Major Diagnostic Criteria Research Articles

Afebrile Kawasaki disease: A case report

Objective: Kawasaki disease (KD) is an acute, self-limiting vasculitis and the most common cause of acquired heart disease in children under 5 years old. Despite over 50 years of research, the etiology and long-term prognosis of KD remain unclear.Case presentation: A 2-year-7-month-old boy presented with all the typical KD symptoms, including conjunctival injection, cracked lips, strawberry tongue, and membranous desquamation of the fingers and toes, but without fever. The patient was admitted with a 9-day history of peeling skin on his fingers, and no history of illness or fever in the past two weeks. Laboratory tests revealed elevated platelet count. An echocardiogram showed normal coronary arteries. The patient was diagnosed with KD and treated with low-dose aspirin and dipyridamole. He was discharged on the third day and showed complete symptom resolution and normal coronary arteries at follow-up.Conclusions: This case report describes an instance of afebrile KD, emphasizing the need for clinical vigilance and comprehensive assessment for diagnosis and treatment. Afebrile KD poses a diagnostic challenge as fever is a major diagnostic criterion. However, clinicians should consider afebrile KD when other clinical features and laboratory results suggest KD, and initiate appropriate treatment to prevent severe complications like coronary artery lesions. This case underscores the importance of early diagnosis, timely intervention, and multidisciplinary team collaboration for effective management of KD.

Unraveling the Genetic Puzzle: Could MAP3K7 Be a Candidate Gene for RASopathies? Case Presentation.

Noonan Syndrome (NS) diagnosis is challenging due to diverse clinical manifestations. Here, our case report highlights MAP3K7's novel role in NS. A 10.4-year-old female patient presented with short stature and suggestive clinical findings of RASopathy. Despite atypical facial features, the patient met two major diagnostic criteria of Van der Burgt.Initial genetic testing for known NS-associated genes did not find any variants. Later, whole exome sequencing (WES) discovered a unique de novo heterozygous variant (c.65C>A, p.(P22H)) in the MAP3K7. This variant, categorized as a variant of uncertain significance (VUS) by the American College of Medical Genetics and Genomics (ACMG) criteria, raised questions about its potential role in NS. The patient's clinical presentation deviated from classical manifestations of MAP3K7-associated syndromes, underscoring the genetic and molecular mechanisms' complexity. Notably, this is the first case reported to associate MAP3K7 variants with NS, advancing knowledge of the condition's genetic causes. Despite challenges in NS diagnosis, proper management, including recombinant growth hormone therapy, is crucial for optimizing growth potential. The case underscores MAP3K7 as a potential candidate gene for NS, and more functional genetic investigations are required to clarify the delicate interaction between genetic abnormalities, the RAS/MAPK pathway, and clinical manifestations observed in NS cases.

DNA Methylation Profiling Confirms a Challenging Glioblastoma, Atypical Mesenchymal Type Which Mimics Intracranial Mesenchymal Tumor

Abstract Introduction/Objective Brain tumors exhibit distinct DNA methylation patterns that reflect their cellular origin, molecular subtype, and clinical behavior. DNA methylation signatures provide valuable insights into tumor heterogeneity, evolution, and treatment response, guiding personalized therapeutic strategies. Our case, glioblastoma, atypical mesenchymal type confirmed by DNA methylation profile and it reflects the clonal evolution of the glioblastoma metaplasia with minimal glial component which was histologically challenging. Methods/Case Report A 56-year-old gentleman presented with headaches. MRI brain demonstrated a heterogeneous enhancing mass with areas of central necrosis in the left temporal lobe, measuring approximately 49 x 34 mm, with surrounding T2 FLAIR hyperintensity extending into the left basal ganglia, causing compression of the left lateral ventricle and uncal herniation. He underwent left-sided craniotomy for tumor resection. Microscopic examination revealed hypercellular spindle cell neoplasm, forming fascicles. Brisk mitotic activity and geographic necrosis were evident. GFAP highlighted narrow margins of the tumor which could represent the entrapped glial tissue. CD99 stained the tumor cells, Other immunohistochemical stains for spindle cell work up, like S100, EMA, PR STAT6 and desmin were all negative. A diagnosis of intracranial mesenchymal tumor /sarcoma was considered. Methylation profiling results showed class calibrated scores of 0.9741, compatible with Glioblastoma, IDH-wildtype, atypical mesenchymal type with a cytogenetic profile including gain of chromosome 7 (including EGFR) and loss of chromosome 10 (including PTEN), and loss of CDKN2A/B. Results (if a Case Study enter NA) NA Conclusion Although histopathological examination and immunohistochemical study are fundamental in diagnosing brain tumors, the rapid development of cytogenetic and molecular diagnostic modalities has significantly contributed to diagnostic accuracy and the potential for targeted treatment. Particularly, DNA methylation profiling has proven valuable in diagnosing morphologically challenging cases with prognostic value. Eventually, DNA methylation profiling will be adopted as a major cancer diagnostic criterion and will become a standard procedure performed at major academic centers.

