Impact of indocyanine green on prolonged air leak in minimally invasive segmentectomy.

BACKGROUND: Video-assisted thoracoscopic segmentectomies have become the gold standard for the treatment of early-stage non-small cell lung cancer less than two centimeters. The main difficulty is the identification of intersegmental boundary lines which dictate postoperative morbidities. METHODS: We conducted a retrospective study to compare the perioperative outcomes of patients who underwent minimally invasive segmentectomy using the traditional deflation-inflation method or the novel indocyanine green (ICG) technique. Using a prospectively maintained database, we performed a retrospective analysis of 197 consecutive anatomical segmentectomies, from 2020 to 2023. Clinical effectiveness, postoperative complications, and histological data were compared. RESULTS: A total of 73 (37%) patients had the inflation-deflation method and 124 (63%) had the intravenous ICG method. There were no significant differences in chest tube duration, prolonged air leak, postoperative complications, and postoperative hospital stays. Surgical margin width was also similar between the two groups. The multivariable analysis confirmed these results. Lastly, intravenous ICG brought no additional value in complex segmentectomies. CONCLUSION: This monocentric and retrospective analysis found no added value of the intravenous ICG on the perioperative results of minimally invasive segmentectomies. The place of this novel technique in the surgical armamentarium remains to be defined. Specific indications such as complex segmentectomy or patients with chronic pulmonary disease require further study.

Evaluation of an acute trust Domestic Abuse Coordinator role: Impact findings and a budget impact model.

Domestic Abuse Coordinators (DACs) work strategically across National Health Service (NHS) hospital and other off-site clinical settings to support clinical staff in domestic abuse enquiry and response, and to co-lead the development and implementation of effective clinical policies and procedures for the management of domestic abuse and the support of survivors. Drawing on data from a large NHS acute trust in central London, we analyse the impact of the DAC role in increasing the rate of referrals of high-risk domestic abuse cases, and generate plausible estimates of the budget impact of the DAC role in respect of costs accrued to NHS trusts. Using eight quarters of clinical data and an interrupted time series design, we find that evidence that implementation of a DAC role is linked with an increase in the rate of high-risk referrals of between 18% and 21% per quarter, indicating improved responses to victim-survivors at highest risk of imminent harm. Under a range of reasonable assumptions, initiation of the DAC role is shown to be cost-saving to an employing acute trust. Future work should seek to quantify the direct impacts to survivor health and wellbeing of the implementation of the DAC role.

Characteristics of patients with atrial fibrillation treated with direct oral anticoagulants and new insights into inappropriate dosing: results from the French National Prospective Registry: PAFF.

AIMS: Since the introduction of direct oral anticoagulant (DOAC) for atrial fibrillation (AF) therapy, inappropriate and/or underdosing of these drugs has been a major clinical challenge. We evaluated the characteristics of patients with AF treated with inappropriate and low-dose DOACs. METHODS AND RESULTS: Patients with AF treated with inappropriate and low-dose DOACs from October 2021 to December 2021 were evaluated from the French National Prospective Registry (PAFF). We evaluated 1890 patients with AF receiving DOACs (apixaban 55%, dabigatran 7%, and rivaroxaban 38%). Inappropriate dosing was noted in 18% of the population. Patients with appropriate dosing had less comorbidities: younger age (75 ± 10 vs. 82 ± 8 years old, P < 0.0001), reduced chronic renal failure (26 vs. 61%, P < 0.0001), and lower CHA2DS2VASc and HASBLED scores (3 ± 2 vs. 4 ± 3, P < 0.0001; 2 ±1 vs. 2 ± 2, P < 0.0001), respectively. In multivariate analysis, older age (P < 0.0001) and a higher CHA2DS2VASc score (P = 0.0056) were independently associated with inappropriate DOAC dosing. Among 472 patients (27%) treated with low-dose rivaroxaban or apixaban, 46% were inappropriately underdosed. Patients inappropriately underdosed were younger (82.3 ± 8.4 vs. 85.9 ± 5.9 years, P < 0.0001) with less chronic renal disease (47 vs. 98%, P < 0.0001). However, these patients had higher rates of prior haemorrhagic events (18 vs. 10%, P = 0.01), clopidogrel use (11 vs. 3%, P = 0.0002), and apixaban prescription (74 vs. 50%, P < 0.0001). CONCLUSION: Within this large registry, DOACs were associated with inappropriate dosing in 18% of cases. Independent predictors of inappropriate dosing were high CHA2DS2VASc scores and older age. Moreover, 46% of patients treated with low-dose DOACs were inappropriately underdosed and more frequently in patients treated with apixaban.

