Gastric vagal afferent signaling to the basolateral amygdala mediates anxiety-like behaviors in experimental colitis mice.

Inflammatory bowel disease (IBD) is a relapsing-remitting disorder characterized by chronic inflammation of the gastrointestinal (GI) tract. Anxiety symptoms are commonly observed in patients with IBD, but the mechanistic link between IBD and anxiety remains elusive. Here, we sought to characterize gut-to-brain signaling and brain circuitry responsible for the pathological expression of anxiety-like behaviors in male dextran sulfate sodium-induced (DSS-induced) experimental colitis mice. We found that DSS-treated mice displayed increased anxiety-like behaviors, which were prevented by bilateral GI vagal afferent ablation. The locus coeruleus (LC) is a relay center connecting the nucleus tractus solitarius to the basolateral amygdala (BLA) in controlling anxiety-like behaviors. Chemogenetic silencing of noradrenergic LC projections to the BLA reduced anxiety-like behaviors in DSS-treated mice. This work expands our understanding of the neural mechanisms by which IBD leads to comorbid anxiety and emphasizes a critical role of gastric vagal afferent signaling in gut-to-brain regulation of emotional states.

A dorsal CA2 to ventral CA1 circuit contributes to oxytocinergic modulation of long-term social recognition memory.

BACKGROUND: Social recognition memory (SRM) is the ability to distinguish familiar from novel conspecifics and is crucial for survival and reproductive success across social species. We previously reported that oxytocin (OXT) receptor (OXTR) signaling in the CA2/CA3a of dorsal hippocampus is essential to promote the persistence of long-term SRM, yet how the endogenous OXT system influences CA2 outputs to regulate long-term SRM formation remains unclear. METHODS: To achieve a selective deletion of CA2 OXTRs, we crossed Amigo2-Cre mice with Oxtr-floxed mice to generate CA2-specific Oxtr conditional knockout (Oxtr-/-) mice. A three-chamber paradigm test was used for studying SRM in mice. Chemogenetic and optogenetic targeting strategies were employed to manipulate neuronal activity. RESULTS: We show that selective ablation of Oxtr in the CA2 suffices to impair the persistence of long-term SRM but has no effect on sociability and social novelty preference in the three-chamber paradigm test. We find that cell-type specific activation of OXT neurons within the hypothalamic paraventricular nucleus enhances long-term SRM and this enhancement is blocked by local application of OXTR antagonist L-368,899 into dorsal hippocampal CA2 (dCA2) region. In addition, chemogenetic neuronal silencing in dCA2 demonstrated that neuronal activity is essential for forming long-term SRM. Moreover, chemogenetic terminal-specific inactivation reveals a crucial role for dCA2 outputs to ventral CA1 (vCA1), but not dorsal lateral septum, in long-term SRM. Finally, targeted activation of the dCA2-to-vCA1 circuit effectively ameliorates long-term SRM deficit observed in Oxtr-/- mice. CONCLUSIONS: These findings highlight the importance of hippocampal CA2 OXTR signaling in governing the persistence of long-term SRM and identify a hippocampal circuit linking dCA2 to vCA1 necessary for controlling long-term SRM formation.

Distinct Contribution of Granular and Agranular Subdivisions of the Retrosplenial Cortex to Remote Contextual Fear Memory Retrieval.

The retrieval of recent and remote memories are thought to rely on distinct brain circuits and mechanisms. The retrosplenial cortex (RSC) is robustly activated during the retrieval of remotely acquired contextual fear memories (CFMs), but the contribution of particular subdivisions [granular (RSG) vs agranular retrosplenial area (RSA)] and the circuit mechanisms through which they interact to retrieve remote memories remain unexplored. In this study, using both anterograde and retrograde viral tracing approaches, we identified excitatory projections from layer 5 pyramidal neurons of the RSG to the CA1 stratum radiatum/lacunosum-moleculare of the dorsal hippocampus and the superficial layers of the RSA in male mice. We found that chemogenetic or optogenetic inhibition of the RSG-to-CA1, but not the RSG-to-RSA, pathway selectively impairs the retrieval of remote CFMs. Collectively, our results uncover a specific role for the RSG in remote CFM recall and provide circuit evidence that RSG-mediated remote CFM retrieval relies on direct RSG-to-CA1 connectivity. The present study provides a better understanding of brain circuit mechanisms underlying the retrieval of remote CFMs and may help guide the development of therapeutic strategies to attenuate remote traumatic memories that lead to mental health issues such as post-traumatic stress disorder.SIGNIFICANCE STATEMENT The RSC is implicated in contextual information processing and remote recall. However, how different subdivisions of the RSC and circuit mechanisms through which they interact to underlie remote memory recall remain unexplored. This study shows that granular subdivision of the RSC and its input to hippocampal area CA1 contributes to the retrieval of remote contextual fear memories. Our results support the hypothesis that the RSC and hippocampus require each other to preserve fear memories and may provide a novel therapeutic avenue to attenuate remote traumatic memories in patients with post-traumatic stress disorder.

