Background & AimsPrimary sclerosing cholangitis (PSC) is an idiopathic, cholestatic liver... more Background & AimsPrimary sclerosing cholangitis (PSC) is an idiopathic, cholestatic liver disease with a diverse range of clinical manifestations. Inter‐regional data on PSC are variable, but its global geoepidemiology has not been well‐studied. We aimed to examine the worldwide incidence, prevalence and features of PSC and PSC‐inflammatory bowel disease (PSC‐IBD).MethodsA systematic search of multiple databases was conducted to identify all original, full‐text studies until December 2020 with data regarding the incidence rate (IR) and/or prevalence of PSC. Outcomes were PSC IR, prevalence, features and IBD concurrence. Additionally, a meta‐analysis of PSC IR was performed. The study was registered in PROSPERO (CRD42021224550).ResultsOf the 1003 studies identified, 17 studies spanning three continents were included. PSC IR was 0.60 per 100 000 person‐years (PY) (95% confidence interval: 0.37‐0.88 per 100 000 PY). In pooled subgroup analysis for studies conducted in Europe and North America, PSC IR was 0.62 and 0.53 per 100 000 PY, respectively. PSC prevalence ranged 0‐31.7 per 100 000 persons, with notable inter‐regional differences. Mean age at PSC diagnosis was bimodally distributed, with relative peaks at 15 and 35 years. Mean concurrence of IBD with PSC was 50%, with 76% having ulcerative colitis, 17% Crohn's disease and 8% indeterminate/unspecified IBD.ConclusionWhile considerable heterogeneity exists in the geoepidemiology of PSC, overall, the classical dogmata of male predilection, bimodal distribution of mean age and high PSC‐IBD concurrence appear to hold true. Despite a seemingly stable IR over time, further studies are needed to better understand the geoepidemiology of PSC.
In this study, we demonstrate a correlation between T antigen expression on a panel of human carc... more In this study, we demonstrate a correlation between T antigen expression on a panel of human carcinoma cell lines and their sensitivity to porcine NK cell lysis. Specifically, the more T antigen is expressed, the more sensitive the cancer cells are to porcine NK cell lysis. Furthermore, this correlation also exists for these cells and their ability to induce tumors in vivo. In this porcine animal model, the less T antigen is expressed, the more prolific the tumor growth in vivo and vice versa. Using the human colorectal adenocarcinoma cell line SW-48, we used limiting dilution to clone 2 populations of cells, one expressing high and the other low levels of T antigen, clones 143 and 111, respectively. In these cloned cells, the clone that expressed more T antigen was more NK-sensitive in vitro and weakly induced tumor growth in vivo. Inversely, the clone that expressed less T antigen clone was more NK-resistant in vitro and grew more prolific tumors in vivo. Using soluble T antigen in a competitive inhibition assay, there was a decrease in porcine NK cell killing of the T antigen+ human cell line Colo 320HSR. Taken together, these findings suggest a novel role for T antigen in the NK cell recognition of cancer cells, specifically as markers for NK sensitivity in carcinoma cell lines. The significance of T antigens as targets for NK cell-mediated lysis is novel and identifies NK cell-T antigen interactions as potentially significant in the immunotherapy of cancer and its associated metastases.
CD69 is a type II membrane protein belonging to C-type lectin family receptor, and expressed on a... more CD69 is a type II membrane protein belonging to C-type lectin family receptor, and expressed on activated leukocytes. Pig CD69 was cloned by RT-PCR using degenerate primers. Pig CD69 cDNA contains a 600 bp open reading frame with its predicted polypeptide sequence of 200 amino acids. Pig CD69 has 75%, 67%, and 57% sequence identity with cow, human, and mouse CD69, respectively. A splicing isoform, which lacks exon 2 encoding the transmembrane domain, was detected. Pig CD69 gene is located on Chromosome (Chr) 5q25 where the NKG2D gene was mapped. In RT-PCR analysis, pig CD69 mRNA was detected in activated PBL, NK cells, macrophages, monocytes, and granulocytes, but not in resting cells. The inducers for CD69 gene expression were PMA, PHA, LPS, G7 mAb, PNK-E mAb, PM16-6 mAb and the K562 cell line. Moreover, CD69 mRNA is expressed in bone marrow, spleen, thymus and lymph nodes but not in muscle, mammary gland, or the pig kidney cell line (LLC-PK(1)). These results indicate that pig Chr 5q25 contains the NK gene complex and CD69 can be used as an activation marker in pig cells of innate as well as acquired immune systems.
