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By H. Zuben. University of Saint Francis. 2019.

Since the use of a single biomarker in the septic patient is limited by either test availability or performance characteristics discount viagra professional 50 mg on-line, it may be helpful to measure several biomarkers together in combination purchase viagra professional overnight. Other studies employing a variety of panels of biomarkers have shown some success in the use of a biomarker panel [175–177] discount viagra professional 50 mg with visa. Microarray studies have shown that apoptotic genes are highly expressed in inflammatory states, and that proinflammatory response genes decrease over time in sepsis [114]. A microarray panel of 42 gene expression mark- ers representing many different immunologic and cellular response pathways was found in one study to be helpful in the early diagnosis of sepsis [180 ]. Functional proteomics is the study of synthesized proteins and their relationship to health and disease. Schuetz Conclusions and Future Directions Numerous studies exist which assess the roles of non-antibody-based host response biomarkers in disease. For example, sensitivities and specificities are difficult to establish, as a gold standard of sepsis diagnosis against which to measure perfor- mance characteristics is not available. Typically, the efficacy of a biomarker must be compared to current methods of diagnosis, which is usually a combination of clini- cal signs and traditional laboratory values. Small sample sizes, heterogeneous popu- lation types, and differences in assay equipment are also problematic in biomarker research. Therefore, direct comparison of testing methods and results between studies can be difficult. Of the many assays available to measure biomarkers, only a few are currently applicable for use in the clinical laboratory. Despite the large number of biomarker publications, differentiation of sepsis from other noninfectious causes of systemic inflammatory responses continues to remain problematic. Further studies relating specifically to test costs, reliability of testing, and rapid- ity of testing for biomarkers are needed. Standardization of assay methodologies and systematic comparison of different systems should also be performed. Additionally, published reports should provide more detailed information about the platforms employed in analyte measurement and calibration characteristics. Given the potential uses of biomarkers, cost-effectiveness studies of their applications would be helpful. However, the exact roles of biomarkers in the management of septic patients and patients in a wide variety of infections remain undefined (55). Clear consensus guidelines concerning the use of such testing would be invaluable in defining applications of biomarkers in the future. Biomarkers De fi nitions Working Group (2001) Biomarkers and surrogate endpoints: pre- ferred definitions and conceptual framework. Stolz D, Smyrnios N, Eggimann P et al (2009) Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomized study. Masia M, Gutierrez F, Shum C et al (2005) Usefulness of procalcitonin levels in community- acquired pneumonia according to patients outcome research team pneumonia severity index. Chalupa P, Beran O, Herwald H, Kasprikova N, Holub M (2011) Evaluation of potential biomarkers for the discrimination of bacterial and viral infections. Bihrer V, Friedrich-Rust M, Kronenberger B et al (2001) Serum miR-122 as a biomarker of necroinflammation in patients with chronic hepatitis C virus infection. Kibe S, Adams K, Barlow G (2011) Diagnostic and prognostic biomarkers of sepsis in critical care. Shehabi Y, Seppelt I (2008) Pro/con debate: Is procalcitonin useful for guiding antibiotic decision making in critically ill patients? Cetinkaya M, Ozkan H, Koksal N, Akaci O, Ozgur T (2009) Comparison of serum amyloid A concentrations with those of C-reactive protein and procalcitonin in diagnosis and follow- up of neonatal sepsis in premature infants. Nakamura A, Wada H, Ikejiri M et al (2009) Efficacy of procalcitonin in the early diagnosis of bacterial infections in a critical care unit. Dong H, Shu W, Liu T et al (2010) Targeting procalcitonin with novel murine monoclonal antibodies. Meisner M, Tschaikowsky K, Hutzler A, Schick C, Schuttler J (1998) Postoperative plasma concentrations of procalcitonin after different types of surgery. Opatrna S, Klaboch J, Opatrny K Jr et al (2005) Procalcitonin levels in peritoneal dialysis patients. Reinhart K, Meisner M (2011) Biomarkers in the critically ill patient: procalcitonin. Monneret G, Venet F, Pachot A, Lepap A (2008) Monitoring immune dysfunction in the sep- tic patient: a new skin for the old ceremony. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference (1992) Definitions for sepsis and organ failure and guidelines for the use of inno- vative therapies in sepsis. Hunter P (2006) Sepsis under siege—a new understanding of sepsis might lead to develop- ment of therapies to treat septic shock. Povoa P, Coehlo L, Almeida E et al (2005) C-reactive protein as a marker of infection in criti- cally ill patients. Sakr Y, Sponholz C, Tuche F, Brunkhorst F, Reinhart K (2008) The role of procalcitonin in febrile neutropenic patients: review of the literature. Tang H, Huang T, Jing J, Shen H, Cui W (2009) Effect of procalcitonin-guided treatment in patients with infections: a systematic review and meta-analysis. Rey C, Los Arcos M, Concha A et al (2007) Procalcitonin and C-reactive protein as markers of systemic inflammatory response syndrome severity in critically ill children. Claeys R, Vinken S, Spapen H et al (2002) Plasma procalcitonin and C-reactive protein in acute septic shock: clinical and biological correlates. Luzzani A, Polati E, Dorizzi R, Rungatscher A, Pavan R, Merlini A (2003) Comparison of procalcitonin and C-reactive protein as markers of sepsis. Reinhart K, Karzai W, Meisner M (2000) Procalcitonin as a systemic inflammatory response to infection. Povoa P, Almeida E, Moreira P et al (1998) C-reactive protein as an indicator of sepsis. Kajiya T, Orihara K, Hamasaki S et al (2008) Toll-like receptor 2 expression level on mono- cytes in patients with viral infections: monitoring infection severity. Chest 137:812–822 7 Infectious Disease Biomarkers: Non-Antibody-Based Host Responses 145 94. Cuquemelle E, Soulis F, Villers D et al (2011) Can procalcitonin help identify associated bacterial infection in patients with severe influenza pneumonia? Briel M, Schuetz P, Mueller B et al (2008) Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Christ-Crain M, Jaccard-Stolz D, Bingisser R et al (2004) Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-ran- domised, single-blinded intervention trial. Christ-Crain M, Stolz D, Bingisser R et al (2006) Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Burkhardt O, Ewig S, Haagen U et al (2010) A simple procalcitonin-guided strategy results in safe reductions of antibiotic use in patients with symptoms of acute respiratory tract infec- tions in primary care. Cetinkaya M, Ozkan H, Koksal N, Akaci O, Ozgur T (2010) The efficacy of serial serum amyloid A measurements for diagnosis and follow-up of necrotizing enterocolitis in prema- ture infants.

Recent improvements to lateral flow assays applied to respiratory virus detection include use of a fluorescent label to enhance sensitivity of detection and insertion of sample cassettes into a fluorescent reader for objective readout purchase 100mg viagra professional fast delivery, accurate timing buy viagra professional uk, and printed results viagra professional 50mg cheap. Use of bar-coded samples and an interface with the laboratory infor- mation system reduce transcription errors and save labor. Landry Characteristics of the Techniques The characteristics of the techniques are presented in Table 3. Rapid membrane and agglutination assays, while gen- erally simple, vary in number of steps. Each laboratory needs to evaluate these methods and establish performance characteristics in its own settings and patient popula- tions. Decisions on which tests to employ should take into account clinical needs, test volumes, time to result, cost of materials and labor, equipment required, and staff expertise. Applications of the Techniques A summary of the applications of antigen techniques to specific pathogens is given in Table 3. Bacteria Rapid antigen testing is routine for diagnosis of group A streptococcal pharyngitis. The value of detection of Streptococcus pneumoniae antigen in urine for the diagnosis of pneumonia is limited by the positive results obtained in patients with mere oropharyngeal colonization, occurring especially in children, and by sensitivities of only 50–85%. The role of this test in management of patients with community- acquired pneumonia is still evolving, but current guidelines for the management of community-acquired pneumonia suggest the use of this antigen test in patients with severe disease [6–8 ]. Antigen detection in urine is a major diagnostic procedure for Legionella infec- tions. Although available tests detect only 80–90% of the serotypes associated with human disease, the method is sensitive and specific for those serotypes, and is much more rapid than culture. Urinary antigen can remain positive for days to weeks after therapy is begun, and thus can be performed on treated patients. Because non-serogroup I is more common in health care-associated infections than in community-acquired disease, the urinary antigen test is most sensitive in detecting community-acquired legionellosis. Landry 3 Rapid Antigen Tests 45 insensitive, even relative to culture, and requires a skilled reader to limit false-positives. Monoclonal reagents are significantly more specific than polyclonal reagents, but both have been described to cross-react with non-Legionella species, and contami- nation of water, buffers, and the environment with environmental Legionella also may produce false-positives. The true sensitivity and specificity of antigen detec- tion methods in Legionella infections are difficult to determine, since culture itself is insensitive, and molecular methods are only available in a limited