Mutations in the leptin-melanocortin pathway and weight loss after bariatric surgery: a systematic review and meta-analysis.

OBJECTIVE: The objective of this meta-analysis was to quantify the overall effects of gene mutations in the leptin-melanocortin pathway on short- and long-term weight loss after bariatric surgery. METHODS: MEDLINE, PubMed, and Embase were searched, and data were analyzed using ReviewManager (RevMan) version 5.4. The datasets were divided into two subgroups based on postoperative time, and the outcome measure was the percentage of total weight loss. Meta-regression analysis was performed, and the outcome was presented as the weighed mean difference of percentage of total weight loss. RESULTS: The results showed that patients with mutations in the leptin-melanocortin pathway experienced 3.03% lower total weight loss after bariatric surgery (mean difference, -3.03; 95% CI: -3.63 to -2.44), mainly reflected in lower long-term postoperative weight loss (mean difference, -3.43; 95% CI: -4.09 to -2.77), whereas mutation carriers exhibited a magnitude of short-term postoperative weight loss that was similar to patients without such mutations (total difference value, -1.13; 95% CI: -2.57 to 0.31). CONCLUSIONS: Mutations in leptin-melanocortin pathway genes reduce long-term weight loss after bariatric surgery, whereas this effect may not be reflected during the period of rapid weight loss within 12 months. These genetic variants increase the difficulties in maintaining patients' long-term weight loss.

Total weight loss induces the alteration in thyroid function after bariatric surgery.

Background: Bariatric surgery is an effective approach to weight loss, which may also affect thyroid function. However, alteration in thyroid-stimulating hormone (ΔTSH) and thyroid hormones after bariatric surgery and the relationship between thyroid function and postoperative weight loss still remains controversial. Methods: Data were collected from euthyroid patients with obesity who underwent sleeve gastrectomy and Roux-en-Y gastric bypass from 2017 to 2022. The alterations of free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), total triiodothyronine (TT3), and TSH were calculated 1 year after surgery. Pearson correlation analysis was used to assess the correlation between the percentage of total weight loss (%TWL) and ΔTSH. Multivariable linear regression was utilized to determine the association between %TWL and ΔTSH. Results: A total of 256 patients were included in our study. The mean %TWL was 28.29% after 1 year. TSH decreased from 2.33 (1.67, 3.04) uIU/mL to 1.82 (1.21, 2.50) uIU/mL (P < 0.001), FT3 decreased from 3.23 ± 0.42 pg/mL to 2.89 ± 0.41 pg/mL (P < 0.001), FT4 decreased from 1.11 ± 0.25 ng/dL to 1.02 ± 0.25 ng/dL (P < 0.001), TT3 decreased from 1.13 (1.00, 1.25) ng/mL to 0.89 (0.78, 1.00) ng/mL (P < 0.001), and TT4 decreased from 8.28 ± 1.69 ug/mL to 7.82 ± 1.68 ug/mL 1 year postoperatively (P < 0.001). %TWL was found to be significantly correlated to ΔTSH by Pearson correlation analysis (Pearson correlation coefficient = 0.184, P = 0.003), indicating that the more weight loss, the more TSH declined. After adjusting for covariates in multivariable linear regression, %TWL was found to be independently associated with ΔTSH (ß = 0.180 [95% confidence interval (CI), 0.048 - 0.312], P = 0.008). Moreover, %TWL was divided into 3 categorical groups (%TWL ≤ 25%, 25% < %TWL ≤ 35%, and %TWL > 35%) for further exploration, and was also found to be an independent predictor for ΔTSH after adjusting for covariates in multivariable linear regression (ß = 0.153 [95% CI, 0.019 - 0.287], P = 0.025). Conclusion: TSH, FT4, FT3, TT4, and TT3 decrease significantly 1 year after bariatric surgery. The decline in TSH is independently mediated by postoperative weight loss; the more the weight loss, the more the TSH decrease.

Effects of mesotherapy introduction of compound glycyrrhizin injection on the treatment of moderate to severe acne.

