The prediction of the risk of developing complications after colorectal surgery for colorectal carcinoma remains imprecise. Body composition measurements on a computed tomography (CT) scan can potentially contribute to a better preoperative risk assessment. The aim of this systematic review is to evaluate the evidence for the use of body composition measurements on CT scans to predict short-term complications after colorectal cancer surgery. A literature search (in PubMed, Embase and Web of Science) was performed up to 1 August 2022. Two researchers independently screened the articles, extracted data and assessed the quality of the studies using the Quality in Prognosis Studies tool. The primary outcome measure was the occurrence of complications within 30 days after surgery. Meta-analysis was conducted using a random-effects model to synthesize a pooled odds ratio (OR). The study protocol was registered in PROSPERO (CRD42021281010). Forty-five articles with a total of 16 537 patients were included. In total, 26 body composition measures were investigated: 8 muscle-related measures, 11 adipose tissue measures, 4 combined muscle and adipose tissue measures, and 3 other measures. These were investigated as potential predictors for more than 50 differently defined postoperative complications. Meta-analysis was only possible for two measurements and showed that higher amounts of visceral fat increase the risk of developing overall complications (OR: 2.52 [1.58-4.00], P < 0.0001) and anastomotic leakage (OR: 1.76 [1.17-2.65], P = 0.006). A wide variety of body composition measurements on preoperative CT scans have been investigated as a predictive factor for postoperative complications. Visceral fat appeared to be associated with overall complications and anastomotic leakage; however, the association is weak, and its clinical relevance or applicability is questionable. The current evidence is limited by methodological heterogeneity and the risk of bias. To improve comparability of results across studies and improve decision-making, future studies should use standardized methods for measuring body composition on CT scans, outcome definitions and statistical analyses.
Background: The association between perioperative changes in the skeletal muscle index (SMI) and colorectal cancer (CRC) outcomes remains unclear. We aim to explore perioperative change patterns of SMI and evaluate their effects on long-term outcomes in CRC patients.
Methods: This retrospective cohort study included Stage I-III CRC patients who underwent curative resection between 2012 and 2019. SMI at the third lumbar vertebra level was calculated using computed tomography scans. Optimal cut-off values for SMI were defined separately for males and females and classified as high or low preoperatively and at 3, 6, 9 and 12 months postoperatively. SMI status was further categorized into different perioperative SMI change patterns: highpre-highpost, highpre-lowpost, lowpre-highpost and lowpre-lowpost. The association with recurrence-free survival (RFS) and overall survival (OS) was examined using Cox proportional hazards models.
Results: A total of 2222 patients (median [interquartile range] age, 60.00 [51.00-68.00] years; 1302 (58.60%) men; 222 (9.99%) with preoperative low SMI) were evaluated. During a median follow-up of 60 months, 375 patients (16.88%) died, and 617 patients (27.77%) experienced a recurrence. Multivariate Cox model analysis showed that, compared to patients with highpre-highpost, those with highpre-lowpost (HR = 3.32, 95% CI: 1.60-6.51; HR = 2.54, 95% CI: 1.03-6.26; HR = 2.93, 95% CI: 1.19-7.19, all p < 0.05) had significantly worse RFS and OS (HR = 4.07, 95% CI: 1.55-10.69; HR = 4.78, 95% CI: 1.40-16.29; HR = 9.69, 95% CI: 2.53-37.05, all p < 0.05), at postoperative 6, 9 and 12 months, respectively. Patients with lowpre-lowpost were an independent prognostic factor for worse OS at postoperative 12 months (HR = 3.20, 95% CI: 1.06-9.71, p = 0.040). Patients with lowpre-highpost had similar risk of RFS compared to those with highpre-highpost at postoperative 3, 6 and 12 months (HR = 1.49, 95% CI: 0.75-2.98; HR = 1.05, 95% CI: 0.45-2.43; HR = 1.36, 95% CI: 0.31-6.06, all p > 0.05) and similar risk of OS at postoperative 3, 6, 9 and 12 months (all p > 0.05).
Conclusions: Patients with a high preoperative SMI that decline postoperatively have poor RFS and OS. Consistently low SMI also correlates with worse OS. Patients with low SMI but increased after resection are not an indicator of better prognosis. Routine measurement of postoperative, rather than preoperative, SMI is warranted. Patients with low SMI are at an increased risk for recurrence and death, especially within the first year after surgery.
Background: ADCK genes encode aarF domain-containing mitochondrial kinases involved in coenzyme Q (CoQ) biosynthesis and regulation. Haploinsufficiency of ADCK2 in humans leads to adult-onset physical incapacity with reduced mitochondrial CoQ levels in skeletal muscle, resulting in mitochondrial myopathy and alterations in fatty acid β-oxidation. The sole current treatment for CoQ deficiencies is oral administration of CoQ10, which causes only partial recovery with postnatal treatment, underscoring the importance of early diagnosis for successful intervention.
