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An electrochemical paper-based sensor was developed for the detection of bacterial infection (BI)-specific biomarker procalcitonin (PCT). Reduced graphene oxide-gold nanoparticles (rGO-AuNP) and poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) were synthesized and were fabricated to a disposable, portable, and inexpensive cellulose fiber paper (CFP) substrate. rGO-AuNP-PEDOT:PSS nanocomposite-modified conductive paper-based biosensing platform was efficaciously fabricated by a constant and simple coating procedure. rGO-AuNP-PEDOT:PSS nanocomposite-modified conductive paper electrode was found to provide a sensitive and conductive substrate for PCT detection. The presence of rGO-AuNP-PEDOT:PSS nanocomposite on CFP substate was investigated by Fourier transform infrared spectrometry, field emission scanning electron microscopy, ultraviolet–visible spectroscopy, and X-ray diffraction studies. The electrochemical behavior of rGO-AuNP-PEDOT:PSS @CFP surface was studied with impedance spectroscopy, cyclic voltammetry, and chronoamperometry techniques. This low-cost paper-based biosensor has a linear range for PCT of 1 × 103 to 6 × 107 fg mL−1. This developed sensor exhibited good reproducibility with a relative standard deviation (RSD) of about 3.7%. The proposed CFP-based biosensor has been proven as an accelerated simple point-of-care (POC) exploratory approach for early PCT diagnosis in inadequate areas with limited production facilities, computational techniques, and highly skilled experts. [ABSTRACT FROM AUTHOR]

The present study reports the fabrication of reduced graphene oxide (rGO)/gold nanoparticles (AuNP) nanocomposites modified cellulose fiber paper‐based electrochemical biosensor for procalcitonin (PCT) biomarker detection. PCT is a biomarker specific for bacterial infection (BI) detection and has gained much attention as a potential solution to the problems associated with determining appropriate antibiotic use. In sepsis and other severe infections, serum PCT levels increase to values above 100 ng mL−1 in response to pro‐inflammatory stimulation. The structural and morphological characterization of the rGO‐AuNP composite are investigated using UV‐Vis spectroscopy, FTIR spectroscopy, X‐ray diffraction, and scanning electron microscopy. Monoclonal antibodies specific to PCT were covalently immobilized onto the rGO‐AuNP nanocomposite modified paper to fabricate an electrochemical biosensor. The fabricated biosensor exhibits linearity in the PCT concentration range 10 −15×103 pg mL−1, with a low detection limit 10 pg mL−1. Furthermore, the proposed biosensor also exhibited good selectivity and could detect PCT biomarkers even in the presence of other interfering electroactive species such as glucose, oxalic acid, and urea. The proposed CF‐based biosensor has been proven as an accelerated simple point‐of‐care (POC) exploratory approach for early PCT diagnosis in inadequate areas with limited production facilities, computational techniques, and highly skilled experts. [ABSTRACT FROM AUTHOR]

This document is a reply to comments made by Ulla Vogel and colleagues regarding the occupational exposure limit (OEL) for zinc oxide (ZnO). The authors disagree with the argument that small elevations of chronic acute phase proteins, such as C-reactive protein (CRP) and serum amyloid A (SAA), increase the risk of cardiovascular disease (CVD). They cite studies that question the causal link between CRP and SAA elevations and CVD. The authors also clarify that the term "zinc-specific mechanism of action" should be understood as a "metal-specific mechanism of action." They criticize studies that attribute acute phase protein responses to insoluble particles without investigating their composition. Additionally, they point out a misrepresentation of the MAK recommendation and highlight the technical challenges of complying with proposed concentration limits. The authors declare no conflict of interest. [Extracted from the article]

Urolithiasis is a common disease that affects approximately one-fifth of the global population. This systematic review explores the predictive role of inflammatory markers for the spontaneous passage of ureteral stones. The literature was systematically searched via Google Scholar, PubMed/MEDLINE, the Cochrane Library, Science Direct, CINAHL, Web of Science, and EMBASE databases to identify papers published until 2023. Overall, 26 articles were identified, of which 10 were excluded. The remaining 16 papers reported 2,695 patients (1,723 males and 972 females), with 1,654 (61.37%) experiencing spontaneous stone passage (SSP) and 1,041 (38.63%) not experiencing it (non-SSP). Stones located in the upper part of the ureter were less likely to pass spontaneously (152/959, 15.94% in the SSP group vs. 180/546, 32.48% in the non-SSP group; p < 0.001). Mid-ureteral stones were present in 180/959 (18.75%) of the SSP group compared to 84/546 (14.52%) of the non-SSP group (p = 0.0974). Lower ureteral stones were more likely to pass spontaneously, with 627/959 (63.31%) in the SSP group compared to 282/546 (49.36%) in the non-SSP group (p < 0.001). No significant correlation was found between most inflammatory markers and SSP (p > 0.05). However, procalcitonin levels were lower in the SSP group compared to the non-SSP group (132.7 ± 28.1 vs. 207 ± 145.1, respectively) (p < 0.001). This systematic review has revealed that except procalcitonin, most inflammatory markers do not offer significant predictive capability for ureteral SSP. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the diagnostic characteristics of biomarker for diabetic foot osteomyelitis (DFO). We searched PubMed, Scopus, Embase and Medline for studies who report serological markers and DFO before December 2022. Studies must include at least one of the following diagnostic parameters for biomarkers: area under the curve, sensitivities, specificities, positive predictive value, negative predictive value. Two authors evaluated quality using the Quality Assessment of Diagnostic Accuracy Studies tool. We included 19 papers. In this systematic review, there were 2854 subjects with 2134 (74.8%) of those patients being included in the meta‐analysis. The most common biomarkers were erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP) and procalcitonin (PCT). A meta‐analysis was then performed where data were evaluated with Forrest plots and receiver operating characteristic curves. The pooled sensitivity and specificity were 0.72 and 0.75 for PCT, 0.72 and 0.76 for CRP and 0.70 and 0.77 for ESR. Pooled area under the curves for ESR, CRP and PCT were 0.83, 0.77 and 0.71, respectfully. Average diagnostic odds ratios were 16.1 (range 3.6–55.4), 14.3 (range 2.7–48.7) and 6.7 (range 3.6–10.4) for ESR, CRP and PCT, respectfully. None of the biomarkers we evaluated could be rated as 'outstanding' to diagnose osteomyelitis. Based on the areas under the curve, ESR is an 'excellent' biomarker to detect osteomyelitis, and CRP and PCT are 'acceptable' biomarkers to diagnose osteomyelitis. Diagnostic odds ratios indicate that ESR, CRP and PCT are 'good' or 'very good' tools to identify osteomyelitis. [ABSTRACT FROM AUTHOR]

