Haploidentical transplantation in high-risk pediatric leukemia: A retrospective comparative analysis on behalf of the Spanish working Group for bone marrow transplantation in children (GETMON) and the Spanish Grupo for hematopoietic transplantation (GETH)

A total of 192 pediatric patients, median age 8.6 years, with high-risk hematological malignancies, underwent haploidentical stem cell transplantation (haplo-HSCT) using post-transplantation cyclophosphamide (PT-Cy), or ex vivo T cell-depleted (TCD) graft platforms, from January 1999 to December 2016 in 10 centers in Spain. Some 41 patients received an unmanipulated graft followed by PT-Cy for graft-vs-host disease (GvHD) prophylaxis. A total of 151 patients were transplanted with CD3-depleted peripheral blood stem cells (PBSCs) by either CD34⁺ selection, CD3⁺CD19⁺ depletion, TCRαβ⁺CD19⁺ depletion or CD45RA⁺ depletion, added to CD34⁺ selection for GvHD prophylaxis. The PBSCs were the only source in patients following ex vivo TCD haplo-HSCT; bone marrow was the source in 9 of 41 patients following PT-CY haplo-HSCT. Engraftment was achieved in 91.3% of cases. A donor younger than 30 years, and the development of chronic GvHD were positive factors influencing survival, whereas positive minimal residual disease (MRD) before transplant and lymphoid disease were negative factors. The probability of relapse increased with lymphoid malignancies, a donor killer-cell immunoglobulin-like receptor (KIR) haplotype A and positive MRD pretransplant. No difference was found in overall survival, disease-free survival or relapse incidence between the two platforms. Relapse is still of concern in both platforms, and it should be the focus of future efforts. In conclusion, both platforms for haplo-HSCT were effective and could be utilized depending on the comfort level of the center.     

Incidence and consequences of systemic arterial thrombotic events in COVID-19 patients

Journal of Thrombosis and Thrombolysis - A high incidence of thrombotic events, particularly deep vein thrombosis and pulmonary embolism, has been clearly documented in COVID-19 patients. In...     

Neuropsychiatric symptoms in Alzheimer's disease are related to functional connectivity alterations in the salience network

Neuropsychiatric syndromes are highly prevalent in Alzheimer's disease (AD), but their neurobiology is not completely understood. New methods in functional magnetic resonance imaging, such as intrinsic functional connectivity or “resting‐state” analysis, may help to clarify this issue. Using such approaches, alterations in the default‐mode and salience networks (SNs) have been described in Alzheimer's, although their relationship with specific symptoms remains unclear. We therefore carried out resting‐state functional connectivity analysis with 20 patients with mild to moderate AD, and correlated their scores on neuropsychiatric inventory syndromes (apathy, hyperactivity, affective syndrome, and psychosis) with maps of connectivity in the default mode network and SN. In addition, we compared network connectivity in these patients with that in 17 healthy elderly control subjects. All analyses were controlled for gray matter density and other potential confounds. Alzheimer's patients showed increased functional connectivity within the SN compared with controls (right anterior cingulate cortex and left medial frontal gyrus), along with reduced functional connectivity in the default‐mode network (bilateral precuneus). A correlation between increased connectivity in anterior cingulate cortex and right insula areas of the SN and hyperactivity syndrome (agitation, irritability, aberrant motor behavior, euphoria, and disinhibition) was found. These findings demonstrate an association between specific network changes in AD and particular neuropsychiatric symptom types. This underlines the potential clinical significance of resting state alterations in future diagnosis and therapy. Hum Brain Mapp 35:1237–1246, 2014. © 2013 Wiley Periodicals, Inc.     

Diagnosis and treatment of latent tuberculosis infection in liver transplant recipients in an endemic area

BACKGROUND: Treatment of latent tuberculosis infection (LTBI) with isoniazid is recommended for transplant recipients with positive tuberculin skin test (TST). However, TST could be an imperfect identifier of LTBI in this population. In addition, the risk of isoniazid hepatotoxicity could be high in liver transplant recipients (LTR). A retrospective cohort study was performed to evaluate the diagnosis and treatment of LTBI in LTR. METHODS: Charts of all 547 patients who received primary liver transplantation at a University Hospital in Spain between 1988 and 1998 were reviewed. RESULTS: TST was performed in 373 patients (71%) before transplantation. The result was positive in 89 (24%). The median follow-up after transplantation was 49 months. None of the TST-positive patients developed tuberculosis (TB), but 5 out of 284 patients with negative TST (1.76%) had active TB (P=0.6). Twenty-three patients received isoniazid as treatment of LTBI according to the decision of the attending physician. None of these patients developed TB, but 4 of them (17%) presented isoniazid hepatotoxicity. Among patients who did not receive isoniazid, 2 out of 21 (9.52%) with radiologic previous TB developed active TB versus 0.44% (2/452) among the remaining patients (relative risk [RR], 27.8, 95% CI, 3.2-147). CONCLUSIONS: Treatment of LTBI with isoniazid can not be recommended to LTR on the basis of a positive TST because it is an imperfect identifier of patients at risk of TB. LTR with radiologic features of previous TB are at higher risk of posttransplant active TB. Isoniazid-related hepatotoxicity is more frequent among LTR than in the general population.     

Endogenous testosterone density is an independent predictor of pelvic lymph node invasion in high-risk prostate cancer: results in 201 consecutive patients treated with radical prostatectomy and extended pelvic lymph node dissection

International Urology and Nephrology - To evaluate the influence of endogenous testosterone density (ETD) on pelvic lymph node invasion (PLNI) in high risk (HR) prostate cancer (PCa) treated with...