Upper endoscopy in elderly patients: a multicentre, cross-sectional study.

BACKGROUND: Both macroscopic and histological lesions are frequently detected at upper endoscopy in elderly patients. We assessed the prevalence of main endoscopic and histological alterations in elderly (> 65 years old) patients. METHODS: In this study, clinical, endoscopic and histological features of patients referred for upper endoscopy in clinical practice were retrieved. Both univariate and multivariate analyses were executed. Comparisons with previous data were performed. RESULTS: A total of 1336 underwent upper endoscopy in the 28 participating centres. At endoscopy, at least one macroscopic lesion was present in overall 420 (31.4%) patients. Erosive gastritis (13.3%) and erosive oesophagitis (9.8%) were the most prevalent lesions, whilst Barrett's oesophagus, gastric ulcer, duodenal ulcer and erosive duodenitis were observed in 1.8%, 2%, 1.4% and 3.1% patients, respectively. Nine (0.6%) cases of oesophageal, 25 (1.8%) gastric and 2 (0.1%) duodenal neoplasia were detected. At histology, Helicobacter pylori infection was diagnosed in 99 (15.9%) patients, and extensive precancerous lesions on gastric mucosa were detected in 80 (14.5%) patients. Endoscopic lesions were more frequent in males, at first endoscopy and in those with alarm symptoms and lower during PPI therapy. At multivariate analysis, PPI therapy significantly reduced the probability of finding endoscopic lesions (OR: 0.68, 95% CI: 0.46-0.99; P = 0.04), whilst neoplastic lesions were associated with presence of alarm symptoms (OR: 1.5, 95% CI: 1.1-2.1; P = 0.005). CONCLUSIONS: We found that the frequency of erosive and neoplastic lesions remained high in elderly patients, whilst the prevalence of both H. pylori infection and peptic ulcer was decreased.

FSH Therapy in Male Factor Infertility: Evidence and Factors Which Might Predict the Response.

Follicle-stimulating hormone (FSH) administration is applied in the management of subjects affected by hypogonadotropic hypogonadism. Whilst this application is widely recognized and established alone or in combination with human chorionic gonadotropin (hCG), a similar strategy is empirically advocated in idiopathic male factor infertility (MFI). In this setting, FSH therapy has been used to increase sperm quantity, quality, and pregnancy rate when FSH plasma concentrations are below 8 IU/L and when the seminal tract is not obstructed. In the literature, several studies suggested that giving FSH to patients with idiopathic MFI increases sperm count and motility, raising the overall pregnancy rate. However, this efficacy seems to be limited, and about 10-18 men should be treated to achieve one pregnancy. Thus, several papers suggest the need to move from a replacement approach to an overstimulating approach in the management of FSH therapy in idiopathic MFI. To this aim, it is imperative to determine some pharmacologic markers of FSH efficacy. Furthermore, it should be useful in clinical practice to distinguish, before starting the treatment, among patients who might respond or not to FSH treatment. Indeed, previous studies suggest that infertile men who have normal levels of gonadotropins in plasma might not respond to FSH treatment and about 50% of patients might be defined as "non-responders". For these reasons, identifying predictive markers of FSH action in spermatogenesis and clinical markers of response to FSH treatment is a fascinating area of study that might lead to new developments with the aim of achieving personalization of the treatment of male infertility. From this perspective, seminal parameters (i.e., spermatid count), testicular cytology, genetic assessment, and miRNA or protein markers in the future might be used to create a tailored FSH therapy plan. The personalization of FSH treatment is mandatory to minimize side effects, to avoid lost time with ineffective treatments, and to improve the efficacy, predicting the most efficient dose and the duration of the treatment. This narrative review's objective is to discuss the role of the different putative factors which have been proposed to predict the response to FSH treatment in idiopathic infertile men.

Endoscopic removal of gastrointestinal lesions by using third space endoscopy techniques.

