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1.
HemaSphere ; 6:770-771, 2022.
Article in English | EMBASE | ID: covidwho-2032093

ABSTRACT

Background: CDK8 and its paralog CDK19 have central roles in maintenance of cancer cell viability and undifferentiated state for a variety of tumor types. (Dannappel et al. 2019;Rzymski et al. 2015;Philip et al. 2018). RVU120 (SEL120), a novel CDK8/CDK19 kinase inhibitor with significant efficacy in preclinical AML models, has shown clinical efficacy in a currently ongoing phase Ib trial in patients with relapsed/refractory (R/R) AML or HR-MDS (NCT04021368). This paper provides update with new available data on disease evaluation from ongoing patients and further enrolment into next cohort level 85 mg. Aims: The primary objective of the study is to determine preliminary safety profile, dose limiting toxicities (DLTs), maximum tolerated dose (MTD) and the recommended phase 2 dose of RVU120 as a single agent. Secondary objectives include PK, antileukemic activity and exploratory PD characterization. Methods: The study comprises at least 7 dose escalating cohorts. The first 3 cohorts followed an accelerated scheme, 1 patient enrolled/cohort from 10 to 50 mg dose levels, from cohort 4 (75 mg) to 7 (100 mg) doses onwards a 3+3 design is followed. Data from each cohort is evaluated by a data review committee (DRC). RVU120 is administered orally every other day, for a total of 7 doses, in a 3-week treatment cycle until disease progression/unacceptable toxicity. Adverse events are graded according to NCI-CTCAE v.5.0. DLTs are assessed at completion of C1. Disease evaluation is performed according to Dohner 2017 and Cheson 2006 response criteria for AML and MDS respectively. PK parameters are calculated by non-compartmental analysis. Pharmacodynamic (PD) activity is assessed by flow cytometry measure of pSTAT5 Ser725 levels, that are highly dependent on the activity of CDK8 and CDK19 in AML/MDS cells. Results: At data cut off of 23rd Feb22, 13 pts have been enrolled, median age 73 years and median 2 previous lines of therapy, ECOG PS 2 in 4 pts, 1 in 7, 0 in 2. No DLTs were observed, all 14 Serious Adverse Events, including 1 COVID19 death and 1 pancreatitis, were not related to study drug (G1 fever, G2 Upper Respiratory Infection, G3: pseudomonas sepsis;urinary tract infection;febrile neutropenia;lung infection, pain, hemoptysis, pleural effusion, G5 pneumonitis, death NOS, pancreatitis). Cohort 1 pt, 10 mg dose level, and cohort 2 pt, 25 mg, showed stable (SD) and progressive disease (PD) respectively at the end of C1. Cohort 3 pt, an 81 YO male HR-MDS, escalated from 50 to 75 mg dose from C7, is SD at C24D13 with Erythroid Hematological Improvement on C5, C7, C10, C18. Cohort 4, 75 mg dose pt, a 62 YO male with AML DNMT3A pos, relapsing after Ven/Dec, achieved CRi at the end of C1 and CR in C7, and progressed at the end of C8. Two out of the remaining 4 pts treated at 75 mg reached SD (1 still ongoing at C3D15 and another died on C3D20 while on SD), 1 pt died of COVID-19 pneumonitis on C1D18, 1 pt with AML secondary to MPN was SD at C2 and progressed on C4. Two pt were treated at 110 mg (cohort 5), 1 not evaluable died for pancreatitis and 1 was SD at the end of C1. 2 pt entered cohort 6, 85 mg, and will be evaluable at the end of March 2022. Summary/Conclusion: Preliminary results from the first 6 cohorts have shown a favorable safety and a predictable PK profile of RVU120. Meaningful PD activity and clinical efficacy were observed at 50 and 75 mg doses. Enrollment is currently ongoing at 85 mg cohort.

2.
Journal of the Canadian Association of Gastroenterology ; 4, 2021.
Article in English | EMBASE | ID: covidwho-2032039

ABSTRACT

Background: The COVID-2019 pandemic continues to restrict access to endoscopy, resulting in delays or cancellation of non-urgent endoscopic procedures. A delay in the removal or exchange of plastic biliary stents may lead to stent occlusion with consensus recommendation of stent removal or exchange at three-month intervals [1-4]. We postulated that delayed plastic biliary stent removal (DPBSR) would increase complication rates. Aims: We aim to report our single-centre experience with complications arising from DPBSR. Methods: This was a retrospective, single-center, observational cohort study. All subjects who had ERCP-guided plastic biliary stent placement in Halifax, Nova Scotia between Dec 2019 and June 2020 were included in the study. DPBSR was defined as stent removal >=90 days from insertion. Four endpoints were assigned to patients: 1. Stent removed endoscopically, 2. Died with stent in-situ (measured from stent placement to documented date of death/last clinical encounter before death), 3. Pending removal (subjects clinically well, no liver enzyme elevation, not expired, endpoint 1 Nov 2020), and 4. Complication requiring urgent reintervention. Kaplan-Meier survival analysis was used to represent duration of stent patency (Fig.1). Results: 102 (47.2%) had plastic biliary stents placed between 2/12/2019 and 29/6/2020. 49 (48%) were female, and the median age was 68 (R 16-91). Median follow-up was 167.5 days, 60 (58.8%) subjects had stent removal, 12 (11.8%) died before replacement, 21 (20.6%) were awaiting stent removal with no complications (median 230d, R 30-332), 9 (8.8%) had complications requiring urgent ERCP. Based on death reports, no deaths were related to stent-related complications. 72(70.6%) of patients had stents in-situ for >= 90 days. In this population, median time to removal was 211.5d (R 91-441d). 3 (4.2%) subjects had stent-related complications requiring urgent ERCP, mean time to complication was 218.3d (R 94-441). Stent removal >=90 days was not associated with complications such as occlusion, cholangitis, and migration (p=1.0). Days of stent in-situ was not associated with occlusion, cholangitis, and migration (p=0.57). Sex (p=0.275), cholecystectomy (p=1.0), cholangiocarcinoma (p=1.0), cholangitis (p=0.68) or pancreatitis (p=1.0) six weeks prior to ERCP, benign vs. malignant etiology (p=1.0) were not significantly associated with stent-related complications. Conclusions: Plastic biliary stent longevity may have been previously underestimated. The findings of this study agree with CAG framework recommendations [5] that stent removal be prioritized as elective (P3). Limitations include small sample size that could affect Kaplan-Meier survival analysis. Despite prolonged indwelling stent time as a result of COVID-19, we did not observe an increased incidence of stent occlusion or other complications.

