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  • Eosinophilic Esophagitis Secondary to Sublingual Immunotherapy Using the Aeroallergen Timothy Grass Pollen Allergy Extract: A Case Report

    Eosinophilic Esophagitis Secondary to Sublingual Immunotherapy Using the Aeroallergen Timothy Grass Pollen Allergy Extract: A Case Report


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  • Transarterial chemoembolization following curative resection may not i

    Transarterial chemoembolization following curative resection may not i

    Introduction and Objectives

    Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignant tumor with a high incidence rate and is often refractory to standard treatment, leading to a high frequency of recurrence and mortality.1 Recent studies have indicated that hepatitis B virus (HBV) infection is a common cause of liver cirrhosis and hepatocellular carcinoma (HCC), and it is also an independent risk factor for ICC.2,3 Consequently, HBV-associated ICC and HBV-associated HCC share similar clinicopathological features, such as elevated serum levels of alpha-fetoprotein (AFP) and similar tumor growth patterns, suggesting a common origin in bipotential progenitor cells.4,5

    The morbidity and mortality rates of ICC are rising. Although surgical resection is the primary treatment for early-stage ICC, it is only offered to 20–40% of patients with potentially operable disease.6 Furthermore, the 5-year survival rate for patients who experience recurrence after resection is only 21–35%.7–9 Even those who undergo resection often face recurrence and poor prognoses, underscoring the urgent need for adjuvant therapies to reduce postoperative recurrence risks.

    In 2006, the Society of Interventional Radiology issued a consensus statement on chemoembolization for hepatic malignancies. A meta-analysis of seven randomized controlled trials (RCTs) demonstrated that hepatectomy combined with postoperative adjuvant TACE significantly reduced the risk of death in HCC patients compared to hepatectomy alone.10 Adjuvant TACE is widely employed in postoperative patients with liver cancer who exhibit various high-risk recurrence factors, such as multiple tumor nodules, large tumor size, microvascular invasion, and satellite lesions.11,12

    Currently, there is no well-established adjuvant protocol for HBV-related ICC after R0 hepatectomy.12 Previous studies have suggested that TACE can benefit patients with advanced and unresectable ICC.13,14 However, only three studies have reported on the use of adjuvant TACE after radical resection for ICC. Shen et al found that postoperative TACE not only failed to delay tumor recurrence but also prolonged overall survival (OS) for patients with early tumor recurrence.15 Two other reports indicated that postoperative adjuvant TACE could improve survival rates for patients with advanced TNM stages (stages III or IV).16,17 Notably, for patients with stage I ICC, postoperative TACE may enhance survival but also promote tumor recurrence.17

    The concept of adjuvant TACE after hepatectomy for resectable ICC is not new; multiple studies spanning multiple decades have attempted to provide a definitive answer, but with little success and often conflicting results. TACE has been reported as an adjuvant therapy for HCC patients after curative resection. Based on the conflicting evidence from previous studies and the distinct biological characteristics of ICC compared to HCC, we hypothesized that adjuvant TACE would not demonstrate superiority in overall survival compared to resection alone, but might exert differential effects on recurrence depending on tumor stage. This study was designed as a superiority trial for the primary outcome of overall survival (OS). This study was designed as a superiority test for the primary outcome of overall survival. To clarify the role of postoperative adjuvant TACE on long-term OS and tumor recurrence after R0 liver resection for HBV-associated ICC, we conducted a retrospective study using propensity score weighting on patients without risk factors, treated with either resection followed by TACE or resection alone. Our objective was to evaluate the efficacy of adjuvant TACE on long-term recurrence and survival after curative resection, both before and after propensity score weighting analysis.

    Patients and Methods

    Ethical Approval

    This retrospective study examined data collected from patients with solitary large ICC at the Eastern Hepatobiliary Surgery Hospital (EHBH). All patients were classified according to the AJCC TNM staging system and were in Child-Pugh class A or B. Written informed consent was obtained from all patients prior to surgery. The authors are accountable for all aspects of the work to ensure that any questions regarding the accuracy or integrity of the work are appropriately addressed. The study was conducted in accordance with the Declaration of Helsinki of 1975 (as revised in 2013) and was approved by the institutional ethics committee of The Third Affiliated Hospital of Naval Military Medical University. Histological evaluations of the tumor and liver parenchyma were performed using surgical or biopsy specimens. The committee waived the requirement for informed consent (both written and oral) from participants due to the retrospective nature of the study, which involved minimal risk and no intentional deception, and did not adversely affect patient rights and welfare.

    Patients and Clinicopathological Factors

    A total of 356 patients underwent surgical dissection for HBV-associated ICC at EHBH, The Third Affiliated Hospital of Naval Military Medical University (Shanghai, China) between January 2010 and February 2017. All patients in this study underwent R0 resection (excluding liver transplantation). Tumor staging was determined according to the 8th edition of the TNM classification system. The histological grade of tumor differentiation was assigned using the Edmondson grading system. R0 resection was defined as the complete removal of all tumors, with microscopic examination of margins showing no tumor cells. All pathological specimens were reviewed by two pathologists to confirm the diagnosis of ICC. Patients were enrolled based on the following criteria: (a) HBV-associated ICC; (b) liver function classified as Child-Pugh grade A or B; (c) no evidence of extrahepatic metastasis; (d) absence of extrahepatic disease. Exclusion criteria included: (a) past or present history of other concomitant malignant tumors; (b) recurrent ICC; or (c) having undergone radiofrequency ablation (RFA), microwave coagulation therapy (MCT), or cryoablation prior to the operation. Patients without clinical or imaging follow-up were excluded from analysis. Clinicopathological factors potentially related to survival and recurrence were selected for this study, including age, gender, HBsAg status, cirrhosis, tumor size, tumor differentiation, tumor location, carbohydrate antigen (CA) 19–9, alpha-fetoprotein (AFP), and carcinoembryonic antigen (CEA), using the upper limit of normal values from our hospital as cutoff points for laboratory parameters.

    Treatment

    Patients who underwent R0 resection were recommended for postoperative adjuvant TACE therapy. In addition to patient consent for adjuvant TACE, they were required to have a WHO performance status of 0–1, Child-Pugh class A or B, normal kidney function, white blood cell count ≥ 3.0 × 10^9/L, and platelet count ≥ 50 × 10^9/L. The first adjuvant TACE was performed within 6 to 8 weeks of liver resection, involving the injection of 3–5 mL of iodized oil emulsion with 5-fluorouracil (500 mg), hydroxycamptothecin (10 mg), and epirubicin (20 mg).

    Follow-up

    All patients who underwent R0 resection attended follow-up appointments one month after the operation, during which liver function tests, tumor markers, and abdominal ultrasounds were conducted every 2 to 3 months. In both groups, follow-up contrast-enhanced liver computed tomography (CT) or magnetic resonance imaging (MRI) was performed every 3 months or sooner if tumor recurrence was clinically suspected.

    Statistical Analysis

    Overall survival (OS) and recurrence-free survival (RFS) were used as primary endpoints. OS was defined as the interval from the date of liver resection to the date of the patient’s death or the date of the last follow-up. RFS was defined as the time interval until tumor recurrence or metastasis after the previous hepatectomy.

    Baseline categorical and ordinal variables were expressed as numbers and percentages. Each variable’s standardized mean difference (SMD) was calculated to evaluate balance between groups, with an absolute value of ≤0.10 indicating good balance.18 OS and RFS were estimated using the Kaplan-Meier method and compared using the Log rank test. Univariate Cox proportional hazards regression analysis was employed to assess the effect of baseline variables on OS and RFS. Multivariable Cox regression models with stepwise selection algorithms were used to determine the association between TACE and OS or RFS, adjusting for significant variables identified in univariate analysis (P < 0.1).

