Updated Classification System Research Articles

Modern Classification of Respiratory Diseases: Innovations in the International Classification of Diseases of the 11th Revision

A comprehensive analysis has been performed on the innovations in the classification of respiratory diseases introduced in ICD-11, comparing it with the previous ICD-10 version. This analysis underscores the critical importance of implementing a more detailed and systematic approach to categorizing diseases of the respiratory system. The enhancements found in ICD-11 have been proven to open up new opportunities for the timely and high-quality provision of medical and pharmaceutical care. This is particularly significant for patients suffering from various injuries, including those resulting from traffic accidents, participation in combat operations, and thoracic injuries. The updated classification system in ICD-11 allows for more precise diagnosis and treatment plans, which is essential for improving patient outcomes. By providing a more granular level of detail in disease categorization, healthcare professionals can better understand the nuances of respiratory conditions. This leads to more effective communication among doctors, pharmacists, and patients, thereby improving the legal and professional relationships within the healthcare system. Integrating the ICD-11 classification into educational and training programs is essential for advancing the qualifications of specialists. By incorporating it into curricula and professional development programs, medical practitioners can stay abreast of the latest advancements in disease classification and patient care. This integration is also vital for eliminating medical errors, as a more detailed classification system reduces the likelihood of misdiagnosis and improper treatment. Furthermore, adopting ICD-11 supports the ongoing development of the healthcare sector in Ukraine. It aligns the country's medical practices with international standards, facilitating better collaboration with global health organizations. This alignment is crucial for enhancing the overall quality of healthcare services provided to the population. In conclusion, the transition to ICD-11 represents a significant advancement in the classification of respiratory diseases. Its implementation is imperative for improving medical and pharmaceutical care, enhancing specialist training programs, and strengthening the doctor-pharmacist-patient relationship. Embracing this updated classification system will not only reduce medical errors but also contribute to the further development of Ukraine's healthcare sector.

Evaluation of the prognostic value of the new 9th edition Tumor-Node-Metastases (TNM) staging system for epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma patients with bone metastases

BackgroundThere are some changes in the new 9th edition Tumor-Node-Metastases (TNM) staging system for lung cancer, including subdividing M1c into M1c1 and M1c2 stage. The aim of this study was to assess the prognostic performance of the updated classification system and try to provide some real-world application data among advanced lung adenocarcinoma patients with bone metastases.MethodsAdvanced lung adenocarcinoma patients in M1c stage with bone metastases who receiving first-line first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and T790M-guided osimertinib as the second-line therapy were retrospectively screened from December 2016 to December 2021. A total of 126 patients were enrolled in this study. 62 patients and 64 patients were subdivided into M1c1 and M1c2 groups according to the 9th edition of TNM staging system.The first-line real-world progression-free survival (1LrwPFS), the second-line real-world progression-free survival (2LrwPFS), post-progression survival (PPS) and real-world overall survival (rwOS) were analyzed.ResultsThe overall median rwOS was 40.1 months (95% CI 35.996–44.204). 1LrwPFS was 13.9 months (95% CI 12.653–15.147) and 2LrwPFS was 14.5 months (95% CI 11.665–17.335) for all patients.Patients in M1c2 stage was inferior to M1c1 stage patients in rwOS (35.2 months vs. 42.9 months, HR = 0.512, P = 0.005). 2LrwPFS was moderately correlated with rwOS (r = 0.621, R2 = 0.568, P = 0.000). Multivariate analysis showed performance status (PS) score ≥ 2 and TP53 alteration positive were independent prognostic factors of worse rwOS.ConclusionsMore refined stratification of M1c according to the 9th edition of TNM staging system is conducive to the judgment of prognosis and the implementation of precision medicine for patients.

The prognosis of pancreatic neuroendocrine tumors according to the WHO 2017 classification: The multi-center experience in Taiwan.