Concurrent and predictive validity of the Global Leadership Initiative on Malnutrition criteria for adult patients in convalescent rehabilitation wards

Background & aimsThe Global Leadership Initiative on Malnutrition (GLIM) criteria has been recognised as major diagnostic criteria for malnutrition in adults worldwide; however, its validity in rehabilitation settings remains unclear. This study investigated the concurrent and predictive validity of the GLIM criteria for adult patients in convalescent rehabilitation wards. MethodsThis retrospective cohort study was conducted using pre-established datasets from convalescent rehabilitation wards in a hospital. The inclusion criteria were adults aged ≥18 years admitted to the wards between November 2018 and October 2020 who were available for body composition assessment. Malnutrition diagnoses were determined by registered dietitians (RDs) using the GLIM criteria. The Subjective Global Assessment (SGA) was performed by another RD and used for the malnutrition reference standard. The GLIM criteria sensitivity and specificity were examined for SGA. The odds ratios and hazard ratios of GLIM-defined malnutrition for the total score of the Functional Independence Measure (tFIM) effectiveness and non-home discharge were calculated using univariable and multivariable logistic regression analyses and Cox proportional hazard models. ResultsData from 723 patients were extracted from the dataset. GLIM-defined malnutrition was confirmed in 207 (28.6%) patients, 87 (12.0%) with moderate malnutrition and 120 (16.6%) with severe malnutrition. The SGA graded 146 (20.2%) patients with moderate malnutrition (grade B) and 86 (11.9%) with severe malnutrition (grade C). The GLIM criteria (malnutrition/ no malnutrition) had fair sensitivity (76.7%, 95% confidence interval [CI]: 70.7–82.0%) and good specificity (94.1%, 95% CI: 91.6–96.0%), indicating acceptable concurrent validity. GLIM-defined moderate malnutrition had poorer sensitivity than severe malnutrition (42.5% vs 81.4%). Logistic regression analyses revealed no evidence for the association between GLIM-defined malnutrition and poor tFIM effectiveness (adjusted odds ratio [AOR]: 1.09, 95% CI: 0.71–1.69) and non-home discharge (AOR: 1.19, 95% CI: 0.76–1.84). The Cox proportional hazard analyses also showed no effect of malnutrition on outcomes. ConclusionThe GLIM criteria had fair sensitivity and good specificity, indicating acceptable criteria for diagnosing malnutrition in rehabilitation settings. However, its predictive validity for functional recovery and discharge outcomes was insufficient.

A positive scratch collapse test in anterior cutaneous nerve entrapment syndrome indicates its neuropathic character.

Chronic abdominal pain is occasionally caused by an abdominal wall entity such as anterior cutaneous nerve entrapment syndrome (ACNES). This syndrome is thought to occur due to intercostal nerve branches (T7-12) that are entrapped in the rectus abdominis muscles. The diagnosis is largely based on subjective clues in patient history and physical examination. A test referred to as the scratch collapse test (SCT) is used as an additional diagnostic tool in peripheral nerve entrapment syndromes such as the carpal tunnel syndrome. The aim of the present study is to investigate whether an SCT was positive in patients with suspected ACNES. If so, this finding may support its hypothesized neuropathic character. A prospective, case-control study was performed among patients with ACNES (n = 20) and two control groups without ACNES (acute intra-abdominal pathology n = 20; healthy n = 20), all were consecutively included. ACNES was diagnosed based on previously published criteria. The SCT test was executed at the painful abdominal area in both patient groups and at a corresponding area in healthy controls. Predictive values, sensitivity, and specificity were calculated. Videos of tests were evaluated by blinded observers. SCT was judged positive in 19 of 20 ACNES patients but not in any of the 40 controls. A 95% sensitivity (confidence interval [CI]: 75-99) and optimal specificity (100%; CI: 83-100) were calculated. The positive SCT supports the hypothesis that ACNES is an entrapment neuropathy. A positive SCT should be considered a major diagnostic criterion for ACNES.

