bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal subset-specific Pten-deficient mice do not exhibit deficits in sensorimotor gating processes
Authors: Binder Matthew S. , Nolan Suzanne O. , Lugo Joaquin N.
Published: October 2019

Background: Deficits in sensorimotor gating have been reported in individuals with autism spectrum disorder (ASD), as well as in ASD murine models. However, this behavior has been rarely examined in the neuronal subset-specific (NS)-Pten knockout (KO) model of ASD. NS-Pten KO mice exhibit hyperactivity of the PI3K/AKT/mTOR signaling pathway which is implicated in the onset of autistic deficits. This study investigates the potential relationship between PI3K/AKT/mTOR signaling and deficits in sensorimotor gating.   

Methods: To assess sensorimotor gating in NS-Pten KO mice we utilized a three-day paradigm. On day 1 (habituation) the mice were administered 80 repetitions of a 120-dB startle stimulus. On day 2, prepulse inhibition was measured with 90 trials of the startle stimulus that was paired with a smaller (70, 75, or 80 dB) prepulse stimulus. Day 3 was assessed one week later, consisting of randomized startle trials and trials with no stimulus and was used to determine the startle threshold.

Results: No significant difference between NS-Pten KO or wildtype (WT) mice was found for habituation (p > 0.05). No significant differences were found between groups when assessing the percentage of prepulse inhibition at 70, 75, and 80 dB (p > 0.05). There was also no difference in startle threshold between groups (p > 0.05).

Conclusion: Our study found that the NS-Pten KO model does not display significant deficits in sensorimotor gating processes. The present findings help to elucidate the relationship between PI3K/AKT/mTOR hyperactivation and sensory reactivity.
Feline alimentary lymphoma: a guide to cytological and histopathological diagnosis for the general practitioner
Authors: Irving Jennifer , Dobromylskyj Melanie J , Holmes Emma
Published: October 2019

Lymphoma is the most common neoplasm in domestic cats and alimentary lymphoma is now the most common anatomical site. This article aims to highlight and explain the shift from FeLV-positive multicentric to FeLV-negative alimentary lymphomas, and to explain the cytological and histopathological methods of diagnosing and classifying alimentary lymphoma, in a way that is useful to the general practitioner. Alimentary lymphoma (AL) in felines can be histologically graded into low-, intermediate- and high-grade lymphoma. Low-grade AL has a fair prognosis, while intermediate- and high-grade have poorer prognoses. Transmural invasion by neoplastic lymphocytes also carries a poor prognosis. Large granular lymphocyte lymphoma is a histological sub-classification determined by cell morphology, can be of any grade, and the prognosis is very poor.
Clinical decision making and the challenges of responding to mental health needs
Authors: Hutchison Trudy , Lees Carolyn , Lotto Robyn , White Alison , Harris Ron
Published: October 2019

The paramedic service responds to emergency calls for a variety of reasons, many relating to mental health concerns. This qualitative study aims to explore the views and experiences of student paramedics in relation to clinical decision making for mental health calls. Focus groups were used to investigate the participants' perspectives. Thematic analysis was used to organise data and identify key issues. Findings suggested some disparity between what paramedic students were prepared for and the reality of public need. Clinical decision making in relation to those with mental health problems was significantly influenced by the current provision of mental health services and the lack of mental health-specific education for student paramedics. Current changes to the paramedic programme make this an opportune time for a review of curriculum content.
From Casualty to A&E: a pleasant surprise
Authors: Price Jolyon
Published: October 2019

After first training as an actor and being strongly influenced by the images of paramedicine depicted on television, 2nd year student paramedic, Jolyon Price, shares his preconceptions about paramedicine and the reality he is now discovering
Cooperative functioning of salicylic acid and phenylalanine ammonia lyase in barley plant challenged with spot blotch and powdery mildew diseases
Authors: Al-Daoude Antonious , Al-Shehadah Eyad , Shoiab Amina , Jawhar Mohammed , Arabi Mohammed Imad Eddin
Published: October 2019

Salicylic acid (SA) and phenylalanine ammonia-lyase (PAL) have been suggested as important signals during plant resistance towards several fungal pathogens. In this work, to better understand the defense responses initiated by resistant and susceptible barley genotypes challenged with a necrotrophic (Cochliobolus sativus; Cs) and a biotrophic (Blumeria graminis; Bg) pathogens, the relative contributions of SA and PAL were investigated at early time points of infection. SA signaling was activated in both genotypes 24 hours post infection (hpi) as compared with the non-inoculated plants. However, with or without pathogen pretreatment, SA significantly increased (P = 0.001) in the resistant genotype that contained three-folds of total SA in comparison with the susceptible one for Bg. Reverse transcription-polymerase chain reaction (RTPCR) analysis revealed that PAL expression increases in the resistant and susceptible genotypes over the inoculation time points, with the maximum expression observed 48 hpi. PAL expression was paralleled by an increase in SA content in leaves as shown by the test coincidence (F3, 32 = 1.09, P = 0.49 for Cs and F3, 32 = 1.03, P = 0.48 for Bg). Results showed that the cooperatively function of SA and PAL in barley responses to both Cs and Bg appeared to be dependent on the plant genotype, and that SA signaling and PAL play a role in barley interactions with these both pathogens. This study might increase our understanding for a deeper molecular research on barley defense responses against pathogens with different lifestyles.
Faktor Risiko Eksternal terhadap Keterlambatan Motorik Kasar pada Anak Usia 6-24 Bulan: Studi Kasus-Kontrol
Authors: Kurniawan Kristian , Mangunatmadja Irawan
Published: October 2019

