Severe Clinical Presentation Research Articles

Clinical Features and Predictors of Treatment Outcome in Patients with Ocular Tuberculosis from the Netherlands and Indonesia: The OculaR TB in Low versus High Endemic Countries (ORTEC) Study

ABSTRACT Purpose To describe and compare clinical features, treatment approaches, and treatment outcomes of ocular tuberculosis (OTB) patients in the Netherlands, a low tuberculosis (TB)-endemic country, and Indonesia, a high TB-endemic country. We also aimed to identify predictors of treatment outcomes. Methods A medical chart review of 339 OTB patients (n = 93 from the Netherlands and n = 246 from Indonesia) was performed. The primary outcome was response to treatment, whether with or without anti-tubercular treatment, after six months of treatment initiation (good versus poor responders). Results Indonesian OTB patients displayed a higher prevalence of chest radiograph findings indicative of TB infection (p < 0.001) and concurrent active systemic TB (p = 0.011). Indonesian cohort exhibited a more acute and severe disease profile, including uveitis duration ≤ 3 months (p < 0.001), blindness (p < 0.001), anterior chamber (AC) cells ≥ 2+ (p < 0.001), and posterior synechiae (p < 0.001). Overall proportions of good responders to treatment were 67.6% in the Netherlands and 71.5% in Indonesia. Presence of AC cell ≥ 2+ (adjusted odds ratio (aOR): 2.12, 95% CI: 1.09–4.14), choroidal lesions other than serpiginous-like choroiditis (SLC) or tuberculoma (aOR: 4.47, 95% CI: 1.18–16.90), and retinal vasculitis (aOR: 2.32, 95% CI: 1.10–4.90) at baseline were predictors for poor response to treatment. Conclusions Despite a more severe initial clinical presentation in the Indonesian cohort, the overall treatment outcomes of OTB was comparable in both cohorts. Three baseline clinical features were identified as predictors of treatment outcomes.

#382 Unexpected diagnoses of ADTKD-MUC1 with the help of VNtyper

Abstract Background and Aims Autosomal dominant tubulointerstitial kidney disease (ADTKD) due to pathogenic variants in the MUC1 gene is difficult to diagnose since these variants lie in a large variable number tandem repeats (VNTR) and require specialized genetic testing, such as SNaPshot minisequencing. We recently developed a computational pipeline, VNtyper, for easier reliable detection of MUC1 VNTR pathogenic variants and have applied this tool to a large cohort of patients with various phenotypes of kidney disease. The aim of this study is to clinically describe patients in whom MUC1 pathogenic variants were unexpectedly detected with the help of VNtyper. Method We applied a computational pipeline, VNtyper, to a large cohort of patients with suspected hereditary kidney disease referred for genetic testing, regardless of their phenotype. This cohort included patients evaluated from 2017 to 2023 in the Molecular Genetics Department of Necker-Enfants Malades Hospital (Paris, France). Clinical characteristics were collected from patients in whom we detected new MUC1 VNTR pathogenic variants. Results 44 out of 3735 patients tested (1.2%) were newly diagnosed with a MUC1 pathogenic variant. Of these patients, ADTKD was clinically suspected in only 31 out of 44 patients (70%). In 2 patients, there was a pathogenic variant in another gene that could explain the phenotype, in addition to the MUC1 pathogenic variant. In fact, one 52-year-old patient had polycystic kidneys, nephrolithiasis, hematuria and normal kidney function. Her mother also had kidney cysts with absence of chronic kidney disease (CKD). This patient had a pathogenic variant in IFT140 gene (c.2399+1G&amp;gt;T) which could explain her autosomal dominant polycystic kidney disease (ADPKD) phenotype. Whether the MUC1 variant contributes to her disease remains unclear, especially seeing as her kidney function is normal at the age of 52 years. On the other hand, one patient had kidney cysts discovered at 3 days of age. A heterozygous HNF1B deletion was detected which could explain the phenotype. The following detection of a pathogenic MUC1 variant was thus an incidental finding and seemed de novo, although parents declined to get tested. These incidental findings can be challenging, especially when it comes to counselling and follow-up. There was no family history of kidney disease in 7 out of 44 patients (16%), and in one patient, we were able to confirm de novo disease since her parents were tested and were negative. It was unfortunately not possible to get DNA from the parents of the other patients. This is the first case of proven de novo ADTKD-MUC1 described to our knowledge. De novo variants in ADTKD-MUC1 are not surprising since the 7C stretch found in VNTR is a hotspot for mutagenesis. Interestingly, these patients seemed to have a more severe clinical presentation with an early onset of disease (median age at diagnosis 28 years [18, 32]). However, this could be due to a selection bias. In fact, young age of onset of CKD may have prompted clinicians to refer these patients for genetic testing despite negative family history, whereas older patients with possible ADTKD-MUC1 and no family history of kidney disease might be presumed to have another etiology of CKD. One way to confirm this would be to test a large cohort of patients with CKD from unknown etiology with no family history of CKD. Considering the nonspecific clinical manifestations of ADTKD-MUC1 and the phenotypic variability, it has previously been suggested that the most important clue to diagnosis is the presence of CKD in first-degree family. The possibility of de novo cases makes the clinical diagnosis of ADKTD-MUC1 even more challenging. Conclusion With VNtyper, we were able to diagnose new cases of ADTKD-MUC1 in a large cohort of patients with various phenotypes, with a significant prevalence of 1.2%. ADTKD-MUC1 was not suspected in 30% of these patients who would have maybe never been diagnosed otherwise. This is also the first study in which we describe a proven de novo case of ADTKD-MUC1. Pathogenic variants in the MUC1 gene should thus be in the differential diagnosis of all unspecified CKD, even if there is no family history since de novo variants are also possible.

