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

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

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

Calcitonin (CT), a hormone secreted by thyroid parafollicular C cells, plays a role in calcium homeostasis and bone health. Understanding the relationship between CT levels and dietary, sociodemographic, and lifestyle factors is essential for public health and hormonal balance studies. This study encompassed 3323 healthy participants from the Croatian biobank. We utilized principal component analysis (PCA) to reduce food items into dietary patterns. Regression analysis was used to investigate the relationship between CT levels and data collected through questionnaires, accounting for age and sex. CT levels exhibited sex-specific differences, with higher values observed in males. Positive associations were found between CT levels and age, body mass index (BMI), as well as weekly consumption of white and red wine mixed with water. While height and sternal notch-finger length initially correlated positively with CT levels, this relationship reversed upon adjusting for age and sex. Regarding sport activities, CT levels were significantly increased in non-participants compared to occasional sport participants (p = 0.043). Dietary factors yielded intriguing findings, with frequent consumption of butter, animal fat and veal associated with lower CT levels, while higher CT levels were associated with the frequent consumption of white fish, blue fish, pasta, and rice. However, no significant correlation was found between CT levels and bone mineral density (BMD), weight, or body surface area (BSA). This study highlights the complex interplay of dietary, lifestyle, and sociodemographic factors influencing CT levels. These findings suggest that a broad range of factors should be considered in hormonal balance studies, underlining their potential implications for public health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A widespread strategy to increase the transport of therapeutic peptides across cellular membranes has been to attach lipid moieties to the peptide backbone (lipidation) to enhance their intrinsic membrane interaction. Efforts in vitro and in vivo investigating the correlation between lipidation characteristics and peptide membrane translocation efficiency have traditionally relied on end-point read-out assays and trial-and-error-based optimization strategies. Consequently, the molecular details of how therapeutic peptide lipidation affects it's membrane permeation and translocation mechanisms remain unresolved. Here we employed salmon calcitonin as a model therapeutic peptide and synthesized nine double lipidated analogs with varying lipid chain lengths. We used single giant unilamellar vesicle (GUV) calcein influx time-lapse fluorescence microscopy to determine how tuning the lipidation length can lead to an All-or-None GUV filling mechanism, indicative of a peptide mediated pore formation. Finally, we used a GUVs-containing-inner-GUVs assay to demonstrate that only peptide analogs capable of inducing pore formation show efficient membrane translocation. Our data provided the first mechanistic details on how therapeutic peptide lipidation affects their membrane perturbation mechanism and demonstrated that fine-tuning lipidation parameters could induce an intrinsic pore-forming capability. These insights and the microscopy based workflow introduced for investigating structure-function relations could be pivotal for optimizing future peptide design strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Tandem mass spectrometry (MS/MS) can provide direct and accurate sequence characterization of synthetic peptide drugs, and peptide drug products including side chain modifications in the Peptide drugs. This article explains a step-by-step guide to developing a high-throughput method using high resolution mass spectrometry for characterization of Calcitonin Salmon injection containing high proportion of UV-active excipients., Methods: The major challenge in the method development of Amino acid sequencing and Peptide mapping was presence of phenol in drug product. Phenol is a UV-active excipient and reacts with both Dithiothreitol (DTT) and Trypsin. Hence Calcitonin Salmon was extracted from the Calcitonin Salmon injection using solid phase extraction after the extraction, Amino acid sequencing and peptide mapping study was performed. Upon incubation of Calcitonin Salmon with Trypsin and DTT, digested fragments were generated which were separated by mass compatible reverse phase chromatography and the molecular mass of each fragment was determined using HRMS., Results: A reverse phase chromatographic method was developed using UHPLC-HRMS for the determination of direct mass, peptide mapping and to determine the amino acid sequencing in the Calcitonin Salmon injection. The method was found Specific and fragments after trypsin digest are well resolved from each other and the molecular mass of each fragment was determined using HRMS. Sequencing was performed using automated identification of b and y ions annotation and identifications based on MS/MS spectra using Biopharma finder and Proteome discoverer software., Conclusion: Using this approach 100% protein coverage was obtained and protein was identified as Calcitonin Salmon and the observed masses of tryptic digest of peptide was found similar with theoretical masses. The method can be used for both UV and MS based Peptide mapping and whereas the UV based peptide mapping method can be used as identification test for Calcitonin Salmon drug substance and drug product in quality control., Competing Interests: Declaration of Competing Interest No Conflict of Interest If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Treating central giant cell granuloma (CGCG) is challenging due to high recurrence rates and variable therapy responses. This study examines the efficacy of various treatments in reducing CGCG recurrence. A literature review explored outcomes of surgical excision, curettage, intralesional corticosteroid injection, and adjuvant therapy, considering factors like lesion location, size, and histological features. Aggressive surgical techniques such as en bloc resection were found to potentially lower recurrence rates compared to conservative approaches. However, treatment should be tailored to individual patient needs. Further research is needed to confirm these findings and improve treatment strategies. A concise literature review was conducted using PubMed, MEDLINE, and Google Scholar, focusing on papers published from 1986 to 2024. Search terms included "central giant cell granuloma", "recurrence", "treatment modalities", and "surgical excision". Studies reporting recurrence rates and treatment outcomes for CGCG were analyzed. Twenty-nine studies were reviewed, including six studies on surgical excision and curettage, eight studies on intralesional corticosteroid injections, six studies on calcitonin therapy, five studies on interferon-alpha therapy, and four studies on the therapy with denosumab. Analysis indicated that aggressive surgical treatments like en bloc resection were associated with lower recurrence rates compared to conservative methods. Predictors of recurrence included lesion size (>3 cm), location (mandible), and aggressive histopathological features. Aggressive surgical excision combined with nonsurgical methods may lower recurrence rates, while conservative techniques remain viable in some cases. Further prospective research is needed to validate these findings and enhance CGCG treatment options. [ABSTRACT FROM AUTHOR]

