Comparison of Surgical or Medical Castration-Related Cardiotoxicity in Patients with Prostate Cancer.

PURPOSE: Androgen deprivation therapy (ADT) includes bilateral orchiectomy or long-acting gonadotropin-releasing hormone (GnRH) agonists/antagonists. It remains controversial with respect to ADT associated cardiovascular outcomes. Hereby, we compared the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with prostate cancer receiving either surgical castration or GnRH therapies. MATERIALS AND METHODS: Using the Taiwan Cancer Registry and Taiwan's National Health Insurance Research Database, we identified 8,413 patients receiving GnRH therapies compared with 694 receiving surgical castration from 2008 to 2017. The median followup duration was 3 years. RESULTS: The crude incidences of 3-year mortality and MACCEs were 19.90% vs 26.51% and 8.23% vs 8.65% in patients receiving GnRH therapies or surgical castration, respectively. After adjusting for age, cancer stage and comorbidities, despite no significant differences in MACCEs between groups there was a slight increase in the incidence of acute myocardial infarction (AMI) in patients receiving surgical castration compared with those receiving GnRH therapies. The mortality adjusted hazard ratios of MACCEs and AMI among patients receiving surgical castration were 1.11- and 1.8-fold higher than those receiving GnRH therapies. Notably, in subgroup analysis regarding cancer stage, patients with cancer stage IV showed the most significantly increasing risk of AMI in those receiving surgical castration compared with GnRH therapies. CONCLUSIONS: Collectively, we indicated an increased risk of AMI in patients with prostate cancer, especially in patients receiving surgical castration rather than those receiving GnRH therapies. Our findings highlight concerns regarding the cardiac safety of surgical castration compared with GnRH therapies.

Dapagliflozin protects against doxorubicin-induced cardiotoxicity by restoring STAT3.

Doxorubicin (Dox), an effective therapy in different types of cancer, is known to exhibit cardiotoxic effects. Despite previous studies indicating the benefits of dapagliflozin (DAPA) in patients experiencing heart failure, it remains uncertain whether DAPA exerts a protective effect on Dox-induced cardiac dysfunction. Signal transducer and activator of transcription 3 (STAT3) participates in various mechanisms of cardioprotection. Herein, we aimed to investigate the effects of DAPA on Dox-induced cardiotoxicity and the role of STAT3. Sprague-Dawley rats were pretreated with oral DAPA for 6 weeks followed by Dox for 4 weeks. Sequential echocardiography was applied to assess cardiac function. For in vitro analysis, cardiomyocytes were treated with 10 µM DAPA and subsequently exposed to 1 µM Dox. The expression of reactive oxygen species- and apoptosis-related proteins was measured. Using STAT3 siRNA, we further examined the effects of STAT3 effect on DAPA-associated protection against Dox-induced apoptosis. In rats treated with Dox, DAPA significantly reduced cardiac fibrosis and improved cardiac function and hemodynamics. Additionally, DAPA effectively inhibited Dox-induced apoptosis and reactive oxygen species (ROS) in cardiomyocytes. Mechanistically, we showed that DAPA decreased cardiac expression of Bax and cleaved caspase 3 but increased Bcl-2 expression. DAPA also significantly rescued Dox-suppressed STAT3 expression. Conversely, knocking down STAT3 in cardiomyocytes reversed the DAPA-related protective effects on Dox-induced cell apoptosis and ROS. Collectively, our findings indicate that DAPA could be useful for preventing Dox-induced cardiotoxicity by restoring STAT3.

Vancomycin-Associated Acute Kidney Injury: A Narrative Review from Pathophysiology to Clinical Application.

