Analysis of clinical factors as possible predictors of response to omalizumab and relapse after treatment discontinuation in chronic spontaneous urticaria.

Omalizumab is a monoclonal anti-IgE antibody which is effective in chronic spontaneous urticaria (CSU), although clinical response appears to be variable in the real-life setting. The aim of this study was to evaluate whether the response of CSU to omalizumab and disease relapse are associated with individual and/or clinical characteristics of patients. We retrospectively evaluated the clinical records of 124 patients treated with omalizumab for moderate to severe CSU refractory to antihistamines. Disease activity was assessed using the urticaria activity score over the last 7 days (UAS7). After 24 weeks of treatment, 91% of patients showed complete remission (UAS7 = 0) or good control (UAS7 < 7) of CSU. Omalizumab was re-administered in 45 patients because of recurrence of moderate to severe symptoms at week 8 after treatment discontinuation or later, and clinical results achieved with retreatment were similar to those observed in the first course. Among the parameters included in our analysis (age and sex of patients, documented history of atopy or autoimmune thyroid disease, CSU duration and baseline severity, concurrent angioedema, and association with chronic inducible urticaria), none was associated with response to omalizumab in our study population. Similarly, these parameters did not significantly differ between patients who experienced CSU relapse and those without relapse. Predictors of response to omalizumab treatment in CSU patients are still unclear, and further studies are needed to evaluate the presence of baseline factors that can influence treatment outcome.

Maternal Psychological Factors and Onset of Functional Gastrointestinal Disorders in Offspring: A Prospective Study.

BACKGROUND/OBJECTIVES: Functional gastrointestinal disorders (FGIDs) are a heterogeneous group of conditions of unclear etiology. The biopsychosocial model approach to FGIDs posits that early-life stressors may trigger a cascade of complex interactions between genetic predisposition and risk factors eventually leading to the occurrence of FGIDs. The relationship between the psychological disposition of the mother and FGIDs occurrence is poorly understood. We conducted a study to investigate if parental psychological factors may contribute to the onset of FGIDs in offspring. METHODS: We performed a prospective cohort study of parent-infant pairs who completed a battery of self-reported psychological questionnaires and a validated Rome III questionnaire for the diagnosis of infant and toddler FGIDs. The Edinburgh Postpartum Depression Scale (EPDS) was used to examine postpartum depression (PPD) symptoms; the Maternity Blues Questionnaire (MBQ) was applied to measure maternity blues severity; the Symptoms Checklist-Revised (SCL90-R) was used to assess the presence of relevant psychiatric symptoms; adult attachment style in mothers was assessed in a continuous way through the five dimensions of the Attachment Style Questionnaire (ASQ). RESULTS: Out of the 360 eligible mothers, 200 were enrolled, 113 completed the 3-month follow-up and were included in the final analysis. PPD symptoms prevalence was 20.4%, 20%, 13.2%, and 13.1% respectively at 3 days, 1 week, 1 month, and 3 months after delivery. 40.4% of mothers suffered from severe blues according to the MBQ. Relevant psychiatric symptoms (SCL90-R) were present in 7.8% and 10.9% of mothers, respectively at 1 week and 3 months after delivery. 48.7% of mothers showed a secure attachment pattern measured through the RQ. At 1-month follow-up, infant regurgitation was diagnosed in 26 (23%) of infants, infantile colic in 31 (27.4%), dyschezia in 17 (15%), and functional constipation in 9 (8%). At 3-month follow-up, FGIDs prevalence was respectively 16 (19.3%), 11 (13.3%), 4 (4.8%), and 11 (13.3%). A significant positive association between PPD symptoms starting 3 days after delivery and the presence of infantile colic on setting 1 month after birth was found (P = 0.028), as well as between PPD symptoms occurrence 7 days after delivery and infantile regurgitation beginning 1 month after birth (P = 0.042). A higher prevalence of infantile colic was found in the offspring of mothers suffering from PPD symptoms from 3 days after delivery (54.5 vs 19.8; P = 0.001). No significant association was found between FGIDs and psychiatric symptoms and maternity blues at any timepoint. On the other hand, mothers of infants with regurgitation with an onset 1 month after birth have higher insecurity score in avoidant and fearful ASQ-related attachment dimensions (respectively, P = 0.03, P = 0.042, P = 0.03). CONCLUSIONS: Maternal psychological factors might contribute to the onset of infant FGIDs in offspring. Early screening of postpartum depression symptoms and early implementation of psychological interventions within the postpartum period might promote the health of the mother-infant dyad.

How often suspected pulmonary embolism is diagnosed and its main diagnostic characteristics, in an emergency nuclear medicine service? Four years experience.