Purpose: Compared with other types of thyroid carcinoma, patients with medullary thyroid carcinoma (MTC) are more likely to develop cervical lymph node metastasis. This study was conducted to clarify the risk factors for cervical lymph node metastasis (central lymph node metastasis or lateral cervical lymph node metastasis) in MTC by meta-analysis, and to provide evidence-based basis for the treatment and prognosis of MTC., Methods: The literatures related to cervical lymph node metastasis in medullary thyroid carcinoma were searched in PubMed, Embase, Web of Science, Cochrane, CNKI and Wanfang databases, and statistical analysis was performed using Revman 5.3 and Stata 14.0 software., Results: A total of 28 papers were included in this paper, and meta-analysis showed that the occurrence of central lymph node metastasis (CLNM) in MTC patients was significantly associated with tumor size (OR = 3.07, 95%CI: 2.04-4.63, P < 0.00001), multifocality (OR = 0.29, 95%CI: 0.19-0.44, P < 0.00001), bilaterality (OR = 3.75, 95% CI: 1.95-7.14, P < 0.0001), capsular invasion (OR = 9.88, 95% CI: 5.93-16.45, P < 0.00001) and extrathyroidal extension (OR = 5.48, 95% CI: 2.61-11.51, P < 0.00001). While the occurrence of lateral cervical lymph node metastasis (LLNM) in MTC patients was strongly correlated with gender (OR = 2.97, 95%CI: 2.46-3.58, P < 0.00001), tumor size (OR = 3.88, 95%CI: 1.90-7.92, P = 0.0002 < 0.05), multifocality (OR = 0.43, 95%CI: 0.35-0.51, P < 0.00001), bilaterality (OR = 2.93, 95% CI: 1.72-4.98, P < 0.0001), capsular invasion (OR = 8.44, 95% CI: 6.11-11.64, P < 0.00001), extrathyroidal extension (OR = 7.04, 95% CI: 5.54-8.94, P < 0.00001), margin of the tumor (OR = 4.47, 95% CI: 2.37-8.44, P < 0.00001), shape of the tumor (OR = 6.81, 95% CI: 3.64-12.73, P < 0.00001), preoperative calcitonin level (SMD = 1.39, 95% CI: 0.98-1.80, P < 0.00001), preoperative carcinoembryonic antigen level (SMD = 0.97, 95% CI: 0.74-1.20, P < 0.00001) and CLNM (OR = 19.70, 95% CI: 14.16-27.43, P < 0.00001)., Conclusion: Tumor size, multifocality, bilaterality, capsular invasion and extrathyroidal extension are the main risk factors for developing CLNM in MTC patients; And risk factors for developing LLNM in MTC patients include: gender, tumor size, multifocality, bilaterality, capsular invasion, extrathyroidal extension, margin of the tumor, shape of the tumor, preoperative calcitonin level, preoperative carcinoembryonic antigen level and central lymph node metastasis. These risk factors can guide the individualized treatment plan and improve the prognosis of MTC patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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]

Peptide drugs through nasal mucous membrane, such as insulin and calcitonin have been widely used in the medical field. There are always two sides to a coin. One side, intranasal drug delivery can imitate the secretion pattern in human body, having advantages of physiological structure and convenient use. Another side, the low permeability of nasal mucosa, protease environment and clearance effect of nasal cilia hinder the intranasal absorption of peptide drugs. Researchers have taken multiple means to achieve faster therapeutic concentration, lower management dose, and fewer side effects for better nasal preparations. To improve the peptide drugs absorption, various strategies had been explored via the nasal mucosa route. In this paper, we reviewed the achievements of 18 peptide drugs in the past decade about the perspectives of the efficacy, mechanism of enhancing intranasal absorption and safety. The most studies were insulin and calcitonin. As a result, absorption enhancers, nanoparticles (NPs) and bio-adhesive system are the most widely used. Among them, chitosan (CS), cell penetrating peptides (CPPs), tight junction modulators (TJMs), soft NPs and gel/hydrogel are the most promising strategies. Moreover, two or three strategies can be combined to prepare drug vectors. In addition, spray freeze dried (SFD), self-emulsifying nano-system (SEN), and intelligent glucose reaction drug delivery system are new research directions in the future., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

