MIS retromuscular repair of lateral incisional hernia: technological deliberations and short-term outcome.

BACKGROUND: Lateral abdominal wall hernias (LAWH) constitute about 1-4% of hernia surgical procedures. They represent a unique surgical challenge on account of their potential for anatomical complexity and consequent operative technical demand. Furthermore, LAWH repairs are currently not standardized, and remain contentious, despite a variety of approaches. These repairs are attendant with not insignificant morbidity and recurrence rates. We profile here our endoscopic and hybrid surgical approach to the management of LAWH and early therapeutic outcomes. METHODS: A retrospective review of our hernia clinical database between March 2018 and December 2020 was performed to extract all LAWH (with and without an associated midline component) patients, who underwent an enhanced-view totally extra peritoneal (eTEP) hernia repair with a transversus abdominis release (TAR), or a hybrid repair. Initial outcome data (6-month follow-up) is profiled here. The primary outcome measures were hernia recurrence and hernia-site bulging. The secondary measures were surgical site occurrence (SSO) and hernia-related quality of life (QoL). RESULTS: A total of 33 LAWH patients underwent an eTEP TAR or hybrid hernia repair. 11 patients had an associated midline defect and 12 were recurrent hernias. The mean hernia defect area was 84.2 ± 49 cm2 and mean mesh size was 859.6 ± 263 cm2. There was no hernia recurrence at initial follow-up of 24 months. The SSO rate was 12%. The CCS QoL scores were 34.6 ± 2 pre-operatively, and improved to 27.2 ± 4 at 6 months. CONCLUSIONS: Our endoscopic and hybrid technique is a safe, reproducible, and technically promising approach for the repair of LAWH. Thorough knowledge of the surgical anatomy of the lateral abdominal wall and advanced endosurgical skills are imperative for good outcomes. We await the long-term results of our LAWH cohort to confirm the findings.

e-TEP repair for midline primary and incisional hernia: technical considerations and initial experience.

INTRODUCTION: The Enhanced-View Totally Extra Peritoneal Rives-Stoppa (e-TEP-RS) Technique for the repair of large, complex, ventral abdominal hernias has gained popularity especially in overcoming the disadvantages with Intra Peritoneal Onlay Mesh (IPOM) repairs and to enable siting of a large prosthetic mesh in an anatomical plane distinct from the abdominal cavity and its contents. Evolving variations of the original technique have allowed the definitive repair of such defects in a reproducible manner. We present our initial experience of this approach and detailed steps of our native technical modifications in overcoming the challenges in performing this complex and potentially challenging procedure. MATERIALS AND METHODS: This is a retrospective review of the clinical data of midline, large, complex, ventral abdominal hernia patients who underwent e-TEP-RS with and without Transversus Abdominis Release (TAR). Patients, with or without Diastasis of Rectus Abdominis Muscle (DRAM) were included. Key outcomes measured were post-operative pain, operative morbidity, readmission, Quality of Life (QoL), hernia recurrence. RESULTS: A total of 58 midline, ventral abdominal hernia patients who underwent e-TEP-RS with and without Transversus Abdominis Release (TAR), between March 2018 and December 2019 were studied. Mean defect area was 41.0 ± 28 cm2 and the mean mesh surface area was 473.5 ± 165 cm2. e-TEP-RS was done in 35 cases, e-TEP RS TAR in 15 cases and e-TEP-RS with e-TEP inguinal in 08 cases. There was no intraoperative morbidity. Mean duration of surgery was 156.2 ± 40 min and mean blood loss was 40.5 ± 26 cc. The CCS QoL scores improved from 34.6 (± 2) pre-operatively to 27.2 (± 4) at the end of 6 months. One patient had a supra-umbilical recurrence following bilateral TAR over the superior edge of the mesh. Follow-up ranged from 6 to 22 months, with a mean of 14 months. Major complications (n = 12; 20.7%) were seroma formation and prolonged ileus. CONCLUSION: The e-TEP-RS technique for large, complex, midline, ventral abdominal hernias can be used with excellent results and acceptable morbidity. This technique is technically challenging and should be mastered in relatively smaller ventral hernias to achieve good results before attempting it in larger, complex ones.

Effect of multi-nutrient insufficiency on markers of one carbon metabolism in young women: response to a methionine load.

