Pretreatment with hydrogen-rich saline reduces the damage caused by glycerol-induced rhabdomyolysis and acute kidney injury in rats

Background

Rhabdomyolysis is a leading cause of acute kidney injury. The pathophysiological process involves oxidative stress and inflammation. Hydrogen-rich saline (HRS) is an antioxidant and anti-inflammatory. This study explored the protective effect of pretreatment with HRS on the development of glycerol-induced rhabdomyolysis acute kidney injury.

Materials and methods

Forty-eight rats were randomly divided into four equal groups. Group 1 served as the control, group 2 was given 50% glycerol (10 mL/kg, intramuscular), group 3 was given glycerol after 7 d pretreatment with high dose HRS (10 mL/kg/d, intraperitoneal), and group 4 was given glycerol after 7 d pretreatment with low dose HRS (5 mL/kg/d, intraperitoneal). Renal health was monitored by serum creatinine (Cr), urea, and histologic analysis; rhabdomyolysis was monitored by creatine kinase (CK) levels; and oxidative stress was monitored by kidney tissue reactive oxygen species (ROS), malondialdehyde, 8-hydroxydeoxyguanosine (8-OH-dG), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) levels. Inflammation was monitored by interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) evaluation.

Results

Glycerol administration resulted in an increase in the mean histologic damage score, serum Cr, urea and CK, kidney tissue ROS, malondialdehyde, 8-OH-dG, GSH-PX, IL-6, and TNF-α, and a decrease in kidney tissue superoxide dismutase activity. All these factors were significantly improved by both doses of HRS, but the mean histologic damage score, urea, Cr, CK, ROS, 8-OH-dG, GSH-PX, IL-6, and TNF-α for the high dose HRS treatment group were even lower.

Conclusions

Pretreatment by HRS ameliorated renal dysfunction in glycerol-induced rhabdomyolysis by inhibiting oxidative stress and the inflammatory response.     

Management and outcome in hepatorenal syndrome: need for renal replacement therapy in non-transplanted patients

Purpose

Hepatorenal syndrome (HRS) type I is a devastating complication of decompensated cirrhosis. Liver transplantation (LT) offers an excellent survival, and renal replacement therapy (RRT) may be useful until transplantation is available. The survival benefit of RRT in the absence of LT is thought to be short and its benefit in these patients is unknown. To investigate this, we studied the outcome of different therapies (pharmacological, RRT, and LT) in patients with type 1 HRS.

Methods

Medical records (2005–2009) of all cirrhotic patients admitted to our facility with abnormal renal function were reviewed. Patients with preexisting renal disease, diagnosis other than type I HRS, or those without long-term follow-up were excluded.

Results

Of 380 patients reviewed, 30 were studied. Nineteen (63.3 %) patients underwent liver transplantation. No difference in baseline liver or renal parameters was noted between those who were or were not transplanted. A decreased mortality was noted (5.3 vs. 64.6 %; p = 0.0005) compared to patients who were not transplanted during the study follow-up median period of 7.8 [CI 1.9–34] months. Among non-transplanted patients, no differences in median survival (8.8 vs. 6.5 months; p = 0.62) or in other parameters studied were found in those patients who received RRT compared to those who did not. Similarly, no survival difference was found comparing those who did or did not receive pharmacological therapy without transplant.

Conclusion

In type I HRS, LT offers better survival. Among patients who do not receive LT, RRT does not provide an improved survival benefit.     

All-trans-retinoic acid counteract the tumor-stimulating effect of hepatectomy and increases survival of rats bearing liver metastases

Background

We previously demonstrated a stimulating effect of hepatectomy on residual tumor cells after resection of liver metastases. The aim of this study was to analyze the effect of all-trans-retinoic acid (ATRA) on the protumor effect of hepatectomy and survival of hepatectomized rats bearing liver metastases. We also explored whether ATRA interfered with the tumor promoting effect of hepatotropic growth factors (GFs).

