Months Of Symptom Onset Research Articles

The Duration of Symptoms Influences Outcomes After Lumbar Microdiscectomies: A Michigan Spine Surgery Improvement Collaborative.

Retrospective Cohort. We investigate whether duration of symptoms a patient experiences prior to lumbar microdiscectomy affects pain, lifestyle, and return to work metrics after surgery. A retrospective review of patients with a diagnosis of lumbar radiculopathy undergoing microdiscectomy was conducted using a statewide registry. Patients were grouped based on self-reported duration of symptoms prior to surgical intervention (Group 1: symptoms less than 3months; Group 2: symptoms between 3months and 1year; and Group 3: symptoms greater than 1year). Radicular pain scores, PROMIS PF Physical Function measure (PROMIS PF), EQ-5D scores, and return to work rates at 90days, 1year, and 2years after surgery were compared using univariate and multivariate analysis. There were 2408 patients who underwent microdiscectomy for lumbar disc herniation for radiculopathy with 532, 910, and 955 in Groups 1, 2, and 3, respectively. Postoperative leg pain was lower for Group 1 at 90days, 1year, and 2years compared to Groups 2 and 3 (P < .05). Postoperative PROMIS PF and EQ-5D scores were higher for Group 1 at 90days, 1year, and 2years compared to Groups 2 and 3 (P < .05). Patients with prolonged symptoms prior to surgical intervention experience smaller improvements in postoperative leg pain, PROMIS PF, and EQ-5D than those who undergo surgery earlier. Patients undergoing surgery within 3months of symptom onset have the highest rates of return to work at 1year after surgery.

B-103 A Single Centre Experience of Anti-carbamylated Protein Antibody Testing in the Routine Evaluation of Rheumatoid Arthritis

Abstract Background Rheumatoid arthritis (RA) early diagnosis and treatment can slow disease progression and potentially prevent bone erosion. Anticyclic citrullinated peptide (CCP) IgG and rheumatoid factors (RF) serological testing supports the diagnosis of RA; however, these markers are not detected in about 20% of RA patients. Recently, IgG antibodies against carbamylated proteins (CarP) emerged with implications on preclinical RA diagnosis and disease severity. CarP testing is offered as part of RA panel (CarP, RF and CCP) and as a standalone test in our institution. In this study, we evaluated the contribution of CarP testing for RA diagnosis in our routine clinical practice. Our objectives were 1) to assess the clinical performance of CarP in combination with CCP and/or RF antibodies 2) to understand the association of CarP with disease severity. Methods Our cohort included 331 subjects submitted for RA panel serology. Retrospective chart-review revealed 136 clinically defined RA-positive and 195 RA-negative patients. Patients’ sera were tested for CCP, CarP (Inova Diagnostics, San Diego, US) and RF (Roche Diagnostics, Indianapolis, US) antibodies. Clinical performance characteristics were evaluated for CarP individually and in combination with CCP and RF. Disease manifestations (bone damage and synovitis), were correlated with CarP testing. Results Single antibody testing for CarP differentiated RA patients from disease-controls with a 27.2% sensitivity, 93.3% specificity, 74.0% positive predictive value and 64.8% negative predictive value. When CarP testing was combined with RF, specificity increased to 95.4%, in combination with CCP it increased to 98.5% and in a triple combination with CCP and RF, specificity increased to 99.5%. The specificity observed in CCP and RF combination (98.5%) was equivalent to CCP and CarP combination or CCP, CarP and RF triple combination. Amongst the RA patients, frequency of bone erosions was slightly greater (P = 0.76) in the presence of CarP positivity (19/37, 51.4%) compared to the presence of CCP (51/107, 47.7%) or RF (50/112, 44.6%) positivity in isolation and/or in combination. Frequency of synovitis was higher in RA patients that tested positive for CarP (20/37, 54.1%) compared to patients who tested positive for CCP (44/107, 41.1%) or RF (43/112, 38.4%). In the seronegative subgroup, 17.2% (5/29) of CCP negative and 14.3% (3/21) of RF negative patients were positive for CarP. Six out of 8 patients in this subgroup displayed bone erosions and/or synovitis. Of the early RA- diagnosed patients (&amp;lt; 6 months of symptom onset), 22.2% (2/9) were CarP positive, of which one patient (11.1%) was seronegative for CCP but positive for RF. Conclusion Despite low sensitivity, individual CarP testing offered a specificity comparable to CCP. In combination with CCP and/or RF, CarP displayed a superior specificity compared to any individual testing, however, was inferior to the CCP and RF combination. CarP positivity independently and/or in combination was associated with a severe disease course. These data support the use of CarP in combination with CCP and RF for assessing disease severity but may not be advantageous for initial diagnosis. In CCP or RF seronegative patients, CarP testing may be beneficial in establishing a diagnosis of RA.

