Outcomes for Children With Vascular Ring Repair Using a Simple Surgical Approach.

INTRODUCTION: Vascular Rings (VRs) are congenital malformations of the aortic arch that can compress the trachea and esophagus producing symptoms. Approximately, 5%-10% of patients experience persistent symptoms postrepair and 9% require reintervention. There are various approaches to repair-simple ligation and division of the ring or more complex procedures. Our objective was to describe outcomes for VR repair using a "simple" surgical approach. METHODS: We identified patients who underwent VR repair from 2012 to 2022 at our institution. Clinical and surgical data, demographics, intraoperative, and postoperative outcomes were extracted from their electronic medical records. Outcomes were analyzed and regression analysis was used to identify risk factors for residual symptoms after repair. RESULTS: Ninety three patients with VR repair were included. Prevalence of symptoms were reduced following surgery (80% preoperative versus 13% postoperative, P 0.03). Tracheomalacia also decreased from 16% to 7% postrepair. No deaths were reported in our cohort and 2% of our patients required reintervention. Multivariable regression analysis showed that preoperative tracheomalacia was associated with having persistent symptoms after VR repair (odds ratio 6.2, 95% CI 1.02-37.6). CONCLUSIONS: Our institutional experience using a simple surgical approach showed a significant decrease in symptoms, a very low reintervention rate and no mortality. Preoperative tracheomalacia can be a risk factor for persistent symptoms postrepair. We believe a simple surgical approach for children with complete VR repair can be effective in relieving symptoms.

Air pollution interacts with genetic risk to influence cortical networks implicated in depression.

Air pollution is a reversible cause of significant global mortality and morbidity. Epidemiological evidence suggests associations between air pollution exposure and impaired cognition and increased risk for major depressive disorders. However, the neural bases of these associations have been unclear. Here, in healthy human subjects exposed to relatively high air pollution and controlling for socioeconomic, genomic, and other confounders, we examine across multiple levels of brain network function the extent to which particulate matter (PM2.5) exposure influences putative genetic risk mechanisms associated with depression. Increased ambient PM2.5 exposure was associated with poorer reasoning and problem solving and higher-trait anxiety/depression. Working memory and stress-related information transfer (effective connectivity) across cortical and subcortical brain networks were influenced by PM2.5 exposure to differing extents depending on the polygenic risk for depression in gene-by-environment interactions. Effective connectivity patterns from individuals with higher polygenic risk for depression and higher exposures with PM2.5, but not from those with lower genetic risk or lower exposures, correlated spatially with the coexpression of depression-associated genes across corresponding brain regions in the Allen Brain Atlas. These converging data suggest that PM2.5 exposure affects brain network functions implicated in the genetic mechanisms of depression.

Sudden-Onset Back Pain and Intermittent Dyspnea While Eating: A Case of Pediatric Achalasia.

A 14-year-old girl with a history of asthma was hospitalized because of sudden-onset back pain around her thoracic region that spread to her chest and abdomen. She had been experiencing dysphagia and breathing difficulties for two years, especially after overeating, which often resulted in vomiting undigested food. CT imaging revealed a severely dilated esophagus narrowing at the gastroesophageal junction, suggestive of type 1 achalasia. Further testing confirmed the diagnosis, with an esophageal manometry showing a lack of esophageal contractions and sphincter relaxation. She then underwent a laparoscopic Heller myotomy with relief to her symptoms. This case underscores the rarity of pediatric-onset achalasia with significant esophageal dilation and secondary airway compression, presenting with unusual musculoskeletal and respiratory symptoms. Timely diagnosis and treatment are crucial to prevent worsening and complications.

Ischemic gastropathy with "leopard skin" stomach.

Ischemic gastropathy is a rare, underreported phenomenon that is associated with a poor prognosis. Patients often present with signs of shock, gastrointestinal bleeding, and anemia. We describe a patient with alcoholic cirrhosis who presented after a fall in hemorrhagic shock. Initial endoscopy revealed evidence of ongoing bleeding, with subsequent endoscopy revealing the "leopard skin" appearance in the stomach. The patient was treated supportively but eventually succumbed to his condition. Prompt diagnosis, treatment, and awareness of the delayed changes on upper endoscopy are imperative in diagnosing ischemic gastropathy. Patients with risk factors for the condition need to be given additional consideration for this diagnosis.