BACKGROUND/OBJECTIVES: Multi-nutrient insufficiencies as a consequence of nutritional and economic factors are common in India and other developing countries. We have examined the impact of multi-nutrient insufficiency on markers of one carbon (1C) metabolism in the blood, and response to a methionine load in clinically healthy young women. SUBJECTS/METHODS: Young women from Pune, India (n=10) and Cleveland, USA (n=13) were studied. Blood samples were obtained in the basal state and following an oral methionine load (50 mg/kg of body weight in orange juice). Plasma concentrations of vitamin B12, folate and B6 were measured in the basal state. The effect of methionine load on the levels of methionine, total homocysteine, cysteine, glutathione and amino acids was examined. RESULTS: Indian women were significantly shorter and lighter compared with the American women and had lower plasma concentration of vitamins B12, folate and B6, essential amino acids and glutathione, but higher concentration of total homocysteine. The homocysteine response to methionine load was higher in Indian women. The plasma concentrations of glycine and serine increased in the Indian women after methionine (in juice) load. A significant negative correlation between plasma B6 and homocysteine (r= -0.70), and plasma folate and glycine and serine levels were observed in the Indian group (P<0.05) but not in the American group. CONCLUSIONS: Multi-nutrient insufficiency in the Indian women caused unique changes in markers of whole body protein and 1C metabolism. These data would be useful in developing nutrient intervention strategies.

Lactate metabolism during exercise: analysis by an integrative systems model.

To provide a framework for quantitative analysis of metabolic and transport processes associated with ATP production during exercise, we adapted a recently developed model that links cellular metabolism and its control to whole body responses at rest. The enhanced model is based on dynamic mass balances for glycogen, glucose, pyruvate (PY), lactate (LA), O(2), and CO(2) and is solved numerically to simulate responses to acute (<20 min), moderate exercise (i.e., below the LA threshold, less than approximately 60% maximal rate of O(2) uptake). Simulations of responses to a step change in muscle ATP turnover predict substrate changes in muscle, splanchnic, and other tissues compartments, as well as changes in other metabolites (e.g., NADH, ADP) whose reactions are coupled to the main reactions. Even a significant (64%) decrease in muscle O(2) concentration (C(m, O(2))) did not affect muscle O(2) consumption. Model simulations of moderate exercise show that 1) muscle oxygenation is sufficient (C(m, O(2)) >2 mM) even during the transient state; 2) transient increases in concentration of muscle LA and arterial concentration of LA are associated with increases in glycolysis from increases in ADP/ATP and in LA production associated with a rise in NADH/NAD; 3) muscle ADP/ATP reaches a higher steady state that stimulates glycolysis, glycogenolysis, and oxidative phosphorylation to match the ATP demand; and 4) muscle NADH/NAD reaches a lower steady state that stimulates LA oxidation. It is suggested that the continuous stimulation of ATP synthesis processes during moderate exercise is mainly due to a higher ADP/ATP, not to a higher NADH/NAD. Critical measurements needed to quantify metabolic control mechanisms are identified.

Gender-dependent alterations in serum leptin in alcoholic cirrhosis.

BACKGROUND & AIMS: Leptin is a peptide that decreases food intake and increases energy expenditure. It is produced in fat cells, is stimulated by cytokines, and its levels in serum are higher in females. Because anorexia, hypermetabolism, and elevated cytokine levels are frequently observed in cirrhosis, we hypothesized that the serum leptin level would be elevated in cirrhosis. The aim of this study was to investigate the relationship of serum leptin to gender, body composition, and tumor necrosis factor (TNF). METHODS: Male (n = 18) and female (n = 10) abstinent alcoholic cirrhotic patients were studied and compared with control subjects (15 male and 8 female). Fat mass, fat-free body mass, and body cell mass were calculated by using H2[18O] and bromide dilution methodology. Serum leptin and TNF concentrations were measured by immunoassays. RESULTS: Fat mass was decreased only in male cirrhotics (P < 0.05), whereas body cell mass was decreased in both male and female cirrhotics (P < 0.01). Leptin levels were elevated in female (P < 0. 001) but not male cirrhotics compared with controls. When expressed per kilogram of fat mass, leptin was elevated in both male (P < 0. 01) and female (P < 0.01) cirrhotics. Women in both cirrhotic and control groups had higher leptin levels than men. TNF was elevated in both male and female cirrhotics and did not correlate with leptin levels. CONCLUSIONS: Cirrhotics have elevated serum leptin levels, which are related to both gender- and gender-dependent alterations in body composition.

Role of O2 in regulation of lactate dynamics during hypoxia: mathematical model and analysis.

