Propensity Score-Matching Analysis Comparing Robotic Versus Laparoscopic Limited Liver Resections of the Posterosuperior Segments: An International Multicenter Study.

OBJECTIVE: The purpose of this study was to compare the outcomes of robotic limited liver resections (RLLR) versus laparoscopic limited liver resections (LLLR) of the posterosuperior segments. BACKGROUND: Both laparoscopic and robotic liver resections have been used for tumors in the posterosuperior liver segments. However, the comparative performance and safety of both approaches have not been well examined in the existing literature. METHODS: This is a post hoc analysis of a multicenter database of 5446 patients who underwent RLLR or LLLR of the posterosuperior segments (I, IVa, VII, and VIII) at 60 international centers between 2008 and 2021. Data on baseline demographics, center experience and volume, tumor features, and perioperative characteristics were collected and analyzed. Propensity score-matching (PSM) analysis (in both 1:1 and 1:2 ratios) was performed to minimize selection bias. RESULTS: A total of 3510 cases met the study criteria, of whom 3049 underwent LLLR (87%), and 461 underwent RLLR (13%). After PSM (1:1: and 1:2), RLLR was associated with a lower open conversion rate [10 of 449 (2.2%) vs 54 of 898 (6.0%); P =0.002], less blood loss [100 mL [IQR: 50-200) days vs 150 mL (IQR: 50-350); P <0.001] and a shorter operative time (188 min (IQR: 140-270) vs 222 min (IQR: 158-300); P <0.001]. These improved perioperative outcomes associated with RLLR were similarly seen in a subset analysis of patients with cirrhosis-lower open conversion rate [1 of 136 (0.7%) vs 17 of 272 (6.2%); P =0.009], less blood loss [100 mL (IQR: 48-200) vs 160 mL (IQR: 50-400); P <0.001], and shorter operative time [190 min (IQR: 141-258) vs 230 min (IQR: 160-312); P =0.003]. Postoperative outcomes in terms of readmission, morbidity and mortality were similar between RLLR and LLLR in both the overall PSM cohort and cirrhosis patient subset. CONCLUSIONS: RLLR for the posterosuperior segments was associated with superior perioperative outcomes in terms of decreased operative time, blood loss, and open conversion rate when compared with LLLR.

Spatial transcriptomics: Technologies, applications and experimental considerations.

The diverse cell types of an organ have a highly structured organization to enable their efficient and correct function. To fully appreciate gene functions in a given cell type, one needs to understand how much, when and where the gene is expressed. Classic bulk RNA sequencing and popular single cell sequencing destroy cell structural organization and fail to provide spatial information. However, the spatial location of gene expression or of the cell in a complex tissue provides key clues to comprehend how the neighboring genes or cells cross talk, transduce signals and work together as a team to complete the job. The functional requirement for the spatial content has been a driving force for rapid development of the spatial transcriptomics technologies in the past few years. Here, we present an overview of current spatial technologies with a special focus on the commercially available or currently being commercialized technologies, highlight their applications by category and discuss experimental considerations for a first spatial experiment.

Value of lymph node dissection in intrahepatic cholangiocarcinoma: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to perform a systematic review and meta-analysis to investigate the impact of lymph node dissection (LND) on outcomes following resection of intrahepatic cholangiocarcinoma (ICC). METHODS: PubMed, EMBASE, and Cochrane were searched from inception to 30th January 2023 for studies that compared LND with no LND (NLND) among patients with ICC. To limit the effect of unbalanced covariates, only studies that utilized propensity score-based methods were included. Subgroup analysis of patients with clinically node-negative (cN0) ICC was analyzed. RESULTS: Among 3776 patients with ICC, individuals in the LND versus NLND cohorts had comparable overall survival (OS) (Hazard ratio [HR] 0.78, 95 % confidence interval [CI] 0.57-1.06, P = 0.11), disease-free survival (DFS) (HR 0.84, 95 % CI 0.70-1.01, P = 0.07) and risk of major complications (odds ratio [OR] 1.07, 95 % CI 0.70-1.62, P = 0.75). Subgroup analysis of cN0 patients, OS was significantly higher in patients who underwent LND (HR 0.61, 95 % CI 0.50-0.74, P < 0.01), with a non-significant trend towards improved DFS (HR 0.81, 95 % CI 0.65-1.01, P = 0.06). CONCLUSION: This study found no differences in long-term survival or morbidity following LND for ICC. Subgroup analysis of cN0 patients, who underwent LND detected improved OS with a trend towards better DFS, compared to patients with NLND.

Propensity-score Matched and Coarsened-exact Matched Analysis Comparing Robotic and Laparoscopic Major Hepatectomies: An International Multicenter Study of 4822 Cases.

