Prospective Trial Research Articles

A Preliminary Controlled Trial of Endoscopic Ultrasound-guided Fiducial Markers to Guide Pancreas Surgery.

Endoscopic ultrasound (EUS) is routinely used for fiducial marker placement (FMP) to guide stereotactic radiation of pancreatic tumors, but EUS-FMP explicitly to guide surgery has not been studied in a prospective, controlled manner. Multipurpose EUS systems have been developed that facilitate simultaneous EUS-FMP at the time of biopsy. We aimed to evaluate the feasibility of EUS-FMP to guide pancreatic resection. In this prospective trial, we enrolled patients with resectable pancreas masses undergoing tissue sampling and placed preloaded fiducials immediately after biopsy. Intraprocedure confirmation of carcinoma, neuroendocrine, and nonlymphomatous neoplasia by rapid on-site evaluation and lesion size <4 cm was required. The main outcomes were the feasibility and ease of preoperative placement and intraoperative detection of the markers using predefined Likert scales. In 20 patients, EUS-FMP was successful before planned surgery and placement was technically straightforward (Likert Scale: 9.1 ± 1.3; range: 1, most challenging to 10, most facile). Intraoperative detection was feasible and improved when compared with a pre-established comparator of 5 representing an equivalent lesion without a marker (Likert Scale: 7.8 ± 2.2; range: 1, most difficult to 10, most facile; P = 0.011). The mean tumor size on EUS was 1.7 ± 0.9 (range: 0.5 to 3.6) cm. EUS-FMP is feasible and safe for resectable pancreatic tumors before surgery and may assist in perioperative detection. Preloaded fiducials may be considered for placement at the time of initial referral for EUS-fine needle biopsy.

Treatment Advances in Lung Cancer with Leptomeningeal Metastasis.

Leptomeningeal metastasis (LM) is a serious and often fatal complication in patients with advanced lung cancer, resulting in significant neurological deficits, decreased quality of life, and a poor prognosis. This article summarizes current research advances in treating lung cancer with meningeal metastases, discusses clinical challenges, and explores treatment strategies. Through an extensive review of relevant clinical trial reports and screening of recent conference abstracts, we collected clinical data on treating patients with lung cancer with meningeal metastases to provide an overview of the current research progress. Exciting progress has been made by focusing on specific mutations within lung cancer, including the use of EGFR tyrosine kinase inhibitors or inhibitors for anaplastic lymphoma kinase gene rearrangement, such as osimertinib, alectinib, and lorlatinib. These targeted therapies have shown impressive results in penetrating the central nervous system (CNS). Regarding whole-brain radiotherapy, there is currently some controversy among investigators regarding its effect on survival. Additionally, immune checkpoint inhibitors (ICIs) have demonstrated reliable clinical benefits due to their ability to retain anticancer activity in CNS metastases. Moreover, combination therapy shows promise in providing further treatment possibilities. Considerable progress has been made in the clinical research of lung cancer with LM. However, the sample size of prospective clinical trials investigating LM for lung cancer is still limited, with most reports being retrospective. Developing more effective management protocols for metastatic LM in lung cancer remains an ongoing challenge for the future.

Efficacy of Dexamethasone in Reducing Pain and Inflammation and Accelerating Total Hip Arthroplasty Postoperative Recovery: A Randomized Controlled Trial

PurposeTo evaluate the efficacy of dexamethasone in reducing pain and accelerating recovery after total hip arthroplasty (THA). DesignA prospective randomized controlled trial. MethodsA total of 98 patients who underwent THA received either low-dose (10 mg) dexamethasone (dexa group) or isotonic saline (placebo group). C-reactive protein and interleukin-6 levels were recorded at 24, 48, and 72 hours after surgery. Pain visual analog scale (VAS) score at rest and walking, the incidence of postoperative nausea and vomiting (PONV), nausea VAS score, postoperative identity-consequence fatigue scale rating, antiemetic use, postoperative length of stay (PLOS), and complications were also recorded and compared. FindingsInflammatory marker (C-reactive protein and interleukin-6) levels at 24, 48, and 72 hours postoperatively in the dexa group were lower than that in the placebo group (P < .05). After 24 hours of rest, the dynamic pain VAS scores in the dexa group were lower than those in the placebo group (P < .05). The incidence of PONV, nausea VAS score, and identity-consequence fatigue scale score in the dexa group were lower than those in the placebo group (P < .05), and the dosages of analgesics and antiemetics were also lower (P < .05). In addition, PLOS in the dexa group was shorter than that in the placebo group (P < .05). No significant difference in perioperative complications between the two groups was observed (P > .05). ConclusionsLow-dose dexamethasone in the THA perioperative period can effectively reduce inflammatory marker levels, pain, nausea, postoperative fatigue, opioid analgesic use, and shorten PLOS without increasing complications.