International Journal of Colorectal Disease, Aug 7, 2021
Despite being the most common healthcare-related infection in the US, nationwide data on readmiss... more Despite being the most common healthcare-related infection in the US, nationwide data on readmission, healthcare consumption, and mortality in Clostridioides difficile infection (CDI) remain limited. We examined these outcomes in a US-based cohort of patients with CDI. We queried the 2017 Nationwide Readmission Database using ICD-10-CM codes to identify all adult patients admitted with a principal diagnosis of CDI. Primary outcomes were 30- and 90-day readmission rates. Secondary outcomes included mortality rates and healthcare consumption. Of the 83,865 patients discharged from an index hospitalization for CDI, 22.37% were readmitted within 30 days, and an additional 15.01% were readmitted within 90 days. Recurrent CDI was responsible for more than 30% of readmissions at both 30 and 90 days. Compared to the index hospitalization, readmissions were characterized by higher mortality (1.41% index vs. 4.86% 30-day vs. 4.40% 90-day) and increased hospital length of stay and charges. Medicaid insurance (HR 1.16), cirrhosis (HR 1.31), Type 1 diabetes mellitus (HR 1.38), and end-stage renal disease (HR 1.36) were independently associated with 30-day readmission (all p < 0.01), with similar findings in 90-day readmissions. In a large cohort of patients hospitalized for CDI, we found that approximately 1 in 5 were readmitted within 30-days, and more than 1 in 3 within 90-days. Readmission was characterized by increased mortality and greater healthcare consumption. Additionally, we found independent associations for readmission that may help identify patients at high-risk. Prospective investigation is needed to identify means to reduce the healthcare consumption and mortality in CDI.
The American Journal of Gastroenterology, Oct 1, 2019
INTRODUCTION: Pancreatitis accounts for 275,000 hospital admissions annually. While alcohol consu... more INTRODUCTION: Pancreatitis accounts for 275,000 hospital admissions annually. While alcohol consumption and gallstones are responsible for the majority of cases, hypertriglyceridemia accounts for only 7%. Most are treated successfully with intravenous hydration, pain control and triglyceride-lowering agents but complications do occur 15% of the time. We present a case of one such complication. CASE DESCRIPTION/METHODS: A 40-year-old previously healthy female presented with a 12-hour history of nausea and severe LUQ abdominal pain. She was admitted with acute pancreatitis secondary to hypertriglyceridemia. Labs revealed a lipase of 3653 U/L and triglycerides of 6160 mg/dL. Abdominal CT scan confirmed acute pancreatitis. She was treated supportively with aggressive IV hydration. Repeat imaging 5 days later showed a large fluid collection inferior to the gastric antrum, an extensive amount of free fluid layering the abdomen and a small to moderate left pleural effusion. Eventually her symptoms due to the evolving pseudocyst improved and she was discharged on day 22 with Fenofibrate and Omega-3-Acid Ethyl Esters. Six days later she was admitted for sepsis secondary to infected pancreatic pseudocyst. CT showed an extensive multi-locular fluid collection and worsening left pleural effusion. Ultrasound-guided drainage was performed and cultures reported E. coli. Antibiotics were tailored but patient remained hypotensive and tachycardic. At that point the patient underwent a diagnostic laparoscopy, which was converted to Roux En Y pancreatic cystjejunostomy for continuous drainage. Repeat imaging on post-op day one demonstrated an interval decrease in size of fluid collection. Eventually the patient was discharged home in stable condition. DISCUSSION: While pancreatitis due to hypertriglyceridemia remains common, life threatening complications are rare. Aggressive supportive care is the mainstay of therapy with early surgical intervention as needed.
