Knocking Out Sodium Glucose-Linked Transporter 5 Prevents Fructose-Induced Renal Oxidative Stress and Salt-Sensitive Hypertension.

BACKGROUND: A fructose high-salt (FHS) diet increases systolic blood pressure and Ang II (angiotensin II)-stimulated proximal tubule (PT) superoxide (O2-) production. These increases are prevented by scavenging O2- or an Ang II type 1 receptor antagonist. SGLT4 (sodium glucose-linked cotransporters 4) and SGLT5 are implicated in PT fructose reabsorption, but their roles in fructose-induced hypertension are unclear. We hypothesized that PT fructose reabsorption by SGLT5 initiates a genetic program enhancing Ang II-stimulated oxidative stress in males and females, thereby causing fructose-induced salt-sensitive hypertension. METHODS: We measured systolic blood pressure in male and female Sprague-Dawley (wild type [WT]), SGLT4 knockout (-/-), and SGLT5-/- rats. Then, we measured basal and Ang II-stimulated (37 nmol/L) O2- production by PTs and conducted gene coexpression network analysis. RESULTS: In male WT and female WT rats, FHS increased systolic blood pressure by 15±3 (n=7; P<0.0027) and 17±4 mm Hg (n=9; P<0.0037), respectively. Male and female SGLT4-/- had similar increases. Systolic blood pressure was unchanged by FHS in male and female SGLT5-/-. In male WT and female WT fed FHS, Ang II stimulated O2- production by 14±5 (n=6; P<0.0493) and 8±3 relative light units/µg protein/s (n=7; P<0.0218), respectively. The responses of SGTL4-/- were similar. Ang II did not stimulate O2- production in tubules from SGLT5-/-. Five gene coexpression modules were correlated with FHS. These correlations were completely blunted in SGLT5-/- and partially blunted by chronically scavenging O2- with tempol. CONCLUSIONS: SGLT5-mediated PT fructose reabsorption is required for FHS to augment Ang II-stimulated proximal nephron O2- production, and increases in PT oxidative stress likely contribute to FHS-induced hypertension.

Angiotensin II-stimulated proximal nephron superoxide production and fructose-induced salt-sensitive hypertension.

Angiotensin II (ANG II) increases proximal tubule superoxide (O2-) production more in rats fed a 20% fructose normal-salt diet compared with rats fed a 20% glucose normal-salt diet. A 20% fructose high-salt diet (FHS) increases systolic blood pressure (SBP), whereas a 20% glucose high-salt diet (GHS) does not. However, it is unclear whether FHS enhances ANG II-induced oxidative stress in proximal tubules and whether this contributes to increases in blood pressure in this model. We hypothesized that FHS augments the ability of ANG II to stimulate O2- production by proximal tubules, and this contributes to fructose-induced salt-sensitive hypertension. We measured SBP in male Sprague-Dawley rats fed FHS and GHS and determined the effects of 3 mM tempol and 50 mg/kg losartan for 7 days. We then measured basal and ANG II-stimulated (3.7 × 10-8 M) O2- production by proximal tubule suspensions and the role of protein kinase C. FHS increased SBP by 27 ± 5 mmHg (n = 6, P < 0.006) but GHS did not. Rats fed FHS + tempol and GHS + tempol showed no significant increases in SBP. ANG II increased O2- production by 11 ± 1 relative light units/µg protein/s in proximal tubules from FHS-fed rats (n = 6, P < 0.05) but not in tubules from rats fed GHS. ANG II did not significantly stimulate O2- production by proximal tubules from rats fed FHS + tempol or FHS + losartan. The protein kinase C inhibitor Gö6976 blunted ANG II-stimulated O2- production. In conclusion, FHS enhances the sensitivity of proximal tubule O2- production to ANG II, and this contributes to fructose-induced salt-sensitive hypertension.NEW & NOTEWORTHY A diet containing amounts of fructose consumed by 17 million Americans causes salt-sensitive hypertension. Oxidative stress is an initiating cause of this model of fructose-induced salt-sensitive hypertension increasing blood pressure. This salt-sensitive hypertension is prevented by losartan and thus is angiotensin II (ANG II) dependent. Fructose-induced salt-sensitive hypertension depends on ANG II stimulating oxidative stress in the proximal tubule. A fructose/high-salt diet augments the ability of ANG II to stimulate proximal tubule O2- via protein kinase C.

