Intermittent bolus feeding does not enhance protein synthesis, myonuclear accretion, or lean growth more than continuous feeding in a premature piglet model

Optimizing enteral nutrition for premature infants may help mitigate extrauterine growth restriction and adverse chronic health outcomes. Previously, we showed in neonatal pigs born at term that lean growth is enhanced by intermittent bolus compared to continuous feeding. The objective was to determine if prematurity impacts how body composition, muscle protein synthesis, and myonuclear accretion respond to feeding modality. Following preterm delivery, pigs were fed equivalent amounts of formula delivered either as intermittent boluses (INT; n = 30) or continuously (CONT; n = 14) for 21 days. Body composition was measured by DXA and muscle growth was assessed by morphometry, myonuclear accretion, and satellite cell abundance. Tissue anabolic signaling and fractional protein synthesis rates were determined in INT pigs in postabsorptive (INT-PA) and postprandial (INT-PP) states and in CONT pigs. Body weight gain and composition did not differ between INT and CONT pigs. Longissimus dorsi (LD) protein synthesis was 34% greater in INT-PP than INT-PA pigs (P < 0.05) but was not different between INT-PP and CONT pigs. Phosphorylation of 4EBP1 and S6K1 and eIF4E·eIF4G abundance in LD paralleled changes in LD protein synthesis. Satellite cell abundance, myonuclear accretion, and fiber cross-sectional area in LD did not differ between groups. These results suggest that, unlike pigs born at term, intermittent bolus feeding does not enhance lean growth more than continuous feeding in pigs born preterm. Premature birth attenuates the capacity of skeletal muscle to respond to cyclical surges in insulin and amino acids with intermittent feeding in early postnatal life.

Effects of Intermittent Bolus Paravertebral Block On Analgesia and Recovery in Open Hepatectomy: A Retrospective, Cohort Study.

Background Experiences of paravertebral block use in hepatectomy were limited. We aimed to investigate the effects of intermittent bolus paravertebral block on analgesia and recovery in hepatectomy. Methods We selected patients receiving two types of analgesia programs, with matched age, sex and body mass index from a prospective perioperative analgesia and nerve block database: (1) PVB: intermittent bolus paravertebral block (0.5% ropivacaine 25ml before surgery plus 0.125ml•kg− 1 0.2% ropivacaine bolus per hour after surgery) and self-controlled intravenous bolus morphine pump till postoperative 48 hours; (2) control: self-controlled intravenous bolus morphine pump till postoperative 48 hours. The baseline, operation, and postoperative analgsia and recovery data were compared between groups. Results Thirty-eight patients in each group were included in the analysis. Intraoperatively, PVB group used less sevoflurane (difference − 0.1 (-0.2, 0.0) %, P = 0.019), and more ephedrine (U = 986, P = 0.004) and crystalloid (U = 936, P = 0.024) than control group. The mean arterial pressure in PVB group was lower than that in control group (difference − 4mmHg, 95%CI -8 ~ 0mmHg, P = 0.031) but similar to its baseline level (difference 2, 95%CI -1 ~ 5, P = 0.153). Postoperatively, PVB group had lower cumulative morphine consumption at postoperative 2 (U = 371.5, P < 0.001), 4 (U = 349.5, P < 0.001), 12 (U = 342.0, P < 0.001), 24 (U = 338.5, P < 0.001) and 48 (U = 392.5, P = 0.001) hour, lower pain numerical rating scale score at rest at postoperative 0 (U = 299.5, P < 0.001), 2 (U = 355.5, P < 0.001) and 4 (U = 332.0, P < 0.001) hour, and on movement at postoperative 0 (U = 269.5, P < 0.001), 2 (U = 405.0, P = 0.001), 4 (U = 382.5, P < 0.001) and 12 (U = 1179.5, P = 0.003) hour than control group. PVB group also had lower rescue analgesia rates (OR 0.29, 95%CI 0.08 ~ 1.00, P = 0.044), higher emergence satisfaction (5 (4, 5) vs 4 (4, 5), P = 0.018) and lower drowsiness score (0 (0,1) vs 1(0,1), P = 0.007) than control group. Three months postoperatively, PVB group had lower rates of hypoesthesia (OR 0.28 (0.11, 0.75), P = 0.009), numbness (OR 0.26 (0.07, 0.88), P = 0.024) and sleep disorder (OR 0.84 (0.73, 0.97), P = 0.025) than control group. Conclusions Intermittent bolus paravertebral block provided anesthetics- and opioids-sparing effects, and enhanced recovery both in hospital and after discharge in patients receiving hepatectomy.

Continuous-infusion von Willebrand factor concentrate is effective for the management of acquired von Willebrand disease

Acquired von Willebrand disease (aVWD) is a rare disorder associated with a reduction in von Willebrand factor (VWF) activity, leading to increased bleeding risk. Monoclonal gammopathy of undetermined significance (MGUS) is the most common cause of lymphoproliferative disorder-associated aVWD and is caused by accelerated clearance of circulating VWF. Standard VWF replacement protocols for congenital VWD based on intermittent bolus dosing are typically less effective for aVWD because of antibody-mediated clearance. Intermittent bolus dosing of VWF concentrates often leads to inadequate peak response and profoundly shortened VWF half-life in aVWD. Intravenous immune globulin (IVIG) has demonstrated efficacy in aVWD; however, treatment effect is delayed up to 4 days, limiting its efficacy in acutely bleeding patients. We report the successful use of continuous-infusion VWF concentrate (with or without concomitant IVIG) in 3 patients with MGUS-associated aVWD who had demonstrated an inadequate response to bolus dosing. VWF concentrate doses required in this cohort were higher than typical doses for bleeding treatment in congenital VWD. This report illustrates that continuous-infusion VWF concentrate administration with or without intravenous immunoglobulin rapidly achieves target ristocetin cofactor activity and provides adequate hemostasis in aVWD associated with immunoglobulin G MGUS.