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Background: Due to their complexity and to the presence of common clinical features, differentiation between asthma and chronic obstructive pulmonary disease (COPD) can be a challenging task, complicated in such cases also by asthma-COPD overlap syndrome. The distinct immune/inflammatory and structural substrates of COPD and asthma are responsible for significant differences in the responses to standard pharmacologic treatments. Therefore, an accurate diagnosis is of central relevance to assure the appropriate therapeutic intervention in order to achieve safe and effective patient care. Induced sputum (IS) accurately mirrors inflammation in the airways, providing a more direct picture of lung cell metabolism in comparison to those specimen that reflect analytes in the systemic circulation., Methods: An integrated untargeted metabolomics and lipidomics analysis was performed in IS of asthmatic (n = 15) and COPD (n = 22) patients based on Ultra-High-Pressure Liquid Chromatography-Mass Spectrometry (UHPLC-MS) and UHPLC-tandem MS (UHPLC-MS/MS). Partial Least Squares-Discriminant Analysis (PLS-DA) was applied to resulting dataset. The analysis of main enriched metabolic pathways and the association of the preliminary metabolites/lipids pattern identified to clinical parameters of asthma/COPD differentiation were explored. Multivariate ROC analysis was performed in order to determine the discriminatory power and the reliability of the putative biomarkers for diagnosis between COPD and asthma., Results: PLS-DA indicated a clear separation between COPD and asthmatic patients. Among the 15 selected candidate biomarkers based on Variable Importance in Projection scores, putrescine showed the highest score. A differential IS bio-signature of 22 metabolites and lipids was found, which showed statistically significant variations between asthma and COPD. Of these 22 compounds, 18 were decreased and 4 increased in COPD compared to asthmatic patients. The IS levels of Phosphatidylethanolamine (PE) (34:1), Phosphatidylglycerol (PG) (18:1;18:2) and spermine were significantly higher in asthmatic subjects compared to COPD., Conclusions: This is the first pilot study to analyse the IS metabolomics/lipidomics signatures relevant in discriminating asthma vs COPD. The role of polyamines, of 6-Hydroxykynurenic acid and of D-rhamnose as well as of other important players related to the alteration of glycerophospholipid, aminoacid/biotin and energy metabolism provided the construction of a diagnostic model that, if validated on a larger prospective cohort, might be used to rapidly and accurately discriminate asthma from COPD., (© 2024. The Author(s).)

Male infertility occurs approximately in about 50% of all infertility cases and represents a serious concern worldwide. Traditional semen analysis alone is insufficient to diagnose male infertility. Over the past two decades, advances in omics technologies have led to the widespread application of metabolomics profiling as a valuable diagnostic tool for various diseases and disorders. Seminal plasma represents a rich and easily accessible source of metabolites surrounding spermatozoa, a milieu that provides several indispensable nutrients to sustain sperm motility and fertilization. Changes of metabolic profiles in seminal plasma reflect male reproductive tract disorders. Here, we performed seminal plasma metabolomics and lipidomics profiling to identify a new pattern of biomarkers of male infertility. Seminal plasma samples from unfertile subjects ( n = 31) and fertile controls ( n = 19) were analyzed using an untargeted metabolomics/lipidomics integrated approach, based on Ultra-High-Pressure Liquid Chromatography-tandem Mass Spectrometry. Partial Least Squares-Discriminant Analysis showed a distinct separation between healthy fertile men and infertile subjects. Among the 15 selected candidate biomarkers based on Variable Importance in Projection scores, phosphatidylethanolamine (PE) (18:1; 18:1) resulted with the highest score. In total, 40 molecular species showed statistically significant variations between fertile and infertile men. Heat-map and volcano plot analysis indicated that acylcarnitines, phosphatidylserine (PS) (40:2) and lactate were decreased, while PE (18:1; 18:1), Phosphatidic acid (PA) (O-19:2; 18:1), Lysophosphatidylethanolamine (LPE) (O-16:1) and Phosphatidylcholine (PC) (O-16:2; 18:1)-CH3 were increased in the infertile group. The present study is the first one to analyze the metabolomics/lipidomics dysregulation in seminal plasma between fertile and infertile individuals regardless of sub-infertility condition. Association of several metabolites/lipids dysregulation with male infertility reinforced data of previous studies performed with different approaches. In particular, we confirmed significantly decreased levels of PS and carnitines in infertile patients as well as the positive correlation with sperm motility and morphology. If validated on a larger prospective cohort, the metabolite biomarkers of infertility in seminal plasma we identified in the present study might inform novel strategies for diagnosis and interventions to overcome male infertility., Competing Interests: Author AF was employed by Urogyn Biotech S. R. L. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Correnti, Preianò, Fregola, Gamboni, Stephenson, Savino, D’Alessandro and Terracciano.)

