Severe Clinical Presentation Research Articles

Lead-In Parenteral Anticoagulation Prior to Direct Oral Anticoagulation for Cerebral Venous Thrombosis.

Growing evidence suggests that direct oral anticoagulants (DOACs) may be suitable for cerebral venous thrombosis (CVT). The optimal strategy regarding lead-in parenteral anticoagulation (PA) prior to DOAC is unknown. In this post hoc analysis of the retrospective ACTION-CVT study, we compared patients treated with DOACs as part of routine care: those given "very early" DOAC (no PA), "early" (<5 days PA) and "delayed" (5-21 days PA). We compared baseline characteristics and outcomes between the very early/early and delayed groups. The primary outcome was a composite of day-30 CVT recurrence/extension, new peripheral venous thromboembolism, cerebral edema and intracranial hemorrhage. Of 231 patients, 11.7% had very early DOAC, 64.5% early (median [IQR] 2 [1-2] days) and 23.8% delayed (5 [5-6] days). More patients had severe clinical/radiological presentations in the delayed group; more patients had isolated headaches in the very early/early group. Outcomes were better in the very early/early groups (90-day modified Rankin Scale of 0-2; 94.3% vs. 83.9%). Primary outcome events were rare and did not differ significantly between groups (2.4% vs. 2.1% delayed; adjusted HR 1.49 [95%CI 0.17-13.11]). In this cohort of patients receiving DOAC for CVT as part of routine care, >75% had <5 days of PA. Those with very early/early initiation of DOAC had less severe clinical presentations. Low event rates and baseline differences between groups preclude conclusions about safety or effectiveness. Further prospective data will inform care.

Cardiac Rehabilitation for Fontan Circulation Patients: A Systematic Review, and Meta-Analysis

Background and Objectives: Despite advances in the surgical management of patients with Fontan circulation, their exercise capacity and quality of life remain significantly impaired. Exercise-based cardiac rehabilitation (CR) offers promising improvements in these areas, but the implementation and adherence to these programmes are often inconsistent. This systematic review and meta-analysis aimed to evaluate the safety, efficacy, and optimal exercise modalities for Fontan patients. Materials and Methods: A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library was conducted on 24 August 2023. Studies were screened and assessed for quality using the Cochrane RoB Tool 2 and STROBE checklist. Meta-analysis was performed using a continuous random-effects model to determine the effectiveness of various CR interventions, including aerobic exercise training (AET), resistance training, and inspiratory muscle training (IMT). Results: A total of 26 studies (7 RCTs, 19 cohorts) comprising 22 distinct cohorts were included, with a total sample size of 428 Fontan patients. The interventions ranged from 4 weeks to 24 months and included AET (18 studies), resistance training (11 studies), and IMT (6 studies). The meta-analysis revealed significant improvements in exercise capacity, with a pooled mean difference in peak VO2 of 1.947 (95% CI: 1.491 to 2.402, p &lt; 0.001). Subgroup analyses showed that combined AET and resistance training had the most robust effect, with a mean difference of 2.11 (95% CI: 1.57 to 2.65, p &lt; 0.001). Home-based interventions showed significant benefits, while supervised and hybrid interventions did not show statistically significant differences. Publication bias was identified, particularly in home-based interventions, where smaller studies demonstrated larger effect sizes, as confirmed by Egger’s test (Intercept = 2.417, 95% CI: 1.498 to 3.337, p = 0.001). However, no significant bias was detected in supervised or hybrid interventions, which displayed symmetrical distributions in funnel plots and non-significant Egger’s test results. Conclusions: CR appears to be an effective intervention for improving exercise capacity in Fontan patients, particularly when combining AET with resistance training. Home-based programmes offer promising results, though the potential for publication bias, especially in smaller studies, warrants cautious interpretation of these findings. Further research is needed to refine protocols, explore long-term outcomes, and determine the underlying mechanisms, particularly for patients with more severe clinical presentations. The low incidence of adverse events across the studies reinforces the safety of these interventions.

