Advances in Laboratory Diagnosis.

Conclusion: ESCMID declaration on meeting the challenges in clinical microbiology and infectious diseases

BackgroundChronic kidney disease affects more than 10% of the world’s population and is a non-communicable disease of global concern and priority. There is a significant implementation gap between best practice guideline recommendations and current kidney disease management. Previous research has shown the need to partner with primary care to improve education, collaboration, and kidney disease awareness. This implementation trial will explore use of an innovative clinical decision support software, Future Health Today, to improve screening, diagnosis, and management of kidney disease in primary care. The program will be supported by tertiary care outreach services. The primary aim is to test the hypothesis that the Future Health Today implementation program will improve screening, diagnosis, and management of kidney disease. Secondary aims are to evaluate primary care satisfaction and broader health service impacts.MethodsThis pre-post implementation trial using an interrupted time series design will evaluate the clinical and service outcomes of Future Health Today, using a mixed methods study in twenty general practices with an estimated population size of 150,000. Deidentified patient data will be extracted from participating practices to examine the primary aims of the study. Surveys and semi-structured interviews with general practice will inform secondary hypotheses. Data linkage between primary care and tertiary care data will examine the broader health service impacts.DiscussionThis investigator driven trial will assess the impact of Future Health Today software coupled with education and clinical outreach support. Investigators hypothesise that there will be improvement in appropriate screening, diagnosis, and management of kidney disease. This program has the potential to be scaled more broadly.Trial RegistrationAustralian New Zealand Clinical Trial Registry: ACTRN12623001096640.

The analysis of heterogeneous protein analytes is very complicated to standardize, but these measurements must be viewed as fundamental to the practice of clinical chemistry. The clinical importance of selected protein measurements such as hemoglobin A1c (Hb A1c),5 thyroid-stimulating hormone, and cardiac troponin I (cTnI) is underscored by their routine use in the diagnosis, prognosis, monitoring, and management of disease, and their incorporation into professional guidelines. Standardization is difficult for proteins because there are few reference measurement procedures for these analytes, few primary (pure substance) reference materials (RMs) have been developed, and some of the RMs that are available can be used only for assay calibration with restrictions. In addition, few secondary (matrix-based) RMs with assigned values are available. In fact, the reference measurement system for the majority of clinically relevant proteins fall into the relatively weak Category 4, according to International Organization for Standardization (ISO) document 17511 (1). Furthermore, protein reference measurements sometimes appear to belong in a higher category but are in fact subject to analytical artifacts and prone to bias. By the criteria of the recently published “roadmap for harmonization” (2), standardization and harmonization of measurement would be regarded as high priority and mission critical for many proteins in laboratory medicine. cTnI is one such protein because its measurement represents the cornerstone for the diagnosis, prognosis, and management of patients with suspected and confirmed acute coronary syndromes (3, 4). Standardization is based on the concept of metrological traceability, as described, for instance, in the ISO 17511 document (1). According to ISO 17511, standardization-of-measurement results for a substance require the metrological traceability chain outlined in Fig. 1A. This chain begins with a primary reference measurement procedure, which assigns quantity values to a primary RM. Primary RMs are used to assign values …

