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Background: New guidelines for cluster headache clinical trials were recently published. We welcome these new guidelines and raise additional considerations in trial methodologies. Main body: We present non-inferiority trials to overcome ethical issues with placebo use, and additionally discuss issues with trial recruitment. Conclusions: We highlight some possible issues and solutions to be considered with the recently published cluster headache trial guidelines. [ABSTRACT FROM AUTHOR]

Objective To evaluate clinical characteristics, effectiveness, and tolerability of preventive anti- calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) in the elderly. Anti-CGRP mAbs have demonstrated efficacy and safety in patients with migraine although there is limited information regarding the elderly. Design We performed a multicenter case-control study of cases (patients over 65 years old) and controls (sex-matched patients under 55 years old) with migraine receiving anti-CGRP mAbs. Methods We included the demographic characteristics, effectiveness—reduction in the number of monthly headache days (MHD) and monthly migraine days (MMD), 30%, 50%, and 75% responder rates—and treatment emergent adverse events (TEAEs). The primary endpoint was the 50% response rate regarding MHD at weeks 20–24; exploratory 50% response predictors in the elderly were evaluated. Results In total, 228 patients were included: 114 cases , 114 controls-. Among cases 84.2% (96/114) were women, 79.8% (91/114) CM; mean age of cases 70.1 years old (range: 66–86); mean age of controls was 42.9 years old(range: 38–49). Cases had a higher percentage of vascular risk factors (P  < .05),older age of onset (P  < .001) and more reported prior preventive treatments (P  < .001). Regarding effectiveness in cases, 50% response rate was achieved by 57.5% (42/73) at 20–24 weeks, with lower reduction in the MHD at 8–12 weeks (5 [7.2], 8 [9.1]; P  = .001) and a higher reduction in MMD at 20–24 weeks (10.7 [9.1], 9.2 [7.7]; P  = .04) compared to the control group. The percentage of TEAEs was similar in the 2 groups. Diagnosis of episodic migraine (EM) (P  = .03) and lower number of MHD at baseline (P  =.001) were associated with a 50% response in the elderly in univariate analysis. Conclusions Our study provides real world evidence of effectiveness and safety of anti-CGRP mAbs for migraine in patients without upper age-limit and possible predictors of anti-CGRP response in the elderly. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers and infections are considered significant health problems worldwide. Turkish Society of Clinical Microbiology and Infectious Diseases Study Group for Diabetic Foot Infections (DAİÇG) prepared a consensus report in 2015 regarding the diagnosis, treatment, and prevention of diabetic foot (DF) ulcers and diabetic foot infections (DFI) in national circumstances. Subsequently, in 2023, representatives assigned through collaboration with relevant national specialty associations reviewed the literature and international guidelines on the pathogenesis, microbiology, assessment and grading, treatment, prevention and control, offloading, post-amputation rehabilitation; identified questions that needed to be addressed, and updated the Consensus Report with answers to these questions. The information in this report is intended to assist healthcare professionals caring for diabetic patients. Some of the answers in the report are listed as follows: 1) Many factors cause DF ulcers, with the main causes being sensorimotor polyneuropathy and the development of peripheral arterial disease (PAD). 2) In a patient with a DF ulcer, the infection should be considered if other causes are ruled out and there are at least two local inflammatory signs, such as purulent discharge or erythema, edema, warmth, pain, tenderness, and induration at the ulcer site. In these cases, the severity of the infection is described as mild, moderate, or severe depending on the depth of the ulcer, its width, and the presence of systemic signs of infection. 3) The causative agents in DFI vary depending on whether the infection is acute or chronic and the severity of the infection. Superficial DFIs that develop in patients with cellulitis and with no previous antibiotic use are mostly caused by aerobic Gram-positive cocci (staphylococci, streptococci). 4) Deep and chronic infections and/ or infections of patients that have received previous antibiotic treatment are generally polymicrobial (Gram-positive cocci + Gram-negative rods). 5) The classification of the Infectious Diseases Society of America (IDSA)/International Working Group on the Diabetic Foot (IWGDF) can be used to assess the severity of DFI. 6) According to this classi- fication, severe and certain special cases of DFI should be hospitalized for treatment. 7) Inflammatory markers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin can be useful in differentiating infection from colonization. 8) Before starting antibiotics in suspected DFI, a suitable tissue sample should be taken from the ulcer base by curettage or biopsy for culture. 9) A three-view plain X-ray of the foot should be taken initially as an imaging method for diagnosis. This can help detect infection and bone deformities, fractures, radiopaque foreign bodies, and gas formation in soft tissues. 10) Magnetic resonance imaging (MRI) is a sensitive and specific method for patients who do not respond to treatment or where osteomyelitis or deep soft tissue abscess is suspected. 11) Culture and a positive result in histopathological examination of the bone are accepted as the gold standard in diagnosing osteomyelitis. 12) To promote ulcer healing and salvage of the limb, it is necessary to perform urgent and aggressive debridement to remove dead and infected tissues, provide proper ulcer care, relieve the foot from pressure, administer appropriate antibiotic therapy, achieve metabolic control, diagnose and treat PAD, and restore foot function. 13) In cases of DFI and PAD coexistence, consultation with the relevant surgical specialty is essential for the planning and timing of surgical procedures, and it is also advisable to seek the opinion of a vascular surgeon for revascularization. Surgical management of DF ulcers can be analyzed in five sections: (a) Urgent ulcer intervention; abscess drainage and/or debridement, (b) surgical interventions for vascular pathologies, (c) ulcer closure interventions; reconstruction methods; graft and flap surgery, (d) reconstruction of bone and foot pathologies for ulcer prevention and treatment (Charcot foot deformity, Achilles lengthening, tenotomy, and osteotomies, etc.), (e) minor and major amputations when necessary. 14) Amputation may be a more appropriate choice when infected tissue cannot be completely cleaned with debridement, when the patient is bedridden or has a non-functional extremity, when it is believed that adequate revascularization cannot be achieved by orthopedic and plastic surgical interventions, in cases where reconstruction is nearly impossible, and in dialysis patients. 15) The goal of post-DFI reconstruction is to allow the ankle to reach a neutral position and to make the plantar surface of the foot have a balanced contact with the ground. 16) Selected ulcer care products can be used based on the characteristics of the ulcer to support and accelerate ulcer healing, reduce the risk of complications, ensure patient comfort during treatment, and improve quality of life. 17) DF ulcers often develop due to improper shoe selection during the structural and biomechanical changes, resulting in fluid accumulation and callus formation around bone surfaces. 18) Orthoses, which distribute pressure over the widest possible area, are the most effective means of reducing plantar pressure in the foot. 19) Hyperbaric oxygen therapy is beneficial in addition to revascularization and antibiotic therapy, which are the primary treatments for pathologies causing tissue hypoxia, such as ischemia, infection, and edema. 20) Negative pressure ulcer therapy is an additional adjunct method to conventional techniques, and it can contribute to the healing process with the correct indications. 21) In cases where the infection is under control, active osteomyelitis is absent, topical epidermal growth factor (EGF) can be used for Meggitt-Wagner ulcer classification grade 1-3, and intralesional EGF applications can be used for grade 3-4 in addition to standard treatments. 22) Preventive medical practices in people with diabetes, collaborative efforts of the patients, their families, and the medical team, and regular patient education are necessary to prevent DF ulcer development. In the event of DF ulcer development, interdisciplinary collaboration in moderate/severe infections is essential for early treatment and infection prevention. [ABSTRACT FROM AUTHOR]

