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1.
Nat Chem Biol ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898166

RESUMEN

Bacterial infection involves a complex interaction between the pathogen and host where the outcome of infection is not solely determined by pathogen eradication. To identify small molecules that promote host survival by altering the host-pathogen dynamic, we conducted an in vivo chemical screen using zebrafish embryos and found that treatment with 3-hydroxykynurenine (3-HK) protects from lethal bacterial infection. 3-HK, a metabolite produced through host tryptophan metabolism, has no direct antibacterial activity but enhances host survival by restricting bacterial expansion in macrophages through a systemic mechanism that targets kainate-sensitive glutamate receptors. These findings reveal a new pathway by which tryptophan metabolism and kainate-sensitive glutamate receptors function and interact to modulate immunity, with important implications for the coordination between the immune and nervous systems in pathological conditions.

2.
J Am Chem Soc ; 146(26): 17669-17678, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38905328

RESUMEN

The genus Mycobacterium includes species such as Mycobacterium tuberculosis, which can cause deadly human diseases. These bacteria have a protective cell envelope that can be remodeled to facilitate their survival in challenging conditions. Understanding how such conditions affect membrane remodeling can facilitate antibiotic discovery and treatment. To this end, we describe an optimized fluorogenic probe, N-QTF, that reports on mycolyltransferase activity, which is vital for cell division and remodeling. N-QTF is a glycolipid probe that can reveal dynamic changes in the mycobacterial cell envelope in both fast- and slow-growing mycobacterial species. Using this probe to monitor the consequences of antibiotic treatment uncovered distinct cellular phenotypes. Even antibiotics that do not directly inhibit cell envelope biosynthesis cause conspicuous phenotypes. For instance, mycobacteria exposed to the RNA polymerase inhibitor rifampicin release fluorescent extracellular vesicles (EVs). While all mycobacteria release EVs, fluorescent EVs were detected only in the presence of RIF, indicating that exposure to the drug alters EV content. Macrophages exposed to the EVs derived from RIF-treated cells released lower levels of cytokines, suggesting the EVs moderate immune responses. These data suggest that antibiotics can alter EV content to impact immunity. Our ability to see such changes in EV constituents directly results from exploiting these chemical probes.


Asunto(s)
Colorantes Fluorescentes , Mycobacterium tuberculosis , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Mycobacterium tuberculosis/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Humanos
3.
Curr Opin Nephrol Hypertens ; 33(2): 161-169, 2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38193301

RESUMEN

PURPOSE OF REVIEW: The transmembrane protein 16A (TMEM16A) Ca 2+ -activated Cl - channel constitutes a key depolarising mechanism in vascular smooth muscle and contractile pericytes, while in endothelial cells the channel is implicated in angiogenesis and in the response to vasoactive stimuli. Here, we offer a critical analysis of recent physiological investigations and consider the potential for targeting TMEM16A channels in vascular disease. RECENT FINDINGS: Genetic deletion or pharmacological inhibition of TMEM16A channels in vascular smooth muscle decreases artery tone and lowers systemic blood pressure in rodent models. Inhibition of TMEM16A channels in cerebral cortical pericytes protects against ischemia-induced tissue damage and improves microvascular blood flow in rodent stroke models. In endothelial cells, the TMEM16A channel plays varied roles including modulation of cell division and control of vessel tone through spread of hyperpolarisation to the smooth muscle cells. Genetic studies implicate TMEM16A channels in human disease including systemic and pulmonary hypertension, stroke and Moyamoya disease. SUMMARY: The TMEM16A channel regulates vascular function by controlling artery tone and capillary diameter as well as vessel formation and histology. Preclinical and clinical investigations are highlighting the potential for therapeutic exploitation of the channel in a range of maladaptive states of the (micro)circulation.


