[Related factors of euthyroid sick syndrome in patients with sepsis].

OBJECTIVE: To evaluate the prevalence of euthyroid sick syndrome (ESS) in sepsis patients and to explore its influencing factors. METHODS: In the study, 365 patients diagnosed with sepsis in the emergency critical care department of Shanghai First People's Hospital from January 2017 to January 2023 were retrospectively enrolled. The patients were divided into ESS and non-ESS groups based on whether the patients were complicated with ESS.Baseline variables and relevant clinical data of the enrolled patients were collected. The prevalence of ESS in sepsis patients and its influencing factors were evaluated by multivariate Logistic regression analysis, and the 30-day survival rates were compared between the two groups. The optimal cutoff value for free triiodothyronine (FT3) was explored to predict death in the patients with sepsis. RESULTS: There were 103 sepsis patients with ESS, accounting for 28.2% of the total cases. The severity of sepsis in ESS group was significantly higher than that in non-ESS group (P < 0.05). The acute physiology and chronic health evaluationⅡ(APACHEⅡ)score and sequential organ failure assessment (SOFA) score of ESS group were significantly higher than those of non-ESS group (P < 0.05). C-reactive protein (CRP), procalcitonin (PCT), serum amyloid A (SAA) and interleukin-6 (IL-6) in ESS group were higher than those in non-ESS group. total cholesterol(TC)and high-density liptein cholesterol(HDL-C)in ESS group were lower than those in non-ESS group, and the differences were statistically significant (P < 0.05).Multivariate Logistic regression analysis showed that PCT, IL-6, CRP, SAA and activated partial thromboplatin time (APTT) were independent risk factors for ESS in the sepsis patients (OR values were 1.105, 1.006, 1.005, 1.009 and 1.033, respectively; 95% CI were 1.044-1.170, 1.001-1.012, 1.001-1.009, 1.005-1.014, 1.004-1.062, respectively, P < 0.05).The 30-day survival rate in ESS group was significantly lower than that in non-ESS group, the Long-rank chi-square test value was 16.611, and the difference was statistically significant (P < 0.05).The receiver operation characteristic area under the curve (AUCROC)of FT3 predicted death in the patients with sepsis was 0.924 (95% CI 0.894-0.954). The serum FT3 cutoff point was 3.705 pmol/L, the specificity was 0.868, and the sensitivity was 0.950. CONCLUSION: In this study, the incidence of ESS in sepsis patients was determined to be 28.2% with poor prognosis. The results showed that PCT, IL-6, CRP, SAA and APTT were independent risk factors for ESS in sepsis patients, while HDL-C was a protective factor (P < 0.05). FT3 is a novel potential biomarker for predicting death in patients with sepsis.

The impact of preoperative calcitonin screening on the prognosis of patients with medullary thyroid cancer: a retrospective multicenter cohort study.

PURPOSE: There is still controversy in different guidelines regarding the necessity of routine preoperative calcitonin (Ctn) testing in medullary thyroid cancer (MTC). The level of preoperative Ctn may influence the extent of surgery. METHODS: This retrospective multicenter cohort study involved 149 MTC patients from 6 centers between 2013 to 2023. Clinical characteristics, surgical procedure and clinical outcomes were compared between Ctn-screened and Non-screened group. Kaplan-Meier method was used to estimate recurrence-free survival (RFS) and overall survival (OS). RESULTS: In total, 127 MTC patients with preoperative Ctn screening and 22 MTC patients without screening were analyzed. MTC patients with preoperative Ctn screening underwent more radical surgical procedures including total thyroidectomy and lymph node dissection, compared to those without screening (84.3% vs. 68.2% and 91.3% vs. 72.7%, respectively). The rate of recurrence and death were lower in the Ctn-screened group (16.1% vs. 36.4%, 0.8% vs. 18.2%, respectively). The survival curve showed a significantly better overall survival in Ctn-screened group than Non-screened group (HR:17.932, 95% CI 1.888-170.294, p-value = 0.001), while no significant difference was observed of RFS between two groups (HR:1.6, 95% CI 0.645-3.966, p-value = 0.307). CONCLUSION: Preoperative Ctn screening can prompt surgeons choosing more radical initial surgical treatment for MTC patients, potentially leading to better long-term outcomes. Further evaluation of the cost-effectiveness of routine Ctn screening in thyroid nodule patients is warranted.