Methods

The in vitro effect of ATRA on proliferation of S4MH rhabdomyosarcoma tumor cells was assessed when cultured with laparotomized or hepatectomized rat serum (HRS), or in the presence of GFs (hepatocyte growth factor, insulin growth factor 2, Platelet Derived Growth Factor (PDGF)-BB, and vascular endothelial growth factor). For the in vivo studies, rats were partially hepatectomized on day 10 after metastasis induction, one group being treated with ATRA from day 7 to 14, and a second receiving cyclophosphamide (CY; on days 10 and 14) alone or with ATRA. We determined the size and number of liver and lung metastases. Finally, we analyzed the effect of treatments on rat survival.

Results

Hepatotropic GFs increased cell proliferation in a similar manner to HRS. In vitro, ATRA blocked the protumor effect of both HRS and GFs. In vivo, ATRA reduced the size and number of liver and lung metastases, and significantly increased rat survival. Furthermore, adding ATRA to CY significantly increased survival compared with CY alone.

Conclusions

In our model, ATRA minimizes the tumor-stimulating effect of hepatectomy, reducing the number and size of liver metastases and improving survival. The results suggest that the ATRA may be useful for blocking the growth-promoting effect of hepatotropic GFs released after liver metastasis resection.     

Prognostic Factors Predicting Poor Outcome in Living-Donor Liver Transplantation for Fulminant Hepatic Failure

Background

Living-donor liver transplantation (LDLT) has been accepted as feasible treatment for fulminant hepatic failure (FHF), although it has generated several debatable issues. In this study, we investigated the prognostic factors predicting fatal outcome after LDLT for FHF.

Experience of Combined Liver-Kidney Transplantation for Acute-on-Chronic Liver Failure Patients With Renal Dysfunction

Background

The aim of this study was to evaluate the outcomes of orthotopic liver transplantation (OLT) or combined liver-kidney transplantation (CLKT) for acute-on-chronic liver failure (ACLF) patients with renal dysfunction.

Methods

From January 2001 to December 2009, 133 patients underwent OLT for ACLF at our center. Among them, 30 had both ACLF and renal dysfunction. Of the 30 patients, 12 underwent CLKT for end-stage renal disease (ESRD), and the other 18 with hepatorenal syndrome type 1 (HRS1) underwent OLT alone. ACLF was defined according to the Asian Pacific Association for the Study of Liver Consensus Meeting. Clinical data were reviewed for survival outcomes.

Results

The median model for end-stage liver disease score (MELD) of patients with ACLF was 28. Among the 133 patients, all of whom received deceased donor liver grafts, 12 also got the kidney grafts from the same deceased donor. The hospital mortality rate was 21.8% for all patients with ACLF. The 5-year survival rates were 72.8% for patients without renal dysfunction and 70% for patients with renal dysfunction. The results of patients with ESRD who underwent CLKT were better than those of subjects without renal dysfunction or patients with HRS1 who underwent OLT alone.

Conclusions

OLT alone improved renal function in most patients with HRS1, including those requiring short-term hemodialysis. Simultaneous liver-kidney transplantation was an excellent strategy for patients with both ACLF and ESRD. It provided protection to the kidney allograft for liver-based metabolic diseases affecting the kidney. The rate of acute rejection episodes in kidneys was low.     

Le syndrome hépatorénal : mise au point

Hepatorenal syndrome (HRS) is a severe complication of cirrhosis. It develops as a result of abnormal hemodynamics, leading to systemic vasodilatation and renal vasoconstriction. Increased bacterial translocation, various cytokines and systemic inflammatory response system contribute to splanchnic vasodilatation, and altered renal autoregulation. An inadequate cardiac output with systolic incompetence increases the risk of renal failure. Type 1 HRS is usually initiated by a precipitating event associated with an exaggerated systemic inflammatory response, resulting in multiorgan failure. Vasoconstrictors are the basic treatment in patients with type 1 HRS; terlipressin is the superior agent. Norepinephrine can be used as an alternative. Transjugular intrahepatic portosystemic stent shunt may be applicable in a small number of patients with type 1 HRS and in most patients with type 2 HRS. Liver transplantation is the definitive treatment for HRS. The decision to do simultaneous or sequential liver and kidney transplant remains controversial. In general, patients who need more than 8 to 12 weeks of pretransplant dialysis should be considered for combined liver–kidney transplantation.     

