Diagnostic Profile Research Articles

Comparison between endoscopic ultrasound-guided fine-needle biopsy and bite-on-bite jumbo biopsy for sampling of subepithelial lesions.

A direct comparison between endoscopic ultrasound (EUS) fine-needle biopsy (FNB) and current endoscopic biopsy techniques in patients with subepithelial lesions (SELs) is still lacking. Aim of this multicenter study was to compare the diagnostic performance and safety profile between EUS-FNB and bite-on-bite jumbo biopsy. Out of 416 patients undergoing endoscopic sampling of SELs between 2017 and 2021, after propensity score matching two groups were compared: 120 undergoing EUS-FNB and 120 sampled with bite-on-bite jumbo biopsy. Primary outcome was sample adequacy. Secondary outcomes were diagnostic accuracy, sensitivity, specificity, and adverse events. Median age was 61 years and most patients were male in both groups. Final diagnosis was GIST in 65 patients (54.1%) in the EUS-FNB group and 62 patients in the bite-on-bite biopsy group (51.6%; p=0.37). Sample adequacy was significantly higher in the EUS-FNB group as compared to the bite-on-bite biopsy group (94.1% versus 77.5%, p<0.001). EUS-FNB outperformed bite-on-bite biopsy also in terms of diagnostic accuracy (89.3% versus 67.1%, p<0.001) and sensitivity (89% vs 64.5%; p<0.001), whereas specificity was 100% in both groups (p=0.89). These findings were confirmed in subgroup analysis according to SEL location, final diagnosis, and wall layers of the sampled SEL. Adverse event rate was 6.6% in the EUS-FNB group and 30% in the bite-on-bite biopsy group (p<0.001). EUS-FNB outperforms bite-on-bite biopsy both in terms of diagnostic yield and safety profile.

Posttreatment Gene Scores Support Histologic and Endoscopic Response Thresholds in Eosinophilic Esophagitis.

The correlation between clinical and molecular treatment response thresholds in eosinophilic esophagitis (EoE) is not well understood. We evaluated posttreatment EoE diagnostic panel gene expression profiles across histologic and endoscopic thresholds (EREFS) in a prospective adult EoE cohort. We observed a strong inverse correlation between posttreatment gene score and eosinophil count (R = -0.66; P &lt; 0.001); biopsies with &lt;15 eos/hpf had higher gene scores (≥425) vs those with ≥15 eos/hpf. Findings for EREFS were similar; EREFS ≤2 was associated with EoE diagnostic panel scores ≥395. Molecular signatures support the use of posttreatment response thresholds &lt;15 eos/hpf and EREFS ≤2 in clinical practice and trials.

Utility of serum and salivary lactate dehydrogenase and uric acid levels as a diagnostic profile in oral squamous cell carcinoma patients.

Background:Lactate dehydrogenase (LDH), an intra-cellular enzyme present in all cells of the body, catalyses the final step of anaerobic glycolysis. This intra-cellular enzyme is released into the extra-cellular space after tissue disintegration, which is evident in oral squamous cell carcinoma (OSCC). However, investigations comparing Lactate dehydrogenase (LDH) levels in OSCC and healthy controls have shown conflicting findings in both serum and saliva samples. Further, Uric acid's anti-oxidant activity has been demonstrated in several diseases. Several cancers have been linked to increased uric acid levels. However, uric acid levels in oral squamous cell cancer have varied. There exists limitted research comparing serum and salivary uric acid with OSCC. Thus, the present investigation was conducted to evaluate the combined diagnostic abilities of serum and salivary LDH and uric acid in OSCC.Aim and Objective:To compare and correlate LDH and uric acid levels in serum and salivary samples of OSCC patients and healthy individuals.Material and Methods:LDH levels and uric acid levels were measured using an enzymatic method in serum and salivary samples of OSCC cases (n = 18) and healthy individuals (n = 18).Results:This study indicated statistically significant elevated levels of LDH in serum and saliva samples of OSCC patients when compared to healthy individuals. Furthermore, serum and salivary uric acid were higher in OSCC patients than in controls. This increased levels of uric acid was significant only in serum but not in saliva samples. However, salivary uric acid was found to be co-relating with serum uric acid. In addition to this, the receiver operating characteristic (ROC) curve when plotted to assess combined diagnostic abilities of all the investigations to predict oscc, indicating the diagnostic ability to be 77%.Conclusion:This study found an increase in uric acid levels in OSCC patients, which contradicts previous existing litratures. Salivary uric acid and LDH levels may be effective indicators for OSCC screening. However, because of the limited sample size, these findings should be viewed with caution.

