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Venous thromboembolism is responsible for a significant burden of disease worldwide. Despite the publication of multiple international guidelines, anecdotal evidence suggests significant clinical variation exists in the diagnostic and management pathways of pulmonary embolism (PE). We conducted a retrospective cohort study using electronic medical records to examine clinical variation in patients admitted to a tertiary referral center in Australia with a diagnosis of PE between November 2018 and January 2020. Three hundred cases met the inclusion criteria; we found variation in rates of compression ultrasonography, acute investigation of the right ventricle, and planning of repeat imaging at specialist follow‐up. Guidelines do not address the use of compression ultrasonography in already diagnosed PE, are conflicting in their recommendation for acute investigation of the right ventricle, and recommend repeat imaging only if there are persistent symptoms at the time of specialist follow‐up. The variations we found in this study may in part be due to physician preference or due to the paucity of evidence for some of these diagnostic practices. Robust future studies are required to guide the use of these investigations in PE. [ABSTRACT FROM AUTHOR]

Background: Patients' compliance to inhalation therapy is usually sub-optimal in young asthmatics. Adolescents poorly compliant to regular anti-asthma treatments and those with tattoos (and the associated attitude) can share some personality traits and maladaptive behaviors. This relationship has not been investigated. Objective: To assess if "extended" tattoos can predict long-term compliance to regular therapy of adolescents with mild-to-moderate asthma. Methods: A 12-month retrospective observational investigation was conducted on non-smoker asthmatic adolescents of both genders. Patients assuming <70% of prescribed vilanterol/fluticasone furoate o.d. were defined as "non-compliant". Tattoo surfaces were defined as "mild" or "extended" if they were < or ≥400 cm2, respectively. The relationship between tattoos and compliance on the evolution of resources consumption at 6 and 12 months was assessed by generalized estimating equation (GEE) models at the first and second semester of the treatment period. Results: It was found that 13.2% of compliant adolescents had mild tattoos, while 47.2% of non-compliant adolescents had mild-to-extended tattoos (odds ratio (OR) 6.91, 95% CI 2.49 to 19.17, p < 0.001). The mean annual adherence to treatment was 57.8% ± 10.1 SD expected doses in non-compliant subjects with "mild tattoos" (54.8 cm2 ± 36.9 SD), but 38.6% ± 11.4 SD expected doses in those with "extended tattoos" (568.4 cm2 ± 111.6 SD, p < 0.001). Total cost proved to be a linear trend from the lowest values of compliant patients with no/mild tattoos (EUR 65.22 at 6 months and EUR 33.63 at 12 months) to the highest values of non-compliant adolescents with extended tattoos (EUR 330.75 at 6 months and EUR 297.34 at 12 months). Conclusions: Tattoo extension might be used as a reliable predictor of poor compliance and higher health care costs in adolescents with mild-to-moderate asthma. Patients characterized by poor compliance to a long-term therapeutic strategy and tattooing attitude likely share some aspects of their personality profile. [ABSTRACT FROM AUTHOR]

Simple Summary: Inorganic polyphosphate, a molecule composed of a few to several hundred orthophosphates, is involved in disparate pathological processes, including cancer development and progression. In this study, by analyzing biopsies derived from 50 subjects carrying colorectal cancer, collected by the Histopathology Unit of IRCCS "S. de Bellis," we showed a significant discrepancy in the level of inorganic polyphosphate between tumoral and peritumoral counterparts, with the former displaying a higher concentration. Moreover, by employing in vitro and ex vivo approaches, we revealed the involvement of inorganic polyphosphate in colorectal cancer cell proliferation. Additionally, we identified the calcium channel TRPM8 as the inorganic polyphosphate receptor responsible for propagating the signal downstream and, ultimately, enhancing the expression of proliferative markers. Thus, our results recognize inorganic polyphosphate as a novel pivotal biomarker linked with colorectal cancer growth. Background: Colorectal cancer (CRC) is characterized by a pro-inflammatory microenvironment and features high-energy-supply molecules that assure tumor growth. A still less studied macromolecule is inorganic polyphosphate (iPolyP), a high-energy linear polymer that is ubiquitous in all forms of life. Made up of hundreds of repeated orthophosphate units, iPolyP is essential for a wide variety of functions in mammalian cells, including the regulation of proliferative signaling pathways. Some evidence has suggested its involvement in carcinogenesis, although more studies need to be pursued. Moreover, iPolyP regulates several homeostatic processes in animals, spanning from energy metabolism to blood coagulation and tissue regeneration. Results: In this study, we tested the role of iPolyP on CRC proliferation, using in vitro and ex vivo approaches, in order to evaluate its effect on tumor growth. We found that iPolyP is significantly increased in tumor tissues, derived from affected individuals enrolled in this study, compared to the corresponding peritumoral counterparts. In addition, iPolyP signaling occurs through the TRPM8 receptor, a well-characterized Na+ and Ca2+ ion channel often overexpressed in CRC and linked with poor prognosis, thus promoting CRC cell proliferation. The pharmacological inhibition of TRPM8 or RNA interference experiments performed in established CRC cell lines, such as Caco-2 and SW620, showed that the involvement of TRPM8 is essential, greater than that of the other two known iPolyP receptors, P2Y1 and RAGE. The presence of iPolyP drives cancer cells towards the mitotic phase of the cell cycle by enhancing the expression of ccnb1, which encodes the Cyclin B protein. In vitro 2D and 3D data reflected the ex vivo results, obtained by the generation of CRC-derived organoids, which increased in size. Conclusions: These results indicate that iPolyP may be considered a novel and unexpected early biomarker supporting colorectal cancer cell proliferation. [ABSTRACT FROM AUTHOR]

