Evidence for spontaneous regulation of the humoral IgM anti-GM1 autoimmune response by IgG antibodies in multifocal motor neuropathy patients.

BACKGROUND AND AIMS: Multifocal motor neuropathy (MMN) is a peripheral nerve disorder characterized by slow progressive distal asymmetric weakness with minimal or no sensory impairment. Currently, a vast evidence supports a direct pathogenic role of IgM anti-GM1 antibodies on disease pathogenesis. Patients with MMN seropositive for GM1-specific IgM antibodies have significantly more weakness, disability and axon loss than patients without these antibodies. During the screening for IgM anti-GM1 antibodies in a cohort of patients with neuropathy we noticed an absence or significant reduction of natural IgM anti-GM1 autoreactivity in some patients with MMN, suggesting a mechanism of self-control of autoreactivity. We aim to understand the lack of natural reactivity against GM1 in MMN patients. METHODS: The presence of free IgM anti-GM1 reactivity or its complex to blocking IgG was analysed by combining high performance thin layer chromatography-immunostaining, soluble binding inhibition assays, Protein-G or GM1-affinity columns and dot blot assays. RESULTS: We identified in MMN patients an immunoregulation of IgM anti-GM1 antibodies mediated by IgG immunoglobulins characterized by: (i) lack of natural IgM anti-GM1 autoreactivity as a result of a immunoregulatory IgG-dependent mechanism; (ii) presence of natural and disease-associated IgM anti-GM1/IgG blocking Ab complexes in sera; and (iii) high levels of IgG blocking against natural IgM anti-GM1 antibodies (Abs. INTERPRETATION: Our observations unmask a spontaneous IgG-dependent mechanism of immunoregulation against IgM anti-GM1 antibodies that could explain, in part, fluctuations in the usually slowly progressive clinical course that characterizes the disease and, at the same time, allows the identification of an autoimmune response against GM1 ganglioside in seronegative patients.

Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in a Georgia School District-United States, December 2020-January 2021.

BACKGROUND: To inform prevention strategies, we assessed the extent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and settings in which transmission occurred in a Georgia public school district. METHODS: During 1 December 2020-22 January 2021, SARS-CoV-2-infected index cases and their close contacts in schools were identified by school and public health officials. For in-school contacts, we assessed symptoms and offered SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) testing; performed epidemiologic investigations and whole-genome sequencing to identify in-school transmission; and calculated secondary attack rate (SAR) by school setting (eg, sports, elementary school classroom), index case role (ie, staff, student), and index case symptomatic status. RESULTS: We identified 86 index cases and 1119 contacts, 688 (61.5%) of whom received testing. Fifty-nine of 679 (8.7%) contacts tested positive; 15 of 86 (17.4%) index cases resulted in ≥2 positive contacts. Among 55 persons testing positive with available symptom data, 31 (56.4%) were asymptomatic. Highest SARs were in indoor, high-contact sports settings (23.8% [95% confidence interval {CI}, 12.7%-33.3%]), staff meetings/lunches (18.2% [95% CI, 4.5%-31.8%]), and elementary school classrooms (9.5% [95% CI, 6.5%-12.5%]). The SAR was higher for staff (13.1% [95% CI, 9.0%-17.2%]) vs student index cases (5.8% [95% CI, 3.6%-8.0%]) and for symptomatic (10.9% [95% CI, 8.1%-13.9%]) vs asymptomatic index cases (3.0% [95% CI, 1.0%-5.5%]). CONCLUSIONS: Indoor sports may pose a risk to the safe operation of in-person learning. Preventing infection in staff members, through measures that include coronavirus disease 2019 vaccination, is critical to reducing in-school transmission. Because many positive contacts were asymptomatic, contact tracing should be paired with testing, regardless of symptoms.

Divergent Rabies Virus Variant of Probable Bat Origin in 2 Gray Foxes, New Mexico, USA.

In the Western Hemisphere, bat-associated rabies viruses (RABVs) have established independent transmission cycles in multiple mammal hosts, forming genetically distinct lineages. In New Mexico, USA, skunks, bats, and gray foxes are rabies reservoir hosts and represent a public health risk because of encounters with humans. During 2015 and 2019, two previously undescribed RABVs were detected in 2 gray foxes (Urocyon cinereoargenteus) in Lincoln County, New Mexico. Phylogenetic analysis of the nucleoprotein gene indicated that the isolates are a novel RABV variant. These 2 cases probably represent repeated spillover events from an unknown bat reservoir to gray foxes. Molecular analysis of rabies cases across New Mexico identified that other cross-species transmission events were the result of viral variants previously known to be enzootic to New Mexico. Despite a robust rabies public health surveillance system in the United States, advances in testing and surveillance techniques continue to identify previously unrecognized zoonotic pathogens.

