The role of community pharmacists and their perception towards antimicrobial stewardship in Baghdad, Iraq.

Background: This study aimed to assess the role of community pharmacists and their perception toward antimicrobial stewardship, in addition to identifying factors influencing their perception and practices in community pharmacy. Methods: A cross-sectional study was carried out among community pharmacists regarding antimicrobial stewardship. Convenience sampling was used to obtain the required sample from a community pharmacy in Baghdad. In total, 381 participants have completed the survey. Results: The majority of the participants (85.6%) strongly agreed/agreed that "antimicrobial stewardship programs reduce the problems of antibiotic resistance"; and 85.5% of them strongly agreed/agreed that community pharmacists required adequate training on antibiotics use. In addition, high percent of community pharmacists (88.4%) strongly agreed/agreed that pharmacists have a responsibility to take a prominent role in antimicrobial stewardship programs and infection-control programs in the health system. The total score of perception was significantly influenced by older age groups, postgraduate degrees, and experience of 6-10 years (p < 0.001). This study also showed that 65.4% of pharmacists always/often advise patients to continue the full course of antimicrobials, and 64.9% of them reported always/often considering clinical and safety parameters before dispensing antibiotics. The role of pharmacists was significantly influenced by the younger age group, females, higher degree in pharmacy, experience of 3-5 years, and medical complex pharmacy (p < 0.001). Conclusion: Community pharmacists have a good perception toward antimicrobial stewardship programs, but their role is still limited. More efforts are needed to design better strategies for antimicrobial stewardship in community pharmacy.

The Long-Term Effect of Weight Loss on the Prevention of Progression to Cirrhosis among Patients with Obesity and MASH-Related F3 Liver Fibrosis.

This multi-center retrospective study examined the effect of weight loss on the prevention of progression to cirrhosis in a sample exclusively composed of patients with obesity and MASH-related F3 liver fibrosis. Adult patients with obesity and biopsy-confirmed MASH-related F3 liver fibrosis (n = 101) from two liver transplant centers in the US were included in the study. A higher proportion of patients who did not progress to cirrhosis achieved >5% weight loss at follow-up (59% vs. 30%, p = 0.045). In multivariable analysis, patients with >5% weight loss at follow-up had a lower hazard of developing cirrhosis compared to patients with no weight loss or weight gain (HR: 0.29, 95%, CI: 0.08-0.96); whereas, diabetes (HR: 3.24, 95%, CI: 1.21-8.67) and higher LDL levels (HR: 1.02, 95%, CI: 1.01-1.04) were associated with higher hazards of progression to cirrhosis. Weight loss >5% has the potential to prevent disease progression to cirrhosis in patients with obesity and MASH-related F3 liver fibrosis. The realization of this benefit requires weight loss maintenance longer than one year. Larger prospective studies are needed to determine how weight loss impacts other patient-centered outcomes such as mortality, hepatic decompensation, and hepatocellular carcinoma in patients with obesity and MASH-related F3 liver fibrosis.

Hepatitis C viremic lung transplantation to aviremic recipients: Comprehensive outcomes and post-transplant viremia.

BACKGROUND/AIMS: Direct-acting antiviral (DAA) therapy has revolutionized solid organ transplantation by providing an opportunity to utilize organs from HCV-viremic donors. Though transplantation of HCV-viremic donor organs into aviremic recipients is safe in the short term, midterm data on survival and post-transplant complications is lacking. We provide a midterm assessment of complications of lung transplantation (LT) up to 2 years post-transplant, including patient and graft survival between HCV-viremic transplantation (D+) and HCV-aviremic transplantation (D-). METHODS: This is a retrospective cohort study including 500 patients from 2018 to 2022 who underwent LT at our quaternary care institution. Outcomes of patients receiving D+ grafts were compared to those receiving D- grafts. Recipients of HCV antibody+ but PCR- grafts were treated as D- recipients. RESULTS: We identified 470 D- and 30 D+ patients meeting inclusion criteria. Crude mortality did not differ between groups (p = .43). Patient survival at years 1 and 2 did not differ between D+ and D- patients (p = .89, p = .87, respectively), and graft survival at years 1 and 2 did not differ between the two groups (p = .90, p = .88, respectively). No extrahepatic manifestations or fibrosing cholestatic hepatitis (FCH) occurred among D+ recipients. D+ and D- patients had similar rates of post-transplant chronic lung allograft rejection (CLAD) (p = 6.7% vs. 12.8%, p = .3), acute cellular rejection (60.0% vs. 58.0%, p = .8) and antibody-mediated rejection (16.7% vs. 14.2%, p = .7). CONCLUSION: There is no difference in midterm patient or graft survival between D+ and D-LT. No extrahepatic manifestations of HCV occurred. No differences in any type of rejection including CLAD were observed, though follow-up for CLAD was limited. These results provide additional support for the use of HCV-viremic organs in selected recipients in LT.

