ABSTRACT
OBJECTIVE: Although pneumonia is the leading cause of death among patients with dementia, the specific underlying causes remain unclear. In particular, the potential connection between pneumonia risk and dementia-related daily living difficulties, such as oral hygiene practice and mobility impairment, and the use of physical restraint as a management practice, has not been extensively studied. METHODS: In our retrospective study, we included 454 admissions corresponding to 336 individual patients with dementia who were admitted to a neuropsychiatric unit due to behavioral and psychological symptoms. The admissions were divided into two groups: those who developed pneumonia while hospitalized (n=62) and those who did not (n=392). We investigated differences between the two groups in terms of dementia etiology, dementia severity, physical conditions, medical complications, medication, dementia-related difficulties in daily living, and physical restraint. To control potential confounding variables, we used mixed effects logistic regression analysis to identify risk factors for pneumonia in this cohort. RESULTS: Our study found that the development of pneumonia in patients with dementia was associated with poor oral hygiene, dysphagia, and loss of consciousness. Physical restraint and mobility impairment showed a weaker, nonsignificant association with the development of pneumonia. CONCLUSIONS: Our findings suggest that pneumonia in this population may be caused by two primary factors: increased pathogenic microorganisms in the oral cavity due to poor hygiene, and an inability to clear aspirated contents due to dysphagia and loss of consciousness. Further investigation is needed to clarify the relationship between physical restraint, mobility impairment, and pneumonia in this population.
Subject(s)
Deglutition Disorders , Dementia , Pneumonia , Humans , Oral Hygiene/adverse effects , Retrospective Studies , Deglutition Disorders/etiology , Deglutition Disorders/complications , Pneumonia/complications , Pneumonia/epidemiology , Dementia/etiology , Dementia/complications , Unconsciousness/complications , Risk FactorsABSTRACT
Although several randomized controlled trials (RCTs) have compared the effectiveness, efficacy, and safety of antipsychotic monotherapy (APM) versus placebo in patients with major depressive disorder (MDD), no meta-analysis has examined this topic. We conducted a systematic literature search using MEDLINE and Embase to identify relevant RCTs and performed a meta-analysis to compare the following outcomes between APM and placebo: response and remission rates, study discontinuation due to all causes, lack of efficacy, and adverse events, changes in total scores on depression severity scales, and individual adverse event rates. A total of 13 studies were identified, with 14 comparisons involving 3,197 participants that met the eligibility criteria. There were significant differences between APM and placebo in response and remission rates and changes in the primary depression severity scale in favor of APM, and study discontinuation due to adverse events and several individual adverse events in favor of placebo. No significant difference was observed in discontinuation due to all causes. APM could have antidepressant effects in the acute phase of MDD, although clinicians should be aware of an increased risk of some adverse events.
Subject(s)
Antipsychotic Agents , Depressive Disorder, Major , Humans , Depressive Disorder, Major/drug therapy , Antipsychotic Agents/adverse effects , Antidepressive Agents/adverse effects , Drug Therapy, CombinationABSTRACT
PURPOSE: It is difficult to perform intestinal anastomosis in low-birth-weight infants because the intestinal diameter is small and the discrepancy in diameter of the proximal and distal intestines is often large, but there has been no optimal-sized training model. Therefore, we developed a new intestinal anastomosis training model that imitated the size of the intestine in low-birth-weight infants, and evaluated its face and construct validity. METHODS: Two intestinal models were developed with crossMedical, Inc. using a hydrophilic acrylic material (wet model) or a polyurethane soft resin (dry model). The inner diameter of the simulated intestinal tract was 15 mm on the oral end and 6 mm on the anal end. Thirteen pediatric surgeons performed anastomosis and responded to the questionnaire. RESULTS: In the questionnaire, the wet model had significantly higher scores than the dry model in "appearance", "softness" and "usefulness for training". In the anastomotic results of the wet model, the anastomosis leak pressure was significantly correlated with the number of intestinal anastomotic experiences in low-birth-weight infants (correlation coefficient = 0.64, P = 0.035). CONCLUSIONS: The wet-type intestinal anastomosis model showed good face validity. Its leak pressure had a significant correlation with clinical experience; thus, construct validity was demonstrated.
