Reducing the harm associated in treating hyperkalaemia with insulin and dextrose.

Inpatient treatment of hyperkalaemia with insulin and dextrose can be complicated by iatrogenic hypoglycaemia. We sought to assess the incidence of hypoglycaemia in hospitalised patients with renal disease and assess the impact of the introduction of a local guideline incorporating the use of sodium zirconium cyclosilicate (SZC) for patients with moderate hyperkalaemia. After, establishing a significant burden of hypoglycaemia in the initial observation period, a requirement for hourly-capillary blood glucose monitoring (for up to 6 hours) following the administration of insulin for hyperkalaemia, was incorporated into the guidelines. The two-fold introduction of SZC alongside changes in patient care after the administration of insulin/dextrose, resulted in more appropriate use of insulin/dextrose as well as a significant (73%) reduction in the iatrogenic burden of hypoglycaemia (P=0.04).

Single stage management of suspected gallbladder cancer guided by intraoperative frozen section analysis: A retrospective cohort study.

BACKGROUND: The management of radiologically suspected gallbladder cancers (GBC) that lack definitive radiological features usually involves performing a first-stage routine laparoscopic cholecystectomy, followed by an open second-stage liver resection (segments IVB and V) and hilar lymphadenectomy (extended cholecystectomy) if subsequent formal histology confirms a malignancy. Performing a cholecystectomy with an intraoperative frozen section to guide the need for conversion to an extended cholecystectomy as a single-stage procedure has multiple benefits compared to a two-stage approach. However, the safety and efficacy of this approach have not yet been evaluated in a tertiary setting. METHODS: A retrospective cohort study was performed using a database of all consecutive patients with suspected GBC who had been referred to our tertiary unit. Following routine cholecystectomy, depending on the operative findings, the gallbladder specimen was removed and sent for frozen-section analysis. If malignancy was confirmed, the depth of tumour invasion was evaluated, followed by simultaneous extended cholecystectomy, when appropriate. The sensitivity and specificity of frozen section analysis for the diagnosis of GBC were measured using formal histopathology as a reference standard. RESULTS: A total of 37 consecutive cholecystectomies were performed. In nine cases, GBC was confirmed by intraoperative frozen section analysis, three of which had standard cholecystectomy only as their frozen section showed adenocarcinoma to be T1a or below (n=2) or were undetermined (n=1). In the remaining six cases, malignant invasion beyond the muscularis propria (T1b or above) was confirmed; thus, a synchronous extended cholecystectomy was performed. The sensitivity (95% CI 66.4%-100%) and specificity (95% CI 87.7%-100%) for identifying GBC using frozen section analysis were both 100%. The net cost of the single-stage pathway in comparison to the two-stage pathway resulted in overall savings of £3894. CONCLUSION: Intraoperative frozen section analysis is a reliable tool for guiding the use of a safe, single-stage approach for the management of GBC in radiologically equivocal cases. In addition to its lower costs compared to a conventional two-stage procedure, intraoperative analysis also affords the benefit of a single hospital admission and single administration of general anaesthesia, thus greatly enhancing the patient's experience and relieving the burden on waiting lists.

Weight loss specific to indication, remission of diabetes, and short-term complications after sleeve gastrectomy conversion to Roux-en-Y gastric bypass: a systematic review and meta-analysis.

Laparoscopic sleeve gastrectomy (SG) is the most frequently performed bariatric procedure worldwide. Long-term complications such as insufficient weight loss (IWL) and gastroesophageal reflux disease (GERD) may necessitate SG conversion to Roux-en-Y gastric bypass (RYGB). The aim of this review was to determine the indication-specific weight loss and diabetes remission after SG conversion to RYGB (STOBY). Our objective was to extract all available published data on indication for conversion, weight loss, remission of diabetes, and short-term complications after STOBY. A systematic literature search was conducted to identify studies reporting outcomes following STOBY. A random effects model was used for meta-analysis. The search identified 44 relevant studies. Overall short-term (12-mo) excess weight loss (EWL) was 54.6% (95% confidence interval [CI], 46%-63%) in 23 studies (n = 712) and total weight loss (TWL) was 19.9% (95% CI, 14%-25%) in 21 studies (n = 740). For IWL, short-term (12-mo) pooled weight loss outcomes were 53.9% EWL (95% CI, 48%-59%) in 14 studies (n = 295) and 22.7% TWL (95% CI, 17%-28%) in 12 studies (n = 219), and medium-term (2-5 yr) outcomes were 45.8% EWL (95% CI, 38%-53%) in 7 studies (n = 154) and 20.6% TWL (95% CI, 15%-26%) in 9 studies (n = 206). Overall diabetes remission was 53% (95% CI, 33%-72%), and the perioperative complication rate was 8.2% (95% CI, 7.6%-8.7%). Revisional SG conversion to RYGB for IWL can achieve good weight loss outcomes and diabetes remission.

Hydroxyurea exposure triggers tissue-specific activation of p38 mitogen-activated protein kinase signaling and the DNA damage response in organogenesis-stage mouse embryos.

Hydroxyurea (HU) is commonly used to treat myeloproliferative diseases and sickle cell anemia. The administration of HU to gestation day 9 CD1 mice causes predominantly hindlimb, tail, and neural tube defects. HU induces oxidative stress and p38 mitogen-activated protein kinase (MAPK) signaling in embryos. HU also inactivates ribonucleotide reductase, leading to DNA replication stress and DNA damage response signaling. We hypothesize that HU exposure induces p38 MAPK activation and DNA damage response signaling during organogenesis preferentially in malformation-sensitive tissues. HU treatment (400 or 600mg/kg) induced the activation of MEK3/6, upstream MAP2K3 kinases, within 30min; phospho-MEK3/6 immunoreactivity was increased throughout the embryo. Activation of the downstream p38 MAPK peaked 3h post-HU treatment. At this time, phospho-p38 MAPK immunoreactivity was enhanced in the cytoplasm and nucleus of cells in the rostral and caudal neuroepithelium and neural tube; significant increases in p38 MAPK signaling were not observed in the somites or heart. Interestingly, the DNA damage response, as assessed by the formation of γH2AX foci, was increased at 3h in HU-exposed embryos in all tissues examined, including the somites and heart. Increases in pyknotic nuclei and cell fragmentation were observed in all tissues except the heart, an organ that is relatively resistant to HU-induced malformations. Thus, although HU induces a widespread DNA damage response, the activation of p38 MAPK is localized to the rostral and caudal neuroepithelium and neural tube, suggesting that p38 MAPK pathways may play a role in mediating the specific malformations observed after HU exposure.