetic features; mixed type tumors can also occur. Atypical adult cases with similar histologic features were also observed. Therefore, the disease spectrum of PedIBCL may be much broader than is currently believed.

Socioeconomic differentials in fertility in South Korea.

BACKGROUND: South Korea has one of the lowest fertility rates in the world, reaching a record low of 0.98 in 2018. Understanding socioeconomic differentials in fertility in South Korea has become an important social and policy issue. OBJECTIVE: This study examines socioeconomic differentials in first and second childbirths among married women using various indicators of socioeconomic status at the individual and household level. METHODS: Using the Korean Labor and Income Panel Study (1998-2017), discrete-time hazard models are used to evaluate the relationships between multiple indicators of socioeconomic status and the transition to first and second births. RESULTS: Higher socioeconomic status (e.g., husband's college education and standard employment, homeownership) is conducive to a transition to parenthood and second births. However, the wife's employment - standard employment in particular - is negatively associated with both first and second childbirth. Among the indicators of socioeconomic resources, stable housing arrangements and the husband's employment security appear to be the most important factors for a married couple's fertility decisions. CONCLUSIONS: Socioeconomically disadvantaged married couples tend to delay their transition to parenthood. In addition, those with high SES are more likely than their counterparts with low SES to have second births. If these patterns persist, they have important implications for the demographic process and social stratification. CONTRIBUTION: The findings of this study contribute to a comprehensive understanding of socioeconomic differentials in fertility in South Korea and therefore have important policy implications. These findings will also prove useful to other societies with very low fertility rates.

Black-white disparities in 2009 H1N1 vaccination among adults in the United States: A cautionary tale for the COVID-19 pandemic.

BACKGROUND: Prior research has highlighted racial and ethnic disparities in H1N1 vaccination in the United States. Our study adds to this literature by utilizing an intersectionality framework to examine the joint influence of race and sex on H1N1 vaccination beliefs and behaviors among non-Hispanic blacks and non-Hispanic whites (hereafter blacks and whites). METHODS: Using data from the National H1N1 Flu Survey of U.S. adults, we measured differences in beliefs about the safety and efficacy of the H1N1 vaccine among black women, black men, white women, and white men. We then estimated a series of nested logistic regression models to examine how race/sex vaccination disparities were influenced by health beliefs, socioeconomic status (SES), pre-existing conditions, and healthcare. RESULTS: Black respondents were more likely than white respondents to express reservations about the safety and efficacy of the H1N1 vaccine. Consistent with those beliefs, white females reported the highest rate of H1N1 vaccination (28.4%), followed by white males (26.3%), black males (21.6%), and black females (17.5%). Differences in health beliefs, SES, pre-existing conditions, and healthcare explained lower odds of H1N1 vaccination among white men and black men, relative to white women. However, black women experienced 35-45% lower odds of vaccination than white women across all models, highlighting the intersectional nature of these associations. DISCUSSION: The 2009 H1N1 influenza pandemic provides a cautionary tale about the distribution of new vaccines across large populations with diverse racial, sex, and socioeconomic characteristics. Despite differences between the H1N1 and COVID-19 pandemics, our study warns that many black Americans will forego COVID-19 vaccines unless swift action is taken to address black-white disparities in access to vital resources. Public health stakeholders can also encourage widespread adoption of COVID-19 vaccines by tailoring health promotion messages for different groups of racial minorities, especially groups like black women who face intersecting disadvantages.

Contributors to the black-white life expectancy gap in Washington D.C.

Although the black-white gap in life expectancy has been shrinking in the U.S., national improvement conceals ongoing disparities. Nowhere is this more evident than Washington D.C., where the black-white gap has persistently exceeded 10 years. Using 1999-2017 mortality data from the National Center for Health Statistics, we employed demographic techniques to pursue three aims: first, we created period life tables to examine longevity trends in Washington D.C.; second, we decomposed black-white life expectancy differences into 23 causes of death in three time periods (2000, 2008, 2016); third, we assessed age-specific contributions for each cause of death. Findings revealed that heart disease (4.14 years), homicide (2.43 years), and cancer (2.30 years) contributed most to the 17.23-year gap among males in 2016. Heart disease and cancer contributed most at ages 55-69; homicide contributed most at ages 20-29. Among females in 2016, heart disease (3.24 years), cancer (2.36 years), and unintentional injuries (0.85 years) contributed most to the 12.06-year gap. Heart disease and cancer contributed most at ages 55-69, and unintentional injuries at ages 50-59. Our investigation provides detailed evidence about contributors to the black-white longevity gap in Washington D.C., which can aid in the development of targeted public health interventions.