COVID-19 vaccine effectiveness against hospitalizations in Paraguay, May 2021—April 2022: A test-negative design

BackgroundVaccine effectiveness (VE) estimates vary by population characteristics and circulating variants. North America and Europe have generated many COVID-19 VE estimates but relied heavily on mRNA vaccines. Fewer estimates are available for non-mRNA vaccines and from Latin America. We aimed to estimate the effectiveness of several COVID-19 vaccines in preventing SARS-CoV-2-associated severe acute respiratory infection (SARI) in Paraguay from May 2021 to April 2022. MethodsUsing sentinel surveillance data from four hospitals in Paraguay, we conducted a test-negative case-control study to estimate COVID-19 vaccine effectiveness against SARI by vaccine type/brand and period of SARS-CoV-2 variant predominance (Gamma, Delta, Omicron). We used multivariable logistic regression adjusting for month of symptom onset, age group, and presence of ≥1 comorbidity to estimate the odds of COVID-19 vaccination in SARS-CoV-2 test-positive SARI case-patients compared to SARS-CoV-2 test-negative SARI control-patients. ResultsOf 4,229 SARI patients, 2,381 (56%) were SARS-CoV-2-positive case-patients and 1,848 (44%) were SARS-CoV-2-negative control-patients. A greater proportion of case-patients (73%; 95% CI: 71–75) than of control-patients (40%; 95% CI: 38–42) were unvaccinated. During the Gamma variant-predominant period, VE estimates for partial vaccination with mRNA vaccines and Oxford/AstraZeneca Vaxzevria were 90.4% (95% CI: 66.4–97.6) and 52.2% (95% CI: 25.0–69.0), respectively. During the Delta variant-predominant period, VE estimates for complete vaccination with mRNA vaccines, Oxford/AstraZeneca Vaxzevria, or Gamaleya Sputnik V were 90.4% (95% CI: 74.3–97.3), 83.2% (95% CI: 67.8–91.9), and 82.9% (95% CI: 53.0–95.2), respectively. The effectiveness of all vaccines declined substantially during the Omicron variant-predominant period. ConclusionsThis study contributes to our understanding of COVID-19 VE in Latin America and to global understanding of vaccines that have not been widely used in North America and Europe. VE estimates from Paraguay can parameterize models to estimate the impact of the national COVID-19 vaccination campaign in Paraguay and similar settings.

Association of delayed diagnosis of pulmonary arterial hypertension with its prognosis

BackgroundCurrently, pulmonary hypertension-targeted therapy has been shown to improve the survival of patients with pulmonary artery hypertension (PAH). However, the importance of early diagnosis has not been investigated. Therefore, this study aimed to investigate whether a delayed diagnosis of PAH is associated with its prognosis. Methods and resultsA total of 66 consecutive untreated patients were diagnosed with PAH from January 2008 to December 2021 at the Kagoshima University Hospital. The time from symptom onset to diagnosis correlated with brain natriuretic peptide levels (p < 0.001), right ventricle (RV) Tei index (p < 0.001), and the tricuspid annular plane systolic excursion/systolic pulmonary artery pressure ratio (p = 0.003). These findings suggest that in patients with PAH, RV function declines with increasing time from symptom onset to diagnosis. Furthermore, older patients with PAH appeared to have a longer time from symptom onset to diagnosis. Next, patients were divided into delayed diagnosis (>3 months) and early diagnosis (≤3 months) groups based on the time from symptom onset to diagnosis. Patients were categorized into three groups according to the European Society of Cardiology (or the European Respiratory Society) risk stratification guidelines. Patients diagnosed with PAH within 3 months of symptom onset were significantly in the low- or intermediate-risk groups (p < 0.001). A Kaplan-Meier analysis revealed that the cumulative event-free rate was significantly lower (p < 0.01) in the delayed diagnosis group than in the early diagnosis group. A delayed diagnosis was significantly associated with a worse outcome than an early diagnosis, after adjusting for different sets of confounding factors. ConclusionsA delayed PAH diagnosis is associated with a poor prognosis. Early diagnosis of PAH may lead to a low-risk treatment. Furthermore, older patients need more careful screening for PAH.

Diagnostic Delay in Pediatric Vestibular Disorders.

Vertigo and dizziness in children can be multi-factorial. Vestibular function tests allow an improved differential diagnosis and treatment. Delay in diagnosis of the diverse etiologies causing dizziness can adversely affect the health of children and is a matter of concern for their families. This study analyzes the delay in diagnosis and the importance of establishing a diagnosis with detailed history and neuro-otological evaluation. A total of 241 children presenting with vertigo to a tertiary otoneurology clinic between January 2019 and April 2022 were analyzed for the duration between the onset of symptoms and diagnosis, presenting complaints, and characteristic findings. Two hundred and forty-one patients with a mean age of 12.5 ± 3.02 years (range, 5-16 years) were evaluated. About 39.4% of patients were diagnosed after over a year (with some over 5 years) of suffering from vertigo and only 18.7% of patients were diagnosed correctly within 1 month of symptom onset. The presenting features were variable with 174 (72.2%) complaining of spinning, unsteadiness, and falls seen in 36+10+37 (34.4%). Vestibular migraine was the most common diagnosis (63.39%), followed by benign paroxysmal positional vertigo (24.48%), of which the posterior canal was most affected (50.85%) followed by horizontal (40.68%) and anterior canal (8.47%). Other etiologies noted were central (14.10%) and peripheral vestibulopathy (17.42%) and variable other causes (6.19%). Many pediatric vertigo and dizziness patients do not reach the correct diagnosis for long durations and are treated as "unspecified dizziness." A detailed examination with a multidisciplinary approach including vestibular evaluation is advocated to give definitive treatment to these children.

