Definite Etiology Research Articles

Axillary lymph node "bubbly" calcifications and body tattoo: A case series and proposed algorithm to minimize lymph node biopsies.

The presence of mammographically evident hyperdense foci within axillary lymph nodes elicits concern for calcium deposits, which in turn have a wide differential diagnosis including both benign and malignant entities. Tissue sampling, most commonly by way of image-guided core needle biopsy, is needed in many cases when a definite etiology cannot be clinically established. In this case series we present history, imaging findings, and pathology results (or long term follow-up stability as biopsy surrogate) of several women with body tattoos who at mammography were noted to have a characteristic pattern of "bubbly" pseudo-calcifications within axillary lymph nodes, and absence of other mammographic, sonographic and clinical abnormalities.

Transient global amnesia associated with acute bacterial endocarditis; A case report

Introduction: Transient global amnesia (TGA) is a sudden loss of memory without definite etiology. Some cardiac conditions like myocardial infarction, mitral valve prolapse, takotsubo syndrome, and arrhythmias have been described in the literature as offenders. To our knowledge, there is no report of an association between TGA and endocarditis or even septicemia.Case presentation: The patient was a 52-year-old man with a history of hypertension and aortic valve surgery which was presented to the emergency department with TGA. On brain CT scan and MRI there was not any pathological finding and EEG revealed normal features without any epileptiform discharge. During evaluations, the diagnosis of acute bacterial endocarditis has been established by the presence of positive blood culture and vegetation on the aortic valve in trans-esophageal echocardiography. At 6 months follow-up, and after receiving appropriate antibiotic therapy and cardiac surgery, he was symptom-free.Conclusion: Association between TGA and cardiovascular disorders like myocardial infarction and takotsubo syndrome has been described. Neurological complications occur in about one-fourth of patients with infective endocarditis, but there is not any report of the association between TGA and acute bacterial endocarditis. Cardiovascular disorder studies are just limited to case reports without any clarification of mechanism and pathophysiology.

Uveitis in the elderly: Clinical and demographic characteristics

AbstractPurpose: To describe clinical characteristics and etiological profile of uveitis presenting for the first time in the elderly and explain its therapeutic challenges and evolutive particularities.Methods: Retrospective review of 170 patients in the department of ophthalmology in Fattouma Bourguiba University Hospital, in the period between January 2007 and January 2021.Results: During the study, 221 eyes of 170 patients were affected by uveitis. The mean age was 59.32 ± 7.32 years and a female gender predominance was registered (61.1% were women). The most prevalent anatomical pattern was anterior uveitis (45/170; 26.4%) followed by panuveitis (33.5%). According to laterality, bilateral involvement (53.6%) was more registered. The majority of cases were chronic (67.2%), acute cases occurred in 31.7%, the rest of the cases (10%) were recurrent. Idiopathic uveitis was diagnosed in 21 cases (12.3%). A definitive or presumed specific aetiology was determined in most of our cases (87.7%), the most common specific aetiology in our case series was sarcoidosis (15.2%) followed by ocular Tuberculosis (12.9%), Herpes simplex virus anterior uveitis (10.5%), and chronic recurrent Vogt‐Koyanagi‐Harada disease (9.4%). An Infectious aetiology was established in 39.4% of the cases and noninfectious systemic autoimmune causes accounted for 24.1%. 53 eyes (16.2%) of 33 patients (19.4%) presented complications during the studied period. The most common ocular complication was uveitic cataract occurring in 38% of the cases.Conclusions: Epidemiological characteristics of uveitis in the elderly population is different from other age categories, which should influence the diagnostic approach in these patients.