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

Patients with intra-abdominal sepsis suffer from significant mortality and morbidity. The main pillars of treatment for intra-abdominal infections are (1) source control and (2) early delivery of antibiotics. Antibiotic therapy should be started as soon as possible. However, the duration of antibiotics remains a matter of debate. Prolonged antibiotic delivery can lead to increased microbial resistance and the development of nosocomial infections. There has been much research on biomarkers and their ability to aid the decision on when to stop antibiotics. Some of these biomarkers include interleukins, C-reactive protein (CRP) and procalcitonin (PCT). PCT's value as a biomarker has been a focus area of research in recent years. Most studies use either a cut-off value of 0.50 ng/mL or an >80% reduction in PCT levels to determine when to stop antibiotics. This paper performs a literature review and provides a synthesized up-to-date global overview on the value of PCT in managing intra-abdominal infections. [ABSTRACT FROM AUTHOR]

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

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

Hydrophobic ion pairing and subsequent incorporation into self-emulsifying drug delivery systems (SEDDS) is a promising strategy to orally deliver hydrophilic macromolecular drugs. Within this study, hydrophobic ion pairs (HIP) between salmon calcitonin (sCT) and highly lipophilic sulfosuccinate counterions were formed and compared to frequently applied commercially available counterions. Bis(isotridecyl) sulfosuccinate resulted in HIPs of the highest lipophilicity and in significantly higher solubility in lipophilic co-solvents. Thus, bis(isotridecyl) sulfosuccinate allowed efficient solubilization of sCT in a SEDDS preconcentrate based on a lipophilic co-solvent and an indigestible lipid, but omitting hydrophilic co-solvents. In addition to the increased solubility in the lipidic matrix, markedly reduced dissociation in biorelevant media resulted in high distribution coefficients between oil droplet and FaSSGF or FaSSIF (logD) of 2.98 ± 0.12 or 2.77 ± 0.14, respectively. The composition of the lipidic matrix preserved integrity of the oil droplets after emulsification and subsequent lipolysis, allowing to fully exploit the potential of the HIP attributed to the high logD. Oral administration of the HIP-loaded SEDDS resulted in an excellent relative pharmacological activity of 13.8 ± 5.6 % measured as hypocalcaemic effect in rats., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

This paper presents a case of urosepsis caused by Escherichia coli in an 11-year-old girl with a neurogenic bladder. The patient had not previously been supervised by a nephrologist or urologist. On admission, significantly elevated serum markers of inflammation (C-reactive protein 32.4 mg/dl, procalcitonin 64.2 ng/ml), kidney failure (creatinine 6.9 mg/dl, pH 7.22, HCO3 6.3 mmol/l), and increased serum urea (399 mg/dl) were detected. Antibiotic therapy with rehydration was started and improved renal function without dialysis. However, a 9-cm-long perirenal abscess site was diagnosed. It required surgical treatment, which was complicated by an anaphylactic reaction to latex. Colitis caused by Clostridium difficile was also diagnosed. Hospital treatment lasted 38 days. After 4 months the patient's glomerular filtration rate was 66 ml/min/1.73 m² and indicated stage 2 chronic kidney disease. Because early diagnosis of urinary tract infection is crucial for preventing complications in children with neurogenic bladder, they should undergo regular nephro-urological care. [ABSTRACT FROM AUTHOR]

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

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

Background: Ewing sarcoma (ES) represents a rare, aggressive bone and soft-tissue cancer. Unlike breast, liver, pancreatic, and prostate cancers, Ewing sarcoma has had no representative tumor marker until now. The use of procalcitonin (PCT) as a tumor marker is also rarely reported. PCT is a clinically recognized and widely used inflammatory marker in recent years. In rare cases, PCT may also be falsely positive due to non-infectious factors. In the few previously reported papers regarding the correlation between tumors and PCT, we learned that abnormalities of PCT level can also be impacted by individual cancers. Case presentation: Here, we first reported a case of Ewing sarcoma with markedly elevated PCT without infection and carried out some literature review. The patient was a middle-aged man with extraskeletal Ewing sarcoma whose lesion was located in the distal abdominal ileum. He had a sudden and unprovoked onset of high fever during chemotherapy before surgery. After multiple examinations, the patient's blood routine, C-reactive protein, blood culture, and CT examination showed no signs of infection, and even the culture from the end of the central venous catheter showed no pathogen growth. Only PCT increased dramatically to more than 200 ng/ml. PCT remained at this level for several months until a single abdominal lumpectomy was performed before it dropped to near-normal levels. Conclusion: In our report, PCT is significantly elevated in Ewing sarcoma in the absence of infection. Not only that, but we particularly highlighted the precipitous drop in PCT following tumor resection. [ABSTRACT FROM AUTHOR]