Pig immunoreceptor DAP10 cDNA was cloned from a peripheral blood lymphocyte (PBL) cDNA library us... more Pig immunoreceptor DAP10 cDNA was cloned from a peripheral blood lymphocyte (PBL) cDNA library using human DAP10 cDNA as a probe. The length of the pig DAP10 cDNA is 465 bp and it contains an open reading frame of 237 bp. The predicted polypeptide ...
The American Journal of Gastroenterology, Oct 1, 2019
INTRODUCTION: Neuroendocrine tumors are a rare group of cancers that can occur in many different ... more INTRODUCTION: Neuroendocrine tumors are a rare group of cancers that can occur in many different organs. Due to their rarity and variable presentation, they are not well understood. In contrast, Barrett's esophagus is a well-known condition frequently associated with the development of esophageal adenocarcinoma. A review of literature has shown only 8 cases demonstrating an association between neuroendocrine tumors and Barrett's esophagus. CASE DESCRIPTION/METHODS: A 73-year-old male presented to the hospital status post fall due to altered mental status. Relevant past medical history included GERD, Barrett's esophagus, and gastric adenocarcinoma which was treated with surgery and chemoradiation 6 years prior. Imaging of the head revealed metastatic lesions. Further investigation with a CT chest, abdomen, and pelvis showed metastatic lesions in the bilateral lung lobes and the left trochanter. Biopsies of the esophagus and stomach on esophagogastroduodenoscopy (EGD) showed Barrett's esophagus with no presence of gastric metaplasia. A biopsy of the trochanter was also performed. Pathology results were positive for synaptophysin, chromogranin, CK7, and CK20, at both sites of biopsy for the esophagus and trochanter. Ultimately, the patient was placed on hospice. DISCUSSION: Neuroendocrine carcinomas of the esophagus are rare, accounting for 0.4-5.9% of all esophageal carcinomas. The rarity of neuroendocrine tumors and their ability to manifest in many different organs often makes diagnosis difficult. As with this patient, the origin of metastatic disease was initially unclear due to the multiple sites involved. Synaptophysin and chromogranin are specific to neuroendocrine tumors which were found in both the esophagus and trochanter. CK7 and CK20 are markers usually found in gastrointestinal mucosa, suggesting that the esophagus was the primary site of cancer. Furthermore, biopsies of the esophagus and stomach were positive for Barrett's esophagus and negative for metaplasia of the stomach, indicating that these metastatic lesions were not from a recurrence of the patient's prior gastric cancer. Further research is needed to determine if these findings are coincidental or if there is a true association between Barrett's esophagus and neuroendocrine tumors.
The American Journal of Gastroenterology, Oct 1, 2019
INTRODUCTION: The incidence of colorectal cancer has been on the rise in young and middle aged ad... more INTRODUCTION: The incidence of colorectal cancer has been on the rise in young and middle aged adults in the United States. While adenocarcinoma remains the most common type of colorectal cancer, lymphoma, particularly mantle cell lymphoma (MCL) is a rare type of lymphoma that can occur in those between the ages of 35-85. We present a case of MCL seen during routine colonoscopy. CASE DESCRIPTION/METHODS: A 51 year old male with recent diagnosis of MCL by oncology was referred to gastroenterology for a screening colonoscopy. During the procedure innumerable large polypoid lesions were visualized in the cecum and ascending colon with similar findings scattered throughout the colon. Biopsies taken from the ascending colon revealed dense atypical lymphoid proliferation with immunohistochemistry confirming MCL. DISCUSSION: MCL comprises about 7% of non-Hodgkin lymphomas. Extranodal manifestations of MCL occurs in 25% of those that are newly diagnosed, with GI involvement estimated to be 15-60%. At the time of diagnosis, most patients present in the advanced stages of MCL. It is associated with poor long term survival and high relapse rates. However, recent advances in potential new therapies for MCL have shown promise. Our case is unusual in that the typical signs of intestinal malaise (abdominal pain, diarrhea, anorexia, and hematochezia) and/or systemic B symptoms were not present. With remission rates being dismal, and treatment strategies based on patient fitness and symptoms, early detection is imperative. It is important to be cognizant to the complaints patients have as it may warrant earlier colonoscopy and therefore diagnosis of colorectal cancer.