Kinetics of specific anti-SARS-CoV-2 IgM, IgA, and IgG responses during the first 12 months after SARS-CoV-2 infection: A prospective longitudinal study.

Coronavirus 2019 (COVID-19) is a global health threat. The kinetics of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) need to be assessed, as the long-term duration of these immunoglobulins remains largely controversial. The aim of this study was to assess the longitudinal dynamics of anti-SARS-CoV-2 antibodies against the nucleocapsid (N) protein and the receptor-binding domain (RBD) of the spike protein up to one year in a cohort of 190 COVID-19 patients. Between March and September 2021, we enrolled patients from two regional hospitals in Casablanca, Morocco. Blood samples were collected and analyzed for antibody levels. We used the commercial Euroimmun ELISA for the determination of anti-N IgM, the Abbott Architect™ SARS-CoV-2 IgG test for the detection of anti-RBD IgG, and an in-house kit for the assay of anti-N IgG and anti-N IgA. IgM and IgA antibodies were assessed 2-5, 9-12, 17-20 and 32-37 days after symptom onset. IgG antibodies were also assessed 60, 90, 120 and 360 days after symptom onset. One-third of patients developed IgM (32%), while two-thirds developed IgA (61%). One month of symptom onset, most patients developed IgG, with 97% and 93% positivity for anti-RBD IgG and anti-N IgG, respectively. The anti-RBD IgG positivity rate remained high up to one year of follow-up. However, the anti-N IgG positivity rate decreased over time, with only 41% of patients testing positive after one year's follow-up. IgG levels were significantly higher in older people (over 50 years) than in other study participants. We also found that patients who had received two doses of ChAdOx1 nCoV-19 vaccine prior to infection had a lower IgM response than unvaccinated patients. This difference was statistically significant two weeks after the onset of symptoms. We present the first study in Africa to measure the kinetics of antibody response (IgA, IgM and IgG) to SARS-CoV-2 over one year. Most participants remained seropositive for anti-RBD IgG after one year but showed a significant decline in antibody titers.

Phenotype and genotype heterogeneity of PLA2G6-associated neurodegeneration in a cohort of pediatric and adult patients

BackgroundPhospholipase-associated neurodegeneration (PLAN) caused by mutations in the PLA2G6 gene is a rare neurodegenerative disorder that presents with four sub-groups. Infantile neuroaxonal dystrophy (INAD) and PLA2G6-related dystonia-parkinsonism are the main two subtypes. In this cohort, we reviewed clinical, imaging, and genetic features of 25 adult and pediatric patients harboring variants in the PLA2G6.MethodsAn extensive review of the patients’ data was carried out. Infantile Neuroaxonal Dystrophy Rating Scale (INAD-RS) was used for evaluating the severity and progression of INAD patients. Whole-exome sequencing was used to determine the disease's underlying etiology followed by co-segregation analysis using Sanger sequencing. In silico prediction analysis based on the ACMG recommendation was used to assess the pathogenicity of genetic variants. We aimed to survey a genotype-genotype correlation in PLA2G6 considering all reported disease-causing variants in addition to our patients using the HGMD database and the chi-square statistical approach.ResultsEighteen cases of INAD and 7 cases of late-onset PLAN were enrolled. Among 18 patients with INAD, gross motor regression was the most common presenting symptom. Considering the INAD-RS total score, the mean rate of progression was 0.58 points per month of symptoms (Standard error 0.22, lower 95% − 1.10, and upper 95% − 0.15). Sixty percent of the maximum potential loss in the INAD-RS had occurred within 60 months of symptom onset in INAD patients. Among seven adult cases of PLAN, hypokinesia, tremor, ataxic gate, and cognitive impairment were the most frequent clinical features. Various brain imaging abnormalities were also observed in 26 imaging series of these patients with cerebellar atrophy being the most common finding in more than 50%. Twenty unique variants in 25 patients with PLAN were detected including nine novel variants. Altogether, 107 distinct disease-causing variants from 87 patient were analyzed to establish a genotype–phenotype correlation. The P value of the chi-square test did not indicate a significant relationship between age of disease onset and the distribution of reported variants on PLA2G6.ConclusionPLAN presents with a wide spectrum of clinical symptoms from infancy to adulthood. PLAN should be considered in adult patients with parkinsonism or cognition decline. Based on the current knowledge, it is not possible to foresee the age of disease onset based on the identified genotype.