Characteristics and outcomes of patients with moderate multivalvular disease in the context of tricuspid regurgitation

Abstract Background The clinical features and the long-term prognosis of patients with moderate tricuspid regurgitation (TR) in the context of concomitant moderate left-sided valvular disease (VD) are poorly characterized. Purpose This study sought to describe the characteristics and the outcomes of patients with combined moderate TR and moderate mitral or aortic VD. Methods Baseline clinical and follow-up data were collected from 2110 patients with moderate TR in combination with a moderate left-sided VD diagnosed at our centers from January 2012 to July 2020; the final cohort was divided in 4 groups as shown in Figure 1. The primary endpoint was all-cause death; secondary EP was the first occurrence of heart failure (HF) hospitalization. Results Group 1 patients (1529, 72.5%) had the highest prevalence of chronic kidney disease (897, 66%) and lowest left ventricular systolic function (LVEF &amp;lt;50%, 298, 21%), as detailed in Table 1. Coronary artery disease was most prevalent in Group 2 patients (43, 41%), which also presented with the lowest average Charlson Index scores (3.95±1.87) and most prevalent dyspnea symptoms (44, 41%). Group 3 patients (41, 1.9%) were the oldest (82±7 years), had the highest rate of comorbidities (mean Charlson score 5.2±1.6), atrial fibrillation (20, 54%) and pulmonary hypertension (17, 46%). Eventually, Group 4 patients (422, 20%) were the youngest (74±13 years), more commonly female (279, 66%) and with the highest right ventricular dysfunction rate (TAPSE &amp;lt; 17 mm, 114, 40%). After a median follow-up of 2.1 years, the primary endpoint occurred in 895 (42.4%) patients, with a significantly higher incidence in Group 3 patients (p&amp;lt;0.001) (Figure 1). The secondary endpoint occurred in 316 (15.0%) patients and, similarly, significantly more frequently in Group 3 patients (p=0.01). Subgroup analysis for the primary and secondary endpoint in patients with preserved ejection fraction (LVEF &amp;gt; 50%) confirmed the results of the primary analysis, with Group 3 as the cohort with the most adverse outcomes. Conclusions Patients with significant TR frequently exhibit concurrent left-sided VD, identifying distinct patient subgroups with varying clinical profiles. Notably, TR combined with moderate AS is associated with the most severe clinical presentation and the poorest long-term prognosis, even in patients with preserved LVEF.Figure 1.

HR-pQCT reveals marked trabecular and cortical structural deficits in women with pregnancy and lactation associated osteoporosis (PLO).

Pregnancy and lactation associated osteoporosis (PLO) is a rare presentation of early-onset osteoporosis characterized by low trauma, spontaneous fractures during late pregnancy/lactation. Herein, we report areal BMD (aBMD) by DXA and volumetric BMD (vBMD), microarchitecture and strength at the distal radius and tibia by HR-pQCT in 59 women with PLO - in comparison to both healthy premenopausal Controls (n= 28) and premenopausal women with idiopathic osteoporotic fractures not associated with pregnancy/lactation (Non-PLO IOP;n= 50). Women with PLO (aged 34 ± 6yrs) had a more severe clinical presentation than Non-PLO IOP: 80% had vertebral and 92% had multiple fractures (P<.001). They had lower DXA aBMD at all sites vs Controls (all P<.001) and non-PLO IOP (all P<.05). By HR-pQCT, PLO had deficits in all radial/tibial density and most microarchitecture parameters, and lower bone strength than Controls (all P<.001). Compared to non-PLO IOP, PLO had lower total and trabecular density at radius and tibia (all P≤.01) and significant deficits in trabecular microstructure and cortical thickness at the radius only. We studied PLO subgroups with clinical factors potentially related to bone physiology: Within PLO, women with vertebral fractures had lower spine aBMD and higher tibial cortical porosity but were otherwise structurally similar to the nonvertebral group. Those with prior heparin exposure had larger bone size and trabecular area, and those with renal stones had smaller bone size and lower 1/3radius aBMD. We also compared groups based on postpartum timing: Recent PLO (n= 25) evaluated ≤12M postpartum, before expected recovery of pregnancy/lactation bone loss, had significantly lower aBMD than Distant PLO (n= 34) evaluated >12M postpartum. However, radial/tibial HR-pQCT measures did not differ, suggesting pre-existing and/or persistent structural deficits. This structural study increases our mechanistic understanding of the severe bone fragility presentation that characterizes PLO and also highlights areas of potential mechanistic heterogeneity that require additional investigation.