Background: Arthritis is an inflammatory condition affecting the diarthrodial joints. A joint's bone, cartilage, and structural design all preserve its integrity, and arthritis alters that integrity, resulting in joint activity loss and discomfort. The primary symptom of arthritis is joint pain, although other symptoms include stiffness, inflammation, and impaired joint motor function. Methods: The cross-sectional study comprised 90 subjects: 70 arthritis sufferers and 20 controls, ages 25-60, both sexes. From September 2023 to March 2024, patients were referred to Kirkuk city in Azadi hospital and Kirkuk general hospital. The research participants were placed into three groups: Group 1 for arthritic patients without Vit D (35). Patients with arthritis who received vitamin D for at least two months (G2), n (35), were the second group. The third group comprised healthy individuals without arthritis n (20). Result: Significant (P<0.05) increase in ETA protein levels in G1 and G2 compared to G3. G1 had ETA protein levels of 28.05±5.34 ng/L, G2 had 24.10±3.67 ng/L, and G3 had 8.92±2.80 ng/L. Sclerostin levels peaked in G1 (0.4273±0.3023 pg/mL) and declined in G2 (P<0.05) compared to G3. Calcitonin levels were higher in G1 (34.72±4.72 pg/mL) and G2 (27.06±5.85 pg/mL) than G3 (14.71±3.71 pg/mL) at (P<0.05). Conclusion: The study found a rise in ETA protein and calcitonin levels in arthritic patients before and after therapy with vitamin D, which was not influenced by vitamin supplementation. Sclerostin levels increase in arthritic patients and decrease following therapy with vitamin D. [ABSTRACT FROM AUTHOR]

Background: Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some types of arthritis, other organs are also affected. Aim: This study aimed to identify the impact of vitamin D therapy on serum level of vitamin D-binding protein and procalcitonin in Patients with arthritis. Methods: This cross-sectional study, was conducted in Kirkuk city between January 1st and March 1st, 2024. A total of 180 subjects were included, categorized into three groups: arthritis patients not receiving vitamin D (Group 1), arthritis patients receiving vitamin D for at least 2 months (Group 2), and a control group comprising 40 healthy subjects. Blood samples were collected from participants, processed, and stored for subsequent analysis. Various biomarkers, including vitamin D-binding protein and procalcitonin, were determined using ELISA kits. Results: The study revealed a higher prevalence of females among arthritis patients (54.29%), with most affected individuals aged above 60 years. Urban residency was predominant among arthritis patients (75.71%). The majority of RA patients had been affected for 6-10 years (40%). Comparative analysis demonstrated significantly higher procalcitonin levels in RA patients without vitamin D supplementation (112.4±24.3 ng/ml) compared to those with supplementation (48.33±10.73 ng/ml) and healthy controls (9.68±5.49 ng/ml). Furthermore, vitamin D binding protein levels were significantly lower in arthritis patients without supplementation (1.26±0.12 ng/ml) compared to those with supplementation (0.75±0.15 ng/ml) and healthy controls (0.23±0.14 ng/ml). Conclusion: These findings underscore the potential role of vitamin D supplementation in modulating inflammatory markers and enhancing vitamin D binding protein levels in arthritis patients, suggesting its therapeutic implications in disease management. [ABSTRACT FROM AUTHOR]

Objectives: To compare long-term results of different treatment modalities in central giant cell granuloma of the maxillofacial-skeleton. Primary resection may result in major defects. Alternative treatments include pharmacological agents. As yet there has been no consensus on the use of the variety of treatment options, and few studies have reported clarifying long-term results. Materials and methods: This retrospective study on 22 patients with 25 lesions evaluated clinical, radiological and histological features, treatment preformed and lesion recurrence. Success was defined as regression/calcification and failure as recurrence, progression or un-responsiveness. Results: Of the presenting patients, 77% were under age 40. Lesion prevalence was higher in the anterior mandible and left posterior maxilla. Most cases exhibited pain, tooth-mobility or mucosal-expansion. The appearance was predominantly unilocular in the maxilla and multilocular in the mandible, which also exhibited higher prevalence of cortical perforation. Up to 80% of lesions were classified as aggressive. Intralesional steroids/calcitonin were used in 7 cases. Mean follow-up was 39.8 months. Two cases showed recurrence. In 71% of the cases treated pharmacologically, calcification/regression were observed. Conclusions: Our analysis indicates better outcomes using a combined approach, including both pharmacological and surgical treatments in large aggressive lesions. Pharmacological treatment resulted in decreased size or well-defined lesions, thus reducing the need for extensive bone resection. Dual treatment with corticosteroids and calcitonin showed no superior outcomes, but a larger cohort should be assessed. Clinical Relevance: There are several protocols for treatment of central-giant-cell-granuloma lesions, but most are not fully established. It is important to report results that contribute to the establishment of proven protocols. This report attempts to establish the relevance of the combined approach: pharmacological treatment followed by surgical resection. [ABSTRACT FROM AUTHOR]

Procalcitonin (PCT) is an inflammatory marker with significance in the early diagnosis of sepsis. The label-free electrochemical impedance immunosensor has good prospects for the determination of this disease marker due to its cost-effectiveness, high specificity and simple operation. However, developing an immunosensor for procalcitonin faces challenges due to the absence of satisfactory electrodes. Herein, a novel label-free electrochemical impedance immunosensor using the three-dimensional (3D) flower-shaped gold nanoparticle@molybdenum(IV) sulfide/graphene (Au NPs@MoS2/graphene) composite is reported for procalcitonin. Under the optimal conditions, the immunosensor presents a linear response from 10 fg mL−1 to 50 ng mL−1 and an ultra-low detection limit of 2.3 fg mL−1 for for procalcitonin. The excellent performance is due to the unique 3D flower-shape and the synergistic effect of Au NPs@MoS2/graphene, generating a large surface area, high electrical conductivity, and increased immobilization of anti-PCT. Additionally, the immunosensor exhibits suitable specificity, stability, and reproducibility, and was used to determine procalcitonin in serum which may allow clinical screening and diagnosis of sepsis. [ABSTRACT FROM AUTHOR]

Background: Erenumab is a monoclonal antibody that targets the calcitonin gene‐related peptide (CGRP) receptor and is approved for the preventative treatment of migraine in adults. CGRP is involved in the regulation of vasomotor tone under physiologic and pathologic conditions, including hypertension. While there has not been evidence of hypertension in preclinical models or clinical trials, post‐marketing data suggest erenumab may be associated with hypertension. This led to a warning in the United States Food and Drug Administration prescribing information for erenumab. Objective: To determine the frequency of worsening blood pressure (BP) after initiation of erenumab in patients with migraine and how this is associated with hypertension. Methods: This is an observational retrospective cohort study evaluating patients at a tertiary headache or neurology department. Systolic and diastolic BPs were compared between the initial visit prior to initiation of erenumab, and follow‐up visit while on erenumab. Worsening BP was defined as moving from a lower stage to a higher stage of BP, as defined by the American Heart Association. Serious adverse vascular events were also recorded. Results: A total of 335 patients were included in the final analysis (mean [SD] age of 45.7 [14.40] years, 83.9% [281/335] female). At baseline, 20.9% (70/335) of patients had a prior diagnosis of hypertension. The median (interquartile range) time to follow‐up appointment from initial appointment was 20.5 (13.3–35.3) weeks. The mean (SD) BP at baseline was systolic 124.7 (15) mmHg and diastolic 77 (11) mmHg, and at follow‐up was systolic 124.0 (15) mmHg and diastolic 77.8 (9) mmHg. Overall, 23.3% (78/335) of all patients had worsening BP, whereas 13/225 (3.9%) patients had improvement in their BP. Patients with atrial fibrillation were more likely to develop worsening BP (odds ratio, 4.9, 95% confidence interval 1.12–21.4; p = 0.035). There was no association between worsening BP and pre‐existing hypertension, sex, body mass index, or age. One patient had non‐ST elevation myocardial infarction attributed to a hypertensive emergency while on erenumab. Conclusion: We found that 23.3% of patients initiated on erenumab may have developed worsening BP, suggesting the need for BP monitoring in patients initiated on erenumab. Plain Language Summary: This study aimed to determine how often blood pressure (BP) increases in patients with migraine after initiation of erenumab, a migraine preventative treatment. We compared patients' BP before starting erenumab versus while on erenumab. We found that nearly a quarter of patients developed higher BP, suggesting the need for BP monitoring in patients taking erenumab. [ABSTRACT FROM AUTHOR]