Oxidative stress,NOx/l-arginine ratio and glutathione/glutathione S-transferase ratio as predictors of ‘sterile inflammation’ in patients with alcoholic cirrhosis and hepatorenal syndrome type II

Continuous intake of alcohol leads to liver cirrhosis because of imbalance of oxidative stress/antioxidative defense and chronic ‘sterile inflammation’. Hepatorenal syndrome (HRS) is the most severe complication of liver cirrhosis. The aim of our study was to assess: (1) the oxidative stress/antioxidative defense markers such as malondialdehyde (MDA), oxidative glutathione (GSH) and glutathione S-transferase (GST), (2) inflammation [C-reactive protein (CRP)], and (3) nitrate/nitrite levels (NOx) and its substrate L-arginine level. The study enrolled three groups: a group with cirrhosis and HRS (48 patients), a group with cirrhosis without HRS (32 patients), and a control group (40 healthy blood donors). All the patients with cirrhosis and HRS had type II HRS. MDA concentration was significantly higher in the groups with cirrhosis with and without HRS. Significant positive correlation was documented between the MDA level and de Ritis coefficient (AST/ALT), a marker of liver damage severity; between MDA and inflammation (CRP); between MDA and NOx concentration in the groups with cirrhosis with and without HRS. The correlation between MDA and creatinine level was significant in the group with HRS. The levels of GSH and GST were significantly lower in the groups with cirrhosis with and without HRS. The results of the study revealed that an increase in MDA and NOx concentration, along with decreased values of antioxidative defense and L-arginine, may indicate that liver damage can have an influence on progression to renal failure.     

Survival after left ventricular assist device implantation correlates with a novel device-based measure of heart rate variability: the heart rate score

Open in a separate window OBJECTIVESThe heart rate score (HRS) serves as a device-based measure of impaired heart rate variability and is an independent predictor of death in patients with heart failure and a cardiac implantable electrical device. However, no data are available for predicting death from the HRS in patients with end stage heart failure and a left ventricular assist device.METHODSFrom November 2011 to July 2018, a total of 56 patients with a pre-existing cardiac implantable electrical device underwent left ventricular assist device implantation at our 2 study sites. The ventricular HRS was calculated retrospectively during the first cardiac implantable electrical device follow-up examination following the index hospitalization. Survival during follow-up was correlated with initial HRS.RESULTSDuring the follow-up period, 46.4% of the patients (n = 26) died. The median follow-up period was 33.2 months. The median HRS after the index hospitalization was 41.1 ± 21.8%. More patients with an HRS >65% died compared to patients with an HRS <30% (76.9% vs 14.4%; P = 0.007).CONCLUSIONSIn our multicentre experience, survival of patients after an left ventricular assist device implant correlates with the HRS. After confirmation of our findings in a larger cohort, the effect of rate-responsive pacing will be within the scope of further investigation.     

Acute diverticulitis in immunosuppressed patients: a 12-year management experience

Background

Diverticular disease of the colon occurs commonly in developed countries. Immunosuppressed patients are thought to be more at risk of developing acute diverticulitis, worse disease, and higher complications secondary to therapy. This study aimed to assess outcomes for immunosuppressed patients with acute diverticulitis.

Method

A retrospective single-centre review was conducted of all patients presenting with acute diverticulitis at a major tertiary Australian hospital from 2006 to 2018.

Result

A total of 751 patients, comprising of 46 immunosuppressed patients, were included. Immunosuppressed patients were found to be older (62.25 versus 55.96, p = 0.016), have more comorbidities (median Charlson Index 3 versus 1, P < 0.001), and undergo more operative management (13.3% versus 5.1%, P = 0.020). Immunosuppressed patients with paracolic/pelvic abscesses (Modified Hinchey 1b/2) were more likely to undergo surgery (56% versus 24%, P = 0.046), while in patients with uncomplicated diverticulitis, there was no difference in immunosuppressed patients undergoing surgery (6.1% versus 5.1% P = 0.815). Immunosuppressed patients were more likely to have Grade III-IV Clavien-Dindo complication (P < 0.001).

