Chitosan-polygalacturonic acid complex dressing improves diabetic wound healing and hair growth in diabetic mice.

Chronic skin wounds decrease the quality of life of millions of diabetic patients worldwide. Chitosan has previously been shown to possess hemostatic properties, decrease inflammation, promote fibroblast proliferation, and hair growth. We developed a relatively low-cost polyelectrolyte complex (PEC) film dressing made of chitosan and polygalacturonic acid and tested it for its ability to accelerate diabetic wound healing. Genetically diabetic male mice were shaved on the dorsum, and one day later a 1 cm diameter full-thickness excisional wound was created. The PEC film was applied immediately after wounding and left in place for 14 days. Controls consisted of wounds treated with a fibrin gel. Wounds covered with the PEC film had closed completely by post-wounding day 42, while untreated wounds were only half-way closed. Histological analysis of wounds confirmed that PEC-treated wounds had fully re-epithelialized, while control wounds lacked a continuous epidermis at the wound center. We also observed that the area of skin under the PEC film experienced much more rapid hair growth. Histologically, there were significantly more hair follicles around the scar area (p < 0.05) in the PEC-treated group as compared to the control group. Thus, chitosan-polygalacturonic acid PEC films can accelerate both wound healing and hair growth in diabetic mice, and should be further investigated as a potential future treatment for diabetic chronic wounds.

National evaluation of harm associated with patient safety incident reports related to the provision of parenteral nutrition to patients, using a national incident reporting system.

BACKGROUND: Parenteral nutrition (PN)-related patient safety incidents have been associated with harm. Large-scale studies are scarce, and little is known about contributory factors. This study evaluated PN-related incident reports that described harm using a national database. MATERIALS AND METHODS: A retrospective evaluation of incident reports involving PN in England and Wales reported to the National Reporting and Learning System between 2015 and 2020. We described frequency by degree of reported harm and incident characteristics. Content analysis was undertaken to understand contributory factors for reports related to moderate/severe harm or death. RESULTS: 12,907 incident reports were identified. After screening, 2242 were evaluated; 1879 (83.8%) reported no harm, 309 (13.8%) low harm, 47 (0.02%) moderate harm, 4 (0.002%) severe harm, 3 (0.001%) deaths. The most reported age group, medication process, and error category were neonates (<28 days) (n = 570/1923, 29.6%), administration (n = 1126/2242, 50%), and omitted medication/ingredient (n = 291/2242, 13%), respectively. Content analysis of reports related to moderate/severe harm and death revealed patient age of <1 year, dependence on home PN (HPN), comorbidities, and staff errors as contributory factors. CONCLUSIONS: This is the first evaluation of PN-related incident reports in England and Wales to our knowledge. We demonstrated a low frequency of reports related to moderate or severe harm or death. More incidents were reported for neonates and during the administration processes. To reduce harm, systems/procedures that reduce errors in high-risk patients (eg, neonates, patients receiving HPN) need to be established within organizations. Database limitations of voluntary reporting systems were recognized.

Immunomodulatory Therapy in Head and Neck Squamous Cell Carcinoma: Recent Advances and Clinical Prospects.

The immune system plays a significant role in the development, invasion, progression, and metastasis of head and neck cancer. Over the last decade, the emergence of immunotherapy has irreversibly altered the paradigm of cancer treatment. The current treatment modalities for head and neck squamous cell carcinoma (HNSCC) include surgery, radiotherapy, and adjuvant or neoadjuvant chemotherapy which has failed to provide satisfactory clinical outcomes. To encounter this, there is a need for a novel or targeted therapy such as immunological targets along with conventional treatment strategy for optimal therapeutic outcomes. The immune system can contribute to promoting metastasis, angiogenesis, and growth by exploiting the tumor's influence on the microenvironment. Immunological targets have been found effective in recent clinical studies and have shown promising results. This review outlines the important immunological targets and the medications acting on them that have already been explored, are currently under clinical trials and are further being targeted.

A review of efficacy and safety of cetuximab and bevacizumab-based monoclonal antibodies in head and neck cancer.

A combination of monoclonal antibodies prescribed along with the conventional standard of care has a potential to provide significant improvement in patients suffering from head and neck cancer. This combination has also shown a significant decrease in toxicities and improved overall quality of life. Cetuximab acts by inhibiting the human epidermal growth factors as its overexpression in head and neck tumours that are responsible for treatment failure, resistance, and metastasis. Whereas, bevacizumab acts by inhibiting the vascular endothelial growth factor since its overexpression leads to induction of tumour angiogenesis. Current research has not shown any remarkable beneficial effect in disease outcomes. Thus, the addition of these monoclonal antibodies to the standard regimen for head and neck cancer can be considered a prospect that might be beneficial. Cetuximab has already been included as an option under special recommendations in recurrent/metastatic head and neck cancer by NCCN in a platinum-based regimen as well as in combination with radiation therapy. This review outlines the applicability of cetuximab and bevacizumab in the treatment of head and neck cancer as well as the clinical trials performed that give an idea about the efficacy and safety of these monoclonal antibodies. Based upon the literature reviewed, it can be deduced that immunotherapy is to be adopted and different targets are to be explored in it in order to combat head and neck cancer. Currently, immunotherapeutic drugs of two major targets have been discussed. These agents are even effective in combination with other therapeutic modalities that are not being able to achieve desirable outcomes due to issues such as resistance and toxicities. Thus, newer targets as well as newer agents acting on established targets are to be explored in order to improve disease outcomes.