[Early Clinical Diagnosis of Anti-NMDA Receptor Encephalitis: Case Series and Literature Review]. / Diagnóstico clínico temprano de la Encefalitis Anti-Receptor NMDA: Serie de casos y revisión bibliográfica.

Autoimmune encephalitis refers to a group of pathologies described in the last two decades, characterized by neuropsychiatric symptoms of subacute presentation, mediated by antibodies directed against neuronal membrane proteins. Within this group, encephalitis mediated by antibodies against the NMDA receptor of glutamate is a particular clinical entity, given that its expression is dominated by psychiatric symptoms that usually occur at the onset of the disease. In this paper we describe five cases of NMDA encephalitis in adult patients followed up in the last four years in a public hospital in the City of Buenos Aires, Argentina. We also include a review of the current literature. We emphasize the clinical description of the psychiatric symptoms of presentation, since these lead to the patient's first contact with the health system. Given the difficulty in our environment to implement the determination of autoantibodies, the ability to clinically recognize this pathology becomes paramount to establish an early preliminary diagnosis and not to delay immunosuppressive therapy, thus allowing for a better prognosis.

A Phase 3 Multicenter, Prospective, Open-Label Efficacy and Safety Study of Immune Globulin (Human) 10% Caprylate/Chromatography Purified in Patients with Myasthenia Gravis Exacerbations.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission. Exacerbations may involve increasing bulbar weakness and/or sudden respiratory failure, both of which can be critically disabling. Management of MG exacerbations includes plasma exchange and intravenous immunoglobulin (IVIG); they are equally effective, but patients experience fewer side effects with IVIG. The objective of this study was to assess the efficacy and safety of immune globulin caprylate/chromatography purified (IGIV-C) in subjects with MG exacerbations. METHODS: This prospective, open-label, non-controlled 28-day clinical trial was conducted in adults with MG Foundation of America class IVb or V status. Subjects received IGIV-C 2 g/kg over 2 consecutive days (1 g/kg/day) and were assessed for efficacy/safety on Days 7, 14, 21, and 28. The primary efficacy endpoint was the change from Baseline in quantitative MG (QMG) score to Day 14. Secondary endpoints of clinical response, Baseline to Day 14, included at least a 3-point decrease in QMG and MG Composite and a 2-point decrease in MG-activities of daily living (MG-ADL). RESULTS: Forty-nine subjects enrolled. The change in QMG score at Day 14 was significant (p < 0.001) in the Evaluable (-6.4, n = 43) and Safety (-6.7, n = 49) populations. Among evaluable subjects, Day 14 response rates were 77, 86, and 88% for QMG, MG Composite, and MG-ADL, respectively. IGIV-C showed good tolerability with no serious adverse events. CONCLUSIONS: The results of this study show that IGIV-C was effective, safe, and well tolerated in the treatment of MG exacerbations.

Host-pathogen evolutionary signatures reveal dynamics and future invasions of vampire bat rabies.

Anticipating how epidemics will spread across landscapes requires understanding host dispersal events that are notoriously difficult to measure. Here, we contrast host and virus genetic signatures to resolve the spatiotemporal dynamics underlying geographic expansions of vampire bat rabies virus (VBRV) in Peru. Phylogenetic analysis revealed recent viral spread between populations that, according to extreme geographic structure in maternally inherited host mitochondrial DNA, appeared completely isolated. In contrast, greater population connectivity in biparentally inherited nuclear microsatellites explained the historical limits of invasions, suggesting that dispersing male bats spread VBRV between genetically isolated female populations. Host nuclear DNA further indicated unanticipated gene flow through the Andes mountains connecting the VBRV-free Pacific coast to the VBRV-endemic Amazon rainforest. By combining Bayesian phylogeography with landscape resistance models, we projected invasion routes through northern Peru that were validated by real-time livestock rabies mortality data. The first outbreaks of VBRV on the Pacific coast of South America could occur by June 2020, which would have serious implications for agriculture, wildlife conservation, and human health. Our results show that combining host and pathogen genetic data can identify sex biases in pathogen spatial spread, which may be a widespread but underappreciated phenomenon, and demonstrate that genetic forecasting can aid preparedness for impending viral invasions.

