Effect of delta carbon dioxide and lactate on prognosis in patients undergoing open-heart surgery.

Background: To identify individuals with an increased mortality and morbidity risk after surgery, different parameters showing impaired tissue perfusion/oxygenation have been investigated, and the balance between tissue oxygen consumption and oxygen delivery has been evaluated in detecting organ failure. Aim: This study aimed to evaluate the efficacy of central venous--arterial partial carbon dioxide difference (ΔPCO2) and lactate (ΔLAC) values within the first week after discharge in predicting mortality in patients undergoing open-heart surgery. Patients and Methods: A total of 102 patients between February and April 2020 were included in the study. The patients' data obtained at the end of cardiopulmonary bypass (hour 0) and during the intensive care follow-up (hour 1, hours 6, and 24) data were prospectively recorded. All statistical analyses were performed using SPSS v. 22.0 for Windows (SPSS Inc, Chicago, IL, USA). Results: The mean age of the patients was 56.88 ± 11.02 (min 18-max 78) years, and 71.6% of the patients were male. It was observed that the area under the curve was not significant for the four measurements performed for ΔLAC. Although the area under the curve of ΔPCO2 measured at hour 6 (0.66) was significant. Conclusion: The ΔPCO2 were found to have a poor ability to predict the development of complications during the intensive care and early postoperative period in patients undergoing open-heart surgery.

Systematic Review: Clinical Symptoms and Laboratory and Radiology Findings in Children with COVID-19.

Coronavirus disease 2019 (COVID-19) caused by the new [novel] coronavirus, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a pandemic with exceeding 72 million cases and 1.2 million deaths by the end of November 2020. We aimed to evaluate clinical, laboratory, and radiology findings of COVID-19 in children as reported worldwide and thereby to increase the clinical knowledge about the disease. Bibliographic searches were conducted in December 2020 using PubMed and Google Scholar. The search was limited to children [below 18 years of age]. The search strategy yielded a total of 336 potential articles but finally a total of 25 valid studies covering a total of 2446 (China: 1109, Europe: 663, North America: 674) pediatric patients. In the studies covered by this review, it was observed that the median age was calculated at various values between the ages of 1 and 7 years. In the studies, overall rate of the asymptomatic patients was 24.8% (ranging between 10.7 and 56.6). Acute upper respiratory tract infection (URTI) [mild disease] was observed in 40.7 (ranging between 22 and 50.6%), mild pneumonia in 27% (ranging between 9.5 and 40.6%), and severe pneumonia in 5.3% (ranging between 1.9 and 10.6%). A total of 3% (ranging between 0.7 and 5.1%) of the patients had critical severity. Among the most common clinical symptoms and findings; 61.7% (ranging between 57.4 and 64.3%) of the patients had fever, 53.2% (ranging between 30.6 and 75.1%) had cough, 16.8% (ranging between 4.6 and 27.2%) had diarrhea or nausea, and 15% had lymphopenia. Abnormal radiological findings were detected in 47.2 of the children with COVID-19 and ground glass opacity was in 22.2%. COVID-19 manifests milder and the clinical signs and symptoms vary widely in children. Laboratory and radiological findings of COVID-19 in pediatric patients are not mostly disease-specific, except lymphopenia may have a limited value, and ground glass opacity may have a significant diagnostic value.

Two Novel CEBPA Mutations in a Turkish Patient with Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) was first categorized in 1976 by French, American and British researchers, and divided into eight subgroups (M0 to M7), depending on the cytochemical or histological changes in the leukemic cells. The gene mutations of FLT3-ITD, CEBPA and NPM1 are the most common that cooperate together in the prognosis of AML. The CEBPA gene that is a hematopoietic transcription factor, is located on chromosome 19q13.11, and its prevalence is between 5.0 and 14.0% in AML. The patient was referred to our clinic suffering from menorrhagia, unplanned weight loss in a month and low platelet levels, and was diagnosed with AML on clinical and laboratory examination. Here, we report a patient carrying two novel pathogenic mutations that create a frameshift mutation on the CEBPA gene, c.940_941insCCGTCG TGGAGACGA CGAAGG and c.221_222delAC by Sanger sequencing methodology.

Pharmacologic anisocoria due to nebulized ipratropium bromide: A diagnostic challenge.

Anisocoria may be physiological or seen in fatal conditions, such as intracranial hemorrhage. Newly developing anisocoria may cause confusion and diagnostic difficulty in the emergency department (ED). A 35-year-old female was admitted to the ED with an asthma attack and dyspnea. On examination, the patient was observed to have bilateral rhonchi and was treated with nebulized albuterol (salbutamol) and ipratropium bromide. After the treatment, the dyspnea improved, and mydriasis developed in the left eye (left pupil diameter 9 mm, right 4 mm). An examination revealed that the left pupil was dilated and unreactive to light, but there was no neurological finding. Afterwards, the patient reported that, during the treatment, some aerosol had leaked from the left side of the mask and may have come into contact with her left eye. Given this information, a pilocarpine test was performed, and the patient was diagnosed with pharmacologic anisocoria. The pupil returned to normal within 24 h. Ipratropium bromide is a drug frequently used in patients presenting to the ED with dyspnea. During treatment, nebulized ipratropium may leak from the edge of the facial mask into the ipsilateral eye and may cause mydriasis. A pilocarpine test can be used to differentiate pharmacological anisocoria from other causes, such as third nerve palsy and Adie's pupil. Through the awareness of emergency physicians and the use of the pilocarpine test, a diagnosis can be made without engaging in time-consuming and costly analyses. In addition, this complication can be prevented using masks that better fit the face, as well as protective goggles or eye patches, during treatment.

