Schulzpollard2977

Background Parathyroidectomy (PTX) has been demonstrated as an effective treatment for patients with secondary hyperparathyroidism (SHPT) of renal origin. However, severe hypocalcemia, called hungry bone syndrome (HBS), is a common complication following PTX in these patients and can lead to poor clinical outcomes, even death. Therefore, exploring risk factors for HBS and establishing a prediction nomogram allow intensive monitoring and prompt treating this postoperative complication, which is the main purpose of this study. Methods From October 2016 to October 2018, PTX with autotransplantation (PTX + AT) procedures were performed in 131 patients with SHPT of renal origin by a surgeon and his team in the Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan University, China. After applying the inclusion and exclusion criteria, a total of 114 patients were enrolled for analyses in this study. Comprehensive data including preoperative, intraoperative, and postoperative variables were prospectivotstrapping demonstrated preoperative iPTH, bone-ALP, preoperative corrected serum calcium, and total weight of resected parathyroid glands were independently associated with postoperative HBS. The nomogram including the abovementioned four independent predictors was constructed and showed better prediction performance than the other four predictors in terms of postoperative HBS. Conclusions On the basis of this study, we found higher preoperative iPTH level, higher bone-ALP level, heavier total weight of resected parathyroid glands, and lower preoperative corrected serum calcium level were independent predictors of postoperative HBS in patients with SHPT of renal origin. The nomogram can expediently, accurately, and objectively predict the risk of postoperative HBS in individual patient with SHPT of renal origin.Background Up to 30% of patients with sickle cell disease (SCD) develop chronic liver disease via etiologies including sickle cell hepatopathy, acquired viral hepatitis, or secondary hemochromatosis. It is unclear how many patients with SCD ultimately undergo liver transplantation (LT) and what factors are associated with survival after LT. In this study, we examined LT outcomes in these patients by reviewing the Scientific Registry of Transplant Recipients (SRTR) and our institutional experience. Methods Analysis of the SRTR identified 23 LT recipients and five simultaneous liver and kidney transplantation (SLKT) recipients with SCD. Patient demographics and graft and patient survival were analyzed. Two patients with SCD at our institution underwent SLKT. Results Review of the SRTR revealed that recipients with SCD had significantly higher model for end-stage liver disease scores (33 versus 21, P = 0.004), preoperative intensive care unit admission (43.5% versus 19.1%, P = 0.007), preoperative dialysis (17.4% versus 4.9%, P = 0.009), and were more likely to be status 1 (26.1% versus 12.1%, P = 0.041) when compared with the reference population of African American LT recipients. Despite being higher risk at the time of LT, patients with SCD had equivalent posttransplant graft and patient survival when compared with the reference population (P = 0.5 and P = 0.2, respectively) and a 21 propensity score-matched group (P = 0.5 and P = 0.2, respectively). Two recent SLKT recipients with SCD from our institution have performed well with stable allograft function. Conclusions Data from the SRTR demonstrate that patients with SCD can expect equivalent graft and patient survival after LT despite exhibiting more comorbidities at the time of LT. The low number of patients with SCD who underwent LT in the SRTR in comparison with the rate of chronic liver disease in this population raises the question as to whether a disparity in access to LT exists for this complex population.Background Anal SCC is a rare disease mainly treated with chemoradiation. Abdominoperineal resection (APR), once the mainstay of treatment for anal cancer, now serves a role as salvage therapy for persistent or recurrent disease after chemoradiation. In addition, clinically positive nodes are currently treated by extending the radiation field to the groin. The role of inguinal lymph node dissection in recurrent or persistent anal SCC is unclear. The aim of the study is to determine the role of inguinal lymph node dissection in the management of inguinal lymph node metastasis for anal squamous cell carcinoma (SCC). Methods Retrospective analysis of patients with anal SCC in the National Cancer Database with positive inguinal nodes undergoing salvage APR between 2004 and 2014 was performed. A comparison of overall survival between patients who underwent APR with lymph node dissection versus APR only was analyzed using Kaplan-Meier plot. Results A total of 3424 patients underwent salvage APR, with 274 (8%) having clinically positive nodes. Within the subgroup that had clinically positive nodes, 195 (71%) underwent APR, whereas 79 (29%) underwent both APR and node dissection. Kaplan-Meier analysis demonstrates no difference in overall survival in the two groups (P = 0.99). Five-year survival for both groups was similar (36% versus 42%; P = 0.987). No significant difference was found when adjusted for age, gender, and Tumor Node Metastasis staging. Conclusions Inguinal lymph node dissection does not appear to improve overall survival in patients with advanced-stage anal cancer requiring salvage APR. Proper patient selection for node dissection is essential to spare patients from additional morbid procedures.Background Local anesthesia (LA) for open inguinal hernia repair (OIHR) is not widely used in the United States. An LA program for OIHR was initiated at the Dallas Veteran Affairs Medical Center in 2015. We hypothesize that outcomes under LA for OIHR are similar to general anesthesia with adequate patient satisfaction. Methods A total of 1422 groin hernias were performed by a single surgeon