OBJECTIVE: Acute Colonic Pseudo-obstruction (ACPO) is a cause of large intestinal dilation and obstruction without any physical transition point. It remains difficult to diagnose and treat. We review the recent updates on diagnosis and management of ACPO.
RESULTS: Recent guidelines have posited that conservative management can be tried in most cases of ACPO, but that early decompression and surgery should be considered. Use of neostigmine is still a viable option but there is also promising data on pyridostigmine as well as prucalopride. Resolution of ACPO should be followed by daily use of polyethylene glycol (PEG) to help prevent recurrence. ACPO warrants early and accurate diagnosis with exclusion of alternate causes of large bowel dilation. Conservative management can be attempted for 48-72 h in those with cecal diameters < 12 cm and without signs of peritonitis and perforation. Early escalation of management should be attempted with neostigmine followed by endoscopy and/or surgery as needed, given that longer periods of dilation are associated with worse outcomes. There is promising new evidence for use of pyridostigmine and prucalopride, but further trials are needed prior to incorporating them into regular use. Finally, studies are lacking regarding prevention of ACPO after initial resolution.

At the neuromuscular junction (NMJ), the binding of the excitatory neurotransmitter acetylcholine (ACh) to postsynaptic receptors leads to muscle contraction. As in vertebrate skeletal muscle, cholinergic signaling in the body wall muscles of the model organism Caenorhabditis elegans is required for locomotion. Exposure to levamisole, a pharmacological agonist of one class of ACh receptors on the body wall muscles, causes time-dependent paralysis of wild-type animals. Altered sensitivity to levamisole suggests defects in signaling at the NMJ or muscle function. Here, a protocol for a liquid levamisole assay performed on C. elegans grown in 24-well plates is presented. Vigorous swimming of the animals in liquid allows for the assessment and quantitation of levamisole-induced paralysis in hundreds of worms over a one-hour time period without requiring physical manipulation. This procedure can be used with both wild-type and mutants that have altered sensitivity to levamisole to demonstrate the functional consequences of altered signaling at the NMJ.

UNASSIGNED: The gastric residual volume (GRV) monitoring in patients with mechanical ventilation (MV) is a common and important challenge. The purpose of this study was to compare the effect of neostigmine and metoclopramide on GRV among MV patients in the intensive care unit (ICU).
UNASSIGNED: In a double-blind randomized clinical trial, a total of 200 mechanically ventilated ICU patients with GRV > 120 ml (6 hours after the last gavage) were randomly assigned into two groups (A and B) with 100 patients in each group. Patients in groups A and B received intravenous infusion of neostigmine at a dose of 2.5 mg/100 ml normal saline and metoclopramide at a dose of 10 mg/100 ml normal saline, within 30 minutes, respectively. GRV was evaluated 5 times for each patient, once before the intervention and 4 times (at 3, 6, 9, and 12 hours) after the intervention. In addition, demographic characteristics including age and gender, as well as severity illness based on the sequential organ failure assessment score (SOFA), were initially recorded for all patients.
UNASSIGNED: After adjusting of demographic and clinical characteristics (age, gender, and SOFA score), the generalized estimating equation (GEE) model revealed that neostigmine treatment increased odds of GRV improvement compared to the metoclopramide group (OR = 2.45, 95% CI: 1.60-3.76, P < 0.001). However, there is a statistically significant time trend (within-subject differences or time effect) regardless of treatment groups (P < 0.001).
UNASSIGNED: According to the results, although neostigmine treatment significantly improved GRV in more patients in less time, within 12 hours of treatment, all patients in both groups had complete recovery. Considering that there was no significant difference between the two groups in terms of side effects, it seems that both drugs are effective in improving the GRV of ICU patients.