Methods: We used Adck2 heterozygous mice to examine the influence of this gene on muscle structure, function and regeneration throughout development, growth and ageing. This investigation involved techniques including immunohistochemistry, analysis of CoQ levels, mitochondrial respiratory content, muscle transcriptome analysis and functional tests.
Results: We demonstrated that Adck2 heterozygous mice exhibit defects from embryonic development, particularly in skeletal muscle (1102 genes deregulated). Adck2 heterozygous embryos were 7% smaller in size and displayed signs of delayed development. Prenatal administration of CoQ10 could mitigate these embryonic defects. Heterozygous Adck2 mice also showed a decrease in myogenic cell differentiation, with more severe consequences in 'aged' mice (41.63% smaller) (P < 0.01). Consequently, heterozygous Adck2 mice displayed accelerated muscle wasting associated with ageing in muscle structure (P < 0.05), muscle function (less grip strength capacity) (P < 0.001) and muscle mitochondrial respiration (P < 0.001). Furthermore, progressive CoQ10 administration conferred protective effects on mitochondrial function (P < 0.0001) and skeletal muscle (P < 0.05).
Conclusions: Our work uncovered novel aspects of CoQ deficiencies, revealing defects during embryonic development in mammals for the first time. Additionally, we identified the gradual establishment and progression of the deleterious Adck2 mouse phenotype. Importantly, CoQ10 supplementation demonstrated a protective effect when initiated during development.
Background: The risk of sarcopenia in older adults with chronic kidney disease (CKD) not yet on dialysis is controversial. The aims of this study were to investigate the association among sarcopenia, diabetes and predialysis CKD and evaluate the impact of gender and ageing on the risk of sarcopenia statuses in older patients with predialysis CKD.
Methods: The participants aged ≥60 years old were recruited from the community of New Taipei City, Taiwan. Handgrip strength, appendicular skeletal muscle mass and the 6-m walk were measured. The diagnosis of sarcopenia was established based on the consensus of Asian Sarcopenia Working Group 2019. These older adults were categorised into G1, G2 and G3-5 according to the guidelines of Kidney Disease Improving Global Outcomes (KDIGO) after calculating the estimated glomerular filtration rate by the Modification of Diet in Renal Disease equation. The Chi-square test and ANOVA were used to estimate the difference of categorical and continuous variables, respectively. Polytomous logistic regression was employed to assess the odds ratio (OR) and 95% confidence intervals (CIs) of the sarcopenia status and sarcopenia-associated risk factors in the predialysis CKD patients. All tests were two-sided, and p < 0.05 was defined as statistical significance.
Results: Among the 3648 older adults (mean age: 71.9 ± 6.07 years), including 1701 males and 1947 females, 870 (23.9%), 94 (2.58%) and 48 (1.32%) had possible sarcopenia, sarcopenia and severe sarcopenia, respectively. After adjustment, the risk for possible sarcopenia, sarcopenia and severe sarcopenia significantly increased with ageing (OR = 1.11, 1.10 and 1.23; 95% CI = 1.10-1.13, 1.07-1.15 and 1.18-1.30, respectively) and male gender (OR = 2.26, 20.3 and 25.4; 95% CI = 1.87-2.73, 11.5-36.0 and 11.3-57.2, respectively). Compared with KDIGO G1, no significant association between KDIGO G3-5 and the statuses of sarcopenia was observed (OR = 0.97, 0.88 and 0.91; 95% CI = 0.75-1.26, 0.43-1.78 and 0.37-2.27, p = 0.821, 0.718, 0.838, for possible sarcopenia, sarcopenia and severe sarcopenia, respectively). Ageing and male gender indicated a significant risk for higher sarcopenia status in older patients with predialysis CKD (0.027-fold/year and 0.284-fold, respectively) (p < 0.0001).
Conclusions: This study illuminated the importance of the male sex and the ageing process on the risk of sarcopenia progression in patients with predialysis CKD. Early clinical screening and aggressive treatment for the prevention of higher sarcopenia status in advanced older male adults with predialysis CKD are recommended.
Background: Orbicularis oris muscle, the crucial muscle in speaking, facial expression and aesthetics, is considered the driving force for optimal lip repair. Impaired muscle regeneration remains the main culprit for unsatisfactory surgical outcomes. However, there is a lack of study on how different surgical manipulations affect lip muscle regeneration, limiting efforts to seek effective interventions.
Methods: In this study, we established a rat lip surgery model where the orbicularis oris muscle was injured by manipulations including dissection, transection and stretch. The effect of each technique on muscle regeneration was examined by histological analysis of myogenesis and fibrogenesis. The impact of tensile force was further investigated by the in vitro application of mechanical strain on cultured myoblasts. Transcriptome profiling of muscle satellite cells from different surgical groups was performed to figure out the key factors mediating muscle fibrosis, followed by therapeutic intervention to improve muscle regeneration after lip surgeries.
