Assessing the Diagnostic Accuracy of TI-RADS in Pediatric Thyroid Nodules: A Multi-institutional Review.

PURPOSE: Thyroid nodules are uncommon in children and adolescents but carry an increased risk of malignancy when present. The Thyroid Imaging Reporting and Data System (TI-RADS) is an adult-validated ultrasound-based risk assessment providing a prediction of malignant potential for thyroid nodules, thereby guiding recommendations for fine needle aspiration biopsy (FNAB). Minimal data exist regarding the applicability of TI-RADS to predict malignancy in pediatric thyroid nodules. This study aims to analyze the performance of TI-RADS for children and adolescents with thyroid nodules, hypothesizing that applying TI-RADS criteria would improve accuracy and reduce the number of recommended FNAB compared to American Thyroid Association (ATA) size criteria alone. METHODS: A multi-institutional retrospective analysis was conducted including patients ≤21 years with a thyroid nodule by sonographic thyroid imaging between 2015 and 2020. TI-RADS scores were assigned at each institution by a pediatric radiologist trained in thyroid imaging and TI-RADS criteria. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy of TI-RADS scoring were compared to existing ATA size-based recommendation for performing a FNAB. Accounting for relative size differences between adults and children, a novel PED TI-RADS category was developed and tested, recommending FNAB for thyroid nodules with a TI-RADS 3 and ≥ 1.5 cm, TI-RADS 4 and ≥ 1.0 cm, and TI-RADS 5 any feasible size. RESULTS: 291 nodules from 260 patients (median age 14.9 years, 78.8% female) were assessed using TI-RADS. Applying adult TI-RADS criteria resulted in recommendation of FNAB for 35.1% of nodules, in contrast to 76.6% recommended by ATA guidelines (p < 0.0001) (Table). Utilizing the adult TI-RADS score ≥3 as an FNAB indicator resulted in 100% sensitivity and 28.5% specificity, with 0 cases of missed malignant nodules on pathology. When novel PED TI-RADS criteria were applied, 88 patients would have been spared an unnecessary FNAB with improved sensitivity and accuracy over ATA criteria. CONCLUSIONS: The application of adult and PED TI-RADS scoring to thyroid nodules in pediatric patients enhances the accuracy of malignancy prediction compared to current American Thyroid Association size criteria alone. The utilization of PED TI-RADS scoring eliminated unnecessary biopsies in many children while not missing a single thyroid malignancy. LEVEL OF EVIDENCE: Level III.

[Current standard treatments and future outlook for follicular lymphoma].

Follicular lymphoma (FL) is the most common subtype of indolent lymphoma. Survival outcomes for FL have improved since the introduction of anti-CD20 monoclonal antibodies, such as rituximab, and median overall survival has reached 15-20 years. However, FL is an incurable disease that subsequently progresses or relapses, and progression-free and overall survival tend to shorten with repeated relapses. For patients with limited-stage disease, radiation therapy is generally the treatment of choice and results in a median survival of approximately nearly 20 years. For advanced-stage patients with low tumor burden, watchful waiting continues to be the appropriate strategy at present. It remains unclear whether rituximab monotherapy might change this watchful waiting approach and result in a benefit from early intervention in patients with low tumor burden. For advanced-stage patients with high tumor burden, chemoimmunotherapy including rituximab or obinutuzumab followed by maintenance therapy is the standard treatment. For relapsed or refractory patients, treatment options such as chemoimmunotherapy, lenalidomide-rituximab, tazemetostat, chimeric antigen receptor T-cell therapies, and CD3/CD20 bispecific antibodies are available or in development. This review presents current standard treatments, recent advances, and future perspectives on the management of FL.

[Sinusoidal obstruction syndrome/veno-occlusive disease: a complication to overcome].

Sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD) is a well-known, potentially fatal liver complication. Some clinical diagnostic criteria have been proposed over the years. Defibrotide is the only approved treatment for SOS/VOD and should be administered within two days of diagnosis. Recently, the EBMT 2023 criteria aimed at early diagnosis were published, and the ultrasound diagnostic tool HokUS-10 has attracted worldwide attention. Although the incidence of SOS/VOD is decreasing, it remains a significant complication that must be addressed. Early diagnosis and prompt treatment are crucial, and achieving this requires multidisciplinary teamwork between physicians, nurses, sonographers, pharmacists, and other healthcare professionals. This collaborative approach is essential to optimize treatment and save SOS/VOD patients.