The concept of submucosal space, or rather the "third space", located between the intact mucosal flap and the muscularis propria layer of the gastrointestinal tract, represents a tunnel that the endoscopist could use to perform interventions in the muscularis propria layer or breech it to enter the mediastinum or the peritoneal cavity without full thickness perforation. The tunnel technique can be used both for the removal of mucosal tumours, called endoscopic submucosal tunnel dissection (ESTD), for the removal of subepithelial tumours (SELs), called submucosal tunnelling endoscopic resection (STER), and for the removal of extra-luminal lesions (for example in the mediastinum or in the rectum), called submucosal tunnelling endoscopic resection for extraluminal tumours (STER-ET). Aim of this updated narrative review, is to summarize the evidences that analyses indications, and outcomes of tunnelling techniques for the treatment of above mentioned lesions.

Male Tract Microbiota and Male Infertility.

In recent years, several studies have analyzed the composition of the male genital tract microbiota and its changes in infertility or in different situations associated with infertility. The aim of this narrative review is to obtain more insight on this topic; in particular, to describe actual evidence about changes in the semen microbiota in patients with infertility, male tract infections, or HPV infections. In semen, an increase in semen Prevotella spp. is associated with oligozoospermia and with obesity-associated asthenozoospermia; an increase in Pseudomonas is more frequently associated with asthenozoospermia and oligozoospermia; a reduction in Lactobacilli spp. (namely in Lactobacillus crispatus) may represent a marker of low semen quality. However, an increase in Lactobacillus iners is considered a risk factor for a reduced sperm concentration. In patients with prostatitis, there is a reduction in Lactobacillus spp. and an increase in Streptococcus spp., opening important perspectives about the role of probiotic treatments in these patients. Finally, an increase in Fusobacteria spp. was observed in patients with an HPV infection. In the conclusion, we underline the interactions between the seminal and vaginal microbiota, so that further studies should focus on the "couple genital microbiota".

Diabetes and male fertility disorders.

Couple infertility is a common condition, defined as being unable to conceive after 12 months of regular unprotected sexual intercourse. Male Factor Infertility (MFI) is responsible, alone or in combination with female factors, for about half of the overall cases of couple infertility. MFI is gradually increasing in prevalence, with a notable decline in semen parameters over the last decades. The aetiologies behind the finding of decreasing sperm counts are difficult to pinpoint but might be due in part to increasing rates of overweight and obesity in men of childbearing age. Diabetes mellitus (DM) is a common and chronic metabolic disease, whose prevalence is also gradually increasing, rising up to 10% of the population. The International Diabetes Federation estimates that there are currently more than 500 million people living with DM worldwide, the vast majority of whom suffering from type 2 DM (T2DM). There is growing awareness of the relationship between unhealthy lifestyle, in particular unhealthy diet, and MFI. Starting from all these premises, the aim of this narrative review is to describe the current evidence on the link between DM and MFI, both in terms of DM as a cause of/a risk factor for MFI and of MFI as a possible predictive marker for T2DM. Finally, we will discuss the risk of DM as a consequence of the therapy of MFI or assisted reproductive techniques.

Technical failure during colorectal endoscopic full-thickness resection: the "through thick and thin" study.

BACKGROUND: Endoscopic full-thickness resection (EFTR) is an effective and safe technique for nonlifting colorectal lesions. Technical issues or failures with the full-thickness resection device (FTRD) system are reported, but there are no detailed data. The aim of our study was to quantify and classify FTRD technical failures. METHODS: We performed a retrospective study involving 17 Italian centers with experience in advanced resection techniques and the required devices. Each center shared and classified all prospectively collected consecutive failures during colorectal EFTR using the FTRD from 2018 to 2022. The primary outcome was the technical failure rate and their classification; secondary outcomes included subsequent management, clinical success, and complications. RESULTS: Included lesions were mainly recurrent (52 %), with a mean (SD) dimension of 18.4 (7.5) mm. Among 750 EFTRs, failures occurred in 77 patients (35 women; mean [SD] age 69.4 [8.9] years). A classification was proposed: type I, snare noncutting (53 %); type II, clip misdeployment (31 %); and type III, cap misplacement (16 %). Among endoscopic treatments completed, rescue endoscopic mucosal resection was performed in 57 patients (74 %), allowing en bloc and R0 resection in 71 % and 64 %, respectively. The overall adverse event rate was 27.3 %. Pooled estimates for the rates of failure, complications, and rescue endoscopic therapy were similar for low and high volume centers (P = 0.08, P = 0.70, and P = 0.71, respectively). CONCLUSIONS: Colorectal EFTR with the FTRD is a challenging technique with a non-negligible rate of technical failure and complications. Experience in rescue resection techniques and multidisciplinary management are mandatory in this setting.

