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Previous studies suggested increased mortality in patients with hepatorenal syndrome type 1 (HRS1) and advanced acute-on-chronic liver failure (ACLF).To assess mortality and respiratory failure (RF) in patients with HRS1 and ACLF treated with terlipressin.In the CONFIRM study, we randomised 299 patients with HRS1 2:1 to terlipressin or placebo, both with albumin. At enrolment, all patients were assessed for organ failure (OF) using a validated ACLF grading system. Post hoc analyses assessed the effects of terlipressin vs. placebo on the incidence of RF and 90-day mortality.The incidence of RF with terlipressin (n = 200) was 9.4% in patients with grades 1-2 ACLF, and 30% with grade 3 ACLF (p = 0.0002); no such difference was observed in placebo-treated patients (n = 99) (6.2% grades 1-2 vs. 0% grade 3 ACLF, p 0.05). RF incidence between terlipressin and placebo in patients with grade 3 ACLF was significant (p = 0.01). Baseline predictors of RF with terlipressin were INR (p = 0.011), mean arterial pressure (p = 0.037), and SpOTerlipressin should be used with caution in patients with HRS1 and grade 3 ACLF. Patients with hypoxaemia are at increased risk of RF and mortality.

Summary Background Hepatorenal syndrome and acute kidney injury are common complications of decompensated cirrhosis, and terlipressin is recommended as first‐line vasoconstrictor therapy. However, data on its use outside of clinical trials are lacking. Aims To assess practice patterns and outcomes around vasoconstrictor use for hepatorenal syndrome in UK hospitals. Methods This was a multicentre chart review study. Data were extracted from medical records of patients diagnosed with hepatorenal syndrome and treated by vasoconstrictor drugs between January 2013 and December 2017 at 26 hospitals in the United Kingdom. The primary outcome was improvement of kidney function, defined as complete response (serum creatinine improved to ≤1.5 mg/dL), partial response (serum creatinine reduction of ≥20% but >1.5 mg/dL) and overall response (complete or partial response). Other outcomes included need for dialysis, mortality, liver transplantation and adverse events. Results Of the 225 patients included in the analysis, 203 (90%) were treated with terlipressin (median duration, 6 days; range: 2‐24 days). Mean (±standard deviation) serum creatinine at vasopressor initiation was 3.25 ± 1.64 mg/dL. Terlipressin overall response rate was 73%. Overall response was higher in patients with mild acute kidney injury (baseline serum creatinine

Hepatorenal syndrome (HRS) is among the leading causes of hospitalization and mortality in patients with chronic liver disease.To assess the HRS patient journey from preadmission to postdischarge to understand patient characteristics, disease progression, treatment patterns, and outcomes.We conducted a retrospective study using real-world data from a nationwide electronic health record database (Cerner Health Facts, Kansas City, Missouri). We used ICD-9/10 diagnosis codes to identify patients hospitalized with HRS between January 1, 2009, and January 31, 2018. We assessed patient characteristics and history, clinical presentation, treatment, and outcomes. Regression analysis was conducted to assess the association between patient characteristics and survival while adjusting for demographic and clinical covariates.The study included 3563 patients (62% men). Precipitants of HRS included gastrointestinal bleeding (18%), diuretics and infections (30%), and paracentesis (26%). Although 21% of patients had liver injury exclusively associated with alcohol use, 20% had hepatitis C, 8% had nonalcoholic steatohepatitis, and the etiology of the remainder (51%) was either some combination of conditions or unknown. A total of 42% of patients received vasopressors, including octreotide and midodrine (10%), other combinations of vasopressors (11%), or another single vasopressor (21%). In-hospital mortality was 34%, and 14% of patients were discharged to hospice. Regression analysis showed patients with acute-on-chronic liver failure had higher mortality in acute-on-chronic liver failure grades 1 (odds ratio = 1.59), 2 (odds ratio = 2.49), and 3 (odds ratio = 4.53) versus no acute-on-chronic liver failure. Among survivor patients, 38% were readmitted within 90 days of discharge; 23% of readmissions were HRS-related.The HRS patient journey presented in this study highlights inconsistencies in, and provides insight into, associated hospital-based treatment strategies. A mortality rate of 34% along with a readmission rate of 23% associated with HRS-related complications warrant more disease awareness and effective treatment. Further research is needed to examine the interactions between the etiology of cirrhosis, precipitants, treatment, and outcomes. (