Post liver transplant short term and survival outcomes in patients living with obesity.

The objectives of our study were to examine and compare patient and graft survival over a 5-year period across BMI groups, and examine immediate and short-term complications post-LT. This was a retrospective study that examined all liver transplants that occurred at our institution between January 2015-October 2022. Patients were divided into 4 BMI groups (n = 888): normal-overweight (BMI 18.5- 29.9 kg/m2), class I obesity (BMI 30-34.9 kg/m2), class II obesity (BMI 35-39.9 kg/m2), and class III obesity (BMI ≥40 kg/m2) patients. Kaplan Meier curves with the log rank test were created to assess survival outcomes and multivariate Cox regression analysis was performed. Patient and graft survival did not differ statistically between each BMI group. However, patient survival was significantly lower in patients with BMI ≥40 compared to patients with BMI <40. In multivariate analysis, BMI ≥40, admission to the ICU, and age were independent predictors of increased risk of mortality. Infection, arrhythmia, cardiac arrest, and myocardial infarction were more frequent immediate complications in the class III obesity group. Efforts to closely monitor patients with BMI ≥40 post LT to maximize survival are needed. Further studies are needed to improve post LT survival among patients with BMI ≥40.

Comparison of fungal vs bacterial infections in the medical intensive liver unit: Cause or corollary for high mortality?

BACKGROUND: Due to development of an immune-dysregulated phenotype, advanced liver disease in all forms predisposes patients to sepsis acquisition, including by opportunistic pathogens such as fungi. Little data exists on fungal infection within a medical intensive liver unit (MILU), particularly in relation to acute on chronic liver failure. AIM: To investigate the impact of fungal infections among critically ill patients with advanced liver disease, and compare outcomes to those of patients with bacterial infections. METHODS: From our prospective registry of MILU patients from 2018-2022, we included 27 patients with culture-positive fungal infections and 183 with bacterial infections. We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts. Data was extracted through chart review. RESULTS: All fungal infections were due to Candida species, and were most frequently blood isolates. Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort (93% vs 52%, P < 0.001). The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure (ACLF) (90% vs 64%, P = 0.02). Patients in the fungal cohort had increased use of vasopressors (96% vs 70%, P = 0.04), mechanical ventilation (96% vs 65%, P < 0.001), and dialysis due to acute kidney injury (78% vs 52%, P = 0.014). On MILU admission, the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation (108 vs 91, P = 0.003), Acute Physiology Score (86 vs 65, P = 0.003), and Model for End-Stage Liver Disease-Sodium scores (86 vs 65, P = 0.041). There was no significant difference in the rate of central line use preceding culture (52% vs 40%, P = 0.2). Patients with fungal infection had higher rate of transplant hold placement, and lower rates of transplant; however, differences did not achieve statistical significance. CONCLUSION: Mortality was worse among patients with fungal infections, likely attributable to severe ACLF development. Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.

Assessing Tissue Damage Around a Tape Spring Steerable Needle With Sharp Turn Radii.

