Synthesis of spin-labeled riboswitch RNAs using convertible nucleosides and DNA-catalyzed RNA ligation.

Chemically stable nitroxide radicals that can be monitored by electron paramagnetic resonance (EPR) spectroscopy can provide information on structural and dynamic properties of functional RNA such as riboswitches. The convertible nucleoside approach is used to install 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) and 2,2,5,5-tetramethylpyrrolidin-1-oxyl (proxyl) labels at the exocyclic N(4)-amino group of cytidine and 2'-O-methylcytidine nucleotides in RNA. To obtain site-specifically labeled long riboswitch RNAs beyond the limit of solid-phase synthesis, we report the ligation of spin-labeled RNA using an in vitro selected deoxyribozyme as catalyst, and demonstrate the synthesis of TEMPO-labeled 53 nt SAM-III and 118 nt SAM-I riboswitch domains (SAM=S-adenosylmethionine).

Assessing circadian rhythms in propofol PK and PD during prolonged infusion in ICU patients.

This study evaluates possible circadian rhythms during prolonged propofol infusion in patients in the intensive care unit. Eleven patients were sedated with a constant propofol infusion. The blood samples for the propofol assay were collected every hour during the second day, the third day, and after the termination of the propofol infusion. Values of electroencephalographic bispectral index (BIS), arterial blood pressure, heart rate, blood oxygen saturation and body temperature were recorded every hour at the blood collection time points. A two-compartment model was used to describe propofol pharmacokinetics. Typical values of the central and peripheral volume of distribution and inter-compartmental clearance were V(C) = 27.7 l, V(T) = 801 l, and CL(D) = 2.73 l/min. The systolic blood pressure (SBP) was found to influence the propofol metabolic clearance according to Cl (l/min) = 2.65 x (1-0.00714 x (SBP-135)). There was no significant circadian rhythm detected with respect to propofol pharmacokinetics. The BIS score was assessed as a direct effect model with EC(50) equal 1.98 mg/l. There was no significant circadian rhythm detected within the BIS scores. We concluded that the light-dark cycle did not influence propofol pharmacokinetics and pharmacodynamics in intensive care units patients. The lack of night-day differences was also noted for systolic blood pressure, diastolic blood pressure and blood oxygenation. Circadian rhythms were detected for heart rate and body temperature, however they were severely disturbed from the pattern of healthy patients.

[First isolation of metallo-beta-lactamase producing Klebsiella pneumoniae strain in Poland]. / Izolacja pierwszego w Polsce szczepu Klebsiella pneumoniae wytwarzajacego metalo-beta-laktamazy.

BACKGROUND: Metallo-beta-lactamases (MBL) are the enzymes that are able to hydrolyse almost the full range of beta-lactame antibiotics--penicillins, cephalosporins and carbapenems. The latter are the drugs of choice for treatment of serious infections caused by Enterobacteriaceae strains, which produce extended-spectrum-beta-lactamases. The presence of MBL-producing strains markedly decreases the therapeutic possibilities in severe, life-threatening infections. CASE REPORT: We present the case of a 61-yr-old man who underwent surgery for acute leg ischemia, and in whom a bifurcation prosthesis was implanted. The postoperative course was complicated with serious nosocomial infection, caused by MBL-positive Klebsiella pneumoniae strains. Despite multi drug treatment and intensive care, the patient died 30 days after surgery due to multi organ failure. All isolates cultured from the patient were resistant to carbapenems with their MICs exceeding 32 microg mL(-1). The presence of MBLs was detected with the double-disk synergy test. The presence of genes encoding MBLs was determined with a commercial kit, hyplex MBL ID (Bag Health Care, USA). The isolate from blood was found to carry the blaVIM-like family gene, located in a conjugative plasmid. CONCLUSION: The MBL-producing isolates were the first K. pneumoniae isolates of the kind identified in Poland. They present a serious danger, limiting the usefulness of carbapenems in ITU patients. We recommend that detection of MBLs in Enterobacteriaceae should be regarded as a standard in Polish hospitals.

Steroid vs. antibiotic impregnated absorbable nasal packing for wound healing after endoscopic sinus surgery: a randomized, double blind, placebo-controlled study.