This article explores the use of biomarkers in diagnosing and predicting the severity of septic shock in patients with sepsis. The study found that procalcitonin (PCT) and presepsin levels were higher in patients with septic shock or a high Sequential Organ Failure Assessment (SOFA) score, indicating more severe organ dysfunction. PCT and presepsin were also identified as independent predictors of septic shock and organ dysfunction severity. However, C-reactive protein (CRP) did not show the same predictive ability. The findings suggest that PCT and presepsin may be valuable biomarkers for early diagnosis and risk stratification in septic patients. [Extracted from the article]

Aim: To compare Presepsin (presepsin) levels in plasma and urine of uninfected newborn infants with perinatal asphyxia with those of controls. Methods: In this prospective study, we enrolled 25 uninfected full‐term infants with perinatal asphyxia and 19 controls. We measured presepsin levels in whole blood or urine. In neonates with perinatal asphyxia, we compared presepsin levels in blood and urine at four time points. Results: In neonates with perinatal asphyxia, blood and urinary presepsin levels matched each other at any time point. At admission, the median presepsin value in blood was similar in both groups (p = 0.74), while urinary levels were higher in hypoxic neonates (p = 0.05). Perinatal asphyxia seemed to increase serum CRP and procalcitonin levels beyond normal cut‐off but not those of presepsin. Conclusion: In uninfected neonates with perinatal asphyxia, median blood and urinary presepsin levels matched each other at any point in the first 72 h of life and seemed to be slightly affected by the transient renal impairment associated with perinatal hypoxia in the first 12 h of life. Perinatal asphyxia did not influence presepsin levels within the first 72 h of life, while those of CRP and procalcitonin increased. [ABSTRACT FROM AUTHOR]

In low-risk febrile neutropenia (LR-FN), the safety of early discontinuation of empiric antibiotics without marrow recovery is not well established. This study aimed to evaluate the safety of procalcitonin (PCT) guided early discontinuation of antibiotics in LR-FN. In this trial, children with LR-FN with an afebrile period of at least 24 h, sterile blood culture, and negative/normalized PCT were randomized at 72 h of starting antibiotics into two groups: intervention arm and standard arm. The antibiotics were stopped in the intervention arm regardless of absolute neutrophil count (ANC), while in the standard arm, antibiotics were continued for at least 7 days or until recovery of ANC (>500/mm3). The primary objective was to determine the treatment failure rates, and the secondary objective was to compare the duration of antibiotics and all-cause mortality between the two arms. A total of 46 children with LR-FN were randomized to either the intervention arm (n = 23) or the standard arm (n = 23). Treatment failure was observed in 2/23 (8.7%) of patients in the intervention arm compared to 1/23 (4.3%) in the standard arm [RR: 2 (95% CI: 0.19–20.6); p = 0.55]. The median duration of antibiotics in the intervention arm and standard arm were 3 days vs 7 days (P= <0.001). There was no mortality in this study. PCT-guided early discontinuation of empirical antibiotics in LR-FN is feasible. There was no significant difference observed in treatment failure between the early discontinuation of antibiotics vs standard therapy. The total duration of antibiotic exposure was significantly lesser in the discontinuation arm. Further, larger multicenter studies are needed to confirm the finding of this study. [ABSTRACT FROM AUTHOR]

This study evaluated and characterized the pharmacological activity of the orally administered interleukin‐1 receptor‐associated kinase 4 (IRAK4) inhibitors BAY1834845 (zabedosertib) and BAY1830839 in healthy male volunteers. Participants received one of either IRAK4 inhibitors or a control treatment (prednisolone 20 mg or placebo) twice daily for 7 days. Localized skin inflammation was induced by topical application of imiquimod (IMQ) cream for 3 days, starting at Day 3 of treatment. The inflammatory response was evaluated by laser speckle contrast imaging (skin perfusion) and multispectral imaging (erythema). At Day 7, participants received 1 ng/kg intravenous lipopolysaccharide (LPS). Circulating inflammatory proteins, leukocyte differentiation, acute phase proteins, and clinical parameters were evaluated before and after the systemic LPS challenge. Treatment with BAY1834845 significantly reduced the mean IMQ‐induced skin perfusion response (geometric mean ratio [GMR] vs. placebo: 0.69 for BAY1834845, 0.70 for prednisolone; both p < 0.05). Treatment with BAY1834845 and BAY1830839 significantly reduced IMQ‐induced erythema (GMR vs. placebo: 0.75 and 0.83, respectively, both p < 0.05; 0.86 for prednisolone, not significant). Both IRAK4 inhibitors significantly suppressed the serum TNF‐α and IL‐6 responses (≥80% suppression vs. placebo, p < 0.05) and inhibited C‐reactive protein, procalcitonin, and IL‐8 responses to intravenous LPS. This study demonstrated the pharmacological effectiveness of BAY1834845 and BAY1830839 in suppressing systemically and locally induced inflammatory responses in the same range as prednisolone, underlining the potential value of these IRAK4 inhibitors as future therapies for dermatological or other immune‐mediated inflammatory diseases. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Trauma & Emergency Surgery / Ulusal Travma ve Acil Cerrahi Dergisi is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Innere Medizin (2731-7080) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We present a 10‐year‐old mongrel dog with progressive weight loss, polyuria and polydipsia. Physical examination revealed poor body condition, systemic hypertension (on average 165 mmHg) and a cervical mass that was confirmed by ultrasound in the right thyroid lobe (diameter 4.0 cm). Blood biochemistry on two different days revealed a low ionised calcium concentration (1.1 and 0.81 mmol/L; reference range: 1.1–1.3 mmol/L) associated with an elevated plasma calcitonin concentration in the same sample (44.8 and 49 pg/mL; reference range: <2 pg/mL). A low urine specific gravity (1.012) was also found. Total thyroxine concentration was low, corresponding to euthyroid sick syndrome. Hypercalcitoninemia, hypocalcaemia and clinical signs resolved after an uncomplicated right thyroidectomy. Positive staining of the neoplasm for calcitonin on immunohistochemistry confirmed a medullary thyroid carcinoma. This is the first report describing the clinical signs and biochemical alterations associated with excess calcitonin in a dog with medullary thyroid carcinoma confirmed by immunohistochemistry. [ABSTRACT FROM AUTHOR]

Background: The sensitivity of cytological (CY) evaluation after fine‐needle aspiration (FNA) for detecting medullary thyroid carcinoma (MTC) is a subject of controversy. The routine use of serum calcitonin (CT) in patients with thyroid nodules is not universally adopted. The authors conducted CT screening of FNA washout fluid (FNA‐CT) to address the diagnostic challenges. The objective was to assess the contributions of serum CT, FNA cytology (FNA‐CY), and FNA‐CT to the diagnosis. Methods: Between February 2019 and June 2022 (group 1), the authors prospectively screened the CT of patients with thyroid nodules. Both FNA‐CY and FNA‐CT were performed for patients with persistently elevated CT values. The sensitivity of FNA‐CY, serum CT, and FNA‐CT for accurate diagnosis was evaluated. Additionally, the authors retrospectively examined data from patients with thyroid nodules before CT screening (2008–2019) (group 2). They compared the characteristics of MTC patients in groups 1 and 2. Results: MTC was identified in 30 patients (0.25%) in group 1 and 19 (0.07%) in group 2. A FNA‐CT cutoff value of 4085.5 pg/mL detected MTC with a sensitivity of 96.8%, and a serum CT cutoff value of 28.3 pg/mL detected MTC with a sensitivity of 86.7%. In contrast, FNA‐CY detected MTC with a sensitivity of 42.4%. In group 1, 18 patients (60%) with MTC were diagnosed with microcarcinoma, whereas only two patients (10.5%) in group 2 had microcarcinoma. Conclusions: This study detected MTC earlier by routinely measuring serum CT in all patients with nodular thyroid disease and performing FNA‐CT in those with elevated values. FNA‐CT and serum CT sensitivities were significantly higher than those of FNA‐CY. This study revealed different FNA‐CT cutoff values compared to other studies, emphasizing the need for determining clinic‐specific cutoff values. The sensitivity of cytology after fine‐needle aspiration (FNA) for detecting medullary thyroid carcinoma (MTC) is a subject of controversy. This study shows that MTC can be detected earlier through the routine measurement of serum calcitonin (CT) in all patients with nodular thyroid disease and CT screening of FNA washout fluid in those with elevated values. [ABSTRACT FROM AUTHOR]