OBJECTIVE: To compare the outcomes between robotic major hepatectomy (R-MH) and laparoscopic major hepatectomy (L-MH). BACKGROUND: Robotic techniques may overcome the limitations of laparoscopic liver resection. However, it is unknown whether R-MH is superior to L-MH. METHODS: This is a post hoc analysis of a multicenter database of patients undergoing R-MH or L-MH at 59 international centers from 2008 to 2021. Data on patient demographics, center experience volume, perioperative outcomes, and tumor characteristics were collected and analyzed. Both 1:1 propensity-score matched (PSM) and coarsened-exact matched (CEM) analyses were performed to minimize selection bias between both groups. RESULTS: A total of 4822 cases met the study criteria, of which 892 underwent R-MH and 3930 underwent L-MH. Both 1:1 PSM (841 R-MH vs. 841 L-MH) and CEM (237 R-MH vs. 356 L-MH) were performed. R-MH was associated with significantly less blood loss {PSM:200.0 [interquartile range (IQR):100.0, 450.0] vs 300.0 (IQR:150.0, 500.0) mL; P = 0.012; CEM:170.0 (IQR: 90.0, 400.0) vs 200.0 (IQR:100.0, 400.0) mL; P = 0.006}, lower rates of Pringle maneuver application (PSM: 47.1% vs 63.0%; P < 0.001; CEM: 54.0% vs 65.0%; P = 0.007) and open conversion (PSM: 5.1% vs 11.9%; P < 0.001; CEM: 5.5% vs 10.4%, P = 0.04) compared with L-MH. On subset analysis of 1273 patients with cirrhosis, R-MH was associated with a lower postoperative morbidity rate (PSM: 19.5% vs 29.9%; P = 0.02; CEM 10.4% vs 25.5%; P = 0.02) and shorter postoperative stay [PSM: 6.9 (IQR: 5.0, 9.0) days vs 8.0 (IQR: 6.0 11.3) days; P < 0.001; CEM 7.0 (IQR: 5.0, 9.0) days vs 7.0 (IQR: 6.0, 10.0) days; P = 0.047]. CONCLUSIONS: This international multicenter study demonstrated that R-MH was comparable to L-MH in safety and was associated with reduced blood loss, lower rates of Pringle maneuver application, and conversion to open surgery.

Association of metabolic-bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174 772 participants.

BACKGROUND: Metabolic-bariatric surgery delivers substantial weight loss and can induce remission or improvement of obesity-related risks and complications. However, more robust estimates of its effect on long-term mortality and life expectancy-especially stratified by pre-existing diabetes status-are needed to guide policy and facilitate patient counselling. We compared long-term survival outcomes of severely obese patients who received metabolic-bariatric surgery versus usual care. METHODS: We did a prespecified one-stage meta-analysis using patient-level survival data reconstructed from prospective controlled trials and high-quality matched cohort studies. We searched PubMed, Scopus, and MEDLINE (via Ovid) for randomised trials, prospective controlled studies, and matched cohort studies comparing all-cause mortality after metabolic-bariatric surgery versus non-surgical management of obesity published between inception and Feb 3, 2021. We also searched grey literature by reviewing bibliographies of included studies as well as review articles. Shared-frailty (ie, random-effects) and stratified Cox models were fitted to compare all-cause mortality of adults with obesity who underwent metabolic-bariatric surgery compared with matched controls who received usual care, taking into account clustering of participants at the study level. We also computed numbers needed to treat, and extrapolated life expectancy using Gompertz proportional-hazards modelling. The study protocol is prospectively registered on PROSPERO, number CRD42020218472. FINDINGS: Among 1470 articles identified, 16 matched cohort studies and one prospective controlled trial were included in the analysis. 7712 deaths occurred during 1·2 million patient-years. In the overall population consisting 174 772 participants, metabolic-bariatric surgery was associated with a reduction in hazard rate of death of 49·2% (95% CI 46·3-51·9, p<0·0001) and median life expectancy was 6·1 years (95% CI 5·2-6·9) longer than usual care. In subgroup analyses, both individuals with (hazard ratio 0·409, 95% CI 0·370-0·453, p<0·0001) or without (0·704, 0·588-0·843, p<0·0001) baseline diabetes who underwent metabolic-bariatric surgery had lower rates of all-cause mortality, but the treatment effect was considerably greater for those with diabetes (between-subgroup I2 95·7%, p<0·0001). Median life expectancy was 9·3 years (95% CI 7·1-11·8) longer for patients with diabetes in the surgery group than the non-surgical group, whereas the life expectancy gain was 5·1 years (2·0-9·3) for patients without diabetes. The numbers needed to treat to prevent one additional death over a 10-year time frame were 8·4 (95% CI 7·8-9·1) for adults with diabetes and 29·8 (21·2-56·8) for those without diabetes. Treatment effects did not appear to differ between gastric bypass, banding, and sleeve gastrectomy (I2 3·4%, p=0·36). By leveraging the results of this meta-analysis and other published data, we estimated that every 1·0% increase in metabolic-bariatric surgery utilisation rates among the global pool of metabolic-bariatric candidates with and without diabetes could yield 5·1 million and 6·6 million potential life-years, respectively. INTERPRETATION: Among adults with obesity, metabolic-bariatric surgery is associated with substantially lower all-cause mortality rates and longer life expectancy than usual obesity management. Survival benefits are much more pronounced for people with pre-existing diabetes than those without. FUNDING: None.