Latar belakang. Keterlambatan perkembangan merupakan kondisi ketidakmampuan anak mencapai milestone perkembangan seusianya. Perkembangan motorik kasar dapat memprediksi tingkat maturasi sistem saraf pusat fungsional sehingga keterlambatan pada domain ini akan berdampak pada keterlambatan penguasaan domain perkembangan lainnya. Tujuan. Mengidentifikasi faktor risiko eksternal terhadap keterlambatan motorik kasar pada anak 6-24 bulan.Metode. Penelitian dilakukan dengan metode kasus-kontrol pada populasi anak usia 6-24 bulan menggunakan data primer yang diperoleh di RSUPN Cipto Mangunkusumo Kiara, Jakarta Pusat dan Klinik Anakku, Jakarta Selatan.Hasil. Diperoleh subjek sebesar 128 anak, dengan perbandingan kasus-kontrol 1:1 pada kelompok rentang usia yang sesuai. Dari hasil analisis pearson kai-kuardat diperoleh 2 faktor signifikan terhadap keterlambatan motorik kasar, yakni: status gizi kurang/buruk (p<0,001; OR=6,576; IK 95%=2,705-13,986) dan tidak diberikannya ASI eksklusif (p=0,032; OR=2,180; IK95%=1,065-4,460).Di sisi lain, faktor urutan anak, usia ibu saat kehamilan, dan cara kelahiran menunjukkan hasil tidak bermakna terhadap keterlambatan motorik kasar. Kemudian, dari analisis multivariat dengan regresi logistik biner, menunjukkan bahwa status gizi kurang/buruk merupakan faktor paling berpengaruh terhadap kejadian keterlambatan motorik kasar pada anak (p<0,001; OR=6,159; IK 95%=2,512-15,099). Kesimpulan. Status gizi kurang/buruk merupakan faktor prediktor keterlambatan motorik kasar yang paling berpengaruh.
51 Eosinophilic Pancreatitis as a Benign Mimicker of Pancreatic Neoplasm: A Systematic Review
Authors: Kuftinec Gabriela , Barkin Jodie A. , Nemeth Zsuzasanna , Barkin Jamie S.
Published: October 2019

INTRODUCTION:

Eosinophilic pancreatitis (EP) is a rare form of pancreatitis characterized by diffuse infiltration of the pancreas with eosinophils & elevated serum immunoglobulin E levels. Diagnosis is clinically difficult as endoscopic/radiographic findings often mimic neoplasm, leading to surgical resection. The aim of this review is to chronicle all cases of EP, describe clinical & radiographic presentation & outcome.

METHODS:

A systematic search was performed with an experienced librarian of PubMed, Embase & Scopus for search terms of “Eosinophilic Pancreatitis” from 1975–4/19/2019. We included all case reports, series, cohorts & randomized studies with diagnosis of EP. Exclusion criteria were articles with other attributable pancreatitis etiology, fetal EP cases, or non-English language. All articles were reviewed by 2 authors. Data was collected on clinical & radiographic findings, comorbidities & outcome.

RESULTS:

The search yielded 1379 results of which 18 case reports/series of 23 total patients were included. 17/23 (73.9%) were men, mean age 43.6 ± 17.0 years (range 14–74). Most common symptoms at presentation were abdominal pain (18/23), jaundice (9/23), weight loss (6/23), nausea/vomiting (6/23), & recurrent acute pancreatitis (2/23). Comorbidities included Diabetes Mellitus (2/23) & asthma/allergies (4/23). Imaging revealed abnormalities (mass, hypodensity, or enlargement) located in the pancreatic head (13/23), body (2/23) & tail (3/23). A pancreatic mass was most commonly found (11/23), followed by pancreatic enlargement (8/23), pancreatic duct dilatation (5/23) & bile duct dilatation (8/23). 4/23 patients had a pseudocyst; none had necrosis. Pathology showed prominent eosinophilic infiltrate in all cases, with 5/23 having few lymphocytes & 9/23 with diffuse inflammatory infiltrates. 16/23 patients underwent surgical resection with EP diagnosis made post-operatively. 5/23 patients had complications (4/23 resolved with steroids; 1 died from systemic hypereosinophilia with renal failure & chylothorax).

CONCLUSION:

EP presents more commonly in men in a 3:1 ratio in the 5th decade. EP should be considered in patients with abdominal pain, jaundice, & weight loss with imaging of a pancreatic mass or enlargement, or ductal dilation. EP masquerades as malignancy; however, diagnostic clues to EP include peripheral eosinophilia & presence of diabetes or asthma/allergies. Awareness of EP may allow for potential non-operative diagnosis, avoidance of surgery, & appropriate medical therapy.
62 Surveillance of High-Risk Individuals for Pancreatic Cancer With EUS and MRI: A Meta-Analysis
Authors: Kogekar Nina , Diaz Kelly E. , Weinberg Alan D. , Lucas Aimee
Published: October 2019

INTRODUCTION:

Early detection of pancreatic cancer is of interest given the significant morbidity and mortality of this disease. The International Cancer of the Pancreas Screening (CAPS) Consortium guidelines recommend surveillance of high-risk individuals (HRI) with a history of familial pancreatic cancer or carriers of genetic cancer syndrome mutations. Surveillance is typically performed with endoscopic ultrasonography (EUS) and/or magnetic resonance imaging (MRI). The aim of this study is to assess the yield of pancreatic cancer surveillance programs of HRI and compare the yield of EUS and MRI.