Utility and safety of sole electromagnetic navigation bronchoscopy under moderate sedation for lung cancer diagnosis.

BackgroundElectromagnetic navigation bronchoscopy (ENB) is an emerging technique for diagnosing pulmonary lesions. However, limited data is available on its sole utility under a least invasive setting without general anesthesia. We aimed to evaluate the diagnostic performance and safety of sole ENB under moderate sedation for diagnosing pulmonary lesions suspicious for lung cancer and to determine clinical factors associated with a better diagnostic yield.MethodsWe performed a retrospective analysis of consecutive patients who underwent sole ENB under moderate sedation for lung lesion biopsy between August 2016 and June 2021 at Seoul National University Bundang Hospital, a tertiary center in South Korea. Diagnostic yield of the ENB-guided biopsy, safety endpoints defined by the incidence and severity of associated complications, and factors associated with higher diagnostic yield were evaluated.ResultsA total of 94 patients were evaluated. The final diagnostic yield of ENB was 81.5% (75/92), excluding two indeterminate cases. The diagnostic yield ranged from 79.8% to 81.9% assuming all indeterminate cases were false-negatives (79.8%) and true-negatives (81.9%). The sensitivity and specificity for malignancy were 77.6% (ranging from 75.6% to 77.6%) and 100%, respectively. Any-grade pneumothorax occurred in 4.3% of the patients, and 2.1% developed pneumothorax requiring additional intervention. Multivariable analyses identified the presence of a class 2 bronchus sign as the only significant predictor for a higher diagnostic yield (odds ratio =4.83, 95% CI: 1.16–20.12). The diagnostic yield of ENB among those with class 2 bronchus sign was 89.8% (53/59).ConclusionsSole ENB under moderate sedation for diagnosing pulmonary lesions displayed a good diagnostic yield and safety profile, thus confirming its utility in a least-invasive setting. Moreover, sole ENB could be possibly be superior to transthoracic needle aspiration for diagnosing lesions with class 2 bronchus sign accounting for similar yields and lower complication rates.

Clinical 1H MRS in childhood neurometabolic diseases - part 2: MRS signatures.

Proton MRS of the brain provides the ability to gather direct information regarding the metabolic status of the brain at the time of MRI. Although selective vulnerability of brain tissue may yield distinct imaging patterns in neurometabolic disorders, it is not uncommon for the brain MRI to be normal, nonspecific, or show ambiguous abnormalities among several possible diagnoses, metabolic, or otherwise. This review highlights childhood neurometabolic diseases in which 1H MRS may show diagnostic or suggestive metabolic profiles without complicated acquisition or postprocessing techniques.