How secure can we expect the surveillance policies to be after the implementation in T1 polyps with carcinoma?

Approximately 7% of the polyps resected endoscopically have an adenocarcinoma focus, with no previous endoscopic evidence of malignancy. This raises the question of whether endoscopic resection has been curative. Furthermore, there is no consensus on what the endoscopic and histological criteria for good prognosis are, the appropriate follow-up strategy and what are the long-term results. The aim of the retrospective study by Fábián et al was to evaluate the occurrence of local relapse or distant metastasis in those tumors that were resected endoscopically compared to those that underwent oncologic surgery. They concluded that, regardless of the treatment strategy chosen, there was a higher recurrence rate than described in the literature and that adherence to follow-up was poor. The management approach for an endoscopically benign polyp histologically confirmed as adenocarcinoma depends on the presence of any of the previously described poor prognostic histological factors. If none of these factors are present and the polyp has been completely resected en bloc (R0), active surveillance is considered appropriate as endoscopic resection is deemed curative. These results highlight, once again, the need for further multicentric clinical practice studies to obtain more evidence for the purpose of establishing appropriate treatment and follow-up strategies.

Pointing to success: a discussion of the role of acad achievements in the selection of specialist surgical trainees.

BACKGROUND: In Australia and New Zealand, competitive selection processes for surgical specialty training programs often use a standardized curriculum vitae (CV) to assess criteria such as professional achievements. This review aims to assess the predictive validity, standardization, and implicit biases of these selection methods, as well as their implications for trainees and the diversity of surgical cohorts. METHODS: The 2023 CV scoring criteria were collected for all available specialty surgical programs in Australia and New Zealand. In 2023, each of the 11 surgical craft programs published publicly available standardized CV scoring criteria. In this study, scored items that constitute 'professional achievements' were recorded and tabulated. Observational analysis of the collected data was then conducted. RESULTS: In 2023, each of the 11 specialty surgical craft programs published publicly available structured CVs, of which 10/11 allocated points for professional achievements. Designated points for professional achievements were classified as awards, scholarships, committee positions, and prior training courses: 4/11 programs offered points for scholarships/grants, 6/11 programs offered points for academic and/or non-academic prizes, and 8/11 programs offered points for professional development courses. Observational analysis of these findings suggests that professional achievements are desired in training program applicants. CONCLUSION: Variability in medical school opportunities and inherent heterogeneity reduce the CV's efficacy, unfairly disadvantaging some applicants. Observational analysis of hence highlights the need for future research to assess potential updates in CV parameters to enhance predictive validity, reduce bias, and promote diversity.

Polypharmacy and potentially inappropriate medicine use in older adults with cancer: a multicenter cross-sectional study in Northwest Ethiopia oncologic centers.

Background: Most patients with cancer have comorbid conditions that necessitate advanced medical treatment. Polypharmacy (PP) and potentially inappropriate medicine (PIM) use is common among older adult patients with cancer. Not much research has been conducted on PP and PIM use among older adult patients with cancer in Ethiopian oncology centers. Therefore, this study aimed to evaluate the prevalence and determinants of PP and PIM use among older adults with cancer in Northwest Ethiopia oncology centers using the American Geriatrics Society (AGS) 2019 updated Beers criteria. Methods: This multicenter cross-sectional study was conducted among older adult patients with cancer from July 15-December 30, 2023 in Northwest Ethiopian oncology centers. The use of at least one drug included in the 2019 Beers criteria revisions was classified as potentially inappropriate medication use. To identify the factors influencing PP and PIM use, logistic regression analysis was performed. Results: Of the 310 samples aproched, 305(98.4% response rate) participated in the study. The prevalence of PP and PIM use were 70.2% (95% CI 64.9-75.1) and 63.0% (95% CI 57.4-68.8) respectively. Being female AOR:3.6; 95% CI:1.7-7.8; p = 0. 001, advanced age [(70-74 years) AOR:3.9; 95% CI:1.2-6.7; p = 0.046 and ≥75 years AOR:3.8; 95% CI:1.7-8.4; p = 0.0028], abnormal body weight (underweight AOR:5.5; 95% CI:1.5-9.6; p = 0.019, overweight AOR:5.1; 95% CI:1.5-7.3; p = 0.01 and obese AOR:5.6; 95% CI:1.5-9.3; p = 0.021) and comorbidities AOR:3.5; 95% CI:1.7-8.3; p = 0.0032 were statistically significant factors for PP. Advanced age [(70-74 years) AOR:5.5; 95% CI:1.4-9.8; p = 0.015 and ≥75 years AOR:3.3; 95% CI:1.5-7.1; p = 0.002)] and polypharmacy; AOR:7; 95% CI:3.4-9.4; p = 0.001 were statistically significant factors for PIM use. Conclusion: Polypharmacy and potentially inappropriate medicine use were prevalent among older adult patients with cancer. Ensuring safe medicines prescription practices for older patients with cancer requires understanding the issue, stopping unwarranted treatment, and replacing it with less toxic, age-appropriate medicines.

