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Women with type 1 diabetes (T1D) are thought to experience menopause earlier than women without diabetes, although not all studies agree. We assessed metabolic predictors of the age at which natural menopause occurs among women with T1D participating in the Epidemiology of Diabetes Complications study.

Women with childhood-onset (<17 y) of T1D who underwent natural menopause without use of hormone therapy during their menopausal transition were included in the analysis (n = 105; mean baseline age, 29.5 and diabetes duration, 20.2 y). Self-reported reproductive history and the Women's Ischemia Syndrome Evaluation hormonal algorithms were used to determine menopause status. Linear regression was used to ascertain whether time-weighted metabolic factors (eg, BMI, lipids, HbA1c, insulin dose, albumin excretion rate [AER]) were associated with age at natural menopause.

Univariately, only insulin dose (β = -4.87, P = 0.04) and log (AER) (β = -0.62, P = 0.02) were associated (negatively) with age at natural1D.Advancements in hematopoietic cell transplantation (HCT) have led to increased survivorship rates in many childhood diseases. However, this growing group of long-term survivors face a myriad of late effects. There are currently limited guidelines for surveillance of gastrointestinal polyps for pediatric transplant patients. Here we describe 5 patients undergoing HCT with total body irradiation-based conditioning regimens for leukemia who developed symptomatic polyps a median of 4.5 (range 0.75 to 5.75) years after HCT. Because of limited surveillance guidelines in children, we conclude that the development of new or progressive symptoms related to the gastrointestinal tract deserves prompt recognition and evaluation.

Roseola infantum is always considered to be among the differential diagnosis of young patients with fever and leukopenia whom to be strictly isolated with the preliminary diagnosis of COVID-19 until otherwise proven during the pandemic.

Human herpes virus-6 (HHV-6) polymerase chain reaction (PCR) blood test was performed in 4 of 7 patients with a clinical diagnosis of roseola infantum and all found to be HHV-6 PCR positive. The most striking laboratory finding in all patients was leukopenia. HHV-6 PCR tests were found to be positive. Severe acute respiratory syndrome coronavirus-2 testing were found to be negative in all patients.

During the peak of the pandemic, children continued to present with fever because of viral infections other than COVID-19.

During the peak of the pandemic, children continued to present with fever because of viral infections other than COVID-19.

Pathologic ejection fraction (EF), shortening fraction (FS), and standard heart failure biomarkers (high sensitive troponin T and N-terminal brain natriuretic peptide) during follow-up after childhood cancer have been associated with irreversible cardiac damage. We aimed to evaluate strain imaging values by echocardiography and new biomarkers for heart failure with preserved ejection fraction (HFpEF) as potential more sensitive parameters for cardiac deterioration in childhood cancer survivors (CCS).

Prospective study with 50 CCS (median 16.2 y) at a median follow-up of 13 years. In addition to standard echo and laboratory parameters for heart failure, strain measurements and new biomarkers, including myocardial inflammation (interleukin 6), extracellular matrix (ECM) remodeling (C-telopeptide for type I collagen, intact N-terminal propeptide of type III procollagen), and other heart failure biomarkers (galectin 3, solutable ST2, growth differentiation factor 15), were obtained and compared with 50 healthlaboratory parameters.

Strain imaging and new cardiac biomarkers used in HFpEF focusing on ECM remodeling appear to be more sensitive in detecting early remodeling processes in CCS than standard echo and laboratory parameters.The etiology and outcomes of posterior reversible encephalopathy syndrome (PRES) in children with cancer are not well understood. We aim to determine the incidence of PRES, describe associated morbidity and mortality, and better understand risk factors in this patient population. A total of 473 children with a hematologic malignancy or postallogeneic hematopoietic cell transplantation between June 2015 and June 2020 were screened for PRES to determine incidence and whether age or underlying diagnosis are associated with development of PRES. We conducted a case-control study to evaluate whether comorbidities or chemotherapeutic agents are associated with PRES. Children with PRES were matched with 2 controls based on age and underlying diagnosis to identify additional risk factors. Fourteen patients developed PRES, with an incidence of 5.9/1000 people/year. Those diagnosed with PRES had commonly described PRES symptoms hypertension, seizures, nausea/vomiting, altered mental status, and headaches. All patients received an magnetic resonance imaging, and most had findings consistent with PRES. Hematopoietic cell transplantation was associated with the development of PRES. The use of Etoposide was associated with PRES but comorbidities, steroids and calcineurin inhibitors were not. While PRES was infrequent in this population, it is associated with high morbidity and mortality, with ICU admissions and an overall hospital mortality, because of secondary causes, of 29%.

Allogeneic hematopoietic stem cell transplantation is a potential curative treatment in Wiskott-Aldrich syndrome (WAS). Here, we analyzed the outcomes in 4 WAS patients who underwent this procedure with peripheral blood stem cell (PBSC) in our center.

Four patients with severe WAS phenotype have received allogeneic hematopoietic stem cell transplantation between January 2014 and December 2019 from matched sibling donors with PBSC. Two different preparative conditioning regimens were provided the first associated busulfan-cyclophosphamide (2 patients) and the second with busulfan-fludarabine administered to the others. Cyclosporine gave as preferred graft-versus-host disease prophylaxis with a short course of methotrexate.

