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The occurrence of bacteremia is critically important for the survival of cancer patients. Therefore, our study aims to evaluate the efficacy of procalcitonin (PCT) and the procalcitonin to albumin ratio (PAR) in predicting bacteremia among this population. In this retrospective test-negative case-control study, we included 903 hospitalized cancer patients, divided into two groups: the bacteremia-positive group (BSI group, n = 384) and the bacteremia-negative group (non-BSI group, n = 519). We assessed the diagnostic significance of PCT and PAR through receiver operating characteristic (ROC) analysis and determined the optimal cut-off values using Youden's index. Both the duration of hospital stay and the 30-day mortality rate were significantly higher in the BSI group. The areas under the curve (AUC) for PAR and PCT were 0.749 (95% CI: 0.715-0.782) and 0.742 (95% CI: 0.708-0.776), respectively, indicating higher levels in the BSI group. The optimal cut-off values for predicting bacteremia were 0.72 for PAR and 1.32 for PCT. PAR showed the highest specificity (92.7%) and positive predictive value (PPV = 83.4%), while PCT demonstrated the highest sensitivity (51.3%) and negative predictive value (NPV = 71.6%). This study is the first in the literature to suggest that PAR and PCT are valuable biomarkers for diagnosing bacteremia in cancer patients. The identified cut-off values offer practical thresholds for bacteremia diagnosis. [ABSTRACT FROM AUTHOR]

The use of procalcitonin (PCT) has grown over the past decade with increasing reliance on the test to rule out bacterial infection. We retrospectively reviewed the medical records of children <18 years old hospitalized at a tertiary care children's hospital from 2017 to 2019 who had PCT testing performed during their admission. Of 4135 PCT levels collected on 1530 children, 982 (23.7%) were diagnostically low and 1993 (48.1%) were diagnostically elevated. Pediatric intensive care, with 6% of total hospital patients, obtained 41.4% of tests. Thirty-one (2%) patients had an average of 27 PCT levels per patient, accounting for 20% of all tests. Many children had symptoms for which testing is not indicated (eg, skin complaints). The differences in PCT testing by service, inappropriate patterns of repeat testing, and testing performed in patients for whom it is not indicated may identify targets for diagnostic stewardship. [ABSTRACT FROM AUTHOR]

Objective: To determine the factors associated with the procalcitonin levels in newborns with hypoxic-ischemic encephalopathy (HIE) who received therapeutic hypothermia (TH). Materials and Methods: The neonates, who had moderate/severe HIE and were treated with TH, were included. The neonates were arranged into 2 groups by procalcitonin (PCT) level after rewarming was completed. The neonates who had a procalcitonin level of < 2.5 ng/ml constituted Group 1 and the ones who had a procalcitonin level of ≥ 2.5 ng/ml constituted Group 2. Univariate and multivariate logistic regression was used to assess the factors related with PCT level. Results: The first group included 123 (87.9%) neonates and the second group included 17 (12.1%) neonates. The median gestational age was 38 (36-39) weeks and the mean birth weight was 3081.7 ± 552.8 grams. In group 2, the rates for severe HIE, cesarean section, antibiotic switch, convulsion, inotrope use and mortality were higher, and duration of hospitalization was longer, whereas Apgar scores were lower (P < .05). The risk of a high procalcitonin level was found to be 6-fold (95% CI 1.9-19.1) higher in severe HIE and 5.2-fold higher (95% CI 1.7-16) in cesarean delivery. Conclusion: In neonates with HIE/TH, high post-rewarming procalcitonin levels were related with severe HIE and cesarean delivery. Some other clinical and laboratory findings, which may reflect worse clinical status, were also associated with high procalcitonin levels. [ABSTRACT FROM AUTHOR]

Background: Presepsin is secreted in response to bacterial phagocytosis, and it has been found that people with liver cirrhosis are at a higher risk of developing bacterial infections. We aimed to evaluate the diagnostic role of presepsin in Patients with liver cirrhosis and bacterial infection. Methods: Our case-control study included 96 cases with liver cirrhosis, divided into 2 groups according to the results of culture and sensitivity. Group I involved 48 patients with liver cirrhosis (child B or C) with a bacterial infection. Group II: involved 48 cases with liver cirrhosis (child B or C) without bacterial infection. Estimation of serum presepsin level was done for all participants. Results: The C reactive protein (CRP), serum procalcitonin, and presepsin (Log PSP) were significantly higher among cirrhotic patients cases with bacterial infection with p-value <0.001 for each when compared to cirrhotic patients without bacterial infection, significant positive correlations were found between Log(PSP) and both CRP and serum procalcitonin (p=0.004, 0.003 respectively). At a cut-off value of <3.1 log PSP could diagnose bacterial infection with the area under the curve 0.698, with specificity of 63.3%, sensitivity of 54.2%, positive predictive value (PPV) of 66.5%, negative predictive value (NPV) of 64.5% and overall accuracy 68.8%. The combination of CRP and Log PSP had the best diagnostic value with the best sensitivity of 95.8%, specificity of 93.7%, PPV of 93.9%, and NPV of 95.7%. Conclusions: Presepsin can play a role in diagnosing bacterial infection in patients with liver cirrhosis. Presepsin and CRP increased the diagnostic accuracy of bacterial infection in cirrhotic patients. [ABSTRACT FROM AUTHOR]

Objective: To analyze the specificity of calcitonin gene–related peptide (CGRP) levels, we measured alpha‐CGRP circulating levels in a large series of patients with a recent diagnosis of inflammatory bowel disease (IBD) who were interviewed regarding comorbid headache. Background: Several studies have found an association between migraine and IBD. Methods: In this cross‐sectional study performed in an IBD clinic, morning serum alpha‐CGRP levels were measured by enzyme‐linked immunosorbent assay in 96 patients who were recently diagnosed with IBD and compared to those from 50 similar patients with chronic migraine (CM) and 50 healthy controls (HC). Results: Alpha‐CGRP levels were higher in patients with IBD (median [interquartile range] 56.9 [35.6–73.9] pg/mL) and patients with CM (53.0 [36.7–73.9] pg/mL) compared to HC (37.2 [30.0–51.8] pg/mL; p = 0.003; p = 0.019, respectively). Regarding IBD diagnostic subtypes, alpha‐CGRP levels for ulcerative colitis (67.2 ± 49.3 pg/mL; 57.0 [35.6–73.4] pg/mL) and Crohn's disease (54.9 ± 27.5 pg/mL; 57.7 [29.1–76.1] pg/mL) were significantly higher than those of HC (p = 0.013, p = 0.040, respectively). Alpha‐CGRP levels were further different in patients with IBD with migraine (70.9 [51.8–88.7] pg/mL) compared to HC (p < 0.001), patients with IBD without headache (57.5 [33.3–73.8] pg/mL; p = 0.049), and patients with IBD with tension‐type headache but without migraine (41.7 [28.5–66.9] pg/mL; p = 0.004), though alpha‐CGRP levels in patients with IBD without migraine (53.7 [32.9–73.5] pg/mL) remained different over HC (p = 0.028). Conclusion: Together with CM, circulating alpha‐CGRP levels are different in patients with IBD, perhaps reflecting a chronic inflammatory state. IBD is an example of how alpha‐CGRP levels are not a totally specific migraine biomarker. However, alpha‐CGRP levels were further increased in patients with IBD who have a history of migraine, which reinforces its role as a biomarker in migraine patients, always bearing in mind their comorbidities. Plain Language Summary: Alpha‐calcitonin gene–related peptide (CGRP) levels may be a potential migraine biomarker, but it is unclear if this is the case because changes in CGRP concentrations can also be present in other conditions. We measured morning serum alpha‐CGRP levels in 96 patients with a recent inflammatory bowel disease (IBD) diagnosis, and compared them to 50 matched healthy participants and 50 matched patients with chronic migraine (CM). We found a significant increase in serum alpha‐CGRP levels in both patients with IBD and CM compared to healthy controls, which we think may reflect chronic inflammation found in IBD; these results offer another example that alpha‐CGRP concentrations are not totally specific for migraine. [ABSTRACT FROM AUTHOR]