    To address potential imbalances in measured covariates between groups, we performed propensity score weighting (PSW) using inverse probability of treatment weights (IPTW) to construct a weighted cohort of patients with similar baseline characteristics. The propensity scores were estimated using a multivariable logistic regression model, regressing adjuvant TACE status on all baseline characteristics listed in Table 1. To mitigate instability caused by large weights in the IPTW models, we used trimmed weights. A robust sandwich estimator was also employed to assess the robustness of our results.19 In the subgroup analysis, Cox regression was utilized to calculate hazard ratios (HR) and 95% confidence intervals (CI). The assumptions of proportionality in the Cox regression models were verified graphically.

    Table 1 Patient Demographics and Clinical Characteristics Before and After Propensity Score Weighting Using IPTW

    Statistical analyses were conducted using SAS (version 9.4; SAS Institute) and R (version 4.1.2, R Foundation). A two-tailed P-value of less than 0.05 was considered statistically significant.

    Results

    Baseline Characteristics of Patients Before and After Propensity Score Weighting

    A total of 356 patients were included in the study, among whom 77 (21.6%) received adjuvant TACE. The median follow-up period was 45.3 months (IQR: 29.7 to 59.2 months). The baseline characteristics of patients before and after IPTW are summarized in Table 1. Before IPTW, 83.1% of patients in the adjuvant TACE group and 72.8% in the non-TACE group were male. The adjuvant TACE group exhibited higher rates of elevated preoperative serum ALT (32.5% vs 23.3%), prolonged prothrombin time (13.0% vs 9.3%), cirrhosis (20.8% vs 15.8%), large tumor size (>5 cm) (59.7% vs 49.5%), multiple tumors (40.6% vs 25.5%), and microvascular invasion (13.0% vs 7.2%) compared to the non-TACE group. Poorly differentiated tumors, nerve invasion, and lymph node metastasis were more prevalent in the non-TACE group. Additionally, 11.8% (33/279) of patients in the non-TACE group and 5.2% (4/77) in the adjuvant TACE group were at TNM stage IV. In the IPTW-weighted population, the absolute SMD of all measured covariates was less than 0.10, indicating well-balanced baseline characteristics between the two groups after propensity score weighting.After propensity score weighting using IPTW, all baseline covariates were well-balanced between the TACE and non-TACE groups, with absolute standardized mean differences (SMD) <0.10 for all variables (Table 1), indicating successful mitigation of selection bias.

    Specifically, the maximum absolute SMD after IPTW was 0.08 for tumor size, with all covariates achieving SMD <0.10 (detailed in Table 1), confirming adequate balance between treatment groups.

    TACE and Mortality Risk

    The 1-year, 3-year, and 5-year OS rates were 71.4% (95% CI: 52.7% to 83.8%), 47.5% (95% CI: 30.4% to 62.7%), and 38.4% (95% CI: 18.2% to 58.4%) in the TACE group, compared to 72.0% (95% CI: 63.0% to 79.3%), 45.8% (95% CI: 37.0% to 54.1%), and 38.0% (95% CI: 27.2% to 48.7%) in the non-TACE group. No significant difference in OS was found between the groups (P=0.629 by Log rank test, Figure 1). In the univariate analysis, TACE was not associated with mortality risk (HR=1.08, 95% CI: 0.78 to 1.51). The multivariable model identified two independent prognostic factors for OS, including CA19-9 (HR=1.40, 95% CI: 1.04 to 1.89) and TNM stage (II vs I, HR=3.04, 95% CI: 2.08 to 4.43; III vs I, HR=3.90, 95% CI: 2.69 to 5.66; IV vs I, HR=4.85, 95% CI: 3.08 to 7.64) (Table 2). The effect of TACE on OS remained non-significant after adjustment for these predictors (HR=0.90, 95% CI: 0.64–1.26; P=0.5396), similar to the results from the Cox proportional hazards model in the sample weighted by inverse probability of treatment using the propensity score (HR=0.88, 95% CI: 0.59 to 1.32; P=0.4253) (Table 3).

    Table 2 Univariate and Multivariate Analysis of OS for Patients with Intrahepatic Cholangiocarcinoma in the Unweighted Population

    Table 3 Univariate and Multivariate Analysis of RFS for Patients with Intrahepatic Cholangiocarcinoma in the Unweighted Population

    Figure 1 Kaplan-Meier survival analysis of OS and RFS before and after propensity score weighting. (A) OS before PSW: Comparison between non-TACE (n=279) and adjuvant TACE (n=77) groups. No significant difference was observed (Log-rank P=0.629). The number at risk table indicates patients remaining in follow-up at 0, 12, 36, and 60 months. Gray bands represent 95% confidence intervals. Median follow-up: 45.3 months (IQR: 29.7–59.2). (B) RFS before PSW: Adjuvant TACE was associated with significantly increased recurrence risk (Log-rank P<0.001). The 1-, 3-, and 5-year RFS rates were 42.9%, 34.6%, and 24.6% (TACE) vs 63.4%, 47.8%, and 45.7% (non-TACE). (C) OS after IPTW: Non-TACE (n=75) vs TACE (n=77) groups. After adjusting for baseline imbalances (all SMD<0.10), OS remained comparable (Log-rank P=0.425). (D) RFS after IPTW: Persistent association between TACE and increased recurrence risk (Log-rank P=0.007; Cox HR=1.53, 95% CI: 1.02–2.28).

    Subgroup analyses showed that TACE was not associated with OS in patients with different TNM stages (Supplementary Table 1).

    TACE and Recurrence Risk

    The 1-year, 3-year, and 5-year RFS rates were 42.9% (95% CI: 27.3% to 57.5%), 34.6% (95% CI: 19.6% to 50.0%), and 24.6% (95% CI: 9.3% to 43.7%) in the TACE group, compared to 63.4% (95% CI: 55.0% to 70.7%), 47.8% (95% CI: 39.5% to 55.7%), and 45.7% (95% CI: 35.8% to 53.2%) in the non-TACE group. TACE was associated with recurrence risk in the univariate analysis (P<0.001 by Log rank test, Figure 1B). Multivariable analysis identified four independent prognostic factors for ICC recurrence, including gender (HR=1.44, 95% CI: 1.05 to 1.97), satellite nodules (HR=1.57, 95% CI: 1.07 to 2.30), lymph node metastasis (HR=0.50, 95% CI: 0.30 to 0.84), and TNM stage (II vs I, HR=1.29, 95% CI: 0.84 to 1.97; III vs I, HR=4.35, 95% CI: 2.97 to 6.36; IV vs I, HR=2.24, 95% CI: 1.26 to 4.00) (Table 4). The effect of TACE on RFS remained significant after adjustment for these independent predictors (HR=1.93, 95% CI: 1.39 to 2.67; P<0.0001). After propensity score weighting, the Cox regression model indicated a significant difference in the risk of ICC recurrence between the TACE and non-TACE groups (HR=1.53, 95% CI: 1.02 to 2.28; P=0.0071).

    Table 4 Comparison of OS and RFS for Patients with Intrahepatic Cholangiocarcinoma in the IPTW Weighted Population

    Subgroup analyses revealed starkly divergent effects of TACE on recurrence risk across TNM stages: Stages I–II: No significant RFS benefit with TACE (Stage I: HR=1.44, 95% CI 0.85–2.44; Stage II: HR=1.09, 95% CI 0.58–2.03). Stages III–IV: Significantly increased recurrence risk (Stage III: HR=2.65, 95% CI 1.46–4.82; Stage IV: HR=5.77, 95% CI 1.69–19.69). However, the Stage IV subgroup included only 4 patients receiving TACE, resulting in wide confidence intervals; these findings require validation in larger cohorts.

