Acute Pancreatitis Following a Lower Extremity Angioplasty

Introduction: Acute pancreatitis affects a significant population globally. Usual etiologies are gallstones, alcohol, hypertriglyceridemia, medications;less frequent are trauma, hypercalcemia, infections, toxins, ischemia, anatomic anomalies, vasculitis, and idiopathic. Pancreatitis post coronary intervention is an uncommon cause with only 19 published cases in the last two decades. Being cognizant of this etiology is important given the increasing number of patients undergoing angiography. Case Description/Methods: An 81-year-old female with hypertension, diabetes, peripheral arterial disease, prior cholecystectomy underwent left lower extremity angioplasty at an outside center. Within a few hours, she started having severe epigastric pain radiating to her back, nausea, vomiting and loose bloody stool. She presented to the emergency department 24 hours after symptom onset. Epigastric tenderness was present on exam. Labs revealed leukocytosis (24,450/muL), elevated lipase (1410 U/L), elevated creatinine (1.3 mg/dL), lactate (3.1 mmol/L), calcium 9.4 mg/dL and triglycerides 161 mg/dL. Incidentally, found to be positive for COVID-19. Normal common bile duct diameter seen on sonogram. CT angiogram of the abdomen/pelvis showed acute pancreatitis, duodenal and central small bowel enteritis (Figure). She was not on any medications known to cause pancreatitis and denied alcohol use. Patient improved with analgesics and intravenous fluids. She had no recurrence of bloody stools and hemoglobin remained stable. On day 4, she was able to tolerate a regular diet, and leukocyte count and creatinine normalized. Patient did not have any COVID respiratory symptoms, and was discharged. Discussion(s): Given the temporal association to angioplasty and no other identifiable cause, acute pancreatitis was presumed to be due to the contrast used during angioplasty. Other possibilities included cholesterol embolism but no peripheral signs of cholesterol embolism were seen. Patient was an asymptomatic COVID-19 case. Although, there are case series of pancreatitis due to COVID, those were found in very sick symptomatic patients. On review of literature, cholesterol embolism was identified as a definite cause only on autopsy or laparotomy (Table). Other possible mechanisms are: high viscosity of the contrast media leading to ischemia and necrosis, contrast causing NF-kB activation followed by epithelial damage, and vasospasm. Pancreatitis after coronary angiography is rare, nonetheless, an important differential especially if there is a temporal relationship.

A Rare Case of Congenital Choledochal Cyst (CCC) Resulting in Recurrent Acute Pancreatitis in an Otherwise Healthy Young Woman

Introduction: Congenital choledochal cyst (CCC) is a rare cystic dilatation of intrahepatic or extrahepatic biliary ducts. We present a case of a type IVb choledochal cyst presenting as recurrent acute pancreatitis in a young healthy female with initial negative screenings. Case Description/Methods: An 18-year-old-female with a history of COVID-19 presented to the emergency department with one month of persistent abdominal pain, nausea, and vomiting. She was hospitalized once prior for similar symptoms and was diagnosed with acute pancreatitis. This admission, blood work showed elevated lipase, elevated liver enzymes, mild bilirubinemia with a normal lipid panel and urine was significant for infection. She received fluids, antiemetics and was started on prophylactic antibiotics for ascending cholangitis. A right upper quadrant ultrasound ruled out cholelithiasis or acute cholecystitis, but showed dilation of the common bile duct. MRCP confirmed dilation with bulbous termination in the periampullary region diagnosed as type IVb choledochal cyst. Discussion(s): CCCs are rare in Western countries with an incidence between 1 in 100,000 to 150,000. 80% of these cysts are diagnosed in patients under the age of 10. They are difficult to diagnose due to variable clinical presentations. A study of 214 CCC patients demonstrated the most common symptom was abdominal pain, followed by jaundice and fever. When cysts are found in adults, symptoms resemble atypical acute biliary tract disease. Surgical cyst removal may be needed for patients with significant risk factors such as older age and age of symptom onset, due to increased risk of malignant transformation. Longer periods of observation have been documented to be associated with an increased chance of developing late complications, such as anastomotic stricture, biliary calculi and recurrent cholangitis. Type IVb CCCs, as seen in this case, consist of multiple extrahepatic cysts and hepaticojejunostomy is the treatment. This patient's young age and recurrent acute pancreatitis combined with her lab and imaging findings strongly suggest the diagnosis of CCC. The anatomical location of the CCC impeded flow of pancreatic enzymes through the ampulla of vater, leading to recurrent pancreatitis in an otherwise healthy young female. CCC, although very rare, should be considered in the differential of acute pancreatitis when other causes such as gallstones and heavy alcohol consumption cannot be identified, as prompt diagnosis and surgical removal is imperative.

