Citations

Study Design: Review article. Objectives: A review of the literature on postoperative spinal infections, their diagnosis, and management. Methods: A systematic computerized Medline literature search was performed using PubMed, Cochrane Database of Systematic Reviews, and EMBASE. The electronic databases were searched for publication dates from the last 10 years. The searches were performed from Medical Subject Headings (MeSH) used by the National Library of Medicine. Specifically, MeSH terms “spine,” “infections,” “management,” and “diagnosis” were used. Results: Currently, the gold standard for diagnosis of postoperative spine infection is positive deep wound culture. Many of the current radiologic and laboratory tests can assist with the initial diagnosis and monitoring treatment response. Currently erythrocyte sedimentation rate, C-reactive protein, computed tomography scan, and magnetic resonance imaging with and without contrast are used in combination to establish diagnosis. Management of postoperative spine infection involves thorough surgical debridement and targeted antibiotic therapy. Conclusions: Postoperative spine infection is a not uncommon complication following surgery that may have devastating consequences for a patient’s short- and long-term health. A high index of suspicion is needed to make an early diagnosis.

Background: We have previously shown in patients with renovascular hypertension (RVH) that elevated urinary mtDNA copy numbers represent surrogate markers of renal mitochondrial injury. Revascularization with percutaneous transluminal renal angioplasty (PTRA) can lead to acute renal reperfusion injury. However, whether PTRA induces renal mitochondrial injury remains unknown. Methods: We prospectively measured urinary copy number of the mtDNA genes cytochrome-c oxidase-3 (COX3) and NADH dehydrogenase subunit-1 (ND1) by qPCR in 5 RVH patients before and 24hrs after PTRA. Five additional patients were treated before and during PTRA with the mitoprotective drug elamipretide (ELAM, 0.05 mg/kg/hr IV infusion). Healthy volunteers (HV) served as controls (n=5). Results: Baseline blood pressure was similarly elevated in both RVH groups, and eGFR lower than HV (Table). Baseline urinary COX3 and ND1 levels were similarly higher in both RVH groups compared with HV (Fig. A), and directly correlated with serum creatinine levels (R 2 =0.74, p=0.001 and R 2 =0.45, p=0.033, respectively). Over 3 months, eGFR increased only in ELAM-treated patients (Fig. B). Furthermore, the rise in urinary mtDNA 24hrs after PTRA was blunted in PTRA+ELAM versus PTRA+Placebo, and inversely correlated with the change in eGFR of 3 months after PTRA (Fig. C). Conclusion: PTRA induces an acute rise in urinary mtDNA levels, likely reflecting renal mitochondrial injury due to reperfusion injury that inhibits renal recovery. Mitoprotection in this cohort limited PTRA-associated mitochondrial injury and improved renal outcomes after revascularization.

Significance The energy-producing organelle mitochondrion contains its own compact genome, which is separate from the nuclear genome. In nearly all mammals, this mitochondrial genome is inherited exclusively from the mother, and transmission of paternal mitochondria or mitochondrial DNA (mtDNA) has not been convincingly demonstrated in humans. In this paper, we have uncovered multiple instances of biparental inheritance of mtDNA spanning three unrelated multiple generation families, a result confirmed by independent sequencing across multiple unrelated laboratories with different methodologies. Surprisingly, this pattern of inheritance appears to be determined in an autosomal dominantlike manner. This paper profoundly alters a widespread belief about mitochondrial inheritance and potentially opens a novel field in mitochondrial medicine.

Thiopurine methyltransferase (TPMT) activity exhibits a monogenic codominant inheritance and catabolizes thiopurines. TPMT variant alleles are associated with low enzyme activity and pronounced pharmacologic effects of thiopurines. Loss‐of‐function alleles in the NUDT15 gene are common in Asians and Hispanics and reduce the degradation of active thiopurine nucleotide metabolites, also predisposing to myelosuppression. We provide recommendations for adjusting starting doses of azathioprine, mercaptopurine, and thioguanine based on TPMT and NUDT15 genotypes (updates on www.cpicpgx.org ).

Abstract Although fast-scan cyclic voltammetry (FSCV) has been widely used for in vivo neurochemical detection, the sensitivity and selectivity of the technique can be further improved. In this study, we develop fast cyclic square-wave voltammetry (FCSWV) as a novel voltammetric technique that combines large-amplitude cyclic square-wave voltammetry (CSWV) with background subtraction. A large-amplitude, square-shaped potential was applied to induce cycling through multiple redox reactions within a square pulse to increase sensitivity and selectivity when combined with a two-dimensional voltammogram. As a result, FCSWV was significantly more sensitive than FSCV (n = 5 electrodes, two-way ANOVA, p = 0.0002). In addition, FCSWV could differentiate dopamine from other catecholamines (e.g., epinephrine and norepinephrine) and serotonin better than conventional FSCV. With the confirmation that FCSWV did not influence local neuronal activity, despite the large amplitude of the square waveform, it could monitor electrically induced phasic changes in dopamine release in rat striatum before and after injecting nomifensine, a dopamine reuptake inhibitor.

Increased amino acids in the dysbiotic gut influences susceptibility to Clostridioides difficile infection in mice and humans.