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.

Biophysical and Biological Mechanisms of Tumor Treating Fields in Glioblastoma.

Glioblastoma (GBM) is one of the most aggressive forms of brain cancer that presents with a median survival rate of 14-30 months and along with a discouraging five-year survival rate of 4-5%. Standard treatment of newly diagnosed GBM, also known as the Stupp protocol, includes a maximally safe surgical resection followed by radiation and chemotherapy. Despite these treatment regimens, recurrence is almost inevitable, emphasizing the need for new therapies to combat the aggressive nature of GBMs. Tumor Treating Fields (TTFs) are a relatively new application to the treatment of GBMs, and results have been promising with both progression-free survival and overall survival when TTFs have been used in combination with temozolomide. This article critically reviews the biophysical and biological mechanisms of TTFs, their clinical efficacy, and discusses the results in clinical trials, including EF-11 and EF-14. Both trials have demonstrated that TTFs can enhance progression free survival and overall survival without compromising quality of life or causing severe adverse effects. Despite the high cost associated with TTFs and the need for further analysis to determine the most effective ways to integrate TTFs into GBM treatments, TTFs represent a significant advancement in GBM therapy and offer hope for improved patient prognosis.

Three-outcome designs for external pilot trials with progression criteria.

BACKGROUND: Whether or not to progress from a pilot study to a definitive trial is often guided by pre-specified quantitative progression criteria with three possible outcomes. Although the choice of these progression criteria will help to determine the statistical properties of the pilot trial, there is a lack of research examining how they, or the pilot sample size, should be determined. METHODS: We review three-outcome trial designs originally proposed in the phase II oncology setting and extend these to the case of external pilots, proposing a unified framework based on univariate hypothesis tests and the control of frequentist error rates. We apply this framework to an example and compare against a simple two-outcome alternative. RESULTS: We find that three-outcome designs can be used in the pilot setting, although they are not generally more efficient than simpler two-outcome alternatives. We show that three-outcome designs can help allow for other sources of information or other stakeholders to feed into progression decisions in the event of a borderline result, but this will come at the cost of a larger pilot sample size than the two-outcome case. We also show that three-outcome designs can be used to allow adjustments to be made to the intervention or trial design before commencing the definitive trial, providing the effect of the adjustment can be accurately predicted at the pilot design stage. An R package, tout, is provided to optimise progression criteria and pilot sample size. CONCLUSIONS: The proposed three-outcome framework provides a way to optimise pilot trial progression criteria and sample size in a way that leads to desired operating characteristics. It can be applied whether or not an adjustment following the pilot trial is anticipated, but will generally lead to larger sample size requirements than simpler two-outcome alternatives.

Toxicodynamics of cadmium in the green mussel Perna viridis (Linnaeus, 1758) using bioenergetic and physiological biomarkers.