Neurological Validation of ASD Diagnostic Criteria Using Frontal Alpha and Theta Asymmetry.

Background/Objectives: Diagnosis of Autism Spectrum Disorder (ASD) relies on the observation of difficulties in social communication and interaction, plus the presence of repetitive and restrictive behaviors. The identification of neurological correlates of these symptoms remains a high priority for clinical research, and has the potential to increase the validity of diagnosis of ASD as well as provide greater understanding of how the autistic brain functions. This study focused on two neurological phenomena that have been previously associated with psychiatric disorders (alpha- and theta-wave asymmetry across the frontal region of the brain), and tested for their association with the major diagnostic criteria for ASD. Methods: A total of 41 male autistic youth underwent assessment with the Autism Diagnostic Observation Schedule (ADOS-2) and 3 min of eyes-closed resting EEG to collect alpha- and theta-wave data from right and left frontal brain sites. Results: Different associations were found for theta versus alpha asymmetry and the ADOS-2 subscales, across different brain regions responsible for a varying range of cognitive functions. In general, theta asymmetry was associated with conversation with others, sharing of enjoyment, and making social overtures, whereas alpha asymmetry was linked with making eye contact, reporting events to others, and engaging in reciprocal social communication. Specific brain regions involved are identified, as well as implications for clinical practice. Conclusions: Specific autism symptoms may be associated with selected brain region activity, providing a neurological basis for diagnosis and treatment.

Atypical Periprosthetic Femoral Fracture Might be Considered a Distinct Subtype of Atypical Femoral Fracture: A Retrospective Study.

The exact relationship among atypical periprosthetic femoral fractures (APFFs), typical periprosthetic femoral fractures (PFFs), and atypical femur fractures (AFFs) remains unclear. This study aimed to investigate the prevalence of APFFs among PFFs and to identify the clinical characteristics, management, and prognosis that distinguish APFFs from typical PFFs and AFFs to further determine the relationship among these three fracture types. In this retrospective study, we reviewed the clinical data of 117 consecutive patients who had PFFs after hip arthroplasty between January 2012 and December 2022 and further classified them into an APFF group and a typical PFF group according to the revised ASBMR diagnostic criteria for AFF. Moreover, patients who had subtrochanteric or femoral shaft fractures in the same period and met the diagnostic criteria for AFF were recruited and classified into the AFF group. Demographic information, minor features of AFF, comorbidities, history of medication usage, management, and complications were collected and compared among patients with typical PFFs, APFFs, and AFFs. Eleven PFFs were identified as APFFs, and the prevalence of APFFs among PFFs was 9.4%. Significant differences were found in generalized increase in cortical thickness (p = 0.019), prodromal symptoms (p < 0.001), and the incidence of bilateral fractures (p = 0.010) among the groups, where the incidences of these minor features in the APFF group and the AFF group were higher than those in the typical PFF group. Of note, the duration of fracture healing of APFFs was significantly longer than that of typical PFFs and AFFs (p < 0.001 and p = 0.004, respectively). In addition, the APFF group and the AFF group had higher proportions of patients with rheumatoid arthritis (p = 0.004 and p = 0.027, respectively), bisphosphonate (BP) usage (p = 0.026 and p < 0.001, respectively), and longer duration of BP usage (p = 0.003 and p = 0.007, respectively) than the typical PFF group. Furthermore, significant differences were found in management (p < 0.001) and complication rate (p = 0.020) among the groups, and the rate of complications in the APFF group and the AFF group was higher than that in the typical PFF group. APFFs not only fulfilled the mandatory and major diagnostic criteria for AFF but also had many clinical characteristics, management and prognosis distinguishing them from typical PFFs but resembling AFFs; hence, the diagnostic criteria for AFF might be revised to incorporate APFF as a distinct subtype of the condition.

