Role and limitations of high-flow nasal oxygen therapy in COVID-19 patients: An observational study.

Background: The management of acute respiratory failure in COVID-19 patients and the role and limitations of high-flow nasal oxygen therapy (HFNOT) remain unclear. Aim: This study aimed to investigate the effect of HFNOT, identify the characteristics of patients who will benefit from therapy, and determine monitoring strategies to decide on endotracheal intubation for patients with COVID-19. Patients and Methods: We conducted a prospective observational study of COVID-19 patients who were admitted to the intensive care unit (ICU) and required HFNOT for at least 2 days between 20 March 2020 and 20 June 2020. The exclusion criteria were a severe respiratory failure, reduced levels of consciousness, combination with other noninvasive ventilation strategies, and exhaustion. The patients were followed up until ICU discharge. The primary outcome was the proportion of patients with COVID-19 who were successfully weaned from HFNOT, whereas failure comprised intubation or death on HFNOT. Results: Thirty-five subjects (24 males, mean-age: 61.62, standard deviation: 14.9 yr.) were included in the study. A total of 20/35 (57.1%) subjects survived to discharge. C-reactive-protein (CRP) and interleukin-6 (IL-6) levels were significantly increased in the treatment failure group (CRP; effect size (r):0.35, P: 0.037, IL-6; r: 0.37, P: 0.03). Although there was a difference between repeated measures of partial-pressure-of-oxygen/fraction-of-inspired-oxygen (PaO2/FiO2:P/F) rates (partial-eta-squared (ηp2):0.79, P < 0.001), no difference was found between carbon dioxide levels (ηp2:0.29, p: 0.44). There was also no difference between ROX (ratio-of-oxygen-saturation/FiO2 to respiratory-rate) rates (Kendall's W: 0.33 P = 0.310). Conclusion: In COVID-19 patients with mild-to-moderate dyspnea and hypoxemia who are nonresponsive to conventional-oxygen-therapies, the initial approach may involve the use of HFNOT. In this study, patient monitoring could be performed with ROX and P/F ratios, and the effectiveness of the treatment could be decided by looking at these rates in the second hour. Prolongation of the period and awake prone positioning did not improve the outcome.

Effects of COVID-19 variation on the treatment response and disease severity in critical illness: a retrospective observational cohort study.

OBJECTIVE: Even though the treatment of the original variant was not fully determined, variants of COVID-19 emerged. Whether the clinic of COVID-19 has changed because of variation is controversial. The present study aimed to examine the COVID-19 severity and treatment responsiveness of critically ill patients between the original virus and emergent variations with a more comprehensive set of measures. PATIENTS AND METHODS: Treatment responses, laboratory findings, and clinical conditions of critically ill patients with COVID-19 who were identified with variants between February 1st, and May 30th, 2021, were examined in two medical Intensive Care Units (ICUs) in tertiary care centers. Each patient received treatment in the ICU for at least one week. RESULTS: Sixty-five (30 patients with the original variant: POV) critically ill patients were included in the study. SOFA scores, blood glucose, total bilirubin, urea-creatinine and lactate dehydrogenase levels decreased significantly in POV (p=.031, p=.002, p=.002, p=.008, and p=.007, respectively). Overall, patients with emergent variants (PEV) (M = 76.58, SD = 8.64) had lower partial-pressure-of-oxygen/fraction-of-inspired-oxygen ratios (P/F) than POV (M = 123.16, SD = 9.49). Use of the prone position and steroid therapy did not result in significant improvements in oxygenation of critically ill PEV. Hypertension was identified as the common comorbidity in PEV (OR=5.287). CONCLUSIONS: We showed that the state of PEV was more severe than POV at the time of ICU admission. However, the prone position and steroids were not efficient in improving the P/F ratios. P/F ratios of PEV were significantly lower in non-invasive ventilation. These results suggest that early intubation might be necessary for PEV.

Evaluation of potential drug-drug interactions in intensive care unit.

