Prognosis of Reflux Symptom Resolution After Bariatric Surgery: How Can Preoperative Esophageal Testing Help?

PURPOSE: The incidence of unresolved postoperative reflux after bariatric surgery varies considerably. Consistent perioperative patient characteristics predictive of unresolved reflux remain unknown. We leverage our institution's comprehensive preoperative esophageal testing to identify predictors of postoperative reflux. MATERIALS AND METHODS: We performed a single-center retrospective review of adult patients with preoperative reflux symptoms who underwent either vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB) from 2015 to 2021. All patients had pH and high-resolution manometry preoperatively. Predictors of postoperative unresolved reflux at 1 year were explored via Fisher's exact test, Kruskal Wallis test, and univariate logistic regression. RESULTS: Unresolved reflux was higher in patients undergoing VSG (n = 60/129,46.5%) vs. RYGB (n = 19/98, 19.4%). Median DeMeester scores were higher (22 vs. 13, p = .07) along with rates of ineffective esophageal motility (IEM) (31.6 vs. 8.9%, p = .01) in the 19 (19.3%) patients with unresolved postoperative reflux after RYGB compared to the resolved RYGB reflux cohort. Sixty (46.5%) of VSG patients had unresolved postoperative reflux. The VSG unresolved reflux cohort had similar median DeMeester and IEM incidence to the resolved VSG group but more preoperative dysphagia (13.3% vs. 2.9%, p = .04) and higher preoperative PPI use (56.7 vs. 39.1%, p = .05). In univariate analysis, only IEM was predictive of unresolved reflux after RYGB (OR 4.74, 95% CI 1.37, 16.4). CONCLUSION: Unresolved reflux was higher after VSG. Preoperative IEM predicted unresolved reflux symptoms after RYGB. In VSG patients, preoperative dysphagia symptoms and PPI use predicted unresolved reflux though lack of correlation to objective testing highlights the subjective nature of symptoms and the challenges in predicting postoperative symptomatology.

Cases of Meningococcal Disease Associated with Travel to Saudi Arabia for Umrah Pilgrimage - United States, United Kingdom, and France, 2024.

Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2).

Biomarkers from subcutaneous engineered tissues predict acute rejection of organ allografts.

Invasive graft biopsies assess the efficacy of immunosuppression through lagging indicators of transplant rejection. We report on a microporous scaffold implant as a minimally invasive immunological niche to assay rejection before graft injury. Adoptive transfer of T cells into Rag2-/- mice with mismatched allografts induced acute cellular allograft rejection (ACAR), with subsequent validation in wild-type animals. Following murine heart or skin transplantation, scaffold implants accumulate predominantly innate immune cells. The scaffold enables frequent biopsy, and gene expression analyses identified biomarkers of ACAR before clinical signs of graft injury. This gene signature distinguishes ACAR and immunodeficient respiratory infection before injury onset, indicating the specificity of the biomarkers to differentiate ACAR from other inflammatory insult. Overall, this implantable scaffold enables remote evaluation of the early risk of rejection, which could potentially be used to reduce the frequency of routine graft biopsy, reduce toxicities by personalizing immunosuppression, and prolong transplant life.

The SAGES MASTERS program bariatric surgery pathway selects 10 seminal publications on adjustable gastric banding.

BACKGROUND: Bariatric surgery is one of the clinical pathways of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Masters Program, and laparoscopic adjustable gastric banding (LAGB) is one of the three anchoring bariatric procedures. To improve surgeon lifelong learning, the Masters Program seeks to identify sentinel articles of each of the 3 bariatric anchoring procedures. In this article, we present the top 10 articles on LAGB. METHODS: A systematic literature search of papers on LAGB was completed, and publications with the most citations and citation index were selected and shared with SAGES Metabolic and Bariatric Surgery Committee members for review. The individual committee members then ranked these papers, and the top 10 papers were chosen based on the composite ranking. RESULTS: The top 10 sentinel publications on LAGB contributed substantially to the body of literature related to the procedure, whether for surgical technique, novel information, or outcome analysis. A summary of each paper including expert appraisal and commentary is presented here. CONCLUSION: These seminal articles have had significant contribution to our understanding and appreciation of the LAGB procedure. Bariatric surgeons should use this resource to enhance their continual education and acquisition of specialized skills.

iGATE analysis improves the interpretability of single-cell immune landscape of influenza infection.

