Delay in prior authorization of biologic therapy: Another possible cause of healthcare disparity in IBD patients.

BACKGROUND: Biologics, a mainstay in inflammatory bowel disease (IBD) treatment, typically require prior authorization from insurance companies. Multiple studies show that African Americans are less likely to be prescribed biologics. The prior authorization process may perpetuate disparities in healthcare. This study evaluated the approval time for biologics in IBD. METHODS: A chart review of IBD patients seen in a university gastroenterology clinic over 5 years was performed. Patient gender, race, IBD subtype, biologic use, and insurance type were recorded. Insurance type was classified as private or public (Medicaid or Medicare). Biologic agents evaluated included infliximab, adalimumab, vedolizumab and ustekinumab. Length of time to approval (TTA) and length of time to first infusion or administration (TFI) were recorded. Analysis was performed using t-testing, Fisher's exact testing, and ANOVA with significance set at p<0.05. The study was IRB approved. RESULTS: 458 charts were analyzed. 66 patients were being treated with a biologic. 42 had private insurance, 16 Medicaid and 8 Medicare. 37 patients had ulcerative colitis, 27 Crohn's disease, and 2 indeterminate colitis. There were 38 men and 28 women. 32 patients were white, 26 African American, 1 Asian, 5 other, and 2 declined identification. Average TTA was 30.5 days (range 1-145) and average TFI was 45.3 days (range 2-166). African Americans were more often on public insurance compared to whites (p=0.0001). Crohn's disease compared to ulcerative colitis patients were more often on public insurance (p=0.017). Significantly more private compared to public insurance patients were on infliximab (p=0.001). Medicaid and Medicare patients had significantly longer mean TTAs than private insurance patients (49.1 and 52.7 vs 19.4 days, p=0.007). African Americans had significantly longer mean TTA compared to whites (45.9 vs 24.8 days, p=0.044). Crohn's disease compared to ulcerative colitis patients had significantly longer mean TTA (39.7 vs 21.8 days, p=0.050). DISCUSSION: This study shows that prior authorization for biologic therapy was longer for African Americans. Patients on public insurance also tend to have a longer TTA, and more African Americans were on public insurance compared to White patients in this study which may explain the difference in biologic access for African Americans.

Gender, BMI, Patient Comorbidities, and Hospital Characteristics Influence 30-Day Readmission Following Vertical Sleeve Gastrectomy.

PURPOSE: Obesity impacts 300 million people worldwide and the number continues to increase. Laparoscopic sleeve gastrectomy (LSG) is one of several bariatric procedures offered to help these individuals achieve a healthier life. Here, we report 30-day readmission rates and risk factors for readmission after gastrectomy. MATERIALS AND METHODS: We used the US Healthcare Utilization Project's Nationwide Readmission Database (NRD) from 2016 to 2019 for patients who underwent laparoscopic gastrectomy and evaluated 30-day readmission rates, comparing readmitted patients to non-readmitted patients. Confounder adjusted and unadjusted analysis were proceeded to the potential factors. RESULTS: The study population consisted of 235,563 patients, with a 3.0% readmission rate. Factors associated with a higher readmission rate included older age, male gender, higher BMI, Medicare as the primary payer, longer length of stay, higher total charge, higher Charlson Comorbidity Index, higher Elixhauser-Comorbidity Index, lower household income, non-elective admission type, and non-routine disposition. Additionally, larger hospital bed size, and private, invest-own hospital ownership were associated with higher readmission rates. After adjusting for confounders, several comorbidities and complications were found to be significantly associated with readmission, including ileus, abnormal weight loss, postprocedural complications of digestive system, acute posthemorrhagic anemia, and history of pulmonary embolism (all p < 0.001). CONCLUSIONS: Patient characteristics including age, BMI, and payment source, as well as hospital characteristics, can impact the 30-day readmission after LSG. Such factors should be considered by CMS when deciding on penalties related to readmission.

The effect of preoperative endoscopic tattooing on lymph node retrieval in colorectal cancer: a systematic review and meta-analysis.

