Much To Do About Frailty Berian, Julia R; Wolf, Joshua H; Kunitake, Hiroko
Diseases of the colon & rectum,
04/2022, Letnik:
65, Številka:
4
Journal Article
Receptor tyrosine kinase signaling cooperates with WNT/β-catenin signaling in regulating many biological processes, but the mechanisms of their interaction remain poorly defined. We describe a potent ...activation of WNT/β-catenin by FGFR2, FGFR3, EGFR and TRKA kinases, which is independent of the PI3K/AKT pathway. Instead, this phenotype depends on ERK MAP kinase-mediated phosphorylation of WNT co-receptor LRP6 at Ser1490 and Thr1572 during its Golgi network-based maturation process. This phosphorylation dramatically increases the cellular response to WNT. Moreover, FGFR2, FGFR3, EGFR and TRKA directly phosphorylate β-catenin at Tyr142, which is known to increase cytoplasmic β-catenin concentration via release of β-catenin from membranous cadherin complexes. We conclude that signaling via ERK/LRP6 pathway and direct β-catenin phosphorylation at Tyr142 represent two mechanisms used by various receptor tyrosine kinase systems to activate canonical WNT signaling.
Malnutrition has been associated with adverse surgical outcomes, but data regarding its impact specifically in rectal cancer are sparse. The goal of this study was to use national data to determine ...the effects of malnutrition on surgical outcomes in rectal cancer resection.
Data were obtained from the American College of Surgeons National Surgical Quality Initiative Program from the years 2012-2015. Patients were included on the basis of International Classification of Disease 9/10 and Current Procedural Terminology codes for rectal cancer and proctectomy. Malnutrition was defined as body mass index <18.5 kg/m2, weight loss >10% in 6 mo, or preoperative albumin <3.5 mg/dL. Associations between malnutrition and postoperative outcomes were assessed by the Student t-test and chi-square test. Multivariate regression models were constructed to adjust for potential confounders of the association between malnutrition and surgical outcomes.
Of the 9289 patients with primary rectal cancer who underwent resection, 1425 (15%) were in a state of malnutrition at the time of surgery. Patients with malnutrition had longer mean length of stay (LOS), and higher rates of 30-d mortality, wound infection, organ-space infection, sepsis, reoperation, prolonged LOS (>30 d), failure to wean off ventilator, renal failure, and cardiac arrest. With the exception of LOS, renal failure, and organ-space infection, malnutrition was still significantly associated with higher rates of these adverse outcomes after adjustment for confounders in multivariate regression models.
Malnutrition is a practical marker associated with a variety of adverse outcomes after rectal cancer surgery, and it represents a potential target for nutritional therapies to improve surgical outcomes.
Patients with Crohn’s disease are particularly susceptible to preoperative frailty owing to the chronic nature of the illness and immunosuppressive therapy. The hypothesis in this study was that ...frailty would have a greater impact on postoperative outcome than age in older individuals with Crohn’s disease.
Data were obtained from the National Surgical Quality Improvement Program (NSQIP) from the years 2012 to 2018. Patients with Crohn’s disease who underwent a bowel resection were identified from diagnostic and procedure codes. Frailty was assessed using the 5-point Simplified Frailty Index (0–not frail, 5–most frail). Age was defined as an ordinal variable with 3 age ranges (18–64, 65–79, >80 years). Aggregate morbidity was classified according to the standard NSQIP definitions. Simplified Frailty Index was evaluated as a potential predictor of morbidity and mortality using covariate-adjusted logistic regression modeling.
A total of 9,023 patients underwent bowel resection for Crohn’s disease during the study period. Patient Simplified Frailty Index ranged from 0 to 3 (Simplified Frailty Index = 0, 82%; 1, 15%; 2, 2.5%; 3, 0.1%), and higher Simplified Frailty Index was associated with increased age (P < .01). In multivariate regression, a Simplified Frailty Index was significantly associated with postoperative morbidity (Simplified Frailty Index ≥ 2: odds ratio = 2.59, 95% confidence interval 1.84–3.63, P < .0001). In contrast, age was not found to be a significant predictor of morbidity when adjusted for Simplified Frailty Index and other covariates (P > .05).