Background &amp; AimsPrimary sclerosing cholangitis (PSC) is an idiopathic, cholestatic liver... more Background &amp; AimsPrimary sclerosing cholangitis (PSC) is an idiopathic, cholestatic liver disease with a diverse range of clinical manifestations. Inter‐regional data on PSC are variable, but its global geoepidemiology has not been well‐studied. We aimed to examine the worldwide incidence, prevalence and features of PSC and PSC‐inflammatory bowel disease (PSC‐IBD).MethodsA systematic search of multiple databases was conducted to identify all original, full‐text studies until December 2020 with data regarding the incidence rate (IR) and/or prevalence of PSC. Outcomes were PSC IR, prevalence, features and IBD concurrence. Additionally, a meta‐analysis of PSC IR was performed. The study was registered in PROSPERO (CRD42021224550).ResultsOf the 1003 studies identified, 17 studies spanning three continents were included. PSC IR was 0.60 per 100 000 person‐years (PY) (95% confidence interval: 0.37‐0.88 per 100 000 PY). In pooled subgroup analysis for studies conducted in Europe and North America, PSC IR was 0.62 and 0.53 per 100 000 PY, respectively. PSC prevalence ranged 0‐31.7 per 100 000 persons, with notable inter‐regional differences. Mean age at PSC diagnosis was bimodally distributed, with relative peaks at 15 and 35 years. Mean concurrence of IBD with PSC was 50%, with 76% having ulcerative colitis, 17% Crohn's disease and 8% indeterminate/unspecified IBD.ConclusionWhile considerable heterogeneity exists in the geoepidemiology of PSC, overall, the classical dogmata of male predilection, bimodal distribution of mean age and high PSC‐IBD concurrence appear to hold true. Despite a seemingly stable IR over time, further studies are needed to better understand the geoepidemiology of PSC.
In this study, we demonstrate a correlation between T antigen expression on a panel of human carc... more In this study, we demonstrate a correlation between T antigen expression on a panel of human carcinoma cell lines and their sensitivity to porcine NK cell lysis. Specifically, the more T antigen is expressed, the more sensitive the cancer cells are to porcine NK cell lysis. Furthermore, this correlation also exists for these cells and their ability to induce tumors in vivo. In this porcine animal model, the less T antigen is expressed, the more prolific the tumor growth in vivo and vice versa. Using the human colorectal adenocarcinoma cell line SW-48, we used limiting dilution to clone 2 populations of cells, one expressing high and the other low levels of T antigen, clones 143 and 111, respectively. In these cloned cells, the clone that expressed more T antigen was more NK-sensitive in vitro and weakly induced tumor growth in vivo. Inversely, the clone that expressed less T antigen clone was more NK-resistant in vitro and grew more prolific tumors in vivo. Using soluble T antigen in a competitive inhibition assay, there was a decrease in porcine NK cell killing of the T antigen+ human cell line Colo 320HSR. Taken together, these findings suggest a novel role for T antigen in the NK cell recognition of cancer cells, specifically as markers for NK sensitivity in carcinoma cell lines. The significance of T antigens as targets for NK cell-mediated lysis is novel and identifies NK cell-T antigen interactions as potentially significant in the immunotherapy of cancer and its associated metastases.
CD69 is a type II membrane protein belonging to C-type lectin family receptor, and expressed on a... more CD69 is a type II membrane protein belonging to C-type lectin family receptor, and expressed on activated leukocytes. Pig CD69 was cloned by RT-PCR using degenerate primers. Pig CD69 cDNA contains a 600 bp open reading frame with its predicted polypeptide sequence of 200 amino acids. Pig CD69 has 75%, 67%, and 57% sequence identity with cow, human, and mouse CD69, respectively. A splicing isoform, which lacks exon 2 encoding the transmembrane domain, was detected. Pig CD69 gene is located on Chromosome (Chr) 5q25 where the NKG2D gene was mapped. In RT-PCR analysis, pig CD69 mRNA was detected in activated PBL, NK cells, macrophages, monocytes, and granulocytes, but not in resting cells. The inducers for CD69 gene expression were PMA, PHA, LPS, G7 mAb, PNK-E mAb, PM16-6 mAb and the K562 cell line. Moreover, CD69 mRNA is expressed in bone marrow, spleen, thymus and lymph nodes but not in muscle, mammary gland, or the pig kidney cell line (LLC-PK(1)). These results indicate that pig Chr 5q25 contains the NK gene complex and CD69 can be used as an activation marker in pig cells of innate as well as acquired immune systems.
