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Background. Infection in acute pancreatitis will worsen the disease prognosis. The aim of our study was to analyze the role of procalcitonin as a prognostic biomarker for infections and clinical severity. Method. A prospective single-cohort observational study of patients diagnosed of acute pancreatitis (n = 152) was designed. PCT determination was tested on admission (first 72 hours). Infections (biliary, extrapancreatic and infected pancreatic necrosis), need for antibiotics, need for urgent ERCP and severity scores for acute pancreatitis was assessed. ROC curves were designed and the area under the curve was calculated. Logistic regression for multivariate analysis was performed to evaluate the association between procalcitonin optimal cut-off level and major complications. Results. PCT > 0.68mg/dL had higher incidence of global infection, acute cholangitis, bacteraemia, infected pancreatic necrosis, use of antibiotics in general, and need for urgent ERCP. In the multivariate regressions analysis, PCT > 0.68mg/dL at admission demonstrated to be a strong risk factor for complications in acute pancreatitis. Discussion. PCT levels can be used as a reliable laboratory test to predict infections and the clinical severity of acute pancreatitis. High levels of PCT predict antibiotics prescription as well as the need for urgent ERCP in patients with concomitant clinically severe cholangitis.

Мета: виявити супутні зміни параметрів нейроендокринно-імунного комплексу і мікробіоценозу товстого кишечника, що супроводжують діуретичний ефект бальнеотерапії на курорті Трускавець. Результати. У спостереженні за 22 чоловіками, хворими на хронічний пієлонефрит в поєднанні з холециститом, виявлено, що 10–12-денний курс бальнеотерапії (пиття біоактивної води «Нафтуся», аплікації озокериту, мінеральні ванни) збільшує добовий діурез на 28 % (p < 0,001). Це поєднується із збільшенням екскреції фосфатів на 103 % (p < 0,001), кальцію — на 76 % (p < 0,01), креатиніну — на 32 % (p < 0,02), сечової кислоти — на 29 % (p < 0,001), сечовини — на 21 % (p < 0,01), магнію — на 19 % (p = 0,05) при відсутності суттєвих змін екскреції хлориду, калію і натрію. При цьому знижується рівень у плазмі креатиніну на 14 % (p < 0,001) і сечовини на 11 % (p < 0,01). Лейкоцитурія зменшується на 16 % (p < 0,02). Екскреторно-депураційний і протизапальний ефекти бальнеотерапії супроводжуються відчутною модуляцією параметрів нейроендокринно-імунного комплексу. Зокрема, зменшується як абсолютна, так і відносна щільність спектральної потужності (PSD) δ- і α-ритмів (p < 0,05–0,01), і підвищується відносна PSD β-ритму (p < 0,05–0,02) базальної електроенцефалограми. Разом з тим знижуються індекси варіабельності ритму серця: (VLF + LF)/HF — на 34 % (p < 0,05) і LF/HF — на 32 % (p > 0,05) за рахунок підвищення PSD HF більшою мірою, ніж LF. Базальний рівень у плазмі кортизолу знижується на 20 % (p < 0,01), тестостерону — на 15 % (p = 0,01), натомість підвищується рівень трийодтироніну — на 4 % (p < 0,05) і особливо кальцитонінової активності — на 92 % (p < 0,001), розрахованої за екскрецією з сечею фосфатів і кальцію. Лейкоцитарний індекс адаптації Поповича зростає на 46 % (p < 0,02). Стосовно параметрів фагоцитарної функції нейтрофілів констатовано підвищення зниженого індексу кілінгу ними Staphylococcus aureus на 19 % (p < 0,001) і Escherichia coli на 18 % (p < 0,01) за відсутності змін початково нормальних фагоцитарних індексів. Мікробне число стосовно Staphylococcus aureus залишається нормальним, а початково підвищена на 15 % інтенсивність фагоцитозу Escherichia coli знижується на 8 % (p < 0,05). Стосовно параметрів імунітету виявлено значуще підвищення рівня в крові лише CD16+ лімфоцитів (+17 %, p < 0,01) при відсутності змін рівнів CD3+CD4+ і CD3+CD8+ Т-лімфоцитів і CD19+ В-лімфоцитів. Не змінюються суттєво ні рівні в сироватці Ig G, M, A, ні циркулюючих імунних комплексів. Імунотропний ефект супроводжується редукцією проявів дисбактеріозу: вміст Bifidumbacter зростає на 19 % (p < 0,02), Lactobacter — на 20 % (p < 0,05), а Escherichia coli — на 48 % (p < 0,01), при цьому доля штамів з ослабленими ферментативними властивостями зменшується на 47 % (p < 0,001), з гемолітичними властивостями — на 77 % (p < 0,01). Висновок. Бальнеотерапія на курорті Трускавець чинить відчутний діуретичний ефект, що поєднується з активацією екскреторної і депураційної функцій нирок та бактерицидної функції нейтрофілів, редукцією дисбактеріозу товстого кишечника, лейкоцитурії і нейроендокринних проявів стресу.

Background and purpose: New prophylactics for migraine, targeting calcitonin gene-related peptide (CGRP), have recently emerged. Real-world data are important for a comprehensive understanding of treatment response. We assessed the consistency of response to erenumab, a monoclonal CGRP receptor antibody, in a real-world setting, in order to determine which patients may be considered responders in clinical practice. Methods: All erenumab-treated patients (n = 100) completed a time-locked daily electronic diary, and an automated algorithm was used to monitor treatment response. Monthly migraine days (MMD), non-migrainous headache days, days of acute medication use (MAMD), well-being and coping with pain were assessed for a 6-month period. The primary outcome was reduction in MMD compared to baseline. Results: The numbers of MMD and MAMD decreased in all months, in both episodic and chronic migraine patients, compared to baseline (p

Calcium plays a key role in skeletal mineralization and several intracellular and extracellular homeostatic networks. It is an essential element that is only available to the body through dietary sources. Daily acquisition of calcium depends, in addition to the actual intake, on the hormonally regulated state of calcium homeostasis through three main mechanisms: bone turnover, intestinal absorption, and renal reabsorption. These procedures are regulated by a group of interacting circulating hormones and their key receptors. This includes parathyroid hormone (PTH), PTH-related peptide, 1,25-dihydroxyvitamin D, calcitonin, fibroblast growth factor 23, the prevailing calcium concentration itself, the calcium-sensing receptor, as well as local processes in the bones, gut, and kidneys.

Objectives We established reference intervals for serum concentrations of hormones from healthy pediatric subjects and investigated their associations with gender, body mass index (BMI), puberty and oral contraceptives (oC). Methods We calculated reference intervals for the thyroid parameters thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and calcitonin (Ct); the bone markers osteocalcin, procolagen type 1 N-propeptide, and carboxy-terminal cross-linking telopeptide of type 1 collagen; the calciotropic hormones 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone and the steroids cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, estradiol, dehydroepiandrosterone sulfate and aldosterone. Up to 10,002 blood serum samples from 3,229 healthy children and adolescents (age interval: 3 months to 20 years) were measured. To investigate the associations between the hormone levels with age, sex, weight status and the role of puberty-based changes, the measurement and BMI values were transformed into standard deviation scores. Results Most of the hormones depended on age- and gender. Puberty was linked to a, in part, temporary decrease in TSH, FT3 (for females), FT4, Ct, cortisol (for girls) and aldosterone (for boys) and peak in the bone marker and calciotropic hormones (excluding 25(OH)D) and nearly all remaining steroids. BMI had effects on the thyroid, bone, and calciotropic parameters, whereas oC led to increased cortisol, suppressed progesterone and estradiol values. Conclusions Age- and gender-specific reference intervals are essential for the interpretation of pediatric patients’ hormone measurements. Influencing factors as puberty, BMI, or oC should be taken into consideration for diagnosis and treatment monitoring.

Background Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide can provoke cluster headache attacks in up to half of cluster headache patients in their active phase. At present, it is unknown whether provoked attacks are mediated via calcitonin gene-related peptide or mast cell activation. Methods All enrolled patients with cluster headache were randomly allocated to receive a continuous infusion of either PACAP38 (10 pmol/kg/min) or vasoactive intestinal polypeptide (8 pmol/kg/min) over 20 min. We collected clinical data and measured plasma levels of calcitonin gene-related peptide and markers of mast cell activation (tryptase and histamine) at fixed time points: at baseline (T0), at the end of the infusion (T20), 10 min after the infusion (T30), and 70 min after the infusion (T90). Results Blood was collected from episodic cluster headache patients in active phase (n = 14), episodic cluster headache patients in remission (n = 15), and chronic cluster headache patients (n = 15). At baseline, plasma levels of calcitonin gene-related peptide, tryptase, and histamine were not different among the three study groups. Plasma levels of calcitonin gene-related peptide ( p = 0.7074), tryptase ( p = 0.6673), or histamine ( p = 0.4792) remained unchanged during provoked attacks compared to attack-free patients. Conclusion Cluster headache attacks provoked by either PACAP38 or vasoactive intestinal polypeptide were not accompanied by alterations of plasma calcitonin gene-related peptide, tryptase or histamine. The provoked attacks may not be mediated by calcitonin gene-related peptide or mast cell activation. Trial Registration: The study is registered at ClinicalTrials.gov (NCT03814226).