KMSubtraction: reconstruction of unreported subgroup survival data utilizing published Kaplan-Meier survival curves.

BACKGROUND: Data from certain subgroups of clinical interest may not be presented in primary manuscripts or conference abstract presentations. In an effort to enable secondary data analyses, we propose a workflow to retrieve unreported subgroup survival data from published Kaplan-Meier (KM) plots. METHODS: We developed KMSubtraction, an R-package that retrieves patients from unreported subgroups by matching participants on KM plots of the overall cohort to participants on KM plots of a known subgroup with follow-up time. By excluding matched patients, the opposing unreported subgroup may be retrieved. Reproducibility and limits of error of the KMSubtraction workflow were assessed by comparing unmatched patients against the original survival data of subgroups from published datasets and simulations. Monte Carlo simulations were utilized to evaluate the limits of error of KMSubtraction. RESULTS: The validation exercise found no material systematic error and demonstrates the robustness of KMSubtraction in deriving unreported subgroup survival data. Limits of error were small and negligible on marginal Cox proportional hazard models comparing reconstructed and original survival data of unreported subgroups. Extensive Monte Carlo simulations demonstrate that datasets with high reported subgroup proportion (r = 0.467, p < 0.001), small dataset size (r = - 0.374, p < 0.001) and high proportion of missing data in the unreported subgroup (r = 0.553, p < 0.001) were associated with uncertainty are likely to yield high limits of error with KMSubtraction. CONCLUSION: KMSubtraction demonstrates robustness in deriving survival data from unreported subgroups. The limits of error of KMSubtraction derived from converged Monte Carlo simulations may guide the interpretation of reconstructed survival data of unreported subgroups.

Minimally Invasive Versus Open Radical Antegrade Modular Pancreatosplenectomy: A Meta-Analysis.

BACKGROUND: Radical antegrade modular pancreatosplenectomy (RAMPS) was introduced to improve the tangential resection margin rates and N1 node clearance following resection of malignancies of the pancreatic body and tail. Owing to its technical complexity, minimally invasive RAMPS (MI-RAMPS) has only been reported by a few centers worldwide. We performed this meta-analysis to compare both short- and long-term outcomes between open RAMPS (O-RAMPS) and minimally invasive RAMPS (MI-RAMPS). METHODS: A systematic search of the electronic databases PubMed, Medline (via PubMed), Cochrane Register of Controlled Trials (CENTRAL), EMBASE, Scopus and Web of Science was performed to identify eligible studies published in the English language regardless of study design. The outcomes of interest were operation time, estimated blood loss, transfusion rates, overall complications, Grade B/C post-operative pancreatic fistula (POPF) rates, post-pancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE), length of stay (LOS), R0 resection rates, lymph node (LN) yield and overall survival (OS). RESULTS: Five non-randomized studies comprising of a total 229 patients (89 MI-RAMPS, 140 O-RAMPS) were included for analysis. Intra-operative blood loss was observed to be significantly reduced in MI-RAMPS as compared to O-RAMPS (MD -256.16, P < 0.001), while LN yield was higher in O-RAMPS as compared to MI-RAMPS (MD -2.73, P = 0.02). There were no statistically significant differences observed for the other perioperative, oncologic and survival outcomes. CONCLUSIONS: This meta-analysis provides early evidence to suggest that MI-RAMPS may produce comparable short- and long-term outcomes to O-RAMPS, when undertaken by appropriately skilled surgeons in well-selected patients. Further large-scale prospective studies are required to corroborate these findings.

Radiofrequency Ablation Versus Repeat Hepatectomy for Recurrent Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: An updated systematic review and meta-analysis was conducted to compare radiofrequency ablation (RFA) versus repeat hepatectomy (RH) for patients with recurrent hepatocellular carcinoma (rHCC) after a previous liver resection. METHODS: PubMed, EMBASE, and Cochrane databases were searched from inception to October 2021 for randomized controlled trials and propensity-score matched studies. Individual participant survival data of disease-free survival (DFS) and overall survival (OS) were extracted and reconstructed followed by one-stage and two-stage meta-analysis. Secondary outcomes were major complications and length of hospital stay (LOHS). RESULTS: A total of seven studies (1317 patients) were analysed. In both one-stage and two-stage meta-analysis, there was no significant difference in OS between the RFA and RH cohorts (Hazard Ratio (HR) 1.15, 95% CI 0.98-1.36, P = 0.094 and HR 1.12, 95% CI 0.77-1.64, P = 0.474 respectively), while the RFA group had a higher hazard rate of disease recurrence compared to the RH group (HR 1.30, 95% CI 1.13-1.50, P < 0.001 and HR 1.31, 95% CI 1.09-1.57, P = 0.013, respectively). RFA was associated with fewer major complications and shorter LOHS versus RH (Odds Ratio 0.34, 95% CI 0.15-0.76, P = 0.009 and Weighted Mean Difference - 4.78, 95% CI - 6.30 to - 3.26, P < 0.001, respectively). CONCLUSIONS: RH may be associated with superior DFS for rHCC, at the expense of higher morbidity rate and longer LOHS. However, OS is comparable between both modalities. As such, these techniques may be utilized as complementary strategies depending on individual patient and disease factors. Large-scale, randomized, prospective studies are required to corroborate these findings.