STRUCTURAL-FUNCTIONAL AND MOLECULAR DIAGNOSTIC PARALLELS IN ARTERIAL HYPERTENSION IN ELDERLY PATIENTS

Abstract: Relevance. Among cardiovascular diseases arterial hypertension (AH) in elderly people over 60 years old is the main risk factor for stroke, heart failure, terminal renal failure and lethal outcome. Today hypertension is defined as accelerated aging of the arterial component of the cardiovascular system with developing of remodeling processes due to age. Studies of a molecular phenotype of hypertension in elderly patients with obtaining molecular profiles of biological samples determining the clinical course of hypertension and its classification characteristics are topical nowadays. The aim of the study is to search correlations between structural, functional and molecular diagnostic parameters in patients with AH of Grade 2 of a moderate and high risk. Methods and materials: The study involved patients over 60 years old with a diagnosis of Grade 2, moderate and high risk hypertension (Group 2, n=200), taking into consideration the criteria of inclusion and non-inclusion into the study. The control group (KG, Group 1) included 30 elderly people with no hypertension. Central blood pressure (BP) in the aorta and pressure on the brachial artery were measured, indicators of daily blood pressure monitoring, structural and functional parameters of the heart were evaluated on the basis of echocardiography. There was fulfilled a qualitative proteomic analysis of blood plasma based on time–of–flight mass spectrometry with a laser desorption and ionization and quantitative assessment of the level of proteins in the blood with the help of enzyme immunoassay. Results: There was revealed an increase of the blood concentration of MPO, apoD, HIF1α, TGFβ1, hyaluronidase 1, kininogen 1, fibulin 5 and their significant correlations with LVMM and ACC. Conclusions: There was determined diagnostic molecular profile of blood of elderly patients with AH of Grade 2 and confirmed the involvement of proteins in myocardial and vascular remodeling in elderly patients with AH.

Trading Patients: Applying the Alternative Model for Personality Disorders to Two Cases of DSM-5 Borderline Personality Disorder Over Time and Across Therapists.

The DSM-5 Alternative Model for Personality Disorders (AMPD) dimensionally defines personality pathology using severity of dysfunction and maladaptive style. As the empirical literature on the clinical utility of the AMPD grows, there is a need to examine changes in diagnostic profiles and personality expression in treatment over time. Assessing these changes in individuals diagnosed with borderline personality disorder (BPD) is complicated by the tendency for patients to cycle through multiple therapists over the course of treatment leaving the potential for muddled diagnostic clarity and disjointed case conceptualizations. Following patient trajectories across therapists offers a unique opportunity to examine the AMPD’s sensitivity to and utility for capturing personality stability and change over time for patients with BPD. This article demonstrates the utility of the AMPD for two clinical cases in three distinct ways: (i) highlighting heterogeneity in BPD between patients, (ii) comparing improvements in personality severity and style over time, and (iii) elucidating profile change across therapist ratings. We present two patients diagnosed with DSM-5 Section II BPD, crossing between two therapists over the course of 3 years of psychodynamic psychotherapy. Treating clinicians rated patients for their respective treatment phases using the Level of Personality Functioning Scale (LPFS), capturing severity, and the Personality Inventory for the DSM-5 (PID-5), capturing style. AMPD diagnostic profiles differentiated patients with BPD in both severity and style, and captured within-patient change beyond within-therapist response bias. Results indicated greater improvements in personality severity while personality style remained more stable. Implications for the patients’ treatment progress and associated challenges are discussed, as are considerations for the utility of the AMPD in therapy.

Management of Double Sensitization to Vespids in Europe.

Wasp allergy with a diagnostic profile of double sensitizations to vespid venom is a frequent clinical problem in areas where different genera of wasps are present. Identification of the insect responsible for serious reactions poses a diagnostic challenge as the only effective treatment to date is immunotherapy based on the specific venom. In southern Europe, the double sensitization to Vespula and Polistes venoms is highly frequent. It has been shown that the major allergenic proteins (Phospholipase A1 and Antigen 5) share sequences across the different genera and species, which would be the cause of cross-reactivity. Additionally, the minor allergens (Dipeptidyl-peptidases, Vitellogenins) have been found to share partial sequence identity. Furthermore, venom contains other homologous proteins whose allergenic nature still remains to be clarified. The traditional diagnostic tools available are insufficient to discriminate between allergy to Vespula and Polistes in a high number of cases. IgE inhibition is the technique that best identifies the cross-reactivity. When a double sensitization has indeed been shown to exist or great uncertainty surrounds the primary sensitization, therapy with two venoms is advisable to guarantee the safety of the patient. In this case, a strategy involving alternate administration that combines effectiveness with efficiency is possible.

Malignant Lymphoproliferative Disorders of the Oral and Maxillofacial Region: Report of Two Institutions.

