Comorbidities Associated With Increased Likelihood of Postoperative Surgical Site Infection in Patients Treated for Hand or Finger Fracture and/or Dislocations.

BACKGROUND: We aimed to determine the relationship between common preoperative comorbidities and subsequent incidence of postoperative surgical site infections (SSIs) in hand and finger fractures and/or dislocations. METHODS: We queried the American College of Surgeons National Safety and Quality Improvement Program from January 1, 2015 to December 31, 2019. Patients were included in our study if they were treated by open or percutaneous fixation for any hand or finger fracture and/or dislocation. Predictor variables were smoking status, diabetes mellitus status, and obesity (body mass index > 30) status. Primary outcome was incidence of postoperative SSI. RESULTS: There were a total of 9245 patients included in our study, and 148 patients (1.6%) experienced postoperative SSI. Of these, 59 patients (39.9%) were only smokers, 7 patients (4.7%) only had diabetes mellitus, and 55 patients (37.2%) were only obese. Overall, patients experienced greater odds of sustaining a postoperative SSI if they were a smoker or diabetic compared to non-smokers and non-diabetics, respectively. Considering only open fixation modality, patients with comorbidities were not at significantly increased odds of sustaining postoperative SSI. Considering only percutaneous fixation modality, patients experienced significantly greater odds of sustaining postoperative SSI if they were a smoker compared to non-smoker. CONCLUSIONS: Common preoperative comorbidities, including smoking status and diabetes mellitus, increase the likelihood of postoperative complication in patients with hand and finger fractures and/or dislocations undergoing surgical treatment. Further investigation into the different relationship of these comorbidities between open and closed fractures with larger sample sizes will be valuable.

Routine Preoperative Nutritional Optimization Not Required in Patients Undergoing Breast Reconstruction.

Purpose: There are no data describing the need for preoperative nutritional optimization in patients undergoing breast reconstruction surgery. The purpose of this research was to identify if preoperative breast reconstruction patients are grossly nutritionally deficient as defined by preoperative serum albumin and, thus, if routine preoperative nutrition screening and optimization is necessary in this patient population. Methods: Adult patients who underwent breast reconstruction surgery between 2015 and 2019 were identified within the National Safety and Quality Improvement Program database. Variables of interest for this group of patients were collected, and comparisons were made for these variables between three different breast reconstruction modalities (implant-based reconstruction [IBR], expander-based reconstruction [EBR], and free tissue-based reconstruction [FTBR]) with χ2 and ANOVA statistical tests. Results: A total of 14,509 patients were included. There was not a significant difference in preoperative serum albumin measurements between the three reconstruction modalities and mean measurements for the three reconstruction modalities were all within normal limits. Secondarily, when comparing groups, FTBR had higher incidence of superficial surgical site infection (SSI) (4.49% vs. 1.6% vs. 1.56%, respectively; p < 0.00001), deep SSI (1.57% vs. 0.48% vs. 0.94%, respectively; p < 0.00001), and wound disruption (2.16% vs. 0.78% vs. 0.94%, respectively; p < 0.00001) than IBR and EBR. Conclusion: Preoperative nutritional status was found to be grossly appropriate in a large population of breast reconstruction patients. Furthermore, the ordering of routine preoperative serum albumin is unnecessary and represents an extraneous healthcare cost that does not lead to improved outcomes in breast reconstruction. FTBR incurred the greatest risk of surgical complication independent of preoperative nutritional status.

Silicone breast implant rupture: a review.

Silicone breast implants have been in use for nearly 6 decades. In this time they have undergone significant changes in design and use. They have been subject to intense scrutiny with regard to safety and efficacy, including an almost 10 years moratorium on their use. The current generations of implants have been followed via the manufacturer's Core studies in order to obtain long term data regarding safety and complications. The results of the more recent studies are compiled in this review. Rupture rates are initially very low and begin to increase after 6-8 years of implantation. Implant rupture may be detected by physical exam, ultrasound or magnetic resonance imaging (MRI). The majority of silicone implant ruptures are clinically undetectable. Symptomatic patients may present with capsular contracture, breast lumps or changes in breast shape. The most common cause of implant rupture is instrument damage during placement. Implant rupture may be confined to the peri-prosthetic capsule or may extravasate into the breast tissue. Patients with ruptured implants have been studied closely and the consensus of the literature states there are no health risks associated with implant rupture. Symptomatic patients with ruptured implants should be offered the choice of observation, or explantation and capsulectomy with or without replacement.

Deep Sequencing of Three Loci Implicated in Large-Scale Genome-Wide Association Study Smoking Meta-Analyses.

INTRODUCTION: Genome-wide association study meta-analyses have robustly implicated three loci that affect susceptibility for smoking: CHRNA5\CHRNA3\CHRNB4, CHRNB3\CHRNA6 and EGLN2\CYP2A6. Functional follow-up studies of these loci are needed to provide insight into biological mechanisms. However, these efforts have been hampered by a lack of knowledge about the specific causal variant(s) involved. In this study, we prioritized variants in terms of the likelihood they account for the reported associations. METHODS: We employed targeted capture of the CHRNA5\CHRNA3\CHRNB4, CHRNB3\CHRNA6, and EGLN2\CYP2A6 loci and flanking regions followed by next-generation deep sequencing (mean coverage 78×) to capture genomic variation in 363 individuals. We performed single locus tests to determine if any single variant accounts for the association, and examined if sets of (rare) variants that overlapped with biologically meaningful annotations account for the associations. RESULTS: In total, we investigated 963 variants, of which 71.1% were rare (minor allele frequency < 0.01), 6.02% were insertion/deletions, and 51.7% were catalogued in dbSNP141. The single variant results showed that no variant fully accounts for the association in any region. In the variant set results, CHRNB4 accounts for most of the signal with significant sets consisting of directly damaging variants. CHRNA6 explains most of the signal in the CHRNB3\CHRNA6 locus with significant sets indicating a regulatory role for CHRNA6. Significant sets in CYP2A6 involved directly damaging variants while the significant variant sets suggested a regulatory role for EGLN2. CONCLUSIONS: We found that multiple variants implicating multiple processes explain the signal. Some variants can be prioritized for functional follow-up.