American Medical Society of Sports Medicine Position Statement: Mononucleosis and Athletic Participation.

Infectious mononucleosis (IM) is a common illness in children and young adults caused primarily by the Epstein-Barr Virus (EBV). Transmission occurs primarily through sharing oral secretions, thus IM is known as the "kissing disease." Common clinical manifestations include fever, pharyngitis, posterior cervical lymphadenopathy, and splenomegaly. Atypical lymphocytosis and transaminase elevations are common, and the diagnosis of IM is confirmed with laboratory findings of a positive heterophile antibody ("Monospot"), polymerase chain reaction, or antibodies specific to EBV. Individuals with acute IM may be quite symptomatic and not feel well enough to participate in sports. Splenic enlargement is common, with rupture a relatively rare occurrence, typically occurring within a month of symptom onset, but this risk complicates sports participation, and is often the reason for restricting activity. The management of IM is primarily supportive, with no role for antivirals or corticosteroids. The variability of clinical presentation and the risk of splenic rupture in patients with IM present clinicians with challenging return to play/return to sport (RTS) decisions. This position statement updates the Evidence-Based Subject Review on Mononucleosis by the American Medical Society for Sports Medicine published in 2008 and reviews the epidemiology, clinical manifestations, laboratory assessment, and management including RTS for the athlete with IM. This statement also addresses complications, imaging, special considerations, diversity and equity considerations, and areas for future clinical research. Understanding the evidence regarding IM and sport is essential when communicating with athletes and their families and incorporating shared decision-making in the RTS decision.

Femoral Neuropathy: A Comprehensive Clinical and Electrodiagnostic Review (P13-8.001)

<h3>Objective:</h3> The aim of this comprehensive study was to gain better understanding of the risk factors, etiologies, electrodiagnostic (EDX) features, and clinical course of femoral neuropathy. <h3>Background:</h3> Femoral neuropathies can cause severe and prolonged debility. Previous literature has reviewed lateral femoral cutaneous neuropathy as well as the femoral predominance in lumbosacral radiculoplexus neuropathy, but there are limited studies addressing femoral neuropathy itself. <h3>Design/Methods:</h3> We identified patients evaluated at Mayo Clinic Rochester between January 1, 1999 and July 31, 2019 with possible new femoral neuropathy ascertained via ICD 9/10 diagnosis codes presenting within 6 months of symptom onset. A retrospective review of 1084 records was performed. <h3>Results:</h3> We identified 165 cases of femoral neuropathy for inclusion. The most common femoral neuropathy etiologies included: compressive (38%) from retroperitoneal/inguinal lesions or prolonged positioning; stretch (35%) post-operatively; and toxic/inflammatory (10%). Presenting symptoms included weakness (96%), sensory loss (73%), and pain (53%). Presenting motor physical exam findings demonstrated moderate weakness (34%) or no activation (26%) of knee extension and mild (32%) or moderate (35%) weakness of hip flexion. 121 (73%) patients underwent EDX testing including 23 with femoral motor nerve conduction studies. Treatment often involved physical therapy (89%) and was otherwise etiology-specific. In patients with follow-up data available (160), 80% experienced subjective clinical improvement at last follow-up with mean time to initial improvement 3.3 months and mean time to recovery at final follow up 14.7 months. 28 (17.5%) of patients experienced no symptomatic improvement at final follow up. <h3>Conclusions:</h3> In our cohort, the most common etiologies of femoral neuropathy are compression or stretch. Although initial morbidity is high, motor recovery is common but often prolonged. <b>Disclosure:</b> Dr. Santilli has nothing to disclose. Dr. Martinez-Thompson has nothing to disclose. Dr. Speelziek has nothing to disclose. Dr. Laughlin has nothing to disclose.

Clinical characterization and outcome of 47 patients with neurologic adverse events of immune-checkpoint inhibitors (P4-5.026)

