The cost implications of Wilson disease among hospitalized patients: analysis of USA hospitals.

BACKGROUND AND AIM: In this study, we used a national cohort of patients with Wilson's disease (WD) to investigate the admissions, mortality rates, and costs over the captured period to assess specific subpopulations at higher burden. METHODS: Patients with WD were selected using 2016-2019 National Inpatient Sample (NIS). The weighted estimates and patient data were stratified using demographics and medical characteristics. Regression curves were graphed to derive goodness-of-fit for each trend from which R2 and P values were calculated. RESULTS: Annual total admissions per 100 000 hospitalizations due to WD were 1075, 1180, 1140, and 1330 ( R2  = 0.75; P  = 0.13) from 2016 to 2019. Within the demographics, there was an increase in admissions among patients greater than 65 years of age ( R2  = 0.90; P  = 0.05) and White patients ( R2  = 0.97; P  = 0.02). Assessing WD-related mortality rates, there was an increase in the mortality rate among those in the first quartile of income ( R2  = 1.00; P  < 0.001). The total cost for WD-related hospitalizations was $20.90, $27.23, $24.20, and $27.25 million US dollars for the years 2016, 2017, 2018, and 2019, respectively ( R2  = 0.47; P  = 0.32). There was an increasing total cost trend for Asian or Pacific Islander patients ( R2  = 0.90; P  = 0.05). Interestingly, patients with cirrhosis demonstrated a decreased trend in the total costs ( R2  = 0.97; P  = 0.02). CONCLUSION: Our study demonstrated that certain ethnicity groups, income classes and comorbidities had increased admissions or costs among patients admitted with WD.

The Impact of Race and Sex on the Clinical Outcomes of Homeless Patients With Alcoholic Liver Disease: Propensity Score Matched Analysis of US Hospitals.

BACKGROUND: Among patients with alcoholic liver disease (ALD), homelessness poses significant medical and psychosocial risks; however, less is known about the effects of race and sex on the hospital outcomes of admitted homeless patients with ALD. METHODS: The National Inpatient Sample database from 2012 to 2017 was used to isolate homeless patients with ALD, and the cohort was further stratified by race and sex for comparisons. Propensity score matching was utilized to minimize covariate confounding. The primary endpoints of this study include mortality, hospital length of stay, and hospital costs; secondary endpoints included the incidence of liver complications. RESULTS: There were 3972 females/males postmatch, as well as 2224 Blacks/Whites and 4575 Hispanics/Whites postmatch. In multivariate, there were no significant differences observed in mortality rate, length of stay, and costs between sexes. Comparing liver outcomes, females had a higher incidence of hepatic encephalopathy [adjusted odds ratio (aOR) 1.02, 95% CI: 1.01-1.04, P<0.001]. In comparing Blacks versus Whites, Black patients had higher hospitalization costs (aOR 1.13, 95% CI: 1.03-1.24, P=0.01); however, there were no significant differences in mortality, length of stay, or liver complications. In comparing Hispanics versus Whites, Hispanic patients had longer length of hospital stay (aOR 1.12, 95% CI: 1.06-1.19, P<0.001), greater costs (aOR 1.15, 95% CI: 1.09-1.22, P<0.001), as well as higher prevalence of liver complications including varices (aOR 1.04, 95% CI: 1.02-1.06, P<0.001), hepatic encephalopathy (aOR 1.03, 95% CI: 1.02-1.04, P<0.001), and hepatorenal syndrome (aOR 1.01, 95% CI 1.00-1.01, P=0.03). However, there was no difference in mortality between White and Hispanic patients. CONCLUSIONS: Black and Hispanic ALD patients experiencing homelessness were found to incur higher hospital charges; furthermore, Hispanic patients also had greater length of stay and higher incidence of liver-related complications compared with White counterparts.

