Factors associated with radiological misstaging of pancreatic ductal adenocarcinoma: A retrospective observational study.

PURPOSE: Accurate staging of disease is vital in determining appropriate care for patients with pancreatic ductal adenocarcinoma (PDAC). It has been shown that the quality of scans and the experience of a radiologist can impact computed tomography (CT) based assessment of disease. The aim of the current study was to evaluate the impact of the rereading of outside hospital (OH) CT by an expert radiologist and a repeat pancreatic protocol CT (PPCT) on staging of disease. METHODS: Patients evaluated at the our institute's pancreatic multidisciplinary clinic (2006 to 2014) with OH scan and repeat PPCT performed within 30 days were included. In-house radiologists staged disease using OH scans and repeat PPCT, and factors associated with misstaging were determined. RESULTS: The study included 100 patients, with a median time between OH scan and PPCT of 19 days (IQR: 13-23 days.) Stage migration was mostly accounted for by upstaging of disease (58.8 % to 83.3 %) in all comparison groups. When OH scans were rereviewed, 21.5 % of the misstaging was due to missed metastases, however, when rereads were compared to the PPCT, occult metastases accounted for the majority of misstaged patients (62.5 %). Potential factors associated with misstaging were primarily related to imaging technique. CONCLUSION: A repeat PPCT results in increased detection of metastatic disease that rereviews of OH scans may otherwise miss. Accessible insurance coverage for repeat PPCT imaging even within 30 days of an OH scan could help optimize delivery of care and alleviate burdens associated with misstaging.

Bacterial second messenger cyclic di-AMP in streptococci.

Cyclic dimeric adenosine monophosphate (c-di-AMP) has been well studied in bacteria, including those of the genus Streptococcus, since the first recognition of this dinucleotide in 2008. Streptococci possess a sole diadenylate cyclase, CdaA, and distinct c-di-AMP phosphodiesterases. Interestingly, cdaA is required for viability of some streptococcal species but not all when streptococci are grown in standard laboratory media. Bacteria of this genus also have distinct c-di-AMP effector proteins, diverse c-di-AMP-signaling pathways, and subsequent biological outcomes. In streptococci, c-di-AMP may influence bacterial growth, morphology, biofilm formation, competence program, drug resistance, and bacterial pathogenesis. c-di-AMP secreted by streptococci has also been shown to interact with the mammalian host and induces immune responses including type I interferon production. In this review, we summarize the reported c-di-AMP networks in seven species of the genus Streptococcus, which cause diverse clinical manifestations, and propose future perspectives to investigate the signaling molecule in these streptococcal pathogens.

Accuracy of pharmacy student self-assessment of a single sterile compounding technique following didactic training.

INTRODUCTION: The primary objective was to determine pharmacy students' ability to self-assess sterile compounding technique in a single evaluation three semesters after training in the curriculum. METHODS: School of pharmacy (SOP) students were trained and assessed on sterile compounding technique during their second year of school, with no additional formal assessments provided later in the curriculum. From 2016 to 2018, 262 students were asked to compound a simulated sterile product in their third year of pharmacy school and self-evaluate their technique, which was compared to an instructor evaluation with both people using the same rubric. RESULTS: Two thresholds were used to define successful assessment: strict (ability to detect ideal technique) and lenient (ability to detect harmful technique). The average match rate was 70.2% and 87.6% in the strict and lenient analyses, respectively, with outcomes varying between categories. In the product preparation and inspecting product categories, students who disagreed with assessors tended to misidentify their incorrect technique as correct. CONCLUSIONS: Pharmacy students who assessed themselves on sterile compounding technique three semesters after formal sterile compounding training were able to accurately self-assess in most cases, but when disagreeing with an assessor, commonly identified their incorrect technique as correct. Most students demonstrated the ability to self-assess sterile compounding technique and are prepared to assess their own sterile compounding in practice. SOPs could consider whether sterile compounding training coupled with self-assessment throughout the curriculum would be beneficial to further improve students' sterile compounding ability and accuracy of self-assessment.

Oncologic resection of pancreatic cancer with isolated liver metastasis: Favorable outcomes in select patients.