Steerable needles are a novel technology that offers a wide range of uses in medical diagnostics and therapeutics. Currently, there exist several steerable needle designs in the literature, however, they are limited in their use by the number of possible turns, turn radius, and tissue damage. We introduce a novel design of a tape spring steerable needle, capable of multiple turns, that minimizes tissue damage. In this study, we measure the turning radius of our steerable needle in porcine liver tissue in vitro with ultrasound and estimate tissue damage in gel blocks using image analysis and 3D plaster casting. We were able to demonstrate our steerable needle's ability to steer through biological tissue, as well as introduce a novel method for estimating tissue damage. Our findings show that our needle design showed lower damage compared to similar designs in literature, as well as tissue stiffness being a protective factor against tissue damage.

Stem Cell Origin of Cancer: Clinical Implications beyond Immunotherapy for Drug versus Therapy Development in Cancer Care.

Although immunotherapy has revolutionized cancer care, there is still an urgent need to enhance its efficacy and ensure its safety. A correct cancer theory and proper scientific method empower pertinent cancer research and enable effective and efficient drug versus therapy development for patient care. In this perspective, we revisit the concept of immune privilege in a cancer cell versus normal cell, as well as in a cancer stem cell versus normal stem cell. We re-examine whether effective immunotherapies are efficacious due to their anti-cancer and/or immune modulatory mechanisms. We reassess why checkpoint inhibitors (CPIs) are not equal. We reconsider whether one can attribute the utility of immunotherapy to specific cancer subtypes and its futility to certain tumor/immune compartments, components, and microenvironments. We propose ways and means to advance immunotherapy beyond CPIs by combining anti-PD1/L1 with various other treatment modalities according to an appropriate scientific theory, e.g., stem cell origin of cancer, and based on available clinical evidence, e.g., randomized clinical trials. We predict that a stem cell theory of cancer will facilitate the design of better and safer immunotherapy with improved selection of its use for the right patient with the right cancer type at the right time to optimize clinical benefits and minimize potential toxic effects and complications.

Process optimization for gold nanoparticles biosynthesis by Streptomyces albogriseolus using artificial neural network, characterization and antitumor activities.

Gold nanoparticles (GNPs) are highly promising in cancer therapy, wound healing, drug delivery, biosensing, and biomedical imaging. Furthermore, GNPs have anti-inflammatory, anti-angiogenic, antioxidants, anti-proliferative and anti-diabetic effects. The present study presents an eco-friendly approach for GNPs biosynthesis using the cell-free supernatant of Streptomyces albogriseolus as a reducing and stabilizing agent. The biosynthesized GNPs have a maximum absorption peak at 540 nm. The TEM images showed that GNPs ranged in size from 5.42 to 13.34 nm and had a spherical shape. GNPs have a negatively charged surface with a Zeta potential of - 24.8 mV. FTIR analysis identified several functional groups including C-H, -OH, C-N, amines and amide groups. The crystalline structure of GNPs was verified by X-ray diffraction and the well-defined and distinct diffraction rings observed by the selected area electron diffraction analysis. To optimize the biosynthesis of GNPs using the cell-free supernatant of S. albogriseolus, 30 experimental runs were conducted using central composite design (CCD). The artificial neural network (ANN) was employed to analyze, validate, and predict GNPs biosynthesis compared to CCD. The maximum experimental yield of GNPs (778.74 µg/mL) was obtained with a cell-free supernatant concentration of 70%, a HAuCl4 concentration of 800 µg/mL, an initial pH of 7, and a 96-h incubation time. The theoretically predicted yields of GNPs by CCD and ANN were 809.89 and 777.32 µg/mL, respectively, which indicates that ANN has stronger prediction potential compared to the CCD. The anticancer activity of GNPs was compared to that of doxorubicin (Dox) in vitro against the HeP-G2 human cancer cell line. The IC50 values of Dox and GNPs-based treatments were 7.26 ± 0.4 and 22.13 ± 1.3 µg/mL, respectively. Interestingly, treatments combining Dox and GNPs together showed an IC50 value of 3.52 ± 0.1 µg/mL, indicating that they targeted cancer cells more efficiently.

Erythrocyte PIG-A mutant frequencies in cancer patients receiving cisplatin.