Prevention of Chemotherapy-Induced Peripheral Neuropathy by Inhibiting C-X-C Motif Chemokine Receptor 2.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major drawback in the use of chemotherapeutic agents for patients with cancer. Although studies have investigated a broad number of molecules that might be related to CIPN, the differences in the chemokine pathways between various chemotherapeutic agents, such as vincristine and oxaliplatin, which are some of the most widely used treatments, have not been fully elucidated. We confirmed that the administration (intraperitoneal injections for seven days) of vincristine (0.1 mg/kg) and oxaliplatin (3 mg/kg) induced pain by using the von Frey behavioral test. Subsequent applications with vincristine and oxaliplatin led to mechanical allodynia that lasted more than one week from the fifth day. After the induction of mechanical allodynia, the mRNA expression of CXCR2, CXCL1, CXCL3, and CXCL5 was examined in the dorsal root ganglia (DRG) and spinal cord of the CIPN models. As a result, the mRNA expression of CXCR2 robustly increased in the lumbar spinal cord in the oxaliplatin-treated mice. Next, to evaluate the involvement of CXCR2 in CIPN, reparixin, a CXCR1/2 inhibitor, was administered intrathecally or intraperitoneally with vincristine or oxaliplatin and was further verified by treatment with ruxolitinib, which inhibits Janus kinase 2 downstream of the CXCR1/2 pathway. Reparixin and ruxolitinib blocked oxaliplatin-induced allodynia but not vincristine-induced allodynia, which suggests that CXCR2-related pathways are associated with the development of oxaliplatin-induced neuropathy. Together with the above results, this suggests that the prevention of oxaliplatin-induced neuropathy by CXCR2 inhibition can lead to successful chemotherapy, and it is important to provide appropriate countermeasures against CIPN development for each specific chemotherapeutic agent.

Clinical implications of gender and race in patients admitted with autoimmune hepatitis: updated analysis of US hospitals.

Background: Autoimmune hepatitis (AIH) can result in end-stage liver disease that requires inpatient treatment of the hepatic complications. Given this phenomenon, it is important to analyse the impact of gender and race on the outcomes of patients who are admitted with AIH using a national hospital registry. Methods: The 2012-2017 National Inpatient Sample database was used to select patients with AIH, who were stratified using gender and race (Hispanics and blacks as cases and whites as reference). Propensity score matching was employed to match the controls with cases and compare mortality, length of stay and hepatic complications. Results: After matching, there were 4609 females and 4609 males, as well as 3688 blacks and 3173 Hispanics with equal numbers of whites, respectively. In multivariate analysis, females were less likely to develop complications, with lower rates of cirrhosis, ascites, variceal bleeding, hepatorenal syndrome, encephalopathy and acute liver failure (ALF); they also exhibited lower length of stay (adjusted OR, aOR 0.96 95% CI 0.94 to 0.97). When comparing races, blacks (compared with whites) had higher rates of ALF and hepatorenal syndrome related to ALF, but had lower rates of cirrhosis-related encephalopathy; in multivariate analysis, blacks had longer length of stay (aOR 1.071, 95% CI 1.050 to 1.092). Hispanics also exhibited higher rates of hepatic complications, including ascites, varices, variceal bleeding, spontaneous bacterial peritonitis and encephalopathy. Conclusion: Males and minorities are at a greater risk of developing hepatic complications and having increased hospital costs when admitted with AIH.

The clinical implications of pre-liver transplant diabetes on post-liver transplant outcomes in patients with NASH: analysis of the UNOS database.

BACKGROUND AND AIMS: The presence of perioperative diabetes may lead to increased mortality risks following liver transplant (LT) in patients with non-alcoholic steatohepatitis (NASH). This risk factor was evaluated using a UNOS-STAR national database. METHODS: The UNOS-STAR liver transplant registry 2005-2019 was used to select patients with NASH (including cryptogenic liver disease). The following populations were excluded: those younger than 18 years old and those with living donors/dual transplants. Selected patients were stratified into those with and without pre-LT diabetes and compared to the individual mortality endpoints using iterative Cox analyses. RESULTS: 6324 recipients with and 8251 without diabetes were selected. The median follow-up time was 3.07 years. Those with diabetes were older (58.50 vs. 54.50 years, p < 0.001), were more likely to be Hispanic or Asian, and had higher BMI than the non-diabetics (31.10 vs. 29.70 kg/m2 p < 0.001); however, there was no difference in gender (female 41.9 vs. 43.1% p = 0.170). Compared to non-diabetics, recipients with diabetes had a higher rate of all-cause mortality (61.68 vs. 47.80 per 1000 person-years). In multivariate iterations, pre-LT diabetes was associated with all-cause mortality (aHR 1.19 95% CI 1.11-1.27) as well as deaths due to cardiac (p = 0.014 aHR 1.24 95% CI 1.04-1.46) and renal causes (p = 0.039 aHR 1.38 95% CI 1.02-1.87). CONCLUSION: The presence of pre-LT diabetes is associated with all-cause mortality and deaths due to cardiac and renal causes following LT. The findings warrant an early preoperative screening procedure to ensure that patients with diabetes have their metabolic risk factors optimized prior to LT.

