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Background/Objectives: Early postmortem mitochondrial function and apoptotic activation affect meat quality development. Nicotinamide riboside (NR) supplementation to pigs prior to harvest can improve pork color stability, but its mechanism remains unclear. This study aimed to evaluate the impact of NR supplementation on early postmortem mitochondrial functionality and apoptosis. Methods: Sixteen pigs (N = 16) were individually fed a control or NR-supplemented diet (30 mg·kg body weight−1·d−1) for 10 days prior to harvest. Longissimus dorsi muscle samples were collected at 45 min and 24 h postmortem and analyzed for mitochondrial functionality using high-resolution respirometry and apoptotic protein abundance (apoptosis regulator Bcl-2-associated X (BAX), apoptotic inducing factor (AIF), and caspase 3 (CASP3)) via immunoblotting. Results: NR-supplemented muscle exhibited lower proton leak-associated respiration at 45 min postmortem (p < 0.05), followed by a slower accumulation of mitochondrial outer membrane permeabilization (MOMP; p < 0.05) and a slower loss of mitochondrial integral function (p < 0.05) from 45 min to 24 h postmortem. NR supplementation decreased BAX abundance at 45 min postmortem but increased mature AIF abundance (62 kDa) at 24 h postmortem (p < 0.05). The abundance of CASP3 fragments (~29 kDa) decreased from 45 min to 24 h postmortem, independent of treatment (p < 0.05). Conclusions: NR supplementation demonstrated the potential to protect mitochondrial integral function and alleviate apoptotic activation in early postmortem porcine skeletal muscle, which might contribute to a higher meat color stability in NR-supplemented pork during retail display. [ABSTRACT FROM AUTHOR]

Background We explored the clinical significance of the residual hematoma cavity 1 year after minimally invasive intracerebral hemorrhage (ICH) evacuation. Methods Patients presenting with spontaneous supratentorial ICH were evaluated for minimally invasive surgical evacuation. Inclusion criteria included age ≥18 years, preoperative hematoma volume (Hv) ≥15 mL, presenting National Institutes of Health Stroke Scale score ≥6, and premorbid modified Rankin Scale (mRS) score ≤3. Patients with longitudinal CT scans at least 3 months after evacuation were included in the study. Remnant cavity volumes (Cv) after evacuation were computed using semi-automatic volumetric segmentation software. Relative cavity volume (rCv) was defined as the ratio of the preoperative Hv to the remnant Cv. Results 108 patients with a total of 484 head CT scans were included in the study. The median postoperative Cv was 2.4 (IQR 0.0-11) mL, or just 6% (0-33%) of the preoperative Hv. The median residual Cv on the final head CT scan a median of 13 months (range 11-27 months) after surgery had increased to 9.4 (IQR 3.1-18) mL, or 25% (10-60%) of the preoperative Hv. rCv on the final head CT scan was negatively associated with measures of operative success including evacuation percentage, postoperative Hv ≤ 15 mL, and decreased time from ictus to evacuation. rCv on the final head CT scan was also associated with a worse 6-month functional outcome (β per mRS point 17.6%, P<0.0001; area under the receiver operating characteristic curve 0.91). Conclusion After minimally invasive ICH evacuation the hematoma lesion decompresses significantly, with a residual Cv just 6% of the original lesion, but then gradually increases in size over time. Early and high percentage ICH evacuation may reduce the remnant Cv over time which, in turn, is associated with improved functional outcomes. [ABSTRACT FROM AUTHOR]

