Morbidity In Patients Research Articles

Combination Therapy for Cryptosporidiosis in Immunocompromised Patients: A Systematic Review

Cryptosporidium sp. is a pathogen that causes gastroenteritis and may increase mortality and morbidity in immunocompromised patients. Cryptosporidium became widely recognized as a human pathogen. Diarrhea is a common problem in AIDS patients and about 30%–60% of patients in developed countries and 90% in developing countries experience diarrhea. This study was conducted using a systematic review design. Two articles with cohort design and two with case report design were selected based on the eligibility criteria. Three of these studies used a combination of nitazoxanide with azithromycin as an intervention, one in cohort design and two in case report design. One cohort study used a nitazoxanide and fluoroquinolone combination as an intervention. 54 samples participated in this study were post kidney transplantation patients and one sample was with acute lymphoblastic leukemia (ALL). Nitazoxanide and fluoroquinolone combination is a better therapy for cryptosporidiosis in immunocompromised patients compared to nitazoxanide and azithromycin combination. The(OR) for stool clearance was significantly lower with nitazoxanide alone compared to that of nitazoxanide and fluoroquinolone (OR: 0.65, 95% CI: 0.34, 0.92, P= 0.01), and the OR for diarrhea stopped was significantly lower with nitazoxanide alone compared to that of nitazoxanide and fluoroquinolone (OR: 0.45, 95% CI: 0.21, 0.81, P= 0.004). The OR for stool clearance was lower with nitazoxanide and azithromycin than monotherapy (OR 0.27, 95% CI: 0.01, 5.77), but P=0.24, which means not statistically significant.

Cardioprotective effect of 19,20-epoxydocosapentaenoic acid (19,20-EDP) in ischemic injury involves direct activation of mitochondrial sirtuin 3.

Although current clinical therapies following myocardial infarction have improved patient outcomes, morbidity, and mortality rates secondary to ischemic and ischemia reperfusion (IR) injury remains high. Maintaining mitochondrial quality is essential to limit myocardial damage following cardiac ischemia and IR injury. The mitochondrial deacetylase sirtuin 3 (SIRT3) plays a pivotal role in regulating mitochondrial function and cardiac energy metabolism. In the current study, we hypothesize that 19,20-epoxydocosapentaenoic acid (19,20-EDP) attenuates cardiac IR injury via stimulating mitochondrial SIRT3. Ex vivo models of isolated heart perfusions were performed in C57BL/6 mice to assess the effect of 19,20-EDP on cardiac function and energy metabolism following IR injury. In vivo permanent occlusion of the left anterior descending coronary artery (LAD) was performed to induce myocardial infarction (MI), mice were administered 19,20-EDP with or without the SIRT3 selective inhibitor 3-TYP. Mitochondrial SIRT3 targets and respiration were assessed in human left ventricular (LV) tissues obtained from individuals with ischemic heart disease (IHD) and compared to non-failing controls (NFC). Binding affinity of 19,20-EDP to human SIRT3 was assessed using molecular modeling and fluorescence thermal shift assay. Results demonstrated hearts treated with 19,20-EDP had improved post-ischemic cardiac function, better glucose oxidation rates and enhanced cardiac efficiency. The cardioprotective effects were associated with enhanced mitochondrial SIRT3 activity. Interestingly, treatment with 19,20-EDP markedly improved mitochondrial respiration and SIRT3 activity in human left ventricle (LV) fibers with IHD compared to NFC. Moreover, 19,20-EDP was found to bind to the human SIRT3 protein enhancing the NAD+ -complex stabilization leading to improved SIRT3 activity. Importantly, the beneficial effects of 19,20-EDP were abolished by SIRT3 inhibition or using the S149A mutant SIRT3. These data demonstrate that 19,20-EDP-mediated cardioprotective mechanisms against ischemia and IR injury involve mitochondrial SIRT3, resulting in improved cardiac efficiency.

Palmitoleic acid sensitizes vancomycin-resistant Staphylococcus aureus to vancomycin by outpacing the expression of resistance genes.