Resolution of SLC6A1 variable expressivity in a multi-generational family using deep clinical phenotyping and Drosophila models.

Variants in SLC6A1 result in a rare neurodevelopmental disorder characterized by a variable clinical presentation of symptoms including developmental delay, epilepsy, motor dysfunction, and autism spectrum disorder. SLC6A1 haploinsufficiency has been confirmed as the predominant pathway of SLC6A1-related neurodevelopmental disorders (NDDs), however, the molecular mechanism underlying the variable clinical presentation remains unclear. Here, through work of the Undiagnosed Diseases Network, we identify an undiagnosed individual with an inherited p.(A334S) variant of uncertain significance. To resolve this case and better understand the variable expressivity with SLC6A1, we assess the phenotypes of the proband with a cohort of cases diagnosed with SLC6A1-related NDDs. We then create an allelic series in the Drosophila melanogaster to functionally characterize case variants. We identify significant clinical overlap between the unsolved case and confirmed cases of SLC6A1-related NDDs and find a mild to severe clinical presentation associated with missense variants. We confirm phenotypes in flies expressing SLC6A1 variants consistent with a partial loss-of-function mechanism. We conclude that the p.(A334S) variant is a hypomorphic allele and begin to elucidate the underlying variability in SLC6A1-related NDDs. These insights will inform clinical diagnosis, prognosis, treatment and inform therapeutic design for those living with SLC6A1-related NDDs.

Critically Ill Patients with Newly Diagnosed Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: Case Series and Literature Review

ANCA-associated vasculitides (AAVs) are rare diseases with a prevalence of less than 200 cases per million persons and an incidence of less than 25 cases per million person-years. Their presenting features can vary from prodromal and nonspecific symptoms to dramatic organ-specific symptoms such as respiratory failure due to diffuse alveolar hemorrhage (DAH) and acute kidney injury (AKI). The latter two are hallmark features of pulmonary-renal syndrome, a potentially fatal condition that necessitates early recognition and treatment in intensive care units (ICUs) and rapid induction of immunosuppressive therapy. Background and case summaries: We described three patients with newly diagnosed AAV during the treatment of critical illness. All patients had DAH and two had AKI. The initial disease severity was extremely high in patients with myeloperoxidase (MPO)-AAV, reaching Sequential Organ Failure Assessment (SOFA) scores of 15 and 14 with predicted mortality ≥ 95.2%. Both patients needed mechanical ventilation, one additional venovenous extracorporeal membrane oxygenation (VV-ECMO), and renal replacement therapy. The patient with proteinase 3 (PR3)-AAV had a less severe disease, SOFA 3, requiring only modest oxygen supplementation and exhibiting only hematuria with normal renal function parameters. Immunosuppressive therapy was initiated during the ICU stay. The patient with the most severe clinical presentation died during the ICU stay because of sepsis, and the other two patients were discharged home. Conclusions: Patients with AAV presenting with pulmonary-renal syndrome necessitate various degrees of organ support. Nevertheless, these patients can be successfully treated in the early, critical stages of the disease and achieve remission.

Insights from a Wolfram syndrome cohort: clinical and molecular findings from a specialized diabetes reference center.

Considering the rarity and clinical and molecular diversity of Wolfram syndrome (WS), the objective of this study was to identify patients with a clinical presentation suggestive of WS following up at a single Brazilian diabetes service and analyze their clinical and molecular characteristics. The study included all patients with a clinical presentation of WS following up between 1991 and 2022 with early-onset diabetes mellitus and other WS signs and symptoms. A retrospective analysis was conducted, including patients' age, sex, consanguinity, age at symptom onset, diagnosis of diabetes mellitus, optic atrophy, diabetes insipidus, neurological and psychiatric disorders, hearing loss, urinary disorders, hypogonadism, and WFS1 molecular analysis. Eight patients were identified, all of whom were diagnosed with diabetes mellitus at an average age of 3.7 years. Optic atrophy, diabetes insipidus, and hearing loss were common, while psychiatric and neurological alterations were observed in some cases. Genetic analysis revealed pathogenic variants in homozygosity or compound heterozygosity. The most frequent variant was p. Val412Serfs29, present in five of the seven families. This study represents the second-largest Brazilian sample of WS and is the first cohort from a single center in Southeast Brazil. The patients had an early, severe, and complete clinical presentation. The genetic variants identified were consistent with previous literature descriptions. The variant p. Val412Serfs29 was particularly common in this cohort, highlighting its relevance in the region.

