Radiological Criteria Research Articles

Radiological indicators of chronicity in patients with acute symptomatic pulmonary embolism treated with ultrasound-assisted catheter-directed thrombolysis: a study of 180 consecutive cases

Abstract Background Radiological signs of chronic thrombi are present in up to 20% of patients that present acutely with pulmonary embolism (PE). Ultrasound-Assisted Catheter-Directed Thrombolysis (USAT) can swiftly reverse right ventricular dysfunction in patients with acute PE. Purpose To investigate the frequency of radiological signs of chronic PE and pre-existing chronic thromboembolic pulmonary hypertension in patients treated with USAT and their impact on early and long-term hemodynamic and clinical outcomes. Methods The index CT scans of patients receiving USAT for acute intermediate-high and high-risk PE at a tertiary academic institution (2017-2022) were adjudicated by three expert radiologists blinded for treatment scheme and outcomes. Changes in invasively-measured mean pulmonary artery pressure (mPAP) at 24 hours post USAT, presence of post-PE impairment (PPEI), and CTEPH diagnoses after at least 3 months were studied. A total of 15 radiological signs of chronicity were assessed, including 6 major criteria that have been previously validated to raise the suspicion of pre-existing CTEPH. In this study, acute-on-chronic PE was defined when at least 3 of the 6 validated radiological criteria for chronicity were present together with acute findings. Pre-existing CTEPH was defined based on the results of follow-up (vs. index) CT scan and on the anatomical consistency of pathology specimens after pulmonary endarterectomy. PPEI was defined by the presence of residual respiratory symptoms and right ventricular dysfunction during follow-up. Results Of 180 consecutive patients (median age 65 years, 61% men, 17% high-risk PE), 31 had at least 3 of 6 radiological criteria at the time of acute presentation; Table 1. The median modified Miller Score was 24 points and baseline mPAP was 35 mmHg in both groups. The absolute mPAP reduction after USAT was 11 (Q1-Q3: 5-17) mmHg in patients with <3 and 10 (Q1-Q3: 5, 17) mmHg in those with ≥3 criteria; Table 2. Three (1.7%) patients were diagnosed with CTEPH after a median of 3 months and underwent pulmonary endarterectomy: in all 3 patients, CTEPH was pre-existing. At least 3 of the 6 previously validated criteria were present in all CTEPH patients at index CT. In the 3 patients with acute PE on pre-existing CTEPH, the median baseline mPAP was much higher (median 53 mmHg) than in the remaining patient group and the absolute reduction after USAT was 9 mmHg, corresponding to a relative reduction of 19%. During follow-up, PPEI was more frequent in patients with <3 signs (n=4, 2.7%) than in those with ≥3 signs (n=4, 12.9%). Conclusion(s) The evaluation of six radiological parameters in initial CT scans successfully identified all cases of pre-existing CTEPH in patients presenting with acute PE. However, these parameters did not prove effective in determining which patients would benefit from USAT in terms of mPAP reduction.Baseline characteristicsHemodynamic and clinical outcomes

Role of clipping in aneurysmal subarachnoid hemorrhage: a post hoc analysis of the Earlydrain trial

The choice between clipping and coiling of ruptured cerebral aneurysms in subarachnoid hemorrhage (SAH) remains controversial. The recently published Earlydrain trial provides the opportunity to analyze the latest clip-to-coil ratio in German-speaking countries and to evaluate vasospasm incidence and explorative outcome measures in both treatment modalities. We performed a post hoc analysis of the Earlydrain trial, a multicenter randomized controlled trial investigating the use of an additional lumbar drain in aneurysmal SAH. The decision whether to clip or to coil the ruptured aneurysm was left to the discretion of the participating centers, providing a real-world insight into current aneurysm treatment strategies. Earlydrain was performed in 19 centers in Germany, Switzerland, and Canada, recruiting 287 patients with aneurysmal SAH of all severity grades. Of these, 140 patients (49%) received clipping and 147 patients (51%) coiling. Age and clinical severity based on Hunt-Hess/WFNS grades and radiological criteria were similar. Clipping was more frequently used for anterior circulation aneurysms (55%), whereas posterior circulation aneurysms were mostly coiled (86%, p < 0.001). In high-volume recruiting centers, 56% of patients were treated with clipping, compared to 38% in other centers. A per-year analysis showed a stable and balanced clipping/coiling ratio over time. Regarding vasospasm, 60% of clipped versus 43% of coiled patients showed elevated transcranial Doppler criteria (p = 0.007), reflected in angiographic vasospasm rates (51% vs. 38%, p = 0.03). In contrast to the Earlydrain main results establishing the superiority of an additional lumbar drain, explorative outcomes after clipping and coiling measured by secondary infarctions, mortality, modified Rankin Score, Glasgow Outcome Scale Extended, or Barthel-Index showed no significant differences after discharge and at six months. In clinical practice, aneurysm clipping is still a frequently used method in aneurysmal SAH. Apart from a higher rate of vasospasm in the clipping group, an exploratory outcome analysis showed no difference between the two treatment methods. Further development of periprocedural treatment modalities for clipped ruptured aneurysms to reduce vasospasm is warranted.

