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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 Medullary thyroid cancer is a neuroendocrine malignancy that can occur sporadically or as the result of genomic rearranged during transfection mutations. Medullary thyroid cancer has a higher rate of metastasis than well-differentiated thyroid cancer. Lateral neck dissection is often performed, and its prophylactic use is controversial. Methods Single-center, retrospective review (2000–2017) of patients undergoing primary surgical treatment for medullary thyroid cancer who had negative lateral neck imaging preoperatively. Demographics, genetic associations, clinical, and imaging findings were analyzed. Locoregional recurrence, overall recurrence, and overall survival were examined. Results A total of 110 patients were identified, of which 18 underwent prophylactic lateral neck dissection and 92 did not. Age, sex distribution, preoperative calcitonin levels, and follow-up were similar among groups. Overall recurrence was 20% for no prophylactic lateral neck dissection and 39% for prophylactic lateral neck dissection (P = .46). Most recurrences were locoregional recurrence, 7.6% for no prophylactic lateral neck dissection versus 22% for prophylactic lateral neck dissection (P = .08), half of it being to the lateral neck in both groups. A total of 7 patients from the no prophylactic lateral neck dissection group required treatment for recurrences versus 4 patients in prophylactic lateral neck dissection group (P = .57). Overall survival at 5 years was similar, 43% the no prophylactic lateral neck dissection group and 31% for prophylactic lateral neck dissection group (P = .52). Conclusion Lateral neck dissection has no effect in decreasing locoregional or overall recurrences in medullary thyroid cancer and has no effect in overall survival when performed prophylactically at index surgical intervention.

Back pain is reported to be the fifth most common reason for referral a patient to a physician and the most common disability in modern society. The present study aimed to evaluate the effects of calcitonin addition on epidural injection in patients with degenerative spinal canal stenosis in comparison with epidural triamcinolone injection.The clinical trial study was performed on 40 patients with degenerative spinal stenosis, referred to pain clinic of RasoulAkram Hospital in 2018, who were randomly divided into two intervention and control groups, including 20 individuals in each group. In the intervention group, 50 units of calcitonin were injected with 8 cc of ropivacaine 0.2% while 80 mg of triamcinolone with 8 cc of ropivacaine 0.2% was injected in the control group. Functional disability was evaluated based on the Oswestry Disability Index (ODI) and pain ratings were assessed using the Visual Analogue Scale (VAS).Pain at 4 and 8 weeks after the procedure was significantly different between the two groups. A significant difference in the patient disability index was observed between two groups at 8 and 12 weeks after the procedure. On the other hand, the rate of analgesic consumption at 4, 8 and 12 weeks after the procedure was significantly decreased in the calcitonin group (P0.001).Based on our results, injection of calcitonin into the epidural space can reduce the pain of the patients and their analgesic consumption compared to the group receiving steroids through the epidural space.

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 There is limited evidence on the safety and efficacy of denosumab for the management of immobilization-related hypercalcemia in hemodialysis patients. We report a case of successful treatment of immobilization-related hypercalcemia with a high dose of denosumab (120 mg). Case presentation A 55-year-old, bed-ridden woman was admitted to the intensive care unit with suspected catheter-related bacteremia and septic shock. 13 days following admission, the patient's corrected serum calcium levels rose from 2.52 mmol/L at baseline to 3.39 mmol/L. Cinacalcet, subcutaneous calcitonin, intravenous zoledronic acid, and subcutaneous 60-mg dose of denosumab were administered but resulted in an inadequate response. Consequently, subcutaneous 120-mg dose of denosumab was administered and resulted in a gradual decline of corrected serum calcium levels from 4.18 mmol/L to 2.45 mmol/L within 3 weeks; corrected serum calcium levels were maintained above 2.10 mmol/L and less than 2.80 mmol/L for 3 months after high-dose denosumab administration. Conclusion High-dose denosumab could be a viable treatment option for end-stage renal disease patients developing immobilization-related hypercalcemia.