Laparoscopic and robotic inguinal hernia repair are safe and effective after prior pelvic or low abdominal surgery.

BACKGROUND: The ideal approach to inguinal hernia repair (IHR) after prior pelvic or low abdominal surgery is not agreed upon. We compared safety and outcomes of IHR between open, laparoscopic, and robotic approaches. METHODS: This retrospective review of a prospective database analyzed demographic, perioperative, and quality of life data for patients who underwent IHR after pelvic or low abdominal surgery. RESULTS: 286 qualifying patients underwent IHR between 2008 and 2020; 119 open, 147 laparoscopic, and 20 robotic. Laparoscopic repair led to faster cessation of narcotics and return to ADLs than open repair (all p <0.05). Post-operative complications, 30-day readmission, recurrences, and quality of life outcomes were equivalent, except less pain at 3-weeks post-op in the minimally invasive groups, p < 0.01. CONCLUSION: Minimally invasive IHR after prior pelvic or low abdominal surgery is safe compared to an open approach. Laparoscopic repair provides faster recovery, yet patient satisfaction is equivalent regardless of surgical approach.

Independent effects of sex and stress on fructose-induced salt-sensitive hypertension.

Proximal tubule fructose metabolism is key to fructose-induced hypertension, but the roles of sex and stress are unclear. We hypothesized that females are resistant to the salt-sensitive hypertension caused by low amounts of dietary fructose compared to males and that the magnitude of the increase in blood pressure (BP) depends, in part, on amplification of the stress response of renal sympathetic nerves. We measured systolic BP (SBP) in rats fed high salt with either no sugar (HS), 20% glucose (GHS) or 20% fructose (FHS) in the drinking water for 7-8 days. FHS increased SBP in both males (Δ22 ± 9 mmHg; p < 0.046) and females (Δ16 ± 3 mmHg; p < 0.0007), while neither GHS nor HS alone induced changes in SBP in either sex. The FHS-induced increase in SBP as measured by telemetry in the absence of added stress (8 ± 2 mmHg) was significantly lower than that measured by plethysmography (24 ± 5 mmHg) (p < 0.014). However, when BP was measured by telemetry simulating the stress of plethysmography, the increase in SBP was significantly greater (15 ± 3 mmHg) than under low stress (8 ± 1 mmHg) (p < 0.014). Moderate-stress also increased telemetric diastolic (p < 0.006) and mean BP (p < 0.006) compared to low-stress in FHS-fed animals. Norepinephrine excretion was greater in FHS-fed rats than HS-fed animals (Male: 6.4 ± 1.7 vs.1.8 ± 0.4 nmole/kg/day; p < 0.02. Female 54 ± 18 vs. 1.2 ± 0.6; p < 0.02). We conclude that fructose-induced salt-sensitive hypertension is similar in males and females unlike other forms of hypertension, and the increase in blood pressure depends in part on an augmented response of the sympathetic nervous system to stress.

Inguinal hernia mesh is safe in 1720 patients.