CT-based morphologic and radiomics features for the classification of MYCN gene amplification status in pediatric neuroblastoma.

PURPOSE: MYCN onco-gene amplification in neuroblastoma confers patients to the high-risk disease category for which prognosis is poor and more aggressive multimodal treatment is indicated. This retrospective study leverages machine learning techniques to develop a computed tomography (CT)-based model incorporating semantic and non-semantic features for non-invasive prediction of MYCN amplification status in pediatric neuroblastoma. METHODS: From 2009 to 2020, 54 pediatric patients treated for neuroblastoma at a specialized children's hospital with pre-treatment contrast-enhanced CT and MYCN status were identified (training cohort, n = 44; testing cohort, n = 10). Six morphologic features and 107 quantitative gray-level texture radiomics features extracted from manually drawn volume-of-interest were analyzed. Following feature selection and class balancing, the final predictive model was developed with eXtreme Gradient Boosting (XGBoost) algorithm. Accumulated local effects (ALE) plots were used to explore main effects of the predictive features. Tumor texture maps were also generated for visualization of radiomics features. RESULTS: One morphologic and 2 radiomics features were selected for model building. The XGBoost model from the training cohort yielded an area under the receiver operating characteristics curve (AUC-ROC) of 0.930 (95% CI, 0.85-1.00), optimized F1-score of 0.878, and Matthews correlation coefficient (MCC) of 0.773. Evaluation on the testing cohort returned AUC-ROC of 0.880 (95% CI, 0.64-1.00), optimized F1-score of 0.933, and MCC of 0.764. ALE plots and texture maps showed higher "GreyLevelNonUniformity" values, lower "Strength" values, and higher number of image-defined risk factors contribute to higher predicted probability of MYCN amplification. CONCLUSION: The machine learning model reliably classified MYCN amplification in pediatric neuroblastoma and shows potential as a surrogate imaging biomarker.

Laparoscopic versus open resection of hepatocellular carcinoma in patients with cirrhosis: meta-analysis.

BACKGROUND: The exact role of laparoscopic liver resection (LLR) in patients with hepatocellular carcinoma (HCC) and underlying liver cirrhosis (LC) is not well defined. In this meta-analysis, both long- and short-term outcomes following LLR versus open liver resection (OLR) were analysed. METHODS: PubMed, EMBASE, Scopus and Web of Science databases were searched systematically for randomised controlled trials (RCTs) and propensity-score matched (PSM) studies reporting outcomes of LLR versus OLR of HCC in patients with cirrhosis. Primary outcome was overall survival (OS). This was analysed using one-stage (individual participant data meta-analysis) and two-stage (aggregate data meta-analysis) approaches. Secondary outcomes were operation duration, blood loss, blood transfusion, Pringle manoeuvre utilization, overall and major complications, length of hospital stay (LOHS), 90-day mortality and R0 resection rates. RESULTS: Eleven studies comprising 1618 patients (690 LLR versus 928 OLR) were included for analysis. In the one-stage meta-analysis, an approximately 18.7 per cent lower hazard rate (HR) of death in the LLR group (random effects: HR 0.81, 95 per cent confidence interval [C.I.] 0.68 to 0.96; P = 0.018) was observed. Two-stage meta-analysis resulted in a pooled HR of 0.84 (95 per cent C.I. 0.74 to 0.96; P = 0.01) in the overall LLR cohort. This indicated a 16-26 per cent reduction in the HR of death for patients with HCC and cirrhosis who underwent LLR. For secondary outcomes, LLR was associated with less blood loss (mean difference [MD] -99 ml, 95 per cent C.I. -182 to -16 ml), reduced overall complications (odds ratio 0.49, 95 per cent C.I. 0.37 to 0.66) and major complications (odds ratio 0.45, 95 per cent C.I. 0.26 to 0.79), and shorter LOHS (MD -3.22 days, 95 per cent C.I. -4.38 to -2.06 days). CONCLUSION: Laparoscopic resection of HCC in patients with cirrhosis is associated with improved survival and perioperative outcomes.

