Alterations in the Gut Microbiota and Metabolomics of Seafarers after a Six-Month Sea Voyage.

Maintaining the health of seafarers is a difficult task during long-term voyages. Little is known about the corresponding changes in the gut microbiome-host interaction. This study recruited 30 seafarers undertaking a 6-month voyage and analyzed their gut microbiota using 16S rRNA gene sequencing. Fecal untargeted metabolomics analysis was performed using liquid chromatography-mass spectrometry. Significant changes in the composition of the gut microbiota and an increased ratio of Firmicutes/Bacteroidetes at the end (day 180) of the 6-month voyage, relative to the start (day 0), were observed. At the genus level, the abundances of Holdemanella and Plesiomonas were significantly increased, while the abundance of Bacteroides was decreased. Predicted microbial functional analysis revealed significant decreases in folate biosynthesis and biotin metabolism. Furthermore, 20 differential metabolites within six differentially enriched human metabolic pathways (including arginine biosynthesis, lysine degradation, phenylalanine metabolism, sphingolipid metabolism, pentose and glucuronate interconversions, and glycine, serine, and threonine metabolism) were identified by comparing the fecal metabolites at day 0 and day 180. Spearman correlation analysis revealed close relationships between the 14 differential microbiota members and the six differential fecal metabolites that might affect specific human metabolic pathways. This study adopted a multi-omics approach and provides potential targets for maintaining the health of seafarers during long-term voyages. These findings are worthy of more in-depth exploration in future studies. IMPORTANCE Maintaining the health of seafarers undertaking long-term voyages is a difficult task. Apart from the alterations in the gut microbiome and fecal metabolites after a long-term voyage, our study also revealed that 20 differential metabolites within six differentially enriched human metabolic pathways are worthy of attention. Moreover, we found close relationships between the 14 differential microbiota members and the six differential fecal metabolites that might impact specific human metabolic pathways. Accordingly, preventative measures, such as adjusting the gut microbiota by decreasing potential pathobionts or increasing potential probiotics as well as offsetting the decrease in B vitamins and beneficial metabolites (e.g., d-glucuronic acid and citrulline) via dietary adjustment or nutritional supplements, might improve the health of seafarers during long-term sea voyages. These findings provide valuable clues about gut microbiome-host interactions and propose potential targets for maintaining the health of seafarers engaged in long-term sea voyages.

Increased severity of complications after therapeutic ERCP in geriatric patients with chronic pancreatitis: An observational study.

Studies of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in geriatric patients have mainly examined patients with biliary diseases, rather than chronic pancreatitis (CP). This study aimed to evaluate the safety and success rate of therapeutic ERCP in geriatric patients with CP. The medical records of patients with CP aged over 65 years (group A) were retrospectively collected in a tertiary hospital from January 2013 to December 2018. Sex-matched CP patients under 65 years (group B) were randomly selected into the control group (matching ratio = 1:2). The success rate and the complication rate of therapeutic ERCP in 2 groups were compared. The risk factors for post-ERCP pancreatitis were investigated by univariate and multivariate analyses. A total of 268 ERCPs were performed in 179 patients of group A and 612 ERCPs in 358 patients of group B. The success rate of ERCP in group A was similar to that of group B (92.16% vs 92.32%; P = .936). The overall incidence of post-ERCP complications was 7.09% (19/268) and 5.72% (35/612) in group A and B, respectively (P = .436). However, geriatric patients had a significantly increased occurrence of moderate to severe complications (2.61% vs 0.16%; P = .002). Female gender (odds ratio [OR] = 3.40; P = .046), pancreas divisum (OR = 7.15; P = .049), dorsal pancreatogram (OR = 7.40; P = .010), and lithotripsy (OR = 0.15; P = .016) were significantly associated with risk of post-ERCP pancreatitis in geriatric patients. Therapeutic ERCP is safe and feasible in elderly patients with CP. However, occurrence of moderate to severe complications after ERCP increased in geriatric patients.