Herpes Gastritis: A Rare Cause of Gastric Outlet Obstruction

Introduction: Gastrointestinal tract involvement from herpes simplex virus is commonly associated with esophagitis. However, herpes simplex infection of the stomach is very rare with only a handful of cases being reported in immunocompromised patients. We present a case of herpes gastritis causing gastric outlet obstruction in an otherwise healthy, immunocompetent individual. Case Description/Methods: A 37-year-old male with a recent past medical history of COVID-19 infection, presented to the hospital with intractable nausea, vomiting, bloating, and early satiety for two days. Upon evaluation, CBC and CMP were remarkable for a WBC of 12.5 k/mm3 and ALT and AST of 124 U/L and 129 U/L, respectively. Lipase was 373 U/L. A CT abdomen/pelvis w/contrast showed circumferential wall thickening with edematous changes in the antrum consistent with localized inflammatory response. There was suspicion for gastric lymphoma and patient was admitted for further workup. An EGD was performed which showed exudative esophagitis and antral wall edema with luminal narrowing of gastric antrum. Endoscopic ultrasound (EUS) showed a 2.5 x 3 cm antral wall lesion worrisome for linitis plastica. Esophageal biopsies showed focal cytologic changes consistent with herpes esophagitis. The FNA of the gastric antral wall showed multinucleation of the basal cell layer with classic ground glass nuclei, consistent with herpes infection. No dysplasia or malignancy was seen. Both HSV1 and HSV2 IgG were elevated. HSV IgM was normal. A HSV PCR was ordered but never resulted. Patient was started on Valacyclovir 1 g PO BID for 10 days. He underwent a follow-up EGD 3 months later which showed complete resolution of the gastric antral changes (Figure). Discussion(s): Herpes gastritis is extremely rare. Literature review has revealed only 3 case reports of herpes gastritis;and all involved immunocompromised patients. To the best of our knowledge, this is the first case of herpes gastritis in an immunocompetent patient. Our patient presented with symptoms of gastric outlet obstruction which was caused by local inflammation from herpes simplex. It is unclear if having a COVID 19 infection altered patient's immunity and lead to herpes gastritis. This may need further investigation. No established guideline exists for treatment duration. Our patient received 10-day course of Valacyclovir, and his symptoms improved. Furthermore, patient had complete resolution of the herpes infection on follow-up EGD, indicating adequate treatment response.

Prognostic Value of Elevated Lipase in Pancreatitis versus Non Pancreatitis Hyperlipasemia (NPHL) due to Non-Malignant Causes

Introduction: While elevated lipase is typically used to diagnose acute pancreatitis, it has also been associated with other critical disease states including sepsis, COVID-19, bowel obstruction, and trauma. In this study we compared outcomes of patients with elevated lipase who had pancreatitis and NPHL. Method(s): Retrospective analysis was performed on all patients who presented to the Emergency Department between February 2016 and August 2020 with lipase >= 3x the upper limit of normal. Patient demographics and past medical history, including active cancer, were noted. Patient outcomes were followed through November 2021. If applicable, dates of death were also documented. Result(s): 414 total patients were included in this study. Upon initial evaluation, 305/414 (74%) were diagnosed with acute pancreatitis (AP) and 109/414 had NPHL. The age (54 617 vs. 58 618, p=0.0220), Sex (male 164/305 vs. 49/109, p=0.1194), and BMI (28.9 67.4 vs. 25.8 64.6, p=0.0066) were compared between the AP and NPHL groups. The serum lipase in the AP and NPHL group were respectively 1471 61070 vs. 605 6555 (p< 0.0001). The most common causes of NPHL were sepsis (10/109;9%) renal failure (7/109;6%), GI bleed (5/109;4%), and bowel obstruction (5/109;4%). The NPHL group had higher rate of malignancy (29/105;28%) compared to those with AP (35/305;11%, p< 0.0001). NPHL patients without malignancy had a higher mortality rate (63/80;80%) compared to those without malignancy in the AP group (17/270;6.3%, p< 0.0001). The most common malignancy in patients with AP was breast (6/35;17%, vs. 3/29;10%, p=0.4943). In NPHL, the most common malignancies were pancreatic (4/29;14%, vs. 3/35;9%, p=0.6920) and bowel malignancies (4/29;14%, vs. 4/35, 11% p51.0000). Conclusion(s): Patients with NPHL without malignancy have higher mortality than those with pancreatitis despite lower serum lipase levels. A limitation of our study is the difference between age and BMI of AP versus NPHL patients. Whether this impacts the prognostic relevance of NPHL on survival need to be explored in future studies.

