Transition from laparoscopic to robotic liver surgery: clinical outcomes, learning curve effect, and cost-effectiveness.

The reproducibility of the implementation of robotic liver surgery (RLS) is still debated. The aim of the present study is to evaluate short-term outcomes and cost differences during the implementation of RLS, performed by an early adopter in laparoscopic liver surgery (LLS). Patients undergoing RLS between February 2020 and May 2021 were included. Short-term outcomes of the robotic group (RG) were compared to the "Initial Phase" group (IP) of 120 LLS cases and the 120 most recent laparoscopic cases or "Mastery Phase" group (MP). A cost analysis per procedure for the three groups was performed. Seventy-one patients underwent RLS during the study period. Median operative time in the RG was comparable to the IP, but significantly shorter in the MP (140 vs 138 vs 120 min, p < 0.001). Median intraoperative blood loss in the RG was lower than in both laparoscopic groups (40 ml [20-90 ml] vs 150 ml [50-250 ml] vs 80 ml [30-150 ml], p < 0.001). Median hospital stay in the RG was significantly shorter than the IP group (p < 0.001). There were no significant differences in postoperative complication, conversion, or readmission rates. Procedural cost analysis was in favor of robotic surgery (€5008) compared to the IP (€ 6913) and the MP (€6099). Surgeons with sufficient experience in LLS can rapidly overcome the learning curve for RLS. In our experience, the short-term outcomes of the implementation phase of RLS are similar to the mastery phase of LLS. The total average cost per procedure is lower for RLS compared to LLS.

Paclitaxel drug-coated balloon angioplasty for the treatment of failing arteriovenous fistulas: a single-center experience.

Objectives: To report our experience of angioplasty with Lutonix (Bard Peripheral Vascular, Inc., Tempe, AZ) drug-coated balloon (DCB) for the treatment of failing arteriovenous fistulas (AVF).Materials and methods: Retrospective, single-center analysis consisting of 14 patients treated with Lutonix paclitaxel DCBs in the period from July 2015 through April 2017. We analyzed technical success, clinical success, primary patency of the target lesion, primary patency of the dialysis circuit, and the rate of complications. Regular follow-up of AVF patency was realized by clinical examination and duplex ultrasonography. The Kaplan-Meier survival method was applied to determine the cumulative primary patency of the target lesion and the dialysis circuit.Results: Technical success was 100% and clinical success 92.9%. There were no major or minor complications. Cumulative target lesion primary patency after DCB was 69.2% at 6 months and 31.6% at 12 months. Cumulative vascular circuit primary patency was 61.5% at 6 months and 31.6% at 12 months.Conclusion: Compared to results reported in literature with plain old balloon angioplasty (POBA), Lutonix paclitaxel DCB angioplasty proved a short-term patency benefit in treatment of dialysis AVF stenosis.

Risk of diabetes in HIV-infected patients is associated with cirrhosis but not with chronic HCV coinfection in a French nationwide HIV cohort.

BACKGROUND: Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections have been reportedly associated with a higher risk of diabetes mellitus (DM) but results are conflicting. AIMS: To determine whether there is an association between chronic HCV and the incidence of DM, and to study the role of factors such as cirrhosis, IFN-based HCV therapy, sustained virologic response (SVR) and chronic HBV infection among patients living with HIV (PLHIV) followed in a large French multicentre cohort in the combination antiretroviral therapy (cART) era. METHODS: All PLHIV followed up in the Dat'AIDS cohort were eligible. Cox models for survival analysis were used to study the time to occurrence of DM. RESULTS: Among 28 699 PLHIV, 4004 patients had chronic HCV infection. The mean duration of HCV follow-up was 12.5 ± 8.1 years. The rate ratio of DM was 2.74 per 1000 person-years. By multivariate analysis, increasing age, body mass index>25, AIDS status, nadir CD4 cell count ≤200/mm3 , detectable HIV viral load and cirrhosis (HR 2.26 95% CI 1.14-1.18; P < 0.0001) were predictors of DM, whereas longer cART duration was associated with a lower risk of DM. Chronic HCV and HBV infection and IFN-based HCV therapy were not associated with DM. In a subanalysis among HCV-infected patients, SVR was not related to DM. CONCLUSIONS: Our study shows that in the HIV population, cirrhosis is associated with an increased occurrence of DM, but not chronic HCV infection or duration of HCV infection.