3.
Colloids and Surfaces B: Biointerfaces ; 219, 2022.
Article in English | EMBASE | ID: covidwho-2031218

ABSTRACT

Cell membrane cloaking is an important biomimetic approach for improving drug residence time in the body due to its distinctive concealment ability, making it highly biocompatible and efficient for targeted drug delivery. Leukocytes are considered a fundamental part of the immune system. Leukocyte membrane cloaked nanoparticles offer site-specificity and can escape the opsonization process besides enhanced systemic circulation time. This review emphasizes the anatomical and physiological features of different leukocytes in addition to the preparation and characterization of leukocyte membrane cloaked nanoparticles. It also covers the recent advancements of this biointerfacing platform in cancer therapy, inflammatory disorders, multifunctional targeted therapy and hybrid membrane-coated nanoparticles. However, leukocytes are complex, nucleated cell structures and isolating their membranes poses a greater difficulty. Leukocyte membrane cloaking is an upcoming strategy in the infancy stage;nevertheless, there is immense scope to explore this biomimetic delivery system in terms of clinical transition, particularly for inflammatory diseases and cancer.

4.
Journal of the Canadian Association of Gastroenterology ; 4, 2021.
Article in English | EMBASE | ID: covidwho-2030670

ABSTRACT

The proceedings contain 243 papers. The topics discussed include: KRT15+ tumor cells as putative cancer stem cells in esophageal cancer;the circadian timing of inflammatory bowel disease;GM-CSF autoantibodies: predictors of Crohn's disease development and a novel therapeutic approach;an INULIN-type Fructan enriched exclusive enteral nutrition formula modulates the gut microbiome and promotes expansion of anti-inflammatory T cell subsets to suppress colitis;dietary tryptophan modulates kynurenine and indole production in healthy individuals;dorsal root ganglia neuronal responses and substance p production are higher in male mice;food antigen-stress interaction leads to increase pain signaling in ileum and colon via STAT6 in an IBS model;risk perception and knowledge of COVID-19 in patients with celiac disease;pre-treatment HLADQA1-hladrb1 testing for the prevention of azathioprine-induced pancreatitis in inflammatory bowel disease: a prospective cohort study;and a high salt diet synergizes with UC microbiota to induce a proinflammatory immune tone in immunocompetent gnotobiotic mice.

5.
Annals of the Rheumatic Diseases ; 81:1432, 2022.
Article in English | EMBASE | ID: covidwho-2008833

ABSTRACT

Background: The etiology of pancreatitis is heterogeneous;it may be due to chronic excessive alcohol use, gallstones, medications, infections, autoimmune diseases, metabolic disorders, trauma, congenital malformations etc. Objectives: The aim of this study has been to describe a hypothetic pathway of chronic pancreatitis in post-Covid 19 condition, based on the role of autoimmune and bacterial septic vasculitis in the pathogenesis of chronic pancreatitis (ChrP) in rheumatoid arthritis (RA). Methods: At the National Institute of Rheumatology 9475 patients died between 1969 and 1992;among them 161 with RA and all of them were autopsied. RA was confrmed clinically according to the criteria of the ACR. Tissue samples of pancreas were available for histologic evaluation in 111 patients. Pancreatitis and vasculitis were determined and characterized histo-logically [1,2]. The possible role of autoimmune vasculitis and bacterial septic vasculitis in the pathogenesis of ChrP was analyzed by Pearson's chi-squared (χ2) test. Results: ChrP-characterized by diffuse and/or focal fbrosis and atrophy-was present in 10 (9.01%) of 111 patients. Systemic vasculitis complicated RA in 28 (25.23%) of 111 patients. Twenty-five (89.3 %) of 28 systemic vasculitis proved to be of autoimmune origin. Autoimmune vasculitis involved the pancreatic blood vessels (pAV) in 8 (32.0 %) of these 25 patients. Non-specifc (n=37), fbrinoid necrotic (n=14), and granulomatous type (n=5) of pAV were detected side by side in the same histologic section, involving pancreatic arteries of different sizes. The veins and venules were not involved. p AV was not associated with chronic pancreatitis. The relationship between p AV and ChrP was inverse with a negative colliquation coefficient (c=-1.0, χ2=0. 0801, p <0.7772-NS). Three (10.7 %) of 28 systemic vasculitis cases proved to be of septic (bacterial) origin. Pancreatic blood vessels (pSV) were involved in 2 (66.7 %) of these 3 patients. Granulomatous vasculitis was not seen with pSV, and the veins and venules were also spared. Non-specifc (n=9), fbrinoid necrotic (n=2) vasculitis involving different size of pancreatic arteries were associated with chronic pancreatitis. The relationship between pAV and ChrP was signifcant (c=0.92308, χ2=6.3201, p <0.012). Conclusion: Chronic pancreatitis is characterized clinically by abdominal pain and diarrhea, which are common in post-Covid 19 condition [2]. The strong and signifcant correlation between pSV and ChrP indicates that subclinical or manifest bacterial septic processes may play a role in the pathogenesis of ChrP. Hypothetically a similar pathway is plausible in post-Covid 19 chronic pancreatitis due to viral infection and vasculitis, analogous to bacterial septic vasculitis. Systemic vasculitis of autoimmune origin involving blood vessels of the pancreas may cause a special multifocal relapsing lipo-necrotic pancreatitis [1,2], and according to our results, do not influence the prevalence of ChrP. The autoimmune origin of pancreatic vasculitis may be excluded histologically by the presence of granulomatous vasculitis of the most frequently involved arterioles and small arteries.