METHODS:

The MEDLINE and Embase (Ovid) databases were searched for prospective studies published up to April 11, 2019 using EUS and/or MRI to screen HRI for pancreatic cancer. Baseline detection of focal pancreatic abnormalities, cystic lesions, solid lesions, high-risk lesions (defined as pancreatic intraepithelial neoplasia grade 3, intrapapillary mucinous neoplasia with high grade dysplasia, or T1N0M0 adenocarcinoma), and pancreatic adenocarcinoma were recorded, as were surgeries performed. Weighted pooled detection rates of outcomes were calculated and were compared between EUS and MRI using random effects modeling.

RESULTS:

A total of 1109 studies were reviewed and 24 were included in analysis, representing 2112 patients who underwent screening. The weighted pooled rate of focal pancreatic abnormalities detected on baseline screen by EUS (0.34, 95% CI 0.30–0.37) was significantly higher (P = 0.006) than by MRI (0.31, 95% CI 0.28–0.33). There were no significant differences between EUS and MRI for detection of other outcomes, including cysts, high-risk lesions, or pancreatic cancer (Table 1). The overall weighted pooled detection rate of high-risk lesions on baseline screening (regardless of imaging modality) was 0.0090 (95% CI 0.0022–0.016), corresponding to a number-needed-to-screen (NNS) of 111 patients to detect one high-risk lesion. The overall weighted pooled detection rate for pancreatic adenocarcinoma was 0.012 (95% CI 0.0051–0.018) and the surgery rate was 0.054 (95% CI 0.045–0.063) (Table 2).

CONCLUSION:

Surveillance programs are successful in detecting high-risk precursor lesions with a NNS compatible with existing screening and surveillance programs. No differences between EUS and MRI were noted in the detection rate of high-risk lesions or pancreatic cancer, which supports the use of either imaging study in surveillance programs.
84 The Role of the GNAS Oncogene in the Immune Microenvironment of Intraductal Papillary Mucinous Neoplasm
Authors: Hernandez-Barco Yasmin G. , Ferrer Christina , Ngo Kenneth , Schiferle Erik , Patra Krushna , Fernandez-Del Castillo C. , Mino-Kenudson Mari , Mostoslavsky Raul , Demehri Shadmehr , Bardeesy Nabeel
Published: October 2019

INTRODUCTION:

Pancreatic ductal adenocarcinoma (PDA) arises from two main precursor lesions, pancreatic intraepithelial neoplasia (PanIN), and intraductal papillary mucinous neoplasia (IPMN). Extensive studies of The PanIN-to-PDA sequence has identified the immunosuppressive microenvironment and recruitment of pro-tumorigenic inflammatory cells as a key hallmark, whereas the immune microenvironment of IPMN remains unexplored. This proposal aims to test the core hypothesis that GNAS-driven IPMN precursor lesions display a distinct inflammatory program that contributes to tumor initiation and progression.

METHODS:

We developed novel genetically engineered mouse models (GEMMs) harboring combinations of the most frequent mutations found in human IPMN of benign and malignant disease. We also utilized genetically characterized and carefully demographically annotated human tissues and perform immunological characterization by immunofluorescence, immunohistochemistry and flow cytometry. We also performed cytokine arrays and early functional studies from the preliminary data generated from this characterization.

RESULTS:

We identified that GNAS-mutant tumors are replete with T-cells and dendritic cells, as compared to the virtual absence of these cell types in “classic” PanIN-PDA (3.0 ± 0.6 vs. 81.4 ± 25.4, P < 0.03) (Figure 1). With the switching off of GNAS, there is an influx of CD8+ T cells 7.2 ± 1.9 vs. 25.4 ± 4.9 (P < 0.004) and loss of CD206+ macrophages 62.6 ± 10.7 vs. 22.9 ± 6.8, P < 0.02 (Figure 2). We observe that GNAS is a potent regulator of these differences through immunomodulatory cytokines, IL33, Arg1; along with the upregulation of CD105 and Reg3G. The human-relevance of our findings is supported by our initial pilot studies of human pancreatic tumor specimens. These early studies indicated that IPMNs with GNAS mutations (alone or in combination with KRAS) have increased CD3+ and CD4+ T cell infiltrate compared to those lacking GNAS mutations, consistent with our murine data (Figure 3).

CONCLUSION:

GNAS mutant IPMNs display a distinct immune infiltrate as compared to classic PanIN-PDA lesions, suggesting that these tumors will likely be amenable to immunopreventative and immunotherapeutic strategies. These studies will link immune dynamics to tumor growth, which is profoundly induced in GNAS-mutant IPMN. Deciphering the interplay between the evolving neoplastic cells and immune system underlying these cystic tumors can inform the development of strategies to prevent or treat GNAS-mutant IPMN.
88 Racial and Gender Disparities Among Obese Patients With Pancreatic Cancer: A Trend Analysis From 2004–2018 in the United States
Authors: Twohig Patrick , Butt Muhammad , Gardner Timothy , Sandhu Sonia , Sandhu Dalbir S.
Published: October 2019

INTRODUCTION:

Obesity increases the risk of pancreatic cancer by up to 50%. Epidemiologic studies indicate that disparities exist in obesity trends across different demographics in the United States. This is suspected to be from modifiable risk factors, comorbidities, and differences in the gut microbiome, along with social determinants of health such as a lack of access to high-volume treatment centers. Our aim is to determine if variation exists in the demographic of obese pancreatic cancer patients over the last 15 years.

METHODS:

We performed a retrospective analysis in the IBM Explorys database (1999–2018), a pooled, de-identified clinical database of unique patient records from 26 health care networks and 300 hospitals across the United States. At the time of analysis there were 63,744,040 patients, of which 9,620 were adults (>18 years old) with both pancreatic cancer and obesity (BMI >30). Patient populations were identified using SNOMED and ICD codes. Cochrane-Armitage testing was performed to analyze trends in obesity among pancreatic cancer patients between 2004–2018. Subgroup analysis for gender, age, race, and mortality rate were assessed.