OBJECTIVE: Potential drug-drug interactions (pDDIs) and adverse drug reactions (ADRs) may be frequently observed in critically ill patients because of multiple drug use. It is important to identify pDDIs before their progression to ADRs. This study aimed to determine the prevalence and effect of pDDIs and possible ADRs in intensive care patients. PATIENTS AND METHODS: In this retrospective cross-sectional study, the medical records of patients in the intensive care unit (ICU) of Bursa Uludag University Faculty of Medicine Hospital between January 1, 2018, and December 31, 2018, were examined. Medication orders were recorded on days 2, 5, and 10. pDDIs, defined using the lexi-interact (UpToDate, 2020), were classified based on the significance level. RESULTS: A total of 144 patients were included in this study, and from the 395 medication orders, 1,776 had pDDIs. Of these interactions, 23.5% were major (n = 418), 71.4% were moderate (n = 1268), and 5.1% (n = 90) were minor. The majority of patients (96.9%) had at least one pDDI. There was a strong correlation between the number of drugs on days 2, 5, and 10 and the number of pDDIs (p < 0.001, ρ = 0.7; p < 0.001, ρ = 0.72; p < 0.001, ρ = 0.73, respectively). No significant correlation was found among the number of pDDIs, the APACHE II score, and the duration of ICU stay. CONCLUSIONS: The prevalence of pDDIs was high and there was a strong correlation between the number of drugs and pDDIs. Detection of potential interactions through clinical decision support systems and checker tools should be used to increase patient safety.

Combination of ultra-low dose bupivacaine and fentanyl for spinal anaesthesia in out-patient anorectal surgery.

This study investigated whether the addition of 25 microg fentanyl to an ultra-low (sub-anaesthetic) dose of intrathecal bupivacaine provides adequate anaesthesia for out-patient anorectal surgery, without increasing side-effects or delaying hospital discharge. Patients were randomly allocated to receive 2.5 mg 0.5% bupivacaine plus 25 microg fentanyl (group BF, n = 18) or 5 mg 0.5% bupivacaine alone (group B, n = 17). There were no significant differences in intra-operative outcomes, but mean recovery and discharge times were significantly shorter in group BF. There were no between-group differences in hypotension, bradycardia or respiratory depression and post-operative complications were comparable, apart from pruritus which was significantly more frequent in group BF. Fewer patients requested analgesic medication in the early post-operative period in group BF than in group B. In conclusion, 25 microg intrathecal fentanyl added to ultra-low dose (2.5 mg) bupivacaine provided good-quality spinal anaesthesia and reduced post-operative analgesic requirement in patients undergoing ambulatory anorectal surgery.

The combination of low-dose levobupivacaine and fentanyl for spinal anaesthesia in ambulatory inguinal herniorrhaphy.

This study investigated whether the addition of 25 microg intrathecal fentanyl to levobupivacaine spinal anaesthesia for outpatient inguinal herniorrhaphy allows a sub-anaesthetic levobupivacaine dose to be used. Forty patients were assigned to receive 5 mg levobupivacaine 0.5% mixed with 25 microg fentanyl (group LF) or 7.5 mg levobupivacaine 0.5% (group L). The highest sensory block levels achieved were T7 (range T5 - T9) and T6 (range T4 - T9) in groups LF and L, respectively. The times to two-segment regression, S2 regression, ambulation, urination and discharge were all significantly shorter in group LF than group L. These results indicate that, for outpatient inguinal herniorrhaphy, intrathecal fentanyl combined with low-dose levobupivacaine provides good quality spinal anaesthesia and minimizes the need for intra-operative analgesia. This protocol is well suited for the outpatient setting because it features rapid recovery of full motor power, sensory function and bladder function.

An unusual cause of ureteral obstruction in a renal transplant recipient: ureteric aspergilloma.

Mycotic infections in various organ transplant recipients represent severe and often fatal complications. Aspergillosis isolated from the urinary tract occurs quite infrequently in renal transplant recipients. Besides, fungus balls are rare causes of ureteral obstruction. We report a 51-year-old patient with the diagnosis of ureteral obstruction caused by aspergillosis in the early post-renal transplant period, who unfortunately died with the clinical picture of disseminated infection and its complications.

Toxic hepatitis in a case of Angelman syndrome associated with Lennox-Gastaut syndrome.