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

Background: We have explored that quantitative PCT detection can be conducted in different sample types (whole blood and/or plasma samples) with good correlation and consistency in clinical use. These findings reduce the sample volume and turnover time of PCT detection in clinical labs. However, different hematocrit (HCT) percentages of whole blood samples may affect the final results, especially abnormal hematocrit (HCT) percentages. To overcome this problem, we established a mathematical model to modify the whole blood test results and evaluated the effects of HCT correction. Methods: First, we prepared a preliminary experiment - various hematocrit (HCT) percentages (15% - 65%) of whole blood samples with different PCT concentrations and established a mathematic model to correct the effects of PCT detection. Then, in this paper, we evaluated the consistency with Pearson's correlation and Kappa analysis between whole bloods detected by the i-Reader S system and plasma detected by the Biomerieux system. Besides, we prepared different HCT values about 15%, 40%, 60% of 9 samples with different PCT concentrations to evaluate the effects of HCT correction Results and Conclusions: Pearson's correlative studies and Kappa analysis indicated that PCT levels measured by i-Reader S (plasma & whole blood samples) were comparable to results from the VIDAS system, and HCT correction could improve consistency of PCT detection between whole blood and plasma. Analysis of samples with abnormal HCT values showed that the mathematical correction model could offset the influences of various HCT values. [ABSTRACT FROM AUTHOR]

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

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

Background: The use of efficient laboratory calcitonin (CT) testing is required for optimal management of medullary thyroid carcinoma. Several pitfalls are related to the calcitonin laboratory assays and a careful evaluation is needed. We report the analytical performances of the new Siemens ADVIA-Centaur-CALCT (CT-XPT) assay and its comparison with our standard method DiaSorin-Calcitonin-II-Gen (CT-LIA) assay. Methods: Analytical performance of the CT-XPT-assay, limit of blank (LOB), limit of detection (LOD), and limit of quantification (LOQ), were determined. We also evaluated the in vitro stability of the sample, together with the linearity and percentage recovery. Results: The CT-XPT-assay showed a better detection limit than the CT-LIA assay, with lower values of LOB (0.86 pg/mL vs 1.00 pg/mL) and LOQ (1.65 pg/mL vs 3.00 pg/mL). Both values were in agreement with those reported by the manufacturer. Within- and between-run precision demonstrated a good concordance of results. Regarding the in vitro stability of CT, the low CT concentration sera showed a much greater decrease in CT levels compared to the high concentration sera. Correlation studies showed a good correlation between the two methods (Kappa Cohen coefficent, KC: 0.68, agreement % for male: 89.58%; KC: 0.63; agreement % for female: 88.33%). Conclusions: Our findings showed a good correlation between the CT-LIA and CT-XPT methods. Moreover, we demonstrated that the analytical performance of the CT-XPT assay, together with its technical specifications, could represent major features of the CT-XPT method. Collectively, the technical evaluation and the analytical results described in the presented paper highlight that the novel CT-XPT is a valid method for CT testing in a clinical diagnostic setting. [ABSTRACT FROM AUTHOR]

Objectives: The aims of this paper were to characterize patients with severe Covid-19 and study the prevalence of positive procalcitonin test in those patients. Methods: In this retrospective cross-sectional study, data were collected in infectious diseases clinic between June 2020 and July 2021. Real time polymerase chain reaction (RTPCR) was conducted to confirm the diagnosis of Covid-19. COBAS system was used to determine procalcitonin positivity following the instructions of manufacturer. Results: During the study period, 454 Covid-19 confirmed patients were referred to the clinic. Among those, 55/494 (11.13%) had severe Covid-19 infection. Fever (89.1%) was the most common clinical features followed by cough (29.1%) and shortness of breath (20%). In this project, we found 4/55 (7.27%) patients had elevated procalcitonin levels. High procalcitonin was not associated with clinical outcome (P = 0.99). Conclusions: In agreement with other studies, fever was the most common symptom in patients with severe Covid-19. Small number of the patients with severe Covid-19 showed elevated procalcitonin levels. This might indicate that antibiotics should not prescribed empirically to such patients. Further studies are needed to investigate this. [ABSTRACT FROM AUTHOR]

Oblique-incidence reflectivity difference (OIRD) is a compelling technique for real-time, label-free and non-destructive detection of antibody microarray chips, but its sensitivity needs essential improvement for clinical diagnosis. In this study, we report an innovative high-performance OIRD microarray by using poly[oligo(ethylene glycol) methacrylate-co-glycidyl methacrylate] (POEGMA-co-GMA) brush grafted fluorine-doped tin oxide (FTO) as the chip substrate. The polymer brush enhances the interfacial binding reaction efficiency of targets from the complicated sample matrix due to its high antibody loading and excellent anti-fouling merits; the FTO-polymer brush layered structure, on the other hand, excites the interference enhancement effect of OIRD to achieve enhanced intrinsic optical sensitivity. Synergistically, the sensitivity of this chip is significantly improved compared to rival chips, achieving a limit of detection (LOD) as low as 25 ng mL−1 for the model target C-reactive protein (CRP) in 10% human serum. This work explores the tremendous influence of the chip interfacial structure on the OIRD sensitivity and proposes a rational interfacial engineering strategy to boost the performance of the label-free OIRD based microarray and other bio-devices. [ABSTRACT FROM AUTHOR]