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

The storage of serum tumor markers (STM) at −18 °C for one year has been a legal requirement in France since 1999, but has been abolished in 2022. This raises the question of the relevance of maintaining these biobanks in terms of conditions of storage. These should only be implemented after validation; in order to maintain the integrity of the biological sample and must be controlled over time according to the laboratoryʼs procedures. The aim of the study was to assess the suitability of storing 10 STMs by evaluating their stability after one year of storage at −18 °C. A new immuno-enzymatic assay (A+1) was conducted on samples that had been stored at −18 °C for one year after an initial assay (A) of one of the following STMs: carcino-embryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 125 (CA125), carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 19-9 (CA19-9), total (TPSA), and free (FPSA) prostate-specific antigen, calcitonin (CT), thyroglobulin (TG), and neuro-specific enolase (NSE). The results were confronted to four different permissible error sources. In total, 1148 A+1 assays were performed. A strong correlation between A+1 and A values was found for all analytes, but with a statistically significant reduction in the mean A+1 concentration compared to the mean A concentration in 7/10 STMs. The bias induced by conservation seems to be technically unsustainable if we rely on the repositories closest to the current analytical performances. These results support the discontinuation of mandatory STM biobank storage at −18 °C, which requires considerable technical time and organizational effort. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the early kinetics of interleukin 6 (IL‐6), procalcitonin (PCT), and C‐reactive protein (CRP) on initial antibiotic efficacy in hematological disorder patients with febrile neutropenia (FN). Methods: A total of 40 patients with 43 episodes of FN were enrolled and divided into initial antibiotic effective group (IAE group, n = 24) and initial antibiotic ineffective group (IAI group, n = 19). The levels of IL‐6, PCT, and CRP before antibacterial treatment (T0), and 12 h (T1), 24 h (T2), 48 h (T3), and 72 h (T4) post‐antibacterial treatment were determined, respectively. Furthermore, the receiver operating characteristic curve (ROC) analysis was performed to evaluate the clinical value of indicators. Results: In IAE group, the IL‐6 levels gradually decreased from T0 to T4, and the CRP levels significantly decreased at 48 to 72 h, whereas both IL‐6 and CRP remained at high levels in the IAI group. The PCT levels in both groups increased at the early stage of anti‐infection (T1–T2) and reached to peak at T1–T2 in effective group. ROC curve analysis identified IL‐6 as a predictive biomarker for initial antibiotic efficacy at 12, 48, and 72 h after treatment, with the AUC of 0.698, 0.744, and 0.821, respectively. In addition, CRP demonstrated predictive ability of initial antibiotics against infection at 24, 48, and 72 h after therapy, with the AUC of 0.724, 0.741, and 0.797, respectively. ROC curve analysis of percentage changes demonstrated that IL‐6 percentage change showed predictive ability of antibiotic efficacy at the early stage, and both the IL‐6 and CRP percentage changes showed the predictive ability of antibiotic efficacy 48 or 72 h after antibiotics therapy. Conclusion: This study confirmed IL‐6 and CRP levels, and the percentage change in IL‐6 as the biomarkers for initial antibiotic efficacy prediction in hematological disorder patients with FN. [ABSTRACT FROM AUTHOR]

Introduction: Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer and the main treatment is surgery. The extent of surgery depends on the spread of tumour and often involves thyroidectomy and neck dissection. Recurrent or metastasis tumour can be detected with raising calcitoninand there are various options of treatment. Methods: This was a retrospective study of MTC over seven years in a tertiary cancer centre which evaluated the treatment outcome and the non-surgical options available in recurrent and metastatic tumours. Results: Among the 601 thyroid cancers, 34 patients (5.3%) were MTC, of which 29 were studied. Majority were women, below 60 years, were diagnosed with fine needle aspiration cytology of thyroid nodule or nodes and had raised calcitonin value (Ctn). The value of Ctn was correlated with tumour burden rather than extent (p=0.7). Recurrence was seen in 35% and all patients with locoregional recurrence had curative surgery whereas metastatic patients were offered palliative treatment. Acceptance of palliative treatment was less due to financial burden. The five year overall survival for nonmetastatic disease was 89.4 % and for patients with metastatic disease at presentation was 54.7 %. Conclusion: The incidence of medullary thyroid carcinoma is low compared to the differentiated thyroid carcinoma. The main treatment is surgery and other treatment options are limited. [ABSTRACT FROM AUTHOR]

Background: Use of noninvasive ventilation in patients with acute respiratory distress syndrome (ARDS) is debated. The COVID-19 pandemic posed challenges due to high patient volumes and worldwide resource strain. Objectives: To determine associations between use of noninvasive ventilation in adult patients with moderate to severe ARDS due to SARS-CoV-2 pneumonia, progression to intubation, and hospital mortality. Methods: This retrospective cohort study included patients in an institutional COVID-19 registry. Adult patients were included if they were admitted for COVID-19 between March 1, 2020, and March 31, 2022, and developed moderate to severe ARDS. Primary outcomes were progression to intubation and hospital mortality in patients who received noninvasive ventilation or mechanical ventilation. A secondary outcome was successful treatment with noninvasive ventilation without intubation. Results: Of 823 patients who met inclusion criteria, 454 (55.2%) did not receive noninvasive ventilation and 369 (44.8%) received noninvasive ventilation. Patients receiving noninvasive ventilation were more likely to require mechanical ventilation than were patients not receiving noninvasive ventilation. Among patients requiring endotracheal intubation, those receiving noninvasive ventilation had a higher likelihood of mortality. Patients receiving noninvasive ventilation had lower severity-adjusted odds of survival to discharge without intubation than did patients not receiving noninvasive ventilation. Conclusion: Patients with moderate to severe ARDS due to SARS-CoV-2 pneumonia treated with noninvasive ventilation had increased likelihood of progression to endotracheal intubation and hospital mortality. [ABSTRACT FROM AUTHOR]

