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Zaire ebolavirus (EBOV) poses a significant threat to public health due to its high case fatality rate and epidemic potential. This is further complicated by the lack of precise immune correlates of protection and difficulties in conducting in vivo animal studies due to species specificity of Ebola virus disease (EVD) and classification as a biosafety level 4 pathogen. Related ebolaviruses have also contributed to the public health threat; Uganda recently experienced an outbreak of Sudan ebolavirus, which also had a high case fatality rate. Vaccination targeting EBOV has demonstrated significant efficacy; however, the protective cellular and humoral responses at play are still poorly understood. Vaccination for vulnerable populations such as pregnant women, young children, and immunocompromised individuals is still limited. Understanding vaccine correlates of protection (vCOP) is key to developing alternative vaccination strategies for these groups. Components of immunity such as neutralizing antibody and cell-mediated immunity are likely responsible for protective responses; however, existing research fails to fully define their roles in protection. Here we investigated vaccine-elicited antibody avidity as a potential correlate of protection and to further characterize the contribution of antibody avidity in protective and nonprotective vaccine responses.

The speed at which several COVID-19 vaccines went from conception to receiving FDA and EMA approval for emergency use is an achievement unrivaled in the history of vaccine development. Mass vaccination efforts using the highly effective vaccines are currently underway to generate sufficient herd immunity and reduce transmission of the SARS-CoV-2 virus. Despite the most advanced vaccine technology, global recipient coverage, especially in resource-poor areas remains a challenge as genetic drift in naïve population pockets threatens overall vaccine efficacy. In this study, we described the production of insect-cell expressed SARS-CoV-2 spike protein ectodomain constructs and examined their immunogenicity in mice. We demonstrated that, when formulated with CoVaccine HTTM adjuvant, an oil-in-water nanoemulsion compatible with lyophilization, our vaccine candidates elicit a broad-spectrum IgG response, high neutralizing antibody (NtAb) titers against SARS-CoV-2 prototype and variants of concern, specifically B.1.351 (Beta) and P.1. (Gamma), and an antigen-specific IFN-γ secreting response in outbred mice. Of note, different ectodomain constructs yielded variations in NtAb titers against the prototype strain and some VOC. Dose response experiments indicated that NtAb titers increased with antigen dose, but not adjuvant dose, and may be higher with a lower adjuvant dose. Our findings lay the immunological foundation for the development of a dry-thermostabilized vaccine that is deployable without refrigeration.

The Ebola virus has caused outbreaks in Central and West Africa, with high rates of morbidity and mortality. Clinical trials of recombinant virally vectored vaccines did not explicitly include pregnant or nursing women, resulting in a gap in knowledge of vaccine-elicited maternal antibody and its potential transfer. The role of maternal antibody in Ebola virus disease and vaccination remains understudied. Here, we demonstrate that a protein subunit vaccine can elicit robust humoral responses in pregnant mice, which are transferred to pups in breastmilk. These findings indicate that an intramuscular protein subunit vaccine may elicit Ebola-specific IgG capable of being transferred across the placenta as well as into the breastmilk. We have previously shown protective efficacy with these vaccines in non-human primates, offering a potential safe and practical alternative to recombinant virally vectored vaccines for pregnant and nursing women in Ebola endemic regions.

