Personal comorbidities and their subsequent risks for liver,gallbladder and bile duct cancers

Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously diagnosed comorbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The 13 comorbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the considered comorbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers.     

Quantitative Monitoring of Cocrystal Polymorphisms in Model Tablets Using Transmission Low-Frequency Raman Spectroscopy

Cocrystallization is a technique for improving the physical properties of active pharmaceutical ingredients. However, cocrystals can transform into more stable polymorphs as well as dissociate to original materials. Therefore, an analytical technique is required to determine the polymorphic transformation quickly and accurately in tablets. The purpose of this study is to develop a method to monitor cocrystal polymorphs in model tablets using transmission low-frequency Raman spectroscopy. The tablets, consisting of only metastable polymorphs of caffeine-glutaric acid cocrystals, were stored under various relative humidity levels. The composition of the cocrystal polymorphs were calculated from a calibration curve relating the actual composition to the predicted values calculated by partial least squares regression processing of low-frequency Raman spectra. The metastable form gradually converted to a stable form, and polymorphic phase transformation occurred with increasing relative humidity. Ninety-six percent of the metastable form converted into a stable form stored at 25 °C after 3 h at 95% RH. In conclusion, transmission low-frequency Raman spectroscopy can be used to quantitatively monitor cocrystal polymorphs. This technique is one of the candidate techniques to quantifiably evaluate the physico-chemical stability of cocrystal polymorphs in tablets.     

Design and in vitro/in vivo Evaluation of Polyelectrolyte Complex Nanoparticles Filled in Enteric-Coated Capsules for Oral Delivery of Insulin

Insulin is one of the most important drugs in the treatment of diabetes. There is an increasing interest in the oral administration of insulin as it mimics the physiological pathway and potentially reduces the side effects associated with subcutaneous injection. Therefore, insulin-loaded polyelectrolyte complex (PEC) nanoparticles were prepared by the ionic cross-linking method using protamine sulfate as the polycationic and sodium alginate as the anionic polymer. Taguchi experimental design was used for the optimization of nanoparticles by varying the concentration of sodium alginate, the mass ratio of sodium alginate to protamine, and the amount of insulin. The optimized nanoparticle formulation was used for further in vitro characterization. Then, insulin-loaded PEC nanoparticles were placed in hard gelatin capsules and the capsules were enteric-coated by Eudragit L100-55 (PEC-eCAPs). Hypoglycemic effects PEC-eCAPs were determined in vivo by oral administration to diabetic rats. Furthermore, in vivo distribution of PEC nanoparticles was evaluated by fluorescein isothiocyanate (FITC) labelled nanoparticles. The experimental design led to nanoparticles with a size of 194.4 nm and a polydispersity index (PDI) of 0.31. The encapsulation efficiency (EE) was calculated as 95.96%. In vivo studies showed that PEC-eCAPs significantly reduced the blood glucose level of rats at the 8^th hour compared to oral insulin solution. It was concluded that PEC nanoparticles loaded into enteric-coated hard gelatin capsules provide a promising delivery system for the oral administration of insulin.     

Health literacy and ophthalmology: A scoping review

As of 2020, it is estimated that 43.3 million people are blind, and an additional 553 million have mild to severe vision impairment.⁵⁰ At least 1 billion worldwide have a vision impairment that could have been prevented or has yet to be addressed.⁵⁴ Poor health literacy may be a significant contributor to the prevalence of eye disease. With implications on disease burden, progression, and health outcomes, a greater understanding of the role health literacy plays in ophthalmology is needed. This is the first scoping review to assess the impact of health literacy on eye health outcomes and blindness, including ocular screening rates and/or follow-up rates, treatment adherence, and self-care practices. PubMed, Embase, and CINAHL databases were searched systematically through November 12, 2021, and we evaluated the association between health literacy and ophthalmic outcomes in 4 domains: clinical outcomes, treatment adherence rates, screening and/or follow-up rates, and self-care practices. There is evidence to suggest that health literacy is associated with ophthalmic outcomes in all these domains. To better understand how health literacy impacts eye health, further longitudinal studies examining the effect of health literacy (using standardized health literacy measures) on ophthalmic outcomes are needed. We believe a specific ophthalmic health literacy survey could help achieve this goal and help target interventions to ultimately improve outcomes among ophthalmology patients.     

Perioperative allogenic blood transfusions are associated with increased fracture related infection rates,but not nonunion in operatively treated distal femur fractures

IntroductionDistal femur fractures are common injuries that remain difficult for orthopedic surgeons to treat. High complication rates, including nonunion rates as high as 24% and infection rates of 8%, can lead to increased morbidity for these patients. Allogenic blood transfusions have previously been identified as risk factors for infection in total joint arthroplasty and spinal fusion surgeries. No studies have explored the relationship between blood transfusions and fracture related infection (FRI) or nonunion in distal femur fractures.Methods418 patients with operatively treated distal femur fractures at two level I trauma centers were retrospectively reviewed. Patient demographics were collected including age, gender, BMI, medical comorbidities, and smoking. Injury and treatment information was also collected including open fracture, polytrauma status, implant, perioperative transfusions, FRI, and nonunion. Patients with less than three months of follow up were excluded.Results366 patients were included in final analysis. One hundred thirty-nine (38%) patients received a perioperative blood transfusion. Forty-seven (13%) nonunions and 30 (8%) FRI were identified. Allogenic blood transfusion was not associated with nonunion (13% vs 12%, P = 0.87), but was associated with FRI (15% vs 4%, P<0.001). Binary logistic regression analysis identified a dose dependent relationship between number of perioperative blood transfusions and FRI: total transfusion ≥2 U PRBC RR= 3.47(1.29, 8.10, P = 0.02), ≥3 RR= 6.99 (3.01, 12.40, P<0.001), and ≥4 RR= 8.94 (4.03, 14.42, P<0.001).DiscussionIn patients undergoing operative treatment of distal femur fractures, perioperative blood transfusions are associated with increased risk of fracture related infection, but not the development of a nonunion. This risk association increases in a dose-dependent relationship with increasing total blood transfusions received.