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

Medullary thyroid carcinoma (MTC) accounts for only 3% of all thyroid carcinomas: 75% as sporadic MTC (sMTC) and 25% as hereditary MTC (hMTC) in the context of multiple endocrine neoplasia type 2 (MEN2). Early diagnosis is possible by determining the tumour marker calcitonin (Ctn) when clarifying nodular goitre and by detecting the mutation in the proto-oncogene RET in the MEN2 families. If the Ctn level is only slightly elevated, up to 30 pg/ml in women and up to 60 pg/ml in men, follow-up checks are advisable. At higher levels, surgery should be considered; at a level of > 100 pg/ml, surgery is always advisable. The treatment of choice is total thyroidectomy, possibly with central lymphadenectomy. In the early stage, cure is possible with adequate surgery; in the late stage, treatment with tyrosine kinase inhibitors is an option. RET A mutation analysis should be performed on all patients with MTC. During followup, a biochemical distinction is made between: healed (Ctn not measurably low), biochemically incomplete (Ctn increased without tumour detection) and structural tumour detection (metastases on imaging). After MTC surgery, the following results should be available for classification in follow-up care: (i) histology, Ctn immunohistology if necessary, (ii) classification according to the pTNM scheme, (iii) the result of the RET analysis for categorisation into the hereditary or sporadic variant and (iiii) the postoperative Ctn value. Tumour progression is determined by assessing the Ctn doubling time and the RECIST criteria on imaging. In most cases, “active surveillance” is possible. In the case of progression and symptoms, the following applies: local (palliative surgery, radiotherapy) before systemic (tyrosine kinase inhibitors). [ABSTRACT FROM AUTHOR]

Objectives: This case-control study aimed to evaluate calcitonin response in naturally occurring hypercalcemia in cats and assess the relationships between calcitonin and ionized calcium (iCa) and examine relationships between calcitonin, iCa and bone turnover. Methods: Hypercalcemic cats (persistently increased iCa concentration [>1.40 mmol/l]) were identified retrospectively via a medical database search; additional hypercalcemic and normocalcemic cats were recruited prospectively. Data regarding routine biochemical and urine testing, diagnostic imaging and additional blood testing were obtained. Serum alkaline phosphatase (ALP) activity was used as a marker of bone turnover. Serum calcitonin concentration was analyzed using a previously validated immunoradiometric assay. Hypercalcemic cats with an increased calcitonin concentration (>0.9 ng/L) were termed responders. Group comparisons were performed using a Mann-Whitney test for continuous variables and a χ² test for categorical variables. Spearman's correlation coefficient was used to examine the relationships between calcitonin, iCa and ALP. Results: Twenty-six hypercalcemic and 25 normocalcemic cats were recruited. Only 5/26 (19.2%) of the hypercalcemic cats were identified as responders, and all were diagnosed with idiopathic hypercalcemia. There was no significant correlation between the concentrations of calcitonin and iCa (p = 0.929), calcitonin and ALP (p = 0.917) or iCa and ALP (p = 0.678) in hypercalcemic cats, however, a significant negative correlation was observed between calcitonin and ALP (p = 0.037) when normocalcemic and hypercalcemic cats with an elevated calcitonin concentration were analyzed together. Discussion: The expected increase in calcitonin concentration was present in only a small subset of hypercalcemic cats; no correlation was found between iCa and calcitonin concentration. The inverse relationship between calcitonin and ALP in cats with increased calcitonin concentrations suggests that the ability of calcitonin to correct hypercalcemia may be related to the degree of bone turnover. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the usefulness of serum procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte count ratio (NLR), and their combination, in distinguishing candidemia from bacteremia in intensive care unit (ICU) patients. Methods: This is a retrospective study in ICU patients with documented bloodstream infections (BSIs) and with both serum PCT and CRP measurements on the day of the positive blood sample. Illness severity was assessed by sequential organ failure assessment (SOFA) score on both admission and BSI day. Demographic, clinical, and laboratory data, including PCT and CRP levels and NLR on the day of the BSI, were recorded. Results: A total of 63 patients were included in the analysis, of whom 32 had bacteremia and 31 had candidemia. PCT, CRP, and NLR values were all significantly lower in candidemia compared with bacteremia (0.29 (0.14–0.69) vs. 1.73 (0.5–6.9) ng/mL, p < 0.001, 6.3 (2.4–11.8) vs. 19 (10.7–24.8) mg/dl, p < 0.001 and 6 (3.7–8.6) vs. 9.8 (5.3–16.3), p = 0.001, respectively). PCT was an independent risk factor for candidemia diagnosis (OR 0.153, 95%CI: 0.04–0.58, p = 0.006). A multivariable model consisting of the above three variables had better predictive ability (AUC-ROC = 0.88, p < 0.001), for candidemia diagnosis, as compared to that of PCT, CRP, and NLR, whose AUC-ROCs were all lower (0.81, p < 0.001, 0.78, p < 0.001, and 0.68, p = 0.015, respectively). Conclusions: A combination of routinely available laboratory tests, such as PCT, CRP, and NLR, could prove useful for the early identification of ICU patients with candidemia. [ABSTRACT FROM AUTHOR]

The article focuses on the role of osteoclasts in bone resorption and the use of denosumab, a monoclonal antibody targeting the RANKL pathway, in treating osteolytic disorders like giant cell tumors of bone (GCTB) and central giant cell granuloma (CGCG). Topics include the effectiveness of denosumab in pediatric patients with various bone disorders and the management of rebound hypercalcemia following denosumab discontinuation in children.

Background and Purpose: Insulin therapies for Type 1 diabetes (T1D) have limitations, such as glucose fluctuations, hypoglycaemia, and weight gain. Only pramlintide is approved with insulin. However, its short half‐life limits efficacy, requiring multiple daily injections and increasing hypoglycaemia risk. New strategies are needed to improve glycaemic control. Dual amylin and calcitonin receptor agonists are potent insulin sensitizers developed for Type 2 diabetes (T2D) as they improve glucose control, reduce body weight, and attenuate hyperglucagonemia. However, it is uncertain if they could be used to treat T1D. Experimental Approach: Sprague Dawley rats received a single intravenous injection of streptozotocin (STZ) (50 mg·kg−1) to induce T1D. Humulin (1 U/200 g·day−1 or 2 U/200 g·day−1) was continuously infused, while half of the rats received additional KBP‐336 (4.5 nmol·kg−1 Q3D) treatment. Bodyweight, food intake, and blood glucose were monitored throughout the study. An oral glucose tolerance test was performed during the study. Key Results: Treatment with Humulin or Humulin + KBP‐336 improved the health of STZ rats. Humulin increased body weight in STZ rats, but KBP‐336 attenuated these increases and maintained a significant weight loss. The combination exhibited greater blood glucose reductions than Humulin‐treated rats alone, reflected by improved HbA1c levels and glucose control. The combination prevented hyperglucagonemia, reduced amylin levels, and increased pancreatic insulin content, indicating improved insulin sensitivity and beta‐cell preservation. Conclusion and Implications: The insulin sensitizer KBP‐336 lowered glucagon secretion while attenuating insulin‐induced weight gain. Additionally, KBP‐336 may prevent hypoglycaemia and improve insulin resistance, which could be a significant advantage for individuals with T1D seeking therapeutic benefits. [ABSTRACT FROM AUTHOR]