Spontaneous and Treatment-Related Changes of Serum Calcitonin in Medullary Thyroid Cancer: Long-Term Experience in a Patient With Multiple Endocrine Neoplasia Type 2B.

PURPOSE: Medullary thyroid carcinoma (MTC) in MEN2B syndrome is associated with germline RET mutation. Patients harboring de novo mutations are usually diagnosed at more advanced disease stages. We present a young woman with Met918Th mutation diagnosed with stage IV MTC at age 10 years. METHODS: The disease progressed despite total thyroidectomy and multiple surgical interventions for cervical lymph node recurrences, leading to distant metastases in the fifth year after the initial diagnosis. Subsequently, she underwent five different types of tyrosine kinase inhibitor (TKI) treatments. The 17-year disease course was divided into periods defined by four surgical interventions and sequential treatment intervals with four multikinase (sunitinib, vandetanib, cabozantinib, and lenvatinib) and one RET-selective TKI (selpercatinib). Tumor growth for different phases of spontaneous development and drug treatment intervals was characterized by changes in serial log-transformed calcitonin measurements (n = 114). RESULTS: Three operations (one for calcitonin-producing adrenal pheochromocytoma) were associated with drops in calcitonin levels. All of the nonselective TKIs were stopped due to adverse effects. As reflected by the negative calcitonin doubling rate, the best treatment response was observed with selpercatinib, which was associated with an initial large drop followed by a decreasing calcitonin trajectory over 514 days without any major side effects. CONCLUSION: This case of MEN2B medullary thyroid cancer with long-term survival presents how the effectiveness of different treatment modalities can be estimated using log-transformed calcitonin levels. Furthermore, our experience supports the view that serial calcitonin measurements may be more sensitive than radiological follow-up in advanced MTC. Our patient also represents a new case of rarely reported calcitonin-producing pheochromocytomas.

[Progress and controversy on the extent of surgery for medullary thyroid carcinoma based on calcitonin levels].

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor originating from the parafollicular cells (C cells) of the thyroid gland, classified as sporadic and hereditary. Calcitonin (Ctn) secreted by the C cells is a specific serological marker for MTC, which is of great value in diagnosis, treatment and postoperative management of MTC. The effect of chemoradiotherapy and 131I therapy on MTC is limited, with surgery being the primary therapy. Given the aggressive nature and relatively poor prognosis of MTC, the reasonable surgical extent is crucial for improving cure rate and prognosis of patients. However, there are still some controversies regarding the extent of surgery for MTC. This article elaborates on the research progress and controversies of serum Ctn levels in assisting the evaluation of the extent of surgery for MTC.

[Early diagnostic value of Presepsin in sepsis: a prospective study on a population with suspected sepsis in fever clinics].

