Background: Peripheral nerve decompression (PND) is generally safe, and newer techniques allow frail patients to undergo PND at less common sites. Current literature suggests patient frailty measures may more accurately predict postsurgical complications versus other proxies, but no current literature examines frailty in PND. Methods: The authors reviewed data from the National Surgical Quality Improvement Program for patients who underwent PND outside the most common sites from 2013 to 2019. The modified 5-Item Frailty Index (mFI-5) and modified Charlson Comorbidity Index (mCCI) scores were calculated, and complications data were gathered. Age, body mass index (BMI), major comorbidities, American Society of Anesthesiologists class, and frailty were compared as predictors of all-cause 30-day complications, 30-day surgical site complications, length of stay, and complication severity, using univariate and multivariate logistic regression. Results: Of 1120 patients, the mean age was 51.3 (15.4) years and mean BMI was 30.6 (7.0) kg/m2. Patients were predominantly white and healthy. The complication rate was 3.4%. All-cause complications were predicted by ≥3 major comorbidities (odds ratio [OR], 95% confidence interval [CI]: 6.26, 1.36-21.32; P = .007), followed by mFI-5 score and mCCI score. Complication severity was associated with major comorbidities and mFI-5 score, while length of stay was most strongly predicted by age ≥ 65 years (OR, 95% CI: 2.17, 1.37-3.42; P = .0008) and mCCI score of 3 (OR, 95% CI: 1.77, 1.01-3.05; P = 0.041). The only risk factor for readmission was mFI-5 score of 1 (OR, 95% CI: 7.00, 1.68-47.16; P = .016). Conclusions: Frailty and risk proxies may predict postoperative complications in PND at uncommon sites. Use of frailty indices may expand the age range of patients offered PND. Further research is necessary to delineate contributing risk factors and to clarify 24-hour observation and admissions.
BACKGROUND: Although age, body mass index (BMI), and major comorbidities were historically used as predictors of surgical risk, recent literature supports patient frailty as a more accurate predictor. Database studies and chart reviews support the modified Charlson Comorbidity Index (mCCI) and the Modified Five-Item Frailty Index (mFI-5) as predictors of postsurgical complications in plastic surgery. The authors hypothesized that the mFI-5 and mCCI are more predictive of abdominoplasty complications than historic risk proxies. METHODS: A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program database was performed for abdominoplasty patients from 2013 to 2019. Demographics, comorbidities, and complications were gathered. The mFI-5 and mCCI scores were calculated per patient. Age, BMI, major comorbidities, American Society of Anesthesiologists class, mFI-5 score, and mCCI score were compared as predictors of all-cause 30-day complications, 30-day surgical-site complications, length of stay, and aggregate Clavien-Dindo complication severity score. RESULTS: Of 421 patients, the strongest predictors for all-cause complications and complication severity were mCCI score greater than or equal to 3 and mFI-5 score greater than or equal to 2. The mFI-5 score was the strongest predictor of unplanned reoperation. Length of stay was best predicted by age greater than or equal to 65. The only predictor of surgical-site complications was BMI greater than or equal to 30.0 kg/m 2 . Smoking was predictive of complication severity, but not any other outcome. CONCLUSIONS: The mFI-5 and mCCI are stronger outcome predictors than historically used factors, which showed little predictive value in this cohort. Although the mCCI is a stronger predictor than the mFI-5, the mFI-5 is easily calculated during an initial consultation. Surgeons can apply these tools to aid in risk stratification for abdominoplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.