OBJECTIVE: Acute pulmonary embolism (APE) is an emergency condition and its treatment must be immediate. Nevertheless, the diagnosis of APE is diffcult because its symptoms and risk factors are not specific. We present our 4 years experience on this subject. SUBJECTS AND METHODS: We retrospectively studied 2178 lung perfusion scintigraphies (LPS). Of them 1846 were performed to patients suspected for APE admitted to the emergency departments of the University Polyclinic of Bari and examined immediately by our Nuclear Medicine Department. Contingency tables and odds ratio (OR) were used to estimate the relation between symptoms, risk factors, D-dimers dosage, other imaging diagnostic tools and LPS results. RESULTS: Lung perfusion scintigraphy was positive for APE in 309/1846 (16.7%) patients which then were treated successfully. In 89.5% of these, 309 patients D-dimer dosage was previously examined and was increased in 97.7% of them, but was not predictive of APE (OR=1.04, P=1). Among all symptoms, a low diagnostic capacity was found for cough (OR=1.25, P=0.066) and for chest pain (OR=0.95, P=649). On the contrary, dyspnea was a significant symptom correlated with positive LPS (OR=1.78, P<0.001). The presence of risk factors was predictive of positive LPS and positively correlated with the number of positive 2 oglin lesions in LPS. x2loglin=6.472, P=0.011). Lung perfusion scintigraphy positive for APE were significantly associated with computed tomography pulmonary angiography and/or chest X-ray results (x =9.618, P=0.022). CONCLUSION: Lung perfusion scintigraphy could early diagnose APE in 16.7% of the cases (referred to our Nuclear Medicine Emergency Service) and exclude APE in 83.3% of these cases. Immediate treatment or release of these patients from the emergency department was thus possible. LPS has a key role in the early diagnosis but even more in exclusion of APE, optimizing the management of patients who do not require admission to intensive care. Our four-year and large-scale experience, based on clinical and resource optimization, support the need of Nuclear Medicine Units to perform LPS as emergency in on-call 24 hrs service.

18F-FDG PET/CT in therapy response and in predicting responders or non-responders in malignant pleural mesothelioma patients, by using semi-quantitative mRECIST and EORTC criteria.

OBJECTIVE: To evaluate the role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in therapy response assessment according modified response evaluating criteria of solid tumors (mRECIST) and the predictive role of volume-based semi-quantitative parameters in patients with malignant pleural mesothelioma (MPM). Furthermore modified RECIST criteria for MPM mRECIST and the European Organization for Research and Treatment of Cancer (EORTC) criteria were compared and the predictive role of 18F-FDG PET/CT in the post-therapy outcome. SUBJECTS AND METHODS: Thirty five selected patients with MPM underwent 18F-FDG PET/CT scan at baseline (1) and after therapy (2). Semi-quantitative 18F-FDG PET/CT parameters were collected for each scan and also differences (Δ) ΔSUVmax, ΔSUVav, ΔMTV, ΔTLG, response index (RI)max% and RIav% were evaluated. Radiologic response to therapy was assessed by using the mRECIST and EORTC. RESULTS: The correlation between response to therapy assessed by EORTC and mRECIST criteria was moderate (K=0.418; 95%CI:0099-0736). According to mRECIST, statistical differences between responders and non-responders were significant in the analysis of semi-quantitative parameters. According mRECIST criteria, all parameters defined a good area under the curve (AUC) but the better AUC resulted for ΔMTV (cut-off≤11.3, sensitivity=91.3%, specificity=91.7%) and ΔTLG (cut-off≤59.1, sensitivity=82.6%, specificity=100%). Kaplan-Meier curves between responders and non-responders did not show statistically significant differences. CONCLUSION: The semi-quantitative analysis of 18F-FDG PET/CT has an important role in MPM therapy response assessment and has a predictive role in distinguishing responders and non-responders.

Vascular Patterns in Cutaneous Ulcerated Basal Cell Carcinoma: A Retrospective Blinded Study Including Dermoscopy.

The aim of this retrospective study was to determine the type and prevalence of vascular patterns in the ulcerated and non-ulcerated portions of histologically proven basal cell carcinomas (BCCs) and correlate them with other dermoscopic and clinical features, including the clinically supposed diagnosis. Three authors retrospectively collected 156 clinical and 156 dermoscopic digital images of ulcerated BCCs (histologically confirmed); each image was blindly evaluated by 2 other authors, who did not know the histological diagnosis. Seventeen lesions were completely ulcerated, while 139 lesions presented ulcerated and non-ulcerated portions. Correct clinical diagnosis was associated with the type of lesion, in particular 90.6% of partially ulcerated lesions were correctly diagnosed with clinical-dermoscopic examination, compared with 11.8% of totally ulcerated lesions (χ2 = 64.00, p = 0.000). Presence of arborizing pattern in the ulcerated portion was associated with a correct diagnosis (Fisher's exact test, p = 0.015). Correct diagnosis was also associated with absence of dotted pattern in the non-ulcerated area (χ2 = 16.18, p = 0.000); the absence of hairpin (χ2 = 6.08, p = 0.000) and glomerular patterns were associated with correct diagnosis in the ulcerated areas (χ2 = 18.64, p = 0.000). In case of completely ulcerated BCC the clinician lacks the means to correctly identify the correct nature of the lesion, and is driven towards an incorrect diagnostic conclusion.