#1954 Effects of lanosterol synthase (LSS) gene on the development of acute kidney injury after cardiac surgery

Abstract Background and Aims Acute kidney injury (AKI) is a common post-cardiac surgery complication, significantly affecting morbidity and mortality. Recent studies reported that high plasma levels of endogenous ouabain (EO), a stress hormone secreted by the adrenal glands, are associated to worse kidney outcomes after cardiac surgery. Our group demonstrated that EO activity is affected by a missense variant (rs2254524, C -&amp;gt; A, Val642Leu) in Lanosterol Synthase (LSS) gene, an enzyme implicated in EO synthesis. The aim of this work is to analyze the relationship between this LSS polymorphism and the development of AKI after cardiac surgery. Method 1237 patients undergoing elective cardiac surgery were enrolled in the study. Preoperative biological samples were collected (Table 1). LSS genotypes were determined for each patient. The primary outcome was AKI development, according to KDIGO 2012 guidelines. Results 21.4% of patients developed AKI. Different preoperative clinical variables were analyzed, identifying five independent risk factors significantly correlated to AKI development in multivariate logistic regression analysis: age (p &amp;lt; 0.001), FE (p = 0.005), NYHA class (p &amp;lt; 0.001), reoperation (p = 0.002) and complex surgical intervention (p &amp;lt; 0.001), Table 2. No significant differences were observed between preoperative EO plasma levels and allelic variants of LSS gene and patients with the less common A allele were not associated to a more severe preoperative clinical presentation, expressed as EuroScore II value (AA 2.54 ± 3.86 vs AC 2.15 ± 2.52 vs CC 2.04 ± 2.73; p = ns). LSS minor variants turned out significantly associated with the incidence of AKI (AA = 29.3%; AC = 25.3%; CC = 17.2%; X2 p &amp;lt; 0.001—Fig. 1). This evidence remains significant after correction for covariates associated to AKI previously reported (Log regression p = 0.002; RR for AA variant: 2.09 (IC95% 1.15-3.78)) Conclusion Patients with at least one mutated allele of LSS variant have a higher probability of developing AKI after cardiac surgery. We think these results could be of interest to further understand cellular mechanisms underlying AKI development, especially in the cardiac surgery field.

Association between emphysema and other pulmonary computed tomography patterns in primary varicella pneumonia: A retrospective cohort study.

This study aims to evaluate chest computed tomography (CT) findings in hospital patients with primary varicella pneumonia (PVP). We retrospectively analyzed CT images of 77 PVP patients using 3D Slicer, an open-source software, to model lesions and lungs. This retrospective cohort study was approved by the Institutional Review Board (Ethical Committee, Renmin Hospital, Hubei University of Medicine, Shiyan, China) and waived the requirement for written informed consent. The left lung was more frequently and severely affected in PVP, with significant differences between the 2 groups in CT involvement percentage of each lung region, except for total lung inflation. Group A showed higher median percentages of lung collapse compared to Group B. The extent of left lung involvement is a critical predictor of emphysema in PVP patients, highlighting the importance of also monitoring the right lung for more severe cases. Lower emphysema levels correspond to more collapsed and infiltrated lung segments, suggesting a more severe clinical presentation.