Nirmatrelvir/ritonavir - A New Culprit of Acute Pancreatitis

Introduction: Nirmatrelvir/ritonavir is a new medication approved for the treatment of COVID-19 infection. It prevents viral replication by inhibiting the SARS-CoV-2 main protease. While mild adverse effects were described, including dysgeusia, diarrhea, hypertension and myalgia1, there were no reported cases of pancreatitis. Case Description/Methods: An 81-year-old female with a past medical history of hypertension and COPD presented to the hospital complaining of abdominal pain and nausea for one day. She had no history of alcohol, tobacco or marijuana use, recent travel, or trauma. Her medications included lisinopril and prednisone, and she had completed a 5-day course of nirmatrelvir/ritonavir for the treatment of COVID-19 infection 2 days prior to presentation. On abdominal exam, she had left upper and lower quadrant tenderness. Blood tests revealed an amylase of 1333 U/L, lipase of 3779 U/L, triglycerides of 297 mg/dL and calcium of 8.7 mg/dL. CT scan revealed an indurated pancreatic body and tail with peripancreatic fluid along the paracolic gutter. Ultrasound of the abdomen and MRCP did not reveal any acute findings. IgG subclasses 1-4 were normal. Discussion(s): According to the revised Atlanta criteria, the patient had clinical findings consistent with acute pancreatitis. Common causes such as gallstone, alcohol, autoimmune and hypertriglyceridemiainduced pancreatitis were ruled out. There were no masses or structural abnormalities on imaging that might have explained her diagnosis. There have been at least 2 reported cases of lisinopril and prednisone induced pancreatitis, however according to Badalov et al.2 both of these medications are class III drugs that lack any rechallenge in the literature. Moreover, the patient had been taking these medications for many years, making them an unlikely cause of the presenting diagnosis. There are no reports of nirmatrelvir/ritonavir associated pancreatitis or known pharmacologic interaction with her home medications, and a meta-analysis conducted by Babajide et al. revealed no association between acute pancreatitis and COVID-19 infection (3). Given the negative findings stated above and the recent initiation of a new medication, nirmatrelvir/ritonavir was the likely cause of acute pancreatitis.

Pancreatitis Secondary to Paxlovid-Induced Tacrolimus Toxicity

Introduction: Pancreatitis is a very common gastrointestinal disease that results in hospital admission. Early detection and treatment leads to better outcomes. This is the first reported case of pancreatitis secondary to elevated tacrolimus in a patient with prior renal transplantation after receiving Paxlovid for a COVID-19 infection. Case Description/Methods: A 57-year-old male with past medical history of 4 renal transplants secondary to posterior urethral valves who presented to the emergency room with acute onset epigastric pain for 24 hours. He was on tacrolimus 5 mg every 48 hours monotherapy for his immunosuppression. 10 days prior to his presentation he had developed chills and anxiety. He tested positive for COVID-19 at that time on a home rapid test. His symptoms had not significantly improved and given his immunosuppressed state he was given Paxlovid (Nirmatrelvir/ritonavir). He took 2 days of Paxlovid, however after his second day of treatment he developed severe epigastric pain requiring him to go to the emergency room. On admission his labs were notable for a lipase of 150 U/L (ULN 63 U/L). He underwent a CT scan was notable for an enlarged pancreatic head and neck with peripancreatic fat stranding (Figure). He also had a right upper quadrant ultrasound without any cholelithiasis and only trace sludge noted. His creatinine was noted to be 1.81 mg/dl which was above his baseline of 1.2 mg/dl. His tacrolimus trough level resulted at a level 45.6 ng/ml and later peaked at 82.2 ng/ml. His liver enzymes were normal. He was treated as acute pancreatitis with hydration and his tacrolimus was held with overall clinical improvement. Discussion(s): Tacrolimus is one of the most common medications used in solid organ transplantation. It is a calcineurin inhibitor that inhibits both T-lymphocyte signal transduction and IL-2 transcription. It is metabolized by the protein CYP3A and levels are monitored closely. Paxlovid is currently prescribed as an antiviral therapy for COVID-19 infection. The ritonavir compound in Paxlovid is potent inhibitor of CYP3A. Currently the guidelines do not recommend Paxlvoid as a therapeutic in patients taking tacrolimus as there is concern about increased drug levels. There have been several case reports of pancreatitis in setting of tacrolimus. This case report helps to demonstrate the need for close monitoring of therapeutics levels, especially in medications with high risk of drug to drug interaction to help prevent serious side effects such as tacrolimus induced pancreatitis.