A Novel T Cell-Engaging Bispecific Antibody for Treating Mesothelin-Positive Solid Tumors.

As mesothelin is overexpressed in various types of cancer, it is an attractive target for therapeutic antibodies. T-cell bispecific antibodies bind to target cells and engage T cells via binding to CD3, resulting in target cell killing by T-cell activation. However, the affinity of the CD3-binding arm may influence CD3-mediated plasma clearance or antibody trapping in T-cell-containing tissues. This may then affect the biodistribution of bispecific antibodies. In this study, we used scFab and knob-into-hole technologies to construct novel IgG-based 1 + 1 MG1122-A and 2 + 1 MG1122-B bispecific antibodies against mesothelin and CD3ε. MG1122-B was designed to be bivalent to mesothelin and monovalent to CD3ε, using a 2 + 1 head-to-tail format. Activities of the two antibodies were evaluated in mesothelin-positive tumor cells in vitro and xenograft models in vivo. Although both antibodies exhibited target cell killing efficacy and produced regression of xenograft tumors with CD8+ T-cell infiltration, the antitumor efficacy of MG1122-B was significantly higher. MG1122-B may improve tumor targeting because of its bivalency for tumor antigen. It may also reduce systemic toxicity by limiting the activation of circulating T cells. Thus, MG1122-B may be useful for treating mesothelin-positive solid tumors.

Invariant NKT cells facilitate cytotoxic T-cell activation via direct recognition of CD1d on T cells.

Invariant natural killer T (iNKT) cells are a major subset of NKT cells that recognize foreign and endogenous lipid antigens presented by CD1d. Although iNKT cells are characteristically autoreactive to self-antigens, the role of iNKT cells in the regulation of cytotoxic T lymphocytes (CTL) has been elucidated using α-galactosylceramide (α-GalCer), a strong synthetic glycolipid that is presented by professional antigen presenting cells (APCs), such as dendritic cells. Despite the well-known effects of α-GalCer and dendritic cells on lipid antigen presentation, the physiological role of endogenous antigens presented by CTLs during crosstalk with iNKT cells has not yet been addressed. In this study, we found that antigen-primed CTLs with transient CD1d upregulation could present lipid self-antigens to activate the iNKT cell production of IFN-γ. CTL-mediated iNKT cell activation in turn enhanced IFN-γ production and the proliferation and cytotoxicity of CTLs. We also found that the direct interaction of iNKT cells and CTLs enhanced the antitumor immune responses of CTLs. This partially explains the functional role of iNKT cells in CTL-mediated antitumor immunity. Our findings suggest that in the absence of exogenous iNKT cell ligands, iNKT cells enhanced the CTL production of IFN-γ and CTL proliferation and cytotoxicity via direct interaction with CD1d expressed on T cells without interacting with APCs.

Contributors to Wisconsin's persistent black-white gap in life expectancy.

BACKGROUND: Although the black-white gap in life expectancy has narrowed in the U.S., there is considerable variability across states. In Wisconsin, the black-white gap exceeds 6 years, well above the national average. Reducing this disparity is an urgent public health priority, but there is limited understanding of what contributes to Wisconsin's racial gap in longevity. Our investigation identifies causes of death that contribute most to Wisconsin's black-white gap in life expectancy among males and females, and highlights specific ages where each cause of death contributes most to the gap. METHODS: Our study employs 1999-2016 restricted-use mortality data provided by the National Center for Health Statistics. After generating race- and sex-specific life tables for each 3-year period of observation (e.g., 1999-2001), we trace recent trends in the black-white life expectancy gap in Wisconsin. We subsequently conduct a series of analyses to decompose the black-white gap in three time periods into 13 separate causes and 19 different age groups. RESULTS: In 2014-16, Wisconsin's black-white gap in life expectancy was 7.34 years for males (67% larger than the national gap), and 5.61 years for females (115% larger than the national gap). Among males, homicide was the single largest contributor, accounting for 1.56 years of the total gap. Heart disease and cancer followed, contributing 1.43 and 1.42 years, respectively. Among females, heart disease and cancer were the two leading contributors to the gap, accounting for 1.12 and 1.00 years, respectively. Whereas homicide contributed most to the racial gap in male longevity during late adolescence and early adulthood, heart disease and cancer exerted most of their influence between ages 50-70 for both males and females. Other notable contributors were unintentional injuries (males), diabetes and cerebrovascular disease (females), and perinatal conditions (males and females). CONCLUSIONS: Our study identifies targets for future policy interventions that could substantially reduce Wisconsin's racial gap in life expectancy. Concerted efforts to eliminate racial disparities in perinatal mortality and homicide early in the life course, and chronic conditions such as cancer and heart disease in later life, promise to help Wisconsin achieve the public health objective of racial parity in longevity.