Subject(s)
Digestive System Surgical Procedures , Anastomosis, Surgical , Anastomotic Leak/epidemiology , Child , Humans , Infant , Infant, Low Birth Weight , Infant, Newborn , Intestines/surgeryABSTRACT
The serotonin transporter (5HTT) may be associated with the pathogenesis of major depressive disorder (MDD). The 5HTT-linked polymorphic region (5HTTLPR) genotype may determine how levels of 5HTT mRNA are influenced by promoter methylation. We examined the association of 5HTT gene methylation, which influences gene expression, and the 5HTTLPR genotype before antidepressant treatment and expression before and after treatment. The aims of this study were (1) to investigate the association between 5HTT methylation or expression in leukocytes and depression and (2) to investigate a possible effect of 5HTT methylation, expression, and genotype on clinical symptoms in MDD. The 5HTTLPR genotype was significantly associated with mean methylation levels in patients only (patients: r = 0.40, p = 0.035, controls: p = 0.96). The mean methylation level was significantly increased in patients compared with controls (patients: 5.30 ± 0.24, controls: 4.70 ± 0.19, unpaired t-test, p = 0.04). 5HTT expression using real-time PCR and Taqman probes was increased in unmedicated patients compared with controls and then decreased 8 weeks after antidepressant treatment. The mean 5HTT expression level was not associated with the 5HTTLPR genotype in patients or controls. Increased depressive symptoms were related to decreased levels of methylation. Copyright © 2016 John Wiley & Sons, Ltd.
Subject(s)
Antidepressive Agents/therapeutic use , Depressive Disorder, Major/genetics , Gene Expression Regulation , Serotonin Plasma Membrane Transport Proteins/genetics , Adult , Case-Control Studies , DNA Methylation , Depressive Disorder, Major/drug therapy , Female , Follow-Up Studies , Genotype , Humans , Male , Middle Aged , Polymorphism, Genetic , Promoter Regions, Genetic , RNA, Messenger/genetics , Real-Time Polymerase Chain ReactionABSTRACT
BACKGROUND: The results of meta-analyses conducted by previous association studies between total homocysteine and schizophrenia suggest that an elevated total homocysteine level is a risk factor for schizophrenia. However, observational studies have potential limitations, such as confounding and reverse causation. In the present study, we evaluated a causal relationship between plasma total homocysteine and schizophrenia by conducting a Mendelian randomization analysis. METHODS: We used the MTHFR C677T polymorphism as an instrumental variable, which affects the plasma total homocysteine levels. To calculate the risk estimate for the association of this single nucleotide polymorphism (SNP) with schizophrenia, we conducted a meta-analysis of case-control studies that comprise a total of 11,042 patients with schizophrenia and 14,557 control subjects. We obtained an estimate for the association of this SNP with the plasma total homocysteine levels from a meta-analysis of genome-wide association studies comprising 44,147 individuals. RESULTS: By combining these two estimates, we demonstrated a significant effect of the plasma total homocysteine on schizophrenia risk, representing an OR of 2.15 (95 % CI = 1.39-3.32; p = 5.3 x 10(-4)) for schizophrenia per 1-SD increase in the natural log-transformed plasma total homocysteine levels. CONCLUSIONS: We provided evidence of a causal relationship between the plasma total homocysteine and schizophrenia, and this result will add insight into the pathology and treatment of schizophrenia.