Vancomycin is the most frequently used antibiotic, accounting for up to 35% of hospitalized patients with infection, because of its optimal bactericidal effectiveness and relatively low price. Vancomycin-associated AKI (VA-AKI) is a clinically relevant but not yet clearly understood entity in critically ill patients. The current review comprehensively summarizes the pathophysiological mechanisms of, biomarkers for, preventive strategies for, and some crucial issues with VA-AKI. The pathological manifestations of VA-AKI include acute tubular necrosis, acute tubulointerstitial nephritis (ATIN), and intratubular crystal obstruction. The proposed pathological mechanisms of VA-AKI include oxidative stress and allergic reactions induced by vancomycin and vancomycin-associated tubular casts. Concomitant administration with other nephrotoxic antibiotics, such as piperacillin-tazobactam, high vancomycin doses, and intermittent infusion strategies compared to the continuous infusion are associated with a higher risk of VA-AKI. Several biomarkers could be applied to predict and diagnose VA-AKI. To date, no promising therapy is available. Oral steroids could be considered for patients with ATIN, whereas hemodialysis might be applied to remove vancomycin from the patient. In the future, disclosing more promising biomarkers that could precisely identify populations susceptible to VA-AKI and detect VA-AKI occurrence early on, and developing pharmacological agents that could prevent or treat VA-AKI, are the keys to improve the prognoses of patients with severe infection who probably need vancomycin therapy.

Acute Kidney Injury and Gut Dysbiosis: A Narrative Review Focus on Pathophysiology and Treatment.

Acute kidney injury (AKI) and gut dysbiosis affect each other bidirectionally. AKI induces microbiota alteration in the gastrointestinal (GI) system, while gut dysbiosis also aggravates AKI. The interplay between AKI and gut dysbiosis is not yet well clarified but worthy of further investigation. The current review focuses on the pathophysiology of this bidirectional interplay and AKI treatment in this base. Both macrophages and neutrophils of the innate immunity and the T helper type 17 cell from the adaptive immunity are the critical players of AKI-induced gut dysbiosis. Conversely, dysbiosis-induced overproduction of gut-derived uremic toxins and insufficient generation of short-chain fatty acids are the main factors deteriorating AKI. Many novel treatments are proposed to deter AKI progression by reforming the GI microbiome and breaking this vicious cycle. Data support the benefits of probiotic treatment in AKI patients, while the results of postbiotics are mainly limited to animals. Prebiotics and synbiotics are primarily discussed in chronic kidney disease patients rather than AKI patients. The effect of adsorbent treatment seems promising, but more studies are required before the treatment can be applied to patients. Immune therapy and some repurposed drugs such as allopurinol are prospects of future treatments and are worth more discussion and survey.

Sepsis and Acute Kidney Injury: A Review Focusing on the Bidirectional Interplay.

Although sepsis and acute kidney injury (AKI) have a bidirectional interplay, the pathophysiological mechanisms between AKI and sepsis are not clarified and worthy of a comprehensive and updated review. The primary pathophysiology of sepsis-associated AKI (SA-AKI) includes inflammatory cascade, macrovascular and microvascular dysfunction, cell cycle arrest, and apoptosis. The pathophysiology of sepsis following AKI contains fluid overload, hyperinflammatory state, immunosuppression, and infection associated with kidney replacement therapy and catheter cannulation. The preventive strategies for SA-AKI are non-specific, mainly focusing on infection control and preventing further kidney insults. On the other hand, the preventive strategies for sepsis following AKI might focus on decreasing some metabolites, cytokines, or molecules harmful to our immunity, supplementing vitamin D3 for its immunomodulation effect, and avoiding fluid overload and unnecessary catheter cannulation. To date, several limitations persistently prohibit the understanding of the bidirectional pathophysiologies. Conducting studies, such as the Kidney Precision Medicine Project, to investigate human kidney tissue and establishing parameters or scores better to determine the occurrence timing of sepsis and AKI and the definition of SA-AKI might be the prospects to unveil the mystery and improve the prognoses of AKI patients.

Warm-water footbath improves dysmenorrhoea and heart rate variability in college students: a randomised controlled trial.