<h3>Objective:</h3> To report the clinical spectrum, treatment, and outcome of a case series of neurologic iAEs. <h3>Background:</h3> Cancer treatment with immune checkpoint inhibitors (ICI) can associate with immune-related adverse events (iAEs) which can be life-threatening. <h3>Design/Methods:</h3> Retrospective assessment of patients with neurologic iAEs whose serum or CSF samples were studied in our laboratory (Jan2018–Sep2022). Clinical information was obtained through a structured questionnaire. Exclusion criteria were lack of clinical information and evidence of other causes of neurologic dysfunction. Treatment response was assessed within one month of symptom onset, and outcome at last follow-up visit. <h3>Results:</h3> 47 patients (29 males, 62%), median age 67 years (IQR60–74) were included. The most frequent tumors were lung cancer (28, 60%) and melanoma (9, 19%). 26 (55%) patients received anti-PD1, 13 (28%) PDL-1, and 8 (17%) both. Median time to neurologic iAEs was 15 weeks (IQR3–32). The initial presentations were: encephalopathy (30 patients, 64%), muscle weakness (9, 19%), ataxia (3, 6%), visual dysfunction (3, 6%), and constipation (2, 4%). Median mRS at nadir was 4 (3–5), and 7 (15%) patients required ICU. Abs were detected in 10 (21%; Ma2=3, Hu=2, GFAP=2, GABAbR=1, GAD65=1, AQP4=1). 42 (89%) were treated; all received steroids, 17 (36%) intravenous immunoglobulins, and 9 (21%) other immunosuppressants. Patients without early neurologic improvement (14, 30%) were more likely to be older, have lung cancer (p=0.01), and higher mRS at nadir (p=0.001) than those who improved. After a median follow-up of 107 days (45–356), mRS was 3 (0–6), and 26 (55%) patients had a poor outcome: 23 (49%) died (10 [21%] related to neurologic iAE) and the other 3 didn’t improve or worsened. Good outcome was associated with early neurologic improvement (p=0.001). <h3>Conclusions:</h3> In this case series with predominant CNS iAEs, half of the patients had poor clinical outcome, and in 20% the neurologic iAE was the cause of death. <b>Disclosure:</b> Elianet Fonseca has nothing to disclose. Mr. Cabrera Maqueda has nothing to disclose. Raquel Ruiz-Garcia has nothing to disclose. Dr. Naranjo Rondan has nothing to disclose. Dr. Blanco Morgado has nothing to disclose. Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas Research Institute of America. Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Research &amp; Development . Dr. Dalmau has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neurology. An immediate family member of Dr. Dalmau has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Dalmau has received research support from Sage Therapeutics. The institution of Dr. Dalmau has received research support from Edmond J.Safra Foundation . The institution of Dr. Dalmau has received research support from La Caixa Foundation. The institution of Dr. Dalmau has received research support from Spanish Ministry of Health (ISCIII). The institution of Dr. Dalmau has received research support from Euroimmun, Inc. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Graus has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink. Dr. Graus has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Martinez-Hernandez has received research support from Instituto de Salud Carlos III. Dr. Martinez-Hernandez has received personal compensation in the range of $0-$499 for serving as a travel and speaking honoraria with Biogen. Dr. Martinez-Hernandez has received personal compensation in the range of $0-$499 for serving as a travel honoraria with UCB.

Phenotype and Genotype Heterogeneity of PLA2G6-associated Neurodegeneration (S2.009)

<h3>Objective:</h3> We reviewed the clinical, imaging, and genetic features of 25 adult and pediatric patients with Phospholipase-associated neurodegeneration (PLAN), and validated a genotype-phenotype correlation in this disorder. <h3>Background:</h3> PLAN is a rare neurodegenerative disorder caused by mutations in <i>PLA2G6</i> and can present four phenotypes including infantile neuroaxonal dystrophy (INAD), atypical NAD, PLA2G6-related dystonia-parkinsonism, and autosomal recessive early-onset parkinsonism (AREP). <h3>Design/Methods:</h3> An extensive chart review of enrolled patients was carried out. INAD Rating Scale (INAD-RS) was used for evaluating the severity and progression of INAD patients. Whole-exome sequencing was performed to determine the disease’s underlying etiology, and co-segregation analysis was examined using Sanger sequencing. In silico prediction analysis based on the ACMG recommendation was utilized to assess the pathogenicity of detected variants. The HGMD professional database and the chi-square statistical approach were utilized considering all reported disease-causing variants in 17 exons of the PLA2G6 gene in addition to our patient. <h3>Results:</h3> 18 cases of INAD and 7 cases of adult-onset NAD with a mean age of disease onset of 22.4 months and 25 years old, respectively, were enrolled. Among 18 INAD patients, gross motor regression was the most common presenting symptom. Considering the INAD-RS total score, 60% percent of the maximum potential loss occurred within 60 months of symptom onset. Among seven adult cases, movement disorders i.e., hypokinesia, tremor, ataxic gait, and cognitive impairment were the most frequent clinical features. Cerebellar atrophy was the most common imaging finding.. We found twenty unique variants in 25 patients including nine novel variants. Based on the retrieved p-value on the chi-Square, no significant phenotype-genotype correlation was obtained in PLAN. <h3>Conclusions:</h3> PLAN presents with a wide spectrum of clinical symptoms spanning from infancy through adulthood. PLAN should be considered in adult patients presenting with parkinsonism or cognitive decline. Genotype of the disease cannot predict the age of disease onset. <b>Disclosure:</b> Dr. Tavasoli has nothing to disclose. Ali Zare Dehnavi has nothing to disclose. Maryam Bemanalizadeh has nothing to disclose. Mohammad Kahani has nothing to disclose. Dr. Rohani has nothing to disclose. Mehran Beriraghi Toosi has nothing to disclose. Prof. Ashrafi has nothing to disclose. Morteza Heidari has nothing to disclose. Mr. Amanat has nothing to disclose. Sareh Hosseinpour has nothing to disclose.