Coronaviruses cause infections in humans and diverse species of animals and birds with a global distribution. Bovine coronavirus (BCoV) produces predominantly two forms of disease in cattle: a respiratory form and a gastrointestinal form. All age groups of cattle are affected by the respiratory form of coronavirus, whereas the gastroenteric form causes neonatal diarrhea or calf scours in young cattle and winter dysentery in adult cattle. The tremendous impacts of bovine respiratory disease and the associated losses are well-documented and underscore the importance of this pathogen. Beyond this, studies have demonstrated significant impacts on milk production associated with outbreaks of winter dysentery, with up to a 30% decrease in milk yield. In North America, BCoV was identified for the first time in 1972, and it continues to be a significant economic concern for the cattle industry. A number of conventional and molecular diagnostic assays are available for the detection of BCoV from clinical samples. Conventional assays for BCoV detection include virus isolation, which is challenging from clinical samples, electron microscopy, fluorescent antibody assays, and various immunoassays. Molecular tests are mainly based on nucleic acid detection and predominantly include conventional and real-time polymerase chain reaction (PCR) assays. Isothermal amplification assays and genome sequencing have gained increased interest in recent years for the detection, characterization, and identification of BCoV. It is believed that isothermal amplification assays, such as loop-mediated isothermal amplification and recombinase polymerase amplification, among others, could aid the development of barn-side point-of-care tests for BCoV. The present study reviewed the literature on coronavirus infections in cattle from the last three and a half decades and presents information mainly on the current and advancing diagnostics in addition to epidemiology, clinical presentations, and the impact of the disease on the cattle industry.

Syphilis is a sexually transmitted disease caused by Treponema pallidum subsp. pallidum. This historical disease has diverse clinical manifestations making laboratory testing crucial for optimal patient management. Direct detection of T.pallidum by dark-field microscopy is possible when lesions are present. Culture of the bacteria is complex and not performed routinely. There is no well-validated commercially available polymerase chain reaction (PCR) test. Serological tests are currently the most common diagnostic methods adapted in clinical laboratories. They provide a presumptive diagnosis and used for screening, diagnosis, and follow-up of the treatment. They are divided into two groups, named as nontreponemal and treponemal tests and performed by the application of the traditional algorithm, the reverse sequence algorithm or European Centre for Disease Prevention and Control (ECDC) algorithm. The traditional algorithm starts with a nontreponemal test and a reactive result is confirmed with a treponemal test. In the reverse sequence algorithm, a treponemal test is used for screening and a reactive result is confirmed by a quantitative nontreponemal test. When the nontreponemal test is negative, a second different treponemal test preferably T.pallidum particle agglutination test (TPPA) is used. The ECDC algorithm recommends screening by a treponemal test such as T.pallidum enzym immunoassay (TP-EIA), T.pallidum chemiluminescence immunoassay (CIA) and if reactive, a reflex confirmatory treponemal test is performed. The treponemal tests become reactive a few weeks after infection and remain reactive even after successful treatment. The nontreponemal tests are used to assess disease activity and response to therapy. Serological tests have many limitations such as false-positivity, falsenegativity in various stages of the disease and also challenging difficulties when evaluating response to therapy. In recent years, rapid syphilis tests which are mostly treponemal-specific tests have been developed for high-prevalence populations in resource limited settings. There has been requirement for the utility of standart PCR and IgM testing in the diagnosis of congenital syphilis and neurosyphilis cases. In this review article, it was aimed to present the diagnostic tests, the algorithms, the correct indications for testing and interpretation of the test results to the likely corresponding clinical stage of the disease with in the perspective of recent advances.

CdTe quantum dots (CdTe-QDs) can emit strong and stable room temperature phosphorescence (RTP) via the perturbation effect of a Pb(2+) ion on the surface of a nitrocellulose membrane (NCM). CdTe-QDs-Ab(GAS), the product of CdTe-QDs labelled gastrin antibodies (Ab(GAS)), can not only maintain good RTP characteristics, but can also be used as a RTP sensor and carry out highly specific immunoreactions with gastrin (GAS) to form GAS-Ab(GAS)-CdTe-QDs causing the ΔI(p) of the system to sharply enhance. Thus, a new solid substrate room temperature phosphorescence immunoassay (SSRTPIA) for the determination of GAS was established based on the linear relativity between the ΔI(p) of the system and the content of GAS. The limit of quantification (LOQ) of this method was 0.43 fg spot(-1) with the corresponding concentration being 1.1 × 10(-12) g mL(-1) and sampling quantity being 0.40 per spot(-1). This highly specific, accurate, selective and sensitive RTP sensor has been applied to the determination of GAS in biological samples and the diagnosis of diseases, and the results agreed well with those obtained by radioimmunometric assay (RIA). Meanwhile, the mechanism of SSRTPIA for the determination of GAS using CdTe-QDs-Ab(GAS) as the RTP sensor was discussed.

