Suppressed basal mitophagy drives cellular aging phenotypes that can be reversed by a p62-targeting small molecule.

Selective degradation of damaged mitochondria by autophagy (mitophagy) is proposed to play an important role in cellular homeostasis. However, the molecular mechanisms and the requirement of mitochondrial quality control by mitophagy for cellular physiology are poorly understood. Here, we demonstrated that primary human cells maintain highly active basal mitophagy initiated by mitochondrial superoxide signaling. Mitophagy was found to be mediated by PINK1/Parkin-dependent pathway involving p62 as a selective autophagy receptor (SAR). Importantly, this pathway was suppressed upon the induction of cellular senescence and in naturally aged cells, leading to a robust shutdown of mitophagy. Inhibition of mitophagy in proliferating cells was sufficient to trigger the senescence program, while reactivation of mitophagy was necessary for the anti-senescence effects of NAD precursors or rapamycin. Furthermore, reactivation of mitophagy by a p62-targeting small molecule rescued markers of cellular aging, which establishes mitochondrial quality control as a promising target for anti-aging interventions.

Prospective Validation of a Prediction Model for the Diagnosis of Acute Pancreatitis.

Importance: While most patients with acute pancreatitis (AP) fulfill diagnostic criteria with characteristic abdominal pain and serum lipase levels of at least 3 times the upper limit of normal (reference range) at presentation, early imaging is often used for confirmation. A prior prediction model and corresponding point-based score were developed using nonimaging parameters to diagnose AP in patients presenting to the emergency department (ED). Objective: To evaluate the performance of the prediction model to diagnose AP in a prospective patient cohort. Design, Setting, and Participants: This prospective diagnostic study included consecutive adult patients presenting to the ED between January 1, 2020, and March 9, 2021, at 2 large academic medical centers in the northeastern US with serum lipase levels at least 3 times the upper limit of normal. Patients transferred from outside institutions or with malignant disease and established intra-abdominal metastases, acute trauma, or altered mentation were excluded. Data were analyzed from October 15 to October 23, 2023. Exposures: Participants were assigned scores for initial serum lipase level, number of prior AP episodes, prior cholelithiasis, abdominal surgery within 2 months, presence of epigastric pain, pain of worsening severity, duration from pain onset to presentation, and pain level at ED presentation. Main Outcome and Measures: A final diagnosis of AP, established by expert review of hospitalization records. Results: Prospective scores in 349 participants (mean [SD] age, 53.0 [18.8] years; 184 women [52.7%]; 66 Black [18.9%]; 199 White [57.0%]) demonstrated an area under the receiver operating characteristics curve of 0.91. A score of at least 6 points achieved highest accuracy (F score, 82.0), corresponding to a sensitivity of 81.5%, specificity of 85.9%, positive predictive value of 82.6%, and negative predictive value of 85.1% for AP diagnosis. Early computed tomography or magnetic resonance imaging was performed more often in participants predicted to have AP (116 of 155 [74.8%] with a score ≥6 vs 111 of 194 [57.2%] with a score <6; P < .001). Early imaging revealed an alternative diagnosis in 8 of 116 participants (6.9%) with scores of at least 6 points, 1 of 93 (1.1%) with scores of at least 7 points, and 1 of 73 (1.4%) with scores of at least 8 points. Conclusions and Relevance: In this multicenter diagnostic study, the prediction model demonstrated excellent AP diagnostic accuracy. Its application may be used to avoid unnecessary confirmatory imaging.

Targeting the autophagy-NAD axis protects against cell death in Niemann-Pick type C1 disease models.

Impairment of autophagy leads to an accumulation of misfolded proteins and damaged organelles and has been implicated in plethora of human diseases. Loss of autophagy in actively respiring cells has also been shown to trigger metabolic collapse mediated by the depletion of nicotinamide adenine dinucleotide (NAD) pools, resulting in cell death. Here we found that the deficit in the autophagy-NAD axis underpins the loss of viability in cell models of a neurodegenerative lysosomal storage disorder, Niemann-Pick type C1 (NPC1) disease. Defective autophagic flux in NPC1 cells resulted in mitochondrial dysfunction due to impairment of mitophagy, leading to the depletion of both the reduced and oxidised forms of NAD as identified via metabolic profiling. Consequently, exhaustion of the NAD pools triggered mitochondrial depolarisation and apoptotic cell death. Our chemical screening identified two FDA-approved drugs, celecoxib and memantine, as autophagy activators which effectively restored autophagic flux, NAD levels, and cell viability of NPC1 cells. Of biomedical relevance, either pharmacological rescue of the autophagy deficiency or NAD precursor supplementation restored NAD levels and improved the viability of NPC1 patient fibroblasts and induced pluripotent stem cell (iPSC)-derived cortical neurons. Together, our findings identify the autophagy-NAD axis as a mechanism of cell death and a target for therapeutic interventions in NPC1 disease, with a potential relevance to other neurodegenerative disorders.

