-
ACS Nano Jul 2023Osteoarthritis (OA) is characterized by the lubrication dysfunction of a cartilage sliding interface caused by chronic joint inflammation, and effective nonsurgical...
Osteoarthritis (OA) is characterized by the lubrication dysfunction of a cartilage sliding interface caused by chronic joint inflammation, and effective nonsurgical therapy for advanced OA remains lacking. Addressing chronic joint inflammation, lubrication dysfunction, and cartilage-tissue degradation simultaneously may hopefully tackle this challenge. Herein, we developed superlubricative zein@alginate/strontium@calcitriol (ZASC) nanospheres to treat advanced OA. ZASC was confirmed to significantly improve joint lubrication through traditional tribological tests and our proposed tribological experiment to mimic the intra-articular condition based on the human medial tibiofemoral joint tissues. This finding was attributed to the hydration lubrication formed around the alginate-strontium spheres that enabled ball-bearing lubrication and the filling of cartilage defects. Moreover, ZASCs that released calcitriol in a sustained manner showed proliferative, anti-inflammatory, and anti-apoptosis effects . Further experiments demonstrated that ZASC exerted chondroprotective effects by inhibiting the breakdown of the extracellular matrix in patient-derived OA cartilage explants. results demonstrated that ZASC can effectively maintain a normal gait to improve joint function, inhibit abnormal bone remodeling and cartilage degradation in early OA and can effectively reverse the advanced OA progression. Therefore, ZASC is a potentially nonsurgical therapeutic strategy for advanced OA treatments.
Topics: Humans; Calcitriol; Cartilage, Articular; Nanospheres; Chondrocytes; Osteoarthritis; Inflammation; Alginates
PubMed: 37326369
DOI: 10.1021/acsnano.3c04241 -
Clinical Gastroenterology and... Sep 2023Hepatorenal syndrome (HRS) can occur in patients with cirrhosis and ascites due to splanchnic vasodilation, renal hypoperfusion, and vasoconstriction. HRS is a diagnosis... (Review)
Review
BACKGROUND & AIMS
Hepatorenal syndrome (HRS) can occur in patients with cirrhosis and ascites due to splanchnic vasodilation, renal hypoperfusion, and vasoconstriction. HRS is a diagnosis of exclusion and portends a poor prognosis, with upward of 80% mortality at 2 weeks without treatment. This review will highlight randomized controlled trials for HRS pharmacotherapy.
METHODS
A PubMed review of randomized controlled trials conducted over the past 25 years was undertaken; 18 studies were included.
RESULTS
Initial studies showed that norepinephrine is as effective as terlipressin for HRS reversal. Midodrine with octreotide and albumin is less effective than terlipressin but better than albumin alone at improving 30-day mortality. Recently, terlipressin with albumin led to significantly higher rates of HRS reversal compared to albumin alone. Non-response to terlipressin can predict 90-day mortality in acute-on-chronic-liver failure.
CONCLUSIONS
Our current understanding of HRS treatment is improved by recent randomized clinical trials. Previous studies using varying medication doses along with the "old" definition of hepatorenal syndrome (HRS type 1) rather than HRS-AKI means that there is still a need for future multicenter prospective studies further refining the risk-benefit ratio of vasoconstrictors for HRS-AKI patients. The Food and Drug Administration has approved terlipressin for use in September 2022. Because it will take time to adapt into clinical practice, less cost-prohibitive vasoconstrictors should still be considered. Opportunities also exist to clarify the safety, timing of initiation, as well as possible discontinuation of terlipressin.
Topics: United States; Humans; Hepatorenal Syndrome; Terlipressin; Prospective Studies; Acute Kidney Injury; Vasoconstrictor Agents; Albumins; Multicenter Studies as Topic
PubMed: 37625864
DOI: 10.1016/j.cgh.2023.06.006 -
Annals of Allergy, Asthma & Immunology... Aug 2023
Topics: Humans; Epinephrine; Anaphylaxis; Injections; Injections, Intramuscular
PubMed: 37530680
DOI: 10.1016/j.anai.2023.06.016 -
Expert Review of Gastroenterology &... 2023Kidney is the most common extra-hepatic organ involved in patients with advanced liver cirrhosis and acute-on-chronic liver failure. Hepatorenal syndrome-acute kidney... (Review)
Review
INTRODUCTION
Kidney is the most common extra-hepatic organ involved in patients with advanced liver cirrhosis and acute-on-chronic liver failure. Hepatorenal syndrome-acute kidney injury (HRS-AKI) accounts for most hospitalizations, and liver transplantation (LT) remains the ultimate and long-term treatment in such patients. However, HRS-AKI, being a functional renal failure, has a fair chance of reversal, and as such, patients who achieve reversal of HRS-AKI have better outcomes post-LT.