6.
World Journal of Clinical Cases ; 10(25):8837-8843, 2022.
Article in English | EMBASE | ID: covidwho-2006525

ABSTRACT

BACKGROUND The United Kingdom government introduced lockdown restrictions for the first time on 23 March 2020 due to coronavirus disease 2019 (COVID-19) pandemic. These were partially lifted on 15 June and further eased on 4 July. Changes in social behaviour, including increased alcohol consumption were described at the time. However, there were no data available to consider the impact of these changes on the number of alcohol-related disease admissions, specifically alcoholrelated acute pancreatitis (AP). This study evaluated the trend of alcohol-related AP admissions at a single centre during the initial COVID-19 lockdown. AIM To evaluate the trend in alcohol-related AP admissions at a single centre during the initial COVID-19 lockdown in the United Kingdom. METHODS All patients admitted with alcohol-related AP from March to September 2016 to 2020 were considered in this study. Patient demographics, their initial presentation with AP, any recurrent admissions, disease severity and length of stay, were evaluated using ANOVA and χ2 and Kruskal–Wallis tests. RESULTS One hundred and thirty-six patients were included in the study. The highest total number of AP admissions was seen in March–September 2019 and the highest single-month period was in March–May 2020. Admissions for first-time presentations of AP were highest in 2020 compared to other year groups and were significantly higher compared to previous years, for example, 2016 (P < 0.05). Furthermore, the rate of admissions decreased by 38.89% between March–May 2020 and June–September 2020 (P < 0.05), coinciding with the easing of lockdown restrictions. This significant decrease was not observed in the previous year groups during those same time periods. Admissions for recurrent AP were highest in 2019. The median length of hospital stay did not differ between patients from each of the year groups. CONCLUSION An increased number of admissions for alcohol-related AP were observed during months when lockdown restrictions were enforced;a fall in figures was noted when restrictions were eased.

7.
Indian Journal of Critical Care Medicine ; 26:S61, 2022.
Article in English | EMBASE | ID: covidwho-2006352

ABSTRACT

Introduction: Sepsis is a common cause of morbidity and mortality with no gold standard diagnostic test for detecting sepsis. Blood cultures are a frequent diagnostic step but the results take at least 48 hours and timely recognition of infection and initiation of appropriate antibiotics remain crucial in the treatment of sepsis. Biomarkers thus come in handy for rapid diagnosis and risk stratification. Objectives: Primary objective: To assess the diagnostic and prognostic value of procalcitonin (PCT), interleukin-6 (IL-6), ferritin, and C-reactive protein (CRP) levels in differentiating between Gram-negative and Gram-positive sepsis patients. Secondary objective: To determine the relationship between serum PCT, IL-6, ferritin, and CRP levels and isolated sepsis pathogens. Materials and methods: We are conducting a cross-sectional study for a period of 2 years on 360 adult patients admitted in an intensive care unit (ICU) of a tertiary care hospital with sepsis or septic shock. Our exclusion criteria are patients with burns, suspected or documented non-bacterial infections, viral hepatitis, iron overload states, and active COVID-19 infection. We are using convenience sampling. Demographic details of patients are collected. Blood is drawn for estimation of the four aforementioned biomarkers as well as body fluids of the patient based on clinical suspicion are sent for microbiological evaluation on admission to ICU before administration of antibiotics. Based on the culture reports, patients are classified as culture-positive or culture-negative sepsis and the biomarkers in each group are analyzed for diagnostic and prognostic accuracy. The primary outcome of the study is the survival or death of the patient while the secondary outcome is the number of days of ICU stay. During the time of submission, only 25 patients had been recruited and an interim analysis is being conducted. Results: During the time of submission, only 25 patients had been recruited and an interim analysis is being conducted. The mean age of our patients was 57.16 years. The study population was predominantly males (20 subjects) with ten subjects of urosepsis, three with pancreatitis, two with pneumonia, and the remaining ten had a miscellaneous diagnosis. The mean values of the inflammatory markers were as follows: PCT = 16.672 (±24.3495), CRP = 85.8428 (±62.1224), IL-6 = 610.268 (±723.3846), and ferritin = 625.0832 (±628.5289). The p value of the biomarkers is <0.00001 and is significant at p < 0.05. The following combinations of biomarkers were found to be statistically significant - PCT with IL-6 (p = 0.00018), PCT with ferritin (p = 0.00012), CRP with IL-6 (p = 0.00116), and CRP with ferritin (p = 0.00079). The sensitivity of CRP and IL-6 was 100% while specificity was highest for PCT at 50%. Eight of the subjects had Gram-negative sepsis. The mean days of hospitalization were 19.92 days. Eight of the subjects died contributing to a mortality rate of 3.2 per 10 subjects. Conclusion: The combination of biomarkers reflects different aspects of sepsis pathophysiology and would be feasible to incorporate as a point of care testing. The biomarker panel that would provide diagnostic information for the investigation of a patient with suspected sepsis earlier than cultures is PCT with IL-6 and ferritin.