Subject(s)
Homocysteine/blood , Mendelian Randomization Analysis , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Schizophrenia/blood , Schizophrenia/epidemiology , Schizophrenia/genetics , Case-Control Studies , Genetic Predisposition to Disease , Humans , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
OBJECTIVES: To elucidate the molecular effects of lithium, we studied global gene expression changes induced by lithium in leukocytes from healthy subjects. METHODS: Eight healthy male subjects participated in this study. Lithium was prescribed for weeks to reach a therapeutic serum concentration. Leukocyte counts and serum lithium concentrations were determined at baseline (before medication), after 1 and 2 weeks of medication and at 2 weeks after stopping medication. Gene expression profiling was performed at each time point using Agilent G4112F Whole Human Genome arrays (The Agilent Technologies, Santa Clara, CA, USA). Expression of some candidate genes was also assessed by real-time polymerase chain reaction (PCR). RESULTS: Gene ontology analysis revealed that the cellular and immune responses to stimulus and stress indeed played a major role in the cellular response to lithium treatment. Pathway analysis revealed that the interleukin 6 pathway, the inhibitor of differentiation pathway, and the methane metabolism pathway were regulated by lithium. Using real-time PCR, we also confirmed that five candidate genes in these pathways were significantly changed, including suppressor of cytokine signaling 3 and myeloperoxidase. CONCLUSIONS: Our investigation suggests that the molecular action of lithium is mediated in part by its effects on the cellular and immune response to stimulus and stress followed by the interleukin 6, inhibitor of differentiation, and methane metabolism pathways.
Subject(s)
Antimanic Agents/pharmacology , Gene Expression/drug effects , Leukocytes/drug effects , Leukocytes/metabolism , Lithium Compounds/pharmacology , Antimanic Agents/blood , Gene Expression Profiling , Humans , Interleukin-6/genetics , Interleukin-6/metabolism , Leukocyte Count , Lithium Compounds/blood , Male , Methane/metabolism , Microarray Analysis , Peroxidase/genetics , Peroxidase/metabolism , Polymerase Chain Reaction , Signal Transduction/drug effects , Signal Transduction/genetics , Signal Transduction/physiology , Suppressor of Cytokine Signaling 3 Protein , Suppressor of Cytokine Signaling Proteins/genetics , Suppressor of Cytokine Signaling Proteins/metabolism , Time FactorsABSTRACT
BACKGROUND/PURPOSE: To clarify the role of interval appendectomy (IA) in pediatric patients with acute appendicitis with an appendiceal inflammatory mass or abscess, we histologically analyzed the appendices removed during IA. PATIENTS AND METHODS: We treated 355 consecutive pediatric patients with acute appendicitis and reviewed the admission charts of patients who started conservative management (CM). The histology of the appendix removed during IA was also examined. The relationships among the clinical features, appendicolith formation at the time of IA and histological findings were analyzed by stepwise regression analyses. RESULTS: (1) CM was started in 48 patients (13.5 %). Recurrence or a remaining abscess was observed in nine patients (18.8 %). (2) Histopathological changes, particularly foreign body reaction with fibrosis and infiltration of inflammatory cells, were observed in about half of the specimens. (3) In a stepwise regression analysis, the presence of an appendicolith at IA was correlated with an appendicolith at diagnosis, foreign body reaction in the appendix and a decrease in the inflammatory reaction at diagnosis. CONCLUSION: More than half the patients had strong histopathological changes in the appendix, suggesting a high possibility of recurrence. The presence of appendicolith formation at IA, which is a risk factor for recurrence, was influenced by the presence of an appendicolith at diagnosis, foreign body reaction in the appendix and the inflammatory status of patients at diagnosis. These clinical findings are indications for IA.