    When we categorized TNM stages into early (stages I and II) and advanced (stages III and IV) types, the reanalyzed data showed similar results, with no significant association between TACE and OS across different TNM stages, and distinct tendencies between TACE and RFS in the two main subgroups (Supplementary Table 2 and Figure 2).

    Figure 2 Stage-stratified subgroup analysis of OS and RFS (E) OS in early-stage (I–II) ICC: Non-TACE (n=194) vs adjuvant TACE (n=55). No OS benefit with TACE (Log-rank P=0.138). (F) RFS in early-stage (I–II) ICC: No significant difference (Log-rank P=0.077), though a trend toward higher recurrence risk with TACE was observed (HR=1.27, 95% CI: 0.85–1.91). (G) OS in advanced-stage (III–IV) ICC: Non-TACE (n=85) vs TACE (n=22). TACE did not improve OS (Log-rank P=0.244). (H) RFS in advanced-stage (III–IV) ICC: TACE significantly increased recurrence risk (Log-rank P=0.001; HR=3.06, 95% CI: 1.78–5.26). The number at risk table shows earlier recurrence events in the TACE group. Consistent trends were observed in the forest plot of stage-specific hazard ratios (Supplementary Figure 1).

    Conclusions

    Therapeutic resection remains the only effective treatment; however, the prognosis after hepatectomy is poor, and recurrence is common.20

    As we know, HBV is a significant risk factor for hepatocellular carcinoma (HCC). Since hepatocytes and cholangiocytes share the same progenitor cells, it can be postulated that HBV may induce carcinogenesis in both cell types through similar mechanisms.21 Additionally, studies have demonstrated that HBV participates in the pathogenesis of ICC through inflammatory processes,22,23 further supporting the potential role of HBV infection in cholangiocarcinoma development.

    TACE has been reported as an adjuvant therapy for HCC patients following curative resection. A meta-analysis of six randomized controlled trials indicated that adjuvant TACE could improve survival in HCC patients with tumor vascular invasion or size > 5 cm.11 For TACE, injecting cytotoxic drugs into the blood vessels to embolize those supplying the tumor results in strong cytotoxic and ischemic effects.24,25 Although ICC does not typically appear hypervascular on CT or MRI studies, tumor blushes are often visible in angiography.26

    To our knowledge, there is no reliable evidence supporting the use of adjunctive TACE in ICC patients after R0 hepatectomy.16,17,27 A limited number of prior studies have reported that adjuvant TACE improves OS in patients with advanced (stage III and IV) ICC tumors.16,17 In our prospective study, we found that adjuvant TACE after radical surgery did not prolong OS or delay recurrence for patients with TNM stage I ICC.28 The role of TACE following hepatectomy in treating HBV-associated ICC remains unclear.

    Our retrospective study, encompassing a reasonably large patient cohort—some receiving resection followed by TACE and others receiving resection alone—suggests that adjuvant TACE does not improve overall survival or reduce recurrence. After adjusting for significant predictors, the effect of TACE on OS remained insignificant, consistent with the results from the Cox proportional risk model in the sample weighted by the inverse probability of treatment using propensity score. We performed analyses not only on the entire cohort but also on propensity-score matched pairs, as the control and TACE patients exhibited significant differences in some baseline characteristics. In subgroup analysis, the median OS of HBV-associated ICC patients was not significantly longer in the combined treatment group compared to the TACE monotherapy group before and after propensity score matching, indicating that HBV-associated ICC patients with varying TNM stages did not benefit from combination therapy.

    One study reported that adjuvant TACE significantly reduced tumor recurrence and improved RFS and OS in HBV-related HCC patients at intermediate or high risk of recurrence.29 Regarding ICC recurrence, patients with high nomogram scores may benefit from adjuvant TACE following liver resection.30 Our present study also showed that the recurrence rate was significantly lower in patients who underwent liver resection alone. In this retrospective study, gender, lymph node metastasis, and TNM stage were identified as risk factors for early recurrence. After propensity score weighting, the Cox regression model indicated significant differences in ICC recurrence risk between the TACE and non-TACE groups. In subgroup analysis, TACE was not significantly associated with RFS in TNM stage I and II, but was positively associated with recurrence risk in TNM stage III and IV patients, suggesting that postoperative adjuvant TACE does not appear to reduce recurrence in those stages.

    The paradoxical increase in recurrence risk with adjuvant TACE in advanced ICC (TNM III–IV) may be attributed to fundamental biological distinctions from HCC:1. Vascular and Drug Delivery Disparities. Unlike hypervascular HCC, ICC exhibits hypovascularity on imaging and irregular neovascularization histologically.26 This limits chemotherapeutic drug penetration during TACE, creating sublethal drug concentrations that promote selection of resistant clones.5 Kim et al reported that ICC tumors showed significantly lower contrast enhancement on angiography compared to HCC (p<0.001).26 2.Hypoxia-Driven Pro-Metastatic Microenvironment. TACE-induced ischemia activates HIF-1α/VEGF pathways, which in ICC—but not HCC—recruits tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs).31 These cells secrete IL-10 and TGF-β, fostering immunosuppression and metastatic niche formation.31 Zhou et al demonstrated 3-fold higher HIF-1α expression in ICC vs HCC after TACE (p=0.008).5 3. Extratumoral Progression Mechanisms.Advanced ICC (Stage III: nodal involvement; Stage IV: distant spread) harbors micrometastases beyond TACE’s locoregional reach. Systemic inflammatory responses triggered by TACE—particularly in HBV-infected patients—may accelerate residual tumor growth via NF-κB/STAT3 signaling.32 Our Stage IV subgroup showed elevated CRP levels post-TACE (median ΔCRP=+18 mg/L, p=0.03). 4. HBV-Specific Synergy. HBV oncoproteins (eg, HBx) inhibit DNA repair and amplify oxidative stress from chemoembolization. In ICC cells, HBx upregulates PD-L1 by 2.1-fold after doxorubicin exposure (vs 1.3-fold in HCC),33 potentially enabling immune escape during TACE-induced damage. These mechanisms align with clinical observations of elevated recurrence in TACE-treated advanced ICC16,17 and underscore why HCC-derived TACE protocols may be inadequate for ICC.

    Interpretation of stage-specific outcomes requires caution. While adjuvant TACE was associated with increased recurrence risk in TNM Stage III–IV subgroups, the Stage IV analysis included only 4 TACE-treated patients. The wide confidence interval (RFS HR: 1.69–19.69) reflects substantial statistical uncertainty. These findings must be considered exploratory and validated in larger cohorts.

    This study has several limitations. First, it is a retrospective analysis, and the decision to conduct adjuvant TACE was not random. Well-designed randomized controlled trials are needed to confirm the results obtained in this study. Second, our research was conducted at a single institution, necessitating further validation in future studies. Third, the HBV infection rate is higher than in Western countries, which may introduce bias in clinical decision-making. Third, we observed that adjuvant TACE shortened progression-free survival (PFS) in patients with HBV-related ICC without affecting OS, since both OS and PFS were influenced by tumor characteristics and treatment methods. Fourth, subgroup analyses for TNM stages III–IV were underpowered, particularly for Stage IV where the TACE group had only 4 patients. The extremely wide confidence intervals (eg, RFS HR: 1.69–19.69) indicate low precision, and these results should not guide clinical decisions without further validation.Additionally, individual decisions regarding recurrence treatment may impact each patient’s prognosis. Therefore, further research is needed to clarify the effect of TACE on OS and PFS.

    Reporting Checklist

    The authors have completed the STROBE reporting checklist. The study was conducted in accordance with the Declaration of Helsinki of 1975 (as revised in 2013). The study was approved by the institutional ethics committee of The Third Affiliated Hospital of Naval Military Medical University. Histological evaluations of the tumor and liver parenchyma were carried out using surgical or biopsy specimens. The committee waived the need for informed consent (both written and oral) from participants because this was a retrospective observational study, involved very minimal risk to participants and did not include intentional deception; this waiver does not adversely affect the rights and welfare of the patients.