Influenza poses a persistent health burden worldwide. To design equitable vaccines effective across all demographics, it is essential to better understand how host factors such as genetic background and aging affect the single-cell immune landscape of influenza infection. Cytometry by time-of-flight (CyTOF) represents a promising technique in this pursuit, but interpreting its large, high-dimensional data remains difficult. We have developed a new analytical approach, in silico gating annotating training elucidating (iGATE), based on probabilistic support vector machine classification. By rapidly and accurately "gating" tens of millions of cells in silico into user-defined types, iGATE enabled us to track 25 canonical immune cell types in mouse lung over the course of influenza infection. Applying iGATE to study effects of host genetic background, we show that the lower survival of C57BL/6 mice compared with BALB/c was associated with a more rapid accumulation of inflammatory cell types and decreased IL-10 expression. Furthermore, we demonstrate that the most prominent effect of aging is a defective T cell response, reducing survival of aged mice. Finally, iGATE reveals that the 25 canonical immune cell types exhibited differential influenza infection susceptibility and replication permissiveness in vivo, but neither property varied with host genotype or aging. The software is available at https://github.com/UmichWenLab/iGATE.

Connectome reorganization associated with temporal lobe pathology and its surgical resection.

Network neuroscience offers a unique framework to understand the organizational principles of the human brain. Despite recent progress, our understanding of how the brain is modulated by focal lesions remains incomplete. Resection of the temporal lobe is the most effective treatment to control seizures in pharmaco-resistant temporal lobe epilepsy (TLE), making this syndrome a powerful model to study lesional effects on network organization in young and middle-aged adults. Here, we assessed the downstream consequences of a focal lesion and its surgical resection on the brain's structural connectome, and explored how this reorganization relates to clinical variables at the individual patient level. We included adults with pharmaco-resistant TLE (n = 37) who underwent anterior temporal lobectomy between two imaging time points, as well as age- and sex-matched healthy controls who underwent comparable imaging (n = 31). Core to our analysis was the projection of high-dimensional structural connectome data-derived from diffusion MRI tractography from each subject-into lower-dimensional gradients. We then compared connectome gradients in patients relative to controls before surgery, tracked surgically-induced connectome reconfiguration from pre- to postoperative time points, and examined associations to patient-specific clinical and imaging phenotypes. Before surgery, individuals with TLE presented with marked connectome changes in bilateral temporo-parietal regions, reflecting an increased segregation of the ipsilateral anterior temporal lobe from the rest of the brain. Surgery-induced connectome reorganization was localized to this temporo-parietal subnetwork, but primarily involved postoperative integration of contralateral regions with the rest of the brain. Using a partial least-squares analysis, we uncovered a latent clinical imaging signature underlying this pre- to postoperative connectome reorganization, showing that patients who displayed postoperative integration in bilateral fronto-occipital cortices also had greater preoperative ipsilateral hippocampal atrophy, lower seizure frequency and secondarily generalized seizures. Our results bridge the effects of focal brain lesions and their surgical resections with large-scale network reorganization and interindividual clinical variability, thus offering new avenues to examine the fundamental malleability of the human brain.

A WORLDWIDE ENIGMA STUDY ON EPILEPSY-RELATED GRAY AND WHITE MATTER COMPROMISE ACROSS THE ADULT LIFESPAN.

Objectives: Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments. Methods: We studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves. Results: In TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions. Conclusions: This study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients.

Clonally expanded memory CD8+ T cells accumulate in atherosclerotic plaques and are pro-atherogenic in aged mice.

Aging is a strong risk factor for atherosclerosis and induces accumulation of memory CD8+ T cells in mice and humans. Biological changes that occur with aging lead to enhanced atherosclerosis, yet the role of aging on CD8+ T cells during atherogenesis is unclear. In this study, using femle mice, we found that depletion of CD8+ T cells attenuated atherogenesis in aged, but not young, animals. Furthermore, adoptive transfer of splenic CD8+ T cells from aged wild-type, but not young wild-type, donor mice significantly enhanced atherosclerosis in recipient mice lacking CD8+ T cells. We also characterized T cells in healthy and atherosclerotic young and aged mice by single-cell RNA sequencing. We found specific subsets of age-associated CD8+ T cells, including a Granzyme K+ effector memory subset, that accumulated and was clonally expanded within atherosclerotic plaques. These had transcriptomic signatures of T cell activation, migration, cytotoxicity and exhaustion. Overall, our study identified memory CD8+ T cells as therapeutic targets for atherosclerosis in aging.

Intertumoral lineage diversity and immunosuppressive transcriptional programs in well-differentiated gastroenteropancreatic neuroendocrine tumors.