Introduction/Objective. Hypothyroidism is a common disease and treatment with levothyroxine (LT4) is effective. However, variations in management are frequent. The aim of this study was to identify practices and attitudes of Serbian physicians relating to the treatment of hypothyroidism. Methods. An anonymized questionnaire was distributed electronically to members of the Serbian Thyroid Society, Serbian Association of Endocrine Surgeons, and Section for Endocrinology of the Serbian Medical Society. Results. Out of 170 invitations, 99 responses were received. LT4 was the first choice for the treatment of hypothyroidism in 90% of patients. After starting LT4 replacement therapy most respondents would recheck thyroid-stimulating hormone (TSH) in 4–6 weeks (n = 51, 62%) and in eight weeks (n = 29, 35%). In total, 61% of respondents (n = 60) indicated that they would consider treating euthyroid patients with LT4, the commonest indication being female infertility with high levels of thyroid antibodies (54%, n = 50). More than half respondents (58%, n = 45) would recommend combined LT4 + LT3 therapy for patients on LT4 with normal serum TSH who still complain of symptoms of hypothyroidism. 53% (n = 41/77), reported that the frequency of patients with normal serum TSH who still complain of hypothyroid symptoms is less than 5%. Conclusion. LT4 was the first choice of therapy for the treatment of hypothyroid patients, whereas LT3 + LT4 combination treatment is considered in patients with persistent symptoms of hypothyroidism despite normalization of TSH. The most common indication for thyroid hormone treatment in euthyroid patients was female infertility with high levels of thyroid antibodies. Alternative LT4 formulations like liquid solution or soft-gel capsules –formulations presently not available in Serbia, were largely reserved for specific conditions (interfering drugs, malabsorption, inability to take LT4 in the fasting state, unexplained poor biochemical control of hypothyroidism).

Background: We assessed the prevalence of complications from percutaneous ethanol injection (PEI) for benign and cystic thyroid nodules (CTNs) and their management. Methods: We conducted a systematic review with meta-analysis of data from published observational studies on PEI of CTNs. We also included unpublished retrospectively collected data on complications after PEI from all consecutive patients with cytologically benign CTNs who underwent PEI at the Unit of Endocrinology and Metabolic Diseases, AOU University of Campania Luigi Vanvitelli (Naples, Italy) between June 1, 2021, and March 31, 2024. A random effects meta-analysis was performed on the prevalence rate data. Pooled prevalence data were presented with confidence intervals (CIs). The I2 statistic index was used to quantify the heterogeneity. The details of the complications and the management were qualitatively described. Results: The literature search yielded 1189 studies, of which 48 studies were included in the systematic review and meta-analysis, in addition to our institutional experience (3670 CTNs in total). The overall quality of each included study was judged as fair. The prevalence of "Overall" complications of PEI was 32% ([CI 25–40%], I2 92.7%, 967 of 3195 thyroid nodules [TNs]). The prevalence of "Minor" complications of PEI was 32% ([CI 25–40%], I2 92.7%, 952 of 3195 TNs). The prevalence of "Major" complications of PEI was 2% ([CI 1–2%], I2 0%, 22 of 3670 TNs). Sensitivity analyses did not modify the results. The pooled prevalence rate of local pain was 21% (CI [16–27] I2 90.3). Local pain was typically transient and mild, sometimes moderate, and requiring analgesics for few days. The pooled prevalence rate of dysphonia was 1% (CI [1–2], I2 0). Dysphonia was transient and could last from several hours to 12 months after PEI. Conclusions: Complications of PEI for benign and CTNs are relatively common, but most are minor and usually transient, not requiring treatment. Dysphonia was a major complication, but it was uncommon and transient. PEI for CTNs could be considered a generally safe technique. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) affecting the gastrointestinal tract that can also cause extra-intestinal complications. Following exposure to the mRNA vaccine BNT162b2 (Pfizer-BioNTech) encoding the SARS-CoV-2 Spike (S) protein, some patients experienced a lack of response to the biological drug Adalimumab and a recrudescence of the disease. In CD patients in progression, resistant to considered biological therapy, an abnormal increase in intestinal permeability was observed, more often with a modulated expression of different proteins such as Aquaporin 8 (AQP8) and in tight junctions (e.g., ZO-1, Claudin1, Claudin2, Occludin), especially during disease flares. The aim of this study is to investigate how the SARS-CoV-2 vaccine could interfere with IBD therapy and contribute to disease exacerbation. We investigated the role of the SARS-CoV-2 Spike protein, transported by extracellular vesicles (EVs), and the impact of various EVs components, namely, exosomes (EXOs) and microvesicles (MVs), in modulating the expression of molecules involved in the exacerbation of CD, which remains unknown. [ABSTRACT FROM AUTHOR]