The objective of this study was to assess the efficacy of calcitonin spray on bone healing following open reduction internal fixation (ORIF) of mandibular fractures. Fourteen patients were subdivided into a study group and a control group. A standardized surgical protocol for ORIF was followed. Postoperatively, salmon calcitonin nasal spray was administered to only the study group. The outcome parameters assessed were serum osteocalcin, pain, and radiographic bone healing. Serum osteocalcin was assessed pre- and postoperatively. Postoperative pain was documented using a visual analogue scale (VAS) on the 7th, 14th, 23rd, and 30th days. An orthopantomogram was used to score fracture healing at four time intervals, as follows: 1 — absence of callus; 2 — presence of minimal callus; 3 — considerable callus; and 4 — complete fusion of fracture. Pain scores were lower for the study group, with no pain from the fifth day, while the control group produced a mean score for day 5 of 2.43 ± 0.98 (p = 0.001). Mean postoperative serum osteocalcin levels were higher for the study group (67.82 ± 8.89) compared with the control group (57.69 ± 6.22; p = 0.029). Bone healing at 12 weeks postoperatively was level 4 for 28.6% of patients in the study group and level 3 for 71.4%. In comparison, 85.7% in the control group demonstrated level 3 healing, while 14.3% remained at level 2 (p = 0.462). Within the limitations of the study, it can be concluded that intranasal salmon calcitonin spray reduces postoperative pain and facilitates fracture healing, although its economic efficiency is still to be proven.

Hypercalcemic disorders are rare in pregnant women and are usually due to primary hyperparathyroidism. Clinical manifestations of hypercalcemia are nonspecific and can be masked by the physiologic changes of pregnancy. Furthermore, routine antenatal screening does not include serum calcium measurement and a hypercalcemia diagnosis may therefore be delayed until term or even after delivery. Timely recognition and appropriate interventions are essential to decrease maternal and fetal complications. Conservative measures are appropriate in the presence of mild hypercalcemia. Parathyroidectomy remains the mainstay of treatment for primary hyperparathyroidism with significant hypercalcemia not responding to conservative measures.

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.

Yusuke Kasai, Koji Aso, Masashi Izumi, Hiroyuki Wada, Junpei Dan, Yoshinori Satake, Toru Morimoto, Masahiko Ikeuchi Department of Orthopedic Surgery, Kochi Medical School, Kochi University, Nankoku, 783-8505, JapanCorrespondence: Koji AsoDepartment of Orthopedic Surgery, Kochi Medical School, Kochi University, 185-1 Oko-cho Kohasu, Nankoku, 783-8505, JapanTel +81-88-880-2386Fax +81-88-880-2388Email koji.aso@gmail.comPurpose: Nonunion bone fracture can be a cause of persistent pain, but the pathophysiology remains largely unknown. The objective of this study was to identify how nonunion affect persistent pain after fracture. Specifically, we evaluated the association of neuropeptide change in dorsal root ganglia (DRG) and nerve proliferation at fracture sites with pain.Methods: Rat union and nonunion fracture models were created. A piece of latex glove was placed at the fracture site to create a nonunion model. At 6 weeks after surgery, bone healing was assessed using radiography. In addition, the presence of calcitonin gene-related peptide-immunoreactive (CGRP-IR) DRG at the level of L3 and anti-growth associated protein 43-immunoreactive (GAP43-IR) nerve fibers in the scar tissue between the bone fragments were evaluated. Pain-related behavior was assessed using forced treadmill running.Results: In radiological images at 6 weeks after surgery, callus formation was formed continuously between bone fragments in the union models. On the one hand, a clear gap was detected between fragments in nonunion models. The percentage of CGRP-IR DRG cells and the density of GAP43-IR nerve fibers in the scar tissue between the bone fragments in nonunion models was significantly higher than that in union models (p < 0.05). An increase in inflammatory cell infiltrate was observed in scar tissues in the nonunion models. During forced treadmill running, rats in the union model could run significantly longer than those in the nonunion models.Conclusion: Increased CGRP expression in DRG cells and abnormal nerve proliferation secondary to prolonged inflammation could lead to persistent pain after bone fracture. In clinical practice, early achievement of bone union may minimize the development of persistent pain after fractures.Keywords: fracture pain, nerve proliferation, nonunion of fractures

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.