Covid-19 Infection Presenting as Acute Pancreatitis

Purpose of study Introduction COVID-19 emerged at the end of 2019 as an epidemic of respiratory disease in Wuhan, China that later spread globally and was declared as pandemic. The common clinical manifestations of COVID-19 infection include fever, cough, myalgias, headache, sore throat, anosmia, nasal congestion, fatigue and chest pain. The most serious complications include bilateral multifocal pneumonia and acute respiratory distress syndrome. Acute pancreatitis is rarely reported in association with COVID-19 infection. We report a case of acute pancreatitis secondary to COVID-19 infection. Case Report: A 69-year-old man with past medical history of hyperlipidemia and seizure disorder presented with two days of epigastric pain radiating to back. The patient reported fever, malaise and dry cough for the last 3 days. Home medication included atorvastatin and carbamazepine for 10 and 15 years respectively. The patient denied smoking and alcohol use. COVID- 19 PCR was positive. Labs showed WBC of 3800/muL, hgb 11.8 g/dL, calcium 8.4 mg/dL , lipase 426 U/L, D-Dimer 179 ng/ml DDU, High sensitivity C-reactive protein 27.5 mg/L (normal <5 mg/L) ALT 26 U/L, AST 31 U/L, alkaline phosphatase 103 U/L and total bilirubin 0.3 mg/dL. Ultrasound of the right upper quadrant and CT abdomen showed normal pancreas, common bile duct and gallbladder with no evidence of gallstones. Triglyceride level was 70 mg/dL (<149 mg/dL) on the lipid panel. The patient was diagnosed with acute pancreatitis and received treatment with IV fluids and pain medication. The symptoms improved gradually and the patient was discharged home with resumption of home medications. Methods used Case Report Summary of results The common differentials for acute pancreatitis include alcohol use, gallstones, hypertriglyceridemia, viral infections like mumps and measles, hypercalcemia and medication-related, etc. Normal AST, ALT, alkaline phosphatase and total bilirubin along with absence of gallstones and normal common bile duct ruled out alcoholic and biliary pancreatitis. Normal calcium level and triglyceride level rule out hypercalcemia and hypertriglyceridemia as the cause of pancreatitis. Carbamazepine has rarely been reported to cause acute pancreatitis typically soon after the initiating the therapy or with increase in the dose. The use of carbamazepine for more than 15 years without any recent dose change makes this unlikely as the cause of pancreatitis. The onset of acute pancreatitis during the timeline of COVID-19 constitutional symptoms and absence of other risk factors suggests that COVID-19 infection is responsible for acute pancreatitis in our patient. Conclusions We report a case of acute pancreatitis secondary to COVID-19 infection. Further studies are warranted to better understand the etiology and the pathophysiology of acute pancreatitis secondary to COVID-19 infection.

The Complexities of Managing Hypertriglyceridemia-Induced Pancreatitis in a Critically-Ill COVID-19 Patient

Introduction: Hypertriglyceridemia-induced pancreatitis (HTP) is a variant of pancreatitis requiring unique management. The complications of COVID-19 and its treatments can make HTP therapy more nuanced. This case describes a patient who presented in diabetic ketoacidosis (DKA) with HTP, and COVID-19. The patient developed renal and respiratory failure, necessitating hemodialysis (HD) and extracorporeal membrane oxygenation (ECMO), complicating an otherwise straightforward medical management plan. Case Description: A morbidly obese (BMI 38.9 kg/m2) 43-year-old male presented to an outside hospital with abdominal pain, and vomiting, and was found to have HTP with triglycerides (TG) >2000 mg/dL (<149 mg/dL) and presumed new-onset type 2 Diabetes (HbA1c 10.9%) with DKA. Treatment with fluids, intravenous (IV) insulin infusion and plasmapheresis were initiated. He developed hypoxia after receiving over 17 liters of fluids and was intubated, subsequently developing renal failure and was transferred to our tertiary center for HD and ECMO. On admission, he tested positive for COVID-19, rhabdomyolysis [creatinine kinase 5600 U/L (30-200 U/L)], HTP [TG 783 mg/dL (<149 mg/dL), lipase 461 U/l (7-60 U/L)], glucose 269 mg/dL (not in DKA), transaminitis [AST 184 U/L (4-40 U/L), ALT 61 U/L (4-41 U/L)] and renal failure (GFR 10 ml/min/1.73m2). IV insulin infusion was initiated for hyperglycemia worsened by COVID-19 dexamethasone treatment. Plasmapheresis was performed twice with minimal effect at maintaining a low TG. Fenofibrate was not initiated due to renal failure;Lovaza could not be given via oral gastric tube;Atorvastatin was attempted once rhabdomyolysis resolved, with subsequent worsening of liver function tests. Heparin infusion was initiated for deep vein thrombosis treatment and HTP but was stopped after development of heparin induced thrombocytopenia. The patient developed worsening hypoglycemia requiring cessation of IV insulin, hypotension requiring maximum pressor support, and worsening sepsis leading to his death. Discussion(s): This case illustrates the challenges of managing a patient with HTP and COVID-19. It demonstrates how a normally straightforward treatment algorithm can become increasingly complex when factoring the patient's comorbid conditions. The case highlights the importance of knowing both treatment indications and contraindications for HTP. In this case, HTP may have been the initial diagnosis, straightforward for most endocrinologists, but its treatments and comorbid conditions ultimately made the landscape more challenging, limiting effective management and ultimately leading to this patient's demise.Copyright © 2023

New Onset Diabetes and Acute Pancreatitis- A Sequela of Long COVID?