Clinical complexity of an Italian cardiovascular intensive care unit: the role of mortality and severity risk scores.

The identification of patients at greater mortality risk of death at admission into an intensive cardiovascular care unit (ICCU) has relevant consequences for clinical decision-making. We described patient characteristics at admission into an ICCU by predicted mortality risk assessed with noncardiac intensive care unit (ICU) and evaluated their performance in predicting patient outcomes. A total of 202 consecutive patients (130 men, 75 ± 12 years) were admitted into our tertiary-care ICCU in a 20-week period. We evaluated, on the first 24 h data, in-hospital mortality risk according to Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score 3 (SAPS 3); Sepsis related Organ Failure Assessment (SOFA) Score and the Mayo Cardiac intensive care unit Admission Risk Score (M-CARS) were also calculated. Predicted mortality was significantly lower than observed (5% during ICCU and 7% at discharge) for APACHE II and SAPS 3 (17% for both scores). Mortality risk was associated with older age, more frequent comorbidities, severe clinical presentation and complications. The APACHE II, SAPS 3, SOFA and M-CARS had good discriminative ability in distinguishing deaths and survivors with poor calibration of risk scores predicting mortality. In a recent contemporary cohort of patients admitted into the ICCU for a variety of acute and critical cardiovascular conditions, scoring systems used in general ICU had good discrimination for patients' clinical severity and mortality. Available scores preserve powerful discrimination but the overestimation of mortality suggests the importance of specific tailored scores to improve risk assessment of patients admitted into ICCUs.

Rare heterozygous genetic variants of NRXN and NLGN gene families involved in synaptic function and their association with neurodevelopmental disorders.

The interaction of neurexins (NRXNs) in the presynaptic membrane with postsynaptic cell adhesion molecules called neuroligins (NLGNs) is critical for this synaptic function. Impaired synaptic functions are emphasized in neurodevelopmental disorders to uncover etiological factors. We evaluated variants in NRXN and NLGN genes encoding molecules located directly at the synapse in patients with neuropsychiatric disorders using clinical exome sequencing and chromosomal microarray. We presented detailed clinical findings of cases carrying heterozygous NRXN1 (c.190C>T, c.1679C>T and two copy number variations [CNVs]), NRXN2 (c.808dup, c.1901G>T), NRXN3 (c.3889C>T), and NLGN1 (c.269C>G, c.473T>A) gene variants. In addition, three novel variants were identified in the NRXN1 (c.1679C>T), NRXN3 [c.3889C>T (p.Pro1297Ser)], and NLGN1 [c.473T>A (p.Ile158Lys)] genes. We emphasize the clinical findings of CNVs of the NRXN1 gene causing a more severe clinical presentation than single nucleotide variants of the NRXN1 gene in this study. We detected an NRXN2 gene variant (c.808dup) with low allelic frequency in two unrelated cases with the same diagnosis. We emphasize the importance of this variant for future studies. We suggest that NRXN2, NRXN3, and NLGN1 genes, which are less frequently reported than NRXN1 gene variants, may also be associated with neurodevelopmental disorders.

The efficacy of the use of atropine in children with reflex anoxic syncope during pallid breath-holding spells: can cardiac pacemaker implantation be avoided?

Reflex anoxic syncope is the result of an overreaction of the vagal system, resulting in hypotension and bradycardia or brief cardiac arrest. Because of the benign character and the absence of complications in short or long term, treatment is only necessary in case of frequent or severe clinical presentation. Treatment options are anticholinergic drugs or cardiac pacemaker placement. We investigated atropine treatment and aimed to examine if pacemaker placement can be avoided. We retrospectively reviewed patients treated with atropine for severe reflex anoxic syncope in our centre from January 2017 until May 2023, and compared our results to those in the literature. The study population consisted of 10 children, 70% female, with an age ranging from 5 months to 3 years (mean 14.5 months) when atropine treatment was started (dose 17-50 microg/kg/day). All patient's parents reported adequate symptom management during atropine treatment, with complete resolution in 10%. Minor side effects were reported in 60% (dry mucosa in 40%, obstipation in 20%, and nausea or blurry vision in 10%). We consider atropine a safe and effective treatment to manage reflex anoxic syncope with similar success rate to pacemaker implantation. However, pacemaker implantation entails substantial risk for complications (up to 25%) such as infection or technical problems and morbidity such as scar formation. This might be considered redundant for a benign and temporary condition, certainly given the possibility of other efficient treatment options. Consequently, we recommend atropine treatment over implantation of a cardiac pacemaker in children with severe reflex anoxic syncope.