High genetic diversity of Anaplasma ovis in sheep from Bosnia and Herzegovina.

Ovine anaplasmosis (sensu stricto) is a rickettsial blood disease caused by the tick-borne species Anaplasma ovis. The disease is characterized by mild anemia, fever, and icterus. A more severe clinical presentation is possible in non-endemic areas. There is no existing data on the presence of Anaplasma ovis in Bosnia and Herzegovina. However, given the country's location within the Mediterranean Basin and the recent molecular detection of Babesia ovis, it is plausible that sheep in the region could naturally be infected with this tick-borne pathogen. Blood samples from 81 sheep in the Podrinje and Herzegovina areas were examined by PCR. PCR positivity was found in 38 (46.9%) cases indicating a high number of infected sheep. Mixed infections with Babesia ovis and A.ovis were observed in 63.3% of cases. A higher number of positive sheep was recorded in the area of Herzegovina. Phylogenetic analysis of the gltA, groEL, and msp4 genes of A. ovis revealed numerous genotypes and significant genetic variability. This diversity was not related to geographic origin, tick-borne infection status, or sheep breeding practices in Podrinje and Herzegovina. The data obtained in this study suggest that the emergence of new genotypes and the high genetic variability of A. ovis are driven by specific local and micro-environmental factors.

Contemporary Multimodality Imaging for Diagnosis and Management of Fabry Cardiomyopathy.

Fabry disease (FD) is an X-linked lysosomal storage disorder which leads to the accumulation of globotriaosylceramide (Gb3) in various organs, including the heart. FD can be subdivided into classic disease resulting from negligible residual enzyme activity and a milder, atypical phenotype with later onset and less severe clinical presentation. The use of multimodality cardiac imaging including echocardiography, cardiac magnetic resonance and nuclear imaging is important for the diagnostic and prognostic evaluation in these patients. There are gaps in the literature regarding the comprehensive description of cardiac findings of FD and its evaluation by multimodality imaging. In this review, we describe the contemporary practices and roles of multimodality cardiac imaging in individuals affected with Fabry disease.

Increased macrolide resistance rate of Mycoplasma pneumoniae correlated with epidemic in Beijing, China in 2023.

We collected respiratory specimens from 128 pediatric patients diagnosed with pneumonia in Beijing in late 2023. Mycoplasma pneumoniae was detected in 77.3% (99/128) patients, with 36.4% (4/11), 82.9% (34/41), 80.3% (61/76) in children aged less than 3 years, 3-6 years, over 7 years, respectively. Mycoplasma pneumoniae (M. pneumoniae) was characterized using P1 gene typing, MLVA typing and sequencing of domain V of the 23S rRNA gene. P1 gene type 1 (P1-1; 76.1%, 54/71) and MLVA type 4-5-7-2 (73.7%, 73/99) were predominant. MLVA identified a new genotype: 3-4-6-2. Macrolide resistance-associated mutations were detected in 100% of samples, with A2063G accounting for 99% and A2064G for 1%. The positive rate of M. pneumoniae was higher compared to previous reports, especially in children less than 3 years, suggesting a M. pneumoniae epidemic showing a younger age trend occurred in late 2023 in Beijing, China. Higher proportions of macrolide-resistant M. pneumoniae, P1-1 and 4-5-7-2 genotype M. pneumoniae indicated increased macrolide resistance rate and genotyping shift phenomenon, which might be attributable to this epidemic. Additionally, complete clinical information from 73 M. pneumoniae pneumonia inpatients were analyzed. The incidence of severe M. pneumoniae pneumonia was 56.2% (41/73). Mycoplasma pneumoniae pneumonia patients exhibited longer duration of fever, with a median value of 10.0 days (IQR, 8.0-13.0), and higher incidence of complications (74.0%, 54/73). However, in this cohort, we found that the severity of M. pneumoniae pneumonia, co-infection, or complications were not associated with M. pneumoniae P1 gene or MLVA types. Clinicians should be aware that patients infected with macrolide-resistant M. pneumoniae exhibited more severe clinical presentations.