Background Hepatorenal syndrome type 1 (HRS-1), a form of acute kidney injury (AKI) in cirrhosis, has a median survival of days to weeks if untreated. The impact of reduction in AKI stage on overall survival in cirrhosis, independent of HRS reversal, is unclear. Methods The Randomized, placEbo-controlled, double-blind study to confirm the reVERSal of HRS-1 with terlipressin study assessed terlipressin versus placebo, both with albumin, as treatment for HRS-1 for ≤14 days. Renal dysfunction severity was categorized by AKI stage at enrollment. Baseline patient characteristics were evaluated as predictors of AKI improvement using a multivariate model; the association between AKI stage reduction and 90-day survival was assessed using linear regression. Results A total of 184 patients (terlipressin: n = 91; placebo: n = 93) with similar numbers in AKI Stages 1–3 (terlipressin/placebo, Stage 1: n = 25/26; Stage 2: n = 35/33; Stage 3: n = 31/34) were included. Predictors of AKI improvement were absence of alcoholic hepatitis, baseline serum creatinine and male gender. Overall survival was not significantly different across AKI stages (range 53–65%). In patients with no AKI worsening, 90-day survival was consistently better when AKI improved independent of HRS reversal, regardless of the initial AKI stage, with patients with Stage 1 at initial diagnosis achieving the greatest clinical benefit. A significant association was observed between AKI reduction and overall 90-day survival (P = 0.0022). Conclusions A reduction in AKI stage, independent of HRS reversal, was sufficient to improve overall survival in patients with HRS-1. The goal for HRS-1 treatment should be less stringent than absolute HRS reversal.

BACKGROUND The outbreak of a coronavirus disease in 2019 (COVID-19) which is associated with respiratory-related illness and high mortality presents a major worldwide need. Problems of information availability to health care providers; difficulties in diagnosis and disease prognosis; and a lack of monitoring tools are some of the obstacles faced by the clinical community. Most importantly, the lack of valid therapies makes the pandemic a devastating universal problem. Current information points to a concept of dysregulation of the immune system which is unable to mount an effective anti-viral response, and on the other hand induces an uncontrolled immune-mediated response manifesting as ARDS, myocarditis and hepatitis. OBJECTIVE In the present paper we describe a novel platform for providing information to physicians, and assisting in diagnosis and monitoring of patients with COVID-19. METHODS Review of the relevant literature publications RESULTS An adjuvant approach is presented, using compounds that can boost a beneficial anti-viral immune response while reducing the immune-mediated target organ damage associated with the virus. CONCLUSIONS Ensuring a prolonged beneficial effect is performed by implementing algorithm-based individualized variability measures into the treatment regimen.

Coronavirus disease 2019 (COVID-19), which is a respiratory illness associated with high mortality, has been classified as a pandemic. The major obstacles for the clinicians to contain the disease are limited information availability, difficulty in disease diagnosis, predicting disease prognosis, and lack of disease monitoring tools. Additionally, the lack of valid therapies has further contributed to the difficulties in containing the pandemic. Recent studies have reported that the dysregulation of the immune system leads to an ineffective antiviral response and promotes pathological immune response, which manifests as ARDS, myocarditis, and hepatitis. In this study, a novel platform has been described for disseminating information to physicians for the diagnosis and monitoring of patients with COVID-19. An adjuvant approach using compounds that can potentiate antiviral immune response and mitigate COVID-19-induced immune-mediated target organ damage has been presented. A prolonged beneficial effect is achieved by implementing algorithm-based individualized variability measures in the treatment regimen.