OBJECTIVE: To analyze the early diagnostic value of plasma soluble cluster of differentiation 14 subtype (sCD14-ST, Presepsin) in sepsis in a population with suspected sepsis in fever clinic. METHODS: A prospective observational study was conducted. The patients admitted to the fever clinic of Beijing Chaoyang Hospital from April to December 2022 were enrolled as the study objects. According to sequential organ failure assessment (SOFA) score, the patients were divided into low SOFA score group (SOFA score ≤3) and high SOFA score group (SOFA score > 3). Venous blood was collected at the time of admission. The level of plasma Presepsin was detected by chemiluminescence enzyme-linked immunoassay. The level of plasma procalcitonin (PCT) was detected by enzyme-linked immunofluorescence method. The level of C-reactive protein (CRP) was detected by scattering turbidimetry. White blood cell count (WBC) and neutrophil count (NEUT) were measured by automatic blood cell analyzer. For patients with fear of cold or chills, venous blood of upper limbs was taken for blood culture at the time of admission. The differences in inflammatory biomarkers were compared between the two groups. Binary multivariate Logistic regression analysis was used to screen the early risk factors of sepsis in fever outpatients with suspected sepsis. Receiver operator characteristic curve (ROC curve) was drawn to investigate the early diagnostic value of Presepsin and other inflammatory markers in sepsis, and to analyze the optimal cut-off value. RESULTS: A total of 149 fever outpatients with suspected sepsis were enrolled, including 92 patients with low SOFA score and 57 patients with high SOFA score. Plasma PCT and Presepsin levels in the high SOFA score group were significantly higher than those in the low SOFA score group [PCT (µg/L): 0.77 (0.18, 2.02) vs. 0.22 (0.09, 0.71), Presepsin (ng/L): 1 129.00 (785.50, 1 766.50) vs. 563.00 (460.50, 772.25), both P < 0.01]. There was no significant difference in WBC, NEUT, CRP or positive rate of blood culture between the high and low SOFA score groups [WBC (×109/L): 11.32±5.47 vs. 11.14±5.29, NEUT (×109/L): 9.88±4.89 vs. 9.60±5.10, CRP (mg/L): 54.05 (15.95, 128.90) vs. 46.11 (19.60, 104.60), blood culture positivity rate: 42.3% (11/26) vs. 29.4% (10/34), all P > 0.05]. Multivariate Logistic regression analysis showed that Presepsin was an early risk factor for sepsis in suspected sepsis patients in fever clinics [odds ratio (OR) = 16.96, 95% confidence interval (95%CI) was 6.35-45.29, P = 0.000]. ROC curve analysis showed that the early diagnostic value of Presepsin in sepsis was significantly better than WBC, NEUT, CRP, PCT, and blood culture [the area under the ROC curve (AUC) and 95%CI: 0.832 (0.771-0.899) vs. 0.522 (0.424-0.619), 0.532 (0.435-0.629), 0.533 (0.435-0.632), 0.664 (0.574-0.753), 0.554 (0.458-0.650)]. When the optimal cut-off value of Presepsin was 646.50 ng/L, its sensitivity and positive predictive value were higher than those of WBC, NEUT, CRP, and PCT (sensitivity: 89.5% vs. 38.6%, 68.4%, 38.6%, 57.9%; positive predictive value: 64.6% vs. 44.9%, 44.3%, 47.8%, 55.9%). CONCLUSIONS: Plasma PCT and Presepsin have early diagnostic value for sepsis in suspected sepsis patients in fever clinics, and Presepsin is more sensitive than PCT and can be used as an early marker of sepsis.