The rise in antibiotic resistance limits the availability of antibiotics to treat bacterial infections. Despite this, antibiotic development pipelines remain sparse which makes using adjuvants to reverse antibiotic resistance a promising therapeutic strategy. The use of vancomycin, a frontline antibiotic used to treat hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) infections, is complicated by high rates of treatment failure. Vancomycin binds to the D-ala-D-ala terminus of the nascent peptidoglycan precursor lipid II, preventing cell wall biosynthesis. Vancomycin-resistant strains of S. aureus and Enterococci typically express a van gene cluster that is induced in response to vancomycin and results in the synthesis of an alternative lipid precursor with a peptide chain ending in D-ala-D-lac. Vancomycin has low affinity for the D-ala-D-lac terminus, and the bacteria can resume growth even in the presence of an otherwise lethal dose of vancomycin. We previously showed that palmitoleic acid, a host-produced monounsaturated fatty acid, combined with vancomycin led to an accumulation of large fluid patches in the bacterial membrane, resulting in membrane destabilization and cell death. In this study, we observed that palmitoleic acid increases the rate of vancomycin killing by more than 50-fold, compared to vancomycin alone. This rapid bactericidal activity by the combined treatment sensitized vancomycin-resistant S. aureus (VRSA) and vancomycin-resistant Enterococcus (VRE) to vancomycin, likely by outpacing the expression of vancomycin resistance genes. This study represents an important step in the ongoing effort to mitigate antibiotic resistance.IMPORTANCEThe development of antibiotics has transformed medicine, reducing the incidence and severity of bacterial infections and allowing for advancements in healthcare, including invasive surgeries and organ transplants. However, the rise of antibiotic resistance poses a significant threat to these medical advancements, leading to treatment failures that result in increased patient morbidity and mortality, as well as substantial healthcare costs. Vancomycin-resistant Enterococcus (VRE) species are prevalent in hospital settings and chronic infections. Although high-level vancomycin resistance in S. aureus is rare, S. aureus can acquire plasmids expressing vancomycin resistance genes from resistant Enterococcal species during infection, further complicating treatment. In this study, we find that palmitoleic acid increases the rate of vancomycin killing and restores sensitivity to vancomycin-resistant S. aureus (VRSA) and VRE isolates.

The effectiveness of waxing or epilation compared to conventional methods of hair removal in reducing the incidence of surgical site infections: a systematic review and meta-analysis

BackgroundSurgical site infections (SSIs) pose a significant challenge to healthcare systems by elevating patient morbidity and mortality and driving up financial costs. Preoperative skin preparation is crucial for preventing SSIs; however, certain traditional methods of hair removal have been found to increase the risk of SSI development. Mechanical epilation and waxing constitute two relatively explored methods of hair removal, which may hold potential to accelerate wound healing due to the activation of stem cells within hair follicles. This review assesses the efficacy of preoperative hair removal via waxing and mechanical epilation in reducing SSI incidence.MethodsThis systematic review was prospectively registered with PROSPERO (ref: CRD42023423798) and a protocol previously published in a peer-reviewed journal. All findings are reported according to PRISMA guidelines. A comprehensive search of Medline, Embase, CENTRAL, ClinicalTrials.gov and CINAHL. Inclusion criteria encompassed adult patients undergoing any surgical procedure, comparing waxing or epilation against other hair removal methods or no hair removal, with SSI incidence as the primary outcome. There was no restriction on study size or quality to ensure a comprehensive literature evaluation.ResultsThe review found no studies meeting the selection criteria out of 576 records screened.Discussion/conclusionThis review has identified no literature regarding the use of waxing and mechanical epilation as methods of preoperative hair removal. The lack of experimental evidence combined with the potential physiological advantages of these techniques indicate that this could be a valuable area of future research. These techniques may represent novel approaches to SSI prevention, particularly beneficial in high-risk surgical disciplines like vascular surgery.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=423798, PROSPERO (CRD42023423798).

Single-port robotic transanal minimally invasive surgery (SPR-TAMIS): another giant leap forward?