BackgroundReport of the incidence of malignant hematologic neoplasms in the oral cavity according to the experience of the two oral and maxillofacial pathology institutions in North Carolina, USA.MethodsA 10-year retrospective review was carried out in the records of patients at ECU SoDM and UNC Adams SoD. Age, sex, location of the lesion, clinical impression, initial diagnosis, and the expression immunohistochemical and molecular markers were recorded for each subject. All diagnoses were reviewed according to the 2016 revision of the WHO classification of lymphoid neoplasms.ResultsA total of 318 records from both institutions were reviewed. Seventy males and 68 females with an average age of 60.7 comprised the study population. The most common neoplasm encountered was plasma cell myeloma, followed by diffuse large B-cell lymphoma, B-lymphoblastic lymphoma, and follicular lymphoma. We encountered primarily intraosseous tumors, with the posterior mandible and posterior maxilla being the most common locations. Twelve cases were identified initially as a periapical radiolucency.ConclusionOur findings are concurrent with the existing literature regarding epidemiologic data. However, the type and location of tumors encountered do not, as the most common lymphoma in the oral cavity is diffuse large B-cell lymphoma, typically present in soft tissue. To aid in diagnosis and treatment, the collection of data should continue over time so that eventually, a more specific diagnostic profile of North Carolina residents with these neoplasms can be made.

Association between C-Reactive Protein Velocity and Left Ventricular Function in Patients with ST-Elevated Myocardial Infarction.

C-reactive protein velocity (CRPv), defined as the change in wide-range CRP concentration divided by time, is an inflammatory biomarker associated with increased morbidity and mortality in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous intervention (PCI). However, data regarding CRPv association with echocardiographic parameters assessing left ventricular systolic and diastolic function is lacking. Echocardiographic parameters and CRPv values were analyzed using a cohort of 1059 patients admitted with STEMI and treated with primary PCI. Patients were stratified into tertiles according to their CRPv. A receiver operating characteristic (ROC) curve was used to evaluate CRPv optimal cut-off values for the prediction of severe systolic and diastolic dysfunction. Patients with high CRPv tertiles had lower left ventricular ejection fraction (LVEF) (49% vs. 46% vs. 41%, respectively; p < 0.001). CRPv was found to independently predict LVEF ≤ 35% (HR 1.3 CI 95% 1.21–1.4; p < 0.001) and grade III diastolic dysfunction (HR 1.16 CI 95% 11.02–1.31; p = 0.02). CRPv exhibited a better diagnostic profile for severe systolic dysfunction as compared to CRP (area under the curve 0.734 ± 0.02 vs. 0.608 ± 0.02). In conclusion, For STEMI patients treated with primary PCI, CRPv is a marker of both systolic and diastolic dysfunction. Further larger studies are needed to support this finding.

Síndrome inflamatória multissistêmica em pacientes pediátricos: uma revisão da literatura

OBJECTIVES: To carry out a literature review in order to characterize epidemiology, pathophysiology, diagnosis and management of multisystem inflammatory syndrome in children (MIS-C), to evaluate economic impact and to differentiate MIS-C from Kawasakis disease and toxic shock syndrome. METHODS: Review performed in two stages: a literature review through PubMed platform and a document search of official agencies. We selected 10 articles containing information on epidemiology, pathophysiology, clinical condition, complementary evaluations, diagnostic criteria, clinical management and/or MIS-C outcome. Were excluded: duplicate articles, articles focused on adult patients, those which do not include description of the amendments and approach of MIS-C. RESULTS: The mean age ranged between 8.5 and 12 years; male sex was the most affected; most of the sample had positive serology for COVID-19; majority admited to ICU; low mortality. There is no well-defined pathophysiology so far. The main symptoms were fever, gastrointestinal symptoms, skin rash, and conjunctivitis. The predominant dysfunctions were shock and respiratory failure. Laboratorially, there was an increase of inflammatory markers, procalcitonin, IL-6, troponin and pro-bnp. The most commonly used treatments were: ventilatory support, vasoactive drugs, immunoglobulin and corticosteroids. CONCLUSION: This study allowed a better understanding of MIS-C, despite the lack of studies covering the subject. It was possible to characterize an epidemiological, clinical, laboratory and diagnostic profile. The treatment of the disease does not yet have defined protocols, but it was similar in most studies. It is therefore necessary to develop new studies and protocols for a better understanding and approach to MIS-C.