We investigated the analgesic effects of tramadol and the arthritic changes following tramadol administration in the rat hip osteoarthritis (OA) model using mono-iodoacetate (MIA). The right hip joints of male Sprague-Dawley rats (n = 5 rats/group) in the Sham group were injected with 25 μl of sterile saline and 1% of fluorogold (FG) retrograde neurotracer. In the MIA + Vehicle and MIA + Tramadol groups, FG and 25 μl of sterile saline with 0.5 mg of MIA were injected into the right hip joint. The MIA + Vehicle and MIA + Tramadol groups were administered daily for 4 weeks, either sterile saline (10 mg/kg, intraperitoneal [i.p.]) or tramadol (10 mg/kg, i.p.). We assessed hyperalgesia every week after MIA administration. Histopathological changes and immunoreactive neurons for calcitonin gene-related peptide (CGRP) in dorsal root ganglia (DRG) were evaluated after 4 weeks of treatment. MIA injection into the hip joint led to mechanical hyperalgesia (p < 0.01), which was significantly reduced by tramadol administration (p < 0.01). Furthermore, daily i.p injection of tramadol significantly suppressed CGRP expression in DRG (p < 0.0001). MIA + Vehicle and MIA + Tramadol groups showed significant cartilage reduction and degeneration compared to the Sham group (p < 0.0001). Interestingly, OA changes significantly progressed in the MIA + Tramadol group compared to the MIA + Vehicle group (p < 0.0001).

Key Points Expression of CALCRL is an independent prognostic factor and a potential therapeutic target in pediatric AML.CALCRL is linked with relapse risk in p ediatric AML, which supports its role as a master regulator of relapse-initiating drug-tolerant cells., Visual Abstract, We have recently identified the G protein-coupled neuropeptide receptor calcitonin receptor‐like (CALCRL) as an independent prognostic biomarker and a therapeutic target in more than 1500 adult patients with acute myeloid leukemia (AML). Here, we confirmed CALCRL expression as a prognostic factor in a cohort of 284 pediatric patients with AML. High CALCRL expression was independently associated with event-free survival (hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.36-2.57; P = .0001), overall survival (HR, 1.55; 95% CI, 1.06-2.27; P = .025), and cumulative incidence of relapse (HR, 2.10; 95% CI, 1.49-1.96; P < .0001) when adjusting for age, white blood cell count, and genetic risk. Despite its association with leukemia stem cell signatures, CALCRL expression remained associated with all end points when compared with the 17-gene leukemic stem cell score. The strong association of CALCRL expression with the risk of relapse also in the pediatric population supports its role as novel age-independent master regulator of relapse-initiating, drug-tolerant AML cells in humans.

Background Erenumab, the first-in-class fully human monoclonal antibody targeting the calcitonin gene-related peptide receptor, was shown to be efficacious and safe for the prophylactic treatment of migraine in adults in randomized clinical trials. Large-scale, real-world evidence in multi-centre settings is still needed to confirm these results. Erenumab patient profiles outside clinical trials and physicians’ treatment patterns, as well as data from patients treated in Germany, a severely impacted population, are not published yet. Methods TELESCOPE was a multi-centre survey gathering real-world data from 45 German headache centres between July 2019 and December 2019. The project consisted of two parts. In the first part, treating physicians shared their experiences on current erenumab treatment with regard to patient profiles, treatment patterns and treatment responses. In the second part, a retrospective chart review was conducted of 542 migraine patients treated with erenumab for at least three months. Treatment responses focused on various aspects of patients’ quality of life. Results The analysis of 542 patients’ charts revealed that three-month treatment with erenumab significantly reduced monthly headaches, migraine and acute medication days. Furthermore, headache intensity and frequency were reduced in over 75 % and accompanying aura in 35 % of patients. The clinical global impression scale revealed a general improvement in 91 % of patients. According to the treating physicians’ professional judgement, 83 % of patients responded to erenumab and 80 % were satisfied with the treatment. Physicians evaluated restricted quality of life, the number of monthly migraine days and previous, prophylactic treatments as the main components of the current patient profile for monoclonal antibody recipients. Based on the assessment of physicians, erenumab reduced migraine symptoms in 65 % and increased quality of life in more than 75 % of their patients. Conclusions TELESCOPE confirms positive treatment responses with erenumab shown in clinical trials in a real-world multi-centre setting. The results show consistently positive experiences of physicians utilizing erenumab in clinical practice and underline that therapy with this monoclonal antibody is effective in migraine patients, particular in those, who have failed several prophylactic therapies.

Objective Although perineural invasion (PNI) is well-known to be correlated with and able to predict lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC), the clinical and molecular correlation between PNI and LNM has not been elucidated, and preoperative biomarkers for LNM prediction in OSCC are urgently needed. Materials and methods The correlation between PNI and LNM was retrospectively evaluated using a cohort of 218 patients diagnosed with OSCC. Candidate neuropeptides were screened based on TCGA database and verified via immunohistochemistry and Western blot analyses. ELISA was used to detect calcitonin gene-related peptide (CGRP) in patient plasma. In vitro assays were used to explore the effects of CGRP on OSCC cells. Results OSCC patients with PNI had a higher incidence of LNM (69.86% vs. 26.2%, P n = 218). CGRP expression was upregulated in the PNI niche and in metastatic lymph nodes, and was correlated with poor overall survival of OSCC patients. Preoperative plasma CGRP levels were higher in OSCC patients (n = 70) compared to healthy donors (n = 60) (48.59 vs. 14.58 pg/ml, P P P = 0.0002). Preoperative plasma CGRP levels alone yielded an AUC value of 0.8088 to predict LNM, and CGRP levels combined with preoperative T stage reached an AUC value of 0.8590. CGRP promoted proliferation and migration abilities of OSCC cells, which could be antagonized by either pharmacological or genetic blockade of the CGRP receptor. Conclusions The neuropeptide CGRP links PNI and LNM in OSCC, and preoperative plasma CGRP levels can be used to predict LNM in OSCC.

Background Medullary thyroid carcinoma (MTC) in the context of multiple endocrine neoplasia type 2 (MEN2) is caused by mutations in the RET proto-oncogene. Therefore, in children with MEN2 and advanced MTC, the RET tyrosine kinase (TK) pathway is a target for treatment with selpercatinib, a selective RET TK inhibitor. Patients and methods A retrospective review of the clinical, genetic, biochemical (calcitonin and carcinoembryonic antigen [CEA]) and imaging data of six medically untreated children with MEN2 and recurrent and or progressive MTC. The main parameters were safety and objective treatment response to selpercatinib. Results Six children (three males and three females, aged 3–12 years), four with MEN2B and two MEN2A, are reported. All had initial total thyroidectomy and extensive neck dissections but subsequently developed recurrent and progressive disease. All experienced an improvement in clinical symptoms with a concomitant biochemical response evidenced by significant fall in serum calcitonin and CEA concentrations. The fall in serum calcitonin was evident within 2 weeks of the start of selpercatinib, and responses were ongoing at a median follow-up of 13 months (range, 11–22 months). Four children with measurable radiological disease had good volume reduction. The most common adverse effects were transient but reversible grade 1 or 2 increase in alanine aminotransferase, serum bilirubin and constipation. No child required a dose modification or had to discontinue selpercatinib because of a drug-related adverse event. Conclusion Selpercatinib has shown excellent therapeutic efficacy with minimal toxicity in children with MEN2 and progressive metastatic RET-mutated MTC.

OBJECTIVE To examine whether serum procalcitonin (PCT) is useful for differentiating acute pyelonephritis (APN) from asymptomatic bacteriuria and acute cystitis during pregnancy. METHODS A multicenter prospective observational study was conducted to compare serum white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and PCT level among pregnant women with asymptomatic bacteriuria, acute cystitis, and APN and healthy pregnant women (controls). Utility of WBC count, ESR, CRP, and PCT biomarkers for the prediction of APN during pregnancy were measured. RESULTS Area under the curve (AUC) values of PCT, CRP, ESR, and WBC count for predicting asymptomatic bacteriuria were 0.576, 0.628, 0.542, and 0.532, respectively; those for predicting acute cystitis were 0.766, 0.735, 0.681, and 0.597, respectively; and those for predicting acute pyelonephritis 0.859, 0.763, 0.711, and 0.732, respectively. Compared with the other inflammatory markers used to predict APN, PCT exhibited the highest AUC (0.859 [95% confidence interval (CI) 0.711-0.935]). A cutoff value of >0.25 ng/ml had a sensitivity of 87% and a specificity of 79%. CONCLUSION Serum PCT can be a valuable addition to existing methods of differentiating asymptomatic bacteriuria, acute cystitis, and APN during pregnancy and can facilitate the early identification of APN during pregnancy.