Bevacizumab-Based Chemotherapy Combined with Regional Deep Capacitive Hyperthermia in Metastatic Cancer Patients: A Pilot Study.

As an angiogenesis inhibitor, bevacizumab has been investigated in combination with different chemotherapeutic agents, achieving an established role for metastatic cancer treatment. However, potential synergic anti-angiogenic effects of hyperthermia have not tested to date in literature. The aim of our study was to analyze efficacy, safety, and survival of anti-angiogenic-based chemotherapy associated to regional deep capacitive hyperthermia (HT) in metastatic cancer patients. Twenty-three patients with metastatic colorectal (n = 16), ovarian (n = 5), and breast (n = 2) cancer were treated with HT in addition to a standard bevacizumab-based chemotherapy regimen. Treatment response assessment was performed, according to the modified Response Evaluation Criteria for Solid Tumors (mRECIST), at 80 days (timepoint-1) and at 160 days (timepoint-2) after therapy. Disease Response Rate (DRR), considered as the proportion of patients who had the best response rating (complete response (CR), partial response (PR), or stable disease (SD)), was assessed at timepoint-1 and timepoint-2. Chi-squared for linear trend test was performed to evaluated the association between response groups (R/NR) and the number of previous treatment (none, 1, 2, 3), number of chemotherapy cycles (<6, 6, 12, >12), number of hyperthermia sessions (<12, 12, 24, >24), and lines of chemotherapy (I, II). Survival curves were estimated by Kaplan-Meier method. DRR was 85.7% and 72.2% at timepoint-1 and timepoint-2, respectively. HT was well tolerated without additional adverse effects on chemotherapy-related toxicity. Chi-squared for linear trend test demonstrated that the percentage of responders grew in relation to the number of chemotherapy cycles (p = 0.015) and to number of HT sessions (p < 0.001) performed. Both overall survival (OS) and time to progression (TTP) were influenced by the number of chemotherapy cycles (p < 0.001) and HT sessions (p < 0.001) performed. Our preliminary data, that need to be confirmed in larger studies, suggest that the combined treatment of bevacizumab-based chemotherapy with HT has a favorable tumor response, is feasible and well tolerated, and offers a potentially promising option for metastatic cancer patients.

The impact of lung perfusion scintigraphy in the emergency management of patients with suspected pulmonary embolism.