The effect of warm-water footbath in improving dysmenorrhoea has been rarely investigated. The study aimed to examine whether a warm-water footbath effectively reduces dysmenorrhoea pain and improves the autonomic nervous system (ANS) activity. The randomised controlled trial was registered at ClinicalTrials.gov. (NCT04071028) We enrolled college students with dysmenorrhoea in Northern Taiwan from December 1 2013 to June 30 2014, and randomised them into footbath (n = 35, median age 19 years) and control groups (n = 33, 18 years). Pain visual analogue scale and Short-Form McGill Pain Questionnaire were used for pain assessment, while heart rate variability (HRV) was measured to assess ANS function. After the interventions, the footbath group significantly improved ANS activity and reduced pain severity comparing to the control group. Furthermore, the changes in HRV positively correlated with the improvement of pain severity. In conclusion, a warm-water footbath is beneficial in improving the pain severity among college students with dysmenorrhoea.Impact StatementWhat is already known on this subject? Dysmenorrhoea is the most common gynaecological condition affecting 34-94% of young women. The existing conventional therapeutic strategies for dysmenorrhoea have potential adverse events. Among the complementary therapies for pain, the warm-water footbath is a widely used thermal therapy in improving peripheral neuropathy symptoms and improving patients' quality of life. The subjects with dysmenorrhoea associate with significantly altered autonomic nervous system (ANS) activity. However, the association among warm-water footbath, menstrual pain and ANS was rarely investigated previously.What the results of this study add? The randomised controlled trial enrolling 68 college students with dysmenorrhoea found warm-water footbath improved ANS activity and reduced pain severity. Furthermore, the changes in heart rate variability positively correlated with pain severity improvement.What the implications are of these findings for clinical practice and/or further research? A warm-water footbath for 20 minutes on menstruation days 1 and 2 is beneficial in improving pain among college students with dysmenorrhoea.

Predictive Ability of Procalcitonin for Acute Kidney Injury: A Narrative Review Focusing on the Interference of Infection.

Acute kidney injury (AKI) is a common yet complicated clinical entity with high morbidity and mortality. An essential strategy to improve AKI patients' prognoses is finding optimal biomarkers to identify AKI in a timely manner. Procalcitonin (PCT), a well-recognized biomarker for diagnosing infection and guiding antibiotics therapy, has been proposed to predict AKI development and recovery in many clinical settings. The current review provides comprehensive and updated information from relevant studies to evaluate PCT's AKI-predictive ability and the influence of infection on this predictive ability. PCT has demonstrated optimal predictive ability for AKI in various populations irrespective of infection. However, the predictive ability seems to be blunted by infection since infection and inflammation have a more potent influence than AKI on PCT elevation. We furthermore explain the complicated association between elevated PCT levels and AKI in infection and inflammation situations and recommend directions for further investigations to clarify the essential issue. In conclusion, although conflicting data exist, serum PCT level is a potential biomarker for predicting AKI in many clinical settings regardless of infection. Nevertheless, further studies are warranted to clarify the association between PCT, infection, and AKI and to confirm the utilization of PCT for AKI prediction.

Angiotensin-converting enzyme inhibitors attenuated advanced glycation end products-induced renal tubular hypertrophy via enhancing nitric oxide signaling.

Advanced glycation end products (AGE) and angiotensin II were closely correlated with the progression of diabetic nephopathy (DN). Nitric oxide (NO) is a protective mediator of renal tubular hypertrophy in DN. Here, we examined the molecular mechanisms of angiotensin-converting enzyme inhibitor (ACEI) and NO signaling responsible for diminishing AGE-induced renal tubular hypertrophy. In human renal proximal tubular cells, AGE decreased NO production, inducible NOS activity, guanosine 3',5'-cyclic monophosphate (cGMP) synthesis, and cGMP-dependent protein kinase (PKG) activation. All theses effects of AGE were reversed by treatment with ACEIs (captopril and enalapril), the NO donor S-nitroso-N-acetylpenicillamine (SNAP), and the PKG activator 8-para-chlorophenylthio-cGMPs (8-pCPT-cGMPs). In addition, AGE-enhanced activation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) were clearly reduced by captopril, enalapril, SNAP, and 8-pCPT-cGMPs. The abilities of ACEIs and NO/PKG activation to inhibit AGE-induced hypertrophic growth were verified by the observation that captopril, enalapril, SNAP, and 8-pCPT-cGMPs decreased protein levels of fibronectin, p21 Waf1/Cip1 , and receptor for AGE. The results of the present study suggest that ACEIs significantly reduced AGE-increased ERK/JNK/p38 MAPK activation and renal tubular hypertrophy partly through enhancement of the NO/PKG pathway.