Since medullary thyroid carcinoma is an aggressive cancer, it is important to have an early detection based on stimulated calcitonin (CT), especially when basal-CT is slightly elevated. The objective of this work was to set specific thresholds for basal-CT- and calcium-stimulated calcitonin for prediction of thyroid malignancy in female population. The study included 2 groups: group A-women with elevated basal-CT (>9.82 pg/ml) and group B-women with normal basal-CT (control group). After calcium stimulation test precise protocol, histopathological reports of those that required surgery were correlated with both basal and stimulated calcitonin. The best basal and stimulated calcitonin cut-offs for distinguishing female patients with medullary thyroid carcinoma or C-Cell-hyperplasia from other pathologies or normal cases were: 12.9 pg/ml, respectively 285.25 pg/ml. For basal-CT above 30 pg/ml, malignancy was diagnosed in 9/9 patients (100%): 9 MTC. For stimulated calcitonin above 300 pg/ml, malignancy was diagnosed in 17/21 patients (80.95%): 12 MTC and 5 papillary thyroid carcinomas. The smallest nodule that proved to be medullary thyroid carcinoma had only 0.56/0.34/0.44 cm on ultrasound, with no other sonographic suspicious criteria. In conclusion, we have identified in Romanian female population basal and stimulated calcitonin thresholds to discriminate medullary thyroid carcinoma or C-Cell-hyperplasia from other cases. We recommend thyroid surgery in all women with stimulated calcitonin above 285 pg/ml. Further studies on larger groups are necessary to establish and confirm male and female cut-offs for early diagnosis of medullary thyroid carcinoma, and interestingly, maybe for macro-papillary thyroid carcinomas alike. The calcium administration has minimum side-effects, but continuous cardiac monitoring is required.

Background Gut microbiota disturbance is increasingly suggested to be involved in the pathogenesis of migraine but this connection remains unsubstantiated. This study aimed to investigate whether the gut microbiome influences migraine-related hyperalgesia. Methods Nitroglycerin-induced hyperalgesia was evaluated in mice with different gut microbiota statuses as follows: Specific pathogen-free mice; germ-free mice; specific pathogen-free mice treated with antibiotics to deplete the gut microbiome (ABX mice); and germ-free mice transplanted with the gut microbial profile from specific pathogen-free mice (GFC mice). Moreover, nitroglycerin-induced hyperalgesia was compared between recipient mice transplanted with gut microbiota from a patient with migraine and those that received gut microbiota from a sex- and age-matched healthy control. Results In specific pathogen-free mice, a decreased mechanical threshold in the hind paw, increased grooming time, increased c-Fos expression level and decreased calcitonin gene-related peptide expression level as well as increased tumor necrosis factor-α concentration in the trigeminal nucleus caudalis were observed after nitroglycerin administration compared with saline treatment. However, increased basal sensitivity and higher basal concentrations of TNF-α in the trigeminal nucleus caudalis were observed in germ-free and ABX mice, while no significant difference in hyperalgesia was observed between the nitroglycerin group and saline group in germ-free and ABX mice. Moreover, significant hyperalgesia was induced by nitroglycerin administration in GFC mice. The mice transplanted with the gut microbial profile from a patient with migraine had more severe nitroglycerin-induced hyperalgesia than the mice receiving microbiota from a matched healthy control. Conclusion Our findings highlight the involvement of the gut microbiome in normal mechanical pain sensation and pathogenesis of migraine.

AIM To determine whether serum procalcitonin (PCT) or C-reactive protein (CRP) can diagnose post-operative sepsis among neonates undergoing major non-cardiac surgery. METHODS In this diagnostic study, we included neonates who underwent major non-cardiac surgery and were monitored for post-operative sepsis. We excluded pre-existing septic, inflammatory or life-threatening conditions. Subjects either had 'definite' (culture-positive, n = 14), 'probable' (clinical sepsis, culture-negative, n = 25) or no sepsis (n = 31). We measured serum CRP and PCT at 48 ± 6 h, 72 ± 6 h and 96 ± 6 h post-operatively and compared 'definite or probable sepsis' with 'no sepsis'. RESULTS Median (Q1, Q3) CRP (mg/L) in 'definite or probable' sepsis group was higher than 'no sepsis' at 72 h (91.48 (57.87, 143.50) vs. 51.32 (33.0, 80.1); P = 0.009) and 96 h (87.51 (45.19, 128.22) vs. 31.00 (25.3, 45.2); P

Irritable bowel syndrome (IBS) is a brain-gut disorder characterized by abdominal pain and altered bowel habits. Although the etiology of IBS remains unclear, stress in adulthood or in early life has been shown to be a significant factor in the development of IBS symptomatology. Evidence suggests that aberrant calcitonin gene-related peptide (CGRP) signaling may be involved in afferent sensitization and visceral organ hypersensitivity. Here, we used a monoclonal anti-CGRP divalent antigen-binding fragment [F(ab′)2] antibody to test the hypothesis that inhibition of peripheral CGRP signaling reverses colonic hypersensitivity induced by either chronic adult stress or early life stress. A cohort of adult male rats was exposed to repeated water avoidance stress. Additionally, a second cohort consisting of female rats was exposed to a female-specific neonatal odor-attachment learning paradigm of unpredictable early life stress. Colonic sensitivity was then assessed in adult animals via behavioral responses to colorectal distension (CRD). To analyze spinal nociceptive signaling in response to CRD, dorsal horn extracellular signal–regulated kinase (ERK) 1/2 phosphorylation was measured via immunohistochemistry. Repeated psychologic stress in adulthood or unpredictable stress in early life induced colonic hypersensitivity and enhanced evoked ERK1/2 phosphorylation in the spinal cord after CRD in rats. These phenotypes were reversed by administration of a monoclonal anti-CGRP F(ab′)2 fragment antibody. Stress-induced changes in visceral sensitivity and spinal nociceptive signaling were reversed by inhibition of peripheral CGRP signaling, which suggests a prominent role for CGRP in central sensitization and the development of stress-induced visceral hypersensitivity. SIGNIFICANCE STATEMENT Targeting peripheral calcitonin gene-related peptide (CGRP) with a monoclonal anti-CGRP divalent antigen-binding fragment antibody reduced central sensitization and attenuated colonic hypersensitivity induced by either chronic adult stress or early life stress. CGRP-targeting antibodies are approved for migraine prevention, and the results of this study suggest that targeting CGRP may provide a novel treatment strategy for irritable bowel syndrome–related, stress-induced visceral pain.

Purpose: The influence of Hashimoto's thyroiditis (HT) on calcitonin (Ct) production is unresolved question. The aim of this study was to explore if basal Ct levels are influenced by the presence/severity of HT or correlated with clinical phenotypes of HT patients. Methods: We included 467 HT patients and 184 control participants, from Croatian Biobank of HT patients (CROHT), in this retrospective study. Calcitonin levels between HT patients and controls were compared using Mann-Whitney test. Ct levels between two subgroups of HT patients, divided by intake of levothyroxine (LT4) therapy, were additionally tested to take into account the illness severity. Spearman rank correlation test was used to analyze correlations between Ct levels and 14 relevant phenotypes. Results: We have not detected significant differences in median Ct levels between HT patients and controls (2.2 vs 2.35 pg/mL, respectively, P = 0.717) nor in-between two subgroups of HT patients (P = 0.347). We have not detected statistically significant correlations between Ct levels and clinical phenotypes, although we identified three weak nominal correlations: negative correlation of Ct with TgAb in all HT patients (r = - 0.1, P = 0.04) ; negative correlation of Ct with age in subgroup of HT patients without LT4 therapy (r = - 0.13, P = 0.04) ; positive correlation of Ct with BSA in subgroup of HT patients on LT4 therapy (r = 0.16, P = 0.042). Conclusion: Our results suggest that HT patients of all disease stages preserve Ct production as healthy individuals and there is no need for Ct measurements in the absence of a nodule. Additional confirmation and clarification of observed nominal correlations are needed due to potential clinical relevance of TgAb and age- dependent Ct decrease in HT women.

Medullary thyroid carcinoma (MTC) is a distinct type of malignant thyroid tumor in cell origin, biological behavior, and natural history. It accounts for 1.6% of all thyroid cancers and presents either sporadically or as a hereditary disease, the latter occurring as a part of multiple endocrine neoplasia (MEN) 2A and MEN2B syndromes or as a familial MTC disease with no other manifestations. The gene responsible for the hereditary form is the rearranged during transfection (RET) gene, a proto-oncogene located to human chromosome 10. Most pediatric MTC cases have been discovered after genetic testing investigations, leading to the concept of prophylactic surgery in presymptomatic patients. Therefore, the genetic status of the child, along with serum calcitonin levels and ultrasonographic findings, determine the appropriate age for prophylactic surgical intervention. Nevertheless, a diagnosis at an early stage of MTC warrants total thyroidectomy and central lymph node dissection with the addition of lateral/contralateral lymph node dissection depending on the tumor size, ultrasonographic evidence of neck disease, or calcitonin levels. Conversely, locally advanced/unresectable or metastatic MTC is primarily treated with multikinase inhibitors, while more specific RET inhibitors are being tested in clinical trials with promising results.

