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.

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.

Long term efficacy and toxicity after stereotactic ablative reirradiation in locally relapsed stage III non-small cell lung cancer.

BACKGROUND: In stage III non-small cell lung cancer (NSCLC) treated with concomitant chemoradiotherapy, there is a high rate of relapse. Some of these relapses are only local and can be treated by stereotactic ablative radiation therapy (SABR). Previous studies reporting outcome after SABR reirradiation of the thorax consisted of a heterogeneous population of various lung cancer stages or even different types of cancer. The purpose of study is to evaluate toxicity and outcome of this strategy in locally relapsed stage III NSCLC only. METHODS: From February 2007 to November 2015, 46 Stage III NSCLC patients treated with SABR, for lung recurrence following conventionally fractionated radiation therapy (CFRT), were retrospectively analyzed. RESULTS: Median follow-up was 47.3 months (1-76.9). The 2 and 4-year progression-free survival (PFS), and overall survival (OS) were of 25.5%/8.6 and 48.9%/30.8%, respectively. Highest presenting toxicity in patients (grade 1 through 5) was: 13 (28.3%), 7 (15.2%), 1 (2.2%), 0 and 2 (4.4%), with deaths due to hemoptysis (n = 1) and alveolitis (n = 1). Although the Biological Effective Dose (at Planning Tumor Volume isocenter) was lower for central tumors treated for an in-field relapse (n = 21, 116 Gy versus 168 Gy, p = 0.005), they had no significant difference in OS than the remaining cohort, but with a higher rate of grade 2-5 toxicities (OR = 0.22, [0.06-0.8], p = 0.02). CONCLUSION: Reirradiation with SABR for local relapse in patients previously treated for stage III NSCLC, is feasible and associated with good outcome. This is also true for central tumors treated for an in-field relapse, but should be radiated with caution to mitigate toxicity.

Is There a Place for Thoracoscopic Enucleation of Esophageal Gastrointestinal Stromal Tumors?

BACKGROUND: Esophageal gastrointestinal stromal tumors (E-GISTs) represent less than 1% of all GISTs. The rarity of this lesion precludes the realization of randomized studies, and its treatment remains a matter of debate. We aimed to evaluate the feasibility of enucleation by video-assisted thoracic surgery (VATS) for low- to intermediate-risk E-GIST. METHODS: We performed a retrospective review of patients treated by enucleation through VATS between January 2004 and January 2014 and reviewed the literature. RESULTS: We included five patients (four men and one woman). Mean age was 53 years (range: 49-79). Three patients were diagnosed because of dysphagia and two others incidentally. The diagnosis was made by immunostaining demonstrating CD117 expression on tumor cells. The mitotic index of all E-GISTs was low (≤ 5 per 50 high-power field). Median postoperative follow-up was 5.5 years, and there was no recurrence. CONCLUSION: Thoracoscopic enucleation of E-GIST seems to represent a valuable option as the postoperative morbidity/mortality is low and the oncological outcome is good for low-to-intermediate grade of malignity tumors.This is a retrospective study focused on minimally invasive treatment of E-GIST. We evaluated the feasibility of VATS enucleation of low-to-medium grade of malignity E-GIST.

Salvage Surgery for Esophageal Cancer: How to Improve Outcomes?

BACKGROUND: Locoregional recurrence rates after definitive chemoradiotherapy (dCRT) for locally advanced esophageal cancer (EC) are high. Salvage surgery (SALV) is considered the best treatment option in case of persistent or recurrent disease for operable patients, but SALV has been associated with increased morbidity and mortality. The aim of this study is to identify factors linked to outcomes after SALV to better select candidates and to optimize perioperative care. STUDY DESIGN: We retrospectively analyzed data from 308 consecutive SALV patients from a large multicenter European cohort. Univariate and multivariate analyses were performed to identify factors associated with in-hospital postoperative morbidity, anastomotic leakage (AL), and overall survival (OS). RESULTS: The in-hospital postoperative mortality and morbidity rates were 8.4 and 34.7%, respectively. Squamous cell histology (p = 0.040) and radiation dose ≥ 55 Gy (p = 0.047) were independently associated with major morbidity. The AL rate was 12.7%, and cervical anastomosis was independently associated with AL (p = 0.002). OS at 5 years was 34.0%. Radiation dose ≥ 55 Gy (p = 0.003), occurrence of postoperative complications (p = 0.006), ypTNM stage 3 (p = 0.019), and positive surgical margins (p < 0.001) were linked to poor prognosis. CONCLUSIONS: SALV is a valuable option for patients with persistent or recurrent disease after dCRT and offers long-term survival. Factors such as radiation dose and anastomosis location identified here will help to optimize outcomes after SALV, which may be considered a standard treatment in the EC therapeutic armamentarium.

Use of circulating tumor cells in prospective clinical trials for NSCLC patients - standardization of the pre-analytical conditions.