MST3 is involved in ENaC-mediated hypertension.

Liddle syndrome is an inherited form of human hypertension caused by increasing epithelial Na+ channel (ENaC) expression. Increased Na+ retention through ENaC with subsequent volume expansion causes hypertension. In addition to ENaC, the Na+-K+-Cl- cotransporter (NKCC) and Na+-Cl- symporter (NCC) are responsible for Na+ reabsorption in the kidneys. Several Na+ transporters are evolutionarily regulated by the Ste20 kinase family. Ste20-related proline/alanine-rich kinase and oxidative stress-responsive kinase-1 phosphorylate downstream NKCC2 and NCC to maintain Na+ and blood pressure (BP) homeostasis. Mammalian Ste20 kinase 3 (MST3) is another member of the Ste20 family. We previously reported that reduced MST3 levels were found in the kidneys in spontaneously hypertensive rats and that MST3 was involved in Na+ regulation. To determine whether MST3 is involved in BP stability through Na+ regulation, we generated a MST3 hypomorphic mutation and designated MST3+/- and MST3-/- mice to examine BP and serum Na+ and K+ concentrations. MST3-/- mice exhibited hypernatremia, hypokalemia, and hypertension. The increased ENaC in the kidney played roles in hypernatremia. The reabsorption of more Na+ promoted more K+ secretion in the kidney and caused hypokalemia. The hypernatremia and hypokalemia in MST3-/- mice were significantly reversed by the ENaC inhibitor amiloride, indicating that MST3-/- mice reabsorbed more Na+ through ENaC. Furthermore, Madin-Darby canine kidney cells stably expressing kinase-dead MST3 displayed elevated ENaC currents. Both the in vivo and in vitro results indicated that MST3 maintained Na+ homeostasis through ENaC regulation. We are the first to report that MST3 maintains BP stability through ENaC regulation.

Urinary biomarkers predict advanced acute kidney injury after cardiovascular surgery.

BACKGROUND: Acute kidney injury (AKI) after cardiovascular surgery is a serious complication. Little is known about the ability of novel biomarkers in combination with clinical risk scores for prediction of advanced AKI. METHODS: In this prospectively conducted multicenter study, urine samples were collected from 149 adults at 0, 3, 6, 12 and 24 h after cardiovascular surgery. We measured urinary hemojuvelin (uHJV), kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL), α-glutathione S-transferase (uα-GST) and π-glutathione S-transferase (uπ-GST). The primary outcome was advanced AKI, under the definition of Kidney Disease: Improving Global Outcomes (KDIGO) stage 2, 3 and composite outcomes were KDIGO stage 2, 3 or 90-day mortality after hospital discharge. RESULTS: Patients with advanced AKI had significantly higher levels of uHJV and uKIM-1 at 3, 6 and 12 h after surgery. When normalized by urinary creatinine level, uKIM-1 in combination with uHJV at 3 h post-surgery had a high predictive ability for advanced AKI and composite outcome (AUC = 0.898 and 0.905, respectively). The combination of this biomarker panel (normalized uKIM-1, uHJV at 3 h post-operation) and Liano's score was superior in predicting advanced AKI (AUC = 0.931, category-free net reclassification improvement of 1.149, and p <  0.001). CONCLUSIONS: When added to Liano's score, normalized uHJV and uKIM-1 levels at 3 h after cardiovascular surgery enhanced the identification of patients at higher risk of progression to advanced AKI and composite outcomes.

Nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study: Design and methods.