Purpose: Bloodstream infection(BSI) is linked with high mortality, underscoring the significance of prompt etiological diagnosis for timely and precise treatment. This study aims to investigate the diagnostic value of droplet digital polymerase chain reaction(ddPCR) in combination with conventional inflammatory markers [interleukin-6(IL-6) and procalcitonin(PCT)] concerning disease progression and treatment prognosis in BSI patients. Furthermore, the study aims to explore a more efficient clinical application strategy. Patients and Methods: This prospective case seried study centers on 176 patients suspected of or confirmed with BSI. Blood samples were collected to extract nucleic acids for identifying pathogens (bacteria, fungi, and viruses) and determining copy loads via ddPCR. Results: The sensitivity of ddPCR was markedly higher compared to the culture method (74.71% vs 31.03%). A positive correlation existed between bacterial load and levels of inflammatory markers [IL-6 (P= 0.0182), PCT (P= 0.0029), and CRP (P= 0.0005)]. In suspected BSI cases, the combination of ddPCR and inflammatory markers could predict sepsis risk [ROC: Area under the curve(AUC)=0.6071, P= 0.0383]. Within confirmed BSI patients, the ddPCR bacterial load of those with SOFA< 7 was lower than that of the SOFA≥ 7 (P= 0.0334). ddPCR (OR: 1.789, P= 0.035) monitoring combined with PCT (OR: 1.787, P= 0.035) holded predictive value for SOFA progression (AUC=0.7913, P= 0.0003). Similarly, BSI survivors displayed a lower burden than non-survivors (P= 0.0170). Additionally, ddPCR combinated with IL-6 provided a more accurate and expedited insight into clinical outcomes prediction for BSI confirmed patients (AUC=0.7352, P= 0.0030). Serial monitoring of bacterial load by ddPCR effectively mirrored the clinical course of BSI in patients. Notably, patients with positive ddPCR virus infection exhibited significantly reduced lymphocyte counts (P= 0.0003). Conclusion: In a clinical context, qualitative ddPCR results and quantitative continuous monitoring can more precisely assess sepsis progression and treatment prognosis in BSI patients. Furthermore, ddPCR results offer quicker and more accurate reference points for clinical antibacterial and antiviral interventions. [ABSTRACT FROM AUTHOR]

Purpose: To investigate potential differences in clinical and computed tomography (CT) features between patients with the SARS‐CoV‐2 Omicron variant and the original strain. Patients and Methods: This retrospective study included 69 hospitalized patients infected with Omicron variant from November to December 2022, and 96 hospitalized patients infected with the original strain from February to March 2020 in Chongqing, China. The clinical features, CT manifestations, degrees of lung involvement in different stages on CT, and imaging changes after the reverse-transcription polymerase chain reaction (RT-PCR) results turned negative were compared between the two groups. Results: For clinical features, patients with Omicron were predominantly old people and females, without manifestation of any clinical symptoms, who had low serum levels of C-reactive protein and procalcitonin. Shorter interval from symptoms onset to initial CT scan was observed in Omicron patients compared to patients with the original strain (all P < 0.05). For CT features, patients with Omicron were more likely to present with round-like opacities and tree-in-bud pattern (all P < 0.05), but less likely to exhibit a diffuse distribution, patchy and linear opacities, as well as vascular enlargement pattern (all P < 0.05). The Omicron group was more susceptible to exhibiting lower CT involvement scores in each stage (all P < 0.05) and imaging progression after the RT-PCR results turned negative (P < 0.001). Conclusion: Patients infected with the Omicron variant exhibited less severe changes on chest CT compared to those infected with the original strain. Furthermore, imaging progression under low viral load conditions was more common in patients with Omicron than in those with the original strain. [ABSTRACT FROM AUTHOR]

Introduction: Procalcitonin and presepsin have been suggested to be able to discriminate bacterial and viral infections, also in children. This scoping review aims to better explore the available evidence around the potential role of these biomarkers in the subgroup of children with respiratory infectious diseases. Methods: We performed a systematic scoping review of studies published until March 2023 in the following bibliographic databases: PubMed, EMBASE, Cochrane and SCOPUS. Results: In children with bacterial infection, procalcitonin values ranged from 0.5 ng/mL to 8.31 ng/dL, while in those hospitalized in an intensive care unit ranged from 0.6 ng/dL to 452.8 ng/dL with PCR from 2 ng/dL to 51.7 ng/dL. In children with viral infections, procalcitonin value values ranged from 0.2 ng/dL to 0.84 ng/dL, while in those hospitalized in an intensive care unit ranged from 0.61 ng/dL to 46.6 ng/dL. No studies on presepsin in children with respiratory infections were retrieved. Conclusions: Although the available literature is highly heterogeneous, evidence does not suggest a role of procalcitonin in accurately differentiating bacterial and viral infections in children with respiratory infections. In future, new approaches based on multiple markers may better help determine which febrile children require antibiotics. [ABSTRACT FROM AUTHOR]

Introduction: The multifaceted impact of COVID-19 extends beyond the respiratory system, encompassing intricate interactions with various physiological systems. This study elucidates the potential association between SARS-CoV-2 infection and anemia, with a particular emphasis on the deformability of red blood cells (RBCs), stability of hemoglobin, enzymatic activities, and proteomic profiles. Methods: The study encompasses a cohort of 74 individuals, including individuals positive for COVID-19, a control group, and patients with other viral infections to discern the specific effects attributable to COVID-19. The analysis of red blood cells was focused on deformability measured by osmotic gradient ektacytometry, hemoglobin stability, and glycolytic enzyme activity. Furthermore, membrane proteins were examined using advanced proteomics techniques to capture molecular-level changes. Results: Findings from the study suggest a correlation between anemia and exacerbated outcomes in COVID-19 patients, marked by significant elevations in d-dimer, serum procalcitonin, creatinine, and blood urea nitrogen (BUN) levels. These observations suggest that chronic kidney disease (CKD) may play a role in the development of anemia in COVID-19 patients, particularly those of advanced age with comorbidities. Furthermore, the proteomic analyses have highlighted a complex relationship between omics data and RBC parameters, enriching our understanding of the mechanisms underlying the disease. Conclusions: This research substantiates the complex interrelationship between COVID-19 and anemia, with a specific emphasis on the potential repercussions of SARS-CoV-2 infection on RBCs. The findings contribute to the growing body of evidence supporting the extensive impact of COVID-19 on RBCs. [ABSTRACT FROM AUTHOR]

Surgical site infections (SSIs) post‐thoracoscopic radical resection in lung cancer patients pose significant clinical challenges. This study aims to comprehensively identify the independent risk factors that influence the occurrence of SSIs following thoracoscopic radical resection for lung cancer. The study employed a retrospective analysis of 130 patients who underwent thoracoscopic radical resection for lung cancer. Inclusion and exclusion criteria were clearly defined, and ethical approvals were obtained. Patients were monitored for SSIs via clinical and biochemical markers, with data comprehensively gathered from electronic health records. Statistical analysis was rigorously conducted using SPSS v27.0, with methodologies including t‐tests, Chi‐square tests and logistic regression. The study aimed to identify independent risk factors for SSIs and incorporated a multidimensional assessment approach to provide robust, clinically relevant findings. Univariate analysis revealed surgical duration ≥3 h, non‐usage of antibiotics, presence of diabetes and elevated levels of C‐reactive protein (CRP) and procalcitonin (PCT) as significant correlates for SSIs. Multivariate analysis substantiated these factors as independent risk variables: surgery duration (odds ratio [OR] = 9.698, p < 0.05), presence of diabetes (OR = 6.89, p < 0.05), elevated CRP (OR = 7.306, p < 0.05) and elevated PCT (OR = 6.838, p < 0.05). Conversely, antibiotic administration served as a protective factor (OR = 0.572, p < 0.05). Surgical duration of 3 h or more, diabetes and elevated levels of CRP and PCT significantly heighten the risk for SSIs after thoracoscopic radical resection in lung cancer patients. Perioperative antibiotic administration acts as a protective factor. Clinicians should implement tailored preventative strategies to mitigate these identified risks. [ABSTRACT FROM AUTHOR]

