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Dupilumab therapy reduces urinary biopyrrin levels in atopic patients: a new possible biomarker of oxidative status in atopic dermatitis

Ital J Dermatol Venerol. 2023 Dec 21. doi: 10.23736/S2784-8671.23.07630-2. Online ahead of print.

ABSTRACT

BACKGROUND: Accumulating evidence suggests that oxidative stress is involved in the inflammatory process of atopic dermatitis (AD). Biopyrrins are the end products of the oxidative reaction of bilirubin with reactive oxygen species. The aim of our study was to explore the correlation between urinary biopyrrin levels and AD severity as well as to assess the possible modification of them in AD patients during biologic therapy with human monoclonal antibody dupilumab.

METHODS: For this purpose, 25 adult patients with moderate-severe AD who were candidates for dupilumab therapy independently from the study, and 15 healthy control subjects, matched by sex and age, were enrolled. Morning urine samples were collected from all study participants. For AD patients, a collection was planned before starting therapy with dupilumab (WO), after 8, 16, 52 weeks (W8, W16, W52, respectively), and two years (Y2) of treatment. The analysis of urinary levels of biopyrrins was performed by ELISA assay.

RESULTS: Our results demonstrated that urinary biopyrrin levels were significantly augmented in AD patients, and interestingly they correlated with disease severity. Furthermore, dupilumab therapy decreased levels of urinary biopyrrins in AD patients after eight and 16 weeks, maintaining the result after 52 weeks as well as after two years of treatment. The correlation analysis showed a statistically significant positive correlation between the urinary concentration of biopyrrins and EASI Index, circulating total IgE as well as plasma C reactive protein levels.

CONCLUSIONS: Dupilumab therapy was able to ameliorate oxidative state in AD patients.

PMID:38127318 | DOI:10.23736/S2784-8671.23.07630-2

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O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET as a potential selection tool for second surgery in glioblastoma patients

J Neurosurg Sci. 2023 Dec 21. doi: 10.23736/S0390-5616.23.06019-8. Online ahead of print.

ABSTRACT

BACKGROUND: Treatment-related changes still represent a diagnostic challenge in the management of patients with suspect of recurrent glioblastoma. The specificity of conventional MRI in detecting recurrence remains limited. Brain PET imaging provides information on tumor metabolism and can contribute to improving the diagnostic accuracy of cerebral neoplasms. We performed a retrospective analysis to evaluate the clinical value of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET in the diagnosis of glioblastoma recurrence.

METHODS: A retrospective analysis on patients considered suitable for salvage surgery for recurrence glioblastoma was performed. 18F-FET-PET was performed to investigate gadolinium enhancement suspected for recurrence. Static and kinetic 18F-FET parameters were analyzed and related to O-6-methylguanine-DNA methyltransferase (MGMT) status.

RESULTS: Forty-two of the 51 patients who underwent 18F-FET-PET were re-operated. In each case, neuropathological diagnosis of tumor recurrence was confirmed. pMGMT hypermethylation was detected in 21 patients. Mean tumor-to-brain ratios (TBR) max was 3.87 (range 2.6-6.0). Static and kinetic 18F-FET parameters were similar according to MGMT status.

CONCLUSIONS: 18FET-PET can be a reliable tool to improve the selection of patients suitable for salvage surgery for glioblastoma recurrence.

PMID:38127301 | DOI:10.23736/S0390-5616.23.06019-8

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Fatal Firearm Violence Among American Indians and Alaska Natives

J Community Health. 2023 Dec 21. doi: 10.1007/s10900-023-01300-x. Online ahead of print.

ABSTRACT

There is a dearth of population-based studies regarding firearm-related deaths and years of potential life lost among American Indians and Alaska Natives (AI/AN). Using the Centers for Disease Control and Prevention’s (CDC) We Based Injury Statistics Query and Reporting System (WISQARS) data for the three most recent years (2018-2020), we analyzed the demographic characteristics of AI/ANs who succumbed to firearm violence. AI/ANs averaged almost 500 firearm-related deaths per year. The majority of these deaths were observed among individuals 20-39 years of age (53%), males (84.4%), and in the West (55.3%). A plurality of these firearm-related deaths were suicides (48.9%) followed by homicides (43.5%). During the 3-year study period, the age-adjusted firearm death rate increased almost 5 times the growth of the AI/AN population. Also, a staggering 67,050 years of potential life were lost before the age of 80 years (YPLL80) during this period. Firearm suicides were responsible for the largest proportion of YPLL80s (48.5%). Traditional legal interventions [e.g., child access prevention (CAP) laws and extreme risk protection orders (ERPO)], if expanded to more states could potentially help reduce AI/AN firearm mortality. None of the 10 states with the highest firearm mortality of AI/AN have ERPOs and 8 of the 10 do not have CAP laws. Also, a renewed focus on cultural continuity and indigenous protective factors is essential to ameliorate the level of firearm violence in AI/ANs.