Epigenetics in Tuberculosis: Immunomodulation of Host Immune Response.

Tuberculosis is a stern, difficult to treat chronic infection caused by acid-fast bacilli that tend to take a long time to be eradicated from the host's environment. It requires the action of both innate and adaptive immune systems by the host. There are various pattern recognition receptors present on immune cells, which recognize foreign pathogens or its product and trigger the immune response. The epigenetic modification plays a crucial role in triggering the susceptibility of the host towards the pathogen and activating the host's immune system against the invading pathogen. It alters the gene expression modifying the genetic material of the host's cell. Epigenetic modification such as histone acetylation, alteration in non-coding RNA, DNA methylation and alteration in miRNA has been studied for their influence on the pathophysiology of tuberculosis to control the spread of infection. Despite several studies being conducted, many gaps still exist. Herein, we discuss the immunopathophysiological mechanism of tuberculosis, the essentials of epigenetics and the recent encroachment of epigenetics in the field of tuberculosis and its influence on the outcome and pathophysiology of the infection.

Patient Safety Incidents Related to the Use of Parenteral Nutrition in All Patient Groups: A Systematic Scoping Review.

INTRODUCTION: There is limited comprehensive literature focussing on the range of patient safety incidents related to parenteral nutrition (PN). OBJECTIVE: The aim of this review was to examine patient safety incidents related to the use of PN in all patient age groups. METHODS: Literature published in the English language between January 2000 and April 2020 were searched across the MEDLINE, CINHAL and Embase databases. Articles were included if they contained PN-related patient safety incidents related to an avoidable event. No restrictions were applied to patient populations. The screening process was undertaken independently by two authors. RESULTS: In total, 108 records were included in the review: 52 case studies, 54 observation studies (e.g. prevalence studies, surveys) and two experimental studies. All age groups were represented, with 62% of studies in paediatrics (of which two-thirds were neonates) and 23% in adults. They included all medication processes: prescribing, dispensing, compounding, administration and monitoring. Incidents were related to microbial contamination, venous access and specific components (e.g. lipid emulsion, amino acids, glucose, micronutrients and electrolytes) or the whole product. Incident outcomes ranging from near miss to death were reported. Intervention studies looked at the impact on patient safety incidents of computerised tools, healthcare processes, e.g. pharmacist screening, and standardisation. One study demonstrated more severe outcomes with paediatric than with adult PN. CONCLUSIONS: This review demonstrates the vast range of PN-related patient safety incidents in all patient age groups and all medication process stages. The need for a national study looking at patient safety incidents related to PN in England is highlighted.

Differential Effect of Proinflammatory Cytokines on Corneal and Conjunctival Epithelial Cell Mucins and Glycocalyx.

Purpose: Ocular surface mucins and glycocalyx are critical for providing ocular hydration as well lubrication and repelling pathogens or allergens. Elevated levels of tear proinflammatory cytokines in dry eye may have detrimental effect on mucins and glycocalyx. The present study tested the effect of proinflammatory cytokines IL-6, TNF-α, and IFN-γ on membrane-tethered mucins expression, glycocalyx, and viability of ocular surface epithelial cells. Methods: Stratified cultures of human corneal and conjunctival epithelial cells were exposed to different concentrations of IL-6, TNF-α, and IFN-γ for 24 hours. The mucins gene and protein expressions were quantified by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). The glycocalyx was imaged using confocal microscopy after staining with Alexa 488-conjugated wheat germ agglutinin lectin. Apoptotic and necrotic cell death was quantified using flow cytometry. Results: IL-6, TNF-α, and IFN-γ treatment resulted in a significant increase in mucins (MUC)1 and MUC4 gene and protein expression in human corneal epithelial cells but caused no significant changes in the levels of these mucins in conjunctival epithelial cells. Further, these cytokines decreased MUC16 expression in both corneal and conjunctival epithelial cells. Moreover, no notable change in glycocalyx or apoptotic cell death in corneal and conjunctival epithelial cells was noted with any of the tested cytokines, but IL-6 and TNF-α exposure increased necrotic cell death in corneal and conjunctival epithelial cells, respectively. Conclusions: Our results demonstrate that proinflammatory cytokines have differential effects on human corneal and conjunctival epithelial cell mucins expression, but do not cause any damage to ocular surface epithelial cell glycocalyx.