The small molecule calcitonin gene–related peptide receptor antagonists (gepants) are the only drug class with medicines indicated for both the acute and preventive treatment of migraine. Given this dual capacity to both treat and prevent, along with their favorable tolerability profiles and lack of an association with medication‐overuse headache, headache specialists have begun to use gepants in ways that transcend the traditional categories of acute and preventive treatment. One approach, called situational prevention, directs patients to treat during the interictal phase, before symptoms develop, in situations of increased risk for migraine attacks. Herein, we present three patients to illustrate scenarios of gepant use for situational prevention. In each case, a gepant was started in anticipation of a period of increased headache probability (vulnerability) and continued for a duration of 1 day to 5 consecutive days. Although this approach may expose patients to medication when headache may not have developed, the tolerability and safety profile and preventive effect of gepants may represent a feasible approach for some patients. Situational prevention is an emerging strategy for managing migraine before symptoms develop in individuals who can identify periods when the probability of headache is high. This paper is intended to increase awareness of this strategy and stimulate future randomized, placebo‐controlled trials to rigorously assess this strategy. Plain Language Summary: A new class of migraine medicines, the gepants, does not cause medication‐overuse headache; these drugs can be taken in periods of increased headache risk, even before symptoms begin, to keep headaches from coming on. This new way of treating migraine is called "situational prevention." Experience in clinical practice suggests that treating migraine patients without current symptoms during times of increased headache risk, for example in connection with the menstrual cycle, travel, stress, or relaxation after stress, may be good times for situational prevention, but studies are needed to confirm when this strategy is most likely to be beneficial. [ABSTRACT FROM AUTHOR]

• The multiplexed ePADs for simultaneous three important CVDs biomarkers was created. • ePADs provide low detection limits and wide linear range for CVDs biomarker detections. • Good selectivity and high sensitivity were achieved. • The sensor was successfully applied to detect CVDs biomarkers in serum sample. Cardiovascular diseases (CVDs) are the number one cause of death globally. Therefore, a sensitive and affordable point-of-care sensing device is needed for the diagnosis and monitoring of diseases. Herein, we demonstrated an electrochemical paper-based analytical device (ePAD) coupled with a label-free immunoassay for simultaneous determination of three important CVDs biomarkers including C-reactive protein (CRP), troponin I (cTnI), and procalcitonin (PCT). The ePAD was created by stacking a wax-patterned paper and a transparency film using laser-cut double-sided adhesive to define the sample inlet, three separate detection zones for each analyte, and fluidic channels that connect the inlet and detection zones. Antibodies to the target biomarkers were immobilized on graphene oxide (GO)-modified carbon electrodes stencil-printed on the ePAD. Concentrations of the CVDs biomarkers were determined by square wave voltammetry (SWV). A significant decrease in current response in a concentration-dependent manner was observed in the presence of the cardiac biomarkers while there was no observable change in current response in the absence of the biomarkers. Good linearity (R2 > 0.99), low detection limits (0.38 ng mL−1, 0.16 pg mL−1, and 0.27 pg mL−1 for CRP, cTnI, and PCT, respectively), and good reproducibility (RSD < 5 %) were achieved for the quantifications. Furthermore, the immunosensor has been applied to simultaneously detect the three biomarkers in serum samples with satisfactory results. The proposed immunosensor can be a great alternative for the early detection of cardiovascular diseases at the point-of-care. [ABSTRACT FROM AUTHOR]

Objective: We conducted this paper to decipher the efficacy of the combined chemotherapy of zoledronic acid and pamidronate in treating bone metastases from nonsmall cell lung cancer (NSCLC) and the effects on pain stress and bone metabolic indices. Methods: Patients with bone metastases from NSCLC were allocated into Group A and Group B. Patients in the Group A were administrated with pamidronate combined chemotherapy and patients in the Group B were administrated with zoledronic acid combined chemotherapy. The efficacy, pain symptom scores, quality of life scores, serum inflammatory factor, serum bone metabolic indices, serum pain stress indicators, and the occurrence of adverse effects were compared in patients of the two groups. Results: The total effective rate of treatment was higher in the Group B than in the Group A. After treatment, reduced Numerical Rating Scale scores and elevated Karnofsky Performance Score score, reduced serum levels of N‐terminal mid‐fragment of osteocalcin, N‐terminal propeptide of type I procollagen, bone‐specific alkaline phosphatase, and type I collagen hydroxyl terminal peptide β special sequence, reduced serum levels of C‐reactive protein, procalcitonin, tumor necrosis factor‐α, and interleukin‐6, as well as decreased levels of bradykinin, substance P, neuropeptide Y, and β‐endorphin were found in the Group B versus the Group A. No notable difference was witnessed in the rate of adverse reactions between the Group A and the Group B. Conclusion: Zoledronic acid combined with chemotherapy can effectively treat bone metastases of NSCLC and improve pain stress and bone metabolic status, which has value that can be promoted and applied in clinical treatment. [ABSTRACT FROM AUTHOR]

Objective: To perform a systematic review of real-world outcomes for anti-CGRP-mAbs. Methods: Following the PRISMA guidelines, we searched PubMed for real-world data of erenumab, galcanezumab, fremanezumab, or eptinezumab in patients with migraines. Results: We identified 134 publications (89 retrospective), comprising 10 pharmaco-epidemiologic and 83 clinic-based studies, 38 case reports, and 3 other articles. None of the clinic-based studies provided follow-up data over more than one year in more than 200 patients. Findings suggest that there are reductions in health insurance claims and days with sick-leave as well as better treatment adherence with anti-CGRP-mAbs. Effectiveness, reported in 77 clinic-based studies, was comparable to randomized controlled trials. A treatment pause was associated with an increase in migraine frequency, and switching to another antibody resulted in a better response in some of the patients. Adverse events and safety issues were addressed in 86 papers, including 24 single case reports. Conclusion: Real-world data on anti-CGRP-mAbs are limited by retrospective data collection, small patient numbers, and short follow-up periods. The majority of papers seem to support good effectiveness and tolerability of anti-CGRP-mAbs in the real-world setting. There is an unmet need for large prospective real-world studies providing long-term follow-ups of patients treated with anti-CGRP-mAbs. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses articles in the issue on topics including dietary interventions for migraine; research on the influence of the gut microbiome on migraine; and the challenge of treating migraine in patients with comorbid vascular disease.

The clinical application of biochemical indicators of bone metabolism provides molecular biological basis for the diagnosis， differential diagnosis， prediction of fracture risk and evaluation of therapeutic effect of anti-osteoporosis treatment of osteoporosis， and has important significance in the epidemiological study of osteoporosis， pathogenesis， and development and research of osteoporosis drugs. Because of the high specificity and sensitivity of bone metabolism biochemical indicators， its application is increasingly widespread. This paper has searched a large number of Chinese and foreign literatures， compiled and reviewed the Expert Consensus on Clinical Application of Bone Metabolism Biochemical Indicators （2023 Revision）， and discussed the classification of bone metabolism biochemical indicators， the methodology and biological significance of bone metabolism biochemical indicators， and the detection and variation of bone metabolism indicators. [ABSTRACT FROM AUTHOR]

An exciting trend in clinical diagnostics is the development of easy-to-use, minimally invasive assays for screening and prevention of disease at the point of care. Proximity Extension Assay (PEA), an homogeneous, dual-recognition immunoassay, has proven to be sensitive, specific and convenient for detection or quantitation of one or multiple analytes in human plasma. In this paper, the PEA principle was applied to the detection of procalcitonin (PCT), a widely used biomarker for the identification of bacterial infection. A simple, short PEA protocol, with an assay time suitable for point-of-care diagnostics, is presented here as a proof of concept. Pairs of oligonucleotides and monoclonal antibodies were selected to generate tools specifically adapted to the development of an efficient PEA for PCT detection. The assay time was reduced by more than 13-fold compared to published versions of PEA, without significantly affecting assay performance. It was also demonstrated that T4 DNA polymerase could advantageously be replaced by other polymerases having strong 3'>5' exonuclease activity. The sensitivity of this improved assay was determined to be about 0.1 ng/mL of PCT in plasma specimen. The potential use of such an assay in an integrated system for the low-plex detection of biomarkers in human specimen at the point of care was discussed. [ABSTRACT FROM AUTHOR]