Asunto(s)
Hipertensión Pulmonar , Accidente Cerebrovascular , Humanos , Canales de Cloruro/genética , Canales de Cloruro/metabolismo , Células Endoteliales/metabolismo , Miocitos del Músculo Liso/fisiología
4.
Clin Gastroenterol Hepatol ; 22(4): 798-809.e28, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38036281

RESUMEN

BACKGROUND & AIMS: Previous studies show that mortality from chronic liver disease (CLD) and cirrhosis is increasing in the United States. However, there are limited data on sex-specific mortality trends by age, race, and geographical location. The aim of this study was to conduct a comprehensive time-trend analysis of liver disease-related mortality rates in the National Center of Health Statistics (NCHS) database. METHODS: CLD and cirrhosis mortality rates between 20002020 (age-adjusted to the 2000 standard U.S. population) were collected from the NCHS database and categorized by sex and age into older adults (≥55 years) and younger adults (<55 years), race (Non-Hispanic-White, Non-Hispanic-Black, Hispanic, Non-Hispanic-American-Indian/Alaska-Native, and Non-Hispanic-Asian/Pacific-Islander), U.S. state, and cirrhosis etiology. Time trends, annual percentage change (APC), and average APC (AAPC) were estimated using Joinpoint Regression using Monte Carlo permutation analysis. We used tests for parallelism and identicalness for sex-specific pairwise comparisons of mortality trends (two-sided P value cutoff = .05). RESULTS: Between 20002020, there were 716,651 deaths attributed to CLD and cirrhosis in the U.S. (35.68% women). In the overall population and in older adults, CLD and cirrhosis-related mortality rates were increasing similarly in men and women. However, in younger adults (246,149 deaths, 32.72% women), the rate of increase was greater in women compared with men (AAPC = 3.04 vs 1.08, AAPC-difference = 1.96; P < .001), with non-identical non-parallel data (P values < .001). The disparity was driven by Non-Hispanic-White (AAPC = 4.51 vs 1.79, AAPC-difference = 2.71; P < .001) and Hispanic (AAPC = 1.89 vs -0.65, AAPC-difference = 2.54; P = .001) individuals. The disparity varied between U.S. states and was seen in 16 states, mostly in West Virginia (AAPC = 4.96 vs 0.88, AAPC-difference = 4.08; P < .001) and Pennsylvania (AAPC = 2.81 vs -1.02, AAPC-difference = 3.84; P < .001). Etiology-specific analysis did not show significant sex disparity in younger adults. CONCLUSIONS: Mortality rates due to CLD and cirrhosis in the U.S. are increasing disproportionately in younger women. This finding was driven by higher rates in Non-Hispanic White and Hispanic individuals, with variation between U.S. states. Future studies are warranted to identify the reasons for these trends with the ultimate goal of improving outcomes.


Asunto(s)
Hepatopatías , Masculino , Humanos , Estados Unidos/epidemiología , Femenino , Anciano , Persona de Mediana Edad , Cirrosis Hepática , Hispánicos o Latinos , Asiático , Pennsylvania
5.
Eur J Ophthalmol ; 34(4): 1085-1094, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38130153

RESUMEN

PURPOSE: To describe the frequency, clinical presentation, and outcomes of neurotrophic keratopathy (NK). METHODS: Retrospective cohort study of Kaiser Permanente Northern California patients diagnosed with NK using ICD-10 code H16.23X from October 1, 2016 through May 31, 2021 was conducted. The electronic medical record was used to obtain demographic information, systemic and ocular comorbidities, corrected distance visual acuity (CDVA), Mackie stage, laterality, etiology, complications, interventions, and medications. The data were analyzed using cross-tabulations. RESULTS: 354 eyes in 322 patients presented with an initial or recurrent episode of NK. 9.9% had bilateral NK, 40% were 75 years and older, and 55% were women. Baseline vision was worse than 20/100 in 47.5%. Mackie staging was stage 1 in 37.3%, stage 2 in 32.5%, and stage 3 in 30.2%. Herpetic causes comprised 34.9%, followed by diabetes (12.4%), ocular surgery (10.4%), and central nervous system etiologies (9.0%). Topical antibiotics (74.5%), steroids (54.0%), autologous serum tears (46.0%), and oral antivirals (43.8%) were the most used treatments. There were 8 eyes with perforation, 4 endophthalmitis, and 3 evisceration/enucleations. An increased difference of approximately 0.1 logMAR in CDVA in the affected eye compared with the unaffected eye over one year was not statistically significant. Clinic utilization for stage 2 (average visits per month, 3.2) and stage 3 (5.0) NK gradually decreased over 6 months. CONCLUSIONS: Summary of the current management, outcomes, and healthcare utilization of NK provides valuable benchmarks in assessing the disease burden in the community and for further development of novel therapies.