Ebola (EBOV), Marburg (MARV) and Sudan (SUDV) viruses are the three filoviruses which have caused the most fatalities in humans. Transmission from animals into the human population typically causes outbreaks of limited scale in endemic regions. In contrast, the 2013-16 outbreak in several West African countries claimed more than 11,000 lives revealing the true epidemic potential of filoviruses. This is further emphasized by the difficulty seen with controlling the 2018-2020 outbreak of EBOV in the Democratic Republic of Congo (DRC), despite the availability of two emergency use-approved vaccines and several experimental therapeutics targeting EBOV. Moreover, there are currently no vaccine options to protect against the other epidemic filoviruses. Protection of a monovalent EBOV vaccine against other filoviruses has never been demonstrated in primate challenge studies substantiating a significant void in capability should a MARV or SUDV outbreak of similar magnitude occur. Herein we show progress on developing vaccines based on recombinant filovirus glycoproteins (GP) from EBOV, MARV and SUDV produced using the Drosophila S2 platform. The highly purified recombinant subunit vaccines formulated with CoVaccine HT™ adjuvant have not caused any safety concerns (no adverse reactions or clinical chemistry abnormalities) in preclinical testing. Candidate formulations elicit potent immune responses in mice, guinea pigs and non-human primates (NHPs) and consistently produce high antigen-specific IgG titers. Three doses of an EBOV candidate vaccine elicit full protection against lethal EBOV infection in the cynomolgus challenge model while one of four animals infected after only two doses showed delayed onset of Ebola Virus Disease (EVD) and eventually succumbed to infection while the other three animals survived challenge. The monovalent MARV or SUDV vaccine candidates completely protected cynomolgus macaques from infection with lethal doses of MARV or SUDV. It was further demonstrated that combinations of MARV or SUDV with the EBOV vaccine can be formulated yielding bivalent vaccines retaining full efficacy. The recombinant subunit vaccine platform should therefore allow the development of a safe and efficacious multivalent vaccine candidate for protection against Ebola, Marburg and Sudan Virus Disease.

The current COVID-19 pandemic has claimed hundreds of thousands of lives and its causative agent, SARS-CoV-2, has infected millions, globally. The highly contagious nature of this respiratory virus has spurred massive global efforts to develop vaccines at record speeds. In addition to enhanced immunogen delivery, adjuvants may greatly impact protective efficacy of a SARS-CoV-2 vaccine. To investigate adjuvant suitability, we formulated protein subunit vaccines consisting of the recombinant S1 domain of SARS-CoV-2 Spike protein alone or in combination with either CoVaccine HT™ or Alhydrogel. CoVaccine HT™ induced high titres of antigen-binding IgG after a single dose, facilitated affinity maturation and class switching to a greater extent than Alhydrogel and elicited potent cell-mediated immunity as well as virus neutralizing antibody titres. Data presented here suggests that adjuvantation with CoVaccine HT™ can rapidly induce a comprehensive and protective immune response to SARS-CoV-2.

Zika Virus (ZIKV), a virus with no severe clinical symptoms or sequelae previously associated with human infection, became a public health threat following an epidemic in French Polynesia 2013–2014 that resulted in neurological complications associated with infection. Although no treatment currently exists, several vaccines using different platforms are in clinical development. These include nucleic acid vaccines based on the prM-E protein from the virus and purified formalin-inactivated ZIKV vaccines (ZPIV) which are in Phase 1/2 clinical trials. Using a recombinant subunit platform consisting of antigens produced in Drosophila melanogaster S2 cells, we have previously shown seroconversion and protection against viremia in an immunocompetent mouse model. Here we demonstrate the efficacy of our recombinant subunits in a non-human primate (NHP) viremia model. High neutralizing antibody titers were seen in all protected macaques and passive transfer demonstrated that plasma from these NHPs was sufficient to protect against viremia in mice subsequently infected with ZIKV. Taken together our data demonstrate the immunogenicity and protective efficacy of the recombinant subunit vaccine candidate in NHPs as well as highlight the importance of neutralizing antibodies in protection against ZIKV infection and their potential implication as a correlate of protection.