Subject(s)
Abscess/pathology , Abscess/surgery , Appendectomy/methods , Appendicitis/pathology , Appendicitis/surgery , Appendix/pathology , Acute Disease , Child , Child, Preschool , Female , Fibrosis , Foreign-Body Reaction/pathology , Humans , Male , Recurrence , Risk FactorsABSTRACT
BACKGROUND: The esophagus is physiologically devoid of eosinophils, so their presence would suggest some underlying pathology. The prevalence of eosinophilic esophagitis (EoE) has steadily increased in Western countries. Previous studies have described EoE in association with congenital esophageal atresia (CEA), which is the most common congenital anomaly of the esophagus. However, the association remains unclear. METHODS: We performed a retrospective histological analysis examining for eosinophil infiltration in the esophagus of patients with CEA following surgical repair or congenital esophageal stenosis (CES) who underwent esophageal biopsy or surgical resection in our hospital between 2005 and 2012. RESULTS: There were 6 patients with CEA following surgical repair or CES who had eosinophil-dominant infiltration in the esophagus. All had associated allergic disorders, including food allergies in 4. Moreover, all except for one fulfilled the histological criteria of EoE. Impairment of eosinophil infiltration and symptomatic improvement were observed in those treated with a proton pump inhibitor (PPI), either alone or in combination with steroids after esophageal dilatation. CONCLUSIONS: These findings suggest that CEA repair or CES in conjunction with allergic conditions and coexisting gastroesophageal reflux disease (GERD) may induce greater esophageal eosinophilic inflammation. In addition, esophageal dilatation followed by PPI treatment, alone or with steroids, may be a therapeutic strategy that can provide symptomatic relief by reducing eosinophilic inflammation in esophageal strictures or GERD associated with CEA or CES.
Subject(s)
Eosinophilic Esophagitis/complications , Esophageal Atresia/complications , Esophageal Stenosis/complications , Adolescent , Child , Child, Preschool , Eosinophilic Esophagitis/pathology , Eosinophilic Esophagitis/therapy , Esophageal Atresia/pathology , Esophageal Atresia/therapy , Esophageal Stenosis/congenital , Esophageal Stenosis/pathology , Esophageal Stenosis/therapy , Esophagoscopy , Female , Humans , Infant , Male , Retrospective StudiesABSTRACT
OBJECTIVE: Corticosteroids can cause psychiatric symptoms known as corticosteroid-induced psychiatric disorders (CIPDs). Little is known regarding the relationship between intravenous pulse methylprednisolone (IVMP) and CIPDs. Therefore, we aimed to examine the relationship between corticosteroid use and CIPDs in this retrospective study. METHODS: Patients who were prescribed corticosteroids during their hospitalization at a university hospital and referred to our consultation-liaison service were selected. Patients diagnosed with CIPDs according to the ICD-10 codes were included. The incidence rates were compared between patients receiving IVMP and those receiving any other corticosteroid treatment. The association between IVMP and CIPDs was examined by classifying patients with CIPD into three groups according to the use of IVMP and timing of CIPD onset. RESULTS: Of the 14,585 patients who received corticosteroids, 85 were diagnosed with CIPDs, with an incidence rate of 0.6%. Among the 523 patients who received IVMP, the incidence rate of CIPDs was 6.1% (n = 32), which was significantly higher than that in patients receiving any other corticosteroid treatment. Among the patients with CIPDs, 12 (14.1%) developed CIPDs during IVMP, 19 (22.4%) developed CIPDs after IVMP, and 49 (57.6%) developed CIPDs without IVMP. There was no significant difference in the doses at the time of CIPD improvement among the three groups when we excluded one patient whose CIPD improved during IVMP. CONCLUSION: Patients receiving IVMP were more likely to develop CIPDs than those who did not receive IVMP. Furthermore, corticosteroid doses at the time of improvement of CIPDs were constant, regardless of IVMP use.
