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Melanoma Management 2024Cutaneous melanocytic neoplasms with diagnostic and/or clinical ambiguity pose patient management challenges. Six randomized case scenarios with diagnostic/clinical...
Cutaneous melanocytic neoplasms with diagnostic and/or clinical ambiguity pose patient management challenges. Six randomized case scenarios with diagnostic/clinical uncertainty were described with/without a benign or malignant diagnostic gene expression profile (GEP) result. Clinical impact was assessed by reporting the mean increase/decrease of management changes normalized to baseline (n = 32 dermatologists). Benign GEP results prompted clinicians to decrease surgical margins (84.2%). Malignant GEP results escalated surgical excision recommendations (100%). A majority (72.2%) reduced and nearly all (98.9%) increased follow-up frequency for benign or malignant GEP results, respectively. There was an overall increase in management plan confidence with GEP results. Diagnostic GEP tests help guide clinical decision-making in a variety of diagnostically ambiguous or clinicopathologically discordant scenarios.
PubMed: 38812731
DOI: 10.2217/mmt-2023-0002 -
Neurological Research and Practice May 2024Depending on the underlying etiology and epilepsy type, the burden of disease for patients with seizures can vary significantly. This analysis aimed to compare direct...
A multicenter, matched case-control analysis comparing burden of illness among patients with tuberous sclerosis complex related epilepsy, generalized idiopathic epilepsy, and focal epilepsy in Germany.
BACKGROUND
Depending on the underlying etiology and epilepsy type, the burden of disease for patients with seizures can vary significantly. This analysis aimed to compare direct and indirect costs and quality of life (QoL) among adults with tuberous sclerosis complex (TSC) related with epilepsy, idiopathic generalized epilepsy (IGE), and focal epilepsy (FE) in Germany.
METHODS
Questionnaire responses from 92 patients with TSC and epilepsy were matched by age and gender, with responses from 92 patients with IGE and 92 patients with FE collected in independent studies. Comparisons were made across the main QoL components, direct costs (patient visits, medication usage, medical equipment, diagnostic procedures, ancillary treatments, and transport costs), indirect costs (employment, reduced working hours, missed days), and care level costs.
RESULTS
Across all three cohorts, mean total direct costs (TSC: €7602 [median €2620]; IGE: €1919 [median €446], P < 0.001; FE: €2598 [median €892], P < 0.001) and mean total indirect costs due to lost productivity over 3 months (TSC: €7185 [median €11,925]; IGE: €3599 [median €0], P < 0.001; FE: €5082 [median €2981], P = 0.03) were highest among patients with TSC. The proportion of patients with TSC who were unemployed (60%) was significantly larger than the proportions of patients with IGE (23%, P < 0.001) or FE (34%, P = P < 0.001) who were unemployed. Index scores for the EuroQuol Scale with 5 dimensions and 3 levels were significantly lower for patients with TSC (time-trade-off [TTO]: 0.705, visual analog scale [VAS]: 0.577) than for patients with IGE (TTO: 0.897, VAS: 0.813; P < 0.001) or FE (TTO: 0.879, VAS: 0.769; P < 0.001). Revised Epilepsy Stigma Scale scores were also significantly higher for patients with TSC (3.97) than for patients with IGE (1.48, P < 0.001) or FE (2.45, P < 0.001). Overall Quality of Life in Epilepsy Inventory-31 items scores was significantly lower among patients with TSC (57.7) and FE (57.6) than among patients with IGE (66.6, P = 0.004 in both comparisons). Significant differences between patients with TSC and IGE were also determined for Neurological Disorder Depression Inventory for Epilepsy (TSC: 13.1; IGE: 11.2, P = 0.009) and Liverpool Adverse Events Profile scores (TSC: 42.7; IGE: 37.5, P = 0.017) with higher score and worse results for TSC patients in both questionnaires.
CONCLUSIONS
This study is the first to compare patients with TSC, IGE, and FE in Germany and underlines the excessive QoL burden and both direct and indirect cost burdens experienced by patients with TSC.
PubMed: 38812055
DOI: 10.1186/s42466-024-00323-6 -
Journal of Neuroengineering and... May 2024Movement smoothness is a potential kinematic biomarker of upper extremity (UE) movement quality and recovery after stroke; however, the measurement properties of...
BACKGROUND
Movement smoothness is a potential kinematic biomarker of upper extremity (UE) movement quality and recovery after stroke; however, the measurement properties of available smoothness metrics have been poorly assessed in this group. We aimed to measure the reliability, responsiveness and construct validity of several smoothness metrics.