An update on pancreatic cancer imaging, staging and use of the PACT-UK radiology template pre- and post-neoadjuvant treatment.

Pancreatic ductal adenocarcinoma continues to have a poor prognosis, although recent advances in neoadjuvant treatments have provided some hope. Imaging assessment of suspected tumours can be challenging and requires a specific approach, with pancreas protocol CT being the primary imaging modality for staging with other modalities used as problem-solving tools to facilitate appropriate management. Imaging assessment post neoadjuvant treatment can be particularly difficult due to a current lack of robust radiological criteria to predict response and differentiate treatment induced fibrosis/inflammation from residual tumour. This review aims to provide an update of pancreatic ductal adenocarcinoma with particular focus on three points: tumour staging pre- and post-neoadjuvant treatment including vascular assessment, structured reporting with introduction of the PACT-UK radiology template (PAncreatic Cancer reporting Template-UK), and the potential future role of artificial intelligence in the diagnosis and staging of pancreatic cancer.

Evaluation of vascular invasion in pancreatic head tumors and its impact on radical surgical treatment

Objective. To evaluate the informativeness and sensitivity of radiological criteria for vascular invasion in pancreatic head tumors in comparison with intraoperative data and results of routine pathological examination. Materials and methods. The study included 98 patients with ductal adenocarcinoma of the pancreatic head with suspected venous invasion and spread of tumor growth along the vessels of the portomesenteric axis, who were operated on at the Department of Pancreatic and Bile Duct Surgery of the National Research Center of Surgery and Transplantation named after O. A. Shalimov in the period from 2019 to 2023. Group 1 included 51 (52.0%) patients who underwent radical surgery with resection of the superior mesenteric/hepatic portal vein and extended lymph and neurodissection, and group 2 included 47 (48.0%) patients who had positive vascular margins of pancreatic resection according to routine pathological examination. Diagnostic criteria for vascular alterations were developed. A comparative analysis of the informativeness of the developed criteria and the results of a routine pathological examination was performed. The edges of the pancreatic resection were evaluated, including the neck of the gland, common bile duct, duodenum/gastric duct, and the bed of the superior mesenteric/hepatic portal vein and superior mesenteric artery separately. R1 status was defined as the presence of tumor cells at a distance of less than 1 mm to the resection margin. Results. According to the criteria of the National Comprehensive Cancer Network (NCCN) 2023.2, 61 (62.2%) patients had a marginally resectable stage of ductal adenocarcinoma of the pancreatic head and tumor contact with the superior mesenteric/hepatic veins according to multislice computed tomography of the abdominal cavity. In group 1, there were 36 (70.6%) such patients, in group 2 – 25 (53.2%). According to the proposed radiologic criteria for vascular invasion, tumor contact with the superior mesenteric/hepatic portal veins was suspected in 76 (77.6%) patients, which is higher than in the standard approach. Determination of vascular alterations according to the results of our study is a more reliable method for diagnosing invasion of the superior mesenteric/hepatic portal vein (χ2 = 5.46, p = 0.019) and predicting the performance of radical surgery, including vascular resection. Conclusions. The proposed criteria for the radiological diagnosis of vascular invasion at the preoperative stage increased the sensitivity of this method from 62.2 to 77.6%. The most frequent radiological signs of vascular alteration are vascular wall irregularity (47.7%) and parapancreatic tissue density (62.5%). In the presence of any of the radiological signs of vascular alteration, resection of the affected area of the superior mesenteric/hepatic portal vein with extended lymph and neurodissection is indicated, which allows a statistically significant increase in the number of R0 resections.

Differentiating the Structural and Functional Instability of the Craniocervical Junction.

