Significant Leukocytosis Research Articles

A novel ITGB2 variant with long survival in patients with leukocyte adhesion defect type-I

Leukocyte adhesion deficiency is an autosomal recessive primary immunodeficiency that has been divided into three types: LAD1 (beta-2 integrin (CD18) family deficiency/defect), LAD2 (absence of fucosylated carbonhydrate ligands for selectins) and LAD3 (defective activation of all beta integrins). However, recently LAD4 has been described in cystic fibrosis patients, with a defect in integrin activation reported in monocytes. LAD-I is the most common type and prevalence of 1 in 1,000,000 live births. Clinical features of LAD patients are recurrent bacterial and fungal infections, omphalitis with delayed umbilical stump separation, significant leukocytosis especially neutrophilia during infection periods, impaired pus formation, and delayed traumatic or surgical wound healing. Flow cytometry is considered a useful tool for rapid diagnosis of the disease. The study of CD18 and CD11 (a, b, c) expression patterns in peripheral blood leukocytes helps to distinguish different phenotypes of LAD-I. In general, patients with ≥ 2% CD18 expression tend to have a less severe infection and often survive until adulthood, whereas < 2% CD18 expression often results in death in infancy. In this case report, three siblings, 10, 15, and 17years old, diagnosed with leukocyte adhesion defect type 1 in adolescence age group, are presented.

English

BACKGROUND Modern automated analysers provide various haematological parameters which have gained a lot of clinical significance. Of these, platelet indices are the most recent one which need to be explored in various diseases. The present study was conducted to evaluate the significance of platelet indices, neutrophil-tolymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and mean platelet volume–to-platelet count in critically ill patients. METHODS This is a prospective study carried out in emergency laboratory of pathology department. 100 patients of intensive care units (ICU) and non-intensive care units (Non-ICU) visiting to the emergency department were included in the study. Fortyfive age and sex matched control patients were taken. The ethylenediamine tetra acetic acid (EDTA) blood sample was analysed on automated analyser. Platelet indices, NLR, MLR and mean platelet volume to platelet counts were calculated in ICU, Non-ICU and control groups. All these values were compared among these groups. RESULTS The study included 400 patients (200 critically ill and 200 non-critically ill) and 45 healthy controls from normal population. The male to female ratio in critically ill and non-critically ill patients was 1.3 : 1 (113 : 87) and 1.08 : 1 (104 : 96) respectively. The critically ill patients had significant leucocytosis (P = 0.019) with neutrophilia (P = 0.005) and lymphopenia (P = 0.048) when compared to noncritically ill patients. There was a significant difference of NLR (P = 0.010), MLR (P = 0.027) and MPV : Platelet count (P = 0.045) in these two groups. However, platelet count and platelet indices were not showing any significant difference in these groups. CONCLUSIONS In the era of modern auto analysers, we should try to utilize the maximum information that could be provided by these machines in forms of various indices and ratios. The present study highlights that neutrophilic leucocytosis with lymphopenia is seen in critically ill patients when compared to non-critically ill patients and normal control population. NLR, MLR and MPV to platelet ratios are also of great importance whereas platelet count and platelet indices are always not helpful in categorization of severity of the patient’s condition. KEYWORDS Intensive Care Unit Patients, Neutrophil Lymphocyte Ratio, Monocyte Lymphocyte Ratio, Mean Platelet Volume

Effect of DNMT3A variant allele frequency and double mutation on clinicopathologic features of patients with de novo AML

The clinicopathologic features of DNA methyltransferase 3A (DNMT3A)-mutated de novo acute myeloid leukemia (AML), and the significance of variant type, variant allele frequency (VAF), and multiple concomitant DNMT3A mutations, remain poorly defined. We examined 104 DNMT3A-mutated de novo AML patients from 2 major centers. Most (82%) had normal karyotype (NK); R882H variants were frequent(38%). The most commonly comutated genes included nucleophosmin (NPM1; 53%), Fms-related tyrosine kinase 3 (FLT3)–internal tandem duplication (25%), IDH1 (23%), IDH2 (23%), and TET2 (21%). Patients with high DNMT3A VAF at diagnosis (≥44%; DNMT3AHIGH) had more significant leukocytosis and higher blast counts in peripheral blood and bone marrow. DNMT3AHIGH cases were associated with much shorter event-free survival (EFS; 14.1 vs 56.8 months) and overall survival (OS; 18.3 months vs not reached) compared with cases of patients with low DNMT3A (DNMT3ALOW). Thirteen patients had 2 DNMT3A variants and similar VAFs at diagnosis that tracked together at multiple time points after chemotherapy and/or stem cell transplantation (SCT). In multivariable analyses performed in NK patients who received standard induction chemotherapy, presence of 2 DNMT3A mutations (hazard ratio [HR] = 3.192; P = .038) and SCT in first complete remission (HR = 0.295; P = .001) independently affected EFS; increasing marrow blast percentage (HR = 1.026; P = .025), high DNMT3A VAF (HR = 3.003; P = .010), and 2 DNMT3A mutations (HR = 4.816; P = .020) had independent effects on OS. These data support the adverse prognostic significance of DNMT3AHIGH reveal a novel association between 2 concomitant DNMT3A mutations and inferior outcome in DNMT3A-mutated de novo AML with a NK.