We report a 26-month-old boy with Angelman syndrome associated with Lennox-Gastaut syndrome, who developed a rash and a persistent toxic hepatitis after lamotrigine was added to valproate therapy. The patient had typical findings of both Angelman and Lennox-Gastaut syndromes. Chromosome analysis performing by FISH analysis showed a deletion in chromosome 15 (q11.2 q11.2). Although some cases of Angelman syndrome associated with Lennox-Gastaut syndrome were reported in the literature, valproate and/or lamotrigine induced toxic hepatitis in Angelman syndrome has hitherto never been described. We conclude that VPA and LTG combination should be given with great caution or avoided in patients with Angelman syndrome.

The value of the levels of acute phase reactants for the prediction of familial Mediterranean fever associated amyloidosis: a case control study.

In order to determine the role of levels of acute phase proteins (APPs) for the development of amyloidosis in familial Mediterranean fever (FMF) patients, the levels of serum amyloid A (SAA), C reactive protein (CRP), fibrinogen and erythrocyte sedimentation rate were measured in paired sera of 36 FMF patients during and in between acute attacks, 39 of their healthy parents (obligate heterozgotes), and 15 patients with FMF associated amyloidosis. To compare the levels of APPs, 39 patients with chronic infections or inflammatory diseases who may develop secondary amyloidosis, 20 patients with acute infections who are known to have elevated acute phase response but will never develop amyloidosis and 19 healthy controls were included. The median levels of all APPs are increased in the patients with FMF during attacks and a significant decrease was observed after the attack was over. The level of SAA was above reference range in all FMF patients during the attack free period and the level of at least one other APP was also above normal in 64% of the patients. Both CRP and SAA levels were found to be higher in obligate heterozygotes compared to controls. The levels of SAA in patients with FMF during the attack-free period, obligate heterozygotes and patients with FMF-amyloidosis were found to be similar. The levels in each group were found to be higher than SAA levels found in healthy controls yet lower than the levels measured in the patients with acute infections and patients with chronic inflammation or chronic infections. In conclusion, our results show that SAA level reflects subclinical inflammation with high sensitivity but its value for the prediction of amyloid formation process seems to be low.

Hepatic damage in gluten sensitive enteropathy.

BACKGROUND: Gluten sensitive enteropathy has been reported to occur concomitantly with liver abnormalities, such as primary biliary cirrhosis, chronic active hepatitis and primary sclerosing cholangitis. METHODS: Duodenal biopsy was performed in nine children (all with short stature, five with chronic diarrhea and three with hepatosplenomegaly of unknown etiology) with a possible diagnosis of gluten sensitive enteropathy. All of the patients had different abnormalities in serum aminotransferase levels. With the help of laboratory investigations, viral, autoimmune, metabolic and toxic etiologies which cause hepatic damage were excluded. Liver biopsy was performed in five of these patients, two showing fibrosis and three nonspecific reactive changes. Gliadin antibodies were measured in six cases. RESULTS: Intestinal mucosal histopathology was compatible with gluten sensitive enteropathy in all patients. While immunoglobulin (Ig) G gliadin antibodies were positive in all cases, only three cases were found to have positive IgA gliadin antibodies. After a gluten-free diet, levels of transaminases fell to normal within 3 months and remained so in seven of these patients. A second intestinal biopsy, which was performed after 1 year of gluten-free diet revealed normal intestinal mucosa in all patients. CONCLUSION: Gluten sensitive enteropathy should be considered when evaluating a child with elevated levels of serum transaminase and in cases with cryptogenic liver disease.

Celiac disease in Turkish short-statured children and the value of antigliadin antibody in diagnosis.