Olfactory misinformation provides refuge to palatable plants from mammalian browsing.

Mammalian herbivores browse palatable plants of ecological and economical value. Undesirable neighbours can reduce browsing to these plants by providing 'associational refuge', but they can also compete for resources. Here we recreated the informative odour emitted by undesirable plants. We then tested whether this odour could act as virtual neighbours, providing browsing refuge to palatable eucalyptus tree seedlings. We found that protection using this method was equivalent to protection provided by real plants. Palatable seedlings were 17-20 times more likely to be eaten by herbivores without virtual, or real, neighbours. Because many herbivores use plant odour to forage, virtual neighbours could provide a useful practical management approach to help protect valued plants.

A Shift Toward Early Oral Feeding in Acute Pancreatitis.

OBJECTIVES: The 2018 American Gastroenterological Association (AGA) guidelines strongly recommended early oral feeding as tolerated in patients with acute pancreatitis (AP). We compare early oral feeding rates in AP patients hospitalized in the periods before (2013-2016, Period A) and after (2019-2020, Period B) publication of the AGA guidelines, hypothesizing increased adherence in Period B. METHODS: We performed a retrospective cohort study of AP patients presenting to the emergency department during each period. Early oral feeding was defined as diet initiation within the first 48 hours of presentation. RESULTS: The cohort included 276 AP cases in period A and 104 in period B. A higher percentage of patients were offered early oral feeding during period B as compared to period A (70.2% vs. 43.5%). Similarly, more patients in period B were started on solid diet as compared to period A (34.6% vs. 20.3%). On multivariable regression analysis, the independent predictors of delayed oral feeding included early opioid analgesics use (OR 0.37), presence of pancreatic necrosis (OR 0.14), and organ failure (OR 0.33). CONCLUSIONS: More AP patients were initiated on early oral feeding in the period following the publication of the AGA guidelines. Opioid analgesics use, pancreatic necrosis, and organ failure were associated with delayed oral feeding.

Grow up, be persistent, and stay focused: keys for solving foraging problems by free-ranging possums.

Individuals within a species often vary in both their problem-solving approach and ability, affecting their capacity to access novel food resources. Testing problem-solving in free-ranging individuals is crucial for understanding the fundamental ecological implications of problem-solving capacity. To examine the factors affecting problem-solving in free-ranging animals, we presented three food-extraction tasks of increasing difficulty to urban common brushtail possums (Trichosurus vulpecula). We quantified two measures of problem-solving performance: trial outcome (success/failure) and time to solve and tested the influence of a range of potential drivers, including individual traits (personality, body weight, sex, and age), mechanistic behaviors that quantify problem-solving approach (work time, functional behavior time, behavioral diversity, and flexibility), and prior experience with the puzzles. We found that mechanistic behaviors were key drivers of performance. Individuals displaying greater persistence (higher work and functional behavior time) were more likely to solve a food-extraction task on their first attempt. Individuals also solved problems faster if they were more persistent and had lower behavioral flexibility. Personality indirectly affected time to solve one of the three problems by influencing time allocated to functional behaviors. Finally, adults solved the most difficult problem faster than juveniles. Overall, our study provides rare insight into the drivers underlying the problem-solving performance of wild animals. Such insight could be used to improve management strategies and conservation efforts, such as food or bait deployment, tailored to suit the innovative foraging abilities of target individuals in new and changing environments.

To eat, or not to eat: a phantom decoy affects information-gathering behavior by a free-ranging mammalian herbivore.

