The intercalated cells of the mouse kidney OMCDis are the target of the vasopressin V1a receptor axis for urinary acidification

Background

Vasopressin V1a receptor (V1aR) null mice have insufficient acid–base balance, but the target cell for V1aR signaling which results in the urinary acidification has not been identified.

Methods

By using a quantitative in situ hybridization technique and a double-staining technique with an anti-AQP3 antibody in mice, we investigated the axial distribution and acidosis-induced expression of V1aR mRNA along the nephron. We also investigated the acidosis-induced morphological change in the tubule cells from wild-type and V1aR-null (V1aR^?/?) mice.

Results

In the normal condition, V1aR mRNA was moderately expressed in the medullary thick ascending limb (MTAL) and highly expressed in the intercalated cell (IC) throughout the collecting duct (CD). However, no expression was observed in the proximal tubule, thin limbs of Henle’s loop, and the principal cell of the CD. Importantly, V1aR mRNA was upregulated significantly both in the TAL and the IC of the CD in the inner stripe of the outer medulla (MTAL_is and IC of OMCD_is, respectively) when mice were treated with NH₄Cl (0.28 mol/L) for 6 days. Acidosis-induced hypertrophy, which was completely attenuated in V1aR^?/? mice, was observed only in the IC of OMCD_is (P < 0.005). In addition, urinary excretion of ammonia (NH₃/NH₄ ⁺) was significantly decreased on day 3 (P < 0.05) and day 6 (P < 0.005) in the V1aR^?/? mice treated with NH₄Cl.

Conclusion

In conclusion, the IC of OMCD_is may be the target cell stimulated by the vasopressin V1aR axis and contribute to urinary acidification, at least during metabolic acidosis.     

The effects of tolvaptan on patients with severe chronic kidney disease complicated by congestive heart failure

Background

Tolvaptan, a diuretic with a new mechanism of action, selectively binds to the vasopressin V2 receptor and inhibits reabsorption of water. Its effect on heart failure is proven, but its benefit for patients with chronic kidney disease (CKD) has not been not confirmed. In this study, we examined the effect of tolvaptan on patients with severe CKD.

Methods

We analyzed patients with stage 4 or higher CKD who had congestive heart failure that was resistant to existing diuretics. The patients were administered an initial tolvaptan dose of 7.5 mg/day. We assumed urine volume and urine osmolality to be the main effective endpoint and recorded free water clearance, serum osmolality, serum creatinine (Cr) level, and adverse events.

Results

There was no instance of clinically significant hypernatremia. The urine volume increased significantly (P < 0.0001), as did the urine osmolality (P = 0.0053). Free water clearance showed a tendency to increase, although the difference was not statistically significant. The serum creatinine level did not change significantly, and there was no clear effect on renal function. However, in patients with stage 5 CKD, the serum creatinine level decreased significantly (n = 5, P = 0.0435). There were no adverse events.

Conclusion

We confirmed that tolvaptan has a diuretic effect in patients with both severe CKD and congestive heart failure without causing either clinically significant hypernatremia or an adverse effect on renal function. Tolvaptan is an effective diuretic for patients with CKD.     

AQP2 in human urine is predominantly localized to exosomes with preserved water channel activities

Background

AQP2 water channel is critical for urinary concentration in the kidney. Interestingly, AQP2 is abundantly excreted in the urine as extracellular vesicles (EVs), which is known to be a useful biomarker for water-balance disorders although the character of AQP2-enriched EVs is poorly understood including water channel function.

Methods

Human urine EVs were obtained by a differential centrifugation method. AQP2-bearing EVs were isolated by immunoprecipitation with an AQP2-specific antibody, and the proteins in the EVs were analyzed by LC–MS/MS proteomic analysis. Osmotic water permeability (Pf) of the AQP2-rich EVs was measured by a stopped-flow method monitoring scattered light intensity in response to outwardly directed osmotic gradient.