Study of thyroid lesions based on cytological and histopathological comparison

Thyroid swelling is one of the most common indications for surgical excision. Since most of the swellings are benign and with euthyroid status, these patients do not require surgical excision. Fine needle aspiration cytology is a rapid, efficient, inexpensive and safe diagnostic method in these cases. FNAC has some limitations, particularly limited to representatives of samples and exact typing of benign and malignant neoplastic lesions. Thus, FNAC alone may not give a confirmative diagnosis regarding few thyroid lesions. Hence, histopathological study has been the standard technique for the diagnosis of thyroid lesions. To study the accuracy of fine needle aspiration cytology (FNAC) of thyroid swellings and to correlate with histopathology so as to avoid unnecessary surgeries for benign lesions.This was a prospective study done on 55 cases wherein Fine Needle Aspiration cytology was done followed by histopathology. The reports on both modalities were correlated and sensitivity, specificity and accuracy were calculated. In the present study, females (72.7%) outnumbered males (27.2%). Non neoplastic lesions constituted 83.3% in our study. Among Non-neoplastic lesions, Nodular goiter was most commonly reported and constituted 49% cases. The sensitivity and specificity for thyroid FNAC are reasonably good. FNAC is a minimally invasive, low cost testing modality. It accurately diagnoses malignant thyroid lesions. It has good specificity and accuracy but is less sensitive in diagnosing definitive etiology. However, it is an important diagnostic test to guide the management of thyroid lesions.

RF17 | PMON23 Argentinian multicentric genetic study of pituitary hormonal deficiencies using a custom panel based on single molecule molecular inversion probes

Abstract Hypopituitarism with deficiency of one or more pituitary hormones (combined pituitary hormone deficiency or CPHD) can vary in severity and age at presentation. Additionally, the hormone abnormalities may evolve with time necessitating frequent evaluation. These hormonal deficits can also be present as part of a syndrome, with patients showing extrapituitary abnormalities such as eye or forebrain malformations. Over the past decade, there has been an explosion in the knowledge of the genetic cascade that orchestrates hypothalamic and pituitary development. Several transcription factors and signaling molecules are critical for cell differentiation and proliferation at a very early stage of gestation. However, more genes remain to be identified in order to provide patients with a definitive aetiology. We studied 95 children with congenital hypopituitarism from seven pediatric hospitals from Argentina. Children with non-endocrine, non-familial idiopathic short stature served as a control group (n=100). A custom exon capture panel based on single-molecule molecular inversion probes sequencing (MIPS) was performed in probands and parents. This panel tests 104 genes: including a selection of reported and candidate genes chosen from our knowledge of pituitary development in mice and PROP1 interacting proteins. We found at least 1 variant in 50 probands. The prevalence of known variants in the pituitary transcription factor genes PROP1 and PIT1 (frequently mutated in CPHD) was low in our cohort. A significant number of disease-causing variants were found in LHX3, LHX4, GLI2 and OTX2. An important advance of our study is the identification of pathogenic variants in recently discovered and novel genes. We found an heterozygous variant in the Roundabout (ROBO) receptor homolog 1 gene: ROBO1;p.Arg1504* in a patient with CPHD and septo-optic dysplasia (SOD); two variants in Steroid Receptor SRA1: p. Ile179Thr and p.Val110delinsArgLeu in a patient with CPHD and hypogonadism hypogonadotropic and a missense variant in Semaphorin 3A SEMA3A: p.Val588Leu in a case of CPHD and aortic coarctation. Our findings support evidence that the etiology of congenital hypopituitarism is highly heterogeneous and may be infrequently monogenic with full penetrance, underlying a more complex pathogenesis. Presentation: Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

PSAT331 A Rare Case of Thrombocytopenia in Concurrence With Severe Hypothyroidism: Are We Still Missing Something?