Appropriateness in Laboratory Medicine has been the object of various types of interventions. From published experiences, it is now clear that to effectively manage the laboratory test demand it is recommended to activate evidence-based preventative strategies stopping inappropriate requests before they can reach the laboratory. To guarantee appropriate laboratory test utilization, healthcare institutions should implement and optimize a computerized provider order entry (CPOE), exploiting the potential of electronic requesting as "enabling factor" for reinforcing appropriateness and sustaining its effects over time. In our academic institution, over the last 15 years, our medical laboratory has enforced various interventions to improve test appropriateness, all directly or indirectly based on CPOE use. The following types of intervention were implemented: (1) applying specific recommendations supported by monitoring by CPOE as well as a continuous consultation with clinicians (tumour markers); (2) removing outdated tests and avoiding redundant duplications (cardiac markers, pancreatic enzymes); (3) order restraints to selected wards and gating policy (procalcitonin, B-type natriuretic peptide, homocysteine); (4) reflex testing (bilirubin fractions, free prostate-specific antigen, aminotransferases, magnesium in hypocalcemia); and (5) minimum retesting interval (D-Dimer, vitamin B12, C-reactive protein, γ-glutamyltranspeptidase). In this paper, we reviewed these interventions and summarized their outcomes primarily related to the changes in total test volumes and cost savings, without neglecting patient safety. Our experience confirmed that laboratory professionals have an irreplaceable role as "stewards" in designing, implementing, evaluating, and maintaining interventions focused to improving test appropriateness. [ABSTRACT FROM AUTHOR]

Neonatal sepsis (NS) is defined as a presence of microorganisms in primarily sterile body fluids and a presence of clinical and/or laboratory signs of a systemic inflammatory response. Given that clinical signs of sepsis are non-specific and the sensitivity of blood culture is low, biological indicators (biomarkers) of infection are essential for the diagnosis and rational therapy of NS. In this comprehensive paper authors present the current possibilities of determining biomarkers in the diagnosis of NS. Commonly used biomarkers are changes in leukocyte and neutrophil counts, C-reactive protein, procalcitonin and interleukin-6. However, sensitivity and specificity of these standard markers are relatively low in the first hours after birth. Biomarkers of NS that are under intensive reasearch are acute-phase proteins, cytokines, leukocyte surface antigens and their soluble forms. Recent studies present the possibility of diagnosing infection by detecting extracellular vesicles (apoptotic bodies, microparticles, exosomes), which are released by cells after exposure to various stress signals, including infection. The aim of the comprehensive paper is to evaluate the standard biomarkers of NS and presentation of new biomarkers that have the potential to refine the diagnosis and therapy of NS. [ABSTRACT FROM AUTHOR]

BACKGROUND: Osteomyelitis remains a challenge for clinical orthopedic surgeons to address until now, and the development of ideal models of osteomyelitis was very important for the evaluation of new treatments. OBJECTIVE: To stably and effectively establish a rabbit tibia model of osteomyelitis, suitable for different experimental requirements. METHODS: A total of 25 New Zealand white rabbits were randomly divided into three animal model groups: pore group (n=10), macropore group (n=10) and sham operation group (n=5). In the pore group, a 1 mm drill was used to drill holes in the tibia and the 100 μL Staphylococcus aureus (2×106 cfu) was injected. In the macropore group, the same method was used but the drill holes were 5 mm. The sham operation group was cut and sutured without drilling or injecting bacteria. The general state, body temperature, X-ray, CT, histopathological observation, serum C-reactive protein and procalcitonin mass concentration were measured within 1 month after surgery. RESULTS AND CONCLUSION: Compared with the sham operation group, the body temperature and serum C-reactive protein mass concentration of rabbits in the pore group and the macropore group increased in varying degrees. Molybdenum target X-ray film and CT examination: The imaging manifestations of the pore group were whole marrow cavity infection, while the macropore group was local bone defect infection. It is suggested that in the preparation of rabbit models of tibial osteomyelitis, the size of the borehole may lead to different consequences of tibial infection. The 5 mm borehole model may be suitable for the study of the efficacy of local anti-infection materials, and the 1 mm borehole model may be suitable for the evaluation of the efficacy of systemic antibiotic drug treatment of osteomyelitis. [ABSTRACT FROM AUTHOR]

Background/Aim: Dehiscence of the colorectal anastomosis is one of the most serious complications in digestive surgery that is still present in a large percentage today, which significantly increases the cost of treatment and can lead to death. Due to all the above, early detection of anastomotic dehiscence is very important, as well as the decision on surgical treatment. Procalcitonin (PCT) is thought to be an important marker of inflammation and sepsis. Aim of this paper was to confirm PCT as a marker of great sensitivity in early diagnosis of anastomotic leakage. Methods: The study included patients who underwent surgery for colorectal cancer in the period from 2016 to 2020. Patients were operated according to an elective protocol and with an open surgical approach. In patients, PCT values were measured on the 2nd and 4th postoperative day (POD) to determine the association between elevated PCT values and the onset of dehiscence of the colorectal anastomosis. Results: A study was conducted in 118 patients in whom a stapler colorectal anastomosis was created. Colorectal anastomosis dehiscence occurred in 10 patients. In 4 patients with dehiscence, no re-surgical intervention was required, but they were taken care of by conservative methods. Repeated surgery was performed in 6 patients. In all patients with dehiscence, there was a multiple increase in the value of PCT above normal. Conclusion: PCT has high sensitivity and specificity (85 and 74 % respectively) as a marker in dehiscence of colorectal anastomosis. In this study it was found that PCT values were significantly correlated with the dehiscence of anastomosis 2nd POD and especially 4th POD. [ABSTRACT FROM AUTHOR]

Selpercatinib, a RET kinase inhibitor, is an effective treatment for patients with medullary thyroid cancer with RET mutations. In this paper, we present the case of a 62-year-old man with ectopic Cushing's syndrome due to medullary thyroid cancer who received treatment with selpercatinib. Six months later, all the cushingoid features had resolved, and s-calcitonin had decreased from 580 pmol/L to 3.5 pmol/L (normal < 3). After further 6 months, s-calcitonin had normalized (1.5 pmol/L), and radiological evaluation showed a profound tumour volume reduction. We are aware of two other cases where treatment with selpercatinib has also been successful. Thus, selpercatinib may be a promising treatment alternative in patients with ectopic Cushing's syndrome due to medullary thyroid cancer, especially when other treatment options are ineffective or not tolerated. [ABSTRACT FROM AUTHOR]

Peptide drugs through nasal mucous membrane, such as insulin and calcitonin have been widely used in the medical field. There are always two sides to a coin. One side, intranasal drug delivery can imitate the secretion pattern in human body, having advantages of physiological structure and convenient use. Another side, the low permeability of nasal mucosa, protease environment and clearance effect of nasal cilia hinder the intranasal absorption of peptide drugs. Researchers have taken multiple means to achieve faster therapeutic concentration, lower management dose, and fewer side effects for better nasal preparations. To improve the peptide drugs absorption, various strategies had been explored via the nasal mucosa route. In this paper, we reviewed the achievements of 18 peptide drugs in the past decade about the perspectives of the efficacy, mechanism of enhancing intranasal absorption and safety. The most studies were insulin and calcitonin. As a result, absorption enhancers, nanoparticles (NPs) and bio-adhesive system are the most widely used. Among them, chitosan (CS), cell penetrating peptides (CPPs), tight junction modulators (TJMs), soft NPs and gel/hydrogel are the most promising strategies. Moreover, two or three strategies can be combined to prepare drug vectors. In addition, spray freeze dried (SFD), self-emulsifying nano-system (SEN), and intelligent glucose reaction drug delivery system are new research directions in the future. [ABSTRACT FROM AUTHOR]