87 Background: The occurrence of pancreatic neuroendocrine tumors (PanNETs) remains infrequent, there is an upward trend in their diagnosis. Our retrospective study, conducted in Taiwan, focuses on exploring the interplay between clinical characteristics, treatment modalities, and prognosis in PanNET cases. Particularly, we aim to assess the implications of the updated WHO classification system on prognosis. Methods: We conducted a retrospective analysis of 176 PanNET cases from Chang Gung Medical Foundation, encompassing Linkou, Taoyuan, and Tucheng Hospitals, spanning the years 2009 to 2022. Pathology reports for all cases were reevaluated by pathologists according to the WHO 2017 classifications. Clinical features and overall survival outcomes were documented. Additionally, we examined the prognosis of distinct subgroups categorized by the WHO 2017 classification and their respective treatments. Results: The 5-year survival rate for all patients in the cohort stood at 58.7%. Among these, individuals diagnosed with NET G1 exhibited the highest survival rate (n = 78, 83.1%), followed by those with NET G2 (n = 57, 55.0%), NET G3 (n = 25, 14.6%), and NEC (n = 16, 9.4%). Univariate analysis highlighted several significant prognostic factors, including age, absence of symptoms at diagnosis, tumor size, lymph node involvement, distant metastasis, higher Ki-67 index, and cellular morphology. Comparative analysis between the WHO 2017 and WHO 2010 classifications revealed both systems as significant independent predictors of overall survival in PanNET cases. Notably, the 95% confidence interval for the WHO 2017 classification (2.892–9.703) showed a slight improvement in prognostic precision compared to the WHO 2010 classification (3.696–10.067). Under the WHO 2010 classification, NET G3 and NEC were combined, with NEC presenting higher rates of distant metastases, lymph node involvement, and Ki-67 index. Further investigation revealed that patients receiving somatostatin analogs, chemotherapy, or targeted therapy exhibited improved survival rates, particularly notable in NET G3 and NEC subgroups. Furthermore, NEC patients displayed extended treatment durations and higher objective response rates to first-line chemotherapy compared to the NET G3 group. Conclusions: Our retrospective analysis has illuminated the interrelation between prognostic factors and the overall survival rate. Furthermore, the updated WHO 2017 classification elucidates the distinctions between G3 and NEC, thus influencing the selection of clinical interventions.

Radiologic-Pathologic Correlation of Cardiac Tumors: Updated 2021 WHO Tumor Classification.

Cardiac tumors, although rare, carry high morbidity and mortality rates. They are commonly first identified either at echocardiography or incidentally at thoracoabdominal CT performed for noncardiac indications. Multimodality imaging often helps to determine the cause of these masses. Cardiac tumors comprise a distinct category in the World Health Organization (WHO) classification of tumors. The updated 2021 WHO classification of tumors of the heart incorporates new entities and reclassifies others. In the new classification system, papillary fibroelastoma is recognized as the most common primary cardiac neoplasm. Pseudotumors including thrombi and anatomic variants (eg, crista terminalis, accessory papillary muscles, or coumadin ridge) are the most common intracardiac masses identified at imaging. Cardiac metastases are substantially more common than primary cardiac tumors. Although echocardiography is usually the first examination, cardiac MRI is the modality of choice for the identification and characterization of cardiac masses. Cardiac CT serves as an alternative in patients who cannot tolerate MRI. PET performed with CT or MRI enables metabolic characterization of malignant cardiac masses. Imaging individualized to a particular tumor type and location is crucial for treatment planning. Tumor terminology changes as our understanding of tumor biology and behavior evolves. Familiarity with the updated classification system is important as a guide to radiologic investigation and medical or surgical management. ©RSNA, 2024 Supplemental material is available for this article.

Delivering on a promise: futureproofing automated insect monitoring methods.

Due to rapid technological innovations, the automated monitoring of insect assemblages comes within reach. However, this continuous innovation endangers the methodological continuity needed for calculating reliable biodiversity trends in the future. Maintaining methodological continuity over prolonged periods of time is not trivial, since technology improves, reference libraries grow and both the hard- and software used now may no longer be available in the future. Moreover, because data on many species are collected at the same time, there will be no simple way of calibrating the outputs of old and new devices. To ensure that reliable long-term biodiversity trends can be calculated using the collected data, I make four recommendations: (1) Construct devices to last for decades, and have a five-year overlap period when devices are replaced. (2) Construct new devices to resemble the old ones, especially when some kind of attractant (e.g. light) is used. Keep extremely detailed metadata on collection, detection and identification methods, including attractants, to enable this. (3) Store the raw data (sounds, images, DNA extracts, radar/lidar detections) for future reprocessing with updated classification systems. (4) Enable forward and backward compatibility of the processed data, for example by in-silico data 'degradation' to match the older data quality. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.

