Impact of different typologies of smoking on ovarian reserve and oocyte quality in women performing ICSI cycles: an observational prospective study.

OBJECTIVE: Within the last few years smoking activities, as well as infertility, have increased in Italy, and so has the consumption of alternative cigarette devices among women of childbearing age. The aim of this observational study was to evaluate the impact of the consumption of cigarettes and alternatives devices, such as electronic cigarettes and heat-not-burn (HnB) products, on infertile women performing in vitro fertilization (IVF), in specific on the quality of oocytes retrieved in women performing intracytoplasmic sperm injection (ICSI) cycles. PATIENTS AND METHODS: Prospective observational longitudinal study involving 410 women referring to the Reproductive Physiopathology and Andrology Unit, Sandro Pertini Hospital, Rome, from 2019-2022. All the women enrolled filled out an elaborate questionnaire investigating smoking consumption, before the beginning of ovarian stimulation by antagonist protocol, ovarian pick-up, and subsequent ICSI technique. The outcomes of the study were the evaluation of clinical and ICSI features between the groups of smokers and non-smokers: the number of retrieved oocytes, immature oocytes, and fertilization rate were confronted between the two groups and between cigarette smokers vs. e-cigarette and heat-not-burn (HnB) products smokers. RESULTS: Clinical parameters were comparable between the group of smokers compared to one of the non-smokers, except for anti-Müllerian hormone (AMH), which was statistically lower in smokers (p<0.05). Regarding IVF hormonal stimulations it appears that the total dose of gonadotropin was statistically lower in the non-smoker's group, compared to smokers (1850±860 UI vs. 1,730±780 p<0.05). Regarding ICSI techniques interestingly the number of oocytes retrieved was lower in the smokers' group compared to non-smokers (5.21±0.9 vs. 6.55±3.5, p<0.001), and the number of empty zona pellucida oocytes was statistically higher in the smokers' group (0.51±0.1 vs. 0.2±0.1, p<0.05). On the other hand, the fertilization rate (FR) was statistically higher in non-smokers compared to the smokers' group (72.16±3.05 vs. 68.12±2.21, p=0.03). Out of the 203 smokers, overall, any statistically significant difference, regarding ICSI results, has been found between the group of cigarette smokers, compared to the group of e-cigarettes plus HnB products smokers. CONCLUSIONS: Smoking negatively impacts human fertility, leading to a reduction of ovarian reserve and ovarian quality, which can negatively impact results in women performing ICSI cycles. Despite the limitation of the study, our results underline that consumption of cigarette alternative devices seems to have a similar negative impact on the quantity and quality of oocytes retrieved in ICSI cycles. Clinicians should emphasize the reduction of exposure to harmful substances derived from the combustion of tobacco smoking, as well as alternative devices, in women of childbearing age.

Assessment of sexual and emotional distress in infertile couple: validation of a new specific psychometric tool.

BACKGROUND: The diagnosis of infertility strongly impacts on psychological and sexological couple health. In this regard, some feelings and psychological states were demonstrated in association with reproductive problems. Depression and anxiety are the most common psychopathologies associated with infertility, although also sexuality is strongly involved in infertility conditions. OBJECTIVES: The aim of this study is to develop a tool to probe and assess the emotional aspects, sexuality, and social relationships of the couple seeking medical care for infertility. MATERIALS AND METHODS: A self-reported questionnaire that we will refer to as SEIq (Sexuality and Emotions in Infertility questionnaire) was constructed and developed and, consequently, administered to 162 heterosexual couples (324 subjects) seeking help for reproductive problems. Hence, we performed a specific statistical analysis to assess and validate this new psychometric tool. RESULTS: About 60% of men and women (both partners in 43% of couples) declare that infertility has changed their life (Q10). Moreover, the incidence of sexual disorder declared by the subjects is quite rare in men (10%) but more frequent in women (29%) (p < 0.01). CONCLUSION AND DISCUSSION: The results of this pilot test show that the diagnosis of infertility impacts on the couple relationship affecting the emotional area, interpersonal relationships, and sexual functions of the couples. Moreover, the SEIq appears a valuable tool to coherently probe and relate sexological, psychological, relational, and emotive aspects in partners and couples facing the infertility diagnosis. The explorative factor analysis of SEIq data allows to understand the women, men, and couples' behavior in our sample, individuating a reduced set of factors, prone to an easier evaluation. On the whole, the psychometric evaluation through SEIq might be suitable for the couples during Assisted Reproductive Technologies treatments.