BACKGROUND: There is substantial media and patient interest in the safety of mesh for hernia repair. However, there is a lack of data regarding health-related quality of life (HRQOL) outcomes in patients who undergo inguinal hernia repair (IHR) with mesh. The purpose of this study is report short and long-term postoperative quality of life outcomes in patients following IHR with mesh. METHODS: We analyzed outcomes of 1720 patients who underwent IHR with mesh between 2008 and 2019 at a single institution from a prospectively maintained quality database. All surgeries were performed by four board-certified surgeons. HRQOL outcomes were measured using the Surgical Outcomes Measurement System (SOMS) and Carolinas Comfort Scale (CCS) surveys that were administered preoperatively, 3 weeks, 6 months, 1, 2, and 5 years postoperatively. Survey responses were summarized as mean with standard deviation or frequency with percentage. Postoperative SOMS scores were compared to preoperative scores using the two-tailed paired t test with a significance level of p < 0.05. RESULTS: One (0.1%) patient experienced a mesh infection postoperatively. In terms of complications, 159 (9.2%) developed a seroma, 31 (1.8%) a hematoma, and 36 (2.1%) patients experienced a recurrence. SOMS Pain Impact, SOMS Pain Quality, and SOMS Pain visual analog scale at 3 weeks, 6 months, 1 year, 2 years, and 5 years were all improved from preoperative (all p < 0.05). At 5 years postoperatively, only 3.9%, 3.2%, and 3.1% of patients reported severe or disabling sensation of mesh, pain, and movement limitations, respectively. CONCLUSION: Inguinal hernia repair with mesh results in a low rate of complications. A minority of patients had severe or disabling symptoms at 5-year follow-up and generally reported improvements in pain impact and quality in long-term follow-up.

Mesh in Elective Hernia Repair: 10-Year Experience with over 6,000 Patients.

BACKGROUND: The use of mesh in hernia repair has faced intense scrutiny, leading patients to become fearful of its use, despite its benefits in reducing hernia recurrence. We report a single institutional experience in performing hernia repair with mesh in terms of hernia-specific outcomes, mesh-related complications, and patient-reported quality of life. STUDY DESIGN: Patients who underwent abdominal wall hernia repair with mesh at a single institution were identified from a prospectively maintained quality database. Demographic, perioperative, and postoperative outcomes data were analyzed. Surgical Outcomes Measurements System (SOMS) and Carolinas Comfort Scale (CCS) surveys were administered pre- and postoperatively at 3 weeks, 6 months, 1, 2, and 5 years. RESULTS: Between 2010 and 2020, a total of 6,387 patients underwent abdominal hernia repair with mesh. Inguinal hernia repairs made up the majority (65%) of the operations. Rates of mesh infection varied by hernia type, with lower rates after umbilical (0.0%) and inguinal (0.4%) repair, and highest after incisional repair (1.3%). Similarly, mesh explantation rates were low after umbilical and inguinal repair (0.0% and 0.4%, respectively) and highest after incisional repair (3.0%). Scores on all SOMS domains were significantly improved from baseline (all p < 0.05). On CCS, 2.9%, 3.3%, and 4.4% of patients reported severe or disabling symptoms postoperatively at 1, 2, and 5 years, respectively. CONCLUSIONS: Rates of mesh-related complications vary by hernia type. A majority of patients report excellent long-term quality of life, although a relatively large percentage of patients experience severe or disabling symptoms at long-term follow-up.

Laparoscopic repair of recurrent inguinal hernia offers similar outcomes and quality of life to primary laparoscopic repair.