This study evaluated the toxicity of cadmium (Cd) on the green mussel Perna viridis, aiming to identify toxicological endpoints and investigate its responses across physiological, bioenergetic, and biochemical parameters. The 96-hour LC50 value for Cd in P. viridis was 3.03 ± 0.12 mg L-1, with a 95% confidence interval of 2.35-3.91 mg L-1. Chronic toxicity tests revealed a No Observable Effect Concentration (NOEC), Lowest Observable Effect Concentration (LOEC), and chronic toxicity values of 0.20, 0.37, and 0.29 mg L-1, respectively. Cadmium accumulation in treated mussels increased 46- to 215-fold compared to the control group. Superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase levels in exposed mussels exhibited a significant increase compared to the control group. The redox index ratio, acetylcholinesterase activity, and lysosomal membrane stability decreased with increasing exposure concentrations. Levels of reduced and oxidized glutathione, glutathione reductase, lipid peroxidation, and metallothionein-like proteins increased in exposed mussels. Clearance rate, respiration rate, and excretion rate decreased in a dose-dependent manner. Protein, carbohydrate, and lipid levels decreased with increasing exposure concentration (p < 0.001). Mitochondrial electron transport system activity increased, while cellular energy allocation (p < 0.001) and scope for growth decreased in a dose-dependent manner (p < 0.01). The significant increase in antioxidants suggests heightened oxidative stress in mussels under Cd exposure. The physiological activities of the mussels were severely affected, ultimately leading to a reduced scope for growth. The toxicological data generated in this study contribute to the development of seawater quality criteria for the metal Cd.

Prevalence and characteristics of fibromyalgia according to three fibromyalgia diagnostic criteria: A secondary analysis study.

Objective: The purpose of this study was to explore the prevalence of fibromyalgia (FM) according to different diagnostic criteria in a clinical sample and to explore the clinical characteristics in cases and non-cases by the diagnostic criteria used. Methods: A sample of 182 participants, both positive (n = 120) and negative (n = 62) FM individuals according to a clinical, pragmatic classification was used. Their characteristics were explored according to three different FM diagnostic criteria, i.e., the American College of Rheumatology (ACR) 1990, ACR 2016, and APS Pain Taxonomy (AAPT), respectively. Thus, impact of FM (FIQ), symptoms of anxiety and depression (HADS), tender point (TP) counts, and mechanical pressure sensitivity (in kPa) were compared in cases versus non-cases depending on diagnostic criteria of FM used. Descriptive analyses used chi-square statistic for categorical variables and non-parametric Mann-Whitney U tests for continuous variables. Results: From the clinical positive FM sample (n = 120), n = 99, 108, and 110 persons were diagnosed positive according to the ACR 1990, ACR 2016, and AAPT FM diagnostic criteria, respectively. All these three diagnostic tools discriminated FM positively from diagnostic FM non-cases when measuring TP-counts, mechanical pressures, and most FIQ-items, but they varied for anxiety and depression. Conclusion: The prevalence of FM differed somewhat with the use of ACR 1990, ACR 2016, and the AAPT as diagnostic tools. The anxiety and depression symptoms differed significantly between cases and non-cases using some but not all the diagnostic criteria. Regarding other FM symptoms, e.g., TPs and most FIQ items, all diagnostic criteria contrasted case from non-case.

Identifying metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus using clinic-based prediction tools.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a global cause of chronic liver disease. The prevalence of MASLD is high in patients with type 2 diabetes mellitus (T2DM). Various non-invasive tools such as the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS), liver ultrasound, and FibroScan can aid in the detection of liver fibrosis in MASLD, while the Hamaguchi ultrasound-based liver grading system has demonstrated high sensitivity and specificity comparable to liver biopsy. Objective: We assessed the frequency of MASLD in patients with T2DM using the liver ultrasound Hamaguchi score and the accuracy of NFS and Fib-4 in identifying MASLD. Patients and methods: We retrospectively collected data and reviewed the charts of all patients with T2DM who underwent liver ultrasound and laboratory tests during the past 5 years. Results: A total of 6,214 medical records were screened, and only 153 patients (68.6% women; mean age, 59 ± 12.2 years) fulfilled the selection criteria. MASLD was diagnosed using the Hamaguchi grading criteria in 45.1% of patients. A high/intermediate NFS had a higher sensitivity (79.7%) for diagnosing MASLD with a specificity of 10.7%, while a high/intermediate Fib-4 score showed only 30.4% sensitivity but a higher specificity of 54.8%. Conclusion: Our study indicates that MASLD is frequent in patients with T2DM, and clinical prediction tools such as NFS and Fib-4 can be applied in clinic/primary care settings with variable results.

Psychopathology and the Validity of Gastrointestisnal Symptom Reporting as Revealed Through Cluster Analyses of MMPI-2-RF Results.