Medullary thyroid carcinoma (MTC) is a rare and challenging type of thyroid cancer originating from parafollicular cells (C cells) that produce calcitonin. Diagnosing and monitoring this carcinoma can be complex due to its unique biomarkers. Procalcitonin (PCT), a precursor of calcitonin, and carcinoembryonic antigen (CEA) are important markers for MTC. Elevated PCT levels, particularly when they remain high post-infection treatment, and elevated CEA levels are significant indicators for suspecting MTC. This report emphasises the diagnostic and prognostic importance of these biomarkers in MTC, highlighting their roles in detecting and monitoring disease progression. Integrating PCT and CEA measurements into routine clinical practice can enhance detection, provide understanding of therapeutic responses and aid in the effective management of MTC.

ObjectivesThis 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.MethodsHypercalcemic 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.ResultsTwenty-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.DiscussionThe 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 Background Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are leading causes of systemic sclerosis (SSc)-related death. In this study, we aimed to identify biomarkers for detecting SSc pulmonary complications that are mild and in the early stages to improve the prognosis. Methods We screened for serum biomarkers using a proteomic antibody microarray that simultaneously assessed 1000 proteins. Differentially expressed proteins were further verified using ELISA. Finally, we performed a correlation analysis using clinical data. Results We identified 125 differentially expressed proteins, of which calcitonin, sclerostin (SOST), CD40, and fibronectin were selected for further verification. Serum calcitonin and SOST levels were significantly elevated in all SSc pulmonary complication subgroups, whereas serum calcitonin levels were higher in the SSc with PAH subgroup than in the SSc without PAH and ILD subgroup. Serum SOST levels were possibly associated with the presence of ILD and positively related to the presence of cardiac and gastrointestinal involvement. Serum CD40 and calcitonin levels appeared to be positively related to the presence of renal involvement, and serum calcitonin was also positively related to the presence of gastrointestinal involvement. Conclusions This study indicated that serum calcitonin and SOST levels may be promising biomarkers for SSc-related PAH and ILD, respectively. Further research is needed to verify this result and understand the underlying mechanisms.

Multiple endocrine neoplasia (MEN) is a rare inherited disease caused by multiple complex mutations in the RET gene. It is characterized by the occurrence of tumors involving more than two endocrine glands in the same patient. MEN is classified into two types: MEN type 1 (Wermer syndrome) and MEN type 2, which is further subclassified into two phenotypes: MEN 2A (Sipple syndrome) and MEN 2B (Shimcke syndrome). Sipple syndrome is the most common type of MEN type 2. It is characterized by the presence of medullary thyroid carcinoma (MTC), unilateral or bilateral pheochromocytoma, and primary hyperparathyroidism due to parathyroid cell hyperplasia or adenoma. In this article, the authors report a case of a 34-year-old Libyan woman with Rh positive B blood group who presented with an enlarged neck mass. Based on clinical, radiological, biochemical, and cytological assessments, the mass was diagnosed as MTC. Two weeks apart, the patient underwent right adrenalectomy and total thyroidectomy, while the parathyroid glands were found to be normal and preserved. In cases where a neck mass is the only symptom manifestation, it is crucial to carefully investigate for other MEN 2A findings, especially if there is a family history of MTC, to ensure a good prognosis. Patients with MEN 2A should undergo regular screening and be managed by a multidisciplinary team.

This article discusses a study that aimed to identify the amyloid precursor protein in a feline C-cell carcinoma. The researchers used stained tissue sections from a surgically excised tumor to perform transmission electron microscopy, mass spectrometry-based proteomic analysis, and immunohistochemistry. The study found that calcitonin receptor-stimulating peptide 1 (CRSP1) was the amyloid precursor protein in feline C-cell carcinoma. The article also highlights the differences in amyloid proteins between cats and humans with C-cell carcinoma and emphasizes the importance of repurposing limited research materials for amyloidosis typing. [Extracted from the article]

Hypercalcemia is rare in women of child-bearing age, and most cases are due to primary hyperparathyroidism. A 28-year-old woman, 14 weeks pregnant with dichorionic diamniotic twins, presented to hospital with vomiting, muscle cramps, and weakness. She had been taking calcium carbonate for gastric reflux and nausea from 5 weeks of gestation. Investigations revealed severe hypercalcemia, metabolic alkalosis, and renal injury. She was transferred to intensive care, receiving fluid resuscitation and subcutaneous calcitonin followed by dialysis. Investigations revealed suppressed PTH and PTH-related peptide, negative malignancy screening and low vitamin D level. Calcium and renal function quickly normalized and with cessation of calcium carbonate remained normal throughout the rest of pregnancy. Reports of calcium-alkali syndrome causing severe hypercalcemia are scarce, with most cases occurring later in gestation. This case represents a dramatic presentation requiring renal replacement therapy early in twin gestation. [ABSTRACT FROM AUTHOR]

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ABSTRACTBackground Surgery for breast malignancy is linked to severe perioperative discomfort. Pain management reduces the need for opioids and general anesthesia. The “erector spinae plane block” (ESPB) recently became an effective choice in this concern. Our trial assessed the effectiveness of calcitonin as an LA adjuvant in ESPB for pain control in patients underwent cancer breast surgery.Patients and Methods One hundred and thirty patients were randomly allocated into two groups, BC and B. BC group received ESPB with 20 mL of bupivacaine 0.25% in addition to 50 IU of calcitonin in 2 mL of saline, while the other group received the same bupivacaine dose in addition to saline (2 ml). Main outcome was time for first rescue analgesia. Secondary outcomes included 24-h total morphine consumption postoperatively, postoperative VAS scores, levels of inflammatory cytokines, total intraoperative fentanyl consumption, and side effects.Results The period before the first-time analgesia was required was extended (12.18 ± 4.969 h vs 6.60 ± 3.116 h, P

Simple Summary: The purpose of our study was to evaluate the effectiveness of procalcitonin (PCT) as a positive predictive factor for the early identification of post-surgical wound complications, such as cutaneous pharyngeal fistulas, in patients undergoing total laryngectomy. We took into consideration 36 patients who underwent total laryngectomy, dividing them into two groups: a first group made up of 27 patients who had no post-operative complications; a second group made up of 9 patients who had the onset of pharyngeal-cutaneous fistula as a complication. In both groups we evaluated the procalcitonin values at various times in order to evaluate the values found with the onset of the complication. Objectives. The aim of this prospective study was to investigate the role of procalcitonin as an early diagnostic marker of pharyngocutaneous fistula (PCF) in a cohort of head and neck patients treated with total laryngectomy for squamous cell carcinoma. Methods. This prospective study was conducted on a sample of patients enrolled from January 2019 to March 2022. All patients were subjected to a "protocol" of blood chemistry investigations, scheduled as follows: complete blood count with formula, ESR dosage, CPR, and PCT. PCT was also dosed by salivary sampling and a pharyngo-cutaneous swab in patients who presented with PCF. The dosage scheme was systematically repeated: the day before the intervention (t0); the 5th day postoperative (t1); the 20th day postoperative (t2); and at time X, the day of the eventual appearance of the pharyngocutaneous fistula. Results. A total of 36 patients met the inclusion criteria. The patients enrolled in the study were subsequently divided into two groups: 27 patients underwent total laryngectomy (TL) for laryngeal cancer without postoperative complications, and 9 patients were undergoing TL with postoperative PCF. Using the Cochran's Q test, statistical significance was found for PCT among T0, T1, Tx, and T2 (p-value < 0.001) between the PCF and non-PCF groups. The Z test demonstrated that there is a difference in PCT levels at T1 and T2 and that this difference is statistically significant (p < 0.001). Conclusions. PCT could be considered an early marker of complications in open laryngeal surgery. According to our results, it could be useful in the precocious detection of pharyngocutaneous fistulas and in the management of antibiotic therapy. [ABSTRACT FROM AUTHOR]

