Profile of and risk factors for early unplanned readmissions in patients with acute necrotizing pancreatitis.

INTRODUCTION: Acute necrotizing pancreatitis (ANP) complicates up to 15% of acute pancreatitis cases. ANP has historically been associated with a significant risk for readmission, but there are currently no studies exploring factors that associate with risk for unplanned, early (<30-day) readmissions in this patient population. METHODS: We performed a retrospective review of all consecutive patients presenting to hospitals in the Indiana University (IU) Health system with pancreatic necrosis between December 2016 and June 2020. Patients younger than 18 years of age, without confirmed pancreatic necrosis and those that suffered in-hospital mortality were excluded. Logistic regression was performed to identify potential predictors of early readmission in this group of patients. RESULTS: One hundred and sixty-two patients met study criteria. 27.7% of the cohort was readmitted within 30-days of index discharge. The median time to readmission was 10 days (IQR 5-17 days). The most frequent reason for readmission was abdominal pain (75.6%), followed by nausea and vomiting in (35.6%). Discharge to home was associated with 93% lower odds of readmission. We found no additional clinical factors that predicted early readmission. CONCLUSION: Patients with ANP have a significant risk for early (<30 days) readmission. Direct discharge to home, rather than short or long-term rehabilitation facilities, is associated with lower odds of early readmission. Analysis was otherwise negative for independent, clinical predictors of early unplanned readmissions in ANP.

Epiphytic hydroid community as sentinels of seagrass condition and human impacts.

Negative human actions on seagrasses affect habitat condition and its associated fauna. Epiphytic hydroid's assemblage response to seagrass condition, water quality, and human impacts was evaluated in two bays of the Sabana-Camagüey Ecosystem of Cuba, using the presence of contamination, causeways, and trawling fishing as impact level proxies to the seagrass meadows. Thirty-eight species composed the hydroid's assemblage including five new records. Symmetroscyphus intermedius was the most abundant species and sensitive to indicators of the seagrass condition. Dynamena disticha and Gastroblasta sp. were sensitive to water quality predictors. Obelia bidentata was exclusive to the most impacted sites. Species richness and abundance were low in impacted sites and were highly affected by fishing trawling and causeways construction. Salinity, depth, NO2, pH, SSV, macroalgae cover, shoot density, and wet weight of Thalassia testudinum were the best predictors for hydroid's assemblages. Results suggest epiphytic hydroids on tropical seagrass meadows as sentinel organisms.

The addition of flexible endoscopic suturing to stenting for the management of transmural esophageal wall defects: a single tertiary center experience.

BACKGROUND AND AIMS: Endoscopic stenting is the standard of care for full thickness esophageal wall defects. The aim of this study is to evaluate outcomes of endoscopic closure of esophageal defects using stenting, with or without endoscopic suturing. METHODS: This is a single-center retrospective study of patients with esophageal wall defects who underwent endoscopic interventions. Outcomes of stenting with or without endoscopic suturing of the defect were assessed. Univariate and multivariate logistic regression models were used to examine factors associated with successful defect closure. RESULTS: One hundred and fourteen patients with esophageal wall defects underwent 254 endoscopies with an overall complete closure rate of 75.8%. Twenty-three (20.2%) patients underwent primary closure using endoscopic suturing and subsequent esophageal stenting, while 91 (79.8%) underwent esophageal stenting only. The dual modality group (versus the stent-only group) had similar defect closure rates (84.2 vs. 73.8%, p = 0.55) and time to stent migration (37 vs. 12.5 days, p = 0.07), but was associated with longer procedure times (60 vs. 36 min, p < 0.01) and fewer additional endoscopic procedures (13.6 vs. 43.2%, p = 0.01). Stent suturing significantly decreased migration (35.5 vs. 58.5%, p = 0.04), was associated with fewer additional endoscopies (15.4 vs. 50%, p < 0.01) and reduced need for additional stents (7.7 vs. 34.3%, p < 0.01). On multivariate analysis, chronic defects (> four weeks old) were 81% less likely to close compared to acute (≤ 4 weeks) defects (OR 0.19, CI 0.04-0.77, p = 0.02), and large diameter stents (23 mm) were associated with higher odds of defect closure (OR 3.36, CI 1.02-11.4, p = 0.04). CONCLUSION: Endoscopic treatment of esophageal wall defects is safe, effective, and more likely to be successful in acute defects using larger caliber stents. Stent suturing reduces migration, need for additional endoscopic procedures, and stent exchanges. Further comparative studies with larger cohorts are needed to validate our results.