A computerized tomography-based study of anatomical variations of the ethmoidal uncinate process

Background: The uncinate process is very relevant with respect to the ventilation and drainage of the frontal, maxillary and anterior ethmoid sinuses in the osteomeatal complex. Aims and Objectives: The study was conducted with the aim to examine and assess various patterns of upper attachment of the ethmoidal uncinate process. The secondary objective of the study was to study the incidence of pneumatization of the uncinate process. Materials and Methods: With the objective to study the various patterns of upper attachment of the uncinate process, the study was conducted at the Department of Ear, Nose, and Throat (ENT) Head and Neck Surgery, at Government Medical College, Doda, J and K, India. The period of study was from November 2020 up to November 2021. The study involved 100 patients who had presented to the ENT outpatient with nasal and or sinus-related complaints. Results: The study included 58 males and 42 females. Among the various patterns, it was the type-2 pattern of the uncinate attachment that was the most prevalent (42%). This was followed by a type-1 pattern (attached to the lamina papyracea) (16%) and then a type-6 pattern (14%). Type-3 in 4%, type-4 in 3%, and type-5 in 7%. In 14% of the cases, there was no upper attachment of the uncinate process. The pneumatization of the uncinate process was noted among 42 of the uncinate processes that we studied. The pneumatization was unilateral in 41% and bilateral in 59% of the uncinate process. The patients with a pneumatized uncinate process had more severe clinical presentation. Conclusions: A thorough computerized tomography scan assessment of the attachments of the uncinate process and its variations aids in minimizing damage to the related landmarks during the surgery and helps minimizing the chances of iatrogenic trauma to the nasolacrimal duct, medial orbital wall, and other surrounding structures. It can also assist in figuring out the likely cause of refractory sinusitis.

Non-Suicidal Self-Injury in Eating and Feeding Disorder Patients: Characteristics and Clinical Implications in a Group of Referred Female Adolescents.

Non-suicidal self-injury (NSSI) and Feeding or Eating Disorders (FEDs) often coexist during adolescence with reciprocal influences on their clinical picture. The present study aimed to identify differences and similarities in the clinical presentation of young patients with both conditions compared to those with the two non-comorbid disorders. We consecutively recruited forty-five female patients aged between 11 and 18 at our third-level hospital and subdivided them into three groups (NSSI: n = 15; FED: n = 15; NSSI + FED: n = 15). Patients underwent a full clinical assessment. Based on our results, the NSSI + FED group was characterized by higher rates of binging/purging behaviors, greater prevalence of Cyclothymic Disorder, and a more severe clinical presentation compared to the non-comorbid groups. Moreover, higher levels of suicidal ideation were found in the NSSI + FED group. Pharmacological treatment patterns also differed, with SSRI being prescribed more frequently to NSSI + FED patients while mood stabilizers were prescribed more frequently to NSSI ones. A Principal Component Analysis identified four main dimensions: "Body Image" impairment was more pronounced in NSSI + FED patients, indicating negative attitudes towards their own body; "Metacognition" deficits were higher in NSSI than FED. The present study underscores distinctive clinical features in patients with comorbid NSSI and FED, emphasizing the urgent need for tailored intervention strategies focusing on specific symptom domains.

Aspergillus-sensitized asthma in children.

Asthma is the most common chronic respiratory disease in childhood. Aspergillus fumigatus sensitivity may be involved in the pathogenesis of asthma by leading to different clinical presentations. To investigate the demographic, clinical, laboratory, and radiological characteristics of A. fumigatus sensitivity in childhood asthma and identify associated risk factors and diagnostic parameters. A total of 259 children with asthma were included in the study, 7 (2.7%) with allergic bronchopulmonary aspergillosis (ABPA), 84 (32.4%) with A. fumigatus-sensitized asthma (Af-SA), and 168 (64.9%) with A. fumigatus-unsensitized asthma (Af-UA). Aspergillus sensitivity was associated with early asthma onset and longer asthma duration. Total IgE level and asthma severity are highest in ABPA and higher in Af-SA. Absolute eosinophil count was higher, and FEV1 was lower in Af-SA and ABPA. Aspergillus fumigatus was associated with greater odds of being male (odds ratio [OR], 2.45), having atopic dermatitis (OR, 3.159), Alternaria sensitivity (OR, 10.37), and longer asthma duration (OR, 1.266). The best cut-off values for detecting A. fumigatus positivity were 363.5 IU/mL for total IgE and 455 cells/μL for absolute eosinophil count. In Af-SA compared to Af-UA, centrilobular nodules and peribronchial thickening were more common, and the bronchoarterial ratio was higher. Aspergillus sensitivity is a strong allergic stimulus in asthma, leading to laboratory, structural, clinical, and functional consequences. Af-SA is a distinct asthma endotype independent of ABPA that is characterized by increased risk of severe clinical presentations and impaired lung function.