ABSTRACT Following the 2015 Zika virus (ZIKV) outbreaks in the South Pacific, Caribbean, and Americas, ZIKV has emerged as a serious threat due to its association with infantile microcephaly and other neurologic disorders. Despite an international effort to develop a safe and effective vaccine to combat congenital Zika syndrome and ZIKV infection, only DNA and mRNA vaccines encoding the precursor membrane (prM) and envelope (E) proteins, an inactivated-ZIKV vaccine, and a measles virus-based ZIKV vaccine are currently in phase I or II (prM/E DNA) clinical trials. A ZIKV vaccine based on a nonreplicating, recombinant subunit platform offers a higher safety profile than other ZIKV vaccine candidates but is still highly immunogenic, inducing high virus-neutralizing antibody titers. Here, we describe the production and purification of Drosophila melanogaster S2 insect cell-derived, soluble ZIKV E protein and evaluate its immunogenicity and efficacy in three different mouse strains. As expected, significant virus-specific antibody titers were observed when using formulations containing clinically relevant adjuvants. Immunized mice challenged with live virus demonstrate inhibition of virus replication. Importantly, plaque reduction neutralization tests (PRNTs) indicate the high-titer production of neutralizing antibodies, a correlate of protection in the defense against ZIKV infection. ZIKV challenge of immunocompetent mice led to full protection against viremia with two doses of adjuvanted vaccine candidates. These data demonstrate a proof of concept and establish recombinant subunit immunogens as an effective vaccine candidate against ZIKV infection. IMPORTANCE The recent outbreaks of Zika virus (ZIKV) infection in French Polynesia, the Caribbean, and the Americas have highlighted the severe neuropathological sequelae that such an infection may cause. The development of a safe, effective ZIKV vaccine is critical for several reasons: (i) the difficulty in diagnosing an active infection due to common nonspecific symptoms, (ii) the lack of a specific antiviral therapy, and (iii) the potentially devastating pathological effects of in utero infection. Moreover, a vaccine with an excellent safety profile, such as a nonreplicating, noninfectious vaccine, would be ideal for high-risk people (e.g., pregnant women, immunocompromised patients, and elderly individuals). This report describes the development of a recombinant subunit protein vaccine candidate derived from stably transformed insect cells expressing the ZIKV envelope protein in vitro, the primary antigen to which effective virus-neutralizing antibodies are engendered by immunized animals for several other flaviviruses; the vaccine candidate elicits effective virus-neutralizing antibodies against ZIKV and provides protection against ZIKV infection in mice.

Post-Acute Sequelae of SARS-CoV-2 infection (PASC), also known as Long-COVID, encompasses a variety of complex and varied outcomes following COVID-19 infection that are still poorly understood. We clustered over 600 million condition diagnoses from 14 million patients available through the National COVID Cohort Collaborative (N3C), generating hundreds of highly detailed clinical phenotypes. Assessing patient clinical trajectories using these clusters allowed us to identify individual conditions and phenotypes strongly increased after acute infection. We found many conditions increased in COVID-19 patients compared to controls, and using a novel method to associate patients with clusters over time, we additionally found phenotypes specific to patient sex, age, wave of infection, and PASC diagnosis status. While many of these results reflect known PASC symptoms, the resolution provided by this unprecedented data scale suggests avenues for improved diagnostics and mechanistic understanding of this multifaceted disease., (© 2024. The Author(s).)

Background: The syndemic nature of gonococcal infections and HIV provides an opportunity to develop a synergistic intervention tool that could address the need for adequate treatment for gonorrhea, screen for HIV infections, and offer pre-exposure prophylaxis (PrEP) for persons who meet the criteria. By leveraging information available on electronic health records, a clinical decision support (CDS) system tool could fulfill this need and improve adherence to Centers for Disease Control and Prevention (CDC) treatment and screening guidelines for gonorrhea, HIV, and PrEP., Objective: The goal of this study was to translate portions of CDC treatment guidelines for gonorrhea and relevant portions of HIV screening and prescribing PrEP that stem from a diagnosis of gonorrhea as an electronic health record-based CDS intervention. We also assessed whether this CDS solution worked in real-world clinic., Methods: We developed 4 tools for this CDS intervention: a form for capturing sexual history information (SmartForm), rule-based alerts (best practice advisory), an enhanced sexually transmitted infection (STI) order set (SmartSet), and a documentation template (SmartText). A mixed methods pre-post design was used to measure the feasibility, use, and usability of the CDS solution. The study period was 12 weeks with a baseline patient sample of 12 weeks immediately prior to the intervention period for comparison. While the entire clinic had access to the CDS solution, we focused on a subset of clinicians who frequently engage in the screening and treatment of STIs within the clinical site under the name "X-Clinic." We measured the use of the CDS solution within the population of patients who had either a confirmed gonococcal infection or an STI-related chief complaint. We conducted 4 midpoint surveys and 3 key informant interviews to quantify perception and impact of the CDS solution and solicit suggestions for potential future enhancements. The findings from qualitative data were determined using a combination of explorative and comparative analysis. Statistical analysis was conducted to compare the differences between patient populations in the baseline and intervention periods., Results: Within the X-Clinic, the CDS alerted clinicians (as a best practice advisory) in one-tenth (348/3451, 10.08%) of clinical encounters. These 348 encounters represented 300 patients; SmartForms were opened for half of these patients (157/300, 52.33%) and was completed for most for them (147/300, 89.81%). STI test orders (SmartSet) were initiated by clinical providers in half of those patients (162/300, 54%). HIV screening was performed during about half of those patient encounters (191/348, 54.89%)., Conclusions: We successfully built and implemented multiple CDC treatment and screening guidelines into a single cohesive CDS solution. The CDS solution was integrated into the clinical workflow and had a high rate of use., (©Saugat Karki, Sarah Shaw, Michael Lieberman, Alejandro Pérez, Jonathan Pincus, Priya Jakhmola, Amrita Tailor, Oyinkansola Bukky Ogunrinde, Danielle Sill, Shane Morgan, Miguel Alvarez, Jonathan Todd, Dawn Smith, Ninad Mishra. Originally published in JMIR Formative Research (https://formative.jmir.org), 15.04.2024.)