8.
Indian Journal of Critical Care Medicine ; 26:S49-S50, 2022.
Article in English | EMBASE | ID: covidwho-2006343

ABSTRACT

Aims and objectives: Gastrointestinal symptoms like abdominal pain can be atypical presentations associated with coronavirus disease. This case report describes the presentation of acute pancreatitis in a patient with moderate COVID-19 infection. Materials and methods: Data were collected from a patient who was admitted with acute pancreatitis as sequelae of COVID-19 infection in our intensive care unit in June 2021. Case presentation: A 25-year-old female with no comorbidities presented to our emergency department with complaints of fever and dry cough for 10 days for which she had taken treatment at home. COVID RTPCR was negative and CT severity was 10/25. She also complained of abdominal pain with vomiting for 2 days. So she was admitted to our hospital on the tenth day of her illness. Laboratory analysis showed >3 times elevation of serum lipase. CT abdomen showed acute pancreatitis with gallbladder sludge. Causes of pancreatitis like gallbladder stones, alcohol, hypercalcemia, and hypertriglyceridemia were excluded by history and investigations. She was diagnosed with acute pancreatitis due to COVID-19. C-reactive protein and D dimer was highly elevated. She was admitted in ICU and was started on conservative management with IV fluids and bowel rest. Oral intake was resumed gradually as tolerated. The patient was maintaining adequate oxygen saturation on room air. Her repeat COVID RTPCR was again negative. However, her CT severity had increased to 14/25. Her total antibody SARS-CoV-2 was highly reactive. She had severe pain which was not improving despite multimodal analgesia which included opioid infusion. She had bilateral minimal pleural effusion and consolidation and required 2-4 L oxygen support. Repeat CT abdomen after a week showed acute necrotizing pancreatitis with gross pancreatic ascites and partial splenic vein thrombosis (modified CT severity index 8). On day 7 of admission, she developed a fever. Blood and urine cultures were sent and empirical antibiotic was started. Urine culture showed Klebsiella pneumoniae and antibiotic was escalated as per sensitivity pattern. Her pain scores persisted to be high despite all measures. On day 14, she developed abdominal distension. Intra-abdominal pressures were normal and repeat CT abdomen showed extensive free fluid with dilated bowel loops which was likely paralytic ileus. A CT-guided pigtail was inserted for continuous drainage of fluid. The ascitic fluid culture showed no organism. Her abdominal distension gradually reduced. We tapered the requirement of opioids day by day and she got symptomatically better. She could tolerate oral feeds better, off oxygen support, and was shifted to wards with pigtail catheter in situ. She stayed in ICU for 26 days. She was doing better in wards and was discharged home after 5 days with oral anticoagulant and other symptomatic medications and was adviced for gastroenterology follow-up after 10 days. Results: A patient was diagnosed with acute pancreatitis associated with SARS-CoV-2 and was treated accordingly. Other causes of acute pancreatitis were excluded in the patient including alcohol, biliary obstruction/gall stones, drugs, trauma, hypertriglyceridemia, hypercalcemia, and hypotension. Conclusion: This case highlights acute pancreatitis as a complication associated with COVID-19 and underlines the importance of evaluating and treating patients with COVID-19 and abdominal pain.

9.
Open Access Macedonian Journal of Medical Sciences ; 10:204-206, 2022.
Article in English | EMBASE | ID: covidwho-2006279

ABSTRACT

BACKGROUND: Hypertensive patients with Coronavirus Disease 2019 (COVID-19) are facing high morbidity and mortality. These morbidities include acute kidney injury (AKI) and acute pancreatitis, which have an incidence of about 17% each. Severe acute respiratory syndrome-corona virus 2 (SARS-CoV2) virus penetrates cells through the angiotensin-converting enzyme 2 (ACE2) receptor which is widely found in the respiratory tract, gastrointestinal tract, kidneys, pancreas, and other organs. The virus multiplies in the airway and then enters circulation bound to ACE2 receptors in the tissue. CASE REPORT: This case report presents a chronic hypertensive patient with COVID-19 accompanied by complications of AKI and acute pancreatitis. CONCLUSION: AKI is a risk factor for death in COVID-19 patients, where kidney involvement in COVID-19 is thought to be due to direct infection with SARS-CoV2 or through other complicating conditions, where acute pancreatitis occurs due to COVID-19.

10.
Clinical Nutrition ESPEN ; 48:522, 2022.
Article in English | EMBASE | ID: covidwho-2003974

ABSTRACT

PEG feeding provides a valuable nutritional access for patients with a functional gastrointestinal tract. The aim of this project was to audit all the PEG procedures performed by a single consultant operator during the Covid-19 pandemic including the indications, outcomes and complications. All the procedure reports were accessed to identify the patients, indications and immediate outcomes. For every patient, all the letters from all specialties were accessed for the dates following the procedure through the clinical records platforms to identify any later complications. A total of 92 procedures were performed between 15/3/2020 and 31/4/2021 in a total of 84 patients. Lists were operating at less than half capacity compared to pre Covid-19. 65 were planned PEG insertions, 17 were planned removals, and 10 were planned replacements. 5 of the procedures were for PEG-J insertion or replacement. The main indication was Head and Neck Ca in 59/92 procedures followed by CVA 9/92, chronic nausea/vomiting/gastroparesis in 6/92, dysphagia with or without aspiration risk in 4/92, MND in 4/92, CNS tumour post-op (pineal gland) in 2/92, cerebral palsy in 1/92, multiple sclerosis in 1/92, neurodegenerative disorder in 1/92, neuromuscular disorder in 1/92, chronic pancreatitis in 1/92, cystic fibrosis in 1/92, depression with poor oral intake in 1/92 and learning difficulties in 1/92. 83/92 procedures were completed successfully. 2 procedures had a failed intubation, 1 because of a subglottal stricture. The rest of the abandoned procedures were due to patient distress (2/92), high oesophageal stricture (1/92), failed cannulation (1/92), body habitus (1/92), stomach not translluminated and patient desaturation (1/92). One of the planned replacements failed because of a buried bumper. In two patients there was a small leak around the PEG site, 1 identified in the endoscopy room, 1 a few weeks later but both were managed conservatively and the PEG was kept in place. No other complications identified. From October 2020 the consistent use of Corflo PEGs reduced the service demands as these can be easily removed in the community. Lists during the COVID-19 pandemic were significantly impacted, especially UGI procedures, as these are aerosol generating procedures. The vast majority of the procedures are completed successfully and there are no significant complications. Most failed procedures are due to patient related factors such as tolerance and anatomical factors. The use of PEGs that can be removed in the community avoiding further endoscopic procedures is a valuable tool especially in this pandemic and early post-pandemic setting.

