Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Exsanguination of a home hemodialysis patient as a result of misconnected blood-lines during the wash back procedure: A case report

BACKGROUND: Home hemodialysis is common in New Zealand and associated with lower cost, improved survival and better patient experience. We present the case of a fully trained home hemodialysis patient who exsanguinated at home as a result of an incorrect wash back procedure. CASE PRESENTATION: The case involves a 67 year old male with a history of well controlled hypertension and impaired glucose tolerance. He commenced on peritoneal dialysis in 2006 following the development of end stage kidney failure secondary to focal segmental glomerulosclerosis. He transferred to hemodialysis due to peritoneal membrane failure in 2010, and successfully trained for home hemodialysis over a 20 week period. Following one month of uncomplicated dialysis at home, he was found deceased on his machine at home in the midst of dialysis. His death occurred during the wash back procedure performed using the “open circuit” method, and resulted from misconnection of the saline bag to the venous end of the extracorporeal blood circuit instead of the arterial end. This led to approximately 2.3L of his blood being pumped into the saline bag resulting in hypovolaemic shock and death from exsanguination. CONCLUSIONS: Despite successful training, critical procedural errors can still be made by patients on home hemodialysis. In this case, the error involved misconnection of the saline bag for wash back. This case should prompt providers of home hemodialysis to review their training protocols and manuals. Manufacturers of dialysis machinery should be encouraged to design machines specifically for home hemodialysis, and consider distinguishing the arterial and venous ends of the extracorporeal blood circuit with colour coding or incompatible connectivity, to prevent occurrences such as these in the future

Exsanguination of a home hemodialysis patient as a result of misconnected blood-lines during the wash back procedure: A case report

Abstract Background Home hemodialysis is common in New Zealand and associated with lower cost, improved survival and better patient experience. We present the case of a fully trained home hemodialysis patient who exsanguinated at home as a result of an incorrect wash back procedure. Case presentation The case involves a 67 year old male with a history of well controlled hypertension and impaired glucose tolerance. He commenced on peritoneal dialysis in 2006 following the development of end stage kidney failure secondary to focal segmental glomerulosclerosis. He transferred to hemodialysis due to peritoneal membrane failure in 2010, and successfully trained for home hemodialysis over a 20 week period. Following one month of uncomplicated dialysis at home, he was found deceased on his machine at home in the midst of dialysis. His death occurred during the wash back procedure performed using the “open circuit” method, and resulted from misconnection of the saline bag to the venous end of the extracorporeal blood circuit instead of the arterial end. This led to approximately 2.3L of his blood being pumped into the saline bag resulting in hypovolaemic shock and death from exsanguination. Conclusions Despite successful training, critical procedural errors can still be made by patients on home hemodialysis. In this case, the error involved misconnection of the saline bag for wash back. This case should prompt providers of home hemodialysis to review their training protocols and manuals. Manufacturers of dialysis machinery should be encouraged to design machines specifically for home hemodialysis, and consider distinguishing the arterial and venous ends of the extracorporeal blood circuit with colour coding or incompatible connectivity, to prevent occurrences such as these in the future.</p

Role of CD14+ CD16+ Monocytes in the Pathogenesis of Periodontitis Associated Systemic Diseases

Monocytes are immune cells that form an important bridge between the innate and adaptive immune response. These cells exist in various phenotypes based on cell surface marker expression and participate in the pathobiology of many systemic diseases. Periodontitis is an inflammatory condition of the tooth attachment apparatus caused by microbial assault from the dental plaque biofilm. It is noteworthy that monocytes play a key role in mediating tissue destruction in periodontitis. The CD14+ CD16+ monocytes that bear both the surface markers are especially involved and upregulated in periodontitis and produce increased amounts of proinflammatory cytokines following microbial challenge. In this context and exploring the available literature, the present chapter aims to unravel the role of CD14+ CD16+ monocytes in periodontitis and systemic disease and also aims to elucidate the possible pathways by which periodontitis could be a key risk factor for systemic disease based on monocyte selection and participation

Potential uses of Adhatoda Vasica in orthodontics

Plaque control, pain control, and modulation of inflammatory mediators to accelerate or stabilize tooth movements are hot issues in orthodontics. The recent advent of phytochemicals as biological mediators has opened new vistas in the aforementioned areas of orthodontics. Adhatoda vasica has caught the attention of investigators due to multiple properties related to orthodontics. This study addresses the potential areas of use of A. vasica in orthodontics, which provide ideas for further investigations. A. vasica possesses antibacterial activity, antifungal activity, anti-oxidant effect, anti-inflammatory activity, analgesic effect, osteogenic, and osteoclastic activities. A. vasica has huge potential in orthodontics, whereas all these vistas need careful and methodical testing before use in clinical orthodontics. In the future, investigators can focus on these aspects of the use of A. vasica to develop products

Cost-Effective Synthesis of Efficient CoWO4/Ni Nanocomposite Electrode Material for Supercapacitor Applications