PMID:38127297 | DOI:10.1007/s10900-023-01300-x

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Flocking and swarming in a multi-agent dynamical system

Chaos. 2023 Dec 1;33(12):123126. doi: 10.1063/5.0168050.

ABSTRACT

Over the past few decades, the research community has been interested in the study of multi-agent systems and their emerging collective dynamics. These systems are all around us in nature, such as bacterial colonies, fish schools, and bird flocks, as well as in technology, such as microswimmers and robotics, to name a few. Flocking and swarming are two key components of the collective behaviors of multi-agent systems. In flocking, the agents coordinate their direction of motion, but in swarming, they congregate in space to organize their spatial position. We propose a minimal mathematical model of a locally interacting multi-agent system where the agents simultaneously swarm in space and exhibit flocking behavior. Various cluster structures are found depending on the interaction range. When the coupling strength value exceeds a crucial threshold, flocking behavior is observed. We do in-depth simulations and report the findings by changing the other parameters and with the incorporation of noise.

PMID:38127290 | DOI:10.1063/5.0168050

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Effectiveness of a new endodontic irrigation system for removing smear layer and dissolving simulated organic matter

Clin Oral Investig. 2023 Dec 21;28(1):10. doi: 10.1007/s00784-023-05418-z.

ABSTRACT

OBJECTIVES: The study aimed to evaluate the potential for the dissolution of organic tissue in areas of simulated complexity and cleaning of root canal walls of the new iVac® endodontic irrigation system.

MATERIAL AND METHODS: Thirty mandibular premolars were evaluated by scanning electron microscopy before and after biomechanical preparation. Then, they were distributed according to the final irrigation protocol into groups with conventional irrigation, ultrasonic agitation with metallic insert (UA), and iVac® system, and new photomicrographs were obtained. For tissue dissolution analysis, glass capillaries filled with catgut were attached to the cervical and apical thirds of twenty-one prototyped upper incisors. They were weighed before and after the previously mentioned irrigation protocols. The data were statistically compared with a significance level of 5%.

RESULTS: The final irrigation provided greater cleaning of the root canal walls in the cervical, middle, and apical thirds of the root canals (P < 0.05), with no statistically significant difference between UA and iVac®, regardless of the analyzed thirds. Both ultrasonic irrigation protocols dissolved a significantly greater volume than the conventional irrigation protocol (P < 0.05), with no difference between the two protocols (P < 0.05).

CONCLUSIONS: The iVac® system showed root canal wall cleaning and tissue dissolution similar to UA with a metallic insert, and both were superior to conventional irrigation.

CLINICAL RELEVANCE: The new irrigation system iVac is more effective than conventional irrigation and has similar root canal wall cleaning and tissue dissolution to UA.

PMID:38127289 | DOI:10.1007/s00784-023-05418-z

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CT findings in idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) and comparison to other colitides

Abdom Radiol (NY). 2023 Dec 21. doi: 10.1007/s00261-023-04129-z. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study is to determine computed tomography (CT) findings that aid in differentiating idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) from other colitides.

METHODS: Retrospective review of histiologic proven cases of IMHMV (n = 12) with contrast enhanced CT (n = 11) and/or computed tomography angiography (CTA) (n = 9) exams. Control groups comprised of CT of infectious colitis (n = 13), CT of inflammatory bowel disease (IBD) (n = 12), and CTA of other colitides (n = 13). CT exams reviewed by 2 blinded gastrointestinal radiologists for maximum bowel wall thickness, enhancement pattern, decreased bowel wall enhancement, submucosal attenuation value, presence and location of IMV occlusion, peripheral mesenteric venous occlusion, dilated pericolonic veins, subjective IMA dilation, maximum IMA diameter, maximum peripheral IMA branch diameter, ascites, and mesenteric edema. Presence of early filling veins was an additional finding evaluated on CTA exams.