A large multicenter cohort on the use of full-thickness resection device for difficult colonic lesions.

BACKGROUND: Introduction of the full-thickness resection device (FTRD) has allowed endoscopic resection of difficult lesions such as those with deep wall origin/infiltration or those located in difficult anatomic locations. The aim of this study is to assess the outcomes of the FTRD among its early users in the USA. METHODS: Patients who underwent endoscopic full-thickness resection (EFTR) for lower gastrointestinal tract lesions using the FTRD at 26 US tertiary care centers between 10/2017 and 12/2018 were included. Primary outcome was R0 resection rate. Secondary outcomes included rate of technical success (en bloc resection), achievement of histologic full-thickness resection (FTR), and adverse events (AE). RESULTS: A total of 95 patients (mean age 65.5 ± 12.6 year, 38.9% F) were included. The most common indication, for use of FTRD, was resection of difficult adenomas (non-lifting, recurrent, residual, or involving appendiceal orifice/diverticular opening) (66.3%), followed by adenocarcinomas (22.1%), and subepithelial tumors (SET) (11.6%). Lesions were located in the proximal colon (61.1%), distal colon (18.9%), or rectum (20%). Mean lesion diameter was 15.5 ± 6.4 mm and 61.1% had a prior resection attempt. The mean total procedure time was 59.7 ± 31.8 min. R0 resection was achieved in 82.7% while technical success was achieved in 84.2%. Histologically FTR was demonstrated in 88.1% of patients. There were five clinical AE (5.3%) with 2 (2.1%) requiring surgical intervention. CONCLUSIONS: Results from this first US multicenter study suggest that EFTR with the FTRD is a technically feasible, safe, and effective technique for resecting difficult colonic lesions.

Does preoperative cross-sectional imaging accurately predict main duct involvement in intraductal papillary mucinous neoplasm?

Main pancreatic duct (MPD) involvement is a well-demonstrated risk factor for malignancy in intraductal papillary mucinous neoplasm (IPMN). Preoperative radiographic determination of IPMN type is heavily relied upon in oncologic risk stratification. We hypothesized that radiographic assessment of MPD involvement in IPMN is an accurate predictor of pathological MPD involvement. Data regarding all patients undergoing resection for IPMN at a single academic institution between 1992 and 2012 were gathered prospectively. Retrospective analysis of imaging and pathologic data was undertaken. Preoperative classification of IPMN type was based on cross-sectional imaging (MRI/magnetic resonance cholangiopancreatography (MRCP) and/or CT). Three hundred sixty-two patients underwent resection for IPMN. Of these, 334 had complete data for analysis. Of 164 suspected branch duct (BD) IPMN, 34 (20.7%) demonstrated MPD involvement on final pathology. Of 170 patients with suspicion of MPD involvement, 50 (29.4%) demonstrated no MPD involvement. Of 34 patients with suspected BD-IPMN who were found to have MPD involvement on pathology, 10 (29.4%) had invasive carcinoma. Alternatively, 2/50 (4%) of the patients with suspected MPD involvement who ultimately had isolated BD-IPMN demonstrated invasive carcinoma. Preoperative radiographic IPMN type did not correlate with final pathology in 25% of the patients. In addition, risk of invasive carcinoma correlates with pathologic presence of MPD involvement.

Effect of adenosine on injury caused by ischemia and reperfusion in rats: functional and morphologic study.