Introduction: The association between worse COVID-19 outcomes and diabetes has been well-established in the literature. However, with more cases of new-onset diabetes and pancreatitis being reported with or after COVID-19 infection, it poses the question if there is a causal relationship between them. Case Description: 31 y/o female with COVID-19 infection 4-6 weeks ago with moderate symptoms (not requiring hospital admission or monoclonal ab), presented to ED with bandlike epigastric pain radiating to back, which is worsened with food, associated with nausea, vomiting, polyuria, and fatigue. Workup showed lipase 232, AST 180, ALT 256. Blood glucose was 281 and HbA1c was 12. CT A/P showed post cholecystectomy status, normal pancreas with mesenteric adenitis. MRCP showed hepatic steatosis with trace fluid around the pancreas s/o inflammation, and no evidence of choledocholithiasis or biliary dilatation. She denied alcohol use and autoimmune workup for pancreatitis was unremarkable. Islet cell antibodies were negative. The patient improved with fluid resuscitation and was discharged home on insulin with plans to transition to oral agents outpatient. Discussion(s): Long COVID is defined as a range of conditions or symptoms in patients recovering from COVID-19, lasting beyond 4 weeks after infection. A retrospective cohort study showed increased new-onset diabetes incidence in patients after COVID-19. This was redemonstrated in a systematic review and meta-analysis that showed a 14.4% increased proportion of new diagnoses of diabetes in patients hospitalized with COVID-19. Possible pathophysiology that have been attributed to this include undiagnosed pre-existing diabetes, hyperglycemia secondary to acute illness and stress from increased inflammatory markers during the cytokine storm, the effect of viral infections on the pancreas, and concurrent steroid use in patients with severe respiratory disease. The binding of SARS-CoV-2 to ACE2 receptors is thought to the other mechanism by which COVID can cause pancreatitis and hyperglycemia. Study showed increased lipase and amylase levels in patients with COVID and the increase in serum levels was proportional to the severity of the disease. Patients who died due to COVID-19 were also found to have degeneration of the islet cells. While, several studies have showed new onset diabetes and pancreatitis during an active COVID infections, we need larger cohort studies to comment on its true association or causation, especially in patients with long COVID symptoms. As more cases of new onset diabetes and pancreatitis with COVID-19 are being reported, there may be a need for more frequent blood sugar monitoring during the recovery phase of COVID-19.Copyright © 2023

Successful matched unrelated donor hematopoietic stem cell transplantation for infantile Wolman disease

Introduction: Wolman disease is a rare genetic disorder with an autosomal recessive inheritance. A mutation in the LIPA gene causes lysosomal acid lipase (LAL) deficiency results in lipid storage and adrenal insufficiency. Death in early infancy is due to liver failure. Patients and methods: We describe the clinical course of a three-month-old infant diagnosed with Wolman disease. A rapid mutational analysis confirmed a LIPA gene defect. Results: He underwent matched unrelated donor peripheral blood stem cell hematopoietic stem cell transplantation (HSCT) at 3 months of age, with a treosulfan-based conditioning, which resulted in engraftment with donor-derived hematopoietic cells. He required supportive care for sinusoidal obstruction syndrome and mucositis. He was administered low dose prednisolone for grade I skin graft versus host disease, and a complete donor chimerism was documented on several occasions. At one year post HSCT, his growth and development were optimal, and there was no hepatosplenomegaly. He is maintained on glucocorticoid and mineralocorticoid supplements for primary hypoaldosteronism. Conclusion: The case emphasizes the timely diagnosis and the potential for successful treatment of Wolman disease by HSCT. © 2022 Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics

Treating Lymphoma in the Pandemic Era: What We Learned from Our Experience at Fondazione Irccs Istituto Nazionale Dei Tumori

From March 2020 to May 2022, when SARS-CoV2 pandemic started spreading in Italy, 15 consecutive patients with non-Hodgkin Lymphoma (NHL) have been treated at the Pediatric Unit of Fondazione IRCCS Istituto Nazionale dei Tumori. Three of 15 patients developed COVID19 while on treatment [1 Burkitt lymphoma (BL), 1 anaplastic large cell lymphoma, 1 lymphoblastic T-cell lymphoma (T-LL)] and one patient at diagnosis [gray zone lymphoma (GZL), previously misdiagnosed as Hodgkin lymphoma]. Median age at diagnosis was 12 years;3 were male. Median positivity time of the nasal swab was 58 days (range 9-107 days). All patients remained asymptomatic or paucisymptomatic (flu-like symptoms) while positive. The first positive patient with T-LL, was in the induction phase of the Euro-LB-02 protocol guidelines: he succeeded in completing the whole treatment during the 107 days of swab positivity, experiencing mild toxicities (grade 2 transaminases and grade 3 lipase increase, both reversible) without significant delays. For this reason, we reduced the total dose of the first HD-MTX (protocol M) and administer the subsequent doses in 6 hours infusion instead of 24 with no further toxicities. After this first experience, all the subsequent patients have been treated accordingly, without major deviations from the established protocols. Minor precautions: the patient with refractory GZL received IEP course instead of IGEV as second-line treatment to avoid severe subsequent immunosuppression;the patient with BL omitted the fourth course of Rituximab during the period of swab positivity. Overall, we did not observe outstanding toxicities except for a toxic MTX level with subsequent reversible acute renal failure. Main teaching from these pilot experiences, which may translate into guidelines: 1) SARS-CoV2 infection is not an absolute contraindication to the oncological treatments. This is of main importance for the patients affected by lymphoma whose dose-intensity has a prognostic value. 2)We need to pay caution during HD-MTX treatment;indeed, we observed unexpected similar toxicities in other patients treated with HD-MTX for other solid malignancies. 3) The clearance of SARS-CoV2 might be exceptionally prolonged with persistent positivity of the nasal swabs for a longer time than the matched healthy population due to the immunosuppression characterizing lymphoma patients. For this reason and given the importance of maintaining the dose-intensity, specific treatments aiming at speeding up the clearing process are warmly suggested. (Figure Presented) Figure 1: (: 091) ITHACA study design and blood sampling time points. (OHT = Orthotopic Heart Transplant).Copyright © 2022 Elsevier Ltd. All rights reserved.