RESULTS:

The percentage of obese patients with pancreatic cancer increased over the 15-year period (2.5% to 8.5%); P = <0.0001). Rates of obesity among pancreatic cancer patients increased among females (P = 0.0004), individuals under age 65 years (P = 0.0002), and all-races, but especially for African Americans (P = 0.0007) and those in minority groups.

CONCLUSION:

Pancreatic cancer is becoming more common among patients who are obese, younger, female, and not Caucasian. African Americans have been shown to have a higher incidence and mortality from pancreatic cancer. This disparity has been attributed to lifestyle habits, co-morbidities including obesity, and a lack of access to high-volume treatment centers. However, differences in gene expression also increase the risk. Although these could be therapeutic targets, low minority enrollment in research studies is a barrier to progress. This is the first study to assess demographic trends in obese pancreatic cancer patients over the last 15 years. Awareness of disparities in pancreatic cancer and applying more precise population approaches to those at increased risk are essential to improving future outcomes. An integrated approach should include increased health care access and recruitment in research studies for minority groups.
133 Impact of Clostridium difficile Infection in Patients With Ulcerative Colitis and Crohn's Disease: A Comparative Analysis
Authors: Khan Ahmad , Sohail Abdullah , Berry Davis B. , Gupta Kamesh , Goyal Hemant
Published: October 2019

INTRODUCTION:

Patients with Inflammatory bowel disease (IBD) are at increased risk of acquiring Clostridium difficile infection (CDI) that leads to an increased in morbidity and mortality. The aim of our study is to compare the outcomes of CDI on in-hospital mortality and resource utilization among adult hospitalized patients with Ulcerative colitis (UC) and Crohn's disease (CD) without CDI in the USA.

METHODS:

A retrospective cohort analysis using the 2004–2014 Nationwide Inpatient Sample is performed. Adult hospitalized patients with IBD (subgrouped into UC and CD) with CDI were identified using validated ICD-9 codes. Outcomes include in-patient mortality, hospital charges, and length of stay (LOS) among two groups. Confounding factors such as age, sex, ethnicity, insurance status, hospital characteristics, and CDI are adjusted with univariate and multivariate regression models.

RESULTS:

Out of total 514,889 UC patient's hospitalizations, 24,783 (4.81%) discharges were related to CDI with mean age 60 ± 3 years and 60% female population. In comparison to that, out of 878,896 CD hospitalizations, 13,120 (1.49%) were related to CDI (see Table 1). In terms of outcomes, patients with UC + CDI had increased mortality (adjusted OR 3.003, 95% CI 2.65–3.39), P = 0.00 and LOS (8.0 days vs 6.5 days) and mean total charges difference of $16,739.33 as compared to UC patients without CDI. However, in contrast to CD patients with CDI, there was no significant difference in mortality (adjusted OR 0.60, 95% CI 0.40–0.90, P = 0.021), mean LOS (6.57 days vs 6.15 days) and total hospitalization charges ($34,137.16 VS $33,020.09) in comparison to CD patients without CDI.

CONCLUSION:

Our study results provide important insight on the effect of CDI on the outcome in patients with IBD. Surprisingly, we found that among US adults with UC and CD-related hospitalizations, CDI is associated with significantly subgrouped in-hospital mortality and healthcare utilization only in patients with UC and CDI infection did not appear to affect the outcomes in the CD-related hospitalizations.
179 Cost-Effectiveness Analysis of Starting a Fecal Microbiota Transplantation (FMT) Unit for the Treatment of Recurrent C. difficile Infection Compared With Antibiotic Therapy
Authors: Shaffer Seth , Rubin David T. , Targownik Laura , Singh Harminder , Witt Julia , Kao Dina , Lee Christine , Bernstein Charles
Published: October 2019

INTRODUCTION:

Despite the proven efficacy of FMT in recurrent Clostridioides difficile infection (CDI), many hospitals and health regions have yet to establish a program for its use. We assessed the cost effectiveness of FMT (including start-up costs) for recurrent CDI (rCDI) to determine how many patients would need to be treated to make this approach cost effective for a centre.

METHODS:

We conducted a decision-analytic model comparing six separate strategies for the management of the third recurrence of CDI: each FMT modality (via capsule, enema (Figure 1), or colonoscopy) versus vancomycin, fidaxomicin, and a combined antibiotic model of vancomycin followed by fidaxomicin. At the end of the decision tree, the patient would be in one of 4 health conditions: healthy, mild-to-moderate CDI, post-colectomy, or death. Costs for a FMT start up centre (preparation of donor material, screening costs, etc. Table 1) were calculated over 10 years, and discounted at 5%/year. Our primary outcome was to estimate how many patients would have to be treated with FMT on an annual basis to make a FMT centre cost-effective (WTP of $50,000/QALY) versus antibiotic therapy for the treatment of rCDI.

RESULTS:

To make any of the FMT modalities cost-effective compared with vancomycin treatment, 26 patients would have to be treated with FMT via enema annually, 32 via capsule, and 31 via colonoscopy (Figure 2). In our base case analysis of all three FMT modalities treating 40 patients/year compared with vancomycin, FMT via enema was the most cost-effective strategy with an incremental cost-effectiveness rate (ICER) of $21,366.03, followed by ICERs of $37,911.01, and $37,743.24 via capsule and colonoscopy, respectively. Treatment with fidaxomicin in these patients was both more expensive and less effective than FMT, as it was dominated by all 3 FMT modalities. When patients were initially treated with vancomycin followed by fidaxomicin if they failed vancomycin, FMT via enema dominated.