BACKGROUND: Psychological state, self-reported gut symptoms, and somatic complaints are recognized relationships that can impact health assessment and subsequent treatment. AIM: To investigate the impact of psychological state and personality on symptom self-reporting and somatization. METHODS: Sixty-two (62) participants from the Hunter region of NSW (Australia) undertook a survey of health and lifestyle along with an MMPI-2-RF assessment of personality, psychopathology, and test-taking attitude. Participants also completed the Rome Criteria to assess functional gastrointestinal disorders (FGIDs). To assist the interpretation of MMPI-2-RF results, clustering was applied to identify similar responses and sub-cohort profiles of reporting. RESULTS: Cluster analysis revealed four sub-cohorts, stratified by psychopathology, gut-related symptoms, and the validity of self-reported somatic complaints. Sample clustering identified one sub-cohort defined by high rates of negative affectivity and suicidal ideation. Apart from these differences, clusters were uniform for age, sex, smoking, mental health diagnoses, as well as for gut-related conditions. CONCLUSION: Results provide further evidence of the interaction of the gut-brain axis and its relationship to serious mental health conditions. It also points to the need to assess the veracity of self-reported symptomatology that may be both pathognomonic for psychopathology but might also be a consequence of gut dysbiosis. Clustering assisted these investigations by defining distinct sub-cohorts based on participant MMPI-2-RF responses.

Routine Use of [64Cu]Cu-DOTATATE PET/CT in a Neuroendocrine Tumor Center: Referral Patterns and Image Results of 2,249 Consecutive Scans.

The role of somatostatin receptor (SSTR) PET/CT, using 68Ga-based tracers or [64Cu]Cu-DOTATATE (64Cu-DOTATATE), in the management of patients with neuroendocrine neoplasm (NEN) is guided by appropriate use criteria (AUC). In this study, we performed systematic analyses of referral patterns and image findings of routine 64Cu-DOTATATE PET/CT scans to support AUC development. Methods: We included all clinical routine 64Cu-DOTATATE PET/CT scans performed between April 10, 2018 (start of clinical use), and May 2, 2022, at Copenhagen University Hospital-Rigshospitalet. We reviewed the referral text and image report of each scan and classified the indication according to clinical scenarios as listed in the AUC. Results: In total, 1,290 patients underwent 2,249 64Cu-DOTATATE PET/CT scans. Monitoring of patients with NEN seen both on conventional imaging and on SSTR PET without clinical evidence of progression was the most common indication (defined as "may be appropriate" in the AUC) and accounted for 703 (31.3%) scans. Initial staging after NEN diagnosis ("appropriate" in the AUC) and restaging after curative-intent surgery ("may be appropriate" in the AUC) accounted for 221 (9.8%) and 241 (10.7%) scans, respectively. Selection of patients eligible for peptide receptor radionuclide therapy ("appropriate" in the AUC) and restaging after peptide receptor radionuclide therapy completion ("appropriate" in the AUC) accounted for 95 (4.2%) and 115 (5.1%) scans, respectively. The number of scans performed for indications not defined in the AUC was 371 (16.5%). Image result analysis revealed no disease in 669 scans (29.7%), stable disease in 582 (25.9%), and progression in 461 (20.5%). In 99 of the 461 (21.5%) scans, progression was detected on PET but not on CT. Conclusion: Our study provided real-life data that may contribute to support development of 64Cu-DOTATATE/SSTR PET/CT guidelines including AUC. Some scenarios listed as "may be appropriate" in the current AUC were frequent in our data. Monitoring of patients with NEN without clinical evidence of progression was the most frequent indication for 64Cu-DOTATATE PET/CT, in which disease progression was detected in more than one third, and a large proportion was visible by PET only. We therefore conclude that this scenario could potentially be classified as appropriate.

Castleman Disease: A Rare Lymphoproliferative Disorder With Diverse Clinical Presentation, Diagnosis, and Treatment Approach.