Migraine is a prevalent medical condition and the second most disabling neurological disorder. Regarding its pathophysiology, calcitonin gene-related peptide (CGRP) plays a key role, and, consequently, specific antimigraine pharmacotherapy has been designed to target this system. Hence, apart from the gepants, the recently developed monoclonal antibodies (mAbs) are a novel approach to treat this disorder. In this review we consider the current knowledge on the mechanisms of action, specificity, safety, and efficacy of the above mAbs as prophylactic antimigraine agents, and examine the possible adverse events that these agents may trigger. Antimigraine mAbs act as direct scavengers of CGRP (galcanezumab, fremanezumab, and eptinezumab) or against the CGRP receptor (erenumab). Due to their long half-lives, these molecules have revolutionized the prophylactic treatment of this neurovascular disorder. Moreover, because of their physicochemical properties, these agents are hepato-friendly and do not cross the blood-brain barrier (highlighting the relevance of peripheral mechanisms in migraine). Nevertheless, apart from potential cardiovascular side effects, the interaction with AMY

To evaluate the effectiveness of non-surgical treatment as an alternative in the management of central giant cell granuloma (CGCG). A literature search was carried out in accordance with the PRISMA statement in order to answer the question “Are non-surgical treatments effective as an alternative in the treatment of CGCG?”. Two examiners independently assessed eligibility, risk of bias, and extracted data, which included therapeutic protocol, side effects, and need for surgical supplementation. Among 1712 studies, 15 were included, totaling 145 patients. Calcitonin, intralesional corticosteroids, and denosumab were the medications used. For calcitonin (n = 61), complete remission was found in 30 cases. For intralesional triamcinolone (n = 68), reduction in size was observed in most cases (n = 39). Four cases received subcutaneous denosumab and showed absence of active bone metabolism in the region, of which three presented ossification. Combination of drug therapies (n = 29) was reported in one study and included subcutaneous interferon and oral imatinib. More and less side effects were found for interferon and corticosteroids, respectively. Forty percent of patients required additional surgical treatment. Despite the side effects presented and the need for additional surgery in some patients, in general, all non-surgical treatments could provide positive results as an alternative for the management of CGCG, especially with regard to reducing the size of the lesion. CGCG is a benign bone lesion that mainly affects young individuals. Although the most common therapy is surgery, its contraindication in some patients, the large extension, and high recurrence rate of the aggressive variant have led the search for non-surgical therapies.

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

Background Atogepant is an oral, small-molecule, calcitonin gene–related peptide receptor antagonist for the preventive treatment of migraine. Methods In the double-blind, phase 3 ADVANCE trial, participants with 4–14 migraine days/month were randomized to atogepant 10 mg, 30 mg, 60 mg, or placebo once daily for 12 weeks. We evaluated the time course of efficacy of atogepant for the preventive treatment of migraine. Analyses included change from baseline in mean monthly migraine days during each of the three 4-week treatment periods, change in weekly migraine days during weeks 1–4, and proportion of participants with a migraine on each day during the first week. Results We analyzed 873 participants (n = 214 atogepant 10 mg, n = 223 atogepant 30 mg, n = 222 atogepant 60 mg, n = 214 placebo). For weeks 1–4, mean change from baseline in mean monthly migraine days ranged from −3.1 to −3.9 across atogepant doses vs −1.6 for placebo ( p Conclusion Atogepant demonstrated treatment benefits as early as the first full day after treatment initiation, and sustained efficacy across each 4-week interval during the 12-week treatment period. Clinical trial registration: ClinicalTrials.gov identifier: NCT03777059

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: Medullary thyroid carcinoma (MTC) is a rare neuro-endocrine tumor that arises from the C-cells of the thyroid. About 20- 25 % of MTC cases may be associated with hereditary syndromes like MEN 2A, MEN 2B and Familial MTC. The survival rate is related mainly to the age of the patient, stage of the disease and completion of the surgical resection. Methods: Retrospective review of 11 patients who were diagnosed with medullary thyroid cancer in our general surgery department during the period from 2011 to 2021. All patients had preoperative assessment including history taking, clinical examination, tumor marker (calcitonin and CEA), thyroid function testing, ultrasonography and FNAC. All patients underwent genetic assessment to exclude any underlying genetic mutation. Results: The mean age of diagnosis was 57.73 ± 16.45 years of age. Three patients were males and eight were females. All patients had total thyroidectomy, central and lateral neck dissection except one patient who had prophylactic thyroidectomy due to familial inherited RET mutation. Two patients had recurrence; both of them had high-stage tumor (T3 and T4) with multiple cervical lymph nodes metastasis. The sensitivity of serum calcitonin for the detection of MTC was about 98%. Patients, who had localized disease and underwent complete surgical resection, had good overall survival rates compared with patients with advanced disease. Conclusion: MTC represent a heterogeneous group of thyroid cancers. The overall survival is better than that of undifferentiated thyroid cancers. Complete resection of the thyroid tumor and any local or regional metastases provides the only cure for patients with MTC. Further researches are still needed to improve our understanding and management of MTC.