Scalp Swelling and Headache in a 12-year-old Boy

1. Kathryn Westphal, MD* 2. Respicius Bakalemwa, MD† 3. Elizabeth Groothuis, MD, MPH* 1. *Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 2. †Department of Pediatrics, Bugando Medical Centre, Mwanza, Tanzania A 12-year-old boy with sickle cell disease (SCD) is admitted to a hospital in Mwanza, Tanzania, with acute onset of periorbital and scalp swelling. Associated symptoms include fever, headache, difficulty breathing, and back pain. Because resources in sub-Saharan Africa are limited, access to comprehensive care for patients with SCD is variable. The general principles of management focus on early diagnosis, parental education, prevention of infection with vaccinations and prophylactic medications, prompt treatment of infection and pain, the use of hydroxyurea for stroke prevention, and blood transfusions for life-threatening anemia. This patient has a known diagnosis of SCD but has infrequent pain episodes and no previous transfusions. He is not receiving hydroxyurea or prophylaxis against bacterial infections or malaria. He has no history of stroke and no known head trauma. On presentation he is afebrile and his heart rate is 120 beats/min, respiratory rate is 40 breaths/min, and blood pressure is 105/75 mm Hg. His oxygen saturation is 92% in room air. Physical examination is significant for pallor, periorbital edema, scalp edema, dyspnea without adventitious lung sounds, and splenomegaly with diffuse abdominal tenderness. His scalp edema is fluctuant and extends posteriorly from the periorbital region, encompassing the entire scalp. Swelling is most prominent in the frontal and parietal areas. The overlying skin is nonerythematous and nontender but is warm to the touch. His neurologic examination has no focal findings, although generally he appears tired. Initial laboratory results demonstrate a white blood cell count of 84,000/μL (84×109/L) with a lymphocytic predominance (57%), a hemoglobin level of …

Is It Necessary to Perform a Routine Antibiotic Prophylaxis before an Elective Surgery of Cesarean Section?

INTRODUCTION: According to the data by World Health Organization, the broad and often insufficiently substantiated prescription of antibiotics, including for prophylactic purposes, has led to the growth of antibiotic-resistant microflora, which is a dangerous and intractable problem of modern medicine. Despite the undoubted benefits of antibiotics in the management of wound infection and endometritis after cesarean section, the routine prophylactic administration of antibacterial drugs can not only carry the risk of growth of resistant nosocomial microflora, but also have doubtful effects on the health of a newborn. PURPOSE OF THE STUDY: The purpose of the study was to justify the possibility of carrying out elective cesarean section operations without routine antibiotic prophylaxis. MATERIALS AND METHODS: An analysis of 333 cases of elective cesarean section operations carried out in the obstetric department in the period from 2017 to 2019 was performed. Routine antibiotic prophylaxis before surgery was not prescribed in 118 healthy patients with an uncomplicated history and a smooth course of the gestational process. The remaining 215 women received a single intravenous injection of 1 g of cefazolin sodium intraoperatively, after extraction of the fetus. A comparative analysis of the clinical groups was carried out according to the following criteria: vaginal microbiocenosis before surgical delivery, duration, and features of the operation, clinical blood count on days 1 and 5 of the post-operative period, condition of postoperative sutures, the presence of discharge from the wound, signs of infectious complications from the uterus or other organs, uterine involution rate, duration of hospital stay before and after surgery, follow-up history for 1 month after discharge from the maternity ward. The data obtained were subjected to statistical processing. RESULTS: We have found no significant differences in the course and number of complications in the postpartum period in the compared clinical groups. The statistically significant transient leukocytosis observed on the 1st day of the postoperative period in patients who did not undergo antibiotic prophylaxis before the surgery seems to be associated with a more pronounced adaptive reaction and was not combined with any clinical symptoms of development of infection. CONCLUSION: No relationship has been identified between the routine prescription of antibiotics before or during an elective cesarean section and the risk of developing infectious complications in the post-operative period. Antibiotic prophylaxis before surgery should be carried out differentially, taking into account the history and features of the course of this pregnancy.