Cloning and functional analysis of the pbr lead resistance determinant of Ralstonia metallidurans CH34.

The lead resistance operon, pbr, of Ralstonia metallidurans (formerly Alcaligenes eutrophus) strain CH34 is unique, as it combines functions involved in uptake, efflux, and accumulation of Pb(II). The pbr lead resistance locus contains the following structural resistance genes: (i) pbrT, which encodes a Pb(II) uptake protein; (ii) pbrA, which encodes a P-type Pb(II) efflux ATPase; (iii) pbrB, which encodes a predicted integral membrane protein of unknown function; and (iv) pbrC, which encodes a predicted prolipoprotein signal peptidase. Downstream of pbrC, the pbrD gene, encoding a Pb(II)-binding protein, was identified in a region of DNA, which was essential for functional lead sequestration. Pb(II)-dependent inducible transcription of pbrABCD from the PpbrA promoter is regulated by PbrR, which belongs to the MerR family of metal ion-sensing regulatory proteins. This is the first report of a mechanism for specific lead resistance in any bacterial genus.

Blood pressure and the susceptibility to renal damage after unilateral nephrectomy and L-NAME-induced hypertension in rats.

BACKGROUND: Fawn-hooded hypertensive (FHH) rats carry several genes which determine the susceptibility to develop renal damage, while renal damage resistant August x Copenhagen Irish (ACI) rats do not. Kidneys from heterozygous (FHH x ACI) F(1) rats, appear to be largely, but not completely, protected after blood pressure elevation with N(omega)-nitro-L-arginine methyl ester (L-NAME). We examined the role of an increased haemodynamic burden on the development of renal damage combining unilateral nephrectomy (UNx)- and L-NAME-induced hypertension in F(1) and ACI rats. Additionally, we investigated whether a general toxic effect of L-NAME, independent from a blood pressure elevation, caused renal damage in F(1) rats in animals simultaneously treated with L-NAME and the ACE inhibitor lisinopril. METHODS: Surgery was performed and L-NAME treatment (50 or 150 mg/l) was started at the age of 15 weeks. Systolic blood pressure (SBP) and urinary albumin excretion (UaV) were measured at 6 and 12 weeks post-UNx, followed by autopsy to determine the incidence of focal glomerulosclerosis (FGS). Using lisinopril (LIS) and L-NAME, another group of rats was evaluated at 12, 18, and 24 weeks after start of treatment. RESULTS: At similar L-NAME intake, F, rats developed more severe hypertension and more UaV than ACI rats. The increase in UaV per mmHg increase in SBP was fivefold higher in F(1) compared with ACI rats. In F(1) rats, the increase in UaV per percentage incidence increase in FGS was three times higher. In LIS treated F(1) rats, no significant UaV or FGS was measured at low blood pressure levels, indicating that renal damage in hypertensive F(1) rats is not a direct effect of L-NAME, but the result of the high blood pressure or another action of the renin-angiotensin system. CONCLUSION: We conclude that heterozygosity for the genes influencing the development of renal damage in the FHH strain increases the susceptibility of the kidney to develop damage after UNx combined with systemic hypertension.

Directing portal flow is essential for graft survival in auxiliary partial heterotopic liver transplantation in the dog.