Bladder dysfunction is a common complication following radical hysterectomy, caused by the damage to pelvic autonomic nerves that innervate the muscles of the bladder, urethral sphincter, and pelvic floor fasciae. Bladder dysfunction increases the rates of urinary tract infection, hospital visits or admission, and patient dissatisfaction. In addition, bladder dysfunction can also negatively impact patient quality of life (QoL). Several postoperative interventions have been proposed to prevent bladder dysfunction following radical hysterectomy. To our knowledge, there has been no systematic review evaluating the effectiveness and safety of these interventions for preventing bladder dysfunction following radical hysterectomy in women with cervical cancer.
To evaluate the effectiveness and safety of postoperative interventions for preventing bladder dysfunction following radical hysterectomy in women with early-stage cervical cancer (stage IA2 to IIA2).
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 4) in the Cochrane Library, MEDLINE via Ovid (1946 to April week 2, 2020), and Embase via Ovid (1980 to 2020, week 16). We also checked registers of clinical trials, grey literature, conference reports, and citation lists of included studies.
We included randomised controlled trials (RCTs) evaluating the effectiveness and safety of any type of postoperative interventions for preventing bladder dysfunction following a radical hysterectomy in women with stage IA2 to IIA2 cervical cancer.
Two review authors independently selected potentially relevant RCTs, extracted data, assessed risk of bias, compared results, and made judgments on the quality and certainty of the evidence. We resolved any disagreements through discussion or consultation with a third review author. Outcomes of interest consisted of spontaneous voiding recovery one week after the operation, quality of life (QoL), adverse events, post-void residual urine volume one month after the operation, urinary tract infection over the one month following the operation, and subjective urinary symptoms.
We identified 1464 records as a result of the search (excluding duplicates). Of the 20 records that potentially met the review criteria, we included five reports of four studies. Most of the studies had unclear risks of selection and reporting biases. Of the four studies, one compared bethanechol versus placebo and three studies compared suprapubic catheterisation with intermittent self-catheterisation. We identified two ongoing studies. Bethanechol versus placebo The study reported no information on the rate of spontaneous voiding recovery at one week following the operation, QoL, adverse events, urinary tract infection in the first month after surgery, and subjective urinary symptoms for this comparison. The volume of post-void residual urine, assessed at one month after surgery, among women receiving bethanechol was lower than those in the placebo group (mean difference (MD) -37.4 mL, 95% confidence interval (CI) -60.35 to -14.45; one study, 39 participants; very-low certainty evidence). Suprapubic catheterisation versus intermittent self-catheterisation The studies reported no information on the rate of spontaneous voiding recovery at one week and post-void residual urine volume at one month following the operation for this comparison. There was no difference in risks of acute complication (risk ratio (RR) 0.77, 95% CI 0.24 to 2.49; one study, 71 participants; very low certainty evidence) and urinary tract infections during the first month after surgery (RR 0.77, 95% CI 0.53 to 1.13; two studies, 95 participants; very- low certainty evidence) between participants who underwent suprapubic catheterisation and those who underwent intermittent self-catheterisation. Available data were insufficient to calculate the relative measures of the effect of interventions on QoL and subjective urinary symptoms.
None of the included studies reported rate of spontaneous voiding recovery one week after surgery, time to a post-void residual volume of urine of 50 mL or less, or post-void residual urine volume at 6 and 12 months after surgery, all of which are important outcomes for assessing postoperative bladder dysfunction. Limited evidence suggested that bethanechol may minimise the risk of bladder dysfunction after radical hysterectomy by lowering post-void residual urine volume. The certainty of this evidence, however, was very low. The effectiveness of different types of postoperative urinary catheterisation (suprapubic and intermittent self-catheterisation) remain unproven.

BACKGROUND: Nerve-cancer interactions are increasingly recognized to be of paramount importance for the emergence and progression of pancreatic cancer (PCa). Here, we investigated the role of indirect cholinergic activation on PCa progression through inhibition of acetylcholinesterase (AChE) via clinically available AChE-inhibitors, i.e. physostigmine and pyridostigmine.
METHODS: We applied immunohistochemistry, immunoblotting, MTT-viability, invasion, flow-cytometric-cell-cycle-assays, phospho-kinase arrays, multiplex ELISA and xenografted mice to assess the impact of AChE inhibition on PCa cell growth and invasiveness, and tumor-associated inflammation. Survival analyses were performed in a novel genetically-induced, surgically-resectable mouse model of PCa under adjuvant treatment with gemcitabine+/-physostigmine/pyridostigmine (n = 30 mice). Human PCa specimens (n = 39) were analyzed for the impact of cancer AChE expression on tumor stage and survival.
RESULTS: We discovered a strong expression of AChE in cancer cells of human PCa specimens. Inhibition of this cancer-cell-intrinsic AChE via pyridostigmine and physostigmine, or administration of acetylcholine (ACh), diminished PCa cell viability and invasion in vitro and in vivo via suppression of pERK signaling, and reduced tumor-associated macrophage (TAM) infiltration and serum pro-inflammatory cytokine levels. In the novel genetically-induced, surgically-resectable PCa mouse model, adjuvant co-therapy with AChE blockers had no impact on survival. Accordingly, survival of resected PCa patients did not differ based on tumor AChE expression levels. Patients with higher-stage PCa also exhibited loss of the ACh-synthesizing enzyme, choline-acetyltransferase (ChAT), in their nerves.
CONCLUSIONS: For future clinical trials of PCa, direct cholinergic stimulation of the muscarinic signaling, rather than indirect activation via AChE blockade, may be a more effective strategy.