Background Recently, presepsin has been reported to be a useful biomarker for early diagnosis of sepsis and evaluation of prognosis in septic patients. However, few reports have evaluated its usefulness in patients with urinary tract infections (UTI). This study aimed to evaluate whether presepsin could be a valuable marker for detecting severe sepsis, and whether it could predict the therapeutic course in patients with UTI compared with markers already used: procalcitonin (PCT) and C-reactive protein (CRP). Methods From April 2014 to December 2016, a total of 50 patients with urinary tract infections admitted to Gunma university hospital were enrolled in this study. Vital signs, presepsin, PCT, CRP, white blood cell (WBC) count, causative agents of urinary-tract infections, and other data were evaluated on the enrollment, third, and fifth days. The patients were divided into two groups: with (n = 11) or without (n = 39) septic shock on the enrollment day, and with (n = 7) or without (n = 43) sepsis on the fifth day, respectively. Presepsin was evaluated as a biomarker for systemic inflammatory response syndrome (SIRS) or septic shock. Results Regarding the enrollment day, there was no significant difference of presepsin between the SIRS and non-SIRS groups (p = 0.276). The median value of presepsin (pg/mL) was significantly higher in the septic shock group (p p = 0.007). ROC curve for diagnosing septic shock indicated an area under the curve (AUC) of 0.881 for presepsin (vs. 0.690, 0.583, and 0.527 for PCT, CRP and WBC, respectively). Regarding the 5th day after admission, the median presepsin value on the enrollment day was significantly higher in the SIRS groups than in the non-SIRS groups (p = 0.006). On the other hand, PCT (≥ 2 ng/ml) on the enrollment day was an independent risk factor for SIRS. ROC curve for diagnosing sepsis on the fifth day indicated an AUC of 0.837 for PCT (vs. 0.817, 0.811, and 0.802 for presepsin, CRP, and WBC, respectively). Conclusions This study showed that presepsin may be a good marker for diagnosing septic shock based on admission data in patients with UTI.

Clinical and preclinical studies have reported that Lactobacillus gasseri BNR17, a probiotic bacterial strain isolated from human breast milk, reduces body weight and white adipose tissue volume. In order to further explore the actions of L. gasseri BNR17, we investigated the anti-menopausal effects of L. gasseri BNR17 in an ovariectomized (OVX) rat model. The serum alanine aminotransferase levels of the rats in the OVX-BNR17 group were lower than those of the rats in the OVX-vehicle only (OVX-Veh) group. Upon administration of L. gasseri BNR17 after ovariectomy, calcitonin and Serotonin 2A levels increased significantly, whereas serum osteocalcin levels showed a decreasing tendency. Compared to the rats in the OVX-Veh group, those in the OVX-BNR17 group showed lower urine deoxypyridinoline levels, lower pain sensitivity, and improved vaginal cornification. Furthermore, L. gasseri BNR17 administration increased bone mineral density in the rats with OVX-induced femoral bone loss. These results suggest that L. gasseri BNR17 administration could alleviate menopausal symptoms, indicating that this bacterium could be a good functional probiotic for managing the health of older women.

Background. Low bone mass (LBM) in the form of osteopenia (Op) and osteoporosis (OP) is one of the most pres­sing public health problems. Рostmenopausal period in women is considered the main risk factor for the development of the pathological process. Objective of the research was to assess the clinical and pathogenetic features of LBM in women with menopause. Materials and methods. 261 non-menstruating women with an average age of 48 years were observed, physiological menopause occurred in 91 % of cases, and pathological in the rest. Exclusion criteria were women with inflammatory rheumatic diseases of the joints, oncological pathology, diseases of the blood system and thyroid gland, who received glucocorticoid hormones and anticonvulsants. In 133 (51 %) women, LBM (main group) was established in the ratio Op and ОР 4 : 1; diagnosis being made by the methods of conventional radiography and densitometry. Among the markers of bone metabolism, the following were used: blood levels of parathyrin (parathyroid hormone), calcitonin, osteocalcin, osteopontin, alkaline phosphatase, and osteo-associated chemical elements. During the examination, biochemical, enzyme immunoassay, atomic emission and atomic absorption methods were used. Results. The age of women correlates with the parameters of bone mineral density, and the LBM in all ca­ses is associated with high blood levels of osteocalcin, in 1/2 of them — osteopontin, depends on the presence of comorbid primary arterial hypertension, type 2 diabetes mellitus, and leukocytoclastic vasculitis. OP formation significantly differs from Op in higher blood levels of parathyrin (by 47 %), alkaline phosphatase (by 19 %), phosphorus (by 9 %) and lead (by 27 %), but lower calcium values (by 4 %), moreover, the acti­vity of alkaline phosphatase has predictive negative significance in relation to the severity of the LBM. Calcitonin, magnesium, strontium and zinc also participate in the pathogenetic constructions of the latter. Conclusions. LBM develops in every second postmenopau­sal woman, and the further development of pathogenetic therapy should be aimed at correcting the concentration of osteocalcin and osteopontin in the body, and inhibition of alkaline phosphatase activity may be a criterion for the effectiveness of therapeutic measures., Актуальность. Сниженная костная масса (СКМ) в виде остеопении (Оп) и остеопороза (ОП) является одной из наиболее актуальных проблем здравоохранения. Постменопаузальный период у женщин считается основным фактором риска развития патологического процесса. Цель исследования: оценить клинико-патогенетические особенности СКМ у женщин в постменопаузальном периоде. Материалы и методы. Под наблюдением находилась 261 неменструирующая женщина, средний возраст 48 лет, у которых в 91 % случаев имела место физиологическая менопауза, а у остальных — патологическая. Критериями исключения были женщины с воспалительными ревматическими болезнями суставов, онкологической патологией, болезнями системы крови и щитовидной железы, получавшие глюкокортикоидные гормоны и антиконвульсанты. У 133 (51 %) женщин установлена СКМ (основная группа) в соотношении Оп и ОП 4 : 1, для диагностики которой применяли методы рентгеновской абсорбциометрии и ультразвуковой денситометрии. Среди маркеров костного метаболизма изучали уровни в крови паратирина (паратгормона), кальцитонина, остеокальцина, остеопонтина, щелочной фосфатазы и остеоассоциированных химических элементов. При обследовании использовали биохимический, иммуноферментный, атомно-эмиссионный и атомно-абсорбционный методы. Результаты. Возраст женщин коррелирует с параметрами минеральной плотности костей, а развитие СКМ во всех случаях связано с высокими показателями в крови остеокальцина, у 1/2 из них — остеопонтина, зависит от наличия коморбидных артериальной первичной гипертензии, сахарного диабета типа 2 и лейкоцитокластического васкулита. От Оп формирование ОП достоверно отличается более высокими уровнями в крови паратирина (на 47 %), щелочной фосфатазы (на 19 %), фосфора (на 9 %) и свинца (на 27 %), но меньшими значениями кальция (на 4 %), причем активность щелочной фосфатазы имеет прогнознегативную значимость в отношении выраженности СКМ. В патогенезе последнего участвуют также кальцитонин, магний, стронций и цинк. Выводы. СКМ развивается у каждой второй женщины в постменопаузальном периоде, а дальнейшая разработка патогенетической терапии должна быть направлена на коррекцию концентраций в организме остеокальцина и остеопонтина, причем критерием эффективности лечебных мероприятий может быть угнетение активности щелочной фосфатазы., Актуальність. Знижена кісткова маса (ЗКМ) у вигляді остеопенії (Оп) й остеопорозу (ОП) є однією з найбільш актуальних проблем охорони здоров’я. Постменопаузальний період у жінок вважається основним фактором ризику розвитку патологічного процесу. Мета дослідження: оцінити клініко-патогенетичні особливості ЗКМ у менопаузальних жінок. Матеріали та методи. Під наглядом перебувала 261 неменструююча жінка, середній вік 48 років, у яких в 91 % випадків мала місце фізіологічна менопауза, а у решти — патологічна. Критеріями виключення були жінки із запальними ревматичними хворобами суглобів, онкологічною патологією, захворюваннями системи крові та щитоподібної залози, які одержували глюкокортикоїдні гормони й антиконвульсанти. У 133 (51 %) жінок встановлено ЗКМ (основна група) у співвідношенні Оп і ОП 4 : 1, для діагностики якої застосовували методи рентгенівської абсорбціометрії та ультразвукової денситометрії. Серед маркерів кісткового метаболізму вивчали рівні в крові паратирину (паратгормону), кальцитоніну, остеокальцину, остеопонтину, лужної фосфатази й остеоасоційованих хімічних елементів. При обстеженні використовували біохімічний, імуноферментний, атомно-емісійний та атомно-абсорбційний методи. Результати. Вік жінок корелює з параметрами мінеральної щільності кісток, а розвиток ЗКМ у всіх випадках пов’язаний з високими показниками в крові остеокальцину, у 1/2 з них — остеопонтину, залежить від наявності коморбідних артеріальної первинної гіпертензії, цукрового діабету типу 2 і лейкоцитокластичного васкуліту. Від Оп формування ОП вірогідно відрізняється більш високими рівнями в крові паратирину (на 47 %), лужної фосфатази (на 19 %), фосфору (на 9 %) і свинцю (на 27 %), але меншими значеннями кальцію (на 4 %), причому активність лужної фосфатази має прогнознегативну значущість щодо вираженості ЗКМ. У патогенезі останнього беруть участь також кальцитонін, магній, стронцій та цинк. Висновки. ЗКМ розвивається у кожної другої жінки в постменопаузальному періоді, а подальша розробка патогенетичної терапії повинна бути спрямована на корекцію концентрацій в організмі остео­кальцину й остеопонтину, причому критерієм ефективності лікувальних заходів може бути пригнічення активності лужної фосфатази.