The progesterone receptor hinge region regulates the kinetics of transcriptional responses through acetylation, phosphorylation, and nuclear retention.

Progesterone receptors (PRs) are critical regulators of mammary gland development and contributors to breast cancer progression. Posttranslational modifications of PR have been shown to alter hormone responsiveness. Site-directed mutagenesis demonstrated that upon hormone binding, PR is acetylated at the consensus sequence, KXKK (amino acids 638-641), located within the hinge region. We created an acetylation-deficient (K-A) mutant as well as acetylation mimics (K-Q or K-T). Interestingly, similar to K-A PR, PR acetylation mimics (K-Q or K-T) displayed delayed phosphorylation and nuclear entry relative to wild-type (wt) PR-B, indicative of disruption of PR nuclear-cytoplasmic shuttling. Wt PR-B, but not K-mutant PRs, induced c-myc at 1 h of progestin treatment. However, at 6 h of treatment, c-myc induction was comparable with levels induced by wt PR-B, suggesting that the precise timing of PR phosphorylation and nuclear retention are critical for cells to rapidly initiate robust transcriptional programs. In contrast to c-myc, progestin-induced serum- and glucocorticoid-regulated kinase (SGK) expression displayed sensitivity to PR acetylation but not nuclear entry. Namely, in the presence of progestin, acetylation-deficient (K-A) mutant PR-B up-regulated SGK mRNA relative to wt PR; progesterone response element-luciferase assays confirmed this result. However, K-Q and K-T acetylation mimics only weakly induced SGK expression independently of nuclear retention. These data reveal the ability of PR acetylation to alter the magnitude of transcriptional response at selected (slow response) promoters (SGK), whereas the hinge region dictates the kinetics of the transcriptional response to hormone at other (rapid response) promoters (c-myc). In sum, the PR hinge region is multifunctional. Understanding the ability of this region to couple acetylation, phosphorylation, and nuclear entry may provide clues to mechanisms of altered hormone responsiveness.

Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors.

Human progesterone receptors (PR) rapidly activate cytosolic signaling pathways, in addition to their classical function as ligand-activated transcription factors. Using ER+/PR-B+ T47D breast cancer cells, we probed the role of progestin-stimulated rapid PR signaling in the transcriptional regulation of target genes involved in breast cancer cell proliferation. Epidermal growth factor receptor (EGFR) was rapidly activated after a 10-min treatment with R5020. Progestin induced EGFR-, c-Src-, and MAPK-dependent phosphorylation of PR-B on the MAPK consensus site, Ser345. Ser345-phosphorylated PR-B receptors strongly associated with specificity protein 1 (Sp1) transcription factors to regulate PR cell cycle (p21) and growth-promoting (EGFR) target genes whose promoters lack canonical progesterone response element sequences. Inhibitors of EGFR, c-Src, or MAPK activities blocked PR tethering to Sp1 and progestin-stimulated S-phase entry. Mutant PR-B receptors defective for c-Src binding (mPro) were not phosphorylated on Ser345 in response to progestin and failed to interact with Sp1. Hormone-induced complexes containing Sp1 and wild-type PR-B, but not S345A or mPro PR-B, were recruited to Sp1 sites within the endogenous p21 promoter. Progestin-induced S-phase entry was attenuated in T47D cells containing wild-type PR-B and treated with EGFR, c-Src, or MAPK kinase inhibitors or in T47D cells stably expressing mPro or mutant DNA-binding domain PR-B. In sum, rapid progestin-activated PR signaling leads to PR Ser345 phosphorylation and tethering to Sp1. These events are critical for progestin-stimulated regulation of Sp1 target genes and breast cancer cell proliferation. Our data demonstrate the therapeutic potential for PR-targeted breast cancer treatment by exploiting multiple nodes along the PR signaling pathway, including PR-B, EGFR, c-Src, MAPK, or Sp1.

Enhancing hepatic glycolysis reduces obesity: differential effects on lipogenesis depend on site of glycolytic modulation.

Reducing obesity requires an elevation of energy expenditure and/or a suppression of food intake. Here we show that enhancing hepatic glycolysis reduces body weight and adiposity in obese mice. Overexpression of glucokinase or 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is used to increase hepatic glycolysis. Either of the two treatments produces similar increases in rates of fatty acid oxidation in extrahepatic tissues, i.e., skeletal muscle, leading to an elevation of energy expenditure. However, only 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase overexpression causes a suppression of food intake and a decrease in hypothalamic neuropeptide Y expression, contributing to a more pronounced reduction of body weight with this treatment. Furthermore, the two treatments cause differential lipid profiles due to opposite effects on hepatic lipogenesis, associated with distinct phosphorylation states of carbohydrate response element binding protein and AMP-activated protein kinase. The step at which hepatic glycolysis is enhanced dramatically influences overall whole-body energy balance and lipid profiles.