The role of serum N-terminal pro-brain natriuretic peptide in transient tachypnea of the newborn.

BACKGROUND AND OBJECTIVES: Transient tachypnea of the newborn (TTN), also known as wet lung disease, is a common cause of respiratory distress in the newborn. It has been demonstrated that, in alveolar type II cell cultures of the rat, receptors affected by the natriuretic peptides are expressed and that atrial natriuretic peptide (ANP) reduced amiloride-sensitive Na+ transport in these cells with a pattern similar to that in renal tubules, thereby inhibiting Na+ re-absorption in a concentration-dependent manner. Brain natriuretic peptide (BNP) is known to act on these receptors and it is suggested that it may be involved in fluid absorption by the lungs. The present study aimed to investigate the role of BNP in the pathogenesis of transient tachypnea of the newborn. PATIENTS AND RESULTS: Serum NT-proBNP (N-terminal-proBNP) level measurements of 43 infants diagnosed with transient tachypnea of the newborn were compared to those of 29 healthy neonates. There were no statistically significant differences in NT-proBNP level between the study group and the control group. CONCLUSIONS: NT-proBNP has no role in the pathophysiology of transient tachypnea of the newborn. Other factors which may potentially be involved in this etiology should be investigated.

A useful and sensitive marker in the prediction of COVID-19 and disease severity: Thiol.

Thiol-disulphide homeostasis (TDH) is a new parameter indicating oxidative stress that plays a role in the pathogenesis of various clinical disorders. Our study planned to investigate TDH in COVID-19 patients. Age and gender-matched healthy subjects (n = 70) and COVID-19 patients (n = 144) were included in the study. In addition to the routine laboratory parameters of the groups, their native thiol (NT), total thiol (TT) and disulphide levels were measured. Primarily, we compared COVID-19 patients to the healthy control group for inflammatory parameters, NT, TT and disulphide levels. Then, COVID-19 patients were divided into two groups according to the severity of the disease as mild to moderate and severe COVID-19, and the three groups were compared with each other. Predictive value of thiol parameters in the diagnosis of COVID-19 and in the determining its severity, and its correlation with presence and duration of symptoms were investigated. Severe COVID-19 patients had lower NT and TT levels compared with healthy controls and mild to moderate patients (P < 0.001 for both). The results of ROC analysis show that the greatest AUC was IL-6 and NT (AUC = 0.97, AUC = 0.96, respectively) between control and COVID-19 patients, while it was CRP and NT (AUC = 0.85, AUC = 0.83) between mild to moderate and severe patients. A negative correlation was found between duration of symptoms of dyspnoea, cough, fever, and sore throat and NT (r = -0.45, P = 0.017, r = -0.418, P < 0.001, r = -0.131, P = 0.084, r = -0.452, P = 0.040, respectively). NT and TT levels have a strong predictive value in the diagnosis of COVID-19 and in determining disease severity. Our results support that changing TDH parameters appears to have an important role in disease pathogenesis and it can be used in clinical management of patients.

Anaphylactic reaction due to cyclopentolate in a 4-year-old child.

Ophthalmologists frequently use mydriatics both for diagnosis (retinal exploration, refraction tests) and for treatment. Cyclopentolate is used to induce quick and successful mydriasis for pediatric eye examination. Hypersensitivity reaction to cyclopentolate is very uncommon, especially in children. We report the case of a child who experienced a hypersensitivity reaction to cyclopentolate during preparation for an eye examination under cycloplegia.

Melatonin can suppress the cytotoxic effects of chlorpyrifos on human hepG2 cell lines.

The cytotoxic effect of chlorpyrifos (CP) on human HepG2 cell lines and the protective role of melatonin were investigated. TD50 of CP for HepGZ cells was also determined. The viability of HepGZ cells decreased with CP treatment in a dose-dependent manner (P <0.05). Preincubation with melatonin prior to CP application caused an increase in cell viability (P <0.05). TD50 of CP for HepG2 was determined as 84.5 microg/mL. A 1-hour melatonin treatment caused a decrease in TD50 from 84.5 to 34.1 microg/mL. The level of thiobarbituric acid reactive substance (TBARS) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were determined in cell lines with or without melatonin administration to find out the possible mechanism of melatonin. CP caused a significant decrease in SOD, GSH-Px and CAT activities and an increase in TBARS level (P <0.05). Pre-incubation of cells with melatonin prevented an increase in TBARS. Melatonin also reduced the CP-caused inhibition of the activities of GSH-Px and CAT (P <0.05). It was suggested that CP shows a cytotoxic effect on HepG2 cell lines and melatonin can suppress cytotoxicity caused by CP with its antioxidant properties. Melatonin also reduces TD50 of CP for HepG2 cell lines.