Minimally invasive transanal platforms are now the standard of care for select low-risk rectal tumours. However, existing platforms come with persistent technical challenges. The da Vinci SP Surgical System™ offers a new alternative designed to work effectively in narrow spaces. This technology has the potential to enhance the feasibility and proximal extent of complex transanal resections. This study aimed to describe the morbidity and technical success in patients undergoing single-port robotic transanal minimally invasive surgery (SPR-TAMIS). Secondary outcomes include rates of local recurrence. A retrospective analysis was conducted on all patients who underwent SPR-TAMIS at our institution between February 2019 and December 2023. The study included 31 patients (19 men, 12 women) with a mean age of 61 ± 13.3 years. The average tumour distance from the anal verge was 10 cm. Thirty patients completed SPR-TAMIS, with one patient requiring conversion to robotic sigmoidectomy due to location in the mid-sigmoid colon. The mean operating time was 106 ± 42 min. Twenty-eight out of 30 patients underwent full-thickness excision and all but two were successfully closed. All specimens were resected intact, and margins were negative in 93.5% of cases. The average tumour size was 13 ± 34 cm2, with 13 lesions classified as adenomas and 16 as adenocarcinomas. All patients who did not undergo associated procedures were discharged on the day of surgery. Two patients experienced 30-day morbidity. At a mean follow-up of 18 months (± 13), no local or systemic recurrences were identified. SPR-TAMIS for excision of low-risk rectal tumours is associated with high rates of technical success and low 30-day morbidity. Further research is needed to compare SPR-TAMIS with other techniques to determine potential advantages over current transanal platforms.

Cardiooncology in the ICU - Cardiac Urgencies in Cancer Care.

Cardiovascular disease is an increasing risk of morbidity and mortality in cancer patients, related to an growing number of aging survivors with pre-existing cardiovascular disease and the use of traditional and novel cancer therapies with cardiotoxic effects. While many cardiac complications are chronic processes that develop over time, there are many acute processes that may arise in hospitalized patients. It is important for hospitalists and critical care physicians to be familiar with the recognition and management of these conditions in this unique population. This article reviews the presentation and management of common cardiac urgencies in critically ill cancer patients including acute decompensated heart failure, acute coronary syndromes, arrhythmias, hypertensive crises, pulmonary embolism, pericardial tamponade and myocarditis.

Telemonitoring for Chronic Heart Failure: Narrative Review of the 20-Year Journey From Concept to Standard Care in Germany.

Chronic heart failure (CHF) is a major cause of morbidity and mortality worldwide, placing a significant burden on health care systems. The concept of telemedicine for CHF was first introduced in the late 1990s, and since 2010, studies have demonstrated its potential to improve patient outcomes and reduce health care costs. Over the following decade, technological advancements and changes in health care policy led to the development of more sophisticated telemedicine solutions for CHF, including remote patient management through invasive or noninvasive telemonitoring devices, mobile apps, and virtual consultations. Years of public funding in Germany have generated evidence that remote patient management improves outcomes for patients with CHF, such as quality of life, and reduces hospital admissions. Based on these data, the Federal Joint Committee (Gemeinsamer Bundesausschuss; G-BA) decided, independently of the current European Society of Cardiology recommendations, to incorporate telemedicine as a standard digital intervention for high-risk patients with reduced left ventricular ejection fraction in Germany in 2020. This review aims to illustrate the journey from the initial concept through pioneering studies that led to telemedicine's integration into standard care, and to share current experiences that have positioned Germany as a leader in cardiovascular telemedicine. We review and discuss existing literature and evidence on the development and implementation of telemonitoring for CHF in Germany over the past 20 years. Relevant studies, reports, and guidelines were identified through a comprehensive search of electronic databases, including PubMed, Google Scholar, and specialized journals focused on CHF telemonitoring. Pioneering studies, such as the TIM-HF2 (Telemedical Interventional Management in Heart Failure II) and IN-TIME (Influence of Home Monitoring on Mortality and Morbidity in Heart Failure Patients with Impaired Left Ventricular Function) trials, demonstrated the effectiveness of remote patient management applications for patients with CHF in Germany and their applicability to current practices involving both invasive and noninvasive methods. Collaborations between researchers and technology developers overcame barriers, leading to sustainable improvements in patient care. Ongoing research on artificial intelligence applications for prioritizing and interpreting individual health data will continue to transform digital health care. The establishment of telemedical care for patients with HF across Europe is likely to benefit from experiences in Germany, where significant improvements have been achieved in the care of patients with HF.