RESULTS: Statistically significant CT findings of IMHMV compared to control groups included greater maximum bowel wall thickness, decreased bowel enhancement, IMV occlusion, and peripheral mesenteric venous occlusion (p < 0.05). Dilated pericolonic veins were seen more frequently in IMHMV compared to the infectious colitis group (64% versus 15%, p = 0.02). Additional statistically significant finding on CTA included early filling veins in IMHMV compared to the CTA control group (100% versus 46%, p = 0.008).

CONCLUSION: IMHMV is a rare chronic non-thrombotic ischemia predominantly involving the rectosigmoid colon. CT features that may aid in differentiating IMHMV from other causes of left-sided colitis include marked bowel wall thickening with decreased enhancement, IMV and peripheral mesenteric venous occlusion or tapering, and early filling of dilated veins on CTA.

PMID:38127281 | DOI:10.1007/s00261-023-04129-z

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Hedgehog Inhibitors Beyond Clinical Complete Response in Basal Cell Carcinoma: Should I Stop or Should I Go?

Oncologist. 2023 Dec 21:oyad319. doi: 10.1093/oncolo/oyad319. Online ahead of print.

ABSTRACT

INTRODUCTION: In advanced basal cell carcinoma (BCC), the issue of whether Hedgehog inhibitors (HHIs) should be stopped or not after clinical complete response (cCR) achievement remains an unmet clinical need.

MATERIALS AND METHODS: We conducted a retrospective, multicenter study across 7 Italian dermato-oncology units including patients with BCC who continued vismodegib after cCR between 2012 and 2019. We assessed the relationship between the duration of vismodegib intake (days to cCR [DTCR], days to stop after cCR [DTS], total treatment days [TTD]), and disease-free survival (DFS). Reasons to stop vismodegib were (R1) toxicity and (R2) disease recurrence. The relationship between DTCR, DTS, TTD, and DFS in the whole population and in R1 subgroup was assessed by Pearson’s correlation coefficient (P < .05) and Bayesian statistics (BF10).

RESULTS: Sixty-eight BCC patients with a median (m) age of 75.5 years (39-100) were included. Most patients were male (N = 43, 63%), without Gorlin syndrome (N = 56, 82%) and with head and neck area as primary site (N = 51, 75%). After cCR, out of 68 patients, 90% (N = 61/68) discontinued vismodegib: 82% (N = 50/61) due to toxicity (R1), and 18% (N = 11/61) due to recurrence (R2). Conversely, 10% (N = 7/68) continued vismodegib until last follow-up. In the whole population (N = 68), cCR was achieved with a mDTCR of 180.50 days. DFS showed a significant correlation with DTS (P < .01, BF10 = 39.2) and TTD (P < .01, BF10 = 35566), while it was not correlated to DTCR (BF10 < 0.1). The analysis of R1 subgroup (N = 50) confirmed these results. DFS correlated with DTS in all recurrent patients (N = 38, r = 0.44, P < .01) and in the recurrent patients who stopped vismodegib for toxicity (N = 26, r = 0.665, P < .01). DFS was longer when vismodegib was maintained for >2 months after cCR (mDFS > 2 months, N = 54 vs. ≤ 2 months, N = 14: 470 vs. 175 d, P < .01).

CONCLUSIONS: Our retrospective results suggest that HHIs should be continued after cCR to improve DFS in BCC.

PMID:38127280 | DOI:10.1093/oncolo/oyad319

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Anti-Müllerian hormone: a novel biomarker for aggressive prostate cancer? Emerging evidence from a prospective study of radical prostatectomies

Hormones (Athens). 2023 Dec 21. doi: 10.1007/s42000-023-00520-z. Online ahead of print.

ABSTRACT

PURPOSE: Prostate cancer patients are a heterogeneous group as regards the aggressiveness of the disease. The relationship of steroid hormones with the aggressiveness of prostate cancer is unclear. It is known that the anti-Müllerian hormone (AMH) inhibits prostate cancer cell lines in vitro. The aim of this study is to investigate the relationship of AMH and steroid hormones with the aggressiveness of prostate cancer.

METHODS: This was a prospective study of consecutive radical prostatectomy patients. We measured the following hormones: total testosterone, sex hormone-binding globulin, albumin, luteinizing hormone, follicle-stimulating hormone, estradiol, dehydroepiandrosterone sulfate, androstenedione, and AMH. The minimum follow-up after radical prostatectomy was 5 years. For the aggressiveness of prostate cancer, we considered the following three variables: post-operative Gleason score (GS) ≥ 8, TNM pΤ3 disease, and prostate-specific antigen (PSA) biochemical recurrence (BCR).