Immediately preceding sudden unexpected death in epilepsy (SUDEP), patients experienced a final generalized tonic-clonic seizure (GTCS), rapid ventilation, apnea, bradycardia, terminal apnea, and asystole. Whether a progressive pathophysiology develops and increases risk of SUDEP remains unknown. Here, we determined (a) heart rate, respiratory rate, and blood oxygen saturation (SaO2 ) in low-risk and high-risk knockout (KO) mice; and (b) whether blocking receptors for orexin, a cardiorespiratory neuromodulator, influences cardiorespiratory function mice or longevity in high-risk KO mice.
Heart rate and SaO2 were determined noninvasively with ECGenie and pulse oximetry. Respiration was determined with noninvasive airway mechanics technology. The role of orexin was determined within subject following acute treatment with a dual orexin receptor antagonist (DORA, 100 mg/kg). The number of orexin neurons in the lateral hypothalamus was determined with immunohistochemistry.
Intermittent bradycardia was more prevalent in high-risk KO mice, an effect that may be the result of increased parasympathetic drive. High-risk KO mice had more orexin neurons in the lateral hypothalamus. Blocking of orexin receptors differentially influenced heart rate in KO, but not wild-type (WT) mice. When DORA administration increased heart rate, it also decreased heart rate variability, breathing frequency, and/or hypopnea-apnea. Blocking orexin receptors prevented the methacholine (MCh)-induced increase in breathing frequency in KO mice and reduced MCh-induced seizures, via a direct or indirect mechanism. DORA improved oxygen saturation in KO mice with intermittent hypoxia. Daily administration of DORA to high-risk KO mice increased longevity.
High-risk KO mice have a unique cardiorespiratory phenotype that is characterized by progressive changes in five interdependent endpoints. Blocking of orexin receptors attenuates some of these endpoints and increases longevity, supporting the notion that windows of opportunity for intervention exist in this preclinical SUDEP model.

After colorectal surgery, anastomotic leakage is a major cause of mortality and morbidity. There are many factors affecting anastomotic leakage. It is known that agents such as neostigmine that is used to reverse neuromuscular blockade have certain effects on anastomosis. In our study, in which we planned to test this hypothesis, we aimed to compare the possible effects of different doses of sugammadex and neostigmine on colon anastomosis strength in a colonic resection anastomosis model in rats.
Forty adult Wistar albino male rats were divided into five groups as control (group C), Sugammadex 16 mg/kg (group SL), sugammadex 96 mg/kg (group SH), neostigmine 0.3 μmol/kg (group NL), and neostigmine 1.5 μmol/kg (group NH). The transverse colons of all rats were resected, and colonic anastomosis was performed. Appropriate drug doses according to the groups were given on the postoperative seventh day, and tissue hydroxyproline (TH) level and anastomotic bursting pressure were measured.
Anastomotic bursting pressure values were statistically significantly different between the groups (P = 0.001). The bursting pressure in group SH was significantly higher compared with group C, group NL, and group NH. The hydroxyproline values were statistically significantly different between the groups (P = 0.015). According to the post hoc test results, the difference was between group SH and group C (P = 0.007). There were no significant differences between the other groups (P > 0.05). There was no significant difference in terms of intra-abdominal adhesion rates between the groups.
In our study, we found that low and high doses of neostigmine had no variable effect on anastomosis, but high dose of sugammadex (96 mg/kg) had an increasing effect on intestinal anastomosis strength.