BACKGROUND: Compound glycyrrhizin has achieved outstanding results in the treatment of various skin diseases. However, the use of mesotherapy to inject compound glycyrrhizin into the skin to treat acne is still understudied. AIMS: This paper aims to explore the effects of mesotherapy introduction of compound glycyrrhizin injection on the acne. MATERIALS & METHODS: A total of 108 patients were included in this study and divided into the control group (n = 54) and the observation group (n = 54). The control group was treated with topical clindamycin gel, while the study group was treated with topical clindamycin gel + mesotherapy and compound glycyrrhizin injection. Skin transepidermal water loss (TEWL), cuticle water content, acne severity, adverse reactions, and inflammatory reactions were documented before and after treatment in the two groups. RESULTS: The usage of mesotherapy to inject compound glycyrrhizin into the skin of acne patients more effectively treat acne than traditional clindamycin gel. The mesotherapy compound glycyrrhizin can more effectively protect the skin barrier of patients and reduce the loss of skin moisture. Compared with the traditional clindamycin gel, the combination of mesotherapy and compound glycyrrhizin more effectively inhibit the inflammatory reaction in acne patients and reduce skin damage in acne patients. DISCUSSION/CONCLUSION: Mesoderm introduction of compound glycyrrhizin injection has better effects on the treatment of moderate to severe acne than clindamycin gel.

Prevalence of anemia and related nutrient deficiencies after sleeve gastrectomy: A systematic review and meta-analysis.

This study aimed to investigate the prevalence of anemia and related nutrient deficiencies after sleeve gastrectomy (SG). Four online databases were searched for relevant articles. Thirty-one studies with 7639 patients were included in the meta-analysis. The pooled anemia prevalence was 7%, 6%, 9%, 10%, 12%, 25%, 20%, and 18% at baseline, 3 months, 6 months, 12 months, 24 months, 36 months, 48 months, and 60 months, respectively. Although the prevalence of vitamin B12 and folate deficiencies remained low postoperatively, the prevalence of ferritin deficiency steadily increased from 6% at baseline to 27% at 60 months. The prevalence of serum iron deficiency decreased from 13% at baseline to 6% at 24 months and increased to 20% at 60 months. Anemia and ferritin deficiency were strongly correlated (Pearson correlation coefficient = 0.774, p = 0.041). Subgroup analysis suggested that age ≤40 years, preoperative anemia, and insufficient iron supplementations were high-risk factors for postoperative anemia. SG is associated with an increased risk of anemia and decreased iron storage over long-term observation. Routine iron supplementations may reduce anemia after SG; however, the dosages recommended by current guidelines may be insufficient. More strict monitoring schedules and supplementation strategies should be established for the timely detection and management of postoperative anemia.

Spatiotemporal genomic analysis reveals distinct molecular features in recurrent stage I non-small cell lung cancers.

Stage I non-small cell lung cancer (NSCLC) presents diverse outcomes. To identify molecular features leading to tumor recurrence in early-stage NSCLC, we perform multiregional whole-exome sequencing (WES), RNA sequencing, and plasma-targeted circulating tumor DNA (ctDNA) detection analysis between recurrent and recurrent-free stage I NSCLC patients (CHN-P cohort) who had undergone R0 resection with a median 5-year follow-up time. Integrated analysis indicates that the multidimensional clinical and genomic model can stratify the prognosis of stage I NSCLC in both CHN-P and EUR-T cohorts and correlates with positive pre-surgical deep next generation sequencing (NGS) ctDNA detection. Increased genomic instability related to DNA interstrand crosslinks and double-strand break repair processes is significantly associated with early tumor relapse. This study reveals important molecular insights into stage I NSCLC and may inform clinical postoperative treatment and follow-up strategies.

Comprehensive Analysis of Clinical Logistic and Machine Learning-Based Models for the Evaluation of Pulmonary Nodules.

Introduction: Over the years, multiple models have been developed for the evaluation of pulmonary nodules (PNs). This study aimed to comprehensively investigate clinical models for estimating the malignancy probability in patients with PNs. Methods: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for studies reporting mathematical models for PN evaluation until March 2020. Eligible models were summarized, and network meta-analysis was performed on externally validated models (PROSPERO database CRD42020154731). The cut-off value of 40% was used to separate patients into high prevalence (HP) and low prevalence (LP), and a subgroup analysis was performed. Results: A total of 23 original models were proposed in 42 included articles. Age and nodule size were most often used in the models, whereas results of positron emission tomography-computed tomography were used when collected. The Mayo model was validated in 28 studies. The area under the curve values of four most often used models (PKU, Brock, Mayo, VA) were 0.830, 0.785, 0.743, and 0.750, respectively. High-prevalence group (HP) models had better results in HP patients with a pooled sensitivity and specificity of 0.83 (95% confidence interval [CI]: 0.78-0.88) and 0.71 (95% CI: 0.71-0.79), whereas LP models only achieved pooled sensitivity and specificity of 0.70 (95% CI: 0.60-0.79) and 0.70 (95% CI: 0.62-0.77). For LP patients, the pooled sensitivity and specificity decreased from 0.68 (95% CI: 0.57-0.78) and 0.93 (95% CI: 0.87-0.97) to 0.57 (95% CI: 0.21-0.88) and 0.82 (95% CI: 0.65-0.92) when the model changed from LP to HP models. Compared with the clinical models, artificial intelligence-based models have promising preliminary results. Conclusions: Mathematical models can facilitate the evaluation of lung nodules. Nevertheless, suitable model should be used on appropriate cohorts to achieve an accurate result.

