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This contribution explores the impact of architect Oswald Mathias Ungers and his innovative urban concepts on contemporary city planning. Ungers, whose career began in the 1960s, played a pivotal role in bridging the gap between modernism and postmodernism while fostering a rich exchange of ideas between American and European architectural circles. He developed significant urban experiments, including The Urban Villa, Urban Garden, Grossform, Archipel City, and City within the City. These projects often used Berlin as a testing ground, transforming the city into a laboratory for his visionary ideas. Ungers’ influence extended beyond conventional architectural practice; this position granted him influence within a network of urban theorists who shaped the urban discourse of the late 20th century. A defining moment occurred in the 1980s with the IBA 87 exhibition in Berlin. This event provided a platform for Ungers’ ideas to permeate the architectural community. Architects like Aldo Rossi, Peter Eisenman, John Hejduk, and Rem Koolhaas, who were working on adjacent projects, diverged from the rules of the competition and proposed innovative systems, fed by Ungers concepts. The architectural visions and methodologies that Ungers pioneered remain highly relevant today as cities grapple with a multitude of challenges. By revisiting Ungers’ groundbreaking concepts and approaches, contemporary urban planners and architects can find valuable insights and inspiration to address the pressing issues facing our cities in the 21st century.

Background & Aims: Safety data for patients with hepatocellular carcinoma (HCC) treated with atezolizumab-bevacizumab in the real-world setting remain uncertain. Thus, the aim of this study was to evaluate the incidence of adverse events (AEs) in patients with HCC treated with atezolizumab-bevacizumab in the literature. Methods: In this systematic review and meta-analysis, we searched PubMed for original studies reporting percentages of AEs in patients with HCC receiving atezolizumab-bevacizumab between 2020 to 2023, using the search terms “Atezolizumab/Bevacizumab”, “HCC” and “Adverse events”. We summarized the incidence of AEs and performed a meta-analysis in order to evaluate the incidence of AEs reported in the literature. Results: A total of 30 studies (3,867 patients) were included. The analysis revealed heterogeneity in AE reporting, with arterial hypertension, proteinuria, and fatigue being the most frequently reported AEs whereas incidence of bleeding was reported in 66.7% of the studies and rare immune-related AEs were reported in 26.7% of the studies. The meta-analysis revealed pooled incidence rates of 79% for any grade AEs: 56% for grade 1/2 and 30% for grade ≥3. While the pooled rates of hypertension, anorexia, bleeding, pruritus, rash, and thyroid dysfunction were similar to those reported in the IMbrave150 trial, higher rates were observed in the literature for proteinuria, fatigue, ALT and AST elevations and gastrointestinal perforation. For grade ≥3 AEs, the percentages were consistent with the IMbrave150 trial, except for lower incidences of arterial hypertension and thrombosis in the literature. The exposure-adjusted incidence rates for proteinuria (55.7%), hypertension (45.3%) and fatigue (33.6%) were high. Heterogeneity was observed in the analysis of AEs across articles within the same cohorts of patients. Conclusion: We observed a significant variability in AE reporting for atezolizumab-bevacizumab treatment in HCC in the literature, underscoring the need for standardized reporting practices. Impact and implications: Considering the demonstrated safety of atezolizumab-bevacizumab in randomized-controlled trials, this meta-analysis offers valuable insights into reported occurrences of adverse events. Our study highlights significant heterogeneity among studies, underscoring the need to improve adverse event recording. Understanding the incidence and severity of treatment-related adverse events beyond clinical trials is essential for prompt intervention and may help in preventing treatment discontinuation and complications, potentially leading to better outcomes without significantly compromising quality of life due to adverse events.