BACKGROUND: Cisplatin is a primary chemotherapy choice for various solid tumors. DNA damage caused by cisplatin results in apoptosis of tumor cells. Cisplatin-induced DNA damage, however, may also result in mutations in normal cells and the initiation of secondary malignancies. In the current study, we have used the erythrocyte PIG-A assay to evaluate mutagenesis in non-tumor hematopoietic tissue of cancer patients receiving cisplatin chemotherapy. METHODS: Twenty-one head and neck cancer patients undergoing treatment with cisplatin were monitored for the presence of PIG-A mutant total erythrocytes and the young erythrocytes, reticulocytes (RETs), in peripheral blood for up to five and a half months from the initiation of the anti-neoplastic chemotherapy. RESULTS: PIG-A mutant frequency (MF) in RETs increased at least two-fold in 15 patients at some point of the monitoring, while the frequency of total mutant RBCs increased at least two-fold in 6 patients. A general trend for an increase in the frequency of mutant RETs and total mutant RBCs was observed in 19 and 18 patients, respectively. Only in one patient did both RET and total RBC PIG-A MFs did not increase at any time-point over the monitoring period. CONCLUSION: Cisplatin chemotherapy induces moderate increases in the frequency of PIG-A mutant erythrocytes in head and neck cancer patients. Mutagenicity measured with the flow cytometric PIG-A assay may serve as a tool for predicting adverse outcomes of genotoxic antineoplastic therapy.

A comparison between patients with various etiologies of cirrhosis and examination of cardiac risk factors limiting survival to liver transplantation.

BACKGROUND & AIMS: Objectives of this retrospective cohort study were to assess differences in patient survival between etiologies of cirrhosis while on the waitlist for liver transplantation (LT), and to identify cardiac risk factors that predict survival failure while on the waitlist for LT. METHODS: This single-center retrospective cohort design included adult patients who were listed for LT at a tertiary academic hospital with a high-volume liver transplant center. RESULTS: Of the 653 patients listed for LT during the study period, 507 (77.6%) survived to transplant and 146 (22.4%) died or clinically deteriorated prior to transplant. Cumulative incidence of death or clinical deterioration did not differ statistically between patient groups (log rank p = .11). In multivariate analysis, compared to patients with NAFLD, there were no significant differences between patients with alcoholic cirrhosis (HR .95, 95%, CI, .62-1.45), cryptogenic cirrhosis (HR 1.31, 95%, CI, .77-2.23), or hepatitis C cirrhosis (HR 1.12, 95%, CI, .66-1.90). However, higher MELD scores (HR = 1.52, 95% CI, 1.12-1.19), severe coronary artery disease (HR = 2.09 95% CI, 1.23-3.55), and tricuspid regurgitation (HR = 2.62, 95% CI, 1.31-5.26) were independently associated with increased risk for survival failure to LT. CONCLUSIONS: The presence of severe coronary artery disease and tricuspid regurgitation at the time of listing for transplant are associated with survival failure while on the LT waitlist across etiologies of liver disease. Diagnostic assessment of coronary and valvular disease should be considered in all patients undergoing evaluation for LT, such as cardiac catheterization and/or stress echocardiogram.

Thromboelastography characteristics in critically ill patients with liver disease.

OBJECTIVE: The purpose of this study was to determine how thromboelastography (TEG) parameters differ by various clinical conditions that commonly occur in patients with cirrhosis, including sepsis, acute on chronic liver failure (ACLF), alcohol-associated hepatitis (AAH) and portal vein thrombosis (PVT). BACKGROUND: TEG, a whole blood assay, is used to assess several parameters of coagulation and is becoming increasingly used in clinical practice. STUDY: This study was a retrospective chart review of 155 patients admitted to the ICU with decompensated cirrhosis from 2017 to 2019. RESULTS: The R time was significantly shorter in patients when they were septic compared to when they were not and longer in patients with vs. without ACLF grade 3. Alpha angle and maximum amplitude was decreased in patients with severe AAH compared to those without severe AAH; and maximum amplitude was increased in patients with acute PVT compared to those with chronic PVT. R time was positively correlated with Chronic Liver Failure Consortium Organ Failure and Chronic Liver Failure Consortium ACLF scores (rho = 0.22, P = 0.020), while alpha angle and maximum amplitude were negatively correlated with MELD-NA. CONCLUSION: Findings suggest TEG parameters vary in several clinical conditions in patients with decompensated cirrhosis who are admitted to the ICU. Prospective research is needed to confirm our findings and to determine how this knowledge can be used to guide clinical practice, as well as blood product transfusions in the setting of bleeding or prior to invasive procedures.