Recurrence quantification analysis with wavelet denoising and the characterization of magnetic flux emergence regions in solar photosphere.

Solar systems complexity, multiscale, and nonlinearity are governed by numerous and continuous changes where the sun magnetic fields can successfully represent many of these phenomena. Thus, nonlinear tools to study these challenging systems are required. The dynamic system recurrence approach has been successfully used to deal with this kind challenge in many scientific areas, objectively improving the recognition of state changes, randomness, and degrees of complexity that are not easily identified by traditional techniques. In this work we introduce the use of these techniques in photospheric magnetogram series. We employ a combination of recurrence quantification analysis with a preprocessing denoising wavelet analysis to characterize the complexity of the magnetic flux emergence in the solar photosphere. In particular, with the developed approach, we identify regions of evolving magnetic flux and where they present a large degree of complexity, i.e., where predictability is low, intermittence is high, and low organization is present.

Clinical assessment and management of severe acute pancreatitis: a multi-disciplinary approach in the XXI century.

Acute pancreatitis (AP) is the most common gastrointestinal disorder requiring hospitalization, with a high rate of morbidity and mortality. Severe AP is characterized by the presence of persistent organ failure involving single or multiple organs. Clinical evolution, laboratory and radiological assessment are necessary to evaluate the prognosis and inform the management of AP. The onset of severe AP may be classified in two principal phases. The early phase, during the first week, is characterized by the activation of the auto-inflammatory cascade, gut dysbiosis, bacterial translocation, and the down-regulation of immune responses. The late phase is characterized by the development of local and systemic complications. Several old paradigms have been amended in the management of AP patients, such as the indication of nutrition, the use of antibiotic therapy, pain control strategies, and even the use of surgery. Real world evidence has shown that in the majority of cases a step-up approach is most effective. In this review, we discuss the clinical assessment and improvements to the management of patients with severe AP in a high volume center where a multi-disciplinary approach is performed.

Combined treatment with myo-inositol, alpha-lipoic acid, folic acid and vitamins significantly improves sperm parameters of sub-fertile men: a multi-centric study.

OBJECTIVE: Reduction in motility and number of spermatozoa and change in their morphology are some of the most relevant causes of male infertility. Production of reactive oxygen species may affect motility, morphology and DNA stability of spermatozoa. This study aimed at evaluating the effect of combined treatment with myo-inositol, alpha-lipoic acid, folic acid, betaine and vitamins (namely, Sinopol®) on semen parameters of sub-fertile men. PATIENTS AND METHODS: We recruited 143 sub-fertile men, 26-53 years aged, no-smokers, without any testicular pathologies, with a normal endocrinological/metabolic profile, and no concomitant consumption of drugs. Out of them, 25 patients did not meet study inclusion criteria mainly due to the history of genital diseases that came to light after Sinopol® prescription. Among the 118 men that fulfilled inclusion criteria, 10 (8.4%) patients were lost at follow-up and in 8 (6.8%) cases the partner got pregnant spontaneously. Thus, 100 patients completed the study and semen analysis was performed before and after 90 days of treatment. RESULTS: Semen quality improved after 90 days of treatments, with a statistically significant increase of sperm concentration (p=0.0009), of number of spermatozoa (p=0.0017), of progressive motility (p=0.0047), of total motile sperm count (p=0.0010), and of normal sperm morphology (p<0.0001). CONCLUSIONS: For the first time we reported that a combination of nutraceuticals composed of myo-inositol, alpha-lipoic acid, folic acid, betaine and vitamins improves sperm parameters in sub-fertile men. We are aware that to clarify the clinical relevance of the data studies with larger sample sizes and longer durations are needed, as well as evaluation of myo-inositol and alpha-lipoic acid co-treatment effectiveness in improving the chances to obtain a pregnancy spontaneously or following assisted reproduction.

Gut Microbiota-Immune System Crosstalk and Pancreatic Disorders.