A dual-emitting electrochemiluminescence (ECL) immunosensor based on manganese dioxide nanoflowers (MnO2NFs) and zinc sulfide quantum dots (ZnSQDs) was constructed for the first time to sensitively detect procalcitonin (PCT) in human serum. rGO@Ag functioned not only to adsorb primary antibodies (Ab1) but also to improve the electrical conductivity of the immunosensor. The MnO2NFs and ZnSQDs in the nanocomposite, synergistically with silver nanoparticles, simultaneously functioned as cathodic ECL emitters to enhance the detection sensitivity of PCT by shortening the electron-transfer path, thereby reducing energy loss. Under the optimized experimental conditions, the ECL immunosensor was capable of quantitatively detecting PCT in the linear range of 0.1 pg mL−1 to 100 ng mL−1 and over the scanning potential range of −2.0–0 V, with a detection limit of 0.033 pg mL−1. Furthermore, the ECL immunosensor demonstrated high specificity for PCT in the presence of other competing antigens, excellent stability over 10 cycles, and excellent reproducibility, corroborating its potential for measuring PCT concentrations in clinical samples. [ABSTRACT FROM AUTHOR]

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

Introduction: Sepsis is a growing problem worldwide and associated with high mortality and morbidity. The early and accurate diagnosis and effective supportive therapy are critical for combating mortality. The aim of the study was to compare the kinetics of four biomarkers in plasma in patients admitted to ICU including sepsis and during antibiotics treatment. Methods: The biomarkers evaluated were HBP (Heparin-binding protein), HNL Dimer (Human Neutrophil Lipocalin), HNL Total and PCT (Procalcitonin). Plasma was obtained at admission to ICU and during follow-up at days 2 and 3. Antibiotic treatment was started or reviewed on admission to ICU. The results were compared to SOFA and KDIGO-scores and to survival. 277 patients admitted to ICU were included of which 30% had sepsis. The other groups were categorized as miscellaneous, other medical and trauma. Results: The plasma concentrations of all four biomarkers were highly elevated with the highest concentrations in sepsis patients. During the follow-up period HNL Dimer decreased already day 2 and further so day 3 (p<0.00001) in contrast to unchanged concentrations of the other three biomarkers. HNL Total showed the strongest relationships to the clinical scores (p<0.0001) and was by multiples regression analysis independently related to these scores. Conclusion: Our data supports and confirms our earlier findings of HNL Dimer being a novel and potentially useful clinical tool in antibiotic stewardship in sepsis. HNL Total reflects epithelial cell activity in the body and is an interesting biomarker for the management of organ failure in such patients. [ABSTRACT FROM AUTHOR]

Background: Most real-world data on CGRP mAbs have been published from high-income countries such as the USA, Western countries, Japan, Korea, and Singapore. However, data from low- and middle-income countries in Southeast Asia is lacking. This is the first real-world study from Thailand to describe the efficacy of CGRP mAbs therapy in migraine patients and to analyze the response trends between episodic migraine and chronic migraine. Methods: We conducted a single-center, real-world retrospective chart review study with an observation period of 6 months after CGRP mAbs initiation. We aim to compare treatment responses to CGRP mAbs between EM and CM patients. Results: A total of 47 Thai patients were enrolled (median [IQR] age 37.2 [28.6–50.4] years; 85.1%F, 44.7% EM; 70.2% galcanezumab). There was no difference in baseline characteristics and migraine disability assessment (MIDAS) between EM and CM. The overall ≥ 30%, ≥ 50%, and ≥ 70% monthly migraine day reduction rates at 6 months were 89.0%, 71.6%, and 58.5% with higher responders in EM. There was a significant decrease in monthly headache days (MHDs) over time (adjusted β = -0.42, p < 0.001) and a significant decrease in MIDAS score over time after the initiation of CGRP mAbs (adjusted β = -1.12, p = 0.003). However, there were no differences between the two diagnoses. There was no significant decrease in the number of abortive medication pills used over time after the initiation of CGRP mAbs. CM had a significantly steeper trend compared to those with EM. Conclusion: The first real-world study in Thailand demonstrated that CGRP mAbs therapy had efficacy for migraine treatment, as evidenced by a reduction in MHDs, decreased disability, and reduced use of abortive medications. Additionally, the response pattern to CGRP mAbs therapy was similar between EM and CM in terms of MHDs reduction and MIDAS score improvement. [ABSTRACT FROM AUTHOR]

We present a case of a PTH-related peptide (PTH-rp) producing uterine myoma, leading to hypercalcemia in pregnancy. Our patient presented with dehydration, hypotension, delirium, and malnutrition. Due to a serum calcium level of 17.9 mg/dL (4.48 mmol/L) (reference range 8.8-11.2 mg/dL; 2.20-2.80 mmol/L), prompt treatment with hydration and calcitonin was initiated. The patient went into labor before we could consider other treatment options. Although uncommon in pregnancy, it is of great importance to identify hypercalcemia since it is related to a high risk of maternal and neonatal morbidity and mortality. Because bisphosphonates are contraindicated in pregnancy, hydration and calcitonin are the cornerstones of treatment for PTH-rp-induced hypercalcemia. [ABSTRACT FROM AUTHOR]