An updated classification of the anatomical variations of the internal iliac venous drainage system: Surgical implications for anterior lumbar spinal approaches

BackgroundAdvanced pelvic surgery is associated with potential vascular risks. The aim of this study was to complete the existing classification of the anatomical variations of the internal iliac veins encountered on a series of preoperative angio CT with a view to performing anterior lumbar spine surgery. Materials and MethodsIn this monocentric retrospective study conducted between 2010 and 2020, all preoperative angio CT performed before an anterior lumbar surgery were systematically analyzed. All the abnormalities of the iliac veins were referenced in an updated classification system. Results910 patients (431 men and 479 women) with a mean age of 49 years [16–88] were included. Apart from the most common variant in the population (type I), 64 anatomical variations (7.0%) in the iliac veins were reported and classified according to our new classification. The percentage of coverage of the L4-L5 intervertebral disc is 52%, including 32% by the inferior vena cava before the confluence of the common iliac veins. At the level of the L5-S1 intervertebral disc, the coverage is 30% (same distribution between left and right). ConclusionsVariations of the iliac veins are frequent, and contrary to what one might think, and even if they can represent an anatomical trap during surgery, certain variations do not limit anterior lumbar spine surgery and are not more associated with vascular complications. Nevertheless, these anatomical variations must be known before any advanced pelvic surgery. Depending on their distribution, level L5-S1 is more suitable for ALIF, level L4-L5 for OLIF approaches.

Arteriovenous shunts of the cervical spine: patient demographics, presentation, patterns of high-risk venous drainage, and updated classification

BackgroundIntracranial dural arteriovenous (AV) fistula classifications focus on presence/absence of retrograde flow in the cortical veins of the brain as this angiographic finding portends a worse prognosis. However, prior categorization...

Cemented Stem Design in Total Hip Arthroplasty: Fixation Philosophies, Biomechanics, and an Updated Classification System.

There is renewed interest in cemented femoral fixation in total hip arthroplasty in the United States, and to fully appreciate the evolution of cemented femoral stem designs, an understanding of their history and design rationale is essential. To adequately study the outcomes of modern-day designs, a comprehensive classification system is also necessary. The biomechanical principles, failure mechanisms, and clinical outcomes associated with various cemented femoral stems are described in this comprehensive review. In addition, an updated version of an existing classification system is described that incorporates the primary design characteristics which differentiate implants currently in use. In this classification, implants are categorized as taper-slip (Type I), which are subdivided by Anatomic (IA), Double-Taper (IB), and Triple-Taper (IC) with subclassification for Traditional and Line-to-Line implants. Composite beam (Type II) implants are similarly divided into Anatomic (IIA), Straight (IIB), and Wedge (IIC) with subclassification for Polished, Satin, or Roughened finish. This classification system provides a basis for comparing cemented femoral stems, thereby improving our understanding of the effect of design characteristics on survivorship to guide future advancements and improve clinical outcomes.

Comparison of the WHO classification (5th edition) 2022 and the International Consensus Classification (ICC) 2022 for diagnosis of acute myeloid leukemia)

In 2022, two classifications were published to define the diagnosis of patients with acute myeloid leukemia (AML). The World Health Organisation (WHO) 5th edition and the International Consensus Classification (ICC) provide an updated summary of current knowledge of the diseases and construct a framework for physicians. Two differing classifications result in discrepancies, which change the definition of AML subtypes and present a challenge in clinical settings. This work summarizes the updated classification systems and discusses their significance in clinical settings while considering the latest findings. Relevant changes affect the i) required blast percentage, ii) AML harbouring CEBPA mutations, iii) AML with KMT2A and MECOM rearrangements, iv) AML with myelodysplasia-related characteristics and in association with this entity AML with mutated RUNX1, and lastly v) AML with TP53 mutation. In summary, a unified classification system would be desirable to achieve harmonized diagnosis and treatment of AML).

TOAST stroke subtype classification in clinical practice: implications for the Get With The Guidelines-Stroke nationwide registry.