ackground. Lung cancer markers are low levels of the hormone calcitonin in the blood, and high levels of proteins osteocalcin and osteopontin, connected to each other, reflect the processes of bone metastasis and have a predictive value. Objective: to evaluate blood levels of calcitonin, osteocalcin and osteopontin, the factors determining them, the nature of relationships and prognostic role in bone metastasis at different variants of lung cancer. Materials and methods. The study included 86 patients with lung cancer aged 24 to 80 years (mean 58 years), among whom there were 84 % of men and 16 % of women. Central lung cancer occurred in 81 % of cases, peripheral — in 19 %. Small-cell lung cancer has been detected in 21 % of patients, non-small-cell — in 79 %, including adenocarcinoma — in 38 %, squamous-cell carcinoma — in 35 %, large-cell carcinoma — in 6 %. IIIA stage of neoplastic process was noted in 12 % of cases, IIIB — in 21 %, IV — in 67 %. Results. Lung cancer is accompanied by a decrease of bone-related hormone calcitonin in the blood of 20 % of patients on the background of increased concentrations of tumor markers osteocalcin and osteopontin (in 76 and 79 % of cases, respectively), which is closely associated with morphological variant (small- and non-small-cell), the stage and severity of pathological process, determines the development of compression syndrome, tumor invasion into the chest wall, metastasis in lymph nodes and bones, occurrence of chemoradiotherapy complications in the form of radiation pulmonary fibrosis, pulmonary hypertension and myelodepression, and indicators of osteocalcin- and osteopontinemia are inversely correlated with the duration of life of patients. Conclusions. In lung cancer, calcitonin, osteocalcin and osteopontin are the markers of the severity of the disease, reflect the metastasis of the tumor process in the skeleton and have a predictive value., Актуальность. Маркерами рака легкого являются низкие уровни в крови гормона кальцитонина, а высокие показатели белков остеокальцина и остеопонтина, связанные между собой, отражают процессы костного метастазирования и обладают прогностической значимостью. Цель исследования: оценить уровни в крови кальцитонина, остеокальцина и остеопонтина, факторы, их определяющие, характер взаимосвязей и прогностическую роль в костном метастазировании при разных вариантах течения рака легкого. Материалы и методы. Обследованы 86 больных раком легкого в возрасте от 24 до 80 лет (в среднем 58 лет), среди которых было 84 % мужчин и 16 % женщин. Центральная форма рака имела место в 81 % наблюдений, периферическая — в 19 %. Мелкоклеточный гистологический вариант заболевания установлен у 21 % от числа больных, немелкоклеточный — у 79 %, в том числе аденокарцинома — у 38 %, плоскоклеточная карцинома — у 35 %, крупноклеточная карцинома — у 6 %. IIIA стадия опухолевого процесса отмечена в 12 % случаев, IIIB — в 21 %, IV — в 67 %. Результаты. Рак легкого сопровождается уменьшением в крови у 20 % больных остеоассоциированного гормона кальцитонина на фоне повышения концентраций опухолевых маркеров остеокальцина и остеопонтина (соответственно в 76 и 79 % наблюдений), что тесно связано с морфологическим вариантом (мелко- и немелкоклеточный), стадийностью и тяжестью течения патологического процесса, определяет развитие компрессионного синдрома, прорастание опухоли в грудную стенку, метастазирование в лимфатические узлы и кости, возникновение осложнений химиорадиотерапии в виде лучевого пневмофиброза, легочной гипертензии и миелодепрессии, а показатели остеокальцин- и остеопонтинемии обратно коррелируют с продолжительностью жизни больных. Выводы: кальцитонин, остеокальцин и остеопонтин при раке легкого являются маркерами тяжести течения заболевания, отражают метастазирование опухолевого процесса в скелет и обладают прогностической значимостью., Актуальність. Маркерами раку легені є низькі рівні в крові гормона кальцитоніну, а високі показники білків остеокальцину й остеопонтину, пов’язані між собою, відображають процеси кісткового метастазування і мають прогностичну значущість. Мета дослідження: оцінити рівні в крові кальцитоніну, остеокальцину та остеопонтину, чинники, що їх визначають, характер взаємозв’язків й прогностичну роль в кістковому метастазуванні при різних варіантах перебігу раку легені. Матеріали і методи. Обстежені 86 хворих на рак легені віком від 24 до 80 років (в середньому 58 років), серед яких було 84 % чоловіків і 16 % жінок. Центральна форма раку відзначалася у 81 % спостережень, периферійна — в 19 %. Дрібноклітинний гістологічний варіант захворювання встановлено у 21 % хворих, недрібноклітинний — у 79 %, у тому числі аденокарцинома — у 38 %, плоскоклітинна карцинома — у 35 %, великоклітинна — у 6 %. IIIA стадію пухлинного процесу відзначено у 12 % випадків, IIIB — у 21 %, IV — в 67 %. Результати. Рак легені супроводжується зменшенням у крові 20 % хворих остеоасоційованого гормона кальцитоніну на фоні підвищення концентрацій пухлинних маркерів остеокальцину й остеопонтину (відповідно в 76 і 79 % спостережень), що тісно пов’язано з морфологічним варіантом (дрібно- та недрібноклітинний), стадійністю й тяжкістю перебігу патологічного процесу, визначає розвиток компресійного синдрому, проростання пухлини в грудну стінку, метастазування в лімфатичні вузли і кістки, виникнення ускладнень хіміорадіотерапії у вигляді променевого пневмофіброзу, легеневої гіпертензії та мієлодепресії, а показники остеокальцин- і остеопонтинемії обернено корелюють із тривалістю життя хворих. Висновки: кальцитонін, остеокальцин й остеопонтин при раку легені є маркерами тяжкості перебігу захворювання, відображають метастазування пухлинного процесу в скелет і мають прогностичну значущість.