OBJECTIVE: Pulmonary Embolism (PE) is an emergency condition that requires immediate treatment. As the symptoms and the risk factors are nonspecific, PE differential diagnosis is often required. Even if angio-CT is considered the gold standard for PE diagnosis, the frequent allergic condition and/or chronic renal failure of patients make, in most cases, not possible the use of contrast enhancement in emergency with even more increasing use of Lung Perfusion Scintigraphy (LPS), as a simple and fast examination with no preparation/contraindication. The aim of our study is to highlight the role of LPS in the management of patients (pts) with suspected PE admitted to our hospital as an emergency in the "on-call" 24 hours (hrs) service. MATERIALS AND METHOD: We retrospectively revised 2166 LPS performed for suspected PE from January 2012 to December 2016, of which 1730 were urgent. LPS was performed according to the EANM guidelines in the 4 standard projections. The relation between symptoms, risk factors, dosage of D-dimers, other imaging diagnostic tools and LPS results were evaluated by contingency tables and Odds Ratio (OR). RESULTS: The origin unit of pts was: emergency (56.7%), pneumology (10.8%), neurology (4.8%), internal medicine (6.5%), surgery (5.2%), cardiology (3.3%) and other departments (11.2%). 59.3% of the examinations were performed during the on-call 24 hrs service. Symptoms were chest pain in 39%, dyspnea in 75%, cough in 22%. In 34% were present two symptoms, while 10% were asymptomatic. D-dimer dosage before LPS was increased in 97% (>500 ug/L). 55.5% had only one risk factor, 18.7% had two or more risk factors. 75.5% of pts had previously performed another diagnostic exam (Chest X-ray in 57%, chest CT in 8.4%, both in 10.1%) while 24.5% did not undergo previous diagnostic exam. The Chest X-ray and/or chest CT resulted negative in 25.4%, suspected for PE in 24.4%, non-specific with pleural effusion in 18.8% and non-specific with inflammatory interstitial diseases in 31.4%. LSP resulted positive for PE in 17% and then treated; LPS resulted negative in the remnant 83%. LPS results were associated with those of CT and Rx (χ2=17.5 P=0.001). LPS resulted positive in 13.8% with negative Chest X-ray and/or CT, in 23.4% with suspected PE, in 15.2% with pleural effusion and in 14.7% with inflammatory interstitial diseases. Furthermore LPS resulted positive in 17.32% without previous diagnostic exam. The increased value of D-Dimers (>500ng/ml) observed in 97% was not predictive of PE (OR=0.598 P=0.152). A similar result was observed for cough (OR=1.146 P=0.395) and chest pain (OR=0.927 P=0.601). Conversely, dyspnea appeared to be a significant symptom of PE (OR=1.596 P=0.003). The presence of risk factors is not predictor of PE detected by LPS (OR=1.297 P=0.089). CONCLUSION: LPS has a key role in the early diagnosis but even more in the exclusion of PE, optimizing the management of pts who do not require admission to intensive care unit with high costs and limited availability. LPS confirms to be a simple, quick and inexpensive examination. It does not require preparation and has no side effect so it can be performed in all types of pts including pregnant women, politraumatized and complicated patients, with great impact on resource optimization for intensive care units. Our multi-year and large-scale experience related to a metropolitan area suggests that, to date, given the great demand and relevance of this examination, Nuclear Medicine Units must necessarily be organized in order to provide LPS as emergency in on-call 24 hrs service.

Orofacial Manifestations and Temporomandibular Disorders of Systemic Scleroderma: An Observational Study.

Scleroderma is a disorder involving oral and facial tissues, with skin hardening, thin lips, deep wrinkles, xerostomia, tongue rigidity, and microstomia. The aim of this study was to investigate the prevalence of oral manifestations and temporomandibular disorders (TMD) in Systemic Sclerosis (SSc) patients compared with healthy people. Eighty patients (6 men, 74 women) fulfilling ACR/EULAR SSc Criteria were enrolled. A randomly selected group of 80 patients, matched by sex and age served as control group. The examination for TMD signs and symptoms was based on the standardized Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) through a questionnaire and clinical examination. SSc patients complained more frequently (78.8%) of oral symptoms (Xerostomia, dysgeusia, dysphagia and stomatodynia) than controls (28.7%) (χ² = 40.23 p = 0.001). TMD symptoms (muscle pain on chewing, difficulty in mouth opening, headaches) were complained by 92.5% of SSc patients and by 76.2% of controls (χ² = 8.012 p = 0.005). At the clinical examination, 85% of SSc patients showed restricted opening versus 20.0% of controls (χ² = 67.77 p = 0.001), 81.2% of SSc showed reduced right lateral excursion versus 50% of controls (χ² = 17.316 p = 0.001); 73.8% of SSc showed limited left lateral excursion versus 53.8% of controls (χ² = 6.924 p = 0.009); and 73.8% of SSc had narrow protrusion versus 56.2% of controls (χ² = 5.385 p = 0.02).

Comparison of (18)F-FDG PET/CT methods of analysis for predicting response to neoadjuvant chemoradiation therapy in patients with locally advanced low rectal cancer.

PURPOSE: The aim of this study was to prospectively investigate the predictive value of (18)F-FDG PET/CT semiquantitative parameters for locally advanced low rectal cancer (LARC) treated by neoadjuvant chemoradiation therapy (nCRT). METHODS: 68 patients with LARC had (18)F-FDG PET/CT scans twice (baseline and 5-6 weeks post-nCRT). All patients underwent surgery with preservation of the sphincter 8 weeks later. (18)F-FDG PET/CT analysis was performed by visual response assessment (VRA) and semiquantitative parameters: SUVmax(baseline), SUVmean(baseline), MTV(baseline), TLG(baseline), SUVmax(post-nCRT), SUVmean(post-nCRT), MTV(post-nCRT), TLG(post-nCRT); ΔSUVmax and mean and Response indexes (RImax% and RImean%). Assessment of nCRT tumor response was performed according to the Mandard's Tumor Regression Grade (TRG) and (y)pTNM staging on the surgical specimens. Concordances of VRA with TRG, and with (y)pTNM criteria were evaluated by Cohen's K. Results were compared by t student test for unpaired groups. ROC curve analysis was performed. RESULTS: VRA analysis of post-nCRT (18)F-FDG PET/CT scan for the (y)pTNM outcome showed sensitivity, specificity, accuracy, PPV, and NPV of 87.5%, 66.7%, 83.8%, 92.5%, and 53.3%, respectively. Concordances of VRA with TRG and with (y)pTNM were moderate. For the outcome variable TRG, the statistical difference between responders and non-responders was significant for SUVmax(post-nCRT) and RImean%; for the outcome variable (y)pTNM, there was a significant difference for MTV(baseline), SUVmax(post-nCRT), SUVmean(post-nCRT), MTV(post-nCRT), RImax%, and RImean%. ROC analysis showed better AUCs: for the outcome variable TRG for SUVmax(post-nCRT), SUVmean(post-nCRT), and RImean%; for the outcome variable (y)pTNM for MTVbaseline, SUVmax(post-nCRT), SUVmean(post-nCRT), MTV(post-nCRT), RImax%, and RImean%. No significant differences among parameters were found. CONCLUSIONS: Qualitative and semiquantitative evaluations for (18)F-FDG PET/CT are the optimal approach; a valid parameter for response prediction has still to be established.