Exposure to Novelty Promotes Long-Term Contextual Fear Memory Formation in Juvenile Mice: Evidence for a Behavioral Tagging.

Episodic memories acquired early in life are fragile and rapidly forgotten in both humans and nonhuman animals. However, early life experiences have been documented to profoundly affect brain function and physiology throughout life, suggesting that in certain circumstances, the developing brain is capable of producing long-term memory (LTM). In this study, we asked whether exposure to a novel environment, a process named "behavioral tagging," may promote the persistence of weak memories in male juvenile mice. Using a contextual fear conditioning (CFC) paradigm, we found that a weak training protocol, which typically induces a transient form of memory, results in LTM when paired with an exploration to a novel but not a familiar environment that occurs close in time to the training session. The promoting effect of the novel context exploration (NCE) on CFC-LTM formation is dependent on the activation of dopamine D1/D5 receptors and requires novel protein synthesis in the dorsal hippocampus. Moreover, NCE increases the size of overlapping CA1 neuronal ensembles engaged by CFC and NCE. These results provide direct support for the existence of a behavioral tagging process, in which exposure to novelty provides newly synthesized proteins to stabilize the contextual fear memory trace in juvenile mice.

Probiotic treatment restores normal developmental trajectories of fear memory retention in maternally separated infant rats.

Early life stress (ELS) can affect brain development and increase lifetime prevalence of psychiatric illnesses. However, the effective therapeutic interventions to ameliorate the deleterious effects of ELS have not yet been well established. Here, we confirmed that maternal separation (MS) for 3 h daily between postnatal days 2-14, a frequently used experimental model of ELS, resulted in early expression of adult-like fear memory retention in male infant rats. Administration of a probiotic formulation, Lacidofil® (95% Lactobacillus rhamnosus R0011 and 5% Lactobacillus helveticus R0052), during the separation period, prevented the precocious transition to adult-like fear memory retention in MS infant rats. Consonant with this effect, probiotic treatment also ameliorated the MS-induced increases in anxiety-like behavior as measured by the elevated plus maze and the light-dark box tests. In addition, probiotic treatment reduced MS-induced increases in neuronal activation and brain-derived neurotrophic factor protein levels in the basolateral nucleus of amygdala (BLA) after auditory fear conditioning. Furthermore, we found that probiotic treatment significantly rescued the heightened hypothalamic-pituitary-adrenal (HPA) axis response to restraint stress in MS infant rats. Taken together, these findings suggest that probiotics can restore normal developmental trajectories of fear memory retention in MS infant rats, at least in part by normalizing HPA axis abnormalities, and that the BLA serves as a critical node to mediate these interventions. Thus, we offer a potential therapeutic intervention to protect children against the harmful effects of ELS.

Perineuronal Nets Restrict the Induction of Long-Term Depression in the Mouse Hippocampal CA1 Region.

Long-term depression (LTD) of synaptic efficacy is widely regarded as a cellular basis of learning and memory. The magnitude of hippocampal CA1 LTD induced by low-frequency stimulation (LFS) declines with age, but the mechanisms involved remain poorly understood. Perineuronal nets (PNNs) are specialized extracellular matrix structures that function in dampening synaptic plasticity during postnatal development, suggesting that PNN formation may restrict LTD induction in the adult hippocampus. Here, we show that PNNs tightly enwrap a subpopulation of parvalbumin (PV) interneurons in the hippocampal CA1 region and enzymatic removal of PNNs with the chondroitinase ABC alters the excitatory/inhibitory synaptic balance toward more excitation and restores the ability of LFS to induce an N-methyl-D-aspartate receptor-dependent LTD at Schaffer collateral-CA1 synapses in slices from male adult mice. Early interference with depolarizing GABA with Na+-K+-2Cl- cotransporter inhibitor bumetanide impairs the maturation of PNNs and enhances LTD induction. These results provide novel insights into a previously unrecognized role for PNNs around PV interneurons in restricting long-term synaptic plasticity at excitatory synapses on hippocampal CA1 neurons in adulthood.