The mechanistic basis of the relationship between O2 and lactate concentration in muscle is not fully understood. Although hypoxia can cause lactate (LA) accumulation, it is possible for LA accumulation to occur without hypoxia. Nevertheless, during conditions of low O2 availability, blood and tissue LA accumulation are used as indicators of hypoxia. To provide a framework for analyzing changes in energy metabolism and its regulation, we developed a mathematical model of human bioenergetics that links cellular metabolic processes to whole-body responses. Our model is based on dynamic mass balances and mechanistic kinetics in muscle, splanchnic and other body tissues for many substrates (glycogen, glucose, pyruvate, LA, O2, CO2, etc.) and control metabolites (e.g., ATP) through coupled reaction processes. Normal substrate concentrations in blood and tissues as well as model parameters are obtained directly or estimated indirectly from physiological observation in the literature. The model equations are solved numerically to simulate substrate concentration changes in tissues in response to disturbances. One key objective is to examine and quantify the mechanisms that control LA accumulation when O2 availability to the muscle is lowered. Another objective is to quantify the contribution of different tissues to an observed increase in blood lactate concentration. Simulations of system responses to respiratory hypoxia were examined and compared to physiological observations. Model simulations show patterns of change for substrates and control metabolites that behave similarly to those found experimentally. From the simulations, it is evident that a large decrease can occur in muscle O2 concentration, without affecting muscle respiration (Um,O2) significantly. However, a small decrease in Um,O2 (1%-2%) can result in a large increase in LA production (50%-100%). The cellular rate of oxygen consumption, Um,O2, which is coupled to ATP formation and NADH oxidation, can regulate other processes (e.g., glycolysis, pyruvate reduction) with high sensitivity through its effects on ADP/ATP and NADH/NAD. Thus, although LA metabolism does not depend directly on O2 concentration, it is indirectly affected by Um,O2, through changes in ADP/ATP, and NADH/NAD. Arterial LA concentration (Ca,LA) follows the pattern of change of muscle LA concentration (Cm,LA). Nevertheless, changes in Ca,LA, due to Cm,LA, are unlikely to be detected experimentally because changes in Cm,LA are small relative to the total LA concentrations in other tissues.

Protein turnover during puberty in normal children.

To investigate whether insulin resistance of puberty involves protein metabolism, we compared whole body leucine kinetics in 20 prepubertal Tanner I (TI), and 21 pubertal Tanner II-IV (TII-IV) healthy children. Leucine flux (LRa), oxidation (LOX), and nonoxidative disposal (NOXLD) were measured during primed constant infusion of [1-13C]leucine at baseline and during a stepwise hyperinsulinemic (10 and 40 mU.m-2.min-1)euglycemic clamp in combination with indirect calorimetry. At baseline LRa and LOX were lower in TII-IV vs. TI [LRa: 3.59 +/- 0.17 vs. 4.05 +/- 0.18 mumol.min-1.kg-1 fat-free mass (FFM), P = 0.036; LOX: 0.45 +/- 0.03 vs. 0.59 +/- 0.04 mumol.min-1. FFM-1, P = 0.005], but NOXLD was similar. Insulin-like growth factor I (IGF-I) levels correlated inversely with LRa, NOXLD, and LOX. Energy expenditure correlated positively with LRa, LOX, and NOXLD. During the clamp absolute and percent suppression in LRa were significantly lower in TII-IV than TI. In conclusion, 1) proteolysis and protein oxidation are lower during puberty compared with prepuberty, whereas protein synthesis is unchanged; 2) insulin action in inhibiting proteolysis is decreased during puberty; and 3) increased pubertal IGF-I levels may play a role in decreased protein degradation.

Quantification of carbohydrate oxidation by respiratory gas exchange and isotopic tracers.

Estimates of glucose oxidation measured by indirect respiratory calorimetry and by [U-13C]glucose tracer were compared as a function of respiratory exchange ratio (RER) in 14 studies performed on 9 healthy adult subjects. RER was varied between 0.7 and 1.04, either by fasting or by infusing glucose. 13C enrichment of plasma glucose and expired CO2 were measured by mass spectrometry. The two methods gave similar results when the nonprotein respiratory quotient (NPRQ) was between 0.76 and 0.90. Glucose oxidation by the tracer method was quantified to be higher than that by respiratory calorimetry when NPRQ was < 0.76; it was lower than the respiratory calorimetry estimate when NPRQ was > 0.90. The discrepancy between the two methods at low RER may represent the contribution of gluconeogenesis, whereas, at high RER, the discrepancy may be the consequence of lipogenesis. We conclude that respiratory calorimetry and [13C]glucose tracer give comparable results only in a narrow range of RER. These data are important when the disposal of glucose is compared using these techniques in different metabolic states with varying respiratory quotients.