Asunto(s)
Agudeza Visual , Humanos , Femenino , Masculino , Estudios Retrospectivos , Anciano , Agudeza Visual/fisiología , Persona de Mediana Edad , Anciano de 80 o más Años , Adulto , Enfermedades de la Córnea/diagnóstico , Enfermedades de la Córnea/epidemiología , California/epidemiología , Adulto Joven , Adolescente , Estudios de Seguimiento
6.
bioRxiv ; 2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37645903

RESUMEN

Bacterial infection involves a complex interaction between the pathogen and host where the outcome of infection is not solely determined by pathogen eradication. To identify small molecules that promote host survival by altering the host-pathogen dynamic, we conducted an in vivo chemical screen using zebrafish embryos and found that treatment with 3-hydroxy-kynurenine protects from lethal gram-negative bacterial infection. 3-hydroxy-kynurenine, a metabolite produced through host tryptophan metabolism, has no direct antibacterial activity but enhances host survival by restricting bacterial expansion in macrophages by targeting kainate-sensitive glutamate receptors. These findings reveal new mechanisms by which tryptophan metabolism and kainate-sensitive glutamate receptors function and interact to modulate immunity, with significant implications for the coordination between the immune and nervous systems in pathological conditions.

7.
Cureus ; 15(1): e33929, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36819381

RESUMEN

Liver abscesses range in presentation from asymptomatic infection to sepsis. Recurrence is rare. We describe a case of an asymptomatic liver abscess that recurred 10 years after a previous abscess. The patient presented with flu-like symptoms and dark urine. Laboratory evaluation showed an elevation of aminotransferases and bilirubin. Triple-phase CT showed a 2.8 cm mass in the right liver lobe with linear enhancement. The abscess was aspirated, with cultures growing Escherichia coli. The patient was started on ceftriaxone and metronidazole and then discharged with outpatient follow-up. We describe an unusual case of asymptomatic pyogenic liver abscess growing E. coli, with the same location and causative organism as an abscess that occurred 10 years prior.

8.
Ophthalmic Plast Reconstr Surg ; 39(3): e75-e78, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36807287

RESUMEN

A 4-year-old boy with a known diagnosis of neurofibromatosis 1 (NF1) and a diffusely infiltrative plexiform neurofibroma (PN) of the left orbit was started on selumetinib treatment for progressively worsening amblyopia. The patient first presented with new-onset left ptosis at 11 months old. He subsequently developed refractory anisometropic amblyopia of the left eye, in addition to clinically significant left proptosis and hypoglobus that interfered with glasses wear for his amblyopia treatment. The plexiform neurofibroma was not amenable to surgical resection and selumetinib treatment was initiated 3 years after the initial diagnosis. The patient showed remarkable clinical and radiographic improvement in tumor burden after treatment. Best corrected visual acuity improved from 20/50 to 20/20- in his amblyopic eye. Relative proptosis of the affected eye also improved from 4mm to 2mm on Hertel measurements, which allowed for consistent glasses wear. Adverse effects from the treatment were limited to an acneiform rash, which resolved following dose reduction according to the FDA dosing guidelines.