Analysis of the structure and dynamics of epidemiological indicators of renal cell carcinoma in the world and Ukraine

Aim. To analyze the structure and dynamics of epidemiological indicators of renal cell carcinoma (RCC) worldwide and in Ukraine. Materials and methods. The study materials were publications in scientific journals, statistical reports of international and national health organizations, including data from the Global Cancer Observatory (GLOBOCAN) and European Association of Urology databases, as well as data from the Ukrainian National Cancer Registry Bulletin and official statistics from various regions of Ukraine. The methods of content analysis, comparative, logical, analytical, mathematical, graphical methods, and generalization of information were used in the study. Results. According to the results of the analysis, it has been found that the incidence of RCC varies considerably around the world, with the highest rates in North America, Eastern and Northern Europe and the lowest in Africa and South Asia. In the United States, about 79,000 new cases of RCC are registered annually, while in Europe, 145,000 cases were reported in 2022. In Ukraine, 3,544 people fell ill with RCC in 2022, of whom 1,238 died. The highest number of cases of RCC was observed in men (2126 cases versus 1418 among women). Among the new cases of RCC in 2022, 20.3 % of patients did not live more than one year. It has been determined that there is heterogeneity in the incidence of RCC in different regions of Ukraine. Thus, the largest number of reported cases of RCC (absolute value) in 2022 was observed in Dnipro (344 cases), Lviv (313 cases) regions and the city of Kyiv (234 cases). The lowest number of new cases of renal malignancies was recorded in the temporarily occupied areas from the active hostilities zone (Luhansk, Donetsk, Kherson regions), as well as in Mykolaiv (39 cases) and Chernivtsi (68 cases) regions. The regional differences identified in the morbidity and mortality of patients with RCC may be due to various factors, including, first of all, epidemiological, socio-demographic, and medical factors. Conclusions. It has been determined that RCC occupies a significant position in the structure of morbidity and mortality among different age and gender groups of the population both in Ukraine and in the world. In general, there is an increase in the number of cases of RCC among both men and women in the world with a significant predominance among men. It has been found that the dynamics of morbidity in Ukraine has a heterogeneous trend with an increase in the number of cases in 2019 compared to 2018; at the same time, a significant decrease in 2020 and 2022 compared to previous years. The study of the data on epidemiological indicators of RCC will further expand the possibilities for evaluating medical technologies and, accordingly, forming directions for improving existing approaches to pharmacotherapy for this group of patients in Ukraine.

Non-invasive infrared thermography for screening, diagnosis and monitoring of skin cancer.

The incidence of skin cancer is rising continuously. The time of diagnosis is decisive for the morbidity and mortality risk of patients. An optimal screening procedure has yet to be established. Non-contact imaging methods are of great interest but have not yet been sufficiently developed and investigated for large-scale use. Compared to digital photography, infrared thermography offers the additional information of heat radiation from the skin surface, which correlates strongly with malignant changes. Literature on the current scientific status of screening, diagnosis and monitoring of skin cancer using thermographic procedures was identified in PubMed, Embase, and Google Scholar. From a technical and information technology point of view, infrared thermography is very well suited for use as a non-invasive, cost-effective, time-saving, and easy-to-use screening instrument. However, there is still a lack of reliable evidence and practical implementation in 3D systems suitable for mass use. Research in this area should be intensified in order to develop, test and establish applicable systems on a large scale.