The Need to Set up a Biobank Dedicated to Lymphoid Malignancies: Experience of a Single Center (Laboratory of Clinical and Experimental Pathology, University Côte d'Azur, Nice, France).

Several therapies to improve the management of lymphoma are currently being investigated, necessitating the development of new biomarkers. However, this requires high-quality and clinically annotated biological material. Therefore, we established a lymphoma biobank including all available biological material (tissue specimens and matched biological resources) along with associated clinical data for lymphoma patients diagnosed, according to the WHO classification, between 2005 and 2022 in the Laboratory of Clinical and Experimental Pathology, Nice, France. We retrospectively included selected cases in a new collection at the Côte d'Azur Biobank, which contains 2150 samples from 363 cases (351 patients). The male/female ratio was 1.3, and the median age at diagnosis was 58 years. The most common lymphoma types were classical Hodgkin lymphoma, diffuse large B-cell lymphoma, and extra-nodal marginal zone lymphoma of MALT tissue. The main sites of lymphoma were the mediastinum, lymph node, Waldeyer's ring, and lung. The Côte d'Azur Biobank is ISO 9001 and ISO 20387 certified and aims to provide high quality and diverse biological material to support translational research projects into lymphoma. The clinico-pathological data generated by this collection should aid the development of new biomarkers to enhance the survival of patients with lymphoid malignancies.

Drug-induced liver injury secondary to increased levonorgestrel exposure in a patient taking ritonavir.

We report the first published case of a drug induced liver injury (DILI) presumed secondary to a drug-drug interaction between ritonavir and levonorgestrel progestogen-only emergency contraception (POEC). Our patient is a 25-year-old female living with human immunodeficiency virus (HIV), taking antiretroviral therapy (ART) containing tenofovir alafenamide/emtricitabine and darunavir/ritonavir. She was found to have elevated transaminases at a routine clinic appointment consistent with hepatocellular DILI. Further investigation found the most likely cause of this was a drug-drug interaction (DDI) between the ritonavir component of her ART and recent use of levonorgestrel POEC 3 days earlier. Evidence suggests that ritonavir increases levonorgestrel exposure, yet our patient received double the usual dose as per dispensing guidance at the time. We review the pharmacokinetics of ritonavir-levonorgestrel DDIs and highlight the need for consistent guidelines on this topic.

Lack of correlation between MET and PD-L1 expression in non-small cell lung cancer revealed by comparative study of matched biopsies and surgical resection samples.

INTRODUCTION: Both MET expression and the PD-L1 tumor proportion score (TPS) are companion diagnostics for treatment of advanced non-small cell lung carcinoma (aNSCLC) patients. We evaluated the rate of correlation between MET expression and the PD-L1 TPS in matched biopsies and surgically resected specimens from NSCLC patients. PATIENTS AND METHODS: This retrospective analysis assessed the prevalence and correlation between MET expression (SP44 clone) and the PD-L1 TPS (22C3 clone) by immunohistochemistry together with molecular alterations determined by targeted next-generation sequencing in matched lung biopsy and surgically lung resected specimens from 70 patients with NSCLC. RESULTS: The study found a significant correlation between the MET H-score in surgical samples and matched biopsies (P-value < 0.0001), as well as between the PD-L1 TPS in paired biopsies and surgical samples (P-value < 0.0001). However, there was no significant correlation between the MET H-score or expression subgroups and the PD-L1 TPS in both types of paired samples (P-value = 0.47, and P-value = 0.90). The MET H-score was significantly higher in adenocarcinoma compared to squamous cell carcinoma (P-value < 0.0001). A mutational analysis showed that the MET H-score was significantly higher in NSCLC cases with targetable molecular alterations (P-value = 0.0095), while no significant correlation was found for the PD-L1 TPS. CONCLUSIONS: Our study found no significant correlation between PD-L1 and MET expression in samples from NSCLC patients, highlighting the importance of personalized treatment strategies based on individual expression profiles. These findings provide valuable insight into the development of effective immunotherapy and targeted therapy for NSCLC patients.

Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that-in the case of the interdependent tumor cell morphology and adapted immune response-reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.

Identifying demographics of high risk male and LGBTQ+ survivors of domestic abuse from acute London hospital referrals - case review.

BACKGROUND: Heterosexual men, and lesbians, gay men, bisexual, transgender and queer (LGBTQ+) people are under-described in research and resources relating to domestic abuse (DA), compared to heterosexual cisgender female survivors. Many of the identified DA cases within our hospital organisation that warrant onward multidisciplinary referral, due to ongoing high harm risk, are for male and LGBTQ+ survivors. We aimed to describe demographics and risk patterns of these cases, to inform and equip our specialist Independent Domestic Violence Advocacy (IDVA) service. METHOD: We performed a retrospective case-note review of all Multi-Agency Risk Assessment Conferences (MARAC) referrals for DA, featuring male & LGBTQ+ subjects, across Chelsea and Westminster Hospital NHS Foundation Trust (CWFT), London, UK between April 2019 - December 2020. We recorded demographic data of referral subjects and perpetrators; the origin of referral; the nature of the initial presenting complaint and whether the DA was identified by the subject or by the healthcare provider on enquiry; and recorded rates of co-marginalising and harm risk factors (dependent children, disability, mental health comorbidity, HIV status, drug use, homelessness). RESULTS: We identified 33 cases: 10.2% of CWFT's total MARAC referrals were for men, and 6.7% for LGBTQ+ people (cf. national figures from the same period: 0.1% and 1.3% respectively). Nearly half (48.5%, 16) of the referrals came from sexual health services, just under half (45.5%, 15) from Emergency Departments. 42% (14) disclosures were elicited incidentally during routine enquiry. Six (18%) subjects were also known survivors of sexual violence in addition to DA. The majority (79%, 26) of perpetrators were current or ex-intimate partners. Eight (24%) of the subjects had children under 18. High rates of co-marginalisation factors were present, including use of recreational drugs (45.5%, 15), belonging to an ethnic minority (39.4%, 13), living with HIV (24.2%, 8), living with a disability (18%, 6), mental health comorbidity (27.3%, 9), and experience or risk of homelessness (9%, 3). CONCLUSIONS: Our trust reports a high rate of male and LGBTQ+ high-risk DA referrals, and amongst these there is a high rate of intersecting disadvantages and risk factors. This underlines a need for inclusivity for marginalised groups, inbuilt into domestic abuse health responses. The high rate of disclosure during routine enquiry for domestic abuse supports the use of DA routine enquiry in sexual health settings, and points towards the utility of selective enquiry in other settings (for example, heterosexual males presenting with injuries to emergency departments). We hope that by working with a specialised LGBTQ+ IDVA, we will improve both prompt identification and better outcomes for more GSM patients.

Deep Learning Facilitates Distinguishing Histologic Subtypes of Pulmonary Neuroendocrine Tumors on Digital Whole-Slide Images.

The histological distinction of lung neuroendocrine carcinoma, including small cell lung carcinoma (SCLC), large cell neuroendocrine carcinoma (LCNEC) and atypical carcinoid (AC), can be challenging in some cases, while bearing prognostic and therapeutic significance. To assist pathologists with the differentiation of histologic subtyping, we applied a deep learning classifier equipped with a convolutional neural network (CNN) to recognize lung neuroendocrine neoplasms. Slides of primary lung SCLC, LCNEC and AC were obtained from the Laboratory of Clinical and Experimental Pathology (University Hospital Nice, France). Three thoracic pathologists blindly established gold standard diagnoses. The HALO-AI module (Indica Labs, UK) trained with 18,752 image tiles extracted from 60 slides (SCLC = 20, LCNEC = 20, AC = 20 cases) was then tested on 90 slides (SCLC = 26, LCNEC = 22, AC = 13 and combined SCLC with LCNEC = 4 cases; NSCLC = 25 cases) by F1-score and accuracy. A HALO-AI correct area distribution (AD) cutoff of 50% or more was required to credit the CNN with the correct diagnosis. The tumor maps were false colored and displayed side by side to original hematoxylin and eosin slides with superimposed pathologist annotations. The trained HALO-AI yielded a mean F1-score of 0.99 (95% CI, 0.939-0.999) on the testing set. Our CNN model, providing further larger validation, has the potential to work side by side with the pathologist to accurately differentiate between the different lung neuroendocrine carcinoma in challenging cases.