Marriage and Women's Health in Japan.

In this study, we evaluate alternative hypotheses about the potentially harmful or beneficial effects of marriage on women's health and examine the factors underlying observed relationships between marriage and health. Using data from the Japanese Panel Survey of Consumers, an annual survey of a nationally representative sample of Japanese women (N = 1,610), our study advances current scholarship on marriage and health by focusing on a context characterized by a high degree of gender inequality. Results from models employing different approaches to the potential role of health-related selection into marriage consistently indicate that marriage is associated with better mental and physical health and that the lower levels of employment among married women play an important role in explaining this relationship. Our findings highlight the importance of considering how the specific pathways linking marriage and health may vary across societies with different gender and institutional contexts.

Educational differences in early childbearing: A cross-national comparative study.

BACKGROUND: Recent research on fertility in industrialized countries focuses primarily on delayed childbearing, despite the facts that large numbers of women continue to enter parenthood at relatively young ages and that early childbearing has been linked to economic disadvantage. OBJECTIVE: This cross-national comparative study describes relationships between women's educational attainment and young age at first birth and evaluates the extent to which these differences have changed over time for women born 1955-1981. METHODS: Defining 'early' childbearing as the age by which 20% of first births have occurred to women in a given birth cohort and country, we describe differences in early childbearing by educational attainment across three cohorts of women in 20 countries. RESULTS: We find a strong negative educational gradient in early childbearing across all 20 countries and some evidence of an increase in the relative prevalence of early childbearing among the least-educated women. In 10 countries, the relative prevalence of early childbearing among women with low education is significantly higher for one or both of the more recent birth cohorts compared to the earliest cohort. However, many countries show no significant change, and in one country (Poland) there is modest evidence of a decreasing educational gap. CONCLUSIONS: Evidence that educational differences in early childbearing have grown in some countries is generally consistent with the notion of family bifurcation and 'diverging destinies' by socioeconomic status. However, the pattern is not universal and future work should examine the various factors that shape these patterns, including the role of public policies.

Nonstandard Work and Educational Differentials in Married Women's Employment in Japan: Patterns of Continuity and Change.

The rapid expansion of nonstandard work has altered the nature of women's employment, but previous research on married women's employment trajectories in japan has paid little attention to the role of nonstandard work. to fill this gap, we examine how patterns of employment in regular and nonstandard positions vary by married women's socioeconomic status using nationally representative longitudinal data. results from discrete-time competing risks models of labor force transitions indicate that university graduates have the most stable labor force attachment in that they are the least likely to move from standard to nonstandard employment and to exit nonstandard jobs. in contrast, married women with a high school degree or less are more likely to reenter the labor force to take low-quality nonstandard jobs. these results are consistent with a scenario characterized by both continuity and change. older patterns of labor force exit and reentry, combined with the rise in nonstandard employment, are most relevant for less educated women while the emergence of more career employment opportunities is most relevant for highly educated women. considering the role of women's income in shaping patterns of inequality, these findings have important implications for stratification in japan.

Infant mortality in Kyrgyzstan before and after the break-up of the Soviet Union.

There is a great deal of uncertainty over the levels of, and trends in, infant mortality in the former Soviet republics of Central Asia. As a result, the impact of the break-up of the Soviet Union on infant mortality in the region is not known, and proper monitoring of mortality levels is impaired. In this paper, a variety of data sources and methods are used to assess levels of infant mortality and their trend over time in one Central Asian republic, Kyrgyzstan, between 1980 and 2010. An abrupt halt to an already established decline in infant mortality was observed to occur during the decade following the break-up of the Soviet Union, contradicting the official statistics based on vital registration. Infants of Central Asian ethnicity and those born in rural areas were also considerably more at risk of mortality than suggested by the official sources. We discuss the implications of these findings, both for health policy in this seldom studied part of the former Soviet Union and for our understanding of the health crisis which it currently faces.