Microbial Etiology of Surgical Site Infections, Bacterial Isolates and their Antibiotic Susceptibility Patterns at Trauma University Hospital in Tirana, Albania

Hospital acquired infections in general and specifically surgical site infections increase significantly the morbidity and mortality of post-surgery patients. They are considered the most frequent postoperative complication worldwide, and a major public health burden especially in low income countries. The preventability and the high treatment costs of these complications, sets the focus towards identification of the most frequent etiological factors, in order to decrease the incidence of the phenomenon in different levels. This is a retrospective study carried out from January 1 to December 31, 2023. We analysed the microbiology and antibiotic susceptibility reports of specimens accepted and examined at the laboratory department of the Trauma University Hospital, Tirana. We reported standard operating procedure on direct microscopic examination with gram staining, and the susceptibility patterns reported by millimetre scaling the zone of inhibition of the examined antibiotics disks. We reported 40% negativity rate on the examined specimens. The most frequently isolated microorganisms within the positive results were Acinetobacter Baumannii (25.4%), Staphylococcus Aureus (13.5%), and Enterococcus faecalis (10.32%). The combination of cephalosporins together with aminoglycosides was found to be the most effective antibiotic prophylaxis formulation. Continuous surveillance of bacterial profiles through variable rich, statistically significant additional studies become crucial. The results will help toward better hospital acquired infection prevention and control. Received: 21 August 2024 / Accepted: 10 November 2024 / Published: 3 December 2024

Efficacy and Safety of LigaSure in Breast Surgery With Axillary Lymph Node Dissection in Patients With Breast Cancer: A Systematic Review and Meta-Analysis.

Conventional axillary lymph node dissection (ALND) is associated with significant post-operative morbidity in patients undergoing breast surgery due to increased lymphatic leakage. LigaSure, an electrothermal bipolar vessel sealing system, provides better closure of the leakage. This study aims to compare the efficacy and safety of LigaSure against conventional techniques in patients with breast cancer underwent ALND and breast surgery. We conducted a comprehensive search across the databases to identify relevant studies. The search results were imported into Covidence for article eligibility screening, and all relevant outcomes data were synthesized using odd ratios (ORs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs) in meta-analysis models using RevMan 5.4. Twelve studies with the total of 895 patients (LigaSure = 441; Conventional technique = 454) with breast cancer underwent breast surgery with ALND were included. LigaSure was associated with significantly lower post-operative drain volume (SMD: -0.39, 95% CI [-0.53, -0.24], P < 0.00001), shortened duration of drain (SMD: -0.51, 95% CI [-0.67, -0.34], P < 0.00001), and reduced hospital stay length (SMD: -0.57, 95% CI [-0.96, -0.18], P = 0.004) compared to conventional techniques. However, no difference observed in total operation time, intra-operative blood loss, seroma related outcomes and post-operative complications between the two groups. LigaSure significantly reduced the lymphorrhea, duration of drain and hospital stay, however, it did not prove be effective in seroma-related outcomes.

Contextualizing prophylactic red blood cell antigen matching in the lifelong care of sickle cell disease and thalassaemia patients.

Alloimmunization to minor red blood cell antigens has been linked to patient morbidity and mortality, especially among people living with sickle cell disease and transfusion-dependent thalassaemia. Prophylactic antigen matching is commonly used to prevent alloimmunization, but the evidence supporting this common practice is very limited. The report by Wolf etal. summarizes the latest literature on this topic and importantly finds that there is insufficient evidence to recommend prophylactic extended antigen matching (beyond ABO, RhD, RhCcEe and K). In an era of chronic blood shortages, this approach may help to assure patient access to elective surgery and cellular therapies, while preserving the supply of extensively antigen-matched red cells for patients with specific needs. Commentary on: Wolf etal. Red cell specifications for blood group matching in patients with haemoglobinopathies: An updated systematic review and clinical practice guideline from the International Collaboration for Transfusion Medicine Guidelines. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19837.

Congenital tracheal stenosis with complete cartilage rings: proposal of a multidisciplinary and tailored surgical approach.