Low-Dose Nivolumab in Renal Cell Carcinoma: A Real-World Experience.

BACKGROUND: The approved doses of the single agent nivolumab - an anti-programmed cell death protein 1 (PD-1) monoclonal antibody - for renal cell carcinoma (RCC) are 3 mg/kg and a 240-mg flat dose, despite efficacy shown at lower doses in earlier CheckMate trials. In view of financial constraints, the minimum dose of nivolumab required for efficacy remains a critical area of inquiry. METHODS: A retrospective review of RCC patients receiving single-agent anti-PD-1 treatment was conducted. Using the median cutoff of the maximum dose per body weight received, we investigated the effect of lower dosages on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and immune-related adverse event-free survival (irAE-FS). Survival analysis was made by Kaplan-Meier, by uni- and multivariable Cox models, and by modeling the statistical interaction between dosages and survival. RESULTS: 32 patients were recruited: 8 patients (25%) receiving first-line treatment and 24 (75%) receiving second-line treatment and beyond. A median split at 2.15 mg/kg yielded 16 patients in both the lower-dose (LD) and the higher-dose (HD) cohort. Hazard ratios (HRs) demonstrated no difference in OS after adjustment for gender (HR = 0.22, 95% CI 0.05-1.05, p = 0.054; favoring LD), as well as in PFS after adjustment for gender and concurrent radiation therapy (HR = 0.58, 95% CI 0.25-1.34, p = 0.210; favoring LD). No differences in ORR were observed (50.0 vs. 43.8%, p = 1.00, in the LD and the HD cohort, respectively). Immune-related phenomena were observed in the LD group, including pseudoprogression and increased all-grade immune-related toxicities (irAE-FS: HR = 1.72, 95% CI 0.48-6.14, p = 0.293; favoring HD). Iterative dichotomization of dosages showed no dose-OS or dose-irAE-FS relationship. CONCLUSION: Our study suggests no apparent reduction in efficacy when using a low-dosage nivolumab regimen.

Intra-Arterial Therapy for Unresectable Colorectal Liver Metastases: A Meta-Analysis.

PURPOSE: To evaluate the efficacy of hepatic arterial infusion (HAI), conventional transarterial chemoembolization, drug-eluting embolic transarterial chemoembolization (DEE-TACE), transarterial radioembolization, and their combinations with systemic chemotherapy (SCT) for unresectable colorectal liver metastases. METHODS: A search was conducted on Embase, Scopus, PubMed, and Web of Science for prospective nonrandomized studies and randomized controlled trials (RCTs) from inception to June 20, 2020. Survival data of patients were recovered from original Kaplan-Meier curves by exploiting a graphical reconstructive algorithm. One-stage meta-analyses were conducted for the median overall survival (OS), survival rates (SRs), and restricted mean survival time (RMST), whereas two-stage meta-analyses of proportions were conducted to determine response rates (RRs) and conversion to resection rates (CRRs). RESULTS: A total of 71 prospective nonrandomized studies and 21 RCTs were identified, comprising 6,695 patients. Among patients treated beyond the first-line, DEE-TACE + SCT (n = 152) had the best survival outcomes of median OS of 26.5 (95% confidence interval [CI], 22.5-29.1) months and a 3-year RMST of 23.6 (95% CI, 21.8-25.5) months. Upon further stratification by publication year, DEE-TACE + SCT appeared to consistently have the highest pooled SRs at 1 year (81.9%) and 2 years (66.1%) in recent publications (2015-2020). DEE-TACE + SCT and HAI + SCT had the highest pooled RRs of 56.7% (I2 = 0.90) and 62.6% (I2 = 0.87) and pooled CRRs of 35.5% (I2 = 0.00) and 30.3% (I2 = 0.80), respectively. CONCLUSIONS: Albeit significant heterogeneity, the paucity of high-quality evidence, and the noncomparative nature of all analyses, the overall evidence suggests that patients treated with DEE-TACE + SCT have the best oncological outcomes and greatest potential to be converted for resection.

Drug Coated Balloons for Dysfunctional Haemodialysis Venous Access: A Patient Level Meta-Analysis of Randomised Controlled Trials.