Acceptability of routine domestic abuse enquiry within sexual health services.

BACKGROUND: Our sexual health services (SHS) introduced routine domestic abuse (DA) enquiry in April 2018 following targeted staff training. A survey was undertaken to ascertain attitudes towards the initiative. METHODS: Between October 2019 and March 2020, patients were invited to respond to an anonymous questionnaire by SMS. Clinical staff were emailed a separate survey. RESULTS: The patient response rate was 40% (226/562): 72% (161/226) female, 80% (179/226) heterosexual, 19% (42) LGBT, 47% (106) aged 25-34 and 25% (57) aged 18-24. Almost all (97%, 220) recalled routine enquiry at their clinic appointment; 91% (206) felt comfortable when asked, and 95% (214) found this acceptable. Fifty-one staff responded (36% response rate), 67% (34) female, 55% (28) heterosexual, 35% (18) LGBT. 43% (22) were nurses, 31% (16) doctors, 12% (6) health advisers and 8% (4) healthcare assistants. The majority of staff 96% (49) were confident with conducting routine enquiry, 92% (47) agreed patients found it acceptable; 92% (47) felt routine enquiry was appropriate and 92% (47) had received targeted training. CONCLUSION: Respondents were overwhelmingly in favour of routine DA enquiry within SHS, and this initiative could be easily adapted in other specialties alongside staff training.

Analytical validation of automated multiplex chromogenic immunohistochemistry for diagnostic and predictive purpose in non-small cell lung cancer.

OBJECTIVES: The evaluation of an increasing number of diagnostic and predictive markers is playing a central role in precision thoracic oncology. Multiplex immunohistochemistry (mIHC), alongside next-generation sequencing, is ideally situated for this purpose and maximizes tumor tissue preservation for molecular analyses that use increasingly large panels. However, the standardization and validation of mIHC that supports routine clinical laboratory processes are mandatory. After a previous proof-of-concept study, we now (i) optimized two automated four-plex assays on a commercially available IHC autostainer for use in daily practices worldwide and (ii) evaluated the repeatability and concordance of the assessment of the cell density. PATIENTS AND METHODS: Two four-plex mIHC assays [i) TTF1, p40, PD-L1, CD8; and, ii) ALK, ROS1, BRAFV600E, NTRK] were optimized on the BenchMark ULTRA autostainer (Ventana Medical Systems, Inc.), as determined in comparison to conventional IHC chromogenic assays. Intra-site repeatability was evaluated on serial tumor sections from non-small cell lung carcinomas (NSCLC). The concordance was assessed by linear fit to plots of the percentage staining evaluated on tumor sections from 89 NSCLC patients. RESULTS: Following optimization, an average concordance for a staining rate of 95.4% was achieved between conventional IHC and mIHC across all selected markers. Assessment of intra-site repeatability showed strong concordance for all these markers (average, R2 = 0.96; P-value < 0.001). CONCLUSIONS: Our optimized mIHC assay gave a sensitive and repeatable assessment of two panels of eight diagnostic and predictive biomarkers for NSCLC. The availability of standardized protocols to determine these biomarkers on a widely available IHC platform will expand the number of pathology laboratories able to determine the eligibility of patients with NSCLC for targeted treatment or immunotherapy in a reliable and concordant manner, thus providing a unique sample-sparing tool to characterize limited tissue samples in thoracic oncology.