A phase I trial evaluating the effects of plerixafor, G-CSF, and azacitidine for the treatment of myelodysplastic syndromes

Interactions between the bone marrow microenvironment and MDS tumor clones play a role in pathogenesis and response to treatment. We hypothesized G-CSF and plerixafor may enhance sensitivity to azacitidine in MDS. Twenty-eight patients with MDS were treated with plerixafor, G-CSF and azacitidine with a standard 3 + 3 design. Subjects received G-CSF 10 mcg/kg D1–D8, plerixafor D4–D8, and azacitidine 75 mg/m2 D4–D8, but the trial was amended to reduce G-CSF dose to 5 mcg/kg for 5 days after 2 patients had significant leukocytosis. Plerixafor was dose escalated to 560 mcg/kg/day without dose limiting toxicity. Two complete responses and 6 marrow responses were seen for an overall response rate (ORR) of 36% in evaluable patients, and ORR of 53% in patients receiving the triplet. Evidence of mobilization correlated with a higher ORR, 60% vs. 17%. Plerixafor, G-CSF and azacitidine appears tolerable when given over 5 days and has encouraging response rates. KEY POINTS Plerixafor and G-CSF can be safely combined with azacitidine for 5 days in patients with MDS. The overall response rate of 53% for evaluable patients with this regimen is higher than expected and more responses were seen in patients with blast mobilization.

Combinatory Effects of Bone Marrow-Derived Mesenchymal Stem Cells and Indomethacin on Adjuvant-Induced Arthritis in Wistar Rats: Roles of IL-1β, IL-4, Nrf-2, and Oxidative Stress.

Rheumatoid arthritis (RA) is a disorder triggered by autoimmune reactions and related with chronic inflammation and severe disability. Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs) have shown a hopeful immunomodulatory effect towards repairing cartilage and restoring joint function. Additionally, indomethacin (IMC), a nonsteroidal compound, has been considered as a potent therapeutic agent that exhibits significant antipyretic properties and analgesic effects. The target of the current research is to assess the antiarthritic efficacy of BM-MSCs (106 cells/rat at 1, 6, 12 and 18 days) and IMC (2 mg/kg body weight/day for 3 weeks) either alone or concurrently administered against complete Freund's adjuvant-induced arthritic rats. Changes in paw volume, body weight, gross lesions, and antioxidant defense system, as well as oxidative stress, were assessed. The Th1 cytokine (IL-1β) serum level and Th2 cytokine (IL-4) and Nrf-2 ankle joint expression were detected. In comparison to normal rats, it was found that the CFA-induced arthritic rats exhibited significant leukocytosis and increase in paw volume, LPO level, RF, and IL-1β serum levels. In parallel, arthritic rats that received BM-MSCs and/or IMC efficiently exhibited decrease in paw edema, leukocytosis, and enhancement in the antioxidant enzymatic levels of SOD, GPx, GST, and GSH in serum besides upregulation of Nrf-2 and anti-inflammatory IL-4 expression levels in the ankle articular joint. Likewise, these analyses were more evidenced by the histopathological sections and histological score. The data also revealed that the combined administration of BM-MSC and IMC was more potent in suppressing inflammation and enhancing the anti-inflammatory pathway than each agent alone. Thus, it can be concluded that the combined therapy with BM-MSC and IMC may be used as a promising therapeutic choice after assessing their efficacy and safety in human beings with RA, and the antiarthritic effects may be mediated via modulatory effects on Th1/Th2 cytokines, ozidative stress, and Nrf-2.

Correlation of refractory hypoxemia with biochemical markers and clinical outcomes of COVID-19 patients in a developing country: A retrospective observational study

ABSTRACT Introduction: COVID-19 is mainly a respiratory illness, causing hypoxemia in the majority of those been infected. In our study, we aimed to correlate the biochemical markers with hypoxemia and predicting the prognosis of COVID-19 patients. Materials and methods: A retrospective, observational study was conducted to include all the admitted COVID-19 patients (n = 183) diagnosed by a real-time Polymerase chain reaction and evaluated those for hypoxemia and disease outcomes by utilizing the biochemical markers. Results: Out of the 183 patients, 117 were in the ward, 66 were in ICU, 148 of them recovered, while 35 deaths were reported, 89 patients were having persisting hypoxemia (despite oxygen therapy) during the hospital stay, and the remaining 94 were non-hypoxemic with or without supplemental oxygen therapy. There were significant differences in mean hemoglobin (p = 0.028), total leukocyte count (p = 0.005), Neutrophil-to-Lymphocyte ratio (p = 0.001), serum urea and creatinine (p = 0.002), serum potassium (p = 0.009), C-reactive protein (p = 0.001), Lactate dehydrogenase (p = 0.005), and Ferritin (p = 0.042) of the hypoxemic patients versus non-hypoxemic group. Amongst the deceased patients, there was significant leukocytosis (p = 0.008), increased Neutrophil-to-Lymphocyte ratio (p = 0.001), elevated C-reactive protein (p = 0.001), and Lactate dehydrogenase (p = 0.009). Receiver operating characteristic curves showed Neutrophil-to-Lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001), and Lactate dehydrogenase (p < 0.001) most significantly associated with hypoxemia and death. Conclusion: The inflammatory markers are a good guide for predicting the hypoxemia and disease outcome. The results concluded Neutrophil-to-Lymphocyte ratio, C-reactive protein, and Lactate dehydrogenase were effective biomarkers in predicting a severe course of COVID-19, but could not establish significant associations of serum Ferritin, Procalcitonin, and D-Dimer.