METHODS
This ancillary study of the REM-AVC trial included 31 participants with hemiparesis in the subacute phase of stroke (median time since stroke: 38 days). Assessments performed at inclusion (Day 0, D0) and at the end of a rehabilitation program (Day 30, D30) included the UE Fugl Meyer Assessment (UE-FMA), the Action Research Arm Test (ARAT), and 3D motion analysis of the UE during three reach-to-point movements at a self-selected speed to a target located in front at shoulder height and at 90% of arm length. Four smoothness metrics were computed: a frequency domain smoothness metric, spectral arc length metric (SPARC); and three temporal domain smoothness metrics (TDSM): log dimensionless jerk (LDLJ); number of submovements (nSUB); and normalized average rectified jerk (NARJ).
RESULTS
At D30, large clinical and kinematic improvements were observed. Only SPARC and LDLJ had an excellent reliability (intra-class correlation > 0.9) and a low measurement error (coefficient of variation < 10%). SPARC was responsive to changes in movement straightness (r=0.64) and to a lesser extent to changes in movement duration (r=0.51) while TDSM were very responsive to changes in movement duration (r>0.8) and not to changes in movement straightness (non-significant correlations). Most construct validity hypotheses tested were verified except for TDSM with low correlations with clinical metrics at D0 (r<0.5), ensuing low predictive validity with clinical metrics at D30 (non-significant correlations).
CONCLUSIONS
Responsiveness and construct validity of TDSM were hindered by movement duration and/or noise-sensitivity. Based on the present results and concordant literature, we recommend using SPARC rather than TDSM in reaching movements of uncontrolled duration in individuals with spastic paresis after stroke.
TRIAL REGISTRATION
NCT01383512, https://clinicaltrials.gov/ , June 27, 2011.
Topics: Humans; Male; Female; Upper Extremity; Middle Aged; Movement; Aged; Biomechanical Phenomena; Stroke; Stroke Rehabilitation; Reproducibility of Results; Paresis; Adult; Recovery of Function
PubMed: 38812037
DOI: 10.1186/s12984-024-01382-1 -
Neurocritical Care May 2024Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain...
BACKGROUND
Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g., brain oximetry) and noninvasive monitoring (NIM) methods (e.g., transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and ICPW in future updates.
METHODS
We conducted a survey among experienced professionals involved in researching and managing patients with severe injury across low-middle-income countries (LMICs) and high-income countries (HICs). We sought their insights on ICP monitoring, particularly focusing on the impact of NIM and ICPW in various clinical scenarios.
RESULTS
From October to December 2023, 109 professionals from the Americas and Europe participated in the survey, evenly distributed between LMIC and HIC. When ICP ranged from 22 to 25 mm Hg, 62.3% of respondents were open to considering additional information, such as ICPW and other monitoring techniques, before adjusting therapy intensity levels. Moreover, 77% of respondents were inclined to reassess patients with ICP in the 18-22 mm Hg range, potentially escalating therapy intensity levels with the support of ICPW and NIM. Differences emerged between LMIC and HIC participants, with more LMIC respondents preferring arterial blood pressure transducer leveling at the heart and endorsing the use of NIM techniques and ICPW as ancillary information.
CONCLUSIONS
Experienced clinicians tend to personalize ICP management, emphasizing the importance of considering various monitoring techniques. ICPW and noninvasive techniques, particularly in LMIC settings, warrant further exploration and could potentially enhance individualized patient care. The study suggests updating guidelines to include these additional components for a more personalized approach to ICP management.
PubMed: 38811514
DOI: 10.1007/s12028-024-02008-z -
Diagnostic Cytopathology May 2024Ocular cytology is an effective method of diagnosing infective, benign, and malignant ocular disease processes due to easy accessibility and rapid turnaround time....
BACKGROUND
Ocular cytology is an effective method of diagnosing infective, benign, and malignant ocular disease processes due to easy accessibility and rapid turnaround time. However, these specimens pose significant diagnostic challenges due to rarity of the specimen type, sparse diagnostic material available for ancillary workup, and unfamiliarity of the diagnostic entities by the cytopathologist.
METHODS
This study conducted a 6-year comprehensive review of 65 eye cytology cases received at a tertiary level hospital. Cytopathologic diagnoses of "negative for malignancy" and "atypical" were categorized as negative findings (70.8%, n = 46) and diagnoses of "suspicious for malignancy" and "positive for malignancy" were categorized as positive findings (23.1%, n = 15). A 44.6% (n = 29) of cases had subsequent histopathology and/or flow cytometry diagnoses. Premalignant and malignant lesions detected on histopathology were considered as significant findings. Statistical analysis was performed to evaluate the concordance of ocular cytology with associated histopathology and/or flow cytometry diagnoses.
RESULTS
The accuracy of final cytology-histopathology and/or cytology-flow cytometry diagnoses in this cohort of cases is 86.2%. The sensitivity and specificity of ocular diagnosis by cytology are 66.6% and 100%, respectively. The positive and negative predictive values of ocular diagnosis by cytology are 100% and 80.9%, respectively.