BACKGROUND/PURPOSE: Auxiliary liver transplantation is an attractive alternative for orthotopic liver transplantation in patients with certain inborn errors of metabolism of the liver in which complete resection of the liver is unnecessary or even contraindicated. Because in these diseases portal hypertension is mostly absent, finding a balance in portal blood distribution between native liver and graft is complicated. The objective of this study was to investigate requirements for long-term (180 days) graft survival in auxiliary partial heterotopic liver transplantation (APHLT) in a dog model. METHODS: A metabolic defect was corrected in 26 dalmation dogs with a 60% beagle heterotopic auxiliary liver graft. Four groups of different portal inflow were studied. In the ligation group the portal vein to the host liver was ligated. In the split-flow group graft and host liver received separate portal inflow. In the banding group the distribution of the portal flow was regulated with an adjustable strapband and in the free-flow group the portal blood was allowed to flow randomly to host or graft liver. RESULTS: Metabolic correction increased in all groups after transplantation from 0.19 +/- 0.02 to 0.70 +/- 0.05 (P< .0001) but remained significantly better in the ligation and split-flow groups (graft survival, 135 +/- 27 and 144 +/- 31 days). In the banding group metabolic correction decreased significantly after 70 days, and although the grafts kept some function for 155 +/- 14 days, in 4 of 6 dogs portal thrombosis was found. In the free-flow group, competition for the portal blood led to reduced correction within 12 days and total loss of function in 96 +/- 14 days. Graft function also was assessed with technetium (Tc) 99m dimethyl-iminodiacetic acid uptake. A good linear association between HIDA uptake and metabolic correction was observed (r = 0.74; P < .0005). Grafts that contributed more than 15% to the total uptake of HIDA showed biochemical correction. This indicates a critical graft mass of about 15% to 20% of the hepatocyte volume to correct this metabolic defect. CONCLUSION: Auxiliary partial heterotopic liver transplantation can be a valuable alternative treatment for inborn errors of hepatic metabolism if the native liver and the graft receive separate portal blood inflow.

How does podocyte damage result in tubular damage?

Severe podocyte damage including detachment from the GBM leads to adhesion of the glomerular tuft to Bowman's capsule, thus to a local loss of the separation of the tuft from the interstitium. Perfused capillaries contained in the tuft adhesion deliver their filtrate no longer into Bowman's space but into the interstitium. In response, interstitial fibroblasts create a cellular cover around the focus of misdirected filtration, interpreted teleologically, aiming at preventing the entry of this fluid into the interstitium. This results in the formation of a crescent-shaped, fluid-filled paraglomerular space overarching the segmental glomerular lesion. Extension of this space over the entire glomerulus leads to global sclerosis; extension of this space via the urinary pole onto the outer aspect of the corresponding tubule leads to the degeneration of the tubule. Since, as we postulate, such misdirected filtration and filtrate spreading is the crucial mechanism of damage progression in 'classic' focal segmental glomerulosclerosis (FSGS), the most characteristic structural injury of FSGS is the merger of the tuft with the interstitium, represented by a tuft adhesion, later a synechia. Therefore, histopathologically, 'classic' FSGS is best defined by an adhesion/synechia of the tuft to Bowman's capsule.

From segmental glomerulosclerosis to total nephron degeneration and interstitial fibrosis: a histopathological study in rat models and human glomerulopathies.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is consistently associated with tubular degeneration and interstitial fibrosis, altogether, accounting for the progressive decline in renal function. The mechanisms which link glomerular injury to tubulo-interstitial fibrosis are controversial. The present study describes the step-by-step sequence of histopathological events, i.e. the evolution of the injury from the initial lesion in the glomerulus to total nephron destruction. METHODS: The investigation was performed in male hypertensive Fawn-hooded rats (6-, 9-, and 12-month-old) and 14-month-old Milan normotensive rats. The kidneys were fixed by in vivo perfusion and processed for structural investigation. Autopsy materials from human cases of focal segmental glomerulosclerosis and diabetic nephropathy were also examined. RESULTS: FSGS as seen in rat models consists of collapsed and hyalinized capillaries and mesangial portions which are included within a synechia between the glomerular tuft and Bowman's capsule. In addition, a synechia generally contains glomerular capillaries which are perfused and continue to filter with the filtrate being delivered into the interstitium rather than into Bowman's capsular space. Such filtration creates a paraglomerular space on the outer aspect of the parietal epithelium. This space becomes separated from the interstitium by a dense layer of sheet-like fibroblast processes. Associated with the progression to global sclerosis, this space spreads around the entire circumference of a glomerulus; all 'sclerotic' tuft portions are eventually contained in this space. Starting from the urinary pole this process also involves the proximal tubule, initially by expanding the tubular basement membrane (TBM) and later, by separating the TBM from its epithelium, thus creating a peritubular space by misdirected filtrate spreading. Similar to the situation observed at the glomerulus this space becomes separated from the interstitium by a layer of fibroblast processes. The final degeneration of the nephron occurs via two pathways. Pathway I whereby development to global sclerosis is dominant or develops concurrently with tubular degeneration, eventually terminating in global and cylindrical remnants of extracellular matrix surrounded by abundant fibrous tissue. Pathway II where the degeneration of the tubule is ahead of damage progression in the glomerulus leading to atubular glomerular cysts. CONCLUSION: The present study suggests that severely injured glomeruli may continue to filter with the filtrate spreading along interstitial routes. Fluid added locally to the interstitium from such 'extraterritorial' glomerular capillaries probably is quite different in quantity and composition compared to that from interstitial capillaries. We propose that this kind of abnormal addition of fluid to the interstitium is the essential mechanism accounting for interstitial progression of the disease. Similar histopathological phenomena in human kidneys with focal segmental glomerulosclerosis suggest that the pathogenetic pathways defined in the rat models operate in human disease as well.