Male infertility has been recognized as a global health problem. Semen analysis, although considered the golden standard, may not provide a confident male infertility diagnosis alone. Hence, there is the urgent request for an innovative and reliable platform to detect biomarkers of infertility. The rapid expansion of mass spectrometry (MS) technology in the field of the 'omics' disciplines, has incredibly proved the great potential of MS-based diagnostic tests to revolutionize the future of pathology, microbiology and laboratory medicine. Despite the increasing success in the microbiology area, MS-biomarkers of male infertility currently remain a proteomic challenge. In order to address this issue, this review encompasses proteomics investigations by untargeted approaches with a special focus on experimental designs and strategies (bottom-up and top-down) for seminal fluid proteome profiling. The studies reported here witness the efforts of the scientific community to address these investigations aimed at the discovery of MS-biomarkers of male infertility. Proteomics untargeted approaches, depending on the study design, might provide a great plethora of biomarkers not only for a male infertility diagnosis, but also to address a new MS-biomarkers classification of infertility subtypes. From the early detection to the evaluation of infertility grade, new MS-derived biomarkers might also predict long-term outcomes and clinical management of infertility.

Seminal plasma (SP) mirrors the local pathophysiology of the male reproductive system and represents a non-invasive fluid for the study of infertility. Matrix-Assisted Laser Desorption/Ionization-Time-of-Flight Mass Spectrometry (MALDI-TOF-MS) provides a high-throughput platform to rapidly extrapolate the diagnostic profiles of information-rich patterns. In this study, dispersive solid phase extraction ( d -SPE) combined with MALDI-TOF-MS was applied for the first time to the human SP, with the aim of revealing a diagnostic signature for male infertility. Commercially available octadecyl (C 18 )-, octyl (C 8 )-bonded silica sorbents and hexagonal mesoporous silica (HMS) were tested and the robustness of MALDI-TOF peptide profiling was evaluated. Best performances were obtained for C 18 -bonded silica with the highest detection of peaks and the lowest variation of spectral features. To assess the diagnostic potential of the method, C 18 -bonded silica d -SPE and MALDI-TOF-MS were used to generate enriched endogenous peptide profiles of SP from 15 fertile and 15 non-fertile donors. Principal component analysis (PCA) successfully separated fertile from non-fertile men into two different clusters. An array of seven semenogelin-derived peptides was found to distinguish the two groups, with high statistical significance. These findings, while providing a rapid and convenient route to selectively enrich native components of SP peptidome, strongly reinforce the prominent role of semenogelins in male infertility.

The balance between cell survival and cell death represents an essential part of human tissue homeostasis, while altered apoptosis contributes to several pathologies and can affect the treatment efficacy. Impaired apoptosis is one of the main cancer hallmarks and some types of lymphomas harbor mutations that directly affect key regulators of cell death (such as BCL-2 family members). The development of novel techniques in the field of immunology and new animal models has greatly accelerated our understanding of oncogenic mechanisms in MYC-associated lymphomas. Mouse models are a powerful tool to reveal multiple genes implicated in the genesis of lymphoma and are extensively used to clarify the molecular mechanism of lymphoma, validating the gene function. Key features of MYC-induced apoptosis will be discussed here along with more recent studies on MYC direct and indirect interactors, including their cooperative action in lymphomagenesis. We review our current knowledge about the role of MYC-induced apoptosis in B-cell malignancies, discussing the transcriptional regulation network of MYC and regulatory feedback action of miRs during MYC-driven lymphomagenesis. More importantly, the finding of new modulators of apoptosis now enabling researchers to translate the discoveries that have been made in the laboratory into clinical practice to positively impact human health.

Introduction: In healthy subjects, Cytomegalovirus infection can be asymptomatic or manifest as mononucleosis syndrome, but organ disease has also been reported. However, in immunocompromised patients this infection can lead to its most significant and severe disease and even mortality. When Cytomegalovirus causes a gastrointestinal tract infection, it more commonly manifests with luminal tract disease and is usually characterized by ulcerative lesions. Appendicitis is a rare manifestation, and has been reported mainly in human immunodeficiency virus-infected patients or patients with other causes of immunocompromise., Case Presentation: The authors report on a case of acute primary Cytomegalovirus infection complicated with acute appendicitis due to Cytomegalovirus in an apparently immunocompetent 24-year-old Caucasian man also suffering from primary sclerosing cholangitis and ulcerative colitis. Diagnosis was based on clinical manifestations, serology results, as well as microbiological and histological findings. Treatment consisted of surgery and anti-Cytomegalovirus therapy., Conclusions: Cytomegalovirus should be included among the etiologic agents of acute appendicitis in patients with primary sclerosing cholangitis and ulcerative colitis. Currently, there are no definitive data regarding the frequency of Cytomegalovirus appendicitis and the role of anti-Cytomegalovirus treatment in human immunodeficiency virus-negative and apparently immunocompetent subjects.