Infantile Amnesia Is Related to Developmental Immaturity of the Maintenance Mechanisms for Long-Term Potentiation.

Infantile amnesia (IA) refers to the inability of adults to recall episodic memories from infancy or early childhood. While several hypotheses have been proposed to explain the occurrence of IA, the neurobiological and molecular bases for this accelerated forgetting phenomenon remain elusive. Using hippocampus-dependent object-location memory and contextual fear conditioning tasks, we confirmed that infant mice trained at postnatal day 20 (P20) displayed deficits in long-term memory retention compared to adult (P60) mice. The percentage of CA1 pyramidal neurons expressing phosphorylated cAMP-responsive element-binding protein after fear conditioning was significantly lower in P20 than P60 mice. P20 mice exhibited attenuated basal excitatory synaptic transmission and early-phase long-term potentiation (E-LTP) at Schaffer collateral-CA1 synapses compared to P60 mice, but conversely, P20 mice have a greater susceptibility to induce time-dependent reversal of LTP by low-frequency afferent stimulation than P60 mice. The protein levels of GluN2B subunit of N-methyl-D-aspartate receptors (NMDARs), protein kinase Mζ (PKMζ), and protein phosphatase 2B (PP2B) in hippocampal CA1 region were significantly higher in P20 than P60 mice. We also found that the levels of calcium/calmodulin-dependent protein kinase II α autophosphorylation at Thr286, GluA1 phosphorylation at Ser831, and PKMζ protein biosynthesis occurred during the ensuing maintenance of E-LTP were significantly lower in P20 than P60 mice. Pharmacological blockade of GluN2B-containing NMDARs or PP2B effectively restored deficits of E-LTP and long-term memory retention observed in P20 mice. Altogether, these findings suggest that developmental immaturity of the maintenance mechanisms for E-LTP is linked to the occurrence of IA.

Effectiveness of the Multidisciplinary Team Model in Treating Colorectal Cancer.

The multidisciplinary team (MDT) model involves multiple medical professionals providing integrated medical care. Colorectal cancer (CRC) has the highest prevalence of cancer in Taiwan. This study examines and evaluates the survival rates of CRC patients treated under the MDT model. In this retrospective and prospective study, 651 CRC patients were recruited. They were divided into 2 groups: the MDT group and the traditional care (TC) group. The MDT group comprised 326 patients who received care from a MDT. The TC group comprised 325 patients who received care from a TC. The outcome variables were survival rates, follow-up appointment compliance, and 14-day readmission rates. Adopting the MDT model for CRC care increased patient follow-up appointment compliance rates at the first week, first month, and third month (p = .032, p = .007, p = .001, respectively). The model also effectively reduced patients' 14-day readmission rates. The results indicated that the survival rates of the MDT care were superior to those of TC. The adoption of the MDT model to treat CRC effectively enhanced clinical treatment adherence, increased survival rates, and reduced the 14-day readmission rate.

Conditional Deletion of Hippocampal CA2/CA3a Oxytocin Receptors Impairs the Persistence of Long-Term Social Recognition Memory in Mice.

Oxytocin (OXT) receptors (OXTRs) are prominently expressed in hippocampal CA2 and CA3 pyramidal neurons, but little is known about its physiological function. As the functional necessity of hippocampal CA2 for social memory processing, we tested whether CA2 OXTRs may contribute to long-term social recognition memory (SRM) formation. Here, we found that conditional deletion of Oxtr from forebrain (Oxtr-/-) or CA2/CA3a-restricted excitatory neurons in adult male mice impaired the persistence of long-term SRM but had no effect on sociability and preference for social novelty. Conditional deletion of CA2/CA3a Oxtr showed no changes in anxiety-like behavior assessed using the open-field, elevated plus maze and novelty-suppressed feeding tests. Application of a highly selective OXTR agonist [Thr4,Gly7]-OXT to hippocampal slices resulted in an acute and lasting potentiation of excitatory synaptic responses in CA2 pyramidal neurons that relied on N-methyl-d-aspartate receptor activation and calcium/calmodulin-dependent protein kinase II activity. In addition, Oxtr-/- mice displayed a defect in the induction of long-term potentiation, but not long-term depression, at the synapses between the entorhinal cortex and CA2 pyramidal neurons. Furthermore, Oxtr deletion led to a reduced complexity of basal dendritic arbors of CA2 pyramidal neurons, but caused no alteration in the density of apical dendritic spines. Considering that the methodologies we have used to delete Oxtr do not rule out targeting the neighboring CA3a region, these findings suggest that OXTR signaling in the CA2/CA3a is crucial for the persistence of long-term SRM.SIGNIFICANCE STATEMENT Oxytocin receptors (OXTRs) are abundantly expressed in hippocampal CA2 and CA3 regions, but there are little known about their physiological function. Taking advantage of the conditional Oxtr knock-out mice, the present study highlights the importance of OXTR signaling in the induction of long-term potentiation at the synapses between the entorhinal cortex and CA2 pyramidal neurons and the persistence of long-term social recognition memory. Thus, OXTRs in the CA2/CA3a may provide a new target for therapeutic approaches to the treatment of social cognition deficits, which are often observed in patients with neuropsychiatric disorders.