Актуальність. Остеоартроз (ОА) є одним із найчастіших захворювань суглобів, що характеризується періодичними загостреннями, наявністю больового синдрому різного ступеня вираженості, прогресуючим перебігом та призводить до деформації суглобів, зниження їх функції та погіршення якості життя хворих. Важливим є зв’язок ОА з низкою метаболічних порушень, а саме вуглеводного та ліпідного обміну. Мета дослідження — вивчення параметрів метаболізму кісткової тканини у хворих на ОА, цукровий діабет (ЦД) 2-го типу та при їх поєднанні в осіб із різним фенотипом, а також взаємозв’язок між показниками маркерів метаболізму кісткової тканини та рівнем прозапальних цитокінів. Матеріали та методи. До дослідження було включено 104 пацієнти (31 чоловік та 73 жінки) з ОА, ЦД 2-го типу та поєднанням ОА та ЦД 2-го типу з різним фенотипом, середній вік яких становив 54,02 ± 0,67 року. Контрольну групу становили 20 практично здорових осіб. Дослідження включало визначення рівня остеоасоційованих елементів (Ca, P, Mg), С-реактивного протеїну (СРП), остеокальцину, кальцитоніну, фактора некрозу пухлин α (ФНП-α) та інтерлейкіну-1β (ІЛ-1β). Усім хворим на ОА було проведене рентгенологічне дослідження суглобів. Результати. Вірогідно вищі показники рівня остеокальцину було визначено у хворих у контрольній групі та в пацієнтів з OA на відміну від пацієнтів з встановленим діагнозом ЦД 2-го типу. Тобто для остеокальцину справедливим є такий ряд: конт­роль = ОА > ЦД 2-го типу = ОА + ЦД 2-го типу = ОА + ЦД 2-го типу + ожиріння. Відмінності в значеннях інших показників метаболізму кісткової тканини між досліджуваними п’ятьма групами були менш вираженими, що не дозволяло сформувати для них єдиний ряд. Дослідження рівня цитокінів показало їх вірогідне підвищення у всіх обстежених хворих на відміну від контрольної групи (р

The human internal carotid nerve (ICN) occasionally has a swelling beneath the external opening of the carotid canal. In this study, the presence and distribution of neuronal cells were investigated in the bilateral ICNs of nine human cadavers. Among 44.4% of the cadavers, swellings were detected in the ICN. Their diameters ranged from 1.7 to 3.6 mm (average ± SD = 2.6 ± 0.7 mm). Thirty-eight percent of these swellings were large (diameter > 3 mm) and showed an oval shape. The large swelling contained many neuronal cells. However, the ICNs with or without a swelling

Monoclonal antibodies targeting the calcitonin gene-related peptide have been introduced into the therapeutic arsenal of migraine prophylaxis. Clinical trials report similar efficacy between them, and there is no evidence of switching to another one after failure. We aim to describe our experience in switching from erenumab to galcanezumab after therapeutic failure. We retrospectively reviewed 30 migraine patients who received monoclonal antibodies, with 15 of them switched after failure to achieve reduction in migraine days per month ≥30%. A ≥30% reduction in migraine days per month compared to baseline was observed in 8/15 (4/15 ≥ 50%) patients after switch. Some nonresponsive patients may benefit from switching between monoclonal antibodies with different therapeutic targets.

Background Calcitonin gene-related peptide (CGRP) (receptor) antibodies (erenumab, fremanezumab and galcanezumab) are increasingly used in prophylactic treatment of migraine. In the approval studies, severely affected patients with migraine and chronic daily headache without any headache free days were excluded. Thus, less is known about the effectiveness of CGRP antibody treatment in this cohort. Methods Clinical routine data of 32 patients with migraine and daily headache were analysed after three months of treatment with a CGRP antibody (16 erenumab, 7 galcanezumab, 9 fremanezumab), including changes of monthly headache days (MHD) monthly migraine days (MMD) and monthly acute medication intake (AMD) as well as migraine characteristics. Statistical analysis was performed with the Wilcoxon-Test. Migraine characteristics were analysed descriptively. Results The number of MHD was significantly reduced (mean reduction (standard error), p-value): (-4.2 (1.3), p = 0.009) as well as MMD (-4.3 (1.6), p = 0.033). Four patients (13 %) reached a 50 % reduction regarding MHD and 8 patients (25 %) regarding MMD, migraine duration and intensity improved under therapy. Conclusions Despite the low responder rate, CGRP antibodies can be effective at least in a few cases of severely affected patients with drug resistant migraine and chronic daily headache. Trial registration Retrospective registered.

У статті висвітлена роль сироваткових пухлинних маркерів у діагностиці та лікуванні захворювань щитоподібної залози, передусім різних форм раку. Систематизовано клінічні показання до призначення та сучасні рекомендації щодо оцінки результатів визначення тиреоглобуліну, кальцитоніну, раково-ембріонального антигена. Наведено перспективи використання тестів на прокальцитонін, хромогранін А, а також окремих молекулярно-генетичних досліджень.

Objectives: During this ongoing pandemic of coronavirus disease 2019 (COVID-19), procalcitonin (PCT) assay has proven to be a useful tool in assisting clinicians to diagnose bacterial superinfection. However, in the absence of signs of infection or at resolution thereof, inappropriately and persistently high PCT may suggest and reveal the presence of other pathologies. We report a patient with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia in whom persistence of initially elevated PCT during recovery prompted the diagnosis of medullary thyroid cancer (MTC). Case report: A 43- year-old man presented with a two-day history of fever, sneezing, sore throat and dry cough. Physical exam revealed decreased sounds and coarse crackles in both lung bases at auscultation. Medical history was positive for cognitive impairment since birth, arterial hypertension, systemic lupus erythematosus with nephritis. Initial studies included mild lymphocytopenia 650/µl (760 - 5000), D-Dimer 0.73 µg/ml (< 0.5), C reactive protein (CRP) of 62 mg/l (< 5) and PCT of 94 ng/ml (0.00 - 0.10). Positivity for SARS-Cov-2 RNA was detected and chest computerized tomography showed bilateral ground-glass opacities in the basilar lung zones and hyperdense and irregular foci in the thoracic vertebral bodies. Empirical antibiotic therapy was started and was maintained for seven days but, despite clinical improvement and the normalization of CRP, serum PCT was persistently high (84 ng/ml). Serum calcitonin (CTN) was 2120 pg/ml (normal up to 12 pg/ml). Neck ultrasound revealed inhomogeneously echogenic lymph nodes with small punctate calcifications and a non-homogeneous thyroid with multiple nodules. Cytological examination by fine needle aspiration and CTN measurement on washing liquid confirmed the suspicion of MTC. The patient underwent total thyroidectomy with bilateral cervical lymph node dissection. Histological analysis confirmed MTC of right thyroid lobe and metastasis at lymph nodes of the central right midneck area. Blood tests performed 48 hours after surgery showed a lowering of CTN (986 pg/mL) and PCT (16 ng/mL). A 6-months follow up showed persistent increased CTN and PCT levels (921 pg/ml and 16 ng/ml, respectively) while a (18)F-fluorodihydro-xyphenylalanine ((18)F-DOPA) PET did not reveal any suspicious fixations at thyroid lodge and cervical lymph node stations while multiple osteoblastic foci in the skeletal area were described. A close follow-up was planned with establishment of the results of RET gene analysis. Discussion: Although CTN is the gold standard biochemical parameter for the diagnosis and follow-up of MTC, PCT can be useful as a biochemical marker of MTC suspicion in patients with inflammatory conditions and persistently elevated PCT even after resolution. In the present CASE, high levels of PCT in a patient with Covid-19 pneumonia without signs of bacterial infection, allowed to diagnose MCT. Conclusion: In the absence of any other signs of infection, a complete clinical assessment, including neck palpation, CTN measurement and thyroid ultrasound should be performed in the presence of persistently elevated PCT.

