Non-interventional Management of Asymptomatic Diminutive Choledocholithiasis Versus Endoscopic Extraction in Consecutive Patients.

BACKGROUND: Current guidelines recommend treating choledocholithiasis, regardless of symptoms or stone size, with endoscopic retrograde cholangiopancreatography (ERCP). However, asymptomatic choledocholithiasis, discovered incidentally on imaging, may carry a higher risk of ERCP-related adverse events, and some asymptomatic and diminutive stones may not cause biliary adverse events during extended follow-up. Therefore, we aimed to clarify the best treatment strategies for asymptomatic choledocholithiasis based on stone size. METHODS: We retrospectively identified patients with incidental imaging-found asymptomatic diminutive (≤ 4 mm) or non-diminutive (> 4 mm) choledocholithiasis and divided them into two groups: those who did not undergo ERCP and were treated when complications arose (on-demand group) and those who underwent ERCP before being symptomatic (intervention group). Adverse events were defined as any biliary or pancreatic complication related to ERCP or arising during observation or after intervention. The primary outcome was the adjusted overall adverse event-free survival using the propensity score-based matching weights method comparing the two groups of stone size. RESULTS: Among 148 patients identified (median follow-up period, 969 days), 68 had diminutive stones and 80 had non-diminutive stones. Of the 68 patients with diminutive stones, 51 were in the on-demand group and 17 in the intervention group. The overall adjusted adverse event-free survival was significantly higher in the on-demand group for diminutive stones (97.4% and 70.1%, respectively, at 3 years; p = 0.01). DISCUSSION: Patients with incidental imaging-detected asymptomatic diminutive choledocholithiasis may benefit from clinical observation, pursuing ERCP when symptoms develop.

Normal saline versus Ringer's solution and critical-illness mortality in acute pancreatitis: a nationwide inpatient database study.

BACKGROUND: Fluid resuscitation is fundamental in acute pancreatitis (AP) treatment. However, the optimal choice between normal saline (NS) and Ringer's solution (RS), and its impact on mortality in critically ill patients, remains controversial. This retrospective cohort study, utilizing a national Japanese inpatient database, investigates this question. METHODS: Using the Japanese Diagnosis Procedure Combination database between July 2010 and March 2021, we identified adult patients hospitalized in intensive care units (ICU) or high-dependency care units (HDU) for AP who survived at least three days and received sufficient fluid resuscitation (≥ [10 ml/kg/hr*1 h + 1 ml/kg/hr*71 h] ml) within three days of admission including emergency room infusions. Patients were classified into groups based on the predominant fluid type received: the NS group (> 80% normal saline) and the RS group (> 80% Ringer's solution). Propensity score matching was employed to reduce potential confounding factors and facilitate a balanced comparison of in-hospital mortality between the two groups. RESULTS: Our analysis included 8710 patients with AP. Of these, 657 (7.5%) received predominantly NS, and 8053 (92.5%) received predominantly RS. Propensity score matching yielded 578 well-balanced pairs for comparison. The NS group demonstrated significantly higher in-hospital mortality than the RS group (12.8% [474/578] vs. 8.5% [49/578]; risk difference, 4.3%; 95% confidence interval, 0.3% to 8.3%). CONCLUSIONS: In patients admitted to ICU or HDU with AP receiving adequate fluid resuscitation, RS can be a preferred infusion treatment compared to NS.

Differential mechanisms for the inhibition of human cytochrome P450 1A2 by apigenin and genistein.

The inhibitory effects of flavonoids on the human cytochrome P450 1A2 (CYP1A2) were examined. Among flavonoids tested, galangin, kaempferol, chrysin, and apigenin were potent inhibitors. Although apigenin belonging to flavones and genistein belonging to isoflavones are similar in the chemical structures, the inhibitory potencies for CYP1A2 were distinguished markedly between these two flavonoids. In computer-docking simulation, apigenin interacted with the same mode of cocrystallized alpha-naphthoflavone in the active site of CYP1A2, and then the B ring of apigenin was placed close to the heme iron of the enzyme with a single orientation. In contrast, the docked genistein conformation showed two different binding modes, and the A ring of genistein was oriented to the heme iron of CYP1A2. Furthermore, the binding free energy of apigenin was lower than that of genistein. These results demonstrate a possible mechanism that causes the differential inhibitory potencies of apigenin and genistein for CYP1A2.