11.
Clinical Nutrition ESPEN ; 48:506-507, 2022.
Article in English | EMBASE | ID: covidwho-2003961

ABSTRACT

Meeting energy and protein requirements in critically ill patients is important for prognosis, yet difficult to achieve as a consequence of disease, management and/or altered nutritional intake[1]. Improvements in achieving energy and protein requirements with a high-energy, high-protein peptide-based tube feed were observed in community patients with impaired gastrointestinal function[2]. To establish whether this remained true in the critical care setting, where feeding intolerance is observed frequently in patients with[3] and without SARS-CoV-2[4], a retrospective multicentre audit was performed. Adults (> 18years) with or without SARS-CoV-2, admitted to critical care across 6 UK hospitals between May 2020 and December 2020, were retrospectively included if they received a peptide-based enteral tube feed (Nutrison Peptisorb Plus HEHP®, Nutricia Ltd), containing 1.5kcal/ml and 7.5g protein/100ml (herein referred to as HEHP). Data were collected from 15 critically ill patients (52±12y;87% male), with mean length of hospital stay being 26days (range: 7-49days). Of these, 10 were SARS-CoV-2 positive, with the remainder having pancreatitis (n=3), delayed gastric emptying (n=1) or unconfirmed diagnosis (n=1). HEHP was used second line (after whole protein) and indications (multiple were cited for some) for use included tolerance issues (n=10), elevated energy and protein requirements (n=5) or due to primary diagnosis (n=2). Estimated energy and protein intakes (% of requirements achieved) were recorded before and during use of HEHP. In addition, Dietitians were asked whether HEHP allowed patients to better meet their nutrient target Mean intake of HEHP was 2008±461kcal/day and 100±23g protein/day provided over a mean of 12days (range: 3-29days). The percentage of estimated energy and protein targets achieved increased albeit non significantly with the use of HEHP (from 76% before vs 87% during use of HEHP for both) and the direction of effect remained true regardless of SARS-CoV-2 status. Two thirds (67%, n=10 of 15) of Dietitians reported HEHP helped patients better meet their nutrient targets and 87% (n=13 of 15) of Dietitians perceived the high protein content of HEHP as beneficial for this patient group. Gastrointestinal tolerance (anecdotal reports) remained largely unchanged in approximately half of SARS-CoV-2 positive patients when using HEHP yet improved for others including non-SARS-CoV-2 patients. Enteral tube feeding in critically ill patients poses numerous difficulties, especially in SARS-CoV-2 positive patients. This audit in critically ill patients demonstrates that a high-energy, high-protein, peptide-based enteral tube feed can help complex patients better achieve energy and protein targets in patients with and without SARS-CoV-2. References 1.Pullen K, Colins R, Stone T et al. Are energy and protein requirements met in hospital? Clin Nutr 2017;31(2): 178-187. 2.Green B, Sorensen K, Phillips M et al. Complex Enterally Tube-Fed Community Patients Display Stable Tolerance, Improved Compliance and Better Achieve Energy and Protein Targets with a High-Energy, High-Protein Peptide-Based Enteral Tube Feed: Results from a Multi-Centre Pilot Study. Nutrients. 2020, 12, 3538. 3.Liu R, Paz M, Siraj L et al. Feeding intolerance in critically ill patients with COVID-19. Clin Nutr 2021. 4.Gungabissoon U, Hacquoil K, Bains C et al. Prevalence, Risk Factors, Clinical Consequences, and Treatment of Enteral Feed Intolerance During Critical Illness. J. Parenter. Enteral. Nutr. 2015, 39, 441–448.