Reirradiation of metastases of the central nervous system: part 1-brain metastasis.

Because of improved survival of cancer patients, more patients irradiated for brain metastases develop intracerebral recurrences requiring subsequent courses of radiotherapy. Five studies focused on reirradiation with whole-brain radiation therapy (WBRT) after initial WBRT for brain metastases. Following the second WBRT course, improvement of clinical symptoms was found in 31-68% of patients. Rates of neurotoxicity, such as encephalopathy or cognitive decline, were reported in two studies (1.4% and 32%). In another study, severe or unexpected adverse events were not observed. Survival following the second WBRT course was generally poor, with median survival times of 2.9-4.1 months. The survival prognosis of patients receiving two courses of WBRT can be estimated by a scoring tool considering five prognostic factors. Three studies investigated reirradiation with single-fraction stereotactic radiosurgery (SF-SRS) following primary WBRT. One-year local control rates were 74-91%, and median survival times ranged between 7.8 and 14 months. Rates of radiation necrosis (RN) after reirradiation were 0-6%. Seven studies were considered that investigated re-treatment with SF-SRS or fractionated stereotactic radiation therapy (FSRT) following initial SF-SRS or FSRT. One-year local control rates were 60-88%, and the median survival times ranged between 8.3 and 25 months. During follow-up after reirradiation, rates of overall (asymptomatic or symptomatic) RN ranged between 12.5% and 30.4%. Symptomatic RN occurred in 4.3% to 23.9% of cases (patients or lesions). The risk of RN associated with symptoms and/or requiring surgery or corticosteroids appears lower after reirradiation with FSRT when compared to SF-SRS. Other potential risk factors of RN include the volume of overlap of normal tissue receiving 12 Gy at the first course and 18 Gy at the second course of SF-SRS, maximum doses ≥40 Gy of the first or the second SF-SRS courses, V12 Gy >9 cm3 of the second course, initial treatment with SF-SRS, volume of normal brain receiving 5 Gy during reirradiation with FSRT, and systemic treatment. Cumulative EQD2 ≤100-120 Gy2 to brain, <100 Gy2 to brainstem, and <75 Gy2 to chiasm and optic nerves may be considered safe. Since most studies were retrospective in nature, prospective trials are required to better define safety and efficacy of reirradiation for recurrent or progressive brain metastases.

Endovascular thrombectomy beyond 24 hours from last known well: a systematic review with meta-analysis

BackgroundDifferent studies have demonstrated the benefit of endovascular treatment (EVT) up to 24 hours after acute ischemic stroke (AIS) onset. Recent cohort observational studies suggest that patients with large vessel...

Treatment of canine perineal hernia with a fascia lata graft is noninferior to the elevation of the internal obturator muscle: a prospective randomized trial of 66 dogs.

To compare the recurrence rate after herniorrhaphy of canine perineal hernia (PH) using elevation of the internal obturator muscle (EIOM) or fascia lata graft (FLG) and assess how clinical signs related to defecation evolve during 12 months postoperatively. 66 client-owned male dogs undergoing PH surgery between March 1, 2017, and December 31, 2020. Dogs were randomized into 2 groups (EIOM = 36; FLG = 30) applying 2 stratification factors: preoperative bladder location and the defecation signs score (DSS). Follow-up visits were at 2 weeks and 3, 6, and 12 months postoperatively. The main outcome, the recurrence of PH was evaluated by rectal examination. We evaluated the noninferiority of FLG to EIOM from the difference in recurrence proportions between the techniques (95% CI), comparing the CI with a pre-defined noninferiority margin (15%). To evaluate defecation signs, the DSS was calculated from the owner questionnaire and assessed with a linear mixed model (P < .05 significant). In 63 dogs attending the 12-month follow-up, the recurrence rate was 8.8% (3/34) in the EIOM and 10.3% (3/29) in the FLG group. The CI (-11.94% to 14.99%) was below the pre-defined margin, indicating the noninferiority of FLG. After surgery, the DSS decreased (P < .001), remaining low during the follow-up. FLG was non-inferior to EIOM when considering recurrence. The DSS decreased postoperatively and complications were uncommon. FLG is a useful alternative for the treatment of canine PH.