Abstract Introduction Hashimoto thyroiditis as an etiology of secondary thrombocytopenia is a very rare phenomenon but has been reported in literature. The concurrence of hypothyroidism and immune thrombocytopenia is not clearly understood. The theory to this association involves a metabolic process in which hypothyroidism induces a shorter life span in platelets through increased phagocytosis, and an immunologic process in which antibodies are formed against platelets and thyroid tissue. Literature suggests that achievement of a euthyroid state corrects the immune imbalance which subsequently improves thrombocytopenia. Although this association is still debatable, we present a case of severe thrombocytopenia in concurrence of severe hypothyroidism that responded to steroid and levothyroxine treatment. Case presentation An 85-year-old female presented to our facility with complaint of diffuse abdominal pain. Abdominal imaging revealed extensive stool throughout the colon. Labs were significant for hemoglobin of 9.1, as well as marked thrombocytopenia, with a platelet count of 9000. She was transfused one unit of platelets. A peripheral blood smear revealed markedly decreased platelets and further workup revealed an elevated TSH level of 62.5 with free T4 less than 0.25. HIV, HCV, B12 and folic acid levels were all within normal limits. Platelet antibody test for HLA class I, IA/IIA, IB/IX and IIB/IIIA antibodies were all negative. Serum protein electrophoresis and immunoglobulin levels of A, G, M, Kappa/lambda results were within normal limits. Patient was started on Levothyroxine, and received steroids which subsequently led to improvement in platelet count. Discussion Immune thrombocytopenia (ITP) is defined as low platelet count due to autoimmune destruction of platelets. Primary ITP also known as idiopathic, is ultimately a diagnosis of exclusion. Secondary ITP may be due to many underlying conditions such as HCV, HIV, DIC, SLE, sepsis, malignancies or drugs [1]. Our patient presented with marked thrombocytopenia without any of the aforementioned definite etiologies. However, the patient was noted to have profound hypothyroidism. Association of thyroid disorders have been described in few case reports and retrospective studies but still a debatable topic. A retrospective study by Shoko et al reviewed 248 patients with newly diagnosed ITP in for whom we had thyroid function data at diagnosis. Of the 248 patients with ITP, 74 patients also had thyroid disease, including 36 with overt thyroid disease (13 Graves’ disease and 23 Hashimoto's thyroiditis) and 38 with subclinical thyroid disease (3 hyperthyroidism and 35 hypothyroidism). Treatment for thyroid disease in 22 patients improved thrombocytopenia in 21 patients, especially in 4 patients who were not treated for ITP [2]. Conclusion Hashimoto thyroiditis is an uncommon etiology for the development of thrombocytopenia, and very few cases have been reported thus far. Hence, clinicians should be aware of this association in the appropriate clinical context when common etiologies are exhausted. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Molecular genetics in autism spectrum disorder: a case series

Autism spectrum disorder (ASD) has emerged as a fairly common yet heterogeneous condition. More evidence towards a large number of specific genetic variations in ASD are now identified. Often we encounter difficulties in counselling the parents on the disease origin. We present a case series of 6 children including a pair of twin sibling who were diagnosed as ASD with a definite genetic aetiology. These children belonged to the age group of 3 to 15 years and were diagnosed as ASD as per DSM V criteria. Of the 6 children, two were otherwise clinically normal and remaining four children had associated medical conditions including hypocalcemia, severe hypotonia, seizures, cardiomyopathy, intellectual disability and neuroregression. In view of an unrecognised aetiology and children being first born in the family, parents were counselled for a genetic evaluation. Genetic test reports revealed gene variation pathogenic for ASD, of which 4 of them had known syndromic association. Though intervention would mostly remain the same, genetic aetiology helped us in prognosticating and improved the family’s outlook towards the disease. Hence it is desirable to identify genetic variations in all possible ASD cases as it has the potential to improve family planning, trigger screening for co-occurring medical problems, aid the prognosis, and start specific interventions.

Metagenomic next-generation sequencing for the diagnosis of fever of unknown origin in pediatric patients with hematological malignancy

Background and aimsThe aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in identifying microbiological etiologies in pediatric patients with hematological malignancies undergoing fever of unknown origin (FUO). MethodsA total of 147 children with hematological malignancy suffering febrile diseases without definite microbiological etiologies under conventional tests were enrolled. The clinical record, serum inflammatory biomarkers and mNGS results were analyzed. ResultsAt least one microorganism was identified by mNGS in 112 of 147 patients (76.2 %). Two or more types of organisms were detected simultaneously in 35.7 % (40/112) of samples. Of the 112 cases with positive mNGS results, the reported microorganisms were considered as etiologies of fever in 50 (44.6 %) cases. The initial antimicrobial regimens were adjusted according to the mNGS results in 48 cases, with 41 patients’ febrile diseases resolved. Totally, 27.9 % (41/147) of patients benefit from mNGS. High IL-6 (>390 pg/mL) level was associated with bacterial infection and could help to interpret the results of mNGS. ConclusionmNGS is a novel approach to determine the microbiological etiology of FUO in hematological malignancy patients, which benefits about a quarter of all patients tested. Integration of IL-6 can improve the diagnostic precision of bacterial infection.

Genetic diagnosis for adult patients at a genetic clinic.