Background: Currently, the treatment and prevention of migraine remain highly challenging. Mendelian randomization (MR) has been widely used to explore novel therapeutic targets. Therefore, we performed a systematic druggable genome-wide MR to explore the potential therapeutic targets for migraine. Methods: We obtained data on druggable genes and screened for genes within brain expression quantitative trait locis (eQTLs) and blood eQTLs, which were then subjected to two-sample MR analysis and colocalization analysis with migraine genome-wide association studies data to identify genes highly associated with migraine. In addition, phenome-wide research, enrichment analysis, protein network construction, drug prediction, and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic drugs. Results: We identified 21 druggable genes significantly associated with migraine (BRPF3, CBFB, CDK4, CHD4, DDIT4, EP300, EPHA5, FGFRL1, FXN, HMGCR, HVCN1, KCNK5, MRGPRE, NLGN2, NR1D1, PLXNB1, TGFB1, TGFB3, THRA, TLN1 and TP53), two of which were significant in both blood and brain (HMGCR and TGFB3). The results of phenome-wide research showed that HMGCR was highly correlated with low-density lipoprotein, and TGFB3 was primarily associated with insulin-like growth factor 1 levels. Conclusions: This study utilized MR and colocalization analysis to identify 21 potential drug targets for migraine, two of which were significant in both blood and brain. These findings provide promising leads for more effective migraine treatments, potentially reducing drug development costs. [ABSTRACT FROM AUTHOR]

Intra-abdominal infections (IAIs) are an important cause of morbidity and mortality in hospital settings worldwide. The cornerstones of IAI management include rapid, accurate diagnostics; timely, adequate source control; appropriate, short-duration antimicrobial therapy administered according to the principles of pharmacokinetics/pharmacodynamics and antimicrobial stewardship; and hemodynamic and organ functional support with intravenous fluid and adjunctive vasopressor agents for critical illness (sepsis/organ dysfunction or septic shock after correction of hypovolemia). In patients with IAIs, a personalized approach is crucial to optimize outcomes and should be based on multiple aspects that require careful clinical assessment. The anatomic extent of infection, the presumed pathogens involved and risk factors for antimicrobial resistance, the origin and extent of the infection, the patient's clinical condition, and the host's immune status should be assessed continuously to optimize the management of patients with complicated IAIs. [ABSTRACT FROM AUTHOR]

Aim: Whether serum concentration of procalcitonin (PCT), brain natriuretic peptide (BNP) and albumin (Alb) have an association with the outcome of hospitalized older patients is unclear. We investigated clinical outcomes and any predictive factors in hospitalized Japanese older patients with a risk of infection. Methods: In the retrospective study, 820 Japanese patients were followed up for 30 days or until death. During the observation period, 656 patients survived and 164 patients died. The predictive factors of death were analyzed according to demographic and clinical variables. Results: The survival rate was decreased as the serum PCT increased from <0.5 to ≥10 ng/mL, as was also the case with BNP from <300 to ≥300 pg./mL, whereas low Alb (<2.5 g/dL) showed a lower survival rate than high Alb (≥2.5 g/dL; P < 0.01). Using the Cox regression model, the multivariable‐adjusted hazard ratios (95% confidence interval) were as follows: PCT 0.5–2 versus <0.5 ng/mL: 1.61(1.04–2.49), PCT 2–10 versus <0.5 ng/mL: 1.91(1.15–3.16), PCT ≥10 versus <0.5 ng/mL: 2.90(1.84–4.59), high BNP 1.26 (0.89–1.76) and low Alb 0.68 (0.52–0.87). The mortality rate increased as the number of scores (PCT + BNP + Alb) increased. Conclusions: Concentration‐dependent high PCT, high BNP and low Alb were positive risk factors associated with poor prognosis in hospitalized older patients with a risk of infection. Geriatr Gerontol Int 2024; 24: 571–576. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to investigate the underlying mechanism of mechanical stimulation in regulating osteogenic differentiation. Materials and methods: Osteoblasts were exposed to compressive force (0–4 g/cm2) for 1–3 days or CGRP for 1 or 3 days. Expression of receptor activity modifying protein 1 (RAMP1), the transcription factor RUNX2, osteocalcin, p38 and p-p38 were analyzed by western blotting. Calcium mineralization was analyzed by alizarin red straining. Results: Using compressive force treatments, low magnitudes (1 and 2 g/cm2) of compressive force for 24 h promoted osteoblast differentiation and mineral deposition whereas higher magnitudes (3 and 4 g/cm2) did not produce osteogenic effect. Through western blot assay, we observed that the receptor activity-modifying protein 1 (RAMP1) expression was upregulated, and p38 mitogen-activated protein kinase (MAPK) was phosphorylated during low magnitudes compressive force-promoted osteoblast differentiation. Further investigation of a calcitonin gene-related peptide (CGRP) peptide incubation, a ligand for RAMP1, showed that CGRP at concentration of 25 and 50 ng/ml could increase expression levels of RUNX2 and osteocalcin, and percentage of mineralization, suggesting its osteogenic potential. In addition, with the same conditions, CGRP also significantly upregulated RAMP1 and phosphorylated p38 expression levels. Also, the combination of compressive forces (1 and 2 g/cm2) with 50 ng/ml CGRP trended to increase RAMP1 expression, p38 activity, and osteogenic marker RUNX2 levels, as well as percentage of mineralization compared to compressive force alone. This suggest that RAMP1 possibly acts as an upstream regulator of p38 signaling during osteogenic differentiation. Conclusion: These findings suggest that CGRP-RAMP1/p38MAPK signaling implicates in osteoblast differentiation in response to optimal magnitude of compressive force. This study helps to define the underlying mechanism of compressive stimulation and may also enhance the application of compressive stimulation or CGRP peptide as an alternative approach for accelerating tooth movement in orthodontic treatment. [ABSTRACT FROM AUTHOR]

The article discusses research which examined the prevalence of invasive bacterial infection (IBI) in febrile young infants in an urban tertiary pediatric emergency department to clarify the role of viral testing when procalcitonin is not available. Data shows the demographic characteristics of infants and prevalence of IBI and viral status among febrile infants classified as high or low risk for IBI based on C-reactive protein, absolute neutrophil count and maximum temperature measurements.