Relationship between the oxidative status and the tumor growth in transplanted triple-negative 4T1 breast tumor mice after oral administration of rhenium(I)-diselenoether.

BACKGROUND: Selective inhibitory effects of rhenium(I)-diselenoether (Re-diSe) were observed in cultured breast malignant cells. They were attributed to a decrease in Reactive Oxygen Species (ROS) production. A concomitant decrease in the production of Transforming Growth Factor-beta (TGFß1), Insulin Growth Factor 1 (IGF1), and Vascular Endothelial Growth Factor A (VEGFA) by the malignant cells was also observed. AIM: The study aimed to investigate the anti-tumor effects of Re-diSe on mice bearing 4T1 breast tumors, an experimental model of triple-negative breast cancer, and correlate them with several biomarkers. MATERIAL AND METHODS: 4T1 mammary breast cancer cells were orthotopically inoculated into syngenic BALB/c Jack mice. Different doses of Re-diSe (1, 10, and 60 mg/kg) were administered orally for 23 consecutive days to assess the efficacy and toxicity. The oxidative status was evaluated by assaying Advanced Oxidative Protein Products (AOPP), and by the dinitrophenylhydrazone (DNPH) test in plasma of healthy mice, non-treated tumor-bearing mice (controls), treated tumor-bearing mice, and tumors in all tumor-bearing mice. Tumor necrosis factor (TNFα), VEGFA, VEGFB, TGFß1, Interferon, and selenoprotein P (selenoP) were selected as biomarkers. RESULTS: Doses of 1 and 10 mg/kg did not affect the tumor weights. There was a significant increase in the tumor weights in mice treated with the maximum dose of 60 mg/kg, concomitantly with a significant decrease in AOPP, TNFα, and TGFß1 in the tumors. SelenoP concentrations increased in the plasma but not in the tumors. CONCLUSION: We did not confirm the anti-tumor activity of the Re-diSe compound in this experiment. However, the transplantation of the tumor cells did not induce an expected pro-oxidative status without any increase of the oxidative biomarkers in the plasma of controls compared to healthy mice. This condition could be essential to evaluate the effect of an antioxidant drug. The choice of the experimental model will be primordial to assess the effects of the Re-diSe compound in further studies.

Survivors of domestic abuse and sexual violence within sexual health services, how we responded, who is missing and what should be done?

BACKGROUND: Reports of domestic abuse (DA) and sexual violence (SV) continue to rise across the UK, and sexual health services are well situated to offer a safe setting for disclosure. METHODS: We performed a retrospective analysis of all safeguarding proformas completed between April and September 2019 across three sexual health clinics in London. RESULTS: 158 patients reported current and/or historical DA and/or SV during the collection period. 70% of cohort identified as female, 28% as male and 2% as transgender. 25% of the cohort identified as gay men. Black and Asian attendees were disproportionately represented in the survivor cohort. 86% were offered a same-day appointment with the health advisor team and assessment for onward referral to specialist services. Almost half of the cohort were asymptomatic at the time of attendance and disclosure. DISCUSSION: With changes to access due to ongoing COVID-19 restrictions, asymptomatic survivors may not receive opportunities to disclose as they are directed to online platforms. Healthcare services must adapt routine enquiry practices to ensure safe disclosure is possible to make all contacts count and expand these practices into other healthcare specialities to provide further disclosure opportunities for survivors not attending sexual health services.

Critical Assessment in Routine Clinical Practice of Liquid Biopsy for EGFR Status Testing in Non-Small-Cell Lung Cancer: A Single-Laboratory Experience (LPCE, Nice, France).