Abstract 4537: Erdheim Chester disease: A retrospective study characterizing the molecular and pathologic footprints with clinical presentation and comparative outcomes in the present era of targeted molecular targeted therapy

Abstract Erdheim Chester Disease (ECD) is a rare, non-Langerhans cell histiocytic disease, characterized as a neoplastic disorder in 2016. MAP Kinase and PI3-AKT pathway somatic mutations and/or fusion genes have been shown to play a significant role in disease pathogenesis. Despite this, molecular sequencing at diagnosis has yet to become a standard of practice. Retrospective analysis of 19 patients diagnosed with ECD at a single institution over a twenty-years (2002-2022) was conducted. Inclusion criteria were patients 18 years or older, histopathologic diagnosis of ECD, and clinical correlation of disease. The following was collected for each patient: biological sex, age at diagnosis, molecular testing (if utilized), immunohistochemistry, imaging results, therapies administered and best treatment outcomes. Information was translated into binary data for statistical analysis. In this analysis, 47% of patients were females; average age at diagnosis was 51.2 years. 36% of patients were diagnosed within 12 months of symptoms onset. Molecular diagnostics were utilized in 100% of patients, (immunohistochemistry 94%, sequencing 26%). Primary disease was most commonly extranodal (94%), followed by osseous (63%), dermal (52%) and the central nervous system (36%). Treatment consisted of targeted molecular therapy most often (57%), followed by myelosuppressive therapy and steroids (42%), and immunotherapy or radiation (10% each). Disease responses were considered stable if grossly unchanged clinical exam or imaging surveillance, partial (PR) if diminished but still present and complete (CR) if disease was grossly or radiographically resolved. A PR or better was observed in 83% of patients. Stable disease was seen more often in patients treated with conventional therapy (33%) as compared to targeted molecular therapy (11%). PR was higher in targeted therapy recipients (55%). CR was more common with conventional therapy than molecular (66% vs 33%). Patients diagnosed within 1 month of symptom onset had higher rates of disease stability, compared to diagnosis at &amp;gt; 24 months (50% compared to 25%). To our knowledge, this is one of the largest studies of its kind conducted in adult ECD. Targeted molecular therapy utilization by this analysis is associated with higher rates of partial disease response as compared to conventional therapy. The opposite was observed in complete responders. Use of targeted molecular therapies is very recent and higher CR rates are expected in ongoing analyses and longer patient follow-up. Moreover, molecular diagnostics were not routinely employed at diagnosis which delayed the initiation of treatment. Thus, we strongly advocate for early genetic profiling at the time of ECD diagnosis and utilization of targeted therapies when actionable mutations are observed. Citation Format: Sabrina R. Wilcox, Samuel B. Reynolds, Jennifer Girard, Asra Ahmed. Erdheim Chester disease: A retrospective study characterizing the molecular and pathologic footprints with clinical presentation and comparative outcomes in the present era of targeted molecular targeted therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4537.

Clinical Reasoning: Rapidly Progressive Dementia in a Man With HIV Infection and Undetectable Plasma Viral Load.

Neurocognitive decline associated with HIV infection remains prevalent even in the antiretroviral therapy (ART) era, albeit usually in less severe forms. The differential diagnosis of cognitive impairment in this population is quite broad, including infectious causes such as CNS opportunistic infections, causes directly related to HIV such as HIV-associated neurocognitive disorders, and causes entirely unrelated to HIV infection such as primary dementia syndromes. In this case report, a 47-year-old man with HIV on ART with an undetectable plasma viral load presented with rapidly progressive dementia to a clinic in Zambia. He had been functioning independently and fully employed before symptom onset but had to stop working within 2 months of symptom onset because of the severity and rapidity of his cognitive decline. Initial workup led to an empiric diagnosis and initiation of an empiric treatment regimen, which was ultimately ineffective. This prompted re-evaluation, additional workup, and, ultimately, discovering the correct diagnosis. This case highlights the stepwise approach to developing a diagnosis in a resource-limited setting where there exists a high burden of HIV infection, including the necessity of empiric diagnoses of treatment plans when investigations are limited and the importance of reconsidering these diagnoses in the face of additional clinical information. In addition, it highlights both infectious and noninfectious causes of cognitive decline in people with HIV.

PERIVASCULAR FLOWER-BUD-LIKE LESIONS ON EN FACE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH VITREORETINAL LYMPHOMA.