PURPOSE: The effect of preoperative endoscopic tattooing (ET) on accurate colorectal cancer localization and resection has been well established. However, its effect on lymph node (LN) retrieval remains unclear. The purpose of this study was to systematically compare LN retrieval between patients with colorectal cancer who underwent preoperative ET and those who did not. METHODS: A systematic search for relevant studies was conducted using the following databases: PubMed, Embase, and Web of Science. Studies that compared LN retrieval in patients with colorectal cancer with and without preoperative ET were included. Weighted pooled odds ratio (OR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) for all outcomes using the random-effects model were calculated. RESULTS: 10 studies, including 2231 patients with colorectal cancer were included. Six studies reported total LN yield and showed significantly higher LN yield in the tattooed group (MD:2.61; 95% CI:1.01-4.21, P=0.001). Seven studies reported the number of patients with adequate LN retrieval and showed a significantly higher number of patients with adequate LN retrieval in the tattooed group (OR:1.89, 95% CI:1.08-3.32, P=0.03). However, subgroup analysis revealed that both outcomes were only statistically significant in patients with rectal cancer, and not in patients with colon cancer. CONCLUSIONS: Our results suggest that preoperative ET is associated with increased LN retrieval in patients with rectal cancer, but not in colon cancer. Further large-scale randomized control trials are necessary to validate our findings.

Quiet & deadly: Painless aortic dissection.

Aortic dissection is a life-threatening condition that classically presents as a sudden, sharp pain with a ripping sensation. This disease is caused by a weakened area within the aortic arterial wall, which can be classified using the Stanford classifications into type A or type B dissections, depending on the location of the tear. It is described that 17.6% of patients died before arriving at the hospital, and 45.2% of patients died within 30 days of diagnosis (Melvinsdottir et al., 2016). However, 10% of patients present without pain, leading to delayed diagnosis. In this case, a 53-year-old male with prior history of hypertension, sleep apnea, and diabetes mellitus presented to the emergency department with complaints of chest pain earlier that day. However, he was asymptomatic on presentation. He had no cardiac history. He was admitted, and a subsequent workup was performed to rule out myocardial infarction. The following morning a slight bump in troponin consistent with a Non-ST Elevated Myocardial Infarction (NSTEMI) was noted. An echocardiogram was ordered and showed aortic regurgitation. This was followed by computed tomography angiography (CTA), which revealed acute type A ascending aortic dissection. He was transferred to our facility and underwent an emergent Bentall procedure. Ultimately, the patient tolerated the surgery well and is recovering. This case is essential because it emphasizes the painless presentation of type A aortic dissection. Mis- or undiagnosed, this condition often leads to death.

Autophagy in Virus Infection: A Race between Host Immune Response and Viral Antagonism.

Virus-infected cells trigger a robust innate immune response and facilitate virus replication. Here, we review the role of autophagy in virus infection, focusing on both pro-viral and anti-viral host responses using a select group of viruses. Autophagy is a cellular degradation pathway operated at the basal level to maintain homeostasis and is induced by external stimuli for specific functions. The degradative function of autophagy is considered a cellular anti-viral immune response. However, autophagy is a double-edged sword in viral infection; viruses often benefit from it, and the infected cells can also use it to inhibit viral replication. In addition to viral regulation, autophagy pathway proteins also function in autophagy-independent manners to regulate immune responses. Since viruses have co-evolved with hosts, they have developed ways to evade the anti-viral autophagic responses of the cells. Some of these mechanisms are also covered in our review. Lastly, we conclude with the thought that autophagy can be targeted for therapeutic interventions against viral diseases.

Autophagic degradation of IRF3 induced by the small-molecule auranofin inhibits its transcriptional and proapoptotic activities.

The ubiquitously expressed transcription factor interferon (IFN) regulatory factor 3 (IRF3) is critical for the induction of antiviral genes, e.g., type-I IFN. In addition to its transcriptional function, IRF3 also activates a nontranscriptional, proapoptotic signaling pathway. While the proapoptotic function of IRF3 protects against viral infections, it is also involved in harmful immune responses that trigger hepatocyte cell death and promote liver disease. Thus, we hypothesized that a small-molecule inhibitor of the proapoptotic activity of IRF3 could alleviate fatty-acid-induced hepatocyte cell death. We conducted a high-throughput screen, which identified auranofin as a small-molecule inhibitor of the proapoptotic activity of IRF3. In addition to the nontranscriptional apoptotic pathway, auranofin also inhibited the transcriptional activity of IRF3. Using biochemical and genetic tools in human and mouse cells, we uncovered a novel mechanism of action for auranofin, in which it induces cellular autophagy to degrade IRF3 protein, thereby suppressing IRF3 functions. Autophagy-deficient cells were unable to degrade IRF3 upon auranofin treatment, suggesting that the autophagic degradation of IRF3 is a novel approach to regulate IRF3 activities. Using a physiologically relevant in vitro model, we demonstrated that auranofin inhibited fatty-acid-induced apoptotic cell death of hepatocytes. In summary, auranofin is a novel inhibitor of IRF3 functions and may represent a potential therapeutic option in diseases where IRF3 is deleterious.