BACKGROUND: Patients with pancreatic ductal adenocarcinoma (PDAC) and liver metastasis are treated with palliative chemotherapy, whereas similar patients with metastatic colorectal cancer are considered for aggressive surgery. METHODS: Using an institutional database, PDAC patients undergoing liver resection for isolated metastasis were identified. Their overall survival (OS), treatment factors, and clinicopathological variables associated with survival were also evaluated. RESULTS: Forty-seven patients underwent curative-intent surgery for metastatic PDAC to the liver between 2000 and 2019. Median OS was 21.9 months from diagnosis. Fourteen patients underwent unplanned resection of radiographically occult liver metastasis during pancreatectomy with median OS of 8.7 months. On the other hand, 29 patients received systemic chemotherapy followed by planned resection; this cohort had the most favorable prognosis following aggressive surgery with median OS being 38.1 months from diagnosis and 24.1 months from surgery. Preoperative chemotherapy (HR = 7.1; p = .002) and moderate to well differentiation of the primary tumor (HR = 3.7; p = .003) were associated with prolonged survival in multivariate analysis, whereas lymph node metastases, response to preoperative therapy, number of liver metastasis, and extent of liver surgery were not. CONCLUSIONS: In select patients with PDAC and isolated liver metastasis, curative-intent surgery can result in meaningful survival. This aggressive approach seems most beneficial in patients following induction chemotherapy.

Evaluating Age as a Predictor of Postoperative Opioid Use and Prescribing Habits in Older Adults With Cancer.

OBJECTIVE: To assess the narcotic use of older patients after oncologic resection. DESIGN: Retrospective review. SETTING AND PARTICIPANTS: Adults with neoplasms undergoing resection at a tertiary academic medical center. METHODS: Open and minimally invasive resections of the pancreas, bowel, rectum, lung, breast, and skin were included. Emergent procedures, chronic opioid users, and benign pathology were excluded. Narcotic use was measured using morphine equivalents (MEQs, milligrams of morphine) at multiple time points and compared between younger and older (aged ≥65 years) patients. Refill requests were within 30 days of index procedure. RESULTS: A total of 445 patients were eligible, and 245 were ≥65 years old. Despite longer length of stay (3 vs 2 days, P = .01), older patients used less narcotic medication [39.8 (150) mg vs 84 (229) mg, P = .004], and reported lower pain scores [1.3 (3.3) vs 2.8 (4.5), P = .0001] over the course of their hospitalization. Additionally, older patients had lower normalized narcotic use [15.3 (150) mg vs 77.4 (240) mg, P = .0001] in the last 48 hours of their admission. Following discharge, older patients had a lower median discharge MEQ (DC MEQ) compared with younger patients, 75 (150) mg vs 112.5 (102.5) mg, P = .002. Further stratifying older patients into age cohorts (65-74 years, 75-84 years, ≥85 years) revealed progressively less narcotic use as measured by total inpatient MEQ and final 48 hours. Additionally, progressively older patients were discharged with progressively lower DC MEQ compared with younger patients, 90 (112.5) mg, 50 (131.3) mg, and 0 (60) mg vs 112.5 (102.5) mg, P < .0001, respectively. Finally, older patients requested refills less often than younger counterparts, 6.5% vs 14.5%, P = .006. CONCLUSIONS AND IMPLICATIONS: Older patients with cancer reported lower pain scores, consumed less narcotics, were discharged with significantly less narcotics, and called for refills less often compared with younger patients after surgery. These data suggest this population may require less opioids for satisfactory pain control, and development of a guideline targeting postoperative multimodal analgesia in older adults is warranted.

Accurate Nodal Staging in Pancreatic Cancer in the Era of Neoadjuvant Therapy.