Background: Poly-4-hydroxybutyric acid (P4HB, Phasix™) is a biosynthetic polymer that degrades by hydrolysis that can be woven into a mesh for use in soft tissue reinforcement. Herein, we describe our initial experience performing complex abdominal wall repair (CAWR) utilizing component separation and P4HB mesh as onlay reinforcement., Methods: All patients undergoing CAWR between June 2014 and May 2017 were followed prospectively for postoperative outcomes. Only those patients who underwent components separation with primary repair of the fascial edges followed by onlay of P4HB mesh were included in this study., Results: 105 patients (52 male, 53 female; mean age 59.2 years, range 22-84) met inclusion criteria. Mean BMI was 29.1 (range 16-48); 52% patients had prior attempted hernia repair, most with multiple medical comorbidities (71% of patients with ASA 3 or greater). 30% of cases were not clean at the time of repair (CDC class 2 or greater). Median follow-up was 36 months (range 9-63). Eighteen patients (17%) developed a hernia recurrence ranging from 2 to 36 months postoperatively. Five (5%) patients developed a localized superficial infection treated with antibiotics, three (2.8%) required re-operation for non-healing wounds, and six (6%) patients developed seroma., Conclusions: These data demonstrate a relatively low rate of hernia recurrence, seroma, and other common complications of CAWR in a highly morbid patient population. Importantly, the rate of mesh infection was low and no patients required complete mesh removal, even when placed into a contaminated or infected surgical field.

Digital therapeutics is a newly described concept in healthcare which is proposed to change patient behavior and treat medical conditions using a variety of digital technologies. However, the term is rarely defined with criteria that make it distinct from simply digitized versions of traditional therapeutics . Our objective is to describe a more valuable characteristic of digital therapeutics, which is distinct from traditional medicine or therapy: that is, the utilization of artificial intelligence and machine learning systems to monitor and predict individual patient symptom data in an adaptive clinical feedback loop via digital biomarkers to provide a precision medicine approach to healthcare. Artificial intelligence platforms can learn and predict effective interventions for individuals using a multitude of personal variables to provide a customized and more tailored therapy regimen. Digital therapeutics coupled with artificial intelligence and machine learning also allows more effective clinical observations and management at the population level for various health conditions and cohorts. This vital differentiation of digital therapeutics compared to other forms of therapeutics enables a more personalized form of healthcare that actively adapts to patients' individual clinical needs, goals, and lifestyles. Importantly, these characteristics are what needs to be emphasized to patients, physicians, and policy makers to advance the entire field of digital healthcare., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 by S. Karger AG, Basel.)

Apocrine hidrocystoma is a benign, cystic lesion often presenting in the periorbital region. Apocrine adenocarcinoma is the rare, malignant counterpart occurring mainly in the axilla and anogenital region. There is a paucity of literature on both entities and co-occurrence has been reported in only 5 cases. We present the case of a 48-year-old man with a history of total body irradiation for chronic myelocytic leukemia, diabetes mellitus, and obesity who presented with a calf mass of two years' duration. Epidermal inclusion cyst was presumed and excisional biopsy was carried out. Pathologic analysis revealed apocrine adenocarcinoma in the setting of a precursor apocrine hidrocystoma. Our patient's unique altered immunity and the direct effects of irradiation on the local microenvironment may have resulted in his rare presentation of co-occurrence of apocrine adenocarcinoma within an existing apocrine hidrocystoma. To our knowledge, our patient is the first reported patient with this presentation in the lower extremity.