This paper presents the anatomical and biomechanical aspects of chronic instability of the craniocervical junction (CCJ) with a discussion on clinical diagnostics based on mobility tests and provocative tests related to ligamentous system injuries, as well as radiological criteria for CCJ instability. In addition to the structural instability of the CCJ, the hypothesis of its functional form resulting from cervical proprioceptive system (CPS) damage is discussed. Clinical and neurophysiological studies have shown that functional disorders or organic changes in the CPS cause symptoms similar to those of vestibular system diseases: dizziness, nystagmus, and balance disorders. The underlying cause of the functional form of CCJ instability may be the increased activity of mechanoreceptors, leading to "informational noise" which causes vestibular system disorientation. Due to the disharmony of mutual stimulation and the inhibition of impulses between the centers controlling eye movements, the cerebellum, spinal motoneurons, and the vestibular system, inadequate vestibulospinal and vestibulo-ocular reactions occur, manifesting as postural instability, dizziness, and nystagmus. The hyperactivity of craniocervical mechanoreceptors also leads to disturbances in the reflex regulation of postural muscle tone, manifesting as "general instability". Understanding this form of CCJ instability as a distinct clinical entity is important both diagnostically and therapeutically as it requires different management strategies compared to true instability. Chronic CCJ instability significantly impacts the quality of life (QOL) of affected patients, contributing to chronic pain, psychological distress, and functional impairments. Addressing both structural and functional instability is essential for improving patient outcomes and enhancing their overall QOL.

The Efficacy, Safety, and Persistence of Therapy after Non-Medical Switching from an Originator Adalimumab in Inflammatory Bowel Disease: Real-Life Experience from Two Tertiary Centres.

During the last two decades, an increased number of molecules with multiple mechanisms of action have been approved for the treatment of inflammatory bowel disease (IBD), with a substantial increase in the costs related to therapy, which has become a concern for payers, regulators, and healthcare professionals. Biosimilars are biologic medical products that are highly structurally similar to their reference products; have no clinically meaningful differences in terms of immunogenicity, safety, or effectiveness; and are available at a lower price. Materials and Methods: This was an observational prospective study conducted in two IBD centres in Bucharest and included 53 patients, 27 male (M) and 26 female (F), diagnosed with IBD according to standard clinical, endoscopic, radiological, and histological criteria, who were non-medically switched at the indication of the National Insurance House to a biosimilar of Adalimumab. Aims: The aim was to determine the rates of clinical remission, adverse effects, and treatment persistence at one year. Results: No significant differences were found in terms of the faecal calprotectin (FC) and C-reactive protein (CRP) levels 6 and 12 months after changing from the originator biologic treatment to a biosimilar. Only one patient required a change in their biological treatment following the clinical and biological loss of response. The main adverse effect reported by the patients was pain at the injection site. Of the 53 patients, only 2 reported pain at the injection site, and 1 patient reported experiencing abdominal pain and rectal bleeding immediately after the switch, but no recurrence was observed clinically or endoscopically. Conclusions: This observational study is the first to be carried out in Romania that shows that, after a non-medical switch, biosimilars of Adalimumab are as efficient and safe as the originator Adalimumab in the clinical treatment of patients with IBD.

Pancreatic steatosis is a strong risk factor for post-ERCP pancreatitis: An emerging concept

ObjectiveThe Endoscopic Retrograde Cholangiopancreatography (ERCP) is the treatment of choice for biliary obstruction but is associated with post-ERCP pancreatitis (PEP) in around 5 % of cases. No radiological criteria have been evaluated for predicting PEP risk. DesignThis retrospective study examined records of 1365 patients who underwent ERCP at our center between 2014–2023. Only sphincterotomy-naïve patients were included. CT scans within 30 days of ERCP were reviewed for radiological criteria. The optimal pancreatic density cut-off was determined using AUROC and Youden index. Logistic regression was used for analyses. ResultsPEP occurred in 75 patients (6.1 %). The CT scan was performed before ERCP for 565 of the total population. A fatty pancreas, defined as a spontaneous density less than -50HU, was statistically associated with PEP (OR: 7.35; 95 % CI: 1.56–26.5 p = 0.004), as well as with biliary obstruction due to stones (OR: 0.61; 95 % CI: 0.38–0.98; P = 0.04), the need for precut (OR: 2.19; 95 % CI: 1.35–3.51; P = 0.001), cannulation of the main pancreatic duct (OR: 2.23; 95 % CI: 1.36–3.59; P = 0.001), and the use of a pancreatic stent (OR: 2.48; 95 % CI: 1.29–4.47; P = 0.004). In multivariate analyses, only obstruction unrelated to gallstones (OR = 2.63; 95 % CI: 1.16–6.25; P = 0.024) and a low pancreatic density (<-50HU) (OR=7.94, 95 %CI: 1.59–31.09; P = 0.005) remains significantly associated with the risk of PEP, including after adjustment for age and sex (P = 0.006). ConclusionA very low pancreatic fat density could be a significant risk factor for post-ERCP pancreatitis with potential clinical and research implications. Further validation is needed.

Endocrine sequelae after pediatric craniopharyngioma treatment: a single-center retrospective cohort study.

