Etiological Diagnosis Research Articles

Redefining chronic mountain sickness: insights from high-altitude research and clinical experience

Abstract Chronic Mountain Sickness (CMS), characterized by increased red blood cells above average values traditionally attributed to chronic hypobaric hypoxia exposure, is being redefined in light of recent research and clinical experience. We propose a shift in perspective, viewing CMS not as a singular entity but as Poly-erythrocythemia (PEH), as the Hematocrit/Hemoglobin/Red Blood Cells (Ht/Hb/RBCs) increase constitutes a sign, not a disease reflecting a spectrum of oxygen transport alterations in multiple diseases in the chronic hypoxia environment in high-altitude populations. Drawing on over five decades of experience at the High Altitude Pulmonary and Pathology Institute (HAPPI-IPPA) in Bolivia, we advocate for altitude-specific blood parameter norms and emphasize the importance of correct etiological diagnosis for effective management. This updated understanding not only aids in managing chronically hypoxemic patients at various altitudes but also offers valuable insights into global health challenges, including the recovery from COVID-19.

Etiologic Diagnosis of Genetic Hearing Loss in an Ethnically Diverse Deafness Cohort.

Hearing loss is a common sensory disorder that impacts patients across the lifespan. Many genetic variants have been identified that contribute to non-syndromic hearing loss. Yet, genetic testing is not routinely administered when hearing loss is diagnosed, particularly in adults. In this study, genetic testing was completed in patients with known hearing loss. A total of 104 patients who were evaluated for hearing loss were enrolled and received genetic testing. Of those 104 patients, 39 had available genetic testing, 20 had one missing allele, and 45 yielded no genetic diagnosis. Of the 39 cases with genetic testing data, 24 were simplex cases, and 15 were multiplex cases. A majority of patients presented with an autosomal recessive inheritance pattern (n = 32), 26 of whom presented with congenital hearing loss. 38% of cases were positive for GJB2 mutation with c.35delG being the most common pathogenic variant. These findings are consistent with previous literature suggesting GJB2 mutations are the most common causes of non-syndromic hearing loss. Given the frequency of genetic variants in patients with hearing loss, genetic testing should be considered a routine part of the hearing loss work-up, particularly as gene therapies are studied and become more widely available. Many genetic variants have been identified that contribute to non-syndromic hearing loss. Given the frequency of genetic variants in patients with hearing loss, genetic testing should be considered a routine part of the hearing loss work-up.

Management and outcomes among patients with hard-to-heal ulcers in Sweden: a national mapping of data from medical records, focusing on diagnoses, ulcer healing, ulcer treatment time, pain and prescription of analgesics and antibiotics

ObjectiveTo investigate whether patients with hard-to-heal ulcers in Sweden were treated according to an aetiological diagnosis and to explore ulcer healing, treatment time, ulcer-related pain and the prescription of analgesics...

In-depth exploration of differences of sex development: 5-year experience in a tertiary center.

Differences/disorders of sex development (DSD) encompass a wide range of conditions. Their clinical spectrum and etiological diagnosis have not been reported in Moroccan patients. The study aims to highlight the clinical spectrum, etiological diagnosis, and management of patients with DSD. This is a retrospective study of all patients diagnosed with DSD under the age of 18 years, who were referred to the Pediatric Endocrinology Department and the Medical Genetics Laboratory at HASSAN II University Hospital of Fez between June 2018 and June 2023. Out of 57 patients, 54.4% (n = 31) were diagnosed with 46,XX DSD, the most common type, while 45.6% (n = 26) had 46,XY DSD. Patients with 46,XX DSD presented earlier than those with 46,XY DSD, at a median age of 0.08 years and 0.96 years, respectively. The most commonly reported complaint was atypical genitalia. At the first presentation, the sex of rearing was already assigned to 26 males and 27 females. All patients with 46,XX DSD were diagnosed with congenital adrenal hyperplasia (CAH) at a median age of diagnosis of 0.92 years. Of these, 11 patients were raised as males. Disorders of androgen action or synthesis were more common in XY patients (69.2%). The consanguinity rate was 46.5%, and there were 19 cases with a positive family history, with 10 siblings having died. DSD are not rare in Morocco. Overall, CAH remains the most frequent DSD etiology. Molecular genetic analyses are needed to determine the accurate etiological distribution of DSD, especially in XY patients.

Respiratory illness in young and adult cattle caused by bovine viral diarrhea virus subgenotype 2b in singular and mixed bacterial infection in a BVDV-vaccinated dairy herd.