Determination of body composition in children and adolescents: validation of bioelectrical impedance with isotope dilution technique.

The determination of body composition as part of the clinical and auxologic follow up of childhood growth disorders necessitates the use of a quick, portable, reliable and simple non-invasive method. The present study was undertaken to validate bioelectrical conductance, height2/resistance (Ht2/R), against isotopically determined total body water (TBW) using heavy water tracer H2[18O]. The subjects (n = 56) consisted of normal children, children with various endocrine disorders, and young adults between the ages of 8-26 years. Isotopically determined TBW and fat free mass (FFM) were highly correlated with Ht2/R (r = 0.94, p = < 0.001, and r = 0.94, p = < 0.001, respectively). In a multiple regression analysis, 96% of the variability in FFM in normal subjects could be predicted by the following equation: FFM = 0.524 Ht2/R + 0.415 Wt-0.32, while in the group of patients by FFM = 0.659 Ht2/R + 0.254 Wt + 2.851. These data suggest that bioelectrical impedance measurements give valid and reliable estimates of FFM in children and adolescents. This easy technique could be incorporated in the auxologic follow up of children on hormone therapy.

Roles of insulin resistance and beta-cell dysfunction in the pathogenesis of glucose intolerance in cystic fibrosis.

The roles of insulin deficiency and insulin resistance in the pathogenesis of glucose intolerance in cystic fibrosis (CF) were evaluated in eight patients (aged 16.5 +/- 1.9 yr), four with normal glucose tolerance (NGT) and four with impaired glucose tolerance (IGT), and in seven healthy control (CN) subjects. First and second phase insulin secretions were evaluated during a hyperglycemic clamp. Hepatic glucose production (HGP) and insulin-stimulated glucose disposal were measured using [6,6-2H2]glucose and a stepwise hyperinsulinemic-euglycemic clamp. First and second phase insulin levels were significantly lower in both groups of CF patients compared with control values. There was an inverse relationship between glycohemoglobin level and first phase insulin (r = -0.81; P = 0.015) and second phase insulin (r = -0.97; P < 0.001). During the hyperglycemic clamp, the insulin sensitivity index was lower in CF-IGT, but not CF-NGT, compared with control values (6.66 +/- 1.79, 12.82 +/- 1.61, and 13.02 +/- 1.78 mumol/kg.min/pmol.L, respectively; P < 0.05). Basal HGP and fasting plasma glucose were higher in CF vs. CN [24.8 +/- 2.9 vs. 16.9 +/- 1.4 mumol/kg.min (P = 0.036) and 5.8 +/- 0.2 vs. 5.4 +/- 0.1 mmol/L (P = 0.035), respectively]. During the hyperinsulinemic euglycemic clamp, insulin-stimulated glucose disposal was significantly lower in CF-IGT (45.68 +/- 4.87 mumol/kg.min) vs. CF-NGT (78.99 +/- 1.34 mumol/kg.min) and CN (71.74 +/- 6.88 mumol/kg.min). Insulin sensitivity was lower in CF-IGT vs. CF-NGT (7.04 +/- 0.86 and 14.38 +/- 0.84 mumol/kg.min/pmol.L; P < 0.05). We conclude that 1) glycohemoglobin is a strong correlate of insulin deficiency in CF; and 2) glucose intolerance in this group of CF patients occurred as a consequence of concomitant insulin deficiency and insulin resistance.

Vasoactive intestinal polypeptide causes relaxation of the pyloric sphincter in the rabbit.

Vasoactive intestinal peptide (VIP), which causes relaxation of gastrointestinal smooth muscle, has been found in high concentrations in the pylorus in many animal species, suggesting a prominent role for VIP in the control of pyloric sphincter function. We infused VIP into the gastric artery of 6 rabbits at rates from 12 to 1,200 ng/min and measured the intensity, duration, and frequency of spontaneous pyloric contractions with an intraluminal balloon and electromyography. VIP produced a dose-dependent reduction in the intensity (55% +/- 15% of baseline, P < .001) and the duration (29% +/- 25%, P < .001) of pyloric contraction. Maximal inhibition was observed at an infusion rate of 240 ng/min. The frequency of contractions did not decrease significantly in response to VIP infusion. Neostigmine infusion increased the intensity of pyloric contraction in a dose-dependent manner in doses of 0.10, 0.15, and 0.25 mg (140% +/- 78%, 273% +/- 76%, and 357% +/- 26% of baseline, respectively; P < .001). VIP infusion at 12 ng/min and 480 ng/min completely inhibited the increased intensity of contraction at neostigmine doses of 0.10 and 0.15 mg, respectively. Our results show that VIP decreases the intensity and the duration of pyloric contraction in a dose-dependent manner. As pyloric spasm may contribute to the pathogenesis of hypertrophic pyloric stenosis, we can postulate a role for reduced VIP-induced relaxation in the pathophysiology of hypertrophic pyloric stenosis.