Phospholipase D-Catalyzed Transphosphatidylation for the Synthesis of Rare Complex Phospholipid Species-Hemi-bis(monoacylglycero)phosphate and Bis(diacylglycero)phosphate

Progress in developing synthetic pathways for novel and complex phospholipid species, such as Hemi-bis(monoacylglycero)phosphates (Hemi-BMPs) and bis(diacylglycero)phosphates (BDPs), is essential for expanding the knowledge and availability of rare and uncommon phospholipid species. These structurally complex phospholipid species have recently gained more attention with promising applications, as active pharmaceutical ingredient carriers in multiple COVID-19 vaccines, or biomarkers for numerous lysosomal storage disorders and certain types of cancers. The presented work facilitates the production of a range of structurally diverse Hemi-BMP and BDP products intending to increase the availability and thereby the understanding of the underlying chemistry for these high-valuable compounds. The transphosphatidylation of phosphatidylcholine with a variety of structurally diverse monoacylglycerols and diacylglycerols is proceeded by phospholipase D (PLD) catalysis in a biphasic system. Optimization in regard to enzyme loading (5 U), substrate mole ratio (1:5 mol/mol), temperature (30 degrees C), and aqueous concentration of (18% v/v) afforded the highest conversion for the model transphosphatidylation of phosphatidylcholine with monoolein, yielding 87% in 2 h. The study additionally proposes a reaction mechanism based on molecular simulation, elegantly elaborating the structural constraints (substrate configuration and character of the fatty acid residues) for access to the active site of PLD accordingly for lower yield of BDPs. The successful system designed for the production of high-valuable Hemi-BMP and BDP-analogues demonstrated in this work promises to enhance the understanding of these complex phospholipids, leading to new scientific breakthroughs.

Acute Pancreatitis in Early Postpartum Woman with Confirmed Covid-19: A Rare Case Report

Background: The Coronavirus disease 2019 (COVID-19) pandemic is a significant challenge for public health and clinical medicine. COVID-19 mainly impairs the respiratory tract. However, gastrointestinal manifestations of COVID-19 are increasingly being recognized. Although acute viral pancreatitis has been described in other viral infections, pancreatic involvement in SARS-CoV-2 disease is still poorly defined. We reported a case of acute maternal pancreatitis in an early postpartum period woman with confirmed COVID-19. Case Presentation: A 31-year-old woman in term pregnancy had a caesarean section due to acute respiratory distress syndrome (ARDS) caused by COVID-19 pneumonia. One day after surgery, her stomach appeared bloated, bowel sounds were weak, and her abdominal circumference increased. Ultrasound examination did not reveal any suspicion of bleeding or hematoma. Her abdominal contrast-enhanced computerized tomography (CT) scan showed small bowel obstruction and oedematous pancreas. Amylase levels increased to 382 units/litre and lipase levels to 724 units/litre. C-reactive protein and procalcitonin were also increased. The diagnosis of sepsis was made, and she received broad-spectrum antibiotics and treatment for the COVID-19 infection. Recovery was characterized by a gradual resolution of abdominal and pulmonary signs and symptoms. A decline of amylase and lipase was observed by the tenth day. On the 13th day, she was extubated and gradually recovered from respiratory symptoms, with a negative result for COVID-19 RT-PCR. Based on this case, we consider that pregnancy and COVID-19 support each other as the cause of acute pancreatitis. Conclusion(s): Early diagnosis and severity classification are essential steps for successful management because late recognition and treatment may allow a greater prevalence of associated complications.Copyright © 2022, Philippine College of Physicians. All rights reserved.