Role of (18)F-FDG PET/CT in the evaluation of response to antibiotic therapy in patients affected by infectious spondylodiscitis.

OBJECTIVE: Spondylodiscitis is characterized by infection involving the intervertebral disc and adjacent vertebrae. It can occur anywhere in the vertebral column but more commonly involves lumbar spine. Our aim was to evaluate the usefulness of (18)F-FDG PET/CT to detect the early response to antibiotic therapy in patients affected by infectious spondylodiscitis and to compare the role of (18)F-FDG PET/CT and MRI in post-treatment evaluation. MATERIALS AND METHODS: 15 patients (12M, 3F), with mean age 65±13 years old, with typical clinical symptoms of Infectious Spondylodiscitis (pain, fever and increase of inflammatory indexes) and confirmed by blood culture or vertebral biopsy underwent within three day-interval a (18)F-FDG PET/CT and Magnetic Resonance (MR) at "baseline" and after antibiotic therapy. Semiquantitative parameters at (18)F-FDG PET/CT "baseline" SUVmax1, MTV1 and TLG1 and after therapy SUVmax2, MTV2 and TLG2 of involved vertebrae were calculated. Follow-up period of at least three months was available for all patients. T-student test for paired groups was performed to compare baseline and after therapy (18)F-FDG PET/CT semiquantitative parameters. RESULTS: According to (18)F-FDG PET/CT parameters all patients showed a response to antibiotic therapy. All patients were positive at "baseline" MRI of the spine, while at follow-up, 7/15 patients showed MR signs of infection and were considered "positive" and 8/15 showed resolution of infectious condition and, therefore they were considered "negative". A statistical significant difference between (18)F-FDG PET/CT "baseline" and after antibiotic therapy was found for all semiquantitative parameters: SUVmax (t=5.8, P=0.01); MTV (t=5.17, P=0.001); TLG (t=5,26, P=0,001). The comparison between the "baseline" and "after treatment" (18)F-FDG semiquantitative parameters showed a significant reduction of all parameters. This reduction was relevant also in patients with positive post-treatment MRI. This can be probably related to the tissue remodeling in the very immediate phase post-treatment, resulted positive at MRI and negative at (18)F-FDG PET/CT. Clinical follow-up of at least three months confirmed these results. CONCLUSIONS: (18)F-FDG PET/CT is useful to detect the early response to antibiotic therapy in patients affected by infectious spondylodiscitis. (18)F-FDG PET/CT semiquantitative parameters provide critical diagnostic information of the infectious process. (18)F-FDG PET/CT should be considered as first-line exam in the early post-treatment evaluation of spondylodiscitis while MR should be preferred for delayed assessment.

Diagnostic and prognostic value of 18F-FDG PET/CT in comparison with morphological imaging in primary adrenal gland malignancies - a multicenter experience.