Del Nido versus cold crystalloid cardioplegia for myocardial protection during ventricular septal defect repair in children under one year of age: a prospective randomized trial

Rationale: The choice of strategy for myocardial protection during procedures with cardiopulmonary bypass and cardioplegic arrest in children is not regulated by clinical guidelines due to insufficient data from clinical studies. The issue of methods to assess myocardial injury remains unresolved.&#x0D; Aim: To assess the frequency and specifics of the development of intraoperative myocardial injury syndrome in children of the first year of life with ventricular septal defect depending on the strategy for cardioplegia.&#x0D; Materials and methods: In a single center, prospective, randomized controlled trial we compared two cardioplegia strategies during surgical closure of ventricular septal defect in infants aged from 1 to 12 months: del Nido blood cardioplegia (n = 102) and cold crystalloid cardioplegia with Custodiol solution (n = 102). The primary endpoint was a persistent over 10-fold increase above the upper limit of the normal in the plasma concentration of high-sensitivity troponin I at 6 hours after surgery persisting after 24 hours. The secondary combined endpoint was myocardial damage verified by persistent increase in troponin I level more than 10-fold above the upper limit of the normal, persisting at 6 and 24 hours, accompanied by new pathological Q waves, acute complete left bundle branch block, abnormalities of the end part of the ventricular complex on the electrocardiography (ST segment elevation 1 mm or ST depression of 1 mm in more than 2 adjacent leads), and a decrease in the global longitudinal strain of the left ventricle by 50% from the initial value at 6 hours after surgery.&#x0D; Results: In 53/204 (26%) patients, the increase in troponin I persisted at 24 hours after the surgery and was associated with electrocardiography abnormalities, changes in the parameters of left ventricle longitudinal mechanics, and in some cases required greater inotropic support. By the end of the 1st postoperative 24 hours, the longitudinal strain of the left ventricle showed more negative changes over time in the Custodiol group compared to that in the del Nido group (-10 [-14.1; -6.27] versus -14.8 [- 16.5; -10]%; p 0.0001). The same was true for the left ventricle global strain rate (-0.71 [-0.9; -0.52] s-1 in the del Nido group and -0.57 [-0.760; - 0.44] s-1 in the Custodiol group; p = 0.0049). The primary endpoint was achieved by 21 (20.6%) and 55 (53.9%) patients in the del Nido and Custodiol groups, respectively (p = 0.032). The combined endpoint in the Custodiol group was achieved by 34 (33.3%) versus 19 (18.6%) patients in the del Nido group (p = 0.049, χ2 = 3.875, DF = 1, φ = 0.191).&#x0D; Conclusion: Del Nido blood cardioplegia compared to cold crystalloid cardioplegia with Custodiol has advantages in terms of preventing intraoperative myocardial damage and minimizing its severity. When assessing myocardial damage, such indicators as left ventricle global longitudinal strain and left ventricle global strain rate are informative, along with an increase in the troponin I level.

MRI-based Texture Analysis in Differentiation of Benign and Malignant Vertebral Compression Fractures.

The diagnosis and characterization of vertebral compression fractures are very important for clinical management. In this evaluation, which is usually performed with diagnostic (conventional) imaging, the findings are not always typical or diagnostic. Therefore, it is important to have new information to support imaging findings. Texture analysis is a method that can evaluate information contained in diagnostic images and is not visually noticeable. This study aimed to evaluate the magnetic resonance images of cases diagnosed with vertebral compression fractures by the texture analysis method, compare them with histopathological data, and investigate the effectiveness of this method in the differentiation of benign and malignant vertebral compression fractures. Fifty-five patients with a total of 56 vertebral compression fractures were included in the study. Magnetic resonance images were examined and segmented using Local Image Feature Extraction (LIFEx) software, which is an open-source program for texture analysis. The results were compared with the histopathological diagnosis. The application of the Decision Tree algorithm to the dataset yielded impressively accurate predictions (≈95% in accuracy, precision, and recall). Interpreting tissue analysis parameters together with conventional magnetic resonance imaging findings can improve the abilities of radiologists, lead to accurate diagnoses, and prevent unnecessary invasive procedures. Further prospective trials in larger populations are needed to verify the role and performance of texture analysis in patients with vertebral compression fractures.