To study whether treatment with adenosine (ADO), an agonist of adenosine receptors, attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), we treated rats with ADO (15 mg/kg or saline solution (SS) intravenously before 60 minutes occlusion of the superior mesenteric artery (I) and/or 120 minutes after its release (R). After I or I/R, isolated jejunal segments (2 cm) were mounted in an organ bath to study nerve-mediated contractions stimulated by electrical pulses or KCI with the use of a digital recording system. Thin jejunal slices were stained with hematoxylin and eosin for optical microscopy. Compared with the sham group, jejunal contractions were reduced in I+SS and IR+SS but similar after treatment with ADO (I+ADO and IR+ADO groups). We concluded that rat jejunal enteric nerves were damaged in I+SS and IR+SS but not in the I+ADO and IR+ADO groups. These results suggested that ADO attenuated intestinal dysfunction due to I and R.

Comportamento de componentes bioquímicos do sangue em equinos submetidos à ozonioterapia / Profile of blood biochemistry components in horses treated with ozone therapy

O comportamento de constituintes bioquímicos sanguíneos (glicose, fibrinogênio, creatina fosfoquinase e gama-glutamiltransferase) foi monitorado, in vivo, em 12 equinos mestiços (seis machos e seis fêmeas), com idade entre 4 e 20 anos, submetidos à ozonioterapia. O tratamento foi realizado mediante administração de 500 ou 1000mL da mistura de oxigênio-ozônio (O2-O3) por via intravenosa, a cada três dias, durante 24 dias. Os equinos foram distribuídos em quatro grupos: MT500 constituído por três machos tratados com 500mL; MT1000 por três machos tratados com 1000mL; FT500, por três fêmeas tratadas com 500mL e FT1000, por três fêmeas tratadas com 1000mL. A ozonioterapia por via intravenosa não ocasionou alterações clínicas nos equinos. Os valores médios mínimos e máximos de glicose, fibrinogênio, creatina fosfoquinase e gama-glutamiltransferase mantiveram-se dentro dos limites de referência para a espécie equina. Houve diminuição nas concentrações da glicose e gama-glutamiltransferase ao longo dos períodos de aplicação e aumento nos valores do fibrinogênio. A creatina fosfoquinase não sofreu efeito do tratamento.

The profile of blood biochemistry variables (glucose, fibrinogen, creatine phosphokinase, and gamma glutamyltransferase) was in vivo monitored in 12 crossbred horses (six males and six females), aging from four to 20-years-old treated with ozone therapy. Treatments were carried out by applying 500 or 1000mL of the mixture oxygen-ozone (O2-O3) via intravenous route, every three days, during 24 days. Horses were assigned to four groups: MT500 (three males given 500mL), MT1000 (three males given 1000mL), FT500 (three females given 500mL) and FT1000 (three females given 1000mL). Ozone therapy by intravenous route caused no clinical changes in the horses. Minimum and maximum mean values of glucose, fibrinogen, creatine phosphokinase, and gamma glutamyltransferase were within the range considered as normal reference for the equine species. There was decrease in glucose and gamma glutamyltransferase concentrations over the period of application, whereas fibrinogen increased and creatine phosphokinase was not affected by the treatment.

l-Arginine supplementation protects against hepatic ischemia-reperfusion lesions in rabbits.

We evaluated the effects of a substrate in the biosynthesis of nitric oxide (NO)-l-arginine (LARG)-on hepatic lesions caused by ischemia/reperfusion (I/R) injury in rabbit livers. Rabbits were pretreated with LARG (150 mg/kg IV) or saline solution 0.9% (SS) before the hepatic I/R procedure. The effects of LARG on hepatic injury were evaluated before and after I/R. The warm hepatic I/R procedure produced profound acute liver injury, as indicated by elevated values of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH), as well as a high apoptotic cell count. All changes were attenuated by treatment with LARG before the hepatic I/R procedure. These results suggested that LARG produced protective effects on hepatic I/R lesions. This protective effect of LARG was probably associated with blocking generation of superoxide anions during the hepatic I/R procedure.