INTRODUCTION: Endoscopic sinus surgery can lead to crusting or synechiae formation, which can affect the healing process. OBJECTIVE: The aim of our study was to compare the influence of steroid versus antibiotic versus saline solution impregnated absorbable nasal spacers on postoperative wound healing and patient satisfaction. METHODS: Eighty patients, 33 women and 47 men, were enrolled in this study. At the end of the surgery, two pieces of 4cm biodegradable material were applied in each ethmoid cavity. One of them was impregnated with saline solution, while the second one with steroid, or with antibiotic. RESULTS: We observed statistically significant differences in the Lund-Kennedy score between the control and both treatment groups: for the Antibiotic-group on days 10 and 30 (p=0.009; p=0.009) and for the Steroid-group on day 90 (p=0.008). The extended endoscopic appearance of nasal mucosa indicated statistically significant differences in crust formation on day 10 comparing the steroid and control dressing (p=0.025), in secretion type on days 10 and 30 comparing the antibiotic and control dressing (p=0.003; p=0.016) and additionally for steroid and control on day 90 (p=0.046). On Day 90 we observed statistically significant differences in the absence of mucosal edema in the S-group compared to controls (p=0.007). CONCLUSIONS: The results of this study reveal the significant positive influence of steroid- and antibiotic-impregnated biodegradable nasal packing on the postoperative healing process and patient satisfaction compared to the saline soaked dressing.

Frailty is associated with an increased mortality among patients ≥ 80 years old treated in Polish ICUs

BACKGROUND: The increasing population of very old intensive care patients (VIPs) is a major challenge currently faced by clinicians and policymakers. Reliable indicators of VIPs' prognosis and purposefulness of their admission to the intensive care unit (ICU) are urgently needed. METHODS: This is a report from the Polish sample of the VIP1 multicentre cohort study (NCT03134807). Patients ≥ 80 years of age admitted to the ICU were included in the study. Information on the type and reason for admission, demographics, utilisation of ICU procedures, ICU length of stay, organ dysfunction and the decision to apply end-of-life care was collected. The primary objective was to investigate the impact of frailty syndrome on ICU and 30-day survival of VIPs. Frailty was assessed with the Clinical Frailty Scale (≥ 5 points on a scale of 1-9). RESULTS: We enrolled 272 participants with a median age of 84 (81-87) years. Frailty was diagnosed in 170 (62.5%) patients. The ICU and 30-day survival rates were equal to 54.6% and 47.3% respectively. Three variables were found to significantly increase the odds of death in the ICU in a multiple logistic regression model: SOFA score (OR = 1.16; 95%CI 1.16-1.24), acute mode of admission (OR = 5.1; 95%CI 1.67-15.57) and frailty (OR = 2.25; 95%CI 1.26-4.01). CONCLUSION: Measuring frailty in critically ill older adults can facilitate making more informed clinical decisions and help avoid futile interventions.

Clinical outcome and patient satisfaction using biodegradable (NasoPore) and non-biodegradable packing, a double-blind, prospective, randomized study.

INTRODUCTION: Nasal packing after endoscopic sinus surgery is used as a standard procedure. The optimum solution to minimize or eliminate all disadvantages of this procedure may be accomplished using biodegradable packs. OBJECTIVE: The aim of this study was to compare patient satisfaction and clinical outcome associated with absorbable and non-absorbable packing after FESS. METHODS: In total, 50 patients were included in a prospective, double-blind, randomized trial. One side was packed with polyurethane foam, while the opposite side was packed with gauze packing. On the 2nd, 10th, and 30th postoperative day, the patients were questioned with the aid of a visual analog scale. The standardized questionnaires for bleeding, nasal breathing, feeling of pressure, and headache were used. The presence of synechiae, infection, or granulation was noted and recorded with the video-endoscopy. RESULTS: A significant difference according to lower pressure was found in the NasoPore group compared to the controls on day ten after surgery. The NasoPore packing had lower scores with respect to postoperative nose blockage on the 2nd and 10th days. Mucosal healing was better for the NasoPore group, both at day ten and 30 compared with the control group. CONCLUSION: The overall patient comfort is higher when using NasoPore compared to non-resorbable traditional impregnated gauze packing. Intensive saline douches applied three to four times per day are mandatory after the operation to prevent synechiae formation and fluid resorption by the packing.

Melatonin and clonidine premedication has similar impact on the pharmacokinetics and pharmacodynamics of propofol target controlled-infusions.

Recently oral melatonin has been proposed as an agent for premedication. In this study, we compared melatonin with clonidine, considering its anxiolytic properties as well as the influence of both agents on the pharmacokinetic, hypnotic, and hemodynamic effects of propofol during propofol-remifentanil total intravenous anesthesia (TIVA). The dataset under analysis included 32 patients scheduled for a functional endoscopic sinus surgery. The population pharmacokinetic modeling was done with NONMEM. The PK of propofol was described with a two-compartment disposition model, whereas the BIS and AAI were described with a sigmoidal Emax model linked with the propofol concentration via the biophase compartment. The anxiolytic effect was assessed by means of the visual analog scale for anxiety (VAS-A). The population PK/PD model was successfully developed to describe the data. No significant differences in the PK/PD of propofol were noted due to the premedication with clonidine and melatonin. Melatonin was less effective than clonidine in reducing patients' anxiety at the induction of anesthesia, whereas clonidine premedication was associated with greater decrease in heart rate and blood pressure. A decreased EC50 (2.47 vs. 3.17 mg/L) and increased slope (2.71 vs. 1.30) of the sigmoidal Emax relationship was observed for the AAI index, as compared with the BIS measurements.