307 Active Exchange of CSF for Rapid Removal of Blood in Hemorrhagic Stroke—Multicenter Experience in 40 Patients

INTRODUCTION: Spontaneous Intracerebral hemorrhage (ICH) and subarachnoidal hemorrhages (SAH) can represent with intraventricular hemorrhage (IVH). Previous studies have demonstrated, patients with IVH have higher mortality and morbidity. Neuroinflammation due to organization of blood in cerebrospinal fluid (CSF) is one of the key contributing factors to poor outcome. METHODS: Data utilizing the new active EVD system were collected from six leading centers in the EU and USA. 40 patients were analyzed, 21 patients had SAH, 13 patients had spontaneous ICH related IVH, and six patient had vascular anomaly related hemorrhage. Blood removal from ventricular system was calculated utilizing daily CT imaging. Actual and expected shunt dependency were calculated for SAH patients with CHESS score. RESULTS: Removal of blood from CSF system with the active EVD was achieved safely. Pace of blood removal was highly related to irrigation volume used during treatment. All the 13 spontaneous ICH patients had IVH clearance of median 91.3% (0.7-100%) in average 7.6 days. Additionally, in the SAH patients, there was lower shunt (2) dependency compared to those observed in literature and to expected (11) calculated based on CHESS score. Vascular anomaly cohort had median IVH clearance 91.3% in average 8.0 days. CONCLUSIONS: It is safe and feasible to remove blood from CSF system in an accelerated fashion via active EVD. Active removal of blood reduced adverse events in this patient population. Removal of blood is highly related to irrigation rate. Prospective trials are needed to demonstrate the target population who will benefit the most from CSF exchange during hemorrhagic stroke treatment.

Comprehensive Assessment of the Functional Outcomes of Partial Turbinectomy: A Prospective Clinical Trial.

The inferior and middle turbinates have crucial roles in nasal function, but their enlargement can cause obstructive effects, which can lead to breathing difficulties, sleep and smell disorders, and headaches. Partial turbinectomy is a common surgical technique used to address this issue during septorhinoplasty, but it carries risks such as empty nose syndrome. A clinical trial was designed to evaluate the functional outcomes of middle and inferior partial turbinectomy with a holistic approach. Patients with NOSE questionnaire scores of 30 or higher, and grade 4 inferior turbinates and/or advanced middle concha bullosa were included. Patients completed questionnaires related to breathing, empty nose syndrome, headache, and olfaction preoperatively and at one-month, three-month, six-month, and first-year periods postoperatively. The partial excisions of the inferior and middle turbinates were carried out with serrated scissors while trying to preserve adequate turbinate size to maintain function. This study found that NOSE scores, headache frequency, and severity improved postoperatively. The olfactory-related quality of life of the patients with impairments in this area significantly improved found to be improved at all postoperative evaluations. None of the patients experienced prolonged bleeding requiring surgical intervention. No cases of anosmia and empty nose syndrome were reported. Partial turbinectomy of middle and inferior turbinates during septorhinoplasty can alleviate symptoms of turbinate hypertrophy, such as breathing issues, olfactory disorders, and headaches. It is an easy, reliable, and efficient surgical maneuver. Proper technique can minimize the risk of empty nose syndrome and other complications of turbinectomy surgery. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Germline Genetic Testing and Survival Outcomes Among Children With Rhabdomyosarcoma