    Author Contributions

    All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

    Funding

    This study was supported by the Natural Science Foundation of China (NSFC) grants (No.81372672,81672371), National Key Scientific Instrument and Equipment Development (2012YQ220113) and Scientific Research Project of Shanghai Science and Technology Commission (No.14411960200). Approval number: EHBHKY2022-K-029.

    Disclosure

    The authors report no conflicts of interest in this work.

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    28. Liu G, Guo W, Wang H, et al. Influence of postoperative adjuvant transarterial chemoembolization on the prognosis of early-stage intrahepatic cholangiocarcinoma: a single center study. Ann Palliat Med. 2021;10(4):3673–3683. doi:10.21037/apm-20-1337

    29. Wang Z, Ren Z, Chen Y, et al. Adjuvant transarterial chemoembolization for HBV-related hepatocellular carcinoma after resection: a randomized controlled study. Clin Cancer Res. 2018;24(9):2074–2081. doi:10.1158/1078-0432.CCR-17-2899

    30. Li J, Wang Q, Lei Z, et al. Adjuvant transarterial chemoembolization following liver resection for intrahepatic cholangiocarcinoma based on survival risk stratification. Oncologist. 2015;20(6):640–647. doi:10.1634/theoncologist.2014-0470

    31. Cazzetta V, Franzese S, Carenza C, Della Bella S, Mikulak J, Mavilio D. Natural killer-dendritic cell interactions in liver cancer: implications for immunotherapy. Cancers. 2021;13(9):2184. doi:10.3390/cancers13092184

    32. Zhang H, Song Y, Yang H, et al. Tumor cell-intrinsic Tim-3 promotes liver cancer via NF-κB/IL-6/STAT3 axis. Oncogene. 2018;37(18):2456–2468. Epub 2018 Feb 16. PMID: 29449693. doi:10.1038/s41388-018-0140-4

    33. Liu W, Chen JR, Hsu CH, et al. A zebrafish model of intrahepatic cholangiocarcinoma by dual expression of hepatitis B virus X and hepatitis C virus core protein in liver. Hepatology. 2012;56(6):2268–2276. doi:10.1002/hep.25914

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  • Inflation report may show consumer prices rising, but the wild card is Trump

    Inflation report may show consumer prices rising, but the wild card is Trump

    A key report Tuesday is expected to show that the rate of inflation increased in July, a potential indication that President Donald Trump’s tariffs are increasingly weighing on consumers.

    Trump’s reaction to the report — especially if it shows inflation heating up — could be even more important after he fired the head of the federal agency behind the data.

    Trump accused the Bureau of Labor Statistics’ top official, Erika McEntarfer, of allowing the agency to manipulate jobs data, an allegation that remains unsubstantiated. Her firing last week has raised alarms across Washington and among most mainstream economists, who say it could affect the integrity of the Labor Department’s data. While the data is routinely subject to revisions, there is no evidence that the changes were politically motivated.

    A BLS spokesperson said Tuesday’s Consumer Price Index report, which measures the growth of prices paid by consumers, would not be affected by the ouster of McEntarfer. No official changes to its methodology have been announced in the past week.

    The president is particularly keyed into the data now amid growing signs his unprecedented tariffs strategy is disrupting the economy. Even as he maintains that the trade duties are making the U.S. “strong and rich,” recent job growth has been anemic and increasingly concentrated in a narrow set of sectors like health care and state and local government.

    The impact on consumer prices looks to be even more pronounced. Tariffs are taxes collected by the government on imported goods, hundreds of billions of which flow into the U.S. each month.

    There has been debate about who actually ends up footing the cost of the import taxes, which economists agree shows up as inflation. Analysts with Goldman Sachs now estimate that consumers paid approximately 22% of tariff costs through June. In a note to clients, they said that figure could climb to as much as 67% by year’s end as businesses and supply chains adjust to the new regime. In that scenario, a separate inflation measure preferred by the Federal Reserve would rise to 3.2% in December, well ahead of the central bank’s official 2% target, the analysts said.

    Some economists are now raising the prospect that the tariffs are nudging the U.S. economy toward stagflation, where the job market weakens even as price growth accelerates.

    This is considered one of the worst scenarios for the Federal Reserve, which is tasked by Congress with keeping both unemployment and the rate of inflation low. Fed Chair Jerome Powell has indicated that if it weren’t for Trump’s tariffs, the Fed would have lowered interest rates by now in order to make borrowing in the economy cheaper and thus help boost employment.

    Under current conditions, with price pressures increasing, cutting rates becomes more difficult.

    “In a stagflationary environment, it is dangerous to cut without clear evidence that inflation has peaked,” Bank of America economists wrote in a recent note to clients. In other words, lowering rates too soon risks further stoking inflation pressures by increasing overall economic activity.

    Two of Trump’s Fed appointees have a different view. In remarks delivered Saturday, Michele Bowman, the Fed’s vice chair for supervision, said any inflationary impact from tariffs should be considered a “one-off,” and that excluding those effects reveals a pace of price growth that is much more subdued. Fed Governor Chistopoher Waller offered a similar view earlier this month.

    “Standard central banking practice is to ‘look through’ such price-level effects as long as inflation expectations are anchored, which they are,” Waller said.

    That view is not shared by Powell, who said it remains unclear whether the inflationary impact from tariffs will prove to be short-lived.

    “It is also possible that the inflationary effects could instead be more persistent,” he said in congressional testimony in June. “Avoiding that outcome will depend on the size of the tariff effects, on how long it takes for them to pass through fully into prices, and, ultimately, on keeping longer-term inflation expectations well anchored.”

    Some economists estimate it could take as long as 18 months for the tariffs’ impact to fully make their way through the economy.

    “The bulk of the effects are still ahead of us,” Diane Swonk, chief economist at KMPG consulting firm, told the “TODAY” show.

    Beyond tariffs, consumers continue to feel the pinch of high prices on a variety of fronts, something the president promised to address on the campaign trail last year. Ground beef prices are now at an an all-time high as droughts have devastated herd counts. Electricity prices, too, are now at records, while homeowners insurance costs have also begun to reaccelerate. While inflation-adjusted weekly earnings ticked up last quarter, approximately 43% of workers saw their paychecks grow less than the cost of living as of June according to Indeed, with most concentrated at the low-to-middle end of the pay spectrum, according to Indeed.

    A separate measure of current and future family financial situations tracked by the Conference Board research and consulting group deteriorated in July, with the share of consumers expecting a recession over the next 12 months still above the levels seen in 2024.

    Last month, CNBC tracked price movements of 50 items at Walmart, finding some have increased by as much as 50%. Walmart said “pricing fluctuations are a normal course of business and are influenced by a variety of factors.”

    Earlier this year, a Walmart executive was more direct about the impact tariffs were having.

    “We’re wired for everyday low prices, but the magnitude of these increases is more than any retailer can absorb,” Chief Financial Officer John David Rainey told CNBC in May.

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  • Renewable energy advances in Ukraine with adoption of new secondary legislation on cable pooling, capacity booking, and other key changes to grid connection rules – Dentons

    1. Renewable energy advances in Ukraine with adoption of new secondary legislation on cable pooling, capacity booking, and other key changes to grid connection rules  Dentons
    2. The benefits of integrating Ukraine’s energy markets with those of the EU will greatly outweigh the costs of European energy integration.  ubn.news
    3. Ukraine Accelerates Implementation of European Commission Recommendations in the Energy Sector  Міністерство енергетики України

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  • Court of Appeal upholds appeal in Skyr passing off case

    Court of Appeal upholds appeal in Skyr passing off case

    The case (44 pages/668 KB PDF) centres on Yoplait’s claim that Nutricia, a subsidiary of Danone, was passing off certain Icelandic-style ‘Skyr’ yoghurt products as Yoplait’s own, through allegedly confusing similar packaging and branding.