Conclusion

Immunosuppressed patients with uncomplicated diverticulitis can be treated safely with non-operative management. Immunosuppressed patients were more likely to have operative management for Hinchey 1b/II and more likely to have grade III/IV complications.     

Assessing the utility of ultrasound-guided vascular access placement with longer catheters in critically ill pediatric patients

Background

Critically ill pediatric patients can have difficulty with establishing and maintaining stable vascular access. A long-dwelling peripheral intravenous catheter placement decreases the need for additional vascular interventions.

Aim

The study sought to compare longevity, catheter-associated complications, and the need for additional vascular interventions when using ultrasound-guided longer peripheral intravenous catheters comparing to a traditional approach using standard-sized peripheral intravenous catheters in pediatric critically ill patients with difficult vascular access.

Methods

This single-center retrospective cohort study included children 0–18 years of age with difficult vascular access admitted to the pediatric intensive care unit between 01/01/2018–06/01/2021.

Results

One hundred and eighty seven placements were included in the study, with 99 ultrasound-guided long intravenous catheters placed and 88 traditionally placed standard-sized intravenous catheters. In the univariate analysis, patients in the traditional approach were at a higher risk of intravenous failure compared to those in the ultrasound-guided approach (HR = 2.20, 95% CI [1.45–3.34], p = .001), with median intravenous survival times of 108 and 219 h, respectively. Adjusting for age, patients in the traditional approach remained at higher risk of intravenous failure (HR = 1.99, 95% CI: [1.28–3.08], p = .002). Adjusting for hospital length of stay, patients in the ultrasound-guided approach were less likely to have additional peripheral intravenous access placed during hospitalization (OR = 0.39, 95% CI [0.18–0.85] p = .017).

Conclusion

In critically ill pediatric patients with difficult vascular access, ultrasound-guided long peripheral intravenous catheters provide an alternative to traditional approach standard-sized intravenous catheters with improved longevity, lower failure rates, and reduced need for additional vascular interventions.     

Pancreaticoduodenectomy can be Performed Safely in Patients Aged 80 years and Older

Background  

Surgery offers the only chance for cure in patients with pancreatic cancer, and a growing number of elderly patients are being offered resection. We examined outcomes after pancreaticoduodenectomy in patients 80 years and older.     

Long‐term safety and efficacy of the novel β3‐adrenoreceptor agonist vibegron in Japanese patients with overactive bladder: A phase III prospective study

Objectives

To evaluate the long‐term safety and efficacy of vibegron 50 mg and 100 mg, a novel β₃‐adrenoreceptor agonist, in Japanese patients with overactive bladder.

Methods

This was a 1‐year, multicenter, open‐label, non‐controlled study. After a 1‐week observation phase, patients were treated with vibegron for 52 weeks. When the efficacy was insufficient after an 8‐week treatment with 50 mg, the dose was increased to 100 mg and maintained for an additional 44 weeks.

Results

Among a total of 169 patients receiving one or more doses of vibegron, 118 (69.8%) received vibegron 50 mg for 52 weeks, and the dose was increased to 100 mg in 51 (30.2%) patients. The incidence of drug‐related adverse events was 18.1% (21/116) in the vibegron 50 mg group and 11.8% (6/51) in the vibegron 100 mg group. Most frequent drug‐related adverse events were dry mouth (3.0%), residual urine volume increased (3.0%), constipation (2.4%) and cystitis (1.8%). Statistically significant changes in overactive bladder symptom variables (daily means of micturitions, urgency episodes, urgency incontinence episodes, incontinence episodes and night‐time frequency) from baseline were observed at week 4 and maintained until week 52. The condition of patients who did not respond well to vibegron 50 mg was much improved by increasing the dose to 100 mg. Vibegron improved the quality of life, and the proportion of patients’ satisfaction after the treatment with vibegron was high.