Assessing the impact of migraine on benign paroxysmal positional vertigo symptoms and recovery

BackgroundDuring episodes of benign paroxysmal positional vertigo (BPPV), individuals with migraine, compared with individuals without migraine, may experience more severe vestibular symptoms because of their hyperexcitable brain structures, more adverse effects on quality of life, and worse recovery processes from BPPV.MethodsAll patients with BPPV were assigned to the migraine group (MG, n = 64) and without migraine group (BPPV w/o MG, n = 64) and completed the Vertigo Symptom Scale (VSS), Vertigo Dizziness Imbalance Symptom Scale (VDI-SS), VDI Health-Related Quality of Life Scale (VDI-HRQoLS), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) at the time of BPPV diagnosis (baseline) and on the one-month follow-up. Headache Impact Test-6 and Migraine Disability Assessment Scale were used for an assessment of headache. Motion sickness was evaluated based on the statement of each patient as present or absent.ResultsCompared with the BPPV w/o MG, the MG had higher VSS scores at baseline [19.5 (10.7) vs. 11.3 (8.5); p < 0.001] and on one-month follow-up [10.9 (9.3) vs. 2.2 (2.7), p < 0.001]; experienced more severe dizziness and imbalance symptoms based on the VDI-SS at baseline (61.9% vs. 77.3%; p < 0.001) and after one month (78.9% vs. 93.7%, p < 0.001); and more significantly impaired quality of life according to the VDI-HRQoLS at baseline (77.4% vs. 91.8%, p < 0.001) and after one month (86.3% vs. 97.6%, p < 0.001).On the one-month follow-up, the subgroups of patients with moderate and severe scores of the BAI were higher in the MG (39.2%, n = 24) than in the BPPV w/o MG (21.8%, n = 14) and the number of patients who had normal scores of the BDI was lower in the MG than in the BPPV w/o MG (67.1% vs. 87.5%, p = 0.038).ConclusionClinicians are advised to inquire about migraine when evaluating patients with BPPV because it may lead to more intricate and severe clinical presentation. Further studies will be elaborated the genuine nature of the causal relationship between migraine and BPPV.

Unusual Presentation of Congenital Chloride Diarrhea Mimicking Colovesical Fistula: A Case Report and Literature Review

Background: Congenital Chloride Diarrhea (CCD) is a rare autosomal recessive condition characterized by lifelong watery diarrhea. CCD is challenging to diagnose because of its severe clinical presentations and differentials. Therefore, it is crucial to be diagnosed early and receive appropriate management as it causes early death if left untreated or due to complications. Case Report: A Saudi newborn baby boy who was passing a large amount of urine through the anal canal and was otherwise healthy. He was referred to our center with a high suspicion of a colovesical fistula. Diagnosed with CCD by exclusion of fistula after confirmation with contrast study. Conclusion: This case highlights an unusual presentation of CCD mimicking a colovesical fistula. To our knowledge, no similar case has been reported in the literature, and we believe this is the first Saudi case report. It underscored the diagnostic challenges of this rare disorder and emphasized the importance of early recognition and accurate diagnosis to prevent such complications.

Metagenomic Analysis for Diagnosis of Hemorrhagic Fever in Minas Gerais, Brazil.

Viral hemorrhagic fever poses a significant public health challenge due to its severe clinical presentation and high mortality rate. The diagnostic process is hindered by similarity of symptoms across different diseases and the broad spectrum of pathogens that can cause hemorrhagic fever. In this study, we applied viral metagenomic analysis to 43 serum samples collected by the Public Health Laboratory (Fundação Ezequiel Dias, FUNED) in Minas Gerais State, Brazil, from patients diagnosed with hemorrhagic fever who had tested negative for the standard local hemorrhagic disease testing panel. This panel includes tests for Dengue virus (DENV) IgM, Zika virus IgM, Chikungunya virus IgM, yellow fever IgM, Hantavirus IgM, Rickettsia rickettsii IgM/IgG, and Leptospira interrogans IgM, in addition to respective molecular tests for these infectious agents. The samples were grouped into 18 pools according to geographic origin and analyzed through next-generation sequencing on the NextSeq 2000 platform. Bioinformatic analysis revealed a prevalent occurrence of commensal viruses across all pools, but, notably, a significant number of reads corresponding to the DENV serotype 2 were identified in one specific pool. Further verification via real-time PCR confirmed the presence of DENV-2 RNA in an index case involving an oncology patient with hemorrhagic fever who had initially tested negative for anti-DENV IgM antibodies, thereby excluding this sample from initial molecular testing. The complete DENV-2 genome isolated from this patient was taxonomically classified within the cosmopolitan genotype that was recently introduced into Brazil. These findings highlight the critical role of considering the patient's clinical condition when deciding upon the most appropriate testing procedures. Additionally, this study showcases the potential of viral metagenomics in pinpointing the viral agents behind hemorrhagic diseases. Future research is needed to assess the practicality of incorporating metagenomics into standard viral diagnostic protocols.