Subject(s)
Mental Disorders , Methylprednisolone , Humans , Methylprednisolone/adverse effects , Retrospective Studies , Adrenal Cortex Hormones/adverse effectsABSTRACT
BACKGROUND: Stathmin 1 (STMN1), a marker for immature neurons and tumors, controls microtubule dynamics by destabilizing tubulin. It plays an essential role in cancer progression and indicates poor prognosis in several cancers. This potential protein has not been clarified in clinical patients with neuroblastoma. Therefore, this study aimed to assess the clinical significance and STMN1 function in neuroblastoma with and without MYCN amplification. METHODS: Using immunohistochemical staining, STMN1 expression was examined in 81 neuroblastoma samples. Functional analysis revealed the association among STMN1 suppression, cellular viability, and endogenous or exogenous MYCN expression in neuroblastoma cell lines. RESULT: High levels of STMN1 expression were associated with malignant potential, proliferation potency, and poor prognosis in neuroblastoma. STMN1 expression was an independent prognostic factor in patients with neuroblastoma. Furthermore, STMN1 knockdown inhibited neuroblastoma cell growth regardless of endogenous and exogenous MYCN overexpression. CONCLUSION: Our data suggest that assessing STMN1 expression in neuroblastoma could be a powerful indicator of prognosis and that STMN1 might be a promising therapeutic candidate against refractory neuroblastoma with and without MYCN amplification.
ABSTRACT
Feeding dysfunction (FD) has recently been considered to comprise a prevalent set of symptoms in eosinophilic gastrointestinal disorders (EGIDs) in young children. We report the case of an 8-month-old girl with an EGID who visited our hospital due to vomiting, poor weight gain and feeding difficulties; her condition was discovered during the examination of the symptoms including FD. Tracheal aspiration and reduced esophageal clearance showed up in a barium swallow test and upper gastrointestinal contrast radiography, respectively. Delayed clearance from the stomach was also detected on gastrointestinal scintigraphy. Gastrointestinal endoscopy and biopsies revealed esophagitis with some eosinophils and duodenitis with eosinophilic inflammation. She was not a likely candidate for eosinophilic esophagitis. On administration of an elemental diet, the patient gained weight. Esophageal and stomach clearance subsequently improved, although the vomiting and FD persisted to some extent. We conclude that it is important to consider other EGIDs as well as eosinophilic esophagitis in the differential diagnosis of FD.
Subject(s)
Eosinophilia/diagnosis , Gastrointestinal Diseases/diagnosis , Diagnosis, Differential , Eosinophilia/diet therapy , Feeding Behavior , Female , Food, Formulated , Gastrointestinal Diseases/diet therapy , Humans , InfantABSTRACT
Transporting pediatric patients with severe cardiovascular complications to the fluoroscopy room can be difficult. Therefore, we started using a portable imaging device with a flat panel detector (FPD) for nasojejunal tube (NJT) placement. The purpose of this study was to investigate the differences in length of time of NJT placement and dosage of radiation exposure using a portable imaging device with FPD versus fluoroscopy. Pediatric patients who underwent NJT placement between April 2016 and December 2018 were identified retrospectively from the clinical records. The age, sex, body weight, and height of each child at the time of the procedure as well as the procedure time, outcomes of the procedure, and dosage of radiation exposure was compared between the two groups. In 76 cases of NJT placement (41 patients), there was no significant difference in the success rate of NJT placement between the FPD (90%) and fluoroscopy groups (95%). However, the NJT placement time was significantly longer in the FPD group than in the fluoroscopy group (488 s vs 291 s). According to our calculations, the radiation dosage was lower in the FPD group than in the fluoroscopy group (136 µGy per procedure vs 2819 µGy per procedure). These results suggest that NJT placement using a portable imaging device with an FPD can be an effective method for children who are difficult to transport with an equal success rate and lower dosage of radiation exposure compared with conventional fluoroscopy.