Results

Sequential centrifugation of human urine showed that AQP2 was present predominantly (80%) in low-density EVs (160,000 g), whereas negligible amount in high-density EVs (17,000 g). Proteomic analysis of the AQP2-bearing EVs identified 137 proteins, mostly in the endosome pathway, including the components of ESCRT (endosomal sorting complex required transporter)-I, II, III. Pf value of the 160,000 g EVs was 4.75?±?0.38?×?10^?4 cm s^?1 (mean?±?SE) with the activation energy of 3.51 kcal mol^?1 which was inhibited with 0.3 mM HgCl₂ by 63%, suggesting a channel-mediated water transport. Moreover, Pf value showed a significant correlation with the abundance of AQP2 protein in EVs.

Conclusion

Taken together, AQP2 is localized predominantly to urinary exosomes with preserved water channel activities.

     

Silencing of TLR4 Increases Tumor Progression and Lung Metastasis in a Murine Model of Breast Cancer

Background

Toll-like receptor 4 (TLR4) is a member of a family of pattern recognition receptors that are involved in the host defense against microbial infection. Little research has investigated the link between TLR4 and cancer. We thus addressed the effect of TLR4 in both the host immune system and cancer cells with regard to its effect on breast cancer progression and metastasis.

Methods

Adult female Balb/c mice aged 6–8 weeks were divided into three groups. In group 1, 15 each wild-type and TLR4^?/? mice were inoculated with 4T1 cells; in group 2, wild-type mice were inoculated with 4T1 cells (n = 15), 4T1 cells transduced with TLR4 lentivirus (n = 15) or with control lentivirus (n = 15); and in group 3, 15 TLR4^?/? mice were inoculated with 4T1 cells transduced with TLR4 lentivirus. Flank tumor volume was measured with calipers during weeks 2–5. Animals were then humanely killed and the number of macroscopic lung nodules counted.

Results

There was a significant increase in tumor volume in weeks 2, 3 and 4 after inoculation of TLR4^?/? mice with 4T1 cells compared with wild-type mice (p < 0.05). The number of metastatic lung nodules was significantly higher in TLR4^?/? mice (p < 0.05), and survival of tumor-bearing TLR4^?/? mice was substantially reduced compared with wild-type mice (p = 0.004). Knockdown of TLR4 from the 4T1 cells led to a relative reduction in lung metastasis, although it did not reach statistical significance.

Conclusions

TLR4 exerts both a defensive role at the host level and a negative role at the cancer cell level in this murine metastatic breast tumor model. Further evaluation of the role of TLR4 in breast cancer is warranted.

     

Mapping the cytokine profile of painful bladder syndrome/interstitial cystitis in human bladder and urine specimens

Purpose

This study investigated the cytokine profile in bladder tissue and urine of painful bladder syndrome/interstitial cystitis (PBS/IC) patients.

Methods

Multiplex analysis of 23 cytokines was performed with a multiple antigen bead assay (Luminex 100 IS) on cold cup bladder biopsy and urine specimens collected during cystoscopy with hydrodistention (HD) under general anesthesia from 10 PBS/IC patients (ICS definition). Collected tissue specimens and urine from pre-HD and post-HD (mean 27 days) were compared to banked urine and tissue specimens (n = 10) collected from control subjects without PBS/IC symptoms.

Results

Univariate comparison of bladder tissue levels found significant elevation of IL-16, IL-18, CTACK, ICAM-1, MCP-3, SCGFβ, TRAIL, and VCAM-1 in PBS/IC relative to controls. Multivariate analysis revealed VCAM-1 and ICAM-1 were responsible for the discrimination of both tissue and urine of PBS/IC from controls. Urine levels of MCP-3 and TRAIL were significantly reduced a month after HD in concert with improvement in standardized measures of clinical symptoms (pain, urgency, and frequency (PUF) overall score [mean 25.8 ± 5.5 vs. 20.3 ± 7, p = 0.04] and symptom score [mean 18.2 ± 3.2 vs. 12.2 ± 5.9; p = 0.009]). Post-HD urine levels of MCSF(r = 0.88; p = 0.003), MCP-3 (r = 0.81; p = 0.01), SDF1α (r = 0.82; p = 0.01), and IL-18 (r = 0.64; p = 0.08) positively correlated with improved symptom scores.

Conclusions

These results indicate significant elevation of cytokines in PBS/IC bladder tissue relative to controls. Significant reduction in post-HD urine levels of MCP-3 and TRAIL relative to pre-HD in PBS/IC was associated with clinical improvement (as measured by PBS/IC symptom scores) to qualify them as biomarker candidates.     