Rectal indometacin to prevent pancreatitis after extracorporeal shock wave lithotripsy (RIPEP): a single-centre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: Pancreatitis is the most common complication of pancreatic extracorporeal shock wave lithotripsy (ESWL). There has been little research into effective prevention of post-ESWL pancreatitis. Therefore, we aimed to assess the efficacy of prophylactic rectal indometacin in preventing post-ESWL pancreatitis. METHODS: In this double-blind, randomised, placebo-controlled trial done at Changhai Hospital (Shanghai, China), patients aged 18 years or older with chronic pancreatitis and pancreatic stones (>5 mm in diameter) who were eligible for treatment with ESWL were randomly allocated using a computer-generated randomisation table, in a 1:1 ratio, to receive 100 mg rectal indometacin or identical glycerin (placebo) suppositories 30 min before ESWL. Patients, endoscopists, and outcome assessors were masked to group allocation. The primary outcome was the incidence of post-ESWL pancreatitis within 24 h of ESWL, analysed by the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT02797067. FINDINGS: Between May 31, 2016, and June 26, 2019, 1370 patients were enrolled, with 685 patients randomly assigned to the rectal indometacin group and 685 patients to the placebo group. All patients received their allocated intervention and completed final follow-up, and were included in the intention-to-treat analysis. Post-ESWL pancreatitis occurred in 60 (9%) patients in the rectal indometacin group and 84 (12%) patients in the placebo group (relative risk 0·71, 95% CI 0·52-0·98; p=0·042). Transient adverse events occurred in 235 (34%) patients in the rectal indometacin group and 252 (37%) patients in the placebo group, with asymptomatic hyperamylasaemia being the most common (189 [28%] patients vs 197 [29%] patients). No difference was noted between groups in the incidence of other complications and transient adverse events. INTERPRETATION: Pre-procedural administration of rectal indometacin is an efficacious and safe means of reducing the incidence of post-ESWL pancreatitis. FUNDING: Programs of Shanghai Municipal Government and the "Ten Thousand Plan"-National High Level Talents Special Support Plan.

Post-ESWL and post-ERCP pancreatitis in patients with chronic pancreatitis: Do they share the same risks?

BACKGROUND: Endoscopic intervention combined with extracorporeal shock wave lithotripsy (ESWL) is recommended as the first line therapy for large pancreatic stones, yet both can cause adverse events. The aim of the study was to identify the risk factors for post-procedural pancreatitis. METHODS: Consecutive patients with chronic pancreatitis and pancreatic stones treated with both ESWL and subsequent endoscopic retrograde cholangiopancreatography (ERCP) from October 2016 to December 2019 were prospectively enrolled. Multivariate logistic analyses were performed to detect risk factors for post-ESWL and post-ERCP pancreatitis (PEP). RESULTS: A total of 714 patients (507 males, 45.60 ± 12.52 years) were included in this study. A total of 80 patients (11.2%) developed post-ESWL pancreatitis,while 33 patients (4.6%) suffered from PEP. Steatorrhea (P = .018), multiple stones (P = .043), and stones located at the head combined with the body or tail of the pancreas (P = .015) were identified as independent protective factors for post-ESWL pancreatitis. The history of acute exacerbations (P = .013), post-ESWL pancreatitis (P < .001) and stricture dilation during ERCP (P = .002) were identified as risk factors for PEP. CONCLUSIONS: More attention should be paid to patients with post-ESWL pancreatitis, as well as a history of acute exacerbations and stricture dilation during ERCP to prevent PEP. (ClincialTrials.gov number, NCT04619511).

SPINK1 mutations and risk of pancreatic cancer in a Chinese cohort.

OBJECTIVE: The relationship between SPINK1 and pancreatic cancer (PC) remains controversial. The current study aimed to determine the effect of SPINK1 mutations on PC development among patients with chronic pancreatitis (CP). METHODS: This is a prospective observational study including a large cohort of 965 CP patients with 11-year follow-up. Patients' demographic characteristics and clinical CP outcomes were documented in detail. Genetic testing was performed. The effect of SPINK1 mutations on the clinical development of PC was explored using Cox proportional hazards regression. Subgroup analyses conducted included the consideration of gender, onset age of CP (early- and late-onset), etiologies of CP, smoking, and alcoholic drinking status. RESULTS: PC was diagnosed in 2.5% (24/965) of patients, and the cumulative incidence rates were 0.2%, 0.8%, and 1.5% at 3, 5, and 10 years since the onset of CP, respectively. In this cohort, SPINK1 c.194+2T > C was the most common variant with a proportion of 39.1%. And the risk of PC development varied marginally between patients with and without SPINK1 mutations (Cox HR 0.39(0.14-1.04), P = 0.059). In the subgroup analyses, patients carrying SPINK1 mutations had a significantly lower risk of PC (Cox HR 0.18(0.04-0.80), P = 0.025) in the non-smoking group. SPINK1 mutations showed no significant effect in the other subgroups considered. CONCLUSIONS: CP patients harboring SPINK1 mutations do not have an elevated risk of PC development compared to mutation-negative CP patients. On the contrary, SPINK1 mutations may be a protective factor in non-smoking patients with CP.

Optimal Timing of Endoscopic Intervention After Extracorporeal Shock-Wave Lithotripsy in the Treatment of Chronic Calcified Pancreatitis.