Background and ObjectivesThe mechanisms of pain in patients with diabetic polyneuropathy are unknown. Studies have suggested a role of inflammation and increased neuropeptides peripherally in pain generation. This study examined the possible skin markers of painful diabetic polyneuropathy (P-DPN): macrophages, substance P (SP), and calcitonin gene-related peptide (CGRP).MethodsThe participants were included from a large Danish cross-sectional clinical study of type 2 diabetes. We diagnosed definite diabetic polyneuropathy using the Toronto criteria and used the Neuropathic Pain Special Interest Group classification for defining P-DPN. We included 60 skin biopsies from patients with diabetic polyneuropathy—30 with P-DPN and 30 with nonpainful diabetic polyneuropathy (NP-DPN)—and 30 biopsies from healthy controls of similar age and sex. The biopsies were stained using PGP 9.5, IbA1, and SP and CGRP primary markers.ResultsThere was increased macrophage density in patients with P-DPN (8.0%) compared with that in patients with NP-DPN (5.1%,p< 0.001), and there was increased macrophage density in patients with NP-DPN (5.1%) compared with that in healthy controls (3.1%,p< 0.001). When controlling for neuropathy severity, body mass index, age, and sex, there was still a difference in macrophage density between patients with P-DPN and patients with NP-DPN. Patients with P-DPN had higher median nerve fiber length density (274.5 and 155 mm−2for SP and CGRP, respectively) compared with patients with NP-DPN (176 and 121 mm−2for SP and CGRP, respectively,p= 0.009 and 0.04) and healthy controls (185.5 and 121.5 mm−2for SP and CGRP, respectively), whereas there was no difference between patients with NP-DPN and controls without diabetes (p= 0.64 and 0.49, respectively). The difference between P-DPN and NP-DPN for SP and CGRP was significant only in female patients, although a trend was seen in male patients.DiscussionThe findings point to a possible involvement of the innate immune system in the pathogenesis of neuropathic pain in patients with DPN, although markers of activated macrophages were not measured in this study.

Procalcitonin (PCT) is a 116 amino acid peptide with a sequence identical to that of prohormone of calcitonin but devoid of hormonal activity. The aim of this study was to determine PCT and it using as a new prognostic pro-inflammatory marker in burn patients and determine the role of PCT level as a mortality indicator in survival and non-survival burn patients. The burn patients in this study were divided into four groups according to the percentage of total body surface area burned carry out on (50) burn patients admitted to the burn unit in West Erbil Emergency Hospital in Erbil governorate and (20) apparently the healthy non-burn individuals who regarded as healthy control group (HC) in this study from February 2012 to April 2012. Out of 50 burnt patients, 20 patients were second sampled to follow-up their immune profile. Regarding PCT there were significant differences (P < 0.05) observed between the mean serum concentration of PCT belong to 18 burn patients of 1st group (G1) (1.24 ± 0.82), 23 patients of 2nd group (G2) (1.52 ± 0.76), six patients of 3rd group (G3) (2. 16 ± 0.11), and three burn patients of 4th group (G4) (6.5 ± 2.87) with mean serum concentration of 18 HC (0.02 ± 0.006). Significant differences obtained when compared to G3 (2.16 ± 0.11) versus G4 (6.5 ± 2.87) using the F-test and t-test. Results show that PCT is a highly productive laboratory parameter involving an easy and rapid beside test for diagnosis and prognosis mortality in burn patients.

Background. Earlier we found that even in intact rats, certain parameters of nitrogenous metabolism fluctuate in a fairly wide range, which further expands in cases of prolonged water loads. Based on this, we have been created three groups that are homogeneous in the parameters of nitrogenous metabolism. We have been shown that each cluster is accompanied by a specific constellation of immune parameters. In this study, an attempt will be made to supplement the immune accompaniment of each constellation of nitrogenous metabolites with parameters of the autonomic nervous and endocrine systems. Material and methods. Experiment was performed on 60 healthy female Wistar rats, both intact and loaded with different mineral waters. Immune status was assessed by thymocytogram, splenocytogram, blood leukocytogram and immunocytogram, as well as by phagocytosis parameters of blood neutrophils and monocytes. The state of autonomous regulation assessed by HRV. The plasma levels of the hormones of adaptation: corticosterone, triiodothyronine and testosterone (by the ELISA) were determined as well as mineralocorticoid, calcitonin and parathyroid activity calculated by their electrolyte markers. Results. 9 neuro-endocrine and 17 immune parameters were identified, the set of which three clusters of nitrogen metabolism clearly differ from each other. The overall accuracy of the classification is 93,3%. Conclusion. The variety of states of exchange of nitrogenous metabolites is accompanied by specific constellations of 26 parameters of neuro-endocrine-immune complex.

The potential transient vanilloid receptor type 1 (TRPV1) plays important functional roles in the vascular system. In the present study, we explored the role of the TRPV1 in the production of nitric oxide (NO), biopterines (BH4 and BH2), cyclic guanosine monophosphate (cGMP), malondialdehyde (MDA), phosphodiesterase-3 (PDE-3), total antioxidant capacity (TAC), and calcitonin gene-related peptide (CGRP) in the rat aorta. Wistar rats were divided into four groups: (1) control, (2) capsaicin (CS, 20 mg/kg), (3) capsazepine (CZ, 24 mg/kg), and (4) CZ + CS. Treatments were applied daily for 4 days before removing the thoracic aortas for testing of aortic tissue and endothelial cells. TRPV1 activation produced increases in BH4 14%, cGMP 25%, NO 29%, and TAC 59.2% in comparison to the controls. BH2 and MDA increased with CZ. CGRP shows a tendency to decrease with CZ. The analysis by immunocytochemistry confirmed that the TRPV1 is present in aortic endothelial cells. Aortic endothelial cells were obtained from healthy rats and cultured to directly explore the effects of CS and CZ. The activation of the TRPV1 (CS 30 μM) produced increases in BH4 17%, NO 36.6%, TAC 56.3%, and CGRP 65%, when compared to controls. BH2 decreased with CZ + CS. CS effects were diminished by CZ in cells and in the tissue. We conclude that the TRPV1 is a structure present in the membrane of aortic endothelial cells and that it participates in the production of NO. The importance of the TRPV1 should be considered in vascular reactivity studies.

Hypercalcemia is a clinical emergency which can cause hypercalcemic crisis and even endanger patients' lives. The increase of serum calcium concentration is caused by the redistribution of calcium in bone and the inhibition of parathyroid secretion, which is known as non-parathyroid hypercalcemia. In this report, we presented a rare case of non-parathyroid hypercalcemia during lactation in order to optimize the diagnosis and treatment of this condition. A 27-year-old female patient was admitted to Wuxi People's Hospital on July 11, 2019 due to "fatigue, anorexia, and pain in both knees for half a month". The patient had fatigue and discomfort, accompanied by pain in both knees without obvious inducement. At the same time, the patient had decreased food intake. In the past 3 days, the symptoms worsened, accompanied by limb numbness. The serum calcium level was increased and the parathyroid hormone (PTH) level was decreased. The patient was diagnosed with hypercalcemia, and was treated with calcitonin and lactation termination. The knee pain disappeared and serum calcium returned to normal during a 2-week follow-up. To conclude, the correlation between hypercalcemia and lactation needs to be considered for non-parathyroid hypercalcemia during lactation. After excluding other possible causes, lactation termination therapy may be an effective therapeutic strategy for non-parathyroid hypercalcemia caused by excessive lactation.

Thyroid gland is one of the important glands of the endocrine system and thyroid disorders are the most common disorders amongst the general population worldwide, as well as in india. Hypothyroidism is caused by inadequate function of the thyroid gland called as primary hypothyroidism or by insufficient stimulation by thyroid- stimulating hormones called as secondary hypothyroidism. Current view the thyroid gland is a butterfly shaped gland. It is located inferior to the larynx and anterior to the trachea. It has two lobes connected by the isthmus. It is made of microscopic spherical masses called follicles. A secretary substance is present in the follicle called colloid. Colloid is made of a glycoprotein called as thyroglobulin. Thyroglobulin produces thyroid hormones. They are triiodothyronine (t3), tetraiodothyronine (t4) and calcitonin. Ayurvedic perspective of subclinical hypothyroidism. Management of hypothyroidism with synthetic thyroid hormone derivatives may bring the value of tsh, t3 and t4 to normal range but the daily intake of medicine for lifetime, the known side-effects thereafter and increase in the dosage with time as the disease become chronic, is troublesome for the patients. Also the quality of life of the patients taking medicine regularly for long durations is compromised.

The role of receptor activity‐modifying proteins (RAMPs) in modulating the pharmacological effects of an amylin receptor selective agonist (NN1213) or the dual amylin–calcitonin receptor agonist (DACRA), salmon calcitonin (sCT), was tested in three RAMP KO mouse models, RAMP1, RAMP3 and RAMP1/3 KO. Male wild‐type (WT) and knockout (KO) littermate mice were fed a 45% high‐fat diet for 20 weeks prior to the 3‐week treatment period. A decrease in body weight after NN1213 was observed in all WT mice, whereas sCT had no effect. The absence of RAMP1 had no significant effect on NN1213 efficacy, and sCT was still inactive. However, the absence of RAMP3 impeded NN1213 efficacy but improved sCT efficacy. Similar results were observed in RAMP1/3 KO suggesting that the amylin receptor 3 (AMY3 = CTR + RAMP3) is necessary for NN1213's maximal action on body weight and food intake and that the lack of AMY3 allowed sCT to be active. These results suggest that the chronic use of DACRA such as sCT can have unfavourable effect on body weight loss in mice (which differs from the situation in rats), whereas the use of the amylin receptor selective agonist does not. AMY3 seems to play a crucial role in modulating the action of these two compounds, but in opposite directions. The assessment of a long‐term effect of amylin and DACRA in different rodent models is necessary to understand potential physiological beneficial and unfavourable effects on weight loss before its transition to clinical trials., AMY3 mediates the effect of the dual amylin receptor agonist NN1213.Subchronic sCT does not reduce body weight in WT mice.Absence of AMY3 allows sCT to be active.