Potential Ameliorative Effects of L-Carnitine on Imidacloprid-Induced Hepato- and Nephrotoxicity in Male Albino Rats

The current study was intended to evaluate the possible protective role of L-Carnitine (LC) against imidacloprid (IM)-induced hepato- and nephrotoxicity in male albino rats. Thirty male albino rats were divided into 6 groups (n=5); control group, IM (32 mg/kg BW, 1/10 LD50)-treated group, LC200 (200 mg/kg BW)-treated group, LC400 (400 mg/kg BW)-treated group, IM+LC200-treated group, and IM+LC400-treated group. All treatments were given by oral route once daily for four weeks. Hematologically, the results exhibited that IM administration induced a significant decrease in red blood cells (RBCs) count, hemoglobin (Hb) and hematocrit (Ht) values. The erythrocytic indices (MCV, MCH and MCHC) displayed non-significant change in all treated groups. However, IM-treated group showed a significant leukocytosis and thrombocytosis after four weeks of treatment as compared to control group. Biochemically, the results revealed that IM convinced a significant elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) activities, as well as serum total bilirubin (TB), direct bilirubin (DB) and indirect bilirubin (IB), globulins, urea, creatinine, potassium (K+), pro-inflammatory cytokines (tumor necrosis factor- alpha and interleukin-6) levels at the end of experiment matching with the control group. However, IM administration resulted in a significant diminution in the serum of total proteins (TP), albumin, and sodium (Na+) levels, with a significant increase and decrease respectively in the levels of lipid peroxidation and antioxidant biomarker in the hepatic and renal tissues of rats after four weeks of treatments as compared to control group. Histopathologically, IM administration revealed marked degenerative and necrotic alterations in the liver and kidney. Conversely, LC treatment at two doses (200 and 400 mg) ameliorated IM-induced alterations in the blood picture, oxidative damage and inflammation in the liver and kidneys.Finally, it could be concluded that treatment with LC at two doses (200 and 400 mg) ameliorated IM-induced oxidative damage, alterations in the hematology, liver and kidney function tests, as well as their histopathology. However, administration of LC at a dose of 400 mg/kg BW showed better protective effects against IM-induced hepato-nephrotoxicity as compared to the low dose (200 mg/kg BW).

Recurrent obstructive uropathy secondary to pyometrocolpos in an 8-month-old infant: a case report

BackgroundPyometrocolpos is accumulation of infected fluid in the uterus and vagina. It is rare in children, mostly seen after menarche as a result of obstructive congenital genital malformation that impairs free drainage of the uterine secretions. In a child, it may present as an acute illness that necessitates urgent and appropriate management and treatment of the underlying cause, which can be a challenge in a resource-limited setting.Case presentationWe report a case of pyometrocolpos in an 8-month-old African infant who presented with fever, vomiting, decreased urine output, and abdominal distension of 12 days’ duration. An abdominal examination revealed a subumbilical midline incision scar and a midline lower abdominal mass. She appeared to have presented at the emergency department with similar complaints 2 months earlier and had been diagnosed with pyometra, which was managed by emergency laparotomy for pus drainage, and she was kept on antibiotics. Recovery was established after 10 days of admission, and the patient was discharged to home. Her symptoms reappeared 2 months after the first presentation. Her blood work showed significant leukocytosis with neutrophilia, and abdominal ultrasound depicted bilateral hydronephrosis with hydroureters and a fluid-filled uterus. Examination under anesthesia in the operating theater revealed normal-looking female genitalia with a cribriform hymen, beneath which lied a transverse vaginal septum. Foul-smelling pus was aspirated through the septum, and septectomy was performed to allow 350 ml of pus to drain. A pus sample was sent for culture and sensitivity, and Escherichia coli sensitive to ceftriaxone and gentamicin was isolated.ConclusionPyometrocolpos is rare in childhood but should be suspected in a girl presenting with a midline lower abdominal mass accompanied with urinary obstructive symptoms associated with fever and gastrointestinal symptoms. Escherichia coli seems to be the most probable offending organism, but pus culture is crucial for antibiotic stewardship in proper management of the infection. Definitive treatment should focus on correcting the obstructive anatomical congenital deformity that caused the obstruction in order to avoid recurrence.