AREAS COVERED
In this review, we discuss the pharmacokinetics, pharmacodynamics and evidence to support the use of terlipressin in HRS-AKI while we also address predictors of response and the associated adverse events. Further, we discuss the role of terlipressin in the context of LT.
EXPERT OPINION
The recommended treatment for HRS-AKI reversal includes a vasoconstrictor in addition to volume expansion with albumin. The three vasoconstrictor regimens generally used to treat HRS-AKI include octreotide plus midodrine, noradrenaline, and terlipressin. Of these, terlipressin is a widely used drug and has been recently approved by US Food and Drug Administration (USFDA) for HRS-AKI. Terlipressin is the most effective drug for HRS-AKI reversal and is associated with a decreased need for renal replacement therapy pre- and post-transplant. Furthermore, terlipressin responders have improved transplant-free and post-transplant survival.
Topics: Humans; Adult; Terlipressin; Hepatorenal Syndrome; Vasoconstrictor Agents; Midodrine; Acute Kidney Injury
PubMed: 37856367
DOI: 10.1080/17474124.2023.2273494 -
British Journal of Anaesthesia Jul 2023Perioperative anaphylaxis is associated with significant morbidity and mortality. Prompt and appropriate treatment is required for optimal outcome. Despite general...
Perioperative anaphylaxis is associated with significant morbidity and mortality. Prompt and appropriate treatment is required for optimal outcome. Despite general knowledge of this condition, delays occur in the administration of epinephrine and in particular the use of i.v. route of administration in the perioperative setting. Barriers should be addressed to allow prompt utilisation of i.v. epinephrine in perioperative anaphylaxis.
Topics: Humans; Anaphylaxis; Epinephrine; Fluid Therapy
PubMed: 37244833
DOI: 10.1016/j.bja.2023.04.036 -
European Journal of Internal Medicine Mar 2024Sepsis remains a critical global health issue, demanding novel therapeutic strategies. Traditional immunomodulation treatments such as corticosteroids, specific... (Review)
Review
Sepsis remains a critical global health issue, demanding novel therapeutic strategies. Traditional immunomodulation treatments such as corticosteroids, specific modifiers of cytokines, complement or coagulation, growth factors or immunoglobulins, have so far fallen short. Meanwhile the number of studies investigating non-conventional immunomodulatory strategies is expanding. This review provides an overview of adjunctive treatments with herbal-based medicine, immunonutrition, vasopressors, sedative treatments and targeted temperature management, used to modulate the immune response in patients with sepsis. Herbal-based medicine, notably within traditional Chinese medicine, shows promise. Xuebijing injection and Shenfu injection exhibit anti-inflammatory and immune-modulatory effects, and the potential to lower 28-day mortality in sepsis. Selenium supplementation has been reported to reduce the occurrence of ventilator-associated pneumonia among sepsis patients, but study results are conflicting. Likewise, the immune-suppressive effects of omega-3 fatty acids have been associated with improved clinical outcomes in sepsis. The immunomodulating properties of supportive treatments also gain interest. Vasopressors like norepinephrine exhibit dual dosage-dependent roles, potentially promoting both pro- and anti-inflammatory effects. Dexmedetomidine, a sedative, demonstrates anti-inflammatory properties, reducing sepsis mortality rates in some studies. Temperature management, particularly maintaining higher body temperature, has also been associated with improved outcomes in small scale human trials. In conclusion, emerging non-conventional immunomodulatory approaches, including herbal medicine, immunonutrition, and targeted supportive therapies, hold potential for sepsis treatment, but their possible implementation into everyday clinical practice necessitates further research and stringent clinical validation in different settings.