Subject(s)
Enteral Nutrition , Humans , Child , Retrospective Studies , Fluoroscopy , Radiation Dosage , Body WeightABSTRACT
BACKGROUND: Although differential diagnosis between autoimmune encephalitis and schizophrenia spectrum disorders is crucial for a good outcome, the psychiatric symptoms that distinguish these two conditions have not been identified even though psychiatric symptoms are often the main manifestation of autoimmune encephalitis. Also, there are many situations in clinical psychiatry in which laboratory testing and imaging studies are not available. Because no comparative study of the psychiatric symptoms between these two conditions has been carried out, we explored diagnostically useful psychiatric symptoms in a retrospective case-control study. METHODS: We recruited 187 inpatients with first-episode psychosis who were admitted to our psychiatric unit and categorized them into two groups: the autoimmune encephalitis group (n = 10) and the schizophrenia spectrum disorders group (n = 177). Differences in the symptoms and signs between the two groups were investigated. RESULTS: Schneider's first-rank symptoms (e.g., verbal commenting hallucinations and delusional self-experience) were observed only in the schizophrenia spectrum disorders group, whereas altered perception was found more frequently in the autoimmune encephalitis group. Functional status was worse in the autoimmune encephalitis group, and neurological and neuropsychological signs were revealed almost exclusively in this group. A history of mental illness was more frequently reported in the schizophrenia spectrum disorders group than in the autoimmune encephalitis group. CONCLUSIONS: The psychiatric symptoms, i.e., Schneider's first-rank symptoms and altered perception, together with neurological and neuropsychological signs, functional status, and past history, may help clinicians accurately differentiate these two conditions among patients with first-episode psychosis.
Subject(s)
Encephalitis , Psychotic Disorders , Schizophrenia , Case-Control Studies , Encephalitis/diagnosis , Hashimoto Disease , Humans , Psychotic Disorders/diagnosis , Retrospective Studies , Schizophrenia/complications , Schizophrenia/diagnosisABSTRACT
BACKGROUND: Eosinophilic gastrointestinal disorders (EGIDs) are disorders characterized by primary eosinophil inflammation in the gastrointestinal tract. There are a small number of reports of eosinophil infiltration in gastrointestinal tracts presenting as EGIDs in infants. In this study, we present Japanese cases of EGIDs in infants. METHODS: Five patients diagnosed with or strongly suspected to have EGIDs in our hospital from 2008 to 2010 were reviewed. Radiographic contrast enema examinations and/or endoscopies were performed in 4 and 3 patients, respectively. RESULTS: There were patients with eosinophilic colitis (1 suspected and 2 biopsy-proven), a patient who was suspected of having allergic eosinophilic enterocolitis, and a patient with eosinophilic gastroenteritis associated with pediatric hypereosinophilic syndrome. CONCLUSIONS: The causes and clinical findings of patients with intestinal eosinophil inflammation vary. Therefore, deliberate examination and observation are important for patients with infantile EGID.
Subject(s)
Enteritis , Eosinophilia , Gastritis , Colon/pathology , Congenital Abnormalities/pathology , Constriction, Pathologic/pathology , Eczema/complications , Enteritis/blood , Enteritis/complications , Enteritis/diagnosis , Enteritis/etiology , Enteritis/pathology , Enteritis/therapy , Eosinophilia/blood , Eosinophilia/complications , Eosinophilia/diagnosis , Eosinophilia/etiology , Eosinophilia/pathology , Eosinophilia/therapy , Eosinophils/pathology , Feces/cytology , Female , Gastric Mucosa/pathology , Gastritis/blood , Gastritis/complications , Gastritis/diagnosis , Gastritis/etiology , Gastritis/pathology , Gastritis/therapy , Humans , Hypereosinophilic Syndrome/blood , Hypereosinophilic Syndrome/complications , Hypereosinophilic Syndrome/pathology , Immunoglobulin E/blood , Immunoglobulin E/immunology , Infant , Infant, Newborn , Intestinal Mucosa/pathology , Japan , Male , Milk Hypersensitivity/complications , Milk Hypersensitivity/immunology , Myocarditis/complications , Occult Blood , Prednisolone/therapeutic use , Rectum/pathology , SyndromeABSTRACT
Background: It is difficult for novice surgeons to manipulate the oblique laparoscope in single-incision laparoscopic percutaneous extraperitoneal closure (SILPEC) for inguinal hernia because of collisions between the instruments. To standardize manipulation of the laparoscope, we studied the viewing direction of the oblique laparoscope, and assessed the optimal manipulation of the laparoscope to avoid collisions. Methods: A retrospective chart review was performed on patients who underwent SILPEC between April 2016 and April 2017. The viewing direction of the 30° oblique laparoscope was measured according to the location of the field stop pointer. Patients were divided into three groups according to the viewing direction at the beginning of the procedure: the inside viewing direction was from -90° to -11°, upward viewing direction was from -10° to 10°, and outside viewing direction was from 11° to 90°. The length of the procedure, viewing direction at the end, and the percentage of cases in which there was a change in viewing direction during the procedure were compared. Results: Ninety-eight cases of SILPEC were performed during the study period. The percentage of patients with a change in category of viewing direction in the inside, upward, and outside groups was 35%, 21%, and 11%, respectively, showing a significant difference among the three groups. Conclusions: Setting the initial viewing direction to the outside can reduce correction of the viewing direction during SILPEC. Because the intersection angle between the outside-viewing laparoscope and forceps is close to a right angle, this might reduce collisions.