Cyclosporine-Induced Kaposi Sarcoma in a Patient With Ulcerative Colitis.

Kaposi sarcoma (KS) is an angioproliferative neoplasm associated with human herpesvirus-8. Gastrointestinal KS has been well documented in immunosuppressed solid organ transplant patients, with only 26 iatrogenic cases published in patients with inflammatory bowel disease. We report a 24-year-old patient with ulcerative colitis, maintained on cyclosporine for 2 years, who presented with watery, nonbloody diarrhea and weight loss. Colonoscopy revealed human herpesvirus-8-positive hemorrhagic nodules throughout the colon and terminal ileum, with diffuse lymphadenopathy on computed tomography consistent with KS. As gastrointestinal KS may present with symptoms that mimic inflammatory bowel disease, it is critical to maintain suspicion in patients on prolonged immunosuppression to reduce complications.

Association of Patients' Perception of Quality of Healthcare Received and Colorectal Cancer Screening Uptake: An Analysis of 2 National Surveys in the USA.

OBJECTIVE: It is not known whether patients' ratings of the quality of healthcare services they receive truly correlate with the quality of care from their providers. Understanding this association can potentiate improvement in healthcare delivery. We evaluated the association between patients' ratings of the quality of healthcare services received and uptake of colorectal cancer (CRC) screening. SUBJECTS AND METHODS: We used 2 iterations of the Health Information National Trends Survey (HINTS) of adults in the USA. HINTS 2007 (4,007 respondents; weighted population = 75,397,128) evaluated whether respondents were up to date with CRC screening while HINTS 4 cycle 3 (1,562 respondents; weighted population = 76,628,000) evaluated whether participants had ever received CRC screening in the past. All included respondents from both surveys were at least 50 years of age, had no history of CRC, and had rated the quality of healthcare services that they had received at their healthcare provider's office in the previous 12 months. RESULTS: HINTS 2007 data showed that respondents who rated their healthcare as good or fair/poor were significantly less likely to be up to date with CRC screening compared to those who rated their healthcare as excellent. We found comparable results from analysis of HINTS 4 cycle 3 data with poorer uptake of CRC screening as the healthcare quality ratings of respondents reduced. CONCLUSION: Our study suggests that patients who reported receiving lower quality of healthcare services were less likely to have undergone and be compliant with CRC screening recommendations. It is important to pay close attention to patient feedback surveys in order to improve healthcare delivery.

High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication.

Interferon (IFN) regulatory factor 3 (IRF3) is the key transcription factor for the induction of IFN and antiviral genes. The absence of antiviral genes in IRF3 deficiency leads to susceptibility to a wide range of viral infections. Previously, we uncovered a function for nontranscriptional IRF3 (nt-IRF3), RLR (RIG-I-like receptor)-induced IRF3-mediated pathway of apoptosis (RIPA), which triggers apoptotic killing of virus-infected cells. Using knock-in mice expressing a transcriptionally inactive, but RIPA-active, IRF3 mutant, we demonstrated the relative contribution of RIPA to host antiviral defense. Given that RIPA is a cellular antiviral pathway, we hypothesized that small molecules that promote RIPA in virus-infected cells would act as antiviral agents. To test this, we conducted a high throughput screen of a library of FDA-approved drugs to identify novel RIPA activators. Our screen identified doxorubicin as a potent RIPA-activating agent. In support of our hypothesis, doxorubicin inhibited the replication of vesicular stomatitis virus, a model rhabdovirus, and its antiviral activity depended on its ability to activate IRF3 in RIPA. Surprisingly, doxorubicin inhibited the transcriptional activity of IRF3. The antiviral activity of doxorubicin was expanded to flavivirus and herpesvirus that also activate IRF3. Mechanistically, doxorubicin promoted RIPA by activating the extracellular signal-regulated kinase (ERK) signaling pathway. Finally, we validated these results using another RIPA-activating compound, pyrvinium pamoate, which showed a similar antiviral effect without affecting the transcriptional activity of IRF3. Therefore, we demonstrate that the RIPA branch of IRF3 can be targeted therapeutically to prevent virus infection.

Gene Therapy Leaves a Vicious Cycle.