Bovine respiratory disease (BRD) is a common global health problem in dairy cattle. The definitive diagnosis of BRD is complex because its etiology involves several predisposing and determining factors. This report describes the etiology of a BRD outbreak in a dairy herd in the mesoregion of Central Eastern Paraná, which simultaneously affected young (calves and heifers) and adult (cows) Holstein-Friesian cattle. Nine biological samples, consisting of five lung samples from two cows and three suckling calves, and four nasal swab samples from heifers, were used for etiological diagnosis. The nucleic acids extracted from lung fragments and nasal swabs were subjected to PCR and RT-PCR assays for partial amplification of the genes of five viruses [bovine viral diarrhea virus (BVDV), bovine alphaherpesvirus 1 (BoAHV1), bovine respiratory syncytial virus (BRSV), bovine parainfluenza virus 3 (BPIV-3), and bovine coronavirus (BCoV)] and four bacteria (Mycoplasma bovis, Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni) involved in the etiology of BRD. All nine biological samples from the animals with BRD tested negative for BoAHV1, BRSV, BPIV-3, BCoV, and H. somni. Therefore, the involvement of these microorganisms in the etiology of BRD outbreak can be ruled out. It was possible to identify the presence of BVDV and M. bovis in singular and mixed infections of the lower respiratory tract in cattle. BVDV was also identified in two nasal swabs: one as a single etiological agent and the other in association with two bacteria (P. multocida and M. haemolytica). The phylogenetic analysis conducted in the nucleotide sequence of the 5'UTR region and Npro gene of the BVDV amplicons demonstrated that the BVDV field strains of this BRD outbreak belong to subgenotype 2b. To the best of our knowledge, this is the first report of BVDV-2b involvement in the etiology of BRD in Brazil. Finally, it is necessary to highlight that the cattle were obtained from an open dairy herd with biannual vaccinations for BVDV-1a and - 2a.

Paenibacillus lautus: A new foe in endogenous endophthalmitis.

To discuss the diagnosis and management of a rare case of endogenous endophthalmitis (EE) caused by Paenibacillus lautus mimicking granulomatous uveitis in a child, highlighting the use of 16S rRNA gene amplicon sequencing as an accurate method to identify rare pathogens. A retrospective chart review of the clinical presentation, microbiologic workup-including microscopy, culture, antibiotic susceptibility, and polymerase chain reaction for pathogen DNA of clinical samples-and the clinical management of the case were recorded. A 13-year-old boy presented with decreased vision in the right eye for one month. On examination, he had uveitis with hypopyon and complicated cataract. The case underwent an anterior chamber tap followed by vitrectomy and lensectomy. The culture of the vitreous aspirate grew Gram-variable bacilli that could not be identified by conventional microbiological techniques. However, PCR-based sequencing of the 16S rRNA gene was performed, and the bacterium was identified as P. lautus. The patient subsequently developed rhegmatogenous retinal detachment, for which he underwent endo laser photocoagulation and oil tamponade. Four months later, silicone oil was removed, and an intraocular lens was implanted. At six weeks follow-up, the retina remained well attached, and intraocular pressure was maintained. P. lautus can cause EE and mimic granulomatous uveitis. Techniques such as 16S rRNA gene sequencing can significantly facilitate aetiological diagnosis in cases where conventional methods fail.

Determinants of possible inflammatory myocardial damage in acute intestinal infections in children

BACKGROUND: Non-coronary cardiomyopathies, including inflammatory cardiomyopathies, are one of the leading causes of disability and mortality in children and adults. Inflammatory cardiomyopathy in most cases is an outcome of myocarditis as a result of direct agent-dependent myocardial damage or autoimmune reactions in the absence of genetic predisposition. AIM: On the basis of clinical assessment of cardiovascular system changes, to develop a discriminant model to predict the possibility of myocardial damage of inflammatory genesis in acute intestinal infections (AII) in children. MATERIALS AND METHODS: In the Intestinal Infections Department of the Children’s Research and Clinical Center for Infectious Diseases of FMBA of Russia in the period 2020-2022, 33 children aged from 1 month to 13 years with AII of different etiology were consecutively observed, in whom, according to clinical, laboratory and instrumental examination data, for the first time in their lives, changes in cardiovascular system were detected. The sample was formed using an algorithm for diagnosing inflammatory myocardial lesions in points, the sum of which concluded that there were no or presence of such, which allowed us to identify group 1 (n = 24) and group 2 (n = 9), respectively. Etiological diagnosis of acute intestinal infections was performed in all children, clinical and laboratory data, results of a 12-channel electrocardiogram (ECG), transthoracic echocardiography (EchoCG) were evaluated. The differences in the groups were revealed using the Pearson chi-squared test and the Mann–Whitney test, which were considered reliable at p 0.05. The method of discriminant analysis was used. RESULTS: Functional systolic noise and increased cardiospecific enzymes were observed less frequently in group 1 than in group 2 (4.2%; 22.2% and 67%; 100%). Of the pathological ECG changes, violations of the repolarization process were observed (16.7%; 33.3%). No significant changes in the Echo-KG were detected. The viral etiology of acute intestinal infections dominated (79.2%; 88.9%). Changes in the hemogram were characterized by a high frequency of leukocytosis in group 1 (29.2%; 0%) and leukopenia in group 2 (4.2%; 22.2%). In group 1, there was a higher frequency of neutrophilosis (79.2%; 44.4%), rod-shaped shift (62.5%; 22.2%), thrombocytosis (29.2%; 0%), lymphocytopenia (95.8%; 55.6%; p 0.05), monocytosis (8.3%; 0%); increased C-reactive protein (41.7%; 33.3%), ALT (29.2%; 11.1%), urea (29.2%; 11.1%), leukocyturia (16.7%; 0%). CONCLUSIONS: Clinical evaluation of cardiovascular system changes in children with acute intestinal infections using a discriminant model allows to exclude myocardial damage of inflammatory genesis with high probability (95.7%), which is of practical importance.