Circadian influence on the microbiome improves heart failure outcomes.

Myocardial infarction (MI) leading to heart failure (HF) is a major cause of death worldwide. Previous studies revealed that the circadian system markedly impacts cardiac repair post-MI, and that light is an important environmental factor modulating the circadian influence over healing. Recent studies suggest that gut physiology also affects the circadian system, but how it contributes to cardiac repair post-MI and in HF is not well understood. To address this question, we first used a murine coronary artery ligation MI model to reveal that an intact gut microbiome is important for cardiac repair. Specifically, gut microbiome disruption impairs normal inflammatory responses in infarcted myocardium, elevates adverse cardiac gene biomarkers, and leads to worse HF outcomes. Conversely, reconstituting the microbiome post-MI in mice with prior gut microbiome disruption improves healing, consistent with the notion that normal gut physiology contributes to cardiac repair. To investigate a role for the circadian system, we initially utilized circadian mutant Clock∆19/∆19 mice, revealing that a functional circadian mechanism is necessary for gut microbiome benefits on post-MI cardiac repair and HF. Finally, we demonstrate that circadian-mediated gut responses that benefit cardiac repair can be conferred by time-restricted feeding, as wake time feeding of MI mice improves HF outcomes, but these benefits are not observed in MI mice fed during their sleep time. In summary, gut physiology is important for cardiac repair, and the circadian system influences the beneficial gut responses to improve post-MI and HF outcomes.

Cardiac Clocks and Preclinical Translation.

Circadian rhythms are fundamentally important for cardiovascular health, including heart rate, blood pressure, and molecular gene and protein responses. Rhythms also play a direct role in the pathophysiology of heart disease, such as in the timing of onset and severity of myocardial infarction, sudden cardiac death, ventricular arrhythmias, and stroke. Importantly, a flurry of new studies reveals translational applications for circadian biology to clinical medicine, and especially cardiology. Circadian medicine is a promising new approach that targets the heart's daily physiologic and molecular rhythms to benefit the treatment of patients with cardiovascular disease.

Cytoreductive surgery with intraperitoneal chemotherapy in the management of peritoneal surface malignancy: a pharmacist's perspective.

OBJECTIVES: To explore the use of intraperitoneal chemotherapy in conjunction with cytoreductive surgery for the treatment of peritoneal surface malignancy and highlight the challenges this provides for the hospital pharmacist. METHODS: A literature search for relevant articles was performed using MEDLINE, PubMed and Cochrane databases. The following keywords and phrases were used: 'hyperthermic intraperitoneal chemotherapy', 'early postoperative intraperitoneal chemotherapy', 'carrier solutions' and 'cytoreductive surgery'. Local experience was also shared, referencing national guidelines and published literature. RESULTS: The rationale behind intraperitoneal chemotherapy is to directly administer drugs into the peritoneal cavity and achieve exposure of higher concentrations of cytotoxic agents to tumour nodules within the abdomen and on peritoneal surfaces for a prolonged period of time, without significant systemic toxicity. This has been widely demonstrated in intraoperative and early postoperative settings. Hydrophilic chemotherapy drugs with high molecular weights and permeable to the peritoneum, but slow plasma clearance create high concentrations of the drug in the peritoneal cavity, with lower systemic circulation. Commonly used drugs include mitomycin C, oxaliplatin, cisplatin, doxorubicin and 5-fluorouracil. Newer drugs such as the taxanes and bevacizumab have also shown promise. Heat increases drug penetration into body tissues and destroys tumour cells directly by causing damage to cells that have inherently faulty heat regulation pathways and also increases the cytotoxic effect of selected chemotherapeutic agents. Optimal temperature for hyperthermic intraperitoneal drug administration is between 41 and 43°C in a carrier solution that is compatible with the drug chosen. For early postoperative intraperitoneal chemotherapy high molecular weight starch carrier solutions prolong intraperitoneal dwell time and exposure of drug to tumour cells. Drugs are administered intraoperatively with the abdomen open or closed for between 30 and 120 min depending on the drug chosen and local protocols. Drug doses are traditionally calculated using body surface area. Toxicity such as neutropenia is encountered far less than with systemic chemotherapy. CONCLUSIONS: This paper discusses the rationale for intraperitoneal drug administration following cytoreductive surgery and describes appropriate drug selection, methods of drug delivery and potential challenges in the use of the intraperitoneal route. It provides evidence and practical guidance for hospital pharmacists who may be involved in the surgical management of peritoneal malignancy particularly in dose calculation, preparation and administration of intraperitoneal chemotherapy.