BACKGROUND: It is generally accepted that celiac disease (CD) must always be taken into consideration when dealing with children manifesting growth failure. It is, therefore, important to have laboratory tests capable of detecting patients who should undergo intestinal biopsy. In this study, we have prospectively evaluated clinical characteristics, gliadin antibody measurements and duodenal biopsies in 47 children with short stature and without gastrointestinal symptoms, in order to determine the incidence of CD and the diagnostic value of immunoglobulin (Ig)A and IgG antigliadin antibodies (AGA) for CD. METHODS: Anthropometric parameters and IgA- and IgG AGA were evaluated in 47 children with short stature. Antigliadin antibodies were measured by enzyme-linked immunosorbent assay (Euroimmun kit). Endoscopic intestinal biopsies were taken from all children. RESULTS: On the basis of intestinal biopsy, 26 (55.3%) patients were found to be probable CD. Sensitivity, specificity, positive predictive (PPV) and negative predictive value (NPV) for IgA AGA was found to be 23, 90, 75 and 48%, respectively. Sensitivity, specificity and PPV for IgG AGA was 100, 0 and 55%, respectively. The NPV for IgG AGA was not determined. CONCLUSIONS: The results of our study demonstrated that because of their incomplete sensitivity, specificity, PPV and NPV, intestinal biopsy can not be replaced by these tests.

Hepatoma with right atrial extension.

The case is described of a 14-year-old boy who had a hepatoma with a right atrial extension. He presented with edema, abdominal pain, and ascites. Two-dimensional echocardiography showed a right atrial tumor that had invaded from the inferior vena cava as an extension into the right atrium of the hepatoma.

Hypertrophic osteoarthropathy in a child with biliary atresia.

Hypertrophic osteoarthropathy is a syndrome characterized by clubbing of the digits of the hand/foot, periosteal reaction and arthralgia or arthritis which is usually secondary to cyanotic congenital heart disease and chronic pulmonary infections. This syndrome rarely occurs in association with chronic liver disease in childhood. Here, we report on a child with biliary atresia who developed arthralgia and arthritis during follow-up and which was diagnosed as hepatic hypertrophic osteoarthropathy. It is emphasized that hypertrophic osteoarthropathy should be considered in the differential diagnosis of arthralgia and arthritis in children with long-standing chronic liver diseases, especially if finger clubbing is also present.

Hereditary pancreatitis: report of a family from Turkey.

Chronic pancreatitis is a rare disease in children and is usually secondary to underlying diseases such as hereditary pancreatitis, cystic fibrosis, hyperlipidemia, prolonged malnutrition, gallstones or anomalies of the biliary-pancreatic duct system. Hereditary pancreatitis is a common cause of chronic pancreatitis in children but is often unrecognized until months or years later. We report here a family with hereditary pancreatitis in which four members are affected.

Bone mineral density and importance of a gluten-free diet in patients with celiac disease in childhood.

OBJECTIVES: Celiac disease (CD), a common cause of malabsorption, is known to be associated with disorders of the skeleton, but there are conflicting data about the effect of diet on bone metabolism. The aims of this study were to investigate the prevalence of osteopenia; to identify the relationship between bone mineral density (BMD), serum calcium, and parathyroid hormone levels; and to determine the effect of gluten-free diet on BMD in children with celiac disease. DESIGN: The study included 32 patients with CD (group 1) and 82 healthy controls (group 2). The patients with CD were evaluated under 2 subgroups, ie, 16 patients with recent diagnosis (group 1a) and 16 patients who follow their diet strictly (group 1b). BMD values and concentrations of calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone were determined on entry to the study and at 12 months in celiac patients. These values were compared with those of healthy control participants. RESULTS: BMD and bone mineral content values in patients with recent diagnosis were found to be significantly lower than the control group. The BMD values in patients with recent diagnosis were significantly increased after a gluten-free diet for 1 year. Osteopenia was found more commonly in patients with recent diagnosis than patients in whom a gluten-free diet had been instituted. At 1-year follow-up, osteopenia was not resolved with the gluten-free diet, and this was especially true in patients without gastrointestinal manifestation. In patients with recent diagnosis (group 1a), the mean calcium level was found to be lower than the patients who follow their diet strictly (group 1b). There was a positive correlation between calcium level and BMD and bone mineral content. CONCLUSIONS: BMD is almost invariably low in newly diagnosed celiac patients in childhood. We therefore recommend that BMD should be evaluated in patients with CD. Strict gluten avoidance promoted a significant increase in BMD. However, values still remained markedly low after 1 year of follow-up in some patients. These patients should be followed for longer periods of time with yearly BMD evaluation, as 1 year of diet therapy was found to be insufficient for osteopenia to be resolved.