Craniopharyngiomas (CP) are rare brain tumors with a low mortality rate, but with significant morbidity, in part due to the various long-term endocrine sequelae related to hypothalamic/pituitary deficiencies. Our objective was to assess the prevalence of endocrine dysfunction and outcome after treatment of CP at our institution and to apply the novel diagnostic criteria for hypothalamic syndrome (HS). In addition, we give an overview of treatments already attempted for hypothalamic obesity (HO). This retrospective cohort study included children treated and followed up for CP at the pediatric oncology and endocrinology department at University Hospitals Leuven between January 2000 and December 2023. Clinical and endocrine characteristics were collected during a five-year period following diagnosis of CP. The Müller radiological criteria and the novel diagnostic criteria for HS were applied. A brief literature review regarding treatments already attempted for HO was conducted. 15 patients with pediatric CP were included in the study, all of whom developed endocrine sequelae over time. Seven patients (47 %) presented with at least one hormonal deficit, and eight patients (53 %) developed panhypopituitarism over time. HO was clinically confirmed in nine patients (60 %). 10 patients (67 %) met the diagnostic criteria for HS. Currently, no overall effective treatment strategies are available for HO. Long-term endocrine sequelae and HO are highly prevalent in pediatric CP. Continuing multidisciplinary care to improve the quality of life of these patients is necessary. International cooperation and further long-term prospective trials for the treatment of HO are needed.

T2 Hyperintensities in Children with Neurofibromatosis Type 1

Areas of increased signal intensity, known as T2 hyperintensities (T2Hs), observed on T2-weighted magnetic resonance imaging (MRI) scans, are linked to a spectrum of brain abnormalities in children with neurofibromatosis type 1 (NF1). Defining the radiological characteristics that distinguish non-neoplastic from neoplastic T2Hs in children with NF1 is crucial. Then, we could identify lesions that most likely to require oncologic surveillance. We conducted a single-center retrospective review of all available brain MRIs from 98 children with NF1 and 50 healthy pediatric controls. All T2Hs identified on MRI were characterized based on location, imaging features, presence of lesion related symptoms. Subsequently, all T2Hs were classified using newly established criteria and categorized into three distinct groups: low-risk tumor lesions, medium-risk tumor lesions, and high-risk tumor lesions. Lesions deemed to be high-risk will be recommended for surgical treatment. T2Hs were present in 61 (62.2%) individuals of the NF1 cohort. T2Hs were a highly sensitive (100%; 95% confidence interval [CI] 92.9%-100.0%) and specific (62.2%; 95% CI 51.9%-71.8%) marker for the diagnosis of NF1. In children aged 4-10, the detection rate of T2Hs is significantly higher than in children under 4 years old and those aged between 10 and 18(P<0.05). T2Hs were most frequently located in basal ganglia, cerebellar hemispheres, and brainstem. During the follow-up process, none of lesions categorized as low-risk or medium-risk tumor lesions progressed to high-risk tumor lesions. Seven patients had high-risk tumor lesions and underwent surgical treatment.The pathological assessment identified 5 cases of glioma among the 7 patients, along with 1 case of gliosis and 1 case of vascular dysplasia. Low-risk and medium-risk tumor lesions can both be classified as unidentified bright objects(UBOs).UBOs constituted the majority of T2Hs in children with NF1. High-risk tumor lesions should be considered as probable tumors.With the application of standardized radiologic criteria, a high prevalence of probable brain tumors will be identified in this at-risk population of children, which underscores the importance of vigilant and appropriate oncological surveillance to ensure timely detection and intervention for these tumors.

A novel radiological index uses the inner canal diameter and the Citak classification index to predict risk factor for aseptic loosening following hinged total knee arthroplasty.

It remains unclear if distal femoral morphology should be a key consideration when selecting the implant or fixation strategy. A novel radiological index has been proposed to classify patients' distal femoral morphology. This study aims to evaluate the validity of this classification system in a cohort of patients undergoing hinged Total Knee Arthroplasty (TKA), and to determine if distal femoral morphology is a risk factor for aseptic loosening or all cause revision following hinged TKA. This study was a retrospective analysis of our institutional database. Fifty-nine patients having undergone hinged TKA with adequate radiographs for examination were eligible for inclusion. Radiographic measurements were performed using the Citak radiological index criteria. The proportion of aseptic loosening and all-cause revisions were compared between the different classification groups. The analysis included 41 females (69.5%) and 18 males (30.5%). The mean age of the participants was 71.2 years (SD = 12.6). For inner canal diameter patients were classified as: Type A (31/59, 53%), Type B (19/59, 32%), and Type C (9/59, 15%). For the Index Classification Group, patients were classified as: Group A (26/59, 44%), Group B (20/59, 34%), and Group C (13/59, 22%). There was no significant difference in overall revision rate between the three groups (χ2 = 3.25, P = .197 from a Chi-square test). There was a significantly higher rate of aseptic loosening in Group C compared to Groups A and B, with no significant difference between Groups A and B in terms of aseptic loosening rates (χ2 = 8.72, P = .013 from a Chi-square test). Distal femoral morphology plays an important role in the risk of aseptic loosening following hinged knee replacement, and should be considered when deciding implant type and fixation in these patients.