Frailty is a stronger predictor than age for morbidity in Crohn’s-related bowel resection. Functional assessments and vulnerability screening should be used to determine surgical candidacy rather than age alone.
•Increased odds of venous thromboembolism occurrence with increased frailty.•1.85-fold increase in venous thromboembolism odds for modified frailty index ≥3.•Frailty more strongly associated with ...venous thromboembolism than age.•Modified frailty index useful as venous thromboembolism risk stratification tool.
Curative surgery for ulcerative colitis can be subdivided into restorative (with pouch and anastomosis) and non-restorative operations. Restorative surgery in older adults is controversial, due to ...concerns about surgical risk and long-term functional outcome. The goal of this study is to compare 30-day outcomes for restorative and non-restorative surgery in older adults with ulcerative colitis.
Data were obtained from the American College of Surgeons National Surgical Quality Initiative Program from 2012-2018. Patients were included if they were >65 years old and had ulcerative colitis. Restorative and non-restorative surgeries were defined with procedure codes. Patient characteristics and adverse surgical outcomes were compared between restorative and non-restorative surgeries utilizing chi-square tests and Fisher's exact tests. Multivariate logistic regression models were constructed to evaluate the association of restorative versus non-restorative surgery with adverse surgical outcomes while adjusting for potential confounders.
Of 392 total patients, 95 had restorative and 297 had non-restorative surgery. Patients undergoing restorative surgery, compared to non-restorative surgery, were significantly younger (P<0.01), had lower incidences of steroid usage (P<0.001) and higher rates of readmission (P = 0.02). There were no differences in post-operative complications between the groups in both unadjusted analyses and covariate-adjusted regression analysis (P > 0.05).
In carefully selected older patients with ulcerative colitis, restorative surgery is associated with increased readmission, but otherwise similar rates of morbidity or mortality compared to non-restorative surgery. Data regarding postoperative functional outcome and quality of life are also needed to help select the most appropriate curative option for older adults.
Older and younger adults are offered similar analgesic options after hemorrhoid surgery (HS), but the differences in pain between the two populations are unknown. This study aims to compare ...postoperative pain outcomes after HS in older and younger individuals.
This is a retrospective analysis of electronic medical records of patients who underwent HS between 2018 and 2023. Patients were excluded if additional anorectal procedures were performed at the time of HS. Data related to pain-related outcomes were compiled: (1) need for narcotic prescription refills; (2) documentation of a pain-related phone call within 30 d; (3) urgent postoperative office visit before regular scheduled follow-up; and (4) pain-related postoperative emergency department visits. Associations between age and pain-related outcomes were tested using Fisher's exact test, chi-square test, and covariate adjusted logistic regression modeling.
There were a total of 249 patients, 60 older adults, and 189 younger adults. Compared to younger patients, older adults demonstrated a reduced frequency of pain-related phone calls (10.3 versus 32.1%, P < 0.01) and opioid refills (0 versus 14.4%, P < 0.01). After adjusting for confounders, older age remained inversely associated with pain-related postoperative phone calls (odds ratio = 0.25, 95% confidence interval = 0.1-0.6, P = 0.003).
Older adults had better pain outcomes after HS in comparison to younger patients. These findings suggest that the postoperative analgesic needs of older patients after HS are lower than those of younger patients. Decisions regarding opioid prescription in older adults recovering from HS should be tailored to avoid narcotic-related complications.
Background: Post-operative day zero (POD-0) discharge after laparoscopic appendectomy for uncomplicated appendicitis has been studied primarily in single-center or pediatric studies. A larger study ...from a national sample addressing high-yield outcomes can update and supplement current literature and evaluate early discharge rates.
Methods: This is a retrospective, observational National Surgical Quality Improvement (NSQIP) database study of laparoscopic appendectomies for uncomplicated appendicitis performed 2016-2019, with discharge POD-0 or post-operative day one (POD-1). Study outcomes included any or serious complication, unplanned readmission, and unplanned return to operating room (OR). Unadjusted outcomes comparisons were estimated via chi-square tests. Multivariate logistic regression models were constructed to adjust for potential confounders (sex, ethnicity, frailty, ASA score, tobacco use and diabetes).