Time Kinetics and prognosis roles of calcitonin after surgery for medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a malignant tumor with low incidence. Currently, most studies have focused on the prognostic risk factors of MTC, whatever, time kinetic and risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) are yet to be elucidated. METHODS: A retrospective study was conducted for 190 MTC patients. Risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) were analyzed. The predictors of calcitonin normalization time (CNT) and biochemical persistent/recurrent time (BPT) were identified. Further, the prognostic roles of CNT and BPT were also demonstrated. RESULTS: The 5- and 10-year DFS were 86.7% and 70.2%, respectively. The 5- and 10-year OS were 97.6% and 78.8%, respectively. CN was achieved in 120 (63.2%) patients, whereas BP was presented in 76 (40.0%) patients at the last follow up. After curative surgery, 39 (32.5%) and 106 (88.3%) patients achieved CN within 1 week and 1 month. All patients who failed to achieve CN turned to BP over time and 32/70 of them developed structural recurrence. The median time of CNT and BPT was 1 month (1 day to 84 months) and 6 month (3 day to 63months), respectively. LNR > 0.23 and male gender were independent predictors for CN and BP. LNR > 0.23 (Hazard ratio (HR), 0.24; 95% CI,0.13-0.46; P < 0.01) and male gender (HR, 0.65; 95% CI, 0.42-0.99; P = 0.045) were independent predictors for longer CNT. LNR > 0.23 (HR,5.10; 95% CI,2.15-12.11; P < 0.01) was still the strongest independent predictor followed by preoperative serum Ctn > 1400ng/L (HR,2.34; 95% CI,1.29-4.25; P = 0.005) for shorter BPT. In survival analysis, primary tumor size > 2 cm (HR, 5.81; 95% CI,2.20-15.38; P < 0.01), CNT > 1 month (HR, 5.69; 95% CI, 1.17-27.61; P = 0.031) and multifocality (HR, 3.10; 95% CI, 1.45-6.65; P = 0.004) were independent predictor of DFS. CONCLUSION: Early changes of Ctn after curative surgery can predict the long-term risks of biochemical and structural recurrence, which provide a useful real-time prognostic information. LNR significantly affect the time kinetic of biochemical prognosis. Tumor burden and CNT play a crucial role in MTC survival, the intensity of follow-up must be tailored accordingly.

Correlations between bone metabolism biomarkers and fluoride exposure in adults and children.

Increased exposure to fluoride, which notably affects bone metabolism, is a global concern. However, the correlations and sensitivity of bone metabolism to fluoride remain controversial. In this cross-sectional study, 549 children (aged 7-12 years) and 504 adults (≥ 18 years old) were recruited in the high-fluoride areas of the Henan Province. Urinary fluoride (UF) level was determined using a fluoride electrode. Fasting venous blood serum was collected to measure bone metabolism biomarkers. The selected bone metabolism biomarkers for children included bone alkaline phosphatase (BALP), serum alkaline phosphatase (ALP), osteocalcin (OCN), calcitonin (CT), parathyroid hormone (PTH), phosphorus (P5+), and calcium (Ca2+). For adults, the biomarkers included ALP, CT, PTH, ß-CrossLaps (ß-CTX), P5+, and Ca2+. The correlations between UF and bone metabolism biomarkers were analyzed using binary logistic regression, a trend test, a generalized additive model, and threshold effect analysis. Regression analysis indicated a significant correlation between serum OCN, PTH, and UF levels in children aged 7-9 years. Serum OCN, PTH, and BALP contents were significantly correlated with UF in boys (P < 0.05). Furthermore, the interaction between age and UF affected serum P5+ and PTH (P < 0.05). The generalized additive model revealed nonlinear dose-response relationships between P5+, BALP, and UF contents in children (P < 0.05). Serum OCN level was linearly correlated with the UF concentration (P < 0.05). Similarly, a significant correlation was observed between ß-CTX and UF levels in adults. In addition, significant correlations were observed between UF-age and serum Ca2+, ß-CTX, and PTH contents. There was a non-linear correlation between serum Ca2+, P5+, and ß- CTX and UF levels (P < 0.05). Overall, serum OCN, BALP, and P5+ levels can serve as sensitive bone metabolism biomarkers in children, while ß-CTX, P5+, and Ca2+ can be considered fluoride-sensitive bone metabolism biomarkers in adults.

Diagnostic tests for medullary thyroid carcinoma: an umbrella review.