The human genetic code encrypted in thousands of genes holds the secret for synthesis of proteins that drive all biological processes necessary for normal life and death. Though the genetic ciphering remains unchanged through generations, some genes get disrupted, deleted and or mutated, manifesting diseases, and or disorders. Current treatment options-chemotherapy, protein therapy, radiotherapy, and surgery available for no more than 500 diseases-neither cure nor prevent genetic errors but often cause many side effects. However, gene therapy, colloquially called "living drug," provides a one-time treatment option by rewriting or fixing errors in the natural genetic ciphering. Since gene therapy is predominantly a viral vector-based medicine, it has met with a fair bit of skepticism from both the science fraternity and patients. Now, thanks to advancements in gene editing and recombinant viral vector development, the interest of clinicians and pharmaceutical industries has been rekindled. With the advent of more than 12 different gene therapy drugs for curing cancer, blindness, immune, and neuronal disorders, this emerging experimental medicine has yet again come in the limelight. The present review article delves into the popular viral vectors used in gene therapy, advances, challenges, and perspectives.

Morbid obesity is an independent risk factor for postoperative renal dysfunction in young adults: a review of the American College of Surgeons National Surgical Quality Improvement Program database.

BACKGROUND: Little information exists on the acute effects of elective surgery on renal function. Our aim was to determine if obesity was an independent risk factor for postoperative renal complications (RCs). METHODS: A total of 119,142 patients aged 18 to 35 years with body mass index (BMI) ≥18 kg/m(2) obtained from American College of Surgeons National Surgical Quality Improvement Project (2005 to 2010) were classified into standard BMI categories. Association between BMI and preoperative estimated glomerular filtration rate (eGFR; calculated using modification of diet in renal disease formula) was analyzed. Postoperative changes in eGFR and RCs were measured. Multivariate regression analysis was performed adjusting for all variables. RESULTS: Postoperatively, there was a reduction in eGFR among the overweight (-3.4 mL/min/1.73 m(2), P < .001), obese class I (-3.9 mL/min/1.73 m(2), P = .001), and obese class II (-5.3 mL/min/1.73 m(2), P < .001). The odds of any postoperative RC was significantly higher in obese class III patients (odds ratio = 2.01 95% confidence interval 1.07 to 3.76, P = .029). CONCLUSIONS: Results seen in patients with BMI greater than 40 indicate that BMI can serve as an independent predictor of RCs.

Alcohol and Apoptosis: Friends or Foes?

Alcohol abuse causes 79,000 deaths stemming from severe organ damage in the United States every year. Clinical manifestations of long-term alcohol abuse on the cardiac muscle include defective contractility with the development of dilated cardiomyopathy and low-output heart failure; which has poor prognosis with less than 25% survival for more than three years. In contrast, low alcohol consumption has been associated with reduced risk of cardiovascular disease, however the mechanism of this phenomenon remains elusive. The aim of this study was to determine the significance of apoptosis as a mediating factor in cardiac function following chronic high alcohol versus low alcohol exposure. Adult rats were provided 5 mM (low alcohol), 100 mM (high alcohol) or pair-fed non-alcohol controls for 4-5 months. The hearts were dissected, sectioned and stained with cresyl violet or immunohistochemically for caspase-3, a putative marker for apoptosis. Cardiomyocytes were isolated to determine the effects of alcohol exposure on cell contraction and relaxation. High alcohol animals displayed a marked thinning of the left ventricular wall combined with elevated caspase-3 activity and decreased contractility. In contrast, low alcohol was associated with increased contractility and decreased apoptosis suggesting an overall protective mechanism induced by low levels of alcohol exposure.

Upcoming biomarkers for the diagnosis of Kawasaki disease: A review.

Kawasaki disease (KD) is a major cause of acquired heart disease among children and increases the risk of myocardial infarction. While the biochemical basis of the disease is unclear, the evidence suggests interplay between a microbial infection and a genetic predisposition in the development of the disease. Diagnosis of KD based on clinical observation is not completely reliable and is problematic due to the time-sensitive nature of the disease. Hence, identification of inflammatory, proteomic, and genetic biomarkers may assist in earlier and more effective diagnosis and treatment. This review of observational studies and clinical trials analyzes biomarkers in recent research that may be used to establish a gold standard test for KD diagnosis. 65 articles in the literature are assessed to investigate these new biomarkers in addition to biomarkers presently in use. ESR≥40mm/h, leukocyte count ≥16∗10(9)/L and increased WBC count are together suggestive of the presence of KD. Among proteomic biomarkers, elevated NT-proBNP and differing levels of several other proteomic biomarkers such as iNOS in monocytes and neutrophils have been observed in KD patients. Genetic polymorphisms of six HLA class I genes have also been linked with the disease, alongside MICA alleles A4 and A5.1. The results suggest that NT-proBNP is currently a very promising biomarker for future investigation; further research is warranted to allow for accurate and early detection of the disease using this biomarker.