OBJECTIVE: To perform an individual patient data level meta-analysis of randomised controlled trials comparing drug coated balloon angioplasty (DCB) against conventional percutaneous transluminal angioplasty (PTA) in the treatment of dysfunctional haemodialysis venous access. METHODS: A search was conducted from inception to 13 November 2020. Kaplan-Meier curves comparing DCB with PTA by target lesion primary patency (TLPP) and access circuit primary patency (ACPP) were graphically reconstructed to retrieve patient level data. One stage meta-analyses with Cox models with random effects shared frailties were conducted to determine hazard ratios (HRs). Dynamic restricted mean survival times (RMST) were conducted in view of violation of the proportional hazards assumption. Conventional two stage meta-analyses and network meta-analyses under random effects Frequentist models were conducted to determine overall and comparative outcomes of paclitaxel concentrations used. Where outliers were consistently detected through outlier and influence analyses, sensitivity analyses excluding those studies were conducted. RESULTS: Among 10 RCTs (1 207 patients), HRs across all models favoured DCB (one stage shared frailty HR 0.62, 95% CI 0.53 - 0.73, p < .001; two stage random effects HR 0.60, 95% CI 0.42 - 0.86, p = .018, I2 = 65%) for TLPP. Evidence of time varying effects (p = .005) was found. TLPP RMST was + 3.54 months (25.0%) longer in DCB treated patients compared with PTA (p = .001) at three years. TLPP at six months, one year, and two years was 75.3% vs. 58.1%, 51.1% vs. 37.1%, and 31.4% vs. 26.0% for DCB and PTA, respectively. The P-Scores within the Frequentist network meta-analysis suggest that higher concentrations of paclitaxel were associated with better TLPP and ACPP. Among six RCTs (854 patients), the one stage model favoured DCB (shared frailty HR 0.72, 95% CI 0.60 - 0.87, p < .001) for ACPP. Conversely, the two stage random effects model demonstrated no significant difference (HR 0.76, 95% CI 0.35 - 1.67, p = .41, I2 = 81%). Sensitivity analysis excluding outliers significantly favoured DCB (HR 0.61, 95% CI 0.41 - 0.91, p = .027, I2 = 62%). CONCLUSION: Overall evidence suggests that DCB is favoured over PTA in TLPP and ACPP.

State-of-the-Art Advancements in Gastroesophageal Cancer Treatment: Harnessing Biomarkers for Precision Care.

Gastroesophageal cancers (GECs) represent a significant clinical challenge. For early resectable GEC, the integration of immune checkpoint inhibitors into the perioperative chemotherapy and chemoradiation treatment paradigms are being explored and showing promising results. Frontline management of metastatic GEC is exploring the role of targeted therapies beyond PD-1 inhibitors, including anti-human epidermal growth factor receptor 2 agents, Claudin 18.2 inhibitors, and FGFR2 inhibitors, which have shown considerable efficacy in recent trials. Looking ahead, ongoing trials and emerging technologies such as bispecific antibodies, antibody-drug conjugates, and adoptive cell therapies like chimeric antigen receptor T cells are expected to define the future of GEC management. These advancements signify a paradigm shift toward personalized and immunotherapy-based approaches, offering the potential for improved outcomes and reduced toxicity for patients with GEC.

Higher odds of periodontitis in systemic lupus erythematosus compared to controls and rheumatoid arthritis: a systematic review, meta-analysis and network meta-analysis.

Introduction: Periodontitis as a comorbidity in systemic lupus erythematosus (SLE) is still not well recognized in the dental and rheumatology communities. A meta-analysis and network meta-analysis were thus performed to compare the (i) prevalence of periodontitis in SLE patients compared to those with rheumatoid arthritis (RA) and (ii) odds of developing periodontitis in controls, RA, and SLE. Methods: Pooled prevalence of and odds ratio (OR) for periodontitis were compared using meta-analysis and network meta-analysis (NMA). Results: Forty-three observational studies involving 7,800 SLE patients, 49,388 RA patients, and 766,323 controls were included in this meta-analysis. The pooled prevalence of periodontitis in SLE patients (67.0%, 95% confidence interval [CI] 57.0-77.0%) was comparable to that of RA (65%, 95% CI 55.0-75.0%) (p>0.05). Compared to controls, patients with SLE (OR=2.64, 95% CI 1.24-5.62, p<0.01) and RA (OR=1.81, 95% CI 1.25-2.64, p<0.01) were more likely to have periodontitis. Indirect comparisons through the NMA demonstrated that the odds of having periodontitis in SLE was 1.49 times higher compared to RA (OR=1.49, 95% CI 1.09-2.05, p<0.05). Discussion: Given that RA is the autoimmune disease classically associated with periodontal disease, the higher odds of having periodontitis in SLE are striking. These results highlight the importance of addressing the dental health needs of patients with SLE. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/ identifier CRD42021272876.

Ablation therapies for paroxysmal atrial fibrillation: A systematic review and patient-level network meta-analysis.