Hepatitis C: Epidemiological, Clinical and Therapeutic Aspects in Dakar (Senegal)

Viral hepatitis C is a major public health problem. The aim of our work was to determine the epidemiological, diagnostic and treatment profiles of patients with HCV in Dakar (Senegal). We conducted a retrospective, descriptive, multicentre study between January 1, 2010, and December 31, 2019. We included 26 patients. The mean age of the patients was 53.5 years [28 - 70 years] and 46.2% were males. Of the 26 patients included, 7 (26.9%) were Senegalese, and the majority were from other African countries. Risk factors for contamination found were surgery in 11 patients (42.3%) and blood transfusion in 1 patient (3.8%). The mean viral load was 6.47 log IU/ml [4.26 - 7.26 log IU/ml]. Ten patients were infected by genotype 4. No patients were co-infected with HIV or HBV. Six patients (23.1% of patients) had significant fibrosis, of which five (19.2% of patients) were in the stage of cirrhosis. Twelve patients (46.2%) started treatment. Eleven were treatment-naïve and 1 did not respond to ribavirin-pegylated interferon-based therapy after 48 weeks. Ten cases of antiviral therapy were based on DAA and ribavirin-pegylated interferon in 2 patients. For the patients treated with peginterferon and ribavirin, a rapid virologic response was observed at 12 weeks in one patient, and the other patient was lost to follow-up. Among DAA-treated patients, 7 had sustained virologic responses at 12 weeks, 2 persisted, and 1 was lost to follow-up. Moderate thrombocytopenia and weight loss were observed in one patient receiving peginterferon and ribavirin. In our study, no patient died on treatment and no patients developed de novo HCC during or after DAA therapy. Conclusion: Viral hepatitis C is rare in Senegal. Despite the progress made in the therapeutic management of viral hepatitis C, it remains a challenge in Senegal. Indeed, DAAs are expensive and are not marketed, which makes them inaccessible to most patients.

A Clinical Study on the Relationship Among Insomnia, Tongue Diagnosis, and Oral Microbiome.

Currently, there is a lack of adequate methods to assess insomnia objectively. This study addresses the usefulness of tongue features and oral microbial profile as a potential diagnostic biomarker of insomnia. One hundred insomniac patients and 20 healthy control subjects were selected. Their demographic and clinical characteristics, as well as the tongue diagnostic indices and oral microbial profile, were examined. Compared to the control group, insomniac patients showed a higher abnormal low-frequency/high-frequency (LF/HF) ratio. In tongue diagnosis, the indices related to lightness of tongue body and tongue coating were higher in the insomniac group vs. the control group. Furthermore, linear discriminant analysis (LDA) of oral microbial population revealed that the relative abundances of Clostridia, Veillonella, Bacillus and Lachnospiraceae were significantly higher in the insomniac patients than the control group. Additionally, the tongue features of the insomniac group exhibited that the non-coating group had a poor sleep condition compared to the thick-coating group, although the difference was insignificant. On the other hand, the oral microbial communities of the insomniac patients revealed greater alpha and beta diversities in the non-coating group vs. the thick-coating group. The alpha and beta diversities were higher in orotype1 than orotype2. Collectively, this study highlighted that the lightness of tongue body and tongue coating as well as oral microbial profiles of SR1, Actinobacteria, Clostridia and Lachnospiraceae_unclassified could be considered potential biomarkers of insomnia.

Sociodemographic and clinical profile of patients receiving disability certificates for psychiatric disorders: An Indian Psychiatric Society Multicentric study.