12.
Pediatrics ; 149, 2022.
Article in English | EMBASE | ID: covidwho-2003078

ABSTRACT

Introduction: As of June 2021, 4 million children have tested positive for COVID-19 in the US. In contrast to adults, children are often hospitalized with gastrointestinal symptoms including persistent vomiting. Pancreatitis has also been seen in MISC, which can lead to malnutrition. Most physician learn about thiamine deficiency and Wernicke Encephalopathy in patients with severe alcoholism or in low-income settings. We cared for a child with Wernicke Encephalopathy due to subacute malnutrition and weight loss after pancreatitis secondary to MISC in the US. Case Description: A 13-year-old female presented to Levine Children's Hospital with weight loss. She was diagnosed with COVID on 1/23/21 with 1 week of URI symptoms, with baseline weight 165 pounds (BMI 31.1). She was seen in an Emergency Department (ED) on 3/1/21 for vomiting with lipase 350u/L;she received fluids and was discharged. She represented on 3/7/21 with persistent symptoms weighing 135.5 pounds (BMI 25.6) with lipase 790u/L. She was discharged after three days with a diagnosis of post-COVID pancreatitis and lipase 600u/L. After discharge, she continued losing weight despite ondansetron. She followed up with GI on 3/15, weighing 130 pounds (BMI 24.5). An abdominal MRI and endoscopy were normal. She was started on omeprazole and cyproheptadine. She presented to Levine Children's Hospital on 3/24/21 for a second opinion. Upon admission, her serum lipase was 895u/L and she weighed 115 pounds (BMI 21.7). She was started on dextrose-containing fluids and developed seizures on 3/27/21. MRI brain was normal. Ophthalmology noted bilateral abducens nerve palsy. She developed worsening mental status and respiratory failure, so was intubated. A repeat MRI brain revealed posterior reversible encephalopathy syndrome and findings specific for Wernicke Encephalopathy. Thiamine level was low, and empiric thiamine was initiated. She was started on feeds and clinically improved. She was then extubated and showed improvements in her motor function and ability to follow commands. She transferred to inpatient rehab and continues to make progress. Discussion: Identification of the degree of malnutrition for this patient was difficult to obtain due to non-communicating EMRs. This limited the providers' ability to accurately quantify the degree of weight loss and the potential for Thiamine deficiency. The combination of limited body storage and short half-life can result in total depletion of thiamine stores within 2 weeks leading to altered mental status. Unfortunately, stigmatization of obesity in children has been well documented and malnutrition may be overlooked due to a normal BMI. Conclusion: Obtaining growth charts for patients presenting with weight loss is important as they provide objective data and help prevent obesity bias. If a child has a history of weight loss and develops altered mental status, vitamin B deficiencies should be considered in the differential. Pancreatitis associated with MIS-C can cause significant malnutrition leading to Wernicke Encephalopathy.

13.
Canadian Medical Association. Journal ; 192(30):E858-E859, 2020.
Article in English | ProQuest Central | ID: covidwho-1998474

ABSTRACT

A 61-year-old previously healthy man who was not taking any medications was admitted to hospital with fever, dyspnea and cough, which he had for 5 days. Our patient had been in close contact with his father, who had confirmed coronavirus disease 2019 (COVID-19). Radiography of his chest showed bilateral opacities compatible with viral pneumonia, and results from testing of nasal and throat swabs using real-time transcription polymerase chain reaction assay were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute pancreatitis is an inflammatory disorder of the pancreas, most commonly caused by gallstones and heavy alcohol consumption. 4 The revised Atlanta classification system defines acute pancreatitis if at least 2 of the following 3 criteria are met in a patient: abdominal pain (acute onset of persistent and severe epigastric pain);increased serum lipase (or amylase) levels to greater than 3 times the upper limit of normal value;or characteristic findings of acute pancreatitis on contrast enhanced CT.

14.
American Journal of Kidney Diseases ; 79(4):S61-S62, 2022.
Article in English | EMBASE | ID: covidwho-1996893

ABSTRACT

It has been reported that older pts adapt better to dialysis than younger pts. We investigated in response by age to various stressors encountered during the COVID-19 pandemic in a population of inner-city dialysis patients. A survey was conducted in a random sample of 32 dialysis patients. Patients were asked about their fluid intake, general attitudes towards medical recommendations, and changes in their wellbeing due to COVID19. The PSS (Perceived Stress Scale) and KAS-R (Kim Alliance Scale Revised) were also used. Mean age was 56.8 ± 18.2 years. 15 pts (46.9%) were <60 yrs (younger) and 17 (53.1%) were ≥60 yrs (older). Mean dialysis time was 88.0 ± 104.0 months. There were 20 (62.5%) male, 29 (90.6%) identified as black, 18 (56%) had a high school diploma or less, and 14 (44%) completed some college or more. 7% (1) of older and 46% (6) of younger pts reported “some of the time” or “never” rather than "most of the time" when asked how often they followed the fluid restriction recommendations (p=0.034). 29% (4) of younger pts reported fluid restrictions were difficult to follow, vs. none of the older pts (p=0.037). 33% (5) of younger pts reported “poor” or “average” when asked about wellbeing prior to the pandemic and 100% (15) of older patients reported “good” (p=0.05). When asked to rate their stress level over the last year, 64% (9) of younger pts reported being somewhat or very stressed and 79% (11) of older pts reported not at all or a little stressed (p=0.015). 29% (4) of younger pts stated they sometimes work well with their provider and 100% (15) of older patients stated always (p=0.026). There were no statistically significant differences between the groups for sex, race, or education. In our population during the pandemic: 1. Younger pts were less adherent to fluid restriction and found them more difficult to follow. 2. Older pts were more likely to report feeling good prior to the pandemic and were less stressed following it. 3. Older pts were more likely to report a good relationship with their provider. 4. Younger pts may need more support through the pandemic as they appear to be coping less well, feel less connected, and are less able to follow important dietary restrictions. (Table Presented) This case highlights the uncommon sequelae of untreated primary hyperparathyroidism which is rare since the introduction of automated chemistry analyzers [2]. Pancreatitis is reported in < 3% of patients with hyperparathyroidism and is seldom seen in current practice. Nephrocalcinosis and pancreatitis are rare complications of untreated hyperparathyroidism and could have been averted with the definitive treatment of parathyroidectomy.