Subgroups of Clinical High Risk for Psychosis Based on Baseline Antipsychotic Exposure: Clinical and Outcome Comparisons Across a 2-Year Follow-up Period.

Antipsychotic (AP) prescription in clinical high risk for psychosis (CHR-P) subjects remains a divisive issue. Although official guidelines currently discourage AP treatment in CHR-P, it is common in clinical practice, especially for psychosis prevention. The aim of this study was to investigate whether baseline AP need (especially in high-dose) indexes a CHR-P subgroup with poorer prognosis and differs from AP-naïve subjects in terms of sociodemographic, clinical, and outcome parameters across a 2-year follow-up. CHR-P participants were treated within an "Early Intervention in Psychosis" program and completed the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale both at baseline and every 12 months. Individuals with baseline AP prescription were included in the high-dose or low-dose CHR-P-AP+ subgroup. The others were grouped as AP-naïve. Cox regression analyses and mixed-design ANOVA were performed. 180 CHR-P individuals were enrolled (32 high-dose, 60 low-dose, and 88 AP-naïve). Compared to AP-naive, CHR-P AP+ subgroups showed older age and more severe clinical presentation. High-dose subgroup also had grater functioning decline at entry and poorer functional recovery at follow-up. No inter-group differences in psychosis transition and symptomatic remission were found. Significant improvement in clinical outcomes were found over time in all subgroups. Baseline AP prescription was specifically associated with a more relevant improvement in PANSS total score, and in negative and disorganized symptoms. Our results suggest that baseline AP need is an important prognostic parameter in CHR-P and should be considered in risk/benefit calculators.

Whole-genome characterisation of Escherichia coli isolates from patients with bacteraemia presenting with sepsis or septic shock in Spain: a multicentre cross-sectional study

Escherichia coli is the most frequent cause of bloodstream infections (BSIs). About one-third of patients with BSIs due to E coli develop sepsis or shock. The objective of this study is to characterise the microbiological features of E coli blood isolates causing sepsis or septic shock to provide exploratory information for future diagnostic, preventive, or therapeutic interventions. E coli blood isolates from a multicentre cross-sectional study of patients older than 14 years presenting with sepsis or septic shock (according to the Third International Consensus Definitions for Sepsis and Septic Shockcriteria) from hospitals in Spain between Oct 4, 2016, and Oct 15, 2017, were studied by whole-genome sequencing. Phylogroups, sequence types (STs), serotype, FimH types, antimicrobial resistance (AMR) genes, pathogenicity islands, and virulence factors were identified. Susceptibility testing was performed by broth microdilution. The main outcome of this study was the characterisation of the E coli blood isolates in terms of population structure by phylogroups, groups (group 1: phylogroups B2, F, and G; group 2: A,B1, and C; group 3: D), and STs and distribution by geographical location and bloodstream infection source. Other outcomes were virulence score and prevalence of virulence-associated genes, pathogenicity islands, AMR, and AMR-associated genes. Frequencies were compared using χ² or Fisher's exact tests, and continuous variables using the Mann-Whitney test, with Bonferroni correction for multiple comparisons. We analysed 224 isolates: 140 isolates (63%) were included in phylogenetic group 1, 52 (23%) in group 2, and 32 (14%) in group 3. 85 STs were identified, with four comprising 44% (n=98) of the isolates: ST131 (38 [17%]), ST73 (25 [11%]), ST69 (23 [10%]), and ST95 (12 [5%]). No significant differences in phylogroup or ST distribution were found according to geographical areas or source of bloodstream infection, except for ST95, which was more frequent in urinary tract infections than in other sources (11 [9%] of 116 vs 1 [1%] of 108, p=0·0045). Median virulence score was higher in group 1 (median 25·0 [IQR 20·5-29·0) than in group 2 (median 14·5 [9·0-20·0]; p<0·0001) and group 3 (median 21 [16·5-23·0]; p<0·0001); prevalence of several pathogenicity islands was higher in group 1. No significant differences were found between phylogenetic groups in proportions of resistance to antibiotics. ST73 had higher median virulence score (32 [IQR 29-35]) than the other predominant clones (median range 21-28). Some virulence genes and pathogenicity islands were significantly associated with each ST. ST131 isolates had higher prevalence of AMR and a higher proportion of AMR genes, notably blaCTX-M-15 and blaOXA-1. In this exploratory study, the population structure of E coli causing sepsis or shock was similar to previous studies that included all bacteraemic isolates. Virulence genes, pathogenicity islands, and AMR genes were not randomly distributed among phylogroups or STs. These results provide a comprehensive characterisation of invasive E coli isolates causing severe response syndrome. Future studies are required to determine the contribution of these microbiological factors to severe clinical presentation and worse outcomes in patients with E coli bloodstream infection. Instituto de Salud Carlos III.