Castleman disease (CD) includes rare and intricate lymphoproliferative disorders characterized by the abnormal growth of lymph nodes and immune system disturbances. It primarily presents in two forms: unicentric Castleman disease (UCD), which affects a single lymph node area, and multicentric Castleman disease (MCD), which involves multiple lymph nodes and systemic manifestations. The disease's underlying mechanisms are often linked to immune system irregularities, especially involving interleukin-6 (IL-6). The condition was first documented by Dr. Benjamin Castleman in 1954, laying the groundwork for understanding this complex disorder. MCD can be further divided into idiopathic MCD (iMCD), which includes thrombocytopenia, ascites, fibrosis, renal impairment, and organ enlargement (TAFRO) syndrome, and human herpesvirus-8 (HHV-8)-associated MCD, which can occur in individuals with or without HIV. The prevalence of CD shows a higher occurrence of UCD, with the disease typically presenting in individuals in their fifth to seventh decades of life and being more common in areas with high HIV prevalence. The clinical presentation of CD can include symptoms such as swollen lymph nodes, fever, anemia, and systemic inflammation. Diagnostic challenges arise due to the disease's rarity, and its symptoms overlap with other conditions. Treatment approaches differ based on the subtype. UCD generally responds favorably to the surgical removal of the affected lymph nodes, while MCD often requires antiviral treatments, interleukin-6 (IL-6) inhibitors, and new biologic therapies. Recent advances in treatment, including innovative biologic agents and combination therapies, offer promising prospects for improving patient outcomes. Accurate diagnosis and customized treatment strategies are essential for the effective management of this complex disease.

Prevalence of unnecessary kidney function exclusion criteria in urologic oncology clinical trials.

INTRODUCTION: Clinical trials play a pivotal role in advancing treatments for people with cancer, but often struggle with low enrollment. Unnecessarily including kidney function eligibility criteria when a trial's interventions do not have any potential kidney effects may contribute to this problem by needlessly limiting the pool of eligible patients, adding complexity to the patient screening process, and raising issues of inequitable access to trials. For these reasons, we applied custom natural language processing to assess renal function eligibility criteria, and the appropriateness of these exclusions, within phase 3 urologic oncology trials. METHODS: We accessed all phase 3 urologic oncology trials registered on ClinicalTrials.gov from 2007 to 2021. We used a custom natural language processing script to extract kidney function requirements (e.g., creatinine, GFR) from trial free-text records. For each trial, we manually coded whether any trial intervention affected renal function or was renally excreted. Additionally, we recorded the formula used to calculate GFR in each trial. RESULTS: Of 850 trials, 299 (35%) listed kidney function eligibility restrictions, and 432 (51%) tested an intervention with possible renal effects. Of the 299 trials with kidney function exclusions, 124 (41%) tested interventions with no kidney effects. CONCLUSION: There is a major disconnect in urologic oncology clinical trials between renal function exclusions and potential harm to the kidneys from the tested interventions. Standardizing eligibility criteria and restricting enrollment based on renal function only when necessary has the potential to increase the success, access, and applicability of clinical trials.

Diagnostic utility of direct immunofluorescence test panels for cutaneous vasculitis: A scoping review.

BACKGROUND: Due to the immune-mediated nature of non-infectious cutaneous vasculitis, skin biopsy specimens are often submitted for direct immunofluorescence (DIF) testing when vasculitis is considered clinically. However, evidence regarding the clinical value of DIF has not been rigorously appraised. OBJECTIVE: In this scoping review, we aimed to systematically evaluate the peer-reviewed literature on the utility of DIF in vasculitis to assist with the development of appropriate use criteria by the American Society of Dermatopathology. METHODS: Two electronic databases were searched for articles on DIF and vasculitis (January 1975-October 2023). Relevant case series involving more than or equal to three patients, published in English, and with full-text availability were included. Additional articles were identified manually via reference review. Due to study heterogeneity, findings were analyzed descriptively. RESULTS: Of 255 articles identified, 61 met the inclusion criteria. Cumulatively representing over 1000 DIF specimens, several studies estimated DIF sensitivity to be 75%. While vascular immunoglobulin A (IgA) deposits on DIF were associated with renal disease, other systemic associations were inconsistent. Vascular IgG deposition may be overrepresented in ANCA-associated vasculitis. Granular vascular and epidermal basement membrane zone Ig deposition differentiated hypocomplementemic from normocomplementemic urticarial vasculitis. Few studies have assessed the added value of DIF over routine microscopy alone in vasculitis. CONCLUSIONS: This scoping review discovered that DIF testing for vasculitis has been performed not only for diagnostic confirmation of vasculitis but also for disease subtype classification and prediction of systemic associations. Future studies on test sensitivity of DIF compared to that of histopathology are needed.

Extra-Limbic Seronegative Encephalitis Preceding Recurrent Hodgkin's Lymphoma and Gastric Diffuse Large B-Cell Lymphoma: A Case Report.