IntroductionCongenital Tracheal Stenosis (CTS) with complete cartilaginous rings is a rare but potentially life-threatening condition in paediatric patients. Currently, the most common approach is slide tracheoplasty (ST) with sternotomy under cardiopulmonary bypass (CPB). Intending to make the procedure less invasive and consider the variety of associated conditions, we have tailored the approach to our patients, who were treated by a multidisciplinary airway team. MethodsPatients with CTS treated surgically between 2012 and 2022 at Gaslini Institute were enrolled. Preoperative, surgical and postoperative details were collected and analysed retrospectively. All patients had angio-computerized tomography (CT) scan, echocardiography and bronchoscopy with bronchography before surgery. Each patient and each procedure have been discussed at Airway Team meetings. ResultsAmong 20 patients with CTS, 15 underwent ST and 5 tracheal resection and anastomosis (TRA). 60% were younger than 12 months. 30% patients had previous tracheal/cardiac surgery. Combined cardiac surgery was performed in 8 patients. 4 patients were approached with cervicotomy and extracorporeal membrane oxygenation (ECMO). Mortality within 30 days was 5%. 8 patients (40%) needed endoscopic dilatation after the surgery and 1 underwent revision surgery. No patient had tracheostomy after the surgery. We did not find a higher rate of mortality and morbidity in patients who had cervicotomy and ECMO. ConclusionWe propose a multidisciplinary and tailored approach for patients with CTS. After evaluating each patient through detailed preoperative studies, including bronchography, the team can choose alternatives to the traditional ST under CPB, such as TRA, cervical approach, and ECMO. Level of evidenceLevel IV Type of studyOriginal article

Multiloculated pyopneumothorax with subcutaneous emphysema and pneumomediastinum in a tuberculosis patient.

Pulmonary tuberculosis with the simultaneous development of the complications of empyema, multiloculated pyopneumothorax, subcutaneous emphysema and pneumomediastinum is rare. The development of these complications leads to remarkably increased incidence of morbidity and mortality in patients. So appropriate and timely management needs to be ensured for better outcomes.

Myosin light chain kinase-mediated epithelial barrier dysfunction as a potential pathogenic mechanism of afatinib-induced diarrheas: A study in human colonoid model

Diarrheas are an important adverse effect of afatinib, a tyrosine kinase inhibitor (TKI) anti-cancer drug, leading to mortality and morbidity in cancer patients with their pathophysiological mechanisms related to intestinal barrier dysfunctions being poorly understood. This study aimed to investigate the effect of afatinib on intestinal epithelial barrier integrity using a human colon-derived organoid model (colonoids). Afatinib (0.5 μM) significantly decreased the transepithelial electrical resistance (TEER) by ∼60% and increased apical-to-basolateral dextran flux by >20 folds without causing apparent cytotoxicity in human colonoids. The delocalization of zonular occluding-1 (ZO-1) and a decrease in mRNA and protein expression of claudin-4 and ZO-1 were also observed in the afatinib-treated human colonoids. Afatinib induced nuclear translocation of nuclear factor kappa B (NF-κB) as well as mRNA and protein expression of NF-κB target including tumor necrosis factor (TNF)-alpha, interleukin-8 (IL-8), and inducible nitric oxide synthase (iNOS) indicating the initiation of the NF-κB-mediated epithelial inflammatory responses. Interestingly, afatinib induced mRNA and protein expression of myosin light chain (MLC) kinase (MLCK) and MLC phosphorylation, a known inducer of intestinal epithelial barrier disruption. Treatment with iNOS inhibitor (1400W) or MLCK inhibitor (ML-7) reversed the effect of afatinib on mRNA expressions of ZO-1 and claudin-4, and TEER. Collectively, our results indicate that afatinib induces intestinal epithelial barrier dysfunction via mechanisms involving NF-κB-iNOS-MLCK pathways. This finding may pave the way for developing therapeutic strategies to reduce adverse effects and enhance efficacy of TKI in cancer patients.

Association between malnutrition-inflammation score (MIS) and quality of life in elderly hemodyalisis patients.