Subject(s)
Hernia, Inguinal/surgery , Laparoscopes , Child, Preschool , Female , Herniorrhaphy , Humans , Laparoscopy , Male , Mechanical Phenomena , Medical Records , Retrospective StudiesABSTRACT
A 1-month-old girl presented with hematemesis and dyspnea. A large amount of blood was aspirated through a nasogastric tube, and chest computed tomography showed bilateral centrilobular opacified lesions, which suggested aspiration pneumonitis due to upper gastrointestinal bleeding. Her respiratory condition exacerbated, and we initiated nitric oxide (NO) therapy. Bleeding stopped with conservative treatment. She was weaned off mechanical ventilation and extubated on Day 6 after admission. Afterward, upper gastrointestinal endoscopy showed a longitudinal linear scar indicative of Mallory-Weiss syndrome (MWS). MWS is rarely reported in early infancy since many of the risk factors are absent in infants. Patients with aspiration pneumonitis usually recover respiratory function within 24 h and severe respiratory failure is rare in aspiration pneumonitis. There are no pediatric case reports describing MWS with severe aspiration pneumonitis. Although MWS is a rare cause of neonatal hematemesis, patients can become severely ill and require multidisciplinary treatment.
ABSTRACT
Sleep disturbance is a common symptom of psychiatric and neurodevelopmental disorders and, especially in childhood, can be a precursor to various mental disorders. However, the genetic etiology of mental illness that contributes to sleep disturbance during childhood is poorly understood. We investigated whether the polygenic features of psychiatric and neurodevelopmental disorders are associated with sleep disturbance during childhood. We conducted polygenic risk score (PRS) analyses by utilizing large-scale genome-wide association studies (GWASs) (n = 46,350-500,199) of five major psychiatric and neurodevelopmental disorders (autism spectrum disorder, schizophrenia, attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and bipolar disorder) and, additionally, anxiety disorders as base datasets. We used the data of 9- to 10-year-olds from the Adolescent Brain Cognitive Development study (n = 9683) as a target dataset. Sleep disturbance was assessed based on the Sleep Disturbance Scale for Children (SDSC) scores. The effects of PRSs for these psychiatric and neurodevelopmental disorders on the total scores and six subscale scores of the SDSC were investigated. Of the PRSs for the five psychiatric and neurodevelopmental disorders, the PRSs for ADHD and MDD positively correlated with sleep disturbance in children (ADHD: R2 = 0.0033, p = 6.19 × 10-5, MDD: R2 = 0.0042, p = 5.69 × 10-6). Regarding the six subscale scores of the SDSC, the PRSs for ADHD positively correlated with both disorders of initiating and maintaining sleep (R2 = 0.0028, p = 2.31 × 10-4) and excessive somnolence (R2 = 0.0023, p = 8.44 × 10-4). Furthermore, the PRSs for MDD primarily positively correlated with disorders of initiating and maintaining sleep (R2 = 0.0048, p = 1.26 × 10-6), followed by excessive somnolence (R2 = 0.0023, p = 7.74 × 10-4) and sleep hyperhidrosis (R2 = 0.0014, p = 9.55 × 10-3). Despite high genetic overlap between MDD and anxiety disorders, PRSs for anxiety disorders correlated with different types of sleep disturbances such as disorders of arousal or nightmares (R2 = 0.0013, p = 0.011). These findings suggest that greater genetic susceptibility to specific psychiatric and neurodevelopmental disorders, as represented by ADHD, MDD, and anxiety disorders, may contribute to greater sleep problems among children.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Autism Spectrum Disorder , Depressive Disorder, Major , Neurodevelopmental Disorders , Attention Deficit Disorder with Hyperactivity/genetics , Brain , Child , Cognition , Depressive Disorder, Major/genetics , Genome-Wide Association Study , Humans , Neurodevelopmental Disorders/genetics , Risk Factors , SleepABSTRACT