Background and Objectives Significant practice variation exists in managing young infants with fever. Quality improvement strategies can aid in risk stratification and standardization of best care practices, along with a reduction of unnecessary interventions. The aim of this initiative was to safely reduce unnecessary admissions, antibiotics, and lumbar punctures (LPs) by 10% in low-risk, febrile infants aged 29 to 90 days presenting to the emergency department (ED) over a 12-month period. Methods Using the Model for Improvement, a multidisciplinary team developed a multipronged intervention: an updated clinical decision tool (CDT), procalcitonin (PCT) adoption, education, a feedback tool, and best practice advisory (BPA) banner. Outcome measures included the proportion of low-risk infants that were admitted, received antibiotics, and had LPs. Process measures were adherence to the CDT and percentage of PCT ordered. Missed bacterial infections and return visits were balancing measures. The analysis was completed using descriptive statistics and statistical process control methods. Results Five hundred and sixteen patients less than 90 days of age were included in the study, with 403 patients in the 29- to 90-day old subset of primary interest. In the low-risk group, a reduction in hospital admissions from a mean of 24.1% to 12.0% and a reduction in antibiotics from a mean of 15.2% to 1.3% was achieved. The mean proportion of LPs performed decreased in the intervention period from 7.5% to 1.8%, but special cause variation was not detected. Adherence to the CDT increased from 70.4% to 90.9% and PCT was ordered in 92.3% of cases. The proportion of missed bacterial infections was 0.3% at baseline and 0.5% in the intervention period while return visits were 6.7% at baseline and 5.0% in the intervention period. Conclusions The implementation of a quality improvement strategy, including an updated evidence-based CDT for young infant fever incorporating PCT, safely reduced unnecessary care in low-risk, febrile infants aged 29 to 90 days in the ED. Purpose To develop and implement a multipronged improvement strategy including an evidence-based CDT utilizing PCT to maximize value of care delivered to well-appearing, febrile infants presenting to EDs. [ABSTRACT FROM AUTHOR]

Objective: There is scarcity of data on diabetic ketoacidosis (DKA) in patients with diabetes mellitus (DM) due to diseases of exocrine pancreas (T3DM). Methods: We did a retrospective record-review of patients admitted with DKA from 2017 to 2022. Clinical and biochemical characteristics were compared among DKA cases in type 1 DM (T1DM), type 2 DM (T2DM), and T3DM. Logistic regression was performed to find independent predictors of death and DKA complications. Results: Out of 107 cases, n = 79 were included (T1DM = 30, T2DM = 37, T3DM = 12). All cases of DKA in T3DM were of mild or moderate severity. The time to resolution of DKA was shortest for T3DM (p = 0.04). Death rates were similar in all groups but in T3DM, all deaths occurred after resolution of DKA. There was a precipitating factor for DKA in 11/12, 91.7% cases in T3DM group, most common being infections (58.3%) followed by glucocorticoid use (16.7%). T3DM cases had shorter duration of DM but higher CRP, procalcitonin, and qSOFA scores for infections precipitating DKA (pall < 0.03). CRP was an independent predictor for DKA-related complications (OR: 1.01, 1.001–1.01, p = 0.04). Conclusion: This is the largest single-center cohort of T3DM with new-onset DKA, suggesting severe infections and glucocorticoid usage as major precipitating factors, while clinical course and outcomes were distinctly different from T2DM and T1DM patients with DKA. [ABSTRACT FROM AUTHOR]

The main goal of this research was to determine whether there is a correlation between adherence to the Mediterranean diet (assessed by the Mediterranean Diet Serving Score (MDSS)) and parameters indicating thyroid gland activity, such as concentration of thyroid-stimulating hormone (TSH), thyroid hormones (free triiodothyronine (fT3), free thyroxine (fT4)), thyroglobulin (Tg), antibodies to thyroid proteins (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)), and calcitonin (CT) in plasma and serum samples. An additional objective was to investigate whether there are differences in the values of the MDSS among clinical groups (euthyroid individuals, euthyroid individuals with positive TgAb and/or TPOAb, and hypothyroid and hyperthyroid participants). This cross-sectional study included 4620 participants over 18 years of age from the islands of Korčula and Vis, and the mainland city of Split. The MDSS was assessed from a food frequency questionnaire (FFQ). MDSS values were significantly higher in females compared to males and showed a positive association with the age of the participants. There was no significant difference in the MDSS values among the examined clinical groups. In the group of subjects with euthyroidism, a significant positive association was found between fT3 and the MDSS, while in the group of subjects with subclinical hypothyroidism, a significant positive association was observed between the MDSS and both fT3 and fT4. CT levels were also positively associated with the MDSS. Considering the significant positive association of the MDSS and both fT3 and fT4 levels in patients with subclinical hypothyroidism, the results of this study could be used to create guidelines for selecting an appropriate, potentially protective diet for these patients. [ABSTRACT FROM AUTHOR]

The study compared two plasma procalcitonin (PCT) assays, the point of care (POC) Finecare™ Procalcitonin Rapid Quantitative Test and the Elecsys® BRAHMS PCT immunoassay, in sepsis ICU patients. Forty-one plasma samples were analyzed, showing a strong correlation (r = 0.98) and no significant difference in PCT values. The mean POC PCT value was 4.46 ng/mL (SD 8.68), and for laboratory BRAHMS PCT, it was 4.67 ng/mL (SD 10.03). The study found a strong linear relationship between plasma POC PCT and laboratory BRAHMS PCT (r = 0.98). Different regression methods showed varying intercepts and slopes: Ordinary Least Squares had an intercept of 0.49 and a slope of 0.85; Deming regression showed an intercept of 0.43 and a slope of 0.86; Passing–Bablok regression showed an intercept of 0.02 and a slope of 1.08. Precision results for cut-offs of 0.5 ng/mL were a coefficient of variation (CV) of 5%, and for 2.5 ng/mL, the CV was 2.5%. The Pearson correlation coefficient (r) for linearity was ≥0.99. The study revealed no significant difference between the POC Finecare™ PCT and Elecsys® BRAHMS PCT immunoassay in sepsis samples from ICU patients, supported by strong correlation, minimal bias, a consistent CV, and linearity. [ABSTRACT FROM AUTHOR]

Introduction: Bacterial Meningitis (BM) is a serious health problem worldwide with high mortality and permanent longterm neurological sequelae. Cerebrospinal Fluid (CSF) analysis is the cornerstone for diagnosing BM, but the lack of specificity creates a difficult clinical scenario for initiating proper treatment. Empiric antibiotic use in patients with suspected meningitis at primary care settings decreases the yield of CSF culture and alters CSF cytological and biochemical findings, making it further difficult to diagnose BM. To overcome this difficulty, there is a need for other biochemical markers with higher sensitivity and specificity. Aim: To determine the diagnostic sensitivity and specificity of Procalcitonin (PCT) in serum and CSF in patients with BM and compare its diagnostic accuracy in both sample types. Materials and Methods: A cross-sectional study was conducted in the Department of Internal Medicine at a tertiary care centre in eastern India from September 2018 to August 2020. A total of 82 adult patients with meningitis were recruited as per the protocol, and CSF analysis was done along with estimation of PCT in serum and CSF. Receiver Operating Characteristics (ROC) curve analysis of serum and CSF PCT was used to determine sensitivity and specificity with a 95% confidence interval. Results: Out of the 82 patients recruited, 30 (36.6%) had BM. CSF PCT with a cut-off value of >0.45 ng/mL had a sensitivity of 86.7% and specificity of 92.3%. The sensitivity of serum PCT with a cut-off value of >0.6 ng/mL was 83.3%, and specificity was 86.5%. There was no statistically significant difference in sensitivity and specificity between CSF and serum PCT in patients with BM (p-value=0.7988). Conclusion: Both serum and CSF PCT were found to have high sensitivity and specificity as markers for diagnosing BM without any statistically significant difference between them. [ABSTRACT FROM AUTHOR]