Background & Aims: We aimed to explore patient expectations regarding their treatments and prognosis in comparison to physicians' assessments in patients with advanced hepatocellular carcinoma (HCC) receiving systemic treatments. Methods: We prospectively enrolled 205 patients in France and Belgium with Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC receiving systemic treatment (NCT04823754). Patients completed a 28-question survey and the hospital anxiety and depression scale (HADS), while physicians filled a 17-question survey after the initial consultation. Univariate and multivariate models were used to assess factors associated with concordant patient-physician responses, HADS, as well as predicted (by physicians) and observed overall survival. Results: Patients had a median age of 68 years with 75% having BCLC C HCC; 86.3% received atezolizumab/bevacizumab. 60% of patients did not discuss life expectancy with the physician. 63% of the patients believed they had a life expectancy >5 years. Among shared questions between patients and physicians, 36.4% concordance was observed; major differences centered on life expectancy with patients more optimistic than physicians. A lower patient-physician concordance was seen with shorter-consultations (p = 0.003), female physicians (p = 0.02), BCLC C (p = 0.03) and >100 HCC patients/year per physician (p = 0.008). Compared to France, patients from Belgium were more likely to be satisfied with the consultation (p

Background & Aims: Despite its growing incidence, hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) in non-cirrhotic livers remains poorly characterized. We compared the characteristics, management, survival, and trends of MASLD-related HCC in patients with or without underlying cirrhosis in a large multicenter cohort. Methods: A total of 354 cases of MASLD-related HCC presented at the liver tumor meetings of four French university hospitals between 2007 and 2018 were included in the study. Data were extracted from the meetings’ databases and from the French Birth and Death Registry. Results: Of HCC cases, 35% occurred in the absence of cirrhosis. HCC was diagnosed through screening in 60% of patients with cirrhosis, and incidentally in 72% of patients without it. Patients without cirrhosis were older, had a greater tumor burden, but also better liver function than patients with cirrhosis. Patients without cirrhosis showed better overall survival than those with cirrhosis (p = 0.043). However, cirrhosis was not independently associated with overall survival, the independent predictors were age, liver function, tumor burden and BCLC classification. Patients without cirrhosis underwent surgery more frequently than patients with cirrhosis (41% vs. 11%, p

Background & Aims: In France, bulevirtide (BLV) became available in September 2019 through an early access program to treat patients with HDV. The aim of this analysis was to evaluate the efficacy and safety of BLV in patients with HIV and HDV coinfection. Methods: Patients received BLV 2 mg ± pegylated interferon-α (pegIFNα) according to the physician’s decision. The primary endpoint (per-protocol analysis) was the virological response rate at Week 48, defined as the proportion of patients with undetectable serum HDV RNA or a HDV RNA decline >2 log10 IU/ml from baseline. Results: The characteristics of the 38 patients were as follows: 28 male, mean age 47.7 years, and mean baseline HDV RNA viral load 5.7 ± 1.2 log10 IU/ml. Median HIV viral load and mean CD4 count were 32 (30–65) copies/ml and 566 ± 307/mm3, respectively. Eight patients stopped treatment before Week 48. At Week 48, 10 of 19 patients (52.6%) in the 2 mg BLV group and five of seven patients (71.4%) in the 2 mg BLV + pegIFNɑ group had reached virological response (no HDV RNA available in four patients). At Week 48, seven of 19 patients in the 2 mg BLV group and three of six patients in the 2 mg BLV + pegIFNɑ group had a combined response (virological response and normal alanine aminotransferase level). Conclusions: Adults living with HIV coinfected with HDV can be treated by BLV with a virological response in more than 50% of patients. The combination of BLV and pegIFNɑ showed a strong virological response. Impact and implications: Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug–drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug–drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug–drug interaction is reported.

