Work Productivity Impairment in Persons with Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: The impact of inflammatory bowel disease (IBD) on work productivity remains unclear. In this systematic review and meta-analysis, we quantify work-related outcomes and employment data among persons with IBD. METHODS: A systematic literature search was conducted in MEDLINE, EMBASE, the Cochrane library, Scopus, ProQuest, and clinicaltrials.gov from inception to February 2023 to identify studies on work productivity in persons with IBD aged >18 years. Work productivity was defined primarily by the Work Productivity and Activity Impairment (WPAI) questionnaire which includes absenteeism, presenteeism, overall work impairment, and non-work activity impairment. In addition, we included data on employment, sick leaves, disability pensions, and indirect costs due to productivity loss. Pooled effect analysis was conducted using a random-effects model for pooled estimates of continuous and proportional data with 95% confidence intervals. RESULTS: Among all patients with IBD, the pooled estimates were 16.4% for absenteeism, 35.9% for presenteeism, 39.4% for overall work impairment, and 46.0% for non-work activity impairment. Indirect costs from overall work impairment were 5,131.09 euros/patient/year. Only two thirds of IBD patients were employed and 1 in 3 patients lost their jobs due to IBD. Among those employed, 39.5% report sick days, 21.3% report work disability, and 12.3% receive disability pensions. Most studies demonstrate clinically meaningful improvements in work productivity with medical and/or surgical therapies. CONCLUSION: Persons with IBD experience significant work impairment and associated indirect costs. This highlights the need for appropriate workplace accommodations and timely medical therapy to alleviate the burden of disease and improve work outcomes.

Perceptions and Prevalence of Cannabis Use in Women With Inflammatory Bowel Disease of Reproductive Age: A Cross-Sectional Study.

Background: Many patients with inflammatory bowel disease (IBD) may use cannabis for relief of symptoms. During pregnancy, however, cannabis exposure may be associated with adverse pregnancy outcomes. We aimed to determine the prevalence and perceptions of cannabis use in women with IBD. Methods: Through recruitment at Mount Sinai Hospital and online platforms such as Twitter, women with IBD (age 18-45) were asked to complete anonymous surveys on demographics, cannabis use, perception of use during pregnancy, and discussing its use with healthcare providers (HCP). Categorical variables were reported as frequencies and compared across groups with the chi-square test. Results: One-hundred and two pregnant patients with IBD were included in this study, 19 (18.6%) reported using cannabis. Current users were more likely to report constant pain in the last 12 months and discuss its use with their HCP. Fifty-three (52.0%) women were unsure of the specific risks associated with cannabis use during pregnancy, and only 15 (14.7%) had ever discussed its use with their HCP. Those who had discussed cannabis use with their HCP were more likely to have prior IBD-related surgery, perceive its use unsafe during pregnancy, and be more likely to be using cannabis. Conclusion: Many women with IBD report uncertainty of the risks of cannabis use during pregnancy and the majority have never discussed cannabis use with their providers. With the increasing legalization of cannabis in many jurisdictions, it is imperative patients and healthcare providers discuss the risks and benefits of its use, particularly during vulnerable times such as pregnancy.

Perigastric Hematoma Masquerading as a Gastric Tumor.

Perigastric and intramural gastric hematomas rarely occur, with most cases associated with trauma, coagulopathy, and peptic ulcer disease. Furthermore, hematomas in the upper gastrointestinal tract are commonly located in the esophagus and duodenum. In this case report, we describe a hematoma masquerading as a gastric tumor on esophagogastroduodenoscopy (EGD) in a 54-year-old male presenting with melena. Initial computed tomography (CT) imaging suggested gastrointestinal stromal tumor (GIST) as the probable cause. We performed endoscopic ultrasound (EUS) with findings consistent with a perigastric hematoma, which aligned with the patient's diagnosis of splenic vein thrombosis (SVT) and numerous collateral vessels communicating with the hematoma. Interventional radiology (IR) was consulted for further management, although we ultimately chose a conservative approach.

Acute Sepsis-Induced Cholestatic Disease Presenting With Isolated Hyper-Bilirubinemia.

Sepsis-induced cholestatic disease occurs in a fair amount of critically-ill patients. Although the mechanism is poorly understood, hypoperfusion to the liver is one of the most common mechanisms that lead to liver dysfunction and subsequently biliary disease. Hepatic conditions such as cirrhosis and hepatitis A may have an impact on how sepsis-induced cholestatic disease can present. Understanding the presentation of sepsis-induced cholestasis and addressing the underlying cause of sepsis can certainly lead to better outcomes without the need for procedure intervention. We explore a patient with acute sepsis-induced cholestatic disease who had recently-resolving hepatitis A infection and underlying cirrhosis.

GABA receptor inhibition and severe hypoxia induce a paroxysmal depolarization shift in goldfish neurons.

