Probiotics and Diet in Rosacea: Current Evidence and Future Perspectives

Rosacea is a common inflammatory skin disease, characterized by erythema, papules and pustules. The pathophysiology of rosacea remains unclear, but the complex interplay between environmental and genetic factors may act as a trigger to an abnormal innate immune response associated with a multifaceted neurovascular reaction. Increasing evidence suggests that the gut microbiota is significantly involved in the pathogenesis of rosacea, playing an important role in the inflammatory cutaneous response. Dysbiosis, small intestinal bacterial overgrowth, Helicobacter pylori infection and innate immune system dysregulation mutually contribute to the pathophysiology of rosacea, but more extensive future research is needed to better clarify their precise mechanisms of action. Many dietary triggers have been postulated for this disease; however, there is a lack of well-made and controlled studies able to undoubtedly demonstrate a causal relationship between rosacea and diet. We analyzed the available studies on the role of diet and gut microbiome in rosacea and the positive clinical effects reported by the current literature on probiotics, prebiotics, postbiotics and nutrients. Ultimately, this article improves our understanding of the gut-skin axis in rosacea, focusing on how probiotic supplementation and diet could improve the clinical management of patients affected by this common and debilitating disease

Modulated Electro-Hyperthermia as Palliative Treatment for Pancreatic Cancer: A Retrospective Observational Study on 106 Patients

Background: Pancreatic adenocarcinoma has a poor prognosis, resulting in a <10% survival rate at 5 years. Modulated electro-hyperthermia (mEHT) has been increasingly used for pancreatic cancer palliative care and therapy. Objective: To monitor the efficacy and safety of mEHT for the treatment of advanced pancreatic cancer. Methods: We collected data retrospectively on 106 patients affected by stage III-IV pancreatic adenocarcinoma. They were divided into 2 groups: patients who did not receive mEHT (no-mEHT) and patients who were treated with mEHT. We performed mEHT applying a power of 60 to 150 W for 40 to 90 minutes. The mEHT treatment was associated with chemotherapy and/or radiotherapy for 33 (84.6%) patients, whereas 6 (15.4%) patients received mEHT alone. The patients of the no-mEHT group received chemotherapy and/or radiotherapy in 55.2% of cases. Results: Median age of the sample was 65.3 years (range = 31-80 years). After 3 months of therapy, the mEHT group had partial response in 22/34 patients (64.7%), stable disease in 10/34 patients (29.4%), and progressive disease in 2/34 patients (8.3%). The no-mEHT group had partial response in 3/36 patients (8.3%), stable disease in 10/36 patients (27.8%), and progressive disease in 23/36 patients (34.3%). The median overall survival of the mEHT group was 18.0 months (range = 1.5-68.0 months) and 10.9 months (range = 0.4-55.4 months) for the non-mEHT group. Conclusions: mEHT may improve tumor response and survival of pancreatic cancer patients

Oligometastatic Gastric Cancer: Clinical Data from the Meta-Gastro Prospective Register of the Italian Research Group on Gastric Cancer

Background: Interest in the field of metastatic gastric cancer has grown in recent years, and the identification of oligometastatic patients plays a critical role as it consents to their inclusion in multimodal treatment strategies, which include systemic therapy but also surgery with curative intent. To collect sound clinical data on this subject, The Italian Research Group on Gastric Cancer developed a prospective multicentric observational register of metastatic gastric cancer patients called META-GASTRO. Methods: Data on 383 patients in Meta-Gastro were mined to help our understanding of oligometastatic, according to its double definition: quantitative/anatomical and dynamic. Results: the quantitative/anatomical definition applies to single-site metastases independently from the metastatic site (p < 0.001) to peritoneal metastases with PCI ≤ 12 (p = 0.009), to 1 or 2 hepatic metastases (p = 0.024) and nodal metastases in station 16 (p = 0.002). The dynamic definition applies to a percentage of cases variable according to the metastatic site: 8%, 13.5 and 23.8% for hepatic, lymphatic and peritoneal sites, respectively. In all cases, the OS of patients benefitting from conversion therapy was similar to those of cases deemed operable at diagnosis and operated after neoadjuvant chemotherapy. Conclusions: META-GASTRO supports the two-fold definition of oligometastatic gastric cancer: the quantitative/anatomical one, which accounts for 30% of our population, and the dynamic one, observed in 16% of our cases

Phase II study of gemcitabine, doxorubicin and paclitaxel (GAT) as first-line chemotherapy for metastatic breast cancer: a translational research experience