Background Diffusion-weighted imaging (DWI) lesions have been linked to poor outcomes after intracerebral hemorrhage (ICH). We aimed to assess the impact of cerebral digital subtraction angiography (DSA) on the presence of DWI lesions in patients who underwent minimally invasive surgery (MIS) for ICH. Methods Retrospective chart review was performed on ICH patients treated with MIS in a single health system from 2015 to 2021. One hundred and seventy consecutive patients who underwent postoperative MRIS were reviewed. Univariate analyses were conducted to determine associations. Variables with p<0.05 were included in multivariate analyses. Results DWI lesions were present in 88 (52%) patients who underwent MIS for ICH. Of the 83 patients who underwent preoperative DSA, 56 (67%) patients demonstrated DWI lesions. In this DSA cohort, older age, severe leukoaraiosis, larger preoperative hematoma volume, and increased presenting National Institutes of Health Stroke Score (NIHSS) were independently associated with DWI lesion identification (p<0.05). In contrast, of 87 patients who did not undergo DSA, 32 (37%) patients demonstrated DWI lesions on MRI. In the non-DSA cohort, presenting systolic blood pressure, intraventricular hemorrhage, and NIHSS were independently associated with DWI lesions (p<0.05). Higher DWI lesion burden was independently associated with poor modified Rankin Scale (mRS) at 6 months on a univariate (p=0.02) and multivariate level (p=0.02). Conclusions In this cohort of ICH patients who underwent minimally invasive evacuation, preprocedural angiography was associated with the presence of DWI lesions on post-ICH evacuation MRI. Furthermore, the burden of DWI lesions portends a worse prognosis after ICH. [ABSTRACT FROM AUTHOR]

Introduction Acute lymphoblastic leukemia (ALL) is a common disseminated malignancy that is cured by combination chemotherapy in approximately 90% of children and 70% of adults (1-3). Achieving sufficient concentrations of [...], BACKGROUND. Interpatient differences in the accumulation of methotrexate&apos;s active polyglutamylated metabolites (MTXPGs) in leukemia cells influence its antileukemic effects. METHODS. To identify genomic and epigenomic and patient variables determining the intracellular accumulation of MTXPGs, we measured intracellular MTXPG levels in acute lymphoblastic leukemia (ALL) cells from 388 newly diagnosed patients after in vivo high-dose methotrexate (HDMTX) (1 g/[m.sup.2]) treatment, defined ALL subtypes, and assessed genomic and epigenomic variants influencing folate pathway genes (mRNA, miRNA, copy number alterations [CNAs], SNPs, single nucleotide variants [SNVs], CpG methylation). RESULTS. We documented greater than 100-fold differences in MTXPG levels, which influenced its antileukemic effects (P = 4 * [10.sup.-5]). Three ALL subtypes had lower MTXPG levels (T cell ALL [T-ALL] and B cell ALL [B-ALL] with the TCF3-PBX1 or ETV6-RUNX1 fusions), and 2 subtypes had higher MTXPG levels (hyperdiploid and BCR-ABL like). The folate pathway genes SLC19A1, ABCC1, ABCC4, FPGS, and MTHFD1 significantly influenced intracellular MTXPG levels (P = 2.9 * [10.sup.-3] to 3.7 * [10.sup.-8]). A multivariable model including the ALL subtype (P = 1.1 * [10.sup.-14]), the SLC19A1/(ABCC1 + ABCC4) transporter ratio (P = 3.6 * [10.sup.-4]), the MTX infusion time (P = 1.5 * [10.sup.-3]), FPGS mRNA expression (P = 2.1 * [10.sup.-3]), and MTX systemic clearance (P = 4.4 * [10.sup.-2]) explained 42% of the variation in MTXPG accumulation (P = 1.1 * [10.sup.-38]). Model simulations indicated that a longer infusion time (24 h vs. 4 h) was superior in achieving higher intracellular MTXPG levels across all subtypes if ALL. CONCLUSIONS. These findings provide insights into mechanisms underlying interpatient differences in intracellular accumulation of MTXPG in leukemia cells and its antileukemic effects FUNDING. THE National Cancer Institute (NCI) and the Institute of General Medical Sciences of the NIH, the Basque Government Programa Posdoctoral de Perfeccionamiento de Personal Investigador doctor, and the American Lebanese Syrian Associated Charities (ALSAC).