Transient abnormal myelopoiesis (TAM) is a unique clonal myeloproliferation characterized by immature megakaryoblasts that occurs in 5-10% of neonates with Down syndrome (DS). Although TAM regresses spontaneously in most patients, approximately 20% of TAM cases result in early death, and approximately 20% of survivors develop acute megakaryoblastic leukemia (AMKL). We retrospectively reviewed records of 35 DS patients with TAM to determine the correlation between clinical characteristics and blast percentage. Thirteen of the 35 patients were classified as low blast percentage TAM (LBP-TAM), defined as TAM with a peak peripheral blast percentage ≤ 10%. Although no patient with LBP-TAM experienced systemic edema, disseminated intravascular coagulation, or early death, eight patients had elevated direct bilirubin levels (> 2 mg/dl) and one developed AMKL. All patients with LBP-TAM had serum markers of liver fibrosis that exceeded the normal limits, and two patients underwent liver biopsy to clarify the etiology of pathological jaundice. Taken together, our results suggest that patients with LBP-TAM may be at risk of liver fibrosis and liver failure, similarly to patients with classical TAM. Although these patients generally have a good prognosis, they should be carefully monitored for potential development of liver disease and leukemia.
Subject(s)
Down Syndrome/complications , Leukemoid Reaction/complications , Adolescent , Adult , Child , Child, Preschool , Down Syndrome/blood , Female , Humans , Infant , Leukemoid Reaction/blood , Liver Cirrhosis/blood , Liver Cirrhosis/complications , Male , Retrospective Studies , Young AdultSubject(s)
Duodenum/pathology , Enteritis/drug therapy , Enteritis/pathology , Eosinophilia/drug therapy , Eosinophilia/pathology , Eosinophilic Esophagitis/drug therapy , Eosinophilic Esophagitis/pathology , Gastritis/drug therapy , Gastritis/pathology , Proton Pump Inhibitors/therapeutic use , Child, Preschool , Enteritis/diagnosis , Eosinophilia/diagnosis , Eosinophilic Esophagitis/diagnosis , Female , Gastritis/diagnosis , Humans , Treatment OutcomeABSTRACT
Biliary atresia (BA) is a destructive inflammatory obliterative cholangiopathy of the neonate that affects various parts of the bile duct. If early diagnosis followed by Kasai portoenterostomy is not performed, progressive liver cirrhosis frequently leads to liver transplantation in the early stage of life. Therefore, prompt diagnosis is necessary for the rescue of BA patients. However, the prompt diagnosis of BA remains challenging because specific and reliable biomarkers for BA are currently unavailable. In this study, we discovered potential biomarkers for BA using deep proteome analysis by data-independent acquisition mass spectrometry (DIA-MS). Four patients with BA and three patients with neonatal cholestasis of other etiologies (non-BA) were recruited for stool proteome analysis. Among the 2110 host-derived proteins detected in their stools, 49 proteins were significantly higher in patients with BA and 54 proteins were significantly lower. These varying stool protein levels in infants with BA can provide potential biomarkers for BA. As demonstrated in this study, the deep proteome analysis of stools has great potential not only in detecting new stool biomarkers for BA but also in elucidating the pathophysiology of BA and other pediatric diseases, especially in the field of pediatric gastroenterology.