Several reports have determined that changes in white blood cell counts and inflammatory biomarkers are related to disease outcome of coronavirus disease 2019 (COVID-19) and they can be utilized as prognostic biomarkers. For introducing a factor as a diagnostic/prognostic biomarker, diagnostic test accuracy (DTA) systematic review and meta-analysis are recommended. For the first time, we aimed to determine the accuracies of white blood cell counts and inflammatory biomarkers for prognosis of COVID-19 patient’s outcome by a DTA meta-analysis. Until August 24, 2020, we searched Web of Sciences, Scopus, and MEDLINE/PubMed databases to achieve related papers. Summary points and lines of included studies were calculated from 2×2 tables by bivariate/hierarchical models. Critical condition and mortality were considered as outcomes. A total of 13387 patients from 28 studies were included in this study. Six biomarkers containing leukocytosis, neutrophilia, lymphopenia, increased level of C-reactive protein, procalcitonin (PCT), and ferritin met the inclusion criteria. Analysis of the area under the curve (AUCHSROC) indicated that the PCT was the only applicable prognostic biomarker for critical condition and mortality (AUCHSROC=0.80 for both conditions). Pooled-diagnostic odds ratios were 6.78 (95% CI, 3.65-12.61) for prognosis of critical condition and 13.21 (95% CI, 3.95-44.19) for mortality. Other biomarkers had insufficient accuracies for both conditions (AUCHSROC< 0.80). Among evaluated biomarkers, only PCT has good accuracy for the prognosis of both critical condition and mortality in COVID-19 and it can be considered as a single prognostic biomarker for poor outcomes. Also, PCT has more accuracy for the prognosis of mortality in comparison to critical conditions. [ABSTRACT FROM AUTHOR]

Objective: To determine the effectiveness and safety of erenumab in patients with chronic migraine in the real‐world setting of 3 headache centers in Australia. Methods: Patients with migraine were prescribed erenumab (70 or 140 mg) in the setting of either a product familiarization program or paid access to the medication in 3 headache centers in Australia. We obtained baseline and monthly prospective data on monthly headache days, monthly migraine days, monthly triptan use days, monthly codeine use days, Headache Impact Test‐6 scores, and adverse reactions. In this paper, we present our data at 3 and 6 months in our subgroup of patients with chronic migraine with and without medication overuse. Results: A total of 170 patients with chronic migraine were prescribed erenumab in the 3 headache centers. At 3 months, 100/170 (58.8%) had 50% or greater reduction in monthly migraine days. At 6 months, 79/170 (46.5%) had 50% or greater reduction in monthly migraine days. At 6 months, there was a mean reduction in monthly headache days of 9.2 days, a mean reduction in monthly migraine days of 10.2 days. There were few adverse events reported. Conclusion: This is the first report from 3 Australian headache centers about erenumab in the real world. Our analysis has supported erenumab as an effective and well‐tolerated migraine preventative therapy for patients with chronic migraine who have failed many preventative therapies. [ABSTRACT FROM AUTHOR]

Calcitonin was a kind of peptide hormones secreted by thyroid parafollicular cells of thyroid, which contained 32 amino acids, regulatedcalcium and phosphorus metabolism of peptide hormones. Its main physiological role is that calcitonin specifically binds to calcitonin receptor (CTR) on the target cell membrane to reduce the activity of osteoclasts, reduce the number of osteoclasts, and inhibit the absorption of osteoclasts. And it has the effect of stabilizing blood calcium.This paper reviewed the chemical structure of calcitonin, the synthesis and secretion of calcitonin, the physiological effects of calcitonin on osteoclasts, osteoblasts and blood calcium, the clinical significance of experimental research on calcitonin, the experimental research progress of calcitonin, the clinical application of calcitonin and the sharing of research results. Calcitonin has important application value in the treatment of clinical osteoporosis, osteoporotic fractures, and deformable osteitis. [ABSTRACT FROM AUTHOR]

Simplifying the procedure of immunoassay is still a challenge due to problems such as multiple washing processes, complicated chemical modification and expensive cost. In this study, we developed a portable centrifugal microchip fluorescence immunoassay for washing-free, rapid, quantitative and point-of-care (POC) detection of protein. The designed microchip was fabricated by polycarbonate and assembled by double-sided adhesive tape using injecting molding with high scalability and low cost. The centrifugal strategy is capable of washing-out the bio-fluid and improving signal-to-noise ratio. Matrix nano-spotting method was employed to facilitate satisfactory immunological binding sites with the advantage of high capture efficiency and reproducibility. The proposed approach was capable of sensitively detecting procalcitonin (PCT) with a wide dynamic ranging from 0.10 ng/mL to 70.00 ng/mL within 10 min. Furthermore, this novel integrated diagnostic tool was successfully applied to detect PCT in 101 clinical samples with good consistency with Roche's method, indicating its attractive practical application capability. With favorable simplicity, rapidity, low cost and excellent analytical performance, our method holds great promise for POC diagnostics of proteins. Image 1 • A microfluidic fluorescence immunoassay was developed for point-of-care (POC) detection of protein. • The simplified and low-cost immunoassay only needs 10 min with a detection limit of 0.05 ng/mL. • The method was applied to detect procalcitonin (PCT) in 101 clinical samples with good consistency with Roche's method. [ABSTRACT FROM AUTHOR]

The bone metabolism biochemical markers included calcium and phosphorus metabolism indicators, bone formation markers,bone resorption markers, hormone and cytokine. The bone metabolism biochemical markers were derived from the bone, cartilage, soft tissue, skin, liver, kidney, small intestine, blood, endocrine glands, and so on. They were enzymes and hormones secreted by osteoblasts or osteoclasts, and the product or non-collagen proteins of metabolic bone collagen matrix. The bone metabolism biochemical markers could reflect the state of bone turnover promptly, with high sensitivity and specificity, it had been used in osteoporosis diagnosis, prediction of fracture risk, curative effect observation of drug treatment, and the differential diagnosis of metabolic bone disease. And it had important clinical significance in epidemiology, pathogenesis and drug research of osteoporosis.In this paper, the "Expert consensus on clinical application of biochemical indicators of bone metabolism(2019)"was revised, A total of 41 amendments were made, the classic literature was retained, some contents were deleted, and the literature for the past three years was added. The experimental reference range of the bone metabolism index were collected and sorted. [ABSTRACT FROM AUTHOR]