Per-patient Negative Predictive Value of the CT and MRI Liver Imaging Reporting and Data System Version 2018 Treatment Response Algorithm for Hepatocellular Carcinoma.

Background The Liver Imaging Reporting and Data System version 2018 (LI-RADS) treatment response algorithm (TRA) is a high-specificity, lower-sensitivity grading system to diagnose hepatocellular carcinoma (HCC) and recurrence after local-regional therapy. However, the emphasis on specificity can result in disease understaging, potentially leading to poorer posttransplant outcomes. Purpose To determine the negative predictive value (NPV) of pretransplant CT and MRI assessment for viable HCC on a per-patient basis using the LI-RADS TRA, considering explant pathology as the reference standard. Materials and Methods Patient records from 218 consecutive adult patients from a single institution with HCC who underwent liver transplant from January 2011 to November 2017 were retrospectively reviewed. Two readers blinded to the original report reviewed immediate (within 90 days) pretransplant imaging and characterized observations according to the LI-RADS TRA. Based on this, patients with LR-4, LR-5, or LR-TR (treatment response) viable tumors were designated as viable tumor; patients with solely LR-3 or LR-TR equivocal tumors were designated as equivocal; and patients with only LR-TR nonviable lesions were designated as no viable disease. Patients were designated as within or outside the Milan criteria. These per-patient designations were compared with the presence of viable disease at explant pathology. Fisher exact test was used to compare the differences between CT and MRI. Weighted κ values were used to calculate interreader reliability. Results Final study sample consisted of 206 patients (median age, 61 years [IQR, 57-65 years]; 157 male patients and 49 female patients). Per-patient LI-RADS TRA assessment of pretransplant imaging had an NPV of 32% (95% CI: 27, 38) and 26% (95% CI: 20, 33) (readers 1 and 2, respectively) for predicting viable disease. Seventy-five percent (reader 1) and 77% (reader 2) of patients deemed equivocal had residual tumors at explant pathology. Weighted interreader reliability was substantial (κ = 0.62). Conclusion Patient-based stratification of viable, equivocal, and nonviable disease at pretransplant CT or MRI, based on LI-RADS TRA, demonstrated low negative predictive value in excluding HCC at explant pathology. © RSNA, 2023 See also the editorial by Tamir and Tau in this issue.

Racial Disparities in Candidates for Hepatocellular Carcinoma Liver Transplant After 6-Month Wait Policy Change.

Importance: Racial disparities in liver transplant (LT) for hepatocellular carcinoma (HCC) may be associated with unequal access to life-saving treatment. Objective: To quantify racial disparities in LT for HCC and mortality after LT, adjusting for demographic, clinical, and socioeconomic factors. Design, Setting, and Participants: This cohort study was a retrospective analysis of United Network Organ Sharing/Organ Procurement Transplant Network (OPTN) data from 2003 to 2021. Participants were adult patients with HCC on the LT waiting list and those who received LT. Data were analyzed from March 2022 to September 2023. Exposures: Race and time before and after the 2015 OPTN policy change. Main Outcomes and Measures: Proportion of LT from wait-listed candidates, the proportion of waiting list removals, and mortality after LT. Results: Among 12 031 patients wait-listed for LT with HCC (mean [SD] age, 60.8 [7.4] years; 9054 [75.3%] male; 7234 [60.1%] White, 2590 [21.5%] Latinx/o/a, and 1172 [9.7%] Black or African American), this study found that after the 2015 model of end-stage liver disease (MELD) exception policy changes for HCC (era 2), the overall proportion of LT for HCC across all races decreased while the proportion of dropouts on the LT waiting list remained steady compared with patients who did not have HCC. In Kaplan-Meier analysis, Asian patients demonstrated the lowest dropout rates in both era 1 and era 2 (1-year dropout, 16% and 17%, respectively; P < .001). In contrast, Black or African American patients had the highest dropout rates in era 1 (1-year dropout, 24%), but comparable dropout rates (23%) with White patients (23%) and Latinx/o/a patients in era 2 (23%). In both eras, Asian patients had the highest survival after LT (5-year survival, 82% for era 1 and 86% for era 2), while Black or African American patients had the worst survival after LT (5-year survival, 71% for era 1 and 79% for era 2). In the multivariable analysis for HCC LT recipients, Black or African American race was associated with increased risk of mortality in both eras, compared with White race (HR for era 1, 1.17; 95% CI, 1.05-1.35; and HR for era 2, 1.31; 95% CI, 1.10-1.56). Conclusions and Relevance: This cohort study of LT candidates in the US found that after the 2015 MELD exception policy change for HCC, the proportion of LT for HCC had decreased for all races. Black or African American patients had worse outcomes after LT than other races. Further research is needed to identify the underlying causes of this disparity and develop strategies to improve outcomes for HCC LT candidates.