Isolated aneurysms of the internal iliac artery are rare and often asymptomatic. They are frequently diagnosed as a result of complications such as rupture. The authors describe in detail two cases of ruptured aneurysms of the internal iliac artery treated by emergency surgery with no perioperative mortality or morbidity.

The authors report their experience with a patient suffering from an intralobar bronchopulmonary sequestration (IBS). The lesion was misdiagnosed as metapneumonic lung abscess. IBS is a rare, diagnostically binding lung congenital malformation. So far, TC and MR angiography achieve pathognomonic findings with low invasivity. The best treatment of IBS could be surgical resection.

Background: Benign biliary strictures are a binding situation for clinicians when choosing the best treatment. This is a benign disease and needs safe, effective and lasting therapy. Up to day non surgical treatment have been suggested as the first therapeutical option but surgery seems to support the best late results., Methods: The authors report their experience in 206 patients, 64 males and 142 females, aged from 27 to 77 years, affected by postoperative (160 patients) or inflammatory (46 patients) biliary strictures. All the patients but three had been treated by surgical procedures., Results: Postoperative morbidity and mortality were 18.4% and 3.4% respectively. Follow-up ranged from 2 to 16 years. Late stricture of bilio-enteric anastomosis has been observed in 8.2% of patients and peptic ulcer or cholangitis in 4.9% of cases. Restenosis appeared after a mean time of 2.5 years (range 20 months-6 years), supporting the need for a long term follow-up. Effective late results have been reported in 91.5% of patients. No late complications of ineffective results have been observed after transduodenal sphincterotomy., Conclusions: The authors propose some guidelines for choice charce of treatment, analysing the limits of non surgical therapy and underlying the best surgical tactics. Bilio-enteric anastomosis is a safe, effective and lasting therapy for biliary strictures; Hepp-Couinaud hepatico-jejunostomy is the best choice for high-medium stricture; transduodenal sphincterotomy preserves its important role in low biliary stenosis.

Background: Early prognostic evaluation of patients affected by acute peritonitis is really desirable to program a correct therapeutic plan, selecting high-risk patients for more aggressive therapeutic procedures. The Mannheim peritonitis index is reliable and easy to apply, so its use is possible without the need of intensive care units., Methods: Between 1991 and 1995 a total of 235 patients were operated on for acute peritonitis. A retrospective study on this group of patients was performed in order to estimate prognostic reliability of Mannheim peritonitis index., Results: The overall mortality was 8.1%; for patients with a score less than 26 the mean mortality rate was 2% and for score greater than 26, 40.5%. This score is the threshold over which the therapeutic approach have to be more aggressive; planned multiple laparotomies or the open abdomen technique could be the best options to explore and clean up the peritoneal cavity from septic debris. In personal experience, all patients who died had residual sepsis in peritoneal cavity.

Background/aims: Islet cell adenomas of the pancreas are both single and benign tumors in more than 90% of the cases. Even with the use of increasingly innovative diagnostic techniques, a percentage of tumors are not located in the preoperative or, sometimes, even intraoperative phase. This study compares the results of various diagnostic techniques and provides a brief review of the literature., Materials and Methods: Between January 1978 and December 1994, 15 patients (11 females and 4 males) averaging 49 years of age (range 27-70) affected by pancreatic insulinoma underwent surgery at the Department of General Surgery of the "R. Silvestrini" Hospital., Results: In 8 cases the tumor intrapancreatic position was indicated in the preoperative stage. On the contrary, intraoperative ultrasonography allowed the correct location in all the cases, but one. Surgery allows for the complete cure from the diseases when the removal of adenoma is complete. All of our patients underwent surgery which involved enucleation or resection of the distal portion of the pancreas., Conclusion: The choice of the type of operation to perform, as well as the consequential morbidity and mortality, seems to depend essentially on the size and position of the insulinoma. All of the patients, except for one who died because of a pancreatic fistula, are alive and normoglycaemic.

Two cases of oesophageal pouches previously operated on the neck and treated surgically employing intraoperative oesophagoscopy are reported. The usefulness of this method is discussed.

The pathogenetic and diagnostic features of false aneurysm of the left branch of the hepatic artery are discussed in the light of a personal case. It is felt that ligation of the vessel constitutes the treatment of choice, whereas hepatic resection should be undertaken in the case of very peripheral aneurysms.

Personal experience with two cases of symptomatic occlusion of the subclavian artery treated with axillo-axillary by-pass is reported. The operating technique, in which the second portion of the axillary artery and a dacron blood conductor are employed, is described and the various transthoracic and extrathoracic operations that have been proposed are reviewed along with the advantages and disadvantages of each. It is concluded that axillo-axillary by-pass is a simple solution for a complex haemodynamic, clinical and therapeutic problem.