Genetic Background Modifies the Effects of Type 2 Cannabinoid Receptor Deficiency on Bone Mass and Bone Turnover

Cannabinoid receptors and their ligands play significant roles in regulating bone metabolism. Previous studies of type 1 cannabinoid receptor-deficient mice have shown that genetic background influences the skeletal phenotype. Here, we investigated the effects of genetic background on the skeletal phenotype of mice with type 2 cannabinoid receptor deficiency (Cnr2 ^?/?). We studied Cnr2 ^?/? mice on a CD1 background and compared the findings with those previously reported in Cnr2 ^?/? C57BL/6 mice. Young female Cnr2 ^?/? CD1 mice had low bone turnover and high trabecular bone mass compared with wild-type (WT), contrasting with the situation in Cnr2 ^?/? C57BL/6 mice where trabecular bone mass has been reported to be similar to WT. The Cnr2 ^?/? CD1 mice lost more trabecular bone at the tibia with age than WT due to reduced bone formation, and at 12 months there was no difference in trabecular bone volume between genotypes. This differs from the phenotype previously reported in C57BL/6 Cnr2 ^?/? mice, where bone turnover is increased and bone mass reduced with age. There were no substantial differences in skeletal phenotype between Cnr2 ^?/? and WT in male mice. Cortical bone phenotype was similar in Cnr2 ^?/? and WT mice of both genders. Deficiency of Cnr2 has site- and gender-specific effects on the skeleton, mainly affecting trabecular bone, which are influenced by genetic differences between mouse strains. Further evaluation of the pathways responsible might yield new insights into the mechanisms by which cannabinoid receptors regulate bone metabolism.     

Preservation of residual renal function by not removing water in new hemodialysis patients: a randomized,controlled study

Purpose

To investigate the effect of no water removal (NWR) on preservation of residual renal function (RRF) in new hemodialysis (HD) patients.

Methods

Fifty-six patients with a daily urine volume ≥1,000 mL were included. Patients were randomized to different fluid management groups of NWR or water removal (WR) for 6 months. If predialysis BP was >150/90 mmHg, patients could take antihypertensive drugs. The primary endpoints included death, cardio-cerebral vascular disease, refractory hypertension, and edema or an auxiliary examination indicating obvious fluid retention. The secondary endpoint was oliguria. A daily urine volume, 24-h urine creatinine clearance, the defined daily dose (DDD) index of antihypertensive drugs, erythropoietin resistance index, cardiothoracic ratio, and left ventricular mass index (LVMI) were recorded.

Results

Eight patients in the NWR group reached the primary endpoints. Nine patients in the WR group reached the secondary endpoint. At the end of the study, patients in the NWR group had more increased systemic blood pressure (9.0 ± 8.3 vs. ?2.4 ± 2.0 mmHg, p < 0.001), DDD index (1.2 ± 1.02 vs. ?0.9 ± 0.51, p < 0.001), daily urine volume (164 ± 351 vs. ?726 ± 342 mL, p < 0.001), cardiothoracic ratio (0.02 ± 0.04 vs. ?0.03 ± 0.03, p < 0.001), LVMI (9.6 ± 17.0 vs. ?12.0 ± 21.4 g/m², p < 0.001), and less decreased urine creatinine clearance (?1.0 ± 0.4 vs. ?2.0 ± 1.0, p < 0.001), compared with those patients in the WR group.

Conclusions

Preservation of RRF by NWR is warranted in new HD patients, but is not appropriate for all patients.     

Real-time navigation by fluorescence-based enhanced reality for precise estimation of future anastomotic site in digestive surgery

Background

Fluorescence-based enhanced reality (FLER) is a technique to evaluate intestinal perfusion based on the elaboration of the Indocyanine Green fluorescence signal. The aim of the study was to assess FLER’s performances in evaluating perfusion in an animal model of long-lasting intestinal ischemia.