Objective: Calcitonin (Ctn) measurement is crucial for the early diagnosis of medullary thyroid carcinoma (MTC). However, Ctn levels can be skewed/elevated due to other reasons, and the Ctn upper reference value remains controversial. In this field, studies have heterogeneous settings, published data are controversial, and no evidence has been achieved. The study's aim was to evaluate all previously investigated Ctn determinants in a population with histological exclusion of MTC. Methods: The institutional records from 2010 to 2022 were reviewed to select patients with thyroid nodules who had undergone total thyroidectomy with histological exclusion of MTC and who had tested for Ctn just before surgery. Thyroid features, demographic and anthropometric data, comorbidities, medications, and lifestyle information were collected. Univariate and multivariate analyses were performed. Results: A total of 127 cases were included. The median age for thyroidectomy was 51 years. Median Ctn was 1.04 pg/mL (interquartile range (IQR) 1.04-2.77), with two cases having values above 10 pg/mL. In univariate analysis, Ctn was correlated with gender (p < 0.001), bodyweight (p = 0.016), height (p = 0.031), body surface area (p = 0.016), thyroid size (p = 0.03), thyroglobulin (p < 0.001), and chronic kidney disease (p < 0.001). After multivariate analysis, the model with the highest accuracy included gender, chronic kidney disease, and thyroid-stimulating hormone (TSH) with an adjusted R-squared of 0.4. Conclusions: This study demonstrates, in a population histologically proven as MTC-free, that the Ctn value is mainly influenced by gender, anthropometric/thyroid features, and chronic kidney disease, with the further impact of TSH. [ABSTRACT FROM AUTHOR]

Background: Prolonged critical illness is often accompanied by an impairment of adrenal function, which has been frequently related to conditions complicating patient management. The presumed connection between hypoxia and the pathogenesis of this critical-illness-related corticosteroid insufficiency (CIRCI) might play an important role in patients with severe acute respiratory distress syndrome (ARDS). Since extracorporeal membrane oxygenation (ECMO) is frequently used in ARDS, but data on CIRCI during this condition are scarce, this study reports the behaviour of adrenal function parameters during oxygenation support with veno-venous (vv)ECMO in coronavirus disease 2019 (COVID-19) ARDS. Methods: A total of 11 patients undergoing vvECMO due to COVID-19 ARDS at the Medical University of Vienna, who received no concurrent corticosteroid therapy, were retrospectively included in this study. We analysed the concentrations of cortisol, aldosterone, and angiotensin (Ang) metabolites (Ang I-IV, Ang 1-7, and Ang 1-5) in serum via liquid chromatography/tandem mass spectrometry before, after 1 day, 1 week, and 2 weeks during vvECMO support and conducted correlation analyses between cortisol and parameters of disease severity. Results: Cortisol concentrations appeared to be lowest after initiation of ECMO and progressively increased throughout the study period. Higher concentrations were related to disease severity and correlated markedly with interleukin-6, procalcitonin, pH, base excess, and albumin during the first day of ECMO. Fair correlations during the first day could be observed with calcium, duration of critical illness, and ECMO gas flow. Angiotensin metabolite concentrations were available in a subset of patients and indicated a more homogenous aldosterone response to plasma renin activity after 1 week of ECMO support. Conclusion: Oxygenation support through vvECMO may lead to a partial recovery of adrenal function over time. In homogenous patient collectives, this novel approach might help to further determine the importance of adrenal stress response in ECMO and the influence of oxygenation support on CIRCI. [ABSTRACT FROM AUTHOR]

Background: Several risk factors are associated with the chronic evolution of migraine. Clinical and preclinical studies have provided data about the role of hypertension (HT) as one of the potential modifiable risk factors of chronic migraine (CM). This review is focused on the biological and clinical evidence supporting common mechanisms underlying HT and migraine and the potential role of HT in the transition from episodic to chronic migraine. Methods: We conducted a narrative review from a literature search covering the available evidence from studies investigating: i) the role of HT in the transition to CM in clinical practice; ii) the biological mechanisms potentially underpinning the association between HT and evolution to CM; iii) the role of antihypertensive medications in migraine prophylaxis. Results: HT proved to be at the base of multiple mechanisms underlying migraine and migraine chronicization. Endothelial dysfunction, blood–brain barrier alterations, calcitonin gene-related peptide signaling, and renin–angiotensin–aldosterone system dysregulation are involved in the worsening effect of HT on migraine frequency, and the role of HT in the transition to CM is supported by clinical observations. Conclusions: The observed evidence supports HT contribution to CM evolution due to shared pathophysiologic mechanisms. While a bidirectional influence appears to be ascertained, data are still lacking about the one-way role of HT as direct risk factor for CM transition. Further research is needed to confirm a causal role of HT in this process. [ABSTRACT FROM AUTHOR]

Objective: To study the clinicopathological characteristics of patients with synchronous medullary and papillary thyroid carcinomas. Methods: The clinical data of patients with medullary thyroid carcinoma (MTC) operated in our hospital (Department of Thyroid Surgery, China-Japan Union Hospital, Jilin University) from February 2009 to February 2023 were evaluated using an analytical review approach. They were divided into an observation group (patients with synchronous MTC and papillary thyroid carcinoma PTC) and a control group (simple MTC) according to whether the clinical data were associated with MTC, in order to compare the clinical features, pathological types, stage characteristics and molecular biology characteristics of the two groups and to investigate the follow-up of the two groups. Results: The study included 122 MTC, 30 with synchronous MTC/PTC and 92 simple MTC. When the data were compared, the sex ratio, preoperative calcitonin level, preoperative CEA level, presence of calcifications in the MTC lesions, surgical methods, number of MTC lesions, presence of nodular goitre and presence of thyroiditis were higher in the observation group than in the control group. There was a significant difference between the groups when the MTC lesion diameter was ≤1cm in terms of preoperative CEA value (P<0.05); when the MTC lesion diameter was >1cm, there was a statistical difference between the two groups in terms of preoperative Ctn value (P<0.05). Type III was significantly different from the simple group, while type IV was more similar to the simple group. The preoperative serum Ctn value was positively correlated with maximum tumour diameter in both groups, although the correlation was stronger in the easy group. Preoperative CEA was positively correlated with maximum tumour diameter in both groups, with a stronger correlation in the combination group. Preoperative Ctn and CEA were positively correlated with lymph node metastasis in the simple group, whereas there was no apparent correlation with lymph node metastasis in the combination group. The cut-off value of preoperative serum Ctn for cervical lymph node metastases in the simple group was 39.2pg/ml and for lateral cervical lymph node metastases 195.5pg/ml. The cut-off value of preoperative serum Ctn for cervical lymph node metastases in the combination group was 60.79pg/ml and for lateral cervical lymph node metastases 152.6pg/ml. In the simple group, prognosis was significantly worse in the progression group (P<0.001), with no statistical difference between the remission and stable groups. In the combination group, the prognosis of the progression and stable groups was significantly worse than that of the remission group (P<0.001), with no statistical difference between the progression and stable groups. Conclusion: In patients with synchronous medullary and papillary thyroid carcinomas, preoperative Ctn and CEA levels, calcifications, solitary lesions, combined goitre or thyroiditis differ significantly from simple MTC. Therefore, clinical management should pay attention to the above factors and early risk screening should be performed to improve prognosis as much as possible. [ABSTRACT FROM AUTHOR]

The article discusses case studies which show bacteremia and/or fungemia after examining peripheral blood smears, especially in critically ill individuals with non-specific symptoms. The patients studied include a 31-year-old woman who was hospitalized for investigation of coma presented with vaginal bleeding, a 27-year-old man with poor limb movement and limb convulsions for two days, and a 53-year-old male patient with progressively reduced consciousness following head, neck and chest trauma.