OBJECTIVES: The interval between extracorporeal shock-wave lithotripsy (ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) may cause differences in cannulation and stone removal. This study was to investigate the optimal timing of ERCP after ESWL. METHODS: Patients with chronic calcified pancreatitis, who underwent ESWL and subsequent ERCP in Changhai Hospital from February 2012 to February 2015, were retrospectively analyzed. The interval between ESWL and ERCP was used to divide patients into groups A (<12 hours), B (12-36 hours), and C (>36 hours). Cannulation success, stone clearance, and post-ESWL/ERCP complications were compared. RESULTS: A total of 507 patients were enrolled. There were no significant differences regarding the successful cannulation and stone removal rates between the 3 groups. In patients without prior ERCP, the successful cannulation rates were 71.4%, 81.9%, and 90.9% (P = 0.004), and the successful clearance rates were 76.2%, 85.1%, and 90.9% (P = 0.031) for these 3 groups, respectively, showing significant differences. There were no differences in the successful cannulation and stone extraction rates for patients with prior ERCP. CONCLUSIONS: The interval between ESWL and ERCP in chronic calcified pancreatitis patients with prior ERCP is not relevant, while delaying endoscopic intervention is recommended in those with native papilla.

Factors associated with prior acute pancreatitis episodes among patients with chronic pancreatitis.

BACKGROUND: The relationship between chronic pancreatitis (CP) and acute pancreatitis (AP) is complex and not well understood. CP could be preceded by antecedent episodes of AP. AIMS: The aim of this study was to explore both genetic and environmental factors associated with AP episodes before the diagnosis of CP. METHODS: This was a cross-sectional study including 1022 patients. Detailed demographic, genetic, and clinical data were collected. Based on the presence of AP episode(s) before diagnosis of CP, patients were divided into AP group (further classified into single episode of AP group and recurrent AP group) and non-AP group. Related factors among these groups were assessed using multivariate logistic regression model. RESULTS: Before diagnosis of CP, 737 patients (72.1%) had a history of AP. Smoking(P = 0.005) and heavy alcohol consumption(P = 0.002) were risk factors for AP while age at CP onset(P < 0.001), harboring the SPINK1 mutation(P < 0.001), diabetes(P < 0.001) and steatorrhea(P < 0.001) were protective factors. Further, alcoholic CP(P = 0.019) was the only independent risk factor for recurrent AP attacks while age at onset of CP(P < 0.001), pancreatic stones(P = 0.024). and pseudocysts(P = 0.018) served as protective factors. CONCLUSIONS: SPINK1 mutations served as protective factor for AP episodes, suggesting SPINK1 mutation might play a pathogenic role in CP occurrence with occult clinical manifestations.

Risk factors for sinistral portal hypertension and related variceal bleeding in patients with chronic pancreatitis.

OBJECTIVES: Sinistral portal hypertension (SPH) is an uncommon complication of chronic pancreatitis (CP) and can result in severe gastrointestinal bleeding. The aim of this study was to determine the prevalence and the potential risk factors for SPH and related gastrointestinal variceal bleeding in patients with CP. METHODS: We retrospectively reviewed all patients with SPH due to CP admitted to our hospital from July 2014 to June 2019 in this case-control study. Patients with CP without SPH were randomly selected as controls during the study period (case: control  =  1:2). The characteristics, medical history, course of CP, characteristics associated with SPH, and follow-up evaluations of the patients were documented in detail. The prevalence rate of SPH in patients with CP and related gastrointestinal bleeding was calculated. Risk factors for SPH and related variceal bleeding were analyzed using univariate or multivariate logistic regression analysis. RESULTS: The prevalence of SPH was 2.7% (89/3358) in patients with CP. Independent risk factors for SPH included alcohol consumption (P = 0.030), history of acute pancreatitis (P = 0.010), diabetes mellitus (P < 0.001), and pseudocysts (P < 0.001). Overall 17 (19.1%) patients suffered from related gastrointestinal bleeding. Between the bleeding and non-bleeding groups, there were significant differences in the types of CP, existence of stones, gastric varices diagnosed before bleeding, splenomegaly and hypersplenism by univariate analysis. CONCLUSION: SPH is a rare complication of CP that is associated with a relatively low risk of variceal bleeding.

Effect of suckling intensity of primiparous sows on production performance during current and subsequent parities1.