The etiological profile of chronic organic non-bloody diarrhea in India: Emergence of inflammatory bowel disease as a dominant cause.

Chronic non-bloody diarrhea may be attributed either to functional or organic diseases. The latter category may present with malabsorption syndrome if there is extensive involvement of the small bowel, whereas diseases of the large bowel may only present with diarrhea sans malabsorption. Indian data has predominantly focussed on the etiological spectrum of malabsorption syndrome in adults. The primary aim of the current study was to evaluate etiological spectrum of chronic organic non-bloody diarrhea in India. This prospective observational study was done at a tertiary care hospital in North India. Patients ≥ 18years presenting with chronic non-bloody diarrhea of > 4weeks duration were enrolled in the study after exclusion of patients with IBS and anal incontinence. During the study period of 12months, 100 patients with chronic organic non-bloody diarrhea were evaluated. A definite etiological diagnosis was made in 97 patients (97%). The mean age of the patients was 48 ± 16.7years (58% males). The median duration of diarrhea was 5.5months (interquartile range [IQR] 3.5, 11). Inflammatory bowel disease (IBD) accounted for 45% of the cases making it the predominant cause for organic diarrhea. GI infections and adult-onset celiac disease accounted for 18% and 9% of the cases, respectively. Pancreatic disease, benign or neoplastic, accounted for 6% of the total cases. Notably, gastrointestinal (GI) malignancies manifesting as chronic non-bloody diarrhea were diagnosed in 5% of the patients. Our data suggests a paradigm shift in the etiological spectrum of chronic organic non-bloody diarrhea in India with the emergence of IBD as the predominant cause displacing GI infections.

Relative Value of Immunohistochemistry in Detection of Mycobacterial Antigen in Suspected Cases of Tuberculosis in Tissue Section.

Due to its infectious nature, complex immunological response, chronic progression, and the necessity for long-term treatment, tuberculosis has always been a major health burden. Immunohistochemistry (IHC) has the capacity to highlight the occurrence of mycobacterial antigens for tissue diagnosis. This study was conducted to understand the advantage of immunostaining over culture of Mycobacterium tuberculosis. A cross-sectional study was conducted on 30 samples of suspected cases of tuberculosis. Specimens received were fixed in 10% formalin and processed; 3-5 µm thick sections were made from paraffin block, stained with hematoxylin and eosin, Ziehl-Neelsen stain, and immunohistochemistry. Culture was done using Lowenstein-Jensen medium. Immunohistochemistry was interpreted as fine granular brownish cytoplasmic, coarse granular brownish cytoplasmic, and bacillus staining. Out of the 30 samples studied, 12 (40.0%) were culture positive while 20 (66.7%) of them were IHC positive. Immunohistochemistry showed 17 granulomatous lesions of which 11 (55.0%) were well-formed granulomas. The sensitivity and negative predictive value were found to be high with immunohistochemistry, while specificity and positive predictive value were found to be on the lower side. Among the 20 positive IHC cases, the degree of staining was fine granular cytoplasmic staining in 13 cases (65.0%) and coarse granular staining in 7 cases (35.0%). Immunohistochemistry is a reliable test with high sensitivity as well as high negative predictive value which can be done rapidly for establishing an etiological diagnosis of tuberculosis in histologic specimens.