Prognosis of Ocular Myasthenia Gravis in an Argentinian Population.

BACKGROUND: We investigated the prognosis of patients with myasthenia gravis (MG) initially presenting with only ocular symptoms in an Argentinian population. SUMMARY: We performed a retrospective analysis of 61 patients with MG with pure ocular involvement at onset. Generalized MG (gMG) developed in 73.7% of patients, while the rest only exhibited ocular symptoms throughout the course of the disease (ocular MG [oMG]). The AChR antibody (AChR-ab) was found in 81.4% of the gMG and 50% of the oMG cases. AChR-ab titers were also significantly higher in the gMG than in the oMG group. Patients with oMG more frequently required treatment only with acetylcholinesterase inhibitors and showed more remissions. Key Messages: Our study showed high generalization in patients with MG debuting with ocular symptoms. Patients with AChR seropositivity and higher AChR-ab titers had an increased risk for gMG, while patients with oMG showed lower corticosteroid requirements and a higher remission rate.

[Neuropsychological performance in patients with myasthenia gravis]. / Rendimiento neuropsicológico en pacientes con miastenia gravis.

Myasthenia gravis is a chronic autoimmune disease that affects the neuromuscular transmission. Controversial findings had been reported about cognitive impairment in this disease. The aim of this study was to investigate the cognitive pattern of patients with myasthenia gravis. There were enrolled 24 patients with myasthenia gravis, anti-acetylcholine receptor antibodies (ACRA) positive, and 24 healthy controls. PATIENTS: age 43.9 ± 14.8, years of education 10.9 ± 3.3. CONTROLS: age 44.5 ± 15.4, years of education 11.5 ± 3.3. The following areas were evaluated: verbal memory: (long-term storage, retrieval, delayed recall) of the Selective Remained Test; attention: Paced Auditory Serial Addition Task (PASAT 2 and 3 seconds); executive functions: analogies and numbers-letters sequence. Also, it was administered the Beck Depression Inventory II (BDI II). About 33.3% of patients obtained abnormal performance in two or more cognitive tests. 37.5% showed deterioration in attention; 33.3% in verbal memory; 29.2% in executive functions. Significant differences between patients and healthy controls were found in long-term storage (p = 0.001); retrieval (p = 0.007); delayed recall (p = 0.000); PASAT 3 (p = 0.009); PASAT 2 (p = 0.009) and analogies (p = 0.003). Evidence of depression was found: mild in 4.2% of patients; moderate in 25% and severe in 29.2%. Neuropsychological performance declines in patients with myasthenia gravis: attention was more affected than other cognitive areas.

[Gender Analysis in the Agreement in Assessing the Signs Between Professionals and Parents Whose Children Have Attention Deficit and/or Hyperactivity Disorder]. / Análisis de género en la concordancia entre profesionales y progenitors en la Valoración de los Signos del Trastorino por Déficit de Atención Con o sin Hiperactividad de los Hijos.

The attention deficit hyperactivity disorder (ADHD) is the most prevalent chronic neuropsychiatric illness in childhood. It interferes with normal development of children. Its impact transcends childhood to appear in adolescence and adulthood. Diagnosis would be developed if the child shows the main symptoms of inattention and/or hyperactivity-impulsivity, with consequences in different aspects of daily life, such as academic achievements, family life or social interactions with other children. These symptoms will come up along life in different ways. When the child is young, hyperactivity and impulsivity prevail, but as he/she grows, the dispersion and difficulty to remember things and facts will become more evident. The aim of the study was to assess with the Vanderbilt scale, based on DSM-IV diagnostic criteria, the differences of the impact of ADHD among parents, in comparison to the medical diagnosis. A retrospective study was carried out by using this questionnaire, which completed by both parents individually. A total of 78 children took part in this study, all of them diagnosed with ages ranging from 6 to 16 years old, who attended to Neuropedriatics at VAlle del Nalón Hospital(Asturias), between October 2011 and March 2013. Regarding attention deficit, the average responses given by mothers (7.38 ± 1.81) was higher than that offered by fathers (647 ± 2/46). The same is true for hyperactivity/impulsivity, with average scores of mothers (5.80 ± 2.90) which were one positive response higher than those given by male patients (4.74 ± 3.04). Mothers show a higher percentage of agreement with the medical diagnosis (86.3%) when the child was a girl and 66% with boys, whereas for fathers the percentage of agreement was less than 50% female children and 44.6% for male children.