BACKGROUND: Circulating tumor cells (CTCs) hold potential for noninvasive diagnosis, prognosis and prediction testing in non-small cell lung cancer (NSCLC) patients. Minimizing degradation or loss of CTCs is pivotal for detection and profiling of the low abundance and fragile CTCs, particularly in clinical trials. We prospectively investigated (NCT02372448) whether a new blood collection device performed better compared to commonly used K3EDTA tubes, when subjected to long-term sample storage. METHODS: Blood samples were drawn into K3EDTA and blood collection tubes (BCT) (Streck), and filtered by the Isolation by SizE of Tumor/Trophoblastic Cells (ISET® system), for CTC detection in two study populations of NSCLC patients; the training set of 14 patients with stage II/IV NSCLC, and the validation set of 36 patients with stage IV NSCLC). MET expression was evaluated by immunocytochemistry (ICC) and anaplastic lymphoma kinase (ALK) gene rearrangement by break-apart fluorescence in situ hybridization (FISH) on ISET-enriched CTCs. RESULTS: Blood processed after 24 h and 48 h in BCT tubes showed stable CTCs counts and integrity, whereas CTCs in K3EDTA tubes showed an altered morphology in all patients. CTCs recovered in BCT or K3EDTA tubes at 24 and 48 h were evaluable by ICC for MET expression and by FISH for ALK rearrangement. CONCLUSIONS: The BCT tubes gave a high yield and preserved the integrity of CTCs after 24 and 48 h of storage at room temperature, which facilitate their molecular characterization in NSCLC patients entering clinical trials.

Chemoradiation Therapy Followed by Surgery in the Treatment of Locoregionally Advanced Non-Small Cell Lung Cancer.

BACKGROUND: The aim of this study was to explore the feasibility of surgery after two induction cycles of cisplatin-docetaxel followed by concomitant 40 Gy chemoradiation in the treatment of initially unresectable stage III non-small cell lung cancer (NSCLC; TAXCIS protocol), and to evaluate overall survival (OS) and recurrence-free survival (RFS) and recurrence risk factors over a larger cohort of patients with a subgroup analysis of patients treated by pneumonectomy. METHODS: Between 2004 and 2014, a total of 37 patients were treated. Only patients responding to induction treatment were included. RESULTS: We operated on 32 stage IIIA and 5 stage IIIB patients. We performed 12 pneumonectomies, 1 bilobectomy, and 23 lobectomies. Status ypT0N0 was obtained for 35% of the patients. Surgery was considered R0 in 86% of the cases. Postoperative morbidity was 21.6% with a mortality of 10.8% (25% after pneumonectomy). OS was 50% at 5 years. The median RFS was 50 months. RFS was 47% at 5 years. Local or locoregional recurrence was diagnosed in 10.8% of the patients, and distant metastasis in 35.1%. Recurrence risk factors were pneumonectomy (p = 0.001) and a histologically incomplete response (p = 0.04). CONCLUSION: The TAXCIS protocol followed by surgery is feasible for initially unresectable NSCLC stage IIIA and B patients. Benefit was noted in responding lesions with better OS and PFS, except after pneumonectomy.

PD-L1 expression in basaloid squamous cell lung carcinoma: Relationship to PD-1+ and CD8+ tumor-infiltrating T cells and outcome.

PD-1/PD-L1 inhibitors demonstrated durable clinical responses in patients with lung squamous cell carcinoma. However, the expression pattern of PD-L1 and the presence of CD8+ and PD-1+ tumor-infiltrating T cells in the basaloid variant of squamous cell carcinoma remain unknown. immunohistochemistry analysis of PD-L1 expression, with three recently validated monoclonal antibodies used in clinical trials (clones SP142, SP263, and 28-8), and detection of CD8+ and PD-1+ tumor-infiltrating T cells was performed on whole-tissue sections from 56 patients following surgery for basaloid squamous cell carcinoma. Data were correlated to clinicopathological parameters and outcome. Fair to poor concordance was observed between the SP142 vs SP263 clones, and SP142 vs 28-8 (κ range, 0.018-0.412), while the 28-8 and SP263 demonstrated a strong correlation in both the tumor cell and immune cell compartments (κ=0.883, and κ=0.721). Expression of PD-L1 correlated with a high content of CD8+ and PD-1+ tumor-infiltrating T cells when using SP142 (P=0.012; P=0.022), but not with SP263 or 28-8 (P=0.314; P=0.611). In the multivariate analysis, we found significantly better disease-free and overall survival rates for high PD-L1 expression with SP142, CD8+ and PD-1+ tumor-infiltrating T cells (P=0.003; P=0.007). No significant prognosis value was observed for SP263 and 28-8 clones, except a correlation between improved overall survival and SP263 in the univariate analysis (P=0.039), not confirmed in the multivariate model. In conclusion, we report that the expression of PD-L1 and the content of CD8+ and PD-1+ tumor-infiltrating T cells is an independent indicator of better outcome in basaloid squamous cell carcinoma patients, although the observed effect is dependent on the PD-L1 immunohistochemistry assay.

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.

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.

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.

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.