The TOAST (Trial of ORG 10172 in Acute Stroke Treatment) is the most commonly used ischemic stroke subtype classification system worldwide and a required field in the US National Get With The Guidelines-Stroke (GWTG-Stroke) registry. However, stroke diagnostics have advanced substantially since the TOAST classification was designed 30 years ago, potentially making it difficult to apply reliably. In this prospective diagnostic accuracy study, we analyzed consecutive ischemic stroke patients admitted to a Comprehensive Stroke Center between July-October 2021. Clinical practice TOAST classification diagnoses rendered by the stroke team in the electronic medical record (EMR) at discharge were retrieved from GWTG-Stroke registry and compared to a reference ("gold") standard diagnosis derived from agreement between two expert raters after review of the EMR and patient imaging. Among 49 patients; age was 72.3 years (±12.1), 53% female, and presenting NIHSS median 3 (IQR 1-11). Work-up included: brain imaging in 100%; cardiac rhythm assessment in 100%; cervical/cerebral vessel imaging in 98%; TTE ± TEE in 92%; and TCD emboli evaluation in 51%. Reference standard diagnoses were: LAA-6%, SVD-14%, CE-39%, OTH-10%, UND-M (more than one cause)-20%, and UND-C (cryptogenic)-10%. GWTG-Stroke TOAST diagnoses agreed with reference standard diagnoses in 30/49 (61%). Among the 6 subtype diagnoses, specificity was generally high (84.8%-97.7%), but sensitivity suboptimal for LAA (33%), OTH (60%), UND-M (10%), and UND-C (20%). Positive predictive value was suboptimal for 5 of the 6 subtypes: LAA (13%), SVD (58%), OTH (75%), UND-M (50%), and UND-C (50%). Clinical practice TOAST classification subtype diagnoses entered into the GWTG-Stroke registry were accurate in only 61% of patients, a performance rate that, if similarly present at other centers, would hamper the ability of the national registry to provide dependable insights into subtype-related care. Development of an updated ischemic stroke subtype classification system, with algorithmic logic embedded in electronic medical records, is desirable.

Anatomical variations of the atlas arches: prevalence assessment, systematic review and proposition for an updated classification system.

This study focuses on the atlas, a pivotal component of the craniovertebral junction, bridging the cranium and spinal column. Notably, variations in its arches are documented globally, necessitating a thorough assessment and categorization due to their significant implications in clinical, diagnostic, functional, and therapeutic contexts. The primary objective is to ascertain the frequency of these anatomical deviations in the atlas arches among a Colombian cohort using cone-beam computed tomography (CBCT). Employing a descriptive, cross-sectional approach, this research scrutinizes the structural intricacies of the atlas arches in CBCT scans. Analytical parameters included sex distribution and the nature of anatomical deviations as per Currarino's classification. Statistical analyses were conducted to identify significant differences, including descriptive statistics and Chi-square tests. A systematic review of the literature was conducted in order to enhance the current Currarino's classification. The study examined 839 CBCT images, with a nearly equal sex distribution (49.7% female, 50.3% male). Anatomical variations were identified in 26 instances (3%), displaying a higher incidence in females (X2 [(1, N = 839) = 4.0933, p = 0.0430]). The most prevalent variation was Type A (2.5%), followed by Type B (0.4%), and Type G (0.2%) without documenting any other variation. The systematic review yielded 7 studies. A novel classification system for these variations is proposed, considering global prevalence data in the cervical region. The study highlights a statistically significant predominance of Type A variations in the female subset. Given the critical nature of the craniovertebral junction and supporting evidence, it recommends an amendment to Currarino's classification to better reflect these clinical observations. A thorough study of anatomical variations of the upper cervical spine is relevant as they can impact important functional aspects such as mobility as well as stability. Considering the intricate anatomy of this area and the pivotal function of the atlas, accurately categorizing the variations of its arches is crucial for clinical practice. This classification aids in diagnosis, surgical planning, preventing iatrogenic incidents, and designing rehabilitation strategies.