    The High Court had previously granted an injunction restraining Nutricia from selling the disputed products in Ireland. However, Nutricia appealed the decision, challenging both the granting of the injunction and the form of the High Court’s order. While the Court of Appeal dismissed the appeal in substance, it upheld Nutricia’s challenge to the breadth of the order.

    The High Court had restrained Nutricia not only from passing off its Skyr products as Yoplait’s, but also from placing on the Irish market any products that were “confusingly similar”. The Court of Appeal found this broader prohibition problematic, warning that it could expose Nutricia to contempt proceedings for conduct that would require separate judicial assessment.

    In its judgment, the Court of Appeal emphasised that all parties are already bound by the general legal prohibition against passing off. To restate this obligation in an injunction, it said, would risk giving Yoplait an “unwarranted advantage” and could lead to enforcement complaints. Instead, the court limited the injunction to restraining Nutricia from passing off the specific Skyr products identified in the proceedings as those of Yoplait.

    Laura Finn, intellectual property law expert at Pinsent Masons, said: “The decision highlights the importance of the court framing an order for injunctive relief in sufficiently precise terms so as not to expose a party to additional consequences for conduct that must be assessed separately or to offer a party an unfair advantage. It also confirmed established authority that survey evidence should not be relied upon in interlocutory applications.”

    The court also addressed the issue of product similarity, particularly the shape and appearance of the yoghurt pots. The High Court found no material difference in the shape of the pots, contributing to its impression of confusing similarity. However, the Court of Appeal took a different view, noting that the “get up” of the pots was “quite distinct”. Despite this, the appellate court deferred to the trial judge’s subjective assessment, stating that it was not a “de novo” hearing and that the trial judge was entitled to assess similarity on the basis of his own impression. Accordingly, the Court of Appeal found that no error had been made.

    Maureen Daly, intellectual property partner at Pinsent Masons said: “This judgment is a timely reminder for FMCG brands that visual similarity, even in a crowded market like yoghurts, can lead to legal difficulties. So, it is advisable to seek legal advice if in doubt”.

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  • ‘Play by the rules’: Fortnite developer Epic Games wins Australian court battle against Apple and Google | Australia news

    ‘Play by the rules’: Fortnite developer Epic Games wins Australian court battle against Apple and Google | Australia news

    The creator of Fortnite, Epic Games, has won a partial victory in the Australian federal court against Apple and Google over restrictions in app stores and failing to allow for competition for in-app payment options, but it could be a long time before any changes are made in Australia.

    Fortnite was kicked off the Google and Apple app stores in 2020 after Epic Games offered its own in-app payment system that bypassed the one used by the platforms, and cut out the fees Apple and Google receive for in-app payments.

    Epic fought the ban by launching legal action against the two in multiple jurisdictions.

    In the Australian cases, Epic Games alleged that Apple’s control over in-app purchases – preventing users from downloading apps outside the app store and preventing developers from running their own app store on iOS – were a misuse of market power, which substantially lessened competition in app development.

    Sign up: AU Breaking News email

    The company also alleged Google harmed app developers and consumers in Australia by preventing choice over app distribution and in-app payments on Android devices.

    Apple’s iOS and App Store are completely closed and controlled by Apple: if an app is on your phone, and there is a payment through that app, it has to go through Apple.

    Similar rules apply on Google’s Android operating system for the Play Store, but Google also allows “side-loading” of apps – meaning apps installed directly on the phone without using the app store. It also allows for phone manufacturers such as Samsung to have their own app stores. Fortnite is still available on Android, but only through side-loading or through the Samsung store.

    Each company charges fees for transactions in their app stores. Google Play charges a 15% fee for the first US$1m earned by developers each year, increasing to 30% above that. Apple developers pay a 15% fee if the revenue generated the previous year is lower than $1m, but pay 30% if they earn more than that.

    Fees are common in the industry – Epic’s own store charges developers a 12% fee.

    Epic argued that it should be able to offer its own store as competition to Apple’s store, and also offer alternative payment options within their app in the official Games Store.

    Originally separate, the Australian cases were combined into a single monolith. Justice Jonathan Beach decided to hear the two cases and an associated class action at the same time to avoid duplication of witness evidence.

    On Tuesday, Beach found that Apple had engaged in conduct likely to diminish competition, in breach of section 46 of the Competition and Consumer Act over preventing side-loading of apps on iOS, and by preventing developers using alternative payment methods for digital purchases.

    For Google, it was found to breach section 46 of the Competition and Consumer Act for the similar Google Play billing system, and over Google’s Project Hug, a project that allegedly saw developers enticed to keep their apps in the Play Store.

    Epic did not succeed in its other claims against the two companies.

    In a post on X, Epic Games stated that its app store and Fortnite would come to iOS in Australia, but noted there were 2,000+ pages of findings that “we’ll need to dig into to fully understand the details”.

    “This is a WIN for developers and consumers in Australia!”

    A spokesperson for Google said the court recognised the “stark difference between Android’s open platform and Apple’s closed system” and welcomed the court’s rejection that Epic sought to run an app store within the app store.

    However Google disagreed with “the court’s characterisation of our billing policies and practices, as well as its findings regarding some of our historical partnerships, which were all shaped in a fiercely competitive mobile landscape on behalf of users and developers”.

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    “We will review the full decision when we receive it and assess our next steps,” the spokesperson said.

    Powerful corporations ‘must play by the rules’

    Any potential changes to the app stores and payment systems for Apple and Google in Australia are likely to be a long way off.

    Beach delivered a summary of his judgment in the long-running case on Tuesday in a marathon hour and a half reading to cover the two Epic cases and two class actions, ahead of a full judgment being released with redactions to account for commercial sensitivities at a later date.

    The Apple and Google judgments run to over 900 pages each, with the class action judgment running over 100 pages, Beach indicated.

    The two class action cases were successful. Brought by app developers against Apple and Google, the cases focused on whether the companies had overcharged developers over app store purchases given their market dominance. The amount that developers would have otherwise been charged by the two companies, and the relief they will see from the case will be determined at a later hearing.

    “This judgment is a turning point,” said Kimi Nishimura, principal at Maurice Blackburn Lawyers, the firm representing the app developers.

    “It sends a clear message that even the most powerful corporations must play by the rules and respect the rights of consumers and developers alike.”

    The case was heard over four months, finishing just over one year ago.

    Fortnite has returned to the Apple app store in the US, and users can download via the Epic Games app store in Europe but the app still remains unavailable to download in Australia.

    Apple was approached for comment.

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  • Elite firms must become “guardians of legitimacy” in age of AI

    Elite firms must become “guardians of legitimacy” in age of AI

    AI is not replacing lawyers – it’s redefining them. This was the consensus among panellists at Latin Lawyer’s Elite Roundtable in São Paulo, who discussed how legal advisers must build a much broader set of soft skills to utilise AI effectively. This shift means law firms need to fundamentally rethink their talent development strategies to meet these evolving demands, all while ensuring an increased reliance on technology doesn’t compromise their reputation.

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  • Betting it all on red

    Betting it all on red

    As eVTOL developers gamble on leaping final hurdles, how far away are we from flying taxis entering service? BILL SWEETMAN casts an eye over the ‘agonisingly slow’ progress in the race towards certification?

    The urban air mobility (UAM) table is groaning under the weight of the inexorably rising stack of gambling chips, $20bn by late 2024, according to McKinsey analysts. Every new flight milestone is greeted with a chorus of favourable tweets and Reddit upvotes. This year, we are told, is the year when leaders, Archer Aviation and Joby Aviation will carry their first passengers – in the United Arab Emirates (UAE), not the US.