Traumatic Brain Injury, Seizures, and Cognitive Impairment Among Older Adults

Traumatic brain injury (TBI), seizures, and dementia increase with age. There is a gap in understanding the associations of TBI, seizures, and medications such as antiseizure and antipsychotics with the progression of cognitive impairment across racial and ethnic groups. To investigate the association of TBI and seizures with the risk of cognitive impairment among cognitively normal older adults and the role of medications in moderating the association. This multicenter cohort study was a secondary analysis of the Uniform Data Set collected between June 1, 2005, and June 30, 2020, from the National Alzheimer's Coordination Center. Statistical analysis was performed from February 1 to April 3, 2024. Data were collected from participants from 36 Alzheimer's Disease Research Centers in the US who were 65 years or older at baseline, cognitively normal at baseline (Clinical Dementia Rating of 0 and no impairment based on a presumptive etiologic diagnosis of AD), and had complete information on race and ethnicity, age, sex, educational level, and apolipoprotein E genotype. Health history of TBI, seizures, or both conditions. Progression to cognitive impairment measured by a Clinical Dementia Rating greater than 0. Among the cohort of 7180 older adults (median age, 74 years [range, 65-102 years]; 4729 women [65.9%]), 1036 were African American or Black (14.4%), 21 were American Indian or Alaska Native (0.3%), 143 were Asian (2.0%), 332 were Hispanic (4.6%), and 5648 were non-Hispanic White (78.7%); the median educational level was 16.0 years (range, 1.0-29.0 years). After adjustment for selection basis using propensity score weighting, seizure was associated with a 40% higher risk of cognitive impairment (hazard ratio [HR], 1.40; 95% CI, 1.19-1.65), TBI with a 25% higher risk of cognitive impairment (HR, 1.25; 95% CI, 1.17-1.34), and both seizure and TBI were associated with a 57% higher risk (HR, 1.57; 95% CI, 1.23-2.01). The interaction models indicated that Hispanic participants with TBI and seizures had a higher risk of cognitive impairment compared with other racial and ethnic groups. The use of antiseizure medications (HR, 1.23; 95% CI, 0.99-1.53), antidepressants (HR, 1.32; 95% CI, 1.17-1.50), and antipsychotics (HR, 2.15; 95% CI, 1.18-3.89) was associated with a higher risk of cognitive impairment, while anxiolytic, sedative, or hypnotic use (HR, 0.88; 95% CI, 0.83-0.94) was associated with a lower risk. This study highlights the importance of addressing TBI and seizures as risk factors for cognitive impairment among older adults. Addressing the broader social determinants of health and bridging the health divide across various racial and ethnic groups are essential for the comprehensive management and prevention of dementia.

Whole Exome Sequencing Revealing a Novel PBX1 Gene Variant in a Chinese Family Causing Recurrent Neonatal Death.

Causative mutations of PBX1 are associated with congenital abnormalities of the kidney and urinary tract (CAKUT), often accompanied by hearing loss, abnormal ear morphology, or developmental delay. The aim of the present investigation was to introduce a novel variant in the PBX1 gene identified in a Chinese family, leading to recurrent neonatal mortality. A pregnant woman (gravida 5, para 0), who had experienced recurrent neonatal deaths, sought genetic etiology diagnosis. Whole exome sequencing (WES) was conducted to identify sequence variants and copy number variants in the fetus presenting with posterior nuchal cystic hygroma and fetal hydrops. A novel NM_002585.4:c.694G>C(p.D232H) in PBX1 was identified in the fetus through trio whole exome sequencing (WES), revealing a paternal mosaic PBX1 variant in blood at 11.54% (6/52 variants reads). Subsequent parental Sanger sequencing confirmed the variant detected by WES. Ultimately, the variant was classified as likely pathogenic, leading the family to elect pregnancy termination at 17 weeks gestation. The novel variant in the PBX1 gene appears to be a significant factor contributing to recurrent neonatal deaths in the Chinese family. Such findings expand the spectrum of PBX1 gene variants and provide valuable perinatal guidance for diagnosing fetuses with PBX1 mutations.

Detection of caprine paratuberculosis (Johne's disease) in pre- and post-vaccinated herds: morphological diagnosis, lesion grading, and bacterial identification.