Asunto(s)
Ambliopía , Exoftalmia , Neurofibroma Plexiforme , Neurofibromatosis 1 , Masculino , Humanos , Preescolar , Lactante , Neurofibroma Plexiforme/complicaciones , Neurofibroma Plexiforme/diagnóstico , Neurofibroma Plexiforme/tratamiento farmacológico , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/diagnóstico , Neurofibromatosis 1/tratamiento farmacológico
9.
Commun Biol ; 6(1): 11, 2023 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-36604600

RESUMEN

Fast synaptic inhibition is dependent on targeting specific GABAAR subtypes to dendritic and axon initial segment (AIS) synapses. Synaptic GABAARs are typically assembled from α1-3, ß and γ subunits. Here, we isolate distinct GABAARs from the brain and interrogate their composition using quantitative proteomics. We show that α2-containing receptors co-assemble with α1 subunits, whereas α1 receptors can form GABAARs with α1 as the sole α subunit. We demonstrate that α1 and α2 subunit-containing receptors co-purify with distinct spectrin isoforms; cytoskeletal proteins that link transmembrane proteins to the cytoskeleton. ß2-spectrin was preferentially associated with α1-containing GABAARs at dendritic synapses, while ß4-spectrin was associated with α2-containing GABAARs at AIS synapses. Ablating ß2-spectrin expression reduced dendritic and AIS synapses containing α1 but increased the number of synapses containing α2, which altered phasic inhibition. Thus, we demonstrate a role for spectrins in the synapse-specific targeting of GABAARs, determining the efficacy of fast neuronal inhibition.


Asunto(s)
Receptores de GABA-A , Espectrina , Receptores de GABA-A/metabolismo , Espectrina/metabolismo , Sinapsis/metabolismo , Proteínas de la Membrana/metabolismo , Ácido gamma-Aminobutírico/metabolismo
10.
Orbit ; 42(2): 148-156, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35298320

RESUMEN

PURPOSE: To examine the clinical and histopathologic characteristics of lacrimal gland biopsies at a tertiary academic center. METHODS: A retrospective chart review of patients undergoing lacrimal gland biopsy or excision between 1962 and 2017 was performed via the ocular pathology specimen log. All cases were reviewed for demographics, clinical presentation, and histopathologic diagnoses. RESULTS: Four hundred and two eyes in 356 patients were included in the analysis. Median age was 49 (range 5-91) with a female predominance (255, 72%, p < .001). Most had unilateral involvement (308, 86.5%) and visual acuity of 20/50 or better (332 eyes, 83%). Limitation in extraocular motility was present in 71 eyes (18%), relative afferent pupillary defect in 10 eyes (2.5%), and intraocular pressure 20 mmHg or above in 80 eyes (20%). The pre-operative radiology report commented on the enlargement of the lacrimal gland in 236 eyes (58.7%), and lack thereof in 73 eyes (18.2%). The most common histopathologic diagnoses were nonspecific inflammation or orbital pseudotumor (170, 42%), lymphoma (65, 16%), pleomorphic adenoma (22, 5.5%), adenoid cystic carcinoma (19, 4.7%), granulomatous inflammation (19, 4.7%), and normal lacrimal gland (16, 4%). Three hundred and seven cases were benign (76%) and 95 malignant (24%). The biopsy specimen was diagnostic in 343 (85%), and non-diagnostic in 59 (15%). CONCLUSIONS: This is a comprehensive review of one of the largest ocular pathology databases of lacrimal gland lesions. This study confirms the wide range of inflammatory and neoplastic conditions affecting the lacrimal gland and highlights the nuances of histopathologic diagnoses and diagnostic yield of biopsies in clinical practice.


Asunto(s)
Adenoma Pleomórfico , Neoplasias del Ojo , Enfermedades del Aparato Lagrimal , Aparato Lagrimal , Humanos , Femenino , Persona de Mediana Edad , Masculino , Aparato Lagrimal/patología , Enfermedades del Aparato Lagrimal/cirugía , Estudios Retrospectivos , Inflamación , Adenoma Pleomórfico/patología , Biopsia , Neoplasias del Ojo/patología
11.
Eur J Clin Invest ; 53(1): e13889, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36205636