15.
International Journal of Obstetric Anesthesia ; 50:100, 2022.
Article in English | EMBASE | ID: covidwho-1996272

ABSTRACT

Introduction: A case of multiple co-existing conditions during pregnancy in a previously fit and well individual. Case Report: A 24-year-old woman presented at 37 weeks during her second pregnancy with a five day history of vomiting and abdominal pain. She had no significant past medical history. Her oxygen saturations were low so she received treatment for aspiration pneumonia. Her initial COVID-19 antigen test was negative however subsequent PCR was positive. The cause of her acute abdomen was unclear, with the differentials being perforated duodenal ulcer, pancreatitis and appendicitis. With input from general surgery, obstetrics and anaesthesia a decision was made to proceed with a diagnostic laparotomy. Classical caesarean section was performed at the beginning of the procedure. A healthy baby was delivered and laparotomy revealed pancreatitis. Due to high intraoperative oxygen requirements, shewas kept intubated and transferred to intensive care post operatively. An echocardiogram revealed biventricular failure and she was commenced on treatment for peripartum cardiomyopathy. Overall, she remained intubated for nine days andwas discharged from hospital 16 days following her surgery. Followup echocardiogram four months after hospital discharge showed her left ventricular ejection fraction remained <35%. Discussion: COVID-19 is increasingly common these days so it is likely to co-exist with other conditions. The incidence of acute pancreatitis during pregnancy is approximately one in 3000 and the incidence of peripartum cardiomyopathy is also approximately one in 3000 in the western world [1,2]. This case serves as a reminder that multiple conditions may be present in one individual and highlights the importance of completing a full set of investigations. This patient had multiple reasons for respiratory failure, however, an echocardiogram was necessary to reveal peripartum cardiomyopathy. Her ejection fraction remains low which puts her at high risk of mortality for future pregnancies. However, this diagnosis has allowed her to receive the appropriate follow up and counselling.

16.
Journal of General Internal Medicine ; 37:S534, 2022.
Article in English | EMBASE | ID: covidwho-1995853

ABSTRACT

CASE: An 81-year-old female with multiple co-morbidities including recent covid-19, presented to the emergency room with shortness of breath. On arrival, she was febrile with a temperature of 101F, pulse 100 beats/min, respiratory rate 14, blood pressure 196/163 and saturating at 75% on 10 L non-rebreather mask. Initial blood work showed WBC 10.9, lactic acid 1.7, BUN/creatinine 27/1.7 (consistent with her baseline), ABG showed pH 7.37, PCO2 49, PO2 88, HCO3 27.9. Chest x-ray demonstrated volume loss in the left hemithorax, airspace disease in the left mid lung and lung base. Due to suspicion for superimposed bacterial pneumonia and positive blood cultures for staphylococcus haemolyticus, she was started on vancomycin and azithromycin. Choice of antibiotics was challenging as she was allergic to penicillin and cephalosporins. During hospitalization, her kidney function deteriorated, vancomycin was substituted with tigecycline on day 3. Day 5 of treatment, she developed multiple episodes of vomiting with epigastric pain, lipase was 4523. Acute pancreatitis was diagnosed with tigecycline presumed to be the inciting agent in the absence of other risk factors such as gall stones, chronic alcohol use, elevated triglycerides, previous known episodes of pancreatitis or any other causative medications. Tigecycline was switched back to vancomycin and she received aggressive IV fluid hydration which also improved her kidney function. Within 48 hours, the patient had improved oxygen saturation, resolution of her abdominal pain, and good oral intake marking significant overall clinical progress. She was discharged on home oxygen and few more days of IV vancomycin for bacteremia. IMPACT/DISCUSSION: Tigecycline is a broad-spectrum glycylcycline antimicrobial agent belonging to the tetracycline class of antibiotics. Tetracyclines have been associated with acute pancreatitis in literature, and concerns about tigecycline-induced acute pancreatitis have been raised over the past decade in post marketing surveys, we described one such case above. Using the Naranjo Adverse Drug reaction probability scale, a score of 6 was achieved, indicating that the patient's pancreatitis was probably related to tigecycline. CONCLUSION: We recommend physicians monitor patients for signs and symptoms of pancreatitis including abdominal pain after initiating treatment with tigecycline. There should be a low threshold for ordering lipase levels and abdominal CT imaging where indicated. If the patient has symptoms concerning for acute pancreatitis, consider stopping tigecycline and switching to a different class of antibiotics immediately.

17.
Journal of General Internal Medicine ; 37:S381, 2022.
Article in English | EMBASE | ID: covidwho-1995664

ABSTRACT

CASE: A 51-year-old man without significant past medical history presented to our hospital with dyspnea on exertion. SARS-CoV-2 was detected on routine occupational screening 2 months prior to admission. He subsequently reported a 100lb weight loss, during which time he experienced dysgeusia and ate primarily cereal, sandwiches, and potatoes and consumed nearly no fruits or vegetables. Three weeks prior to admission he developed postprandial nausea and vomiting and anorexia. A week later he developed progressive epigastric pain, lower extremity edema, and dyspnea while walking around the college campus where he worked as a security guard, and sought medical attention. He did not have fever, chills, night sweats, cough, orthopnea, paroxysmal nocturnal dyspnea, rash, or diarrhea. He had not seen a doctor in 20 years and took no medications. He did not drink alcohol, smoke cigarettes, or use illicit substances. Vital signs were T 36.6°F HR 104 BP 149/111 RR 20 and SpO2 97%. Physical examination revealed a cachectic man with bitemporal wasting, sunken orbits, poor dentition, and severe periodontal disease. JVP was 14cm of H2O at 45°. An S3 was present. The abdomen was tender to palpation in the mid epigastrium. The extremities were cool with 3+ pitting edema. Pancreatitis was diagnosed after discovery of markedly elevated lipase levels and peripancreatic fat stranding on abdominal CT. TTE showed biventricular systolic dysfunction with LVEF 15%. He developed cardiogenic shock complicated by oliguric renal failure, congestive hepatopathy and obtundation, requiring ICU transfer for diuresis and inotropic support. Further workup revealed deficiencies of thiamine, zinc, and vitamins A, C, and D. A regadenoson myocardial perfusion PET/CT showed no flow-limiting coronary artery disease, and workup for inflammatory, infectious, and toxic-metabolic causes of heart failure was unrevealing. While COVID myocarditis and multisystem inflammatory syndrome in adults (MIS-A) were considered, ultimately, a diagnosis of wet beriberi was made. After 5 months of aggressive nutritional supplementation via percutaneous gastrostomy tube and initiation of guideline-directed medical therapy, LVEF improved to 53% and weight increased by 35lbs. IMPACT/DISCUSSION: Wet beriberi is a potentially underrecognized cause of dilated cardiomyopathy in resource-rich areas. Within 3 months, thiamine deficiency can cause high-output heart failure due to impaired myocardial energy metabolism and dysautonomia. Risk factors include alcohol use disorder, prolonged vomiting, and history of bariatric surgery. CONCLUSION: The laboratory evaluation of non-ischemic dilated cardiomyopathy should include measurement of serum thiamine, carnitine, and selenium levels in select patients, alongside iron studies, ANA, screening for HIV, Chagas disease, and viral myocarditis, and genetic testing in patients with a suggestive family history. Empiric thiamine repletion should be considered in all critically ill patients with evidence of malnutrition.