CONCLUSION:

FMT, including start-up and ongoing costs, is cost-effective compared to conventional antibiotics in the treatment of recurrent CDI. Only 26 patients are required to be treated each year with FMT via enema for it to be a cost-effective strategy for rCDI. In healthcare regions where FMT is not currently a therapeutic option, this analysis suggests that despite its higher initial costs, starting up a FMT unit will lead to healthcare savings over time.
189 Colon Ischemia Is Associated With a Low Rate of Subsequent C. difficile-Associated Diarrhea
Authors: Zheng Kevin , Gnanapandithan Karthik , Feuerstadt Paul , Brandt Lawrence , Aroniadis Olga
Published: October 2019

INTRODUCTION:

Studies suggest an association between colon ischemia (CI) and C. difficile-associated diarrhea (CDAD). It is unclear, however, if CI disease severity, attendant antibiotic use, or both are risk factors for CDAD. The aim of our study was to answer these questions.

METHODS:

A retrospective cohort study was performed on patients admitted to Montefiore Medical Center and Yale New Haven Hospital between 2005 and 2017 with a diagnosis of biopsy-proven CI. Patients who developed CDAD within 90 days of diagnosis of CI were identified. Various epidemiological factors were included (e.g., demographics, medical history, medication exposures, outcome, etc.). CDAD was defined by diarrhea and a positive C. difficile toxin assay. Patients with prior CDAD diagnosed within 90 days before admission for CI were excluded. Severity of CI was defined according to ACG Clinical Guideline recommendations. Bivariate analyses were performed to compare incidence of CDAD between groups with mild, moderate, and severe CI. Additionally, bivariate analyses were performed to compare epidemiological factors between cohorts with and without CDAD.

RESULTS:

Of 853 patients with biopsy-proven CI, 16 (1.9%) acquired CDAD within 90 days. There was a trend for those who developed CDAD to be older than those who did not (75 [64,82] vs 70 [61,80] years, respectively; P = 0.37; Table 1). Severity of CI was not significantly associated with incidence of CDAD (mild: 0%; moderate: 1.5%; severe: 2.1%; P = 0.63). Antibiotic use was more common in patients who developed CDAD than in those who did not (80% vs 69.3%), however, this finding was not statistically significant (P = 0.57; Table 1). Demographic data, ICU admission, length of stay, inpatient PPI use, and colectomy for CI were not significantly associated with CDAD development (Table 1).

CONCLUSION:

Typically, antibiotic use is strongly associated with CDAD but the similar incidence of CDAD between those who did and did not receive antibiotics in our cohort remains unexplained. One possible explanation is that the unique type of injury and healing of the colon wall in CI along with other factors play an important role independent of antibiotic use. The low CDAD incidence might reflect a compromised immune epithelial barrier, allowing more serologically-driven antibodies access to the bowel lumen, thereby minimizing CDAD development by (neutralizing) toxin A and B. Larger studies are needed to better understand the relationship between CDAD and CI.
194 Cadazolid vs. Vancomycin for Treatment of Clostridioides difficile Infection: Systematic Review With Meta-Analysis
Authors: Aziz Muhammad , Weissman Simcha , Fatima Rawish , Alshati Ali , Malik Fahad , Rajani Sabih , Eid Albert , Nawras Ali
Published: October 2019

INTRODUCTION:

Current guidelines recommend the use of vancomycin for the initial treatment of Clostridioides difficile infection (CDI). Cadazolid, an experimental drug, has been utilized and compared in several studies with varying results.

METHODS:

A systematic literature search was performed using the following electronic databases [Medline, Google Scholar, and Cochrane] for eligible studies. Randomized controlled trials (RCTs) comparing cadazolid with vancomycin for CDI treatment were included. Demographic variables and outcomes (CDI resolution, CDI recurrence, adverse events) were collected.

RESULTS:

Two studies with three RCTs met the inclusion criteria with a total of 1283 patients with CDI who received either cadazolid 250 mg twice daily (624 patients) or vancomycin 125 mg four times daily (659 patients). Clinical cure rate at the end of treatment was not statistically significant (pooled odds ratio (OR) = 0.82; 95% confidence interval (CI) = 0.61 to 1.11; P = 0.20; I2 = 0%). Sustained clinical response at clinical follow-up was also not significantly different (pooled OR = 1.14; 95% CI = 0.91 to 1.43; P = 0.27; I2 = 0%). Cadazolid had a lower recurrence rate than vancomycin (pooled OR = 0.71; 95% CI = 0.52 to 0.98; P = 0.04; I2 = 13%).

CONCLUSION:

To our knowledge, this is the first systematic review and meta-analysis comparing the efficacy, recurrence rates, and safety profile of cadazolid and vancomycin, for the treatment of CDI. Our results indicate that cadazolid did not differ significantly from vancomycin in terms of achieving a higher clinical cure rate, sustained clinical response rate, or fewer adverse effects. However, cadazolid was associated with a lower rate of recurrences than vancomycin. Clostridioides difficile is a challenging pathogen to treat from a clinical perspective. In the last two decades, there has been a dramatic increase in both the incidence and severity of CDI. Hence, while cadazolid and vancomycin are generally safe and well tolerated, cadazolid had a lower CDI recurrence rate than vancomycin thus meriting its further evaluation.
203 Outcomes of Colon Self-Expandable Metal Stents Placed for Malignant and Benign Obstruction at a Tertiary Care Academic Center
Authors: Johannes Andrew , Benson Mark , Akhter Ahmed , Nelsen Eric , Pfau Patrick , Soni Anurag , Reichelderfer Mark , Gopal Deepak
Published: October 2019

INTRODUCTION:

Endoscopically placed self-expandable metal stent (SEMS) is a minimally invasive treatment for the management of colonic obstruction. SEMS are increasingly being used in benign strictures as a bridge to one step surgery, to avoid ileostomy. There is limited data regarding efficacy, complications and outcomes in benign disease. The aim of this study was to review long- and short-term clinical success of SEMS use for colonic obstruction at our center.