[Display omitted] • The method based on the quenching of the luminescence intensity of Tb3+-HCTZ complex by PCT. • The luminescent photo probe was synthesized and characterized through absorption and emission. • The change in the luminescence intensity Tb3+-HCTZ is used for determining the PCT. • This method was practical, simple and relatively free from interference effect. A simple, selective and sensitive spectrofluorimetric method has been reported in this paper for the assessment of procalcitonin (PCT) as a biomarker in serum samples of cancer patients by using optical sensor Tb3+-hydrochlorothiazide (Tb3+-HCTZ) complex. The method based on the quenching of the luminescence intensity of Tb3+-HCTZ complex by addition of different concentrations of PCT. The optical sensor was synthesized and characterized by absorption and fluorescence measurements. The performance of the designed sensor is determined through monitoring the quenching of the fluorescence intensity at 545 nm by (PCT) after excitation at 320 nm and pH = 7 in DMSO. The calibration of this method was performed in the concentration range of (3.37–100.62 ng/mL) with a limit of detection (LOD) and quantitation limit of detection (LOQ) are (0.038 and 0.114) ng/mL, respectively and a correlation coefficient of (0.98). This method was practical, simple and relatively free from interference effect. It was successfully applied to measure PCT in samples of human serum and from this method we can assess some biomarkers of cancer related diseases in human body. [ABSTRACT FROM AUTHOR]

Background: The purpose of this paper was to analyze the general diagnostic strength and performance of in vitro diagnostics for C-reactive protein and procalcitonin based on the results of external quality assessment schemes (EQAs). Methods: We analyzed qualitative and quantitative data on both markers collected by the Society for Promotion Quality Assurance in Medical Laboratories (INSTAND e.V.) from 20 EQAs. The C-reactive protein evaluation was method-specific and the procalcitonin evaluation manufacturer-specific (pseudonymized). Coefficients of variation were determined in order to evaluate interlaboratory comparability and the performance of individual laboratories during the analyzed period was examined. Results: Overall most of our participants were able to correctly distinguish the positive from the negative samples, but we occasionally observed also false-positive results for the immunological detection of C-reactive protein. For the semi-quantitative results of C-reactive protein we observed an overall median difference below 5% except for dry chemistry methods (≤ 21%). For procalcitonin two manufacturer collectives showed a good comparability, while one manufacturer detected up to 42% higher results. The coefficients of variation are promising for both analytes even though they surpass the manufacturer’s indication for some collectives. The performance of individual laboratories during the analyzed period was more stable for C-reactive protein than for procalcitonin. Conclusion: In-vitro diagnostic testing for C-reactive protein and procalcitonin showed promising results in our EQAs but still further improvements are needed. We recommend stepping up research on reference measurement methods for both parameters to possibly enhancing the accuracy and diagnostic strength of such assays. [ABSTRACT FROM AUTHOR]

A central giant cell lesion (CGCL) is a reactive lesion that causes destruction of bone and soft tissues and has a high recurrence rate. Only 16 percent of CGCLs are observed in children. Treatment is determined by the aggressiveness and size of the lesion and it usually involves curettage or resection. Alternative treatments, such as nasal calcitonin and intralesional corticosteroid injections, are also used. The purposes of this paper are: (1) to report the case of a nine-year-old patient who presented with a CGCL; (2) to describe its pharmacological management; and (3) to review the literature about the clinical, radiographic, and histological features of CGCL. [ABSTRACT FROM AUTHOR]

Although these two forms of thyroid cancer share certain similarity in the selection of multi-target tyrosine kinase inhibitors (TKIs), the pathogenesis followed by treatment varies. Dear editor, We read with great interest the paper by Liu et al. entitled "Tyrosine kinase inhibitors for advanced or metastatic thyroid cancer: a meta-analysis of randomized controlled trials"[1]. [Extracted from the article]

Generally, calcitonin (CT) values below the upper reference limit rule-out medullary thyroid carcinoma (MTC) with very high accuracy. However, sparse cases of serum-calcitonin-negative MTC (CT-NEG-MTC) have been reported. Here we reviewed CT-NEG-MTC reported in literature, discussed the potential causes and proposed a practical laboratory and clinical approach. A comprehensive literature search was conducted by using the terms "medullary thyroid carcinoma" AND "non-secreting calcitonin" OR "undetectable calcitonin". The search was updated until December 2014. Original articles that described CTNEG- MTC were eligible for inclusion. Only MTC cases with preoperative CT below the upper reference limit were included in the present review. Eleven papers with 18 CTNEG- MTC cases (age 50 years, size 26 mm) were retrieved. Four patients with poorly differentiated MTC died within 3 years. Different CT assays were employed and different reference values were adopted. Preoperative serum CT values were below the institution cut-off levels in all cases, and undetectable in four patients. In some papers negative CT results were confirmed by additional tests. Further laboratory investigations were performed in some of the included studies. In patients with well founded suspicious of MTC and within the reference limits/undetectable CT other laboratory investigations [carcinoembryonic antigen (CEA), procalcitonin, CT stimulation, CT in washout of nodule's aspiration] have to be performed. Surgical approach to CT-NEG-MTC does not differ from those secreting CT. Postoperative follow-up of these rare cases should include periodical imaging and measurement of all potential markers. Patients with poorly differentiated MTC are at higher risk of disease-related death, and require more aggressive follow-up strategy. [ABSTRACT FROM AUTHOR]

Background: Calcitonin measurement is pivotal in the management of medullary thyroid carcinoma (MTC), but several pitfalls can affect its reliability. Other potential markers have been proposed, and procalcitonin (ProCT) has been reported as promising. The present study was undertaken to summarize the published data and provide more robust estimates on the reliability of ProCT as marker in the management of patients with MTC. Methods: The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines. The sources comprised studies published through May 2018. Original articles that reported series of MTC patients undergone ProCT during postoperative follow-up were searched. A random-effects model was used for statistical pooling of the data. The I2 index was used to quantify the consistency among the studies. The Egger test evaluated the possible presence of significant publication bias. Quality assessment of the studies was performed according to Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Results: According to inclusion and exclusion criteria five papers, reporting 296 MTC patients undergone ProCT evaluation, were finally selected. The number of MTC with recurrence was 140. The pooled sensitivity of ProCT in detecting recurrence was 96% (95% confidence interval [CI], 92% to 99%), with neither heterogeneity (I2=0%) nor publication bias (Egger test, 3.16; P=0.99). The pooled specificity was 96% (95% CI, 87% to 100%) with mild heterogeneity (I2=66.6%), while Egger test was not calculable. Conclusion: The present meta-analysis provides evidence that ProCT is reliable to manage MTC patients during their postoperative follow-up. [ABSTRACT FROM AUTHOR]

Background Point-of-care testing has been developed to provide rapid test results. Most published studies focus on analytical performance, neglecting its impact on patient outcomes. Objective To review the analytical performance and accuracy of point-of-care testing specifically planned for immunoassay and to evaluate the impact of faster results on patient management. Methods A search of electronic databases for studies reporting immunoassay results obtained in both point-of-care testing and central laboratory scenarios was performed. Data were extracted concerning the study details, and the methodological quality was assessed. The analytical characteristics and diagnostic accuracy of six points-of-care testing: troponin, procalcitonin, parathyroid hormone, brain natriuretic peptide, C-reactive protein and neutrophil gelatinase-associated lipocalin were evaluated. Results A total of 116 scientific papers were analysed. Studies measuring procalcitonin, parathyroid hormone and neutrophil gelatinase-associated lipocalin reported a limited impact on diagnostic decisions. Seven studies measuring C-reactive protein claimed a significant reduction of antibiotic prescription. Several authors evaluated brain natriuretic peptide or troponin reporting faster decision-making without any improvement in clinical outcome. Forty-four per cent of studies reported analytical data, showing satisfactory correlations between results obtained through point-of-care testing and central laboratory setting. Half of studies defined the diagnostic accuracy of point-of-care testing as acceptable for troponin (median sensitivity and specificity: 74% and 94%, respectively), brain natriuretic peptide (median sensitivity and specificity: 82% and 88%, respectively) and C-reactive protein (median sensitivity and specificity 85%). Conclusions Point-of-care testing immunoassay results seem to be reliable and accurate for troponin, brain natriuretic peptide and C-reactive protein. The satisfactory analytical performance, together with an excellent practicability, suggests that it could be a consistent tool in clinical practice, but data are lacking regarding the patient outcomes. [ABSTRACT FROM AUTHOR]