The malnutrition-inflammation process is one of the main causes of morbidity and mortality in patients with chronic kidney disease (CKD), influencing quality of life. The aim of this study was to identify the inflammatory and nutritional status of elderly hemodialysis (HD) and its association with quality of life. This study was carried out in health services in three different cities. The Malnutrition-Inflammation Score (MIS) was used to assess the inflammatory and nutritional status, with anthropometric measurements, protein status, lean mass and function. The quality of life was assessed using KDQOL-SFTM. Data were analyzed using multivariate analysis and the Poisson model to evaluate the factors that increased the risk of developing malnutrition and inflammation. The MIS identified a 52.2% prevalence of malnutrition and inflammation in the population. In univariate analysis, most KDQOL-SFTM domains presented higher scores for nourished elderly. Anthropometric measures associated with muscle mass and functionality were lower in the malnourished elderly. Multivariate modeling revealed a higher nutritional risk of 50.6% for women and older age, since with each additional year of life the risk of malnutrition increased by 2.4% and by 0.4% with each additional month on HD. Greater arm muscle circumference (AMC) and higher serum albumin were factors for reducing malnutrition by 4.6% and 34.7%, respectively. Higher serum albumin and preserved AMC have been shown to be good indicators of better nutritional status. Higher MIS was associated with poorer quality of life, older age, lower income and education, longer time on dialysis, and presence of comorbidities.

EP300-mediated H3 acetylation elevates MTHFD2 expression to reduce mitochondrial dysfunction in lipopolysaccharide-induced tubular epithelial cells.

Sepsis represents an organ dysfunction resulting from the host's maladjusted response to infection, and can give rise to acute kidney injury (AKI), which significantly increase the morbidity and mortality of septic patients. This study strived for identifying a novel therapeutic strategy for patients with sepsis-induced AKI (SI-AKI). Rat tubular epithelial NRK-52E cells were subjected to lipopolysaccharide (LPS) exposure for induction of in-vitro SI-AKI. The expressions of E1A binding protein p300 (EP300) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) in NRK-52E cells were assessed by western blot and qRT-PCR, and their interaction was explored by chromatin immunoprecipitation performed with antibody for H3K27 acetylation (H3K27ac). The effect of them on SI-AKI-associated mitochondrial dysfunction of tubular epithelial cells was investigated using transfection, MTT assay, TUNEL staining, 2',7'-Dichlorodihydrofluorescein diacetate probe assay, Mitosox assay, and JC-1 staining. MTHFD2 and EP300 were upregulated by LPS exposure in NRK-52E cells. LPS increased the acetylation of H3 histone in the MTHFD2 promoter region, and EP300 suppressed the effect of LPS. EP300 ablation inhibited the expression of MTHFD2. MTHFD2 overexpression antagonized LPS-induced viability reduction, apoptosis promotion, reactive oxygen species overproduction, and mitochondrial membrane potential collapse of NRK-52E cells. By contrast, MTHFD2 knockdown and EP300 ablation brought about opposite consequences. Furthermore, MTHFD2 overexpress and EP300 ablation counteracted each other's effect in LPS-exposed NRK-52E cells. EP300-mediated H3 acetylation elevates MTHFD2 expression to reduce mitochondrial dysfunction of tubular epithelial cells in SI-AKI.

Aspiration after Anesthesia: Chemical versus Bacterial, Differential Diagnosis, Management, and Prevention.

Aspiration following anesthesia is a major patient issue and a difficulty for anesthesiologists. Aspiration syndromes are more common than anticipated, and the condition is frequently undetected. Clinical signs are often dictated by the characteristics of aspiration, such as the infectivity of the material, its volume, and the severity of the underlying clinical condition. Pulmonary aspiration can cause an acute or persistent inflammatory response in the lungs and upper airways that can be complicated by tracheobronchitis, aspiration pneumonia, aspiration pneumonitis, acute respiratory distress syndrome, and subsequent bacterial infection due to particle, acid, and bacteria-related processes. Aspiration during anesthesia, while relatively rare, poses significant risks for patient morbidity and mortality. Chemical and bacterial aspiration provide distinct diagnostic and management issues. Preventive strategies such as a complete preoperative risk assessment, adherence to fasting rules, proper patient positioning, and the use of protective airway devices are critical in reducing aspiration risk. In addition, drugs such as proton pump inhibitors can help lower stomach acidity and volume. Innovations in monitoring techniques, better training, and awareness activities are critical to enhancing aspiration event management. Given the importance of this entity, this narrative review sought to make an updated overview of the management of aspiration after anesthesia: chemical versus bacterial, differential diagnosis, management, and prevention.