To explore the usefulness of neutrophil-to-lymphocyte count ratio (NLR), procalcitonin (PCT), and interleukin-6 (IL-6) for the severity assessment of bacterial sepsis. This study enrolled 100 patients with bacterial sepsis (disease group) who presented to Jinhua Central Hospital between March 2022 and March 2023 and 90 healthy individuals (control group). The patients were categorized into sepsis (64 cases), severe sepsis (18 cases), and septic shock (18 cases) groups according to the disease severity. The groups were compared in terms of the NLR, PCT, and IL-6, as well as the usefulness of these parameters, both alone and in combination, for the severity assessment of bacterial sepsis. The NLR, PCT, and IL-6 levels were significantly different among the three groups, with increasing values corresponding with disease aggravation. The area under the curve (AUC) values of the combinations of NLR, PCT, and IL-6 levels were higher than those of single markers. The sensitivity and AUC value of the combination of PCT and IL-6 levels were the highest (0.87), with a similar AUC value of the combination of NLR, PCT, and IL-6 (0.865); however, the specificity was significantly improved with the latter (0.938 vs. 0.859). NLR, PCT, and IL-6 levels are significantly increased in bacterial sepsis, and the combination of PCT, and IL-6 levels can improve the sensitivity of the evaluation ability for severe sepsis, and is more economical. [ABSTRACT FROM AUTHOR]

Background: Sarcoidosis is a multisystemic disease that is histologically characterized by non-caseating granulomas in one or more organs. Although hypercalcemia is commonly seen in sarcoidosis, clinically significant hypercalcemia as the initial presentation of sarcoidosis is exceedingly rare. Long-standing hypercalcemia can lead to several complications and needs to be adequately managed to prevent irreversible damage. Currently, there are no standard treatment guidelines for sarcoidosis-induced hypercalcemia, although glucocorticoids have often been used as first-line therapy. Case Report: We describe a 55-year-old male patient who presented with dull right upper quadrant abdominal pain and a 30-pound weight loss over one month. He was found to have severe hypercalcemia, which was treated with intravenous (IV) normal saline and intramuscular calcitonin. Imaging studies revealed hypodense lesions throughout the bilateral hepatic lobes, spleen, and bilateral kidneys, with no pathologic mediastinal, hilar, supraclavicular, or axillary lymphadenopathy or pulmonary parenchymal disease. A splenic biopsy confirmed extrapulmonary sarcoidosis. After initial discharge, the patient was re-admitted weeks later for severe hypercalcemia, which was successfully treated with the initiation of prednisone. Conclusions: In this report, we present an atypical case of isolated extrapulmonary sarcoidosis with severe hypercalcemia as the initial presentation, successfully treated with steroids. [ABSTRACT FROM AUTHOR]

To investigate the role of the triple combination serum heparin-binding protein (HBP), procalcitonin (PCT), and C-reactive protein (CRP) in children with acute bacterial upper respiratory tract infection (ABURTI). A total of 130 children with upper respiratory tract infection admitted to the Department of Pediatrics of Fujian Maternity and Child Health Hospital from September 2019 to January 2021 were selected as the research group. According to the results of pathogenic analysis, children were further subdivided into a bacterial infection group (n = 67) and a viral infection group (n = 63). Additionally, 65 children who underwent physical examinations in our hospital during the same period were collected and included into the control group (n = 65). All patients selected were treated with cefixime granules orally for 5 days. Serum HBP level, serum PCT level, and serum CRP level were measured by double antibody Sandwich Enzyme Linked Immunosorbent Assay (ELISA), fluorescence method, and immunoturbidimetric assay, respectively. The expression levels of the three indicators in the serum of all subjects were compared, and the receiver operating characteristic (ROC) curve was used to analyze their diagnostic value in children with ABURTI. Furthermore, according to clinical efficacy of children with bacterial infections, they were divided into a good efficacy group (markedly effective) and a poor efficacy group (effective + ineffective) to compare serum HBP, PCT, and CRP levels between the two groups. The ROC curve was drawn to analyze the value of the three indicators in predicting the curative effect in children with ABURTI. Pearson test was used to analyze the correlation among the expression of HBP, PCT, and CRP. Results showed that the expression levels of HBP, PCT, and CRP in the serum of children in the bacterial infection group were significantly higher than those in the other two groups. The positive rates of HBP, PCT, and CRP in children in the bacterial infection group were also significantly higher than those of the other two groups. The area under the curve (AUC) of the combined diagnosis of HBP, PCT, and CRP was 0.973, which was significantly higher than that of the single detection by any of the three indicators, which were 0.849, 0.819, and 0.854, respectively. The expression levels of HBP, PCT, and CRP in the serum of children in the good efficacy group were significantly lower than those in the poor efficacy group, and the AUC of the triple combination for predicting treatment efficacy was 0.959. Pearson test showed that there was a positive correlation between the serum expression of HBP, PCT, and CRP in children. HBP, PCT, and CRP were highly correlated in children with ABURTI, and their combined detection was of high diagnostic value among ABURTI patients, indicating that the three were expected to become potential indicators for efficacy prediction. [ABSTRACT FROM AUTHOR]