International Journal of Colorectal Disease, Aug 7, 2021
Despite being the most common healthcare-related infection in the US, nationwide data on readmiss... more Despite being the most common healthcare-related infection in the US, nationwide data on readmission, healthcare consumption, and mortality in Clostridioides difficile infection (CDI) remain limited. We examined these outcomes in a US-based cohort of patients with CDI. We queried the 2017 Nationwide Readmission Database using ICD-10-CM codes to identify all adult patients admitted with a principal diagnosis of CDI. Primary outcomes were 30- and 90-day readmission rates. Secondary outcomes included mortality rates and healthcare consumption. Of the 83,865 patients discharged from an index hospitalization for CDI, 22.37% were readmitted within 30 days, and an additional 15.01% were readmitted within 90 days. Recurrent CDI was responsible for more than 30% of readmissions at both 30 and 90 days. Compared to the index hospitalization, readmissions were characterized by higher mortality (1.41% index vs. 4.86% 30-day vs. 4.40% 90-day) and increased hospital length of stay and charges. Medicaid insurance (HR 1.16), cirrhosis (HR 1.31), Type 1 diabetes mellitus (HR 1.38), and end-stage renal disease (HR 1.36) were independently associated with 30-day readmission (all p < 0.01), with similar findings in 90-day readmissions. In a large cohort of patients hospitalized for CDI, we found that approximately 1 in 5 were readmitted within 30-days, and more than 1 in 3 within 90-days. Readmission was characterized by increased mortality and greater healthcare consumption. Additionally, we found independent associations for readmission that may help identify patients at high-risk. Prospective investigation is needed to identify means to reduce the healthcare consumption and mortality in CDI.
The American Journal of Gastroenterology, Oct 1, 2019
INTRODUCTION: Pancreatitis accounts for 275,000 hospital admissions annually. While alcohol consu... more INTRODUCTION: Pancreatitis accounts for 275,000 hospital admissions annually. While alcohol consumption and gallstones are responsible for the majority of cases, hypertriglyceridemia accounts for only 7%. Most are treated successfully with intravenous hydration, pain control and triglyceride-lowering agents but complications do occur 15% of the time. We present a case of one such complication. CASE DESCRIPTION/METHODS: A 40-year-old previously healthy female presented with a 12-hour history of nausea and severe LUQ abdominal pain. She was admitted with acute pancreatitis secondary to hypertriglyceridemia. Labs revealed a lipase of 3653 U/L and triglycerides of 6160 mg/dL. Abdominal CT scan confirmed acute pancreatitis. She was treated supportively with aggressive IV hydration. Repeat imaging 5 days later showed a large fluid collection inferior to the gastric antrum, an extensive amount of free fluid layering the abdomen and a small to moderate left pleural effusion. Eventually her symptoms due to the evolving pseudocyst improved and she was discharged on day 22 with Fenofibrate and Omega-3-Acid Ethyl Esters. Six days later she was admitted for sepsis secondary to infected pancreatic pseudocyst. CT showed an extensive multi-locular fluid collection and worsening left pleural effusion. Ultrasound-guided drainage was performed and cultures reported E. coli. Antibiotics were tailored but patient remained hypotensive and tachycardic. At that point the patient underwent a diagnostic laparoscopy, which was converted to Roux En Y pancreatic cystjejunostomy for continuous drainage. Repeat imaging on post-op day one demonstrated an interval decrease in size of fluid collection. Eventually the patient was discharged home in stable condition. DISCUSSION: While pancreatitis due to hypertriglyceridemia remains common, life threatening complications are rare. Aggressive supportive care is the mainstay of therapy with early surgical intervention as needed.