The erythrocyte sedimentation rate and other markers of inflammation in cats tested for Leishmania infantum and feline immunodeficiency virus antibodies

BackgroundIn endemic areas, Leishmania infantum and feline immunodeficiency virus (FIV) co-infection occurs in cats, and may favour a progressive course of feline leishmaniosis. Abnormalities in serum protein fractions have been reported, but inflammation markers have scarcely been studied. Erythrocyte sediment rate (ESR) is a marker of inflammation that is poorly used in veterinary medicine, but it has been evaluated in EDTA blood using a recently introduced automatic device. We studied ESR and a pool of feline markers of inflammation (MoI) in cats L. infantum (Li+) and/or FIV antibody-positive (Li+FIV+/FIV+) with the aims (a) to evaluate ESR as MoI in cats with the infectious and clinical conditions considered and (b) to provide data about a pool of MoI never investigated in the feline infections studied and in other cat diseases before.MethodsThis prospective controlled study included 35 study group cats (Li+, n = 20; FIV +, n = 8; Li+FIV+, n = 7) and ten healthy antibody-negative control cats. Clinical findings at physical examination and selected clinical pathological abnormalities related to inflammation were statistically analysed in relation to the infectious status and ESR values.ResultsESR values were higher in Li+, FIV+, and Li+FIV+ cats compared with control cats, and 40% of the study group cats had ESR values above the reference interval (RI). ESR positively correlated with some positive MoI and negatively with some negative MoI studied. Additionally, a higher prevalence of ESR values above the RI has been detected in cats with hypoalbuminemia or hypergammaglobulinemia and higher ESR values were measured in cats with serum protein electrophoresis (SPE) fraction abnormalities. Correlations were also found with erythrocytes, hemoglobin, hematocrit and some erythrocyte indices. FIV+ and Li+FIV+ cats had a higher prevalence of increased ESR values, and almost all had SPE abnormalities and more severe clinical presentations compared with Li+ cats.ConclusionsAbnormal levels of MoI were found in almost all parameters studied, particularly in FIV+ and Li+FIV+ cats. Also, ESR can be used as a marker of inflammation in cats with L. infantum and/or FIV infection.Graphical

The Clinical Approach to Interstitial Lung Disease in Childhood: A Narrative Review Article.

Interstitial lung disease (ILD) comprises a group of respiratory diseases affecting the interstitium of the lungs, which occur when a lung injury triggers an abnormal healing response, and an inflammatory process leads to altered diffusion and restrictive respiratory dysfunction. The term "interstitial" may be misleading, as other components of the lungs are usually also involved (epithelium, airways, endothelium, and so on). Pediatric conditions (childhood interstitial lung disease, chILD) are different from adult forms, as growing and developing lungs are affected and more diverse and less prevalent diseases are seen in childhood. Diffuse parenchymal lung disease (DPLD) and diffuse lung disease (DLD) can be used interchangeably with ILD. Known etiologies of chILD include chronic infections, bronchopulmonary dysplasia, aspiration, genetic mutations leading to surfactant dysfunction, and hypersensitivity pneumonitis due to drugs or environmental exposures. Many forms are seen in disorders with pulmonary involvement (connective tissue disorders, storage diseases, malignancies, and so on), but several conditions have unknown origins (desquamative pneumonitis, pulmonary interstitial glycogenosis, neuroendocrine cell hyperplasia in infancy, and so on). Currently, there is no consensus on pediatric classification; however, age grouping is proposed as some specific forms are more prevalent in infancy (developmental and growth abnormalities, surfactant dysfunction mutations, etc.) and others are usually seen in older cohorts (disorders in normal or immunocompromised hosts, systemic diseases, etc.). Clinical manifestations vary from mild nonspecific symptoms (recurrent respiratory infections, exercise intolerance, failure to thrive, dry cough, etc.) to a severe clinical picture (respiratory distress) and presentation related to the child's age. The diagnostic approach relies on imaging techniques (CT), but further investigations including genetic tests, BAL, and lung biopsy (VATS) are needed in uncertain cases. Pharmacological treatment is mostly empiric and based on anti-inflammatory and immunomodulatory drugs. Lung transplantation for selected cases in a pediatric transplantation center could be an option; however, limited data and evidence are available regarding long-term survival. International collaboration is warranted to understand chILD entities better and improve the outcomes of these patients.