Childhood urbanicity interacts with polygenic risk for depression to affect stress-related medial prefrontal function.

Urbanization is increasing globally, and is associated with stress and increased mental health risks, including for depression. However, it remains unclear, especially at the level of brain function, how urbanicity, social threat stressors, and psychiatric risk may be linked. Here, we aim to define the structural and functional MRI neural correlates of social stress, childhood urbanicity, and their putative mechanistic relevance to depressive illness risk, in terms of behavioral traits and genetics. We studied a sample of healthy adults with divergent urban and rural childhoods. We examined childhood urbanicity effects on brain structure as suggested by MRI, and its functional relevance to depression risk, through interactions between urbanicity and trait anxiety-depression, as well as between urbanicity and polygenic risk for depression, during stress-related medial prefrontal cortex (mPFC) engagement. Subjects with divergent rural and urban childhoods were similar in adult socioeconomic status and were genetically homogeneous. Urban childhood was associated with relatively reduced mPFC gray matter volumes as suggested by MRI. MPFC engagement under social status threat correlated with the higher trait anxiety-depression in subjects with urban childhoods, but not in their rural counterparts, implicating an exaggerated physiological response to the threat context with urbanicity, in association with behavioral risk for depression. Stress-associated mPFC engagement also interacted with polygenic risk for depression, significantly predicting a differential mPFC response in individuals with urban but not rural childhoods. Developmental urbanicity, therefore, appears to interact with genetic and behavioral risk for depression on the mPFC neural response to a threat context.

Parietal-Prefrontal Feedforward Connectivity in Association With Schizophrenia Genetic Risk and Delusions.

OBJECTIVE: Conceptualizations of delusion formation implicate deficits in feedforward information updating across the posterior to prefrontal cortices, resulting in dysfunctional integration of new information about contexts in working memory and, ultimately, failure to update overfamiliar prior beliefs. The authors used functional MRI and machine learning models to address individual variability in feedforward parietal-prefrontal information updating in patients with schizophrenia. They examined relationships between feedforward connectivity, and delusional thinking and polygenic risk for schizophrenia. METHODS: The authors studied 66 schizophrenia patients and 143 healthy control subjects during performance of context updating in working memory. Dynamic causal models of effective connectivity were focused on regions of the prefrontal and parietal cortex potentially implicated in delusion processes. The effect of polygenic risk for schizophrenia on connectivity was examined in healthy individuals. The authors then leveraged support vector regression models to define optimal normalized target connectivity tailored for each patient and tested the extent to which deviation from this target could predict individual variation in severity of delusions. RESULTS: In schizophrenia patients, updating and manipulating context information was disproportionately less accurate than was working memory maintenance, with an interaction of task accuracy by diagnosis. Patients with delusions also tended to have relatively reduced parietal-prefrontal feedforward effective connectivity during context updating in working memory manipulation. The same connectivity was adversely influenced by polygenic risk for schizophrenia in healthy subjects. Individual patients' deviation from predicted "normal" feedforward connectivity based on the support vector regression models correlated with severity of delusions. CONCLUSIONS: These computationally derived observations support a role for feedforward parietal-prefrontal information processing deficits in delusional psychopathology and in genetic risk for schizophrenia.

Anemias excluding cobalamin and folate deficiencies.

Anemias are one of the commonest maladies affecting humans. They result from either a failure of production by the bone marrow (hypoproliferative), or from premature destruction or loss (hyperproliferative) of red cells. Hypoproliferative anemias typically result from deficiencies of essential nutrients, stem cell abnormalities or deficiency, and infiltrative processes of the bone marrow. In the hyperproliferative forms, the bone marrow function is normal and anemia results from bleeding or shortened erythrocyte lifespan due to hemoglobinopathies, red cell enzyme disorders, membrane defects, or external factors such as antibodies, trauma, or heat injury. The etiology of anemia is frequently obvious, but when obscure, a systematic diagnostic approach frequently yields the answer. It is important to realize that anemias are usually a consequence of another disease process, which must be identified. Without correction of the underlying disease process, the treatment is likely to fail.