The article discusses the challenges in diagnosing sepsis and the need for biomarkers that can be used in the emergency department (ED) to rapidly identify high-risk patients. A study conducted in German tertiary hospitals tested the performance of various biomarkers, with procalcitonin performing the best in identifying patients with sepsis. However, the accuracy of procalcitonin was still moderate, and other promising biomarkers were not tested in this study. The study suggests that while procalcitonin testing can be used in selected patients with suspected sepsis, it should not override clinical judgment. The study provides preliminary data for future trials examining the impact of biomarkers on clinical management and patient outcomes. [Extracted from the article]

Objective The aim of the study is to analyze the risk factors for neonatal acute respiratory distress syndrome (NARDS) development based on the Montreux definition among near- and full-term neonates with sepsis and received meropenem. Study Design This was a single-center, case–control, retrospective trial from January 2019 to June 2020. Newborns of gestational ages (GAs) ≥35 weeks, diagnosed with sepsis and received meropenem were included. Patients who developed NARDS subsequently were defined as the study group (NARDS group), while the others without NARDS were enrolled in the control group (non-NARDS group). Results Out of 213 eligible neonates, NARDS occurred in 52 (24.4%) cases. In univariate analysis, infants with NARDS had a lower GA and birth weight, but a higher rate of premature birth (p <0.05). The median onset times of sepsis were earlier among neonates with NARDS compared with those without NARDS (1 [1,1] vs. 6 [1,15] days, p <0.001). Neonates with NARDS were more likely to suffer from early-onset sepsis (EOS), persistent pulmonary hypertension of newborns, pulmonary hemorrhage, septic shock, and patent ductus arteriosus (p <0.05). During labor, women whose neonates experienced NARDS were more likely to have a cesarean delivery (67.3 vs. 46.6%, p = 0.009) and likely to receive at least one dose of corticosteroids (21.2 vs. 5.0%, p = 0.001). In multivariable analyses, factors remaining independently associated with NARDS were premature birth, cesarean delivery, EOS, and septic shock. Compared with conventional inflammatory markers for NARDS, procalcitonin (PCT) was correlated with septic neonates who developed NARDS (p = 0.012) but had a low diagnostic value (area under the curve [AUC] = 0.609). C-reactive protein, white blood cells, and PLT did not correlate with morbidity of NARDS (AUC <0.05 and p >0.05). Conclusion Premature birth, cesarean delivery, EOS, and septic shock were independently associated with NARDS among near- and full-term septic neonates. PCT showed limited predictive value for NARDS. Key Points NARDS is serious and sepsis is proved as a cause for it. But rare study suggests the risk factors of NARDS based on the Montreux definition. This study may first found the independent risk factors associated with NARDS in septic neonates. [ABSTRACT FROM AUTHOR]

Calcitonin is a 32-amino acid peptide, which causes a decrease in blood calcium levels and bone resorption in the human body. It is produced in different species. Salmon calcitonin is used as a medicine for diseases such as osteoporosis, Paget's disease, and hypercalcemia. However, the salmon calcitonin peptide used as a medicine, could induce immune responses in humans. Decreasing the antigenicity of salmon calcitonin could improve this molecule for pharmaceutical usage. In this study, improving physicochemical properties and reducing allergenicity and especially the antigenicity of salmon calcitonin were followed. The calcitonin sequences of different species were evaluated, and those with better properties were considered as a guide for peptide engineering. In silico methods were utilized to characterize the properties of the reviewed calcitonin sequences, and the best sequences (the calcitonin of sheep, dog, rat, and human) were used as a template to decrease the antigenicity of salmon calcitonin. The epitopic parts, i.e., amino acids 16 to 29, were identified by different servers. Hot spot residues including Y22, N26, T27, and S29 were characterized based on the main criteria of being a B-cell epitope including convexity index, hydrophilicity, and surface accessibility. These residues were replaced with lower antigenic counterparts. Results showed the final selected mutant (T27V/S29V) had a lower antigenicity and higher solubility and stability than salmon calcitonin. Thus, our suggested mutant could be a potential alternative candidate to salmon calcitonin. However, future in vitro and in vivo evaluations are needed to confirm its suitability for clinical usage. [ABSTRACT FROM AUTHOR]

Background efficacy of therapeutic cholecalciferol supplementation for severe COVID-19 is sparingly studied. Objective effect of single high-dose cholecalciferol supplementation on sequential organ failure assessment (SOFA) score in moderate-to-severe COVID-19. Methods participants with moderate to severe COVID-19 with PaO2/FiO2 ratio < 200 were randomized to 0.6 million IU cholecalciferol oral (intervention) or placebo. Outcomes primary outcome was change in Day 7 SOFA score and pre-specified secondary outcomes were SOFA and 28-day all-cause mortality. Results in all, 90 patients (45 each group) were included for intention-to-treat analysis. 25(OH)D3 levels were 12 (10–16) and 13 (12–18) ng/ml (P  = 0.06) at baseline; and 60 (55–65) ng/ml and 4 (1–7) ng/ml by Day 7 in vitamin D and placebo groups, respectively. The SOFA score on Day 7 was better in the vitamin D group [3 (95% CI, 2–5) versus 5 (95% CI, 3–7), P  = 0.01, intergroup difference − 2 (95% CI, −4 to −0.01); r  = 0.4]. A lower all-cause 28-day mortality [24% compared to 44% (P  = 0.046)] was observed with vitamin D. Conclusions single high-dose oral cholecalciferol supplementation on ICU admission can improve SOFA score at Day 7 and reduce in-hospital mortality in vitamin D-deficient COVID-19. ClinicalTrials.gov   id: NCT04952857 registered dated 7 July 2021. What is already known on this topic —vitamin D has immunomodulatory role. Observational and isolated intervention studies show some benefit in COVID-19. Targeted therapeutic vitamin D supplementation improve outcomes in severe COVID-19 is not studied in RCTs. What this study adds —high-dose vitamin D supplementation (0.6 Million IU) to increase 25(OH)D > 50 ng/ml is safe and reduces sequential organ failure assessment score, in-hospital mortality in moderate to severe COVID-19. How this study might affect research, practice or policy— vitamin D supplementation in vitamin D-deficient patients with severe COVID-19 is useful may be practiced. [ABSTRACT FROM AUTHOR]