METHODS:

We retrospectively reviewed all the patients who underwent colonic SEMS placement over a fourteen-year period (August 2004 through November 2018) at our academic center. Demographics including age, gender, indication (malignant and benign), technical success, clinical success, complications (perforation, stent migration), mortality, and outcomes were recorded.

RESULTS:

Fifty-six patients underwent colon SEMS over a 14-year period. Forty-eight cases were for malignant indications, 8 were for benign conditions. The benign strictures included post-surgical anastomotic narrowing's (n = 2), extrinsic fibroid compression (n = 1) and diverticular disease (n = 5). Thirty-eight of the malignant cases were due to intrinsic obstruction from primary or recurrent colon cancer; 10 were from extrinsic compression. Fifty strictures occurred on the left side, 6 occurred on the right. The total malignant case (n = 48) procedural success rate was 96% vs. 100% for benign cases (P = 1.0, NS). Overall complication rate was 3.6%: No complications were observed in the malignant group vs. 2 of 8 (25%) for benign obstruction (1-perforation, 1-stent migration) (P = 0.02). When stratifying complications of perforation and stent migration there was no significant difference between the two groups (P = 0.14, NS).

CONCLUSION:

Colon SEMS remains a worthwhile option for colonic obstruction related to malignancy and has a high procedural and clinical success rate. Benign indications for SEMS placement appear to have similar success to malignant. While there appears to be a higher overall complication rate in benign cases, it is limited by sample size. When evaluating for perforation alone there does not appear to be any significant difference between the two groups. SEMS placement may be a practical option for indications other that malignant obstruction. Interventional endoscopists should be aware and discuss the risk for complications in setting of benign conditions. Indications in these cases should be discussed in a multi-disciplinary fashion with colorectal surgery.
204 Impact of Antibiotic Therapy on the Development and Response to Treatment of Immune Checkpoint Inhibitor-Mediated Diarrhea and Colitis
Authors: Abu-Sbeih Hamzah , Herrera Lauren Nicholas , Altan Mehmet , Chaftari Anne-Maria , Okhuysen Pablo , Jenq Robert , Wang Yinghong
Published: October 2019

INTRODUCTION:

The gut microbiome impacts the efficacy of immune checkpoint inhibitor (ICI) therapy and the development of ICI-mediated diarrhea and/or colitis (IMDC). Antibiotic therapy, especially that with anaerobic activity, has profound effects on the gut microbiome. Therefore, we sought to assess the effect of antibiotics on the development of IMDC.

METHODS:

Patients who received ICI therapy from January 2016 to January 2018 were examined retrospectively. A Cox regression model was used to assess factors associated with overall survival.

RESULTS:

A total of 826 patients were included. Of these patients, 51.6% received inhibitors of programmed cell death protein-1 or its ligand, 32.0% received inhibitors of cytotoxic T-lymphocyte-associated antigen-4, and 16.5% received a combination of the two. IMDC developed in 52.5% of the patients after a median of 8 weeks. Overall, 569 patients (68.9%) received antibiotic therapy. Antibiotic use at any time was associated with reduced IMDC occurrence and recurrence rates but also with frequent hospitalization and intensive care unit admission for IMDC as well as increased IMDC severity. Compared with patients who received antibiotic therapy only before ICI therapy initiation, those receiving it after ICI had a higher IMDC rate and more often needed immunosuppressive therapy and hospitalization for IMDC. Antibiotics with anaerobic activity were included in 51% of the antibiotic therapy regimens and were associated with increased immunosuppressant use, hospitalization, intensive care unit admission for IMDC, and IMDC grades (Table 1). Forty-one patients received empiric prophylactic antibiotic therapy at IMDC onset. These patients more often needed immunosuppressive therapy, intravenous steroids, and infliximab/vedolizumab; had more frequent and longer hospitalization for IMDC and higher IMDC grades; and more frequently had IMDC recurrence than did patients who did not receive antibiotic therapy at the time of IMDC symptom onset (Table 2).

CONCLUSION:

Whereas antibiotic therapy appeared to be protective against IMDC onset, use of antibiotics, especially those with anaerobic activity, after ICI therapy was associated with increased risk of severe IMDC.
212 Retrospective Analysis of Liquid Nitrogen Cryospray Ablation in the Colon
Authors: Battish Raman , Kisiel Kym , Kachaamy Toufic , Vashi Pankaj
Published: October 2019

INTRODUCTION:

Liquid nitrogen cryospray ablation (CA) is a modality for targeted destruction. Ablation of malignant strictures, premalignant conditions, and for hemostasis have been described. Active venting is required for use of this device in the GI tract due to rapid expansion of liquid nitrogen to gas, thus restricting use. There is limited data on liquid nitrogen CA in the colon.

METHODS:

Retrospective analysis of electronic health record, billing and endoscopic databases from 10/1/2013 to 6/1/2019. This study was determined to be IRB exempt by our research committee.