Clinical utility of genetic testing has rapidly increased in the past decade to identify the definitive diagnosis, etiology, and specific management. The majority of patients receiving testing are children. There are several barriers for genetic tests in adult patients; barriers may arise from either patients or clinicians. Our study aims to realize the detection rate and the benefits of genetic tests in adults. We conducted a prospective study of 10 adult patients who were referred to a genetic clinic. Exome sequencing (ES) was pursued in all cases, and chromosomal microarray (CMA) was performed for six cases. Our result is impressive; six cases (60%) received likely pathogenic and pathogenic variants. Four definitive diagnosis cases had known pathogenic variants in KCNJ2, TGFBR1, SCN1A, and FBN1, whereas another two cases revealed novel likely pathogenic and pathogenic variants in GNB1 and DNAH9. Our study demonstrates the success in genetic diagnosis in adult patients: four cases with definitive, two cases with possible, and one case with partial diagnosis. The advantage of diagnosis is beyond obtaining the diagnosis itself, but also relieving any doubt for the patient regarding any previous questionable diagnosis, guide for management, and recurrence risk in their children or family members. Therefore, this supports the value of genetic testing in adult patients.

Sudden Sensorineural Hearing Loss (SSNHL): Case Report

Background
 Sudden sensorineural hearing loss (SSNHL) commonly known as sudden deafness, is an unexplained, rapid loss of hearing either all at once or over a few days in which patients experience a sudden drop in hearing. It is commonly linked to infections, head trauma, autoimmune diseases, iatrogenic, severe infections, blood circulation problems, neurological disorders, such as multiple sclerosis, disorders of the inner ear, such as Ménière’s disease, and even metabolic disorders such as diabetes mellitus. We presented a case of sudden sensorineural hearing loss in a secondary hospital in Indonesia to add more knowledge on this topic.
 Case presentation 
 A 76-year-old male, had chief complain of a sudden right sided hearing loss. There were no other symptoms and he had no history of trauma to the ear. The patient had hypertension and consumed amlodipine and clonidine regularly. Patient had normal otoscopic and rhinoscopy examination results. Audiometry shown a hearing threshold of 37 dB in the left ear and 117 dB in the right ear, both in air and bone conducted pure-tone stimuli and tympanogram showed type As in both ears. A diagnosis of right ear sudden sensorineural hearing loss was made, and medical treatment consisted of methylprednisolone, acyclovir, mecobalamin, vitamin B6, ranitidine and omeprazole were given to the patient.
 Conclusion 
 Pathophysiology of this disease are labyrinthine viral infection, labyrinthine vascular compromise, intracochlear membrane ruptures, and immune-mediated inner ear disease. In our case, we suspect that both ischemic vascular disease and viral infection as the cause of ISHHL. If there is no definitive or treatable etiology found, treatment regimen should be dictated by the most likely factors involved, which were systemic steroids and acyclovir in our case.

The frequency and seasonal distribution of viral infection in patients with community-acquired pneumonia and its impact on the prognosis.

Studies on the effects of viral coinfection on bacterial pneumonia are still scarce in South Korea. This study investigates the frequency and seasonal distribution of virus infection and its impact on the prognosis in patients with community-acquired pneumonia (CAP). The medical records of CAP patients with definite etiology, such as viruses and bacteria, were retrospectively reviewed. Their epidemiologic and clinical characteristics, microbiologic test results, the severity of illness, and 30-day mortality were analyzed. Among 150 study subjects, 68 patients (45.3%) had viral infection alone, 47 (31.3%) had bacterial infection alone, and 35 (23.3%) had viral-bacterial coinfection, respectively. Among 103 patients with viral infections, Influenza A virus (44%) was the most common virus, followed by rhinovirus (19%), influenza B (13%), and adenovirus (6%). The confusion-urea-respiratory rateblood pressure-age of 65 (CURB-65) score of the viral-bacterial coinfection was higher than that of the viral infection (median [interquartile range]: 2.0 [1.0-4.0] vs. 2.0 [0.3-3.0], P=0.029). The 30-day mortality of the viral infection alone group (2.9%) was significantly lower than that of bacterial infection alone (19.1%) and viral-bacterial coinfection (25.7%) groups (Bonferroni-corrected P<0.05). Viral-bacterial coinfection was the stronger predictor of 30-day mortality in CAP (odds ratio [OR], 18.9; 95% confidence interval [CI], 3.0-118.3; P=0.002) than bacterial infection alone (OR, 6.3; 95% CI, 1.1-36.4; P=0.041), compared to viral infection alone on the multivariate analysis. The etiology of viral infection in CAP is different according to regional characteristics. Viral-bacterial coinfection showed a worse prognosis than bacterial infection alone in patients with CAP.