OBJECTIVE: To report on postoperative outcomes related to the administration of neostigmine for reversal of nondepolarizing neuromuscular blocking agents in cardiovascular surgery patients, with a specific focus on the duration of postoperative mechanical ventilation as the primary endpoint.
METHODS: A retrospective cohort study design was followed to achieve the study objectives.
METHODS: This was a single-center, chart review study conducted at a large academic medical center of adult patients post-cardiovascular surgery.
METHODS: Patients were included if they had received a bolus dose of perioperative nondepolarizing neuromuscular blocking agent and underwent one of the targeted cardiovascular surgeries.
METHODS: Final analysis comprised of 175 patients, 95 of whom received neostigmine and 80 who did not receive neostigmine.
RESULTS: The primary endpoint was the duration of postoperative mechanical ventilation. When controlling for all covariates, neostigmine use was associated with a 0.34-hour reduction (∼20.4 min) in duration of mechanical ventilation (parameter estimate: 0.66, 95% confidence interval 0.49-0.89; p = 0.0071). More patients who received neostigmine met the early extubation benchmark of less than 6 hours (55 v 34 patients; p = 0.04). Finally, neostigmine use was not found to be associated with increased risk of respiratory complications or postoperative nausea and/or vomiting.
CONCLUSIONS: The use of neostigmine was found to have a protective effect on the duration of postoperative mechanical ventilation without increasing the risk of adverse complications.

Asthma is a chronic inflammatory lung disease of the airway; the incidence and prevalence of asthma remain high worldwide. Astragaloside IV (AS-IV) is the main active constituent of Astragalus membranaceus. Accumulating evidence suggests that AS-IV possesses anti-inflammatory and anti-asthmatic ability, but the potential molecular mechanism is required to further clarify. In this study, the anti-asthmatic effects of AS-IV on mice with ovalbumin (OVA)-induced allergic inflammation were analysed. We analysed airway hyperresponsiveness (AHR), numbers of inflammatory cells, inflammation situation in lung tissue and cytokines level in bronchoalveolar lavage fluid (BALF) between OVA-induced mice with and without AS-IV treatment. Moreover, we explored the possible signalling pathway behind the anti-asthmatic effects. Our results revealed that AS-IV treatment ameliorates airway inflammation and AHR in an OVA-induced asthma model. Besides, AS-IV treatment inhibits the interleukin (IL)-4, -5 and -13 production, and further study indicated that AS-IV treatment downregulates the expression level of p-JAK2/p-STAT6 proteins. Taken together, the present study suggested that the inhibitory effects of AS-IV on asthma therapy are at least partially involved in inhibiting the JAK2/STAT6 signalling pathway.

• Background: Caudal epidural is the most commonly used technique for the management of postoperative pain in children. The aim of the present study was to assess and compare the efficacy of caudal bupivacaine as a postoperative analgesic alone or combined with midazolam, ketamine, and neostigmine in pediatric patients undergoing lower abdominal surgery.
Eighty pediatric patients categorized under the American Society of Anesthesiologists Physical Status I and II Classification System, who have been scheduled to undergo lower abdominal surgery were randomly designated into four groups to receive caudal block with either 1 ml/kg of 0.25% caudal bupivacaine for group B, 1 ml/kg of 0.25% caudal bupivacaine mixed with 2 μg/kg neostigmine for group BN, 1 ml/kg of 0.25% caudal bupivacaine mixed with 0.5 mg/kg ketamine for group BK or 1 ml/kg of 0.25% caudal bupivacaine mixed with 50 mcg/kg midazolam for group BM. Postoperative analgesia was examined by a blinded anesthetist utilizing a Revised Faces Pain Scale.Consumption of the total amount of rescue analgesic each 24 h, postoperative time to requirement of the first dose and any adverse effects were noted.
The four groups were comparable as regards age, sex, weight, duration of surgery, heart rate, blood pressure and the time from induction of anesthesia to response to voice. The Revised Faces Pain Scale was 2.6±1.5 in group BN, 3.1±1.8 in group BM, 4.4±2.4 in group BK, and 5.6±1.3 in group B (p=0.005). Postoperative duration of analgesia was 433±68 min, 769±118 min, 1097±126 min and 1254±176 min in groups B, BK, BM and BN respectively (P=0.001). The dose of rescue analgesic within 24 h in group B was significantly higher than those of the other three groups (P<0.05).
Addition of either neostigmine, midazolam, or ketamine to caudal bupivacaine extended analgesia time and decreased rescue analgesic compared to bupivacaine alone in children who underwent lower abdominal surgery.