Temporal trends in the clinical presentation of Graves’ orbitopathy: a single–center retrospective study

PurposeGraves’ ophthalmopathy (GO) is an autoimmune disease that affects orbital soft tissues and represents the most common extrathyroidal manifestation of Graves’ disease (GD). The European Group of Graves’ Ophthalmopathy (EUGOGO) has attempted to shed light on the European epidemiological picture of GO, suggesting that GO in newly diagnosed patients in recent years has a trend towards a less severe clinical presentation. There are no studies that focus this issue on the population of our area; we aimed to evaluate the trend of GO clinical presentation in our outpatient clinic through an observation period of 10 years.MethodsWe compared 55 consecutive patients, 11 males (F) and 44 females (M), who came to our observation from January 2005 to December 2006 [Group 1 (G1)], with 56 patients, 15 males, and 41 females, who were referred to us from 2015 to 2016 [Group 2 (G2)]. We studied the following putative predictors of GO presentation and severity: thyroid function, smoking, diabetes, hypercholesterolemia, time from GO diagnosis to referral to our thyroid centre (TGOD), sex and age.ResultsGO severity was significantly reduced in G2 vs. G1 (p = 0.04). TGOD ≥ 3 months was related to clinical characteristics of GO (severity and Clinical Activity Score ≥ 4) and was an independent predictor of GO severity (p = 0.01). The other variables evaluated had no independent effects.ConclusionsWe found that GO severity at presentation was significantly reduced over a ten-year observation period (2005–2006 vs. 2015–2016) in GO patients referred to our tertiary thyroid centre. TGOD ≥ 3 months was an independent predictor of GO severity.

Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: A RECOVER trial report

BackgroundRECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention. ObjectiveTo describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine. MethodsMedical, psychiatric, and treatment records were reviewed by study investigators and an independent Study Eligibility Committee prior to study qualification. Clinical characteristics and treatment history (using Antidepressant Treatment History [Short] Form) were compared in those qualified (N = 493) versus not qualified (N = 228) for RECOVER, and among the qualified group as a function of exposure to INTs during the current major depressive episode (MDE). ResultsUnipolar MDD patients who qualified for RECOVER had marked TRD (median of 11.0 lifetime failed antidepressant treatments), severe disability (median WHODAS score of 50.0), and high rate of baseline suicidality (77% suicidal ideation, 40% previous suicide attempts). Overall, 71% had received at least one INT. Compared to the no INT group, INT recipients were younger and more severely depressed (QIDS-C, QIDS-SR), had greater suicidal ideation, earlier diagnosis of MDD, and failed more antidepressant medication trials. ConclusionsRECOVER-qualified unipolar patients had marked TRD and marked treatment resistance with most failing one or more prior INTs. Treatment with ≥1 INTs in the current MDE was associated with earlier age of MDD onset, more severe clinical presentation, and greater treatment resistance relative to patients without a history of INT. Trial registrationClinicalTrials.gov Identifier NCT03887715.

3q29 duplications: A cohort of 46 patients and a literature review.