Gut microbiota is key to the development and modulation of the mucosal immune system. It plays a central role in several physiological functions, in the modulation of inflammatory signaling and in the protection against infections. In healthy states, there is a perfect balance between commensal and pathogens, and microbiota and the immune system interact to maintain gut homeostasis. The alteration of such balance, called dysbiosis, determines an intestinal bacterial overgrowth which leads to the disruption of the intestinal barrier with systemic translocation of pathogens. The pancreas does not possess its own microbiota, and it is believed that inflammatory and neoplastic processes affecting the gland may be linked to intestinal dysbiosis. Increasing research evidence testifies a correlation between intestinal dysbiosis and various pancreatic disorders, but it remains unclear whether dysbiosis is the cause or an effect. The analysis of specific alterations in the microbiome profile may permit to develop novel tools for the early detection of several pancreatic disorders, utilizing samples, such as blood, saliva, and stools. Future studies will have to elucidate the mechanisms by which gut microbiota is modulated and how it tunes the immune system, in order to be able to develop innovative treatment strategies for pancreatic disorders.

The association of pancreatic cystosis and IPMN in cystic fibrosis: case report and literature review.

Pancreatic cystosis is a rare presentation of cystic fibrosis involving pancreatic gland. To date, only very few cases of pancreatic cystosis have been described in literature. Pancreatic cystosis may begin during the second decade of life and is the rarest presentation of cystic fibrosis. This disease is characterized by the presence of multiloculated cysts without ductal system communication of different sizes in all the pancreatic tissue. Herein, we report a case of a young woman affected by cystic fibrosis that was admitted to our Pancreatic Centre to evaluate a picture of diffuse multiloculated pancreatic cysts. After magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) assessment, we perform the diagnosis of the concomitant presence of the rare condition of pancreatic cystosis with Branch Duct-Intraductal Papillary Mucinous Neoplasm (BD-IPMN). To our knowledge, this is the first reported case of a cystic fibrosis patient with the combination of pancreatic cystosis and IPMN.

Uptodate in the assessment and management of intraductal papillary mucinous neoplasms of the pancreas.

Intraductal Papillary Mucinous Neoplasms (IPMNs) are the most common cystic tumors of the pancreas and are considered premalignant lesions. IPMNs are characterized by the papillary growth of the ductal epithelium with rich mucin production, which is responsible for cystic segmental or diffuse dilatation of the main pancreatic duct (MPD) and/or its branches. According to the different involvement of pancreatic duct system, IPMNs are divided into main duct type (MD-IPMN), branch duct type (BD-IPMN), and mixed type (MT-IPMN). IPMNs may be incidentally discovered in asymptomatic patients, particularly in those with BD-IPMNs, when imaging studies are performed for unrelated indications. The increase in their frequency may reflect the combined effects of new diagnostic techniques, the improvement of radiologic exams and progress in the recognition of the pathology. MD-IPMNs present a higher risk of malignant progression than BD-IPMNs; as a consequence, all the guidelines strictly suggest the need of surgery for MD- and MT- IPMNs with MPD > 10 mm, while the management of BD-IPMNs is still controversial and depends on several cysts and patients features. The choice between non-operative and surgical management depends on the distinction between benign and invasive IPMN forms, assessment of malignancy risk, patient's wellness and its preferences. This manuscript revises the different guidelines for the management of IPMNs that have been published in different world countries: the international (Sendai 2006 and Fukuoka 2012), the 2013 European, the 2014 Italian, and finally the 2015 American guidelines. In summary, this review will integrate the recent insights in the combination of diagnostic techniques, such as Magnetic Resonance Imaging (MRI) and endoscopic ultrasound (EUS), pathology classification, and management of IPMNs.

Controlled, prospective, observational study on the efficiency and tolerability of a combination of potential Nrf2-inducing antioxidants and micronutrients as pre-treatment for ICSI in dyspermic patients with previous failure.