A Comprehensive Study of Risk Factors, Etiology, and Infarction Patterns in Cerebrovascular Accidents at a Tertiary Care Hospital in India.

Background Stroke is a debilitating cerebrovascular condition characterized by sudden neurological deficits. The incidence of stroke is rising in India, posing significant public health concerns. This study aims to examine the risk factors and etiology of stroke using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification and analyze infarct areas in cerebrovascular accidents (CVA) at a tertiary care hospital. Methodology This cross-sectional, hospital-based observational study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed to Be University), Pune, India, from January 2023 to January 2024. The study included 100 adult patients diagnosed with CVA based on clinical and radiological criteria. Patients aged 18 years and older were eligible, while those with a history of head trauma or those below 18 years were excluded. The investigation protocol included routine biochemical assessments and radiological investigations, such as computed tomography (CT), magnetic resonance imaging (MRI) with angiography or venography, and Doppler ultrasound of bilateral carotid arteries. Results The study population consisted of 100 patients, with 84 males (84%) and 16 females (16%). Age distribution showed 44% were over 60 years old, 23% aged 51-60 years, 15% aged 31-40 years, 14% aged 41-50 years, and 4% aged 21-30 years. Hypertension was the most prevalent risk factor, affecting 75% of patients, with a higher occurrence in males (62%), compared to females (13%). Smoking was observed in 51% of patients, and alcohol consumption was seen in 50%. Other significant risk factors included dyslipidemia (39%), diabetes mellitus (33%), chronic kidney disease (11%), ischemic heart disease (10%), atrial fibrillation (4%), valvular heart disease (4%), and pregnancy or postpartum conditions (2%). Ischemic stroke was predominant, occurring in 80% of patients, while hemorrhagic stroke occurred in 20%. High occurrences of ischemic strokes were noted in the frontal lobe (41%), parietal lobe (37%), occipital lobe (27%), and temporal lobe (26%), with the internal capsule region also showing significant numbers (27%). According to the TOAST classification, the most prevalent cause of stroke in this study was undetermined etiology with two or more causes, accounting for 32% of cases, followed by large artery atherosclerosis, which accounted for 30%. Cardioembolic stroke was identified in 11% of the patients, with 4% due to atrial fibrillation, 3% due to acute myocardial infarction, 3% due to rheumatic valvular heart disease, and 1% due to infective endocarditis. Conclusion This study highlights the significant prevalence of hypertension, smoking, alcohol consumption, and hyperhomocysteinemia as major risk factors for stroke. Ischemic strokes were predominant, with high occurrences in the cerebral lobes and gangliocapsular region. These findings emphasize the need for targeted prevention strategies, including managing hypertension and lifestyle modifications such as smoking cessation and reducing alcohol consumption, to mitigate the risk of stroke. Effective management of blood pressure, lipid levels, and blood glucose is crucial for stroke prevention. Recognizing gender-specific differences and addressing comorbidities through an integrated approach can enhance patient outcomes and reduce the burden of stroke.

Chordoma: Site-Wise Predilections and Pathological Tenets

Abstract Background: Chordomas are rare tumours of presumptive notochordal origin, mostly occurring in the axial skeleton of the body. These tumours are slow growing but are locally invasive neoplasms. Diagnosis requires qualification of the radiological, histopathological, and immunohistochemical criteria. Management predominantly comprises surgical resection with negative margins. Objective: Our study aimed to analyse the clinico-pathological spectrum of these rare chordoma cases visiting our tertiary care institute. Materials and Methods: The study was retrospective, comprising chordoma cases reported histopathologically between January 01, 2013, and August 31, 2023 (a total period of 10.5 years). Clinico-radiological data were recorded. Histopathological diagnosis was separately reviewed by two pathologists. All data were statistically analysed. Results: In total, 41 chordoma cases were received, with a mean age of 43.2 + 17.4 years (6–72 years). Male:female ratio was 1.2:1. Spheno-occipital region chordomas (27 cases) were most common, followed by sacrococcygeal (8 cases) and vertebral (6 cases) chordomas. Symptoms varied with location. However, the commonest presenting complaint was pain. These region-wise chordoma categories were statistically compared in terms of patients’ age, male:female ratio, symptomatic duration, tumour size, histopathological tumour type, and recurrence on follow-up. Of these, only patients’ age and tumour size were found to be statistically significant (P value was 0.011 and 0.0004, respectively). Conclusion: Clinico-pathological parameters vary with the anatomical location of chordoma. We present the experience of this rare tumour in terms of clinico-radiopathological features visiting our tertiary care institute in northern India.