number of places [ 9, 10 ] For diagnosis of enterocolitis due to Clostridium dif fi cile toxins, there is no “gold standard. As simpler molecular methods have become available, the role of antigen and other methods has become increasingly controver- sial. It serves as a diagnostic option to the urea breath test, serology, and endoscopy. False- negative results are common in patients on proton-pump inhibitor therapy, bismuth, or antibiotics. The stool antigen test can also be used as a test-of-cure, though the time required after treatment is still unclear [14]. Antigen testing for genital Chlamydia infections has been almost entirely replaced by nucleic acid testing, which is substantially more sensitive and specific. Due to the lack of infrastructure for nucleic acid tests, and the high prevalence and disease burden of Chlamydia in the less devel- oped parts of the world, Chlamydia antigen tests may have a role in those settings despite disappointing sensitivity [16, 17 ]. Bacterial antigen testing for meningitis is rapid, but has fallen out of use in recent years due to inadequate sensitivity and specificity and the use of empiric antibiotic therapy. Empiric antibiotic choices cover the organisms detected by the antigen tests [18, 19 ]. Antigen testing may be per- formed directly on stool, but improved sensitivity is available if an overnight enrichment in selective broth is performed. The sensitivity of antigen tests, even after broth enrichment, falls short of 100%, so selective culture on sorbitol-Mac- Conkey agar is still recommended. Aspergillus galactomannan antigen is used for surveillance in at-risk patients, and may also be of value in monitoring therapy. The combination of radiologic and antigen testing allows early initiation of antifungal therapy and improves outcome in neutropenic patients. The test is less sensitive in non-neutropenic patients, due likely to lower organism loads. False-positives are a problem, occurring frequently in patients who receive piperacillin–tazobactam or amoxicillin–clavulanate, and in patients with other fun- gal infections [21 ] For Cryptococcus, antigen testing is the mainstay of diagnosis. The sensitivity in cryptococcal meningitis approaches that of culture while providing more rapid diagnosis [22]. Parasites For infections by Giardia and Cryptosporidium, antigen testing has become the method of choice, with sensitivities that exceed those of routine microscopic exam [27]. Cost-saving strategies using pooled specimens screened with antigen detection 3 Rapid Antigen Tests 47 have been described. Many different formats are available, and laboratories select a method based on technical (e. Since Trichomonas rapidly loses motility below body temperature, the wet prep has always been an insensitive approach to diagnosis, particularly if specimens needed to be transported prior to viewing. Rapid diagnosis of malaria by antigen detection, primarily using lateral-flow immunochromatography, is a promising approach to field diagnosis. The prolifera- tion of chloroquine-resistant strains and the expense of newer antimalarial drugs may make these tests economical in endemic regions. It does not replace thick and thin smears but provides a sim- ple, rapid diagnostic test usable in virtually any laboratory, with a sensitivity of roughly 95% for P. Worldwide, rapid malarial antigen tests vary significantly in sensitivity, ease of use, and quality control, and dissemination of high-quality tests is a priority for worldwide malaria control [34 ]. They appear to be more sensitive than direct microscopy, and approach or exceed the sensitivity of concentration techniques in some studies [35 ]. Viruses Antigen tests have long been the diagnostic mainstay for viruses that do not grow in routine cell culture, such as hepatitis B and rotavirus. With the advent of therapy with neuraminidase inhibitors, rapid testing for influenza increased dramatically in clin- ics, emergency departments, and hospitals, for patients of all ages. In pediatric patients, having a test result available within 10–30 min has been shown to reduce the use of antibiotics and ordering of diagnostic tests, allow earlier discharge, and permit early administration of antiviral agents [38–40]. While less sensitive than other methods, these tests can perform sufficiently 48 S. Current tests require approximately 100,000 viral copies for a positive result, a titer most commonly found in samples from very young children. The 2009 H1N1 influenza pandemic focused attention on the insensitivity of rapid flu tests, with some hospitals reporting abysmal specificity as well [41, 42]. Nevertheless, many hospitals still consider rapid antigen tests their best option [43] and efforts are underway to improve accuracy. Preliminary studies indicate that incorporating fluorescent immunoassay technology into the lateral flow format, together with a small instrument to analyze the data, can increase sensitivity significantly while retaining a 20-min time to result [44, 45]. Use of cytocentrifugation to prepare slides enhances slide quality and test sensitivity.