Pig immunoreceptor DAP10 cDNA was cloned from a peripheral blood lymphocyte (PBL) cDNA library us... more Pig immunoreceptor DAP10 cDNA was cloned from a peripheral blood lymphocyte (PBL) cDNA library using human DAP10 cDNA as a probe. The length of the pig DAP10 cDNA is 465 bp and it contains an open reading frame of 237 bp. The predicted polypeptide ...
The American Journal of Gastroenterology, Oct 1, 2019
INTRODUCTION: Neuroendocrine tumors are a rare group of cancers that can occur in many different ... more INTRODUCTION: Neuroendocrine tumors are a rare group of cancers that can occur in many different organs. Due to their rarity and variable presentation, they are not well understood. In contrast, Barrett's esophagus is a well-known condition frequently associated with the development of esophageal adenocarcinoma. A review of literature has shown only 8 cases demonstrating an association between neuroendocrine tumors and Barrett's esophagus. CASE DESCRIPTION/METHODS: A 73-year-old male presented to the hospital status post fall due to altered mental status. Relevant past medical history included GERD, Barrett's esophagus, and gastric adenocarcinoma which was treated with surgery and chemoradiation 6 years prior. Imaging of the head revealed metastatic lesions. Further investigation with a CT chest, abdomen, and pelvis showed metastatic lesions in the bilateral lung lobes and the left trochanter. Biopsies of the esophagus and stomach on esophagogastroduodenoscopy (EGD) showed Barrett's esophagus with no presence of gastric metaplasia. A biopsy of the trochanter was also performed. Pathology results were positive for synaptophysin, chromogranin, CK7, and CK20, at both sites of biopsy for the esophagus and trochanter. Ultimately, the patient was placed on hospice. DISCUSSION: Neuroendocrine carcinomas of the esophagus are rare, accounting for 0.4-5.9% of all esophageal carcinomas. The rarity of neuroendocrine tumors and their ability to manifest in many different organs often makes diagnosis difficult. As with this patient, the origin of metastatic disease was initially unclear due to the multiple sites involved. Synaptophysin and chromogranin are specific to neuroendocrine tumors which were found in both the esophagus and trochanter. CK7 and CK20 are markers usually found in gastrointestinal mucosa, suggesting that the esophagus was the primary site of cancer. Furthermore, biopsies of the esophagus and stomach were positive for Barrett's esophagus and negative for metaplasia of the stomach, indicating that these metastatic lesions were not from a recurrence of the patient's prior gastric cancer. Further research is needed to determine if these findings are coincidental or if there is a true association between Barrett's esophagus and neuroendocrine tumors.
The American Journal of Gastroenterology, Oct 1, 2019
INTRODUCTION: The incidence of colorectal cancer has been on the rise in young and middle aged ad... more INTRODUCTION: The incidence of colorectal cancer has been on the rise in young and middle aged adults in the United States. While adenocarcinoma remains the most common type of colorectal cancer, lymphoma, particularly mantle cell lymphoma (MCL) is a rare type of lymphoma that can occur in those between the ages of 35-85. We present a case of MCL seen during routine colonoscopy. CASE DESCRIPTION/METHODS: A 51 year old male with recent diagnosis of MCL by oncology was referred to gastroenterology for a screening colonoscopy. During the procedure innumerable large polypoid lesions were visualized in the cecum and ascending colon with similar findings scattered throughout the colon. Biopsies taken from the ascending colon revealed dense atypical lymphoid proliferation with immunohistochemistry confirming MCL. DISCUSSION: MCL comprises about 7% of non-Hodgkin lymphomas. Extranodal manifestations of MCL occurs in 25% of those that are newly diagnosed, with GI involvement estimated to be 15-60%. At the time of diagnosis, most patients present in the advanced stages of MCL. It is associated with poor long term survival and high relapse rates. However, recent advances in potential new therapies for MCL have shown promise. Our case is unusual in that the typical signs of intestinal malaise (abdominal pain, diarrhea, anorexia, and hematochezia) and/or systemic B symptoms were not present. With remission rates being dismal, and treatment strategies based on patient fitness and symptoms, early detection is imperative. It is important to be cognizant to the complaints patients have as it may warrant earlier colonoscopy and therefore diagnosis of colorectal cancer.
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