Notes

Defeating Radiation treatment Resistance throughout SCLC.
Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication of autologous stem cell transplant (ASCT) in children with historically high mortality rates. Defibrotide has shown proven benefit in its treatment and may have a modest role in prevention. We report our experience with SOS in children undergoing autologous transplant.

Case records of 82 consecutive patients undergoing ASCT following high-dose chemotherapy between 2010 and 2017 were reviewed. Defibrotide was used for treatment of all with SOS and prophylactically in patients receiving busulfan-based conditioning until 2014.

Fourteen of the 82 children (17%) were diagnosed with SOS. The incidence was higher in those receiving busulfan-based conditioning (13/42vs 1/40, P=0.008). Mean (±SD) time to diagnosis of SOS was 19 (±5.6) days following stem cell rescue. Bilirubin levels and ultrasound were normal in 7/14 and 3/14 patients. Coagulopathy was noted in 10/14; one child developed multiorgan involvement. Nine children had mild SOS, wibrotide.
Percutaneous mitral valve repair (PMVR), such as MitraClip, is performed on high-risk patients and involves hemodynamic alternations that may cause acute kidney injury (AKI). We aimed to evaluate the incidence of AKI, predictors for developing AKI and the correlation with mortality after MitraClip.

We performed a retrospective analysis of collected data from patients who underwent PMVR in two tertiary medical centers in Israel to identify factors associated with AKI.

The study population included 163 patients. The median age was 77 years; 60.7% of patients were male. The median eGFR significantly decreased post-procedure from 49 (35-72) to 47.8 (31-65.5) ml/min/1.73 m
(p < .001). Forty-seven patients (29%) developed AKI. None of the patients who developed AKI required hemodialysis. Predictors of AKI included baseline eGFR ≤30 ml/min/1.73 m
, severity of residual MR, TMPG>5 mmHg, diuretic use, and re-do procedures. Among the patients who developed AKI there was an improvement in kidney function during follow-up, and creatinine levels significantly decreased from a peak mean creatinine of 179.5 (143-252) mmol/l to 136 (92-174) mmol/l (p < .001). However, 19% (9 out of 47) of patients experienced partial recovery and their creatinine level, when compared to their baseline, remained elevated. One-year survival showed a trend for increased mortality among patients who developed AKI (86.2% vs. 80.9%, p = .4), and patients who developed AKI that persisted had increased 1-year mortality compared with patients that had recovered their kidney function (86.8% vs. 55.6%, p = .01).

The incidence of AKI after MitraClip is high. AKI is reversible in most patients; however, the persistence of kidney injury is associated with increased 1-year mortality.
The incidence of AKI after MitraClip is high. AKI is reversible in most patients; however, the persistence of kidney injury is associated with increased 1-year mortality.Realizing the promise of precision medicine will require breaking down communication barriers between genomic, screening and literature "big data." We discuss the opportunities and challenges of reconciling data science approaches with the scientific method and the critical role of chemical biologists as a bridge between data and mechanism. Finally we propose next steps on the road to precision medicine and give examples of new tools designed to catalyze these steps.Refractory B cell responses to T cell-independent (TI) carbohydrate antigens (Ags) are critical drivers of rejection reactions to ABO-incompatible allogeneic grafts and xenogeneic grafts from other species. To explore the biological significance of crosstalk between Toll-like receptors (TLRs) and B cell receptors (BCRs) in the TI B cell immunity, we here used MyD88-, TRIF-, and α-galactosyltransferase-deficient mice to study B cell phenotypes and functional properties during TI transplant-related glycan Ag exposure. BCR stimulation alone induced differentiation into CD5high (B-1a) cells, which were highly sensitive to a calcineurin inhibitor (CNI), while co-stimulation of TLRs and BCRs induced differentiation into CD5dim (B-1b) cells in MyD88-dependent and CNI-resistant manner. MyD88-dependent TLR stimulation in B-1b cells enhanced downstream factors in the BCR-calcineurin pathway, including a nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). TLR inhibitor together with CNI abrogated refractory B-1b cell immune responses against the ABO-blood group Ags, while blocking both BCRs and TLR-MyD88 by using Bruton's tyrosine kinase inhibitor and histone deacetylase inhibitor abrogated refractory B-1b cell immune responses against Gal-glycan Ags. Thus, this study provides a rationale for a novel therapeutic approach to overcome refractory transplant-related anti-glycan Ab production by blocking both BCR and TLR-MyD88 signals.Electrocatalytic energy conversion is one of the most promising pathways to develop clean and renewable energy technologies, and the development of high-performance electrocatalysts to improve the energy conversion efficiency is of paramount importance. Metal nanocrystals with twin defects possess unique features, including lattice strain and high density of low-coordinated atoms at the twin boundary, endowing them with excellent catalytic performance in various electrocatalytic reactions. Herein, we briefly summarize recent advances in the synthesis of metal nanocrystals with various twin structures, recent breakthroughs related to electrocatalytic applications of twin metal nanocrystals are also overviewed. Darovasertib Finally, the major challenges and perspectives for future development of twin metal nanocrystals in electrochemical applications are proposed.
Little evidence exists for prediction error in iris-sutured intraocular lenses.

To determine the magnitude of prediction error in iris-sutured intraocular lenses, associated factors and their long-term stability.

Retrospective, nonrandomized, noncomparative case series conducted at the Wilmer Eye Institute (Baltimore, Maryland, United States).

Adult patients with subluxated intraocular lenses that underwent iris-suture fixation between January 2000 and December 2014 by a single surgeon. Pregnant women, children (below the age of 18) and cases with follow-up under 1 month were excluded.

Prediction error was calculated in 60 eyes and survival analysis was performed on 99 eyes.

Prediction error (the difference between the postoperative manifest refraction in spherical equivalent and the spherical equivalent predicted by the Barrett Universal II, Holladay 2 and SRK/T formulas), preoperative and postoperative distance-corrected visual acuity, manifest refraction, frequency of postoperative complications and time until re-subluxation.
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