When foraging, making appropriate food choices is crucial to an animal's fitness. Classic foraging ecology theories assume animals choose food of greatest benefit based on their absolute value across multiple dimensions. Consequently, poorer options are considered irrelevant alternatives that should not influence decision-making among better options. But heuristic studies demonstrate that irrelevant alternatives (termed decoys) can influence the decisions of some animals, indicating they use a relative rather than absolute evaluation system. Our aim was to test whether a decoy influenced the decision-making process-that is, information-gathering and food choice-of a free-ranging mammalian herbivore. We tested swamp wallabies, Wallabia bicolor, comparing their behavior toward, and choice of, two available food options over time in the absence or presence of the decoy. We used a phantom decoy-unavailable option-and ran two trials in different locations and seasons. Binary preferences (decoy absent) for the two available food options differed between trials. Irrespective of this difference, across both trials the presence of the decoy resulted in animals more likely to overtly investigate available food options. But, the decoy only shifted food choice, weakly, in one trial. Our results indicate that the decoy influenced the information-gathering behavior during decision-making, providing the first evidence that decoys can affect decision-making process of free-ranging mammalian herbivores in an ecologically realistic context. It is premature to say these findings confirm the use of relative evaluation systems. Whether the foraging outcome is more strongly affected by other decoys, food dimensions, or ecological contexts, is yet to be determined.

Investigating the function and design of molecular materials through terahertz vibrational spectroscopy.

Terahertz spectroscopy has proved to be an essential tool for the study of condensed phase materials. Terahertz spectroscopy probes the low-frequency vibrational dynamics of atoms and molecules, usually in the condensed phase. These nuclear dynamics, which typically involve displacements of entire molecules, have been linked to bulk phenomena ranging from phase transformations to semiconducting efficiency. The terahertz region of the electromagnetic spectrum has historically been referred to as the 'terahertz gap', but this is a misnomer, as there exist a multitude of methods for accessing terahertz frequencies, and now there are cost-effective instruments that have made terahertz studies much more user-friendly. This Review highlights some of the most exciting applications of terahertz vibrational spectroscopy so far, and provides an in-depth overview of the methods of this technique and its utility to the study of the chemical sciences.

The ethics of intervening in animal behaviour for conservation.

Conservation behaviour is a growing field that applies insights from the study of animal behaviour to address challenges in wildlife conservation and management. Conservation behaviour interventions often aim to manage specific behaviours of a species to solve conservation challenges. The field is often viewed as offering approaches that are less intrusive or harmful to animals than, for example, managing the impact of a problematic species by reducing its population size (frequently through lethal control). However, intervening in animal behaviour, even for conservation purposes, may still raise important ethical considerations. We discuss these issues and develop a framework and a decision support tool, to aid managers and researchers in evaluating the ethical considerations of conservation behaviour interventions against other options.

Hospital Frailty Risk Score (HFRS) Predicts Adverse Outcomes Among Hospitalized Patients with Chronic Pancreatitis.

INTRODUCTION: The prevalence of frailty among patients with chronic pancreatitis (CP) and its impact on clinical outcomes is unclear. We report the impact of frailty on mortality, readmission rates, and healthcare utilization among patients with chronic pancreatitis in the United States. METHODS: We extracted data on patients hospitalized with a primary or secondary diagnosis of CP from the Nationwide Readmissions Database 2019. We applied a previously validated hospital frailty risk scoring system to classify CP patients into frail and non-frail on index hospitalization and compared the characteristics of frail and non-frail patients. We studied the impact of frailty on mortality, readmission, and healthcare utilization. RESULTS: Of 56,072 patients with CP, 40.78% of patients were classified as frail. Frail patients experienced a higher rate of unplanned and preventable hospitalizations. Almost two-thirds of frail patients were younger than 65, and one-third had no or only single comorbidity. On multivariate analysis, frailty was independently associated with two times higher mortality risk (adjusted hazard ratio [aHR], 2.05; 95% CI 1.7-2.5). Frailty was also associated with a higher risk of all-cause readmission with an aHR of 1.07; (95% CI 1.03-1.1). Frail patients experienced a longer length of stay, higher hospitalization costs, and hospitalization charges. Infectious causes were the most common cause of readmission among frail patients compared to acute pancreatitis among non-frail patients. CONCLUSIONS: Frailty is independently associated with higher mortality, readmission rates, and healthcare utilization among patients with chronic pancreatitis in the US.

Repurposing drugs with specific activity against L-form bacteria.

