Type B Lactic Acidosis: A Very Rare but Fatal Complication of Gastrointestinal Solid Tumor.

Type B lactic acidosis, secondary to solid cancer, is very rare. It is mostly seen in patients with hematological malignancies. Although its exact pathogenesis is unknown, it is believed to be caused by overproduction and the inability of tumor cells to remove lactate. In the last 26 years, a systematic review of the literature only identified two previous reports of colorectal cancer-related type B lactic acidosis. Here, we report the third case of severe type B lactic acidosis due to stage IV colorectal with liver metastasis. Besides, this case is unique in that serum lactate levels reaching as high as 24 mmol/L were not reported in association with colorectal cancer. In most cases, the prognosis is still very poor because there are no standardized treatment recommendations. Early chemotherapy is still the only intervention that provides some survival benefits.

Umbrella review and network meta-analysis of diagnostic imaging test accuracy studies in Differentiating between brain tumor progression versus pseudoprogression and radionecrosis.

PURPOSE: In this study we gathered and analyzed the available evidence regarding 17 different imaging modalities and performed network meta-analysis to find the most effective modality for the differentiation between brain tumor recurrence and post-treatment radiation effects. METHODS: We conducted a comprehensive systematic search on PubMed and Embase. The quality of eligible studies was assessed using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. For each meta-analysis, we recalculated the effect size, sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio from the individual study data provided in the original meta-analysis using a random-effects model. Imaging technique comparisons were then assessed using NMA. Ranking was assessed using the multidimensional scaling approach and by visually assessing surface under the cumulative ranking curves. RESULTS: We identified 32 eligible studies. High confidence in the results was found in only one of them, with a substantial heterogeneity and small study effect in 21% and 9% of included meta-analysis respectively. Comparisons between MRS Cho/NAA, Cho/Cr, DWI, and DSC were most studied. Our analysis showed MRS (Cho/NAA) and 18F-DOPA PET displayed the highest sensitivity and negative likelihood ratios. 18-FET PET was ranked highest among the 17 studied techniques with statistical significance. APT MRI was the only non-nuclear imaging modality to rank higher than DSC, with statistical insignificance, however. CONCLUSION: The evidence regarding which imaging modality is best for the differentiation between radiation necrosis and post-treatment radiation effects is still inconclusive. Using NMA, our analysis ranked FET PET to be the best for such a task based on the available evidence. APT MRI showed promising results as a non-nuclear alternative.

Small-Molecule Activation of Protein Phosphatase 2A Counters Bleomycin-Induced Fibrosis in Mice.

The activity of protein phosphatase 2A (PP2A), a serine-threonine phosphatase, is reduced in the lung fibroblasts of idiopathic pulmonary fibrosis (IPF) patients. The objective of this study was to determine whether the reactivation of PP2A could reduce fibrosis and preserve the pulmonary function in a bleomycin (BLM) mouse model. Here, we present a new class of direct small-molecule PP2A activators, diarylmethyl-pyran-sulfonamide, exemplified by ATUX-1215. ATUX-1215 has improved metabolic stability and bioavailability compared to our previously described PP2A activators. Primary human lung fibroblasts were exposed to ATUX-1215 and an older generation PP2A activator in combination with TGFß. ATUX-1215 treatment enhanced the PP2A activity, reduced the phosphorylation of ERK and JNK, and reduced the TGFß-induced expression of ACTA2, FN1, COL1A1, and COL3A1. C57BL/6J mice were administered 5 mg/kg ATUX-1215 daily following intratracheal instillation of BLM. Three weeks later, forced oscillation and expiratory measurements were performed using the Scireq Flexivent System. ATUX-1215 prevented BLM-induced lung physiology changes, including the preservation of normal PV loop, compliance, tissue elastance, and forced vital capacity. PP2A activity was enhanced with ATUX-1215 and reduced collagen deposition within the lungs. ATUX-1215 also prevented the BLM induction of Acta2, Ccn2, and Fn1 gene expression. Treatment with ATUX-1215 reduced the phosphorylation of ERK, p38, JNK, and Akt and the secretion of IL-12p70, GM-CSF, and IL1α in BLM-treated animals. Delayed treatment with ATUX-1215 was also observed to slow the progression of lung fibrosis. In conclusion, our study indicates that the decrease in PP2A activity, which occurs in fibroblasts from the lungs of IPF subjects, could be restored with ATUX-1215 administration as an antifibrotic agent.

Role of point of care ultrasound in the absence of radial pulse and unrecordable blood pressure during the assessment of shock: Case report.

INTRODUCTION: Point-of-care ultrasound (POCUS) has been an integral part of patient evaluation in the Emergency Department. It has been used increasingly for the evaluation of critically ill and trauma patients. CASE PRESENTATION: We report a case of 60-year-old male patient who presented to the Emergency department with flank pain and urinary symptoms suggesting pyelonephritis with unrecordable blood pressure indicating potential septic shock, but the absence of bilateral radial pulses triggered the use of POCUS which reveal bilateral radial artery occlusion. CASE DISCUSSION: Assessment of the peripheral pulses (usually radial pulse) is an important clue to estimate the systolic blood pressure with presence of a pulse correlating to a systolic SBP of ≥80 mmHg. this case report showed there was an absent peripheral radial and brachial pulse despite the patient appearing hemodynamically stable and no other signs of shock. By utilizing vascular POCUS, the patient's diagnosis completely changed. The use of POCUS led to an instant diagnosis and appropriate patient management. CONCLUSION: Point-of-Care ultrasound is a valuable diagnostic tool that can help narrow down differential diagnostics and guide early proper management and intervention.