Results: A total of 25,629 patients were included in this analysis. More patients were discharged POD-1 (n = 15,229) than POD-0 (n = 10,440). Rate of any or serious complication was lower in patients discharged POD-0 than POD-1 (any complication: 2.0 vs. 2.8, p = 0.0002, serious complication: 1.4 vs. 2.1, p < 0.0001). Unplanned return to OR and unplanned readmission rates were not different between POD-0 and POD-1 discharged groups (p = 0.9 and p = 0.6, respectively). These findings were robust to adjustment for covariates in logistic regression modeling.
Conclusions: This study found that unplanned readmission and other outcomes do not appear to be adversely affected by early discharge after laparoscopic appendectomy for uncomplicated appendicitis, confirming prior evidence on the topic in a large, national sample. It also found that early discharge does not appear to be used in most of these patients.
Post-operative day 0 discharge after laparoscopic appendectomy for uncomplicated appendicitis does not increase readmission or return to OR - but is it happening in practice?
Introduction
Discharging older individuals to rehabilitation facilities is associated with adverse outcomes, including readmission or increased mortality rate. As preoperative functional status is an ...important factor impacting patient outcome, we hypothesized that this would be associated with patient disposition to nonhome locations.
Materials and Methods
A retrospective analysis was performed using data from the 2013–2018 American College of Surgeons National Surgical Quality Improvement Program, including targeted variables from the Geriatric Pilot Project. Patients aged 65 and older in 33 institutions across the nation were included (n = 44,219). Preoperative functional status was categorized as independent, partially dependent, and dependent. The primary outcome was home versus nonhome disposition. Nonhome was defined as rehabilitation facility and nursing home. Descriptive analyses were performed. Variables associated with postoperative discharge to nonhome were identified using logistic regression.
Results
The largest percentage of operations was orthopedics (40.8%), followed by general surgery (29.2%) and vascular operations (10.0%). The majority of the patients were independent before operations (93.1% independent, 6% partially dependent, and 0.9% totally dependent). In regression analyses, patients who were partially dependent preoperatively had five times higher odds of discharging to nonhome, compared to patients who were independent (odds ratio OR 5.04, p < 0.01). Similarly, patients who were totally dependent had 3.2 higher odds of discharging to nonhome than patients who were independent (OR 3.22, p < 0.01).
Conclusion
Better preoperative functional status is associated with patient discharge to home in older adults. Preoperative interventions aimed at improving functional status, such as prehabilitation, may be beneficial in improving patient outcomes.
Background
Podocytes have a remarkable ability to recover from injury; however, little is known about the recovery mechanisms involved in this process. We recently showed that formoterol, a ...long-acting β
2
-adrenergic receptor (β
2
-AR) agonist, induced mitochondrial biogenesis (MB) in podocytes and led to renoprotection in mice. However, it is not clear whether this effect was mediated by formoterol acting through the β
2
-AR or if it occurred through “off-target” effects.
Methods
We genetically deleted the β
2
-AR specifically in murine podocytes and used these mice to determine whether formoterol acting through the podocyte β
2
-AR alone is sufficient for recovery of renal filtration function following injury. The podocyte-specific β
2
-AR knockout mice (β
2
-AR
fl/fl
/PodCre) were generated by crossing β
2
-AR floxed mice with podocin Cre (B6.Cg-Tg(NPHS2-cre)295Lbh/J) mice. These mice were then subjected to both acute and chronic glomerular injury using nephrotoxic serum (NTS) and adriamycin (ADR), respectively. The extent of injury was evaluated by measuring albuminuria and histological and immunostaining analysis of the murine kidney sections.
Results
A similar level of injury was observed in β
2
-AR knockout and control mice; however, the β
2
-AR
fl/fl
/PodCre mice failed to recover in response to formoterol. Functional evaluation of the β
2
-AR
fl/fl
/PodCre mice following injury plus formoterol showed similar albuminuria and glomerular injury to control mice that were not treated with formoterol.
Conclusions
These results indicate that the podocyte β
2
-AR is a critical component of the recovery mechanism and may serve as a novel therapeutic target for treating podocytopathies.
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