Screening Modalities for Coronary Artery Disease in Liver Transplant Candidates: A Review of the Literature.

Patients with cirrhosis undergoing liver transplant (LT) are at high risk of postoperative cardiopulmonary complications. It is known that patients with coronary artery disease (CAD) have greater rates of post-LT morbidity and mortality than patients without CAD. Thus, identifying significant CAD in LT candidates is of the utmost importance to optimize survival posttransplant. Consensus is lacking on the ideal screening test for CAD in LT candidates. Traditional exercise and many pharmacologic stress tests are impractical and inaccurate in patients with cirrhosis due to their unique physiology. The purpose of this review is to describe different screening modalities for CAD among LT candidates. The background, diagnostic accuracy, and limitations of each screening modality are described to achieve this goal.

CRISPR-based knockout and base editing confirm the role of MYRF in heart development and congenital heart disease.

High-throughput DNA sequencing studies increasingly associate DNA variants with congenital heart disease (CHD). However, functional modeling is a crucial prerequisite for translating genomic data into clinical care. We used CRISPR-Cas9-mediated targeting of 12 candidate genes in the vertebrate model medaka (Oryzias latipes), five of which displayed a novel cardiovascular phenotype spectrum in F0 (crispants): mapre2, smg7, cdc42bpab, ankrd11 and myrf, encoding a transcription factor recently linked to cardiac-urogenital syndrome. Our myrf mutant line showed particularly prominent embryonic cardiac defects recapitulating phenotypes of pediatric patients, including hypoplastic ventricle. Mimicking human mutations, we edited three sites to generate specific myrf single-nucleotide variants via cytosine and adenine base editors. The Glu749Lys missense mutation in the conserved intramolecular chaperon autocleavage domain fully recapitulated the characteristic myrf mutant phenotype with high penetrance, underlining the crucial function of this protein domain. The efficiency and scalability of base editing to model specific point mutations accelerate gene validation studies and the generation of human-relevant disease models.

Artificial neural network approach for prediction of AuNPs biosynthesis by Streptomyces flavolimosus, characterization, antitumor potency in-vitro and in-vivo against Ehrlich ascites carcinoma.

Gold nanoparticles (AuNPs) have emerged as promising and versatile nanoparticles for cancer therapy and are widely used in drug and gene delivery, biomedical imaging, diagnosis, and biosensors. The current study describes a biological-based strategy for AuNPs biosynthesis using the cell-free supernatant of Streptomyces flavolimosus. The biosynthesized AuNPs have an absorption peak at 530-535 nm. The TEM images indicate that AuNPs were spherical and ranged in size from 4 to 20 nm. The surface capping molecules of AuNPs are negatively charged, having a Zeta potential of - 10.9 mV. FTIR analysis revealed that the AuNPs surface composition contains a variety of functional groups as -OH, C-H, N-, C=O, NH3+, amine hydrochloride, amide group of proteins, C-C and C-N. The bioprocess variables affecting AuNPs biosynthesis were optimized by using the central composite design (CCD) in order to maximize the AuNPs biosynthesis. The maximum yield of AuNPs (866.29 µg AuNPs/mL) was obtained using temperature (35 °C), incubation period (4 days), HAuCl4 concentration (1000 µg/mL) and initial pH level 6. Comparison was made between the fitness of CCD versus Artificial neural network (ANN) approach based on their prediction and the corresponding experimental results. AuNPs biosynthesis values predicted by ANN exhibit a more reasonable agreement with the experimental result. The anticancer activities of AuNPs were assessed under both in vitro and in vivo conditions. The results revealed a significant inhibitory effect on the proliferation of the MCF-7 and Hela carcinoma cell lines treated with AuNPs with IC50 value of 13.4 ± 0.44 µg/mL and 13.8 ± 0.45 µg/mL for MCF-7 and Hela cells; respectively. Further, AuNPs showed potential inhibitory effect against tumor growth in tumor-bearing mice models. AuNPs significantly reduced the tumor volume, tumor weight, and decreased number of viable tumor cells in EAC bearing mice.