BACKGROUND: Nodal disease is prognostic in pancreatic ductal adenocarcinoma (PDAC); however, optimal number of examined lymph nodes (ELNs) required to accurately stage nodal disease in the current era of neoadjuvant therapy remains unknown. The aim of the study was to evaluate the optimal number of ELNs in patients with neoadjuvantly treated PDAC. METHODS: A retrospective study was performed on patients with PDAC undergoing resection following neoadjuvant treatment between 2011 and 2018. Clinicopathological data were extracted and analyzed. RESULTS: Of 546 patients included, 232 (42.5%) had lymph node metastases. The median recurrence free survival (RFS) was 10.6 months (95% confidence interval: 9.7-11.7) and nodal disease was independently associated with shorter RFS (9.1 vs 11.9 months; p < 0.001). A cutoff of 22 ELNs was identified that stratified patients by RFS. Patients with N1 and N2 disease had similar median RFS (9.1 vs 8.9 months; p = 0.410). On multivariable analysis, ELN of ≥ 22 was found to be significantly associated with longer RFS among patients with N0 disease (14.2 vs. 10.9 months, p = 0.046). However, ELN has no impact on RFS for patients with N1/N2 disease (9.5 vs. 8.4 months, p = 0.190). Adjuvant therapy was associated with RFS only in patients with residual nodal disease. CONCLUSIONS: Lymph node metastases remain prognostic in PDAC patients after neoadjuvant treatment. Among N0 patients, a cutoff of 22 ELN was associated with improved RFS and resulted in optimal nodal staging.

Impact of Postoperative Glycemic Control on Postoperative Morbidity in Patients Undergoing Open Pancreaticoduodenectomy.

OBJECTIVE: To evaluate the impact of postoperative glycemic control on postoperative morbidity in patients undergoing a pancreaticoduodenectomy. METHODS: A retrospective study was performed on patients at The Johns Hopkins Hospital between April 2015 and April 2016. Data were collected on postoperative insulin regimens, blood glucose, rates of hyperglycemia and hypoglycemia, and postoperative complications and were evaluated. RESULTS: Out of 244 patients, 114 (46.7%) experienced at least 1 hyperglycemic (>180 mg/dL) episode and 16 (6.6%) experienced at least 1 hypoglycemic episode (<70 mg/dL) during the first postoperative 24 hours. Early postoperative hyperglycemia (>180 mg/dL) was associated with a significantly higher rate of surgical site infections (15.7% vs 7%; P = 0.031). Late postoperative hyperglycemia (>180 mg/dL) was associated with a significantly higher rate of fistulas (4.3% vs 14.6%; P = 0.021). CONCLUSIONS: Early hyperglycemia (>180 mg/dL) is associated with a higher risk of surgical site infections while late hyperglycemia is associated with a higher risk of fistulas. Intensive glucose control (<150 mg/dL) was not demonstrated to decrease the risk of postoperative complications. Similar to other critically ill populations, targeting a glucose goal of <180 mg/dL may be an appropriate target to reduce morbidity without increasing the risk of hypoglycemia.

Autoimmune Pancreatitis: A Critical Analysis of the Surgical Experience in an Era of Modern Diagnostics.

OBJECTIVE: The aim of this study was to critically analyze the surgical experience of managing autoimmune pancreatitis (AIP) in an era of modern diagnostics and compare these patients with those who were managed conservatively. METHODS: Two prospectively maintained databases were used to retrospectively identify patients with AIP who were either managed conservatively or underwent pancreatectomy. RESULTS: Eighty-eight patients were included in the study, of which 56 (63.6%) underwent resection and 32 (36.4%) were managed conservatively. Patients who underwent resection were more likely to present with jaundice (64.3% vs 18.1%, P < 0.001) and weight loss (53.6% vs 15.6%, P = 0.005). The cohort who underwent resection had a significantly higher median carbohydrate antigen 19-9 (40.0 vs 18.6 U/mL, P = 0.034) and was less likely to have elevated immunoglobulin G4 (26.1% vs 50.0%, P < 0.001). The most frequent initial diagnosis in the cohort who underwent resection was ductal adenocarcinoma (82.1%). Nine patients (28.1%) in the conservatively managed cohort experienced AIP relapse compared with 6 patients (10.7%) in the cohort who underwent resection. CONCLUSIONS: The most frequent reason for surgical resection of AIP is concern for malignancy. Carbohydrate antigen 19-9 elevations were more common than immunoglobulin G4 in our cohort, suggesting that this laboratory profile is suboptimal for this population.

Role of Lymph Node Resection and Histopathological Evaluation in Accurate Staging of Nonfunctional Pancreatic Neuroendocrine Tumors: How Many Are Enough?

