PKM2 ablation enhanced retinal function and survival in a preclinical model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a neurodegenerative disorder that causes irreversible vision loss in over 1.5 million individuals world-wide. The genetic heterogeneity of RP necessitates a broad therapy that is able to provide treatment in a gene- and mutation- non-specific manner. In this study, we identify the therapeutic benefits of metabolic reprogramming by targeting pyruvate kinase M2 (PKM2) in a Pde6ß preclinical model of RP. The genetic contributions of PKM2 inhibition in retinal degeneration were evaluated through histology and electroretinogram (ERG) followed by a statistical analysis using a linear regression model. Notably, PKM2 ablation resulted in thicker retinal layers in Pde6ß-mutated mice as compared to the controls, suggesting greater photoreceptor survival. Consistent with these anatomical findings, ERG analyses revealed that the maximum b-wave is on average greater in Pkm2 knockout mice than in mice with intact Pkm2, indicating enhanced photoreceptor function. These rescue phenotypes from Pkm2 ablation in a preclinical model of RP indicate that a metabolome reprogramming may be useful in treating RP.

Nonutility of procalcitonin for diagnosing bacterial pneumonia in patients with severe COVID-19.

Background: Patients hospitalized with COVID-19 are at significant risk for superimposed bacterial pneumonia. However, diagnosing superinfection is challenging due to its clinical resemblance to severe COVID-19. We therefore evaluated whether the immune biomarker, procalcitonin, could facilitate the diagnosis of bacterial superinfection. Methods: We retrospectively identified 185 patients hospitalized with severe COVID-19 who underwent lower respiratory culture; 85 had evidence of bacterial superinfection. Receiver operating characteristic curve and area under the curve (AUC) analyses were performed to assess the utility of procalcitonin for diagnosing superinfection. Results: This approach demonstrated that procalcitonin measured at the time of culture was incapable of distinguishing patients with bacterial infection (AUC, 0.52). The AUC not affected by exposure to antibiotics, treatment with immunomodulatory agents, or timing of procalcitonin measurement. Conclusion: Static measurement of procalcitonin does not aid in the diagnosis of superinfection in severe COVID-19.

Nonutility of procalcitonin for diagnosing bacterial pneumonia in COVID-19.

Patients hospitalized with COVID-19 are at significant risk for superimposed bacterial pneumonia. However, diagnosing superinfection is challenging due to its clinical resemblance to severe COVID-19. We therefore evaluated whether the immune biomarker, procalcitonin, could facilitate the diagnosis of bacterial superinfection. To do so, we identified 185 patients with severe COVID-19 who underwent lower respiratory culture; 85 had superinfection. Receiver operating characteristic curve analysis showed that procalcitonin at the time of culture was incapable of distinguishing patients with bacterial infection (AUC, 0.52). We conclude that static measurement of procalcitonin does not aid in the diagnosis of superinfection in severe COVID-19.

Robotic pancreaticoduodenectomy provides better histopathological outcomes as compared to its open counterpart: a meta-analysis.

The aim of this meta-analysis was to evaluate whether robotic pancreaticoduodenectomy (PD) may provide better clinical and pathologic outcomes compared to its open counterpart. The Pubmed, EMBASE, and Cochrane Library were systematically searched. Overall postoperative morbidity and resection margin involvement rate were the primary endpoints. Secondary endpoints included operating time, estimated blood loss (EBL), incisional surgical site infection (SSI) rate, length of hospital stay (LOS), and number of lymph nodes harvested. Twenty-four studies totaling 12,579 patients (2,175 robotic PD and 10,404 open PD were included. Overall postoperative mortality did not significantly differ [OR (95%CI) = 0.86 (0.74, 1.01); p = 0.06]. Resection margin involvement rate was significantly lower in robotic PD [15.6% vs. 19.9%; OR (95%CI) = 0.64 (0.41, 1.00); p = 0.05; NNT = 23]. Operating time was significantly longer in robotic PD [MD (95%CI) = 75.17 (48.05, 102.28); p < 0.00001]. EBL was significantly decreased in robotic PD [MD (95%CI) = - 191.35 (- 238.12, - 144.59); p < 0.00001]. Number of lymph nodes harvested was significantly higher in robotic PD [MD (95%CI) = 2.88 (1.12, 4.65); p = 0.001]. This meta-analysis found that robotic PD provides better histopathological outcomes as compared to open PD at the cost of longer operating time. Furthermore, robotic PD did not have any detrimental impact on clinical outcomes, with lower wound infection rates.