PURPOSE: To summarize the more robust evidence about the performance of tools useful for diagnosis of medullary thyroid carcinoma (MTC) such as calcitonin (Ctn) and other circulating markers, ultrasound (US), fine-needle aspiration (FNA), and other imaging procedures. METHODS: This systematic review of systematic reviews was carried out according to a predefined protocol. A search string was created. An electronical comprehensive search of literature was performed on December 2022. Quality assessment of eligible systematic reviews was performed and main findings were described. RESULTS: Twenty-three systematic reviews were included and several findings were achieved. Ctn is the most reliable diagnostic marker of MTC with no evidence of improvement with stimulation test. CEA doubling time is more reliable than Ctn in identifying MTC with poorer prognosis. US sensitivity is suboptimal in MTC and only just over half of cases are at high risk according to Thyroid Imaging And Reporting Data Systems. Cytology can correctly detect MTC in just over half of cases and measuring Ctn in washout fluid from FNA is necessary. PET/CT is useful for detecting recurrent MTC. CONCLUSIONS: Future guidelines of both thyroid nodule management and MTC diagnosis should consider these evidence-based data.

Beyond the Recommendations of the Clinical Guidelines for Medullary Thyroid Cancer - A Case Report.

Medullary thyroid cancer (MTC) is a rare disease from parafollicular C cells. Calcitonin has been suggested as a screening; its levels are proportional to the tumor size and predictive of metastatic disease. We present a case where an early action was taken with lower cut-off points. Male patient, 49 years old. Thyroid ultrasound (US) with a suspicious nodule. Fine Needle Aspiration Biopsy (FNAB) suggests MTC, with pre-operative serum calcitonin (CTN) of 591 pg/mL. Total thyroidectomy with central and bilateral dissection was performed. Biopsy: MTC in left nodule of 26 mm without lymph nodes (LN) metastases. Follow-up with undetectable CTN for six years. After that, CT was 4.7 pg/mL, and carcinoembryonic antigen (CEA) was 1.2 ng/mL. Neck US showed bilateral LN. FNAB of LN does not show recurrence. A progressive rise of markers with doubling time of CTN and CEA was 16 and 51.3 months, respectively. CTN raised until 112 pg/mL. Given the lack of cervical compromise, a neck and lung CT, liver MRI, and bone scintigraphy were ordered despite CTN levels < 150 pg/mL. MRI showed hypervascular hepatic lesions, contrasted with gadoxetic acid. PET Ga68-DOTATATE showed lesions with overexpression of somatostatin receptors in the liver. Surgery was done, and a biopsy confirmed metastases. Conclusions: The clinical guidelines may allow the management of cases; however, they should be used considering each case context. In our patient, if the guidelines had been strictly followed, it would not have been possible to detect liver metastases to achieve a surgical resection with curative intent.

Value of combined detection of serum amyloid A, C-reactive protein and procalcitonin in differential diagnosis of respiratory tract infection in children of China.

OBJECTIVE: To explore the diagnostic value of combined detection of serum amyloid A (SAA), C-reactive protein (CRP) and procalcitonin (PCT) in children with bacteria or non-bacterial respiratory tract infection. METHODS: 200 children with respiratory tract infections diagnosed in our hospital were included in the study. According to the results of the aetiological examination, they were divided into bacterial infection group and non-bacterial infection group. At the same time, 100 healthy children admitted to the hospital for physical examination during the same period were selected as the healthy subjects control group. Changes in serum SAA, PCT and CRP in three groups were compared. Comparison of a positive rate of the single index and combined detection were performed. Children with bacterial infections were treated with conventional antibiotics. The changes in serum SAA, PCT and CRP in the infection group before and after treatment were compared. The efficacy of SAA, PCT and CRP alone and in combination was compared. RESULTS: The serum SAA, PCT and CRP levels in the bacterial infection group were higher than those in the non-bacterial infection group and healthy children, and the differences were statistically significant. The positive detection rates and combined detection rates of serum SAA, PCT and CRP in the bacterial infection group were higher than those in the non-bacterial infection group and the healthy subject's control group. After conventional antibiotic treatment, serum SAA, PCT and CR levels in children with bacterial infection were significantly decreased. CONCLUSION: The combined detection based on SAA, CRP and PCT can effectively identify and diagnose respiratory tract infection in children, providing a certain reference for the promotion of the diagnostic scheme. Key messagesSerum SAA, PCT and CRP were highly expressed in children with respiratory tract infection, and the expression level was the highest in children with bacterial pneumonia.The combined detection of serum SAA, CRP and PCT indicators have higher diagnostic efficiency and can effectively make a differential diagnosis of respiratory tract infection in children.