Cutler Beard Procedure for Bilateral Upper Eyelid Coloboma in Charge’s Syndrom: Surgical Outcome

Ocular coloboma is one of the anomalies that commonly seen in CHARGE syndrome. This syndrome is an autosomal dominant malformation which includes six major features: coloboma, heart defect, atresia of the choanae, retarded growth and development delay, genital hypoplasia, ear anomalies. Cutler-Beard procedure is one of the major technic when a total or near total upper eyelid is missing. To report the surgical outcome in bilateral upper eyelid coloboma in CHARGE syndrome patient after Cutler Beard’s procedure. A 8 month-old boy presented to the hospital with bilateral upper eyelid coloboma since birth. Other clinical manifestations including bilateral optic nerve coloboma, external ear anomalies, bilateral undecensus testis, growth and developmental delay, and CHARGE facies which were consistent with 2 and 4 major and minor diagnostic criteria. The patient underwent eyelid reconstruction by using Cutler Beard procedure in both of eyes. Cutler Beard procedure may be used as the primary reconstruction method in bilateral upper eyelid coloboma in CHARGE syndrome.

Contemporary Role of Positron Emission Tomography (PET) in Endocarditis: A Narrative Review.

Endocarditis, a serious infectious disease, remains a diagnostic challenge in contemporary clinical practice. The advent of advanced imaging modalities has contributed significantly to the improved understanding and management of this complex disease. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging has shown remarkable potential in improving the diagnostic accuracy of endocarditis. In the update of the Modified Duke Criteria, in 2023, The International Society for Cardiovascular Infectious Diseases (ISCVID) Working Group recognized specific 18F-FDG PET/CT findings as a major diagnostic criterion, particularly in patient with prosthetic valve endocarditis. The ability of PET to visualize metabolic activity allows for the identification of infective foci and could differentiate between infective and non-infective processes. This review examines the clinical utility of PET in differentiating infective endocarditis from other cardiovascular pathologies, highlighting its sensitivity and specificity in detecting native and prosthetic valve infections, including patients with transcatheter aortic valve implantation (TAVI), cardiac implantable devices (CIEDs), and left ventricular assistance devices (LVAD). Also, practical aspects and indications are illustrated to optimize the quality of imaging and reduce potential false positive results. In conclusion, the current use of PET in endocarditis has become a valuable diagnostic tool; as technological advances continue, PET will play an increasingly important role in the multidisciplinary approach to the management of endocarditis.

How I diagnose large granular lymphocytic leukemia.

Large granular lymphocytic leukemia (LGLL) represents a rare neoplasm of mature T cells or natural killer (NK) cells, with an indolent clinical course. Diagnosing LGLL can be challenging because of overlapping features with reactive processes and other mimickers. By presenting 2 challenging cases, we elucidate the differentiation of LGLL from its mimics and highlight potential diagnostic pitfalls. A comprehensive review of the clinicopathologic features of LGLL was conducted. Large granular lymphocytic leukemia displays a diverse spectrum of clinical presentations, morphologies, flow cytometric immunophenotypes, and molecular profiles. These features are also encountered in reactive conditions, T-cell clones of uncertain significance, and NK cell clones of uncertain significance. In light of the intricate diagnostic landscape, LGLL workup must encompass clinical, morphologic, immunophenotypic, clonal, and molecular findings. Meeting major and minor diagnostic criteria is imperative for the accurate diagnosis of LGLL.

POSITIVE SCRATCH COLLAPSE TEST IN ANTERIOR CUTANEOUS NERVE ENTRAPMENT SYNDROME (ACNES): EVIDENCE FOR A PERIPHERAL NEUROPATHY?

Abstract Background Chronic abdominal pain is occasionally caused by an abdominal wall entity such as Anterior Cutaneous Nerve Entrapment Syndrome (ACNES). This syndrome is thought to occur due to entrapped intercostal nerve branches (Th7-12) within the rectus abdominis muscles. This clinical diagnosis is based on subjective clues in patient history and physical examination. In contrast, in carpal tunnel syndrome an additional diagnostic test is used, which is referred to as the scratch collapse test (SCT). The SCT has shown positive results not only in other peripheral entrapment neuropathies involving the ulnar, peroneal, and long thoracic nerve, but also in three recently described ACNES patients. We investigated whether the SCT is of diagnostic use in patients suspected of having ACNES. Method A prospective, case-control study was performed among patients with ACNES (n = 20) and two control groups without ACNES (acute abdomen n = 20; healthy n = 20), all were consecutively included. ACNES was diagnosed based on previously published criteria. The SCT test was executed at the painful abdominal area in both patient groups and at a corresponding area in healthy controls. Predictive values, sensitivity, and specificity were calculated. Videos of tests were evaluated by blinded observers. Results SCT was judged positive in 19 of 20 ACNES patients, but not in any of the 40 controls. A 95% sensitivity (CI:75–99) and 100% specificity (CI: 83–100) were calculated. Conclusion This study provides strong evidence that ACNES should be considered as an entrapment neuropathy, while a positive SCT should be considered as a major diagnostic criterion.