The Clinical Impact of Advanced Age on the Postoperative Outcomes of Patients Undergoing Gastrectomy for Gastric Cancer: Analysis Across US Hospitals Between 2011-2017.

PURPOSE: This study systematically evaluated the implications of advanced age on post-surgical outcomes following gastrectomy for gastric cancer using a national database. MATERIALS AND METHODS: The 2011-2017 National Inpatient Sample was used to isolate patients who underwent gastrectomy for gastric cancer. From this, the population was stratified into those belonging to the younger age cohort (18-59 years), sexagenarians, septuagenarians, and octogenarians. The younger cohort and each advanced age category were compared in terms of the following endpoints: mortality following surgery, length of hospital stay, charges, and surgical complications. RESULTS: This study included a total of 5,213 patients: 1,366 sexagenarians, 1,490 septuagenarians, 743 octogenarians, and 1,614 under 60 years of age. Between the younger cohort and sexagenarians, there was no difference in mortality (2.27 vs. 1.67%; P=0.30; odds ratio [OR], 1.36; 95% confidence interval [CI], 0.81-2.30), length of stay (11.0 vs. 11.1 days; P=0.86), or charges ($123,557 vs. $124,425; P=0.79). Compared to the younger cohort, septuagenarians had higher rates of in-hospital mortality (4.30% vs. 1.67%; P<0.01; OR, 2.64; 95% CI, 1.67-4.16), length of stay (12.1 vs. 11.1 days; P<0.01), and charges ($139,200 vs. $124,425; P<0.01). In the multivariate analysis, septuagenarians had higher mortality (P=0.01; adjusted odds ratio [aOR], 2.01; 95% CI, 1.18-3.43). Similarly, compared to the younger cohort, octogenarians had a higher rate of mortality (7.67% vs. 1.67%; P<0.001; OR, 4.88; 95% CI, 3.06-7.79), length of stay (12.3 vs. 11.1 days; P<0.01), and charges ($131,330 vs. $124,425; P<0.01). In the multivariate analysis, octogenarians had higher mortality (P<0.001; aOR, 4.03; 95% CI, 2.28-7.11). CONCLUSIONS: Advanced age (>70 years) is an independent risk factor for postoperative death in patients with gastric cancer undergoing gastrectomy.

The clinical implication of psychiatric illnesses in patients with alcoholic liver disease: an analysis of US hospitals.

BACKGROUND: In this study, we evaluate the clinical impact of psychiatric illnesses (PI) on the hospital outcomes of patients admitted with alcoholic liver disease (ALD). METHODS: From the National Inpatient Sample from 2012-2017, patients with alcoholic cirrhosis or alcoholic hepatitis were selected and stratified using the presence/absence of PI (which was a composite of psychiatric conditions). The cases were propensity score-matched to PI-absent controls and were compared to the following endpoints: mortality, death due to suicide, length of stay (LOS), hospitalization charges, and hepatic complications. RESULTS: After matching, there were 122,907 PI with and 122,907 without PI. Those with PI were younger (51.8 vs. 51.9 years p = 0.02) and more likely to be female (39.2 vs. 38.7% p = 0.01); however, there was no difference in race. Patients with PI had lower rates of alcoholic cirrhosis but higher rates of alcoholic hepatitis/alcoholic hepatic steatosis. In multivariate, patients with PI had lower rates of all-cause mortality (aOR 0.51 95%CI 0.49-0.54); however, they experienced higher rates of deaths due to suicide (aOR 3.00 95%CI 1.56-5.78) and had longer LOS (aOR 1.02 95%CI 1.01-1.02). CONCLUSION: Presence of PI in ALD patients is associated with prolonged hospital stay and higher rates deaths due to suicide.

The clinical impact of frailty on the postoperative outcomes of patients undergoing gastrectomy for gastric cancer: a propensity-score matched database study.

