The impact of preoperative sarcopenia on postoperative ileus following colorectal cancer surgery.

PURPOSE: Sarcopenia is associated with poor short- and long-term patient outcomes following colorectal surgery. Despite postoperative ileus (POI) being a major complication following colorectal surgery, the predictive value of sarcopenia for POI is unclear. We assessed the association between sarcopenia and POI in patients with colorectal cancer. METHODS: Elective colorectal cancer surgery patients were retrospectively included (2018-2022). The cross-sectional psoas area was calculated using preoperative staging imaging at the level of the 3rd lumbar vertebrae. Sarcopenia was determined using gender-specific cut-offs. The primary outcome POI was defined as not achieving GI-2 by day 4. Demographics, operative characteristics, and complications were compared via univariate and multivariate analyses. RESULTS: Of 297 patients, 67 (22.6%) were sarcopenic. Patients with sarcopenia were older (median 74 (IQR 67-82) vs. 69 (58-76) years, p < 0.001) and had lower body mass index (median 24.4 (IQR 22.2-28.6) vs. 28.8 (24.9-31.9) kg/m2, p < 0.001). POI was significantly more prevalent in patients with sarcopenia (41.8% vs. 26.5%, p = 0.016). Overall rate of complications (85.1% vs. 68.3%, p = 0.007), Calvien-Dindo grade > 3 (13.4% vs. 10.0%, p = 0.026) and length of stay were increased in patients with sarcopenia (median 7 (IQR 5-12) vs. 6 (4-8) days, p = 0.013). Anastomotic leak rate was higher in patients with sarcopenia although the difference was not statistically significant (7.5% vs. 2.6%, p = 0.064). Multivariate analysis demonstrated sarcopenia (OR 2.0, 95% CI 1.1-3.8), male sex (OR 1.9, 95% CI 1.0-3.5), postoperative hypokalemia (OR 3.2, 95% CI 1.6-6.5) and increased opioid use (OR 2.4, 95% CI 1.3-4.3) were predictive of POI. CONCLUSION: Sarcopenia demonstrates an association with POI. Future research towards truly identifying the predictive value of sarcopenia for postoperative complications could improve informed consent and operative planning for surgical patients.

Effect of neuromuscular reversal with neostigmine/glycopyrrolate versus sugammadex on postoperative ileus following colorectal surgery.

BACKGROUND: Postoperative ileus (POI) is a common complication following colorectal surgery and is mediated in part by the cholinergic anti-inflammatory pathway (CAIP). Neostigmine (acetylcholinesterase inhibitor), co-administered with glycopyrrolate, is frequently given for neuromuscular reversal before tracheal extubation and modulates the CAIP. An alternative reversal agent, sugammadex (selective rocuronium or vecuronium binder), acts independently from the CAIP. The aim of our study was to assess the impact of neuromuscular reversal agents used during anaesthesia on gastrointestinal recovery. METHODS: Three hundred thirty-five patients undergoing elective colorectal surgery at the Royal Adelaide Hospital between January 2019 and December 2021 were retrospectively included. The primary outcome was GI-2, a validated composite measure of time to diet tolerance and passage of stool. Demographics, 30-day complications and length of stay were collected. Univariate and multivariate analyses were performed. RESULTS: Two hundred twenty-four (66.9%) patients (129 [57.6%] males and 95 [42.4%] females, median age 64 [19-90] years) received neostigmine/glycopyrrolate and 111 (33.1%) received sugammadex (62 [55.9%] males and 49 [44.1%] females, median age 67 [18-94] years). Sugammadex patients achieved GI-2 sooner after surgery (median 3 (0-10) vs. 3 (0-12) days, p = 0.036), and reduced time to first stool (median 2 (0-10) vs. 3 (0-12) days, p = 0.035). Rates of POI, complications and length of stay were similar. On univariate analysis, POI was associated with smoking history, previous abdominal surgery, colostomy formation, increased opioid use and postoperative hypokalaemia (p < 0.05). POI was associated with increased complications, including anastomotic leak and prolonged hospital stay (p < 0.001). On multivariate analysis, neostigmine, bowel anastomoses and increased postoperative opioid use (p < 0.05) remained predictive of time to GI-2. CONCLUSIONS: Patients who received sugammadex had a reduced time to achieving first stool and GI-2. Neostigmine use, bowel anastomoses and postoperative opioid use were associated with delayed time to achieving GI-2.