Systemic C-Reactive Protein Predicts Cerebral Vasospasm and Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Retrospective Observational Study

Aneurysmal subarachnoid hemorrhage (aSAH) is often complicated by cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI), which significantly impact patient outcomes. The study aimed to investigate the predictive value of systemic serum biomarker levels for CVS and DCI following aSAH. We retrospectively analyzed data for 450 aSAH patients admitted to University Hospital Düsseldorf between January 2011 and October 2021. Serum biomarkers were measured on admission. The occurrence of CVS and DCI was assessed based on clinical and radiological criteria. Multivariate logistic regression analysis was performed to determine the independent association of serum biomarkers with CVS and DCI. We compared the predictive values of various models using the area under the receiver operating characteristic curve. Of the 450 patients, 126 (28.0%) developed CVS, 123 (27.3%) developed DCI, and 62 (13.8%) developed co-occurring CVS and DCI. Patients with CVS, DCI, or both had significantly higher admission C-reactive protein (CRP) levels than those without these complications (P<0.001). Elevated CRP levels were independently associated with an increased risk of CVS, DCI, and co-occurring CVS and DCI (P<0.05). CRP demonstrated a higher predictive value for CVS (area under the curve [AUC]: 0.811) and co-occurring CVS and DCI (AUC: 0.802) compared to DCI alone (AUC: 0.690). Our findings suggest that admission systemic CRP levels can serve as a more valuable predictor for developing CVS than DCI following aSAH. Incorporating CRP into clinical assessments may aid in risk stratification and early intervention strategies for patients at high risk of these complications.

High-Dose Furmonertinib in Patients With EGFR-Mutated NSCLC and Leptomeningeal Metastases: A Prospective Real-World Study

IntroductionLeptomeningeal metastasis (LM) is one of the most severe complications of NSCLC. Furmonertinib is a pan-EGFR tyrosine kinase inhibitor (TKI) with a high rate of brain penetration and a wide therapeutic window. Here, we evaluated the efficacy and safety of high-dose furmonertinib in patients with EGFR-mutated NSCLC and LM. MethodsThis prospective real-world study included patients with EGFR-mutated NSCLC and LM treated with a high-dose furmonertinib (240 mg once daily) as a monotherapy or in combination with other treatments. The primary end point was overall survival, and the secondary end points included time to treatment discontinuation and clinical response rate. Additional efficacy evaluations included changes in brain magnetic resonance imaging by the response assessment in neuro-oncology–LM radiologic criteria. We also introduced next-generation sequencing–based assays to evaluate genomic and epigenomic features of cell-free DNA (cfDNA) in patients’ cerebrospinal fluid (CSF) samples and to analyze their associations with patient outcomes. ResultsWe enrolled 48 patients, of whom 35 (72.9%) had received third-generation EGFR TKIs. The median overall survival was 8.43 months (95% confidence interval: 5.48–11.39 mo), while the median time to treatment discontinuation was 8.27 months (95% confidence interval: 5.40–11.14 mo), and the clinical response rate was 75%. The LM objective response rate and disease control rate assessed with response assessment in neuro-oncology-LM radiologic criteria were 50.0% and 92.1%, respectively. The adverse event profiles were consistent with previous reports of furmonertinib. Briefly, 22 (45.8%) had adverse events possibly related to furmonertinib and 3 (6.3%) had a grade 3-elevated aminotransaminase or nausea or leucopenia, leading to a dose reduction to 160 mg daily. Furthermore, methylation analysis of cfDNA in CSF revealed that there was a considerable correlation between the changes of aberrant methylated fragments from lung cancer cells and the response of the patients. Meanwhile, the copy number burden scores derived from the low-pass whole genome sequencing assay may offer another objective and effective method for the diagnosis and evaluation of treatment efficacy in LM. ConclusionsIn the real world, the high-dose furmonertinib-based treatment may potentially have clinical efficacy and tolerable safety in patients of EGFR-mutated NSCLC with LM, even in patients previously treated with other third-generation EGFR TKIs. Methylation and copy number burden analysis of cfDNA in CSF may be considered objective indicators for the diagnosis of LM and evaluation of treatment response.