Surgeons’ perspectives for a future obstetric fistula classification system: exploring the key parameters

Background There is currently no unified classification scheme for accurately describing vesico-vaginal fistulas, thereby limiting communication between surgeons and the ability to compare research. Many factors related to surgical failure or success have not been explored, and surgeons currently do not universally use the same classifications. The objective of this study is to determine which factors are the most important to include in a future obstetric fistula classification scheme. Methods Members of the International Society of Obstetric Fistula Surgeons were surveyed using a non-validated questionnaire to explore their experience and factors they think were most important to include in an updated comprehensive obstetric fistula classification scheme. Based on the surgeons’ response, an average ranking of each determinant of obstetric fistula classification system was computed. Results The most critical factors that surgeons found necessary to include in an updated fistula classification system are the bladder size (88.9%, n=16, rank=8.53), degree of fibrosis of the vagina (83.3%, n=15, rank=8.12), degree of urethral damage (88.9%, n=16, rank=9.34), location of the fistula (100%, n=18, rank=9.22), urethral length (94.4%, n=17, rank=9.06), and whether the fistula is circumferential or not (94.4%, n=17, rank=9.18). The least important factors were how long the patient had had a fistula (11.1%, n=2, rank=2.28) and intraoperative complications (22.2%, n=4, rank=4.59). For most factors important in repair, there was a non-significant correlation between experience level and ratings from 0-10. Scores for urethral length showed a significant correlation between increased surgical experience and higher ratings of importance. Conclusions Three most commonly used classification schemes by Goh, Waaldjik, and the World Health Organization (WHO) only capture some important factors determined by the surveyed surgeons. Given the inconsistency between what experienced and expert surgeons deem to be important determinants for the classification of obstetric fistula and what is currently included in classification systems, we call for constructing a new, validated classification system.

Validation of the updated Bosniak classification (2019) in pathologically confirmed CT-categorised cysts.

The updated Bosniak classification in 2019 (v2019) addresses vague imaging terms and revises the criteria with the intent to categorise a higher proportion of cysts in lower-risk groups and reduce benign cyst resections. The aim of the present study was to compare the diagnostic accuracy and inter-observer agreement rate of the original (v2005) and updated classifications (v2019). Resected/biopsied cysts were categorised according to Bosniak classifications (v2005 and v2019) and the diagnostic accuracy was assessed with reference to histopathological analysis. The inter-observer agreement of v2005 and v2019 was determined. The malignancy rate of the cohort was 83.6% (51/61). Using v2019, a higher proportion of malignant cysts were categorised as Bosniak ≥ III (88.2% vs 84.3%) and a significantly higher percentage were categorised as Bosniak IV (68.9% vs 47.1%; p = 0.049) in comparison to v2005. v2019 would have resulted in less benign cyst resections (13.5% vs 15.7%). Calcified versus non-calcified cysts had lower rates of malignancy (57.1% vs 91.5%; RR,0.62; p = 0.002). The inter-observer agreement of v2005 was higher than that of v2019 (kappa, 0.70 vs kappa, 0.43). The updated classification improves the categorisation of malignant cysts and reduces benign cyst resection. The low inter-observer agreement remains a challenge to the updated classification system.

RUNX1 Mutation Does Not Significantly Impact the Outcome of Newly Diagnosedadult AML: A Retrospective Study of Chinese AML Patients