BACKGROUND: Nodal involvement has been identified as one of the strongest prognostic factors in patients with nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs). Sufficient lymphadenectomy and evaluation is vital for accurate staging. The purpose of this study was to identify the optimal number of examined lymph nodes (ELN) required for accurate staging. METHODS: The SEER database was used to identify patients with resected NF-PanNETs between 2004 and 2014. The distributions of positive lymph nodes (PLN) ratio and total lymph nodes were used to develop a mathematical model. The sensitivity of detecting nodal disease at each cutoff of ELN was estimated and used to identify the optimal cutoff for ELN. RESULTS: A total of 1098 patients were included in the study of which 391 patients (35.6%) had nodal disease. The median ELN was 12 (interquartile range [IQR]: 7-19.5), and the median PLN was 2 (IQR: 1-4) for patients with nodal disease. With an increase in ELN, the sensitivity of detecting nodal disease increased from 12.0% (ELN: 1) to 92.2% (ELN: 20), plateauing at 20 ELN (< 1% increase in sensitivity with an additional ELN). This sensitivity increase pattern was similar in subgroup analyses with different T stages. CONCLUSIONS: The sensitivity of detecting nodal disease in patients with NF-PanNETs increases with an increase in the number of ELN. Cutoffs for adequate nodal assessment were defined for all T stages. Utilization of these cutoffs in clinical settings will help with patient prognostication and management.

Melanocyte Precursors in the Hair Follicle Bulge of Repigmented Vitiligo Skin Are Controlled by RHO-GTPase, KCTD10, and CTNNB1 Signaling.

In repigmentation of human vitiligo, the melanocyte (MC) precursors in the hair follicle bulge proliferate, migrate, and differentiate to repopulate the depigmented epidermis. Here, we present a comprehensive characterization of pathways and signals in the bulge that control the repigmentation process. Using biopsies from patients with vitiligo, we have selectively harvested, by laser capture microdissection, MC and keratinocyte precursors from the hair follicle bulge of untreated vitiligo skin and vitiligo skin treated with narrow-band UVB. The captured material was subjected to whole transcriptome RNA-sequencing. With this strategy, we found that repigmentation in the bulge MC precursors is driven by KCTD10, a signal with unknown roles in the skin, and CTNNB1 (encoding ß-catenin) and RHO guanosine triphosphatase [RHO GTPase, RHO], two signaling pathways previously shown to be involved in pigmentation biology. Knockdown studies in cultured human MCs of RHOJ, the upmost differentially expressed RHO family component, corroborated with our findings in patients with vitiligo, identified RHOJ involvement in UV response and melanization, and confirmed previously identified roles in melanocytic cell migration and apoptosis. A better understanding of mechanisms that govern repigmentation in MC precursors will enable the discovery of molecules that induce robust repigmentation phenotypes in vitiligo.

An Aggressive Approach to Locally Confined Pancreatic Cancer: Defining Surgical and Oncologic Outcomes Unique to Pancreatectomy with Celiac Axis Resection (DP-CAR).

BACKGROUND: Modern chemotherapeutics have led to improved systemic disease control for patients with locally advanced pancreatic cancer (LAPC). Surgical strategies such as distal pancreatectomy with celiac axis resection (DP-CAR) are increasingly entertained. Herein we review procedure-specific outcomes and assess biologic rationale for DP-CAR. METHODS: A prospectively maintained single-institution database of all pancreatectomies was queried for patients undergoing DP-CAR. We excluded all patients for whom complete data were not available and those who were not treated with contemporary multi-agent therapy. Data were supplemented with dedicated chart review and outreach for long-term oncologic outcomes. RESULTS: Fifty-four patients underwent DP-CAR between 2008 and 2018. The median age was 62.7 years. Ninety-eight percent received induction chemotherapy. Arterial reconstruction was performed in 17% and concomitant visceral resection in 30%. The R0 resection rate was 87%. Postoperative complications were common (43%) with chyle leak being the most frequent (17%). Length of stay was 8 days, readmission occurred in one-third, and 90-day mortality was 2%. Disease recurrence occurred in 74% during a median follow up of 17.4 months. Median recurrence-free (RFS) and overall survival (OS) were 9 and 25 months, respectively. CONCLUSIONS: Following modern induction paradigms, DP-CAR can be performed with low mortality, manageable morbidity, and excellent rates of margin-negative resection in high-volume settings. The profile of complications of DP-CAR is distinct from pancreaticoduodenectomy and simple distal pancreatectomy. OS and RFS are similar to those undergoing resection of borderline resectable and resectable disease. Improved systemic disease control will likely lead to increasing utilization of aggressive surgical approaches to LAPC.