Neuroendocrine tumors (NETs) are rare cancers that most often arise in the gastrointestinal tract and pancreas. The fundamental mechanisms driving gastroenteropancreatic (GEP)-NET growth remain incompletely elucidated; however, the heterogeneous clinical behavior of GEP-NETs suggests that both cellular lineage dynamics and tumor microenvironment influence tumor pathophysiology. Here, we investigated the single-cell transcriptomes of tumor and immune cells from patients with gastroenteropancreatic NETs. Malignant GEP-NET cells expressed genes and regulons associated with normal, gastrointestinal endocrine cell differentiation, and fate determination stages. Tumor and lymphoid compartments sparsely expressed immunosuppressive targets commonly investigated in clinical trials, such as the programmed cell death protein-1/programmed death ligand-1 axis. However, infiltrating myeloid cell types within both primary and metastatic GEP-NETs were enriched for genes encoding other immune checkpoints, including VSIR (VISTA), HAVCR2 (TIM3), LGALS9 (Gal-9), and SIGLEC10. Our findings highlight the transcriptomic heterogeneity that distinguishes the cellular landscapes of GEP-NET anatomic subtypes and reveal potential avenues for future precision medicine therapeutics.

Telemedicine Use Decreases the Carbon Footprint of the Bariatric Surgery Preoperative Evaluation.

BACKGROUND: Healthcare-associated activity accounts for 10% of the United States' carbon dioxide (CO2) emissions. Using telemedicine for bariatric surgery evaluations decreases emissions and reduces patient burden during the multiple required interdisciplinary visits. After adopting telemedicine during COVID, our clinic continues to utilize telemedicine for preoperative bariatric evaluations. We evaluated the reduced environmental impact associated with this practice. METHODS: A retrospective review of all new evaluations for vertical sleeve gastrectomy (SG) or Roux-en Y gastric bypass (RYGB) from 2019 and 2021 was conducted. The 2019 year represents pre-pandemic, in-person evaluations and 2021 represents telemedicine evaluations during the COVID pandemic. Carbon emissions were calculated using the Environmental Protection Agency's (EPA's) validated formula of 404g CO2 per car-mile. Preoperative evaluation time was calculated from the initial clinic visit to the operation date. RESULTS: There were 51 patients in the 2019 cohort and 55 patients in the 2021 cohort. In the 2019 in-person cohort, there was significantly more kg of estimated CO2 emitted (10,225 vs. 2011.4, p<.001) compared to the 2021 cohort. For time required to complete the preoperative workup, there was no statistically significant difference between the two groups (162 days vs. 193 days, p=.226). The attrition rate was lower in the 2021 cohort (22.22% v. 35.9%, p<.001). CONCLUSIONS: Implementation of telemedicine for bariatric preoperative evaluations reduced patient travel, carbon emissions, and improved attrition rate. We encourage bariatric providers to use telemedicine as we believe this eases patient burdens and, with wider adoption, could significantly reduce our carbon footprint.

Enhanced Detection of Charged N-Glycans in the Brain by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometric Imaging.

N-linked glycosylation represents a structurally diverse, complex, co- and posttranslational protein modification that bridges metabolism and cellular signaling. Consequently, aberrant protein glycosylation is a hallmark of most pathological scenarios. Due to their complex nature and non-template-driven synthesis, the analysis of glycans is faced with several challenges, underlining the need for new and improved analytical technologies. Spatial profiling of N-glycans through direct imaging on tissue sections reveals the regio-specific and/or disease pathology correlating tissue N-glycans that serve as a disease glycoprint for diagnosis. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is a soft hybrid ionization technique that has been used for diverse mass spectrometry imaging (MSI) applications. Here, we report the first spatial analysis of the brain N-linked glycans by IR-MALDESI MSI, leading to a significant increase in the detection of the brain N-sialoglycans. A formalin-fixed paraffin-embedded mouse brain tissue was analyzed in negative ionization mode after tissue washing, antigen retrieval, and pneumatic application of PNGase F for enzymatic digestion of N-linked glycans. We report a comparative analysis of section thickness on the N-glycan detection using IR-MALDESI. One hundred thirty-six unique N-linked glycans were confidently identified in the brain tissue (with an additional 132 unique N-glycans, not reported in GlyConnect), where more than 50% contained sialic acid residues, which is approximately 3-fold higher than the previous reports. This work demonstrates the first application of IR-MALDESI in N-linked glycan imaging of the brain tissue, leading to a 2.5-fold increase in the in situ total brain N-glycan detection compared to the current gold standard of positive-mode matrix-assisted laser desorption/ionization mass spectrometry imaging. This is also the first report of the application of the MSI toward the identification of sulfoglycans in the rodent brain. Overall, IR-MALDESI-MSI presents a sensitive glycan detection platform to identify tissue-specific and/or disease-specific glycosignature in the brain while preserving the sialoglycans without any chemical derivatization.