Objective: This study sought to assess the sensitivity, specificity, and predictive utility of serum procalcitonin (PCT) in the diagnosis of pediatric osteomyelitis. Methods: A systematic computer-based search was conducted for eligible literature focusing on PCT for the diagnosis of osteomyelitis in children. Records were manually screened according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Statistical analysis was performed using Review Manager software 5.3, Meta-disc software1.4, STATA 12.0, and R 3.4 software. Result: A total of 5 investigations were included. Of these, 148 children with osteomyelitis were tested for bacterial cultures in PCT. For PCT in the diagnosis of pediatric osteomyelitis, diagnostic meta-analysis revealed a pooled sensitivity and specificity of 0.58 (95% confidence interval (CI): 0.49 to 0.68) and 0.92 (95% CI: 0.90 to 0.93) respectively. The PCT had the greatest area under the curve (AUC) at 0.80 for the diagnosis of osteomyelitis in children. The Deeks' regression test for asymmetry results indicated that there was no publication bias when evaluating publication bias (P = 0.90). Concusion: This study provided a comprehensive review of the literature on the use of PCT in pediatric osteomyelitis diagnosis. PCT may be used as a biomarker for osteomyelitis diagnosis; however, its sensitivity was low. It still needs to be validated by a large sample study. [ABSTRACT FROM AUTHOR]

Objective: To determine the presepsin and procalcitonin significance in cord blood and compare with lactate and C-Reactive protein for early prediction of neonatal sepsis. Study Design: Case Control Study. Setting: Military Hospital Rawalpindi. Period: Sep 2018 to July 2019. Methods: Mothers, having deliveries with early or prolonged rupture of membrane, preterm, dai handled, meconium and failure of induction have been included. Out of 60 neonates, nineteen were cases with a clearly documented suspicion of sepsis and confirmed by neonatologists, remaining were control. Mean and Standard Deviation were calculated. The difference in all biochemical markers levels among case and control groups were assessed by independent t-test. Sensitivity, specificity, accuracy, and predictive value of both markers were calculated by medcalc diagnostic calculator. Regression analysis to access the strength. Receiver Operating Characteristics curve for most accurate cut off values and Area Under the Curve was calculated. Results: Independent sample t test revealed the strong association of procalcitonin and presepsin with neonatal sepsis. Presepsin has higher positive predictive value 83.33% and negative predictive value 90.48% with 88.33% accuracy while procalcitonin has positive predictive value 62.50%, negative predictive value 88.89% and accuracy 78.33%. Stepwise regression analysis showed better in combination than single in predication of neonatal sepsis. The cutoff value for procalcitonin was 0.4ng/ml (AUC of 84.5%.) and for presepsin was 305pg/ml (AUC of 86.5%). Conclusion: In comparison to lactate and CRP, a prediction model that incorporates two biochemical indicators, procalcitonin and presepsin, can reduce infant mortality and morbidity by spotting neonatal sepsis early. [ABSTRACT FROM AUTHOR]

Introduction: Complicated intra-abdominal infection (cIAI) still has a high mortality rate due to organ dysfunction despite advances in supportive care. Unlike other sources of septicemia, cIAI requires source control surgery, which is crucial for improving outcomes. The strategy for source control varies depending on the degree of inflammation associated with cIAI; the more severe the inflammation, the less aggressive the surgery needs to be. Therefore, we need a reliable parameter to predict the degree of inflammation before any physiological rearrangement or organ dysfunction occurs due to excessive inflammation from surgery. The literature shows that CRP, procalcitonin, lactate, and albumin are associated with the degree of inflammation. Thus, it's necessary to study about mentioned parameters for being reference determination strategy of surgery in cIAI, classical definitive laparotomy, or rapid source control laparotomy (RSCL). Methods: We have collected data from CIAI patients at Dr. Soetomo Regional General Hospital in Surabaya, Indonesia, covering November 2022 to April 2024. Our primary focus is assessing the inflammation level associated with the compensated or decompensated phase. The decompensated phase signifies an excessive inflammatory response, with one indication being in-hospital mortality. Subsequently, we performed univariate and multivariate analyses using the SPSS program to determine which laboratory parameters (CRP, Procalcitonin, Lactate, and Albumin) are most associated with in-hospital mortality. Results: Between November 2022 and April 2024, there were 309 patients with complicated intra-abdominal infections (cIAI). Among the patients, 61.8% were male and 38.2% were female. The majority of patients (27.17%) were aged 61-70. The causes of cIAI included perforated appendicitis (22.65%), perforated peptic ulcer (21.69%), complications from previous surgeries (18.13%), large bowel perforation (12.29%), small bowel perforation (11.33%), intraperitoneal abscess (11.33%), and other causes (2.58%). Statistically, lactate was found to be the most accurate predictor of intraoperative hemodynamic instability (p-value < 0.001; correlation coefficient of 0.481), followed by albumin (p-value < 0.001; correlation coefficient of 0.357). CRP and Procalcitonin were less accurate, with correlation coefficients of 0.182 and 0.272, respectively. The determined cut-off points for lactate and albumin were 1.94 and 2.73, for CRP and Procalcitonin were 23,24 and 47,95. Abnormal laboratory finding in our study mean CRP above cut off point, Procalcitonin above cut off point, lactate above cut off point and albumin below cut off point. More than 2 laboratories finding, in-hospital mortality 66,7%, 2 laboratory finding in-hospital mortality 42,8% and only 1 laboratory finding in-hospital mortality 28,4%. Conclusions: CRP, Procalcitonin, Lactate and Albumin have relation statistically significant with in-hospital mortality. Lactate and albumin are better than CRP and procalcitonin in our study, and consider RSCL for more than 2 parameter abnormal laboratory findings CRP, procalcitonin, lactate or albumin. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