Comparison of clonidine and midazolam premedication before endoscopic sinus surgery: results of clinical trial.

OBJECTIVES: Premedication with clonidine has been found to reduce the bleeding during endoscopic sinus surgery (ESS), therefore lowering the risk of surgical complications. Premedication is an essential part of pre-surgical care and can potentially affect magnitude of systemic stress response to a surgical procedure. The aim of this study was to compare the efficacy of premedication with clonidine and midazolam in patients undergoing sinus surgery. METHODS: Forty-four patients undergoing ESS for chronic sinusitis and polyp removal were enrolled and randomly assigned to receive either oral clonidine or midazolam as a premedication before receiving propofol/remifentanil total intravenous anesthesia. The effect of this premedication choice on anesthetic requirements, intraoperative hemodynamic profile, preoperative anxiety and sedation as well as postoperative pain and shivering were examined in each premedication group. RESULTS: Total intraoperative remifentanil requirement was lower in the clonidine group as compared to the midazolam group 503.2±147.0 µg vs. 784.5±283.8 µg, respectively (P<0.001). There was no difference between groups in required induction dose of propofol, level of preoperative anxiety, level of sedation and postoperative shivering. Intraoperative systemic blood pressure and heart rate response had a more favorable profile in patients premedicated with clonidine. Postoperative pain assessed by visual analogue scale for pain was lower in the clonidine group compared with to the midazolam premedication group. CONCLUSION: Premedication with clonidine provides better attenuation of hemodynamic response and reduction of intraoperative remifentanil requirements in patients undergoing ESS. Postoperative pain seems to be better controlled after clonidine premedication as well.

Improved quality of surgical field during endoscopic sinus surgery after clonidine premedication--a pilot study.

BACKGROUND: Inadequate surgical field visualization due to intraoperative bleeding during endoscopic sinus surgery (ESS) can cause major complications. The aim of this prospective study was to compare the effect of preoperative administration of clonidine and melatonin on the quality of the surgical field visualization and selected aspects of presurgical premedication. METHODS: Twenty-six patients undergoing ESS for chronic sinusitis and polyp removal were enrolled and randomly assigned to receive either oral clonidine or melatonin as preoperative premedication. During the operation, the quality of the surgical field was assessed and graded using the scale proposed by Boezaart. The evaluations were done at 15, 30, and 60 minutes after incision. The effect of this premedication choice on the intraoperative and postoperative hemodynamic profile was examined in each group. Anxiolytic effects of both premedication agents were assessed using the visual analogue scale for anxiety (VAS-A). Propofol dose and induction time (the time for bispectral index [BIS] to reach 45), anesthesia and surgical procedures time, and recovery time (the time for BIS to reach 90) were assessed in both groups as well. RESULTS: The quality of the surgical field was consistently better in 2 of 3 time points in the clonidine group. Perioperative mean arterial pressure and intraoperative heart rate had a more favorable profile in patients premedicated with clonidine. There were no differences in other measured parameters between groups. CONCLUSION: Premedication with clonidine before ESS provides better quality of surgical field and more favorable hemodynamic profile as compared to melatonin.

Steroid vs. antibiotic impregnated absorbable nasal packing for wound healing after endoscopic sinus surgery: a randomized, double blind, placebo-controlled study / Tampão nasal absorvível embebido em esteroides versus antibióticos para cicatrização de feridas após cirurgia endoscópica nasossinusal: estudo randomizado, duplo cego, placebo controlado