The main objective of the study was to verify whether levels of procalcitonin (PCT) could guide us toward determining the type of bacteria causing the sepsis and to identify the discriminatory cut-off point in the first urgent laboratory test. This study is a single center retrospective analysis that includes 371 patients with a mean age of 71.7 ± 15.6 years who were diagnosed with sepsis or septic shock. The yield of blood cultures in demonstrating the causative microbiological agent was 24.3% (90), and it was 57, 1% (212) when evaluating all types of cultures. Statistically significant positive differences were observed in the mean value of the PCT between the group that obtained positive cultures and the group that did not (p < 0.0001). The AUC-ROC of PCT values as a guide to the causal bacteria type was 0.68 (95%CI: 0.57–0.78, p < 0.0021). The PCT value that showed the best diagnostic characteristics for identifying Gram-negative rods (GNR) as the causative agent in blood cultures was 2.1 ng/mL. The positive predictive value (PPV) was 78, 9% (66.3–88.1%). The AUC-ROC of the PCT values for sepsis diagnosis, with any positive culture that could be assessed, was 0.67 (95%CI: 0.63–0.73, p < 0.0001). The PCT value that showed the best diagnostic characteristic for predicting sepsis was 3.6 ng/mL. [ABSTRACT FROM AUTHOR]

Background: The optimal cutoff value of calcitonin (Ctn) levels measured using an electrochemiluminescence immunoassay (ECLIA) obtained from the washout fluid of fine needle aspiration (FNA-Ctn) for the diagnosis of medullary thyroid carcinoma (MTC) is currently not established. We evaluated the diagnostic accuracy and clinical utility of FNA-Ctn for the diagnosis and location of MTC in patients with nodular or multinodular goiters. Methods: This was a case–control study nested on a prospective multicenter cohort of patients with nodular or multinodular goiter, normal or elevated serum Ctn, and thyroidectomy indications. Ctn and FNA-Ctn were measured using ECLIA methodology before surgery. From this nested cohort, MTC cases and controls (non-medullary pathology) were identified from the final pathological analysis. Cumulative incidence sampling of controls was randomly performed at a ratio of 1:2. Sensitivity, specificity, and area under the receiver operator curve (AUROC) were calculated for patients and the total number of thyroid nodules. Results: From 1272 patients included in the prospective cohort, 50 MTC cases and 105 controls were included. In this study, 286 thyroid nodules were evaluated (63 MTC and 223 non-MTCs). The median serum Ctn value was significantly higher in cases (525 pg/mL [interquartile range (IQR), 162.5–1.200]) than in controls (1.6 pg/mL [IQR, 0.5–5.6]; p < 0.001). The median FNA-Ctn value was significantly higher in MTC nodules (3.100 pg/mL [IQR, 450–45,200]) than in non-MTC nodules (0.5 pg/mL [IQR, 0.5–0.5]; p < 0.0001). In 11 MTC patients with multinodular goiter, the FNA-Ctn value was significantly higher in non-medullary nodules located in the same lobe where an MTC nodule was diagnosed (p = 0.0002). Overall, the FNA-Ctn AUROC was 0.99 [95% confidence interval, 0.98–1.0], and a threshold of ≥220 pg/mL showed 100% sensitivity and 98% specificity for MTC diagnosis. Conclusions: The use of FNA-Ctn measured by ECLIA showed adequate diagnostic accuracy for MTC diagnosis. Moreover, it may be clinically useful for localization in multinodular goiter when lobectomy is considered. Clinical Trial Registration: Clinicaltrials.gov NCT06067594. [ABSTRACT FROM AUTHOR]

Model-informed precision dosing (MIPD) might be used to optimize antibiotic treatment. Procalcitonin (PCT) is a biomarker for severity of infection and response to antibiotic treatment. The aim of this study was to assess the impact of MIPD on the course of PCT and to investigate the association of PCT with pharmacodynamic target (PDT) attainment in critically ill patients. This is a secondary analysis of the DOLPHIN trial, a multicentre, open-label, randomised controlled trial. Patients with a PCT value available at day 1 (T1), day 3 (T3), or day 5 (T5) after randomisation were included. The primary outcome was the absolute difference in PCT concentration at T1, T3, and T5 between the MIPD and the standard dosing group. In total, 662 PCT concentrations from 351 critically ill patients were analysed. There was no statistically significant difference in PCT concentration between the trial arms at T1, T3, or T5. The median PCT concentration was highest in patients who exceeded 10× PDT at T1 [13.15 ng/mL (IQR 5.43–22.75)]. In 28-day non-survivors and in patients that exceeded PDT at T1, PCT decreased significantly between T1 and T3, but plateaued between T3 and T5. PCT concentrations were not significantly different between patients receiving antibiotic treatment with or without MIPD guidance. The potential of PCT to guide antibiotic dosing merits further investigation. [ABSTRACT FROM AUTHOR]

The evaluation and management of young infants presenting with fever remains an area of significant practice variation. While most well-appearing febrile young infants have a viral illness, identifying those at risk for invasive bacterial infections, specifically bacteremia and bacterial meningitis, is critical. This statement considers infants aged ≤90 days who present with a rectal temperature ≥38.0°C but appear well otherwise. Applying recent risk-stratification criteria to guide management and incorporating diagnostic testing with procalcitonin are advised. Management decisions for infants meeting low-risk criteria should reflect the probability of disease, consider the balance of risks and potential harm, and include parents/caregivers in shared decision-making when options exist. Optimal management may also be influenced by pragmatic considerations, such as access to diagnostic investigations, observation units, tertiary care, and follow-up. Special considerations such as temperature measurement, risk for invasive herpes simplex infection, and post-immunization fever are also discussed. [ABSTRACT FROM AUTHOR]

Objective To investigate the ultrasonographic features of medullary thyroid carcinomas (MTCs) of different sizes and supply valid information for separating MTCs from papillary thyroid carcinomas (PTCs). Methods There were 87 patients with MTC and 220 patients with PTC detected by ultrasonography and confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital from June 2018 to March 2022. Nodules were divided into the large nodule group (the maximum diameter of the tumor was＞1 cm) and the small nodule group (the maximum diameter of the tumor was ≤1 cm). There were 97 cases in the small nodule group, including 28 cases of MTC and 69 cases of PTC. There were 210 cases in the large nodule group, including 59 cases of MTC and 151 cases of PTC. After stratification by thyroid nodules, ultrasonographic features of thyroid nodules and metastatic lymph nodes, preoperative serum calcitonin (CT) and carcinoembryonic antigen (CEA) levels were compared between MTC and PTC patients. Results In the small nodule group, the proportion of MTCs exhibiting hypoecho, smooth margins, and having blood flow signals was higher than that of PTCs, with statistically significant differences (all P＜0.05). In the large nodule group, the proportion of MTCs showing cystic solidity, hypoecho, smooth margins, blood flow, and the type Ⅳvascular distribution was higher than PTCs, and the difference of calcification type between them was also statistically significant (all P＜0.05). In contrast, the differences in the number of lesions and aspect ratio between MTCs and PTCs were not statistically significant regardless of nodule size (all P＞0.05). In the small nodule group,6 metastatic lymph nodes of medullary thyroid carcinoma (LNM-MTC) and 11 metastatic lymph nodes of papillary thyroid carcinoma (LNM-PTC) were correctly diagnosed by ultrasound, respectively. The diagnostic compliance rate of ultrasound was 78.6% (22/28) and 78.3% (54/69), respectively, with no statistically significant difference ( P=0.973). In the large nodule group, 28 LNM-MTC and 11 LNM-PTC were correctly diagnosed by ultrasound, respectively. The diagnostic compliance of ultrasound was 88.1% (52/59) and 73.5% (111/151), respectively, which was statistically significant ( P=0.022). Among them, 82.1% of LNM-MTC and 56.6% of LNM-PTC showed abnormal blood flow signals, with a statistically significant difference ( P=0.016). There were significant differences in preoperative serum CT and CEA levels of different sizes of MTCs (all P＜0.05). Conclusions Different sizes of MTCs require diverse demonstrative criteria. Abnormal blood flow signal is of great significance in the diagnosis of LNM-MTC. Within the absence of ultrasonic characteristics, preoperative serum CT test can provide confidence for the diagnosis of MTC. [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]