RESUMEN

BACKGROUND: The impact of the COVID-19 pandemic on palliative care intervention (PCIs) in patients with do-not-resuscitate (DNR) status remains uncertain. METHODS: Case-control study of patients with DNR order with RT-PCR confirmed SARS-COV2 infection (cases), and those with DNR order but without SARS-COV2 infection (controls). The primary outcome measures included timing and delivery of PCIs, and secondary measures included pre-admission characteristics and in-hospital death. RESULTS: The ethnicity distribution was comparable between 69 cases and 138 controls, including Black/African Americans (61% vs. 44%), Latino/Hispanics (16% vs. 26%) and White (9% vs. 20%) (trend-p = .54). Cases were employed more (17% vs. 6%, adjusted-p = .012), less frail (fit 47% vs. 21%; mildly frail 22% vs. 36%; frail 31% vs. 43%, trend-p = .018) and had fewer comorbidities than controls. Cases had higher chances of intensive care unit admission (HR 1.76 [95% CI: 1.03-3.02]) and intubation (53% vs. 30%, p = .002), lower chances to be seen by palliative care team (HR .46 [.30-.70]) and a longer time to palliative care visit than controls (ß per ln-day .67 [.00-1.34]). In the setting of no-visiting hospitals policy, we did not find significant increase in utilisation of video conferencing (22% vs. 13%) and religious services (12% vs. 12%) both in case and in controls. CONCLUSION: Do-not-resuscitate patients with COVID-19 had better general health and higher employment status than 'typical' DNR patients, but lower chances to be seen by the palliative care team. This study raises a question of the applicability of the current palliative care model in addressing the needs of DNR patients with COVID-19 during the pandemic.


Asunto(s)
COVID-19 , Cuidados Paliativos , Humanos , Mortalidad Hospitalaria , Pandemias , COVID-19/epidemiología , Estudios de Casos y Controles , ARN Viral , SARS-CoV-2 , Estudios Retrospectivos
12.
Cureus ; 14(11): e31691, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36561579

RESUMEN

Physicians need to recognize the potential complications of endoscopic retrograde cholangiopancreatography (ERCP), which are rare but can be serious. We describe a case of post-ERCP subcapsular hepatic hematoma (SHH). A 39-year-old man with a history of alcohol use, complicated by chronic pancreatitis and common bile duct (CBD) stricture, presented with right upper quadrant pain two weeks after the placement of a stent for CBD stricture. He was managed with pain control and antibiotics. SHH is a rare complication of ERCP. Hematomas can expand, resulting in significant anemia and liver function test (LFT) elevation, or can become infected. Patients with SHH must be carefully monitored in the post-ERCP setting.

13.
Front Mol Neurosci ; 15: 1017404, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36263376

RESUMEN

Impaired inhibitory signaling underlies the pathophysiology of many neuropsychiatric and neurodevelopmental disorders including autism spectrum disorders and epilepsy. Neuronal inhibition is regulated by synaptic and extrasynaptic γ-aminobutyric acid type A receptors (GABA A Rs), which mediate phasic and tonic inhibition, respectively. These two GABA A R subtypes differ in their function, ligand sensitivity, and physiological properties. Importantly, they contain different α subunit isoforms: synaptic GABA A Rs contain the α1-3 subunits whereas extrasynaptic GABA A Rs contain the α4-6 subunits. While the subunit composition is critical for the distinct roles of synaptic and extrasynaptic GABA A R subtypes in inhibition, the molecular mechanism of the subtype-specific assembly has not been elucidated. To address this issue, we purified endogenous α1- and α4-containing GABA A Rs from adult murine forebrains and examined their subunit composition and interacting proteins using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and quantitative analysis. We found that the α1 and α4 subunits form separate populations of GABA A Rs and interact with distinct sets of binding proteins. We also discovered that the ß3 subunit, which co-purifies with both the α1 and α4 subunits, has different levels of phosphorylation on serines 408 and 409 (S408/9) between the two receptor subtypes. To understand the role S408/9 plays in the assembly of α1- and α4-containing GABA A Rs, we examined the effects of S408/9A (alanine) knock-in mutation on the subunit composition of the two receptor subtypes using LC-MS/MS and quantitative analysis. We discovered that the S408/9A mutation results in the formation of novel α1α4-containing GABA A Rs. Moreover, in S408/9A mutants, the plasma membrane expression of the α4 subunit is increased whereas its retention in the endoplasmic reticulum is reduced. These findings suggest that S408/9 play a critical role in determining the subtype-specific assembly of GABA A Rs, and thus the efficacy of neuronal inhibition.