КЛИНИЧЕСКИЙ СЛУЧАЙ УСПЕШНОГО 120-ДНЕВНОГО КОМПЛЕКСНОГО ЛЕЧЕНИЯ ИНФЕКЦИОННОГО ЭНДОКАРДИТА МИКСОМАТОЗНО-ИЗМЕНЕННОГО МИТРАЛЬНОГО КЛАПАНА, ОСЛОЖНЕННОГО КАРДИОГЕННЫМ И СЕПТИЧЕСКИМ ШОКОМ С ПОЛИОРГАННОЙ НЕДОСТАТОЧНОСТЬЮ

Annotation. Estimated incidence of infectious endocarditis (IE) is 13.8 cases per 100.000 subjects per year while mortality as high as 0.87 death cases per 100.000 patients demonstrating upstroke trend in majority countries in the world over past 30 years. Imaging positive for IE is among major diagnostic criteria of which transthoracic echocardiography is recommended as the first-line imaging modality in suspected IE. Negative, non-diagnostic or inconclusive results of echocardiography make diagnosis of IE challenging followed by treatment delays and poor outcomes. Within current clinical case we discuss the experience of diagnosis and successful treatment of IE of mitral valve with mixomatous degeneration and rupture of chordae tendineae that challenged vegetations detection and delayed surgical treatment followed by development of complications as cardiogenic and septic shock with multiple organ failure.

Culture-negative endocarditis with multifocal spread and flail mitral valve leaflet: a case report

Introduction: Blood culture-negative infective endocarditis is the condition in which a causative organism cannot be identified after inoculation of at least three samples using standard blood-culture systems for 7 days. It has a low reported incidence of about 2.5–31%. Causes may be infectious or non-infectious; use of prior antibiotic therapy is usually the leading factor. Case presentation: The authors present a case of true culture-negative endocarditis involving the mitral valve, with multiple foci of spread including brain, spleen, liver, and Intervertebral disc, which remained persistent despite treatment with intravenous broad-spectrum antibiotics on an inpatient and outpatient basis but eventually improved after upgrading alternative broad-spectrum antibiotic for an extended duration. The patient had complications in the form of a flail mitral valve with persistent mitral regurgitation, requiring mitra-clip placement. Discussion: Positive blood culture is one of the major diagnostic criteria to establish infective endocarditis. Patients may have persistent negative cultures due to previous antibiotic use, the presence of fastidious organisms, or the use of inappropriate techniques or media. Involvement of a multidisciplinary team, use of multimodal investigations, and appropriate antibiotic stewardship are crucial. Extended duration of treatment and upgrading antibiotics can be helpful next steps in highly suspicious cases. With multifocal spread as in our case, it further becomes challenging to control and treat the infection as it is frequently connected with higher morbidity and mortality. Conclusion: Blood culture-negative endocarditis is an entity that can present with early complications. It is diagnostically and therapeutically challenging to treat such patients. Multimodal approaches for early diagnosis and appropriate treatment are crucial owing to its high morbidity and mortality.

Further Expanding the Mutational Spectrum of Gorlin Syndrome in Three Unrelated Families