Window Deroofing with Dental Roll Suturing for Pseudocyst Pinna, Simple Solution for Notorious Disease

Background: Pseudocyst of the pinna is a benign cystic lesion on the lateral surface of the pinna with no definitive etiology or treatment. Various methods are currently used to manage this disease. Most of the treatment options are prone to disease recurrence and are associated with cosmetic sequelae. We report 16 cases of unilateral pseudocyst that were treated with window deroofing and pressure dressing with dental roll suturing. Aim: This study aimed to study the effectiveness of window deroofing with dental roll suturing in the treatment of pseudocyst of the auricle with respect to recurrence and postprocedural sequelae. Materials and Methods: A prospective study at a tertiary care center for 2 years, which included 16 patients with a diagnosis of pseudocyst pinna. All the patients were treated by excising a small triangular piece of skin along with perichondrium, followed by dental roll suturing for pressure dressing; and were followed up after 1 week and 1 month of surgery. Results: All 16 cases were completely relieved of the disease at the end of 1 month. None of our patients had a recurrence and only 2 cases (12.5%) showed thickening of the pinna skin. Conclusions: The surgical treatment by window deroofing with dental roll suturing technique gave a reliable result in all cases of pseudocyst pinna with no evidence of recurrence and acceptable cosmetic results.

Contribution and Effectiveness of Laboratory Testing in the Diagnostic Assessment of Juvenile Ischemic Stroke and Transient Ischemic Attack.

IntroductionStrokes in young people require an extensive diagnostic workup to detect their possible several etiopathogenetic mechanisms. There is no consensus indicating what and when it should be tested. The clinical benefit and cost-effectiveness ratio of laboratory tests is unclear as well.MethodsIn one series of 104 consecutive juvenile ischemic stroke patients, under 45 years old, admitted between January 1, 2012, and December 31, 2017, we considered a wide panel of laboratory biomarkers exploring both the patient’s basal status and specific risk factors for thrombotic disorders. To combine conventional and unconventional risk factors, structural defects, and other stroke-related diseases, we defined four categories of etiologic probability. We then studied the contribution of laboratory testing in changing the rate of “definite or probable stroke etiology” and the “proportion of patients with at least one additional risk factor” for stroke.ResultsThe mere clinical assessment clarified stroke etiopathogenesis in 31% of cases. Abnormal values of the panel of biomarkers we considered were found in 30.1% of young ischemic strokes, while 11.5% of patients had unclear or borderline values. The benefit of laboratory assessment consisted of a relevant 14% gain in patients with a “definite or probable stroke etiology.”ConclusionSeveral areas of uncertainty are still pending and herein discussed, such as the low re-testing rate during follow-up and the neglect of some relevant biomarkers. However, our results support the importance of laboratory testing in this setting. An improvement of diagnostic protocols in juvenile ischemic stroke would even increase their effectiveness, and this is still an unsolved issue in the field of cerebrovascular diseases. The same age limit, conventionally considered for juvenile stroke, could be better defined according to the effectiveness of both laboratory and clinical assessment in identifying unconventional stroke risk factors.

GARBHOPAGHATAKARA BHAVA, PRECONCEPTIONAL RISK FACTORS FOR AUTISM: A CROSS-SECTIONAL SURVEY

Background: Garbhopaghatakara bhava, inclusive of altered maternal habits, diet, behaviours, and exposures in the perinatal period disrupt normal growth and development of the foetus. Autism spectrum disorders (ASD) are characterized by impaired social behaviour and communication skills. Many risk factors for ASD are identified but with no generalization of definite aetiology. Psychosocial anomalies in Ayurveda have been explained under the spectrum of unmada. Such diseases are said to present early in life and persist throughout the lifespan when associated with garbhopaghatakara bhava. This study explores the association of garbhopaghatakara bhava with the etiopathogenesis of ASD. Materials and Methods: Parents of 50 children who have ASD enquired about garbhopaghatakara bhava using a structured survey format. Results: Male preponderance (80%) with middle socio-economic strata (62%) predominated the study population. 48% had delayed speech and communication with poor eye contact, and 24% with delay in gross motor milestones. Garbhopaghatakara bhava leading to ashaya dushti (structural and functional variation in uterine milieu) were secondary to abortions (22%), hypothyroidism (10%), advanced parental age (64%), diabetes mellitus (8%). Amongst diet and activities in the mother, madhura- katu rasa (22%), eating less (28%), frequent meals (28%), day sleep (42%), night wakening (54%), excess travel (18%) and withhold of urges (16%) were seen. The genetic risk was sporadic (14%). Discussion: Garbhopaghatakara bhava can act by changing the epigenetics or disturbing the nutrition, psyche, and intellectual faculties in the child. Conclusion: Baseline information about the association of garbhopaghatakara bhava with ASD was identified. However, further analytical studies can provide substantial information and evidence.