Variable evolutionary routes to host establishment across repeated rabies virus host shifts among bats.

Determining the genetic pathways that viruses traverse to establish in new host species is crucial to predict the outcome of cross-species transmission but poorly understood for most host-virus systems. Using sequences encoding 78% of the rabies virus genome, we explored the extent, repeatability and dynamic outcome of evolution associated with multiple host shifts among New World bats. Episodic bursts of positive selection were detected in several viral proteins, including regions associated with host cell interaction and viral replication. Host shifts involved unique sets of substitutions, and few sites exhibited repeated evolution across adaptation to many bat species, suggesting diverse genetic determinants over host range. Combining these results with genetic reconstructions of the demographic histories of individual viral lineages revealed that although rabies viruses shared consistent three-stage processes of emergence in each new bat species, host shifts involving greater numbers of positively selected substitutions had longer delays between cross-species transmission and enzootic viral establishment. Our results point to multiple evolutionary routes to host establishment in a zoonotic RNA virus that may influence the speed of viral emergence.

Rates of viral evolution are linked to host geography in bat rabies.

Rates of evolution span orders of magnitude among RNA viruses with important implications for viral transmission and emergence. Although the tempo of viral evolution is often ascribed to viral features such as mutation rates and transmission mode, these factors alone cannot explain variation among closely related viruses, where host biology might operate more strongly on viral evolution. Here, we analyzed sequence data from hundreds of rabies viruses collected from bats throughout the Americas to describe dramatic variation in the speed of rabies virus evolution when circulating in ecologically distinct reservoir species. Integration of ecological and genetic data through a comparative bayesian analysis revealed that viral evolutionary rates were labile following historical jumps between bat species and nearly four times faster in tropical and subtropical bats compared to temperate species. The association between geography and viral evolution could not be explained by host metabolism, phylogeny or variable selection pressures, and instead appeared to be a consequence of reduced seasonality in bat activity and virus transmission associated with climate. Our results demonstrate a key role for host ecology in shaping the tempo of evolution in multi-host viruses and highlight the power of comparative phylogenetic methods to identify the host and environmental features that influence transmission dynamics.

Molecular inferences suggest multiple host shifts of rabies viruses from bats to mesocarnivores in Arizona during 2001-2009.

In nature, rabies virus (RABV; genus Lyssavirus, family Rhabdoviridae) represents an assemblage of phylogenetic lineages, associated with specific mammalian host species. Although it is generally accepted that RABV evolved originally in bats and further shifted to carnivores, mechanisms of such host shifts are poorly understood, and examples are rarely present in surveillance data. Outbreaks in carnivores caused by a RABV variant, associated with big brown bats, occurred repeatedly during 2001-2009 in the Flagstaff area of Arizona. After each outbreak, extensive control campaigns were undertaken, with no reports of further rabies cases in carnivores for the next several years. However, questions remained whether all outbreaks were caused by a single introduction and further perpetuation of bat RABV in carnivore populations, or each outbreak was caused by an independent introduction of a bat virus. Another question of concern was related to adaptive changes in the RABV genome associated with host shifts. To address these questions, we sequenced and analyzed 66 complete and 20 nearly complete RABV genomes, including those from the Flagstaff area and other similar outbreaks in carnivores, caused by bat RABVs, and representatives of the major RABV lineages circulating in North America and worldwide. Phylogenetic analysis demonstrated that each Flagstaff outbreak was caused by an independent introduction of bat RABV into populations of carnivores. Positive selection analysis confirmed the absence of post-shift changes in RABV genes. In contrast, convergent evolution analysis demonstrated several amino acids in the N, P, G and L proteins, which might be significant for pre-adaptation of bat viruses to cause effective infection in carnivores. The substitution S/T242 in the viral glycoprotein is of particular merit, as a similar substitution was suggested for pathogenicity of Nishigahara RABV strain. Roles of the amino acid changes, detected in our study, require additional investigations, using reverse genetics and other approaches.