Materials and methods

An ischemic segment was created in 18 small bowel loops in 6 pigs. After 2 h (n = 6), 4 h (n = 6), and 6 h (n = 6), loops were evaluated clinically and by FLER to delineate five regions of interest (ROIs): ischemic zone (ROI 1), presumed viable margins (ROI 2a–2b), and vascularized areas (3a–3b). Capillary lactates were measured to compare clinical vs. FLER assessment. Basal (V ₀ ) and maximal (V _max) mitochondrial respiration rates were determined according to FLER.

Results

Lactates (mmol/L) at clinically identified resection lines were significantly higher when compared to those identified by FLER (2.43 ± 0.95 vs. 1.55 ± 0.33 p = 0.02) after 4 h of ischemia. Lactates at 2 h at ROI 1 were 5.45 ± 2.44 vs. 1.9 ± 0.6 (2a–2b; p < 0.0001) vs. 1.2 ± 0.3 (3a–3b; p < 0.0001). At 4 h, lactates were 4.36 ± 1.32 (ROI 1) vs. 1.83 ± 0.81 (2a–2b; p < 0.0001) vs. 1.35 ± 0.67 (3a–3b; p < 0.0001). At 6 h, lactates were 4.16 ± 2.55 vs. 1.8 ± 1.2 vs. 1.45 ± 0.83 at ROI 1 vs. 2a–-2b (p = 0.013) vs. 3a–3b (p = 0.0035). Mean V ₀ and V _max (pmolO2/second/mg of tissue) were significantly impaired after 4 and 6 h at ROI 1 (V ₀ ^4h  = 34.83 ± 10.39; V _max ^4h  = 76.6 ± 29.09; V ₀ ^6h  = 44.1 ± 12.37 and V _max ^6h  = 116.1 ± 40.1) when compared to 2a-–2b (V ₀ ^4h  = 67.1 ± 17.47 p = 0.00039; V _max ^4h  = 146.8 ± 55.47 p = 0.0054; V ₀ ^6h  = 63.9 ± 28.99 p = 0.03; V _max ^6h  = 167.2 ± 56.96 p = 0.01). V ₀ and V _max were significantly higher at 3a–3b.

Conclusions

FLER may identify the future anastomotic site even after repetitive assessments and long-standing bowel ischemia.     

The role of short daily hemodialysis in the control of hyperphosphatemia, secondary hyperparathyroidism and anemia

Background

Hyperphosphatemia, secondary hyperparathyroidism (SHPT) and anemia are common secondary complications in hemodialysis patients with end-stage renal disease (ESRD). Compared with conventional hemodialysis (CHD), short daily hemodialysis (sDHD) has been found to be more effective in patients with ESRD. The objective of this study was to determine whether sDHD could improve hyperphosphatemia, SHPT and anemia in patients with ESRD.

Methods

Twenty-seven patients (11 women and 16 men, 46.8 ± 13.4 years old) were switched from CHD to sDHD. All hematologic parameters were measured prior to the switch (baseline), at 3 months after the switch (sDHD₁) and at 6 months after the switch (sDHD₂).

Results

The serum phosphate decreased from 2.54 ± 0.32 mmol/L at baseline to 2.15 ± 0.36 mmol/L (p < 0.001) at sDHD₁ and 1.97 ± 0.33 mmol/L (p < 0.001) at sDHD₂. Calcium-phosphate product decreased from 5.18 ± 1.24 mmol²/L² at baseline to 4.20 ± 0.71 mmol²/L² (p < 0.001) at sDHD₁ and 4.02 ± 0.83 mmol²/L² (p < 0.001) at sDHD₂. The serum PTH levels decreased from 223.9 ± 124.7 pmol/L at baseline to 196.3 ± 101.3 pmol/L (p < 0.05) at sDHD₂. The hemoglobin concentration increased significantly from CHD to sDHD. However, the requirement for erythropoietin (EPO) dose decreased from 6847.8 ± 1057.3 u/week at baseline to 5869.6 ± 1094.6 u/week (p < 0.05) at sDHD2.

Conclusions

sDHD may decrease serum phosphate, calcium-phosphate product and PTH, increase hemoglobin levels and decrease exogenous EPO dose requirements compared with CHD in hemodialysis patients.     