High comorbidity rates in congenital lobar emphysema and the effect on clinical presentation.

The presence of comorbidities (CM) in congenital lobar emphysema (CLE) has been previously described with varying rates. However, the clinical implication of CM on the clinical presentation and patient outcome in CLE is unclear. This was a retrospective cohort study between 2000 and 2022 in a single institution. The study included pediatric patients diagnosed with CLE. During the study period, 36 patients were identified with CLE. The presence of respiratory symptoms at diagnosis was documented in 69% (24/35) of the patients with 48% admitted to intensive care units. The presence of CM was documented in 14/36 (39%) of the patients, with cardiovascular anomalies as the most common (22%), followed by genitourinary anomalies (11%) and large airway anomalies (8%). When comparing the CM group (n = 14) vs the non-CM group (N = 22), there was no significant difference regarding gender, term birth, age of diagnosis, and the location of the lesion. The CM group had significantly higher rates of intensive care unit (ICU) admissions (75% vs 33%, p = 0.02), longer duration of admission (median 46days vs 9, p = 0.02), and need for pre-operative non-invasive respiratory support (50% vs 5%, p = 0.002).Conclusion: The presence of CM in CLE was associated with a more severe presentation as reflected with significantly higher rates of ICU admissions, prolonged admissions, and higher need for non-invasive respiratory support. Screening for CM, mostly for cardiac anomalies, is recommended at time of CLE diagnosis. What is Known: • Congenital lobar emphysema (CLE) is a developmental lung anomaly generally associated with other comorbidities; however, their clinical implication on presentation is unclear • The prevalence of comorbidities in CLE was previously reported around 15-20%, with cardiovascular anomalies as the most common What is New: • Comorbidities are very common (39%) in CLE, and their presence is related to a more severe clinical presentation and need for respiratory support • Screening for comorbidities is recommended in CLE, specifically for cardiovascular and genitourinary anomalies.

Early Invasive Strategy for Octogenarians and Nonagenarians With Acute Myocardial Infarction.

Background: Older adults with acute myocardial infarction (AMI) are currently a rapidly growing population. However, their clinical presentation and outcomes remain unresolved. Methods and Results: A total of 268 consecutive AMI patients were analyzed for clinical characteristics and outcomes with major adverse cardiovascular events (MACE) and all-cause mortality within 1 year. Patients aged ≥80 years (Over-80; n=100) were compared with those aged ≤79 years (Under-79; n=168). (1) Primary percutaneous coronary intervention (PCI) was frequently and similarly performed in both the Over-80 group and the Under-79 group (86% vs. 89%; P=0.52). (2) Killip class III-IV (P<0.01), in-hospital mortality (P<0.01), MACE (P=0.03) and all-cause mortality (P<0.01) were more prevalent in the Over-80 group than in the Under-79 group. (3) In the Over-80 group, frail patients showed a significantly worse clinical outcome compared with non-frail patients. (4) Multivariate analysis revealed Killip class III-IV was associated with MACE (odds ratio [OR]=3.51; P=0.02) and all-cause mortality (OR=9.49; P<0.01) in the Over-80 group. PCI was inversely associated with all-cause mortality (OR=0.13; P=0.02) in the Over-80 group. Conclusions: The rate of primary PCI did not decline with age. Although octogenarians/nonagenarians showed more severe clinical presentation and worse short-term outcomes compared with younger patients, particularly in those with frailty, the prognosis may be improved by early invasive strategy even in these very old patients.