Aim:To study the sociodemographic and clinical profile of subjects receiving disability certificates (DCs) issued for psychiatric disorders across multiple centres in India.Materials and Methods:Eleven centres, including ten government and one non-governmental organization spread across the country, participated in the study. Data on the sociodemographic and clinical profiles of patients who were issued DC in the calendar year 2019 were collected on a proforma designed for the study.Results:Overall, 2018 patients were issued DC for various psychiatric disorders across 11 centres in 2019. The number of certificates issued across different centres varied from 34 to 622. In terms of diagnostic profile, intellectual disability accounted for most of the certificates issued. In terms of psychiatric diagnosis, schizophrenia was the most common psychiatric diagnosis, followed by bipolar disorder, for which a DC was issued. When the diagnosis was considered, centre wise, intellectual disability (6 centres), mental illness (MI; 4 centres), and autism and specific learning disability (1 centre) accounted for the most DCs issued. Schizophrenia (9 centres), bipolar affective disorder (1 centre), and dementia (1 centre) were the most common MI for which DC was issued. Across centres, more than two-thirds of DC were issued to males.Conclusion:There is a wide variation in the number and clinical profile of DC issued across centres.

Crown-Cut Endobronchial Ultrasound Guided Transbronchial Aspiration Needle: First Real-World Experiences.

Advancements in personalized medicine have increased the demand for quantity and preservation of tissue architecture of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples. These demands may be addressed by the SonoTip TopGain® needle, which has a 3-point crown-cut design that contrasts with the standard single bevel design of the ViziShot 2®. The objective was to compare the SonoTip TopGain® and ViziShot 2® needles by considering biopsy sample characteristics, diagnostic accuracy, and patient safety. The primary endpoint of the study was the number of high-power fields (HPFs) in the center of the formalin-fixed paraffin-embedded cell block per sample. The lymph node with the highest probability for malignant infiltration based on size and sonographic appearance was chosen as the target lymph node for 20 patients. The same lymph node in each patient was sampled using both the ViziShot 2® and SonoTip TopGain® needles. The samples were measured, sliced, and analyzed by a pathologist. Sixteen patients were biopsied with both needles. Four patients could not be biopsied with the SonoTip TopGain® needle since it could not penetrate cartilage or be repositioned to bypass cartilage. HPFs and sample dimensions were significantly greater in the patients where sampling with the SonoTip TopGain® needle was possible (p = 0.007 and p = 0.005, respectively). Diagnostic accuracy and safety profiles were comparable. Significantly more material can be sampled using the SonoTip TopGain® needle when cartilage penetration can be avoided. This improves the yield for molecular workup in the era of personalized medicine.

Identifying Disease-Specific Neural Reactivity to Psychosocial Stress in Borderline Personality Disorder

BackgroundPatients with borderline personality disorder (BPD) typically present emotion dysregulation (ED) when faced with adversity. However, it is argued that altered stress response may be more influenced by ED than BPD-specific traits. Here, we investigated this issue with functional magnetic resonance imaging using another ED condition as clinical control, i.e., bipolar disorder (BD), and controlling for ED traits. MethodsWe recruited 17 patients with BD, 24 patients with BPD, and 32 healthy control (HC) subjects. We adapted a functional magnetic resonance imaging–compatible psychosocial stressor task (Montreal Imaging Stress Task) in which participants are placed under time pressure when performing mental calculations and then receive immediate performance feedback (positive, negative, and neutral). ED traits were measured via self-report questionnaires targeting cognitive emotion dysregulation, affective lability, and trait anger and anxiety. ResultsRelative to patients with BD and HC subjects, patients with BPD exhibited overactive corticolimbic reactivity across all conditions, particularly in self-monitoring and emotion regulation regions such as the orbitofrontal cortex and anterior insula, even when controlling for ED. Conversely, patients with BD exhibited hypoactive corticolimbic reactivity to all feedback conditions compared with patients with BPD and HC subjects, even after controlling for ED. HC subjects exhibited significantly lower amygdala/hippocampus activity compared with both clinical groups, although this did not survive when controlling for ED. ConclusionsThis study provides new insight into BPD-specific neural stress responding, suggesting hyperactive self- and emotion-regulatory neural psychosocial stress responding, independent of ED traits. The findings also highlight the importance of considering BPD as a diagnostic profile distinguishable from other ED disorder clinical groups.