Background RUNX1 is one of the recurrent mutated genes in newly diagnosed acute myeloid leukemia (AML) with a frequency of 6%~15%. Although historically recognized as a provisional distinct entity, the AML subtype with RUNX1 mutations (AML- RUNX1mut) was eliminated from the 2022 WHO classification system. With the update of AML diagnosis and treatment protocol, different outcomes of AML- RUNX1muthave been reported. However, an in-depth study about the prognostic value of RUNX1 mutations, epecifically the classification change related to AML- RUNX1mut in a large well-annotated cohort is lacking. Methods The clinical data of 1065 AML (excluding acute promyelocytic leukemia and RUNX1 germline mutations) patients according to WHO 2016 and treated from January 2017 to December 2021 at Jiangsu Institute of Hematology were retrospectively collected and analyzed after informed consent. All AML diagnosis samples were analyzed by targeted Next Generation Sequencing (NGS) panel covering 172 frequently mutated genes in hematological malignancies. Demographic and clinical data, disease characteristics at diagnosis, first-line treatment and clinical outcome data were available for all patients. The survival time of allogeneic hematopoietic stem cell transplantation patients was censored at the time of stem cell transfusion. Cytogenetic and molecular characteristics were used to classify patients into ELN2017 and ELN2022 risk groups (excluding the effect of RUNX1 mutation). Results RUNX1 mutations were detected in 112 (10.5%) patients, namely, 66 (58.9%) male and 46 (41.1%) female. A total of 132 RUNX1 alterations were detected with a medianvariant allelic frequency of 40% (3%~93%). RUNX1 mutations were associated with older age (48.5 vs. 46.0 years old, P=0.087) and antecedent myeloid disorders (6.3% vs. 1.0%, P<0.001). One or more comutations were detected in 106 (94.7%) AML- RUNX1mut patients. The most frequent co-gene abnormalities were FLT3-ITD and DNMT3A mutations which represented the 23.2% and 18.7%. Mutations of CEBPA bZIP, NPM1 and translocations of t(8;21), t(16;16)/inv(16) were uncommon in AML- RUNX1mut with a frequency of 6.3%, 1.8%, 2.7%, 0%, respectively (Table 1). Compared with AML with wild-type RUNX1 (AML- RUNX1wt), AML- RUNX1mut patients had a lower complete remission rate (19.6% vs. 29.7%, P=0.034), lower overall response rate (ORR) (73.5% vs. 84.3%, P=0.006) and higher no response rate (26.5% vs. 15.5%, P=0.021) in the first induction chemotherapy. When comparing groups based on the ELN2017 risk stratification criteria, no significant difference in ORR was observed between RUNX1mut and RUNX1wt patients in the favorable (91.2% vs. 94.0%, P=0.572), intermediate (75.0% vs. 78.4%, P=0.570) and adverse (63.3% vs. 71.4%, P=0.370 ) subgroups (Table 2). The median duration of follow-up of the entire cohort was 8.7 months ( RUNX1wt: 8.4 months; RUNX1mut: 10.0 months). Comparing the two groups, patients with RUNX1 mutations had a lower 5-year overall survival (OS) rate (35.4% vs. 42.3%; HR=1.563; 95% CI: 1.091~2.237, P=0.026), but no significant difference was observed in the 5-year event-free survival (EFS) rate (40.8% vs. 35.4%; HR=1.084; 95% CI: 0.750~1.570, P=0.098) (Table 2). However, when patients were stratified according to the ELN2017 guidelines (excluding the effect of RUNX1 mutation), outcomes did not differ between patients withor without RUNX1 mutation in the favorable (OS: P=0.629, EFS: P=0.137), intermediate (OS: P=0.629, EFS: P=0.114) and adverse (OS: P=0.544; EFS: P=0.714) subgroups. Similar results were obtained according to the ELN2022 guidelines. In multivariate analysis, RUNX1 was not an independent prognostic factor for OS (HR=1.353, 95% CI: 0.922~1.985, P=0.122) and EFS (HR=1.422, 95% CI: 0.975~2.075, P=0.068), while significantly worse OS and EFS were observed in patients with mutated FLT3-ITD, TP53, and DNMT3A ( P-values were all less than 0.05). Conclusion RUNX1 mutations were rarely isolated genetic abnormities that conferred inferior outcomes. However, on the basis of ELN prognosis risk stratification, RUNX1mutation had no impact on the clinical outcomes of AML patients in stratified subgroups. RUNX1 was not an independent prognostic factor for survival. Overall, our findings agree with the updated WHO classification system for AML that AML- RUNX1mut should not be recognized as a distinct AML entity.

Mammalian orthoreoviruses exhibit rare genotype variability in genome constellations.

Mammalian orthoreoviruses (reoviruses) are currently classified based on properties of the attachment protein, σ1. Four reovirus serotypes have been identified, three of which are represented by well-studied prototype human reovirus strains. Reoviruses contain ten segments of double-stranded RNA that encode 12 proteins and can reassort during coinfection. To understand the breadth of reovirus genetic diversity and its potential influence on reassortment, the sequence of the entire genome should be considered. While much is known about the prototype strains, a thorough analysis of all ten reovirus genome segment sequences has not previously been conducted. We analyzed phylogenetic relationships and nucleotide sequence conservation for each of the ten segments of more than 60 complete or nearly complete reovirus genome sequences, including those of the prototype strains. Using these relationships, we defined genotypes for each segment, with minimum nucleotide identities of 77-88% for most genotypes that contain several representative sequences. We applied segment genotypes to determine reovirus genome constellations, and we propose implementation of an updated reovirus genome classification system that incorporates genotype information for each segment. For most sequenced reoviruses, segments other than S1, which encodes σ1, cluster into a small number of genotypes and a limited array of genome constellations that do not differ greatly over time or based on animal host. However, a small number of reoviruses, including prototype strain Jones, have constellations in which segment genotypes differ from those of most other sequenced reoviruses. For these reoviruses, there is little evidence of reassortment with the major genotype. Future basic research studies that focus on the most genetically divergent reoviruses may provide new insights into reovirus biology. Analysis of available partial sequences and additional complete reovirus genome sequencing may also reveal reassortment biases, host preferences, or infection outcomes that are based on reovirus genotype.