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.

Medullary thyroid carcinoma (MTC) is an aggressive form of thyroid cancer. Early detection is essential because only complete resection of the thyroid tumor and any local metastases can cure MTC. Calcitonin (CT) is a marker used for diagnosis of MTC. In controversial cases of slightly elevated CT levels, stimulation tests have shown their utility, but their safety should also be taken into account. Our aim is to present our own experience regarding the safety of CT stimulating tests. We applied a specific protocol of calcium stimulation test in 176 patients after informed consent (115 women with a median age of 46 years, range 21–79; 61 men with a median age of 54 years, range 22–78). We recorded the side effects and a further analysis was performed. The most frequent side effects noted were hot flashes in 159 out of 176 patients (90.34%), followed by dysgeusia (32/176) and bradycardia (10/176). Severe bradycardia was reported in only one patient (0.568%), which was rapidly reversible. There was no correlation between patients’ age, weight, height, body mass index, basal CT or peak stimulated CT, and grade of severity, but men were more likely to develop cardiovascular side effects than women, namely, bradycardia, tachycardia, ventricular or atrial extrasystoles, hypertension, hypotension, or angina (p = 0.024), with an odds ratio of 2.94 (CI: 1.11–7.76). We recommend thyroid surgery in all women with sCT above 285 pg/ml. The calcium stimulation test is well tolerated, with few adverse reactions. The test should be performed with appropriate precautions (i.e., ECG monitoring during and after the test) to minimize the possibility of a serious event.

Migraine is ranked as a leading cause of years lived with disability among all neurological disorders. Therapies targeting the calcitonin gene-related peptide (CGRP) signaling pathway, including monoclonal antibodies against the receptor or ligand and small molecule CGRP receptor antagonists (gepants), are today approved for migraine prophylaxis with additional compounds expected to be introduced to the market soon. In this review, we consider other putative prophylactic migraine drugs in development, including compounds targeting G-protein coupled receptors, glutamate, ion channels, and neuromodulatory devices. Emergence of these new interventions could complement our current treatment armamentarium for migraine management.