Determining the impact of germline cancer-predisposition variants (CPVs) on outcomes could inform novel approaches to testing and treating children with rhabdomyosarcoma. To assess whether CPVs are associated with outcome among children with rhabdomyosarcoma. In this cohort study, data were obtained for individuals, aged 0.01-23.23 years, newly diagnosed with rhabdomyosarcoma who were treated across 171 Children's Oncology Group sites from March 15, 1999, to December 8, 2017. Data analysis was performed from June 16, 2021, to May 15, 2023. The presence of a CPV in 24 rhabdomyosarcoma-associated cancer-predisposition genes (CPGs) or an expanded set of 63 autosomal-dominant CPGs. Overall survival (OS) and event-free survival (EFS) were the main outcomes, using the Kaplan-Meier estimator to assess survival probabilities and the Cox proportional hazards regression model to adjust for clinical covariates. Analyses were stratified by tumor histology and the fusion status of PAX3 or PAX7 to the FOXO1 gene. In this study of 580 individuals with rhabdomyosarcoma, the median patient age was 5.9 years (range, 0.01-23.23 years), and the male-to-female ratio was 1.5 to 1 (351 [60.5%] male). For patients with CPVs in rhabdomyosarcoma-associated CPGs, EFS was 48.4% compared with 57.8% for patients without a CPV (P = .10), and OS was 53.7% compared with 65.3% for patients without a CPV (P = .06). After adjustment, patients with CPVs had significantly worse OS (adjusted hazard ratio [AHR], 2.49 [95% CI, 1.39-4.45]; P = .002), and the outcomes were not better among patients with embryonal histology (EFS: AHR, 2.25 [95% CI, 1.25-4.06]; P = .007]; OS: AHR, 2.83 [95% CI, 1.47-5.43]; P = .002]). These associations were not due to the development of a second malignant neoplasm, and importantly, patients with fusion-negative rhabdomyosarcoma who harbored a CPV had similarly inferior outcomes as patients with fusion-positive rhabdomyosarcoma without CPVs (EFS: AHR, 1.35 [95% CI, 0.71-2.59]; P = .37; OS: AHR, 1.71 [95% CI, 0.84-3.47]; P = .14). There were no significant differences in outcome by CPV status of the 63 CPG set. This cohort study identified a group of patients with embryonal rhabdomyosarcoma who had a particularly poor outcome. Other important clinical findings included that individuals with TP53 had poor outcomes independent of second malignant neoplasms and that patients with fusion-negative rhabdomyosarcoma who harbored a CPV had outcomes comparable to patients with fusion-positive rhabdomyosarcoma. These findings suggest that germline CPV testing may aid in clinical prognosis and should be considered in prospective risk-based clinical trials.

Abstract 1536: Deciphering the crosstalk within the tumor microenvironment of NSCLC by a virtual microdissection approach

Abstract Introduction: Non-small cell lung cancer (NSCLC) is a highly heterogenous disease with the largest number of cancer-related mortality worldwide, one of the reasons for this is the complex and diverse tumor microenvironment (TME) comprising of numerous cell types. Several studies have already highlighted the importance of TME in dictating progression steps and response to therapies; however, a transcriptome-based molecular subtyping of patients in lung adenocarcinomas (LUADs) and lung squamous cell carcinomas (LUSCs) can further determine the distinct tumor immune microenvironment (TiME), which can eventually provide a systematic overview to improve the diagnosis and prognosis of patients. Material and method: To elucidate such nature of interactions between tumor cells and cells comprising the TME, we exploited the transcriptome of 300 early stages (Ib-IIIa) NSCLC recruited in the prospective observational clinical trial PROMOLE. With the help of a clustering approach, initially we performed a molecular-based virtual stratification/dissection on the NSCLC patients. Next, to elucidate the relative cell-type abundance, a deconvolution approach was applied to identify the possibility of tumor infiltrating immune cells within these subgroups. Immunohistochemistry (IHC) was then used to substantiate these predictions on tumor cells. Results and discussion: The resulting subgroups of LUADs and LUSCs are biologically well-characterized by mutational and gene expression profiles. Cell-type abundance approach identified samples which are enriched with tumor infiltrating immune cells like Neutrophils, Tcells, macrophages, etc. These findings were positively confirmed by IHC with multiple cell markers such as MPO, CD4, CD8, CD68, etc. Integrating these two results highlighted the proportion of TiME in the two different sub-populations along with shedding some light on the crosstalk happening between different cancer-/immune- cell lines. Conclusion: The in-silico predictions on bulk RNA data by virtual micro-dissection, distinguished the two distinct NSCLC subtypes, each associated with clinical and molecular features. Furthermore, the immune cells infiltration suggests a possible role of infiltrating tumor immune cells with the prognosis of patients. Our analysis successfully performed an intra-sample and inter-sample comparison, which can unveil new prognostic markers that can provide relevant information for cancer immunotherapy. Citation Format: Sushant Parab, Francesca Napoli, Davide Corà, Gabriella Doronzo, Valentina Communanza, Luisella Righi, Luca Primo, Valentina Monica, Lorenzo Manganaro, Bianco Selene, Paolo Bironzo, Giorgio Scagliotti, Federico Bussolino. Deciphering the crosstalk within the tumor microenvironment of NSCLC by a virtual microdissection approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1536.