In the present study, the synthesis of CoWO4 (CWO)&ndash;Ni nanocomposites was conducted using a wet chemical method. The crystalline phases and morphologies of the Ni nanoparticles, CWO, and CWO&ndash;Ni composites were analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDAX). The electrochemical properties of CWO and CWO&ndash;Ni composite electrode materials were assessed by cyclic voltammetry (CV), and galvanostatic charge&ndash;discharge (GCD) tests using KOH as a supporting electrolyte. Among the CWO&ndash;Ni composites containing different amounts of Ni1, Ni2, and Ni3, CWO&ndash;Ni3 exhibited the highest specific capacitance of 271 F g&minus;1 at 1 A g&minus;1, which was greater than that of bare CWO (128 F g&minus;1). Moreover, the CWO&ndash;Ni3 composite electrode material displayed excellent reversible cyclic stability and maintained 86.4% of its initial capacitance after 1500 discharge cycles. The results obtained herein demonstrate that the prepared CWO&ndash;Ni3 nanocomposite is a promising electrode candidate for supercapacitor applications

The Expression of Allele Changes in NLRP3 (rs35829419) and IL-1β (+3954) Gene Polymorphisms in Periodontitis and Coronary Artery Disease

Background: Inflammasomes have been shown to play a pivotal role in periodontal disease pathogenesis. However, their role in periodontitis subjects with coronary heart disease remains unclear. This study aimed to obtain the expression of NLRP3 (rs35829419) and IL-1β (+3954) gene polymorphisms in the subgingival plaque and blood samples of generalized periodontitis (GP) subjects with and without coronary heart disease (CHD). Methods: A total of 70 subjects were grouped into two; GP and GP with CHD. Demographic variables and periodontal and cardiac parameters were recorded from both the groups. Subgingival plaque and blood samples were obtained from both the groups and were further subjected to the identification of NLRP3 (rs35829419) and IL-1β (+3954) expression and allele change using a conventional polymerase chain reaction (PCR) and gene sequencing (Sanger’s method). Results: Amongst the demographic variables, age and monthly income were statistically significant between the two groups. Plaque index (PI), clinical attachment level (CAL), high-density lipoprotein (HDL), and low density-lipoprotein (LDL) exhibited statistically significant levels between the two groups. The NLRP3 (rs35829419) and IL-1β (+3954) genes showed a statistically significant association with allele change (frequency) among the groups. The general comparison of all the parameters with the allele change of NLRP3 (rs35829419) and IL-1β (+3954) in the subgingival plaque and blood samples showed statistically significant associations among the two groups. Conclusion: The present study highlighted an allele change in IL-1β (+3954) gene polymorphisms which may play an important role in the pathogenesis of periodontitis and coronary heart disease

Genetic Polymorphisms of NLRP3 (rs4612666) and CARD8 (rs2043211) in Periodontitis and Cardiovascular Diseases

Background: The existing data show that inflammasomes play a role in periodontal disease pathogenesis. However, their role in the pathogenesis of periodontitis and coronary heart disease remains unclear. This study had the objective of assessing NLRP3 (rs4612666) and CARD8 (rs2043211) gene polymorphisms in dental plaque and blood of generalized chronic periodontitis (CP) patients in the presence and absence of coronary heart disease (CHD). Methods: A total of 70 subjects were divided into two groups, including CP and CP + CHD subjects. Demographic variables, periodontal, and cardiac parameters were recorded from both groups. Subgingival plaque and blood samples were obtained from both groups and were subjected to further molecular analysis for NLRP3 (rs4612666) and CARD8 (rs2043211) expression and allele change using conventional polymerase chain reaction (PCR) and gene sequencing (Sanger’s method). Results: Amongst the demographic variables, age, and monthly income were statistically significant between the two groups. Plaque index (PI), clinical attachment level (CAL), high-density lipoprotein (HDL), and low density-lipoprotein (LDL) exhibited statistically significant levels between the two groups. NLRP3 (rs4612666) and CARD8 (rs2043211) genes showed a statistically significant association of allele change (frequency) among the groups. In general, when all of the parameters were compared to the allele change of the genes, statistically significant relationships were found between the two groups. Conclusions: The present study expressed an allele change of the investigated genes which could profoundly affect the pathobiology of the two diseases under investigation

Melatonin as a topical/systemic formulation for the management of periodontitis: a systematic review

Objectives: To qualitatively and quantitatively review the use of melatonin as a topical/systemic formulation for the management of periodontitis. Materials and methods: PubMed; Scopus; and Web of Science databases were searched using the MesH terms “melatonin” and “periodontitis”. Title and abstracts were screened to eliminate irrelevant and duplicate articles. The full text data of the screened articles were assessed using the selection criteria. Results: Of 176 identified articles (PubMed-66; Scopus-56; Web of Science-52; Cross-reference-2), only 12 studies qualified to be included in the systematic review. Four studies assessed the independent effect of 1% topical melatonin formulation while 8 articles assessed the adjunctive use of systemic melatonin formulation (1–10 mg) following scaling and root planing (SRP). All studies showed an improvement in periodontal parameters such as pocket depth, clinical attachment loss, periodontal disease index, community periodontal index, gingival bleeding scores, and prognostic marker levels in saliva and serum. A meta-analysis of data from 2 studies revealed that 1–2 mg (systemic) melatonin supplementation reduced pocket depth; although the difference was not statistically significant and hence cannot be interpreted or used for conclusive evidence. Risk of Bias Assessment tool (RoBANS) and Cochrane Collaboration RoB tool elicited a high risk of bias in the included studies. GRADE (recommendation assessment, development, and evaluation) inferred a weak recommendation for the use of melatonin in periodontitis management. Conclusions: Melatonin supplementation (topical and systemic) in periodontitis patients improved key periodontal parameters including pocket depth and clinical attachment loss. Clinical relevance: Melatonin could be a potential host modulatory agent for periodontitis management; although the data from the present review should be interpreted carefully due to the associated high risk of bias