Duplications of the 3q29 cytoband are rare chromosomal copy number variations (CNVs) (overlapping or recurrent ~1.6 Mb 3q29 duplications). They have been associated with highly variable neurodevelopmental disorders (NDDs) with various associated features or reported as a susceptibility factor to the development of learning disabilities and neuropsychiatric disorders. The smallest region of overlap and the phenotype of 3q29 duplications remain uncertain. We here report a French cohort of 31 families with a 3q29 duplication identified by chromosomal microarray analysis (CMA), including 14 recurrent 1.6 Mb duplications, eight overlapping duplications (>1 Mb), and nine small duplications (<1 Mb). Additional genetic findings that may be involved in the phenotype were identified in 11 patients. Focusing on apparently isolated 3q29 duplications, patients present mainly mild NDD as suggested by a high rate of learning disabilities in contrast to a low proportion of patients with intellectual disabilities. Although some are de novo, most of the 3q29 duplications are inherited from a parent with a similar mild phenotype. Besides, the study of small 3q29 duplications does not provide evidence for any critical region. Our data suggest that the overlapping and recurrent 3q29 duplications seem to lead to mild NDD and that a severe or syndromic clinical presentation should warrant further genetic analyses.

Respiratory Syncytial Virus Bronchiolitis Before and After COVID-19 Pandemic: Has the Immunity Debt Been Paid Off?

Our aim was to hypothesize that the COVID-19 pandemic influenced the characteristics of viral bronchiolitis by comparing the last 3 epidemics with 3 pre-COVID-19 epidemics in infants hospitalized with bronchiolitis. We prospectively enrolled 637 consecutive infants (median age 3.0 ± 2.1 months, 58.5% males), hospitalized for bronchiolitis during 6 consecutive annual epidemic seasons from 2017 to 2023. All parents of the children were given a structured anamnestic questionnaire. A nasopharyngeal aspirate was tested for 15 respiratory viruses. As measures of severity, we evaluated the O 2 supplementation and the admission at the pediatric intensive care unit. A total of 166 were hospitalized with bronchiolitis in 2017-2018, 97 in 2018-2019, 69 in 2019-2020, 0 in 2020-2021, 129 in 2021-2022 and 176 in 2022-2023. Taking together the 332 bronchiolitis cases hospitalized during the 3 prepandemic seasons, they peaked between December and January; after the flat curve in 2020-2021, the cases of bronchiolitis peaked in November 2021 and in December 2022. While the 2021-2022 season registered a less severe clinical presentation, O 2 supplementation and pediatric intensive care unit admissions increased in 2022-2023 with respect to the prepandemic seasons ( P < 0.001). This study represents an important scientific demonstration of the impact of primary prevention measures on the epidemiology of viral infections; their fluctuations were related to the intensity of restrictive measures and to the changing trend of respiratory viruses. It is essential to predict the real temporal trend of bronchiolitis not to leave high-risk children uncovered and to guide hospitals to maintain a high level of readiness.

Tricuspid regurgitation: Frequency, clinical presentation, management and outcome among patients with severe left-sided valvular heart disease in Europe. Insights from the ESC-EORP Valvular Heart Disease II survey.

Tricuspid regurgitation (TR) is commonly observed in patients with severe left-sided valvular heart disease (VHD). This study sought to assess TR frequency, management and outcome in this population. Among 6883 patients with severe native left-sided VHD or previous left-sided valvular intervention enrolled in the EURObservational Research Programme prospective VHD II survey, moderate or severe TR was very frequent in patients with severe mitral VHD (30% when mitral stenosis, 36% when mitral regurgitation [MR]), especially in patients with secondary MR (46%), and rare in patients with severe aortic VHD (4% when aortic stenosis, 3% when aortic regurgitation). An increase in TR grade was associated with a more severe clinical presentation and a poorer 6-month survival (p < 0.0001). Rates of concomitant tricuspid valve (TV) intervention at the time of left-sided heart valve surgery were high at the time of mitral valve surgery (50% when mitral stenosis, 41% when MR). Concordance between class I indications (patients with severe TR) for concomitant TV surgery at the time of left-sided valvular heart surgery according to guidelines and real-practice decision-making was very good (88% overall, 95% in patients operated on for MR). In this large international prospective survey among patients with severe left-sided VHD, moderate/severe TR was frequent in patients with mitral valve disease and was associated with a poorer outcome as TR grade increased. In patients with severe TR, compliance to guidelines for class I indications for concomitant TV surgery at the time of left-sided heart valve surgery was very good.

Tiny Lungs, Big Differences: Navigating the Varied COVID-19 Landscape in Neonates vs. Infants via Biomarkers and Lung Ultrasound.