Association between echocardiographic features and inflammatory biomarkers with clinical outcomes in COVID-19 patients in Saudi Arabia.

Background: Respiratory infections are one of the most common comorbidities identified in hospitalized patients. The coronavirus disease 2019 (COVID-19) pandemic greatly impacted healthcare systems, including acute cardiac services. Aim: This study aimed to describe the echocardiographic findings of patients with COVID-19 infections and their correlations with inflammatory biomarkers, disease severity, and clinical outcomes. Methods: This observational study was conducted between June 2021 and July 2022. The analysis included all patients diagnosed with COVID-19 who had transthoracic echocardiographic (TTE) scans within 72 h of admission. Results: The enrolled patients had a mean age of 55.6 ± 14.7 years, and 66.1% were male. Of the 490 enrolled patients, 203 (41.4%) were admitted to the intensive care unit (ICU). Pre-ICU TTE findings showed significantly higher incidence right ventricular dysfunction (28 [13.8%] vs. 23 [8.0%]; P = 0.04) and left ventricular (LV) regional wall motion abnormalities (55 [27.1%] vs. 29 [10.1%]; p < 0.001) in ICU patients compared to non-ICU patients. In-hospital mortality was 11 (2.2%), all deaths of ICU patients. The most sensitive predictors of ICU admission (p < 0.05): cardiac troponin I level (area under the curve [AUC] = 0.733), followed by hs-CRP (AUC = 0.620), creatine kinase-MB (AUC = 0.617), D-dimer (AUC = 0.599), and lactate dehydrogenase (AUC = 0.567). Binary logistic regression showed that reduced LV ejection fraction (LVEF), elevated pulmonary artery systolic pressure, and dilated right ventricle were echocardiographic predictors of poor outcomes (p < 0.05). Conclusion: Echocardiography is a valuable tool in assessing admitted patients with COVID-19. Lower LVEF, pulmonary hypertension, higher D-dimer, C-reactive protein, and B-type natriuretic peptide levels were predictors of poor outcomes.

Efficacy of Perioperative Intravenous Dexamethasone on Postoperative Analgesia in Scleral Buckle Surgery: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVE: Postoperative pain is frequently reported following scleral buckle (SB) surgery. This study assessed the efficacy of perioperative dexamethasone on postoperative pain and opioid use following SB. MATERIALS AND METHODS: Forty-five patients with rhegmatogenous retinal detachments undergoing SB or SB and pars plana vitrectomy were randomly assigned to either standard care of postoperative oral acetaminophen and oxycodone/acetaminophen as needed or standard care plus 8 mg single-dose peri-operative intravenous dexamethasone. A questionnaire was administered on postoperative days 0, 1, and 7 to determine visual analog scale 0 to 10 pain score and number of opioid tablets consumed. RESULTS: Mean visual analog scale score and opioid use were significantly lower in the dexamethasone group on postoperative day 0 compared with control (2.76 ± 1.96 vs 5.64 ± 3.40, P = 0.002; 0.41 ± 0.92 vs 1.34 ± 1.43, P = 0.016). The dexamethasone group also demonstrated significantly lower total opioid use (0.97 ± 1.88 vs 3.69 ± 5.32, P = 0.047). No significant differences in pain score or opioid use were observed on days 1 or 7 (P = 0.078; P = 0.311; P = 0.326; P = 0.334). CONCLUSION: Single-dose intravenous dexamethasone following SB can significantly reduce postoperative pain and opioid use. [Ophthalmic Surg Lasers Imaging Retina 2023;54:238-242.].