Chronic kidney disease (CKD) represents one of today's main public health problems. Serum creatinine measurement and estimation of the glomerular filtration rate (GFR) are the main tools for evaluating renal function. There are several equations to estimate GFR, and CKD-EPI equation (Chronic Kidney Disease - Epidemiology) is the most recommended one. There are still some controversies regarding serum creatinine measurement and GFR estimation, since several factors can interfere in this process. An important recent change was the removal of the correction for race from the equations for estimating GFR, which overestimated kidney function, and consequently delayed the implementation of treatments such as dialysis and kidney transplantation. In this consensus document from the Brazilian Societies of Nephrology and Clinical Pathology and Laboratory Medicine, the main concepts related to the assessment of renal function are reviewed, as well as possible existing controversies and recommendations for estimating GFR in clinical practice.

As he/she approaches the end of life, the healthy elderly person comes to be seen rather as a "biological curiosity" than as a normal case. For laboratory testing it becomes increasingly difficult to determine appropriately stratified and statistically relevant reference groups. More appropriate would be individual monitoring, which, however, requires long-term stable quality in laboratory analyses. Despite "consolidation" in laboratory medicine, the pre-analytical phase, which is especially important in the elderly, remains underestimated. This problem is aggravated by insufficient harmonisation between laboratory tests, especially when point-of-care testing is included. Since in geriatrics, maintenance of life quality is more important than curative therapy, clinicians are forced to undergo therapeutic compromises applying symptomatic, supportive or palliative therapies. In this situation, information on "still remaining functional capacities" of organs is particularly helpful. Diagnostic problems resulting from underestimation of "multi-morbidity" and especially "multi-aetiology" can be complicated by "degradation of clinical information", especially in patients in cognitive and/or physical decline. The specific purpose of "geriatric" laboratory medicine seems to induce a change of paradigms: not only statistically established "evidence", but "individuality" in a single patient will need more profound insight. Not so much differentiation between "physiology" and "pathology", but the consideration of "clinical individuality" as relative risk in dimension of time is of importance.