Although rare in adults, Wilms tumor is the most common pediatric renal tumor. Treatment typically involves radical nephrectomy followed by adjuvant chemotherapy or radiation, although outcomes differ between children and adults which may be due to challenges in accurately diagnosing these patients. In this article, we present a case report of an adult patient with Jeune syndrome and multiple urologic abnormalities who underwent radical nephrectomy for a large renal mass and was subsequently diagnosed with an epithelial predominant Wilms tumor. Epithelial predominant Wilms tumor may have distinct origins from other Wilms tumor histological subtypes and may incur better outcomes. Herein, we discuss the literature surrounding this rare entity as well as the anticipated treatment course. [ABSTRACT FROM AUTHOR]

Recent genomic profiling of childhood acute lymphoblastic leukemia (ALL) identified a high-risk subtype with an expression signature resembling that of Philadelphia chromosome-positive ALL and poor prognosis (Ph-like ALL). However, the role of inherited genetic variation in Ph-like ALL pathogenesis remains unknown. In a genome-wide association study (GWAS) of 511 ALL cases and 6,661 non-ALL controls, we identified a susceptibility locus for Ph-like ALL (GATA3, rs3824662; P = 2.17 × 10(-14), odds ratio (OR) = 3.85 for Ph-like ALL versus non-ALL; P = 1.05 × 10(-8), OR = 3.25 for Ph-like ALL versus non-Ph-like ALL), with independent validation. The rs3824662 risk allele was associated with somatic lesions underlying Ph-like ALL (CRLF2 rearrangement, JAK gene mutation and IKZF1 deletion) and with variation in GATA3 expression. Finally, genotype at the GATA3 SNP was also associated with early treatment response and risk of ALL relapse. Our results provide insights into interactions between inherited and somatic variants and their role in ALL pathogenesis and prognosis.

Background Minimally invasive evacuation may help ameliorate outcomes after intracerebral hemorrhage (ICH). However, hospital length of stay (LOS) postevacuation is often long and costly. Objective To examine factors associated with LOS in a large cohort of patients who underwent minimally invasive endoscopic evacuation. Methods Patients presenting to a large health system with spontaneous supratentorial ICH qualified for minimally invasive endoscopic evacuation if they met the following inclusion criteria: age ≥18, premorbid modified Rankin Scale (mRS) score ≤3, hematoma volume ≥15 mL, and presenting National Institutes of Health Stroke Scale (NIHSS) score ≥6. Demographic, clinical, radiographic, and operative characteristics were included in a multivariate logistic regression for hospital and ICU LOS dichotomized into short and prolonged stay at 14 and 7 days, respectively. Results Among 226 patients who underwent minimally invasive endoscopic evacuation, the median intensive care unit and hospital LOS were 8 (4-15) days and 16 (9-27) days, respectively. A greater extent of functional impairment on presentation (OR per NIHSS point 1.10 (95% CI 1.04 to 1.17), P=0.007), concurrent intraventricular hemorrhage (OR=2.46 (1.25 to 4.86), P=0.02), and deep origin (OR=per point 2.42 (1.21 to 4.83), P=0.01) were associated with prolonged hospital LOS. A longer delay from ictus to evacuation (OR per hour 1.02 (1.01 to 1.04), P=0.007) and longer procedure time (OR per hour 1.91 (1.26 to 2.89), P=0.002) were associated with prolonged ICU LOS. Prolonged hospital and ICU LOS were in turn longitudinally associated with a lower rate of discharge to acute rehabilitation (40% vs 70%, P<0.0001) and worse 6- month mRS outcomes (5 (4-6) vs 3 (2-4), P<0.0001). Conclusions We present factors associated with prolonged LOS, which in turn was associated with poor long-term outcomes. Factors associated with LOS may help to inform patient and clinician expectations of recovery, guide protocols for clinical trials, and select suitable populations for minimally invasive endoscopic evacuation. [ABSTRACT FROM AUTHOR]