Introduction: Gorlin syndrome is a rare, autosomal dominant multi-systemic disorder with a predisposition to the development of cancers such as medulloblastoma and nevoid basal cell carcinoma. Heterozygous pathogenic variants in PTCH1 are responsible for 90% of Gorlin syndrome cases. Pathogenic variants in PTCH1 cause overstimulation of the sonic hedgehog signaling pathway, which plays a role in the development of embryonic structures and tumorigenesis. Clinical major and minor diagnostic criteria for Gorlin syndrome have been determined. Odontogenic keratocyst (OKC) is the most common reason for medical admission in Gorlin syndrome. In this article, it is aimed to draw attention to the fact that patients with Gorlin syndrome are not very rare in our country and the variability in phenotypic and dysmorphic findings may be a clue for the diagnosis. Methods: Exome sequencing was performed on the Illumina NextSeq550 System platform by using the Ion Ampliseq exome RDY kit for Illumina. Sanger sequencing was performed accordingly for the other affected individuals in both families. Results: In this study, the clinical and molecular findings of 9 Gorlin syndrome patients from three unrelated families are presented. Macrocephaly, calcification of falx cerebri, palmar-plantar pits, rib anomalies, and OKC were detected in decreasing order in more than half of the patients. A novel heterozygous frameshift PTCH1 variant in family 1, a nonsense previously reported PTCH1 variant in family 2, and a novel heterozygous splice-site PTCH1 variant in family 3 were detected. Conclusion: Gorlin syndrome should be kept in mind in patients presenting with macrocephaly, palmoplantar pits, and OKC history. Careful examination of all family members is essential in the timely diagnosis of other affected individuals with minor phenotypic findings.

Three-dimensional Transesophageal Echocardiography in Infective Endocarditis: What Does It Add?

Infective endocarditis (IE) diagnosis is based on a clinical suspicion supported by consistent microbiological and instrumental data. Evidence of involvement of cardiac valves (native or prosthetic) or prosthetic intracardiac material is a major diagnostic criterion of IE. Transthoracic echocardiography (TTE) is the initial technique of choice for the diagnosis while transesophageal echocardiography (TEE) is recommended in patients with an inconclusive or negative TTE, in patients with high suspicion of IE, as well as in patients with a positive TTE, in order to document local complications. Repeating TTE and/or TEE should be considered during follow-up of uncomplicated IE, in order to detect new silent complications and monitor vegetation size. In the setting of IE, the role of three-dimensional (3D) TEE is increasing; in fact, this technique has also been shown to be useful for the diagnosis of IE and its complications as it allows to obtain infinite planes and volumetric reconstructions. In this review, we will describe the usefulness of 3D-TEE and its added value in the management of IE.

Idiopathic multicentric Castleman's disease with TAFRO syndrome: a case report

Abstract Introduction/Objective Multicentric Castleman's disease(MCD) is a nonneoplastic lymphoproliferative disorder. Individuals affected by MCD exhibit systemic symptoms accompanied by the presence of multiple enlarged lymph nodes. MCD can be associated with human herpesvirus type-8, POEMS syndrome, or idiopathic (iMCD). TAFRO syndrome, a clinical subtype of MCD is a recently recognized disorder with an unclear cause, it comes with a combination of symptoms, namely thrombocytopenia, anasarca, fever, renal dysfunction, and organomegaly. This case report aims to shed light on the diagnostic challenges due to the rarity and nonspecific nature of TAFRO syndrome. Methods/Case Report We report a 30-year-old female who presented with night sweats, fever, fatigue, and cough. She had significant leucocytosis, lymphopenia, thrombocytopenia, anemia requiring transfusion, and elevated creatinine, CT showed ground glass opacities in the lungs and extensive lymphadenopathy. Axillary lymph node excisional biopsy revealed paracortical hyperplasia with increased vascularity, extensive polytypic plasmacytosis, and some follicular hyperplasia. On IHC staining it was positive for CD20, CD79a, PAX 5, and negative cyclin D1 for B lymphocytes. T lymphocytes were positive for CD3, CD5, CD2, CD7, CD4&amp;gt;CD8, Bcl2 and CD43. Plasma cells were composed mainly of IgG cells and some IgG4(IgG4/IgG &amp;lt;20%). HHV8 was negative. Flow cytometry showed 89% lymphocytes with a heterogenous population of T-cells and polytypic B cells. Serology revealed markedly elevated IL- 6, IL-2, VEGF CRP, and ESR while HIV and ANA were negative. Bone marrow biopsy was suggested. A final diagnosis of idiopathic multicentric castle man disease suggestive of TAFRO syndrome was made. The patient received steroids and is currently on siltuximab. Results (if a Case Study enter NA) NA Conclusion Our case fulfills at least four of the five major diagnostic criteria of TAFRO syndrome. It serves as a valuable addition to the scarce literature on TAFRO syndrome, providing insights into its diagnostic challenges

The challenge of hypophosphatasia diagnosis in adults: results from the HPP International Working Group Literature Surveillance.