This study was conducted to evaluate the effects of suckling intensity (litter size and lactation length) to primiparious sows on production performance during current and subsequent parities. Upon farrowing, 115 primiparous sows (farrowing weight: 222.7 ± 20.0 kg) were initially allotted to 4 treatments in a 2 × 2 factorial arrangement with 2 litter sizes: 10 and 13 piglets (LS10 vs. LS13), and 2 lactation lengths: 21 and 27 d (LL21 vs. LL27). Upon weaning, sows were rebred and those farrowed successfully (n = 66) kept 10 piglets and weaned at 21 d in the second parity. Sows were fed ad libitum during lactation in both parities. Feed intake, BW loss, backfat loss, litter size, and litter weight gain during lactation in both parities were determined. Litter weight gain in LS13 was greater (P < 0.05) than that in LS10 (54.4 vs. 47.7 kg) during the first lactation. Sows in LS13 had a greater (P < 0.05) BW loss than sows in LS10 (24.1 vs. 17.4 kg). Body weight loss was not different between LL27 and LL21. Sows in LS13 tended to have a greater (P = 0.075) removal rate than those in LS10 (47.5 vs. 32.2%). Sows in LL27 had a smaller (P < 0.05) removal rate than those in LL21 (28.0 vs. 51.7%). In the second parity, gestation BW gain in LL27 tended to be greater (P = 0.098) than that in LL21 when the previous litter size was 10 piglets (56.1 vs. 33.2 kg). Litter performance and feed intake of sows were not affected by previous litter size, lactation length, and their interaction. The farrowing weight, farrowing body protein and lipid, body weight loss was not different between LS13 and LS10, whereas backfat loss in LS13 was smaller (P < 0.05) than that in LS10 during the second lactation (0.9 vs. 2.4 mm). The predicted body lipid loss in LS13 was also smaller than that in LS10 (2.3 vs. 5.3 kg) during the second lactation. Sows in LL27 had a smaller (P < 0.05) BW loss and body lipid loss during the second lactation than sows in LL21 (4.0 vs. 9.0 kg; 2.3 vs. 4.8 kg). The concentration of milk fat in LL27 was smaller (P < 0.05) than that in LL21 (7.9 vs. 9.1%). In conclusion, increasing suckling intensity to primiparous sows increased litter weight gain but increasing litter size reduced piglet ADG. Sow performance in the second lactation was not negatively affected by increasing suckling intensity of the first lactation. Interestingly, sows with an increased suckling intensity in the first lactation had reduced loss of body reserves in the second lactation.

Lowering dietary cation-anion difference increases sow blood and milk calcium concentrations.

A study was conducted to evaluate the effects of feeding an acidogenic diet with a low dietary cation-anion difference (DCAD) on acid-base balance, blood, milk, and urine Ca concentrations of sows during lactation. A total of 30 multiparous sows (parity: 4.5 ± 2.9, Smithfield Premium Genetic, Rose Hill, NC) were allotted to 1 of 2 dietary treatments: CON (control diets were corn-soybean meal based with a calculated DCAD of 170 and 226 mEq/kg during late gestation and lactation, respectively) or ACI (acidogenic diets had a DCAD 100 mEq/kg lower than the control diets). The lower DCAD was achieved by the addition of an acidogenic mineral. The DCAD was calculated as mEq (Na + K - Cl)/kg diet. Sows had a daily access to 2-kg feed from day 94 of gestation to parturition and ad libitum access to feed during lactation. Blood and urine pH and Ca, serum macrominerals, serum biochemistry, Ca-regulating hormones, and milk composition were measured. Sows in ACI had a lower (P < 0.05) blood pH than sows in CON at day 1 of lactation. Sows in ACI had a lower (P < 0.05) urine pH at day 108 of gestation, days 1, 9, and 18 of lactation compared with sows in CON. Sows in ACI had greater (P < 0.05) concentrations of serum total Ca at days 1 and 18 of lactation than sows in CON. There was a greater (P < 0.05) concentration of colostrum Ca in ACI than in CON. There was no difference in urine Ca concentration between treatments during lactation. Concentrations of parathyroid hormone and 1,25-dihydroxycholecalciferol were not different between treatments at either day 1 or 18 of lactation. Sows in ACI tended to have a smaller (P = 0.086) concentration of total alkaline phosphatase in serum at day 18 of lactation compared with sows in CON. At day 1 of lactation, the concentration of serum Cl in ACI was greater (P < 0.05) than that in CON. Feed intake, BW loss, and litter performance were not different between treatments. Collectively, feeding an acidogenic diet with a low DCAD to sows can induce a mild metabolic acidosis at farrowing, reduce the urine pH consistently, and increase serum total Ca and colostrum Ca concentrations during lactation but without altering the parathyroid hormone and 1,25-dihydroxycholecalciferol levels during lactation.