OBJECTIVE: To evaluate the efficiency of pre-treatment in dyspermic males in IVF couples with a combination of micronutrients, for the purpose of improving the fertilization rate, the implantation rate and the outcome of the pregnancy. PATIENTS AND METHODS: This controlled prospective clinical study was performed in two medically assisted reproduction centers. 59 males with mild oligo-astheno-teratospermia (OAT) were admitted to the study. All of them had a history of previous in vitro fertilization (IVF) attempts with female partners aged < 40 diagnosed having tubal or idiopathic infertility. The subjects upon enrolment underwent a semen test and afterward were treated with alpha lipoic acid and glutathione (Fertiplus SOD®, Idi-Pharma, Catania, Italy) for 4 weeks (short-term). The primary endpoints that were evaluated are the following: fertilization rate (mean fertilization), implantation rate and pregnancy rate. RESULTS: At the end of this study all the males (mean age 39.5 ± 5.1) reported in not having any side effects during the administration of Fertiplus. Their female partners (mean age 34.9 ± 4.5) underwent IVF using the ICSI technique. The number of oocytes retrieved and inseminated was not statistically different in comparison to previous attempts, but with the same number of oocytes treated, the fertilization rate per couple demonstrated statistically significant increase (p<0.001). We did not observe a percentage increase in evolutionary embryos, but we noticed an improvement in embryo quality per individual couple (p<0.001), associated with a net increase in the implantation rate per couple (p<0.001) in terms of clinical pregnancy. The estimated miscarriage risk after treatment was five times lower (p<0.001). CONCLUSIONS: Short-term treatment with micronutrients in dyspermic subjects can improve the reproductive outcome of the IVF procedure.

Nutritional support in acute pancreatitis: from physiopathology to practice. An evidence-based approach.

Acute Pancreatitis (AP) is a potentially fatal syndrome, associated with a hyper-catabolic state as well as early and late complications that may lead to multi-organ failure and death. Clinical researches produced in recent years suggest that acute pancreatitis may benefit from early oral or enteral nutrition. Nevertheless, many clinicians still believe erroneously that fasting - particularly in the early phase - may reduce AP complications and mortality. The goal of our review is to demonstrate that such false belief may harm the patients and that the whole management paradigm must change, adopting a more rational, evidence-based approach. First, we will describe AP physiopathology and the clinical assessment of its severity. Then we will discuss evidence-based data supporting early oral or enteral nutrition in AP. Finally, we will offer some practice recommendations as regards nutritional support.

Gut Microbiota: A Key Modulator of Intestinal Healing in Inflammatory Bowel Disease.

Mucosal healing (MH) represents a crucial factor for maintaining gut homeostasis. Indeed, in inflammatory bowel disease, MH has become the standard therapeutical target, because it is associated with more effective disease control, more frequent steroid-free remission, lower rates of hospitalization and surgery, and improved quality of life. In this scenario, gut microbiota is a crucial player in modulating intestinal repair and regeneration process. It can act on the tumor necrosis factor-α production, modulation of reactive oxygen and nitrogen species, activity of matrix metalloproteinases and on many other mechanisms strictly involved in restoring gut health. In this review, we analyze and review the literature on the role of gut microbiota in sustaining mucosal injury and achieving MH.

Progesterone supplement in pregnancy: an immunologic therapy?

One of the most interesting functions of the placenta is the regulation of the maternal immune response such that the fetal semi-allograft is tolerated during pregnancy. Trophoblasts are presumed to be essential to this phenomenon because they lie at the maternal-fetal interface, where they are in direct contact with cells of the maternal immune system. Trophoblasts do not express classic major histocompatibility complex (MHC) class II molecules. Surprisingly, cytotrophoblasts express more HLA-G, a MHC class Ib molecule, as they invade the uterus. Progesterone plays an important role in postovulatory regulation of the menstrual cycle. If fertilization occurs, progesterone supports implantation of the ovum and maintains the pregnancy. Progesterone has been named the 'hormone of pregnancy', because in preparing the endometrium for embryo implantation and facilitating endometrial development, it is critical to the very survival of a pregnancy. In addition, this key hormone inhibits the rejection of T cell-mediated tissue and also decreases myometrial activity and sensitivity throughout pregnancy. The cellular actions of progesterone are mediated through intracellular progesterone receptors (PRs), which are well studied gene regulators, not express classic major histocompatibility complex. The more used paradigm is relative to the alteration of relationship TH1/TH2, but the complexity of the respective distributions of cytokines at the materno-fetal interface, strongly suggest that, as useful as it certainly was for a while, the Th1/Th2 paradigm must now be considered as an oversimplification. Rather, the existing data point to sequential windows and are suggestive of a system where an extreme complexity is allied to very precise timing and tuning. They also suggest that the materno-fetal relationship is not simply maternal tolerance of a foreign tissue, but a series of intricate mutual cytokine interactions governing selective immune regulation and also control of the adhesion and vascularization processes during this dialogue. However, as shifting the immune response toward the Th2 pattern (IL-4, IL-5, IL-6) may benefit the fetus, whereas development of proinflammatory Th1 cells (secreting IL-2, IFN g, TNF a) may be harmful. Now we are working to open comprise the precise behaviour of NK populations, with the hope of obtaining a diagnostic test of the condition of abortion from 'immunological causes'.