Background Pneumonia causes significant morbidity and mortality in children worldwide, especially in resource-poor settings. Accurate identification of bacterial etiology leads to timely antibiotic initiation, minimizing overuse, and development of resistance. Host biomarkers may improve diagnostic sensitivity and specificity. We assessed the ability of biomarkers to correctly identify bacterial pneumonia in children who present with respiratory distress. Methods A librarian-directed search was conducted of MEDLINE, EMBASE, CENTRAL, Global Health, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov to May 2020 with no language restriction. Included studies compared a diagnostic biomarker in children with bacterial pneumonia to those with nonbacterial respiratory distress. Results There were 31 observational studies of 23 different biomarkers. C-reactive protein (CRP), procalcitonin (PCT), white blood cell (WBC) count, and erythrocyte sedimentation rate (ESR) were the biomarkers with sufficient data for meta-analysis. Meta-analysis revealed that CRP and PCT best differentiated bacterial from viral pneumonia with CRP summary AUROC (area under the receiver operating characteristic curve) 0.71 (0.69-0.73), Youden index 53 mg/L, sensitivity 0.70 (0.68-0.78), and specificity 0.64 (0.58-0.68) and PCT summary AUROC 0.70 (0.67-0.74), Youden index 0.59 ng/mL, sensitivity 0.69 (0.65-0.77), and specificity 0.64 (0.60-0.68). WBC and ESR did not perform as well. Nineteen other inflammatory and immunologic biomarkers were identified including CRP/mean platelet value, neutrophil/leukocyte ratio, interleukin 6, and interferon-alpha, with sensitivities from 60% to 85% and specificities from 76% to 83%. Conclusion CRP and PCT performed better than WBC and ESR but had suboptimal sensitivity. Some less well-studied novel biomarkers appear to have promise particularly in combination.

Introduction: Calcitonin measurement is important for the diagnosis and monitoring of medullary thyroid carcinoma. Unfortunately, in clinical practice, different detection systems assays are used in the follow-up of the patients, which can be misleading. Objective: To identify the correction factor for calcitonin measurement on two different immunoanalysers: DiaSorin-LiaisonXL (immunochemiluminescence) and CobasE601 (electro-immunochemiluminescence). Methods: We selected 89 registered CT samples (28-from men; 61-from women), that were analysed on CobasE601 with reported values between 0.5 pg/ml and 2812 pg/ml (128.5±513.98). These CT samples were selected randomly to cover as wide a range of values as possible, and represented either basal CT (n=38) or selected from CT stimulation tests (n=51). Samples were evaluated subsequently on DiaSorin-LiaisonXL. All patients gave their informed consent. Results: Between the two assays a segmented linear correlation was noted. We identified the following general linear regression equation: 1.108x+19.337 (p Conclusions: Calcitonin correction factors are highly important in the dynamic follow up of a patient suffering from medullary thyroid carcinoma when different detection systems assays are used to determine calcitonin. We identified the correction factors for calcitonin determination between two different frequently used chemiluminescence immunoanalysers: DiaSorin-LiaisonXL and CobasE601. However, it is strongly advisable to use the same analyser in order to establish biochemical evolution of calcitonin.

Hypercalcemia of malignancy (HCM) can present secondary to hypersecretion of parathyroid hormone (PTH)-related protein (PTHrP) from malignant tumors, but rare cases of HCM have also been documented due to inappropriate PTH secretion from ectopic neoplasms. Here, we report an unusual case of HCM due to hypersecretion of PTH suspected secondary to a disseminated mucinous ovarian adenocarcinoma. A 45-year-old female presented with severe hypercalcemia and significant elevations in both PTH and PTHrP two weeks after total abdominal hysterectomy with bilateral salpingo-oophorectomy and suboptimal debulking of a newly discovered left ovarian mucinous adenocarcinoma with numerous metastases. Ectopic PTH secretion was highly suspected after a negative parathyroid ultrasound. Pamidronate, calcitonin, and fluid resuscitation were unable to normalize her serum calcium, resulting in the need for dialysis and subsequent continuous renal replacement therapy. Further intervention with denosumab, etelcalcetide, and cinacalcet was attempted. Serum calcium began to decline, but repeat PTH resulted greater than 2,500 pg/mL. Unfortunately, the patient died just one week into her hospital course from septic shock and multi-organ system failure. While patients with localized PTH-secreting tumors carry a good prognosis, disseminated malignancies can result in significant morbidity and mortality due to severe treatment-resistant hypercalcemia.

Objectives To evaluate concentrations of procalcitonin (PCT) in transplant recipients receiving immunosuppressive therapy compared with nonimmunosuppressed patients. Methods We analyzed a data set of 9,500 inpatient encounters to compare levels of PCT and other biomarkers of infection (C-reactive protein [CRP], WBC count, and absolute neutrophil count [ANC]) between immunosuppressed and nonimmunosuppressed cohorts. We also assessed the correlation between PCT and clinical variables in immunosuppressed patients. Results Patients receiving immunosuppressive drugs had significantly higher levels of maximal and minimal PCT compared with the nonimmunosuppressed patients (P Conclusions Our results from real-world data demonstrated that PCT dynamics remain intact despite immunosuppressive therapy, in contrast to other biomarkers such as CRP, WBC, and ANC. In addition, higher PCT levels are associated with systemic infections and reflect disease severity.

We took an interdisciplinary view to examine the potential contribution of perilacunar/canalicular remodeling to declines in bone fracture resistance related to age or progression of osteoporosis. Perilacunar remodeling is most prominent as a result of lactation; recent advances further elucidate the molecular players involved and their effect on bone material properties. Of these, vitamin D and calcitonin could be active during aging or osteoporosis. Menopause-related hormonal changes or osteoporosis therapies affect bone material properties and mechanical behavior. However, investigations of lacunar size or osteocyte TRAP activity with age or osteoporosis do not provide clear evidence for or against perilacunar remodeling. While the occurrence and potential role of perilacunar remodeling in aging and osteoporosis progression are largely under-investigated, widespread changes in bone matrix composition in OVX models and following osteoporosis therapies imply osteocytic maintenance of bone matrix. Perilacunar remodeling-induced changes in bone porosity, bone matrix composition, and bone adaptation could have significant implications for bone fracture resistance.

Background Endogenous calcitonin gene-related peptide (CGRP) induces cardioprotective effects through coronary vasodilation. However, the systemic administration of CGRP induces peripheral vasodilation and positive chronotropic and inotropic effects. This study aims to examine the net effect on coronary perfusion of the systemically administered α-calcitonin gene-related peptide analogue, SAX, in rats during myocardial infarction. Methods Forty Sprague-Dawley rats underwent myocardial infarction. Following left anterior descending artery occlusion, [99mTc]Tc-sestamibi was administered to determine the myocardial perfusion before treatment. Twenty minutes, 24 and 48 h after [99mTc]Tc-sestamibi injection, the rats were treated with either SAX or placebo. Final infarct size was determined three weeks later by [99mTc]Tc-sestamibi SPECT/CT scan. Results Thirty-one rats survived the surgery and 20 completed the follow-up SPECT/CT scan (SAX n = 12; Placebo n = 8). At baseline, there was no difference in size of perfusion defect between the groups (P = .88), but at follow-up the SAX group had improved myocardial recovery compared to the placebo group (P = .04), corresponding to a relative perfusion recovery of 55% in SAX-treated rats. Conclusion The CGRP analogue, SAX, has a cardioprotective effect in this rat model of myocardial infarction, improving myocardial perfusion recovery after chronic occlusion of the coronary artery.

In Senegal, reducing neonatal mortality remains a challenge. The management of neonatal infections remains problematic and presents a strong clinical focus. Indeed, like all developing countries, the difficulty of acquiring state-of-the-art infrastructure and the financial cost impact on the routine use of biomarkers. It is in this context that we conducted this study to identify the best biological strategy for making a reliable diagnosis. Ninety-nine newborns were recruited at the pediatric service of the Diamniadio Children's Hospital (Senegal). CRP was assayed by latex immuno-agglutination method, IL-6 and IL-8 using Luminex® technology, PCT by chemiluminescence, orosomucoid by immunoturbidimetry and SAA by ELISA technique. 20 newborns had probable infection and six established infection. Deaths and complications were significantly greater in these groups. With an optimal decision threshold of 16.3 mg/L, CRP performed better (compared to the other tested blood biomarkers) with AUC, sensitivity and specificity of 94%, 88% and 99%, respectively. With the performance obtained from CRP in the diagnosis of neonatal bacterial infections, the installation of panels with other biomarkers with advanced and expensive technology is not necessary. Thus, optimal care and within a reasonable timeframe can be done in our health facilities, with this accessible marker that is CRP.