Topics: Humans; Sepsis; Vasoconstrictor Agents; Immunity; Immunomodulation; Anti-Inflammatory Agents; Hypnotics and Sedatives
PubMed: 37919123
DOI: 10.1016/j.ejim.2023.10.032 -
Rhinology Apr 2024Topical anaesthesia and decongestion of the sinonasal mucosa are used commonly in rhinology practice to facilitate nasal endoscopy, as well as debridement and biopsies.... (Review)
Review
Topical anaesthesia and decongestion of the sinonasal mucosa are used commonly in rhinology practice to facilitate nasal endoscopy, as well as debridement and biopsies. Topical agents used for sinonasal anaesthesia include lignocaine, tetracaine and cocaine. Unlike lignocaine and tetracaine, cocaine also has a decongestant effect. Phenylephrine, oxymetazoline, xylometazoline or adrenaline are usually added to lignocaine and tetracaine to provide decongestion. Several studies have been performed seeking to identify the optimal nasal preparation for nasal endoscopy in the clinic setting. However, there remains no clear consensus in the literature resulting in ongoing wide variation between anaesthetic-decongestant preparations used in clinical practice. Indeed, some authors have argued that no anaesthetic is required at all for flexible nasendoscopy despite the apparent consensus that nasal instrumentation is generally uncomfortable, inferred by the persistence of ongoing research in this area. This review provides a practical summary of local anaesthetic and decongestant pharmacology as it relates to rhinologic practice and summarises the literature to date, with the goal of identifying current gaps in the literature and guiding future research efforts.
Topics: Humans; Nasal Decongestants; Tetracaine; Anesthesia, Local; Cocaine; Lidocaine
PubMed: 37942998
DOI: 10.4193/Rhin23.285 -
American Journal of Physiology.... Oct 2023Obesity is associated with hypertension. However, the mechanisms involved are not fully understood. Therefore, we investigated the relationship between obesity and...
Obesity is associated with hypertension. However, the mechanisms involved are not fully understood. Therefore, we investigated the relationship between obesity and vasoactive mediators. In this cross-sectional study, blood pressure (BP) and vasoactive mediators of hypertension are compared among 135 adults in the nonobese, obese, and morbidly obese body mass index (BMI) ranges (BMI ≤27, 30-40, and >40 kg/m, respectively). Angiotensinogen, angiotensin II, renin, aldosterone, endothelin-1 (ET-1), neprilysin, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cyclic guanosine monophosphate (cGMP), and cyclic adenosine monophosphate (cAMP) levels were measured and their relationship to BP, BMI, race, and gender were investigated. Systolic and diastolic BP (SBP and DSP) were significantly higher in subjects with obesity and morbid obesity compared with nonobese. Angiotensin II, ET-1, and neprilysin were significantly higher in subjects with morbid obesity while BNP was lower. Levels of angiotensinogen, renin, aldosterone, ANP, cGMP, and cAMP did not differ between the groups. BMI was positively related to SBP, DBP, angiotensin II, ET-1, and neprilysin, and inversely related to cGMP and BNP. Age, male gender, and African-American race were associated with higher SBP. SBP was positively related to angiotensin II and ET-1 and inversely related to aldosterone, renin, and cGMP. On multivariate analyses, age, BMI, gender, and race were the main determinants of SBP, and excluding these variables, angiotensin II, aldosterone, renin, and ET-1 accounted for 21.1% ability to predict SBP. Obesity, especially morbid obesity, is associated with higher BP, higher angiotensin II and ET-1 (vasoconstrictors), and lower levels BNP and cGMP (vasodilators). SBP variability can be partly explained by angiotensin II, aldosterone, renin, and ET-1. Our data show that obesity, especially morbid obesity, is associated with higher blood pressure levels and increases angiotensin II and endotherlin-1 (ET-1) (vasoconstrictors) and lower levels BNP and cGMP (vasodilators) and that systolic blood pressure variability can be partly explained by levels of angiotensin II, aldosterone, renin, and ET-1. The effect of these mediators on blood pressure is in addition to the effects of other known factors related to age, male gender, and AA race.