Epidemiologic characteristics and outcomes of major trauma patients requiring prolonged mechanical ventilation.

The epidemiologic characteristics and outcomes of severe trauma patients requiring prolonged mechanical ventilation (PMV) remain unclear. This retrospective study aims to investigate the outcomes of PMV in this specific group. All patients with major trauma admitted to the respiratory care center (RCC) requiring PMV (duration ≥21 days between January 2014 and December 2016) were enrolled. A total of 36343 trauma patients visited our emergency department for management, and 1388 (3.82%) were admitted to the intensive care unit (ICU) after initial resuscitation. After ICU management, 93 major trauma patients required PMV, and were then transferred to the RCC. Their mean age of these 93 patients was 68.6 ±â€Š18.3 years and 65 patients (70.0%) were older than 65 years. Head/neck trauma (n = 78, 83.9%) were the most common injury, followed by thoracic trauma (n = 30, 32.2%), and extremity trauma (n = 29, 31.2%). Their median injury severity score was 25 (interquartile range [IQR] 16-27). The median length of hospital stay was 50 days (IQR, 39-62). Six patients died of ventilator-associated pneumonia for an in-hospital morality rate of 6.5%. In addition, 11 PMV patients became mechanical ventilator-dependent and were transferred to the respiratory care ward for further long-term care. In conclusion, <0.3% of trauma patients required PMV, and their in-hospital mortality rate was only 6.5%. Ventilator-associated pneumonia was the main cause of death and nosocomial infections were common in patients with long-term mechanical ventilator dependence.

Alleviating Bone Cancer-induced Mechanical Hypersensitivity by Inhibiting Neuronal Activity in the Anterior Cingulate Cortex.

BACKGROUND: The anterior cingulate cortex (ACC) is a brain region that has been critically implicated in the processing of pain perception and modulation. While much evidence has pointed to an increased activity of the ACC under chronic pain states, less is known about whether pain can be alleviated by inhibiting ACC neuronal activity. METHODS: The authors used pharmacologic, chemogenetic, and optogenetic approaches in concert with viral tracing technique to address this issue in a mouse model of bone cancer-induced mechanical hypersensitivity by intratibia implantation of osteolytic fibrosarcoma cells. RESULTS: Bilateral intra-ACC microinjections of γ-aminobutyric acid receptor type A receptor agonist muscimol decreased mechanical hypersensitivity in tumor-bearing mice (n =10). Using adenoviral-mediated expression of engineered Gi/o-coupled human M4 (hM4Di) receptors, we observed that activation of Gi/o-coupled human M4 receptors with clozapine-N-oxide reduced ACC neuronal activity and mechanical hypersensitivity in tumor-bearing mice (n = 11). In addition, unilateral optogenetic silencing of ACC excitatory neurons with halorhodopsin significantly decreased mechanical hypersensitivity in tumor-bearing mice (n = 4 to 9), and conversely, optogenetic activation of these neurons with channelrhodopsin-2 was sufficient to provoke mechanical hypersensitivity in sham-operated mice (n = 5 to 9). Furthermore, we found that excitatory neurons in the ACC send direct descending projections to the contralateral dorsal horn of the lumbar spinal cord via the dorsal corticospinal tract. CONCLUSIONS: The findings of this study indicate that enhanced neuronal activity in the ACC contributes to maintain bone cancer-induced mechanical hypersensitivity and suggest that the ACC may serve as a potential therapeutic target for treating bone cancer pain.