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Finally viagra professional 100 mg overnight delivery, in addition to improvement in task comple­ transsphenoidal buy discount viagra professional 100mg, transplanum transtuberculum approach for resec­ tion discount viagra professional 50mg, it will likely decrease the barrier of entry into endoscopy tion of suprasellar lesions. Comparison of two- dimensional and three-dimensional suturing: is there a diference in a robotic surgery setting? Endoscopic pituitary surgery: a second-generation 3D endoscope on the laparoscopic precision of systematic review and meta-analysis. Causes and prevention of laparo­ tions associated with the endoscopic endonasal transsphenoidal ap­ scopic bile duct injuries: analysis of 252 cases from a human factors proach for pituitary adenomas. Curr Biol 1994;4:604–610 dimensional vs three­dimensional camera systems in laparoscopic 12. Infuence of two­dimensional versus three­dimensional imaging on performance three-dimensional vision on surgical telemanipulator performance. Comparison of three-dimensional and two-dimensional laparo­ improves surgical performance for both novice and experienced oper­ scopic video systems. A new 3-D laparoscope in neuroendoscopy: initial descriptions of application to clinical prac­ gastrointestinal surgery. Comparison of learn­ sional endoscopic sinus surgery: feasibility and technical aspects. Microendoscopic lumbar sional endoscopic exposure of midline cranial base targets using discectomy: technical note. Neurosurgery 2002;51(5, Suppl):S129– expanded endonasal and transcranial approaches. J Vasc Surg 2004;39:1305–1311 2009;64(5, Suppl 2):288–293, discussion 294–295 Endoscope-Assisted Transsphenoidal 20 Surgery Joshua R. Kelly The direct endonasal transsphenoidal approach for re- I Surgical Technique moval of pituitary adenomas was described over two decades ago. The panoramic vision provided by the endoscope allows one to visualize and access parasellar areas not pos- fcations as described below and in our recent publica- tions. Efective endoscopic assistance in endonasal pituitary adenoma removal can are given and continued for 24 hours. In patients with nor- translate into a more complete tumor removal in a wid- mal preoperative adrenal function or those with Cushing’s disease, no preoperative glucocorticoids are administered. This chapter describes the technique of endoscopic-assisted Those with adrenal insufciency or borderline adrenal func- endonasal pituitary surgery and methods of complication tion are given 100 mg of intravenous hydrocortisone. Transsphenoidal surgery emerged into the microsurgi- Patient Positioning and Room Setup cal era in the early 1970s with the advent of the operating microscope3,4 and the technique of selective adenomec- The endotracheal tube emerges from the left corner of the tomy as described by Hardy. An arterial line and Foley catheter are safety and efcacy of transsphenoidal surgery. The patient is placed supine with the head resting and Veerapen2 in 1987 and Cooke and Jones1 in 1994 freely in the horseshoe head-holder and angled approximately subsequently described the direct endonasal approach, 30 degrees toward the left shoulder as originally described by Laws,37 which allows the surgeon to stand comfortably on which minimizes patient discomfort associated with the sublabial approach. The patient’s head is typically inclined minimal posterior nasal mucosal dissection and no turbi- in a neutral plane (0 degrees) relative to the foor for most nate removal, is now commonly used with the operating pituitary adenomas. The nos- in the technique have resulted largely from better instru- trils and the perinasal and right lower abdominal areas are mentation, surgical navigation, and, most importantly, prepped and draped in standard fashion. Regardless of the tech- nique used, the surgical goal for patients with pituitary Surgical navigation for trajectory guidance is recommended adenomas should be a selective adenomectomy with pres- for all endonasal transsphenoidal surgeries, unless one is ervation or improvement of pituitary gland function. For most patients goal is best achieved by performing a wide and tall sphe- with a pituitary adenoma, C-arm fuoroscopy is simple and noidotomy and complete sellar bony opening to maximize efective for giving excellent trajectory guidance in the sag- sellar exposure and instrument maneuverability. It is particularly helpful in 202 20 Endoscope-Assisted Transsphenoidal Surgery 203 patients with prior surgery or large invasive tumors with markedly distorted anatomical landmarks. If