We describe a patient with extra-limbic seronegative encephalitis with relapsing progressive course as the harbinger of sequential Hodgkin's lymphoma and Diffuse Large B-Cell lymphoma. Diagnosis of probable paraneoplastic neurologic syndrome (PNS) was arrived at by exhaustive elimination of alternative causes and supportive tissue diagnosis. This case highlights the phenotypic variety of paraneoplastic neurologic syndromes associated with hematologic malignancies and the challenges in their recognition, diagnosis, and treatment. We discuss and apply the updated consensus diagnostic criteria for paraneoplastic syndromes to our case as a means of bolstering probability in cases of diagnostic uncertainty.

Multiple myeloma clinical trials exclude patients with the highest-risk disease: a systematic review of trial exclusion criteria.

Patients with certain subsets of multiple myeloma continue to have poor outcomes and are in need of novel treatment approaches. Strict eligibility criteria for randomized controlled trials (RCTs) limit access to clinical trials and limit the external validity of trial results for these patients. We systematically reviewed RCTs in newly diagnosed myeloma from 2006 to 2023 to ascertain the prevalence of 12 key exclusion criteria and trends over time. 80 RCTs were included. Exclusion criteria included: age in 43 (51%) trials; projected life expectancy in 20 (24%); performance status in 74 (87%); non-secretory and/or oligosecretory disease in 47 (55%), hepatic function in 64 (79%), renal function in 63 (74%), hematological thresholds in 50 (59%), prior malignancy in 68 (80%), and neuropathy in 50 (59%). For 53 trials which had detailed exclusion criteria available, plasma cell leukemia was excluded in 21 (40%), extramedullary disease in 5 (9%) and CNS disease in 13 (25%). The percentage of studies invoking each of these exclusion criteria did not significantly improve over time on univariate regression analysis, and exclusion criteria relating to neuropathy have worsened. The restrictive eligibility criteria of most myeloma RCTs perpetuate a cycle where limited data exists to treat challenging myeloma subtypes.

Idiopathic intracranial hypertension in Asians: a retrospective dual-center study.

BACKGROUND: There have been limited data on idiopathic intracranial hypertension (IIH) in Asians and there remain uncertainties whether a cerebrospinal fluid (CSF) pressure of 250 mm CSF is an optimum diagnostic cutoff. The aims of the present study included (1) characterization of IIH patients in Taiwan, (2) comparisons among different diagnostic criteria for IIH, and (3) comparisons between patients with CSF pressures of > 250 and 200-250 mm CSF. METHODS: This retrospective study involved IIH patients based on the modified Dandy criteria from two tertiary medical centers in Taiwan. Clinical manifestations were retrieved from electronic medical records, and findings on ophthalmologic examination and magnetic resonance images (MRIs) were reviewed. RESULTS: A total of 102 patients (71 F/31 M, mean age 33.4 ± 12.2 years, mean CSF pressure 282.5 ± 74.5 mm CSF) were identified, including 46 (45.1%) with obesity (body-mass index ≥ 27.5), and 57 (62.6%) with papilledema. Overall, 80 (78.4%), 55 (53.9%), 51 (50.0%), and 58 (56.9%) patients met the Second and Third Edition of International Classification of Headache Disorders, Friedman, and Korsbæk criteria, respectively. Patients in the 200-250 mm CSF group (n = 40) were less likely to have papilledema (48.5% vs. 70.7%, p = 0.035), transient visual obscuration (12.5% vs. 33.9%, p = 0.005), and horizontal diplopia (10.0% vs. 30.6%, p = 0.006), and had fewer signs on MRIs (2.2 ± 1.3 vs. 2.8 ± 1.0, p = 0.021) when compared with those with CSF pressures > 250 mm CSF (n = 62). However, the percentages of patients with headache (95.0% vs. 87.1%, p = 0.109) at baseline, chronic migraine at six months (31.6% vs. 25.0%, p = 0.578), and visual field defect (86.7% vs. 90.3%, p = 0.709) were similar. CONCLUSIONS: It was found that obesity and papilledema were less common in Asian IIH patients when compared with Caucasian patients. Although patients with CSF pressures of 200-250 mm CSF had a less severe phenotype, the risks of having headache or visual loss were comparable to those in the > 250 mm CSF group. It is possible that a diagnostic cutoff of > 200 mm CSF could be more suitable for Asians, although further studies are still needed.