AIM: Acute kidney injury (AKI) carries an increasing incidence rate worldwide and increases the risk of developing end-stage renal disease (ESRD) as well as the medical expenses during the post-AKI course. The Taiwan Consortium for Acute Kidney Injury and Renal Diseases (CAKs) has thus launched a nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study, which prospectively enrols critically ill patients with AKI. Through thoroughly evaluating the risk and prognostic factors of AKI, we hope to lower the incidence of AKI and ESRD from the perspective of AKI-ESRD interaction. METHODS: The CAKs includes 30 hospitals which distribute widely through the four geographical regions (north, middle, south, and east) of Taiwan, and have a 1:1 ratio of medical centres to regional hospitals in each region. The NEP-AKI-D study enrols intensive care unit-based AKI patients who receive dialysis in the four seasonal sampled months (October 2014, along with January, April, and July 2015) in the included hospitals. The collected data include demographic information, pertaining laboratory results, dialysis settings and patient outcomes. The data are uploaded in a centre website and will be audited by on-site principal investigators, computer logic gates, and the CAKs staffs. The outcomes of interest are in-hospital mortality, dialysis-dependency and readmission rate within 90 days after discharge. CONCLUSION: The NEP-AKI-D study enrols a large number of representative AKI patients throughout Taiwan. The results of the current study are expected to provide more insight into the risk and prognostic factors of AKI and further attenuated further chronic kidney disease transition.

Renal Protective Effects of Low Molecular Weight of Inonotus obliquus Polysaccharide (LIOP) on HFD/STZ-Induced Nephropathy in Mice.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in diabetes mellitus. Oxidative stress, insulin resistance and pro-inflammatory cytokines have been shown to play an important role in pathogeneses of renal damage on type 2 diabetes mellitus (DM). Inonotus obliquus (IO) is a white rot fungus that belongs to the family Hymenochaetaceae; it has been used as an edible mushroom and exhibits many biological activities including anti-tumor, anti-oxidant, anti-inflammatory and anti-hyperglycemic properties. Especially the water-soluble Inonotus obliquus polysaccharides (IOPs) have been previously reported to significantly inhibit LPS-induced inflammatory cytokines in mice and protect from streptozotocin (STZ)-induced diabetic rats. In order to identify the nephroprotective effects of low molecular weight of IOP fraction (LIOP), from the fruiting bodies of Inonotus obliquus, high-fat diet (HFD) plus STZ-induced type 2-like diabetic nephropathy C57BL/6 mice were investigated in this study. Our data showed that eight weeks of administration of 10-100 kDa, LIOP (300 mg/kg) had progressively increased their sensitivity to glucose (less insulin tolerance), reduced triglyceride levels, elevated the HDL/LDL ratio and decreased urinary albumin/creatinine ratio(ACR) compared to the control group. By pathological and immunohistochemical examinations, it was indicated that LIOP can restore the integrity of the glomerular capsules and increase the numbers of glomerular mesangial cells, associated with decreased expression of TGF-ß on renal cortex in mice. Consistently, three days of LIOP (100 µg/mL) incubation also provided protection against STZ + AGEs-induced glucotoxicity in renal tubular cells (LLC-PK1), while the levels of NF-κB and TGF-ß expression significantly decreased in a dose-dependent manner. Our findings demonstrate that LIOP treatment could ameliorate glucolipotoxicity-induced renal fibrosis, possibly partly via the inhibition of NF-κB/TGF-ß1 signaling pathway in diabetic nephropathy mice.

Rapid identification of bacteria and Candida pathogens in peritoneal dialysis effluent from patients with peritoneal dialysis-related peritonitis by use of multilocus PCR coupled with electrospray ionization mass spectrometry.

PCR coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) was compared with culture for pathogen detection in peritoneal dialysis (PD)-related peritonitis. Of 21 samples of PD effluent, PCR/ESI-MS identified microorganisms in 18 (86%) samples, including Mycobacterium tuberculosis in 1 culture-negative sample. Of 15 double-positive samples, PCR/ESI-MS and culture reached levels of agreement of 100% (15/15) and 87.5% (7/8) at the genus and species levels, respectively. PCR/ESI-MS can be used for rapid pathogen detection in PD-related peritonitis.