Background: Endoscopic ultrasound-guided gallbladder drainage (EGBD) with a lumen apposing metal stent is becoming a widely accepted alternative to percutaneous gallbladder drainage (PTGD) for patients who are not candidates for cholecystectomy (CCY). In some patients, medical comorbidites can improve, allowing them to undergo CCY. We compare feasibility and outcomes of interval CCY after EGBD versus PTGD., Methods: We conducted a multicentered international cohort study of patients who underwent EGBD or PTGD and then underwent interval CCY. Baseline patient demographics, procedural details, and follow-up data were recorded and compared., Results: In total, 34 patients were included. Thirteen patients underwent EGBD followed by CCY (mean age, 53.77±17.27, 46.15% male), and 21 patients underwent PTGD followed by CCY (mean age, 62.14±13.06, 61.9% male). There was no statistically significant difference in mean Charlson Comorbidity Index (P=0.12) or etiology of cholecystitis (P=0.85) between the 2 groups. All patients had a technically successful CCY. There was no difference between rates of open versus laparoscopic CCY (P=1). In addition, there was no difference in postsurgical adverse events (P=0.23)., Conclusions: Surgical CCY after EGBD with lumen apposing metal stent is safe and feasible for the management of cholecystitis. If patient's underlying medical conditions improve, previous EUS-GLB drainage should not preclude patients from undergoing CCY as part of standard of care.

Purpose: Epigenetic silencing of tumor suppressor genes (TSG) is an acquired abnormality observed in cancer and is prototypically linked to DNA methylation. We postulated that pretreatment (priming) with 5-azacitidine would increase the efficacy of chemotherapy by reactivating TSGs. This study was conducted to identify a tolerable dose of 5-azacitidine prior to EOX (epirubicin, oxaliplatin, capecitabine) neoadjuvant chemotherapy in patients with locally advanced esophageal/gastric adenocarcinoma (EGC). Experimental Design: Eligible patients had untreated, locally advanced, resectable EGC, ECOG 0-2, and adequate organ function. 5-Azacitidine (V, 75 mg/m 2 ) was given subcutaneously for 3 (dose level, DL 1) or 5 (DL 2) days prior to each 21-day cycle of EOX (E, 50 mg/m 2 ; O, 130 mg/m 2 ; X, 625 mg/m 2 twice daily for 21 days). Standard 3+3 methodology guided V dose escalation. DNA methylation at control and biomarker regions was measured by digital droplet, bisulfite qPCR in tumor samples collected at baseline and at resection. Results: All subjects underwent complete resection of residual tumor (R0). Three of the 12 patients (25%) achieved a surgical complete response and 5 had partial responses. The overall response rate was 67%. The most common toxicities were gastrointestinal and hematologic. Hypomethylation of biomarker genes was observed at all dose levels and trended with therapeutic response. Conclusions: Neoadjuvant VEOX was well-tolerated with significant clinical and epigenetic responses, with preliminary evidence that priming with V prior to chemotherapy may augment chemotherapy efficacy. The recommended phase II trial schedule is 5-azacitidine 75 mg/m 2 for 5 days followed by EOX chemotherapy every 21 days. Clin Cancer Res; 23(11); 2673-80. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Background: Surgery for pancreatic branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) is indicated for therapy of symptomatic patients and to prevent development of invasive cancer. There is currently no consensus on management of BD-IPMN patients after surgical resection. The aim of this retrospective multicenter study was to determine the recurrence and long-term survival after surgical resection of BD-IPMN and to determine the predictive factors of recurrence., Methods: All patients who underwent surgery for BD-IPMN from 2005 to 2011 at 2 centers were identified. The diagnosis of BD-IPMN was based upon imaging and endosonographic analysis, and was confirmed by pathological analysis. The lesions were classified into 4 categories according to the WHO classification. Data on cyst characteristics, operative procedure, recurrence, and follow-up were evaluated. Recurrence was defined as the presence of BD-IPMN or mass in the remnant pancreas after surgery as seen on follow-up imaging. Recurrence suspected on imaging was confirmed via histological analysis when possible., Results: A number of 271 patients (67% female; mean age 63.4 yrs) with BD-IPMN underwent surgical resection. The mean size of the cyst was 24.2mm (range, 12-80). There were 34 (12.5%) patients with an associated mass. 82 (30.3%) patients had worrisome features in the cyst on pre-operative EUS, included mural nodules (N.=25), solid component (N.=27), debris (N.=25), and a dilated major pancreatic duct (N.=5). 144(53%) patients had a pancreaticoduodenectomy for head lesions, 125 (46%) had distal pancreatectomy for tail/body lesions, and 1 (1%) underwent a total pancreatectomy. Histology showed 86% with noninvasive IPMN (adenoma 31%, moderate dysplasia 24%, severe dysplasia or carcinoma in situ 31%) and 14% with invasive IPMN. The mean patient follow-up was 28 months (range, 10-180 months). Recurrence in the remnant pancreas occurred in 34 (12.5%) patients. Of the patients with recurrence, 3/34 had invasive carcinoma and 31/34 had noninvasive cystic lesions; all patients with invasive carcinoma recurrence were those with a previous invasive IPMN. On MVA, risk factors for cyst recurrence were severe dysplasia/intraductal carcinoma in situ and invasive IPMN even after adjusting for elevated CEA (>193 ng/mL), type of surgery, and cyst size (OR 2.8, 95% CI=1.1-7.3; P=0.028). 3 patients who had invasive IPMN and 1 who had severe dysplasia patient with recurrence died, all because of recurrent cancer, with the mean time from recurrence to death being 36 months., Conclusions: The risk of BD-IPMN recurrence after resection depends upon the histological type, with the highest-risk groups being those with severe dysplasia/intraductal carcinoma in situ and invasive IPMN. Even after negative resection margins, the pancreatic remnant still harbors a risk of recurrence which requires long-term surveillance.