Comparison of diffusion weighted, imaging‐derived, fractional anisotropy with a novel MRI contrast‐weighted ratio method for measuring myelin in older adults at risk for Alzheimer’s disease

AbstractBackgroundMRI measures sensitive to myelin integrity have been investigated as potential AD biomarkers. T1‐weighted/T2‐weighted ratio is a simple yet informative measure, but many cohorts have transitioned to only T1‐weighted and T2‐weighted Fluid Attenuated Inversion Recovery (FLAIR) acquisitions. We previously obtained similar results using FLAIR instead of T2 (T1w/T2FLAIRw). Our goal now is to compare T1w/T2FLAIRw to fractional anisotropy (FA) from diffusion weighted imaging (DWI).MethodPearson’s correlations of T1w/T2FLAIRw and FA values of hippocampal white matter (WM) integrity were calculated in two independent cohorts acquired on different scanners: Cohort 1 (21 CN; 7 SCD; 20 MCI; 4 AD) and Cohort 2 (40 CN; 43 SCD; 45 MCI; 20 AD). Image‐processing algorithms were designed in‐house, building on previous methods and implemented using SPM12 and FSL dtifit. Diagnostic group differences were assessed in both cohorts using one‐way ANOVA and independent sample T‐tests with Tukey correction.ResultCohort 1 demonstrated significant correlation of WM integrity values between methods in the left hippocampus (p=.002) and approached significance in the right (p = .074). Between‐group analyses showed significant differences in left hippocampal WM between cognitively unimpaired (CU [CN and SCD]) and cognitively impaired (CI [MCI and AD]) groups, with follow‐up tests showing differences between CN and AD patients in both methods. Right hippocampal T1w/T2FLAIRw ratio values showed significant differences between CU and CI, though no significant diagnostic group differences. Right hippocampal FA values were not significant.Cohort 2 demonstrated significant bilateral correlation between imaging methods (p &lt; .001), with bilateral significant differences between CU and CI groups in both methods. CN and MCI right hippocampal values were significantly different from each other in both methods. Box plots demonstrated clear similarities in patterns of diagnostic profile between methods.ConclusionA similar overall pattern was observed across the T1w/T2FLAIRw and DWI‐FA methods. This may reflect myelin disruption although further studies are needed to address source of signal differences on imaging. Differences in FA effect sizes for the hippocampus across samples and scanners merits further exploration.

Comparing Copy Number Variations in a Danish Case Cohort of Individuals With Psychiatric Disorders

Although the association between several recurrent genomic copy number variants (CNVs) and mental disorders has been studied for more than a decade, unbiased, population-based estimates of the prevalence, disease risks and trajectories, fertility, and mortality to contrast chromosomal abnormalities and advance precision health care are lacking. To generate unbiased, population-based estimates of prevalence, disease risks and trajectories, fertility, and mortality of CNVs implicated in neuropsychiatric disorders. In a population-based case-cohort study, using the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) 2012 database, individuals born between May 1, 1981, and December 31, 2005, and followed up until December 31, 2012, were analyzed. All individuals (n = 57 377) with attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), schizophrenia (SCZ), autism spectrum disorder (ASD), or bipolar disorder (BPD) were included, as well as 30 000 individuals randomly drawn from the database. Data analysis was conducted from July 1, 2017, to September 7, 2021. Copy number variants at 6 genomic loci (1q21.1, 15q11.2, 15q13.3, 16p11.2, 17p12, and 17q12). Population-unbiased hazard ratio (HR) and survival estimates of CNV associations with the 5 ascertained psychiatric disorders, epilepsy, intellectual disability, selected somatic disorders, fertility, and mortality. Participants' age ranged from 1 to 32 years (mean, 12.0 [IQR, 6.9] years) during follow-up, and 38 662 were male (52.3%). Copy number variants broadly associated with an increased risk of autism spectrum disorder and ADHD, whereas risk estimates of SCZ for most CNVs were lower than previously reported. Comparison with previous studies suggests that the lower risk estimates are associated with a higher CNV prevalence in the general population than in control samples of most case-control studies. Significant risk of major depressive disorder (HR, 5.8; 95% CI, 1.5-22.2) and sex-specific risk of bipolar disorder (HR, 17; 95% CI, 1.5-189.3, in men only) were noted for the 1q21.1 deletion. Although CNVs at 1q21.1 and 15q13.3 were associated with increased risk across most diagnoses, the 17p12 deletion consistently conferred less risk of psychiatric disorders (HR 0.4-0.8), although none of the estimates differed significantly from the general population. Trajectory analyses noted that, although diagnostic risk profiles differed across loci, they were similar for deletions and duplications within each locus. Sex-stratified analyses suggest that pathogenicity of many CNVs may be modulated by sex. The findings of this study suggest that the iPSYCH population case cohort reveals broad disease risk for some of the studied CNVs and narrower risk for others, in addition to sex differential liability. This finding on genomic risk variants at the level of a population may be important for health care planning and clinical decision making, and thus the advancement of precision health care.