Samples from the mesenteric lymph nodes (MS LNs) and ileocecal valves (ICV) of 105 goats, comprising 61 non-vaccinated and 44 vaccinated against Mycobacterium avium subspecies paratuberculosis (MAP), were collected at slaughter from a farm with a confirmed history of paratuberculosis (PTB). These goats had subclinical infections. PTB-compatible lesions in the MS LNs, ICV lamina propria (LP), and Peyer's patches (PPs) were graded separately. Furthermore, the load of acid-fast bacilli was quantified using Ziehl-Neelsen staining (ZN), MAP antigens by immunohistochemistry (IHC), and MAP DNA by PCR targeting the IS900 sequence. Gross PTB-compatible lesions were found in 39% of the goats, with 31.72% vaccinated (V) and 68.29% non-vaccinated (nV). Histopathological lesions induced MAP were observed in 58% of the animals, with 36.07% vaccinated and 63.93% non-vaccinated. The inclusion of histopathology as a diagnostic tool led to a 28% increase in diagnosed cases in MS LNs and 86.05% in ICV. Grade IV granulomas with central mineralization and necrosis were the most common lesions in MS LNs. In the ICV, mild granulomatous enteritis with multifocal foci of epithelioid macrophages was predominant, occurring more frequently in the PPs than in the LP. Furthermore, statistical differences in the presence of histopathological lesions between vaccinated and non-vaccinated goats were noted in MS LNs, ICV LPs, and ICV PPs. Non-vaccinated animals showed higher positivity rates in ZN, IHC, and PCR tests, underscoring the benefits of anti-MAP vaccination in reducing PTB lesions and bacterial load in target organs. Our findings emphasize the necessity of integrating gross and histopathological assessments with various laboratory techniques for accurate morphological and etiological diagnosis of PTB in both vaccinated and non-vaccinated goats with subclinical disease. However, further studies are required to refine sampling protocols for subclinical PTB in goats to enhance the consistency of diagnostic tools.

Оценка некоторых закономерностей процессов перекисного окисления липидов при увеитах у детей

Original article Assessment of some patterns of lipid peroxidation processes in uveitis in children O.S. Komarov, M.R. Guseva, S.A. Obrubov, N.M. Galkina Pirogov Russian National Research Medical University, Moscow, Russian Federation Uveitis is characterized by a variety of clinical forms, chronic and recurrent course, severe outcomes, and not always effective therapy. In addition, etiological diagnosis and treatment of patients require more subtle and advanced laboratory methods and deciphering the incompletely studied mechanisms of the pathogenesis of the disease. The work, based on significant clinical material, shows that the activation of polymorphonuclear leukocytes (PMN) in the blood is one of the main reasons for the increased processes of lipid peroxidation (LPO) in uveitis. The activity levels of PMN and LPO clearly correlate and reflect the degree of depth and dynamics of the inflammatory process in uveitis. These indicators more subtly characterize the course of the disease and the dynamics of recovery compared to traditional generally accepted criteria for assessing inflammation. Simultaneous study of the intensity of PMN and LPO on the one hand and assessment of the antioxidant activity (AOA) of the system makes it possible to predict the course of the disease, prescribe adequate therapy and judge the severity and completeness of the process. It has been proven that one of the main blood antioxidant proteins, ceruloplasmin, changes parallel to the clinical picture of uveitis, which can be used as a basis for prescribing antioxidant therapy or for assessing the effectiveness of treatment. Key words: uveitis, lipid peroxidation, antioxidants, ceruloplasmin, polymorphonuclear leukocytes

Spontaneous Non-Aneurysmal Convexity Subarachnoid Hemorrhage: A Scoping Review of Different Etiologies beyond Cerebral Amyloid Angiopathy.

Spontaneous convexity subarachnoid hemorrhage (cSAH) is a vascular disease different from aneurysmal SAH in neuroimaging pattern, causes, and prognosis. Several causes might be considered in individual patients, with a limited value of the patient's age for discriminating among these causes. Cerebral amyloid angiopathy (CAA) is the most prevalent cause in people > 60 years, but reversible cerebral vasoconstriction syndrome (RCVS) has to be considered in young people. CAA gained attention in the last years, but the most known manifestation of cSAH in this context is constituted by transient focal neurological episodes (TFNEs). CAA might have an inflammatory side (CAA-related inflammation), whose diagnosis is relevant due to the efficacy of immunosuppression in resolving essudation. Other causes are hemodynamic stenosis or occlusion in extracranial and intracranial arteries, infective endocarditis (with or without intracranial infectious aneurysms), primary central nervous system angiitis, cerebral venous thrombosis, and rarer diseases. The diagnostic work-up is fundamental for an etiological diagnosis and includes neuroimaging techniques, nuclear medicine techniques, and lumbar puncture. The correct diagnosis is the first step for choosing the most effective and appropriate treatment.

Upper Gastrointestinal Bleeding in Patients with Chronic Renal Failure: What are the Particularities?