Association between blood lead levels and markers of calcium homeostasis: a systematic review and meta-analysis.

Chronic Pb exposure associated systemic illness are partly posited to involve calcium homeostasis. Present systematic review aims to comprehensively evaluate the association between chronic lead exposure and markers of calcium homeostasis. Observational studies documenting the changes in calcium homeostasis markers (i.e. serum calcium, parathyroid hormone, vitamin D & calcitonin) between occupationally Pb exposed group and control group were systematically searched from pubmed-Medline, Scopus, and Embase digital databases since inception to September 24, 2021. The protocol was earlier registered at PROSPERO (ID: CRD42020199503) and executed adhering to PRISMA 2020 guidelines. Mean differences of calcium homeostasis markers between the groups were analysed using random-effects model. Conventional I2 statistics was employed to assess heterogeneity, while the risk for various biases were assessed using Newcastle Ottawa Scale. Sub-group, sensitivity and meta-regression analyses were performed where data permitted. Eleven studies including 837 Pb exposed and 739 controls were part of the present study. Pb exposed group exhibited higher mean blood lead level [i.e. 36.13 (with 95% CI 25.88-46.38) µg/dl] significantly lower serum calcium (i.e. - 0.72 mg/dl with 95% CI - 0.36 to - 1.07) and trend of higher parathyroid levels and lower vitamin D levels than controls. Heterogeneity was high (I2 > 90%) among the studies. Considering the cardinal role of calcium in multiple biological functions, present observations emphasis the need for periodic evaluation of calcium levels and its markers among those with known cumulative Pb exposure.

Preoperative calcitonin testing improves the diagnosis of medullary thyroid carcinoma in female and male patients.

AIM: Calcitonin (Ctn) measurement in patients with thyroid disease could potentially increase the detection rates of medullary thyroid carcinoma (MTC) but remains a controversial issue. The aim of this study was to evaluate routine preoperative Ctn measurements. METHODS: All patients with thyroid surgery documented in the prospective StuDoQ|Thyroid registry between March 2017 and September 2020 were included. Cutoff levels for Ctn were determined with receiver-operating characteristic analyses to assess the preoperative diagnosis of MTC in subgroups for females and males. FINDINGS: In 29 590 of 39 679 patients (75%) participating in the registry, routine preoperative Ctn testing was performed. In 357 patients (227 females and 130 males), histopathology confirmed MTC with a mean tumor size of 14.7 mm (±12.43). Biochemical cure was achieved in 71.4% of the patients. Ctn levels between 11 and 20 pg/mL were seen in 2.6% of the patients, and only 0.7% of the patients had Ctn levels above 21 pg/mL. Cutoff levels for the diagnosis of MTC were 7.9 pg/mL for females and 15 pg/mL for males (P < 0.001). The sensitivity and specificity for females were 95 and 98%, and 96 and 97% for males, respectively. CONCLUSION: Routine Ctn testing is a reliable predictor for MTC and provides the opportunity for earlier thyroidectomy before lymph node metastases occur, resulting in a better prognosis. Females with Ctn levels >7.9 pg/mL and males >15 pg/mL without any other extrathyroidal sources for an elevated Ctn should be monitored. Thyroid surgery should be considered if Ctn levels are increasing or ultrasound detects suspicious thyroid lesions.

Clinical challenges with calcitonin-negative medullary thyroid carcinoma: three case reports and a review of the literature.