Clinical and Diagnostic Findings in Dogs Infected with Trichuris vulpis: A Retrospective Study.

Trichuris vulpis is a parasite of the large intestine of canids and has a global distribution. Despite its well-established epidemiology, the question of its pathogenicity in dogs remains debated. It has been suggested that younger age and concurrent infection with Ancylostoma caninum may be responsible for more severe clinical presentations. This retrospective study aimed to describe the clinical and diagnostic features of T. vulpis-infected dogs and to compare these findings with dogs infected with both T. vulpis and other intestinal parasites (poly-infected dogs). Forty-five dogs were included, with twenty-five being solely infected by T. vulpis and twenty poly-infected dogs. Only weight loss was more frequent (p = 0.006) in poly-infected dogs compared to T. vulpis mono-infected dogs. No significant differences were observed in laboratory abnormalities between mono-infected and poly-infected dogs. Only diarrhea was more frequent (p = 0.007) in younger dogs compared to adults. The egg shedding pattern was significantly higher (p = 0.04) among adult dogs compared to young ones, and there was a significant positive correlation between egg shedding and age (r = 0.41; p = 0.005). These findings suggest that T. vulpis might be responsible for both clinical signs and laboratory abnormalities in dogs, irrespective of the host's age and the presence of other intestinal parasites.

Antifungal efficacy and immunomodulatory effect of PLGA nanoparticle-encapsulated itraconazole in histoplasmosis in vivo model

IntroductionHistoplasma capsulatum is the etiological agent of histoplasmosis, the most common endemic pulmonary mycosis. Itraconazole (ITZ) is the choice for mild disease and a step-down therapy in severe and disseminated clinical presentations. Drug encapsulation into nanoparticles (NPs) is an alternative to improve drug solubility and bioavailability, reducing undesirable interactions and drug degradation and reaching the specific therapeutic target with lower doses. Objectiveevaluate the antifungal and immunomodulatory effect of ITZ encapsulated into poly(lactic-co-glycolic acid) (PLGA) NPs, administrated orally and intraperitoneally in an in vivo histoplasmosis model. ResultsAfter intranasal infection and treatment of animals with encapsulated ITZ by intraperitoneal and oral route, fungal burden control, biodistribution, immune response, and histopathology were evaluated. The results showed that the intraperitoneal administered and encapsulated ITZ has an effective antifungal effect, significantly reducing the Colony-Forming-Units (CFU) after the first doses and controlling the infection dissemination, with a higher concentration in the liver, spleen, and lung compared to the oral treatment. In addition, it produced a substantial immunomodulatory effect on pro- and anti-inflammatory cytokines and immune cell infiltrates confirmed by histopathology. ConclusionsOverall, results suggest a synergistic effect of the encapsulated drug and the immunomodulatory effect contributing to infection control, preventing their dissemination.

Incidence and Outcomes of Brucella Endocarditis in a High-Prevalence Area: A Single-Center Study.

To analyze the clinical characteristics of Brucella endocarditis (BE) and observe the factors related to death to provide guidance for clinical treatment. This study examined all patients with BE admitted to The First People's Hospital of Kashi Prefecture between January 2017 and November 2023. Clinical characteristics and follow-up outcomes were collected for analysis. This study revealed 774 cases of brucellosis and 14 cases of BE, with an overall incidence rate of 1.88%. Most of the patients were male (71.43%) and lived in areas where brucellosis is common. Patients ranged in age from 26 to 68years. Common symptoms reported among patients included chest tightness and fatigue, and a significant portion also presented with congestive heart failure. Most patients exhibited normal white blood cell counts (WBC) but had elevated levels of C-reactive protein (CRP). Transthoracic ultrasound (TTE) revealed cardiac valve vegetation in all patients, along with positive blood cultures. Six patients (42.86%) completed heart surgery, and ten (71.43%) completed anti-infection treatment. Six patients died, five of whom did not undergo surgery. The other patient with Marfan syndrome died after surgery. Sex, WBC count, neutrophil (NEUT) and total bilirubin (TBIL) were significant factors associated with regression in BE patients (P < 0.05) according to univariate analysis. Patients with BE in Kashi have a severe clinical presentation at diagnosis, but early detection with improved cardiac ultrasound and aggressive treatment can improve the prognosis.