Rabies death attributed to exposure in Central America with symptom onset in a U.S. detention facility - Texas, 2013.

On June 7, 2013, a man was diagnosed in a Texas hospital with rabies. He had been detained in a U.S. detention facility during his infectious period. To identify persons exposed to rabies who might require rabies postexposure prophylaxis (PEP), CDC and the Texas Department of State Health Services (DSHS) conducted investigations at four detention facilities, one medical clinic, and two hospitals. In all, 25 of 742 persons assessed for rabies exposure were advised to receive PEP. Early diagnosis of rabies is essential for implementation of appropriate hospital infection control measures and for rapid assessment of potential contacts for PEP recommendations.

Metabolomics of cerebrospinal fluid from humans treated for rabies.

Rabies is a rapidly progressive lyssavirus encephalitis that is statistically 100% fatal. There are no clinically effective antiviral drugs for rabies. An immunologically naïve teenager survived rabies in 2004 through improvised supportive care; since then, 5 additional survivors have been associated with use of the so-called Milwaukee Protocol (MP). The MP applies critical care focused on the altered metabolic and physiologic states associated with rabies. The aim of this study was to examine the metabolic profile of cerebrospinal fluid (CSF) from rabies patients during clinical progression of rabies encephalitis in survivors and nonsurvivors and to compare these samples with control CSF samples. Unsupervised clustering algorithms distinguished three stages of rabies disease and identified several metabolites that differentiated rabies survivors from those who subsequently died, in particular, metabolites related to energy metabolism and cell volume control. Moreover, for those patients who survived, the trajectory of their metabolic profile tracked toward the control profile and away from the rabies profile. NMR metabolomics of human rabies CSF provide new insights into the mechanisms of rabies pathogenesis, which may guide future therapy of this disease.

Enzootic and epizootic rabies associated with vampire bats, peru.

During the past decade, incidence of human infection with rabies virus (RABV) spread by the common vampire bat (Desmodus rotundus) increased considerably in South America, especially in remote areas of the Amazon rainforest, where these bats commonly feed on humans. To better understand the epizootiology of rabies associated with vampire bats, we used complete sequences of the nucleoprotein gene to infer phylogenetic relationships among 157 RABV isolates collected from humans, domestic animals, and wildlife, including bats, in Peru during 2002-2007. This analysis revealed distinct geographic structuring that indicates that RABVs spread gradually and involve different vampire bat subpopulations with different transmission cycles. Three putative new RABV lineages were found in 3 non-vampire bat species that may represent new virus reservoirs. Detection of novel RABV variants and accurate identification of reservoir hosts are critically important for the prevention and control of potential virus transmission, especially to humans.

Raccoon rabies virus variant transmission through solid organ transplantation.

IMPORTANCE: The rabies virus causes a fatal encephalitis and can be transmitted through tissue or organ transplantation. In February 2013, a kidney recipient with no reported exposures to potentially rabid animals died from rabies 18 months after transplantation. OBJECTIVES: To investigate whether organ transplantation was the source of rabies virus exposure in the kidney recipient, and to evaluate for and prevent rabies in other transplant recipients from the same donor. DESIGN: Organ donor and all transplant recipient medical records were reviewed. Laboratory tests to detect rabies virus-specific binding antibodies, rabies virus neutralizing antibodies, and rabies virus antigens were conducted on available specimens, including serum, cerebrospinal fluid, and tissues from the donor and the recipients. Viral ribonucleic acid was extracted from tissues and amplified for nucleoprotein gene sequencing for phylogenetic comparisons. MAIN OUTCOMES AND MEASURES: Determination of whether the donor died from undiagnosed rabies and whether other organ recipients developed rabies. RESULTS: In retrospect, the donor's clinical presentation (which began with vomiting and upper extremity paresthesias and progressed to fever, seizures, dysphagia, autonomic dysfunction, and brain death) was consistent with rabies. Rabies virus antigen was detected in archived autopsy brain tissue collected from the donor. The rabies viruses infecting the donor and the deceased kidney recipient were consistent with the raccoon rabies virus variant and were more than 99.9% identical across the entire N gene (1349/1350 nucleotides), thus confirming organ transplantation as the route of transmission. The 3 other organ recipients remained asymptomatic, with rabies virus neutralizing antibodies detected in their serum after completion of postexposure prophylaxis (range, 0.3-40.8 IU/mL). CONCLUSIONS AND RELEVANCE: Unlike the 2 previous clusters of rabies virus transmission through solid organ transplantation, there was a long incubation period in the recipient who developed rabies, and survival of 3 other recipients without pretransplant rabies vaccination. Rabies should be considered in patients with acute progressive encephalitis of unexplained etiology, especially for potential organ donors. A standard evaluation of potential donors who meet screening criteria for infectious encephalitis should be considered, and risks and benefits for recipients of organs from these donors should be evaluated.