Cell wall deficient "L- form" bacteria are of growing medical interest as a possible source of recurrent or persistent infection, largely because of their complete resistance to cell wall active antibiotics such as ß-lactams. Antibiotics that specifically kill L-forms would be of potential interest as therapeutics, but also as reagents with which to explore the role of L-forms in models of recurrent infection. To look for specific anti-L-form antibiotics, we screened a library of several hundred FDA-approved drugs and identified compounds highly selective for L-form killing. Among the compounds identified were representatives of two different classes of calcium channel blockers: dihydropyridines, e.g., manidipine; and diphenylmethylpiperazine, e.g., flunarizine. Mode of action studies suggested that both classes of compound work by decreasing membrane fluidity. This leads to a previously recognized phenotype of L-forms in which the cells can continue to enlarge but fail to divide. We identified a considerable degree of variation in the activity of different representatives of the two classes of compounds, suggesting that it may be possible to modify them for use as drugs for L-form-dependent infections.

An invasive human commensal and a native marsupial maintain tick populations at the urban fringe.

Ticks (Acari: Ixodidae) are major disease vectors globally making it increasingly important to understand how altered vertebrate communities in urban areas shape tick population dynamics. In urban landscapes of Australia, little is known about which native and introduced small mammals maintain tick populations preventing host-targeted tick management and leading to human-wildlife conflict. Here, we determined (1) larval, nymphal, and adult tick burdens on host species and potential drivers, (2) the number of ticks supported by the different host populations, and (3) the proportion of medically significant tick species feeding on the different host species in Northern Sydney. We counted 3551 ticks on 241 mammals at 15 sites and found that long-nosed bandicoots (Perameles nasuta) hosted more ticks of all life stages than other small mammals but introduced black rats (Rattus rattus) were more abundant at most sites (33%-100%) and therefore important in supporting larval and nymphal ticks in our study areas. Black rats and bandicoots hosted a greater proportion of medically significant tick species including Ixodes holocyclus than other hosts. Our results show that an introduced human commensal contributes to maintaining urban tick populations and suggests ticks could be managed by controlling rat populations on urban fringes.

Acute pancreatitis precedes chronic pancreatitis in the majority of patients: Results from the NAPS2 consortium.

INTRODUCTION: The mechanistic definition of chronic pancreatitis (CP) identifies acute pancreatitis (AP) as a precursor stage. We hypothesized that clinical AP frequently precedes the diagnosis of CP and is associated with patient- and disease-related factors. We describe the prevalence, temporal relationship and associations of AP in a well-defined North American cohort. METHODS: We evaluated data from 883 patients with CP prospectively enrolled in the North American Pancreatitis Studies across 27 US centers between 2000 and 2014. We determined how often patients had one or more episodes of AP and its occurrence in relationship to the diagnosis of CP. We used multivariable logistic regression to determine associations for prior AP. RESULTS: There were 624/883 (70.7%) patients with prior AP, among whom 161 (25.8%) had AP within 2 years, 115 (18.4%) within 3-5 years, and 348 (55.8%) >5 years prior to CP diagnosis. Among 504 AP patients with available information, 436 (86.5%) had >1 episode. On multivariable analyses, factors associated with increased odds of having prior AP were a younger age at CP diagnosis, white race, abdominal pain, pseudocyst(s) and pancreatic duct dilatation/stricture, while factors associated with a lower odds of having prior AP were exocrine insufficiency and pancreatic atrophy. When compared with patients with 1 episode, those with >1 AP episode were diagnosed with CP an average of 5 years earlier. CONCLUSIONS: Nearly three-quarters of patients were diagnosed with AP prior to CP diagnosis. Identifying which AP patients are at-risk for future progression to CP may provide opportunities for primary and secondary prevention.

Side-chain torsional dynamics strongly influence charge transport in organic semiconductors.

The role of low-frequency (terahertz) vibrational motions on charge carrier dynamics in organic semiconductors (OSCs) is becoming well-known, and efforts are underway to rationally design new materials to mitigate these detrimental effects. However, most efforts have focused on stabilizing the fused-ring semiconducting 'core', often by functionalizing with various side-groups, yet questions regarding the role of such modifications on electron-phonon couplings are still outstanding. In this work, the influence of thiophene rings σ-bonded directly to the π-conjugated cores is explored. The manner in which these groups alter low-frequency vibrational, and resulting electronic, dynamics is quantified using a theoretical approach employing fully-periodic density functional theory (DFT) simulations. Ultimately, these results showcase how the equilibrium geometry and corresponding electronic structure are directly related to detrimental electron-phonon coupling, which have important implications for the design of improved organic optoelectronic materials.