OBJECTIVE: To evaluate the diagnostic and prognostic role of fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in comparison to morphological imaging such as computed tomography in primary adrenal malignancies. MATERIALS AND METHODS: In this multicenter retrospective study, 68 patients with adrenal malignancy were included. All patients had histologically proven diagnosis of primary adrenal malignancy (adrenocortical carcinoma, malignant pheochromocytoma, neuroblastoma and lymphoma), one whole body (18)F-FDG PET/CT scan and one whole-body contrast enhancement computed tomography (CECT) scan acquired within one month and were followed clinically and by performing morphological tests for at least 12 months. RESULTS: Overall sensitivity, specificity, accuracy, positive and negative predictive values for CECT and (18)F-FDG PET/CT were respectively, 59%, 100%, 65%, 100%, 27% and 75%, 100%, 82%, 100% and 63%. For adrenocortical carcinomas, (18)F-FDG PET/CT showed a better accuracy (93.4%) than CECT (75%). For neuroblastomas (18)F-FDG PET/CT also showed better accuracy (70.4%) than CECT (66.7%). For malignant pheochromocytomas (18)F-FDG PET/CT and CECT showed the same accuracy (90%). For primary adrenal lymphomas, (18)F-FDG PET/CT showed better accuracy (100%) than CECT (74.41%). Kaplan-Mayer curves showed that "histotypes" and "metastases at the last follow-up" were similarly detected for both disease free survival (DFS) and overall survival (OS), while "global 18F-FDG PET/CT" and "presence of metastases at diagnosis" were significant for DFS. Stratifying the sample by the presence or absence of metastases at diagnosis, standardized uptake value (SUVmax) was a significant prognostic factor for DFS when metastases were absent (Wald test=7.035, P=0.008). CONCLUSION: Our multicenter study demonstrated that (18)F-FDG PET/CT better than CECT diagnosed adrenal malignancies achieving also a good prognostic performance. Therefore management algorithms should include (18)F-FDG PET/CT.

Current clinical use of 18FDG-PET/CT in patients with thoracic and systemic sarcoidosis.

PURPOSE: This study assessed the role of whole-body (18)fluorodeoxyglucose positron-emission tomography/computed tomography ((18)FDG PET/CT) in the restaging and follow-up of patients with sarcoidosis previously studied by multidetector computed tomography (MDCT). MATERIALS AND METHODS: This retrospective study enrolled 21 patients to evaluate the sensitivity, specificity and accuracy of (18)FDG-PET/CT and MDCT. The results of the two techniques were compared with the Mc Nemar test. Cohen's K was used to compare concordance at the different lesion sites. RESULTS: The sensitivity, specificity and accuracy of (18)FDG-PET/CT were 80, 66.67, and 76.19 %, respectively. The sensitivity, specificity and accuracy of MDCT were 93.33, 33.33, and 76.19 %, respectively. In 16 patients who underwent whole-body MDCT, the sensitivity, specificity and accuracy values were 91.67, 81.25, and 50 % (MDCT) and 100, 50, and 87.5 % ((18)FDG-PET/CT). CONCLUSIONS: (18)FDG-PET/CT is useful in evaluating the extent of sarcoidosis and recognising lesions at different sites, including lymph nodes, lungs, liver, spleen and bone. It also improves the interpretation of the morphological lesions seen on MDCT and depicts a larger number of lesions. Therefore, (18)FDG-PET/CT could be used to complement other more traditional techniques for the restaging and follow-up in patients with sarcoidosis.

Mast cell density in Merkel cell carcinoma and its correlation with prognostic features and MCPyV status: a pilot study.

Merkel cell carcinoma (MCC) is a rare, highly aggressive, primitive neuroendocrine carcinoma of the skin, the origin of which is not yet fully understood. Numerous independent prognostic factors have been investigated in an attempt to understand which are the most important parameters to indicate in the histological diagnostic report of MCC. Of these, mast cells have only been studied in one paper before this one. We present a retrospective descriptive study of 13 cases of MCC, received at the Department of Pathology over a 20-year period (2003-2023 inclusive) on which we performed a study using whole-slide (WSI) morphometric analysis scanning platform Aperio Scanscope CS for the detection and spatial distribution of mast cells, using monoclonal anti-tryptase antibody and anti-CD34 monoclonal antibody to study the density of microvessels. In addition, we analyzed MCPyV status with the antibody for MCPyV large T-antigen (Clone CM2B4). We found statistically significant correlation between mast cell density and local recurrence/distant metastasis/death-of-disease (p = 0.008). To our knowledge, we firstly reported that MCPyV ( -) MCC shows higher mast cells density compared to MCPyV ( +) MCC, the latter well known to be less aggressive. Besides, the median vascular density did not show no significant correlation with recurrence/metastasis/death-of-disease, (p = 0.18). Despite the small sample size, this paper prompts future studies investigating the role of mast cell density in MCC.

Serum sarcosine is a risk factor for progression and survival in patients with metastatic castration-resistant prostate cancer.