Pathogenesis of glomerular injury in the fawn-hooded rat: effect of unilateral nephrectomy.

Fawn-hooded (FH) rats with congenital proteinuria and systemic and glomerular hypertension are very susceptible to renal damage at a young age. In this study, the effects of unilateral nephrectomy (UNX) on the function and structure of the remaining kidney in the FHH substrain were assessed. A long-term study was performed to determine the changes in systemic blood pressure, renal function, and proteinuria during the development of chronic renal failure in UNX-FHH and two-kidney (2K) FHH rats. Renal micropuncture and morphologic studies were performed at 4 wk after surgery. The long-term study showed that, after UNX, systolic blood pressure did not differ significantly (from that of 2K-FHH rats. After UNX, there was compensatory hyperfiltration, at about 70% of the 2K level, that could be maintained for 12 wk only. The subsequent fall in GFR was preceded by severe proteinuria. The mean survival time of UNX-FHH rats was only 35 wk. Micropuncture studies showed that the high mean glomerular capillary pressure of 2K-FHH rats was further elevated after UNX. The glomerular capillary ultrafiltration coefficient did not differ significantly between UNX-FHH and 2K-FHH rats. The weight of the remaining kidney and the mean glomerular tuft volume in UNX-FHH were, on average, 36 and 31% greater than in 2K rats. The results indicate that the FHH rat is extremely vulnerable to the adverse renal effects of UNX.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of age at the time of unilateral nephrectomy and dietary protein on long-term renal function in rats.

Glomerular filtration rate (GFR) and urinary protein excretion (UpV) were studied in male rats with a uninephrectomy at 3 (UNX-3) or 15 weeks of age (UNX-15) and fed a low (12%, LP), normal (24%, NP) or high (36%, HP) protein diet. Measurements were made every 12 weeks throughout the entire life-span. The UNX rats were compared with sham-operated (2K) rats of the same age and on the same diets. At 12 weeks after surgery, the GFR of UNX rats, corrected for differences in body weight, age and protein intake (GFRcor), ranged between 73% and 77% of that of 2K rats. On the HP and NP diet, UpV was higher in UNX-3 than in UNX-15 rats. On the LP diet, UpV was equally low in both groups. Long-term follow-up indicated that the GFR of UNX rats on the HP diet started to decline first, followed by those on an NP diet, while those on an LP diet had the longest period of stable GFR. For UNX rats, the time to reach a GFRcor of 50% was used as an indicator of the length of renal survival. Analysis of variance of the renal survival times indicated a highly significant interaction between the protein diet and age at the time of UNX. On the HP diet, UNX-3 rats have a shorter renal survival time than UNX-15, while on the LP diet UNX-3 rats have a longer renal survival time. This indicates that the long-term outcome of UNX at young age depends on the protein intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal function up to 50 years after unilateral nephrectomy in childhood.