Remission of nephrotic syndrome diminishes urinary plasmin content and abolishes activation of ENaC

Background

Urinary plasmin activates the epithelial Na⁺ channel (ENaC) in vitro and may possibly be a mechanism of sodium retention in nephrotic syndrome (NS). This study used a paired design to test the hypothesis that remission of NS is associated with a decreased content of urinary plasmin and reduced ability of patients’ urine to activate ENaC.

Methods

Samples were collected during active NS and at stable remission from 20 patients with idiopathic NS, aged 9.1?±?3.2 years. Plasminogen–plasmin concentration was measured with an enzyme-linked immunosorbent assay. Western immunoblotting for plasminogen–plasmin was performed in paired urine samples. The patch clamp technique was used to test the ability of urine to evoke an inward current on collecting duct cells and human lymphocytes.

Results

The urinary plasminogen–plasmin/creatinine ratio was 226 [95 % confidence interval (CI) 130–503] μg/mmol in nephrotic urine versus 9.5 (95 % CI 8–12) μg/mmol at remission (p?<?0.001). Western immunoblotting confirmed the presence of active plasmin in urine collected during active NS, while samples collected at remission were negative. Nephrotic urine generated an inward amiloride- and α₂-anti-plasmin- sensitive current, whereas the observed increase in current in urine collected at remission was significantly lower (201?±?31 vs. 29?±?10 %; p?=?0.005).

Conclusions

These findings support the hypothesis that aberrantly filtered plasminogen–plasmin may contribute to ENaC activation and mediate primary renal sodium retention during active childhood NS.     

Global longitudinal strain by two-dimensional speckle tracking imaging predicts exercise capacity in patients with chronic heart failure

Background

Left ventricular ejection fraction (LVEF) predicts mortality in patients with chronic heart failure (CHF). However, a weak correlation was found between LVEF and peak oxygen uptake ( $ \dot{V}{\text{O}}_{2} $ ) in CHF patients. Global longitudinal strain measured by two-dimensional (2D) strain is regarded as a more useful predictor of cardiac events than LVEF. We investigated whether 2D strain obtained at rest could predict peak $ \dot{V}{\text{O}}_{2} $ in patients with CHF.

Methods

Fifty-one patients (mean age of 54.0 ± 12.0 years, 14 females, LVEF 46.0 ± 15.0%) with stable CHF underwent resting echocardiography and cardiopulmonary exercise testing. Leg muscle strength was measured for the evaluation of peripheral factors. Global longitudinal strain (GLS) in the apical 4-, 3-, and 2-chamber views and global circumferential strain (GCS) in the parasternal mid short-axis view were measured.

Results

In all patients, peak $ \dot{V}{\text{O}}_{2} $ correlated with leg muscle strength (r = 0.55, p < 0.0001), LVEF (r = 0.46, p < 0.001), GLS (r = ?0.45, p < 0.001), and GCS (r = ?0.41, p = 0.005), respectively. No significant correlation was found between the ratio of early transmitral velocity to peak early diastolic mitral annulus velocity (E/E′) and peak $ \dot{V}{\text{O}}_{2} $ . In the patients with heart failure and reduced LVEF, a multiple stepwise linear regression analysis based on leg muscle strength, LVEF, E/E′, GLS, and GCS was performed to identify independent predictors of peak $ \dot{V}{\text{O}}_{2} $ , resulting in leg muscle strength and GLS (R ² = 0.888) as independent predictors of peak $ \dot{V}{\text{O}}_{2} $ .

Conclusion

Global longitudinal strain at rest could possibly predict exercise capacity, which appeared to be more useful than LVEF, E/E′, and GCS in CHF patients with reduced LVEF.     

Intratumoral acetic acid injection eradicates human prostate cancer tumors in a murine model

Introduction

To treat localized prostate cancer without substantial morbidity, an ideal treatment would be an effective local therapy with minimal morbidity. Direct injections have been used to treat benign prostatic hyperplasia without major complications, but in limited cases. We evaluated the local oncotoxic effects of acetic acid in a prostate cancer xenograft murine model.

Materials and methods

PC3 and LNCaP human prostate cancer cell lines were used to grow subcutaneous tumors in SCID mice. For each cell line, 14 mice underwent intratumor injection with 25 % acetic acid (0.05 ml/100 cm³ of tumor) after the tumor was >300 mm³. Post-treatment one mouse/group was euthanized after 2 h, 24 h, 1 and 2 weeks; remaining mice (n = 10) were killed at 120 days. Control mice (8/group) were euthanized after they met the humane criteria for tumor burden and overall health.