Genetic Causes of Qualitative Sperm Defects: A Narrative Review of Clinical Evidence.

Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in male factor infertility (MFI). However, there are still few genetic analyses that are currently recommended for use in clinical practice. In this manuscript, we reviewed the genetic causes of qualitative sperm defects. We distinguished between alterations causing reduced sperm motility (asthenozoospermia) and alterations causing changes in the typical morphology of sperm (teratozoospermia). In detail, the genetic causes of reduced sperm motility may be found in the alteration of genes associated with sperm mitochondrial DNA, mitochondrial proteins, ion transport and channels, and flagellar proteins. On the other hand, the genetic causes of changes in typical sperm morphology are related to conditions with a strong genetic basis, such as macrozoospermia, globozoospermia, and acephalic spermatozoa syndrome. We tried to distinguish alterations approved for routine clinical application from those still unsupported by adequate clinical studies. The most important aspect of the study was related to the correct identification of subjects to be tested and the correct application of genetic tests based on clear clinical data. The correct application of available genetic tests in a scenario where reduced sperm motility and changes in sperm morphology have been observed enables the delivery of a defined diagnosis and plays an important role in clinical decision-making. Finally, clarifying the genetic causes of MFI might, in future, contribute to reducing the proportion of so-called idiopathic MFI, which might indeed be defined as a subtype of MFI whose cause has not yet been revealed.

Artificial intelligence in detection of small bowel lesions and their bleeding risk: A new step forward.

The present letter to the editor is related to the study with the title "Automatic detection of small bowel (SB) lesions with different bleeding risk based on deep learning models". Capsule endoscopy (CE) is the main tool to assess SB diseases but it is a time-consuming procedure with a significant error rate. The development of artificial intelligence (AI) in CE could simplify physicians' tasks. The novel deep learning model by Zhang et al seems to be able to identify various SB lesions and their bleeding risk, and it could pave the way to next perspective studies to better enhance the diagnostic support of AI in the detection of different types of SB lesions in clinical practice.

Proteomics for the identification of peripheral markers in pituitary disease.

Although precision medicine moved its first steps from genomic medicine, it has gone far beyond genomics, considering the full complexity of cellular physiology. Therefore, the present time might be considered as the "post-genomic era." In detail, proteomics captures the overall protein profile of an analyzed sample. The goals of proteomic analysis are to perform a global analysis of protein expression and function, to systematically define the role proteins in physiological and pathological condition, to increase mechanistic understanding of the biological processes and to discover new biomarkers and therapeutic targets. In this narrative mini-review, the role of proteomics is discussed with a particular focus on the few attempts of the application of proteomic platforms for the identification of new biomarkers in pituitary diseases, namely in acromegaly, GH deficiency and male secondary hypogonadism.

A New Step-Up Dual Endoscopic Approach for Large-Size Infected Pancreatic Necrosis: Percutaneous Endoscopic Necrosectomy Followed by Transluminal Endoscopic Drainage/Necrosectomy.

BACKGROUND: Acute pancreatitis in 10% to 20% of cases can be associated with necrosis of the pancreatic gland, peripancreatic tissue, or both. We report a case series of a new endoscopic approach to treat infected pancreatic necrosis (IPN). PATIENTS AND METHODS: Consecutive patients with IPN, extending from the perigastric area up to the paracolic gutters or into the pelvis, were prospectively studied from January 2017 to June 2022. The treatment protocol was radiologic percutaneous drainage as the first step, followed by fully covered metal stent placement (FC-SEMS) in the track of the catheter. Percutaneous endoscopic necrosectomy (PEN) was performed 2 to 4 days later using a flexible endoscope through the percutaneous tract. About 2 to 4 weeks later, when a matured sac was visible, EUS-guided endoscopic transluminal drainage (ETD) with lumen-apposing metal stents (LAMS) was performed. Control of sepsis with resolution of collection(s) was the primary outcome measure. RESULTS: We included 18 patients, males in 50% of cases with age 60±12 years old. Most frequent cause of pancreatitis was biliary (7 cases) followed by alcoholic in 6 cases; in 3 cases pancreatitis was caused by hyperlipemia and in 2 cases was idiopathic. Mean size of WON was 18±2 cm. For PEN, SEMSs used were esophageal FC-SEMS. LAMS used for ETD were Hot Axios, Hot Spaxus and Nagistent. Mean time of endoscopic intervention for PEN and ETD was 18±3 and 37±4 days, respectively. In 5 cases adverse events occurred: 3 cases of overinflations resolved with introduction of Verres needles in abdomen. In 2 cases postprocedural GI bleeding required endoscopic intervention. In all cases control of sepsis was reached together with resolution of collections. No cases of deaths were observed. CONCLUSIONS: Step-up percutaneous and transluminal endoscopic necrosectomy therapy is an effective strategy for large-size IPN with combined central and peripheral necrosis.