Hematological parameters predicting severity and mortality in COVID-19 patients of Pakistan: a retrospective comparative analysis

ABSTRACT Background and Objectives: COVID-19 is a global pandemic. In our study, we aimed to utilize the hematological parameters in predicting the prognosis and mortality in COVID-19 patients. Materials and methods: A retrospective, observational study was conducted to include all the admitted patients (n = 191) having COVID-19 Polymerase chain reaction (PCR) positive, and evaluated those for prognosis and disease outcome by utilizing several biochemical and hematological markers. Results: Amongst the patients admitted in the ward versus in the intensive care unit (ICU), there were significant differences in mean hemoglobin (P = 0.003), total leukocyte count (P = 0.001), absolute neutrophil and lymphocyte counts (P < 0.001), absolute monocyte count (P = 0.019), Neutrophil-to-Lymphocyte ratio (NLR) and Lymphocyte-to-Monocyte ratio (LMR) (P < 0.001), Platelet-to-Lymphocyte ratio (PLR) and Lymphocyte-to C-reactive protein ratio (LCR) (P = 0.002), and C-reactive protein (CRP) levels (P < 0.001). Amongst the deceased patients, there was significant leukocytosis (P = 0.008), neutrophilia and lymphopenia (P < 0.001), increased NLR (P = 0.001), decreased LMR (P < 0.001), increased PLR (p = 0.017), decreased LCR (p = 0.003), and elevated CRP level (P < 0.001). A receiver operating characteristic curve obtained for the above parameters showed NLR (AUC: 0.841, PPV: 83.6%) and PLR (AUC: 0.703, PPV: 81.8%) for ICU patients, while NLR (AUC: 0.860, PPV: 91.1%) and PLR (AUC: 0.677, PPV: 87.5%) for the deceased patients had significant accuracy for predicting the disease severity of COVID-19 in comparison to survivors. Conclusion: The inflammatory markers and hematological indices are a good guide for predicting the severity and disease outcome of coronavirus disease. NLR and PLR are elevated in severe disease while LMR and LCR are inversely correlating with disease severity.

S3402 Toxic Megacolon Disguised as Fecal Impaction

INTRODUCTION: Clostridium difficile colitis is a disease rising in incidence over the years with increasing mortality, especially with complications such as toxic megacolon which can affect 0.4-3% of cases. This case report shows the need to keep a high index of suspicion, especially with atypical presentations to help reduce the mortality rate. CASE DESCRIPTION/METHODS: A 77 year old male with a history of Alzheimer’s Disease had a prolonged hospital course after admission for a fracture requiring surgery after a ground level fall. One and a half month into the hospital course, the patient was diagnosed with suppurative parotitis with associated leukocytosis up to 33,000. He was begun on empiric antibiotics which were eventually de-escalated to daptomycin & zosyn with subsequent resolution in leukocytosis one week into the planned two week antibiotic course. On the last day of antibiotics, patient was noted to having uptrending leukocytosis up to 24,000 despite staying afebrile, vitally stable, and with no symptoms reported including abdominal pain or diarrhea. His antibiotics were escalated with continued worsening of leukocytosis up to 42K. At that time, patient began complaining of abdominal pain with subsequent CT scan noting significant colonic stool with possible fecal impaction. Given the leukocytosis and imaging, he was evaluated by surgery due to concern of possible perforation. Surgery had low concern for perforation and recommended aggressive bowel regimen after which patient began stooling frequently. Shortly thereafter, he became hypotensive requiring vasopressor support. He subsequently tested positive for clostridium difficile and was begun on treatment for fulminant C. difficile with toxic megacolon. However, the patient died a few days later. DISCUSSION: C. difficile colitis and its complications, including toxic megacolon, are important to recognize early to ensure prompt treatment of this potentially fatal disease. There are the known expected signs and symptoms including abdominal pain, diarrhea, fevers, lactic acidosis, elevated creatinine, significant leukocytosis. However, it is important to not be confounded by unusual presentations such as in this case. Other rare case reports include Burke et al. who describe a patient with toxic megacolon from C. difficile without diarrhea. Malkan et al. also describe a case series of uncommon presentations though most are noted to have known risk factors including prolonged hospital or antibiotic courses.