BACKGROUND: Frailty aggregates a composite of geriatric and elderly features that is classified into a singular syndrome; literature thus far has proven its influence over postoperative outcomes. In this study, we evaluate the effects of frailty following gastrectomy for gastric cancer. METHODS: 2011-2017 National Inpatient Sample was used to isolate patients with gastric cancer undergoing gastrectomy; from this, the Johns Hopkins ACG frailty criteria were applied to segregate frailty-present and absent populations. The case-controls were matched using propensity-score matching and compared to various endpoints. RESULTS: Post match, there were 1171 with and without frailty who were undergoing gastrectomy for gastric cancer. Those with frailty had higher mortality (6.83 vs 3.50% p < 0.001, OR 2.02 95% CI 1.37-2.97), length of stay (16.7 vs 12.0d; p < 0.001), and costs ($191,418 vs $131,367; p < 0.001); frail patients also had higher rates of complications including wound complications (3.42 vs 0.94% p < 0.001, OR 3.73 95% CI 1.90-7.31), infection (5.98 vs 3.67% p = 0.012, OR 1.67 95% CI 1.13-2.46), and respiratory failure (6.32 vs 3.84% p = 0.0084, OR 1.69 95% CI 1.15-2.47). In multivariate, those with frailty had higher mortality (p < 0.001, aOR 2.04 95% CI 1.38-3.01), length of stay (p < 0.001, aOR 1.40 95% CI 1.37-1.43), and costs (p < 0.001, aOR 1.46 95% CI 1.46-1.46). CONCLUSION: This study finding demonstrates the presence of frailty is an independent risk factor of adverse outcomes following gastrectomy; as such, it is important that these high-risk patients are stratified preoperatively and provided risk-averting procedures to alleviate their frailty-defining features.

The Role of Prostaglandin E1 as a Pain Mediator through Facilitation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 via the EP2 Receptor in Trigeminal Ganglion Neurons of Mice.

Cyclooxygenase metabolizes dihomo-γ-linolenic acid and arachidonic acid to form prostaglandin (PG) E, including PGE1 and PGE2, respectively. Although PGE2 is well known to play an important role in the development and maintenance of hyperalgesia and allodynia, the role of PGE1 in pain is unknown. We confirm whether PGE1 induced pain using orofacial pain behavioral test in mice and determine the target molecule of PGE1 in TG neurons with whole-cell patch-clamp and immunohistochemistry. Intradermal injection of PGE1 to the whisker pads of mice induced a reduced threshold, enhancing the excitability of HCN channel-expressing trigeminal ganglion (TG) neurons. The HCN channel-generated inward current (Ih) was increased by 135.3 ± 4.8% at 100 nM of PGE1 in small- or medium-sized TG, and the action of PGE1 on Ih showed a concentration-dependent effect, with a median effective dose (ED50) of 29.3 nM. Adenylyl cyclase inhibitor (MDL12330A), 8-bromo-cAMP, and the EP2 receptor antagonist AH6809 inhibited PGE1-induced Ih. Additionally, PGE1-induced mechanical allodynia was blocked by CsCl and AH6809. PGE1 plays a role in mechanical allodynia through HCN2 channel facilitation via the EP2 receptor in nociceptive neurons, suggesting a potential therapeutic target in that PGE1 could be involved in pain as endogenous substances under inflammatory conditions.

The clinical impact of chronic liver disease in patients undergoing transcatheter and surgical aortic valve replacement: Systematic analysis of the 2011-2017 US hospital database.

OBJECTIVES: In this study, we use a national database to evaluate post-transcatheter (TAVR)/surgical aortic valve replacement (SAVR) outcomes stratified using chronic liver disease (CLD). BACKGROUND: In patients undergoing TAVR and SAVR, the surgical risks should be optimized; this includes evaluating hepatic diseases that may pose an operative risk. METHODS: 2011-2017 National Inpatient Sample was used to select in-hospital TAVR and SAVR cases, which were stratified according to CLD (cirrhosis, hepatitis B/C, alcoholic/fatty/nonspecific liver disease). The cases-controls were matched using propensity score matching and compared with various endpoints. RESULT: After matching for demographics and comorbidities, for TAVR, 606 and 1818 were with or without CLD; for SAVR, 1353 and 4059 were with and without CLD. In TAVR, there was no differences in mortality (2.81% vs. 2.75% OR 1.02 95% CI 0.58-1.78) or length of stay (6.29 vs. 6.44d p = 0.29), and CLD-present patients had marginally increased costs ($228,415 vs. $226,682 p = 0.048). There were no differences in complications. In multivariate, there was no difference in mortality (aOR 1.02 95% CI 0.58-1.79). In SAVR, CLD patients had higher mortality (7.98% vs. 3.23% OR 2.60 95% CI 2.00-3.38), length of stay (13.3 vs. 11.3 days p < 0.001), and costs ($273,487 vs. $238,097 p < 0.001). CLD patients also had increased respiratory failure (9.02% vs. 7.19% OR 1.28 95% CI 1.03-1.59) and bleeding (8.43% vs. 6.33% OR 1.36 95% CI 1.08-1.71). In multivariate, CLD had higher mortality (aOR 2.60 95% CI 2.00-3.38). CONCLUSION: CLD is associated with higher mortality and complications in patients undergoing SAVR; however, no correlation was found in patients undergoing TAVR.