AIM: Sarcosine has been identified as a differential metabolite that is greatly increased during progression from normal tissue to prostate cancer and metastatic disease. In this study we assessed the role of serum sarcosine in metastatic castration-resistant prostate cancer (mCRPC) patients. PATIENTS & METHODS: Data from 52 mCRPC patients treated with docetaxel-based chemotherapy were retrospectively analyzed. Receiver operating characteristic curves, and Kaplan-Meier and Cox multivariate analyses were performed. RESULTS: Median sarcosine values were significantly higher in mCRPC versus non-mCRPC patients (0.81 vs 0.52 nmol/µl; p < 0.0001). A significant correlation resulted between serum sarcosine levels and the duration of hormone sensitivity (Spearman's correlation coefficient: -0.51; p = 0.001). At multivariate analysis sarcosine was an independent prognostic factor of outcome in terms of overall and progression-free survival. CONCLUSION: Serum sarcosine values were significantly increased in patients with metastatic disease. Moreover, this biomarker is a risk factor for progression and survival in chemotherapy-treated mCRPC patients.

Placental Angiodysplasia: A New Sign for Prediction of Fetal Outcome?

The study of the placenta is of great importance, not only in the attempt to understand the etiopathogenesis of various maternal-fetal pathologies, but also in the attempt to understand whether it is possible to find the cause of pathological neonatal outcomes. On the other hand, abnormalities of blood vessel formation, such as angiodysplasias, have been poorly characterised in the literature, and there is a need for more studies investigating the potential impact on the fetus. In this paper, we retrospectively analysed 2063 placentas received at the Department of Pathology of the University of Bari 'Aldo Moro', among which we identified 70 placentas affected by angiodysplasia. On these placentas, we carried out histochemical staining with Masson's Trichrome, orcein-alcian blue, and, subsequently, immunostaining with anti-CD31, CD34, and desmin and actin muscle smoothness antibodies. Finally, we performed a morphometric analysis on the allantochorionic and truncal vessels and correlated the results with neonatal outcomes. We studied the characteristics of the angiodysplasias in detail, dividing the patients into two classes (A and B) according to the morphology and histochemical characteristics of the affected vessels; statistical analysis reported a statistically significant association (p < 0.05) between the ratio of maximum thickness to maximum diameter (Tmax/Dmax) and neonatal outcome, with only 30% physiological outcome in the cohort of the placentas affected by angiodysplasia. These results shed light on a rather neglected aspect in the 2015 Amsterdam Classification, as well as in the literature, and provided strong evidence that placental angiodysplasia is predictive of an increased likelihood of the pathological fetal outcome, while other factors remain in the field. Studies with larger case series and guidelines with more attention to these aspects are mandated to further investigate the predictive potential of this pathology.

Oral semaglutide improves body composition and preserves lean mass in patients with type 2 diabetes: a 26-week prospective real-life study.

Background: Oral semaglutide is the first glucagon-like peptide-1 receptor agonist (GLP-1RA) designed for oral administration; it offers a promising opportunity to facilitate an early approach to Type 2 Diabetes (T2D). The study aimed to evaluate, in a real-life setting, the effects of oral semaglutide on the body composition of patients with T2D after 26 weeks of therapy. Methods: Thirty-two patients with T2D were evaluated at baseline (T0) and after three (T3) and six (T6) months of therapy with oral semaglutide. At each time point, body composition was assessed using a phase sensitive bioimpedance analyzer. Clinical, anthropometric and laboratory parameters, and the main biometric surrogates of liver steatosis and fibrosis, were also analyzed and compared. Results: A significant and early reduction in anthropometric and glucometabolic parameters, alanine aminotransferase, Fatty Liver Index, and Fat Mass was observed. Visceral Adipose Tissue (VAT) decreased, while Fat Free Mass and Skeletal Muscle Mass (SMM) were preserved during therapy, resulting in a beneficial increase in the SMM/VAT ratio. Finally, an overall improvement in body fluid distribution was observed. Conclusion: Our real-world data confirm the clinical efficacy of oral semaglutide and highlight its ability to improve the nutritional status of patients with T2D.

Serum sarcosine increases the accuracy of prostate cancer detection in patients with total serum PSA less than 4.0 ng/ml.

BACKGROUND: Sarcosine is reported to be a differential metabolite that is greatly increased during prostate cancer (PCa) progression. In this study, we assessed the role of serum sarcosine as a biomarker for PCa, as well as any association between sarcosine levels and clinical-pathological parameters. METHODS: Sarcosine was measured by fluorometric assay in serum samples from 290 PCa patients and 312 patients with no evidence of malignancy (NEM), confirmed by 8-12 core prostate biopsies. Nonparametric statistical tests and receiver operating characteristics (ROC) analyses were performed to assess the diagnostic performance of sarcosine in different (prostate-specific antigen) PSA ranges. RESULTS: ROC analyses in subjects with PSA < 4 ng/ml showed a higher predictive value of sarcosine (AUC = 0.668) versus total PSA (AUC = 0.535) (P = 0.03), whereas for the other two PSA ranges (4-10 ng/ml and >10 ng/ml), percent ratio of free to total PSA (%fPSA) showed a predictive superiority over sarcosine. Moreover, in patients with a PSA < 4 ng/ml, the percentage of low/intermediate-grade cancers was positively associated with sarcosine levels (P = 0.005). The specificities for serum sarcosine, %fPSA, PSA, and the logistic regression model at 95% sensitivity were 24.4, 3.41, 2.22, and 28.4%, respectively. CONCLUSIONS: We provide evidence that serum sarcosine has a higher predictive value than tPSA and %fPSA in patients with PSA < 4 ng/ml. Moreover, sarcosine levels were significantly different in low grade versus high grade cancers in this subset of patients, suggesting that this marker may be a further tool not only for diagnosing PCa in normal PSA and abnormal DRE/TRUS patients but also for selecting candidates for non-aggressive therapies and active surveillance.