Episodic Ataxias: Primary and Secondary Etiologies, Treatment, and Classification Approaches.

Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1 and EA2 are most frequently encountered, caused by mutations in KCNA1 and CACNA1A. EA3-8 are reported in rare families. Advances in genetic testing have broadened the KCNA1 and CACNA1A phenotypes, and detected EA as an unusual presentation of several other genetic disorders. Additionally, there are various secondary causes of EA and mimicking disorders. Together, these can pose diagnostic challenges for neurologists. A systematic literature review was performed in October 2022 for 'episodic ataxia' and 'paroxysmal ataxia', restricted to publications in the last 10 years to focus on recent clinical advances. Clinical, genetic, and treatment characteristics were summarized. EA1 and EA2 phenotypes have further broadened. In particular, EA2 may be accompanied by other paroxysmal disorders of childhood with chronic neuropsychiatric features. New treatments for EA2 include dalfampridine and fampridine, in addition to 4-aminopyridine and acetazolamide. There are recent proposals for EA9-10. EA may also be caused by gene mutations associated with chronic ataxias (SCA-14, SCA-27, SCA-42, AOA2, CAPOS), epilepsy syndromes (KCNA2, SCN2A, PRRT2), GLUT-1, mitochondrial disorders (PDHA1, PDHX, ACO2), metabolic disorders (Maple syrup urine disease, Hartnup disease, type I citrullinemia, thiamine and biotin metabolism defects), and others. Secondary causes of EA are more commonly encountered than primary EA (vascular, inflammatory, toxic-metabolic). EA can be misdiagnosed as migraine, peripheral vestibular disorders, anxiety, and functional symptoms. Primary and secondary EA are frequently treatable which should prompt a search for the cause. EA may be overlooked or misdiagnosed for a variety of reasons, including phenotype-genotype variability and clinical overlap between primary and secondary causes. EA is highly treatable, so it is important to consider in the differential diagnosis of paroxysmal disorders. Classical EA1 and EA2 phenotypes prompt single gene test and treatment pathways. For atypical phenotypes, next generation genetic testing can aid diagnosis and guide treatment. Updated classification systems for EA are discussed which may assist diagnosis and management.

Abstract TMP49: Accuracy Of Toast Subtype Classification In Clinical Practice: Implications For The Get With The Guidelines National Stroke Registry

Background: TOAST is the most commonly used ischemic stroke subtype classification system worldwide and a required field in the US National GWTG-Stroke registry. However, stroke diagnostics have advanced substantially since TOAST was designed 30 years ago, potentially making it difficult to now apply reliably. Methods: We analyzed consecutive ischemic stroke patients admitted to a CSC between July-Oct 2021. Clinical practice TOAST diagnoses rendered by the stroke team in the EMR at discharge were retrieved from GWTG-Stroke registry and compared to a reference (“gold”) standard diagnosis derived from agreement between 2 expert raters after review of the EMR and patient imaging. Results: Among 49 patients, age was 72.3y (±12.1), 53% female, and presenting NIHSS median 3 (IQR 1-11). Work-up included: brain imaging in 100%; cardiac rhythm assessment in 100%; cervical/cerebral vessel imaging in 98%; TTE±TEE in 92%; and TCD emboli eval in 51%. Reference standard diagnoses were: LAA-6%, SVD-14%, CE-41%, OTH-8%, UND-more than one cause-18%, and UND-cryptogenic-12%. The Figure shows a bubble plot of congruence between EMR/GWTG-Stroke and reference standard diagnoses. GWTG-Stroke TOAST diagnoses agreed with reference standard diagnoses in 29/49 (59%). Among the 6 subtype diagnoses singly, specificity was generally high (83%-100%), but sensitivity suboptimal for LAA (33%), OTH (75%), UND-MT1 (0%), and UND-CRYPT (17%). Positive predictive value was suboptimal for all: LAA (13%), SVD (58%), CE (77%), OTH (75%), SVD OTH (75%), UND-MT1 (0%), and UND-CRYPT (33%). Conclusion: Clinical practice subtype diagnoses using TOAST and entered into GWTG-Stroke were accurate in only 59% of patients, hampering the ability of the national registry to provide dependable insights into subtype-related aspects of care. Development of an updated ischemic stroke subtype classification system, with algorithmic logic directly embedded in electronic medical records, is desirable.