Preoperative esophageal testing predicts postoperative reflux status in sleeve gastrectomy patients.

BACKGROUND: Patients who undergo vertical sleeve gastrectomy (VSG) are at risk of postoperative GERD. The reasons are multifactorial, but half of conversions to Roux-en Y gastric bypass are for intractable GERD. Our institution routinely performs preoperative pH and high-resolution manometry studies to aid in operative decision making. We hypothesize that abnormal pH studies in concert with ineffective esophageal motility would lead to higher rates of postoperative reflux after VSG. METHODS: A single institution retrospective review was conducted of adult patients who underwent preoperative pH and manometry testing and VSG between 2015 and 2021. Patients filled out a symptom questionnaire at the time of testing. Postoperative reflux was defined by patient-reported symptoms at 1-year follow-up. Univariate logistic regression was used to examine the relationship between esophageal tests and postoperative reflux. The Lui method was used to determine the cutpoint for pH and manometric variables maximizing sensitivity and specificity for postoperative reflux. RESULTS: Of 291 patients who underwent VSG, 66 (22.7%) had a named motility disorder and 67 (23%) had an abnormal DeMeester score. Preoperatively, reflux was reported by 122 patients (41.9%), of those, 69 (56.6%) had resolution. Preoperative pH and manometric abnormalities, and BMI reduction did not predict postoperative reflux status (p = ns). In a subgroup analysis of patients with an abnormal preoperative pH study, the Lui cutpoint to predict postoperative reflux was a DeMeester greater than 24.8. Postoperative reflux symptoms rates above and below this point were 41.9% versus 17.1%, respectively (p = 0.03). CONCLUSION: While manometry abnormalities did not predict postoperative reflux symptoms, GERD burden did. Patients with a mildly elevated DeMeester score had a low risk of postoperative reflux compared to patients with a more abnormal DeMeester score. A preoperative pH study may help guide operative decision-making and lead to better counseling of patients of their risk for reflux after VSG.

Readability and Suitability of Online Uveitis Patient Education Materials.

PURPOSE: This study assesses readability, suitability, and accountability of online uveitis patient education materials (PEMs). METHODS: Two uveitis specialists reviewed the top 10 websites on Google for keyword "uveitis," with a PubMed review control. Readability was assessed using an online calculator, suitability using the Suitability Assessment of Materials (SAM) tool, and accountability using JAMA benchmarks. RESULTS: The mean SAM score was 21.05, indicating that websites were on average adequately suitable to educate patients. WebMD Uveitis website scored the highest at 25.5, while allaboutvision.org scored the lowest at 18.0. The average Flesch Reading Ease (FRE) score was 44.0 (95% CI: 34.2, 53.8). The average reading grade score was 11.0 (95% CI: 9.4, 12.6). WebMD Uveitis page scored highest on readability. The average accountability score among sites was 2.36 out of 4. CONCLUSIONS: Uveitis websites are only adequately suitable as PEMs, and all are above the recommended reading level. Uveitis specialists should advise patients on quality of online PEMs.

A vascular syphilitic iris lesion.

Purpose: To describe examination and imaging characteristics of presumed iris papulosa in a case of ocular syphilis. Observations: A 60-year-old man who presented with granulomatous anterior uveitis in his left eye was also noted to have an unusual vascularized iris papule associated with posterior synechiae at the nasal pupillary margin. Anterior segment OCT (AS-OCT) of the iris lesion demonstrated a hyperreflective anterior surface with multiple vascular lumen, internal hyperreflectivity, and shadowing. Ultrasound biomicroscopy (UBM) imaging revealed an echodense mass with relative hyperechogenicity in the anterior portion of the lesion. Systemic work-up confirmed a diagnosis of syphilis, and he was treated with topical steroids and parenteral penicillin. Conclusion and Importance: We characterize the rare finding of iris papulosa that may be encountered in syphilitic uveitis and its distinctive features on both UBM and AS-OCT. This report highlights that syphilis should be considered as a possible diagnosis for an undifferentiated vascular iris mass.