Medullary thyroid carcinoma (MTC) is relatively rare, and has the main feature of calcitonin (Ct) secretion. However, a few cases of MTC with negative serum calcitonin have been reported in the literature, so the diagnosis and follow up of Ct-negative MTCs are still a challenge. Here we present three cases of Ct-negative MTCs, illustrating the rarity of the disease and challenges in managing it, together with a review of the literature of 39 MTCs with negative serum Ct.

Presence or severity of Hashimoto's thyroiditis does not influence basal calcitonin levels: observations from CROHT biobank.

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.

The inflammatory biomarkers profile of hospitalized patients with COVID-19 and its association with patient's outcome: A single centered study.

Several reports highlighted the central role of inflammation in the pathogenesis of corona virus disease-19 (COVID-19) disease. Also, the hyper-inflammatory response that is triggered by severe acute respiratory syndrom-Covid-2 (SARS-CoV-2) infection was believed to play an essential role in disease severity and adverse clinical course. For that reason, the classical inflammatory markers were proposed as a possible indicator for COVID-19 severity. However, an extensive analysis of the predictive value of inflammatory biomarkers in large patients' cohorts is still limited and critically needed. In this study we investigated the predictive value of the classical inflammatory biomarkers in a patient cohort consists of 541 COVID-19 patients admitted to Al Kuwait Hospital, Dubai, UAE. A detailed analysis of the association between the essential inflammatory markers and clinical characteristics as well as clinical outcome of the patients were made. In addition, the correlation between those markers and a wide range of laboratory biomarkers and incidence of acute organs injury were investigated. Our results showed a significant elevation of many inflammatory markers including white cell count (WBC) count, neutrophils count, C-reactive protein (CRP), D-Dimer, ferritin, procalcitonin (PCT), and lactate dehydrogenase (LDH) levels in patients with more severe illness. Also, our results highlighted that higher levels of those markers can predict worse patient outcome including the need of ventilation, intensive care unit (ICU) admission, multiple organs dysfunction as well as death. In addition, Our results showed that the presence of lymphopenia and lower absolute lymphocyte count (ALC) at the time of admission were associated with severe to critical COVID-19 illness (P<0.0001), presence of acute respiratory distress syndrome (ARDS) (P<0.0001) and the need for ventilation and ICU admission., Moreover, our results showed a strong association between lower ALC count and multiple organs dysfunction and patient's death (P<0.0001). In conclusion, our results highlighted the possible use of classical inflammatory biomarkers at time of admission as a potential predictive marker for more severe clinical course in COVID-19 patients that might need more aggressive therapeutic approach including the need of ventilators and ICU admission. The presence of such predictive markers might improve patient's stratification and help in the direction of the available resources to patients in need, which in turn help in improving our response to the disease pandemic.

Circulating miR-147b as a diagnostic marker for patients with bacterial sepsis and septic shock.

BACKGROUND: Early diagnosis, precise antimicrobial treatment and subsequent patient stratification can improve sepsis outcomes. Circulating biomarkers such as plasma microRNAs (miRNAs) have proven to be surrogates for diagnosis, severity and case management of infections. The expression of four selected miRNAs (miR-146-3p, miR-147b, miR-155 and miR-223) was validated for their prognostic and diagnostic potential in a clinically defined cohort of patients with sepsis and septic shock. METHODS: The expression of plasma miRNAs was quantified by quantitative PCR (qPCR) in patients with bacterial sepsis (n = 78), in patients with septic shock (n = 52) and in patients with dengue haemorrhagic fever (DHF; n = 69) and in healthy controls (n = 82). RESULTS: The expression of studied miRNA was significantly increased in patients with bacterial sepsis and septic shock. The plasma miR-147b was able to differentiate bacterial sepsis from non-sepsis and septic shock (AUC = 0.77 and 0.8, respectively, p≤ 0.05), while the combination of plasma miR-147b and procalcitonin (PCT) predicted septic shock (AUC = 0.86, p≤ 0.05). CONCLUSIONS: The plasma miR-147b may be an useful biomarker independently or in combination with PCT to support clinical diagnosis of sepsis and equally prognosis of patients with septic shock.