Cancer screening with multicancer detection tests: A translational science review.

Multicancer detection (MCD) tests use a single, easily obtainable biospecimen, such as blood, to screen for more than one cancer concurrently. MCD tests can potentially be used to improve early cancer detection, including cancers that currently lack effective screening methods. However, these tests have unknown and unquantified benefits and harms. MCD tests differ from conventional cancer screening tests in that the organ responsible for a positive test is unknown, and a broad diagnostic workup may be necessary to confirm the location and type of underlying cancer. Among two prospective studies involving greater than 16,000 individuals, MCD tests identified those who had some cancers without currently recommended screening tests, including pancreas, ovary, liver, uterus, small intestine, oropharyngeal, bone, thyroid, and hematologic malignancies, at early stages. Reported MCD test sensitivities range from 27% to 95% but differ by organ and are lower for early stage cancers, for which treatment toxicity would be lowest and the potential for cure might be highest. False reassurance from a negative MCD result may reduce screening adherence, risking a loss in proven public health benefits from standard-of-care screening. Prospective clinical trials are needed to address uncertainties about MCD accuracy to detect different cancers in asymptomatic individuals, whether these tests can detect cancer sufficiently early for effective treatment and mortality reduction, the degree to which these tests may contribute to cancer overdiagnosis and overtreatment, whether MCD tests work equally well across all populations, and the appropriate diagnostic evaluation and follow-up for patients with a positive test.

Clofarabine monotherapy in aggressive, relapsed and refractory Langerhans cell histiocytosis.

Over 50% of patients with systemic LCH are not cured with front-line therapies, and data to guide salvage options are limited. We describe 58 patients with LCH who were treated with clofarabine. Clofarabine monotherapy was active against LCH in this cohort, including heavily pretreated patients with a systemic objective response rate of 92.6%, higher in children (93.8%) than adults (83.3%). BRAFV600E+ variant allele frequency in peripheral blood is correlated with clinical responses. Prospective multicentre trials are warranted to determine optimal dosing, long-term efficacy, late toxicities, relative cost and patient-reported outcomes of clofarabine compared to alternative LCH salvage therapy strategies.

Intensive Care Treatment of Pulmonary Embolism: An Update Based on the Revised AWMF S2k Guideline.

Acute pulmonary embolism (PE) remains a significant cause of morbidity and requires prompt diagnosis and management. The prognosis of affected patients depends on the clinical severity. Therefore, risk stratification is imperative for therapeutic decision-making. Patients with high-risk PE need intensive care. These include patients who have successfully survived resuscitation, with obstructive shock or persistent haemodynamic instability. Bedside diagnostics by means of sonographic procedures are of outstanding importance in this high-risk population. In addition to the treatment of hypoxaemia with noninvasive and invasive techniques, the focus is on drug-based haemodynamic stabilisation and usually requires the elimination or reduction of pulmonary vascular thrombotic obstruction by thrombolysis. In the event of a contraindication to thrombolysis or failure of thrombolysis, various catheter-based procedures for thrombus extraction and local thrombolysis are available today and represent an increasing alternative to surgical embolectomy. Mechanical circulatory support systems can bridge the gap between circulatory arrest or refractory shock and definitive stabilisation but are reserved for centres with the appropriate expertise. Therapeutic strategies for patients with intermediate- to high-risk PE in terms of reduced-dose thrombolytic therapy or catheter-based procedures need to be further evaluated in prospective clinical trials.

Optimizing the consent process for emergent laparoscopic cholecystectomy using an interactive digital education platform: a randomized control trial.