Duodenal, ampullary, and pancreatic neuroendocrine tumors: Oncologic outcomes are driven by tumor biology and tissue of origin.

BACKGROUND: Periampullary neuroendocrine tumors (NETs) arise from the duodenum, ampulla, and periampullary pancreas. Duodenal and ampullary NETs are rare and may have distinct biologic behavior from pancreatic NETs (P-NETs). We examined the outcomes of these entities. METHODS: An institutional database was queried for patients undergoing resection for pancreatic head, duodenal, or ampullary NETs from 2000 to 2018. Patients with MEN1 syndrome or follow up less than 12 months were excluded. RESULTS: Three hundred and ten patients were identified. Tumor locations were ampulla (n = 15), duodenum (n = 35) and pancreas (n = 260). Median follow-up and recurrence-free survival (RFS) were 60.9 (interquartile range [IQR]: 34.8-99.3) and 171.7 (IQR: 84.0-NR) months. Clinicopathologic data and survival outcomes were similar for duodenal and ampullary NETs (RFS: p = .347 and overall survival [OS]: p = .246) and were combined into an intestinal subtype (IS) group. There were no differences in OS or RFS when comparing IS-NET and P-NET. On multivariate analysis, tissue of origin was not associated with risk of recurrence. The current American Joint Committee on Cancer staging guidelines, which account for origin tissue, were predictive of outcomes for all subtypes. CONCLUSION: Tissue of origin does not appear to impact long-term outcomes when comparing IS-NETs and P-NETs. The AJCC staging system offers good discriminatory capacity in the context of the tissue type.

Impact of Margin Status on Survival in Patients with Pancreatic Ductal Adenocarcinoma Receiving Neoadjuvant Chemotherapy.

BACKGROUND: Historically, a positive margin after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) was associated with decreased survival. In an era when neoadjuvant chemotherapy (NAC) is being used frequently, the prognostic significance of margin status is unclear. STUDY DESIGN: Patients with localized PDAC who received NAC and underwent pancreatectomy from 2011 to 2018 were identified from a single-institution database. Patients with fewer than 2 months of NAC, R2 resection, or fewer than 90 days of follow-up were excluded. A positive margin included tumors within 1 mm of the surgical margin. RESULTS: Four hundred and sixty-eight patients met inclusion criteria. Median age was 65 years and 53% were female. Preoperative clinical staging demonstrated that most had locally advanced (n = 222 [47%]) or borderline resectable (n = 172 [37%]) disease. Median follow-up was 18.5 months (interquartile range 10.6 to 30.0 months). Median duration of NAC was 119 days (interquartile range 87 to 168 days). FOLFIRINOX was first-line therapy for 67%, and 73% received neoadjuvant radiotherapy. Most underwent pancreaticoduodenectomy (69%). Forty percent were node-positive and 80% had an R0 resection. Fifty-six percent received at least 1 cycle of adjuvant therapy. Median overall survival and recurrence-free survival were 22.0 months (95% CI, 19.4 to 25.1 months) and 11.0 months (95% CI, 10.0 to 12.1 months). On multivariate analysis, margin status was not a significant predictor of overall survival or recurrence-free survival. Factors associated with overall survival included clinical stage, duration of NAC, nodal status, histopathologic treatment response score, and receipt of adjuvant chemotherapy. CONCLUSIONS: Microscopic margin positivity is not associated with recurrence and survival in localized PDAC patients resected after treatment with NAC. Aggressive surgical extirpation in high-volume centers should be considered in selected patients after extensive NAC.

Pancreatic Nerve Sheath Tumors: a Single Institutional Series and Systematic Review of the Literature.