Mirubactin C rescues the lethal effect of cell wall biosynthesis mutations in Bacillus subtilis.

Growth of most rod-shaped bacteria is accompanied by the insertion of new peptidoglycan into the cylindrical cell wall. This insertion, which helps maintain and determine the shape of the cell, is guided by a protein machine called the rod complex or elongasome. Although most of the proteins in this complex are essential under normal growth conditions, cell viability can be rescued, for reasons that are not understood, by the presence of a high (mM) Mg2+ concentration. We screened for natural product compounds that could rescue the growth of mutants affected in rod-complex function. By screening > 2,000 extracts from a diverse collection of actinobacteria, we identified a compound, mirubactin C, related to the known iron siderophore mirubactin A, which rescued growth in the low micromolar range, and this activity was confirmed using synthetic mirubactin C. The compound also displayed toxicity at higher concentrations, and this effect appears related to iron homeostasis. However, several lines of evidence suggest that the mirubactin C rescuing activity is not due simply to iron sequestration. The results support an emerging view that the functions of bacterial siderophores extend well beyond simply iron binding and uptake.

A new conceptual and quantitative approach to exploring and defining potential open-access olfactory information.

All organisms emit odour, providing 'open-access' olfactory information for any receiver with the right sensory apparatus. Characterizing open-access information emitted by groups of organisms, such as plant species, provides the means to answer significant questions about ecological interactions and their evolution. We present a new conceptual framework defining information reliability and a practical method to characterize and recover information from amongst olfactory noise. We quantified odour emissions from two tree species, one focal group and one outgroup, to demonstrate our approach using two new R statistical functions. We explore the consequences of relaxing or tightening criteria defining information and, from thousands of odour combinations, we identify and quantify those few likely to be informative. Our method uses core general principles characterizing information while incorporating knowledge of how receivers detect and discriminate odours. We can now map information in consistency-precision reliability space, explore the concept of information, and test information-noise boundaries, and between cues and signals.

The Olfactory Landscape Concept: A Key Source of Past, Present, and Future Information Driving Animal Movement and Decision-making.

Odor is everywhere, emitted across the landscape from predators, prey, decaying carcasses, conspecifics, vegetation, surface water, and smoke. Many animals exploit odor to find food, avoid threats, and attract or judge potential mates. Here, we focus on odor in terrestrial ecosystems to introduce the concept of an olfactory landscape: real-time dynamic olfactory contours reflecting the patchy distribution of resources and risks, providing a key source of information used by many animals in their movement and decision-making. Incorporating the olfactory landscape into current frameworks of movement ecology and animal behavior will provide a mechanistic link to help answer significant questions about where, why, and when many animals move, and how they do so efficiently in both space and time. By understanding how animals use the olfactory landscape to make crucial decisions affecting their fitness, we can then manipulate the landscape to modify ecological interactions and, ultimately, ecosystem consequences of these interactions.

Metatranscriptomic profiling reveals diverse tick-borne bacteria, protozoans and viruses in ticks and wildlife from Australia.

Tick-borne zoonoses are emerging globally due to changes in climate and land use. While the zoonotic threats associated with ticks are well studied elsewhere, in Australia, the diversity of potentially zoonotic agents carried by ticks and their significance to human and animal health is not sufficiently understood. To this end, we used untargeted metatranscriptomics to audit the prokaryotic, eukaryotic and viral biomes of questing ticks and wildlife blood samples from two urban and rural sites in New South Wales, Australia. Ixodes holocyclus and Haemaphysalis bancrofti were the main tick species collected, and blood samples from Rattus rattus, Rattus fuscipes, Perameles nasuta and Trichosurus vulpecula were also collected and screened for tick-borne microorganisms using metatranscriptomics followed by conventional targeted PCR to identify important microbial taxa to the species level. Our analyses identified 32 unique tick-borne taxa, including 10 novel putative species. Overall, a wide range of tick-borne microorganisms were found in questing ticks including haemoprotozoa such as Babesia, Theileria, Hepatozoon and Trypanosoma spp., bacteria such as Borrelia, Rickettsia, Ehrlichia, Neoehrlichia and Anaplasma spp., and numerous viral taxa including Reoviridiae (including two coltiviruses) and a novel Flaviviridae-like jingmenvirus. Of note, a novel hard tick-borne relapsing fever Borrelia sp. was identified in questing H. bancrofti ticks which is closely related to, but distinct from, cervid-associated Borrelia spp. found throughout Asia. Notably, all tick-borne microorganisms were phylogenetically unique compared to their relatives found outside Australia, and no foreign tick-borne human pathogens such as Borrelia burgdorferi s.l. or Babesia microti were found. This work adds to the growing literature demonstrating that Australian ticks harbour a unique and endemic microbial fauna, including potentially zoonotic agents which should be further studied to determine their relative risk to human and animal health.