Cost analysis and related factors in patients with traumatic hand injury.

The aim of this study was to measure the direct and indirect costs and factors influencing these costs in patients presenting following traumatic hand injury. We assessed patients aged 18-65 years who were in work. Hand injury severity and functional status were assessed. Direct costs, including medical care expenses, and indirect costs, including lost productivity, were calculated. Seventy-nine patients of a mean age of 32 years were included. The mean direct cost for each patient was $1772 (47% of total cost), and the indirect cost was $1891 (53% of total cost). Injury severity, time to return to work, and hospitalization time were the main parameters of increased total cost in a linear regression analysis.

Epidermal growth factor suppresses interferon-induced accumulation of p53 and p21 by using protein kinase C.

The tumor suppressor protein p53 is the most frequently mutated gene in human cancers. Since its discovery, p53 has evolved from a potential oncogene to the principal tumor suppressor in humans. p53 protects not only against oncogenic stress but also against the presence of DNA damage. Now, p53 is positioned at the vertex of cellular signals warning of threats of genomic damage and oxidative stress. Under these conditions p53 is phosphorylated by multiple kinases and these phosphorylations not only increase its half-life but also increase its localization in the nucleus. p53 localized in the nucleus induces cell-cycle arrest to allow repair processes or, failing that, promotes cellular senescence or cell death. In this study it is shown that treatment of ME180S cells with interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma) result in time-dependent accumulation of p53 and its transcriptional target, p21. Pretreatment of ME180S cells with epidermal growth factor (EGF) inhibits IFN-dependent induction of p53 and p21 by protein kinase C dependent pathways.

N-acetylcysteine enhances multidrug resistance-associated protein 1 mediated doxorubicin resistance.

BACKGROUND: Resistance of cancer cells against anticancer agents is caused partly by multidrug resistance-associated protein 1 (MRP1). The exact mechanism of MRP1-involved multidrug resistance has not yet been clarified, although glutathione (GSH) is likely to have a role for the resistance to occur. N-acetylcysteine (NAC) is a pro-glutathione drug. DL-buthionine (S,R)-sulfoximine (BSO) inhibits GSH synthesis. The aim of our study was to investigate the effect of NAC and BSO on MRP1-mediated doxorubicin resistance in human embryonic kidney (HEK293) and its MRP1-transfected 293MRP cells. MATERIALS AND METHODS: Human embryonic kidney cells were transfected with a plasmid encoding the whole MRP1 gene. Both cells were incubated with doxorubicin in the presence or absence of NAC and/or BSO. The viability of both cells was determined under different incubation conditions. Glutathione, glutathione S-transferase (GST) and glutathione peroxidase (GPx) levels were measured in the cell extracts obtained from both cells incubated with different drugs. RESULTS: N-acetylcysteine increased the resistance of both cells against doxorubicin. DL-buthionine (S,R)-sulfoximine decreased NAC-enhanced MRP1-mediated doxorubicin resistance, indicating that induction of MRP1-mediated doxorubicin resistance depends on GSH synthesis. Doxorubicin decreased the cellular GSH concentration and increased GPx activity. Glutathione S-transferase activity was decreased by NAC. CONCLUSION: Our results demonstrate that NAC enhances MRP1-mediated doxorubicin resistance and this effect depends on GSH synthesis. DL-buthionine (S,R)-sulfoximine seems a promising chemotherapy improving agent in MRP1 overexpressing tumour cells.

A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1.

Tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) by the insulin receptor permits this docking protein to interact with signaling proteins that promote insulin action. Serine phosphorylation uncouples IRS-1 from the insulin receptor, thereby inhibiting its tyrosine phosphorylation and insulin signaling. For this reason, there is great interest in identifying serine/threonine kinases for which IRS-1 is a substrate. Tumor necrosis factor (TNF) inhibited insulin-promoted tyrosine phosphorylation of IRS-1 and activated the Akt/protein kinase B serine-threonine kinase, a downstream target for phosphatidylinositol 3-kinase (PI 3-kinase). The effect of TNF on insulin-promoted tyrosine phosphorylation of IRS-1 was blocked by inhibition of PI 3-kinase and the PTEN tumor suppressor, which dephosphorylates the lipids that mediate PI 3-kinase functions, whereas constitutively active Akt impaired insulin-promoted IRS-1 tyrosine phosphorylation. Conversely, TNF inhibition of IRS-1 tyrosine phosphorylation was blocked by kinase dead Akt. Inhibition of IRS-1 tyrosine phosphorylation by TNF was blocked by rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), a downstream target of Akt. mTOR induced the serine phosphorylation of IRS-1 (Ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that TNF impairs insulin signaling through IRS-1 by activation of a PI 3-kinase/Akt/mTOR pathway, which is antagonized by PTEN.