To describe perivascular flower-bud-like lesions (PFBLs) as novel characteristics of vitreoretinal lymphoma on en face optical coherence tomography (OCT) angiography. A retrospective chart review was performed on 23 consecutive patients (35 eyes), who had biopsy-proven vitreoretinal lymphoma between January 2018 and March 2021. En face OCT angiography images were analyzed before and after intervention. PFBLs were initially identified on midretinal slabs of en face OCT angiography, and were further characterized by other imaging modalities. Perivascular flower-bud-like lesions were detected in 12 eyes (34.3%) of 8 patients, of which 8 eyes had best-corrected visual acuity of 20/40 or better. In 10 of the 12 eyes, PFBLs were detected within 6 months of symptom onset. On en face OCT angiography, PFBLs presented as punctate points or confluent bands surrounding retinal vessels, with arterial and venous involvement. In 4 of the 12 eyes, arteries were mainly affected. On OCT B-scans, PFBLs commonly appeared as hyperreflective full-thickness intraretinal lesions that colocalized with subretinal pigment epithelium deposits (3 eyes, 25%) and retinal pigment epithelium irregularities (4 eyes, 33.3%). However, PFBLs could not always be identified on other imaging modalities such as fundus photographs and fundus fluorescein angiography. In all eyes with follow-up, PFBLs attenuated or resolved months after receiving chemotherapy or diagnostic vitrectomy. PFBLs are characteristic imaging findings of vitreoretinal lymphoma and may facilitate an early diagnosis of vitreoretinal lymphoma, which would in turn lead to more timely and effective treatment.

Clinical Spectrum and Outcome of Guillain-Barré Syndrome with Plasmapheresis

Context: Guillain-Barré syndrome (GBS) is an acute inflammatory neuropathy and has several electrophysiological subtypes and clinical variants. Treatment is mainly supportive and immunotherapy is given to shorten the disease course. Aims: The aim of this study was to define the outcome of GBS with plasmapheresis and to determine its clinical spectrum. Materials and Methods: The prospective study was done at Mayo Hospital, Lahore, for 1 year from November 2020 to November 2021. The diagnosis of GBS was made on Brighton criteria for GBS. The outcome of therapy was assessed at 3 and 6 months, using the Medical Research Council Scale and Hughes Functional Grading Scale (HFGS). Results: A total of 50 patients were enrolled in the study. Twenty-seven (54%) were males and 23 (46%) were females. Seventeen (34%) had acute motor axonal neuropathy, 16 (32%) had acute motor and sensory axonal neuropathy, 15 (30%) had acute inflammatory demyelinating polyradiculoneuropathy, and 2 (4%) had Miller-Fisher syndrome. Plasmapheresis was done in all patients. HFGS score was assessed at discharge, at 3 months, and after 6 months of illness onset. The improvement in mean HFGS score was 2.79 ± 0.41 at 3 months and 1.94 ± 0.25 at 6 months of symptoms onset from the mean score of 3.46 ± 0.93 at the time of discharge from the hospital. Conclusion: Excellent outcome was observed after plasmapheresis. Majority of participants were able to walk without support at the 6-month follow-up. Plasmapheresis should be initiated early in the management of GBS where intravenous immunoglobulins are costly.

The potential role of community pharmacy staff in reducing patient delay in consulting with symptoms of rheumatoid arthritis: a qualitative study

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory arthritis which can cause joint damage and reduced quality of life. Early treatment of RA within 3 months of symptom onset is associated with improved clinical outcomes. However, this window of opportunity is often missed. One important contributing factor is patients with symptoms of RA delaying consulting their general practitioner (GP). Previous research indicates that patients with inflammatory arthritis are likely to visit pharmacies for advice before consulting their GP. Therefore, pharmacists are well positioned to identify patients with symptoms of early inflammatory arthritis and signpost them appropriately. This research examines community pharmacy staff’s knowledge, perceptions, and approaches to management of patients presenting with symptoms of RA in order to identify training needs and other opportunities for intervention to enhance the role of pharmacy staff in the pathway to care.MethodsSemi-structured interviews were conducted with 19 community pharmacy staff in the West Midlands (UK), during a 12-month period (2017–2018). The interviews were audio-recorded, transcribed, and analyzed using thematic analysis facilitated by NVivo 12.ResultsThere was considerable variation in knowledge and perceptions of RA and the need for early treatment amongst pharmacists and other pharmacy staff. The potential role of pharmacists and other pharmacy staff in reducing delay in help-seeking was also discussed. Four themes emerged from thematic analysis: (1) Variations in perceptions and knowledge about RA. (2) The role of the pharmacy in increasing public awareness about RA. (3) The role of the pharmacy staff in facilitating access to the GP. (4) Practical considerations for pharmacy-based interventions.ConclusionVariability in knowledge and perceptions of RA amongst pharmacists, and amongst other pharmacy staff will affect effective signposting of suspected RA cases. This study identifies opportunities for enhanced training of community pharmacists and other pharmacy staff in relation to inflammatory arthritis as well as other pharmacy-based interventions, such as public awareness campaigns about RA and other musculoskeletal conditions. Together with existing referral services and other pharmacy-based initiatives this could result in enhanced signposting to GP consultation or other appropriate NHS services for inflammatory symptoms and reduced treatment delay.

Perceptions of patient disease burden and management approaches in systemic mastocytosis: Results of the TouchStone Healthcare Provider Survey.