HFE and ALK3 act in the same signaling pathway.

Hepcidin deficiency leads to iron overload by increased dietary iron uptake and iron release from storage cells. The most frequent mutation in Hfe leads to reduced hepcidin expression and thereby causes iron overload. Recent findings suggested that HFE activates hepcidin expression predominantly via the BMP type I receptor ALK3. Here, we investigated whether HFE exclusively utilizes ALK3 or other signaling mechanisms also. We generated mice with double deficiency of Hfe and hepatocyte-specific Alk3 and compared the iron overload phenotypes of these double knockout mice to single hepatocyte-specific Alk3 deficient or Hfe knockout mice. Double Hfe-/-/hepatic Alk3fl/fl;Alb-Cre knockouts develop a similar iron overload phenotype compared to single hepatocyte-specific Alk3 deficient mice hallmarked by serum iron levels, tissue iron content and hepcidin levels of similar grades. HFE protein levels were increased in Alk3fl/fl;Alb-Cre mice compared to Alk3fl/fl mice, which was caused by iron overload - and not by Alk3 deficiency. The data provide evidence by genetic means that 1. HFE exclusively uses the BMP type I receptor ALK3 to induce hepcidin expression and 2. HFE protein expression is induced by iron overload, which further emphasizes the iron sensing function of HFE.

Prognostic understanding, quality of life and mood in patients undergoing hematopoietic stem cell transplantation.

Little is known about how patients undergoing hematopoietic stem cell transplantation (HCT) and their family caregivers (FC) perceive their prognosis. We examined prognostic understanding in patients undergoing HCT and their FC and its relationship with quality of life (QOL) and mood. We conducted a longitudinal study of patients (and FC) hospitalized for HCT. We used a questionnaire to measure participants' prognostic understanding and asked the oncologists to estimate patients' prognosis prior to HCT. We assessed QOL and mood weekly and evaluated the relationship between prognostic understanding, and QOL and mood using multivariable linear mixed models. We enrolled 90 patients undergoing (autologous (n=30), myeloablative (n=30) or reduced intensity allogeneic (n=30)) HCT. About 88.9% of patients and 87.1% of FC reported it is 'extremely' or 'very' important to know about prognosis. However, 77.6% of patients and 71.7% of FC reported a discordance and more optimistic prognostic perception compared to the oncologist (P<0.0001). Patients with a concordant prognostic understanding with their oncologists reported worse QOL (ß=-9.4, P=0.01) and greater depression at baseline (ß=1.7, P=0.02) and over time ((ß=1.2, P<0.0001). Therefore, Interventions are needed to improve prognostic understanding, while providing patients with adequate psychological support.

Development of a Postpartum Stressor Measure.

To develop a brief self-report assessment of the type and magnitude of stressors during the postpartum period. A cross-sectional study of a convenience sample of 138 women at Massachusetts General Hospital in Boston, MA completed a measure of postpartum stressors at their 6-week postpartum visit. Item analyses were conducted; items were eliminated based on low relevance, low endorsement, and cross-loadings, resulting in a 9-item measure. Items were summed to create a total postpartum stressors score. To establish concurrent validity with perceived stress, the total postpartum stressors score was correlated with the 4-item Perceived Stress Scale (PSS-4). The stressors score was tested for bivariate associations with depression (Patient Health Questionnaire-2) and with social support (three items adapted from the MOS Social Support Scale). The 9-item measure, which was comprised of three factors (baby care, well-being, and work) demonstrated good reliability (Cronbach's α = .74) and concurrent validity with the PSS-4 (r = .53; p < .001) in the current sample. The stressors total score was negatively associated with social support (p < .001) and was positively associated with depression symptoms (p < .001). The early psychometric results on this measure are promising and associated with postpartum social support and depressive symptoms. With additional research to enhance external validity, this measure could be used and tested in an intervention study at the 6-week postpartum visit to identify women at risk for distress.