All patients achieved engraftment after PBSC with a median CD34+ cell count 13.6×106/kg (8 to 24.9×106/kg). Chronic graft-versus-host disease developed in 2 patients treated by cyclosporine-steroids with complete resolution. Chimerism for all the patients was fully donor (>95% donor). After a median follow-up of 41 months (8 to 74 mo), all patients (100%) are alive, healthy, with complete clinical, immunologic, and hematologic recovery, without signs of WAS.

This limited study with high-dose PBSC transplantation approach for WAS, demonstrated a safe and effective treatment option, with rapid engraftment, without complications, excellent long-term outcomes, independent of conditioning regimen.

This limited study with high-dose PBSC transplantation approach for WAS, demonstrated a safe and effective treatment option, with rapid engraftment, without complications, excellent long-term outcomes, independent of conditioning regimen.

Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction (LVEF) in patients with Takotsubo syndrome (TTS), recent studies have demonstrated a long-lasting functional impairment in those patients. The present study sought to evaluate the predictors of incomplete recovery following TTS and its impact on cardiovascular mortality.Methods and ResultsPatients with TTS between 2008 and 2018 were retrospectively enrolled at 3 different institutions. After exclusion of in-hospital deaths, 407 patients were split into 2 subgroups according to whether their LVEF was >50% (recovery group; n=341), or ≤50% (incomplete recovery group; n=66) at the chronic phase. Multivariate logistic regression analysis found that LVEF (odds ratio [OR] 0.94; 95% confidence interval [CI] 0.91-0.98; P<0.001) and C-reactive protein levels (OR 1.11; 95% CI 1.02-1.22; P=0.02) at discharge were independent predictors of incomplete recovery. At a median follow up of 52 days, a higher cardiovascular mortality was evident in the incomplete recovery group (16% vs. 0.6%; P<0.001).

This study demonstrated that incomplete recovery after TTS is characterized by residual systemic inflammation and an increased cardiac mortality at follow up. Altogether, the present study findings determined that patients with persistent inflammation are a high-risk subgroup, and should be targeted in future clinical trials with specific therapies to attenuate inflammation.

This study demonstrated that incomplete recovery after TTS is characterized by residual systemic inflammation and an increased cardiac mortality at follow up. Altogether, the present study findings determined that patients with persistent inflammation are a high-risk subgroup, and should be targeted in future clinical trials with specific therapies to attenuate inflammation.MicroRNA-221 (miRNA-221) is upregulated in several malignant tumors and is associated with poor patient prognosis. Therefore, the present study aimed to investigate the role and underlying mechanism of miRNA-221 in doxorubicin (DOX) resistance in osteosarcoma cells. We constructed DOX-resistant Saos-2/DOX cells and treated them with DOX. Cell viability was determined by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cells were transfected with either miRNA-221 mimic or miRNA-221 inhibitor; quantitative (q)RT-PCR was performed to detect the expression of miRNA-221. Flow cytometry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling (TUNEL) staining were used to detect cell apoptosis. The immunofluorescence method was also used to detect cell signal transduction and activator of transcription 3 (Stat3) protein expression distribution. FG-4592 in vitro In addition, Western blotting was used to detect changes in the expression of each protein. We found that miRNA-221 was upregulated in Saos-2/DOX cells. Moreover, the miRNA-221 mimic induced DOX resistance in Saos-2 cells, whereas the miRNA-221 inhibitor enhanced DOX sensitivity in Saos-2/DOX cells. The miRNA-221 mimic upregulated the expression of phosphorylated-Stat3, P-glycoprotein (P-gp), and B-cell lymphoma-2 (Bcl-2) proteins in Saos-2 cells and induced the entry of Stat3 into the nucleus, whereas the miRNA-221 inhibitor exerted the opposite effect. Pretreatment with the Stat3 chemical inhibitor, STAT3-IN-3, significantly inhibited the upregulation of P-gp and Bcl-2 protein expression induced by the miRNA-221 mimic in Saos-2 cells; it also caused the Saos-2 cells to overcome DOX resistance induced by the miRNA-221 mimic. Thus, miRNA-221 increased the expression of P-gp and Bcl-2 by activating the Stat3 pathway to promote DOX resistance in osteosarcoma cells, indicating a potential use of miRNA-221 in osteosarcoma treatment.Elderly patients with dementia suffer from cognitive dysfunctions and neuropsychiatric symptoms (NPS) such as anxiety and depression. Alzheimer's disease (AD) is a form of age-related dementia, and loss of cholinergic neurons is intimately associated with development of AD symptoms. We and others have reported that neural cell transplantation ameliorated cognitive dysfunction in AD model mice. It remains largely unclear whether neural cell transplantation ameliorates the NPS of AD. It would be interesting to determine whether NPS correlates with cognitive dysfunctions before and after neural cell transplantation in AD model mice. Based on the revalidation of our previous data from a Morris water maze test, we found that neural cell transplantation improved anxiety and depression significantly and marginally affected locomotion activity in AD mice. A correlation analysis revealed that the spatial learning function of AD mice was correlated with their NPS scores both before and after cell transplantation in a similar manner.