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Background: Community-acquired pneumonia (CAP) is a type of lung infection that people can acquire outside of the hospital. One of the most serious complications of bacterial pneumonia is sepsis. It is a life-threatening condition caused by the body's response to an infection. The aim of this research is to find potential diagnostic and prognostic markers for community-acquired pneumonia and sepsis. Specifically, the study examined the diagnostic value of procalcitonin (PCT) and complete blood count (CBC) markers. Methods: One hundred twenty participants were selected and divided into 20 patients with sepsis due to CAP, 60 patients with bacterial CAP, and 40 control patients. All participants were between the ages of 23-95 years old. Blood samples were collected from both male and female patients. All samples were diagnosed by doctors specializing in respiratory and chest diseases and internal medicine. The study was conducted at Imam Al-Sadiq Hospital in Babylon Governorate and Imam Al-Hussein Medical City in Kerbela Governorate from December 2022 to June 2023. Results: The results showed significant differences in PCT, white blood cells (WBC), lymphocytes (LYM), monocyte, granulocyte (GRA), haematocrit, platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR). Haemoglobin also showed significant differences, except for platelets, which did not show significant differences. The study found that PCT, WBC, GRA, NLR, and PLR were valuable markers for diagnosing patients with CAP and sepsis due to CAP. Other CBC parameters were found to be less useful. Conclusion: The study highlights the importance of using PCT and CBC markers to diagnose and manage patients with community-acquired pneumonia and sepsis. [ABSTRACT FROM AUTHOR]

Objective: Role of serum procalcitonin (PCT) in critically ill patients is well defined for identification of bacterial infection but it’s role in prediction of survival is not well established. We studied plasma kinetics of PCT, over the first three critical care days to validate its role in prediction of survival of patients with sepsis according to plasma level. Methods: A prospective observational study was conducted in CCU (KGMU). Total 53 consecutive patients either sex were recruited. Patients with systemic inflammatory response syndrome (SIRS) were recruited. PCT was measured on 1st and 3rd days. We studied 50 days survival using Kaplan-Meier analysis and diagnostic accuracy of PCT using ROC analysis. Results: In our study, PCT was statistically significantly higher in non-survivor patients compared to survivor patients (p<0.05). ROC curve was made with PCT based on culture at both time intervals. On the basis of ROC curve, we determined a cut-off value as 12.21 ng/ml of PCT on day 3 to predict sepsis with high sensitivity (93.7%) and specificity (71.4%). Area under curve (AUC) was also higher observed at day 3 (AUC=0.864, p<0.001) compared to day 1 (AUC=0.658, p<0.05). According to Kaplan-Meier curve, risk of mortality was by 83% (HR 0.17(95% 0.07-0.44)) lower in low sepsis category group (≤12.21 ng/ml) compared to high sepsis category group (>12.21 ng/ml). Conclusion: According to our study results, we conclude that serum PCT has good clinical diagnostic and prognostic values in prediction of survival in patients with sepsis. Kinetic studies of PCT can improve sensitivity and accuracy when evaluating the prognosis of patients with sepsis as well as survival rate. [ABSTRACT FROM AUTHOR]

Background: Procalcitonin (PCT) is a useful biomarker in humans in the identification of bacterial respiratory infections. Objectives: The aim of this study was to investigate the utility of serum PCT measurements as a diagnostic biomarker in canine bacterial lower respiratory tract diseases. Methods: PCT concentrations were measured in serum samples with an ELISA method previously validated for dogs. All dogs underwent thorough clinical examinations, and the diagnosis of respiratory disease was based on clinical and laboratory findings, diagnostic imaging, as well as cytology and bacterial culture of respiratory samples. PCT concentrations between different cohorts of dogs were compared with an ANOVA-model. Results: Sixty-two privately owned dogs with respiratory diseases, 25 with bacterial pneumonia (BP), 17 with bacterial bronchitis caused by Bordetella bronchiseptica (BB), and 20 with chronic bronchitis (CB) as well as 44 healthy controls were included in the study. Serum PCT concentrations in dogs with bacterial respiratory diseases (BP mean 51.8 ng/L ± standard deviation [SD] 40.6 ng/L and BB mean 61.4 ng/L ± SD 35.3 ng/L) were not significantly different when compared with dogs with a non-bacterial respiratory disease (CB mean 89.7 ± SD 73.5 ng/L) or healthy dogs (mean 51.0 ng/L ± SD 37.5 ng/L, p> .05 in all comparisons). Conclusions: These results indicate that despite being a valuable diagnostic, prognostic, and follow-up marker in humans with pneumonia, serum PCT concentrations are not elevated in dogs with bacterial respiratory diseases and, therefore, cannot be used as a diagnostic biomarker in dogs. [ABSTRACT FROM AUTHOR]

Objective: The present research was conducted to evaluate the negative effects of nicotine powder on the blood physiology, and biochemical and histological alterations of Labeo rohita. Materials and Methods: Fish were divided into four groups (1-4). Fish groups 2, 3, and 4 were exposed to different concentrations of nicotine, such as 0.75, 1.25, and 1.75 mg/l, while group 1 acted as a control. To find out the long-term impact of nicotine on body physiology, we conducted a 42-day experiment. After the completion of the experiment, hematology, biochemical assays, and histology were done. Results: Results revealed a considerable increase in HGB, red blood cells, WBCs, hematocrit, mean corpuscular volume, red cell distribution width -SD, procalcitonin, neutrophils, lymphocytes, monocytes, triglycerides, total cholesterol, low-density lipoprotein, very low-density lipoprotein, alanine transaminase, aspartate aminotransferase, globulin, thyroid stimulating hormone, BUN, creatinine, and blood glucose levels, whereas mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, RDW, platelet, high-density lipoprotein, albumin, total proteins, and T3 levels were significantly (p = 0.05) decreased in exposed fish as compared to control group fish. Histological alterations showed that exposure to smokeless nicotine causes deleterious and degenerative effects in the liver, kidney, and gills of exposed fish. Conclusion: Nicotine administration in fish results in adverse effects on different biochemical and hematological parameters and causes histological alterations in some vital organs of exposed fish. [ABSTRACT FROM AUTHOR]

Since October 2022, alerts have spread from several countries about the increase in invasive group A streptococcal (iGAS) and scarlet fever cases affecting young children. We aim to analyze the epidemiology of GAS infections in the last 12 years in our hospital and identify the clinical features of invasive cases observed in 2023. We conducted a retrospective study enrolling children and adolescents hospitalized at our pediatric clinic from January to December 2023 for a definitive diagnosis of iGAS infection. Clinical, laboratory, and imaging data were collected and analyzed. Comparing 2016 and 2023, we observed a similar number of GAS infections (65 vs. 60 cases). Five children with iGAS infection were hospitalized between March and April 2023. The median age was five years. At admission, all patients showed tachycardia disproportionate to their body temperature. Vomiting was a recurrent symptom (80%). Laboratory tests mostly showed lymphopenia, hyponatremia, and high inflammatory markers. The number of pediatric iGAS cases significantly increased in 2023. Clinical (pre-school-aged children with high fever, unexplained tachycardia, and vomiting) and laboratory parameters (high procalcitonin levels, hyponatremia, and lymphopenia) could help identify and suspect a potential iGAS infection. [ABSTRACT FROM AUTHOR]