Transition in the thin-filament arrangement in rat skeletal muscle.

The transition in thin-filament arrangement from tetragonal near the Z-band to trigonal in the A-band was investigated by computer-assisted analysis of thin-filament arrangement in serially cross-sectioned rat muscle. Extensor digitorum longus (EDL; fast) muscle from adult rats and adult, 9-day and 3-day neonatal soleus (slow) muscle were serially cross-sectioned from the H-zone of one sarcomere to the H-zone of an adjacent sarcomere. Thin-filament arrangement was analysed throughout the I-band, and particularly at three levels of the sarcomere: in the I-band, one section (0.06 microns) from the Z-band; six sections (0.36 microns) from the Z-band; in the A-band, two sections from the A-I junction (0.72 microns from the Z-band). Data for radical distributions and annular distributions were obtained by computer. In all muscles studies, thin-filament arrangement exhibited four-neighbour ordering throughout the I-band. Thin-filament arrangement exhibited three-neighbour ordering only in the A-band. The transition in thin-filament arrangement from four-neighbour to three-neighbour ordering occurred within 0.12 microns of the A-I junction in muscles fixed at rest length. In adult soleus that had been stretched 20% so that the A-I junction moved away from the N2-line, the transition in thin-filament arrangement occurred in the I-band within a region 0.4-0.5 microns from the Z-band. This region corresponds to the N2-line region of the I-band. Thus, the transition from four-neighbour to three-neighbour ordering occurs in the I-band independent of the thin filament-thick filament interaction. We conclude that some inherent feature of the I-band or thin filament-thin filament interaction imposes a four-neighbour ordering on thin filaments from the Z-band to the N2-line.

Thin filaments are not of uniform length in rat skeletal muscle.

The variation in thin filament length was investigated in slow and fast muscle from adult and neonatal rats. Soleus (slow) muscle from adult, 3-, 7-, and 9-d-old rats, and extensor digitorum longus (EDL; fast) muscle from adult rats were serially cross-sectioned. The number of thin filaments per 0.06 microns2 (TF#) was counted for individual myofibrils followed from the H zone of one sarcomere, through the I-Z-I region, to the H zone of an adjacent sarcomere TF# was pooled by distance from the Z band or AI junction. In both adult muscles, thin filament length varied from 0.18 to 1.20 microns, with approximately 25% of the thin filaments less than 0.7 microns in length. In 7- and 9-d soleus, thin filament length ranged from 0.18 to 1.08 microns; except for the longest (0.18 to 1.20 microns) filaments, the distribution of thin filament lengths was similar to that in adult muscle. In 3-d soleus, thin filament length was more uniform, with less than 5% of the filaments shorter than 0.7 microns. In all neonatal muscles, there were approximately 15% fewer thin filaments per unit area as compared to adult muscles. We conclude: (a) In rat skeletal muscle, thin filaments are not of uniform length, ranging in length from 0.18 to 1.20 microns. (b) There may be two stages of thin filament assembly in neonatal muscle: between 3 and 7 d when short thin filaments may be preferentially or synthesized or inserted near the Z-band, and between 9 d and adult when thin filaments of all lengths may be synthesized or inserted into the myofibril.

Effects of dietary carnitine on myocardial palmitate oxidation in the aging rat.

Aging is associated with decreases in myocardial fatty acid oxidation and carnitine concentration. The purpose of this study was to investigate the effects of dietary carnitine manipulation on myocardial palmitate oxidation and carnitine content in young adult and middle-aged rats. Rats were fed either a carnitine-free or a carnitine-supplemented diet for nine weeks and killed at ages 6.5 and 18 months. Myocardial carnitine content was unaffected by age or diet. However, in 18 months rats fed a carnitine-free diet, myocardial palmitate oxidation was 77% higher, carnitine palmitoyltransferase activity 39% higher, and lipid droplet volume density 55% higher compared to 18 month rats fed a carnitine-supplemented diet. In 6.5 month rats, dietary carnitine had no effect on these variables. These results indicate that dietary carnitine restriction increases myocardial fatty acid metabolism in middle-aged but not in young adult rats.