The impact of compensated and decompensated cirrhosis on the postoperative outcomes of patients undergoing hernia repair: a propensity score-matched analysis of 2011-2017 US hospital database.

BACKGROUND AND AIMS: Since there is clinical overlap between populations with cirrhosis and those who require hernia repair (i.e. due to stretching of abdominal walls), we systematically evaluate the effects of cirrhosis on post-hernia repair outcomes. METHODS: 2011-2017 National Inpatient Sample was used to identify patients who underwent hernia repair (included: inguinal, umbilical, and other abdominal hernia repairs). The population was stratified into those with compensated cirrhosis (CC), decompensated cirrhosis (DC), and no cirrhosis; hepatic decompensation was defined as those with portal hypertension, ascites, and varices. The propensity score was used to match the no-cirrhosis controls to CC and DC using the 1:1 nearest neighbor mechanism. Endpoints included mortality, length of stay, costs, and complications. RESULTS: Postmatch, there were 392/446 CC/DC with equal number controls in those undergoing inguinal hernia repair, 714/1652 CC/DC with equal number controls in those undergoing umbilical hernia repair, and 784/702 CC/DC. In multivariate, for inguinal repair, there was no difference in mortality [CC vs. no-cirrhosis aOR 2.61, 95% confidence interval (CI) 0.50-13.52; DC vs. no-cirrhosis: aOR 1.75, 95% CI 0.84-3.63]. For umbilical repair, there was no difference in mortality for CC vs. no-cirrhosis: aOR 0.94, 95% CI 0.36-2.42); however, DC had higher mortality (aOR 2.86, 95% CI 1.76-4.63) when comparing DC vs. no-cirrhosis. For other abdominal repairs, there was no difference in mortality for CC vs. no-cirrhosis (aOR 1.10, 95% CI 0.54-2.23); however, DC had higher mortality (P < 0.001, aOR 2.58, 95% CI 1.49-4.46) when comparing DC vs. no-cirrhosis. CONCLUSION: This study demonstrates that the presence of DC affects postoperative survival in patients undergoing umbilical or other abdominal hernia repair surgery.

Facile Tumor Spheroids Formation in Large Quantity with Controllable Size and High Uniformity.

A facile method for generation of tumor spheroids in large quantity with controllable size and high uniformity is presented. HCT-116 cells are used as a model cell line. Individual tumor cells are sparsely seeded onto petri-dishes. After a few days of growth, separated cellular islets are formed and then detached by dispase while maintaining their sheet shape. These detached cell sheets are transferred to dispase-doped media under orbital shaking conditions. Assisted by the shear flow under shaking and inhibition of cell-to-extracellular matrix junctions by dispase, the cell sheets curl up and eventually tumor spheroids are formed. The average size of the spheroids can be controlled by tuning the cell sheet culturing period and spheroid shaking period. The uniformity can be controlled by a set of sieves which were home-made using stainless steel meshes. Since this method is based on simple petri-dish cell culturing and shaking, it is rather facile for forming tumor spheroids with no theoretical quantity limit. This method has been used to form HeLa, A431 and U87 MG tumor spheroids and application of the formed tumor spheroids in drug screening is also demonstrated. The viability, 3D structure, and necrosis of the spheroids are characterized.

The use of electronic monitoring (MEMS) to evaluate antipsychotic compliance in outpatients with schizophrenia.

Compliance with antipsychotic treatment is a well-recognized concern in the ongoing management of individuals with schizophrenia. The present investigation incorporated the Medication Event Monitoring System (MEMS) to evaluate compliance in a group of outpatients (N=52) with schizophrenia or schizoaffective disorder. Evaluating compliance as a dichotomous variable and using a threshold of 80%, the rate of noncompliance as measured by MEMS was 52%, considerably higher than self-report (3%), clinician rating (24%) and pill count (25%). The ability of treating clinicians to predict compliance/noncompliance was limited: 13 of 31 (42%) subjects they rated as compliant were noncompliant while 4 of 9 (44%) rated as noncompliant were actually compliant according to MEMS. Factors most consistently associated with noncompliance were higher total symptom scores and dosing complexity i.e., greater than once daily. Based on MEMS data, the overall mean level of compliance was 66%; however, it remains unclear as to what threshold is associated with a compromise in clinical response. More sophisticated measurement tools such as MEMS may assist us in better understanding how level and pattern of antipsychotic noncompliance, factors that at present remain poorly understood, impact on symptom exacerbation.