Frailty , Humans , Frailty/complications , Frailty/diagnosis , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Comorbidity , Quality Improvement , Reoperation/adverse effects , Retrospective Studies , Risk Factors , Risk Assessment
Background: The ability to predict breast implant augmentation complications can significantly inform patient management. A frailty measure, such as the modified 5-item frailty index (mFI-5), is becoming an increasingly established risk factor for adverse postoperative outcomes. The authors hypothesized that the mFI-5 is predictive of 30-day postoperative complications in breast augmentation. Objectives: To investigate if mFI-5 can predict the likelihood and magnitude of 30-day complications resulting from breast augmentations. Methods: A retrospective review study of the National Surgical Quality Improvement Program database for patients who underwent breast implant augmentation without other concurrent procedures, from 2015 to 2019. Age, BMI, number of major comorbidities, American Society of Anesthesiologists (ASA) classifications, smoking status, mFI-5 score, and modified Charlson comorbidity index score were compared as predictors of all-cause 30-day complications and 30-day surgical-site complications using regression analyses. Results: Overall, 2478 patients were analyzed, and among them, 53 patients developed complications (2.14%). mFI-5 score significantly predicted surgical-site infection (SSI) complications (odds ratio [OR] = 4.24, P = .026). Frail patients had a higher occurrence of SSIs than nonfrail patients (P = .049). Multivariable analyses showed ASA class predicted 30-day SSI complications (OR = 5.77, P = .027) and mFI-5 approached, but did not reach full significance in predicting overall 30-day complications (OR = 3.14, P = .085). Conclusions: To date, the impact of frailty on breast implant procedure outcomes has not been studied. Our analysis demonstrates that the mFI-5 is a significant predictor for SSIs in breast implant augmentation surgery and is associated with overall complications. By preoperatively identifying frail patients, the surgical team can better account for postoperative support to minimize the risk of complications.
PURPOSE: The present study sought to evaluate whether the mFI-5 and modified Charlson Comorbidity Index (mCCI) are stronger predictors of 30-day postoperative complications after open reduction of facial fractures compared with historic risk proxies. METHODS: A retrospective review of the American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) database was conducted to investigate patients who underwent open reduction facial fracture surgery between 2013 and 2018. Risk factors including age, smoking status, body mass index (BMI), comorbidities, and American Society of Anesthesiologists (ASA) class were extracted for each patient. The mFI-5 score and mCCI score were calculated based on this data. Univariate logistic regressions were performed (P<0.05). RESULTS: A total of 2667 cases were included. Of these, 2131 (80%) were male. The strongest predictors for overall 30-day complications and complication severity were ASA class ≥3 (Odds Ratio [OR]=3.34), comorbidities ≥2 (OR=2.78), mCCl score ≥2 (OR=2.19), and mFI-5 ≥1 (OR=1.96). Smoking status and BMI were not strong predictors of total complications or complication severity. Age was found to be a statically significant, but low-impact, predictor of complications, and severity (OR=1.02, P<0.001). The only significant predictors of surgical site infections (SSI) were smoking status (OR=1.56) and ASA class ≥3 (OR=2.40). mFI-5 ≥1 was a significant predictor of hospital readmission. BMI was not associated with any increased risk. CONCLUSIONS: The mCCI and mFI-5 are statistically significant predictors of total complications and complication severity in open reduction of facial fracture repair, and thus provide a tool to inform decision making and improve care. Smoking status may increase risk for SSIs following facial fracture repair.
Frailty , Skull Fractures , Humans , Male , Female , Open Fracture Reduction/adverse effects , Surgical Wound Infection/epidemiology , Patient Readmission
BACKGROUND: Hand and wrist injuries can cause painful, everyday obstacles for patients. Carefully indexing preoperative patient health conditions may better inform surgical care, leading to improved postoperative outcomes. The purpose of the present study is to evaluate if the Modified-Five Item Frailty Index (mFI-5) can accurately predict postoperative complications for hand and wrist surgical repair. METHODS: A retrospective review of the American College of Surgeons' National Surgical Quality Improvement Program database was conducted to investigate patients who underwent hand and wrist surgical repair from January 2013 to December 2019. Patient demographics, comorbidities, surgical logistics, and 30-day readmission due to postoperative complications were extracted. Surgical risk proxies including the mFI-5, age, body mass index (BMI), smoking status within 1 year, the Modified Charlson Comorbidity Index (mCCI), comorbidities, and American Society of Anaesthesiologists Physical Status Classification (ASA class) were calculated. RESULTS: A total of 11 369 patients were included. Thirty-day readmission for total postoperative complications (n = 258) was significantly associated with all surgical risk proxies. However, age, mFI-5 > 2, mCCI > 2, comorbidities > 1, and ASA class 2/3 had the highest statistical significance (P = <.001). Thirty-day readmission rates for surgical site infections (n = 118) had the highest statistical significance with age, BMI, mFI-5 > 2, and ASA class 2/3 (P = <.001). A Clavien-Dindo score > 1 (n = 224) had the highest statistical significance with age, mCCI > 2, comorbidity of 1, and an ASA class 3 (P = <.001). CONCLUSIONS: The mFI-5 may have value in predicting 30-day readmission due to postoperative complications after surgical repair of hand and wrist injuries.