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.

Atogepant is an oral, small-molecule, calcitonin gene-related peptide receptor antagonist that is being investigated for the preventive treatment of migraine.In a phase 3, double-blind trial, we randomly assigned adults with 4 to 14 migraine days per month in a 1:1:1:1 ratio to receive a once-daily dose of oral atogepant (10 mg, 30 mg, or 60 mg) or placebo for 12 weeks. The primary end point was the change from baseline in the mean number of migraine days per month across the 12 weeks. Secondary end points included headache days per month, a reduction from baseline of at least 50% in the 3-month average of migraine days per month, quality of life, and scores on the Activity Impairment in Migraine-Diary (AIM-D).A total of 2270 participants were screened, 910 were enrolled, and 873 were included in the efficacy analysis; 214 were assigned to the 10-mg atogepant group, 223 to the 30-mg atogepant group, 222 to the 60-mg atogepant group, and 214 to the placebo group. The mean number of migraine days per month at baseline ranged from 7.5 to 7.9 in the four groups. The changes from baseline across 12 weeks were -3.7 days with 10-mg atogepant, -3.9 days with 30-mg atogepant, -4.2 days with 60-mg atogepant, and -2.5 days with placebo. The mean differences from placebo in the change from baseline were -1.2 days with 10-mg atogepant (95% confidence interval [CI], -1.8 to -0.6), -1.4 days with 30-mg atogepant (95% CI, -1.9 to -0.8), and -1.7 days with 60-mg atogepant (95% CI, -2.3 to -1.2) (P0.001 for all comparisons with placebo). Results for the secondary end points favored atogepant over placebo with the exceptions of the AIM-D Performance of Daily Activities score and the AIM-D Physical Impairment score for the 10-mg dose. The most common adverse events were constipation (6.9 to 7.7% across atogepant doses) and nausea (4.4 to 6.1% across atogepant doses). Serious adverse events included one case each of asthma and optic neuritis in the 10-mg atogepant group.Oral atogepant once daily was effective in reducing the number of migraine days and headache days over a period of 12 weeks. Adverse events included constipation and nausea. Longer and larger trials are needed to determine the effect and safety of atogepant for migraine prevention. (Funded by Allergan; ADVANCE ClinicalTrials.gov number, NCT03777059.).

Amiodarone (AM) is one of the most effective antiarrhythmic drugs and normally administrated by intravenous infusion which is liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. Intermedin (IMD), a member of calcitonin family, has a broad spectrum of biological effects including anti-inflammatory effects, antioxidant activities, and antiapoptosis. But now, the protective effects of IMD against amiodarone-induced phlebitis and the underlying molecular mechanism are not well understood. In this study, the aim was to investigate the protective efficiency and potential mechanisms of IMD in amiodarone-induced phlebitis. The results of this study revealed that treatment with IMD obviously attenuated apoptosis and exfoliation of vascular endothelial cells and infiltration of inflammatory cells in the rabbit model of phlebitis induced by intravenous infusion of amiodarone compared with control. Further tests in vitro demonstrated that IMD lessened amiodarone-induced endothelial cell apoptosis, improved amiodarone-induced oxidative stress injury, reduced inflammatory reaction, and activated the Wnt/β-catenin signal pathway which was inhibited by amiodarone. And these effects could be reversed by Wnt/β-catenin inhibitor IWR-1-endo, and si-RNA knocked down the gene of Wnt pathway. These results suggested that IMD exerted the protective effects against amiodarone-induced endothelial injury via activating the Wnt/β-catenin pathway. Thus, IMD could be used as a potential agent for the treatment of phlebitis.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor of parafollicular C cells. The majority of MTCs occur sporadically, but about 30% of the cases are associated with multiple endocrine neoplasia type 2 (MEN2) syndrome or familial MTC. Generally, MTCs have no clinical manifestation, but infrequently the patients develop symptoms of hypercortisolism by secreting adrenocorticotropic hormone (ACTH) or corticotropin-releasing hormone (CRH). Although ectopic Cushing syndrome is only found in 0.7% of MTC patients, it can lead to fatal consequences if left untreated. Over 50 cases of MTC-related Cushing syndrome have been reported, and few autopsy cases exist in the literature. In those cases, the tumor cells are positive for calcitonin, but mostly display negative immunostaining for ACTH or CRH. The authors report an autopsy case of a 22-year-old woman who was found dead with no medical history whose cause of death was diabetic ketoacidosis associated with MTC, which showed poor calcitonin stainability.