using a standardized technique at the Dallas Veteran Affairs Medical Center (2015-2019). Only unilateral, primary, elective, OIHRs were included (n = 1092). LA was used in 26.0% (n = 285) and compared with patients undergoing general anesthesia. Univariate analysis was performed by the Student t-test for continuous variables and χ2 test (or the Fisher exact test) for categorical variables. Results OIHR performed with LA increased from 15.5% in 2015 to 76.6% in 2019. Patients undergoing LA were older and had significantly more comorbidities. Holding time to operating room (OR), OR to start of the operation, skin-to-skin time, and end of the operation to out of the OR were all reduced with LA (all P values less then 0.05). Inguinodynia, recurrence, and overall complications were similar. Patients undergoing LA indicated that they were comfortable (93.0%), rated their worst pain as 2.03 ± 2.2 (of 10), and would undergo LA if they had to do it again (94.0%). Conclusions LA was associated with decreased OR times and had good patient satisfaction. Overall complication rates were similar despite a higher burden of comorbid conditions in patients undergoing LA.Selective serotonin reuptake inhibitors (SSRIs) are the predominant drugs prescribed for Major Depressive Disorder. The immediate pharmacological target of SSRIs is the serotonin transporter. However, the delayed therapeutic effect and high rate of patient non-response make it highly likely that SSRIs also have other molecular targets that are yet to be identified. Cellular thermal shift assay (CETSA) is a method based on thermal stabilization of target proteins upon drug binding. In the present study, we show that the SSRI paroxetine binds to phosphofructokinase (PFK) protein using CETSA. We found that mouse brain PFK and recombinant human PFK proteins are stabilized by paroxetine incubation. Chronic paroxetine treatment also significantly increased mouse brain PFK thermal stability. Paroxetine significantly elevated in vitro and in vivo PFK activity. Levels of several metabolites in glutamate- and energy metabolism-related pathways are significantly correlated with PFK activity in mouse hippocampus. Our data show that paroxetine can bind to PFK and affect its activity. Resveratrol nmr Implications of these results for the antidepressant mode of action of paroxetine are discussed.T-cell acute lymphoblastic leukemia (T-ALL) is a highly heterogeneous malignant hematological disorder arising from T-cell progenitors. This study was aimed to evaluate the cytotoxic effect of CP55940 on human peripheral blood lymphocytes (PBL) and on T-ALL cells (Jurkat). PBL and Jurkat cells were treated with CP55940 (0-20 μM), and morphological changes in the cell nucleus/ DNA, mitochondrial membrane potential (ΔΨm), and intracellular reactive oxygen species levels were determined by fluorescence microscopy and flow cytometry. Cellular apoptosis markers were also evaluated by western blotting, pharmacological inhibition and immunofluorescence. CP55940 induced apoptotic cell death in Jurkat cells, but not in PBL, in a dose-response manner with increasing fragmentation of DNA, arrest of cell cycle and damage of ΔΨm. CP55940 increased dichlorofluorescein fluorescence (DCF) intensity, increased DJ-1 Cys106- sulfonate, a marker of intracellular stress, induced the up-regulation of p53 and phosphorylation of transcription factor c-JUN. It increased the expression of BAX and PUMA, up-regulated mitochondrial proteins PINK1 and Parkin, and activated CASPASE-3. Antioxidant NAC, pifithrin-α, and SP600125 blocked CP55940 deleterious effect on Jurkat cells. However, the potent and highly specific cannabinoid CB1 and CB2 receptor inverse agonist SR141716 and SR144528 were unable to blunt CP55940-induced apoptosis in Jurkat cells. Conclusively CP55940 provokes cell death in Jurkat through CBR-independent mechanism. Interestingly, CP55940 was also cytotoxic to ex vivo T-ALL cells from chemotherapy-resistant pediatric patients. In conclusion, CP55940 selectively induces apoptosis in Jurkat cells through a H2O2-mediated signaling pathway. Our findings support the use of cannabinoids as a potential treatment for T-ALL cells.Background Perfluoralkylated substances (PFASs) are persistent and bioaccumulative environmental contaminants. They are included on the list of emergent compounds monitored in the frame of HBM4EU project. Objectives To analyze PFASs levels in human milk samples collected in the period 2006 through 2017, to follow their time trends, to assess the PFASs exposure in breastfed infants, to calculate the daily intake of PFASs and to compare it with the tolerable daily/weekly) intakes and to quantify risk from exposure using the hazard quotient and hazard index approach. Material and methods A broad spectrum of PFASs were analyzed by means of UHPLC-MS/MS in primipara human milk samples collected in four consecutive time periods 2006, 2010/11, 2014, and 2017; N = 46, 183, 164 and 232, respectively. Mothers living in urban and suburban residences were recruited after their delivery at maternity hospitals, and milk samples were taken within 2 and 8 weeks after delivery. The questionnaire was focused on possible sourceselow these limits. Using the new, more conservative EFSA Provisional Tolerably Weekly Intake (PTWI) values set in 2018, we demonstrated a considerable exceedance of PTWI, with a hazard index above 1. Conclusion Significant time-related decreasing trends in the PFOS and PFOA levels in human milk were observed. Nevertheless, the body burden of infants from breastfeeding might pose an enhanced health risk to infants when the current PTWI values are applied. These findings strongly support the present EU efforts to phase out PFOA, its salts and PFOA related compounds. Since PFOS exposure there has still been widely detected despite PFOS usage reduction measures, the major exposure routes should be further monitored and, if possible, eliminated.