Informed consent is essential for any surgery. The use of digital education platforms (DEPs) can enhance patient understanding of the consent discussion and is a method to standardize the consent process in elective, ambulatory settings. The use of DEP as an adjunct to standard verbal consent (SVC) has not been studied in an acute care setting. We conducted a prospective randomized control trial with patients presenting to the emergency department of a tertiary care hospital with acute biliary pathology requiring a laparoscopic cholecystectomy (LC) between August 2021 and April 2023. Participants were randomized 1:1 to receive either a DEP module with SVC or SVC alone. Baseline procedure-specific knowledge and self-reported understanding of risks and benefits of LC were collected using a questionnaire. Primary outcome was immediate post-intervention knowledge assessed using a 21-question multiple choice questionnaire. Secondary outcomes were delayed procedure-specific knowledge and participants' satisfaction with the consent discussion. We recruited 79 participants and randomized them 1:1 into the intervention group (DEP + SVC, n = 40) and the control group (SVC, n = 39). Baseline demographics and baseline procedure-specific knowledge were similar between groups. The immediate post-intervention knowledge was significantly higher for participants in the intervention versus the control group with a Cohen's d effect size of 0.68 (85.2(10.6)% vs. 78.2(9.9)%; p = 0.004). Similarly, self-reported understanding of risks and benefits of LC was significantly greater for participants in the intervention versus the control group with a Cohen's effect size of 0.76 (68.5(16.4)% vs. 55.1(18.8)%; p = 0.001). For participants who completed the delayed post-intervention assessment (n = 29), there continued to be significantly higher retention of acquired knowledge in the intervention group with a Cohen's effect size of 0.61 (86.5(8.5)% vs. 79.8 (13.1)%; p = 0.024). There was no difference in participants' self-reported satisfaction with the consent discussion between groups (69.5(6.7)% vs. 67.2(7.7)%; p = 0.149). The addition of digital education platform to standard verbal consent significantly improves patient's early and delayed understanding of risks and benefits of LC in an acute care setting.

Mid-term surgical success after transscleral ab interno glaucoma gel stent implantation.

To investigate the surgical success and efficacy of XEN45 implantation (XEN45 μm, AbbVie Inc., USA) with and without combined cataract surgery up to the first 5 years. In a prospective observational monocentric trial, 192 eyes of 157 patients with open-angle glaucoma received either XEN45 implants only (solo surgery group) or combined surgery/cataract surgeries (combined surgery group). Surgical success (qualified and full success; IOP-limit: ≤12, 15, 18, 21 mmHg), time to secondary IOP-lowering procedure, IOP and number of IOP-lowering medications were analysed for 1, 2, 3, 4 and 5 years. Compared to baseline, IOP (24.1 ± 8.1 to 12.6 ± 2.8 mmHg, -48%, p < 0.001) and the number of IOP-lowering medications (3.0 ± 1.0 to 1.5 ± 1.2, -50%, p < 0.001) decreased significantly at 5 years. Although no differences between IOP and the number of IOP-lowering medication courses between the groups were detected at 5 years (p > 0.11), the combined procedure (63%, 37%) showed better success rates compared to the solo procedure (36%, 13%) in the definition IOP ≤18 and ≤12 mmHg (p = 0.035, 0.028). Solo XEN45 procedures had a higher rate of secondary IOP-lowering procedures compared to combined XEN45 cataract procedures (hazard ratio: 2.02, 95%CI: 1.03-3.97, p = 0.04). Twenty per cent of the eyes, including both procedures, required a secondary IOP-lowering procedure within 5 years. The XEN45 implant is effective in lowering IOP and the number of IOP-lowering medications in patients with open-angle glaucoma in the mid-term. Comparing XEN45 implant results with the results of trabeculectomy available in current literature, we speculate that there might be a higher surgical success rate without medications in favour of trabeculectomy.

PEC-PRO: A new prognostic score from a series of 87 patients with localized perivascular epithelioid cell neoplasms (PEComas) treated with curative intent.