PURPOSE: To investigate the changes in tear neuromediators and corneal subbasal nerve plexus following small incision lenticule extraction (SMILE) and to study its association with different refractive power of corrections. METHODS: Thirty patients were included for tear neuromediator analysis (40 eyes) and corneal nerve analysis using in vivo confocal microscopy scans (20 eyes). Tear samples were collected preoperatively and 1 week and 1, 3, 6, and 12 months postoperatively and analyzed for the substance P, calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) concentrations using the enzyme-linked immunosor-bent assay (ELISA). RESULTS: Corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), and corneal nerve branch density (CNBD) decreased significantly postoperatively, then gradually increased from 3 months onward, but did not recover to the baseline levels at 12 months. Tear substance P and CGRP levels remained stable over 12 months. Tear NGF levels demonstrated a small peak at 1 week before decreasing significantly compared to preoperative levels at 6 months ( P = .03) and 12 months ( P = .007). The 1-month reduction in CNFL, tear substance P, and CGRP concentrations were significantly correlated with the corrected spherical equivalent (SE) ( r = 0.71 for CNFL; r = −0.33 to −0.52 at different time points for substance P and CGRP, respectively, all P < .05). Compared to the low to moderate myopia group, the high myopia group (corrected SE greater than −6.00 diopters) had a significantly greater decrease in CNFD, significantly higher tear substance P concentrations at 1 week, 1 month, and 6 months, and significantly higher tear CGRP concentrations at 1 and 6 months. CONCLUSIONS: These results provide new insight into the neurobiological responses and their potential implications in corneal nerve damage and recovery after SMILE. High myopia treatment was associated with greater corneal denervation and neuroinflammation. [ J Refract Surg . 2021;37(8):516–523.]

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.

Postoperative infections are a common entity following elective gastrointestinal surgery among which intra-abdominal infection is notorious and life threatening. Early detection could reduce postoperative morbidity and permit safe and early discharge. This study was aimed to establish the usefulness of procalcitonin (PCT) and C-reactive protein (CRP) on postoperative day 3 as reliable markers for early detection of intra-abdominal infection and other postoperative infections following elective gastrointestinal cancer surgery. A total of 125 patients following elective gastrointestinal cancer surgery were prospectively observed until discharge from January 2018 to December 2019. The incidence of intra-abdominal infections and other postoperative infections was recorded. Serum PCT and CRP were estimated on postoperative day 3 for all the patients. ROC analysis of PCT and CRP was performed to establish their predictability in detecting these infections. Risk factors for postoperative infections were also studied. The incidence of intra-abdominal infection (IAI) was 24%. The difference in PCT between the infected and non-infected patients was statistically significant (p = 0.001) but not in CRP (p = 0.223). On ROC analysis of CRP and PCT in detecting IAI, the areas under the curve were 0.494 and 0.615 respectively. Raised serum PCT values on postoperative day 3 indicate the presence of infections and should prompt the surgeon to consider other investigations to confirm the presence of IAI and other postoperative infections and plan early intervention thus expediting the postoperative recovery. CTRI/2018/12/016695

The CGRP system has emerged as a key pharmacological target for the treatment of migraine. However, some individuals who suffer from migraine have low or no response to anti-CGRP or other treatments, suggesting the need for additional clinical targets. CGRP belongs to the calcitonin family of peptides, which includes calcitonin, amylin, adrenomedullin and adrenomedullin 2. These peptides display a range of pro-nociceptive and anti-nociceptive actions, in primary headache conditions such as migraine. Calcitonin family peptides also show expression at sites relevant to migraine and pain. This suggests that calcitonin family peptides and their receptors, beyond CGRP, may be therapeutically useful in the treatment of migraine and other pain disorders. This review considers the localisation of the calcitonin family in peripheral pain pathways and discusses how they may contribute to migraine and pain. LINKED ARTICLES: This article is part of a themed issue on Advances in Migraine and Headache Therapy (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.3/issuetoc.

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.