A cryptozoospermic infertile male with Y chromosome AZFc microdeletion and low FSH levels due to a simultaneous polymorphism in the FSHB gene: a case report.

Genetic causes account for 10-15% of male factor infertility, making the genetic investigation an essential and useful tool, mainly in azoospermic and severely oligozoospermic men. In these patients, the most frequent findings are chromosomal abnormalities and Y chromosome long arm microdeletions, which cause a primary severe spermatogenic impairment with classically increased levels of FSH. On the other hand, polymorphisms in the FSH receptor (FSHR) and FSH beta chain (FSHB) genes have been associated with different FSH plasma levels, due to variations in the receptor sensitivity (FSHR) or in the production of FSH from the pituitary gland (FSHB). Here, we describe an unusual patient with a combined genetic alteration (classic AZFc deletion of the Y chromosome and TT homozygosity for the -211G>T polymorphism in the FSHB gene (rs10835638)), presenting with cryptozoospermia, severe hypospermatogenesis, and normal LH and testosterone plasma concentrations, but low FSH levels. The patient partially benefitted from treatment with FSH (150 IU three times/week for 6 months) which allowed him to cryopreserve enough motile spermatozoa to be used for intracytoplasmic sperm injection. According to our knowledge, this is the first report of an infertile man with AZFc microdeletion with low FSH plasma concentrations related to homozygosity for the -211G>T polymorphism in the FSHB gene.

Observational Cross-Sectional Study on Mediterranean Diet and Sperm Parameters.

Infertility, affecting 15 to 25% of couples in the most developed countries, is recognized by the World Health Organization as a public health issue at a global level. Different causes are acknowledged to reduce fertility in both sexes. In particular, about 40-50% of cases recognize a male factor. Dietary habits and lifestyle are acknowledged to influence sperm quality and are therefore important modifiable factors in male reproductive health. Conditions such as overweight/obesity, impaired glucose metabolism and determinants of metabolic syndrome, together with unhealthy lifestyle behavior, i.e., smoking cigarettes and physical inactivity, are suggested to have a negative impact on male fertility. While individual elements and characteristics of the Western diet and habits are considered risk factors for male infertility, the Mediterranean diet (MD) seems to promote reproductive potential for improving sperm quality. It is also interesting to note that previous observational studies reported a positive correlation between the consumption of the single food classes of the MD pattern (i.e., vegetables and fruits, poultry, fish and seafood, whole grains, low-fat dairy products) and the quality of several sperm parameters. To evaluate the relationship between sperm parameters and MD adherence, we performed a cross-sectional study on the seminal data of 300 males (mean age 34.6 ± 9.1 years) who spontaneously referred to our center of reproductive medicine. The evaluation of adherence to MD was performed with a validated 14-point Mediterranean Diet Adherence Screener (MEDAS) questionnaire. Our findings showed that sperm parameters such as sperm count, motility, viability and normal morphology are significantly and positively correlated with MEDAS, independently of BMI and age. In addition, the application of an ROC curve on MEDAS value vs. seminal alterations identified 6.25 as the score threshold value below which altered sperm parameters were more likely to occur [AUC = 0.096 (CI: 0.059-0.133; p < 0.00)]. Therefore, adhering to the MD with at least a MEDAS score of 6.26 increases the probability of normozoospermia. Moreover, subjects who had a MEDAS value lower than 6.25 had an Odds Ratio of 6.28 (CI = 3.967-9.945) for having at least one altered sperm parameter compared to those who were more adherent to the MD. In conclusion, our findings show that a higher adherence to the MD is associated with better semen parameters, in particular in relation to sperm count, sperm concentration, typical sperm morphology, and sperm progressive motility.