Systemic mastocytosis (SM) is a rare clonal neoplasm driven by the KIT D816V mutation and has a broad range of debilitating symptoms. In this study, the authors evaluated SM disease perceptions and management strategies among US health care providers (HCPs). Hematologist/oncologist (H/O) HCPs and allergist/immunologist (A/I) HCPs who were treating four or more patients with SM completed an online, 51-item TouchStone HCP Survey, which queried provider characteristics, perceptions of disease burden, and current management. Descriptive analyses by specialty and SM subtype were performed. Of 304 HCPs contacted, 111 (37%) met eligibility criteria, including 51% A/I specialists and 49% H/O specialists. On average, the HCPs had 14 years of practice experience and cared for 20 patients with SM. A/I HCPs saw more patients with nonadvanced SM (78%) compared with H/O HCPs, who saw similar proportions of patients with nonadvanced SM (54%) and advanced SM (46%). HCPs reported testing 75% of patients for the KIT D816V mutation and found an estimated prevalence of 47%. On average, HCPs estimated 8 months between symptom onset and SM diagnosis. HCPs reported that 62% of patients with indolent SM felt depressed or discouraged because of symptoms. In terms of treatment goals for SM, both types of specialists prioritized symptom improvement for nonadvanced SM and improved survival for advanced SM while also prioritizing improving patient quality of life. Both A/I and H/O specialists highlighted unmet needs for patients with SM. The HCPs surveyed reported a lower rate of KIT D816V mutations and a perceived shorter time between symptom onset and SM diagnosis compared with published estimates. Specialists treating systemic mastocytosis (SM) completed a 51-item questionnaire about their clinical practices and perceptions of disease impact. The study included 111 hematology, oncology, allergy, and immunology physicians. Physicians reported that most patients had nonadvanced disease, yet SM symptoms significantly disrupted their patients' lives. Physicians estimated that SM is diagnosed within months of symptom onset, in contrast with published reports of years' long delays reported by patients with SM. This study identified unmet needs that can inform educational and patient management priorities in this rare disease.

Onset-to-treatment time and aneurysmal regression predict improvement of cranial neuropathy after flow diversion treatment in patients with symptomatic internal carotid artery aneurysms

BackgroundAlthough flow diversion plays a pivotal role in treating internal carotid artery aneurysms presenting with cranial neuropathy, predictors of symptom improvement have not been established.ObjectiveTo investigate improvement of symptoms after...

Diagnostic value of mouth opening width in patients with temporomandibular disorders

Introduction: mouth opening amplitude allows the evaluation of joint and muscle function, constituting a valuable tool to diagnose alterations in the stomatognathic system. Objective: to characterize the buccal opening amplitude of patients who attended the temporomandibular disorders consultation of the Clinical Surgical “Dr. Miguel Enriquez” Teaching Hospital, in the period January 2017-January 2020. Method: a retrospective observational descriptive study was carried out in the period January 2017-January 2020, forming a database from the information obtained directly from the medical records. Literature review and synthesis was performed and descriptive statistics were used for data analysis by means of absolute frequency distribution expressed in percentages. Results: normal mouth opening width predominated in 61 % of the cases. Severe mouth opening restrictions below 20 mm affected 7 % of the females and 21 % of the males. Twenty-three percent of the 30-39-year-old group presented severe limitations below 20 mm, while 19 % of the 19-29-year-old group presented hypermobility. 65 % of the patients who attended before 1 month of symptom onset recorded limitation of mouth opening. Conclusions: in patients diagnosed with temporomandibular disorders, normal mouth opening amplitude predominated, so the ability of the individual to perform this movement within the established range is not necessarily an indicator of absence of joint and/or muscle damage

Neuroimaging and neurological outcome of children with acute encephalitis.

AimTo investigate the severity of acute phase magnetic resonance imaging (MRI) findings and severity of acute illness as risk factors for disability after recovery from encephalitis.MethodChildren with encephalitis (n = 98; median age 6 years 10 months, interquartile range 3 years–11 years 6 months; 59 males, 39 females) treated in Turku University Hospital during the years 1995 to 2016 were identified in this retrospective cohort study. The acute phase (<2 months of symptom onset) brain MRIs were re‐evaluated and classified based on the severity of neuroimaging finding by a neuroradiologist. Neurological outcome at discharge, at short‐term (<3 months from discharge) follow‐up, and at long‐term (>1 year from discharge) follow‐up was assessed from medical records using the Glasgow Outcome Scale.ResultsLong‐term recovery was poor in 24 of 82 (29%) children with follow‐up data. Two children died, eight had severe disability, and 14 had moderate disability. Acute phase MRI was available for re‐evaluation from 74 of 82 patients with follow‐up data. The increasing severity of MRI findings was associated with need for ventilator therapy and with poor recovery.InterpretationThe risk for poor recovery in paediatric encephalitis is high, and it is associated with the severity of MRI findings.What this paper adds Poor long‐term recovery was found in 29% of children with encephalitis.Severe disability measured by Glasgow Outcome Scale was found in 8%.The most severe neuroimaging findings were a risk factor for severe acute illness and poor long‐term recovery.