In April 2015, Oregon Health & Science University (OHSU) deployed a web-based, electronic medical record-embedded application created by third party vendor Vynca Inc. to allow real-time education, and completion of Physician Orders for Life Sustaining Treatment (POLST). Forms are automatically linked to the Epic Systems™ electronic health record (EHR) patient header and submitted to a state Registry, improving efficiency, accuracy, and rapid access to and retrieval of these important medical orders. POLST Forms, implemented in Oregon in 1992, are standardized portable medical orders used to document patient treatment goals for end-of-life care. In 2009, Oregon developed the first POLST-only statewide registry with a legislative mandate requiring POLST form signers to register the form unless the patient opts out. The Registry offers 24/7 emergency access to POLST Forms for Emergency Medical Services, Emergency Departments, and Acute Care Units. Because POLST is intended for those nearing end of life, immediate access to these forms at the time of an emergency is critical. Delays in registering a POLST Form may result in unwanted treatment if the paper form is not immediately available. An electronic POLST Form completion system (ePOLST) was implemented to support direct Registry submission. Other benefits of the system include single-sign-on, transmission of HL7 data for patient demographics and other relevant information, elimination of potential errors in form completion using internalized logic, built-in real-time video and text-based education materials for both patients and health care professionals, and mobile linkage for signature capture.

Background/aims: Surgery is the mainstay of treatment for cholecystitis. However, gallbladder stenting (GBS) has shown promise in debilitated or high-risk patients. Endoscopic transpapillary GBS and endoscopic ultrasound-guided GBS (EUS-GBS) have been proposed as safe and effective modalities for gallbladder drainage., Methods: Data from patients with cholecystitis were prospectively collected from August 2004 to May 2013 from two United States academic university hospitals and analyzed retrospectively. The following treatment algorithm was adopted. Endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy and cystic duct stenting was initially attempted. If deemed feasible by the endoscopist, EUS-GBS was then pursued., Results: During the study period, 139 patients underwent endoscopic gallbladder drainage. Among these, drainage was performed in 94 and 45 cases for benign and malignant indications, respectively. Successful endoscopic gallbladder drainage was defined as decompression of the gallbladder without incidence of cholecystitis, and was achieved with ERCP and cystic duct stenting in 117 of 128 cases (91%). Successful endoscopic gallbladder drainage was also achieved with EUS-guided gallbladder drainage using transmural stent placement in 11 of 11 cases (100%). Complications occurred in 11 cases (8%)., Conclusions: Endoscopic gallbladder drainage techniques are safe and efficacious methods for gallbladder decompression in non-surgical patients with comorbidities.