Comparison of Clinical and Pathological Characteristics Between Extremely Multiple GGNs and Single GGNs.

OBJECTIVE: This study aims to compare the clinical and pathological characteristics between patients undergoing surgery for extremely multiple ground-glass nodules (GGNs) and those for single GGN. METHODS: We defined extremely multiple GGNs as follows: (i) number of GGNs ≥3, (ii) GGN diameter between 3 and 30 mm, and (iii) no less than three nodules that were surgically removed and pathologically diagnosed. Patients with extremely multiple GGNs and single GGNs who underwent surgery at the same time were retrospectively analyzed. The patients were divided into three groups according to the number of nodules: exceedingly multiple nodules (EMN) group (>10), highly multiple nodules (HMN) group (three to 10), and single nodule (SN) group. The clinical and pathological characteristics, surgical methods and prognosis were analyzed. RESULTS: Ninety-nine patients with single nodules and 102 patients with extremely multiple nodules were enrolled. Among the patients with extremely multiple nodules, 43 (42.2%) had >10 nodules. There were no significant differences in demographic characteristics, such as age, sex, and smoking history, between the groups, but there were differences in tumor characteristics. All patients with >10 nodules showed bilateral pulmonary nodules and presented with both pure and mixed GGNs. The single GGNs were smaller in diameter, and the proportion of mixed GGNs and pathologically invasive adenocarcinoma was lower than that of the primary nodules in the exceedingly multiple GGNs group (p < 0.05). However, the proportion of both mixed GGNs and malignant nodules decreased significantly with the increasing number of total lesions. During postoperative follow-up, one patient in the highly multiple nodules group had a local recurrence, and 16 (15.7%) patients in the extremely multiple GGNs group and 10 (9.8%) patients in the single GGN group had enlarged unresected GGNs or additional GGNs. CONCLUSIONS: Our study revealed the clinical and pathologic characteristics, surgical methods, and prognosis of patients with extremely multiple GGNs and compared them with those of patients with a single GGN. Although the primary nodules in extremely multiple GGNs may have higher malignancy than those in the single nodule group, the proportion of both mGGNs and malignant nodules decreased significantly with the increasing number of lesions, and the prognosis of patients with extremely multiple GGNs was satisfied.

Molecular Alterations in Lung Adenocarcinoma With Ground-Glass Nodules: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Nodular ground-glass lesions have become increasingly common with the increased use of computed tomography (CT), while the genomic features of ground-glass opacities (GGOs) remain unclear. This study aims to comprehensively investigate the molecular alterations of GGOs and their correlation with radiological progression. METHODS: Studies from PubMed, Embase, Cochrane Library, and Web of Science, using PCR, targeted panel sequencing, whole exosome sequencing, and immunohistochemistry, and reporting genomic alterations or PD-L1 expressions in lung nodules presenting as GGOs until January 21, 2021 were included in this study. Chi-square test, random-effects model, and Z-test analysis were adopted to analyze the data. RESULTS: A total of 22 studies describing mutations in lung adenocarcinoma (LUAD) with GGOs were analyzed. EGFR was the most frequently mutative gene (51%, 95%CI 47%-56%), followed by TP53 (18%, 95%CI 6%-31%), HER2 (10%, 95%CI 0%-21%), ROS1 (6%, 95%CI 0%-18%), and KRAS (6%, 95%CI 3%-9%). The correlation between the frequency of EGFR mutation and radiological was observed and the differences were found to be not statistically significant in the subgroups, which are listed as below: radiological: gGGO 47.40%, 95%CI [38.48%; 56.40%]; sGGO 51.94%, 95%CI [45.15%; 58.69%]. The differences of the frequency of KRAS mutation in the different subgroups were also consistent with this conclusion, which are listed as: radiological gGGO 3.42, 95%CI [1.35%; 6.13%]; sGGO 12.27%, 95%CI [3.89%; 23.96%]. The pooled estimated rate of PD-L1 was 8.82%, 95%CI [5.20%-13.23%]. A total of 11.54% (3/26) of the SMGGNs were confirmed to be intrapulmonary spread by WES. CONCLUSIONS: Somatic genetic alterations are considered in early-stage GGO patients without distinct changes of the frequency following the progress of the tumor. This review sheds insight on molecular alterations in LUAD with GGOs.