Multi-center nationwide study on pediatric psychiatric inpatients 2000–2018: length of stay, recurrent hospitalization, functioning level, suicidality, violence and diagnostic profiles

Inpatient treatment is an important part of child and adolescent psychiatric (CAP) care. This nationwide study explores the changes in length of stay, recurrent hospitalization, functioning level, suicidality, violence and diagnoses of CAP inpatients in Finland in 2000, 2011 and 2018. We obtained comprehensive questionnaire data on each study year from 93 to 95% of all CAP wards in Finland. We split the 1276 inpatients into two age groups in each study year: under 13 and 13–18. The median length of stay in inpatient treatment decreased from 82.0 days in 2000 to 20.5 days in 2018 (p < 0.001) and recurrent hospitalization increased from 38 to 46%. General functioning, which was evaluated by the Children’s Global Assessment Scale, deteriorated by an average of six points between 2000 and 2018. Violent threats decreased from 21.5 to 16.6% and violent acts decreased from 26.9 to 20.3%. Suicidal threats decreased from 42.6 to 23.3% in those aged under 13 and remained stable among those aged 13–18. In the 13–18 group, there was an increase in the diagnoses of ADHD, from 5.0 to 16.9% and depression, from 25.1 to 41.7%. However, psychosis decreased from 23.2 to 12.6% in the older age group. In the whole cohort, anxiety disorders increased from 7.6 to 15.6%. The overall picture does not show that CAP inpatients have become more disturbed. While the general functioning of CAP inpatients deteriorated somewhat over the 2000–2018 study period, symptoms of suicidality and violence remained stable or decreased. There was also a continuous increase in short-term treatment.

Generating diagnostic profiles of cognitive decline and dementia using magnetoencephalography

Accurate identification of the underlying cause(s) of cognitive decline and dementia is challenging due to significant symptomatic overlap between subtypes. This study presents a multi-class classification framework for subjects with subjective cognitive decline, mild cognitive impairment, Alzheimer's disease, dementia with Lewy bodies, fronto-temporal dementia and cognitive decline due to psychiatric illness, trained on source-localized resting-state magnetoencephalography data. Diagnostic profiles, describing probability estimates for each of the 6 diagnoses, were assigned to individual subjects.A balanced accuracy rate of 41% and multi-class area under the curve value of 0.75 were obtained for 6-class classification. Classification primarily depended on posterior relative delta, theta and beta power and amplitude-based functional connectivity in the beta and gamma frequency band. Dementia with Lewy bodies (sensitivity: 100%, precision: 20%) and Alzheimer's disease subjects (sensitivity: 51%, precision: 90%) could be classified most accurately. Fronto-temporal dementia subjects (sensitivity: 11%, precision: 3%) were most frequently misclassified.Magnetoencephalography biomarkers hold promise to increase diagnostic accuracy in a noninvasive manner. Diagnostic profiles could provide an intuitive tool to clinicians and may facilitate implementation of the classifier in the memory clinic.