Introduction: Upper Gastrointestinal bleeding (UGIB) is a major cause of mortality in patients with renal failure. The aim of our study is to determine the epidemiological, lesional and prognostic profile of UGIB in chronic kidney disease (CKD) patients. Materials and Methods: This was a single-center study conducted from September 2017 to August 2023, including all patients with CKD admitted to the emergency department for upper GI bleeding who underwent Esogastroduodenoscopy (EGD). The various data were collected from endoscopy registries. Results: Of 662 patients admitted via the emergency department for UGIB, 59 cases of CKD (8.9%) were included, of which 43 cases were at the hemodialysis stage (72.88%). The mean age was 57.17 years, with a male predominance (sex ratio M/F 1.55). Isolated melena was the main reason for admission in 35 cases (59.32%), followed by hematemesis with melena in 9 cases (15.25%), and hematemesis without melena in 10 cases (16.94%), while massive rectal bleeding was present in 5 cases (8.47%). Esogastroduodenoscopy established the etiological diagnosis of UGIB in 40 cases (67.8%) and revealed the following lesions: 25 cases of peptic ulcer (62. 5%):2 cases (8%) of antral gastric ulcer,1 case (4%) of Forrest IIc bulbar ulcer, 12 cases (48%) of Forrest III bulbar ulcer and 10 cases (40%) of ulcerative bulbitis, 12 cases (30%) of gastric and duodenal angiodysplasia, 2 cases (5%) of Los Angelos grade B and C esophagitis and 1 case (2. 5%) of grade II of oesophageal varices ligatured in an unknown patient with portal hypertension. EGD was negative in 32.2% of cases. Conclusion: Upper GI bleeding is common in patients with chronic renal failure and is primarily caused by peptic ulcer disease and angiodysplasia.

Application of metagenomic next-generation sequencing in the etiological diagnosis of refractory pneumonia in children.

Metagenomic next-generation sequencing (mNGS) was used to analyze the etiological distribution of refractory pneumonia in children. We compared its efficacy in pathogen diagnosis against traditional methods to provide a basis for clinical adjustment and treatment. A total of 60 children with refractory pneumonia treated at the Department of Respiratory Medicine, Children's Hospital Affiliated with the Capital Institute of Paediatrics, from September 2019 to December 2021 were enrolled in this study. Clinical data (including sex, age, laboratory tests, complications, and discharge diagnosis) and lower respiratory tract specimens were collected, including bronchoalveolar lavage fluid (BALF), deep sputum, pleural effusion, lung abscess puncture fluid, traditional respiratory pathogens (culture, acid-fast staining, polymerase chain reaction, serological testing, etc.), and mNGS detection methods were used to determine the distribution of pathogens in children with refractory pneumonia and to compare the positive rate and diagnostic efficiency of mNGS and traditional pathogen detection for different types of pathogens. Among the 60 children with refractory pneumonia, 43 specimens were positive by mNGS, and 67 strains of pathogens were detected, including 20.90% (14 strains) of which were Mycoplasma pneumoniae, 11.94% (8 strains) were Streptococcus pneumoniae, 7.46% (5 strains) were cytomegalovirus, and 5.97% (4 strains) were Candida albicans. Thirty-nine strains of Mycoplasma pneumoniae (41.03%, 16 strains), Streptococcus pneumoniae (10.26%, 4 strains), Candida albicans (7.69%, 3 strains), and Aspergillus (5.13%, 2 strains) were detected using traditional methods. The positive rate of mNGS detection was 90.48%, and the positive rate of the traditional method was 61.90% (p = 0.050), especially for G+ bacteria. The positive rate of mNGS was greater than that of traditional methods (p < 0.05), but they had no significant difference in detecting G- bacteria, viruses, fungi, or Mycoplasma/Chlamydia. Among the 60 patients, 21 had mixed infections, 25 had single infections, and the other 14 had unknown pathogens. Mycoplasma pneumoniae was most common in both mixed infections and single infections. The sensitivity, specificity, positive predictive value, and negative predictive value of mNGS were 95.45, 37.50, 80.77, and 75.00%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the traditional methods were 72.72, 62.50, 84.21, and 45.45%, respectively. The clinical compliance of mNGS was 80.00%, and that of the traditional method was 70.00%. The sensitivity and negative predictive value of mNGS were high, and the difference in the sensitivity for detecting G+ bacteria was statistically significant (p < 0.05). However, the differences in G- bacteria, fungi, and Mycoplasma/Chlamydia were not statistically significant (p > 0.05). Due to the small sample size, statistical analysis could not be conducted on viral infections. mNGS has higher overall efficacy than traditional methods for the etiological diagnosis of refractory pneumonia in children. The application of mNGS can significantly improve the detection rate of pathogens in children with refractory pneumonia. The sensitivity and negative predictive value of mNGS for detecting G+ bacteria are greater than those of other methods, and it can exclude the original suspected pathogenic bacteria. Unnecessary antibiotic use was reduced, but there was no statistically significant difference in G- bacteria, fungi, or Mycoplasma/Chlamydia.