Intraoperative fluid management is a crucial aspect of cancer surgery, including colorectal surgery and pancreatoduodenectomy. The study tests if intraoperative multimodal monitoring reduces postoperative morbidity and duration of hospitalisation in patients undergoing major abdominal surgery treated by the same anaesthetic protocols with epidural analgesia. A prospective study was conducted in 2 parallel groups. High-risk surgical patients undergoing major abdominal surgery were randomly selected in the control group (CG), where standard monitoring was applied (44 patients), and the protocol group (PG), where cerebral oxygenation and extended hemodynamic monitoring were used with the protocol for intraoperative interventions (44 patients). There were no differences in the median length of hospital stay, CG 9 days (interquartile range [IQR] 8 days), PG 9 (5.5), p = 0.851. There was no difference in postoperative renal of cardiac impairment. Procalcitonin was significantly higher (highest postoperative value in the first 3 days) in CG, 0.75 mcg/L (IQR 3.19 mcg/L), than in PG, 0.3 mcg/L (0.88 mcg/L), p = 0.001. PG patients received a larger volume of intraoperative fluid; median intraoperative fluid balance +1300 ml (IQR 1063 ml) than CG; +375 ml (IQR 438 ml), p < 0.001. There were significant differences in intraoperative fluid management and vasopressor use. The median postoperative value of procalcitonin was significantly higher in CG, suggesting differences in immune response to tissue trauma in different intraoperative fluid status, but there was no difference in postoperative morbidity or hospital stay. [ABSTRACT FROM AUTHOR]

Prostate‑derived calcitonin (CT) and its receptor induce tumorigenicity and increase metastatic potential of prostate cancer (PC). CT‑inducible genes in human prostate were identified by subtraction hybridization. Among these genes, zinc finger protein like 1 (ZFPL1) protein was interesting since it was abundantly expressed in malignant prostates but was almost absent in benign prostates. ZFPL1 expression was upregulated by CT and androgens, and ZFPL1 protein was secreted by prostate tumor cells through exosomal secretion. Serum levels of ZFPL1 in cancer patients were at least 4‑fold higher than those in the sera of cancer‑free individuals. Cell biology of ZFPL1 suggests its localization in Golgi bodies and exosomes, and its colocalization with chromogranin A and CD44. These results suggested that ZFPL1 is secreted by tumor cells of neuroendocrine (NE)/stem cell phenotype. The knockdown of endogenous ZFPL1 in (PC) cells led to a remarkable decrease in cell proliferation, and invasion while increasing their apoptosis. As expected, the overexpression of ZFPL1 in prostate cells had an opposite effect on these functions. The knockdown of ZFPL1 in PC cells also decreased Akt phosphorylation, suggesting the actions of ZFPL1 may be mediated through the PI3K‑Akt pathway. Moreover, the present results revealed that ZFPL1 is released by tumors cells of NE or androgen‑independent phenotype and its serum levels are significantly higher in cancer patients, suggesting that it may serve as a blood‑based non‑invasive biomarker of aggressive PC.

Abstract 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 0.23 (HR,5.10; 95% CI,2.15–12.11; P 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 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.

Shuzhou Liu,1,&ast; Hao Zhao,2,&ast; Xiaoyi Li2 1Department of Head & Neck Surgery, Hainan General Hospital, Haikou, 570311, People’s Republic of China; 2Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyi Li, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuai Fu Yuan, Dongcheng District, Beijing, 100730, People’s Republic of China, Email li.xiaoyi@263.netIntroduction: Medullary thyroid carcinoma (MTC), a rare malignancy, requires early diagnosis for optimal patient outcomes. An important aspect of MTC diagnosis is the assessment of serum biomarkers. This review aimed to evaluate the use of serum biomarkers in the diagnosis, prognosis, and follow-up of MTC.Methods: A thorough search of PubMed covering 1975 to 2022 was conducted to identify English-language articles on MTC serum biomarkers.Results: The review revealed that calcitonin (Ctn) and carcinoembryonic antigen (CEA) remain the most important serum biomarkers for MTC diagnosis and management. Despite limited studies on procalcitonin (PCT), its stability and ability to exclude interference from inflammation make it a valuable potential marker of MTC. Although the positive rate of serum CA19-9 levels in MTC patients was not high, it can be used as an indicator of poor prognosis in advanced MTC. Other serum markers, including chromogranin A, gastrin-releasing peptide precursor, and neurospecific enolase, did not show any unique value in MTC diagnosis and management.Conclusion: Taken together, this review emphasized the importance of serum biomarkers, particularly Ctn and CEA, in the diagnosis and management of MTC. PCT shows promise as a valuable potential marker, whereas CA19-9 can be used as a prognostic indicator of advanced MTC. Further research is needed to validate the significance of these serum biomarkers in MTC and determine the effects of confounding factors on their levels. Clinicians should consider using these markers in MTC diagnosis, prognosis, and follow-up, particularly for patients with advanced disease.Keywords: medullary thyroid carcinoma, serum biochemical markers, calcitonin, carcinoembryonic antigen, procalcitonin

BackgroundThe Procalcitonin Antibiotic Consensus Trial (ProACT) found provision of a procalcitonin antibiotic prescribing guideline to hospital-based clinicians did not reduce antibiotic use. Possible reasons include clinician reluctance to follow the guideline, with an observed 64.8% adherence rate. In this study we sought to determine the threshold adherence rate for reduction in antibiotic use, and to explore opportunities to increase adherence.MethodsThis study is a retrospective analysis of ProACT data. ProACT randomized 1656 patients presenting to 14 U.S. hospitals with suspected lower respiratory tract infection to usual care or provision of procalcitonin assay results and an antibiotic prescribing guideline to the treating clinicians. We simulated varying adherence to guideline recommendations for low procalcitonin levels and determined which threshold adherence rate could have resulted in rejection of the null hypothesis of no difference between groups at alpha = 0.05. We also performed sensitivity analyses within specific clinical settings and grouped patients initially prescribed antibiotics despite low procalcitonin into low, medium, and high risk of illness severity or bacterial infection.ResultsOur primary outcome was number of antibiotic-days by day 30 using an intention-to-treat approach and a null hypothesis of no difference in antibiotic use. We determined that an 84% adherence rate in the hospital setting (emergency department and inpatient) for low procalcitonin could have allowed rejection of the null hypothesis (3.7 vs 4.3 antibiotic-days, p = 0.048). The threshold adherence rate was 76% for continued guideline adherence after discharge. Even 100% adherence in the emergency department alone failed to reduce antibiotic-days. Of the 218 patients prescribed antibiotics in the emergency department despite low procalcitonin, 153 (70.2%) were categorized as low or medium risk.ConclusionsHigh adherence in the hospital setting to a procalcitonin antibiotic prescribing guideline is necessary to reduce antibiotic use in suspected lower respiratory tract infection. Continued guideline adherence after discharge and withholding of antibiotics in low and medium risk patients with low procalcitonin may offer impactful potential opportunities for antibiotic reduction. Trial registration Procalcitonin Antibiotic Consensus Trial (ProACT), ClinicalTrials.gov Identifier: NCT02130986. First posted May 6, 2014.