Development and Validation of Machine Learning-based Model for the Prediction of Malignancy in Multiple Pulmonary Nodules: Analysis from Multicentric Cohorts.

PURPOSE: Nodule evaluation is challenging and critical to diagnose multiple pulmonary nodules (MPNs). We aimed to develop and validate a machine learning-based model to estimate the malignant probability of MPNs to guide decision-making. EXPERIMENTAL DESIGN: A boosted ensemble algorithm (XGBoost) was used to predict malignancy using the clinicoradiologic variables of 1,739 nodules from 520 patients with MPNs at a Chinese center. The model (PKU-M model) was trained using 10-fold cross-validation in which hyperparameters were selected and fine-tuned. The model was validated and compared with solitary pulmonary nodule (SPN) models, clinicians, and a computer-aided diagnosis (CADx) system in an independent transnational cohort and a prospective multicentric cohort. RESULTS: The PKU-M model showed excellent discrimination [area under the curve; AUC (95% confidence interval (95% CI)), 0.909 (0.854-0.946)] and calibration (Brier score, 0.122) in the development cohort. External validation (583 nodules) revealed that the AUC of the PKU-M model was 0.890 (0.859-0.916), higher than those of the Brock model [0.806 (0.771-0.838)], PKU model [0.780 (0.743-0.817)], Mayo model [0.739 (0.697-0.776)], and VA model [0.682 (0.640-0.722)]. Prospective comparison (200 nodules) showed that the AUC of the PKU-M model [0.871 (0.815-0.915)] was higher than that of surgeons [0.790 (0.711-0.852), 0.741 (0.662-0.804), and 0.727 (0.650-0.788)], radiologist [0.748 (0.671-0.814)], and the CADx system [0.757 (0.682-0.818)]. Furthermore, the model outperformed the clinicians with an increase of 14.3% in sensitivity and 7.8% in specificity. CONCLUSIONS: After its development using machine learning algorithms, validation using transnational multicentric cohorts, and prospective comparison with clinicians and the CADx system, this novel prediction model for MPNs presented solid performance as a convenient reference to help decision-making.

Surgical Prognosis of Synchronous Multiple Primary Lung Cancer: Systematic Review and Meta-Analysis.

BACKGROUND: We evaluated the long-term prognosis of synchronous multiple primary lung cancer (SMPLC) patients after surgical treatment and explored prognostic factors for overall survival (OS). MATERIALS AND METHODS: A systematic review and meta-analysis was performed regarding the surgical prognosis of SMPLC. A literature search was performed using online databases. All studies were rigorously categorized following the 8th edition of the tumor, node, metastasis classification (TNM) staging rules for multiple lung cancers: SMPLC and multifocal ground-glass/lepidic (GG/L) lung cancers. Five-year OS after surgery was pooled, and hazard ratios (HRs) for prognostic factors were synthesized. Specific subgroup analysis and sensitivity analysis were conducted (PROSPERO registration CRD42019142420). RESULTS: An analysis of 26 studies including 1788 patients was performed. The pooled 5-year OS was 45% (95% confidence interval [CI], 37-53) of true SMPLC patients and 62% (95% CI, 57-67) of patients with pathologic stage I disease, which was different from the 5-year OS of 93% (95% CI, 85-100) of patients with multifocal GG/L lung cancers. Poor prognostic factors for SMPLC were lymph node metastasis (HR = 2.36; 95% CI, 1.75-3.20; P < .001) and pneumonectomy (HR = 2.96; 95% CI, 1.36-6.45; P = .006], whereas histology (HR = 1.11; 95% CI, 0.82-1.50; P = .508), laterality (HR = 1.16; 95% CI, 0.93-1.44, P = .190), sublobar resection (HR = 1.29; 95% CI, 0.90-1.84; P = .159), and adjuvant therapy (HR = 1.07; 95% CI, 0.64-1.80; P = .791) were not found to influence the outcome. CONCLUSION: The long-term prognosis of SMPLC patients after surgery is acceptable, especially in patients with early-stage disease. Sublobar resection can be applied, although pneumonectomy should be avoided. Advanced criteria are needed to diagnose SMPLC and distinguish it from multifocal GG/L lung cancer to perform accurate surgical evaluation.