BACKGROUND: Patients with metastatic breast cancer are frequently treated with anthracyclines and taxanes, which are among the most active agents in this disease. Gemcitabine is an interesting candidate for a three-drug combination because of its different mechanism of action and non-overlapping toxicity with respect to the other two drugs. We aimed to evaluate the activity and toxicity of the GAT (gemcitabine, doxorubicin and paclitaxel) regimen, derived from experimental preclinical studies, as first-line chemotherapy in patients with stage IIIB-IV breast cancer. METHODS: Patients with locally advanced or metastatic breast cancer and at least one bidimensionally measurable lesion were included in the present study. Adequate bone marrow reserve, normal cardiac, hepatic and renal function, and an ECOG performance status of 0 to 2 were required. Only prior adjuvant non anthracycline-based chemotherapy was permitted. Treatment consisted of doxorubicin 50 mg/m(2 )on day 1, paclitaxel 160 mg/m(2 )on day 2 and gemcitabine 800 mg/m(2 )on day 6, repeated every 21–28 days. RESULTS: Thirty-three consecutive breast cancer patients were enrolled onto the trial (7 stage IIIB and 26 stage IV). All patients were evaluable for toxicity and 29 were assessable for response. A total of 169 cycles were administered, with a median of 6 cycles per patient (range 1–8 cycles). Complete and partial responses were observed in 6.9% and 48.3% of patients, respectively, for an overall response rate of 55.2%. A response was reported in all metastatic sites, with a median duration of 16.4 months. Median time to progression and overall survival were 10.2 and 36.4 months, respectively. The most important toxicity was hematological, with grade III-IV neutropenia observed in 69% of patients, sometimes requiring the use of granulocyte colony-stimulating factor (27%). Non hematological toxicity was rare and mild. One patient died from sepsis during the first treatment cycle before the administration of gemcitabine. CONCLUSION: The strong synergism among the three drugs found in the preclinical setting was confirmed in terms of both clinical activity and hematological toxicity. Our results seem to indicate that the GAT regimen is effective in anthracycline-naïve metastatic breast cancer and provides a feasible chemotherapeutic option in this clinical setting

A pragmatic approach improves the clinical management of stage IV gastric cancer: Comparison between the Meta-Gastro results and the GIRCG's retrospective series

Introduction: The Italian Research Group for Gastric Cancer developed a prospective database about stage IV gastric cancer, to evaluate how a pragmatic attitude impacts the management of these patients. Materials and methods: We prospectively collected data about metastatic gastric cancer patients thanks to cooperation between radiologists, oncologists and surgeons and we analyzed survival and prognostic factors, comparing the results to those obtained in our retrospective study. Results: Three-hundred and eighty-three patients were enrolled from 2018 to September 2022. We observed a higher percentage of laparoscopic exploration with peritoneal lavage in the prospective cohort. In the registry only 3.6 % of patients was submitted to surgery without associated chemotherapy, while in the retrospective population 44.3 % of patients were operated on without any chemotherapy. At univariate and multivariate analyses, the different metastatic sites did not show any survival differences among each other (OS 20.0 vs 16.10 vs 16.7 months for lymphnodal, peritoneal and hepatic metastases, respectively), while the number of metastatic sites and the type of treatment showed a statistical significance (OS 16,7 vs 13,0 vs 4,5 months for 1, 2 and 3 different metastatic sites respectively, p &lt; 0.001; 24,2 vs 12,0 vs 2,5 months for surgery with/without chemotherapy, chemotherapy alone and best supportive treatment respectively, p &lt; 0.001). Conclusions: Our data highlight that the different metastatic sites did not show different survivals, but survival is worse in case of multiple localization. In patients where a curative resection can be achieved, acceptable survival rates are possible. A better diagnostic workup and a more accurate staging impact favorably upon survival

Circulating biomarkers and cardiac function over 3 years after chemotherapy with anthracyclines: the ICOS-ONE trial

Aims: A multicentre trial, ICOS-ONE, showed increases above the upper limit of normality of cardiac troponin (cTn) in 27% of patients within 12&nbsp;months after the end of cancer chemotherapy (CT) with anthracyclines, whether cardiac protection with enalapril was started at study entry in all (prevention arm) or only upon first occurrence on supra-normal cTn (troponin-triggered arm). The aims of the present post hoc analysis were (i) to assess whether anthracycline-based treatment could induce cardiotoxicity over 36&nbsp;month follow-up and (ii) to describe the time course of three cardiovascular biomarkers (i.e. troponin I cTnI-Ultra, B-type natriuretic peptide BNP, and pentraxin 3 PTX3) and of left ventricular (LV) function up to 36&nbsp;months. Methods and results: Eligible patients were those prescribed first-in-life CT, without evidence of cardiovascular disease, normal cTn, LV ejection fraction (EF) &gt;50%, not on renin-angiotensin aldosterone system antagonists. Patients underwent echocardiography and blood sampling at 24 and 36&nbsp;months. No differences were observed in biomarker concentration between the two study arms, ‘prevention' vs. ‘troponin-triggered'. During additional follow-up 13 more deaths occurred, leading to a total of 23 (9.5%), all due to a non-cardiovascular cause. No new occurrences of LV-dysfunction were reported. Two additional patients were admitted to the hospital for cardiovascular causes, both for acute pulmonary embolism. No first onset of raised cTnI-Ultra was reported in the extended follow-up. BNP remained within normal range: at 36&nbsp;months was 23.4&nbsp;ng/L, higher (N.S.) than at baseline, 17.6&nbsp;ng/L. PTX3 peaked at 5.2&nbsp;ng/mL 1&nbsp;month after CT and returned to baseline values thereafter. cTnI-Ultra peaked at 26&nbsp;ng/L 1&nbsp;month after CT and returned to 3&nbsp;ng/L until the last measurement at 36&nbsp;months. All echocardiographic variables remained stable during follow-up with a median LVEF of 63% and left atrial volume index about 24&nbsp;mL/m2. Conclusions: First-in-life CT with median cumulative dose of anthracyclines of 180&nbsp;mg/m2 does not seem to cause clinically significant cardiac injury, as assessed by circulating biomarkers and echocardiography, in patients aged 51&nbsp;years (median), without pre-existing cardiac disease. This may suggest either a 100% efficacy of enalapril (given as preventive or troponin-triggered) or a reassuringly low absolute cardiovascular risk in this cohort of patients, which may not require intensive cardiologic follow-up