Spontaneous bilateral perirenal hemorrhage following prolonged fever: an uncommon presentation of polyarteritis nodosa.

A 68-year-old man presented with a spontaneous bilateral perirenal hemorrhage following a 2-month fever of unknown origin. A renal biopsy for a pathologic diagnosis seemed very risky because of the patient's bilateral perirenal hemorrhage. Therefore, we diagnosed polyarteritis nodosa using an abdominal computed tomography scan, a renal angiogram, and American College of Rheumatology criteria. The patient's multiple symptoms then responded well to the prescribed immunosuppressive regimen. This case is an uncommon presentation of polyarteritis nodosa with fever of unknown origin before a spontaneous bilateral perirenal hemorrhage.

Increased risk of mortality among haemodialysis patients with or without prior stroke: a nationwide population-based study in Taiwan.

BACKGROUND & OBJECTIVES: Patients with prior stroke (PS) undergoing chronic dialysis are at a high risk of mortality. However, little is known about the cumulative risk and survival rate of dialysis patients with long-term follow up. The aim of this study was to assess risks for mortality between patients with and without PS undergoing chronic haemodialysis (HD). METHODS: The Taiwan National Health Insurance Research Database (NHRI-NHIRD-99182) was used and all adult patients (≥18 yr) with end stage renal disease (ESRD) who started maintenance HD between January 1, 1999, and December 31, 1999, were selected. The patients were followed from the first reported date of HD to the date of death, end of dialysis or December 31, 2008. A Cox's proportional hazard model was applied to identify the risk factors for all-cause mortality. RESULTS: Among 5672 HD patients, 650 patients (11.5%) had PS. A higher proportion of stroke history at baseline was found in men (52.8%) and those aged ≥ 55 yr (80.9%). After adjusting for age, sex and other covariates, the patients with PS were found to have a 36 per cent increased risk of mortality compared to those without PS (HR 1.36, 95% CI: 1.22-1.52). The cumulative survival rates among HD patients without PS were 96.0 per cent at the first year, 68.4 per cent at the fifth year, and 46.7 per cent at the ninth year, and 92.9, 47.3 and 23.6 per cent, respectively, in those with PS (log-rank: P<0.001). INTERPRETATION & CONCLUSIONS: Our findings showed that PS was an important predictor for all-cause mortality and poor outcome in patients undergoing chronic HD.

Using Rasch KIDMAP to identify whether China dominates the research area of computer science (CS) based on the specialization index of article citations: Bibliometric analysis.

BACKGROUND: Scientific comparative advantage is measured by using a specialization index (SI) of article citations. The profile data have been published in the literature. However, no such research has been conducted to determine which countries dominate the field of computer science (CS) (subject category [SC]) using the SI. A KIDMAP in the Rasch model has been applied to the display of individual student performance in school. Based on the SI of article citations, we used KIDMAP to determine whether China dominates the field of CS. METHODS: The data were derived from published research in the Web of Science, which included 199 countries and 254 subject categories (SC, between 2010 and 2019). A total of 96 SC related to biomedicine were extracted. We examined 7 factors associated with CS using exploratory factor analysis. Based on the SI in CS under the Rasch model, 1-dimensional SCs on CS were displayed on Wright Maps and KIDMAPs. An analysis of the dominance of CS in China was presented on the basis of a scatter plot. RESULTS: Our findings indicate that (1) CS domains are divided into 2 groups (traditional and advanced domains); (2) no evidence has been found that China dominates CS; based on SI indicators, China was ranked third with --2.62 and 0.79 logits after Taiwan and Slovenia (-(-2.62 and 9.24 logits in Factors 1 and 2) in the period from 2010 to 2019. CONCLUSIONS: There is insufficient evidence to demonstrate that China has a dominant role over other countries/regions despite ranking third in CS. In future studies, it is recommended to include a KIDMAP visual to assess dominant roles in other areas of research, rather than to confine ourselves to CS as we did in this study.