The role of p53-MDM2 signaling in missed abortion and possible pathogenesis.

Missed abortion is one of the common obstetrical and gynecological complications, angiogenesis is the most important factor in fetal and placental development. However, the definite etiology and pathogenesis are not fully understood. The mRNA levels of p53, MDM2, VEGF, and HIF-lα were detected in 60 villous samples of missed abortion patients and 64 healthy controls by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Immunohistochemistry was used to explore the expression and correlation of p53, MDM2, VEGF, and HIF-lα in villous tissues. Furthermore, we upregulated MDM2 expression in JEG-3 and BeWo cells under hypoxia, combined with Nutlin3, the cell cycle was determined using flow cytometry and the expressions of p53, MDM2, VEGF, and HIF-1α were determined by qRT-PCR and western blot. qRT-PCR demonstrated that the expressions of p53, MDM2, and HIF-1α were significantly increased and VEGF was decreased in missed abortion group compared with normal pregnancies. Correlation analysis found that p53 was positively correlated with MDM2 and HIF-1α, and negatively correlated with VEGF in missed abortion group. After administration of Nutlin3, overexpression of MDM2 could arrest cell cycle in G1 phase and reduce the proportion of S phase. The expression of p53 and MDM2 of JEG-3 cells and BeWo cells which transfected with pcDNA3.1-MDM2 plasmid were markedly increased after Nutlin3 addition under hypoxic conditions, while the expression of VEGF and HIF-1α decreased. Our data indicated that during the development of villi in early pregnancy, p53-MDM2 signaling regulate cell cycle and angiogenesis through interaction with HIF-1α and VEGF, which may be a crucial factor affecting pregnancy outcomes.

The Role of Neuro-Immune Interaction in Chronic Pain Conditions; Functional Somatic Syndrome, Neurogenic Inflammation, and Peripheral Neuropathy.

Functional somatic syndromes are increasingly diagnosed in chronically ill patients presenting with an array of symptoms not attributed to physical ailments. Conditions such as chronic fatigue syndrome, fibromyalgia syndrome, or irritable bowel syndrome are common disorders that belong in this broad category. Such syndromes are characterised by the presence of one or multiple chronic symptoms including widespread musculoskeletal pain, fatigue, sleep disorders, and abdominal pain, amongst other issues. Symptoms are believed to relate to a complex interaction of biological and psychosocial factors, where a definite aetiology has not been established. Theories suggest causative pathways between the immune and nervous systems of affected individuals with several risk factors identified in patients presenting with one or more functional syndromes. Risk factors including stress and childhood trauma are now recognised as important contributors to chronic pain conditions. Emotional, physical, and sexual abuse during childhood is considered a severe stressor having a high prevalence in functional somatic syndrome suffers. Such trauma permanently alters the biological stress response of the suffers leading to neuroexcitatory and other nerve issues associated with chronic pain in adults. Traumatic and chronic stress results in epigenetic changes in stress response genes, which ultimately leads to dysregulation of the hypothalamic-pituitary axis, the autonomic nervous system, and the immune system manifesting in a broad array of symptoms. Importantly, these systems are known to be dysregulated in patients suffering from functional somatic syndrome. Functional somatic syndromes are also highly prevalent co-morbidities of psychiatric conditions, mood disorders, and anxiety. Consequently, this review aims to provide insight into the role of the nervous system and immune system in chronic pain disorders associated with the musculoskeletal system, and central and peripheral nervous systems.

When All Is Not as It Seems: Recurrent Fever and New-onset Joint Pain in a 17-Month-old Girl.