Terlipressin, a synthetic, systemic vasoconstrictor with selective activity at vasopressin-1 (V1) receptors, is a pro-drug for the endogenous/natural porcine hormone [Lys8]-vasopressin (LVP). We investigated binding and receptor-mediated cellular activities of terlipressin, LVP, and endogenous human hormone [Arg8]-vasopressin (AVP) at V1 and vasopressin-2 (V2) receptors. Cell membrane homogenates of Chinese hamster ovary cells expressing human V1 and V2 receptors were used in competitive binding assays to measure receptor-binding activity. These cells were used in functional assays to measure receptor-mediated cellular activity of terlipressin, LVP, and AVP. Binding was measured by [3H]AVP counts, and the activity was measured by fluorometric detection of intracellular calcium mobilization (V1) and cyclic adenosine monophosphate (V2). Binding potency at V1 and V2 was AVP>LVP>>terlipressin. LVP and terlipressin had approximately sixfold higher affinity for V1 than for V2. Cellular activity potency was also AVP>LVP>>terlipressin. Terlipressin was a partial agonist at V1 and a full agonist at V2; LVP was a full agonist at both V1 and V2. The in vivo response to terlipressin is likely due to the partial V1 agonist activity of terlipressin and full V1 agonist activity of its metabolite, LVP. These results provide supportive evidence for previous findings and further establish terlipressin pharmacology for vasopressin receptors.

This study evaluated the characteristics, healthcare resource utilization (HCRU), and costs, from the payer perspective, of hepatorenal syndrome (HRS) patients covered by commercial and Medicare insurance. Mortality was assessed as a secondary outcome.Patients were identified from claims databases of commercially insured patients (OptumHealth Care Solutions Inc.) in 1998-2014 and Medicare beneficiaries in 2009-2013 (5% Standard Analytic Files). At the time of their first inpatient admission ("index date") with an HRS diagnosis (ICD-9 code 572.4), commercially insured patients must be aged 18-64 and Medicare patients must be aged 65 and older.A total of 784 commercially insured and 1061 Medicare HRS patients met the sample selection criteria. Patients were disproportionately male (commercial: 63.0%; Medicare: 57.9%) with a mean age of 54.1 among commercially insured and 74.1 among Medicare patients. Within the first 30 days, the average hospital length of stay (LOS) was 12.3 days among commercially insured and 10.8 days among Medicare patients. Based on Kaplan-Meier analyses, 36% of commercially insured and 26% of Medicare patients were readmitted within the next 30 days. During follow-up, many patients received dialysis (commercial: 33.0%; Medicare: 22.1%) or liver transplant (commercial: 10.7%; Medicare: 1.6%). Average costs within the 90 day follow-up were $157,665 for commercially insured and $48,322 for Medicare patients, with 68.3% and 78.3% of the costs incurred within the first 30 days. The primary cost driver was inpatient visits (commercial: 90.3% of costs; Medicare: 83.1% of costs), with differences between the populations consistent with lower mortality, higher dialysis rates, and higher transplant rates (both liver and kidney) among the commercially insured. Using US population and prevalence statistics, these results suggest that HRS imposes an annual total direct medical cost burden of approximately $3.0-$3.8 billion to payers over the period.HRS imposes a significant economic burden.

Summary Background The goal of hepatorenal syndrome type 1 (HRS‐1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS‐1, where it is available. Aim To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS‐1. Methods Pooled patient‐level data from two large phase 3, randomised, placebo‐controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 μmol/L], 90‐day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1–2 mg every 6 hours plus albumin or placebo plus albumin up to 14 days. Results The pooled analysis comprised 308 patients (terlipressin: n = 153; placebo: n = 155). HRS reversal was significantly more frequent with terlipressin vs. placebo (27% vs. 14%; P = 0.004). Terlipressin was associated with a more significant improvement in renal function from baseline until end of treatment, with a mean between‐group difference in SCr concentration of −53.0 μmol/L (P

Background: The aim of this research work is to compare the time duration of operation and the frequency of difficulties in the procedures of the Snodgrass and Mathieu for the repairing of initial anterior hypospadias. Methods: The duration of this study was from March 2014 to February 2018 in Arar Central Hospital Arar Northern Border Zone KSA. 80 patients were the participant of our study with primary anterior hypospadias and the children’s which were included in our study was from 2 to 10 years of age. In our study only those patients were to be included who had never repaired their hypospadias and all those patients who had repaired their hypospadias previously were to be excluded from this study and also all those patients were also excluded from our who had significant chordee. All the patients are to be distributed in two groups in which one group had Mathieu and group II is Snodgrass procedure (Tabularized incised plate (TIP), Urethroplasty). By frequent irrigation the stent was kept patent. Operative time duration for both the procedures was calculated and after the procedures completed, patients were to be follow up for the complications. Results: In this study we have studied 80 patients. We have divided the patients into two groups, group I was Mathieu repair procedure and Group II was Snodgrass repair procedure, so the Mathieu repair procedure were performed in 40 patients and the Snodgrass procedure were performed in the remaining 40 patients. In the Snodgrass repair the cosmetic results were very good with a normal cut looking like meatus. In both the procedures wound breakdown and meatal stenosis was equal however in Mathieu procedure the proximal stricture and urocutaneous fistula were frequently seen. Meatal stenosis and wound breakdown was equal in each group whereas urocutaneous fistula and proximal urethral stricture were seen more frequently in Mathieu group. Key Words: Urethral, Proximal Stricture, Mathieu repair, Tubularized Incised Plate urethroplasty, Snodgrass procedure, Cosmetic