Characteristics of 30-Day All-Cause Hospital Readmissions Among Patients with Acute Pancreatitis and Substance Use.

BACKGROUND/OBJECTIVES: Previous studies on healthcare resource utilization and 30-day readmission risks among patients with acute pancreatitis (AP) have focused upon opioid and alcohol use. The data on other substance types are lacking. In this study we aim to estimate the 30-day readmission rates, predictors of readmission, impact of readmission on patient outcomes and resulting economic burden among patients with AP and substance use in the USA. METHODS: This was a retrospective cohort study, based upon data from 2017 National Readmission Database of adult patients with AP and substance use (alcohol in combination, opioid, cannabis, cocaine, sedatives, other stimulants, other hallucinogens, other psychoactive, inhalant and miscellaneous). We estimated the 30-day readmission rates and predictors of 30-day readmission. RESULTS: Among 25,795 eligible patients, most were male, belonged to the lower income quartile, resided in the urban facility and had a Charlson comorbidity score of 0 or 1. The use of a combination of substances was the most common in 17,265 (66.9%) patients followed by only opioids in 4691 (18.2%) patients and only marijuana in 3839 (14.9%) patients. A total of 14.6% patients were readmitted within 30 days after discharge for non-elective causes with the highest risk of readmission within the 1st week after discharge with 5.2% readmissions. Among top ten causes of readmission, most of the principal diagnosis were related to AP in 53.1%. Compared to index admission, readmitted patients had significantly higher rates of acute cardiac failure, shock, and higher in-hospital mortality rate. Overall, readmission attributed to an additional 17,801 days of hospitalization resulting in a total of $150 million in hospitalization charges and $36 million in hospitalization costs in 2017. On multivariate analysis, chronic pancreatitis, self-discharge against medical advice, treatment at the highest volume centers, higher Charlson comorbidity index, increasing length of stay and severe disease were associated with higher odds of readmission while female gender and private insurance were associated with lower odds. CONCLUSION: Readmission was associated with higher morbidity and in-hospital mortality among patients with AP and substance use and resulted in a significant monetary burden on the US healthcare system. Several factors identified in this study may be useful for categorizing patients at higher risk of readmission warranting special attention during discharge planning.

Provider Differences in Monitoring and Management of Exocrine Pancreatic Insufficiency in Chronic Pancreatitis.

OBJECTIVES: Chronic pancreatitis (CP) is a common cause of exocrine pancreatic insufficiency (EPI). Regular monitoring and treatment are recommended to decrease morbidity. This study evaluates whether provider type impacts EPI monitoring and management in CP. METHODS: Fecal elastase 1 (FE-1) testing and pancreatic enzyme replacement therapy (PERT) utilization were retrospectively compared between primary care providers (PCPs), gastroenterologists and pancreas specialists using pairwise comparisons. Multivariate analysis was conducted to study the association between adequate PERT and age, sex, race, insurance status, provider type, and etiology. RESULTS: Among 256 patients, FE-1 was measured in 115 (44.9%) and of 143 (55.9%) patients who received PERT, 100 (69.9%) received adequate dosage. Fecal elastase 1 testing was performed in 7/57 (12.3%) by PCP, 11/38 (28.9%) by gastroenterologists, and 97/161 (60.2%) by pancreas specialists (P < 0.0001). Adequate PERT was prescribed in 7/24 (29.2%) patients by PCPs, 11/20 (55.0%) by gastroenterologists, and 82/99 (82.8%) by pancreas specialists (P < 0.0001). On multivariate analysis, pancreas specialists were significantly more likely to prescribe adequate PERT compared with PCP (odds ratio, 11.3; 95% confidence interval, 3.3-38.2; P < 0.001). CONCLUSIONS: Many patients with CP receive inadequate surveillance and EPI treatment. Pancreas specialists are more likely to surveil and treat EPI adequately.