Time to update the sectional classification ofIlex(Aquifoliaceae): New insights fromIlexphylogeny, morphology, and distribution

AbstractResolving the infrageneric classification of species‐rich genera has been challenging in plant taxonomy.IlexL. is a subcosmopolitan genus with over 600 species of dioecious trees and shrubs. Many classification systems based on morphological data have been proposed during the past 250 years. However, these systems (such as Loesener's and Galle's systems) may not truly reflectIlex's evolutionary trajectories because most of those system's infrageneric hierarchies are not monophyletic. In this study, we reconstructed a phylogeny ofIlexL. comprising 15 moderately to highly supported clades using rigorously identified samples (202 species) and closely authenticated gene sequences of three nuclear genes [internal transcribed spacer (ITS), external transcribed spacer (ETS), andnepGS]. The newly generated phylogenetic tree resembles essentially that of the nuclear tree of Manen et al., but shows conspicuous topological differences with the phylogeny of Yao et al. Closely scrutinizing morphological variation and distributional patterns of 202 species, this study found that most lineages ofIlexidentified herein are well defined by a particular trait or a combination of morphological and distributional traits, displaying phylogeny–morphology–distribution conformity that has seldom been uncovered in previous studies. Given the general phylogeny–morphology–distribution conformity revealed in this genus, we put forward an updated sectional classification system forIlexthat temporarily contains 14 sections. The new classification will provide a robust framework for studying the evolution and diversification of this ecologically and economically important genus.

Mature T-cell and NK-cell lymphomas: updates on molecular genetic features.

Mature T-cell and NK-cell lymphomas are a heterogeneous group of rare and typically aggressive neoplasms. Diagnosis and subclassification have historically relied primarily on the integration of clinical, histologic, and immunophenotypic features, which often overlap. The widespread application of a variety of genomic techniques in recent years has provided extensive insight into the pathobiology of these diseases, allowing for more precise diagnostic classification, improved prognostication, and development of novel therapies. In this review, we summarize the genomic features of the most common types of mature T-cell and NK-cell lymphomas with a particular focus on the contribution of genomics to biologic insight, classification, risk stratification, and select therapies in the context of the recently published International Consensus and updated World Health Organization classification systems.

Classification(s) of Cervical Deformity.

Cervical spine deformities (CSD) are complex surgical issues with currently heterogenous management strategies. The classification of CSD is still an evolving field. Rudimentary classification schemas were initially proposed in the late 20th century but were largely informal and based on the underlying etiology (i.e. , postsurgical, traumatic, or inflammatory). The first formal classification schema was proposed by Ames et al. in 2015 who established a standard nomenclature for describing these deformities. This classification system established 5 deformity descriptors based on curve apex location (cervical, cervicothoracic, thoracic, craniovertebral junctional, and coronal deformities) and 5 deformity modifiers which helped surgeons utilize a standard language when discussing CSD patients. Koller et al. in 2019 subsequently established a classification system for patients with rigid cervical kyphosis based on regional and global sagittal alignment. Most recently, Kim et al. in 2020 proposed an updated classification system utilizing dynamic cervical spine imaging to guide surgical treatment of CSD patients. It identified 4 major groups of deformities - (1) those with "flat-neck" deformities caused by cervical lordosis T1 slope mismatch; (2) those with focal kyphotic deformities between 2 cervical vertebrae; (3) those with cervicothoracic deformities caused by large T1 slope; and (4) those with coronal deformities. Group 2 deformities most often required combined anterior-posterior approaches with short constructs, and group 3 deformities most often required posterior-only approaches with 3-column osteotomies.