Rix7 is an essential AAA+ ATPase that functions during the early stages of ribosome biogenesis. Rix7 is composed of three domains including an N-terminal domain (NTD) and two AAA+ domains (D1 and D2) that assemble into an asymmetric stacked hexamer. It was recently established that Rix7 is a presumed protein translocase that removes substrates from preribosomes by translocating them through its central pore. However, how the different domains of Rix7 coordinate their activities within the overall hexameric structure was unknown. We captured cryo-electron microscopy (EM) structures of single and double Walker B variants of full length Rix7. The disordered NTD was not visible in the cryo-EM reconstructions, but cross-linking mass spectrometry revealed that the NTD can associate with the central channel in vitro. Deletion of the disordered NTD enabled us to obtain a structure of the Rix7 hexamer to 2.9 Å resolution, providing high resolution details of critical motifs involved in substrate translocation and interdomain communication. This structure coupled with cell-based assays established that the linker connecting the D1 and D2 domains as well as the pore loops lining the central channel are essential for formation of the large ribosomal subunit. Together, our work shows that Rix7 utilizes a complex communication network to drive ribosome biogenesis.
BACKGROUND: Breast reduction is a generally well-tolerated procedure with high patient satisfaction and low risk of surgical site infection and other complications. Although age, obesity, and comorbidities have historically been used as surgical risk proxies, recent literature suggests "frailty" measures, such as the modified 5-item Frailty Index (mFI-5), may be a superior predictor. OBJECTIVES: The aim of this study was to investigate if mFI-5 can predict the likelihood and magnitude of 30-day complications resulting from breast reductions. METHODS: A retrospective review was performed of the National Surgical Quality Improvement Program (NSQIP) database to assess patients who underwent breast reduction without other concurrent procedures, from 2013 to 2019. mFI-5 scores were calculated for each patient, and complication data were gathered. Age, BMI, number of major comorbidities, American Association of Anesthesiologists class, smoking status, diabetes, steroid use, and mFI-5 score were compared as predictors of all-cause 30-day complications, 30-day surgical site complications of any kind, length of stay, and aggregate Clavien-Dindo complication severity score. Univariate logistic, linear regressions, and multivariate logistic regression analyses were performed to evaluate predictive value. Statistical significance was set at Pâ <â 0.05. RESULTS: A total of 14,160 patients were analyzed. The overall complication rate was 5.6%. The mFI-5 score significantly predicted overall 30-day complications, surgical site complications, complication severity, overnight stay, and likelihood of readmission (all Pâ <â 0.0001). CONCLUSIONS: The mFI-5 is a statistically significant predictor for adverse outcomes in breast reduction surgery. The mFI-5 is a simple and reliable tool that can be efficiently used to conduct a preoperative evaluation of patients requesting breast reductions.