Hypophosphatasia (HPP) is an inborn error of metabolism caused by reduced or absent activity of the tissue non-specific alkaline phosphatase (TNSALP) enzyme, resulting from pathogenic variants in the ALPL gene. Clinical presentation of HPP is highly variable, including lethal and severe forms in neonates and infants, a benign perinatal form, mild forms manifesting in adulthood, and odonto-HPP. Diagnosis of HPP remains a challenge in adults, as signs and symptoms may be mild and non-specific. Disease presentation varies widely; there are no universal signs or symptoms, and the disease often remains underdiagnosed or misdiagnosed, particularly by clinicians who are not familiar with this rare disorder. The absence of diagnosis or a delayed diagnosis may prevent optimal management for patients with this condition. Formal guidelines for the diagnosis of adults with HPP do not exist, complicating efforts for consistent diagnosis. To address this issue, the HPP International Working Group selected 119 papers that explicitly address the diagnosis of HPP in adults through a Medline, Medline In-Process, and Embase search for the terms "hypophosphatasia" and "HPP," and evaluated the pooled prevalence of 17 diagnostic characteristics, initially selected by a group of HPP clinical experts, in eligible studies and in patients included in these studies. Six diagnostic findings showed a pooled prevalence value over 50% and were considered for inclusion as major diagnostic criteria. Based on these results and according to discussion and consideration among members of the Working Group, we finally defined four major diagnostic criteria and five minor diagnostic criteria for HPP in adults. Authors suggested the integrated use of the identified major and minor diagnostic criteria, which either includes two major criteria, or one major criterion and two minor criteria, for the diagnosis of HPP in adults.

Abstract 13286: Co-Morbidities Clustering According to Imaging Diagnostic Criteria in Cardiac Sarcoidosis

Background: Cardiac sarcoidosis (CS) diagnostic guidelines updated in 2006 and in 2017 now include imaging findings of left ventricular (LV) dysfunction (LV EF &lt; 50%) on cardiac MRI and echocardiography as major diagnostic criterion. Limited data is available with regards to co-morbidities clustering in sarcoidosis and CS according to the 2017 updated guideline diagnostic criteria. Methods: A case control, single tertiary medical center study included 558 sarcoidosis patients with documented extracardiac sarcoidosis and completed electrocardiogram and/or cardiac MRI imaging. CS 2006 and 2017 diagnostic criteria and co-morbidity data were extracted from electronic charts and were available for comparison in 540 patients. Results: The total study population was composed of 52.7% (281/540) females, aged 58.9+/-12.6 years old, with diabetes mellitus (DM) present in 29.6% (160/540), HTN in 51.7% (279/540), CAD in 13.3% (72/540), moderate to severe aortic, mitral, or tricuspid valvular disease in 14.8% (80/540), ESRD in 2.4% (13/540), and COPD or asthma in 21.9% (118/540). There was a significant clustering of co-morbidities according to the imaging CS diagnostic criteria. Patients meeting the 2017 CS imaging criteria were found to be older (61.4+/-11.3 vs 58.8+/-12.8 years old in patients not meeting criteria, p=0.085), predominantly male (69.2%, (54/78) vs. 44.4%, (205/462), p&lt;0.001), and demonstrated significantly increased prevalence of DM (39.7%, (31/78) vs. 27.9%, (129/462), p=0.034), and valvular disease (33.3%, (26/78) vs. 11.7%, (54/462), respectively, p&lt;0.001). However, there were no statistically significant difference in the prevalence of HTN (60.3%, (47/78) vs. 50.2%, (232/462), p=0.101), ESRD (3.9%, (3/76) vs. 2.2%, (10/456), p=0.361), and COPD or asthma (19.2%, (15/78) vs. 22.3%, (103/462), p=0.544) in patients meeting 2017 CS criteria compared to those that did not. Conclusion: CS patients meeting 2017 imaging diagnostic criteria were found to have statistically significant clustering of the following co-morbidities: male gender, DM, and valvular disease. These findings underscore importance of comprehensive care in CS patients and warrant caution in assigning LV abnormalities observed on imaging solely to CS etiology.

Histopathological characteristics analysis of giant melanocytic naevi in children.