S2309 Acute Pancreatitis in Ulcerative Colitis: An Easily Overlooked Diagnosis

INTRODUCTION: Ulcerative colitis (UC) is often associated with extraintestinal manifestations (EIM) including musculoskeletal, ocular, dermatologic, and hepatobiliary. Very rarely, pancreatitis has been associated with UC. This abstract presents an interesting case of pancreatitis occurring simultaneously with a new diagnosis of UC. CASE DESCRIPTION/METHODS: A 59-year-old male with no significant medical history initially presented to the emergency room with a several day history of abdominal pain. He was hemodynamically stable and had no significant leukocytosis, anemia, or serum chemistry abnormalities. However, his serum lipase was elevated to >4,000U/L. An abdominal CT scan showed pancreatic tail pancreatitis and fat-stranding of the descending and sigmoid colon consistent with colitis. Stool studies were negative for any infectious etiology. The patient was discharged with ciprofloxacin and metronidazole for presumptive diverticulitis and uncomplicated pancreatitis. The patient returned several days later with similar complaints and was admitted for further workup. Repeat CT scan showed unchanged pancreatitis but worsening of pericolonic fat stranding. The patient underwent colonoscopy which showed continuous, circumferential, pancolonic erythema, friability, and ulceration consistent with Mayo Score 3 colitis. Biopsies were consistent with ulcerative colitis. The patient was started on methylprednisolone and experienced significant improvement. DISCUSSION: While increased incidence of pancreatitis in IBD patients has been previously identified, the concurrent occurrence of a UC flare with pancreatitis is significantly more rare. This case emphasizes the importance of recognizing this association early, as the diagnosis of fulminant colitis can be overlooked or improperly treated. Furthermore, this case highlights the interesting possibility that the fulminant UC may have directly led to pancreatitis. As in the general population, the most common causes of pancreatitis among UC patients are gallstones and alcohol abuse—neither of which apply to this patient. Furthermore, isolated pancreatic tail pancreatitis is even more unlikely. Thus, the degree of colonic inflammation and location of pancreatitis suggest a novel mechanism for acute pancreatitis stemming from inflammation of adjacent retroperitoneal structures.

PANCREATICO-PLEURAL FISTULA AND SUBSEQUENT FUNGAL EMPYEMA

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: A rare pancreatitis complication is pancreatico-pleural fistula with empyema development being even more scarce. CASE PRESENTATION: A 48-year-old male with a history of alcoholic pancreatitis, subsequent mediastinitis with recurrent pleural effusions and pneumonia presented to the outpatient pulmonology office for persistent dyspnea. We ordered basic labs, showing significant leukocytosis and anemia, and a thoracentesis, removing 600 milliliters. Upon transferring to the hospital, further workup revealed elevated lipase and C-reactive protein. Pleural fluid studies indicated an amylase-rich exudative process. Chest-x ray showed bilateral pleural effusions and multilobar pneumonia. Computed Tomography (CT) Angiography of chest showed loculated moderate right and small left pleural effusion, multilobar pneumonia especially in lower lobes. CT of abdomen/pelvis showed acute pancreatitis and pancreatic cystic lesions in the head and uncinate process. We initiated broad coverage with Vancomycin, Cefepime, and Metronidazole. On day 3 of admission, a chest tube was placed and 6 doses of lytic therapy were administered. Endoscopic Retrograde Cholangio-Pancreatography (ERCP) was performed and confirmed pancreatico-pleural fistula (PPF). Thus, sphincterotomy was performed and a stent was placed; however, the pancreatic duct could not be cannulated. Video-Assisted Thoracoscopic Surgery was not indicated at this time. Pleural fluid cultures grew Candida Albicans and Micafungin was added. Upon receiving sensitivities, we discontinued the current regimen and started Fluconazole. Chest tube was removed on day 10 of admission. The patient was discharged home with instructions to continue Fluconazole for 6 weeks, weekly lab monitoring, repeat ERCP with pancreatic duct cannulation in 3 weeks, and repeat Chest x-ray in 2 months. DISCUSSION: PPF with pleural effusion is reported with an incidence of 0.4%. A pancreatic duct disruption causes persistent leakage of pancreatic secretions. Initially, a fluid collection forms, known as a pseudocyst. Eventually, the secretions can cause a spontaneous erosion into a neighboring organ or cavity, the pleural cavity in our case. Patients with PPF present similarly to pleural effusions, as they are recurrent and refractory to repeated thoracentesis. 1 In rare cases, an empyema can develop that can cause life-threatening sepsis. 2 Classical PPF patients are middle-aged men, chronic pancreatitis from alcoholism, dyspneic, no acute abdominal symptoms, left pleural effusions, pseudocyst on CT, and elevated pleural fluid amylase, lipase, and albumin. These were observed in our case, except bilateral pleural effusions, which has a 19% incidence compared to 74% for left sided. 1 CONCLUSIONS: As clinicians, we should consider the rare complications of PPF in the differential for patients with a history of pancreatitis presenting for dyspnea and sepsis. Reference #1: Machado, NO. Pancreaticopleural Fistula: Revisited. Diagnostic and Therapeutic Endoscopy. 2011;2012:1-5. Reference #2: Kim E, Ahn HY, Kim YD, Hoseok, Cho JS. Successful Diagnosis and Treatment of a Pancreaticopleural Fistula in a Patient Presenting with Unusual Empyema and Hemoptysis. Korean J Thorac Cardiovasc Surg. 2019;52(3):174-177. doi: 10.5090/kjtcs.2019.52.3.174. DISCLOSURES: No relevant relationships by Jacob Burch, source=Web Response No relevant relationships by James Choi, source=Web Response No relevant relationships by Rakesh Gami, source=Web Response No relevant relationships by Tyler Kemnic, source=Web Response No relevant relationships by Jason Liu Liu, source=Web Response No relevant relationships by Rohan Prasad, source=Web Response No relevant relationships by Fazal Raziq, source=Web Response No relevant relationships by Eric Smith, source=Web Response

Leucocytosis and Stroke in a Lung Cancer Patient.