Training Program for Orthopedic Residents in Forefoot Osteotomy Skills: Transference From a Simulator to a Cadaveric Surgical Scenario.

INTRODUCTION: An effective simulation program allows both the acquisition of surgical skills on the simulated model and the transfer of these skills to a surgical scenario. We designed a forefoot osteotomy training program and sought to determine the transferability to a cadaveric surgical scenario. METHODS: Eleven orthopedic residents and 2 foot and ankle surgeons were included. A foot simulator was used. All residents were instructed on the surgical techniques of Chevron, Akin, and triple Weil osteotomies. Eight junior residents (trainees) were enrolled in a supervised simulation program. Baseline assessment was performed on the simulator with the Objective Structured Assessment of Technical Skills (OSATS) and the Imperial College Surgical Assessment Device (ICSAD). After baseline, trainees completed a training program and had a final evaluation of proficiency on the simulator and on cadaveric specimens. Three senior residents with no simulated training (controls) and experts were assessed for comparison. RESULTS: All trainees improved from a baseline OSATS score of 11 points (9-20) to a final score of 35 points (33-35) in the simulator and 34 points (32-34) in the cadaveric specimen ( P < 0.01). Compared with baseline, the ICSAD results improved in path length (391 [205-544] to 131 [73-278] meters, P < 0.01) and number of movements (2756 [1258-3338] to 992 [478-1908], P < 0.01). The final OSATS and ICSAD scores did not differ from experts ( P = 0.1) and were significantly different from untrained residents ( P = 0.02). CONCLUSIONS: Simulated training of Chevron, Akin, and triple Weil osteotomies in orthopedic residents improved procedural proficiency, enabling successful skill transfer to a surgical scenario in cadavers. LEVEL OF EVIDENCE: II (Prospective Cohort Study).

Posterior Malleolar Fracture Assessment: An Independent Interobserver and Intraobserver Validation of Three Computed Tomography-Based Classifications.

BACKGROUND: Posterior malleolus fractures occur in up to 50% of all ankle fractures. Several classification systems exist for their characterization, especially under CT. However, those classifications do not report the level of agreement or do it incompletely. This study aims to independently assess three posterior malleolus fracture classifications (Haraguchi, Bartonícek/Rammelt, and Mason). METHODS: This study was designed according to the Guidelines for Reporting Reliability and Agreement Studies. Ninety-four CT scans of patients with ankle fractures that had posterior malleolus fractures were included. Posterior malleolus fractures were assessed by six evaluators (three attending foot and ankle surgeons and three orthopaedic surgery residents) according to Haraguchi, Bartonícek/Rammelt, and Mason classifications. All images were reassessed by the same evaluators in a random sequence 3 weeks later. The kappa (k) coefficient was used to determine the interobserver and intraobserver agreement. Statistical significance was established using P < 0.05 with a 95% confidence interval (CI). RESULTS: The interobserver agreement was moderate for Haraguchi, Bartonícek/Rammelt, and Mason classifications with a global k value of 0.52 (95% CI, 0.43 to 0.60), 0.53 (95% CI, 0.46 to 0.61), and 0.54 (95% CI, 0.47 to 0.62), respectively. The intraobserver agreement was substantial for Haraguchi, Bartonícek/Rammelt, and Mason classifications, with an overall k value of 0.70 (95% CI, 0.64 to 0.74), 0.73 (95% CI, 0.68 to 0.78), and 0.73 (95% CI, 0.69 to 0.78), respectively. Interobserver and intraobserver agreement among orthopaedic surgeons and residents had no significant difference. CONCLUSION: The current classifications for posterior malleolus fractures showed a substantial intraobserver agreement. Nevertheless, the interobserver agreement obtained was just moderate for all classifications, independent of the level of expertise of the evaluators.