In this paper, we propose an impulsive mathematical model of bone formation and resorption accounting for the number of active osteoclastic cells, bone resorbing cells, and the number of active osteoblastic cells, bone forming cells, based on the effects of parathyroid hormone and calcitonin with impulsive estrogen supplement. The model is then analyzed theoretically in terms of its stability, permanence and oscillatory behavior. The conditions on the model parameters, for which the desirable behaviors of the solution of the system can be expected, are derived. Numerical simulations are also carried out in order to support our theoretical predictions. The results indicate that the frequency and dosage of the estrogen supplements are important since the behavior of the solution of the system depends on the frequency and dosage of the estrogen supplements. [ABSTRACT FROM AUTHOR]

During all stages of protein drug development, aggregation is one of the most often encountered problems. Covalent conjugation of poly(ethylene glycol) (PEG), also called PEGylation, to proteins has been shown to reduce aggregation of proteins. In this paper, new excipients based on PEG are presented that are able to reduce aggregation of salmon calcitonin (sCT). Several PEG polymers consisting of a hydrophobic dansyl-headgroup attached to PEGs of different molecular weights have been synthesized and characterized physicochemically. After addition of dansyl-methoxypoly(ethylene glycol) (mPEG) 2 kDa to a 40 times molar excess of sCT resulted in an increase in dansyl-fluorescence and a decrease in 90° light scatter suggesting possible interactions. The aggregation of sCT in different buffer systems in presence or absence of the different dansyl-PEGs was measured by changes in Nile red fluorescence and turbidity. Dansyl-mPEG 2 kDa in a 1:1 molar ratio to sCT strongly reduced aggregation. Reduction of sCT aggregation was also measured for the bivalent dansyl-PEG 3 kDa in a 1:1 molar ratio. Dansyl-mPEG 5 kDa deteriorated sCT aggregation. Potential cytotoxicity and hemolysis were investigated. This paper shows that dansyl-PEGs are efficacious in reducing aggregation of sCT. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:1648-1662, 2011 [ABSTRACT FROM AUTHOR]

The article presents abstracts of papers presented at the 47th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology on topics including point-of-care testing (POCT) management and the use of procalcitonin and presepsin in sepsis diagnosis.

Also, a protein-based primary calibrator has the advantage of behaving the closest to endogenous PCT, and no bias between calibrators and patient samples can be introduced during sample preparation (protein extraction, protein digestion). Dear Editor, In this issue, Tölke et al. responded to our recently published paper describing an antibody-free method for procalcitonin (PCT) quantification by isotope-dilution coupled to liquid chromatography and tandem mass spectrometry (ID-LC-MS/MS) [[1]]. [Extracted from the article]

Abstract: Although common and severe, mixed states are rarely the subject of proper clinical trials. The aim of this paper is to systematically review data published in 2013 on the pharmacological treatment of mixed states. Methods: The Medline database was searched for 2013 publications using the following keywords: ‘treatment’; ‘mixed’; ‘bipolar’. Results: Medline search returned 118 results. Manual inspection of abstracts allowed selecting six papers for further review. The first meta-analysis of the efficacy of second-generation antipsychotics in mixed episodes, published in 2013, showed the efficacy of these agents. Other papers suggested that asenapine and olanzapine were efficacious for mixed episodes, with olanzapine being equally effective in patients with or without substance abuse. Aripiprazole and ziprasidone were reported to be efficacious and safe in treating manic/mixed episodes in children and adolescents. In another trial, Calcitonin was not found to be superior to placebo in treating manic/mixed episodes. Conclusion: Although data suggest that most agents efficacious for mania may also be efficacious for mixed episodes, further studies are needed to confirm this assumption. [Copyright &y& Elsevier]

The aim of the present study was to perform a systematic review of published studies to provide a robust estimation of the use of procalcitonin (ProCT) as a diagnostic marker of medullary thyroid carcinoma (MTC), with particular focus on its specificity and negative predictive value in excluding MTC. A comprehensive computer literature search was conducted to find relevant published articles on the topic. We used a search algorithm based on a combination of the terms 'medullary,' 'thyroid,' and 'ProCT.' The search was updated until February 2015. To expand our search, references of the retrieved articles were also screened. A total of 39 articles were retrieved, of which nine original papers published from 2003 to 2014 were selected for the review. Some of these studies used ProCT in the preoperative diagnosis of MTC, whereas others measured ProCT during the follow-up of patients who had been previously treated for MTC. Other laboratory measurements were performed in some of the included studies. The results of the majority of the studies indicate that ProCT measurement appears to be a very promising and reliable serum marker for the diagnosis of MTC, and it is not inferior to calcitonin (CT). The sample handling is less laborious, and in the few CT-negative cases reviewed, the assay had even greater sensitivity. It would be worthwhile to establish cutoff levels using larger patient series, because we speculate that this assay could potentially replace CT measurement in the future. [ABSTRACT FROM AUTHOR]

This paper updates the histopathology and cytopathology of thyroid tumors and proliferations derived from the para-follicular or C cells. Beginning with an historical over view, including the recognition of medullary thyroid carcinoma as a distinct histologic entity, its relationship to the hormone, calcitonin, (which was discovered in the same decade) and to thyroid C cells, medullary carcinoma and its variants are reviewed. The molecular biology of the tumors and the associated mutations in the tumors (somatic mutations) are discussed. Additionally the genetic features (germline mutations) including familial clusters and associations with other endocrine and neuroendocrine lesions are reviewed. Screening for the tumor and its precursors is included with a review of the latest American Thyroid Association guidelines for treatment as well as timing and approach to surgery. Tabular data of specific germline mutations and their relationships to tumor virulence, and prognosis are illustrated. Precursor and early C cell lesions such as C-cell hyperplasia and micro-medullary carcinoma are discussed. Difficulties and controversies in the definition of C-cell proliferations which are neoplastic and those which are 'reactive" are reviewed. The entity of medullary microcarcinoma or medullary microcarcinoma is illustrated and the distinction between C cell nodules and microcarcinoma is defined using the latest available criteria. Finally the latest approved chemotherapeutic agents and their results in metastatic medullary thyroid carcinoma are included. [ABSTRACT FROM AUTHOR]

The oral delivery of peptides and proteins has been hampered by an array of obstacles. However, several promising novel oral delivery systems have been developed. This paper reviews the most advanced oral formulation technologies, and highlights key lessons and implications from studies undertaken to date with these oral formulations. Special interest is given to oral salmon calcitonin ( CT), glucagon-like peptide-1 ( GLP-1), insulin, PYY-(3-36), recombinant human parathyroid hormone ( rhPTH(1-31)- NH2) and PTH(1-34), by different technologies. The issues addressed include (i) interaction with water, (ii) interaction with food, (iii) diurnal variation, (iv) inter- and intra-subject variability, (v) correlation between efficacy and exposure and (vi) key deliverables of different technologies. These key lessons may aid research in the development of other oral formulations. [ABSTRACT FROM AUTHOR]