Objectives: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. Design: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. Results: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%–83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7–0.9) and respondents >60 years (OR: 0.7; 0.6–0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0–1.9], "daily" [OR: 1.8; CI: 1.3–2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3–1.9) were most likely to consider LT4. Conclusions: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment. [ABSTRACT FROM AUTHOR]

The VLCKD is a diet recognized to promote rapid fat mobilization and reduce inflammation, hepatic steatosis, and liver fibrosis. Extracellular vesicles (EVs) mediate cell-to-cell communication. The aim of the study is to investigate the role of circulating EVs in cell proliferation, ketone bodies, and ROS production in patients on an 8-week VLCKD regimen. Participants were classified as responders (R) or non-responders (NR) to VLCKD treatment based on their fibroscan results. In vitro experiments with the hepatic cell lines HEPA-RG (normal hepatocytes) and LX-2 (stellate cells) were conducted to investigate the effects of circulating EVs on cell viability, ROS production, and ketone body presence. The findings reveal a notable reduction in cell viability in both cell lines when treated with exosomes (EXOs). In contrast, treatment with microvesicles (MVs) did not appear to affect cell viability, which remained unchanged. Additionally, the levels of ketone bodies measured in urine were not consistently correlated with the reduction of fibrosis in responders (R). Similarly, an increase in ketone bodies was observed in non-responders (NR), which was also not aligned with the expected reduction in fibrosis. This inconsistency stands in stark contrast to the levels of Reactive Oxygen Species (ROS), which exhibited a clear and consistent pattern in accordance with the dietary intervention. Finally, in this preliminary study, ROS has been identified as a potential diet adherence marker for VLCKD patients; the ROS levels reliably follow the progression of the fibrosis response, providing a more accurate reflection of the therapeutic effects. [ABSTRACT FROM AUTHOR]

Background: Thermal ablation (TA) is an established therapeutic option alternative to surgery in patients with solid benign thyroid nodules causing local symptoms. However, a variable part of thyroid nodules remain viable after these nonsurgical treatments, and as many as 15% of nodules treated with TA may require a second treatment over time. This study aimed to evaluate the outcomes of TA re-treatment on symptomatic benign thyroid nodules where the volume decreased by <50% after the first procedure ( = technique inefficacy). Methods: We performed a multicenter retrospective cohort study including patients who underwent re-treatment with TA for benign thyroid nodules, whose volume decreased by <50% after initial treatment. The primary aim was to evaluate volume and volume reduction ratio (VRR) over time and compare the 6- and 12-month VRR after first versus second treatment. The secondary aim was to identify protective or risk factors for technique inefficacy, regrowth, and further treatments, expressed as adjusted hazard ratios (HRs) and confidence interval [CI], after adjustment for sex, age, nodule volume, structure and function, nodule regrowth or symptom relapse, technique used and if the same technique was used for the first and second TA and time between them. Results: We included 135 patients. Re-treatment led to VRR of 50% and 52.2% after 6 and 12 months. VRR after re-treatment was greater than after first treatment in small and medium size nodules (<30 mL), while there were no differences for large nodules (>30 mL). After re-treatment technique inefficacy rate was 51.9%, regrowth rate was 12.6%, and further treatment rate was 15.6%. Radiofrequency ablation (RFA) was protective toward technique inefficacy (HR = 0.40 [CI 0.24–0.65]) and need of further treatments (HR = 0.30 [CI 0.12–0.76]). Large nodule volume (>30 mL) was associated with increased risk of re-treatment (HR = 4.52 [CI 1.38–14.82]). Conclusions: This is the first study evaluating the outcomes of re-treatment on symptomatic benign thyroid nodules with a VRR <50% after the initial TA treatment. Best results were seen in small and medium nodules (<30 mL) and after RFA. Prospective confirmatory studies are needed. [ABSTRACT FROM AUTHOR]