Objective: The disease of Dry Eye is very common problem of health. Most of the painful symptoms of this disease leads to depression and medication against the depression is also the cause of the disease of dry eye. The aim of this research work is to determine the association between the disease of dry eye and symptoms of depression among the aged population. Methodology: This study was a transverse research work was conducted in eighteen months in Ameer Abdul Aziz Bin Mosaed Hospital Arar Northern Border Zone KSA. Ethical committee of the hospital gave the permission to conduct this research work. We took the consent of 1400 willing patients having 36 to 76 years of age from both genders who were undergoing study for dry eye. We evaluated all the patients into 2 steps. In the initial, we managed a questionnaire (DEQ-6) and then we performed tests for dry eyes. We carried out the diagnosis of the dry eye in accordance with the diagnosis standard for dry eye of Japan. In the next step, we used SGDS-K (Korean Short Geriatric Depression Scale) for all the patients, scoring one single point for every answer designated. SPSS V.17 was in use for the analysis of the collected information. Results: Out of total 1400 patients, 28.28% patients were present with disease of dry eye. Total 24.68% patients were present with depression in accordance with SGDS-K among the patients of dry eye disease. The most frequent symptoms in this research work are watering in 32.58% and 58.0% females were present as post-menopausal. Majority of the patients of dry eye were present with old age from more than 48 year of age, more were living in the city areas, disease was dominant in men and these patients had high income and very low visual acuity in comparison wo the patients with no disease of dry eye. Conclusion: The occurrence of the depression was high in the patients suffering from disease of dry eye as compared to the patients with no dry eye disease. Key Words: Dry Eye, Depression, Occurrence, Menopausal, Comparison, SGDS-K, Symptoms.

Objectives: Hepatorenal Syndrome (HRS) is characterized by renal failure in patients with advanced chronic liver disease (CLD) and is the leading cause of hospitalizations in CLD. This study examines the clinical and economic burden, outcomes, and unmet need of HRS treatment in US hospitals. Method: A retrospective cohort study was conducted based on a large electronic health records database (Cerner HealthFacts) with records for hospitalized HRS patients from January 2009–June 2015. Demographics, clinical characteristics, treatment patterns, and economic outcomes were analyzed. Prognostic indicators of cirrhosis, kidney injury, end-stage liver disease, and acute-on-chronic liver failure were used to determine mortality risk. Results: A total of 2,542 patients hospitalized with HRS were identified (average age = 57.9 years, 61.8% males, 74.2% Caucasian), with an average total hospital charge of $91,504 per patient and a mean length of stay (LOS) of 30.5 days. The mortality rate was 36.9% with 8.9% of patients discharged to hospice. Of all patients, 1,660 patients had acute kidney injury, 859 with Stage 3 disease, and 26.7% had dialysis. The 30-day readmission rate was 33.1%, 41% of which were unplanned. Nearly one-third of study patients had commercial insurance (30.2%), followed by Medicare (29.9%); hospital charges varied by LOS, receipt of dialysis, and discharge status. Regression analysis demonstrated that HRS costs are associated with LOS, dialysis, and hospital mortality. Conclusion: HRS is associated with poor outcomes and high hospital costs. Analysis of HRS cost drivers demonstrated an unmet need for additional treatment options to improve outcomes in this patient population.