Results: Evaluation of lip muscle regeneration till 56 days after injury revealed that the stretch group resulted in the most severe muscle fibrosis (n = 6, fibrotic area 48.9% in the stretch group, P < 0.001, and 25.1% in the dissection group, P < 0.001). There was the lowest number of Pax7-positive nuclei at Days 3 and 7 in the stretch group (n = 6, P < 0.001, P < 0.001), indicating impaired satellite cell expansion. Myogenesis was impaired in both the transection and stretch groups, as evidenced by the delayed peak of centrally nucleated myofibers and embryonic MyHC. Meanwhile, the stretch group had the highest percentage of Pdgfra+ fibro-adipogenic progenitors infiltrated area at Days 3, 7 and 14 (n = 6, P = 0.003, P = 0.006, P = 0.037). Cultured rat lip muscle myoblasts exhibited impaired myotube formation and fusion capacity when exposed to a high magnitude (ε = 2688 μ strain) of mechanical strain (n = 3, P = 0.014, P = 0.023). RNA-seq analysis of satellite cells isolated from different surgical groups demonstrated that interleukin-10 was the key regulator in muscle fibrosis. Administration of recombinant human Wnt7a, which can inhibit the expression of interleukin-10 in cultured satellite cells (n = 3, P = 0.041), exerted an ameliorating effect on orbicularis oris muscle fibrosis after stretching injury in surgical lip repair.
Conclusions: Tensile force proved to be the most detrimental manoeuvre for post-operative lip muscle regeneration, despite its critical role in correcting lip and nose deformities. Adjunctive biotherapies to regulate the interleukin-10-mediated inflammatory process could facilitate lip muscle regeneration under conditions of high surgical tensile force.
Background: Cancer cachexia complicates advanced non-small cell lung cancer (NSCLC); however, it remains unclear how often cachexia occurs and how it affects the course of chemotherapy in patients receiving first-line systemic therapy.
Methods: We conducted a multicentre, prospective observational study and enrolled previously untreated NSCLC patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2 and cachexia between September 2020 and September 2021. The primary outcome measure was the trends in the Functional Assessment of Anorexia/Cachexia Treatment and Anorexia/Cachexia Subscale [FAACT (A/CS)] scores by cohort. Secondary outcome measures included the incidence of cachexia before the initiation of first-line systemic therapy, quality of life (QOL) measures, body weight (BW) changes, and efficacy and safety of first-line systemic therapy.
Results: A total of 887 consecutive patients with previously untreated advanced NSCLC and ECOG PS of 0-2 who were initiated on first-line systemic therapy were evaluated. A total of 281 patients (31.7%) experienced BW loss consistent with the criteria of cachexia, and 186 were evaluated for QOL, BW and outcome measurements. Overall, 180/186 patients received first-line systemic therapy. Cohort 1 (targeted therapy), cohort 2 [cytotoxic chemotherapy (CTx) ± immune checkpoint inhibitors (ICIs)] and cohort 3 (ICIs) included 42, 98 and 40 patients, respectively. There were significant variations in QOL trends by cohort, with chemotherapy-associated emesis affecting early appetite-related QOL. The change in the FAACT (A/CS) score at 1 week from baseline was worse in cohort 2 (the least square mean change ± standard error: -3.0 ± 0.9) than in cohorts 1 (1.6 ± 1.2, p = 0.003) and 3 (1.8 ± 1.0, p = 0.002); meanwhile, the change at 6 weeks was worse in cohort 1 (-1.5 ± 1.2) than in cohorts 2 (3.6 ± 0.9, p = 0.001) and 3 (3.5 ± 1.1, p = 0.004). BW reduction was observed in all cohorts within 6 weeks of therapy initiation. The targeted therapy cohort demonstrated superior progression-free survival (PFS) and overall survival (OS) to CTx ± ICIs cohort or ICIs cohort (median PFS was 9.7 months, 6.3 months, 3.1 months, in cohort 1, 2, 3, respectively (cohort 1 vs. cohort 2: HR, 0.58, p = 0.018; cohort 1 vs. cohort 3: HR, 0.41, p = 0.001); median OS was not reached, 15.8 months, 9.9 months, respectively (cohort 1 vs. cohort 2: HR, 0.52, p = 0.033; cohort 1 vs. cohort 3: HR, 0.37, p = 0.003).
Conclusions: Approximately 1/3 patients with previously untreated advanced NSCLC have cachexia. Appetite-related QOL trends vary based on the type of first-line systemic therapy in cachectic NSCLC patients, and the PFS and OS of these patients seemed to be shorter.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：