BACKGROUND: The introduction of liquid biopsy using PCR-based assays into routine practice has had a strong impact on the treatment of EGFR-mutated lung adenocarcinoma and is now commonly used for routine testing of EGFR mutations in certain clinical settings. To assess whether the claimed benefits of PCR-based assays hold true in daily practice at a multicenter clinical institution, we assessed how treatment decisions are affected by PCR-based assays for the analysis of EGFR mutations from plasma samples in a centralized laboratory (LPCE, Nice, France). PATIENTS AND METHODS: A total of 345 samples were analyzed using the US Food and Drug Administration-approved Cobas EGFR Mutation Test v2 and 103 using the Therascreen EGFR Plasma RGQ PCR Kit over 3 years (395 samples from 324 patients). Eleven plasma samples were validated independently using Cobas at 3 institutions, and 130 samples were analyzed using Stilla digital PCR. Clinical data were collected for 175 (54%) of 324 patients. RESULTS: Cobas was superior to the Therascreen assay and demonstrated 100% reproducibility. Digital PCR showed only 48%, 83%, and 58% concordance with Cobas for exon 19 deletions, L858R mutations, and T790M mutations, respectively. Liquid biopsies helped inform and change treatment when resistance occurred and enabled the detection of EGFR mutations in patients when biopsy tissue results were unavailable. CONCLUSION: PCR-based assays are a fast and convenient test, allowing the detection of primary and secondary EGFR mutations from plasma. Cobas proved to be a reliable test, whereas digital PCR produced too many inconclusive results to be currently recommended as a principal testing device.

Video-assisted mediastinoscopy is safe in patients taking antiplatelet or anticoagulant therapy.

BACKGROUND: The aim of this study was to report our experience with video-assisted mediastinoscopy (VAM) in patients taking antiplatelet (AP) or anticoagulant therapies focusing on perioperative complications (especially haemorrhagic). PATIENTS AND METHODS: We have done a retrospective study from a prospectively maintained database with diagnostic VAM (01/2008-06/2012). We included 54 patients with AP (41 patients - Group A) and anticoagulant (13 patients - Group B) therapies. The control group was formed by 263 patients (Group C). Data regarding the clinical records of the patients, operative time, per- and post-operative complications, total numbers of biopsies and the results of the pathologic examination were collected. We compared the groups A+B versus C, and then A versus C. Statistical differences were calculated by Chi-square test. RESULTS: In Group A, we had two minor complications: cardiac arrhythmia and peroperative minor haemorrhage. The mean operative time was 29 min and the mean post-operative stay was 1.08 days. In Group B, we had one minor complication: Peroperative minor haemorrhage. The mean operative time was 35 min and the mean post-operative stay was 1.07 days. In Group C, the mean operative time was 28 min. One death occurred (mortality rate of 0.38%) because of cardiac arrest at the induction of anaesthesia. One major complication occurred (severe respiratory insufficiency needing re-intubation) and eight minor complications. Morbidity rate was 2.28%. Mean post-operative stay was 1.14 days. No statistical difference was noted between groups. CONCLUSION: VAM can be safely performed in patients receiving AP or anticoagulant treatments. There is no increase in peroperative bleeding or post-operative compressive cervico-mediastinal haematoma.

Anatomical pulmonary resections for primary lung cancer in octogenarians within a dedicated care protocol.

BACKGROUND: The aim of this study was to assess the feasibility of major pulmonary resection for a limited non-small cell lung cancer (NSCLC) in octogenarians within a dedicated care protocol. METHODS: We retrospectively analyzed data of 55 octogenarians operated on in a single institution between January 2005 and December 2016. They were all included in a specific care protocol with systematic geriatric assessment and adaptation of the peri-operative care. We describe the results of post-operative morbidity, mortality, and survival after anatomical resection and radical lymphadenectomy. RESULTS: Mean age at the time of surgery was 82.1 years (80-86 years). Median Charlson's comorbidity score was 0 (0-3). All patients were classified Balducci 1 or 2. We performed 2 pneumonectomies (3%), 3 bilobectomies (5%), 47 lobectomies (85%) and 3 segmentectomies (5%). The median hospital stay was 11.5 days (7-31 days). The 30-day mortality rate was 3%. The total of relevant clinical complications (Clavien 3 to 5) was 16% (n=9). The Overall Survival at one, three and five years were, respectively: 83% (95% CI: 75-95%); 70% (95% CI: 56-87%); 58% (95% CI: 43-79%). CONCLUSIONS: Major pulmonary resection for primary lung cancer in octogenarians seems to be safe, with an acceptable morbidity, mortality and long-term survival rate, when processing to rigorous selection of the patients, within a dedicated care protocol.