The efficacy and safety of modified transbronchial cryobiopsy in the diagnosis of interstitial lung disease.

The objective of this study is to investigate the efficacy and safety of flexible transbronchial cryobiopsy (TBCB) in the diagnosis of diffuse parenchymal lung disease (DPLD) in a routine bronchoscopy examination room under analgesia and sedation, using neither endotracheal intubation or rigid bronchoscope nor fluoroscopy or general anesthesia. The data from 50 DPLD patients with unknown etiology who were treated in the Affiliated Hospital of Guilin Medical College from May 2018 to September 2020 were collected, and 43 were eventually included. The specimens obtained from these 43 patients were subjected to pathological examination, pathogenic microorganism culture, etc, and were analyzed in the clinical-radiological-pathological diagnosis mode to confirm the efficacy of TBCB in diagnosing the cause of DPLD. Subsequently, the intraoperative and postoperative complications of TBCB and their severity were closely observed and recorded to comprehensively evaluate the safety of TBCB. For the 43 patients included, a total of 85 TBCB biopsies were performed (1.98 [1, 4] times/case), and 82 valid tissue specimens were obtained (1.91 [1, 4] pieces/case), accounting for 96.5% (82/85) of the total sample. The average specimen size was 12.41 (1, 30) mm2. Eventually, 38 cases were diagnosed, including 11 cases of idiopathic pulmonary fibrosis, 5 cases of connective tissue-related interstitial lung disease, 5 cases of nonspecific interstitial pneumonia, 4 cases of tuberculosis, 4 cases of occupational lung injury, 3 cases of interstitial pneumonia with autoimmune characteristics, 1 case of lung cancer, 2 cases of interstitial lung disease (unclassified interstitial lung disease), 1 case of hypersensitivity pneumonitis, 1 case of pulmonary alveolar proteinosis, and 1 case of fungal infection. The remaining 5 cases were unclarified. For infectious diseases, the overall etiological diagnosis rate was 88.4% (38/43). With respect to complications, pneumothorax occurred in 4 cases (9.3%, 4/43, including 1 mild case and 3 moderate cases), of which 3 cases (75%) were closed by thoracic drainage and 1 case (25%) was absorbed without treatment. In addition, 22 cases experienced no bleeding (51.2%) and 21 cases suffered bleeding to varying degrees based on different severity assessment methods. TBCB is a minimally invasive, rapid, economical, effective, and safe diagnostic technique.

Effect of Ultrasound-Guided Renal Biopsies on Urinary N-Acetyl-Beta-D-Glucosaminidase Index Activity in Dogs with Diffuse Parenchymal Nephropathies.

Ultrasound-guided kidney biopsy is an essential diagnostics method that can increase the accuracy of the differential diagnosis between acute and chronic nephropathies. In addition, it will help clinicians perform an etiologic diagnosis, issue a prognosis, and orient therapy for the majority of parenchymal nephropathies. Due to the relative invasiveness and potential adverse effects, the use of kidney biopsies is limited among practitioners. Twenty-eight dogs, of mixed breed and variable ages, of which 11 (39, 29%) were males and 17 (60, 71%) were females, were examined and underwent an ultrasound-guided kidney biopsy to establish a definitive diagnosis. The patients were presented with a variety of diffuse nephropathies, such as kidney lymphoma: 1 (3.57%), glomerulonephritis: 13 (46.43%), tubulointerstitial nephritis: 11 (39.29%), and nephrocalcinosis. A total of 3 (10.71%) of 18 (64.29%) were in acute kidney injury, and 10 (35.71%) were CKD patients. The type and the severity of the kidney lesions were correlated with changes in the urinary n-acetyl-beta-d-glucosaminidase index (iNAG. To quantify the side effects of percutaneous kidney biopsy, the magnitude of post-biopsy hematuria and changes in urinary iNAG activity were evaluated. The results indicate a significant post-biopsy increase in the urinary iNAG activity in all the patients that underwent this procedure (100.08 ± 34.45 U/g), with a pre-biopsy iNAG vs. 147.65 ± 33.26 U/g post-biopsy iNAG (p < 0.001), suggesting an intensification in the kidney tubular damage that comes consecutives to kidney puncture and sampling. Transitory macro- or microhematuria were constant findings in all the dogs that underwent ultrasound-guided kidney biopsy, but the magnitude and extent could not be associated with the platelet count (PLT 109/L), aPTT (s), and PT (s) levels in our patients, and they were also resolved after 12-24 h without therapeutic interventions. Ultrasound-guided renal biopsy was shown to be a minimally invasive diagnostic procedure that causes transient and limited effects on kidney structures. Although these effects were minor and resolved without intervention, we feel that the benefit of obtaining higher-quality biopsied tissue outweighs the higher risks associated with this procedure.