Background The early detection of medullary thyroid carcinoma ( MTC) can improve patient prognosis, because histological stage and patient age at diagnosis are highly relevant prognostic factors. As a consequence, delay in the diagnosis and/or incomplete surgical treatment should correlate with a poorer prognosis for patients. Few papers have evaluated the specific capability of fine-needle aspiration cytology ( FNAC) to detect MTC, and small series have been reported. This study conducts a meta-analysis of published data on the diagnostic performance of FNAC in MTC to provide more robust estimates. Research Design and Methods A comprehensive computer literature search of the PubMed/ MEDLINE, Embase and Scopus databases was conducted by searching for the terms 'medullary thyroid' AND 'cytology', ' FNA', ' FNAB', ' FNAC', 'fine needle' or 'fine-needle'. The search was updated until 21 March 2014, and no language restrictions were used. Results Fifteen relevant studies and 641 MTC lesions that had undergone FNAC were included. The detection rate ( DR) of FNAC in patients with MTC (diagnosed as ' MTC' or 'suspicious for MTC') on a per lesion-based analysis ranged from 12·5% to 88·2%, with a pooled estimate of 56·4% (95% CI: 52·6-60·1%). The included studies were statistically heterogeneous in their estimates of DR (I-square >50%). Egger's regression intercept for DR pooling was 0·03 (95% CI: −3·1 to 3·2, P = 0·9). The study that reported the largest MTC series had a DR of 45%. Data on immunohistochemistry for calcitonin in diagnosing MTC were inconsistent for the meta-analysis. Conclusions The presented meta-analysis demonstrates that FNAC is able to detect approximately one-half of MTC lesions. These findings suggest that other techniques may be needed in combination with FNAC to diagnose MTC and avoid false negative results. [ABSTRACT FROM AUTHOR]

Distinction between infection and febrile disease flare in patients with systemic lupus erythematosus (SLE) is fundamental but often difficult to make, because clinical presentation can be similar. A systematic review of all articles indexed in PubMed through October 2013 was performed, in order to examine the potential role of procalcitonin (PCT) for the discrimination between SLE flare and infection. Among the 12 papers identified, 5 articles reported on PCT levels in SLE patients without infection, 6 compared PCT levels between SLE patients with flare versus those with infection, and 1 analyzed PCT levels in active patients with and without bacterial infection. These data suggest the absence of correlation between PCT levels and SLE disease activity. Furthermore, PCT levels detected during disease flares are lower than those observed during bacterial infections. PCT can therefore be used accurately in the early differentiation between bacterial infection and flare in febrile SLE patients. Raised PCT levels ≥0.5 μg/L should strongly suggest bacterial infection in the context of SLE, keeping in mind the limited data available in case of hemophagocytic syndrome. Elevated PCT levels in SLE patients should always prompt a thorough search for sources of potential infection. [ABSTRACT FROM AUTHOR]

Abstract: We report about a point-of-care device for the diagnosis of sepsis. For this a useful set of diagnostic parameters must be analyzed in parallel, to combine the diagnostic benefit of each parameter. By this the severity of sepsis can be diagnosed, predictive indicators can be gathered and it is possible to differentiate between viral and bacterial sepsis being all essential information for septic patients. Therefore the protein biomarkers C-reactive protein (CRP), interleukin 6 (IL-6), procalcitonin (PCT) and neopterin (NPT) are integrated in a multiparameter on-chip immunofluorescence assay. Furthermore important criteria for point-of-care testing (POCT) such as low testing time, small sample volume, compactness, cost efficiency, accurate fluid handling, automated operation, sensitive detection and good reproducibility are closely examined. The measurement system is based on Total Internal Reflection Fluorescence (TIRF) by use of special biochips. The system reads out microarray based multiparameter immunofluorescence assays. To characterize the device several standard curves were generated by three-fold replicates in a serum model with 4% human serum albumin and human plasma containing spiked standard analytes. PCT and IL-6 are carried out in a sandwich assay format whereas NPT and CRP are processed in a binding inhibition format. Both assay types are processed in parallel by the fluidic unit. The assay time for a single multiparameter assay is 25min. An accurate execution of the two assays formats in parallel needs several fluid handling steps like dilution, mixing, metering, separating, pre-incubating and incubating to be carried out. The protein chip is processed fully automated using 10–75μl human plasma or serum sample. An additional important demand for POCT is the accuracy and precision of the measurements. This paper shows a method how imprecision and inaccuracy can be drastically reduced by using on-chip reference assay signals to reference the sepsis parameter signals. The on-chip reference assay runs parallel to the multiparameter assay. The method is analyzed with standard curves using human plasma matrix. To investigate the performance of a new a point-of-care device, it is necessary to run the assays with clinical specimen of healthy and pathological patients. For this the IL-6 levels were first investigated by established clinical systems in two different hospitals and then compared with the new platform. It was possible to resolve the clinical relevant IL-6 levels and a required LOD in the lower pg/ml range was achieved. [Copyright &y& Elsevier]

One of the most discussed and controversial issue in the management of thyroid nodules is the need to perform a routine measurement of serum Calcitonin (Ct) in all cases. The American Thyroid Association guidelines do not recommend in favor or against this procedure since they retain that there are not enough evidences that it can determine an advantage to the health outcomes of these patients. This is not the view of many European experts who met in Lisbon in 2009 at the European Thyroid Association-Cancer Research Network meeting to discuss all the still open controversial issues on the management of medullary thyroid cancer patients. This paper is focused on the routine measurement of serum Ct in all patients with thyroid nodule(s): the evidences, the rational and the benefits of this procedure are deeply analysed following the discussion that was done in Lisbon. The conclusions reached at that time are reported in detail. [ABSTRACT FROM AUTHOR]

Charcot arthropathy is a major complication of diabetes and it poses management challenges to health care professionals. Early diagnosis and timely intervention are essential for improved outlook of these patients. Casting therapy has been accepted as the mainstay treatment of the acute Charcot foot, although there are still controversies regarding its duration, the choice of removable and non-removable device and weight-bearing casts vs. non-weight-bearing casts. Two groups of antiresorptive therapies have been evaluated in the treatment of the acute Charcot foot, bisphosphonates (intravenous and oral) and calcitonin. These therapies have clearly shown a reduction of bone turnover, although, they have not shown a significant effect on temperature reduction. Current evidence to support their use is weak. An anabolic agent to speed up clinical resolution and fracture healing may be helpful and a clinical trial to evaluate the possible benefit of 1-84 recombinant human parathyroid hormone on fracture healing in the acute Charcot foot is in progress. This paper summarises the current approach to medical management of acute Charcot arthropathy with specific emphasis on casting and pharmacological therapy. Emerging new studies of the pathogenesis of this condition are also discussed. [ABSTRACT FROM AUTHOR]

The rationale to target bone for treating osteoarthritis (OA) relies on the known cross-talk between subchondral bone and cartilage and the demonstration that subchondral bone resorption occurs at an early stage in the development of OA. Therefore, the possible OA disease-modifying effects of bone antiresorptive agents are of interest. This paper aims to review the published data on the effect of estrogens, selective estrogen receptor modulators, calcitonin, strontium ranelate, and bisphosphonates on cartilage biomarkers levels used as surrogate endpoints in clinical trials. Except for findings for tibolone, most observations indicated that these antiresorptive therapies decreased the urinary levels of CTX-II, a biomarker of type II collagen degradation. These data, which should be cautiously interpreted, suggest that these drugs might favorably affect cartilage homeostasis. [ABSTRACT FROM AUTHOR]