Due to their susceptibilities, neonates and infants face unique SARS-CoV-2 challenges. This retrospective study will compare the illness course, symptoms, biomarkers, and lung damage in neonates and infants with SARS-CoV-2 infection from February 2020 to October 2023. This study was conducted at two hospitals in Timisoara, Romania, using real-time multiplex PCR to diagnose and lung ultrasonography (LUS) to assess lung involvement. Neonates had a more severe clinical presentation, an increased immune response, and greater lung involvement. Neonates had more PCR-positive tests (p = 0.0089) and longer hospital stays (p = 0.0002). In neonates, LDH, CRP, and ferritin levels were higher, indicating a stronger inflammatory response. Reduced oxygen saturation in neonates indicates respiratory dysfunction. The symptoms were varied. Infants had fever, cough, and rhinorrhea, while neonates had psychomotor agitation, acute dehydration syndrome, and candidiasis. This study emphasizes individualized care and close monitoring for neonatal SARS-CoV-2 infections. Newborn lung ultrasonography showed different variances and severity levels, emphasizing the need for targeted surveillance and therapy. Newborns have high lung ultrasound scores (LUSS), indicating significant lung involvement. Both groups had initial lung involvement, but understanding these modest differences is crucial to improving care for these vulnerable populations.

From plan to practice: A qualitative study of public mental health therapists' session-planning practices.

Therapists must dedicate considerable time to session plan to implement evidence-based practices (EBPs) flexibly and with fidelity. It is unclear whether public mental health settings offer the structural and organizational support for therapists to engage in session planning and, therefore, whether they provide the necessary infrastructure for EBP implementation. In Fall 2022, 18 therapists working in public mental health settings in New York City were recruited through snowball sampling to participate in 90-min semistructured qualitative interviews. Therapists were prompted to review their session-planning practices using a chart-stimulated recall strategy; to describe structural, organizational, and individual barriers and facilitators to session planning; and to generate recommendations to support their session planning. Qualitative data were analyzed using thematic analysis. A diverse group of therapists participated in the study-22% identified as Black; 22% as Asian; and 11% as Hispanic/Latinx. Seventy-eight percent of therapists were social workers; and they had on average 6.18 (SD = 5.70) years of clinical experience. The research team identified four multilevel session-planning barriers and three multilevel session-planning facilitators. Therapists proposed seven multilevel recommendations to support their session planning. Overall, therapists indicated that managing high productivity standards, severe clinical presentations, and clients' social needs often prevent them from having time to plan for sessions. Efforts to implement EBPs in public mental health settings cannot neglect the structural realities faced by agencies, therapists, and clients. Multilevel resources and reforms to support therapists' session planning are necessary. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Abstract WP149: Duration of Lead-In Parenteral Therapy and Outcomes in Individuals Treated With DOAC for Cerebral Venous Thrombosis: The ACTION-CVT Study

Background: Direct oral anticoagulants (DOACs) are suitable for some patients with cerebral venous thrombosis (CVT). The optimal transition strategy from parenteral anticoagulation (PA) to DOAC is not known. We examined duration of PA prior to DOAC initiation and outcomes in ACTION-CVT, an international retrospective study. Methods: We compared three groups: no lead-in PA, 1-4 days (d) of PA, and 5-21d of PA. The primary outcome at day 90 (D90) was a composite of CVT recurrence/extension and symptomatic intracranial hemorrhage (sICH). Secondary outcomes (D90) were complete venous recanalization and mRS of 0-2. We evaluated outcomes using descriptive statistics and crude and adjusted logistic regression modeling. Results: Of 231 patients treated with DOAC, 11.7% had no lead-in PA, 64.5% 1-4d, 23.8% 5-21d. Compared to those with &lt;5d, those with 5-21d had worse clinical-radiological presentations at baseline, including more focal deficits, encephalopathy, and ICH (Table 1). Primary outcome events were low overall; all 6 occurred in the &lt;5d group. Odds of complete recanalization were lower in the &lt;5d group, although this difference attenuated with adjustment for baseline characteristics. There were no differences in odds of mRS 0-2. (Table 2) Conclusions: Individuals treated with DOAC for CVT who received 5-21d of PA had more severe clinical and radiological presentations compared to those with &lt;5d. Rates of CVT extension, recurrence and sICH were too low to reach conclusions regarding safety of one strategy over another. Odds of complete recanalization were higher in those with 5-21d PA, but these differences attenuated after adjustment for baseline patient characteristics.