Exploring potential of tobramycin complexes for combating biofilms: In silico and In vitro studies

Nosocomial infections linked to medical implants, wound infections, and cystic fibrosis infections are mostly caused by biofilms linked to Pseudomonas aeruginosa. The development of biofilms on medical equipment continues to a growing health and financial burden with increased the risk of infections and patient morbidity associated with indwelling medical devices. Pseudomonas aeruginosa exhibited high antibiotic resistance, posing challenges for effective treatment of infections associated with medical implants. Therefore, our objective was to adopt a combinatorial approach for formulating antibiotic complexes for maximum eradication of biofilms associated with medical implants.In this study, we optimized the ratio of Tobramycin (TOB) complexes with complexing agents such as sodium bicarbonate (BC), β-cyclodextrin (β-CD), and ethylenediaminetetraacetic acid (EDTA). Further stability and flexibility of the complexes were examined through molecular docking and dynamics. Subculturing and gram staining were performed for the isolation and identification of Pseudomonas aeruginosa. The antibacterial activity was tested using the broth dilution method and well diffusion method to calculate the MIC (minimum inhibitory concentration) against Pseudomonas aeruginosa planktonic cells and biofilms, respectively. The MIC tests indicated that optimised complexes required a concentration of 8 μg/ml to eradicate both planktonic cells as well as biofilms. However, the TOB-BC-(β-CD)-EDTA complex showed lower optical density (OD) compared to other complexes exhibiting better biofilm inhibition. Subsequently a gel formulation using this optimised (TOB-BC-(β-CD)-EDTA) complex that could be applied to medical equipment or potentially converted into a film using different polymer concentrations was developed. The TOB-BC-(β-CD)-EDTA gel formulation was characterized for pH, viscosity, spread-ability, % yield, moisture content, drug content, in-vitro drug diffusion, and antibacterial efficacy assay. Among all batches, F2 demonstrated the highest % drug diffusion after 24 hours and fit well to the Korsmeyer-Peppas kinetic model. The viscosity of the F2 batch remained within acceptable limits and was stable at 40 ± 0.5 ºC and 75.0 ± 5% RH. The gel efficiently delivered antimicrobial drugs to bacteria within biofilms. In conclusion, tobramycin complex gel showed promising potential for addressing infections related to biofilms on medical implants.

Bone Erosions and Systemic Bone Loss on HR-pQCT in Men With Tophaceous Gout.

Gout, a prevalent inflammatory arthropathy, predominantly affects males and arises from persistent hyperuricemia, resulting in monosodium urate crystal deposition. Hyperuricemia is associated with comorbidities, exacerbating patient morbidity. Conflicting literature exists regarding uric acid's impact on bone mineral density (BMD), with potential proinflammatory effects in gout patients. Localized bone destruction (erosions) is a hallmark of gout, necessitating early detection due to its predictive role in musculoskeletal disability. This cross-sectional study included 26 tophaceous gout patients. Clinical and densitometric parameters were assessed, and high-resolution peripheral quantitative computed tomography (HR-pQCT) was used for bone microarchitecture evaluation, as well as bone erosions in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. A healthy control group of 52 age and BMI-matched individuals was included. Despite normal areal bone mineral density (BMD), tophaceous gout patients exhibited impaired HR-pQCT parameters, including lower cortical volumetric BMD (Ct.vBMD) and higher cortical porosity at the distal radius. Similar trends were observed at the tibia. Bone erosions were prevalent (96%), with distribution across MCP and PIP joints. Patients with ≥ 4 erosions displayed increased tophi prevalence and longer uricosuric use. Erosions correlated with compromised microarchitecture, emphasizing their association with disease activity. Despite normal BMD, tophaceous gout patients manifest systemic bone loss, with bone microarchitectural deterioration and localized bone erosions, underscoring the need for detailed clinical approaches to prevent musculoskeletal disabilities, including fragility fractures, in this population.