RESULTS: In total, 91 patients were enrolled. The mean age and PSA were 64.8 years and 9.3 ng/dl, respectively. The median post-operative GS was 7. Low AMH blood levels were correlated with higher post-operative GS (p = 0.001), as well as with PSA BCR (p = 0.043). With pT3 disease, only albumin was (negatively) correlated (p = 0.008). ROC analysis showed that AMH is a good predictor of BCR (AUC 0.646, 95% CI 0.510-0.782, p = 0.043); a cutoff value of 3.06 ng/dl had a positive prognostic value of 71.4% and a negative prognostic value of 63.3% for BCR. Cox regression analysis showed that AMH is a statistically significant and independent prognostic marker for BCR (p = 0.013). More precisely, for every 1 ng/ml of AMH rise, the probability for PSA BCR decreases by 20.8% (HR = 0.792). Moreover, in Kaplan-Meier analysis, disease-free survival is more probable in patients with AMΗ ≥ 3.06 ng/ml (p = 0.004).

CONCLUSIONS: Low AMH blood levels were correlated with aggressive prostate cancer in this radical prostatectomy cohort of patients. Therefore, AMH could be a prognostic biomarker for the aggressiveness of the disease.

PMID:38127275 | DOI:10.1007/s42000-023-00520-z

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Operative versus non-operative treatment of extra-articular distal humeral shaft fractures: a retrospective comparative study evaluating clinical and radiological outcomes

Eur J Orthop Surg Traumatol. 2023 Dec 21. doi: 10.1007/s00590-023-03785-7. Online ahead of print.

ABSTRACT

PURPOSE: There is limited evidence for comparing operative and non-operative management of closed, extra-articular distal humeral shaft fractures. This study aims to evaluate these outcomes.

METHODS: A comparative retrospective study was performed for patients who underwent either operative fixation or conservative management with a humeral brace, with clinical and radiological outcomes at minimum 2-year follow-up.

RESULTS: Forty-two patients with median 4.6 years follow-up were included; 24 had surgical fixation and 18 were managed with humeral brace. Assessment of clinical and radiological outcomes demonstrated few statistically significant functional differences between the two groups. Surgical patients achieved faster union for non-comminuted fractures. All patients maintained functional range of motion, with similar complication rates.

CONCLUSION: This study suggests that similar outcomes can be achieved with both managements, though faster union times may be seen in the operative group. Further studies are recommended to evaluate the impact of fracture comminution causing delayed unions.

PMID:38127272 | DOI:10.1007/s00590-023-03785-7

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Outcomes of mechanical thrombectomy in acute stroke patients with atrial fibrillation detected after stroke versus known atrial fibrillation

J Thromb Thrombolysis. 2023 Dec 21. doi: 10.1007/s11239-023-02923-6. Online ahead of print.

ABSTRACT

We aim to compare the outcomes in patients with atrial fibrillation detected after stroke (AFDAS) and their counterparts with known AF (KAF) presenting with large vessel occlusion (LVO) treated with mechanical thrombectomy (MT). This observational, prospective study included consecutive patients with acute LVO ischemic stroke of the anterior circulation with AFDAS, KAF and without AF. The primary study outcome was functional independence at 90 days after stroke. The secondary study outcomes were variation of the NIHSS score at 24 h, rate of successful reperfusion, death at 90 days and rate of immediate complications post-procedure. Overall, our cohort included 518 patients with acute ischemic stroke and LVO treated with MT, with 289 (56.8%) without a diagnosis of AF; 107 (21%) with AFDAS; 122 (22.2%) with KAF. There was no significant difference in terms of functional independence at 90 days after stroke between the three groups. Regarding the secondary study outcome, the rate of symptomatic intracranial haemorrhage (sICH) and/or parenchymal hematoma (PH) were significantly higher in the group of patients without AF (respectively, P = 0.030 and < 0.010). Logistic regression analysis showed that the subtypes of AF were not statistically significantly associated with functional independence at 90 days after stroke and with the likelihood of any ICH. Our results suggest that the subtypes of AF are not associated with clinical and safety outcomes of MT in patients with acute stroke and LVO. Further studies are needed to confirm our findings.

PMID:38127260 | DOI:10.1007/s11239-023-02923-6