Serial Interval and Incubation Period Estimates of Monkeypox Virus Infection in 12 Jurisdictions, United States, May-August 2022.

Using data from 12 US health departments, we estimated mean serial interval for monkeypox virus infection to be 8.5 (95% credible interval 7.3-9.9) days for symptom onset, based on 57 case pairs. Mean estimated incubation period was 5.6 (95% credible interval 4.3-7.8) days for symptom onset, based on 35 case pairs.

Age-associated adipose tissue inflammation promotes monocyte chemotaxis and enhances atherosclerosis.

Although aging enhances atherosclerosis, we do not know if this occurs via alterations in circulating immune cells, lipid metabolism, vasculature, or adipose tissue. Here, we examined whether aging exerts a direct pro-atherogenic effect on adipose tissue in mice. After demonstrating that aging augmented the inflammatory profile of visceral but not subcutaneous adipose tissue, we transplanted visceral fat from young or aged mice onto the right carotid artery of Ldlr-/- recipients. Aged fat transplants not only increased atherosclerotic plaque size with increased macrophage numbers in the adjacent carotid artery, but also in distal vascular territories, indicating that aging of the adipose tissue enhances atherosclerosis via secreted factors. By depleting macrophages from the visceral fat, we identified that adipose tissue macrophages are major contributors of the secreted factors. To identify these inflammatory factors, we found that aged fat transplants secreted increased levels of the inflammatory mediators TNFα, CXCL2, and CCL2, which synergized to promote monocyte chemotaxis. Importantly, the combined blockade of these inflammatory mediators impeded the ability of aged fat transplants to enhance atherosclerosis. In conclusion, our study reveals that aging enhances atherosclerosis via increased inflammation of visceral fat. Our study suggests that future therapies targeting the visceral fat may reduce atherosclerosis disease burden in the expanding older population.

PURTSCHER-LIKE RETINOPATHY IN A PATIENT WITH MILK-ALKALI SYNDROME AND PANCREATITIS.

PURPOSE: To report a case of Purtscher-like retinopathy in a patient with milk-alkali syndrome and pancreatitis. METHODS: Case report and review of the literature. RESULTS: A 46-year-old woman presented with decreased vision following discharge from the intensive care unit, where she had been admitted for milk-alkali syndrome secondary to long-term calcium supplementation and over-the-counter antacid use, and pancreatitis. Dilated examination showed ischemic retinal whitening and retinal hemorrhages in the posterior pole bilaterally consistent with Purtscher-like retinopathy. Over three months, the retinopathy resolved and her vision improved. CONCLUSION: Milk-alkali syndrome is the clinical triad of hypercalcemia, renal failure, and metabolic alkalosis and occurs secondary to the consumption of large amounts of calcium and alkali. The hypercalcemia associated with milk-alkali syndrome may cause pancreatitis, which can lead to Purtscher-like retinopathy.

Delayed Recognition of Coronavirus Disease 2019 (COVID-19) in New York City: A Descriptive Analysis of COVID-19 Illness Prior to 29 February 2020.

BACKGROUND: On 30 January 2020, COVID-19 was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization. Almost a month later, on 29 February 2020, the first case in New York City (NYC) was diagnosed. METHODS: Three hundred sixty persons with COVID-19-like illness were reported to the NYC Department of Health and Mental Hygiene (DOHMH) before 29 February, but 37 of these tested negative and 237 were never tested for severe acute respiratory syndrome coronavirus 2. Records of 86 persons with confirmed COVID-19 and reported symptom onset prior to 29 February 2020 were reviewed by 4 physician-epidemiologists. Case-patients were classified as possible delayed recognition (PDR) of COVID-19 when upon medical review the reported onset date was believed to reflect the initial symptoms of COVID-19, or insufficient evidence to classify, when the onset could not be determined with confidence. Clinical and epidemiological factors collected by DOHMH and supplemented with emergency department records were analyzed. RESULTS: Thirty-nine PDR COVID-19 cases were identified. The majority had severe disease with 69% presenting to an emergency department within 2 weeks of symptom onset. The first PDR COVID-19 case had symptom onset on 28 January 2020. Only 7 of the 39 cases (18%) had traveled internationally within 14 days of onset (none to China). CONCLUSIONS: COVID-19 was in NYC before being classified as a PHEIC, and eluded surveillance for another month. The delay in recognition limited mitigation efforts; by the time city- and statewide mandates were enacted, 16 and 22 days later, there was already widespread community transmission.