INTRODUCTION: Improvement in imaging has resulted in frequent diagnosis of benign and premalignant pancreatic tumors. Pancreatic nerve sheath (PNS) tumors are one of the rarest pancreatic tumors. Literature on PNS is limited and their biology is poorly understood. Here, we report the largest series of PNS tumors to date and review the literature to evaluate the current data available on PNS tumors. METHODS: An institutional database was used to identify patients who underwent resection for PNS tumors. Clinicopathological characteristics and outcomes of these patients were reported. Furthermore, a review of literature was performed. RESULTS: From January 1994 through December 2016, seven patients underwent resection for PNS tumors. The median age was 57.7 years (IQR, 44.9-61.9) and the sex was approximately equally distributed (male = 4; 57.1%). Three (42.9%) patients were diagnosed incidentally and six (85.7%) were misdiagnosed as having other pancreatic tumors. The median tumor size was 2.1 (IQR 1.8-3.0) cm and six (85.7%) had no nodal disease. At a median follow-up of 15.5 (IQR 13.7-49.3) months, six patients were alive without evidence of disease and one patient was lost to follow-up. The literature review identified 49 studies reporting 54 patients with PNS tumors. Forty-six were misdiagnosed as having other pancreatic tumors. The median tumor size was 3.6 (range 1-20) cm, nodal disease was present in six patients (22.2%), and no patient had distant metastatic disease. At the time of last follow-up, all patients were free of disease. CONCLUSION: This is the largest single institution series on PNS tumors reported to date. These tumors are rare and are often misdiagnosed, given their radiological characteristics. PNS tumors have a benign course of disease and surgical resection results in favorable long-term outcomes.

Surgical Resection of 78 Pancreatic Solid Pseudopapillary Tumors: a 30-Year Single Institutional Experience.

BACKGROUND: Solid pseudopapillary tumors (SPTs) are rare, benign tumors of the pancreas that present as heterogeneous masses. We sought to evaluate the short- and long-term outcomes of surgical resected SPTs. Patients managed via initial surveillance were compared to those who underwent upfront resection. METHODS: A prospectively maintained institutional database was used to identify patients who underwent surgical resection for a SPT between 1988 and 2018. Data on clinicopathological features and outcomes were collected and analyzed. RESULTS: Seventy-eight patients underwent surgical resection for SPT during the study period. The mean age was 34.0 ± 14.6 years and a majority were female (N = 67, 85.9%) and white (N = 46, 58.9%). Thirty patients (37.9%) were diagnosed incidentally. Imaging-based presumed diagnosis was SPT in 49 patients (62.8%). A majority were located in the body or tail of the pancreas (N = 47, 60.3%), and 48 patients (61.5%) underwent a distal pancreatectomy. The median tumor size was 4.0 cm (IQR, 3.0-6.0), nodal disease was present in three patients (3.9%), and R0 resection was performed in all patients. No difference was observed in clinicopathological features and outcomes between patients who were initially managed via surveillance and those who underwent upfront resection. None of the patients under surveillance had nodal disease or metastasis at the time of resection; however, one of them developed recurrence of disease 95.1 months after resection. At a median follow-up of 36.1 months (IQR, 8.1-62.1), 77 (%) patients were alive and one patient (1.3%) had a recurrence of disease at 95.1 months after resection and subsequently died due to disease. CONCLUSIONS: SPTs are rare pancreatic tumors that are diagnosed most frequently in young females. While a majority are benign and have an indolent course, malignant behavior has been observed. Surgical resection can result in exceptional outcomes.

Disparities in the Use of Chemotherapy in Patients with Resected Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Introduction of effective systemic therapies for pancreatic ductal adenocarcinoma (PDAC) has demonstrated survival benefit. However, chemotherapy remains underutilized in these patients. We sought to investigate the implications of disparities on the trends in utilization of chemotherapy. METHODS: A retrospective study using the Surveillance, Epidemiology, and End Results (SEER) database identified patients who underwent surgical resection for PDAC from 1998 to 2014. Clinicopathologic, demographic, racial, and geographical factors were analyzed to assess associations with receipt of chemotherapy and disease-specific survival. RESULTS: A total of 15,585 patients were included in the study. A majority (N = 9953, 63.9%) received chemotherapy. Factors associated with poorer odds of receiving chemotherapy included older age (p < 0.001), African-American race (p = 0.003), and living in the Southwest region of the USA (p < 0.001). Married patients were at higher odds of receiving chemotherapy (all p < 0.001). Receipt of chemotherapy was independently associated with improved disease-specific survival (p < 0.001). CONCLUSIONS: Receipt of chemotherapy results in an improved survival in patients with resected PDAC. Demographic, racial, and geographic factors influence the rate of receipt of chemotherapy. Despite prior reports, these trends have not changed over the recent decades.

The impact of high body mass index on patients undergoing robotic pancreatectomy: A propensity matched analysis.