Topics: Adult; Humans; Male; Renin; Angiotensinogen; Renin-Angiotensin System; Obesity, Morbid; Aldosterone; Angiotensin II; Cross-Sectional Studies; Neprilysin; Hypertension; Blood Pressure; Vasodilator Agents; Vasoconstrictor Agents
PubMed: 37672250
DOI: 10.1152/ajpendo.00209.2022 -
Advances in Wound Care Oct 2023Pressure injury (PI) is a common critical presentation in intensive care units (ICU) and is an important clinical concern in critical care settings. Some developing... (Meta-Analysis)
Meta-Analysis Review
Pressure injury (PI) is a common critical presentation in intensive care units (ICU) and is an important clinical concern in critical care settings. Some developing data support the vasoconstrictor agent administration as a potential risk factor; however, synthesis of available evidence has not been completed. Comprehensive tactics were employed to search electronic databases PubMed, Web of Science, and Ovid Embase for data on vasoconstrictor agent administration associated with PI in ICU patients. Extraction was limited to studies that matched the inclusion criteria. The pooled odds ratio and 95% confidence intervals (95% CI) were calculated for dichotomous outcomes. Twenty-six studies were included, involving 50,192 patients who matched the selection criteria. Around 5.8% of patients (2,523/43,210) got PI in total. PI occurred in 10.9% (1,496/13,675) of the vasoconstrictor agent administration population and 3.5% (1,027/29,503) of the drug-free population. The pooled unadjusted odds ratio was 2.83 (95% CI = 2.21-3.64, < 0.001). The adjusted odds ratio was 1.83 (95% CI = 1.26-2.68, = 0.002). Subgroup analysis and meta-regression found that the risk of PI did not vary with research design, time of occurrence, patient age, or male proportion. Vasoconstrictor agent administration raised the risk of PI in critical care patients by nearly twofold. More emphasis should be placed on the timely prevention of PI in patients receiving vasoconstrictor agent administration in the ICU.
Topics: Humans; Male; Pressure Ulcer; Critical Care; Intensive Care Units; Risk Factors
PubMed: 36448592
DOI: 10.1089/wound.2022.0081 -
Anesthesia and Analgesia Oct 2023Previous studies on the association between the timing of corticosteroid administration and mortality in septic shock focused only on short-term mortality and produced...
BACKGROUND
Previous studies on the association between the timing of corticosteroid administration and mortality in septic shock focused only on short-term mortality and produced conflicting results. We performed a retrospective review of a large administrative database of intensive care unit (ICU) patients to evaluate the association between the timing of hydrocortisone initiation and short- and long-term mortality in septic shock. We hypothesized that a longer duration between the first vasopressor use for sepsis and steroid initiation was associated with increased mortality.
METHODS
Data were extracted from the Medical Information Mart in the Intensive Care-IV database. We included adults who met Sepsis-3 definition for septic shock and received hydrocortisone. The exposure of interest was the time in hours from vasopressor use to hydrocortisone initiation (>12 as late and ≤12 as early). The primary outcome was 1-year mortality. Secondary outcomes included 28-day mortality, 90-day mortality, in-hospital mortality, and length of hospital stay. Cox proportional hazard models were used to estimate the association between exposure and mortality. Competing risk regression models were used to evaluate the association between exposure and length of hospital stay.
RESULTS
A total of 844 patients were included in this cohort: 553 in the early group and 291 in the late group. The median time to hydrocortisone initiation was 7 hours (interquartile range, 2.0-19.0 hours). After multivariable Cox proportional hazard analysis, we found that hydrocortisone initiation >12 hours after vasopressor use was associated with increased 1-year mortality when compared with initiation <12 hours (adjusted hazard ratio, 1.39; 95% confidence interval, 1.13-1.71; P = .002, E-value = 2.13). Hydrocortisone initiation >12 hours was also associated with increased 28-day, 90-day, and in-hospital mortality and prolonged length of hospital stay.
CONCLUSIONS
In patients with septic shock, initiating hydrocortisone >12 hours after vasopressor use was associated with an increased risk of both short-term and long-term mortality, and a prolonged length of hospital stay.
Topics: Adult; Humans; Shock, Septic; Hydrocortisone; Sepsis; Retrospective Studies; Hospital Mortality; Vasoconstrictor Agents; Intensive Care Units
PubMed: 37171987
DOI: 10.1213/ANE.0000000000006516