Early life stress dampens stress responsiveness in adolescence: Evaluation of neuroendocrine reactivity and coping behavior.

Stressful experiences during early life (ELS) can affect brain development, thereby exerting a profound and long-lasting influence on mental development and psychological health. The stress inoculation hypothesis presupposes that individuals who have early experienced an attenuated form of stressors may gain immunity to its more virulent forms later in life. Increasing evidence demonstrates that ELS may promote the development of subsequent stress resistance, but the mechanisms underlying such adaptive changes are not fully understood. The present study evaluated the impact of fragmented dam-pup interactions by limiting the bedding and nesting material in the cage during postnatal days 2-9, a naturalistic animal model of chronic ELS, on the physiological and behavioral responses to different stressors in adolescent mice and characterized the possible underlying mechanisms. We found that ELS mice showed less social interaction deficits after chronic social defeat stress and acute restraint-tailshock stress-induced impaired long-term potentiation (LTP) and enhanced long-term depression (LTD) in hippocampal CA1 region compared with control mice. The effects of ELS on LTP and LTD were rescued by adrenalectomy. While ELS did not cause alterations in basal emotional behaviors, it significantly enhanced stress coping behaviors in both the tail suspension and the forced swimming tests. ELS mice exhibited a significant decrease in corticosterone response and trafficking of glucocorticoid receptors to the nucleus in response to acute restraint stress. Altogether, our data support the hypothesis that stress inoculation training, via early exposure to manageable stress, may enhance resistance to other unrelated extreme stressors in adolescence.

Melatonin set out to ER stress signaling thwarts epithelial mesenchymal transition and peritoneal dissemination via calpain-mediated C/EBPß and NFκB cleavage.

Peritoneal dissemination of tumor has high mortality and is associated with the loss of epithelial features, acquisition of motile mesenchymal morphology characteristics, and invasive properties by tumor cells. Melatonin is an endogenously produced molecule in all plant species that is known to exert antitumor activity, but to date, its underlying mechanisms and antiperitoneal metastasis efficacy is not well defined. This study determined the antiperitoneal dissemination potential of melatonin in vivo and assessed its association with the inhibition of epithelial-to-mesenchymal transition (EMT) signaling mechanism by endoplasmic reticulum (ER) stress, which may be a major molecular mechanism of melatonin against cancer. The results demonstrate that melatonin inhibited peritoneal metastasis in vivo and activated ER stress in Cignal ERSE Reporter Assay, organelle structure in transmission electron microscopy images, calpain activity, and protein biomarkers like p-elf2α. Moreover, the overexpression of transcription factor C/EBPß in gastric cancer interacted with NFκB and further regulates COX-2 expression. These were dissociated and downregulated by melatonin, as proven by immunofluorescence imaging, immunoprecipitation, EMSA, and ChIP assay. Melatonin or gene silencing of C/EBPß decreased the EMT protein markers (E-cadherin, Snail, and Slug) and Wnt/beta-catenin activity by Topflash activity, and increased ER stress markers. In an animal study, the results of melatonin therapy were consistent with those of in vitro findings and attenuated systemic proangiogenesis factor production. In conclusion, C/EBPß and NFκB inhibition by melatonin may impede both gastric tumor growth and peritoneal dissemination by inducing ER stress and inhibiting EMT.

Development and application of telephone counseling services for care of patients with colorectal cancer.

BACKGROUND: The number of colorectal cancer (CRC) patients in Taiwan has increased in recent years; therefore, the effective dissemination of information related to symptom care has become especially important. Previous studies indicated that the physical and psychological status of cancer patients can be effectively improved by telephone counseling services (TCS). Thus, determining the most effective means of establishing a TCS to support the clinical practice of oncology has become a crucial goal for nursing. The purposes of this study were to analysis the content of the TCS for CRC and explore stratification of the TCS. MATERIALS AND METHODS: The study design was retrospective. A total of 850 calls were made to CRC patients in the cancer center of Southern Taiwan during the period of January 2007- December 2011. A structure questionnaire was adopted to analysis satisfaction. RESULTS: Responses provided by the TCS included information regarding nutrition, side effects resulting from chemotherapy and pain. Moreover, 28.7% of CRC patients needed advanced treatment. More than 90% satisfaction with all aspects of the calls was found. CONCLUSIONS: The TCS coulkd be shown to provide an effective means by which to expand the reach of nursing care to different times, places and patients, allowing for greater cost efficiency and more rapid service.