Unopposed appetite (orexigenic) mechanisms in the near-term ovine fetus: central leptin does not inhibit sucrose ingestion.

OBJECTIVE: Leptin is produced in adipocytes and is present in the term fetus. In the adult, leptin acts centrally to inhibit neuropeptide Y-induced carbohydrate intake. We sought to examine if central leptin alters fetal ingestion of oral sucrose in the near-term ovine fetus. METHODS: Five pregnant ewes and fetuses were prepared with fetal vascular, sublingual and intracerebroventricular (ICV) catheters and esophageal electromyogram electrodes, and studied at 132 +/- 1 days' gestation (term 145-150 days). Following a 2-h baseline period, 10% sucrose was infused sublingually (0.25 ml/min) for the duration of the study. At time 4 h, leptin (0.075 mg/kg) was administered ICV and fetal swallowing was monitored for an additional 6 h. RESULTS: During the basal period, fetal swallowing averaged 0.7 +/- 0.1 swallows/min. Fetal swallowing increased significantly in response to 10% sucrose (1.2 +/- 0.1 swallows/min; p < 0.05). In response to ICV leptin, fetal swallowing remained significantly elevated at 2, 4 and 6 h (1.3 +/- 0.4, 1.4 +/- 0.3 and 1.5 +/- 0.2 swallows/min, respectively; p < 0.05 vs. control). CONCLUSIONS: These results indicate that central leptin inhibition of sucrose ingestion is not functional in the near-term fetus. We speculate that a leptin-mediated anorexigenic response is not present at birth, such that unopposed appetite stimulatory mechanisms in the newborn may facilitate rapid newborn weight gain despite high body fat levels.

In utero development of fetal thirst and appetite: potential for programming.

Thirst and appetite-mediated ingestive behavior develop and are likely programmed in utero, thus preparing for newborn and adult ingestive behavior. Fetal swallowing activity is markedly different from that of the adult, as spontaneous fetal swallowing occurs at a markedly (six-fold) higher rate compared with spontaneous adult drinking activity. This high rate of fetal swallowing is critical for the regulation of amniotic fluid volume and the development of the fetal gastrointestinal tract. Disordered fetal swallowing has been associated with both a decrease (oligohydramnios) and increase (polyhydramnios) in amniotic fluid volume. Both conditions are associated with a significant increase in perinatal morbidity and mortality, and limited treatment modalities are currently available. The mechanisms underlying the high rate of human fetal swallowing are regulated, in part, by tonic activity of central angiotensin II, glutamate N-methyl-D-aspartate receptors, and neuronal nitric oxide synthase. Fetal hypertonicity-mediated dipsogenesis is likely programmed in utero, as offspring of water-restricted ewes demonstrate a programmed syndrome of plasma hypertonicity, with significant hematologic and cardiovascular alterations. Similar to dipsogenic mechanisms, peripheral and central fetal orexic mechanisms also develop in utero, as demonstrated by increased fetal swallowing after both oral sucrose infusion and central injection of neuropeptide Y. The role of leptin in regulating fetal ingestive behavior is interesting because, contrary to actions in adults, leptin does not suppress fetal ingestive behavior. Teleologically, this may be of value during the newborn period, as unopposed appetite stimulatory mechanisms may facilitate rapid fetal and newborn weight gain. An adverse intrauterine environment, with altered fetal orexic factors during the critical developmental period of fetal life, may alter the normal setpoints of appetitive behavior and potentially lead to programming of adulthood hyperphagia and obesity. Further research is needed to delineate the mechanistic relationship between the intrauterine environment and the development of the setpoints of adult appetite and thirst.

Effects of central angiotensin II receptor antagonism on fetal swallowing and cardiovascular activity.