Conclusions

Long‐term (52‐week) treatment with vibegron is safe, well‐tolerated and effective in patients with overactive bladder.     

Management of patients with incurable colorectal cancer: a retrospective audit

Aim

Counselling patients and their relatives about non‐curative management options in colorectal cancer is difficult because of a paucity of published data. This study aims to determine outcomes in patients unsuitable for curative surgery and the rates of subsequent surgical intervention.

Method

This was an analysis of all colorectal cancers managed without curative surgery in a district general hospital from a prospectively maintained cancer registry between 2009 and 2016, as decided by a multidisciplinary team. Primary outcomes were overall survival and secondary outcomes were subsequent intervention rates and impact of tumour stage.

Results

In all, 183 patients out of 976 patients (18.8%) were identified. The median age at diagnosis was 81 years [interquartile range (IQR) 71–87 years]. Overall median survival from diagnosis was 205 days (IQR 60–532 days). One‐year mortality was 62.3%. Patients were classified into two groups depending on the reason for a non‐curable approach: patient‐related (PR) or disease‐related (DR). The difference in survival between PR (median 277 days, IQR 70–593) and DR (median 179 days, IQR 51–450) was 98 days (P = 0.023). Twenty‐four patients were alive at the end of the study period; 19 out of 91 cases in PR (20.8%) and five out of 92 cases in DR (5.4%). Overall intervention rates were 11.9%, with higher rates in the DR group (P = 0.005). Disease stage was not associated with subsequent surgical intervention between the two groups (P = 0.392).

Conclusion

Life expectancy for non‐curatively managed patients within our unit was 6.8 months with one in nine patients requiring subsequent surgical admission for palliation. This information may be useful when counselling patients with incurable colorectal malignancy.     

Rectus fascia sling for the treatment of total urethral incontinence in males

Objectives  

Urinary incontinence in patients with neurological disease is a major health problem. A modified rectus fascial sling has been assessed in incontinent male patients.     

Demographics,management and treatment outcomes of benign and malignant retroperitoneal tumors in Japan

Objectives

To show the demographics, type of treatment and clinical outcomes of patients with retroperitoneal tumors in Japan.

Methods

We carried out a retrospective analysis of patients with retroperitoneal tumors treated between 2000 and 2012 at 12 university hospitals in Japan. Histology was re‐evaluated using the 2013 World Health Organization classification.

Results

A total of 167 patients were included in the analysis. The number of diagnosed patients increased over the 12‐year study period. Liposarcoma and schwannoma were the most common histological types among intermediate/malignant and benign tumors, respectively. The intermediate/malignant tumors were larger and were more frequently found in older people. Surgical resection was the primary treatment for 151 patients. The median survival duration for patients with malignant tumors was 91 months, and was significantly shorter than that for patients with benign and intermediate tumors (P < 0.01). R2 resection was associated with significantly shorter survival than R0/R1 resection for malignant tumors (P < 0.01), but not for intermediate. Grossly complete resection of the recurrent tumors improved survival.

Conclusion

The number of patients diagnosed with retroperitoneal tumors increased over time. R2 resection of primary tumors was found to be associated with poor prognosis in malignant tumors, but not in intermediate tumors. Complete surgical resection of recurrent tumors was associated with a better oncological outcome.     

Thoracotomy in Thoracic Injuries: Results from a Tertiary Referral Hospital

Introduction:   

Critically injured patients may require thoracotomy after a thoracic injury. This study is a retrospective analysis of the results of thoracotomy in patients with thoracic injury.     

