A simplified clinical risk score predicts the need for early endoscopy in non-variceal upper gastrointestinal bleeding

BackgroundPre-endoscopic triage of patients who require an early upper endoscopy can improve management of patients with non-variceal upper gastrointestinal bleeding.AimsTo validate a new simplified clinical score (T-score) to assess the need of an early upper endoscopy in non variceal bleeding patients. Secondary outcomes were re-bleeding rate, 30-day bleeding-related mortality.MethodsIn this prospective, multicentre study patients with bleeding who underwent upper endoscopy were enrolled. The accuracy for high risk endoscopic stigmata of the T-score was compared with that of the Glasgow Blatchford risk score.ResultsOverall, 602 patients underwent early upper endoscopy, and 472 presented with non-variceal bleeding. High risk endoscopic stigmata were detected in 145 (30.7%) cases. T-score sensitivity and specificity for high risk endoscopic stigmata and bleeding-related mortality was 96% and 30%, and 80% and 71%, respectively. No statistically difference in predicting high risk endoscopic stigmata between T-score and Glasgow Blatchford risk score was observed (ROC curve: 0.72 vs. 0.69, p = 0.11). The two scores were also similar in predicting re-bleeding (ROC curve: 0.64 vs. 0.63, p = 0.4) and 30-day bleeding-related mortality (ROC curve: 0.78 vs. 0.76, p = 0.3).ConclusionsThe T-score appeared to predict high risk endoscopic stigmata, re-bleeding and mortality with similar accuracy to Glasgow Blatchford risk score. Such a score may be helpful for the prediction of high-risk patients who need a very early therapeutic endoscopy.     

Clinical and genetic analysis in a family with familial renal glucosuria: Identification of an N101K mutation in the sodium–glucose cotransporter 2 encoded by a solute carrier family 5 member 2 gene

We report the identification of a mutation in the solute carrier family 5 member 2 (SLC5A2) gene, which encodes sodium–glucose cotransporter 2, in a family with familial renal glucosuria. The proband was a 26‐year‐old Japanese man referred to the diabetes division with repeated glucosuria without hyperglycemia. His mother, uncle and grandfather also had a history of glucosuria. A heterozygous missense mutation (c.303T>A:p.N101K) in SLC5A2 was identified in the patient and his mother, but not in 200 chromosomes from 100 healthy and unrelated individuals, or in 3,408 Japanese individuals in the Tohoku Medical Megabank. Furthermore, bioinformatics software predicted that this lesion would be pathogenic. We infer that the mutation led to clinically relevant sodium–glucose cotransporter 2 dysfunction. The patient showed no symptoms of hypoglycemia, but continuous glucose monitoring confirmed asymptomatic hypoglycemia.     

Long‐term efficacy of the sodium–glucose cotransporter 2 inhibitor,ipragliflozin, in a case of type A insulin resistance syndrome

Type A insulin resistance (IR) syndrome is a severe IR form caused by insulin receptor (INSR) gene defects. Antidiabetic drugs, including high‐dose insulin and insulin‐sensitizing agents, often fail to control associated hyperglycemia. Therapy with recombinant human insulin‐like growth factor 1 can be more effective, but it is expensive. We report a case of type A IR syndrome with an in‐frame INSR heterozygous deletion (ΔLeu999) that was treated with a combination of conventional therapy and ipragliflozin, a sodium–glucose cotransporter 2 inhibitor. Treatment reduced hemoglobin A1c levels (10.0–7.5%) and induced weight loss (54.4–52.0 kg) within 2 months, and the effects were sustained for >3 years. Sodium–glucose cotransporter 2 inhibitors might be useful to normalize blood glucose in type A IR syndrome by reducing bodyweight and ameliorating glucotoxicity.     

Long‐term dexamethasone treatment alters the histomorphology of acinar cells in rat parotid and submandibular glands

Glucocorticoids (GCs) induce insulin resistance (IR), a condition known to alter oral homeostasis. This study investigated the effects of long‐term dexamethasone administration on morphofunctional aspects of salivary glands. Male Wistar rats received daily injections of dexamethasone [0.1 mg/kg body weight (b.w.), intraperitoneally] for 10 days (DEX), whereas control rats received saline. Subsequently, glycaemia, insulinaemia, insulin secretion and salivary flow were analysed. The parotid and submandibular glands were collected for histomorphometric evaluation and Western blot experiments. The DEX rats were found to be normoglycaemic, hyperinsulinaemic, insulin resistant and glucose intolerant (P < 0.05). DEX rat islets secreted more insulin in response to glucose (P < 0.05). DEX rats had significant reductions in the masses of the parotid (29%) and submandibular (16%) glands (P < 0.05) that was associated with reduced salivary flux rate. The hypotrophy in both glands observed in the DEX group was associated with marked reduction in the volume of the acinar cells in these glands of 50% and 26% respectively (P < 0.05). The total number of acinar cells was increased in the submandibular glands of the DEX rats (P < 0.05) but not in the parotid glands. The levels of proteins related to insulin and survival signalling in both glands did not differ between the groups. In conclusion, the long‐term administration of dexamethasone caused IR, which was associated with significant reductions in both mass and flux rate of the salivary glands. The parotid and submandibular glands exhibited reduced acinar cell volume; however, the submandibular glands displayed acinar hyperplasia, indicating a gland‐specific response to GCs. Our data emphasize that GC‐based therapies and insulin‐resistant states have a negative impact on salivary gland homeostasis.     

The benefits of tight glycemic control in critical illness: Sweeter than assumed?

Hyperglycemia has long been observed amongst critically ill patients and associated with increased mortality and morbidity. Tight glycemic control (TGC) is the clinical practice of controlling blood glucose (BG) down to the “normal” 4.4–6.1 mmol/L range of a healthy adult, aiming to avoid any potential deleterious effects of hyperglycemia. The ground-breaking Leuven trials reported a mortality benefit of approximately 10% when using this technique, which led many to endorse its benefits. In stark contrast, the multi-center normoglycemia in intensive care evaluation–survival using glucose algorithm regulation (NICE-SUGAR) trial, not only failed to replicate this outcome, but showed TGC appeared to be harmful. This review attempts to re-analyze the current literature and suggests that hope for a benefit from TGC should not be so hastily abandoned. Inconsistencies in study design make a like-for-like comparison of the Leuven and NICE-SUGAR trials challenging. Inadequate measures preventing hypoglycemic events are likely to have contributed to the increased mortality observed in the NICE-SUGAR treatment group. New technologies, including predictive models, are being developed to improve the safety of TGC, primarily by minimizing hypoglycemia. Intensive Care Units which are unequipped in trained staff and monitoring capacity would be unwise to attempt TGC, especially considering its yet undefined benefit and the deleterious nature of hypoglycemia. International recommendations now advise clinicians to ensure critically ill patients maintain a BG of <10 mmol/L. Despite encouraging evidence, currently we can only speculate and remain optimistic that the benefit of TGC in clinical practice is sweeter than assumed.