Mammalian neurons undergo rapid excitotoxic cell death when deprived of oxygen; however, the common goldfish (Carassius auratus) has the unique ability of surviving in oxygen-free waters, under anoxia. This organism utilizes γ-amino butyric acid (GABA) signaling to suppress excitatory glutamatergic activity during anoxic periods. Although GABAA receptor antagonists are not deleterious to the cellular survival, coinhibition of GABAA and GABAB receptors is detrimental by abolishing anoxia-induced neuroprotective mechanisms. Here we show that blocking the anoxic GABAergic neurotransmission induces seizure-like activity (SLA) analogous to a paroxysmal depolarization shift (PDS), with hyperpolarization of action potential (AP) threshold and elevation of threshold currents. The observed PDS was attributed to an increase in excitatory postsynaptic currents (EPSCs) that are normally attenuated with decreasing oxygen levels. Furthermore, for the first time, we show that in addition to PDS, some neurons undergo depolarization block and do not generate AP despite a suprathreshold membrane potential. In conclusion, our results indicate that with severe hypoxia and absence of GABA receptor activity, telencephalic neurons of C. auratus manifest a paroxysmal depolarization shift, a key feature of epileptic discharge.NEW & NOTEWORTHY This work shows that the combination of anoxia and inhibition of GABA receptors induces seizure-like activities in goldfish telencephalic pyramidal and stellate neurons. Importantly, to prevent seizure-like activity, an intact GABA-mediated inhibitory pathway is required.

Beneficial Effects of Amnion-Chorion Stem Cell Grafting in the Long Term Management of Nonuremic Calciphylaxis Wounds.

Calciphylaxis is a poorly understood disease with high morbidity and mortality. The current primary literature on treatment is lacking; however, disease management often involves a multifaceted approach with a primary focus on consistent wound care. This report describes a case outlining the long-term management of nonuremic calciphylaxis wounds in a patient with severe malnutrition with the use of human amniotic membrane grafts, aggressive surgical debridement, nutritional therapy, and advanced wound healing techniques. A 38-year-old African American female with a history of non-uremic calciphylaxis presented from a transitional facility with numerous non-healing wounds in the setting of severe malnutrition secondary to bariatric surgery. Biweekly wound debridement was initiated utilizing an amniotic stem cell skin graft, dry applicable absorbent dressing, high-frequency ultrasonic ablation, and wound vacuum-assisted closure (VAC) over the course of approximately nine months. Nutritional supplementation was given in the form of jejunostomy tube feed due to a gastric bypass and a perforated viscus. At the current date, the patient demonstrates significant improvement in pain and wound healing. The patient is also able to ambulate with care and has begun steps towards independent management of wounds. Future goals of care include independent bedside wound management, placement of allograft, and discharge to a long-term care facility. Most patients with refractory pain, widespread necrotic wounds, and dangerous comorbidities will inevitably be referred to palliative care. This case creates a framework for the long term management of medically complex patients with nonuremic calciphylaxis using human amniotic membrane stem cell grafts and appropriate advanced wound care techniques.

Taurine activates glycine and GABAA receptor currents in anoxia-tolerant painted turtle pyramidal neurons.

Unlike anoxia-intolerant mammals, painted turtles can survive extended periods without oxygen. This is partly accomplished by an anoxia-mediated increase in gamma-aminobutyric acid (GABA) release, which activates GABA receptors and mediates spike arrest in turtle neurons via shunting inhibition. Extracellular taurine levels also increase during anoxia; why this occurs is unknown but it is speculated that glycine and/or GABAA/B receptors are involved. Given the general importance of inhibitory neurotransmission in the anoxia-tolerant painted turtle brain, we investigated the function of taurine as an inhibitory neuromodulator in turtle pyramidal neurons. Using whole-cell patch-clamp electrophysiological methods to record from neurons within a cortical brain sheet, we found that taurine depolarized membrane potential by ∼8 mV, increased whole-cell conductance ∼2-fold, and induced an inward current that possessed characteristics similar to GABA- and glycine-evoked currents. These effects were mitigated following glycine receptor antagonism with strychnine and GABAA receptor antagonism with gabazine, bicuculine or picrotoxin, but were unchanged following GABAB or glutamatergic receptor inhibition. These data indicate that a high concentration of taurine in vitro mediates its effects through both glycine and GABAA receptors, and suggests that taurine, in addition to GABA, inhibits neuronal activity during anoxia in the turtle cortex.

Stellate and pyramidal neurons in goldfish telencephalon respond differently to anoxia and GABA receptor inhibition.

With oxygen deprivation, the mammalian brain undergoes hyper-activity and neuronal death while this does not occur in the anoxia-tolerant goldfish (Carassius auratus). Anoxic survival of the goldfish may rely on neuromodulatory mechanisms to suppress neuronal hyper-excitability. As γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, we decided to investigate its potential role in suppressing the electrical activity of goldfish telencephalic neurons. Utilizing whole-cell patch-clamp recording, we recorded the electrical activities of both excitatory (pyramidal) and inhibitory (stellate) neurons. With anoxia, membrane potential (Vm) depolarized in both cell types from -72.2 mV to -57.7 mV and from -64.5 mV to -46.8 mV in pyramidal and stellate neurons, respectively. While pyramidal cells remained mostly quiescent, action potential frequency (APf) of the stellate neurons increased 68-fold. Furthermore, the GABAA receptor reversal potential (E-GABA) was determined using the gramicidin perforated-patch-clamp method and found to be depolarizing in pyramidal (-53.8 mV) and stellate neurons (-42.1 mV). Although GABA was depolarizing, pyramidal neurons remained quiescent as EGABA was below the action potential threshold (-36 mV pyramidal and -38 mV stellate neurons). Inhibition of GABAA receptors with gabazine reversed the anoxia-mediated response. While GABAB receptor inhibition alone did not affect the anoxic response, co-antagonism of GABAA and GABAB receptors (gabazine and CGP-55848) led to the generation of seizure-like activities in both neuron types. We conclude that with anoxia, Vm depolarizes towards EGABA which increases APf in stellate neurons and decreases APf in pyramidal neurons, and that GABA plays an important role in the anoxia tolerance of goldfish brain.