Systematic Review of Signs and Symptoms Associated with Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy.

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication of the transplantation process that has been consistently associated with substantially greater morbidity and mortality compared with HSCT recipients who do not develop TMA. This study aimed to systematically review published signs and symptoms of HSCT-TMA and compare patients with HSCT-TMA and HSCT recipients who do not develop TMA. Publications were identified using multiple search term variations for stem cell transplantation that were entered into the PubMed, Embase, and CINAHL databases. Two reviewers screened references at the abstract level before reviewing full texts against inclusion and exclusion criteria using a PICOS-T framework. Complication proportions were grouped by organ class and then by complication type. Meta-analyses were conducted using a random-effects model in RevMan 5.4. After 2338 references were screened, a total of 30 studies were included in our analyses. The majority of studies (n = 23; 14 adult, 5 pediatric, 4 both) examined allogeneic transplantations only. Four studies examined autologous transplantation only (all pediatric), and 3 studies included both transplantation types (all pediatric). HSCT-TMA was associated with renal dysfunction (odds ratio [OR], 11.04 for adult, allogeneic and 7.35 for pediatric, all transplantations), renal failure (OR, 2.41 for adult and pediatric, allogeneic), renal replacement therapy (OR, 6.99 for pediatric, all transplantations and 60.85 for adult, allogeneic), and hypertension (OR, 5.44 for adult, allogeneic). HSCT-TMA was associated with respiratory failure (OR, 8.00 for adult and pediatric, allogeneic), pulmonary hypertension (OR, 9.86 for adult and pediatric, allogeneic), need for pleurocentesis (OR, 5.45 for pediatric, all transplantations), noninvasive ventilation (OR, 6.15 for pediatric, all transplantations), and invasive mechanical ventilation (OR, 5.18 for pediatric, all transplantations). Additionally, HSCT-TMA was associated with neurologic symptoms (OR, 2.28 for adult and pediatric, allogeneic), pericardial effusion (OR, 2.56 for adult and pediatric, allogeneic and 8.76 for pediatric, all transplantations), liver injury (OR, 3.87 for adult, allogeneic), infection (OR, 9.25 for adult, allogeneic; 2.06 for pediatric, all transplantations), gastrointestinal (GI) bleeding (OR, 7.78 for adult and pediatric, allogeneic), and acute graft-versus-host disease grade III-IV (OR, 3.29 for adult and pediatric, allogeneic). This study represents the first systematic review of HSCT-TMA signs and symptoms. Current diagnostic criteria systems involve laboratory markers for multiorgan dysfunction, including renal dysfunction, liver injury, and general tissue damage. Diagnostic criteria include neurologic symptoms, increased need for transfusions, and hypertension. This study identified additional associations with HSCT-TMA, including increased pulmonary hypertension, respiratory failure, fever, GI bleeding, and pericardial effusion. These symptoms might be included for evaluation in future diagnostic criteria and current practice.

Sex differential in methylation patterns of selected genes in Singapore Chinese.

To date there have been few reports of a gender difference in methylation levels of genes. When examining the methylation levels of four autosomal genes (ESR1, MTHFR, CALCA and MGMT) in the white blood cells of a random sample of Singapore Chinese Health Study cohort participants (n = 291), we encountered an unexpected gender differential. Using MethyLight technology, we calculated a gene-specific percentage of methylated reference (PMR) value, which quantified the relative level of gene methylation for each study subject (134 males and 157 females). Two summary methylation indices were constructed by assigning gene-specific rank scores. We then used ANCOVA to compare logarithmically transformed individual PMR values and summary methylation indices by age and gender simultaneously. Adjustment was made for plasma homocysteine. For ESR1, for which a large proportion of subjects were negative for methylation, we also used polytomous regression to compare methylation across age and gender. Increasing age and the male gender independently predicted increasing PMR values for CALCA and MGMT. For the MTHFR gene, male gender was associated with higher PMR values (P = 0.002), while age was not (P = 0.75). Neither age nor gender had any statistically significant influence on the PMR values for ESR1 (P = 0.13 and 0.96, respectively). Our data suggest that gender is at least as strong a predictor of methylation level in the four genes under study as age, with males showing higher PMRs.