Recent reports of genomic sequencing leading to innovative and effective clinical management—perhaps most notably the story of the Wisconsin boy for whom whole genome sequencing led to a curative bone marrow transplant1—provide a glimpse of a new world for diagnostic medicine and for diagnostic laboratories, in particular. Such genomic successes strongly suggest that “personalized medicine” will increase the role of clinical laboratories in patient management. These changes have profound implications for the discipline of pathology and laboratory medicine and for how laboratory diagnosticians relate to medicine as a whole. This “Editorial” provides a succinct, but challenging, vision from the perspective of large, academic pathology departments about how we anticipate the field of pathology will change during the next 5 to 10 years.Deep-sequencing technology is just one of several remarkable opportunities for clinical laboratories. Technologic advances (automation, molecular diagnostics, pathology imaging, and informatics) are transforming the field. Automated systems now provide a large percentage of high-volume, fluid-based test results, and even the traditionally manual areas of histopathology may become automated in the near future. Molecular diagnostics has made inroads into nearly all areas of pathology, particularly cancer diagnosis, microbiology, and hereditary disease testing. The pace of change is dizzying, both in numbers of tests and in the complexity of the results, as is the emerging need to integrate massive data sets to reach a clinical interpretation. Informatics—information systems, computational informatics, and digital imaging and its applications—has made substantial inroads, not only based on new “-omic” data sets but also on conventional clinical laboratory data and histologic images with synoptic data capture of morphologic parameters. Such data are being incorporated at some institutions into huge and continuously updated data warehouses that can be mined for diagnostic and policy decisions. Indeed, the application of informatics and computational biology and its integration with hospital clinical systems may alter how we make diagnoses—leading to development of “computational diagnostics” as a tool for clinical laboratories.Diagnostic laboratories are complicated places, with advanced technologies, large staffs, and detailed regulations. They remain oriented around the historically separate, technologically defined areas of clinical pathology and anatomic pathology. The changes described above, however, blur that traditional distinction. Molecular technologies are being implemented on both sides of the historic divide, and even the traditionally human interpretation–based areas of anatomic pathology are using automated approaches that rely on computer-assisted diagnostics. Overall, automation shifts physician emphasis away from technical oversight, creating opportunities to provide value in other ways.With these changes, one can anticipate a day in which complete epigenetic, genetic, proteomic, and metabolomic signatures will be generated at high quality and low cost. In a value-oriented health care system, the pathologist will then become the integrator of large, complex data sets to continue to fulfill the classic central role of determining diagnosis, prognosis, and appropriate therapy. Furthermore, with this increase in clinical data, pathologists can extend their traditional roles in the appropriate use and integration of laboratory information. Pathologists would not only work to contain costs but also would justify testing in light of clinical necessities—putting considerable pressure on laboratory-based physicians to understand clinical and overall health care needs in detail.The exponential growth of information makes the old model of a single pathologist running a hospital laboratory difficult to sustain. As in the rest of medicine, the complexity of biomedical information, the need for efficiency, and performance improvement are driving subspecialization in laboratory diagnostics. A major advantage of subspecialty practice is that pathologists become more integrated members of health care teams. Subspecialty pathologists are already core members of multidisciplinary cancer teams, as critical as the surgeon or oncologist. Indeed, subspecialization in pathology will become necessary because of subspecialization in the rest of medicine. Subspecialist physicians derive improved service from pathologists who speak their language, and who understand the details of their needs and the patients' needs.A greater need for pathologist involvement has thus arisen at the interface of the laboratory with the clinic. The pathologist can no longer be solely within the laboratory, but must be positioned at the door, able to look both into and out of the laboratory. For instance, the growing number of different laboratory tests creates a challenge for the typical physician to remain appropriately informed. Furthermore, the complexity of individual tests has escalated: witness the difficulties of interpreting the significance of polymorphisms detected in genetic testing. Given that “shotgun” approaches to laboratory test ordering lead to wasteful overordering and affect quality outcomes adversely through delays in diagnosis and pursuit of false-positives, the laboratory diagnostician will need to define ordering practices, ensure cost containment and quality assessment to evaluate the utility of diagnostic procedures in specific clinical settings, and integrate information from different platforms.Pan-laboratory subspecialization will likely provide the best model for all laboratory-based diagnostics relevant to a disease. In such a model, pathology reports would become comprehensive, integrating the results of imaging, biochemical, histologic, molecular genetic, cytogenetic, genomic, and epigenetic analyses into a cohesive, clinically relevant, and valuable diagnostic, predictive, and prognostic document. Such pan-laboratory subspecialization emphasizes the need for subspecialists to span the breadth of current laboratory technologies and to centralize them under the aegis of a particular organ system or group of diseases.If this model is around the corner, pathology and laboratory medicine needs to prepare its trainees appropriately—to provide a strong foundation in emerging technologies and quality measures and to prepare pathologists to become credible consultants in their fields. This cannot be accomplished by simply extending the time of training, and pathology training programs may need to undergo transitions like those that occurred decades ago for subspecialties such as urology and neurosurgery—instead of full general surgical training, a year of general surgery followed by lengthy specialty training. It may be necessary for the next generation of pathologist trainees to undertake a single internship year in basic anatomic pathology and clinical pathology, followed by additional years of either organ-based or technology-based subspecialty training, which would include extensive exposure to laboratory diagnosis and clinical medicine. Pathologists would thus work together with their subspecialist laboratory colleagues, clinicians, and patients to develop their craft. Such programs will not be easy to generate and will require greater overlap with medical and surgical training tracks.Pathology today is laboratory focused, with the attendant benefits of consistency and reliability. However, to foster the current opportunities in diagnostic laboratories, the discipline should transform rapidly into a subspecialty-oriented, pan-laboratory medical field that operates at the critical interface between the laboratory and the clinic—even closer to the medical and surgical specialties. Next-generation pathologists must ensure progress in obtaining faster, better, more-integrated results for patients, and they may look very different to their medical and surgical colleagues. With these changes, the old aphorism from Sir William Osler will remain true: “As is your pathology, so goes your clinical care.”