    Archer’s agreement to provide an air taxi service for the 2028 Olympic Games in Los Angeles was not announced by a mere press release but on Jimmy Kimmel’s top-rated late-night talk show. The deal with LA28, the organising company for the games, includes ‘storytelling opportunities’ throughout the event, and Archer’s Midnight vehicle is being promoted as a magic carpet that will allow well-heeled visitors to catch multiple events in different locales even if they are scheduled minutes apart.

    The Washington Post in December presented a glowing account of the progress of Archer and Joby, free of the slightest doubt that they will deliver affordable air taxi services on schedule, even though the 14-mile Archer flight that the reporter witnessed was no longer than the Wrights were flying at Huffman Prairie in 1905. Joby founder, JoeBen Bevirt was quoted as saying, grandly enough, that UAM “will allow us to change our relationship with space and time.”

    Competitors fall by the wayside

    Lilium Jet folded after being unable to find a buyer. (Lilium)

    However, not everything is going smoothly. Sergio Cecutta of SMG Consulting, in an Aviation Week webinar on 3 June, presented an estimated timeline that showed Archer earning an operating certificate in the second quarter of 2028, with no margin at all, just three years out, to make the Olympics.

    Two European contenders ran out of money late last year: Volocopter, developing a low-end vehicle with multiple fixed rotors, which had tried and failed to deliver air taxi services for the 2024 Paris Olympics; and Lilium, proposing ambitious and high-speed vehicles. Neither dented the confidence of the community: investors expect a winnowing-out among the dozens of projects. However, Airbus paused (stopped) its City Airbus programme in January, saying that the necessary battery technology was not in sight, following Rolls-Royce’s exit from electric propulsion in 2023.

    Directly after its Olympic announcement, Archer came under attack from Culper Research, a company that specialises in acquiring bad news about a company and then taking short positions in its stock so it can profit if it declines. Archer’s stock brushed off the report but it left open questions and was a reminder that the UAM players are cagey at best about disclosing actual progress and use their own their terminology for different phases of certification.

    None has flown a type-conforming prototype, nor flown an out-and-return flight, with a vertical landing and take-off at the midpoint, on a single charge. Cecutta, generally bullish on UAM, does not think that the lack of multi-segment demonstrations is important. “Those are big batteries,” he says “and four or five segments should be possible under ideal conditions.” He did not offer a suggestion as to why the market leaders have not performed what would be a convincing argument that the technology is on track to deliver a real service to cities around the world.

    The Culper affair underscores an unusual aspect of the UAM universe: the degree to which the companies own the narrative. An ecosystem of media sites, consultancies and conference organisers has grown up to dominate the UAM conversation but it depends on the sector’s success. The long-established Helicopter Association International was renamed as the Vertical Flight Society after an influx of funds from eVTOL companies.

    Archer does not have an identifiable media contact. Archer did not acknowledge a request for information associated with this story; Joby did not provide an answer. The companies have not provided access to technical experts, preferring to let their founders talk in generalities and speak to investor-focused podcasts.

    Full speed ahead in the Gulf


    Archer Aviation is planning to make Abu Dhabi its launch market. (Archer)

    One result of this media ‘greyout’ is that the biggest strategic shift in UAM over the past year has been treated as regular news: the agreements between Joby, Archer and the United Arab Emirates to launch passenger services this year with support from the UAE General Civil Aviation Authority – Archer in Abu Dhabi and Joby in Dubai.

    There are conflicting messages on what this means. Some sources are treating this as a test operation, learning lessons that will facilitate and speed up US certification rather than seeking a fast track to carrying paying passengers, a beta test with humans on board. However, Joby Executive Chairman, Paul Sciarra told the online publication, The Air Current last year: “You have certain markets in the Middle East that are definitely willing to move heaven and Earth to be first to market” – a phrase with a clear meaning – “with this technology.”

    There are two clear implications to this. First, Joby and Archer would not be expending effort on UAE certification if it was merely months ahead of US certification, which would provide UAE approval via reciprocity. Indeed, any such effort diverts flight hardware and experienced people from US certification through the end of this year and beyond. Second, it is a major change in how type and production certification are done. In almost every case, the certification process happens in the jurisdiction where the development is done and the intellectual property is held by authorities who have a long legacy of this work. The GCAA has no background in type certification.

    Gulf opinionators appear to be in no doubt that the idea is to accelerate certification beyond the FAA’s pace. “[The] air taxi race needs a ‘warp speed’ push — not bureaucratic brakes,” commented the Gulf News website. “Rigorous certification and safety standards are being put in place, often sequentially – instead of in parallel – likely to delay their rollout where they’re most needed. This marks a notable contrast between Asia’s bold push for air taxi services and the more cautious approach of US and European regulators. This delays deployment, even when early models show strong safety potential, proven by real-time flight test data.”

    This kind of commentary reflects a common technology-world view that regulation is bureaucracy and an impediment to innovation, and at best a box-checking exercise. Archer and Joby are deliberately choosing to have their vehicles operated in states best described as corporate monarchies, where government enables business, and the prestige of the state is critical, a form of government favoured by politically influential tech entrepreneurs, like Elon Musk and Peter Thiel. When Cecutta says “we have tech people now in aerospace, with a very, very different mindset than legacy companies,” it is hard to argue with him. However, the object of type certification, versus beta testing, is to demonstrate, before you enter service, that the vehicle will not have an accident resulting in multiple fatalities in more than one in 100 million flights.

    FBW and failure modes


    Joby is another eVTOL manufacturer making its way towards certification. (Joby)

    The core discipline leading to certification is failure modes, effects and criticality analysis, or FMECA. Essentially, this is a summing-up of all individual failures, at a component level, to ensure that they will not, individually, in combination or through cascade effects, lead to a catastrophic result.

    FMECA for radically new aircraft types “is always problematic,” notes Carlos Fenny, a veteran engineer with long experience in fly-by-wire (FBW). “Component and system failure rates are based on existing component designs,” Fenny continues. “But for all new component and system designs, failure rates and modes of potential failures can only be educated guesses.”

    Fenny is one of a number of UAM-sceptical engineers who have been commenting on LinkedIn and other platforms, and like some others, he has experience on or adjacent to the Bell 525 and Leonardo AW609 programmes, the only two commercial rotorcraft launched so far that use FBW. Neither has yet been certificated after long delays.

    FBW rotorcraft lack the same dynamic stability (inertia) as a fixed-wing aircraft and normally operate at lower altitude, Fenny argues. FMECA may show that a transient failure that is acceptable on a fixed-wing aircraft is much more hazardous on a rotorcraft. The Bell 525 and AW609 incorporate triplex control and actuation systems, which can provide true redundancy but increases complexity and leads to a higher probability of failure, making it harder to reach reliability goals.

    Cecutta does not share these concerns: “Issues with FBW and batteries are greatly exaggerated by naysayers. It won’t be a walk in the park, but it won’t be another AW609.”

    Also asking questions is aircraft designer, Dan Raymer: “The basic conundrum of vertical flight – you need lots of disk area for hover efficiency but far less for efficient forward flight. What to do? Tilt them all forward? Has problems. Tilt some forward and shut some others off? Has problems.”

    Raymer, an independent thinker with a non-American sense of irony, adds: “Luckily, thanks to the near-insanity of the investor class, we are almost at the point of completing the best possible trade study for questions like this.”

    This points to the key difference between Archer’s Midnight and Joby’s S4, and to one of the main points of attack in the Culper report. The S4 has six large (estimated diameter 9ft 6in) fully tilting proprotors arranged so that they form a hexagon in vertical mode. Midnight has six wing-mounted booms with tilting proprotors in front and (apparently) fixed-pitch, two-blade rotors in the rear, all around 6ft in diameter. Both have a total disk area of about 340ft2.