The 95% control lines on both confirmed cases and days of infection with COVID-19 were applied to compare the impact on public health between 2020 and 2021 using the hT-index.

BACKGROUND: COVID-19, the disease caused by the novel coronavirus, is now a worldwide pandemic. The number of infected people has continually increased, and currently, this pandemic continues to present challenges to public health. Scatter plots are frequently used to interpret the impact in relation to confirmed cases. However, the 95% confidence intervals are rarely given to the scatter plot. The objective of this study was to; Develop 95% control lines on daily confirmed cases and infected days for countries/regions in COVID-19 (DCCIDC) and; Examine their impacts on public health (IPH) using the hT-index. METHODS: All relevant COVID-19 data were downloaded from GitHub. The hT-index, taking all DCCIDCs into account, was applied to measure the IPHs for counties/regions. The 95% control lines were proposed to highlight the outliers of entities in COVID-19. The hT-based IPHs were compared among counties/regions between 2020 and 2021 using the choropleth map and the forest plot. The features of the hT-index were explained using the line chart and the box plot. RESULTS: The top 2 countries measured by hT-based IPHs were India and Brazil in 2020 and 2021. The outliers beyond the 95% confidence intervals were Hubei (China), with a lower hT-index favoring 2021 ( = 6.4 in 2021 vs 15.55 in 2020) and higher hT indices favoring 2021 in Thailand (28.34 vs 14,77) and Vietnam (27.05 vs 10.88). Only 3 continents of Africa, Asia, and Europe had statistically and significantly fewer DCCIDCs (denoted by the hT-index) in 2021. The hT-index generalizes the h-index and overcomes the disadvantage without taking all elements (e.g., DCCIDCs) into account in features. CONCLUSIONS: The scatter plot combined with the 95% control lines was applied to compare the IPHs hit by COVID-19 and suggested for use with the hT-index in future studies, not limited to the field of public health as we did in this research.

The mortality of hospitalized patients with COVID-19 and non-cirrhotic chronic liver disease: a retrospective multi-center study.

Background: Patients with chronic liver disease (CLD) have a higher risk of mortality when infected with severe acute respiratory syndrome coronavirus 2. Although the fibrosis-4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and albumin-bilirubin grade (ALBI) score can predict mortality in CLD, their correlation with the clinical outcomes of CLD patients with coronavirus disease 2019 (COVID-19) is unclear. This study aimed to investigate the association between the liver severity and the mortality in hospitalized patients with non-cirrhotic CLD and COVID-19. Methods: This retrospective study analyzed 231 patients with non-cirrhotic CLD and COVID-19. Clinical characteristics, laboratory data, including liver status indices, and clinical outcomes were assessed to determine the correlation between liver status indices and the mortality among patients with non-cirrhotic CLD and COVID-19. Results: Non-survivors had higher levels of prothrombin time-international normalized ratio (PT-INR), alanine aminotransferase, aspartate aminotransferase, and high-sensitivity C-reactive protein (hs-CRP) and lower albumin levels. Multivariable analysis showed that ALBI grade 3 (odds ratio (OR): 22.80, 95% confidence interval (CI) [1.70-305.38], p = 0.018), FIB-4 index ≥ 3.25 (OR: 10.62, 95% CI [1.12-100.31], p = 0.039), PT-INR (OR: 19.81, 95% CI [1.31-299.49], p = 0.031), hs-CRP (OR: 1.02, 95% CI [1.01-1.02], p = 0.001), albumin level (OR: 0.08, 95% CI [0.02-0.39], p = 0.002), and use of vasopressors (OR: 4.98, 95% CI [1.27-19.46], p = 0.021) were associated with the mortality. Conclusion: The ALBI grade 3 and FIB-4 index ≥ 3.25, higher PT-INR, hsCRP levels and lower albumin levels could be associated with mortality in non-cirrhotic CLD patients with COVID-19. Clinicians could assess the ALBI grade, FIB-4 index, PT-INR, hs-CRP, and albumin levels of patients with non-cirrhotic CLD upon admission.