Native renal function after combined liver‐kidney transplant for type 1 hepatorenal syndrome: initial report on the use of postoperative Technetium‐99 m‐mercaptoacetyltriglycine scans

Type 1 hepatorenal syndrome (HRS) is characterized by rapid deterioration of renal function. We sought to assess native kidney function after combined kidney‐liver transplant (CLKTx) performed for type 1 HRS. We performed a retrospective, cross‐sectional, single‐center study. All patients with Type 1 HRS who received a CLKTx at the University of California, San Francisco from 1997 to 2007 were screened for enrollment. Patients with a baseline estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m² were eligible. Twenty‐three patients were identified and consented to receive a Technetium‐99 m‐mercaptoacetyltriglycine (MAG3) nuclear scan to measure the native kidney contribution to overall renal function. Only 4 of the 23 subjects (17.4%) demonstrated native renal function that consisted of a contribution ≥50% of total renal function. Several factors and comorbidities such as age, gender, race, duration of HRS, need for and duration of renal replacement therapy, need for pressors, urine sodium, proteinuria, and use of octreotide/midodrine were analyzed and not found to be significant in predicting native renal function. The assessment of post‐transplant native renal function following CLKTx may allow for improved accuracy in identifying the patients in need of CLKTx, and thus allow for greater optimization of dual‐organ allocation strategies in patients with concomitant liver and renal failure.     

Are health outcomes in the older colorectal cancer patients treated by curative intent surgery any different to the younger patients?

Background

Colorectal cancer poses a major burden. Its incidence increases with age and older patients with comorbidities have a higher likelihood of major complications. This study investigated the impact of age on health outcomes in colorectal cancer patients treated by surgery.

Methods

A prospective database of all patients undergoing colorectal cancer surgery with curative intent between 2012 and 2017 was used to identify patients. A retrospective review of existing medical records investigating health-related outcomes in colorectal cancer patients undergoing surgery was performed. Primary outcomes measured were overall survival (OS) and disease-free survival (DFS). Difference in restricted mean survival times (RMST) up to a pre-specified time point of 24 months was used to compare four age groups.

Results

Six-hundred and fifty-one patients were divided into four age group categories: ≤65-years (n = 244), 66 to 75-years (n = 213), 76 to 85-years (n = 162) and >85-years (n = 32). Older patients were found to have a higher rate of post-operative medical complications (including confusion) (P = 0.001) and a longer length of stay (LOS) (P = 0.01). There was no difference between the 76 to 85-year age group and >85-year age group in OS and DFS. However, there was a reduced OS in older patients (>65) compared to their younger cohorts (<65) (P = 0.04).

Conclusion

Older patients who undergo curative surgery have reduced OS, increased LOS and higher complication rates. Complex older patients may benefit from geriatric assessment and management in the peri-operative period.     

A novel risk score for severe ARDS patients undergoing ECMO after retrieval from peripheral hospitals

Background

Extracorporeal Membrane Oxygenation in severe ARDS unresponsive to conventional protective ventilation is associated with elevated costs, resource and complications, and appropriate risk stratification of candidate patients could be useful to recognize those more likely to benefit from ECMO. We aimed to derive a new outcome prediction score for patients retrieved by our ECMO team from peripheral centers, including systematic echocardiographic evaluation before ECMO start.

Methods

Sixty‐nine consecutive patients with refractory ARDS requiring ECMO transferred from peripheral centers to our ICU (a tertiary ECMO referral center), from 1 October 2009 to 31 December 2015, were assessed.

Results

All patients were transported on ECMO (distance, median 77, range 4–456 km) The mortality rate was 41% (28/69). Our new risk score included age ≥ 42 years, BMI < 31 kg/m², RV dilatation, and pH < 7.35. The proposed cut off (Youden's index method) of nine had a sensitivity of 96% and a specificity of 30% (AUC‐ROC: 0.85, 95% CI: 0.76–0.94, P < 0.001). When assessing the discriminatory ability of our risk score in the population of local patients, survivors had a mean value of 15.4 ± 8.6, whereas non‐survivors showed a mean value of 20.1 ± 7.4 (P < 0.001).

Conclusions

Our new risk score shows good discriminatory ability both in patients retrieved from peripheral centers and in those implanted at our center. This score includes variables easily available at bedside, and, for the first time, a pathophysiologic element, RV dilatation.     

Effects of renal dysfunction on cardiovascular events in diabetic patients with hypertension: Challenge-DM Study subgroup analysis

Background  

This study investigated the relation between renal dysfunction and cardiovascular events in patients from the Challenge-DM Study (a large-scale investigation of Japanese diabetic patients with hypertension on candesartan therapy).