Objective: To determine the effect of the introduction of the calcitonin gene–related peptide monoclonal antibodies (CGRP mAbs) in 2018 on the prescribing of older medications for the prevention of chronic migraine. Background: Prior to 2018, the preventive treatment of migraine borrowed from medications intended to treat other illnesses with the last medication, onabotulinumtoxinA, receiving Food and Drug Administration (FDA) approval for the prevention of chronic migraine in 2010. The FDA approval of three CGRP mAbs in 2018 provided the ideal natural experiment to assess how the introduction of these medications, and a fourth in 2020, affected the generally stable migraine preventive medications market. Methods: We performed a retrospective cohort analysis using the aggregated de‐identified data of 6595 patients. The percentage of patients with chronic migraine who had been prescribed one of ten most prescribed oral preventive medications or onabotulinumtoxinA, or any of the four CGRP mAbs, were calculated relative to the total number of patients with chronic migraine who received a prescription for any medication from our clinic during the pre‐CGRP mAb years of 2015–2017 and post‐approval years of 2019–2021. Results: We observed a statistically significant decrease in the prescription of the top 10 most prescribed medications after the introduction of the CGRP mAbs overall (1456/3144, 46.3%, to 1995/4629, 43.1%, p = 0.001), as well as with most individual medications, including large decreases in verapamil (230/3144, 7.3%, to 125/4629, 2.7%; p < 0.001), the tricyclic antidepressants (494/3144, 15.7%, to 532/4629, 11.5%; p < 0.001), topiramate (566/3144, 18.0%, to 653/4629, 14.1%; p < 0.001), and onabotulinumtoxinA (861/3144, 27.4%, to 1134/4629, 24.5%; p = 0.001). Conclusion: The introduction of the CGRP mAbs during 2018 resulted in a decrease in utilization of most oral medications and onabotulinumtoxinA for the prevention of migraine. Future work should continue to observe how the prescription patterns of these medications evolve with time. [ABSTRACT FROM AUTHOR]

Background: Hypoparathyroidism is the destruction of the parathyroid gland by the immune system, as part of a multiple endocrine insufficiency syndrome. Tissue resistance to PTH's activities can occur in rare cases, resulting in hypoparathyroidism with increased PTH levels. Hypothyroidism is more common in females than males. 1,25-dihydroxyvitamin D3 (active vitamin D) levels must be evaluated to rule out vitamin D deficiency as a contributor to or cause of hypocalcemia. Hypocalcemia and phosphatemia are common symptoms of hypoparathyroidism. Antinuclear antibodies (ANA) and double strand DNA (DsDNA) are the important biomarkers for diagnosis and prognosis of patients with autoimmune diseases. ANA and DsDNA occur in different endocrine disorders including thyroid disorders like hypoparathyroidism. Methods: Thirty Hypoparathyroidism patients with age range 21-74 years with (20 female and 10 male) were attending international Baghdad Medical Hospital, during the period from December 2019 to February 2021 and thirty apparently healthy were chosen as healthy control groups respectively. For these two study groups, the blood samples were collected to evaluate the serum level of serum phosphorus, calcitonin, Calcium, Vitamin D3, DsDNA and ANA. The type of kits used for serum DsDNA and ANA in humans were an indirect enzyme immunoassay (ELISA) and the kits for serum level of serum Vitamin D3 and calcitonins were a sandwich ELISA. Finally, these kits for the calcium and phosphorus inorganic Colorimetric method were used. Results: Using Student's t-test, the present study's data revealed a statistically significant difference in the mean of age group cases and controls (P=0.005), as well as a statistically significant difference in serum mean values of each Serum phosphorus (P=0.005), calcitonin (P=0.005), calcium (P=0.002), and vitamin D3 centration (P=0.005) between these two groups. By using Chi-square test sex was not significant between hypoparathyroid and control (P=0.787) and DsDNA was not significantly more positive in hypoparathyroid subjects than control (P=0.112); while ANA was significant (P=0.024). Conclusion: The study sheds light on the necessity to screen the hypo parathyroid patients for vitamin D, calcium and phosphorous levels and calcitonin for better prognosis of patients and for each of antinuclear antibodies (ANA) and double strand DNA (DsDNA). [ABSTRACT FROM AUTHOR]

Introduction: Procalcitonin levels have been studied to predict the benefit of adding antibiotics in a patient with acute pancreatitis. Through this study, we are searching for any possible correlation between serum procalcitonin levels and the severity of acute pancreatitis (included acute on chronic cases) to determine whether procalcitonin levels can predict a benefit from antibiotic therapy in acute pancreatitis. Methods: This is a retrospective cohort study involving patients with acute pancreatitis and acute on chronic pancreatitis. We included all hospitalized patients admitted to Kern Medical from January 2020 to October 2022 with a diagnosis of acute pancreatitis in a consecutive manner. The primary outcome studied was mortality related to the pancreatitis episode. Logistic regression was used to control numerous confounders. Results: Based on univariate analysis of procalcitonin, we found starting antibiotics on the day of admission statistically significant. We also found the median differences in mortality to be mildly significant (difference = 0.79, p = 0.0640) based on procalcitonin values. In a multivariate analysis of ln(procalcitonin), we found lipase (p = 0.0249), duration of antibiotics (p = 0.0009), multi-organ failure (p = 0.0045) to be statistically significant, and lactate being mildly significant in the multivariate model (p = 0.0643). Conclusion: The procalcitonin level can predict the initiation of antibiotics, duration of antibiotics, multi-organ failure, and mortality in patients with acute pancreatitis. [ABSTRACT FROM AUTHOR]

Purpose: In this pilot study, we investigated the cardiac autonomic activity of coronavirus disease 2019 (COVID-19)-infected hospitalized patients. COVID-19 is characterized by cough, fever, and dyspnea, which in some severe cases can lead to hypoxia, respiratory failure, and shock. Since breathing disorders and pulmonary diseases are tightly linked to autonomic dysfunction, we analyzed the cardiac autonomic activity by measuring the deceleration capacity (DC) in COVID-19 patients. Methods: In 14 adults (4 men and 10 women) with a median age of 63.5 years and positive for SARS-CoV-2 by polymerase chain reaction (PCR) with severe symptoms requiring hospital treatment, a high-resolution digital 30 min electrocardiogram (ECG) in Frank leads configuration was performed in a resting supine position within the first 48 h after hospital admission. DC was assessed using validated software and associated with several markers of inflammation and clinical course. Results: The study revealed a significant association between reduced DC (≤ 2.5 ms) and older age (74 years) in COVID-19 patients, compared to those with a higher DC > 2.5 ms (56.5 years). However, the duration of hospitalization was similar for both groups. There was a nonsignificant trend towards a higher maximum viral load in patients with reduced DC. Further, patients with a DC ≤ 2.5 ms showed higher levels of inflammatory markers such as C-reactive protein (CRP) and procalcitonin (PCT), as well as leukocytosis, compared to patients with a DC > 2.5 ms. Also, the COVID-19-severity marker ferritin was significantly elevated in patients with lower DC. Other markers associated with COVID-19, such as lactate dehydrogenase (LDH) and creatine kinase (CK), exhibited comparable levels in both groups. Conclusions: Reduced DC (≤ 2.5 ms) was significantly associated with older age, increased inflammatory markers, and elevated ferritin in patients with COVID-19. These findings suggest that DC might serve as a valuable indicator for predicting the risk of severe inflammation in COVID-19 and possibly complications associated with this disease, such as heart failure. Further studies are needed to confirm these observations and clarify the clinical significance of DC in COVID-19 and other infectious diseases. [ABSTRACT FROM AUTHOR]