14.
Cureus ; 14(6): e26450, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35923677

RESUMEN

This case describes a 49-year-old man who presented with a several-month history of melena, and unintentional weight loss. Prior esophagogastroduodenoscopy and colonoscopy were unrevealing. Further evaluation with capsule endoscopy showed patchy erythematous mucosa in the jejunum creating suspicion for Crohn's Disease. Subsequent push enteroscopy found nodular and congested patchy mucosa of jejunum, and stigmata of bleeding in the proximal and mid-jejunum. Repeat colonoscopy showed a diffuse area of erythematous mucosa in the recto-sigmoid colon, and moderately congested mucosa in the ascending colon, but a normal terminal ileum. A small bowel biopsy eventually revealed large B-cell lymphoma. This is one of the first seven reported cases of small bowel lymphoma mimicking Crohn's Disease and the first to not have any ileal involvement.

15.
Cureus ; 14(5): e25418, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35774644

RESUMEN

INTRODUCTION: Alcoholic hepatitis (AH) is a common cause of hospital admissions and is associated with a high mortality rate. AH occurs frequently in patients with heavy alcohol use. Alcohol use disorder (AUD) commonly presents with comorbid psychiatric disorders such as bipolar disorder. Bipolar disorder patients are also known to be at an increased risk for chronic liver diseases. Bipolar 1 disorder (B1D) is often considered the most severe presentation among different types of bipolar disorder. This study assesses the clinical outcomes of patients admitted for AH with concomitant B1D. METHODS: Adult patients with AH were identified within the 2014 National Inpatient Sample (NIS) database. International Classification of Diseases, Ninth Edition Revision, Clinical Modification (ICD-9 CM) codes were used to select for all of the diagnoses for this study. AH patients were subdivided into those with and without B1D. The outcomes of interest were sepsis, hepatic encephalopathy, acute respiratory failure, acute kidney injury, ischemic stroke, hepatic failure, coagulopathy, and inpatient mortality. A multivariate logistic regression analysis was performed to explore whether B1D is an independent predictor for the outcomes. RESULTS: Among 4,453 patients with AH identified, 166 patients also had B1D. AH patients with comorbid B1D were seen to be younger (42.9 years old vs. 46.2 years old, p < 0.05) and more commonly female (55.4% vs. 36.5%, p < 0.05). The B1D subgroup of AH patients were found to less likely develop acute hepatic failure (adjusted odds ratio (aOR) 0.13, 95% confidence interval (CI): 0.02-0.97, p < 0.05). The adjusted odds ratios for the remaining outcomes were not statistically significant. CONCLUSIONS: Our study indicates that B1D may be an independent protective factor against acute hepatic failure in patients hospitalized with AH. This finding can be explained by frequent laboratory monitoring and psychiatric assessments performed by psychiatrists treating B1D patients, as well as the impact B1D has on cortisol release induced by hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis.

16.
Cureus ; 14(6): e25636, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35795501

RESUMEN

Laparoscopic gastric banding has been favored for the treatment of morbid obesity because it is minimally invasive, effective, and reversible. One of the complications is gastric band erosion which can cause abdominal pain, hematemesis, and hematochezia. Erosions can be partial and can lead to intra-abdominal free air, peritonitis, and sepsis. Endoscopic removal of the gastric band can be done safely and effectively using a wire and a mechanical lithotripter. We describe a patient with a rare case of an incidental near-complete gastric band erosion without perforation and subsequent endoscopic removal.