OBJECTIVE: Fetal plasma angiotensin II levels are 10 times the levels found in adults. Despite these high levels, central injection of angiotensin II may stimulate fetal swallowing and increase fetal arterial blood pressure. We postulated that the high rate of spontaneous fetal swallowing and normal fetal pressor regulation may be dependent, in part, on central angiotensin II. In view of the potential dipsogenic role of both type 1 and type 2 angiotensin II receptors, we examined the central effect of the nonselective angiotensin II receptor antagonist saralasin on fetal swallowing and cardiovascular responses. STUDY DESIGN: Six time-dated pregnant ewes and fetuses were chronically prepared with fetal vascular and intracerebroventricular catheters, electrocorticograms, and esophageal electromyogram electrodes and studied at 130 +/- 1 days' gestation. After an initial 2-hour baseline period (0 to 2 hours), saralasin (1 mL, 64 microg) was injected intracerebroventricularly (2 to 4 hours). After 4 hours the dose of saralasin was repeated together with angiotensin II (1 mL, 6.4 microg), and the fetuses were monitored for a final 2 hours. Four fetuses also underwent an identical control study (on an alternate day) in which saralasin was replaced with artificial cerebrospinal fluid. RESULTS: Blockade of central angiotensin II receptors by intracerebroventricular saralasin significantly reduced mean (+/- SEM) spontaneous fetal swallowing (1.3 +/- 0.1 to 0.4 +/- 0.1 swallows per minute; P <.001) but did not alter fetal mean blood pressure (50 +/- 5 versus 56 +/- 5 mm Hg). Intracerebroventricular angiotensin II, in the presence of saralasin, did not affect swallowing (0.6 +/- 0.1 swallows per minute) or fetal blood pressure. In the control study, intracerebroventricular artificial cerebrospinal fluid did not change fetal swallowing (0.9 +/- 0.1 versus 1.0 +/- 0.1 swallows per minute), whereas intracerebroventricular angiotensin II significantly increased swallowing activity (1.0 +/- 0.1 versus 2.0 +/- 0.1 swallows per minute; P <.001) and fetal blood pressure (51 +/- 2 to 59 +/- 3 mm Hg; P =.003). CONCLUSIONS: Tonic activity of central angiotensin II receptor stimulation contributed to the high rate of basal ovine fetal swallowing but not fetal basal blood pressure. Angiotensin II-mediated fetal dipsogenic and pressor responses are a result of specific angiotensin II receptor binding in central brain regions. These results indicate that fetal exposure to angiotensin II antagonists or angiotensin-converting enzyme inhibitors may have adverse effects on fetal and amniotic fluid homeostasis.

Nitric oxide modulates angiotensin II-induced drinking behavior in the near-term ovine fetus.

OBJECTIVE: Human and ovine fetuses demonstrate an enhanced rate of spontaneous and angiotensin II-stimulated swallowing. Angiotensin II and nitric oxide synthase have been localized to thirst centers in the brain. This study was performed to determine whether central nitric oxide contributes to the regulation of angiotensin II-induced fetal swallowing. STUDY DESIGN: Six pregnant ewes with near-term singleton fetuses were chronically prepared with fetal vascular and lateral ventricle catheters and electrocorticogram and esophageal electromyogram electrodes. After a 2-hour control period, fetuses were administered serial lateral ventricle injections (1 mL) of angiotensin II (3.2 microg; time, 2 hours) and N omega-nitro-L -arginine methyl ester (3 mg; time, 3 hours) and a repeat angiotensin II injection (3.2 microg; time, 5 hours). All fetuses received an additional control study of lateral ventricle injections of artificial cerebrospinal fluid on a previous day. RESULTS: Angiotensin II injection significantly increased mean +/- SEM fetal swallowing (0.9 +/- 0.1 to 2.7 +/- 0.4 swallows/min). N omega-nitro-L -arginine methyl ester significantly decreased fetal swallowing to below the basal rate (0.4 +/- 0.1 swallows/min), and swallowing did not increase with the second angiotensin II dose (in the presence of nitric oxide blockade). CONCLUSIONS: These results demonstrate that inhibition of central nitric oxide suppresses fetal swallowing behavior in response to central angiotensin II. We speculate that tonic nitric oxide facilitates angiotensin II swallowing stimulation by maintenance of glutamate activation of hypothalamic N -methyl-D -aspartate receptors.