Frailty , Mammaplasty , Female , Frailty/complications , Humans , Mammaplasty/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Quality Improvement , Retrospective Studies , Risk Assessment , Risk Factors , United States/epidemiology
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the United States, and effective therapies for PDAC are currently lacking. Moreover, PDAC is promoted and exacerbated by obesity, while cachexia and sarcopenia are exceptionally common comorbidities that predict both poor survival and treatment response. Managing PDAC with immunotherapies has thus far proven ineffective, partly due to the metabolically hostile tumor microenvironment. ß-hydroxy-ß-methylbutyrate (HMB), a metabolite of leucine commonly used as a dietary supplement to boost muscle growth and immune function, may be an attractive candidate to augment PDAC therapy. We therefore sought to test the hypothesis that HMB would enhance antitumor immunity while protecting mouse muscle mass. Control and diet-induced obese C57BL/6 male mice bearing subcutaneously injected Panc02 tumors were supplemented with 1% HMB and treated with or without 50 mg/kg gemcitabine (n = 15/group). HMB was associated with reduced muscle inflammation and increased muscle fiber size. HMB also reduced tumor growth and promoted antitumor immunity in obese, but not lean, mice, independent of the gemcitabine treatment. Separately, in lean tumor-bearing mice, HMB supplementation promoted an anti-PD1 immunotherapy response (n = 15/group). Digital cytometry implicated the decreased abundance of M2-like macrophages in PDAC tumors, an effect that was enhanced by anti-PD1 immunotherapy. We confirmed that HMB augments M1-like macrophage (antitumor) polarization. These preclinical findings suggest that HMB has muscle-sparing and antitumor activities against PDAC in the context of obesity, and that it may sensitize otherwise nonresponsive PDAC to immunotherapy.
Cancer cells experience unique and dynamic shifts in their metabolic function in order to survive, proliferate, and evade growth inhibition in the resource-scarce tumor microenvironment. Therefore, identification of pharmacological agents with potential to reprogram cancer cell metabolism may improve clinical outcomes in cancer therapy. Cancer cells also often exhibit an increased dependence on the process known as autophagy, both for baseline survival and as a response to stressors such as chemotherapy or a decline in nutrient availability. There is evidence to suggest that this increased dependence on autophagy in cancer cells may be exploitable clinically by combining autophagy modulators with existing chemotherapies. In light of the increased metabolic rate in cancer cells, interest is growing in approaches aimed at "starving" cancer through dietary and pharmacologic interventions that reduce availability of nutrients and pro-growth hormonal signals known to promote cancer progression. Several dietary approaches, including chronic calorie restriction and multiple forms of fasting, have been investigated for their potential anti-cancer benefits, yielding promising results in animal models. Induction of autophagy in response to dietary energy restriction may underlie some of the observed benefit. However, while interventions based on dietary energy restriction have demonstrated safety in clinical trials, uncertainty remains regarding translation to humans as well as feasibility of achieving compliance due to the potential discomfort and weight loss that accompanies dietary restriction. Further induction of autophagy through dietary or pharmacologic metabolic reprogramming interventions may enhance the efficacy of autophagy inhibition in the context of adjuvant or neo-adjuvant chemotherapy. Nonetheless, it remains unclear whether therapeutic agents aimed at autophagy induction, autophagy inhibition, or both are a viable therapeutic strategy for improving cancer outcomes. This review discusses the literature available for the therapeutic potential of these approaches.
Immune checkpoint inhibitor (ICI) therapy has shown extraordinary promise at treating cancers otherwise resistant to treatment. However, for ICI therapy to be effective, it must overcome the metabolic limitations of the tumor microenvironment. Tumor metabolism has long been understood to be highly dysregulated, with potent immunosuppressive effects. Moreover, T cell activation and longevity within the tumor microenvironment are intimately tied to T cell metabolism and are required for the long-term efficacy of ICI therapy. We discuss in this review the intersection of metabolic competition in the tumor microenvironment, T cell activation and metabolism, the roles of tumor cell metabolism in immune evasion, and the impact of host metabolism in determining immune surveillance and ICI therapy outcomes. We also discussed the effects of obesity and calorie restriction-two important systemic metabolic perturbations that impact intrinsic metabolic pathways in T cells as well as cancer cells.