Upper Gastrointestinal Endoscopy Quality in Italy: A Nationwide Study.

BACKGROUND AND AIMS: International guidelines advise improving esophagogastroduodenoscopy (EGD) quality in Western countries, where gastric cancer is still diagnosed in advanced stages. This nationwide study investigated some indicators for the quality of EGD performed in endoscopic centers in Italy. METHODS: Clinical, endoscopic, and procedural data of consecutive EGDs performed in one month in the participating centers were reviewed and collected in a specific database. Some quality indicators before and during endoscopic procedures were evaluated. RESULTS: A total of 3,219 EGDs performed by 172 endoscopists in 28 centers were reviewed. Data found that some relevant information (family history for GI cancer, smoking habit, use of proton pump inhibitors) were not collected before endoscopy in 58.5-80.7% of patients. Pre-endoscopic preparation for gastric cleaning was routinely performed in only 2 (7.1%) centers. Regarding the procedure, sedation was not performed in 17.6% of patients, and virtual chromoendoscopy was frequently (>75%) used in only one (3.6%) center. An adequate sampling of the gastric mucosa (i.e., antral and gastric body specimens) was heterogeneously performed, and it was routinely performed only by 23% of endoscopists, and in 14.3% centers. CONCLUSIONS: Our analysis showed that the quality of EGD performed in clinical practice in Italy deserves to be urgently improved in different aspects.

Recurrent pregnancy loss: a male crucial factor-A systematic review and meta-analysis.

BACKGROUND: Recurrent pregnancy loss (RPL), defined as two or more failed clinical pregnancies, affects 1%-3% of couples trying to conceive. Nowadays up to 50% of cases remain idiopathic. In this context, paternal factors evaluation is still very limited. The aim is to address the topic of the male factor in RPL with a broad approach, analyzing collectively data on sperm DNA fragmentation (SDF) and semen parameters. We systematically searched in Pubmed/MEDLINE and Google Scholar from inception to February 2023. A protocol has been registered on PROSPERO (ID number CRD42022278616). PRISMA guidelines were followed. METHODS: Pooled results from 20 studies revealed a higher DNA fragmentation rate in the RPL group compared to controls (mean difference [MD] 9.21, 95% CI 5.58-12.85, p < 0.00001, I2 98%). Age, body mass index (BMI), smoking, and alcohol intake were not associated with DNA fragmentation. Subgroup analysis by different SDF assays (TUNEL and COMET at a neutral pH vs. indirect assessment with other assays) and ethnicity did not highlight different results (p = 0.25 and 0.44). RESULTS: Results pooled from 25 studies showed a significant difference comparing RPL and control groups regarding ejaculation volume (MD -0.24, 95% CI -0.43; -0.06, p 0.01, I2 66%), total sperm number (MD -10.03, 95% CI -14.65; -5.41, p < 0.0001, I2 76%), total sperm motility (MD -11.20, 95% CI -16.15; -6.25, p < 0.0001, I2 96%), progressive sperm motility (MD -7.34, 95% CI -10.87; -3.80, p < 0.0001, I2 97%), and normal sperm morphology (MD -5.99, 95% CI -9.08; -2.90, p 0.0001, I2 98%). A sub-analysis revealed that Asian and Africans, but not white-European RPL men had lower progressive sperm motility compared to controls. CONCLUSION: In conclusion, current review and meta-analysis findings suggested that SDF and some specific semen parameters were associated with RPL in a multi-ethnic evaluation. This effort opens future direction on a growing awareness of, first, how the male factor plays a key role and, second, how appropriate would be to establish a direct dialogue between the gynecologist and the urologist. PATIENT SUMMARY: We performed a systematic review and meta-analysis on the male component of RPL. We found that sperm DNA fragmentation and some specific sperm parameters are significantly associated with RPL.