The major diagnostic criterion for the giant congenital melanocytic nevus (GCMN) is a size larger than 20 cm in diameter. However, the histopathological origin, pathogenesis, and GCMN progression are not yet completely clear. Unlike other medium or small superficial lesions, histomorphological evaluation is significant for GCMN pathological classification, malignant transformation assessment, and early detection of prognosis. This study aimed to investigate the pathological features of GCMN, including its satellite lesions. Twenty-three giant naevi and seventeen "satellite lesions" were collected from children aged 1 to 10 in Shanghai Ninth People's Hospital from 2018 to 2020. A histological study was conducted to evaluate their histological appearance. All the data observed and recorded data were statistically analyzed. In 23 cases of GCMN primary nevus, nevus cells were mainly distributed in the dermal region, with melanocyte proliferation and the presence of nevus nests at the dermal-epidermal junction. However, in satellite nevus, a junctional growth pattern was noted. Additionally, other histopathologic features, including epidermal contour, cell morphology, and architecture disorder also showed significant differences between primary nevus and satellite nevus. We demonstrated that the congenital pattern of the main nevus is more obvious than one of the satellite nevus, suggesting that the satellite nevus and the main nevus may occur slightly later than the main nevus. "Satellite nevus" happens as a result of a separate genetic event.

58 Right Anterior Temporal Lobe Atrophy is Associated with Informant-Reported Socioemotional Dysfunction in Patients with Frontotemporal and Early Onset Alzheimer's Dementia

Objective:Abnormalities in social and emotional behavior are the major diagnostic criteria for behavioral variant frontotemporal dementia (bvFTD). Investigators have attributed their behavioral disturbances to disease in mesial prefrontal and related networks, such as the salience network. This study examined the main neural correlates of informant-reported socioemotional dysfunction among patients with bvFTD compared to those with early-onset (before age 65) Alzheimer's Disease (EOAD).Participants and Methods:Participants included 13 patients with bvFTD and their caregivers and 18 patients with EOAD and their caregivers. The caregivers consisted of a spouse, family member, or other informant who resided with the patient. They completed the informant-based Socioemotional Dysfunction Scale (SDS), a 40-item scale which rates common disturbances in social and emotional behavior on a five-point Likert scale (1-5). The patients underwent magnetic resonance imaging (MRI) with tensor-based morphometry (TBM) analysis of the 3D T1-weighted MRI scans. Computations of mean Jacobian values within select regions of interest (ROIs) in frontal and temporal lobes generated numerical summaries of regional volumes, and voxel-wise regressions created 3D statistical maps of the association between tissue volume and SDS total scores. Statistical analyses included independent samples t-tests group differences in ROIs and SDS scores, Pearson correlations between SDS scores and brain volumes, and multiple regression of ROIs with SDS scores and group as predictor variables.Results:Compared to the EOAD group, the bvFTD group had significantly higher SDS scores (p &lt; .001; d = 2.24), smaller frontal lobe volumes (specifically dorsolateral-prefrontal cortex, p = .003; d = 1.24), and larger temporal lobe volumes (specifically hippocampus, p = .014; d = 0.979). Within the bvFTD group, higher SDS scores were associated with a smaller right anterior temporal lobe (ATL; p = .005; r = -.729), especially the lateral ATLs (p = .002; r = -.776), and a smaller bilateral orbitofrontal cortex (OFC; p = .016; r = -.650). In contrast, within the EOAD group, higher SDS scores were associated with a smaller right parietal cortex (p = .030; r = .542). In the entire sample (both bvFTD and EOAD), higher SDS scores was associated with a smaller lateral ATL volumes (p = .019; r = -.431). Regression analyses confirmed that SDS score predicted lateral ATL volume (p = .041; b = -.262) after controlling for diagnosis (p &lt; .001; b = -.692).Conclusions:These findings are consistent with greater socioemotional dysfunction, smaller frontal, and larger mesial temporal regions in bvFTD, when compared to EOAD. The findings, however, suggest that positively disturbed socioemotional behavior in bvFTD, as reported by caregivers, results from involvement of the right temporal lobe and the lateral temporal region, with further contribution from disease in OFC. The association of SDS scores and ATL volume across diagnostic groups suggests that this region is instrumental in socioemotional functioning and that the SDS may have diagnostic value in distinguishing the "right-temporal variant" of bvFTD.