The basic tenets of medical ethics are: autonomy of the patient, beneficence, non-maleficence and justice. These are usually interpreted in the light of the practice of clinical medicine but also apply to pathology and laboratory medicine, a field in which there is often no direct patient contact. We wished to evaluate these basic tenets of medical ethics with respect to laboratory medicine and to provide insights into some of the issues that laboratory physicians, in routine practice and in academia, face on a regular basis. This was done by using the published literature related to the topic of medical ethics, with a special focus on laboratory medicine, as well as the authors' interpretations and opinions, based on their experience. We conclude that the idea of autonomy of the patient or research participant is pertinent with respect to specimens, autopsies and in legal issues such as consent for publication in the media and social media. Beneficence is relevant with respect to laboratory values in reports, financial issues and in research and education. The concept of non-maleficence is important from the point of view of doing no harm, communication with patients and colleagues, reducing/containing error and misdiagnosis in medicine, screening for disease and in over diagnosis. Justice is applicable to issues of distribution of resources and manpower, and their equitable usage. Many of the tenets, however, need to be interpreted in the light of local laws and customs which differ across the world. We conclude with an Oath for pathologists and laboratory physicians. Key words: medical ethics, misconduct, autonomy, beneficence, non-maleficence, justice, informed consent, medical research, oaths.

Skin diseases in remote African regions are often exacerbated due to a lack of resources and expertise with little current research addressing the challenges that patients and healthcare systems experience. Although skin diseases in remote African regions are prevalent and pose a substantial health burden, they remain neglected and understudied. This review aims to explore current challenges in the diagnosis and management of skin diseases in African regions and focus on the need for enhanced understanding and improved healthcare strategies. We reviewed papers that were retrieved from PubMed, Google Scholar, and other relevant academic search sites to analyze the prevalence, screening techniques, as well as management strategies and obstacles associated with dermatological diseases in remote African regions. Current literature suggests there is indeed a high prevalence of skin diseases where other infections are predominant. Further, different factors, such as socioeconomic status and environmental conditions, make it challenging for optimal screening and treatment of skin diseases in remote African regions. Common screening methods for skin diseases involve clinical examination and laboratory tests, while management includes pharmacotherapy, surgery, and counseling approaches. Overall, access to medications and adequate healthcare services remains limited. Early diagnosis and management of skin diseases in remote African regions have significant challenges, including a lack of funding for dermatology, education, and research. Future promising strategies such as teledermatology, point-of-care diagnostic technologies, and task shifting show promise in improving access to care. However, there is a need for sustained efforts to address the underlying socioeconomic factors and improve healthcare delivery in remote African regions.

The Clinical Application of Oncomine Myeloid Next Generation Sequencing (NGS): Comparison of Cytogenetics and NGS in Patients with Suspected Myelodysplastic Syndrome