fuoroscopy is used, the base of the operating microscope is placed just outside the arc of the C-arm above the patient’s head, with the microscope to the patient’s right side. Endoscopic Equipment and Setup The endoscope video monitor and tower are placed above the patient’s head on the patient’s left side to allow for com- fortable viewing by the surgeon and the assistant who will be standing on the patient’s right side. Standard 4-mm rigid endoscopes (18 cm long) with 0-, 30-, and 45-degree angled lenses should be available. An endoscope holder, which is often helpful, can also be positioned with the insertion device fxed to the leftmost cephalad aspect of the operating table. The width of exposure at the 100-mm target is 37 mm for tion and to maximize instrument maneuverability. For ex- the 60-mm speculum compared with 30 mm for the 70-mm speculum ample, Cottle dissectors, microdissectors, ring curettes, and and 24 mm for the 80-mm speculum. Instrumentation assessment: short trapezoidal sors and tumor forceps are of a single-shaft pistol-grip con- speculums for suprasellar and infrasellar exposure in endonasal trans- struction to minimize visual obstruction. A micro-Doppler probe is also used for all cases to localize the cavernous carotid arteries prior to dural opening. The speculum increase exposure compared with longer speculums as is then gently passed along the trajectory of the middle turbi- shown in Fig. The speculum blades gently displace the middle turbinate laterally and pass further Nasal Approach and Sphenoidotomy into the nasal cavity to expose the junction of the keel of the The initial portion of the procedure is performed with the sphenoid and the posterior nasal septum. For tumors a bipolar cautery in a vertical swath, and a vertical mucosal projecting more to one side of the sella, the contralateral incision of approximately 2 cm is made with a Cottle eleva- nostril is used, given that exposure across the midline to the tor. This rule also ap- cally superolateral to the equator of the keel at the 10 o’clock plies in the great majority of patients with septal deviations. The posterior nasal septum is then In patients with relatively midline tumors, the right nostril displaced of the midline by the distal tips of the handheld is used, given that the surgeon stands on the patient’s right speculum to allow exposure of the contralateral side of the side, and this afords a more comfortable operating position. The Cottle elevator can also A relaxing alar incision, although used occasionally early in be used to further refect this contralateral mucosa. If the ostia are seen higher than the 10 o’clock and 2 o’clock Sellar Bony Opening and Carotid Localization positions, the speculum trajectory is likely to be too far inferior and should be re-angled more superiorly and con- After the sphenoidotomy, the sellar face is identifed and the frmed with fuoroscopy or surgical navigation. The added operative view of intrasphenoidal bony septations should be exposure from the use of a shorter speculum is shown in correlated with those septations seen on the patient’s pre- Fig. Septations ending on the sellar face are re- A wide and tall sphenoidotomy is next performed with moved with a rongeur down to the sella; those that end over pituitary and Kerrison rongeurs. Sphenoid bone and muco- a carotid artery should be removed with care, and excessive sal removal should extend beyond the lateral edges of the torquing of the bone fragments should be avoided. Mucosa ostia bilaterally and allow visualization of the tuberculum over the sella is removed, but sphenoid sinus mucosa in the sella and sellar foor. To maximize maneuverability of in- lateral aspects and roof of the sphenoid sinus can be left un- struments during the endoscopic phase of the procedure disturbed. In patients with large smaller and less complete sphenoidotomy will otherwise invasive tumors, the sellar bone may be markedly thinned restrict maneuverability and visualization and has been as- or absent and tumor may be directly under the mucosa or sociated with incomplete tumor removal (Fig. The black circle indicates the optimal bony gery, only bone to the right of the keel had been removed, whereas removal of the sphenoid keel to provide maximal exposure into the the midline keel and left half of sphenoid bone and sphenoid ostium sphenoid sinusf. Selective adenomectomy with preservation of normal gland function should be the surgical goal. Avoidance of carotid artery in- juries in transsphenoidal surgery with the Doppler probe and micro- hook blades.

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