Secondary peritonitis due to Rhizobium radiobacter.

BACKGROUND: Rhizobium radiobacter rarely causes human infections, most of which develop in immunocompromised patients, and especially those with intravenous catheters. Although R. radiobacter has been reported in association with peritonitis, all such reported cases have been due to intra-peritoneal devices in patients undergoing peritoneal dialysis. Herein we report the first case of a perforated ulcer complicated by peritonitis caused by R. radiobacter in a healthy adult, which was treated successfully with surgery and antibiotics. METHODS: Case report and literature review. RESULTS: A 33-year-old male presented with epigastric abdominal pain of sudden onset. Physical examination was unremarkable except for the finding of diffuse abdominal tenderness with rebound tenderness. Exploratory laparotomy revealed a perforated duodenal ulcer with secondary peritonitis. The patient underwent pyloroplasty with bilateral truncal vagotomy and peritoneal toilet. Turbid ascites was sent for culture and yielded R. radiobacter and Streptococcus viridans. The patient was treated with a 10-d course of ceftazidime on the basis of drug susceptibility results, and recovered completely without complications. CONCLUSIONS: We report a case of secondary peritonitis caused by R. radiobacter, which expands the spectrum of infectious diseases caused by this organism.

Peritonitis caused by Aeromonas species at a hospital in southern Taiwan.

OBJECTIVE: This study was conducted to investigate the clinical characteristics of patients with Aeromonas peritonitis, particularly secondary peritonitis. METHODS: Patients with Aeromonas peritonitis treated between July 2004 and December 2011 were identified from the computerized database of a regional hospital in southern Taiwan. The medical records of these patients were retrospectively reviewed. RESULTS: A total of 50 patients with Aeromonas peritonitis were identified. Nine cases were classified as spontaneous bacterial peritonitis, and 41 cases were classified as secondary peritonitis. The most common etiology of secondary peritonitis was acute appendicitis (n=26), followed by small bowel perforation (n=7) and colon perforation (n=6). The patients with spontaneous bacterial peritonitis were more likely to be immunocompromised (p=0.0013) and more frequently had an initial presentation of shock (p=0.0129), an abnormal liver function (p<0.05) and concomitant bacteremia (p=0.0024) than the patients with secondary peritonitis. Although the patients with secondary peritonitis had higher levels of inflammatory parameters, including leukocytes and C-reactive protein, and more frequent polymicrobial infections, their survival outcome rates, such as in-hospital mortality, were significantly lower (p=0.0007). The overall in-hospital mortality rate was 20%, and initial shock was the only independent prognostic factor for mortality (p=0.012). CONCLUSION: The clinical characteristics, including outcomes, of patients with spontaneous and secondary Aeromonas peritonitis differ. In-hospital mortality is significantly associated with the initial presentation of shock.

The relationship between volume and outcome after bariatric surgery: a nationwide study in Taiwan.

BACKGROUND: This study purposed to explore the impact of hospital volume and surgeon volume on hospital resource utilization after bariatric surgery and to identify the predictors of length of stay (LOS) and hospital treatment cost in a nationwide population in Taiwan. METHODS: This population-based cohort study retrospectively analyzed 2,674 bariatric surgery procedures performed from 1997 to 2008. Hospitals were classified as low- and high-volume hospitals if their annual number of bariatric surgeries were <35 and ≥ 35, respectively. Surgeons were classified as low- and high-volume surgeons if their annual number of bariatric surgeries were <15 and ≥ 15, respectively. Hierarchical linear regression models were used to predict LOS and hospital treatment cost. RESULTS: The mean LOS was 7.67 days and the LOS for high-volume hospitals/surgeons was, on average, 28%/31% shorter than that for low-volume hospitals/surgeons. The mean hospital treatment cost was US$2,344.08, and the average hospital costs for high-volume hospitals/surgeons were 10%/13% lower than those for low-volume hospitals/surgeons. Advanced age, male gender, high Charlson co-morbidity index, and current treatment in a low-volume hospital, by a low-volume surgeon, and via open gastric bypass were significantly associated with long LOS and high hospital treatment cost (P < 0.001). CONCLUSIONS: The data suggest that annual surgical volume is the key factor in hospital resource utilization. The results improve the understanding of medical resource allocation for this surgical procedure and can help to formulate public health policies for optimizing hospital resource utilization for related diseases.