To illustrate an unusual presentation of progression of non-small-cell lung adenocarcinoma.To highlight the prognostic significance of extreme leucocytosis and hypereosinophilia in patients with an underlying malignancy.

Poor Prognostic Biochemical Markers Predicting Fatalities Caused by COVID-19: A Retrospective Observational Study From a Developing Country.

Background and objectivesInfections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are rapidly spreading, posing a serious threat to the health of people worldwide, resulting in the World Health Organization officially declaring it a pandemic. There are several biochemical markers linked with predicting the severity of coronavirus disease. This study aims to identify the most effective predictive biomarker such as C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), procalcitonin (PCT), and D-dimer, among others, in predicting the clinical outcome of the disease.Materials and methodsThis study was conducted as a retrospective, observational, multi-centric study, including all admitted COVID-19 positive patients only. The disease outcome was followed along with the hospital course of every patient at the time of analysis. Baseline laboratory investigations of all patients were monitored both at admission and discharge. A comparative analysis was done between the survivors (n=263) and non-survivors (n=101). Statistical analysis was conducted using IBM SPSS Statistics for Windows Version 25 (Armonk, NY: IBM Corp.).ResultsOf 364 patients, 65.7% were in the isolation ward, and 34.3% were in the intensive care unit; 72.3% of patients survived, while 27.7% of patients died. The mean age of the study population was 52.6 ± 15.8 years with female patients significantly younger than male patients (p=0.001) and 50 to 75 years being the most common age group (p=0.121). Among the survivors versus non-survivors of COVID-19, there were significant differences in total leukocyte count (p<0.001), neutrophil count, (p<0.001), lymphocyte count (p<0.001), urea (p<0.001), serum bicarbonate (p=0.001), CRP levels (p<0.001), LDH (p=0.013), and D-dimer (p<0.001) at admission. At discharge, the laboratory values of non-surviving patients showed significant leukocytosis (p<0.001), neutrophilia (p<0.001), lymphocytopenia (p<0.001), decreased monocytes (p<0.001), elevated urea and creatinine (p<0.001), hypernatremia (p<0.001), decreased serum bicarbonate levels (p<0.001), elevated CRP level (p=0.040), LDH (p<0.001), ferritin (p=0.001), and D-dimer (p<0.001).Among the recovered patients, the laboratory investigations at admission were significantly different from those at discharge like increased platelets (p=0.007), lower neutrophil count (p=0.001), higher lymphocyte count (p=0.005), an improved creatinine (p=0.020), higher sodium (p=0.008), increased bicarbonate levels (p<0.001), decreased CRP levels (p<0.001), and a lower LDH (p=0.039). However, the laboratory values of non-surviving patients had shown a lower hemoglobin (p=0.016), increased mean cell volume (p<0.001), significantly increased total leukocyte count (p<0.001), increased urea and creatinine (p<0.001), hypernatremia (p<0.001), increased bicarbonate (p=0.025), elevated D-dimer levels (p=0.043), and elevated PCT (p=0.021) on discharge. Receiver operating characteristic analysis concluded LDH (area under the curve [AUC]: 0.875), D-dimer (AUC: 0.803), and PCT (AUC: 0.769) were superior biomarkers to ferritin (AUC: 0.714) and CRP (AUC: 0.711) in predicting the fatality of COVID-19.ConclusionInflammatory markers are a useful guide for predicting mortality, and the study results concluded that LDH, PCT, D-dimer, CRP, and ferritin were effective biomarkers.

Toxicity of a methotrexate metronomic schedule in Wistar rats

Metronomic chemotherapy is a relevant strategy that uses low doses of antineoplastic drugs for sustained periods to control tumor growth, an alternative frequently utilized in veterinary patients. This work aimed to evaluate the toxic effects of a metronomic oral dose of methotrexate (MTX) for 45 days in tumor-free Wistar rats when compared with control animals. Clinical alterations, body weight, food, and water intake were monitored daily, and bone marrow suppression, hematological, biochemical, and histopathological analyses were performed at three points (days 30, 45, and 60). MTX-treated animals did not demonstrate severe systemic involvement. At 30 days, compared with control animals, MTX-treated animals showed significant leukocytosis (11.9 ± 2.3 vs. 7.8 ± 0.2 106/μL; P < .05) and augmentation of immature myeloid populations from bone marrow (9.0 ± 0.8 vs. 6.5 ± 1.5%; P < .05), and at 60 days, treated animals showed significant neutrophilia (35.0 ± 11.0 vs. 23.00 ± 3.0%; P < .05), depletion of bone marrow lymphocytes (8.2 ± 0.7 vs. 11.5 ± 1.9%; P < .05), and immature myeloid populations (7.2 ± 0.7 vs. 8.3 ± 0.6%; P < .05). At a histopathological level, splenic hypoplasia and respiratory inflammatory lesions were significant when compared with control animals, presenting mild to moderate myelotoxicity, immune suppression, and associated clinical compromise that persisted beyond treatment withdrawal. This suggested that MTX metronomic toxicity should not be neglected owing to the observed residual side-effects and special care should be taken regarding myelosuppression.