Comparison of open and endoscopic techniques of isolated calcaneoplasty in the surgical treatment of insertional tendinopathy of the Achilles tendon

IntroductionInsertional Achilles tendinopathy (IAT) is primarily caused by mechanical overload. Running and obesity are major risk factors. Medical treatment is limited, and surgery, particularly calcaneoplasty, is sometimes necessary. However, the choice between an endoscopic and open approach remains controversial. HypothesisThis study is based on the hypothesis that endoscopic surgery would allow for better functional recovery with a faster return to sports activity compared to traditional open techniques. Materials and methodsOur multicenter prospective study compared the outcomes of endoscopic (Endo) and open (Open) calcaneoplasty in patients with IAT resistant to medical treatment. Clinical outcomes were assessed using the EFAS (daily life and sports) and VISA-AF scores. The radiological criteria studied were the calcaneal slope and the X/Y ratio. An MRI was used to quantify tendon involvement. ResultsOf the 85 patients included, 51 underwent endoscopic surgery, and 34 had open surgery. The two groups were comparable in terms of demographic, clinical, and radiographic characteristics. At 3 months postoperatively, significantly more patients had returned to sports in the Endo group (41.6% vs. 20.6% in the Open group; p = 0.004), and the EFAS sports score showed a significant difference in favor of the Endo group at 6 months postoperatively (9.3 vs. 5.7 / 16; p = 0.008). DiscussionThe results confirm faster recovery after endoscopic surgery, with comparable complication rates between the two approaches. However, long-term, the differences between the two techniques diminish, with similar functional outcomes at 12 months postoperatively. ConclusionEndoscopic calcaneoplasty is a safe and effective option for the treatment of IAT. However, further studies with longer follow-up are needed to confirm these results and assess recurrence rates. Level of evidenceIII.

Relation between vitamin D and COVID-19 in Egyptian patients

BackgroundInsufficient vitamin D (VD) levels have been linked to a higher vulnerability to acute respiratory infections and the severity of COVID-19 sickness.ObjectiveThe purpose of this research is to investigate whether or not there is a connection between the amounts of VD produced by patients from Egypt and the severity of COVID-19, as well as the consequences of the disease.MethodsThis research used a case–control design and included a total of 90 adult patients who had been diagnosed with COVID-19, as well as 90 healthy controls who were matched in terms of age and sex. Patients were classified into mild, moderate, and severe categories according to clinical and radiological criteria. The study included measuring levels of VD and analyzing their relationships with illness severity, inflammatory markers, radiological findings, and outcomes.ResultsCOVID-19 patient(s) had notably reduced levels of serum VD versus the control group (11.78 ± 3.24 ng/mL vs. 20.88 ± 7.76 ng/mL, p < 0.001). Lower VD levels were associated with more severe disease (p < 0.001), dyspnea (p < 0.001), radiological abnormalities (p = 0.001), and higher mortality (p < 0.001). A serum VD level ≤ 14.8 ng/mL could differentiate COVID-19 patients from controls with 86.67% sensitivity and 77.78% specificity (AUC = 0.881).ConclusionsCOVID-19 patients often had a deficiency of VD, which was linked to more severe illness, respiratory issues, aberrant radiological findings, and higher fatality rates. VD levels may be used as a biological surrogate marker to assess the risk and predict the outcome of COVID-19.

Improving the clinical meaning of surrogate endpoints: An empirical assessment of clinical progression in phase III oncology trials.

Disease progression in clinical trials is commonly defined by radiologic measures. However, clinical progression may be more meaningful to patients, may occur even when radiologic criteria for progression are not met, and often requires a change in therapy in clinical practice. The objective of this study was to determine the utilization of clinical progression criteriawithin progression-based trial endpoints among phase III trials testing systemic therapies for metastatic solid tumors. The primary manuscripts and protocols of phase III trials were reviewed for whether clinical events, such as refractory pain, tumor bleeding, or neurologic compromise, could constitute a progression event. Univariable logistic regression computed odds ratios (OR) and 95% CI for associations between trial-level covariates and clinical progression. A total of 216 trials enrolling 148,190 patients were included, with publication dates from 2006 through 2020. A major change in clinical status was included in the progression criteria of 13% of trials (n = 27), most commonly as a secondary endpoint (n = 22). Only 59% of trials (n = 16) reported distinct clinical progression outcomes that constituted the composite surrogate endpoint. Compared with other disease sites, genitourinary trials were more likely to include clinical progression definitions (16/33 [48%] vs. 11/183 [6%]; OR, 14.72; 95% CI, 5.99 to 37.84; p < .0001). While major tumor-related clinical events were seldom considered as disease progression events, increased attention to clinical progression may improve the meaningfulness and clinical applicability of surrogate endpoints for patients with metastatic solid tumors.

Weight-bearing pain and implant migration, progressive radiolucencies, radiolucency more than 2 mmand subsidence on radiographs and CT are generally accepted criteria for knee arthroplasty loosening: An international Delphi consensus study.