RESULTS:

17 subjects underwent 28 CA procedures in the colon. The most common indication was tumor bleeding. The average age of subjects was 56. Dosimetry was typically 3 cycles of 30 seconds per site for tumor bleeding and 10 seconds per site for radiation proctopathy. Treatment for stent patency was 30 seconds per site. The most proximal treated portion of the colon was 30 cm in a subject with colonic stent. All subjects underwent cancer directed treatment and CA was part of a multimodality approach. 9 subjects had radiation treatment prior to CA and four subjects had it following CA. CA has been used as a bridge to chemoradiation in anal cancer and to palliative radiation treatment for tumor bleeding. There were no immediate or delayed complications following procedures. No subjects required hospitalization within 30 days of procedure. CA was effective for hemostasis of tumor bleeding. Tumor bleeding was the indication for 3 of 4 subjects undergoing repeat CA. Stent patency required repeat CA in one subject. The time interval for repeat procedures ranged from 2 weeks to one year. Stent patency was maintained for 17 and 11 months respectively in 2 subjects. Both subjects eventually required placement of a second colonic stent. In this series, when radiation proctopathy was the indication repeat CA was not needed.

CONCLUSION:

Our data suggests CA is technically successful and safe in the colon. Furthermore it can be used as part of multimodality cancer directed treatment without additional complications. Prospective studies are needed to determine optimal interval for repeat treatments for stent patency and tumor bleeding. Other areas that warrant attention regarding CA are analgesic effects, abscopal effect, potential survival benefit, and proximal extent active venting can safely be performed in the colon. This series highlights the safety and efficacy of CA in the colon as part of multimodality cancer treatment.
219 Impact of Hospital Size and Teaching Status on Patients With Clostridium difficile Colitis Treatment Outcomes
Authors: Berry Davis B. , Abougergi Marwan S. , Khan Ahmad , Gupta Kamesh
Published: October 2019

INTRODUCTION:

The efficiency and delivery of care has been at the center of the current healthcare debate and reform. Clostridium Difficile Infection (CDI) is the leading cause of hospital acquired infectious diarrhea. This study sought to investigate the effect of hospital size, urban location and teaching status on in-hospital mortality and resource utilization among patients admitted to hospital with CDI.

METHODS:

This is a retrospective cohort study using the National Inpatient Sample (NIS) 2016. NIS is the largest publicly available all-payer inpatient care database in the United States. Patients were included if they had a principal diagnosis of CDI, and were excluded if they were younger than 18 years. The primary outcome was in-hospital mortality. The secondary outcome was resource utilization as measured by hospital length of stay (LOS) and total hospitalization charges. The exposure of interest was hospital size, urban location and teaching status. Multivariate regression analysis was utilized to account for confounders.

RESULTS:

19,580 patients were included in this study. The mean age was 64 years and 64% of patients were females. Adjusted odds ratios (aOR) and mean differences (aMD) are presented in Table 1. After adjusting for confounders, the odds of in-hospital mortality were similar for patients at rural, urban teaching and urban non-teaching hospitals as well as at small, medium and large hospitals. However, patients treated at urban teaching and non-teaching hospitals had significantly longer LOS compared with those treated at rural hospitals. Similarly, patients treated at large and medium hospitals had significantly longer mean LOS compared with those treated at small hospitals. Patients treated at urban teaching and non-teaching hospitals had significantly higher mean total hospitalization charges compared with those treated at rural hospitals, and patients treated at large and medium hospitals had significantly higher mean total hospitalization charges compared with those treated at small hospitals.

CONCLUSION:

Despite significantly higher resource utilization (LOS and total hospitalization charges) at larger urban teaching hospitals, CDI in-hospital mortality was similar to those treated at small, rural non-teaching hospitals. One possible explanation lies in the complexity of CDI larger teaching referral centers. Another possibility is the variable adherence to C. difficile infection guidelines.
227 A Retrospective Evaluation of Compliance to Clostridium difficile Treatment Guidelines
Authors: Aslam Rida , Tabbaa Hazem , Yarbrough Alex
Published: October 2019

INTRODUCTION:

Nearly half a million Americans suffered from Clostridium difficile (C. diff.) infections in a single year according to a study released by the Centers for Disease Control and Prevention (CDC). Studies indicate that C. diff. has become the most common microbial cause of Healthcare-Associated Infections found in U.S. hospitals driving up healthcare costs in acute care facilities alone. Our goal with this study is to investigate via retrospective chart review over the past 12 months to find out how often proper treatment was administered for patients admitted with a diagnosis of C. diff. infection.

METHODS:

This study is a retrospective chart review on patients admitted between Feb 2018–Feb 2019 at Franciscan Health St James Olympia Fields. Subjects were randomly selected with ICD-10 code for CDI. Age, gender, comorbidities, admission laboratory values, admission and discharge dates, and clinical course were obtained from EMR. The compliance to guidelines was assessed at initial treatment and as subjects further stratified into the categories non-severe, severe and fulminant disease. Compliance to guidelines was determined by type and duration of therapy. Secondary endpoints such as clinical outcomes such as 90-day mortality, therapy escalation and clinical cure which were also evaluated.

RESULTS:

A total of 118 patients were included in this study. This study shows that physician adherence to evidence-based guidelines for treatment of CDI was poor (50%). The study also found that compliance was lower in subjects with severe and fulminant disease. Overall, mortality associated with Clostridium Difficile treatment was 19.4% across all patients diagnosed with CDI regardless of severity of illness.