Results

Tumor necrosis was noted immediately post-injection; by 24 h, ulceration and crusting of overlying skin were noted, which healed into scars by 23 ± 5 days. Histological examination showed tumor degeneration and necrosis with blood vessel obstruction. Ten treated mice in both groups survived for 120 days, which was much longer than the mean survival of PC3 (40 ± 9 days) and LNCaP (56 ± 10) control mice.

Conclusions

Direct injection of acetic acid successfully eradicated both tumors. This treatment option could potentially be used in humans for treatment of early localized prostate cancer and nonoperative management of locally advanced cases. This is the first report of successful local chemical therapy for prostate cancer.     

Percutaneous nephrolithotomy under combined sonographic/radiologic guided puncture: results of a learning curve using the modified Clavien grading system

Purpose

Aim of our study was to evaluate the results of percutaneous nephrolithotomy (PNL) with sonographic/fluoroscopic guided puncture during a learning curve and to compare them to an expert.

Methods

The first 75 consecutive patients undergoing conventional PNL or Mini-PNL by a novice percutaneous surgeon without direct supervision by an expert were evaluated and divided into three groups of 25 patients each. The results were compared to 50 cases treated by an expert.

Results

For mean stone sizes of 22.3 ± 12.9, 22.7 ± 14.9, and 31.1 ± 25.5 mm, the OR-time was 124 ± 35, 106 ± 37, and 99 ± 31 min for the novice groups 1, 2, and 3, respectively. In contrast, the expert required an OR-time of 85 ± 28 min for a mean stone size of 19.7 ± 4.2 mm (p < 0.001; p < 0.01; n.s.). Stone free rates were 100, 96, and 100 %; however, second-look procedures were necessary in 24, 16, and 20 % of cases, whereas the expert needed only 8 % second-look procedures. No complications Clavien IIIb–V occurred. 16, 4, and 8 % of patients required a double-J placement (Clavien IIIa) due to hydronephrosis or urine leakage. One patient in the novice group 2 needed transfusion (Clavien II). Other minor complications (Clavien I) occurred in 28, 20 and 12 % in the novice groups 1, 2 and 3, respectively, in comparison with 22 % in the expert group.

Conclusions

Percutaneous stone treatment under combined sonographic/fluoroscopic guided puncture can be performed safe and efficiently during the learning curve. The lower expertise causes longer operation times and a higher re-intervention rate without compromising the patients’ safety.     

RAGE Gene Deletion Inhibits the Development and Progression of Ductal Neoplasia and Prolongs Survival in a Murine Model of Pancreatic Cancer

Background

The receptor for advanced glycation end-products (RAGE) is implicated in pancreatic tumorigenesis. Activating Kras mutations and p16 inactivation are genetic abnormalities most commonly detected as pancreatic ductal epithelium progresses from intraepithelial neoplasia (PanIN) to adenocarcinoma (PDAC).

Objective

The aim of this study was to evaluate the effect of RAGE (or AGER) deletion on the development of PanIN and PDAC in conditional Kras ^G12D mice.

Materials and Methods

Pdx1-Cre; LSL-Kras ^G12D/+ mice were crossed with RAGE ^?/? mice to generate Pdx1-Cre; LSL-Kras ^G12D/+ ; RAGE ^?/? mice. Pdx1-Cre; LSL-Kras ^G12D/+; p16 ^Ink4a?/? mice were crossed with RAGE ^?/? mice to generate Pdx1-Cre; LSL-Kras ^G12D/+; p16 ^Ink4a?/?; RAGE ^?/? mice. Pancreatic ducts were scored and compared to the relevant RAGE ^+/+ controls.