Removal of one kidney during childhood differs from removal of a kidney from an adult as the child's future depends on an adequate function of the remaining kidney during a longer period of time. We assessed the long-term effect of unilateral nephrectomy in childhood on renal function, protein excretion, and blood pressure. Data were obtained from 111 subjects undergoing uninephrectomy for unilateral renal disease before the age of 16 years who had no evidence of renal abnormalities in the contralateral kidney at the time of surgery. At investigation the patients were 18 to 56 years of age with an interval of up to 52 years after uninephrectomy. On average, renal function was well maintained at approximately 75% of the reported normal two-kidney value. Blood pressure in men was higher than in women. Stratification for age showed no statistically significant differences between those undergoing uninephrectomy before or after the age of 4.5 years. Stratification for post-uninephrectomy interval revealed renal function to be lower and blood pressure, urinary albumin excretion, and protein excretion to be higher in those with an interval of more than 25 years. In men over 30 years of age, linear regression analysis indicated a decrease in glomerular filtration rate, effective renal plasma flow, and creatinine clearance, and an increase in blood pressure and albumin excretion with time. Controlled longitudinal studies are needed to detect true changes and to ascertain whether such changes are different from the age-related changes seen in individuals with two kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

A new type of Alcaligenes eutrophus CH34 zinc resistance generated by mutations affecting regulation of the cnr cobalt-nickel resistance system.

Spontaneous mutants that were resistant to zinc were isolated from Alcaligenes eutrophus CH34 containing either the native plasmid pMOL28 or a derivative derepressed for its self-transfer, pMOL50. With the cured plasmid-free derivative of CH34, strain AE104, such mutants were not detected. The mutations, which were shown to be located in the plasmid, increased the level of the nickel and cobalt resistance determined by the cnr locus. The chromate resistance closely linked to the cnr locus was not affected by these mutations. In the Znr mutants, the resistance to zinc and nickel was constitutively expressed. Uptake studies showed that the zinc resistance in a Znr mutant resulted from reduced accumulation of zinc ions in comparison with that in the plasmid-free strain. Reduced accumulation of zinc was also observed to a lesser degree in the parental strain induced with nickel, suggesting that zinc interferes with the Ni2+ and Co2+ efflux system. A 12.2-kb EcoRI-XbaI restriction endonuclease fragment containing the cnr locus was cloned from plasmid pMOL28 harboring the mutation and shortened to an 8.5-kb EcoRI-PstI-PstI fragment conferring resistance to zinc, nickel, and cobalt. The 12.2-kb EcoRI-XbaI fragment was also reduced to a 9.7-kb BamHI fragment still encoding weak resistance to nickel and cobalt but not to zinc. Complementation studies demonstrated the recessivity of the cnr mutations with a Znr phenotype. Such mutations thus allow positive selection of mutants affected in the expression of the cnr operon.

Sequential changes in relative liver function assessed by 99mTc-HIDA scintigraphy after auxiliary heterotopic liver transplantation in dogs.

Auxiliary heterotopic liver transplantation (HLT) was used to achieve functional repair in a dog model with an inborn error of metabolism. For the interpretation of the results, information on separate liver function is essential when a normal host liver is also present. We developed a radionuclear method to quantitate the relative contribution of each liver to the total uptake of intravenously (IV) injected 99mTc-HIDA. The HLT was performed between 20 mismatched pairs of dogs from two different strains. Four surgical procedures were used. After autopsy the outcome of the premortem HIDA-scan was compared with the wet weight of the graft and the host liver. A good linear correlation was noted between the relative contribution of the uptake and weight of the graft to the total HIDA uptake and total liver weight. Therefore, the relative contribution of an auxiliary heterotopic liver graft to the total liver function can be quantitated with a 99mTc-HIDA scan. With this technique, changes in relative function after an HLT under various flow conditions can be sequentially followed.

The effect of protein intake on the lifelong changes in renal function of rats with a solitary kidney damaged at young age.

Changes in renal function were followed lifelong in male rats with only 1 kidney either intact or damaged by ureteral obstruction or ischemia. After surgery the rats were given a low (12%) or a high (36%) protein diet. After a period with a stable glomerular filtration rate, which was longer on the low protein diet, there was a linear decline in rats with an intact single kidney. The rate of decline was highest on the high protein diet, resulting in a shorter survival time. A decrease in urine osmolality and an increase in protein excretion preceded the decrease in filtration rate, while it was followed by an increase in blood pressure. The glomerular filtration rate of the rats with a single damaged kidney initially recovered to 75 to 80% of that of rats with an intact single kidney on the same diet. There was a linear decrease in the glomerular filtration rate, with the highest rate of decrease on the high protein diet. The mean survival time was less than that of rats with a single intact kidney. Proteinuria preceded the decrease in filtration rate, while hypertension was observed later. We conclude that in rats with a solitary kidney renal failure eventually develops. A low protein diet postpones and attenuates this development but it does not prevent it.