Background: Confocal endomicroscopy provides real-time evaluation of various sites and has been used to provide detailed endomicroscopic imaging of the biliary tree. We aimed to evaluate the feasibility and utility of probe-based confocal laser endomicroscopy of the pancreatic duct as compared to cytologic and histologic results in patients with indeterminate pancreatic duct strictures., Methods: Retrospective data on patients with indeterminate pancreatic strictures undergoing endoscopic retrograde cholangiopancreatography (ERCP) and confocal endomicroscopy were collected from two tertiary care centres. Real-time confocal endomicroscopy images were obtained during ERCP and immediate interpretation according to the Miami Classification was performed., Results: 18 patients underwent confocal endomicroscopy for evaluation of pancreatic strictures from July 2011 to December 2012. Mean pancreatic duct size was 4.2mm (range 2.2-8mm). Eight cases were interpreted as benign, 4 as malignant, 4 suggestive of intraductal papillary mucinous neoplasms, and 2 appeared normal. Cytology/histopathology for 15/16 cases showed similar results to confocal endomicroscopy interpretation. Kappa coefficient of agreement between cyto/histopathology and confocal endomicroscopy was 0.8 (p=0.0001). Pancreatic confocal endomicroscopy changed management in four patients, changing the type of surgery from total pancreatectomy to whipple., Conclusions: Confocal endomicroscopy is effective in assisting with diagnosis of indeterminate pancreatic duct strictures as well as mapping of abnormal pancreatic ducts prior to surgery., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Obscure gastrointestinal bleeding is a common clinical scenario. In the upper gastrointestinal tract, gastric varices can be frequently overlooked on endoscopy, particularly if not suspected or volume depleted. We report a case of suspected gastrointestinal bleeding in a patient with a childhood history of pancreatitis, who also experienced severe epigastric pain while in hospital. After transfer to an academic medical centre, the presence of gastric varices was identified and presumed to be due to splenic vein thrombosis. Pancreatitis is the most common cause of splenic vein thrombosis and accords with the patient's history, even though it occurred many years previously. This case highlights the importance of recognising pancreatitis-induced splenic vein thrombosis as a possible aetiology for upper gastrointestinal bleeding.

Background: Endoscopic necrosectomy for necrotizing pancreatitis has been increasingly used as an alternative to surgical or percutaneous interventions. The use of fully covered esophageal self-expandable metallic stents may provide a safer and more efficient route for internal drainage. The aim of this study was to evaluate the safety and efficacy of endoscopic treatment of pancreatic necrosis with these stents., Methods: A retrospective study at 2 US academic hospitals included patients with infected pancreatic necrosis from July 2009 to November 2012. These patients underwent transgastric placement of fully covered esophageal metallic stents draining the necrosis. After necrosectomy, patients underwent regular sessions of endoscopic irrigation and debridement of cystic contents. The efficacy endpoint was successful resolution of infected pancreatic necrosis without the need for surgical or percutaneous interventions., Results: Seventeen patients were included with the mean age of 41±12 years. A mean of 5.3±3.4 sessions were required for complete drainage and the follow-up period was 237.6±165 days. Etiology included gallstone pancreatitis (6), alcohol abuse (6), s/p distal pancreatectomy (2), postendoscopic retrograde cholangiopancreatography pancreatitis (1), medication-induced pancreatitis (1), and hyperlipidemia (1). Mean size of the necrosis was 14.8 cm (SD 5.6 cm), ranging from 8 to 19 cm. Two patients failed endoscopic intervention and required surgery. The only complication was a perforation during tract dilation, which was managed conservatively. Fifteen patients (88%) achieved complete resolution., Conclusions: Endoscopic necrosectomy with covered esophageal metal stents is a safe and successful treatment option for infected pancreatic necrosis.

We report a case of a cutaneous renocolic fistula in a patient with staghorn calculus and diverticulitis. The most common origins of renocolic fistula are primary renal diseases including xanthogranulomatous pyelonephritis, trauma, malignancy or tuberculosis. While diverticulitis has rarely been associated with renocolic fistula, previous instances of fistulae have been noted in patients with simultaneous kidney disease. Inflammation resulting from kidney disease may place patients with colonic diverticulitis at higher risk for developing renocolic or cutaneous renocolic fistulas.