A targeted proteomics approach to amyloidosis typing

Background: Amyloidosis is a life threatening disease caused by deposition of various types of blood serum proteins in organs and tissues. Knowing the type of protein involved is the basis of a correct diagnosis and personalized medical treatment. While the classical approach uses immunohistochemistry, in recent years, laser micro-dissection, followed by high resolution LC-MS/MS, has been shown to provide superior diagnostic sensitivity and specificity. This techniques, however, is only available at major reference proteomics centers. // Objective: To perform clinical amyloid protein typing using low-resolution mass spectrometry and no laser micro dissection (LMD), we developed a targeted proteomics approach for the determination of both frequently encountered amyloid proteins (i.e., κ and -λ immunoglobulin light chains and transthyretin (TTR)) and specific reference proteins (i.e., actin (A) for cardiac muscle tissue, or fatty acid binding protein 4 (FBP4) for subcutaneous adipose tissue) in histologic specimens. // Method: Small tissue fragments and/or histological sections were digested to yield a protein mixture that was subsequently reduced, alkylated and trypsinized to obtain a peptide mixture. After SPE purification and LC separation, proteotypic peptides were detected by their MRM transitions. // Results: The method showed high specificity and sensitivity for amyloid protein proteotypic peptides. LODs were 1.0, 0.1, 0.2 picomoles in cardiac muscle tissue (CMT) and 0.1, 0.2, 0.5 picomoles in subcutaneous adipose tissue (SAT) for TTR, κ-, and λ-LC proteins, respectively. Amyloid to tissue-specific protein signal ratios correlated with the presence of amyloid deposits in clinical samples. // Conclusions: This targeted proteomics approach enables sensitive and specific discrimination of amyloidosis affected tissues for the purpose of clinical research

Why do paediatricians prescribe antibiotics? Results of an Italian regional project

<p>Abstract</p> <p>Background</p> <p>To investigate determinants of antibiotic prescription in paediatric care, as a first step of a multilevel intervention to improve prescribing for common respiratory tract infections (RTIs) in a northern Italian region with high antibiotic prescription rate.</p> <p>Methods</p> <p>A two-step survey was performed: in phase I, knowledge, and attitudes were explored involving all family and hospital paediatricians of Emilia-Romagna and a sample of parents. In phase II, patient care practices were explored in a stratified random sample of visits, both in hospitals and family physician's clinics; parent expectations were investigated in a sub-sample of these visits.</p> <p>Results</p> <p>Out of overall 4352 visits for suspected RTIs, in 38% of children an antibiotic was prescribed. Diagnostic uncertainty was perceived by paediatricians as the most frequent cause of inappropriate prescription (56% of 633 interviewed paediatricians); but, rapid antigen detecting tests was used in case of pharyngitis/pharyngotonsillitis by 36% and 21% of family and hospital paediatricians only. More than 50% of paediatricians affirmed to not adopt a "wait and see strategy" in acute otitis. The perceived parental expectation of antibiotics was not indicated by paediatricians as a crucial determinant of prescription, but this perception was the second factor most strongly associated to prescription (OR = 12.8; 95% CI 10.4 - 15.8), the first being the presence of othorrea. Regarding parents, the most important identified factors, potentially associated to overprescribing, were the lack of knowledge of RTIs and antibiotics (41% of 1029 parents indicated bacteria as a possible cause of common cold), and the propensity to seek medical care for trivial infections (48% of 4352 children accessing ambulatory practice presented only symptoms of common cold).</p> <p>Conclusion</p> <p>A wide gap between perceived and real determinants of antibiotic prescription exists. This can promote antibiotic overuse. Inadequate parental knowledge can also induce inappropriate prescription. The value of this study is that it simultaneously explored determinants of antimicrobial prescribing in an entire region involving both professionals and parents.</p