In nature certain proteins are self-assembled inside cells to form nanoscale particles (named "proteinticles") with constant structure and surface topology. Unlike chemically synthesized nanomaterials (e.g., various metal, carbon, and polymer nanoparticles), a variety of functional proteinticles can be easily created through genetic modification of the proteinticle surface, i.e., by adding or inserting specified proteins/peptides to the N- or C-terminus or the internal region of the protein constituent. Here we present proteins/peptides that recognize disease-specific antibodies on the surface of human ferritin based proteinticles for accurate 3D diagnosis of human autoimmune and infectious diseases. The surface display of the extracellular domain of myelin oligodendrocyte glycoprotein (MOG) with native conformation successfully discriminated between autoantibodies to native or denatured MOG, leading to the reliable diagnosis of multiple sclerosis with enhanced accuracy. Also we simultaneously displayed different antigenic peptides from hepatitis C virus (HCV) on the same proteinticle surface with modulating the composition of each peptide. The proteinticles with the heterogeneous peptide surface detected anti-HCV antibodies in patient sera with 100% accuracy. The proposed method of proteinticle engineering can be applied in general to the sensitive and specific diagnosis of many other human diseases.

To the Editor.—We read with considerable interest the editorial written by James S. Hernandez, MD,1 from the October 2011 edition of the Archives of Pathology & Laboratory Medicine, entitled “‘No Pay, No Play': The End of Professional Ethics in Pathology?” Dr Hernandez discussed the need for improved, direct communications between patients and pathologists in all fields.The editorial by Timothy Craig Allen, MD, JD,2 from the April 2012 edition of the Archives of Pathology & Laboratory Medicine, entitled: “‘No Pay, No Play': Game Over” comments and further expands the contents of the editorial by Dr Hernandez. We fully agree with Dr Allen in what he says, in particular, when he affirms that: “Now is the time for pathologists to send a message, and send it appropriately, regarding our professionalism. Pathologists have no time for any more word games…” and “Many pathologists, probably almost all pathologists, are, like Dr Hernandez, willing or even enthused to speak with patients directly.”We are firmly convinced that what was written by Dr Hernandez and expanded and clarified by Dr Allen applies to the pathology communities not only in the United States but also in the rest of the world.From the time of publication of the editorial on “The End of the Professional Ethics in Pathology?” by Dr Hernandez to the very recent “Game Over” by Dr Allen, we published, in the ‘Words of Wisdom' section of European Urology,3 a commentary on the former. The main issues of our contribution were the following.In many instances, there is no feedback information about the immediate and remote consequences of what is included in the pathology reports. This might be especially true for specimens for which the clinical significance is perceived of as limited or of no clinical value. Basically, little time is spent speaking with the clinician in charge of that specimen or with the patient, mainly only when the pathologist has to defend his or her diagnosis. This can be called defensive or passive pathology.During the years, some of us, having practiced the specialty of uropathology since the mid-1970s, have witnessed 2 major challenges that have convinced us of what professional ethics in pathology should be like:In conclusion, for many of us, it is not a burden, but a joy, to consult with colleagues in other specialties, such as the urologists and uro-oncologists, and speak with the patient, sharing our in-depth knowledge and understanding of the pathophysiology of disease. All this requires a profound knowledge of clinical medicine as well as anatomic and clinical pathology. This means that it is time for us to move from defensive or passive uropathology to active, clinically oriented uropathology. The former, that is, defensive or passive pathology, could have been one of the reasons why, in recent years, fewer and fewer medical doctors have embraced a career in pathology, fearing that a lack of personal contact with a patient would not be fulfilling the true nature of the medical practice.

The purpose of this work is to make a brief review of the impact that new technologies including automation, cybernetics, informatics, robotics, and telecommunications have had in today's society with a particular focus on the Clinical Laboratory where significant evolution has been evolving through the last two decades of the 20th Century and the first two decades of the 21st Century. Laboratory Medicine is a specialty in which multiple disciplines converge, including Clinical Chemistry and Clinical Pathology, so that nowadays the concept of Clinical Laboratory Professionals has been increasingly accepted. Given that the Medical Relevance is currently the fundamental premise, the understanding and application of the Biological Variability and its importance on the establishment of Analytical Goals is better understood and accepted day. The recognition of the suitability of the laboratory should include the human dimension and the technological dimension starting with the fulfillment of bioethics so each laboratory must have a Code of Ethics dated and signed by all personnel in which they commit themselves not to incur in conflicts of interest, always placing the patient's interest above any other.