Abstract Introduction: Endoscopic sinus surgery can lead to crusting or synechiae formation, which can affect the healing process. Objective: The aim of our study was to compare the influence of steroid versus antibiotic versus saline solution impregnated absorbable nasal spacers on postoperative wound healing and patient satisfaction. Methods: Eighty patients, 33 women and 47 men, were enrolled in this study. At the end of the surgery, two pieces of 4 cm biodegradable material were applied in each ethmoid cavity. One of them was impregnated with saline solution, while the second one with steroid, or with antibiotic. Results: We observed statistically significant differences in the Lund-Kennedy score between the control and both treatment groups: for the Antibiotic-group on days 10 and 30 (p = 0.009; p = 0.009) and for the Steroid-group on day 90 (p = 0.008). The extended endoscopic appearance of nasal mucosa indicated statistically significant differences in crust formation on day 10 comparing the steroid and control dressing (p = 0.025), in secretion type on days 10 and 30 comparing the antibiotic and control dressing (p = 0.003; p = 0.016) and additionally for steroid and control on day 90 (p = 0.046). On Day 90 we observed statistically significant differences in the absence of mucosal edema in the S-group compared to controls (p = 0.007). Conclusions: The results of this study reveal the significant positive influence of steroid- and antibiotic-impregnated biodegradable nasal packing on the postoperative healing process and patient satisfaction compared to the saline soaked dressing.

Resumo Introdução: A cirurgia endoscópica nasossinusal pode levar à formação de crostas e sinéquias, o que pode afetar o processo de cicatrização. Objetivo: O objetivo do nosso estudo foi comparar a influência do espaçador nasal absorvível embebido em esteroide versus antibiótico versus solução salina na cicatrização de ferida pós-operatória e na satisfação do paciente. Método: Oitenta pacientes, 33 mulheres e 47 homens, foram incluídos neste estudo. Ao final da cirurgia, dois tampões de material biodegradável de 4 cm foram aplicados em cada cavidade etmoidal. Um deles foi embebido em solução salina, enquanto no segundo foi utilizado esteroide, ou antibiótico. Resultados: Observamos diferenças estatisticamente significantes no escore de Lund-Kennedy entre os grupos controle e ambos os grupos tratamentos: para o grupo antibiótico nos dias 10 e 30 (p = 0,009; p = 0,009) e para o grupo esteroide no dia 90 (p = 0,008). O aspecto endoscópico da mucosa nasal indicou diferenças estatisticamente significantes na formação de crostas no dia 10, na comparação do esteroide com o curativo controle (p = 0,025), no tipo de secreção nos dias 10 e 30, na comparação do antibiótico com o curativo controle (p = 0,003; p = 0,016) e adicionalmente para esteroide e controle no dia 90 (p = 0,046). No dia 90, observamos diferenças estatisticamente significantes na ausência de edema da mucosa no grupo E (esteroide) em relação aos controles (p = 0,007). Conclusões: Os resultados deste estudo revelam uma influência positiva significante no uso de tampão nasal biodegradável embebido em esteroides e antibióticos no processo de cicatrização pós-operatória e satisfação do paciente em comparação com o curativo embebido em solução salina.

Kartagener's syndrome--anaesthetic considerations for ENT surgery.

Kartagener's syndrome is a rare autosomal recessive disorder presenting a triad of sinusitis, bronchicetasis and situs inversus with dextrocardia. It occurs in 50% of patients with situs inversus. The most important anesthetic implications of Kartegener's syndrome surgery are assessement of pulmonary and cardiac structure and function. We present a case of 43-year-old woman with chronic rhinosinusitis with polyps and bilateral sectetory otitis media. The chest radiograph and CT scans showed dextrocardia and situs inversus with chronic bronchitis without bronchiectasis. Spirometry showed forced expiratory volume in one second (FEV1) of 2.66 L and forced vital capacity (FVC) of 3.62 L. Electroechography showed no cardiac abnormalities with 55-60% of EF. The anesthetic implications of Kartagener's syndrome are varied. The regional or general anesthesia might be involved with sinus surgery, ear surgery, pulmonary surgery, infertility or abdominal and cardiac surgery. The main anesthetic considerations among patients with Kartagener's syndrome are related to the pulmonary function which include preoperative respiratory infections due to bronchiectasis. We should also monitor potentially occluded congenital heart diseases. Kartagener's syndrome is a rare disease and when the patient need an operation we have to consider surgery with regional or general anesthesia. The general anesthesia would be safe after complete preanaesthetic examination of the patient. The ECG, chest CT scans, spirometry and echocardiography are mandatory before the operation.

Analysis of nutrition mixtures in ITU patients.