Impact of nonalcoholic fatty liver disease on clinical outcomes in patients with COVID-19 among persons living with HIV: A multicenter research network study.

BACKGROUND: People living with human immunodeficiency virus (PLWH) are at an increased risk of nonalcoholic fatty liver disease (NAFLD) but how these patients react to COVID-19 infection is unclear. We examined the clinical characteristics and outcomes of patients with and without nonalcoholic fatty liver disease (NAFLD) among people living with human immunodeficiency virus (PLWH) diagnosed with COVID-19. METHODS: A multicenter, retrospective cohort study was conducted using TriNetX. Participants diagnosed with COVID-19 between January 20, 2020, and October 31, 2021, in PLWH were identified and divided into cohorts based on preexisting NAFLD. The primary outcome was all-cause mortality, and secondary outcomes were hospitalization, severe disease, critical care, need for mechanical ventilation, and acute kidney injury(AKI). Propensity score matching (PSM) mitigated the imbalance among group covariates. Risk ratios (RR) with 95 % confidence intervals (CI) were calculated. RESULTS: Of the 5012 PLWH identified with confirmed COVID-19 during the study period, 563 had a diagnosis of NAFLD. After PSM, both groups were well-matched with 561 patients. The primary outcome did not differ between the cohorts at 30-days, even after a fully adjusted analysis, and the risk of all-cause mortality did not differ at 60 and 90 days. NAFLD had a significantly higher risk for hospitalization rates (RR 1.32; 95 % CI, 1.06-1.63) and AKI (RR 2.55; 95 % CI 1.42-4.57) than the non-NAFLD group at 30 days. No other differences were detected in other secondary outcome measures. CONCLUSIONS: Preexisting NAFLD is associated with an increased risk for hospitalization and AKI among PLWH infected with COVID-19. The potential role of NAFLD in developing severe COVID-19 among PLWH remains to be elucidated in future studies. Still, this study indicates the need for careful monitoring of this at-risk population.

Risk of adverse cardiovascular outcomes among people with HIV and nonalcoholic fatty liver disease.

OBJECTIVE: To examine and compare the risk of major adverse cardiovascular events (MACEs) between people with HIV (PWH) with and without nonalcoholic fatty liver disease (NAFLD). DESIGN: Population-based, multicenter, retrospective cohort study. METHODS: Data on PWH between January 1, 2008, and December 31, 2020 were extracted from the TriNetX database. Primary outcomes were defined as the first incidence of myocardial infarction (MI), MACE, new-onset heart failure (HF), and a composite of cerebrovascular disease. Cox models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 151 868 patients were identified as having HIV. After exclusions, 4969 patients were identified as having NAFLD. Of them, 4463 (90%) were propensity matched to a non-NAFLD control. Patients with NAFLD were older (42.9 versus 40.8 years). Among the NAFLD cohort, most participants were male and had a smoking history (12.3 versus 9.8%) than non-NAFLD. The mean follow-up was 4.8 ±â€Š1.1 years for the NAFLD group and 5.3 ±â€Š1.2 years for the non-NAFLD group. The risk of all outcomes was statistically significantly higher in NAFLD patients compared to those without NAFLD: MI (HR, 1.49; 95% CI, 1.11-2.01) MACE (HR, 1.49; 95% CI, 1.25-1.79), HF (HR, 1.73; 95% CI 1.37-2.19) and, cerebrovascular diseases (HR, 1.25; 95% CI, 1.05-1.48) and sensitivity analysis showed similar magnitude to the one generated in the primary analysis. CONCLUSIONS: Patients with NAFLD have an elevated risk of adverse cardiovascular events (CVEs). The results indicate the need for targeted efforts to improve awareness of risks factors associated with adverse CVEs risk in PWH with NAFLD.