Chronic intestinal pseudo-obstruction (CIPO) may be a primary or secondary phenomenon and is often multifactorial. Treatment is largely directed at improving colonic motility. The use of ...cholinesterase inhibitors such as pyridostigmine has been hypothesized to increase acetylcholine in the bowel, improving symptoms and transit times.
A systematic review of the use of pyridostigmine in CIPO was conducted using scientific and commercial search engines identifying scientific studies enrolling adult human subjects, published from 2000 to 2022 in the English language.
Four studies were identified including two randomized controlled trials (RCT) and two observational studies. The studies had heterogenous inclusion criteria, dosing regimens and reported outcomes. Two studies were identified as being at high risk of bias. All studies reported improved patient outcomes with use of pyridostigmine, and low rates (4.3%) of mild cholinergic side effects. No major side effects were reported.
The use of pyridostigmine in management of CIPO is biologically plausible due to its ability to increase colonic motility, and early studies on its role are uniformly suggestive of benefit with low side-effect profile. Four clinical studies have been conducted to date, with small sample sizes, heterogeneity and high risk of bias. Further high-quality studies are required to enable assessment of pyridostigmine's utility as an effective management strategy in CIPO.
•cSCC is the commonest cause of NMSC mortality largely due to propensity for LNM.•Whilst overall LNM rates are low, several factors confer significantly higher risks.•More proactive approaches to ...elective treatment of nodal basins have been proposed.•SLNB is emerging as a promising strategy in cSCCHN and merits investigation in a RCT.•First, further high-quality study to provide clarity on patient selection is required.
Non-melanoma skin cancer (NMSC) is among the most common cancers worldwide, with an incidence that continues to rise. Although cutaneous squamous cell carcinoma (cSCC) constitutes only approximately 20% of such cases, it represents the most common cause of NMSC mortality, owing largely to the propensity for development of regional lymph node metastases (LNM), which, when present, carry a dismal prognosis. Whilst overall rates of LNM are low, there are a number of patient and tumour factors that likely confer considerably higher risks, which has led several investigators to propose more proactive elective management of regional nodal basins in selected high-risk cases. Current international guidelines, however, do not recommend any elective treatment or sampling of regional nodal basins in the absence of clinically apparent disease. The purpose of this review is to explore in detail the fundamental issues underlying this controversy, focusing specifically on cSCC of the head and neck (cSCCHN). In particular the rationale for more a proactive elective approach to regional nodal basins, including the evidence-base underlying identification of potentially high-risk factors for development of LNM is discussed, along with oncological outcomes for those patients that do go onto suffer LNM. We also provide contemporary perspectives and evidence for approaches to electively managing regional nodal basins, and offer insight into how these may develop both in the clinical and research arenas.
The scope of intramolecular Diels−Alder and a novel tandem Diels−Alder/1,3-dipolar cycloaddition cascade of 1,3,4-oxadiazoles is disclosed. In the cases examined, the tandem cycloadditions construct ...three new rings with formation of four new C−C bonds and set all six stereocenters about a central six-membered ring in a single step including three contiguous and four total quaternary centers without a trace of a second diastereomer.
Over the last decades, native Amazonians have put increasing pressure on animal wildlife owing to growth in demand. Across societies, household monetary income and wealth shape food consumption; ...hence, so it is natural to ask what effect might these variables have on the demand for wildlife consumption among native Amazonians, particularly as they gain a stronger foothold in the market economy and increasing de jure stewardship over their territories. Prior estimates of the effects of household monetary income and household wealth on wildlife consumption among native Amazonians have relied on cross-sectional data and produced unclear results. The goal of this research was to improve the precision of previous estimates by drawing on a larger sample and on longitudinal data. The analysis draws on a dataset composed of five consecutive annual surveys (2002-2006, inclusive) from 324 households in a native Amazonian society of foragers and farmers in Bolivia (Tsimane'). Multiple regression analysis is used to estimate the association between wildlife consumption and monetary income and wealth. Wildlife consumption bore a positive association with the level of household wealth and no significant association with household monetary income. Among Tsimane', the main internal threat to wildlife conservation in the short run will likely arise from increases in wealth, probably from the enhanced capacity that selected physical assets (e.g. guns) have in the capture of animal wildlife.