Health Care Costs After Genome-Wide Sequencing for Children With Rare Diseases in England and Canada

Etiologic diagnoses for rare diseases can involve a diagnostic odyssey, with repeated health care interactions and inconclusive diagnostics. Prior studies reported cost savings associated with genome-wide sequencing (GWS) compared with cytogenetic or molecular testing through rapid genetic diagnosis, but there is limited evidence on whether diagnosis from GWS is associated with reduced health care costs. To measure changes in health care costs after diagnosis from GWS for Canadian and English children with suspected rare diseases. This cohort study was a quasiexperimental retrospective analysis across 3 distinct English and Canadian cohorts, completed in 2023. Mixed-effects generalized linear regression was used to estimate associations between GWS and costs in the 2 years before and after GWS. Difference-in-differences regression was used to estimate associations of genetic diagnosis and costs. Costs are in 2019 US dollars. GWS was conducted in a research setting (Genomics England 100 000 Genomes Project [100KGP] and Clinical Assessment of the Utility of Sequencing and Evaluation as a Service [CAUSES] Research Clinic) or clinical outpatient setting (publicly reimbursed GWS in British Columbia [BC], Canada). Participants were children with developmental disorders, seizure disorders, or both undergoing GWS between 2014 and 2019. Data were analyzed from April 2021 to September 2023. GWS and genetic diagnosis. Annual health care costs and diagnostic costs per child. Study cohorts included 7775 patients in 100KGP, among whom 788 children had epilepsy (mean [SD] age at GWS, 11.6 [11.1] years; 400 female [50.8%]) and 6987 children had an intellectual disability (mean [SD] age at GWS, 8.2 [8.4] years; 2750 female [39.4%]); 77 patients in CAUSES (mean [SD] age at GWS, 8.5 [4.4] years; 33 female [42.9%]); and 118 publicly reimbursed GWS recipients from BC (mean [SD] age at GWS, 5.5 [5.2] years; 58 female [49.2%]). GWS diagnostic yield was 143 children (18.1%) for those with epilepsy and 1323 children (18.9%) for those with an intellectual disability in 100KGP, 47 children (39.8%) in the BC publicly reimbursed setting, and 42 children (54.5%) in CAUSES. Mean annual per-patient spending over the study period was $5283 (95% CI, $5121-$5427) for epilepsy and $3373 (95% CI, $3322-$3424) for intellectual disability in the 100KGP, $724 (95% CI, $563-$886) in CAUSES, and $1573 (95% CI, $1372-$1773) in the BC reimbursed setting. Receiving a genetic diagnosis from GWS was not associated with changed costs in any cohort. In this study, receiving a genetic diagnosis was not associated with cost savings. This finding suggests that patient benefit and cost-effectiveness should instead drive GWS implementation.

AI-based differential diagnosis of dementia etiologies on multimodal data

Differential diagnosis of dementia remains a challenge in neurology due to symptom overlap across etiologies, yet it is crucial for formulating early, personalized management strategies. Here, we present an artificial intelligence (AI) model that harnesses a broad array of data, including demographics, individual and family medical history, medication use, neuropsychological assessments, functional evaluations and multimodal neuroimaging, to identify the etiologies contributing to dementia in individuals. The study, drawing on 51,269 participants across 9 independent, geographically diverse datasets, facilitated the identification of 10 distinct dementia etiologies. It aligns diagnoses with similar management strategies, ensuring robust predictions even with incomplete data. Our model achieved a microaveraged area under the receiver operating characteristic curve (AUROC) of 0.94 in classifying individuals with normal cognition, mild cognitive impairment and dementia. Also, the microaveraged AUROC was 0.96 in differentiating the dementia etiologies. Our model demonstrated proficiency in addressing mixed dementia cases, with a mean AUROC of 0.78 for two co-occurring pathologies. In a randomly selected subset of 100 cases, the AUROC of neurologist assessments augmented by our AI model exceeded neurologist-only evaluations by 26.25%. Furthermore, our model predictions aligned with biomarker evidence and its associations with different proteinopathies were substantiated through postmortem findings. Our framework has the potential to be integrated as a screening tool for dementia in clinical settings and drug trials. Further prospective studies are needed to confirm its ability to improve patient care.