Isolated deficiency of glucocorticoids presenting with cholestasis.

BACKGROUND: Isolated deficiency of glucocorticoids is characterized by elevated levels of adrenocorticotropin (ACTH) and normal aldosterone production. It is rare for isolated deficiency of glucocorticoids to be associated with liver involvement. A case of an infant with isolated deficiency of glucocorticoids presenting with cholestasis is presented in this article. A male infant on his 39th postnatal day was referred to our hospital for evaluation of prolonged jaundice and convulsion. He had two episodes of hypoglycemic convulsion on postnatal 8th and 39th day, after which he was admitted to our hospital. RESULTS: Physical examination revealed systemic jaundice, hyperpigmentation of the skin, hepatomegaly and splenomegaly on admission. He had normal male genitalia with 3.5 cm of penis and bilateral scrotal testes. Laboratory values were as follows: glucose 45 mg/dL, total biluribin 18.14 mg/dL, direct biluribin 6.54 mg/dL, aspartate aminotransferase 378 IU/L, alanine aminotransferase 46 IU/L, and alkaline phosphatase (ALP) 1302 IU/L. In abdominal ultrasound and biliary tract scanning, extra- and intrahepatic biliary tracts were shown to be normal. Finally, biopsy of the liver revealed cholestasis. An endocrinological evaluation showed high levels of adrenocorticotropin (ACTH, 1000 pg/mL), low levels of cortisol (1 microgram/dL) and normal aldosterone levels. CONCLUSIONS: The diagnosis of cholestasis secondary to isolated glucocorticoid deficiency was suspected with clinical and laboratory findings. Hydrocortisone treatment (30 mg/m2 per day) was initiated after which hyperpigmentation and jaundice decreased and ACTH and ALP levels reduced to 39 pg/mL and 440 IU/l, respectively. We emphasize that cholestasis in infants may be a component of isolated deficiency of glucocorticoids.

Effects of cisapride on ventricular repolarization in children.

Life-threatening ventricular dysrhythmias mainly attributed to QTc prolongation have been reported in adults and children who were using cisapride, a prokinetic agent that facilitates gastrointestinal motility. Recent adult and paediatric case reports have suggested an association of malignant ventricular dysrhythmias with administration of cisapride in conjunction with drugs that inhibit its cytochrome P-450 metabolism. Therefore, to analyse the time- and dose-related effects of cisapride on ventricular repolarization, we prospectively studied infants and children receiving cisapride with no concomitant medications. Standard 12-lead resting ECGs were obtained from 38 patients (mean age: 6.6 +/- 4.4 y) before the first dose of cisapride (0.8-1.2 mg/kg/d) therapy, and 3 d, 7 d and 1 mo after the first dose of continuing cisapride therapy. The corrected QT interval (QTc), dispersion of QT and QTc (QTD, QTcD) were calculated. Patients were divided into two groups according to dose of cisapride: Group 1 (n = 22) (0.8 mg/kg/d), Group 2 (n = 16) (1.2 mg/ kg/d). Data obtained from these patients were compared with a control group consisting of 372 normal children. No clinical adverse effects such as palpitations, presyncope or syncope were noted during the study. Baseline QTc, QTD and QTcD measurements of the study group were not different from those of the control group. Mean QTc values of the study group on days 7 and 30 of cisapride therapy were found to be significantly higher than those of the control group (p < 0.001 and <0.0001, respectively). Mean QTc values of the study group on days 7 and 30 of therapy were also significantly higher than those of baseline value (p < 0.01 and <0.001, respectively). Mean QTD and mean QTcD values that were recorded throughout the cisapride treatment in the study group were not found to be different from the baseline values and the values of the controls. Mean QTD and QTcD were also not found to be different between Groups 1 and 2. However, mean QTc was found to be more significantly increased from baseline at the first month of therapy in Group 2 (p < 0.05). The results of this study suggest that cisapride treatment cause prolongation of ventricular repolarization without causing increased heterogeneity of repolarization (QT dispersion). However, the clinical significance of this effect is unclear, because all the patients in this study group remained asymptomatic, without signs of dysrhythmia.