Acute kidney injury in patients with COVID-19 compared to those with influenza: a systematic review and meta-analysis.

Background: COVID-19 and influenza can both lead to acute kidney injury (AKI) as a common complication. However, no meta-analysis has been conducted to directly compare the incidence of AKI between hospitalized patients with COVID-19 and influenza. The objective of our study aims to investigate the incidence and outcomes of AKI among hospitalized patients between these two groups. Materials and methods: A systematic search of PubMed, Embase, and Cochrane databases was conducted from December 2019 to August 2023 to identify studies examining AKI and clinical outcomes among hospitalized patients with COVID-19 and influenza. The primary outcome of interest was the incidence of AKI, while secondary outcomes included in-hospital mortality, recovery from AKI, hospital and ICU stay duration. The quality of evidence was evaluated using Cochrane and GRADE methods. Results: Twelve retrospective cohort studies, involving 17,618 hospitalized patients with COVID-19 and influenza, were analyzed. COVID-19 patients showed higher AKI incidence (29.37% vs. 20.98%, OR: 1.67, 95% CI 1.56-1.80, p < 0.01, I2 = 92.42%), and in-hospital mortality (30.95% vs. 5.51%, OR: 8.16, 95% CI 6.17-10.80, p < 0.01, I2 = 84.92%) compared to influenza patients with AKI. Recovery from AKI was lower in COVID-19 patients (57.02% vs., 80.23%, OR: 0.33, 95% CI 0.27-0.40, p < 0.01, I2 = 85.17%). COVID-19 patients also had a longer hospital stay (SMD: 0.69, 95% CI 0.65-0.72, p < 0.01, I2 = 98.94%) and longer ICU stay (SMD: 0.61, 95% CI 0.50-0.73, p < 0.01, I2 = 94.80%) than influenza patients. In our study, evidence quality was high (NOS score 7-9), with low certainty for AKI incidence and moderate certainty for recovery form AKI by GRADE assessment. Conclusion: COVID-19 patients had higher risk of developing AKI, experiencing in-hospital mortality, and enduring prolonged hospital/ICU stays in comparison to influenza patients. Additionally, the likelihood of AKI recovery was lower among COVID-19 patients.

Dapagliflozin protects against doxorubicin-induced nephrotoxicity associated with nitric oxide pathway-A translational study.

Doxorubicin (Dox) is a potent anticancer agent, but its associated organ toxicity, including nephrotoxicity, restricts clinical applications. Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 inhibitor, has been shown to slow the progression of kidney disease in patients with and without diabetes. However, the effect of DAPA to counteract Dox-induced nephrotoxicity remains uncertain. Therefore, in this study, we aimed to elucidate the effects of DAPA in mitigating Dox-induced nephrotoxicity. We analyzed the Taiwan National Health Insurance Database to evaluate the incidence of renal failure among breast cancer patients receiving Dox treatment compared to those without. After adjusting for age and comorbidities, we found that the risk of renal failure was significantly higher in Dox-treated patients (incidence rate ratio, 2.45; confidence interval, 1.41-4.26; p = 0.0014). In a parallel study, we orally administered DAPA to Sprague-Dawley rats for 6 weeks, followed by Dox for 4 weeks. DAPA ameliorated Dox-induced glomerular atrophy, renal fibrosis, and dysfunction. Furthermore, DAPA effectively suppressed Dox-induced apoptosis and reactive oxygen species production. On a cellular level, DAPA in HK-2 cells mitigated Dox-mediated suppression of the endothelial NOS pathway and reduced Dox-induced activities of reactive oxygen species and apoptosis-associated proteins. DAPA improved Dox-induced apoptosis and renal dysfunction, suggesting its potential utility in preventing nephrotoxicity in patients with cancer undergoing Dox treatment.