Establishing the diagnosis of loosening in total or unicondylar knee arthroplasty remains a challenge with different clinical and radiological signs evaluated in study designs with high risk of bias, where few or incomplete criteria are formulated for establishing the diagnosis of implant loosening. This study aimed at evaluating the variability between different clinical and radiological criteria and establish a consensus regarding clinical and radiological criteria for the diagnosis of knee arthroplasty loosening. Highly specialized knee surgeons focusing on revision arthroplasty were invited to take part in an international panel for a Delphi consensus study. In the first round, the participants were asked to state their most important clinical and radiological criteria for implant loosening. In a second round, the panel's agreement with the collected criteria was rated on a 5-point Likert scale (1-5). High variability was defined by receiving at least one score each indicating complete disagreement and complete agreement. Consensus was established when over 70% of participants rated a criterion as 'fully agree' (5) or 'mostly agree' (4). High variability was observed in 56% of clinical criteria and 38% of radiological criteria. A consensus was reached on one clinical (weight-bearing pain [82%]) and four radiological criteria, that is, implant migration, progressive radiolucencies, subsidence and radiolucencies >2 mm on X-ray or computed tomography (CT) (84%-100%). Amongst specialized knee revision surgeons, there is high variability in clinical and radiological criteria that are seen as important contributing factors to diagnosis of knee implant loosening. A consensus was reached on weight-bearing pain as clinical criterion and on implant migration, progressive radiolucencies, subsidence and radiolucencies of more than 2 mm on X-ray or CT as radiological criteria. The variability rates observed, along with the criteria that reached consensus, offer important insights for the standardization of diagnostic protocols. Level V.

Addition of Metastasis-Directed Therapy to Systemic Therapy for Oligometastatic Pancreatic Ductal Adenocarcinoma (EXTEND): A Multicenter, Randomized Phase II Trial.

The EXTEND trial tested the hypothesis that adding comprehensive metastasis-directed therapy (MDT) to chemotherapy would improve progression-free survival (PFS) over chemotherapy alone among patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC). EXTEND (ClinicalTrials.gov identifier: NCT03599765) is a multicenter, phase II basket trial randomly assigning patients with ≤five metastases 1:1 to MDT plus systemic therapy versus systemic therapy. Disease progression was defined by radiologic criteria (RECIST v1.1), clinical progression, or death. The primary end point was PFS in the per-protocol population, evaluated after all patients achieved at least 6 months of follow-up. Exploratory end points included systemic immune response measures. Between March 19, 2019, and February 13, 2023, 41 patients were randomly assigned and 40 were eligible for the primary analysis of PFS (19 patients in the MDT arm; 21 patients in the control arm). At a median follow-up time of 17 months, the median PFS time was 10.3 months (95% CI, 4.6 to 14.0) in the MDT arm versus 2.5 months (95% CI, 1.7 to 5.1) in the control arm. PFS was significantly improved by the addition of MDT to systemic therapy (P = .030 for stratified log-rank test) with a hazard ratio of 0.43 (95% CI, 0.20 to 0.94). No grade ≥3 or greater adverse events related to MDT were observed. Systemic immune activation events were associated with MDT and correlated with improved PFS. This study supports the addition of MDT to systemic therapy for patients with oligometastatic PDAC. Induction of systemic immunity is a possible mechanism of benefit. These results warrant confirmatory trials to refine treatment strategy and provide external validation.

A Retrospective Analysis of Micafungin Prophylaxis in Children Under 12 Years Undergoing Chemotherapy or Hematopoietic Stem Cell Transplantation.

Literature is limited regarding ideal micafungin dosing in pediatric patients with hematologic malignancies receiving chemotherapy or hematopoietic stem cell transplantation. Micafungin is an intravenous echinocandin with activity against Candida and Aspergillus species and has a favorable safety profile compared with other antifungal classes. Our objective was to evaluate the breakthrough invasive fungal infection (IFI) rate in pediatric patients who received a prophylactic micafungin course at our institution. A single-center, retrospective study was conducted between January 1, 2011, and July 31, 2017, to determine the IFI rate in patients receiving micafungin prophylaxis. Patients with suspected IFI were evaluated for probable or proven infection based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group Consensus Group invasive fungal disease definitions. Statistical analyses were descriptive. A total of 170 prophylactic micafungin courses from 129 unique patients ages <12 years at a median dose of 3 mg/kg daily were identified. The rate of probable or proven breakthrough IFIs was 2.4% as determined by clinical, radiologic, microbiologic, and histopathologic criteria. A low rate of breakthrough IFI was seen with micafungin prophylaxis that is consistent with prior published adult hematopoietic stem cell transplantation studies. Micafungin was well tolerated, with liver function test elevations being transient in most cases and thought to be related to alternative factors.