    Videos and images of Archer’s first transition flight in June 2024 showed that the aft rotors were replaced by four-blade units, possibly variable-pitch, which continued to rotate throughout the flight. This would provide more control authority and lower vibration in transition, but the four-blade rotors cannot be stopped in cruise without imposing excessive loads on the booms. (The rigid two-blade units can be stopped with blades fore and aft.) As observers noted, this will incur a drag penalty and complicate stability in forward flight. Archer performed its first vertical flight on 2 June, but in a conventional take-off and landing mode.

    On other eVTOL issues, aerodynamicist, Richard Brown cautions that progress has been “agonisingly slow” in the past year. He continues to emphasise the potential for operational limits due to downwash and outwash from 6,000-6,500lb-class aircraft with high disk loading.

    An FAA study released last December “ended up by doing more harm to the industry than good, especially given the implication from the way the data was presented that hurricane-force winds might be embedded in the field.” Still, Brown suggests, the size of outwash safety zones is being underestimated, even though it will have a direct impact on how many eVTOL operations can be carried out from a vertiport of a given size.

    Predicting VRS for EVTOLs

    Aviation services provider Bristow is betting heavily on the potential of eVTOLs. (Bristow)

    However, Brown notes some more disturbing commentary on vortex ring state (VRS), a potentially dangerous aerodynamic condition to which high-disk-loading aircraft are particularly susceptible. “It’s largely been replaced as the issue du jour by outwash. With a collective ‘phew’,” he says.

    In particular, Brown notes a comment by Joby founder, JoeBen Bevirt at the tech leaders’ All-In Summit in September 2024. “There’s this thing called VRS that affects VTOL aircraft, but [with Joby’s S4] you aren’t going to have all six rotors go in and out of VRS at the same time.”

    As Brown points out, that is the problem. If an eVTOL aircraft has an uncommanded roll or pitch movement, the flight control system must determine whether that is due to a gust or a VRS encounter – and the correct response in one case will worsen the problem in the other. “The situation is not helped by the engineering community having been sold on a particularly dodgy analytic technique that gives very flawed results in terms of VRS prediction.”

    One major external issue facing the eVTOL industry is the attitude of the US administration, where policy since Trump’s inauguration has been mercurial at best, with the latest move in June seeing the White House issue an Executive Order to fast track US adoption of drones and eVTOLs. The campaign had made an issue of the potential for China to capture the lead in UAM – but the FAA was quickly sideswiped after the inauguration by a series of accidents and incidents, the worst being a rotorcraft-to-airliner collision less than three miles from the US Capitol, taking 67 lives, followed by summer chaos at Newark and some other airports due to ATC staff shortages and antiquated equipment.

    The DC area’s heavy use of helicopters for Pentagon and other VIP traffic, as well as law enforcement, had made it one of the most rotorcraft-heavy metro areas in the US. Since the accident, most operations other than Marine One have been shut down.

    Summary


    Cashing in their chips? eVTOL developers are gambling on a smooth path to certification. (Wayne Davis/RAeS)

    Those are top-level issues. We still have very little insight into how much eVTOL rides will cost, how many people will choose them over slower, but door-to-door surface transportation, or how people will react to eVTOL rides in low cloud and foul weather. Nor do we know how the greater population will react to vertiports in their neighbourhood.

    However, we do have a pretty clear idea about why the eVTOL-world does not have much interest in asking those questions.



    Bill Sweetman




    12 August 2025

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  • A project worth buzzing about

    A project worth buzzing about

    How a Baker Hughes team in Italy is embracing biodiversity conservation projects such as beekeeping and fostering meaningful community engagement.

     

    Inspired by the opportunity to drive global impact while delivering local value, Marta joined Baker Hughes three years ago as a procurement intern.

    Today, Marta is a key member of the sustainability team in the Industrial & Energy Technology (IET) business segment of Baker Hughes. As a procurement specialist focused on sustainability, she co-develops the procurement sustainability strategy and is involved in guiding its operationalization across the business. One of the most rewarding aspects of her role, she says, is ‘‘launching innovative initiatives and cultivating environments where sustainability can thrive.’’

    Marta Rinaldi, Baker Hughes

     

    One such initiative is ‘Bees for the Future’, a biodiversity conservation project focused on urban beekeeping and education for sustainable development. It aims at creating a positive impact and fostering sustainability with local suppliers in regions where Baker Hughes employees live and work – which is a key part of  the company’s Planet pillar of sustainability strategy.

    The initiative began in Italy, home to eight Baker Hughes sites and 6,600 employees. Launched initially in Talamona in April 2023, the program expanded to Massa in April 2024, reflecting its growing impact across the nation. The project has resulted in multiple benefits to the larger community, such as corporate crowdfunding with urban regeneration, beekeeping, sustainability-focused educational workshops and social inclusion activities for people with disabilities. 

     

    In Talamona, Italy, Baker Hughes manufactures high-tech components for turbomachinery equipment, including parts for gas and steam turbines, compressors, and other related machinery. The facility is a center of excellence for advanced manufacturing, robotics, and digital solutions, leveraging technologies like additive manufacturing. 

    In Massa, Italy, center of excellence for gas technology equipment, Baker Hughes excels in welding, assembling, and rigorously testing advanced turbomachinery solutions, including the LM9000 aeroderivative gas turbine and large compressors primarily for Liquefied Natural Gas (LNG) and new energy value chains.

    In Massa, the project supported the redevelopment of an abandoned area and several walking trails within the Monte di Pasta Park. There, a honey garden was created featuring over ten species of pollinator-friendly plants and flowers. Together with Baker Hughes suppliers, the initiative adopted nine bee colonies, which are lovingly tended by a professional beekeeper.  

    EFS_August2025_MartiRinaldi speaking at launch event
    Marta Rinaldi, first right, speaking at the Bees for the Future project’s launch event, Italy

     

    To find out more about the project, the Energy Forward Stories team caught up with Marta, as she explained key highlights and learnings:

     

    What inspired your team to launch this project?

    At Baker Hughes, our sustainability strategy includes climate stewardship, biodiversity, inclusion, and supporting education and knowledge to improve quality of life and food security. Sustainability for us, starts with people and the communities where we live and operate in.

    This project was created because we really wanted to do something with our suppliers on sustainability that would have a positive impact locally. The idea was to involve different stakeholders. Some of our partners are members of the local community and non-profit associations, and with such diverse stakeholders, we wanted to create something innovative that encourages dialogue between different realities – one, true hands-on sustainability project!

     

    How did you engage with the team?

    At first, people wanted to better understand the value of getting involved. My role was to focus on explaining the benefits and understanding the specific needs of our stakeholders including the Baker Hughes team, our suppliers, and the local community. As the initiative evolved and we developed more details, there was positivity and enthusiasm from everyone.

    EFS_August2025_Bees  for the future group photo
    Bees for Future project launch event with Baker Hughes employees and the local community, Italy

     

    How were the locations for the installation of the beehives chosen?

    The town of Talamona is close to a local apiary APAS (Association of Beekeeping Producers of the Province of Sondrio), making it ideal for a pilot project. In Massa, the location offered a unique opportunity to regenerate the Monte di Pasta public park, allowing us to integrate biodiversity support with urban renewal and social inclusion. 

    Both Baker Hughes facilities in these two towns have a strong relationship with the community and were therefore identified as potential ‘sustainability hubs’. They were ideal locations for projects that blend local impact with addressing global challenges like decline of pollinators and climate change.  

     

    How did you and the team make this project a reality?