Minimally invasive surgery versus thoracotomy for resectable stage II and III non-small-cell lung cancers: a systematic review and meta-analysis.

OBJECTIVES: The study aimed to compare the long-term oncological efficacy and perioperative outcomes of patients with locally advanced non-small-cell lung cancers who underwent minimally invasive surgery (MIS) or thoracotomy. METHODS: Cochrane Library, PubMed and EMBASE databases, ClinicalTrials.gov and reference lists were searched for relevant studies. Two reviewers independently assessed the quality of the studies. Recurrence-free survival (RFS) and overall survival (OS) and perioperative outcomes were synthesized. Random-effects models were used to summarize hazard ratios (HRs), relative risks and standardized mean differences (SMDs) with 95% confidence intervals (CIs). RESULTS: Twenty-three retrospective cohort studies were reviewed with a total of 3281 patients, of whom 1376 (41.9%) received MIS and 1905 (58.1%) received thoracotomy. Meta-analysis showed no significant differences in both RFS (HR, 1.02; 95% CI, 0.89-1.17; P = 0.78) and OS (HR, 0.91; 95% CI, 0.80-1.03; P = 0.15) between MIS versus thoracotomy approaches. Similar results were observed in propensity score matched studies (RFS, HR, 0.94; 95% CI, 0.73-1.20; P = 0.62; OS, HR, 0.96; 95% CI, 0.72-1.30; P = 0.81). No significant difference was found in lymph node clearance and margin positivity. As for perioperative outcomes, MIS was associated with a significant reduction in postoperative complications (relative risk, 0.83; P = 0.01), intraoperative blood loss (standardized mean difference, -0.68; P = 0.007), chest tube drainage (standardized mean difference, -0.38; P = 0.03) and length of hospital stay (standardized mean difference, -0.79; P = 0.002) when compared with thoracotomy. CONCLUSIONS: The use of MIS for resectable stage II and III non-small-cell lung cancers is an eligible alternative to conventional thoracotomy without compromising the long-term survival and short-term outcomes.

Perioperative Dynamic Changes in Circulating Tumor DNA in Patients with Lung Cancer (DYNAMIC).

PURPOSE: No study has investigated the precise perioperative dynamic changes in circulating tumor DNA (ctDNA) in any patients with early-stage cancer. This study (DYNAMIC) investigated perioperative dynamic changes in ctDNA and determined the appropriate detection time of ctDNA-based surveillance for surgical patients with lung cancer.Experimental Design: Consecutive patients who underwent curative-intent lung resections were enrolled prospectively (NCT02965391). Plasma samples were obtained at multiple prespecified time points including before surgery (time A), during surgery after tumor resection (time B-time D), and after surgery (time P1-time P3). Next-generation sequencing-based detection platform was performed to calculate the plasma mutation allele frequency. The primary endpoint was ctDNA half-life after radical tumor resection. RESULTS: Thirty-six patients showed detectable mutations in time A. The plasma ctDNA concentration showed a rapid decreasing trend after radical tumor resection, with the average mutant allele fraction at times A, B, C, and D being 2.72%, 2.11%, 1.14%, and 0.17%, respectively. The median ctDNA half-life was 35.0 minutes. Patients with minimal residual disease (MRD) detection had a significant slower ctDNA half-life than those with negative MRD (103.2 minutes vs. 29.7 minutes, P = 0.001). The recurrence-free survival of patients with detectable and undetectable ctDNA concentrations at time P1 was 528 days and 543 days, respectively (P = 0.657), whereas at time P2 was 278 days and 637 days, respectively (P = 0.002). CONCLUSIONS: ctDNA decays rapidly after radical tumor resection. The ctDNA detection on the third day after R0 resection can be used as the baseline value for postoperative lung cancer surveillance.