Coronary artery disease particularly myocardial infarction remains the leading cause of mortality and morbidity worldwide, There are few modifiable and un-modifiable risk factors of MI. Myocardial infarction is diagnosed on the basis of typical chest pain raised cardiac enzymes and ECG changes, any two of them lead to the diagnosis, In this study old patients of MI, patients with complicated heart disease and the patients who underwent cardiac surgery were excluded, Results: Amongst 50 patients 36(72%) were males and 14(28%) were females. 70% presented with typical chest pain, 48% had anterior wall MI, 32% had anterolateral MI, 16% had anteroseptal MI and 21% had inferior wall MI, whereas 8% had global Ml, Conclusion: Anterior wall is commonest area involved in MI and 70% of all patients presented with typical chest pain and the most important risk factor is smoking.

Background & Aims Patients with systemic inflammatory response syndrome (SIRS) along with decompensated cirrhosis and renal dysfunction have a poor prognosis and a lower response to treatment. We evaluated the effect of SIRS on the response of hepatorenal syndrome type 1 (HRS-1) to terlipressin. Methods We performed a retrospective study of data from a trial of the effects of terlipressin (1 mg every 6 hours or placebo with concomitant albumin) in 198 patients with HRS-1, performed at 50 investigational sites in the United States and 2 in Canada from October 2010 through February 2013. We identified patients with 2 or more criteria for SIRS, without untreated infections (28 received terlipressin and 30 received placebo), and patients with less than 2 criteria for SIRS (control subjects). Primary endpoints included HRS reversal (a decrease in serum level of creatinine to ≤1.5 mg/dL), confirmed HRS reversal (defined as 2 serum creatinine levels ≤1.5 mg/dL, ≥ 48 hours apart), and survival for 90 days after treatment. Results Baseline characteristics were similar between groups, apart from slightly higher white blood cell counts and heart rates, and slightly lower serum levels of bicarbonate in patients with SIRS versus without SIRS. HRS was reversed in 42.9% of patients who received terlipressin with SIRS (12/28) versus 6.7% of patients who received placebo (2/30) ( P = .0018); confirmed HRS reversal occurred in 32.1% of patients who received terlipressin with SIRS (9/28) versus 3.3% who received placebo (1/30) ( P = .0048). A larger proportion of patients with SIRS who received terlipressin survived for 90 days without a transplant (13/28; 46.4%) than patients with SIRS who received placebo (7/30; 23.3%) ( P = .076). Conclusions In an analysis of data from a placebo-controlled study, we found that terlipressin improved renal function and reversed HRS in a higher proportion of patients with HRS-1 and SIRS than patients who received albumin plus placebo. ClincialTrials.gov, number NCT 01143246.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Hydrogen sulphide (H2S) is a biological mediator and a potential therapeutic agent. In animal studies, the metabolism and pharmacokinetics of H2S have been characterized. WHAT THIS STUDY ADDS • This study is first to demonstrate the pharmacokinetics of an intravenously administered H2S formulation in humans, and to characterize the exhaled H2S response in humans. INTRODUCTION Hydrogen sulphide (H2S) is an endogenous gaseous signaling molecule and potential therapeutic agent. Emerging studies indicate its therapeutic potential in a variety of cardiovascular diseases and in critical illness. Augmentation of endogenous sulphide concentrations by intravenous administration of sodium sulphide can be used for the delivery of H2S to the tissues. In the current study, we have measured H2S concentrations in the exhaled breath of healthy human volunteers subjected to increasing doses sodium sulphide in a human phase I safety and tolerability study. METHODS We have measured reactive sulphide in the blood via ex vivo derivatization of sulphide with monobromobimane to form sulphide-dibimane and blood concentrations of thiosulfate (major oxidative metabolite of sulphide) via ion chromatography. We have measured exhaled H2S concentrations using a custom-made device based on a sulphide gas detector (Interscan). RESULTS Administration of IK-1001, a parenteral formulation of Na2S (0.005–0.20 mg kg−1, i.v., infused over 1 min) induced an elevation of blood sulphide and thiosulfate concentrations over baseline, which was observed within the first 1–5 min following administration of IK-1001 at 0.10 mg kg−1 dose and higher. In all subjects, basal exhaled H2S was observed to be higher than the ambient concentration of H2S gas in room air, indicative of on-going endogenous H2S production in human subjects. Upon intravenous administration of Na2S, a rapid elevation of exhaled H2S concentrations was observed. The amount of exhaled H2S rapidly decreased after discontinuation of the infusion of Na2S. CONCLUSION Exhaled H2S represents a detectable route of elimination after parenteral administration of Na2S.