18.
Drug Des Devel Ther ; 16: 2479-2495, 2022.
Article in English | MEDLINE | ID: covidwho-1993629

ABSTRACT

Background: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas without specific treatment. Shenmai injection (SMI) was reported to eliminate the severity of experimental AP. This study aimed to explore the mechanisms underlying the synergistic protective effects of SMI on AP based on network pharmacology and experimental validation. Methods: Network pharmacology analysis and molecular docking based on identified components were performed to construct the potential therapeutic targets and pathways. The principal components of SMI were detected via ultra-high-performance liquid chromatography-coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Effect of SMI and the identified components on cellular injury and IL6/STAT3 signaling was assessed on mouse pancreatic acinar cell line 266-6 cells. Finally, 4% sodium taurocholate (NaT) was used to induce AP model to assess the effects of SMI in treating AP and validate the potential molecular mechanisms. Results: By searching the TCMSP and ETCM databases, 119 candidate components of SMI were obtained. UHPLC-QTOF/MS analysis successfully determined the representative components of SMI: ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D. Fifteen hub targets and eight related pathways were obtained to establish the main pharmacology network. Subnetwork analysis and molecular docking indicated that the effects of these four main SMI components were mostly related to the interleukin (IL) 6/STAT3 pathway. In vitro, SMI, ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D increased the cell viability of NaT-stimulated mouse pancreatic acinar 266-6 cells and decreased IL6 and STAT3 expression. In vivo, 10 mL/kg SMI significantly alleviated the pancreatic histopathological changes and the expression of IL6 and STAT3 in the AP mice. Conclusion: This study demonstrated SMI may exert anti-inflammatory effects against AP by suppressing IL6/STAT3 activation, thus providing a basis for its potential use in clinical practice and further study in treating AP.


Subject(s)
Drugs, Chinese Herbal , Pancreatitis , Acute Disease , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Drug Combinations , Interleukin-6 , Mice , Molecular Docking Simulation , Network Pharmacology , Pancreatitis/metabolism
19.
Bali Medical Journal ; 11(2):514-519, 2022.
Article in English | Scopus | ID: covidwho-1994628

ABSTRACT

Background: Children on dialysis seem to be at greater risk for COVID-19. Acute pancreatitis (AP) is an infrequent but severe complication of chronic peritoneal dialysis (PD). It contributes to morbidity and mortality rates of up to 25%. Patients with PD are exposed to a series of factors associated with AP risk. This report aimed to describe rare and interesting cases of acute pancreatitis in children with CAPD following PD-related peritonitis with a favorable response to conservative treatment. Case report: We present two cases admitted to our emergency room (ER) with severe abdominal pain preceded by PD-related peritonitis. Poor adherence, lack of monitoring, and healthcare service restriction during the COVID-19 pandemic predisposed these patients to PD-related complications. Patients were diagnosed as AP based on the revised Atlanta criteria. Both met the criteria as they had abdominal pain, a threefold increase of pancreatic enzymes, and evidence of pancreatitis through ultrasonography (USG) investigation. Both patients presented a rapid resolution of AP after receiving conservative treatment, including fasting, total parenteral nutrition (TPN), prophylactic antibiotics, and analgesics. None of them experienced invasive intervention due to AP. Conclusion: Diagnosing AP in children with CAPD may be challenging since the symptoms mimic other abdominal problems. Our cases are likely to be associated with PD-related peritonitis. This report may prove conservative treatment as a recommendation for managing AP in children with CAPD. The rapid development of innovative clinical management strategies in response to the COVID-19 pandemic is crucial to improving children’s health care quality with CAPD. © 2022, Sanglah General Hospital. All rights reserved.

20.
Abdom Radiol (NY) ; 47(8): 2584-2603, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1971678

ABSTRACT

Percutaneous pancreatic interventions performed by abdominal radiologists play important diagnostic and therapeutic roles in the management of a wide range of pancreatic pathology. While often performed with endoscopy, pancreatic mass biopsy obtained via a percutaneous approach may serve as the only feasible option for diagnosis in patients with post-surgical anatomy, severe cardiopulmonary conditions, or prior non-diagnostic endoscopic attempts. Biopsy of pancreatic transplants are commonly performed percutaneously due to inaccessible location of the allograft by endoscopy, usually in the right lower quadrant or pelvis. Percutaneous drainage of collections in acute pancreatitis is primarily indicated for infection with clinical deterioration and may be performed alone or in combination with endoscopic drainage. Post-surgical pancreatic collections related to pancreatic duct fistula or leak also often warrant therapeutic percutaneous drainage. Knowledge of appropriate indications, strategies of approach, technique, and complications associated with these procedures is critical for a successful clinical practice.


Subject(s)
Pancreatic Ducts , Pancreatitis , Acute Disease , Biopsy , Drainage/methods , Endoscopy, Gastrointestinal , Humans , Pancreas/diagnostic imaging , Pancreas/pathology , Pancreas/surgery , Pancreatic Ducts/pathology , Pancreatitis/complications , Treatment Outcome
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