OBJECTIVE: Open repair of recurrent inguinal hernias has been shown to result in significantly poorer perioperative outcomes when compared to open primary hernia repair. However, limited data exist comparing primary and recurrent laparoscopic inguinal hernia repair (LIHR). The aim of our study was to compare quality of life and clinical outcomes between these two groups. METHODS: Patients undergoing LIHR at a single institution from 2012 to 2018 were reviewed from a prospectively managed quality database. Quality of life outcomes were measured using the surgical outcomes measurement system and Carolinas Comfort Scale surveys administered preoperatively and at 3 weeks, 6 months, 1 year, and 2 years postoperatively. RESULTS: A total of 1298 patients undergoing LIHR were analyzed (1139 primary, 159 recurrent). There were older and more male patients in the recurrent group. There were no major complications, and recurrence rates were not significantly different between primary and recurrent groups (1.3% vs 2.4% p = 0.56), while hematoma occurred more commonly in the recurrent group (1.5% vs 4.4% p = 0.0205). Short- and long-term quality of life were similar between the groups except lower (worse) physical function at 3 weeks (32.9 ± 4.2 vs 31.9 ± 4.4: p = 0.0186) and 6 months (34.6 ± 2.8 vs 33.8 ± 3.0: p = 0.0175) and increased sensation of mesh (3 weeks) in the recurrent group (2.3 ± 5.4 vs 3.3 ± 5.3: p = 0.0160). CONCLUSION: Recurrent inguinal hernia repair using laparoscopic totally extraperitoneal approach is as safe and effective as primary repair with similar quality of life.

Short-term quality of life comparison of laparoscopic, open, and robotic incisional hernia repairs.

BACKGROUND: Outcomes of incisional hernia repair (IHR) include recurrence and quality of life (QOL). Operative approaches include laparoscopic, open, and robotic approaches. Data regarding comparative QOL outcomes among these repair types are unknown. Our study evaluates quality of life after three approaches to IHR. STUDY DESIGN: Patients undergoing open (OHR), laparoscopic (LIHR), and robotic extra-peritoneal (RIHR) at a single institution from 2009 to 2019 were reviewed from a prospectively managed quality database. Short-term QOL was compared among the three procedures using the Surgical Outcomes Measurement System (SOMS) and Carolinas Comfort Scale (CCS), objective pain scores and postoperative narcotic use. Data regarding length of stay (LOS), emergency department (ED) visits, readmission, reoperations and surgical site infection (SSI) were also collected. RESULTS: A total of 795 patients undergoing IHR were analyzed (418 open, 300 laparoscopic and 77 robotic). Patient were similar in age, gender and co-morbidities. LIHR patients had higher BMI and RIHR patients had larger hernia and mesh size. LOS was longer and rate of SSI was higher for OIHR compared to laparoscopic and RIHR. Patients undergoing LIHR reported increased narcotic use, Visual Analogue Scale (VAS) and CCS pain scores compared to open and robotic repair. Return to daily activity was 4 days shorter for robotic than open and laparoscopic repair; ED visits, readmissions, reoperations, and other QOL domains were similar. CONCLUSION: Our data suggests that short-term quality of life after robotic extra-peritoneal IHR is improved compared to open and laparoscopic repair. Additional follow up is required to determine differences in long-term QOL after IHR.

Predictors of chronic pain after laparoscopic inguinal hernia repair.

BACKGROUND: Multiple studies have analyzed predictors for chronic pain after open hernia repair. The purpose of this study is to determine which factors predict the development of chronic pain after a laparoscopic inguinal hernia repair. METHODS: We identified patients who underwent laparoscopic inguinal hernia repair between 2008 and 2020 at a single institution. Quality of life was measured using the Surgical Outcomes Measurement System and Carolinas Comfort Scale. We categorized patients with chronic pain if their score on Carolinas Comfort Scale was greater than or equal to 3. Multivariable logistic regression analysis was used to identify predictors of chronic pain. RESULTS: A total of 960 patients met inclusion criteria. Mean age was 59 (± 14, standard deviation) years, 89 (9.3%) of whom were female. Six percent of patients met criteria for chronic pain (Carolinas Comfort Scale ≥3). On multivariable analysis, predictors for chronic pain were age 45 (P < .001), female sex (P = .006), preoperative pain visual analog scale ≥1 (P = .025), prior inguinal hernia repair (P = .045), higher American Society of Anesthesiologists class (P = .041), use of multifilament polyester mesh (P = .0448), and intraoperative placement of a urinary catheter (P = .009). CONCLUSION: Laparoscopic inguinal hernia repair results in 6.0% of patients experiencing chronic pain. We identified multiple predictors for chronic pain.