17.
Am J Ophthalmol Case Rep ; 25: 101335, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35128166

RESUMEN

PURPOSE: Periocular molluscum contagiosum can cause a chronic secondary follicular conjunctivitis or keratoconjunctivitis that rarely leads to corneal scarring and visual impairment. We describe two cases of follicular conjunctivitis due to periocular molluscum contagiosum that were successfully treated with topical adapalene 0.1%. OBSERVATIONS: Case 1 is a 9-year old female with a history of leg molluscum contagiosum who presented with three 1mm flesh-colored umbilicated papules on the periocular skin of the right eye with associated follicular conjunctivitis and diffuse corneal punctate epithelial erosions. Ocular symptoms were persistent for 6 months. Case 2 is a 4-year old female with a 3-month history of right periocular bumps and one month of conjunctival redness with eyelid edema. Examination revealed umbilicated flesh colored nodules on the right upper and lower eyelids with associated trace conjunctival injection. Both patients experienced rapid resolution of both eyelid involvement and conjunctivitis following the use of twice daily topical adapalene 0.1% to the eyelid lesions, with no reported side effects. CONCLUSIONS AND IMPORTANCE: Topical adapalene 0.1% is a cost-effective, convenient, and non-toxic over-the-counter retinoid cream that should be considered for first-line therapy in the treatment of periocular molluscum contagiosum and any associated conjunctivitis.

18.
Ophthalmic Genet ; 43(3): 385-388, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34889688

RESUMEN

BACKGROUND: Papillorenal syndrome is an autosomal dominant disorder associated with mutations in the gene PAX2 and often presents with characteristic and specific optic disc findings, frequently with renal dysplasia. In at least half of cases, an identifiable mutation in the PAX2 gene can be detected. We report the ocular findings in a second case of papillorenal syndrome with the c.350 G > C (p.Arg117Pro) mutation detected within the PAX2 gene. METHODS: A case report of papillorenal syndrome due to PAX2 mutation. Complete ophthalmologic examination was performed as well as color fundus photography, fundus autofluorescence, and optical coherence tomography (OCT). Genetic testing was performed using a next-generation sequencing with CNV calling (NGS-CNV) panel test containing 55 genes associated with nephrotic syndrome or focal segmental glomerulosclerosis. RESULTS: An 11-year-old boy who presented with hypertension and proteinuria was found to have stage IV chronic kidney disease. Presenting visual acuity was 20/25 in the right eye and 20/20 in the left eye. The fundus exam showed bilateral centrally excavated optic discs with absent central retinal vessels and a compensatory multiplicity of cilioretinal vessels, characteristic and specific for papillorenal syndrome. OCT showed outer retinal atrophy and macular schisis. Genetic testing identified the likely pathogenic c.350 G > C (p.Arg117Pro) mutation in PAX2. CONCLUSIONS: We report the first description, to our knowledge, of the clinical presentation, ocular and systemic findings, and ophthalmic imaging in an individual with papillorenal syndrome associated with the PAX2 c.350 G > C (p.Arg117Pro) mutation. Our case adds to the current understanding of papillorenal syndrome and demonstrates that this condition is associated with a pathognomonic optic disc appearance and significant renal disease.


Asunto(s)
Coloboma , Disco Óptico , Coloboma/complicaciones , Coloboma/diagnóstico , Coloboma/genética , Humanos , Mutación , Disco Óptico/patología , Factor de Transcripción PAX2/genética , Fenotipo , Insuficiencia Renal , Reflujo Vesicoureteral
19.
J Clin Gastroenterol ; 56(3): 257-265, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33471483