Protein aggregation is a major instability that can occur during all stages of protein drug production and development. Protein aggregates may compromise the safety and efficacy of the final protein formulation. In this paper, various new excipients [phenylbutylamino-, benzyl-, and cholesteryl-polyethylene glycols (PEGs)] and their use for the reduction of aggregation of salmon calcitonin (sCT) and hen egg-white lysozyme (HEWL) by noncovalent PEGylation are presented. The ability to suppress aggregation of sCT in various buffer systems at a 1:1 molar ratio was assessed by following changes in protein conformation and aggregation state over time. The results are compared with that of dansyl- and l-tryptophan (Trp)-PEGs described in earlier publications. Furthermore, the influence of the different PEG-based excipients on the aggregation of HEWL was measured. HEWL aggregation was completely suppressed in the presence of cholesteryl-PEGs (2 and 5 kDa), whereas deterioration was observed using benzyl-methoxy polyethylene glycols (mPEGs; 2 and 5 kDa). Phenylbutylamino- and Trp-mPEG (2 kDa), as well as dansyl-PEGs of different molecular weight prolonged the lag phase of aggregation and reduced the aggregation velocity of HEWL. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:1995-2008, 2012 [ABSTRACT FROM AUTHOR]

The accuracy of fine needle aspiration cytology (FNAC) is low in medullary thyroid carcinomas (MTC). Recently, a few papers analyzed the measurement of calcitonin (Ct) in washout of the needle after aspiration (WO-Ct) suggesting that this approach may be useful in patients with high serum Ct. Here we reported, for the first time in our best knowledge, 3 patients with multinodular goiter, moderately elevated serum Ct, high value of WO-Ct, and medullary outcome. These findings suggest that in presence of high serum Ct, FNAC should be performed in all nodules, and it should be combined with WO-Ct in all cases. [ABSTRACT FROM AUTHOR]

Purpose. Measurement of serum calcitonin is important in the followup of patients with medullary thyroid carcinoma (MTC) and reliably reflects the presence of the disease. This is the largest study so far in bibliography investigating the diagnostic accuracy of combined [18F]FDG-PET/CT in patients with MTC and elevated calcitonin levels. Methods. Between February 2007 and February 2011, 59 [18F]FDG-PET/CT were performed on 51 patients with MTC and elevated calcitonin levels for localization of recurrent disease. Conventional morphologic imaging methods were negative or showed equivocal findings. Results. Among the 59 [18F]FDG-PET/CT, 29 were positive (26 had true-positive and 3 false-positive findings) and 30 negative. The overall per-patient sensitivity of [18F]FDG-PET/CT was 44.1%. Using as cut-off point the calcitonin value of 1000 pg/ml, in patients with calcitonin exceeding this value, sensitivity raised to 86.7%. The overall sensitivity of [18F]FDG-PET/CT was lower (23%) in patients with MEN IIA syndrome. Conclusion. The findings of this paper show that [18F]FDG-PET/CT is valuable for the detection of recurrence in patients with highly elevated calcitonin levels, > 1000 pg/mL, but in patients with lower calcitonin levels, its contribution is questionable. Also, there is evidence that the sensitivity of [18F]FDG-PET/CT is lower in patients with MTC as part of MEN IIA syndrome. [ABSTRACT FROM AUTHOR]

Abstract: Protein aggregation, which is triggered by various factors, is still one of the most prevalent problems encountered during all stages of protein formulation development. In this publication, we present novel excipients, tryptophan-mPEGs (Trp-mPEGs) of 2 and 5kDa molecular weight and suggest their use in protein formulation. The synthesis and physico-chemical characterization of the excipients are described. Possible cytotoxic and hemolytic activities of the Trp-mPEGs were examined. Turbidity, 90° static light scatter, intrinsic fluorescence, fluorescence after staining the samples with Nile Red and fluorescence microscopy were used to study the inhibitory effect of the Trp-mPEGs on the aggregation of salmon calcitonin (sCT) in different buffer systems and at various molar ratios. Aggregation of sCT was reduced significantly with increasing concentrations of Trp-mPEG 2kDa. A 10-fold molar excess of Trp-mPEG 2kDa suppressed almost completely the aggregation of sCT in 10mM sodium citrate buffer (pH 6) for up to 70h. Trp-mPEG 5kDa also reduced the aggregation of sCT, though less pronounced than Trp-mPEG 2kDa. Low aggregation of sCT was measured after approximately 10days in 10mM sodium citrate buffer, pH 5, with a 10-fold molar excess of Trp-mPEG 2kDa. This paper shows that Trp-mPEGs are potent excipients in reducing the aggregation of sCT. Trp-mPEGs are superior to dansyl-PEGs concerning the stabilization of sCT in a harsh environment, wherein sCT is prone to aggregation. Trp-mPEGs might therefore also be used for stabilization of other biopharmaceuticals prone to aggregation. [Copyright &y& Elsevier]

Please cite this paper as: Ahn et al. (2011) Role of procalcitonin and C-reactive protein in differentiation of mixed bacterial infection from 2009 H1N1 viral pneumonia. Influenza and Other Respiratory Viruses 5(6), 398-403. Background Mixed bacterial infection is an important contributor to morbidity and mortality during influenza pandemics. We evaluated procalcitonin (PCT) and C-reactive protein (CRP) in differentiating pneumonia caused by mixed bacterial and 2009 H1N1 influenza infection from 2009 H1N1 influenza infection alone. Methods Data were collected retrospectively over a 7-month period during the 2009 H1N1 influenza pandemic. Patients visiting emergency department and diagnosed as community-acquired pneumonia caused by 2009 H1N1 infection were included ( n = 60). Results Mixed bacterial and viral infection pneumonia ( n = 16) had significantly higher PCT and CRP levels than pneumonia caused by 2009 H1N1 influenza alone ( n = 44, P = 0·019, 0·022 respectively). The sensitivity and specificity for detection of mixed bacterial infection pneumonia was 56% and 84% for PCT > 1·5 ng/ml, and 69% and 63% for CRP > 10 mg/dl. Using PCT and CRP in combination, the sensitivity and specificity were 50% and 93%, respectively. Conclusion Procalcitonin and CRP alone and their combination had a moderate ability to detect pneumonia of mixed bacterial infection during the 2009 H1N1 pandemic. Considering high specificity, combination of low CRP and PCT result may suggest that pneumonia is unlikely to be caused by mixed bacterial infection. [ABSTRACT FROM AUTHOR]

Medullary thyroid carcinoma accounts for 4% of thyroid carcinoma and originates from parafollicular cells, secreting calcitonin and carcinoembryonic antigen (CEA). Conventional radiographic modalities such as Computerized Tomography (CT), Magnetic Resonance Imaging (MRI), and Ultrasonography (U/S), are used for detecting recurrences following total thyroidectomy. However, metastatic disease frequently escapes detection by the above modalities, even when its presence is suggested by persistently elevated serum calcitonin levels. In this paper, we report a case of medullary thyroid carcinoma in a 40 year-old woman who had whole body octreotide scintigraphy to evaluate and detect the origin of calcitonin and CEA secretion. [ABSTRACT FROM AUTHOR]