Results

At 16?weeks of age, Pdx1-Cre; LSL-Kras ^G12D/+; RAGE ^?/? mice had significantly fewer high-grade PanIN lesions than Pdx1-Cre; LSL-Kras ^G12D/+; RAGE ^+/+ controls. At 12?weeks of age, none of the Pdx1-Cre; LSL-Kras ^G12D/+; p16 ^Ink4a?/?; RAGE ^?/? mice had PDAC compared to a 45.5% incidence of PDAC in Pdx1-Cre; LSL-Kras ^G12D/+; p16 ^Ink4a?/?; RAGE ^+/+ controls. Finally, Pdx1-Cre; LSL-Kras ^G12D/+; p16 ^Ink4a?/?; RAGE ^?/? mice also displayed markedly longer median survival.

Conclusion

Loss of RAGE function inhibited the development of PanIN and progression to PDAC and significantly prolonged survival in these mouse models. Further work is needed to target the ligand?CRAGE axis for possible early intervention and prophylaxis in patients at risk for developing pancreatic cancer.     

Laparoscopic Gastric Bypass vs. Sleeve Gastrectomy in the Super Obese Patient: Early Outcomes of an Observational Study

Background

Super obesity [body mass index (BMI)?>?50 kg/m²] can yield to higher morbidity/mortality in bariatric surgery, this could be related to patient's characteristics and/or surgeon's experience. In morbid obesity, both techniques proved to have a positive impact and sometimes comparable outcomes during the first 2 years. This has not been clearly analyzed in the super obese patient.

Methods

Retrospective study comparing the records of 77 consecutive super obese patients (BMI: 50–59.9 kg/m²) submitted to either laparoscopic gastric bypass (LGBP, n?=?32) or laparoscopic sleeve gastrectomy (LSG, n?=?45) between 2010 and 2012 at a single institution. The primary objective was to analyze baseline demographics, comorbidities, operative outcomes, and early complications (<30 days). Secondarily, weight loss [BMI and % excess weight loss (%EWL)] was also described and compared during the first year.

Results

Female sex comprised 72.7 % of all cases. Both groups had comparable BMI (52.7?±?2.1 kg/m² for LGBP vs. 53.87?±?2.8 kg/m² for LSG; p?=?0.087) and homogeneous baseline characteristics. Operative time was lower for the LSG group (113.1?±?35.3 vs. 186.9?±?39 min for LGBP; p?≤?0.001). Overall, early complications were observed in 16.8 % of patients (LGBP 9 % vs. LSG 22 %; p?=?0.217). There were four major complications (two in each group), with two reinterventions. Weight loss (%EWL) at 6, 9, and 12 months was significantly higher in the LGBP group (51.6?±?12.9 %, 56.5?±?13 %, 63.9?±?13.3 %, respectively) than in the LSG group (40?±?12.8 %, 45.1?±?15.5 %, 43.9?±?10.4 %, respectively).

Conclusions

Just like in morbid obesity, LGBP and LSG are effective and safe procedures in super obese patients. LGBP had better weight loss at 1 year.     

Induction of anesthesia does not alter tricuspid annular velocities: a tissue Doppler assessment

Purpose

In this prospective observational cohort study, we investigated whether tricuspid annular velocities (TAV) are altered after induction of anesthesia in patients undergoing coronary artery bypass graft (CABG) surgery.

Methods

Twenty-four elective CABG patients were assessed before and after induction of anesthesia, and a convenience sample of nine healthy volunteers was used for comparison of TAV only. Measurements included mean arterial pressure (MAP), heart rate (HR), pulmonary artery pressure (PAP), and cardiac index (CI) as assessed post-induction. Tricuspid annular plane systolic excursion (TAPSE) was measured in anatomical M-mode. The S (systolic) wave velocity and isovolemic acceleration (IVA) were measured from colour tissue Doppler (TD). Paired and unpaired Student’s t tests were used to compare all variables pre-and post-induction.

Results

In response to anesthetic induction, MAP decreased from 105 ± 14 to 79 ± 9 mmHg, but HR was unchanged (67 ± 13 beats · min^?1 pre-induction compared with 67 ± 9 beats · min^?1 post-induction). The mean PAP and CI post-induction were 20 ± 6 mmHg and 2.3 ± 0.4 L · min^?1 · m^?2, respectively. While there was no change post-induction in either S velocity (8.80 ± 1.23 vs 9.0 ± 1.92 cm · sec^?1) or IVA (1.63 ± 0.61 vs 1.84 ± 0.83 m · sec^?2), TAPSE decreased from 23 ± 4 to 21 ± 4 mm (P = 0.039). All pre-induction echocardiographic variables were lower in the CABG group compared with the normal group (IVA: 2.34 ± 0.34 m · sec^?2, S wave: 11.14 ± 2.78 cm · sec^?1, TAPSE 2D: 26 ± 4 mm), respectively.