CONCLUSION
Ocular cytology is a fast, effective, and sensitive method for diagnosing ocular pathology specimens. Familiarity with these specimen types by cytopathologists can help in diagnosing ocular diseases effectively on small, challenging cytologic preparations.
PubMed: 38808690
DOI: 10.1002/dc.25341 -
Nucleic Acids Research May 2024Recognition of RNA from invading mobile genetic elements (MGE) prompts type III CRISPR systems to activate an HD nuclease domain and/or a nucleotide cyclase domain in...
Recognition of RNA from invading mobile genetic elements (MGE) prompts type III CRISPR systems to activate an HD nuclease domain and/or a nucleotide cyclase domain in the Cas10 subunit, eliciting an immune response. The cyclase domain can generate a range of nucleotide second messengers, which in turn activate a diverse family of ancillary effector proteins. These provide immunity by non-specific degradation of host and MGE nucleic acids or proteins, perturbation of membrane potentials, transcriptional responses, or the arrest of translation. The wide range of nucleotide activators and downstream effectors generates a complex picture that is gradually being resolved. Here, we carry out a global bioinformatic analysis of type III CRISPR loci in prokaryotic genomes, defining the relationships of Cas10 proteins and their ancillary effectors. Our study reveals that cyclic tetra-adenylate is by far the most common signalling molecule used and that many loci have multiple effectors. These typically share the same activator and may work synergistically to combat MGE. We propose four new candidate effector protein families and confirm experimentally that the Csm6-2 protein, a highly diverged, fused Csm6 effector, is a ribonuclease activated by cyclic hexa-adenylate.
PubMed: 38808661
DOI: 10.1093/nar/gkae462 -
Minerva Cardiology and Angiology May 2024Anticoagulation is indicated for treatment and prevention of arterial and venous thrombosis. Targeting different steps of the coagulation process, currently available...
Anticoagulation is indicated for treatment and prevention of arterial and venous thrombosis. Targeting different steps of the coagulation process, currently available anticoagulants entail an increased risk of bleeding, which detrimentally impacts on prognosis and hinders the administration of an effective antithrombotic regimen. Factor XI (FXI) inhibition has emerged as a strategy to uncouple prevention of thrombosis from bleeding. Indeed, while FXI is crucial for the amplification phase in pathological thrombosis, it is ancillary in physiological hemostasis. A comprehensive search in several scientific databases has been performed to identify relevant studies in the field. In addition, ongoing trials have been searched for in proper datasets to provide an updated and comprehensive assessment of the current state of investigations on FXI inhibition. Many compounds have been tested to inhibit FXI at different stages (i.e., synthesis, activation, or interactions with target molecules and coagulation factors). These include antisense oligonucleotides, monoclonal antibodies, small molecules, natural peptides and aptamers. In phase 2 studies, FXI inhibitors reduced thrombotic complications without any corresponding increase in bleeding. FXI inhibitors were noninferior and potentially superior to low-molecular-weight heparin in orthopedic surgery and reduced bleeding compared to apixaban in patients with atrial fibrillation. FXI inhibition is also under testing in other conditions, including end-stage renal disease, cancer, or noncardioembolic stroke. FXI inhibition represents a promising and rapidly emerging approach for a number of clinical indications. This article reviews the rationale, evidence, pharmacology, and future applications of FXI inhibition.
PubMed: 38804623
DOI: 10.23736/S2724-5683.23.06474-8 -
Nursing Reports (Pavia, Italy) Apr 2024Music evokes positive emotions and reduces stress and anxiety. Operating room (OR) staff face various challenges which can lead to high levels of stress. The aim of the...
BACKGROUND
Music evokes positive emotions and reduces stress and anxiety. Operating room (OR) staff face various challenges which can lead to high levels of stress. The aim of the study is to assess whether listening to music during intraoperative phases improves the work environment by reducing anxiety and stress in the entire surgical team.
METHODS
A prospective observational study was conducted from February to September 2023, involving medical personnel, nursing staff, and nursing students. They were divided into two groups: Group 1 with music during surgical procedures, and Group 2 without music. Participants were administered two validated instruments: the Zung Anxiety Self-Assessment Scale (SAS) to measure anxiety, and the Positive and Negative Affect Schedule to assess emotions generating stress. Additional items were included for demographics, job satisfaction, and the organization method.
RESULTS
Music did not impact anxiety, but increased positive emotions while reducing negative ones. Music had an ancillary effect, highlighting the need for significant organizational interventions aimed at increasing operator satisfaction, including offering voluntary instead of mandatory assignments to nursing staff.
CONCLUSIONS
Music appears to reduce stress in the intraoperative team when supported by a positive work environment in which assigned operators have chosen to work in the OR.