Hematological and immunological responses in the African catfish Clarias gairepinus exposed to sublethal concentrations of herbicide Ronstar®.

The aim of the study was to investigate the effects of sublethal concentrations (0.3, 0.6 and 1.2mgL-1) of the herbicide Ronstar on the hematology and some immune parameters in Clarias gariepinus juvenile (mean weight and length 58.72±2.46g and 27.60±1.62cm, respectively). The hematological and some immune parameters were studied for 21 days in a static renewal bioassay system in which the water and the herbicide were changed daily. The erythrocyte count, hemoglobin concentration (Hb), and packed cell volume (PCV) were significantly (p<0.05) reduced in the treatment groups. When compared with the control, there were significant (p<0.05) leucocytosis, lymphocytosis, neutropenia and monocytopenia in the treatment groups. Both the mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) were reduced ((p<0.05) in the Ronstar-exposed fish. The result showed that the treated fish suffered hypochromic microcytic anemia. The total immunoglobulin and phagocytic indices (phagocytic capacity and phagocytic index) were significantly (p<0.05) reduced in the treatment groups. while the respiratory burst was significantly (p<0.05) increased in the treatment groups. The result showed that exposure to Ronstar had adverse effects on the hematology and immunocompetency of the fish.

Clinical Predictors of Histologic Chorioamnionitis at Term [06N

INTRODUCTION: The objective of this study was to determine the diagnostic criteria for clinical chorioamnionitis (CC) that best predict histologic chorioamnionitis (HC). METHODS: This is an IRB-approved retrospective cohort study of women diagnosed with CC over a 5-year period. Inclusion criteria were: gestational age 37 to 42 weeks, diagnosis of CC as determined and documented by the provider, and available placental pathology records. CC diagnostic criteria (maternal temperature, maternal or fetal tachycardia, leukocytosis, fundal tenderness, and purulent amniotic fluid) were compared between those with and without HC. RESULTS: 223 women met inclusion criteria; 159 (71.3%) had HC. Prostaglandin use, diabetes, epidural use, and duration from initiation of antibiotics to delivery were similar. Mean maximum body temperature and presence of other diagnostic criteria were similar between the groups. Those with HC were more likely to have a peak white blood cell count greater than or equal to 25.0x10^9cells/L (13.2 vs 3.1%, P=.03). Twenty-one (13.2%) women in the HC group and 12 (18.8%) in the normal pathology group had no documented fever despite a diagnosis of CC. Of the women without a fever, 64% had HC. CONCLUSION: Normal placental pathology was found in a large proportion of women with CC. Although none of the assessed clinical findings predicted HC, a significant leukocytosis was more frequent in women with HC. For women diagnosed with CC without fever, the majority had findings of HC. This study highlights the challenge of diagnosing CC. Providers should consider the diagnosis of CC in the absence of fever when other clinical criteria are present.

Aberrant TRPM4 expression in MLL-rearranged acute myeloid leukemia and its blockade induces cell cycle arrest via AKT/GLI1/Cyclin D1 pathway

Transient Receptor Potential Melastatin Subfamily Member 4 (TRPM4) has been demonstrated to be aberrantly expressed in several cancers but seldom reported in acute leukemia. Based on database mining and validated experiments, our present data show that TRPM4 is selectively overexpressed in AML patients and cell lines with the MLL gene rearrangement. We analyzed the correlation between TRPM4 expression and clinical parameters in a validated cohort of AML patients. Increased TRPM4 expression was associated with significant leukocytosis (p = .028), M4/M5 subtype (p = .000), FLT3-ITD mutation (p = .034), MLL status (p = .007) and a higher risk stratification (p = .001). Knockdown of TRPM4 mediated by siRNA impaired proliferation and arrested the cell cycle at the G0/G1 phase in MLL-rearranged leukemia cells. We suggested that TRPM4 may be involved in the pathogenesis of MLL-rearranged leukemia through regulating the AKT/GLI1/Cyclin D1 pathway. The transcription factor HOXA9 was found to be responsible for upregulation of TRPM4 expression by binding to its promoter. In conclusion, TRPM4 is overexpressed in MLL-rearranged AML and blockade of TRPM4 may be an alternative therapeutic approach in AML patients with high TRPM4 expression.