When All Is Not as It Seems: Recurrent Fever and New-onset Joint Pain in a 17-Month-old Girl.

Cochlear Implantation Outcomes in Patients with Auditory Neuropathy Spectrum Disorder of Genetic and Non-Genetic Etiologies: A Multicenter Study.

With diverse etiologies and clinical features, the management of pediatric auditory neuropathy spectrum disorder (ANSD) is often challenging, and the outcomes of cochlear implants (CIs) are variable. This study aimed to investigate CI outcomes in pediatric patients with ANSD of different etiologies. Thirty-six children with ANSD who underwent cochlear implantation between 2001 and 2021 were included. Comprehensive etiological analyses were conducted, including a history review, next-generation sequencing-based genetic examinations, and imaging studies using high-resolution computed tomography and magnetic resonance imaging. Serial behavioral and speech audiometry were performed before and after surgery, and the outcomes with CI were evaluated using the Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) scores. By etiology, 18, 1, 1, and 10 patients had OTOF-related, WFS1-related, OPA1-related, and cochlear nerve deficiency (CND)-related ANSD, respectively. Six patients had no definite etiology. The average CI-aided behavioral threshold was 28.3 ± 7.8 dBHL, and those with CND-related ANSD were significantly worse than OTOF-related ANSD. The patients’ median CAP and SIR scores were 6 and 4, respectively. Favorable CI outcomes were observed in patients with certain etiologies of ANSD, particularly those with OTOF (CAP/SIR scores 5–7/2–5), WFS1 (CAP/SIR score 6/5), and OPA1 variants (CAP/SIR score 7/5). Patients with CND had suboptimal CI outcomes (CAP/SIR scores 2–6/1–3). Identifying the etiologies in ANSD patients is crucial before surgery and can aid in predicting prognoses.

Metagenomic Next-Generation Sequencing Successfully Detects Pulmonary Infectious Pathogens in Children With Hematologic Malignancy.

BackgroundPulmonary infection is a leading cause of mortality in pediatric patients with hematologic malignancy (HM). In clinical settings, pulmonary pathogens are frequently undetectable, and empiric therapies may be costly, ineffective and lead to poor outcomes in this vulnerable population. Metagenomic next-generation sequencing (mNGS) enhances pathogen detection, but data on its application in pediatric patients with HM and pulmonary infections are scarce.MethodsWe retrospectively reviewed 55 pediatric patients with HM and pulmonary infection who were performed mNGS on bronchoalveolar lavage fluid from January 2020 to October 2021. The performances of mNGS methods and conventional microbiological methods in pathogenic diagnosis and subsequently antibiotic adjustment were investigated.ResultsA definite or probable microbial etiology of pulmonary infection was established for 50 of the 55 patients (90.9%) when mNGS was combined with conventional microbiological tests. The positive rate was 87.3% (48 of 55 patients) for mNGS versus 34.5% (19 of 55 patients) with conventional microbiological methods (P < 0.001). Bacteria, viruses and fungi were detected in 17/55 (30.9%), 25/55 (45.5%) and 19/55 (34.5%) cases using mNGS, respectively. Furthermore, 17 patients (30.9%) were identified as pulmonary mixed infections. Among the 50 pathogen-positive cases, 38% (19/50) were not completely pathogen-covered by empirical antibiotics and all of them were accordingly made an antibiotic adjustment. In the present study, the 30-day mortality rate was 7.3%.ConclusionmNGS is a valuable diagnostic tool to determine the etiology and appropriate treatment in pediatric patients with HM and pulmonary infection. In these vulnerable children with HM, pulmonary infections are life-threatening, so we recommend that mNGS should be considered as a front-line diagnostic test.

Genetic characteristics of microtia-associated syndromes in neonates

Microtia is the second most common maxillofacial birth defect in neonates and has an prevalence rate of 3.06/10 000 in China, and 20%-60% of microtia cases is associated with a certain type of syndrome. This article elaborates on the clinical phenotypes and genetic characteristics of three microtia-associated syndromes (MASs) with high prevalence, high incidence rate of ear deformity, and definite genetic etiology, i.e., oculo-auriculo-vertebral spectrum, branchio-oto-renal spectrum disorder, and Treacher-Collins syndrome, and summarizes another three common MASs, so as to provide a reference for the genetic diagnosis of neonatal MAS.