Hepatic and pancreatic manifestations of COVID-19

Background: Since its first detection in November 2019, the outbreak of severe acute respiratory syndrome coronavirus 2 has influenced over 200 countries, areas or territories worldwide. The virus was initially thought to be a primary respiratory pathogen, but has been reported to have multisystem involvement, including cardiovascular, neurological and gastrointestinal manifestations. The manifestations of liver damage are usually mild and generally asymptomatic. While abdominal symptoms such as pain and diarrhoea are a known presentation, little is known about pancreatic injury as a complication of COVID-19 infection. Aims and Objectives: The aim of the study was to describe the abnormality in liver enzymes and pancreatic enzymes and to correlate it with the severity and outcome of COVID-19 patients. Materials and Methods: A total of 200 patients were enrolled during the study period from August-2020 to July-2021. Data were collected from case files of patients fulfilling the inclusion criteria. Results: A cross sectional study conducted among 200 patients showed that the mean aspartate transaminase and alanine transaminase values were 41.89+or-50.22U/L and 37.69+or-41.41U/L respectively and mean amylase and lipase levels were 97.77+or-126.42U/L and 90.34+or-127.76U/L. The percentage of transaminitis that was present in patients who were discharged was 29.41% when compared to those who died which was 53.33% and this difference is statistically significant(P=0.02). However, there was no statistically significant difference observed in patients with elevated pancreatic enzymes with their outcomes. Conclusion: Hepatic injury is more commonly associated with an increased severity of the disease and also as a contributor for the greater mortality of the COVID-19 patients.

Another Cause of DKA in T2DM in COVID-19 Pandemic

Background: 47-year Emirati female, has history of T2DM since age of 39. Her overall diabetes poorly controlled with HbA1C of 8.6% (69 mmol/mol IFCC) on Empagliflozin 10 mg OD over the last 2 years well tolerated. NO micro- or macrovascular complications of her diabetes. No other significant medical history apart from hypertension she is taking Amlodipine 10 mg OD for it with good control. She has presented twice to the hospital 24 hours apart. 1st Visit to ER in our Hospital with fever epigastric pain discharged on Ciprofloxacin suspected gastroenteritis with PPI and sent home. Approximately, 24 hours later she presented again with same symptoms namely fever and epigastric pain but this time associated with diarrhea and nausea for last 20 hours. There was no shortness of Breath or cough. This time she has been admitted to isolating room giving suspicion of COVID-19. Vital signs as following: Temp 38.5 HR 105, BP 135/65 mmHg O2 Sats 96%. on RA. On examination, she was conscious, oriented to time place person. No signs of dehydration. abdomen soft non tender, Chest good air entry no added sound. Hear S1-S2 no murmurs. HRCT has been done at ER. HRCT shows wide spread area of multifocal ground glass opacification are seen in both lungs most of them shows peripheral sub-pleural distribution Around small size consolidation are seen within the ground glass opacification, CT findings are in favour of possibility of COVID-19. Result(s): Blood test as following On admission, FBC was normal, with Hb 13.2, WBC 8.0, Plt 388 cellX 10/ul, U/Es: S.NA 132, s.K 4.2 mmo/l, s. Creatinine normal (58 umol/L -NR 49-90 umol/L) LFTs, Amylase and lipase normal, LDH mild elevation 304 U/L (NR 81-234), Very low Phosphate 03 mmol/L (NR 0.87-1.45), D-Dimer 0.6 mg/L (NR 0.0- 0.5), Corrected Calcium normal, S. Ferritin was 242 ug/L (NR 8.00- 388.00 ug/L), Urinalysis Protein =1 and 4+ ketones, CRP was normal 1 mg/dl ( increased to 214 mg/ l 3rd day) before it goes done 41 mg/L on 7th day of admission. Giving the pandemic of COVID 19 and according to MOHAP Criteria for presenting symptoms. This lady underwent HRCT and COVID19 test by Nasal Swab. Meanwhile, Her Venous Blood gas shows sever metabolic acidosis pH 7.107, PCO2 12.90, PCO2 69.10 On RA, BC 8.9, BE -25.5. Blood sugar 13.2 mmol/L with Urinary Ketones of 4+. Patient has put on DKA Protocol according to our Hospital DKA protocol in addition Stopped her SGLT2 and start on Lantus as a basal. She has put on Scale C (which is the higher scale with infusion about 10 units per hour, for about 96 hours (i.e. 4 days till the blood sugar back to normal for Ketones to disappear, her acidosis didn't improve 1st 24 hours till we give her 1.26% of 500 ml of Sodium Bicarbonate over 6 hours. COVID 19 Test back after 72 hours with positive results. Once out of DKA Diabetes team has stopped her Lantus a stared-on Humalog mix 50% 25 unit TDS. Meanwhile, she has received the following medications waiting for COVID 19 test. Treated with Favipiravir 1600 mg BD for 1 day and 600 mg BD, Start Tazocin 4.5 (stopped after 3 days) Metronidazole, and with prophylactic dose of Clexane. The Hydroxychloroquine hasn't started as Prolong QTC has been notice). Discussion(s): This patient presentation with DKA is another example how COVID- 19 could be a reason for DKA, though SGLT2 could be another cause of her presentation, however the huge insulin requirement and unusual prolong DKA status even with sever acidosis is making COVID-19 more likely causing her presentation It. Conclusion(s): We report this case to highlight the fact DKA - and in fact sever resistant DKA need prolong treatment can happen to Patient with T2DM and COVID 19 positive, and special attention to be paid (with early referral to the diabetes team) if the patient already on SGLT2. And we recommend that to have low threshold to start investigation and treatment as early as possible, regardless the type of Diabetes these patient might have.