Background: Low immune function after laparoscopic total gastrectomy puts patients at risk of infection-related complications. Low-dose naloxone (LDN) can improve the prognosis of patients suffering from chronic inflammatory diseases or autoimmune diseases. The use of LDN during perioperative procedures may reduce perioperative complications. The purpose of this study was to examine the effects of LDN on endogenous immune function in gastric cancer patients and its specific mechanisms through a randomized controlled trial. Methods: Fifty-five patients who underwent laparoscopic-assisted total gastrectomy were randomly assigned to either a naloxone group (n = 23) or a nonnaloxone group (n = 22). Patients in the naloxone group received 0.05 µg/kg-1.h− 1naloxone from 3 days before surgery to 5 days after surgery via a patient-controlled intravenous injection (PCIA) pump, and patients in the nonnaloxone group did not receive special treatment. The primary outcomes were the rates of postoperative complications and immune function assessed by NK cell, CD3+ T cell, CD4+ T cell, CD8+ T cell, WBC count, neutrophil percentage, and IL-6 and calcitonin levels. The secondary outcomes were the expression levels of TLR4 (Toll-like receptor), IL-6 and TNF-α in gastric cancer tissue. Results: Compared with the nonnaloxone group, the naloxone group exhibited a lower incidence of infection (in the incision, abdomen, and lungs) (P < 0.05). The numbers of NK cells and CD8+ T cells in the naloxone group were significantly greater than those in the nonnaloxone group at 24 h after surgery (P < 0.05) and at 96 h after surgery (P < 0.05). Compared with those in the nonnaloxone group, the CD3 + T-cell (P < 0.05) and CD4 + T-cell (P < 0.01) counts were significantly lower in the naloxone group 24 h after surgery. At 24 h and 96 h after surgery, the WBC count (P < 0.05) and neutrophil percentage (P < 0.05) were significantly greater in the nonnaloxone group. The levels of IL-6 (P < 0.05) and calcitonin in the nonnaloxone group were significantly greater at 24 h after surgery. At 24 h following surgery, the nonnaloxone group had significantly greater levels of IL-6 (P < 0.05) and calcitonin than did the naloxone group. Compared with those in the naloxone group, the expression levels of TLR4 (P < 0.05) in gastric cancer tissue in the naloxone group were greater; however, the expression levels of IL-6 (P < 0.01) and TNF-α (P < 0.01) in the naloxone group were greater than those in the nonnaloxone group. Conclusion: Laparoscopic total gastrectomy patients can benefit from 0.05 ug/kg− 1. h− 1 naloxone by reducing their risk of infection. It is possible that LDN alters the number of cells in lymphocyte subpopulations, such as NK cells, CD3 + T cells, and CD4 + T cells, and the CD4+/CD8 + T-cell ratio or alters TLR4 receptor expression in immune cells, thereby altering immune cell activity. Trial registration: The trial was registered at the Chinese Clinical Trial Registry on 24/11/2023 (ChiCTR2300077948). [ABSTRACT FROM AUTHOR]

Background: Pneumonia is a major public health problem with an impact on morbidity and mortality. Its management still represents a challenge. The aim was to determine whether a new diagnostic algorithm combining lung ultrasound (LUS) and procalcitonin (PCT) improved pneumonia management regarding antibiotic use, radiation exposure, and associated costs, in critically ill pediatric patients with suspected bacterial pneumonia (BP). Methods: Randomized, blinded, comparative effectiveness clinical trial. Children < 18y with suspected BP admitted to the PICU from September 2017 to December 2019, were included. PCT was determined at admission. Patients were randomized into the experimental group (EG) and control group (CG) if LUS or chest X-ray (CXR) were done as the first image test, respectively. Patients were classified: 1.LUS/CXR not suggestive of BP and PCT < 1 ng/mL, no antibiotics were recommended; 2.LUS/CXR suggestive of BP, regardless of the PCT value, antibiotics were recommended; 3.LUS/CXR not suggestive of BP and PCT > 1 ng/mL, antibiotics were recommended. Results: 194 children were enrolled, 113 (58.2%) females, median age of 134 (IQR 39–554) days. 96 randomized into EG and 98 into CG. 1. In 75/194 patients the image test was not suggestive of BP with PCT < 1 ng/ml; 29/52 in the EG and 11/23 in the CG did not receive antibiotics. 2. In 101 patients, the image was suggestive of BP; 34/34 in the EG and 57/67 in the CG received antibiotics. Statistically significant differences between groups were observed when PCT resulted < 1 ng/ml (p = 0.01). 3. In 18 patients the image test was not suggestive of BP but PCT resulted > 1 ng/ml, all of them received antibiotics. A total of 0.035 mSv radiation/patient was eluded. A reduction of 77% CXR/patient was observed. LUS did not significantly increase costs. Conclusions: Combination of LUS and PCT showed no risk of mistreating BP, avoided radiation and did not increase costs. The algorithm could be a reliable tool for improving pneumonia management. Clinical Trial Registration: NCT04217980. [ABSTRACT FROM AUTHOR]