PubMed: 38804415
DOI: 10.3390/nursrep14020082 -
Diagnostic Pathology May 2024Current diagnostic criteria of adrenocortical neoplasms are mostly based on morphology. The utility of immunohistochemistry (IHC) and histochemistry is limited.
BACKGROUND
Current diagnostic criteria of adrenocortical neoplasms are mostly based on morphology. The utility of immunohistochemistry (IHC) and histochemistry is limited.
MATERIALS AND METHODS
To evaluate the diagnostic and prognostic utility of clinicopathological features, morphology, ancillary biomarkers, and reticular histochemistry in adrenocortical neoplasms. We examined 28 adrenocortical carcinomas (ACCs) and 50 adrenocortical adenomas (ACAs) obtained from pathology archives. Clinical data were retrieved from medical records. Two pathologists independently assessed hematoxylin and eosin-stained slides, employing modified Weiss criteria for all tumors and Lin-Weiss-Bisceglia criteria for oncocytic variants. Immunohistochemical markers (Calretinin, alpha-inhibin, MelanA, SF-1, Ki-67, PHH3, IGF-2, β-catenin, P53, CYP11B1, CYP11B2, MLH1, MSH2, MSH6, PMS2, EPCAM) and Gomori's Silver histochemistry were applied. Statistical analysis utilized SPSS Statistics 26.
RESULTS
ACCs exhibited larger tumor sizes (P<0.001) and symptomatic presentations (P = 0.031) compared to ACAs. Parameters of modified Weiss criteria and angioinvasion demonstrated diagnostic value for ACCs. Six immunohistochemical antibodies((MelanA, Ki-67, IGF-2, β-catenin, P53 and CYP11B1) and reticulin framework alterations showed diagnostic value. Notably, Ki-67 and reticulin staining were most recommended. Evident reticulin staining was frequently present in ACCs (P<0.001). Ki-67 was significantly higher in ACCs (P<0.001). Twenty-one conventional and seven oncocytic entities showed different necrosis frequencies. Symptoms and Ki-67 index ≥ 30% were prognostic for ACCs, correlating with shorter survival.
CONCLUSIONS
This study emphasizes the diagnostic value of reticulin framework alterations and a high Ki-67 index. Markers such as CYP11B1, IGF2, P53, β-catenin and MelanA also contribute to the diagnosis of ACCs. Symptoms and Ki-67 index ≥ 30% predict shorter survival. These findings encourges the use of ancillary markers such as reticulin histochemistry and Ki-67 in the workup of evaluations of adrenocortical neoplasms.
Topics: Humans; Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Male; Female; Biomarkers, Tumor; Middle Aged; Immunohistochemistry; Adult; Prognosis; Aged; Young Adult; Adolescent; Adrenocortical Adenoma; Child
PubMed: 38802933
DOI: 10.1186/s13000-024-01496-z -
The British Journal of Ophthalmology May 2024To report distinctive clinical and imaging features of iris freckles to differentiate them from iris nevi.
PURPOSE
To report distinctive clinical and imaging features of iris freckles to differentiate them from iris nevi.
DESIGN
Retrospective observational study.
SUBJECTS
53 patients (277 freckles) with incidental iris freckles and 102 patients (104 nevi) with iris nevi that are either clinically stable or pathologically confirmed.
METHODS
Patient data were collected from the Department of Ophthalmic Oncology, Cleveland Clinic, Cole Eye Institute database (2012-2023). Lesion characteristics were recorded from slit-lamp examination descriptions and review of colour photographs. Ancillary imaging features observed using anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) were assessed in patients (where available).
MAIN OUTCOME MEASURES
Comparison of clinical and imaging features of iris freckles and iris nevi.
RESULTS
A total of 277 iris freckles and 104 iris nevi were analysed. Iris freckles were more frequently bilateral (17%; nevi 0%) and multiple (69%; nevi 2%) and located centrally (89%; nevi 17%) compared with iris nevi (p<0.001). The median freckle largest basal diameter and thickness were 0.8 mm (nevi; 2.1 mm, p<0.001) and 0.04 mm (nevi 1.0 mm, p<0.001), respectively. All iris freckles had irregular margins without any secondary effects compared with iris nevi. Iris freckles appeared flat without effacement of iris folds compared with iris nevi on AS-OCT (p<0.001). Iris freckles were not detectable by UBM. Heat map revealed that freckles demonstrated several features with uniform or near uniform values, whereas nevi demonstrated more variability in values across features.
CONCLUSIONS
Iris freckles exhibit specific clinical and imaging features reflective of their characteristic histological composition that support their classification as a distinct entity within the spectrum of iris pigmented lesions.
PubMed: 38802168
DOI: 10.1136/bjo-2023-325009