Purpose: To analyze the outcomes following conventional internal limiting membrane (ILM) peeling versus perfluoro octane-assisted inverted flap technique for large macular holes (MH). Methods: A consecutive 99 eyes of 99 patients were enrolled {45 – conventional group and 54 – inverted flap (InFlap) group}. The primary outcome was a difference in closure rate. Secondary outcomes were differences in best-corrected visual acuity (BCVA), restoration of external limiting membrane (ELM) and ellipsoid zone (EZ) between groups at 3 (primary endpoint), 6 and 12 (secondary endpoints) months. Additionally, the effect of different gas tamponades on closure rates, ILM flap disintegration in InFlap group, and subfoveal thickness (SFT) between groups in closed. Results: At 3 months, there was no difference in the closure rate and BCVA between groups. At six months, closure rate was significantly better in the InFlap group. However, this difference was not maintained at 12 months. There was no difference in BCVA between groups at any visit. The ELM recovery was significantly higher in the conventional group at three months; however, there was no difference in ELM/EZ recovery between groups at other visits. The closure rate in the InFlap group was the same irrespective of gas tamponade. The ILM flap was identifiable in one-third of patients at 12 months. In closed MH, SFT was significantly more in InFlap group. Conclusion: The closure rate and visual outcomes remained similar in both groups in the immediate and long term. Conventional ILM peeling technique seems to have early ELM recovery when compared to inverted flap technique.

Abstract Tumor endothelial cells (TECs) actively repress inflammatory responses and maintain an immune‐excluded tumor phenotype. However, the molecular mechanisms that sustain TEC‐mediated immunosuppression remain largely elusive. Here, we show that autophagy ablation in TECs boosts antitumor immunity by supporting infiltration and effector function of T‐cells, thereby restricting melanoma growth. In melanoma‐bearing mice, loss of TEC autophagy leads to the transcriptional expression of an immunostimulatory/inflammatory TEC phenotype driven by heightened NF‐kB and STING signaling. In line, single‐cell transcriptomic datasets from melanoma patients disclose an enriched InflammatoryHigh/AutophagyLow TEC phenotype in correlation with clinical responses to immunotherapy, and responders exhibit an increased presence of inflamed vessels interfacing with infiltrating CD8+ T‐cells. Mechanistically, STING‐dependent immunity in TECs is not critical for the immunomodulatory effects of autophagy ablation, since NF‐kB‐driven inflammation remains functional in STING/ATG5 double knockout TECs. Hence, our study identifies autophagy as a principal tumor vascular anti‐inflammatory mechanism dampening melanoma antitumor immunity.

Sleep disturbances and drug-resistant seizures significantly impact people with idiopathic generalized epilepsy (IGE). Thalamic deep brain stimulation (DBS) offers potential treatment, but its effect on sleep and seizure control needs clarification. In this study, we combined wearable sleep monitoring with electroencephalogram (EEG) confirmation to investigate the impact of nocturnal centromedian nucleus (CM) DBS parameters in a patient with drug-resistant IGE. We found that high-frequency (125 Hz) CM stimulation during sleep severely disrupted sleep macro architecture and exacerbated seizures. Conversely, switching to low-frequency (10 Hz) stimulation enhanced both sleep quality and seizure control. This study underscores the critical need to personalize DBS settings, tailoring them to individual patients’ sleep patterns to maximize therapeutic benefits. While larger-scale trials are needed, our findings pave the way for patient-centric approaches to thalamic neuromodulation, offering a transformative path to improve treatment outcomes and quality of life for those with refractory epilepsy.

Abstract Background The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax. Methods Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management. Results Five hundred twenty-eight practitioners (80% from France) responded to this survey. 75% were hepatogastroenterologists, 20% pulmonologists and the remaining 5% belonged to other specialities. The Hepatic hydrothorax can be located on the left lung for 64% of the responders (66% hepatogastroenterologists vs 57% pulmonologists; p = 0.25); The Hepatic hydrothorax can exist in the absence of clinical ascites for 91% of the responders (93% hepatogastroenterologists vs 88% pulmonologists; p = 0.27). An Ultrasound pleural scanning was systematically performed before a puncture for 43% of the responders (36% hepatogastroenterologists vs 70% pulmonologists; p