INTRODUCTION: Despite promising trials, catheter ablation is still regarded as an adjunct to antiarrhythmic drugs (AADs) in the treatment of paroxysmal atrial fibrillation (PAF). This study aimed to compare the effectiveness of various ablation therapies and AADs. METHOD: Randomised controlled trials or propensity score-matched studies comparing atrial tachyarrhythmia recurrence among any combination of ablation modalities or AAD were retrieved. Kaplan-Meier curves and risk tables for this outcome were graphically reconstructed to extract patient-level data. Frequentist network meta-analysis (NMA) using derived hazard ratios (HRs), as well as 2 restricted mean survival time (RMST) NMAs, were conducted. Treatment strategies were ranked using P-scores. RESULTS: Across 24 studies comparing 6 ablation therapies (5,132 patients), Frequentist NMA-derived HRs of atrial fibrillation recurrence compared to AAD were 0.35 (95% confidence interval [CI]=0.25-0.48) for cryoballoon ablation (CBA), 0.34 (95% CI=0.25-0.47) for radiofrequency ablation (RFA), 0.14 (95% CI=0.07-0.30) for combined CBA and RFA, 0.20 (95% CI=0.10-0.41) for hot-balloon ablation, 0.43 (95% CI=0.15-1.26) for laser-balloon ablation (LBA), and 0.33 (95% CI=0.18-0.62) for pulmonary vein ablation catheter. RMST-based NMAs similarly showed significant benefit of all ablation therapies over AAD. The combination of CBA + RFA showed promising long-term superiority over CBA and RFA, while LBA showed favourable short-term efficacy. CONCLUSION: The advantage of ablation therapies over AAD in preventing atrial tachyarrhythmia recurrence suggests that ablation should be considered as the first-line treatment for PAF in patients fit for the procedure. The promising nature of several specific therapies warrants further trials to elicit their long-term efficacy and perform a cost-benefit analysis.

Comparing bronchial thermoplasty with biologicals for severe asthma: Systematic review and network meta-analysis.

BACKGROUND: Bronchial thermoplasty (BT) has shown favorable safety and efficacy in several randomized controlled trials (RCTs), but has not been directly compared to biological therapies. METHODS: Electronic literature searches were performed on PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, to retrieve RCTs of BT or FDA-approved biologicals against controls in patients with severe asthma. Six outcomes were analyzed: Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ), the number of patients experiencing ≥1 asthma exacerbation, annualized exacerbation rate ratio (AERR), oral corticosteroid dose reduction (OCDR), and morning peak expiratory flow rate (amPEF). Random-effects, Frequentist network meta-analysis (NMA) were performed, and therapies were ranked using P-scores. RESULTS: Twenty-nine RCTs (15,547 patients) were included. Fewer patients treated with BT experienced ≥1 asthma exacerbation (risk ratio [RR] = 0.66, 95%CI = 0.45-0.98) compared to control. AERR of BT versus control was non-significant, but significant improvements in ACQ score (mean difference [MD] -0.41, 95%CI -0.63 to -0.20), AQLQ score (MD = 0.54, 95%CI = 0.30-0.77), amPEF and OCDR were found. No significant differences between BT and biologics were seen across indirect comparisons of all studies. CONCLUSIONS: Despite the lack of head-to-head comparative trials, this NMA suggests that BT is non-inferior to biologicals in terms of quality-of-life scores, and represents a promising alternative for patients with severe asthma.

Recurrent Heerfordt-Waldenström Syndrome with thyroid and meningeal involvement in a Chinese woman.

Sarcoidosis is a multisystem granulomatous disorder of unknown etiology, manifesting with bilateral hilar adenopathy, pulmonary reticular opacities, skin, joint or eye lesions. Heerfordt-Waldenström Syndrome - a constellation of facial palsy, fever, uveitis and parotitis - is a rare presentation of this disorder. A 47-year-old Chinese woman presented with unintentional weight loss, lethargy with mediastinal and hilar lymphadenopathy. Biopsy of the right paratracheal lymph node via mediastinoscopy showed mycobacterial granulomatous lymphadenitis consistent with tuberculosis with several acid-fast bacilli identified. Lymphoproliferative disorder was ruled out. She was started on treatment for tuberculosis. Eleven weeks into treatment, she developed a right facial palsy accompanied with fever, uveitis and occipital headache. At this juncture, further history revealed a background of recurrent alternating facial palsy and parotid gland enlargement which was treated for Bell's palsy by three different doctors. New nodules appeared in the left lobe of the thyroid gland. Biopsy of a palpable thyroid nodule and a right supraclavicular lymph nodule showed histological features suggestive of sarcoidosis. Fungal and mycobacterial infections were ruled out. In addition, examination of her cerebral spinal fluid showed lymphocytic inflammation. The serum ACE level was not raised. A diagnosis of sarcoidosis with incomplete features of Heerfordt-Waldenström Syndrome along with thyroid and meningeal involvement was made. The patient was commenced on prednisolone and azathioprine and her symptoms responded shortly after. We present a rare case of Heerfordt-Waldenström Syndrome with thyroid and meningeal involvement in a Chinese woman.

Low-Dose Computed Tomography (LDCT) Lung Cancer Screening in Asian Female Never-Smokers Is as Efficacious in Detecting Lung Cancer as in Asian Male Ever-Smokers: A Systematic Review and Meta-Analysis.