Effects of growth hormone releasing hormone on insulin action and insulin secretion in a hypopituitary patient evaluated by the clamp technique.

The effect of growth hormone releasing hormone (GHRH-44) therapy on insulin action and secretion was evaluated in a hypopituitary patient after one month and one year of treatment. Hepatic and peripheral insulin action was studied with the hyperinsulinemic-euglycemic clamp in combination with [6,6-2H2]glucose tracer infusion. First and second phase insulin secretion was assessed with the hyperglycemic clamp. Prior to GHRH-44 therapy the hypopituitary patient had higher insulin mediated glucose disposal rate and lower basal and stimulated insulin concentrations by more than two standard deviations from the mean of a control group. Following therapy there was no change in basal hepatic glucose production; however, there was evidence of diminished peripheral insulin action. This was manifested by decreased insulin mediated glucose disposal during the hyperinsulinemic-euglycemic clamp, and increased insulin secretion during the hyperglycemic clamp. We conclude that GHRH-44 therapy in this patient was associated with decreased peripheral insulin action which was compensated for by increased insulin secretion.

Body cell mass and leucine metabolism in cirrhosis.

To investigate the influence of body composition on leucine metabolism, leucine turnover and oxidation were measured in six patients with stable biopsy-proven cirrhosis and in six age- and gender-matched controls using [1-14C]leucine tracer. Fat-free body mass and body cell mass were estimated from quantified measurements of H2(18)O and bromide dilution. Although there were no differences in body weight, body surface area, body mass index, or fat-free body mass between study groups, body cell mass was decreased in cirrhotic patients (37.6 +/- 0.1 vs. 46.4 +/- 1.8 kg; P less than 0.05). Leucine turnover did not significantly differ between groups in absolute values or when corrected for body weight or fat free body mass. However, cirrhotic patients had accelerated leucine turnover based on body cell mass (171.3 +/- 8.2 vs. 143 +/- 7.6 mumol.kg-1.h-1; P less than 0.03). Plasma leucine levels were decreased in cirrhosis (76.9 +/- 9.7 vs. 117.9 +/- 8.1 mumol/L; P less than 0.001) and correlated with an expanded extracellular water compartment (r = -0.91; P less than 0.001) and leucine oxidation (r = 0.91; P less than 0.01) in the cirrhotic patients but not in the control subjects. These data indicate that body composition and fluid compartments are important factors influencing leucine metabolism in cirrhosis and should be considered in future studies.

Glucose, insulin, gastric inhibitory polypeptide, and pancreatic polypeptide responses to polycose during pregnancy.

Polycose, a glucose polymer produced by controlled acid enzyme hydrolysis of starch, has been proposed as an effective substitute for glucose solution in antepartum screening for glucose intolerance. The purposes of this study were to examine the glucose and hormonal responses to 50 g of glucose polymer (polycose) solution in pregnant and nonpregnant women and to compare these with the standard 50-g oral glucose challenge test. In addition, the subject's acceptance of the glucose polymer solution was evaluated. Subjects were examined after an overnight fast following a 3-day dietary preparation. There was no difference in glucose or insulin responses to glucose or polycose in either pregnant or nonpregnant women. In contrast, the gastric inhibitory polypeptide response to polycose was significantly higher than to glucose. No differences were observed in plasma pancreatic polypeptide responses to glucose and polycose. In the pregnant subjects, even though the plasma insulin response to carbohydrate challenge was higher than in the nonpregnant subjects, gastric inhibitory polypeptide levels were significantly lower. Patient satisfaction was similar with both carbohydrate solutions. These data suggest that polycose can be used as a substitute for glucose in antepartum testing, although the differences in the hormonal responses should be recognized. Further studies in a subject population with carbohydrate intolerance will be required before polycose use can be recommended in abnormal states.