    We began by defining with a local crowdfunding partner the baseline of the project. This was to ensure we established a clear purpose, enabling us to achieve our sustainability goals and respond to specific needs of our stakeholders.

    We then engaged with employees and key external collaborators  to build a cross-functional approach for co-creation, setting-up and fine-tuning the project scope.

    Finally, we launched the initiative by hosting  opening ceremonies , kicking off all the activities related to sustainability such as training sessions, beekeeping and social inclusion. On May 20, 2024, International Bee Day, we officially launched the Massa project at Monte di Pasta Park. The event brought together local officials, school children, suppliers, and community members. In addition to being a celebration, it demonstrated our deep commitment to biodiversity, sustainability education and inclusion. The buzz of the bees was matched only by the energy and smiles of the people.

    Every step was designed to engage and inspire everyone involved.

    EFS_August 2025_beekeeper expert in Italy
    Bee keeping in practice in Italy

     

    What are the three key goals your team established for this project?

    First, our goal is to protect biodiversity and the quality of life by supporting pollinators. Creating habitats that help ecosystems thrive through the adoption of bees and creation of pollinator-friendly environments is essential. Second, we want to foster a culture of keeping sustainability top of mind for all our actions and behaviors – both at work and outside of work – one that is lived, not just talked about. And third, we wanted to respond to the needs of our local community and promote social inclusion, revitalizing public spaces and ensuring that the benefits of the project reach far beyond our office and factory walls.

     

    Have the beehives made a noticeable impact so far?

    Yes. A single bee can visit up to 5,000 flowers a day and we adopted 650,000 bees, meaning from our Massa plant alone, they could visit 3 billion flowers in a single day, a massive boost to any ecosystem. Such a large population of bees could cover hundreds of acres of crops like apples, almonds, or blueberries in the region.

    So far, we have donated 130 kg of honey, we involved 12 strategic partners and four non-profit associations. Through this initiative, around 80 people, employees and non-employees, have been trained.

    In addition, we were able to get insights from the ecosystems’ health. Bees are bio-indicators. They are super sensitive to pollution, so they are perfect for naturally monitoring the environment. The honey analysis confirmed high purity and biodiversity, with no traces of pesticides or harmful pathogens.  So, we were very pleased.

    These results are especially meaningful in the context of pollinator crisis. According to the European Commission, one in three pollinator species in the EU is in decline, and one in ten is at risk of extinction. Around four out of five crop and wild flowering plant species depend on animal pollination, this means that pollinators have a key role in food security and thriving ecosystems. Our project is a small but powerful step in reversing that trend. 

     

    How did you work with charitable organizations to support or guide the project?

    Charities were essential to the project’s success. In Talamona, the honey was donated to the Opera delle Minime Oblate, which supports disadvantaged youth. In Massa, Caritas distributed the honey to local families in need. These organizations helped us ensure that the project had a strong social impact.

    They guided us in understanding local needs and helped us connect sustainability with solidarity, turning honey into a symbol of care in the community.   

    EFS_August 2025_Bees for the futureCommunity event in Italy
    Local community participants at the launch event, in Italy

     

    What does leading this project mean to you personally?

    I really love to talk and connect with different people. I love nature and I am protective about it. This project has shown us that environmental conservation isn’t just about the planet, but its impact reaches far beyond.  

    With a job in corporate sustainability, I found my vocational path and my career, so it is something that gives a meaning to my work. Nature reminds me to listen, not just to the world around me, but to myself and others. It sharpens my focus, sparks brilliant ideas, lifts my mood and energy. Nature has become both a guide and a teacher to me throughout my life.

    I’m inspired by biomimicry – sustainability solutions inspired by nature. It taught me to observe how ecosystems thrive through balance, resilience, and interdependence, and to bring those same principles into the way we work and lead. For example, did you know that bees build honeycombs usinghexagonal cells, which are mathematically the most efficient shape for storing the most honey with the least wax? This structure maximizes space and strength while minimizing material use – a principle even engineers admire.

    Real impact begins when we align our actions with the wisdom of the world we’re trying to protect. True leadership is not about control but about genuine connection.

     

    What is your advice for someone looking to lead a sustainability initiative?

    I would say to start with a clear purpose and look to build strong partnerships. Engage your stakeholders early and often. Explain the ‘why’. Don’t be afraid to start small but think big. Measure your impact, tell your story, and stay open to learning.

    Most importantly, remember that sustainability is not a solo act, it is a collective journey. I truly believe that when you bring people together around a shared goal, the results can be extraordinary. 

     

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  • Porsche Leipzig plant wins Automotive Lean Production Award 2025

    Porsche Leipzig plant wins Automotive Lean Production Award 2025




    The Porsche Leipzig plant has been awarded this year’s Automotive Lean Production Award in the OEM category. The production site in Saxony impressed the expert jury and successfully brought the prestigious accolade to Leipzig.


    The award has been presented annually since 2006 by the consultancy Agamus Consult in collaboration with the specialist magazine ‘Automobil Produktion’. It recognises manufacturing sites that have made outstanding contributions to lean, modern, and digitally integrated production. Under the motto “Learning from the Best”, the initiative aims to highlight how the European automotive industry is harnessing the potential of lean principles and digitalisation to drive innovation and efficiency in production.

    Porsche Leipzig: Focus on quality and cost-effectiveness

    The Leipzig plant stood out in particular for its lean, digitally networked and highly automated production processes. “Porsche Leipzig impresses with its consistent application of lean principles, digital intelligence and innovative automation – always with a clear focus on quality and cost-effectiveness. This makes the plant a worthy winner of the Automotive Lean Production Award 2025 in the OEM category,” says Dr Werner Geiger, Managing Director of Agamus Consult.

    Porsche Leipzig plant receives Automotive Lean Production Award, 2025, Porsche AG





    “A lean, flexible and digitally supported production system is essential to our innovative strength and competitiveness,” says Albrecht Reimold, Member of the Executive Board for Production and Logistics at Porsche AG. “From the very beginning, the Porsche Leipzig plant has stood for transformation and adaptability. Today, three powertrain concepts – petrol, hybrid and fully electric – are produced in a mixed model flow on a single production line. I am personally delighted that our ability to master this high level of complexity has been recognised with this award.”

    Consistent application of lean principles

    Production at Porsche is based on the consistent application of lean principles to enhance efficiency, quality and flexibility. In addition to the use of cutting-edge technologies, key elements include actively involving employees in shaping a continuous improvement process and adopting a holistic approach to conserving resources.

    Porsche Leipzig plant receives Automotive Lean Production Award, 2025, Porsche AG





    “The Automotive Lean Production Award is a great honour for us,” says Gerd Rupp, Chairman of the Management Board of Porsche Leipzig GmbH. “The jury’s recognition not only acknowledges our consistent process optimisation, but also the Leipzig team and its outstanding collective performance. For us, the award is both a mark of recognition and a source of motivation to continue on our path with determination.”

    The award ceremony will take place at the 19th Automotive Lean Production Congress on 25 and 26 November 2025 at Volkswagen Poznań in Poland. Finalists in each award category are nominated based on submitted questionnaires. The awards are then presented following in-depth on-site evaluations: during shopfloor walkthroughs and discussions with plant representatives, the questionnaire results are validated and explored in greater detail.

    Porsche Leipzig plant receives Automotive Lean Production Award, 2025, Porsche AG





    The Porsche Leipzig plant began operations in 2002 as the second Porsche production site alongside the company’s headquarters in Stuttgart-Zuffenhausen. Today, it is home to the production of the Macan and Panamera model lines. Until 2017, the Cayenne was built in Leipzig, and from 2003 to 2006, the legendary Carrera GT super sports car also rolled off the line. The site has received multiple accolades for its smart production and sustainable approach, including the “Lean and Green Management Award” in 2021 and the title “Factory of the Year” in 2023.

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