Laminar Necrosis and Hypoxic Damage of the Placenta: A Case-Control Study.

The aim of this study is to verify the role of laminar necrosis (LN) in the diagnosis of hypoxic damage of the placenta. This is a retrospective case-control study in which 50 cases with laminar necrosis were compared with 100 gestational age-matched controls without laminar necrosis in a 1:2 ratio. The parameters analyzed were: the presence of other placental lesions, obstetric characteristics and neonatal outcome. For each of the 50 cases, the area affected by the lesion was detected, and the lesions were classified into three groups based on the morphology and time of onset of the lesion in order to understand whether these characteristics of the lesion had a clinical-pathology. The results showed that including the search for LN among placental lesions generally examined is useful to guide the pathologist in the diagnosis of placental dysfunction of hypoxic origin.

Once-Weekly Semaglutide Induces an Early Improvement in Body Composition in Patients with Type 2 Diabetes: A 26-Week Prospective Real-Life Study.

BACKGROUND: Body weight (BW) loss is an essential therapeutic goal in type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists are effective in reducing BW, but their effect on body composition has not yet been fully explored. The study aim was to assess the impact of Semaglutide on body composition in patients with T2D. METHODS: Forty patients with T2D were treated with subcutaneous Semaglutide and evaluated at the baseline (T0) and after three (T3) and six (T6) months. Body composition was assessed by a phase-sensitive bioimpedance analyzer. Visceral adipose tissue (VAT) thickness was also measured with an ultrasonographic method (US-VAT). Anthropometric variables, muscular strength, and laboratory tests were analyzed and compared. RESULTS: A significant decrease in VAT, the fat mass index (FMI), and BW loss was observed at all observation times. US-VAT, the skeletal mass index (SMI), the fat-free mass index (FFMI), waist circumferences, and glycated hemoglobin had lessened after three months and remained stable at T6. No variations in muscle strength, the muscle quality index, and body water were found. DISCUSSION: In a real-life setting, Semaglutide provided significant weight loss mainly due to a reduction in the FMI and VAT, with non-clinically relevant changes in the SMI, the FFMI, and muscle strength. Most importantly, the results were obtained after three months of treatment and persisted thereafter.

Lead exposure of rats during and after pregnancy induces anti-myelin proteolytic activity: a potential mechanism for lead-induced neurotoxicity.

Toxic effects of lead (Pb) are principally manifested in the central nervous system (CNS) and a mounting body of evidence indicates that excessive chronic exposure to Pb participates in the pathological processes of numerous neurodegenerative disorders in humans.In this study we evaluated whether the prolonged pre- and postnatal exposure of rat pups to lead, administrated through ingestion in drinking water, as a typical environmental exposure, can determine alterations of the protein pattern of CNS myelin and the induction of myelin-associated proteinases. Pregnant dams were given distilled water or 0.3 mg/mL lead acetate in drinking water during gestation and lactation. At postnatal day (PND) 21, pups born from mothers poisoned with Pb continued the treatment with the metal. On PND 35 and 56, pups were sacrificed, and brains were subjected to myelin purification and extraction of myelin-associated proteinases. The SDS-PAGE analysis of protein pattern of myelin incubated in vitro with an oxidative system indicated that myelin proteins from Pb-treated pups were more sensitive to the toxicity of reactive oxygen species in comparison with those from untreated pups. The zymografic analysis of NaCl-extracts from myelin of Pb-treated pups showed a band of digestion of 54 kDa that increased in pups sacrificed at PND 56 in comparison with those sacrificed at PND 35 and correlated with the concentration of Pb, detected in purified myelin. The incubation of the NaCl-extract from Pb-treated pups with purified myelin basic protein (MBP) evidenced the presence of different MBP-degrading activities. These results suggest that Pb may influence the integrity of the myelin sheath, probably through the induction of anti-myelin proteinases.