INTRODUCTION: Lung cancer in never-smokers is the major cancer cause of death globally. We compared the efficacy of low-dose computed tomography (LDCT) lung cancer screening among never-smokers versus ever-smokers using systematic review and meta-analysis. METHODS: LDCT lung cancer screening studies that simultaneously included both ever-smoker and never-smoker participants published by April 30, 2021, were searched through PubMed and Scopus. Primary outcome measure was relative risk (RR) of lung cancer diagnosed among never-smokers versus ever-smokers. RESULTS: A total of 14 studies (13 from Asia) were included (141,396 ever-smokers, 109,251 never-smokers, 1961 lung cancer cases diagnosed). RR of lung cancer diagnosed between ever-smokers versus never-smokers overall was 1.21 (95% confidence interval [CI]: 0.89-1.65), 1.37 (95% CI: 1.08-1.75) among males, and 0.88 (95% CI: 0.59-1.31) among females. RR was 1.78 (95% CI: 1.41-2.24) and 1.22 (95% CI: 0.89-1.68) for Asian female never-smokers versus male never-smokers and versus male ever-smokers, respectively, and 0.99 (95% CI: 0.65-1.50) versus high-risk ever-smokers (≥30 pack-years). Proportional meta-analysis revealed significantly more lung cancers diagnosed at first scan (95.4% [95% CI: 84.9-100.0] versus 70.9% [95% CI: 54.6-84.9], p = 0.010) and at stage 1 (88.5% [95% CI: 79.3-95.4] versus 79.7% [95% CI: 71.1-87.4], p = 0.071) among never-smokers versus ever-smokers, respectively. RR of lung cancer death and 5-year all-cause mortality in never-smokers versus ever-smokers was 0.27 (95% CI: 0.1-0.55, p < 0.001) and 0.13 (95% CI: 0.05-0.33, p < 0.001), respectively. CONCLUSIONS: The RR of lung cancer detected by LDCT screening among female never-smokers and male ever-smokers in Asia was statistically similar. Overall and lung cancer specific mortality from the lung cancer diagnosed from LDCT screening was significantly reduced among never-smokers compared to ever-smokers.

Effectiveness of Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma: A Meta-analysis Including Low PD-L1 Subgroups.

Importance: Immune checkpoint inhibitors (ICIs) have improved survival outcomes of patients with advanced esophageal squamous cell carcinoma in both first- and second-line settings. However, the benefit of ICIs in patients with low programmed death ligand 1 (PD-L1) expression remains unclear. Objective: To derive survival data for patient subgroups with low PD-L1 expression from clinical trials comparing ICIs with chemotherapy in esophageal squamous cell carcinoma and to perform a pooled analysis. Data Sources: Kaplan-Meier curves from the randomized clinical trials were extracted after a systematic search of Scopus, Embase, PubMed, and Web of Science from inception until October 1, 2021. Study Selection: Randomized clinical trials that investigated the effectiveness of anti-PD-1-based regimens for advanced esophageal squamous cell carcinoma and that reported overall survival (OS), progression-free survival, or duration of response were included in this meta-analysis. Data Extraction and Synthesis: Kaplan-Meier curves of all-comer populations, subgroups with high PD-L1, and those with low PD-L1 (when available) were extracted from published articles. A graphic reconstructive algorithm was used to calculate time-to-event outcomes from these curves. In studies with unreported curves for subgroups with low PD-L1 expression, KMSubtraction was used to impute survival data. KMSubtraction is a workflow to derive unreported subgroup survival data with from subgroups. An individual patient data pooled analysis including previously reported and newly imputed subgroups was conducted for trials with the same treatment line and PD-L1 scoring system. Data analysis was conducted from January 1, 2022, to June 30, 2022. Main Outcomes and Measures: Primary outcomes included Kaplan-Meier curves and hazard ratios (HRs) for OS for subgroups with low PD-L1 expression. Secondary outcomes included progression-free survival and duration of response. Results: The randomized clinical trials CheckMate-648, ESCORT-1st, KEYNOTE-590, ORIENT-15, KEYNOTE-181, ESCORT, RATIONALE-302, ATTRACTION-3, and ORIENT-2 were included, totaling 4752 patients. In the pooled analysis of first-line trials that evaluated a tumor proportion score (CheckMate-648 and ESCORT-1st), no significant benefit in OS was observed with immunochemotherapy compared with chemotherapy in the subgroup of patients who had a tumor proportion score lower than 1% (HR, 0.91; 95% CI, 0.74-1.12; P = .38) compared with chemotherapy. In the pooled analysis of first-line trials that evaluated combined positive score (KEYNOTE-590 and ORIENT-15), there was a significant but modest OS benefit for immunochemotherapy compared with chemotherapy in the subgroup with a combined positive score lower than 10 (HR, 0.77; 95% CI, 0.62-0.94; P = .01). Conclusions and Relevance: Findings suggest a lack of survival benefit of ICI-based regimens in the first-line setting compared with chemotherapy alone in the subgroup with a tumor proportion score lower than 1%.