Impact of FDA advisory on reported vacuum-assisted delivery and morbidity.

OBJECTIVE: In May 1998 the US Food and Drug Administration (FDA) issued a health advisory reporting neonatal injuries/deaths following vacuum delivery and encouraged voluntary reports of future adverse events. We compared FDA reports of vacuum delivery adverse events prior to and following the advisory. METHODS: The FDA database (MAUDE) was searched for vacuum deliveries using brand name, manufacturer name, and procedure "string searches." Cases were sorted by report date, source, and manufacturer. Neonatal morbidity was quantified as deaths and life-threatening or nonlife-threatening events. RESULTS: A total of 80 reported adverse cases were identified after duplicate cases were consolidated. Twenty-five were reported to the FDA prior to the 1998 advisory and 55 in the immediate 6-month period following the advisory. There was a 22-fold increase in reported events from five events/year prior to the advisory to an estimated 110 events/year following the advisory. The distribution of reporting sources changed significantly following the advisory with increased "manufacturer" (8-43%) and decreased "voluntary" reports (56-20%). All major brand names were represented. During the 6 months following the FDA advisory there were 10 neonatal deaths, 30 life-threatening events, 12 nonlife-threatening events, and three equipment-related reports. Infant deaths were due to intracranial or subgaleal hematomas. Injuries included skull fracture, scalp abrasions, and cephalohematomas. CONCLUSIONS: The FDA advisory was associated with a 22-fold increase in the rate of reported adverse events. This increase in reporting likely represents both enhanced awareness of complications as well as an increase in vacuum-related adverse neonatal sequelae. As vacuum delivery is associated with greater neonatal morbidity/ mortality than was previously recognized, the adage that the vacuum is "designed to come off before infant damage occurs" appears unsubstantiated. It is recommended that manufacturers quantify the suction and traction capabilities of present and new proposed vacuum cup designs.

Nitric oxide modulates spontaneous swallowing behavior in near-term ovine fetus.

Human and ovine fetuses demonstrate an enhanced rate of swallowing, an activity critical for amniotic fluid regulation. Fetal swallowing may be modulated by both systemic and central factors. Nitric oxide (NO) is a central neuromodulator that has been localized to brain regions regulating thirst and swallowing. We sought to determine if NO contributes to the regulation of spontaneous ovine fetal swallowing. Six time-dated pregnant ewes with singleton fetuses (129 +/- 1 day) were chronically prepared with fetal vascular and lateral ventricle catheters and electrocorticogram (ECoG) and esophageal electromyogram electrodes. After a 2-h control period, fetuses were given lateral ventricle injection of NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME) and monitored for 2 h. NO precursor L-arginine was then injected into the lateral ventricle, and fetuses were monitored for a final 2 h. All fetuses received an additional control study of fetal swallowing before and after lateral ventricle injection of artificial cerebrospinal fluid (aCSF). Data were analyzed with repeated-measures ANOVA and paired t-test (P < 0.05). Suppression of a central NO with central L-NAME significantly reduced mean (+/-SE) spontaneous fetal swallowing (1.2 +/- 0.1-0.6 +/- 0.1 swallows/min low-voltage ECoG; P < 0.01). Restoration of central NO by L-arginine significantly increased fetal swallowing to pre-L-NAME levels (1.2 +/- 0.1 swallows/min low voltage). There were no changes in fetal swallowing during the control study of aCSF. Fetal ECoG activity and blood pressure did not change during the study or control aCSF injection. We conclude that NO is an important neuromodulator of fetal swallowing activity. Central NO synthase activity may contribute to the heightened level of spontaneous fetal swallowing and thus amniotic fluid regulation.