Serum Calcitonin-Negative Medullary Thyroid Carcinoma: A Case Series of 19 Patients in a Single Center.

Introduction: Medullary thyroid carcinoma (MTC) is a rare cancer that accounts for 5% of thyroid cancers. Serum calcitonin is a good biomarker for MTC, which is used for diagnosis, prognosis, and monitoring of recurrence. Calcitonin-negative MTC (CNMTC) is rare but confounds diagnostic and prognostic directions. This study introduces 19 cases of CNMTC in a single center. Method: From 2002 March to 2020 July, more than 76,500 patients had undergone thyroid surgery due to thyroid cancer at the Severance Hospital, and a total of 320 patients were diagnosed with MTC (0.4%). Serum calcitonin levels were obtained from every patient who was suspected with MTC. These patients had undergone either bilateral total thyroidectomy or unilateral thyroidectomy with central compartment lymph node dissection, and additional modified radical lymph node dissection if lateral lymph node metastasis was positive. Postoperative monitoring and out-patient clinic follow-up were performed with obtaining the serum calcitonin levels. Result: Nineteen patients tested negative for calcitonin preoperatively (6%). The mean preoperative calcitonin level was 5.1pg/mL if undetectable level is regarded as 0pg/mL. Only two patients were males, and the female bias was significant (p = 0.017). No one except two patients with modified radical neck dissection showed central compartment lymph node metastasis. Every patient's postoperative calcitonin level remained low. The median follow-up period was 71 months. There was no recurrence and only one fatality, and the overall survival rate was 95%. Conclusion: Since incidence of CNMTC is not negligible, MTC should not be ruled out in the diagnostic phase even if serum calcitonin is negative in preoperative examination. We presented 19 cases of CNMTC whose prognosis in general were favorable. Markers of serum and immunohistochemical samples other than calcitonin should be actively examined.

Prognostic Value of Preoperative Serum Calcitonin Levels for Predicting the Recurrence of Medullary Thyroid Carcinoma.

Background: Serum calcitonin level is a useful biomarker for predicting primary tumor size, the extent of lymph node, and distant metastasis in patients with medullary thyroid carcinoma (MTC). However, the association between preoperative serum calcitonin levels and long-term oncologic outcomes has not yet been established. The aims of this study were to determine the preoperative serum calcitonin cut-off value for predicting disease recurrence and to evaluate its prognostic value. Methods: Patients with MTC (n = 169) who were treated at a tertiary referral hospital in Korea between 1995 and 2019 were enrolled. To determine the preoperative serum calcitonin cut-off value for predicting structural recurrence, the maximum of the standardized log-rank statistics of all possible cut-off values was used. Multivariable Cox regression analysis was used to determine prognostic factors for disease-free survival. Results: The overall disease-free survival rate was 75.7%. The preoperative serum calcitonin cut-off value that predicted structural recurrence was 309 pg/mL. Preoperative serum calcitonin levels of > 309 pg/mL were the strongest independent predictor of disease recurrence (hazard ratio (HR) 5.33, 95% confidence interval (85% CI) 1.67-16.96; P = 0.005). Lateral lymph node metastasis (HR 3.70, 95% CI 1.61-8.51; P = 0.002) and positive resection margins (HR 3.57, 95% CI 1.44-8.88; P = 0.006) were also significant predictors of disease recurrence. Conclusions: The preoperative serum calcitonin cut-off value is useful in clinical practice. It is also the best predictive factor for disease-free survival. Preoperative serum calcitonin levels may help determine the optimal postoperative follow-up strategy for patients with MTC.

Thresholds of Basal- and Calcium-Stimulated Calcitonin for Diagnosis of Thyroid Malignancy.

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.