BACKGROUND: Patients with high body mass index are associated with a higher risk of complications after open pancreatectomy. We aimed to investigate the perioperative outcome for patients with high body mass index after robotic pancreatectomy. METHODS: This is a retrospective, propensity-score matched cohort analysis. From our prospectively maintained database, we identified consecutive patients with body mass index >25 who underwent robotic pancreatectomy between January 2016 and December 2018. Propensity score matching with open pancreatectomy was applied in 1:2 fashion based on age, gender, American Society of Anesthesiologists classification, surgery type, histology, neoadjuvant therapy, and body mass index during the same study period. RESULTS: A total of 127 patients were included. The mean age for all patients was 61.7 ± 12.8 years and 65 (51.2%) were male. Median body mass index was 29.9 (interquartile range, 27.0-31.8) for both groups. Propensity score matching provided equally distributed general demographic and clinicopathological factors. Robotic pancreatectomy was associated with decreased blood loss (100 mL vs 300 mL, P < .001) and shorter hospital stay (7 vs 9 days, P = .019). CONCLUSION: Robotic pancreatectomy is associated with decreased blood loss and shorter length of hospital stay in overweight patients. Robotic approach may help alleviate morbidity in overweight patients undergoing pancreatectomy.

Internal standards in regulated bioanalysis: putting in place a decision-making process during method development.

It is common practice to utilize an internal standard (IS) to minimize variance in bioanalytical assays employing liquid chromatography coupled to mass spectrometry. For assays to be deployed in regulated drug development studies, ensuring the IS will compensate for differences in recovery, liquid handling and ionization efficiency should be determined early in the method development process. In this perspective article, we outline key considerations when selecting an IS and propose experiments to perform within the method development phase to demonstrate suitability of the IS within the assay prior to validation. Finally, a series of case studies will be presented, which illustrate analytical challenges related to internal standardization that we have observed in our laboratory.

Design, synthesis and biological evaluation of indane derived GPR40 agoPAMs.

GPR40 (FFAR1 or FFA1) is a G protein-coupled receptor, primarily expressed in pancreatic islet ß-cells and intestinal enteroendocrine cells. When activated by fatty acids, GPR40 elicits increased insulin secretion from islet ß-cells only in the presence of elevated glucose levels. Towards this end, studies were undertaken towards discovering a novel GPR40 Agonist whose mode of action is via Positive Allosteric Modulation of the GPR40 receptor (AgoPAM). Efforts were made to identify a suitable GPR40 AgoPAM tool molecule to investigate mechanism of action and de-risk liver toxicity of GPR40 AgoPAMs due to reactive acyl-glucuronide (AG) metabolites.

Identification and typing of Yersinia enterocolitica and Yersinia pseudotuberculosis isolated from human clinical specimens in England between 2004 and 2018.

PurposeandMethodology. Epidemiological and microbiological data on Yersinia enterocolitica (n=699) and Yersinia pseudotuberculosis (n=35) isolated from human clinical specimens in England between April 2004 and March 2018 were reviewed. Traditional biochemical species identification and serological typing results were compared with species identifications and serotypes derived from whole-genome sequencing (WGS) data for a sub-set of these isolates (n=179).Results. Most Y. enterocolitica isolates were from faecal specimens (74.4%) from adults (80.7%) and 50.7  % of isolates were from male patients. Most Y. pseudotuberculosis isolates were from blood cultures (68.6%) from adults (91%) and 60.0  % of isolates were from male patients. All sequenced isolates of Y. enterocolitica (n=158) and Y. pseudotuberculosis (n=21), as well as isolates belonging to other Yersinia species (n=21), were correctly identified from genomic data using a kmer-based identification approach. Traditional phenotypic serotyping typed 82/158 and 12/21 isolates of Y. enterocolitica and Y. pseudotuberculosis, respectively, while 118/158 and 21/21 isolates of Y. enterocolitica and Y. pseudotuberculosis, respectively, were typed by the genome-derived serotyping method. In addition, WGS data provided a multi-locus sequence type profile and virulence gene profile for all isolates.Conclusion. The use of WGS for typing Y. enterocolitica and Y. pseudotuberculosis at Public Health England will facilitate the monitoring of animal-to-human transmission of these important foodborne pathogens in the UK and improve public health surveillance of the pathogenic lineages.