Ongoing in vivo immunoglobulin class switch DNA recombination in chronic lymphocytic leukemia B cells.

Chronic lymphocytic leukemia (CLL) results from the expansion of malignant CD5(+) B cells that usually express IgD and IgM. These leukemic cells can give rise in vivo to clonally related IgG(+) or IgA(+) elements. The requirements and modalities of this process remain elusive. Here we show that leukemic B cells from 14 of 20 CLLs contain the hallmarks of ongoing Ig class switch DNA recombination (CSR), including extrachromosomal switch circular DNAs and circle transcripts generated by direct S micro -->Sgamma, S micro -->Salpha, and S micro -->Sepsilon as well as sequential Sgamma-->Salpha and Sgamma-->Sepsilon CSR. Similar CLL B cells express transcripts for activation-induced cytidine deaminase, a critical component of the CSR machinery, and contain germline I(H)-C(H) and mature V(H)DJ(H)-C(H) transcripts encoded by multiple Cgamma, Calpha, and Cepsilon genes. Ongoing CSR occurs in only a fraction of the CLL clone, as only small proportions of CD5(+)CD19(+) cells express surface IgG or IgA and lack IgM and IgD. In vivo class-switching CLL B cells down-regulate switch circles and circle transcripts in vitro unless exposed to exogenous CD40 ligand and IL-4. In addition, CLL B cells that do not class switch in vivo activate the CSR machinery and secrete IgG, IgA, or IgE upon in vitro exposure to CD40 ligand and IL-4. These findings indicate that in CLL at least some members of the malignant clone actively differentiate in vivo along a pathway that induces CSR. They also suggest that this process is elicited by external stimuli, including CD40 ligand and IL-4, provided by bystander immune cells.

The burden of selected digestive diseases in the United States.

BACKGROUND & AIMS: Gastrointestinal (GI) and liver diseases inflict a heavy economic burden. Although the burden is considerable, current and accessible information on the prevalence, morbidity, and cost is sparse. This study was undertaken to estimate the economic burden of GI and liver disease in the United States for use by policy makers, health care providers, and the public. METHODS: Data were extracted from a number of publicly available and proprietary national databases to determine the prevalence, direct costs, and indirect costs for 17 selected GI and liver diseases. Indirect cost calculations were purposefully very conservative. These costs were compared with National Institutes of Health (NIH) research expenditures for selected GI and liver diseases. RESULTS: The most prevalent diseases were non-food-borne gastroenteritis (135 million cases/year), food-borne illness (76 million), gastroesophageal reflux disease (GERD; 19 million), and irritable bowel syndrome (IBS; 15 million). The disease with the highest annual direct costs in the United States was GERD ($9.3 billion), followed by gallbladder disease ($5.8 billion), colorectal cancer ($4.8 billion), and peptic ulcer disease ($3.1 billion). The estimated direct costs for these 17 diseases in 1998 dollars were $36.0 billion, with estimated indirect costs of $22.8 billion. The estimated direct costs for all digestive diseases were $85.5 billion. Total NIH research expenditures were $676 million in 2000. CONCLUSIONS: GI and liver diseases exact heavy economic and social costs in the United States. Understanding the prevalence and costs of these diseases is important to help set priorities to reduce the burden of illness.

Progressive osseous heteroplasia in the face of a child.

We describe a rare case of progressive osseous heteroplasia of the face in a child. Biopsy showed osteoma cutis superficially with ectopic bone formation in the deeper tissues including skeletal muscle. Analysis of DNA from peripheral blood leukocytes showed mutations in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase (GNAS1), confirming the diagnosis of progressive osseous heteroplasia.