BACKGROUND: The aim of this study was to analyse the composition of parenteral nutrition (PN) mixtures used in the ITU. METHODS: Restrospective analysis involved 2124 prescriptions for individual PN bags. They were administered over an 18-month period, to 160 ITU patients with the mean APACHE II score of 26 points (range: 5-61), calculated on admission. The mortality rate was 40%. Nutrition programs were prepared individually following the 2009 ESPEN guidelines. The prescription was modified according to the individual patient's clinical condition. One hundred and sixty prescriptions were analysed on the first day of PN (T1), 139 - on the second day (T2) and 1825 on the third and subsequent days (T3). RESULTS: The mean energy supplies were: 1381 kcal/day (range: 456-2612) on T1, 1467 kcal/day (range: 524-2860) on T2, and 1654 kcal/day (range: 390-2969) on T3. The mean supplies of amino acids, glucose and lipids were as follows: amino acids 68.3 g/day (range:20-120) on T1; 71.6 g/ day (range:27.5-125) on T2; 88.0 g/day (range:11-196) on T3; glucose 210.25 g/day (range: 120- 400) on T1; 218.34 g/day (range: 65-480) on T2; 278.5 g/day (range: 18-520) on T3; lipids 34.9 g/ day (range: 0-100) on T1; 38.7 g/day (range: 0-100) on T2; 52.66 g/day (range: 0-117) on T3. The percentages of non-protein energy from lipids were: 29.25 (0-73) on T1; 31.58 (range: 0-60) on T2; 33.5 (0-60) on T3. The following statistically significant differences were found: T2-T3- (p<0.05). CONCLUSIONS: The compositions of nutrition bags prepared for ITU patients were consistent with the ESPEN guidelines. The composition varied on different days of nutrition. The differences in the supply of nutrition components indirectly confirm the need for individual prescriptions for ITU patients.

Clinical outcome and patient satisfaction using biodegradable (NasoPore) and non-biodegradable packing, a double-blind, prospective, randomized study / Desfecho clínico e satisfação do paciente com o uso de tampão biodegradável (NasoPore) e não biodegradável: estudo prospectivo, duplo-cego e randomizado

Abstract Introduction Nasal packing after endoscopic sinus surgery is used as a standard procedure. The optimum solution to minimize or eliminate all disadvantages of this procedure may be accomplished using biodegradable packs. Objective The aim of this study was to compare patient satisfaction and clinical outcome associated with absorbable and non-absorbable packing after FESS. Methods In total, 50 patients were included in a prospective, double-blind, randomized trial. One side was packed with polyurethane foam, while the opposite side was packed with gauze packing. On the 2nd, 10th, and 30th postoperative day, the patients were questioned with the aid of a visual analog scale. The standardized questionnaires for bleeding, nasal breathing, feeling of pressure, and headache were used. The presence of synechiae, infection, or granulation was noted and recorded with the video-endoscopy. Results A significant difference according to lower pressure was found in the NasoPore group compared to the controls on day ten after surgery. The NasoPore packing had lower scores with respect to postoperative nose blockage on the 2nd and 10th days. Mucosal healing was better for the NasoPore group, both at day ten and 30 compared with the control group. Conclusion The overall patient comfort is higher when using NasoPore compared to non-resorbable traditional impregnated gauze packing. Intensive saline douches applied three to four times per day are mandatory after the operation to prevent synechiae formation and fluid resorption by the packing.

Resumo Introdução O tamponamento nasal após cirurgia sinusal endoscópica é procedimento de rotina. A solução ideal para minimizar ou eliminar as desvantagens desse procedimento pode ser alcançada com o uso de tampões biodegradáveis. Objetivo Comparar a satisfação do paciente e o desfecho clínico associados ao uso de tampões absorvíveis e não absorvíveis após a cirurgia funcional dos seios paranasais (FESS- Functional Endoscopic Sinus Surgery). Método Foram incluídos 50 pacientes neste estudo prospectivo, duplo-cego e randomizado. Um dos lados foi tamponado com espuma de poliuretano, enquanto no outro lado foi feito um tamponamento com gaze. Nos 2º, 10º e 30º dias após a operação, os pacientes foram perguntados com a ajuda de uma escala analógica visual. Foram empregados questionários padronizados para sangramento, respiração nasal, sensação de pressão e cefaleia. A presença de sinequias, infecção ou granulação foi registrada por videoendoscopia. Resultados Foi observada diferença significante, da sensação de pressão, menor no lado tratado com NasoPore vs. controles no 10º dia após a cirurgia. O tamponamento com NasoPore obteve escores mais baixos com respeito ao bloqueio nasal pós-operatório no 2º e 10º dias. A cicatrização da mucosa foi melhor no lado do NasoPore, mas no 10º e 30º dias os resultados foram comparáveis com os do lado de controle. Conclusão O conforto geral do paciente é maior com o uso de NasoPore vs. tamponamento tradicional com gaze besuntada não reabsorvível. O uso vigoroso de jatos de solução salina aplicados 3-4 vezes ao dia é um procedimento obrigatório após a cirurgia, para evitar a formação de sinequias e para uma absorção natural do tampão.