BACKGROUND: The diagnosis of osteomyelitis is a key step of diabetic foot management. Procalcitonin (PCT) is a novel infection marker. This study aimed to investigate the diagnostic value of procalcitonin and other conventional infection markers and clinical findings in diagnosis of osteomyelitis in diabetic foot patients. METHODS AND MATERIALS: This diagnostic value study was carried out on ninety patients with diabetic infected foot ulcers admitted in Kashan Beheshti Hospital, 2016. After obtaining consent, 10 cc blood sample was taken for measuring serum PCT, CBC, ESR, CRP and FBS. Clinical characteristics of the wounds were noted. Magnetic resonance imaging of the foot was performed in all patients to diagnose osteomyelitis. All statistical analyses were done with the use of SPSS-16. RESULTS: PCT levels were 0.13 ± 0.02 ng/mili patients with osteomyelitis (n= 45) and 0.04 ± 0.02 ng/ml in patients without osteomyelitis (n= 45). PCT, Erythrocyte sedimentation rate and C-reactive protein was found significantly higher in patients with osteomyelitis (p< 0.001). The ROC curve was calculated for PCT. The area under the ROC curve for infection identification was 1 (p< 0.001). The best cut-off value for PCT was 0.085 ng/ml. Sensitivity, specificity, and positive and negative predictive values were 100%, 97.8%,97.8% and 100%, respectively. CONCLUSION: In this group of patients, PCT was useful to discriminate patients with bone infection. Also, Erythrocyte sedimentation rate and C-reactive protein can be used as a marker of osteomyelitis in diabetic patients.

Background: The dramatic increase in the acquisition cost of injectable calcitonin led to creating a pharmacy-driven calcitonin protocol to improve the appropriate use of calcitonin and other treatment modalities for hypercalcemia. Objective: This study aimed to characterize the use of calcitonin before and after implementation of a pharmacy-driven calcitonin protocol. Methods: This was a multi-center, retrospective study of the use of injectable calcitonin in adult hospitalized patients with hypercalcemia. The study included patients treated with calcitonin from October 2014 to September 2016 and from October 2017 to September 2019. The primary outcomes were percentage of patients with a complete response, partial response, and non-responders. The secondary outcomes were time to relapse, duration of partial response, number of doses, and associated costs of calcitonin. Results: Of the 131 patients included in this study, 93 were included in a pre-protocol group and 38 were included in a post-protocol group. The primary outcome of complete response by 3 days was met in 28% of patients in the pre-protocol group and 53% of patients in the post-protocol group ( P = 0.007). Calcitonin spending in dollars in the pre-protocol group was $818,956 compared to $224,320 in the post-protocol group; a difference of $594,636. Conclusion: Implementation of a pharmacy-driven calcitonin protocol effectively improved calcium levels, reduced inappropriate calcitonin use, and reduced calcitonin spending during a period of 2 fiscal years.

Objectives: In our study, we investigated whether the undercarboxylated osteocalcin (ucOC) is an indicator of bone turnover for patients treated with hemodialysis (HD) or peritoneal dialysis (PD). Furthermore, we have examined the relationships between ucOC levels and other bone inidicators such as osteocalcin (OC), bone specific alkaline phosphatase (B-ALP), calcitonin, vitamin D, intact parathyroid hormone (iPTH), calcium (Ca), phosphate (P), magnesium (Mg) and bone mineral density (BMD). Methods: Study group was consisted of 24 HD, 30 PD patients and 30 control subjects. ucOC measurements were based on precipitation of carboxylated OC with barium sulfate. After precipitation, ucOC was measured in supernatant by ELISA. Results: In chronic kidney disease (CKD), increased ucOC levels were present both in HD and PD groups. The ucOC levels in HD group were higher than those of PD group. ucOC levels in samples after HD were lower than in samples before HD. But there is no difference between groups for ucOC% levels. We observed that ucOC levels for CRF were higher compared to that of control group and statistically significant. ucOC levels were positively correlated with OC, B-ALP, ALP, iPTH, P and Mg levels. There were negative and significant correlations between ucOC levels and BMD values. ucOC has a good discrimination power for both high and low turnover ROD groups. Conclusions: ucOC is a useful marker to evaluation of bone metabolism in patients undergone hemodialysis or peritoneal dialysis in end-stage renal disease.

Amylin is a 37-amino acid endocrine hormone secreted from the pancreas in response to nutrient intake, acting centrally to promote meal-ending satiation. With many studies linking amylin action to the nervous system, determining the distribution or expression of amylin in the nervous system is critical. However, amylin shares sequence identity and structural homology to the related neuropeptide calcitonin gene-related peptide (CGRP). This creates challenges in identifying selective amylin antibodies that do not cross-react with CGRP, especially in neural tissues, where CGRP is densely packed into secretory vesicles. Here, we characterized eight amylin antibodies to determine their ability to detect amylin and cross-react with rat or human αCGRP, using immunoblots and preabsorption controls in rat pancreas. We observed that amylin antibodies frequently cross-reacted with αCGRP and are therefore not suitable for use in tissues that highly express CGRP. Earlier work using these antibodies should be revisited in light of our findings.

Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an ectopic source of calcitonin secretion can represent a complex diagnostic conundrum for managing physicians, with cases of unnecessary thyroidectomy reported in the literature. This manuscript reports a case of ectopic hypercalcitonaemia from a metastatic neuroendocrine neoplasm of the lung with concurrent thyroid pathology and summarises the results of a systematic review of the literature. Medical Literature Analysis and Retrieval System Online, Excerpta Medica, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and SCOPUS databases were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori. The protocol for this systematic review was developed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols, and followed methods outlined in The Cochrane Handbook for Systematic Reviews of Interventions. This systematic review is registered with PROSPERO. It is vital to consider diagnoses other than medullary thyroid carcinoma when presented with a patient with raised calcitonin, as it is not pathognomonic of medullary thyroid carcinoma. Lung neuroendocrine neoplasms can appear similar to medullary thyroid carcinoma histologically, they can secrete calcitonin and metastasize to the thyroid. Patients with medullary thyroid carcinoma may show stimulated calcitonin values over two or more times above the basal values, whereas calcitonin-secreting neuroendocrine neoplasms may or may not show response to stimulation tests. The present review summarises existing evidence from cases of ectopic hypercalcitonaemia to lung neuroendocrine neoplasms.

Objective: The objective of this meta-analysis was to compare the efficacy and safety of teriparatide versus salmon calcitonin for the treatment of osteoporosis in Asian patients and to investigate whether the results of global studies could be applicable to Asian patients. Methods: PubMed, OVID, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE up to December 2018 were searched. Eligible randomized controlled trials (RCTs) that compared teriparatide versus salmon calcitonin in Asian osteoporosis population were included. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data synthesis, and Cochrane Collaboration software Review Manager 5.3 was used to analyze the pooled data. Results: Three RCTs involving 529 patients were included (mean age 68.7 yr; 93.4% females; mean follow-up 6 months); outcome measures included bone mineral density (BMD) of the femoral neck, total hip and lumbar spine; bone markers and adverse events. We found that the period of 6-months of teriparatide treatment was helpful for the improvement of the BMD of lumbar vertebra, however, the improvement of BMD was not significant in the femoral neck and total hip joint. There was a positive correlation between bone-specific alkaline phosphatase (BSAP) and osteocalcin (OCN) and the response of Asian patients to subcutaneous injection of 20 micrograms per day of teriparatide. The proportion of the occurrence of adverse effects was more obvious in the teriparatide group compared with salmon calcitonin, but there was no significant difference. Conclusion: Results suggested that the use of teriparatide could improve the lumbar BMD by shortterm (six months) application in Asian osteoporosis patients, which is beneficial to the patients who cannot tolerate adverse events of long-term treatment. The BSAP and OCN bone markers could be useful to monitor the responses of Asian osteoporosis patients to teriparatide treatment. Finally, both of teriparatide and salmon calcitonin were well tolerated by Asian patients.

Osteoporosis is defined as the thinning of bone resulting from the imbalance between bone resorption and bone formation, the two cellular mechanisms that regulate the remodeling of skeletal tissue. This loss of bone ultimately results in an increased risk of fracture. One therapeutic approach to treating patients with osteoporosis is to inhibit the process of bone resorption. This has been clinically manifested by the development of a number of large and small molecules that include calcitonin, integrin inhibitors, cathepsin K inhibitors, OPG/RANKL inhibitors, bisphosponates, and SERMS. This chapter describes recent advances in the anti-resorptive field with a focus on clinically validated targets and the molecules that have been developed to regulate these pathways. Keywords: Osteoporosis; Osteoclast; Osteoblast; Calcitonin; Cathepsin K Inhibitors; Osteoprotegerin; RANKL; Bisphosponates; Selective Estrogen Receptor Modulators; SERMs