RESUMEN

BACKGROUND: Cannabinoid receptors are potential therapeutic targets in a variety of gastrointestinal tract disorders. The authors hypothesize that the use of cannabis use is associated with better control of symptoms associated with irritable bowel syndrome (IBS). This study aimed to examine the utilization of inpatient services by patients with IBS who did and did not report the use of cannabis. METHODS: This is a retrospective cohort study that utilized the 2016 Nationwide Readmissions Database. Inclusion criteria included a principal diagnosis of IBS. The primary outcome was 30-day hospital readmission rates for IBS-specific causes. Secondary outcomes included the 30-day hospital readmission rates for all causes, resource utilization, and the 5 most common principal diagnoses and independent risk factors associated with readmission. RESULTS: Of the 7163 patients with IBS identified in the National Readmission Database, 357 reported the use of cannabis. The 30-day IBS-specific readmission rates were 1.5% in patients who reported cannabis use and 1.1% in those who did not report cannabis use (P=0.53). Among the cannabis users, none of the variables evaluated served as a significant predictor of IBS-specific readmission; median income was a predictor for readmission among those who did not report cannabis use (odds ratio, 2.77; 95% confidence interval, 1.15-6.67; P=0.02). The 30-day readmission rates for all causes were 8.1% and 12.7% for patients who did and did not report cannabis use, respectively. After adjusting for confounders, the odds of 30-day readmission for all causes were lower among patients who reported cannabis use compared with those who did not (adjusted odds ratio, 0.53; 95% confidence interval, 0.28-0.99; P=0.04). The 5 most frequent diagnoses at readmission among patients who did not report cannabis use were enterocolitis because of Clostridioides difficile, IBS without diarrhea, sepsis, noninfective gastroenteritis and colitis, and acute kidney failure. By contrast, the 5 most frequent readmission diagnoses for cannabis users were cyclical vomiting, IBS with diarrhea, endometriosis, right upper quadrant abdominal pain, and nausea with vomiting. A discharge disposition of "against medical advice" was identified as an independent risk factor for 30-day hospital readmission for all causes among patients who reported cannabis use. By contrast, higher comorbidity scores and discharges with home health care were independent predictors of 30-day hospital readmission for all causes among patients who did not report cannabis use. Private insurance was an independent factor associated with lower rates of readmission for all causes among those who did not report cannabis use. CONCLUSION: Our review of the National Readmission Database revealed no statistically significant differences in 30-day readmission rates for IBS-specific causes when comparing patients who reported cannabis use with those who did not. However, the authors found that cannabis use was associated with reduced 30-day hospital readmission rates for all causes.


Asunto(s)
Cannabis , Síndrome del Colon Irritable , Cannabis/efectos adversos , Femenino , Humanos , Síndrome del Colon Irritable/epidemiología , Alta del Paciente , Readmisión del Paciente , Estudios Retrospectivos , Factores de Riesgo
20.
J Clin Gastroenterol ; 56(1): 81-87, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33405433

RESUMEN

BACKGROUND: Bariatric surgery (BS) has been proven to be effective in the treatment of obesity and weight-related diseases, but the anatomic changes after BS make endoscopic retrograde cholangiopancreatography (ERCP) technically challenging. This study aims to assess the safety and clinical outcomes of ERCP in patients with previous BS. MATERIALS AND METHODS: The National Inpatient Sample from 2007 to 2013 was queried for hospitalizations of adults over 18 years of age with procedure diagnoses of ERCP. Those with prior BS were selected as cases and those without BS as controls. Case-control matching at a ratio of 1 case to 2 controls was performed based on sex, age, race, comorbidities, and obesity. The primary outcomes were inpatient mortality and ERCP-related complications. Multivariate regression analysis was used to identify independent risk factors associated to the primary outcomes. RESULTS: A total of 1,068,862 weighted hospitalizations with ERCP procedure codes were identified. Of these, 6689 with BS were selected as cases, and 13,246 were matched as controls. The reason for hospital admission was most often biliary stone disease (60.7% vs. 55.5%), followed by malignancy (3.5% vs. 12.1%) and cholangitis (7.7% vs. 4.5%) with and without BS, P<0.05. The BS group had lower rates of post-ERCP pancreatitis (0.1% vs. 1.3%), cholecystitis (0.1% vs. 0.3%), bleeding (1.0% vs. 1.4%), and inpatient mortality (0.2% vs. 0.5%), but had higher rates of cholangitis (5.0% vs. 3.7%) and systemic infections (6.2% vs. 4.8%), all P<0.05. CONCLUSIONS: BS group had lower post-ERCP pancreatitis, cholecystitis and bleeding while had more cholangitis, and systemic infection compared with those without BS. Also, BS was independently associated with reduced inpatient mortality after adjusted for age, race, and comorbidity.


Asunto(s)
Cirugía Bariátrica , Colangitis , Adolescente , Adulto , Cirugía Bariátrica/efectos adversos , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Humanos , Pacientes Internos , Estudios Retrospectivos
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