ABSTRACT Deep brain stimulation (DBS) is a promising treatment for drug‐refractory epilepsies (DRE) when targeting the anterior nuclei of thalamus (ANT). However, targeting other thalamic nuclei, such as the pulvinar, shows therapeutic promise. Our pioneering case study presents the application of ambulatory seizure monitoring using spectral fingerprinting (12.15–17.15 Hz) recorded through Medtronic Percept DBS implanted bilaterally in the medial pulvinar thalami. This technology offers unprecedented opportunities for real‐time monitoring of seizure burden and thalamocortical network modulation for effective seizure reduction in patients with bilateral mesial temporal and temporal plus epilepsies that are not suitable for resection.

Hypnopompic seizures, characterized by arousal from sleep as the primary clinical manifestation, are a rare and challenging seizure type. Their exact localization has been elusive, often requiring stereotactic EEG (SEEG) for accurate identification. We present the case of a 23-year-old male with drug-resistant focal epilepsy, in whom hypnopompic seizures were localized to the mesial orbitofrontal cortex, with rapid recruitment of the middle temporal gyrus, fusiform gyrus, rostral cingulate, and amygdala. SEEG captured multiple seizures, with arousal occurring 4–5 s after EEG onset, followed by ictal central apnea. The patient underwent resection of the right orbitofrontal and mesial temporal lobe regions and has remained seizure-free for over seven months. This case provides new insights into the neuroanatomical origins of seizure-induced arousal, identifying the mesial orbitofrontal cortex as a potential site for hypnopompic seizures. The findings underscore the critical role of SEEG in accurately localizing seizure foci in complex epilepsy cases, enabling targeted surgical interventions. Additionally, we discuss the orbitofrontal cortex’s role as a site for extra-thalamic arousal pathways, offering new perspectives on the mechanisms underlying hypnopompic seizures.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) and the most common symptoms include fever, dry cough, dyspnea, fatigue, anorexia, ageusia, and anosmia. Cutaneous manifestations are less common and we share our experience with an otherwise healthy and asymptomatic young man. The patient presented with painless acrocynosis of the left toes which progressed to desquamation by day 16 of disease onset. Disease progression is documented via multiple photographs that portray progression of disease and subsequent resolution over approximately six weeks. Symptomatic treatment included non-steroidal anti-inflammatory medications, leg elevation, and warm compresses.

Abstract Objectives To examine the characteristics of the first Advanced Practice Nurses in France and to compare the French model to international standards. Background Common barriers and facilitators to their integration in healthcare provision have been identified internationally. In France, the legislative framework was introduced in 2016, and the first graduates entered the workforce in 2019. Methods The French model was examined in comparison with Hamric's conceptual framework and to the International Council of Nurses' guidelines and definitions. A cross‐sectional survey was also conducted, using three self‐administered online questionnaires. Two were distributed to 2019 and 2020 graduates and a third to the accredited programme directors. The characteristics of advanced practice nursing graduates were described and compared based on employment status and field of practice (primary vs secondary/tertiary care). Results Although the French model of advanced practice nursing meets Hamric's primary criteria and core competencies, it does not differentiate between Nurse Practitioner and Clinical Nurse Specialist roles. Of the 320 students enrolled in one of the 11 accredited training programmes 165 participated in the survey. Mean age was 40, and mean prior nursing experience was 15 years. By February 2021, 30% of respondents were still employed as Registered Nurses. Barriers to practice included insufficient income generation (primary care), the lack of position creation (secondary/tertiary care), the physician‐dependent patient referral process and delays in prescription credentials approval. Conclusions The implementation of advanced practice nursing in France faces several barriers. Legislative adjustments and greater financial incentives to practice seem warranted. Relevance to clinical practice: as in other countries, France introduced advanced practice nursing to respond to the Public Health challenge of improving access to quality health care in the context of increasing chronic disease prevalence and limited resource allocation. Facilitating its integration in the healthcare provision landscape seems paramount.