Perivascular epithelioid cell neoplasms (PEComas) encompass a heterogeneous family of mesenchymal tumors. Previously described clinicopathologic features aimed at distinguishing benign from malignant variants but lacked prognostic value. This retrospective analysis examined clinicopathologic data from patients who had localized PEComa across French Sarcoma Network centers. The authors analyzed 12 clinicopathologic features in a Cox proportional hazard framework to derive a multivariate prognostic risk model for event-free survival (EFS). They built the PEComa prognostic score (PEC-PRO), in which scores ranged from 0 to 5, based on the coefficients of the multivariate model. Three groups were identified: low risk (score=0), intermediate risk (score=1), and high risk (score≥2). Analyzing 87 patients who had a median 46-month follow-up (interquartile range, 20-74 months), the median EFS was 96.5 months (95% confidence interval [CI], 47.1 months to not applicable), with 2-year and 5-year EFS rates of 64.7% and 58%, respectively. The median overall survival was unreached, with 2-year and 5-year overall survival rates of 82.3% and 69.3%, respectively. The simplified Folpe classification did not correlate with EFS. Multivariate analysis identified three factors affecting EFS: positive surgical margins (hazard ratio [HR], 5.17; 95% CI, 1.65-16.24; p=.008), necrosis (HR, 3.94; 95% CI, 1.16-13.43; p=.030), and male sex (HR, 3.13; 95% CI, 1.19-8.27; p=0.023). Four variables were retained in the prognostic model. Patients with low-risk PEC-PRO scores had a 2-year EFS rate of 93.7% (95% CI, 83.8%-100.0%), those with intermediate-risk PEC-PRO scores had a 2-year EFS rate of 67.4% (95% CI, 53.9%-80.9%), and those with high-risk PEC-PRO scores had a 2-year EFS rate of 2.3% (95% CI, 0.0%-18.3%). The PEC-PRO score reliably predicts the risk of postoperative recurrence in patients with localized PEComa. It has the potential to improve follow-up strategies but requires validation in a prospective trial.

Evolution of European prostate cancer screening protocols and summary of ongoing trials.

Population-based organised repeated screening for prostate cancer has been found to reduce disease-specific mortality, but with substantial overdiagnosis leading to overtreatment. Although only very few countries have implemented a screening programme on a national level, individual prostate-specific antigen (PSA) testing is common. This opportunistic testing may have little favourable impact, while stressing the side-effects. The classic early detection protocols as were state-of-the-art in the 1990s applied a PSA and digital rectal examination threshold for sextant systematic prostate biopsy, with a fixed interval for re-testing, and limited indication for expectant management. In the three decades since these trials were started, different important improvements have become available in the cascade of screening, indication for biopsy, and treatment. The main developed aspects include: better identification of individuals at risk (using early/baseline PSA, family history, and/or genetic profile), individualised re-testing interval, optimised and individualised starting and stopping age, with gradual invitation at a fixed age rather than invitation of a wider range of age groups, risk stratification for biopsy (using PSA density, risk calculator, magnetic resonance imaging, serum and urine biomarkers, or combinations/sequences), targeted biopsy, transperineal biopsy approach, active surveillance for low-risk prostate cancer, and improved staging of disease. All these developments are suggested to decrease the side-effects of screening, while at least maintaining the advantages, but Level 1 evidence is lacking. The knowledge gained and new developments on early detection are being tested in different prospective screening trials throughout Europe. In addition, the European Union-funded PRostate cancer Awareness and Initiative for Screening in the European Union (PRAISE-U) project will compare and evaluate different screening pilots throughout Europe. Implementation and sustainability will also be addressed. Modern screening approaches may reduce the burden of the second most frequent cause of cancer-related death in European males, while minimising side-effects. Also, less efficacious opportunistic early detection may be indirectly reduced.

Thrombosis in Acute Promyelocytic Leukemia: The Current Understanding.

Despite enormous improvement in the management of patients with acute promyelocytic leukemia (APL), the distinctive coagulopathy observed at presentation in affected patients is often life-threatening. While hemorrhagic manifestations are well known and described in this setting, APL-related thromboses are underappreciated. Data regarding this complication are scarce showing variable incidence. Furthermore, risk factors for thrombosis are inconsistent and unreliable; so, differentiation of increased risk of hemorrhage from an increased thrombotic risk is quite difficult in the absence of adequate predictive scores. Besides, prophylactic use of anticoagulants and recombinant thrombomodulin are a matter of ongoing debate. Also, due to the common feature of thrombocytopenia and other hemorrhagic risks, patients with APL are excluded from trials analyzing anticoagulant prophylaxis in cancers; so, data from prospective trials are lacking. A detailed analysis of thrombotic risks in APL with the development of a reliable risk stratification model is needed to further improve the care of APL patients.