Effect of protein intake on lifelong changes in renal function of rats unilaterally nephrectomized at young age.

Changes in glomerular filtration rate (GFR) and urinary protein excretion were determined during a lifelong follow-up period in male WAG/Rij rats, unilaterally nephrectomized (NX) just after weaning, and compared with changes in control rats with both kidneys intact (2K). After surgery, the animals were given either a low-protein (LP; 12%), normal-protein (NP; 24%) or high-protein (HP; 36%) diet. The GFR of 2K-rats was highest with the HP diet and lowest with the LP diet. With all three diets, the GFR of 2K rats remained stable for about 2 years. The mean survival time of 2K rats was not affected by the dietary protein intake and amounted to about 120 weeks. Initially, the GFR of NX rats was highest with the HP and lowest with the LP diet. The GFR remained stable for a period of 36 weeks with the HP diet, 48 weeks with the NP diet, and 72 weeks with the LP diet. Subsequently, the GFR fell linearly in the great majority of cases with all three diets. The highest rate of decline was found in NX rats given the HP diet. As a result, from week 72, the GFR of the NX rats on the LP diet was significantly higher than that of NX rats on either the NP or the HP diet. With all three diets the mean survival time of NX rats was less than that of 2K rats on the same diet. The mean survival time of NX rats on the HP diet was also less than that of NX rats on the LP or NP diet. Proteinuria preceded the fall in GFR in NX rats. The proteinuria was most severe in NX rats on the HP diet, but only moderate with the LP diet. We conclude that, in a rat strain not very prone to develop renal lesions, the GFR of a solitary kidney eventually declines. An LP diet postpones but does not prevent the decline.

Renal function in single-kidney rats.

Can a single kidney survive for a normal life span? This is the type of question frequently asked by patients and especially by parents of children who lose one kidney in early childhood. Based on our wide experience with single-kidney rats, we will try to give an answer to this question. After the removal of its counterpart, the single remaining kidney will rapidly adapt to the new situation by a compensatory increase in the glomerular filtration rate (GFR) and renal mass. This is true not only for intact kidneys but also for damaged ones. The GFR level obtained by damaged kidneys will be less than that of intact single kidneys, however, depending on the degree of initial damage. The GFR is stable for a certain period of time, which is longer for intact single kidneys than for damaged kidneys and also depends on the daily protein intake; after that renal function will deteriorate. This decline in GFR is preceded by a marked increase in urinary protein excretion. Although the follow-up period is not completed yet, the survival time of single intact kidneys in rats on a normal diet is expected to be 15%-20% less than the normal rat life span. In rats on a lifelong high protein intake the kidney survival time drops to 40% below the normal rat life span. In rats on a moderately reduced protein intake, however, single intact kidneys may survive for a normal life span. The situation is worse for single damaged kidneys. Depending on the severity of the initial damage, kidney survival time will be much less than a normal life span. We studied rats with an initial recovery to 75% of renal function. Despite this initial recovery, the animals died of renal failure within 50% of the expected life span. A low-protein diet prolonged the renal survival by about 12%, a high-protein diet shortened it by the same percentage.

Potentiation of cis-diamminedichloroplatinum nephrotoxicity by amikacin in rats.

The nephrotoxic interaction between cis-diamminedichloroplatinum (CDDP) and amikacin (AMI) was studied in rats. Following a single dose of CDDP (5 mg/kg i.v.), AMI (60 mg/kg s.c.) was given for 14 days. When given alone CDDP caused a 40% fall in the glomerular filtration rate (GFR), whereas AMI alone had no effect on GFR. This nonnephrotoxic course of AMI potentiated the CDDP-induced fall in GFR. Only a limited recovery of renal function was observed during a 15-week follow-up period.