Acute Necrotizing Pancreatitis with Cystic Lesion Concomitant with SARS-CoV-2.

SARS-CoV-2 causes severe acute respiratory distress and other clinical complications such as thromboembolic events and gastrointestinal tract disorders, which generally present with abdominal pain. In the case report, we describe a patient who had severe viral necrotizing pancreatitis associated with COVID-19 infection. LEARNING POINTS: In patients with COVID-19, gastrointestinal symptoms should raise suspicion of pancreatitis and additional evaluation should be carried out.Further research to investigate if COVID-19 is associated with acute pancreatitis is warranted.

Acalculous Acute Pancreatitis in a COVID-19 Patient.

Coronavirus disease 2019 (COVID-19) is a multisystemic condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with manifestations ranging from mild upper respiratory symptoms to cytokine storm causing acute respiratory distress syndrome. Pancreatic exocrine tissue and endocrine islets both express angiotensin-converting enzyme 2 (ACE2), the proven receptor for SARS-CoV-2 cell internalization. An increase in pancreatic enzymes has been increasingly recognized in patients with COVID-19, but little is known about the real prevalence of acute pancreatitis in this population. We report a case of acute acalculous pancreatitis in a COVID-19 patient. LEARNING POINTS: Acute pancreatitis may be a manifestation of SARS-CoV-2 infection.Future studies must address the real impact of pancreatic involvement in COVID-19 patients.

The Endocannabinoid System as a Biomarker for Diagnostic and Therapeutic Applications in Depression and Anxiety.

BACKGROUND: Depression and anxiety belong to a family of mental disturbances that has increased significantly in recent years. The etiology of both disorders comprises multiple and complex factors, from genetic background to environmental influence. Since depression and anxiety present severe symptoms, they represent a greater clinical burden and greater therapeutic difficulty. Currently, standardized diagnostic procedures for depression and anxiety allow for addition of further treatments, including psychotherapy and/or pharmacological intervention with effective outcomes. However, further steps should be considered with regards to consideration of the endocannabinoid system's role in depression and anxiety. OBJECTIVE: To review the evidence from animal research and clinical studies of the role of cannabinoid receptors, the major endocannabinoids -anandamide (AEA) and 2-arachidonoylglycerol (2-AG)- and the enzymes related to synthesis and degradation of these chemicals as putative biomarkers for diagnostic and therapeutic elements of depression and anxiety. METHOD: This review included the online search, identification, and analysis of articles (basic and clinical trials) published in English in PubMed linked to the role of cannabinoid receptors, AEA, 2-AG, and the enzymes associated to the synthesis and degradation of these endocannabinoids in depression and anxiety. RESULTS: The neurobiological relevance of the endocannabinoid system offers genetic or pharmacological manipulation of this system as a potential strategy for the diagnostic and clinical management of mood disorders, including depression and anxiety. CONCLUSION: Although the described approach in this review is promising, no solid evidence is yet available, and along with additional experiments using animal models that mimic human depression and anxiety, clinical trials are needed to explore the role of the endocannabinoid system's elements as well as the anandamide membrane transporter, none of which have been adequately studied in depression and anxiety.

COVID-19 and Serum Amylase and Lipase Levels.

Blood levels of amylase and lipase are the result of a balance between production and clearance of these enzymes. Normal blood level of amylase and lipase is 0-90 U/L and 0-70 U/L, respectively. Rise in blood levels of lipase and amylase was observed in pancreatic injury. This is an observational, cross-sectional study involving 279 patients [176 COVID-positive and 103 COVID-negative] admitted at a tertiary care hospital in Mumbai during COVID pandemic. The mean age was 45 years with SD of 15 years with men:women ratio of 2.7:1. Serum lipase and amylase were raised in 101 cases (57.4%) and 57 patients (32.4%), respectively. Out of the 101 patients with raised lipase levels, 44 (25%) patients showed a severe rise (> 3 times the normal), and out of 57 patients with raised amylase levels, 12 patients (6.8%) showed a severe rise (> 3 times the normal). From this study, it can be concluded that the prevalence of hyperamylasemia was 32.4% and that of hyperlipasemia was 57.4% in the involved study population with COVID-positive status.

Acute Pancreatitis and Disseminated Intravascular Coagulopathy in COVID-19 Infection: A Case Report.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can be a plausible trigger for both disseminated intravascular coagulopathy (DIC) and acute pancreatitis. We present an 85-year-old male patient who presented with altered mental status and tested positive for COVID-19 infection. He was hypoxic with an incremental need for oxygen. He had clinical as well as imaging evidence of acute pancreatitis. Clinical evidence of bleeding was noted and lab findings were suggestive of DIC. Despite aggressive initial management, his clinical status continued to deteriorate and comfort care was sought eventually. This case highlights COVID-19 infection as a possible trigger for acute pancreatitis as well as DIC. It also highlights some of the differences in COVID-19-induced DIC, which fulfills the diagnostic criteria of DIC but has atypical findings.