CONCLUSION:

CDI is a highly morbid condition and places a heavy burden on the healthcare system. Failing to adhere to the guidelines for treatment of Clostridium Difficile is detrimental to patients and results in worse clinical outcomes. This study identified that compliance to treatment guidelines is poor and barriers to compliance still exist despite education and guideline availability. To improve compliance to treatment guidelines in our hospital, we are currently developing an electronic order set through EPIC based on guidelines to allow for accurate treatment delivery and provide better outcomes.
234 Higher Serrated Detection Rate Is Associated With Lower Risk for Post-Colonoscopy Colorectal Cancer
Authors: Anderson Joseph C. , Butterly Lynn F. , Robinson Christina N. , Mackenzie Todd
Published: October 2019

INTRODUCTION:

The serrated pathway may account for a significant proportion of colorectal cancer (CRC). Achieving adequate serrated polyp detection rates (SDR) may reduce the incidence of post colonoscopy CRC (PCCRC). We used data from the New Hampshire Colonoscopy Registry (NHCR) to determine if exams performed by endoscopists who have a clinically significant serrated polyp detection rate (CSSDR) of 7% or greater, proposed by Anderson/Butterly (GIE 2017), had a reduced incidence of PCCRC. In addition, we compared CSSDR to the adenoma detection rate (ADR), the currently used benchmark.

METHODS:

We defined PCCRC as any CRC diagnosed between 6 and 36 months after an exam with an adenoma on index and between 6 and 60 months following a normal exam. Exclusion criteria were any CRC diagnosed at index or within 3 months, incomplete exams, IBD, and genetic syndromes. Clinically significant serrated polyps (CSSP) were defined as any sessile serrated polyp, traditional serrated adenoma, serrated polyp >1 cm anywhere in the colon and any serrated polyp >5 mm proximal to the sigmoid. CSSDR was defined as number of screening exams with at least one CSSP divided by all screening exams. The exposure variable was a CSSDR of 7% and adenoma detection rate of 25%. Cox regression was used to model the risk of PCCRC in terms of the covariates at index exam. Covariates were age, BMI, smoking, index findings (large serrated polyp, advanced adenoma or any adenoma), followup time (months), bowel prep quality, having more than 1 surveillance exam and family history of CRC. We also compared receiver operating characteristics (ROC) for CSSDR 7% to an ADR 25% using probabilities derived from a logistic regression analysis.

RESULTS:

In our sample (142,950 index exams) 75 CRCs were diagnosed during the 6–60 month period (45 CRCs diagnosed between 6–36 months) after the index exam. The hazard ratio (HR) for CSSDR of 7% (HR = 0.37 95% CI 0.17–0.83) was similar to that for an ADR of 25% (HR = 0.45 95% 0.23–0.89) (Table 1). The ROCs were similar for CSSDR and ADR and the combination of the 2 rates did not alter the ROC (Table 2).

CONCLUSION:

Having an exam performed by an endoscopist with a CSSDR of 7% or greater was associated with a decrease incidence of PCCRC (HR = 0.37). The performance of CSSDR and ADR for PCCRC incidence were similar. These data suggest that a CSSDR of 7% or greater may be associated with lower PCCRC rates. However, it may not add an information to that provided by the current primary colonoscopy benchmark, ADR.
254 Young Onset Rectal Cancer: A Growing National Concern?
Authors: Ramai Daryl , Ofosu Andrew , Aloredi Khalil , Etienne Denzil , Reddy Madhavi
Published: October 2019

INTRODUCTION:

The incidence of rectal cancer in the United States is increasing at an alarming rate among patients under the age of 45 years. The objective of this study was to investigate the incidence, demographics, tumor characteristics, treatment, and survival of rectal cancer in patients under 45 years of age.

METHODS:

Data on young-onset rectal cancer between 2000 and 2016 was extracted from the Surveillance, Epidemiology and End Results Registry. The clinical epidemiology of these tumors was analyzed using SEER*Stat. Only malignant cases were included. American Joint Committee on Cancer (AJCC) staging was used. IBM SPSS Statistics was used for Cox proportional hazard regression modeling to determine predictors of survival. Survival was calculated for primary rectal cancer only. Cases in which survival duration was unknown were excluded.

RESULTS:

A total of 10,375 patients with young-set rectal cancer were identified where 54.7% were male. Median age at diagnosis was 40 ± 5.7 years. The overall age-adjusted incidence of rectal cancer between 2000 and 2016 was 1.24 per 100,000 per year. Incidence increased with age, with the highest incidence occurring in the 40–44 year age group. Over the 16-year study period, the annual incidence of rectal cancer increased by 3.0% in a given year. Most tumors on presentation were moderately differentiated (48.3%) while the most common stage at presentation localized disease (40.7%). Moreover, 78.4% of these tumors were surgically resected while 50.9% received radiation, and 60.6% received chemotherapy. One- and 5-year cause-specific survival for rectal cancer was 92.7% and 70.8% respectively. On Cox proportional hazard regression analysis, worse outcomes were noted with Asians or Pacific Islanders [HR] 1.12, 95% confidence interval [CI] 1.03–1.21, P = 0.011), and increasing N stage (N1 HR 1.18, 95% CI 1.10–1.28, P = 0.000). Surgical intervention reduced mortality by 30% (HR 0.70, 95% CI 0.65–0.76, P = 0.000), while radiation therapy reduced mortality by 15% (HR 0.85, 95% CI 0.78–0.94, P = 0.001). Chemotherapy did not significantly affect survival outcomes (HR 1.04, 95% CI 0.94–1.15, P = 0.452).

CONCLUSION:

Our study highlights an increasing incidence of rectal cancer in the younger population under the age of 45 years. Further research is needed in understanding factors contributing to this alarming rise, and inform screening guidelines aimed at decreasing the incidence and mortality of this potentially curable disease in this population.