The complex relation between obstructive sleep apnoea syndrome, hypogonadism and testosterone replacement therapy.

Obstructive sleep apnoea syndrome (OSAS) is an under-recognized medical disease. The main risk factors for OSAS are male sex, older age, obesity, and metabolic syndrome, that are also associated with male hypogonadism (MH). Therefore, obesity has been classically identified as the most evident link between OSAS and MH. However, OSAS is per se linked to the development of MH by a combined effect of hypoxia, increased night-time awakenings, reduced sleep efficiency and fragmented sleep. Similarly, MH might represent a risk factor for OSAS, mainly related to sleep disturbances that are frequently associated with low testosterone. Data on testosterone replacement therapy (TRT) in patients with OSAS are limited. Nevertheless, TRT is generally contraindicated by guidelines in the presence of untreated or severe OSAS. TRT might in fact worse OSAS symptoms in different ways. Furthermore, OSAS has been proposed to be a risk factor for secondary polycythaemia and TRT might exacerbate polycythaemia. Therefore, TRT in hypogonadal men affected by untreated OSAS or severe OSAS should be considered with caution and in a personalised way. Nevertheless, the type and dosage of TRT should be considered, as short-term high-dose TRT might worsen OSAS, whereas long-term lower doses could eventually determine a clinical improvement of symptoms of OSAS. Here we reviewed the data on the association between OSAS, MH and TRT, including the opportunity of assessment of patients who develop signs and symptoms of OSAS during TRT by polysomnography.

Dietary Supplements for Erectile Dysfunction: Analysis of Marketed Products, Systematic Review, Meta-Analysis and Rational Use.

The use of nutraceutical products to enhance male sexual performance has a long history, especially with regard to the treatment of erectile dysfunction (ED). Alternative treatments for ED are becoming increasingly popular, with growing interest from consumers, as well as increased revenue for manufacturers. Dietary supplements (DSs), which are a mixture of active ingredients, are mainly sold online. In randomized controlled trials, the molecules contained in DSs have demonstrated varying degrees of effectiveness, or even have no evidence to support their use. However, none of the studies carried out provided sufficient evidence to consider these products a first-line therapy. Therefore, the combination of the various active ingredients, especially in relation to the daily dose, leaves doubts about the real effectiveness. In order to evaluate the potential efficacy of DS formulations, we analyzed the products marketed in Italy using a scoring approach. A systematic review of the literature was performed to evaluate the effect of DS and to detect the active ingredients able to improve erectile function-called effective ingredients (EIs)-and their minimal effective daily dose (mED). A metanalysis identified some nutraceuticals, such as Panax ginseng, Tribulus terrestris and L-arginine, that are able to improve male sexual function. Based on the scoring system, 2 (8%) supplements matched with the cluster of higher expected efficacy, 3 (12%) with the lower efficacy cluster and 20 (80%) matched with the criterion of no expected efficacy. DSs marketed in Italy are usually blends of many substances that are frequently employed at a negligible dose or without any evidence.

Acquired Male Hypogonadism in the Post-Genomic Era-A Narrative Review.

Although precision medicine took its first steps from genomic medicine, it has gone far beyond genomics, considering the full complexity of cellular physiology. Therefore, the present time can be considered as the "post-genomic era". In detail, proteomics captures the overall protein profile of an analyzed sample, whilst metabolomics has the purpose of studying the molecular aspects of a known medical condition through the measurement of metabolites with low molecular weight in biological specimens. In this review, the role of post-genomic platforms, namely proteomics and metabolomics, is evaluated with a specific interest in their application for the identification of novel biomarkers in male hypogonadism and in the identification of new perspectives of knowledge on the pathophysiological function of testosterone. Post-genomic platforms, including MS-based proteomics and metabolomics based on ultra-high-performance liquid chromatography-HRMS, have been applied to find solutions to clinical questions related to the diagnosis and treatment of male hypogonadism. In detail, seminal proteomics helped us in identifying novel non-invasive markers of androgen activity to be translated into clinical practice, sperm proteomics revealed the role of testosterone in spermatogenesis, while serum metabolomics helped identify the different metabolic pathways associated with testosterone deficiency and replacement treatment, both in patients with insulin sensitivity and patients with insulin resistance.