Conclusions

Induction of anesthesia for CABG surgery does not alter velocity-based parameters of RV function. There was a small decrease in TAPSE. The TD parameters were lower in CABG patients compared with the normal group.     

The role of vasopressin V1A receptors in cytotoxic brain edema formation following brain injury

Background

The hormone and neuropeptide arginine-vasopressin is designated to the maintenance of osmotic homoeostasis and blood pressure regulation. While experimental data show vasopressin V_1A receptors to regulate aquaporin (AQP)4 water channel dependent brain water movement, the specific role in vasogenic and cytotoxic edema formation remains unclear. The present study was designed to quantify the V_1A receptor mediated regional brain edema formation in two clinically relevant experimental models, brain injury combined with secondary insult and focal ischemia.

Methods

Male Sprague–Dawley rats were randomly assigned to a continuous infusion of vehicle (1 % DMSO) or the selective non-peptide V_1A antagonist SR49059 (83nM?=?1 mg/kg) starting before controlled cortical impact (CCI) injury plus hypoxia and hypotension (HH, 30 min), or middle cerebral artery (MCA) occlusion (2 h?+?2 h reperfusion).

Results

A global analysis of brain water content by the wet/dry weight method allowed optimizing the SR49059 dosage, and demonstrated the down-regulation of brain AQP4 expression by immunoblotting. Microgravimetrical quantification in 64 one mm³ samples per animal (n?=?6 per group) from bregma +2.7 to ?6.3 mm analysis demonstrated brain edema to be reduced at 4 h by SR49059 treatment in the injured and contralateral cortex following CCI?+?HH (p?=?0.007, p?<?0.001) and in the infarct area following MCA occlusion (p?=?0.013, p?=?0.002, p?=?0.004).

Conclusions

Our findings demonstrate that an early cytotoxic brain edema component following brain injury plus secondary insult or focal ischemia results from a vasopressin V_1A receptor mediated response, and occurs most likely through AQP4 up-regulation. The V_1A antagonist SR49059 offers a new avenue in brain edema treatment and prompts further study into the role of vasopressin following brain injury.     

Diagnostic Value of BRAFV600E Mutation Analysis of Thyroid Nodules According to Ultrasonographic Features and the Time of Aspiration

Background

We investigated the diagnostic value of the BRAF^V600E mutation of thyroid nodules according to ultrasonography (US) features and the time of BRAF^V600E mutation analysis.

Methods

A total of 304 nodules in 295 patients (mean age, 49.4 years) were included. Thyroid nodules were classified as suspicious or probably benign on US. Group 1 (n = 168) included nodules with BRAF^V600E mutation analysis at the time of the initial US-guided fine needle aspiration biopsy (US-FNAB) and group 2 (n = 136) included nodules with analysis at the time of the repeat US-FNAB. The frequency of malignancy and the BRAF^V600E mutation were compared between suspicious and probably benign nodules on US and between groups 1 and 2.

Results

Of 304 nodules, 113 were malignant and 59 (52.2%) had the BRAF^V600E mutation. Also, 58 of 196 nodules suspicious on US (29.6%) had the BRAF^V600E mutation, whereas 1 of 108 (0.9%) probably benign nodules had the BRAF^V600E mutation (P value <.0001). The BRAF^V600E mutation was more frequently found in nodules suspicious on US than those probably benign in both groups 1 and 2 (P value <.0001 and .0058, respectively). Preoperative detection of the BRAF^V600E mutation led surgeons to perform surgery in 5.8% of 103 nodules with benign and nondiagnostic results on cytology in group 1 and 1% of 98 nodules in group 2 without treatment delay.

Conclusions

The BRAF^V600E mutation analysis was a useful adjunctive diagnostic tool, especially in nodules suspicious on US, and was more effective if performed at the time of the initial US-FNAB.