The -174 G/C polymorphism of the interleukin-6 gene promoter is associated with peripheral artery occlusive disease.

OBJECTIVE AND DESIGN: high plasma levels of Interleukin-6 (IL-6) are found in patients with atherosclerotic disorders. Recently, a common polymorphism of the IL-6 gene promoter, influencing the transcription rate of the gene, has been described and associated with atherosclerosis of carotid and coronary arteries. The objective of this study was to test whether IL-6 gene promoter polymorphism is associated with peripheral artery occlusive disease (PAOD) in a case-control study. METHODS: IL-6 gene promoter polymorphism was evaluated by polymerase chain reaction followed by restriction enzyme analysis in 84 patients affected by PAOD and 183 controls. RESULTS: the distribution of IL-6 genotypes was: patients with PAOD: 44 GG, 30 GC, 10 CC; control subjects: 53 GG, 80 GC, 50 CC. The GG genotype was significantly more common in the PAOD group (p<0.0001), while the CC genotype was significantly more common in control patients (p=0.005). CONCLUSIONS: this study indicates a strong association between IL-6 gene polymorphism and PAOD and support the hypothesis that IL-6 and IL-6 gene polymorphism are important in the pathophysiology and evolution of ischaemic diseases of the lower limbs.

Effects of propionyl-L-carnitine on peripheral arterial obliterative disease of the lower limbs: a double-blind clinical trial.

The authors evaluated the efficacy of propionyl-l-carnitine, a drug able to reduce peripheral resistance and protect the cells against oxidative stress damage, in patients affected by peripheral arterial obliterative disease at class II of Fontaine. The study was performed on 22 patients according to a double-blind, randomized design in parallel with placebo. The drug was administered at a dosage of 1 g three times a day orally for 90 days. At recruitment and at the end of the study all patients underwent physical examination, treadmill test, doppler C.W. of the lower limbs, ankle/brachial index, dosage of tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), hematocrit, hematic filtration, and viscosity. In the group treated with propionyl-l-carnitine a statistically significant increase of claudication distance, blood flow velocity, PAI-1 activity and red blood cell deformity was observed. These data suggest the usefulness of propionyl-l-carnitine in the treatment of patients affected by peripheral arterial obliterative disease.

Raynaud's Phenomenon and Helicobacter Pylori Infection.

Raynaud's phenomenon is an intermittent vasospasm of the arterioles of the distal limbs which occurs mostly following exposure to cold or emotional stimuli. Helicobacter pylori infection, the most relevant cause of gastritis, has been associated with some vascular diseases. The aim of this study was to assess the prevalence of H. pylori infection and effects of eradication on Raynaud attacks. Twenty-five patients affected by primary Raynaud's phenomenon were evaluated. H. pylori infection was assessed by the 13C urea breath test and 20 subjects were found to be infected by the bacterium. Triple therapy consisting of amoxicillin, clarithromycin, and lansoprazole was given to the patients for 7 days at the time of diagnosis. Duration and frequency of clinical attacks of Raynaud's phenomenon per week were assessed for 12 weeks after eradication. In 80 percent of the patients Raynaud's was eradicated after therapy. Clinical attacks of Raynaud's phenomenon completely disappeared in 18% of the eradicated patients. Duration and frequency of attacks were significantly reduced in 68% of the remaining patients. The preliminary findings from this study show that H. pylori eradication significantly ameliorates primary Raynaud's disease.

Helicobacter pylori eradication ameliorates primary Raynaud's phenomenon.

Raynaud's phenomenon is defined by an intermittent vasospasm of the arterioles of the distal limbs. Helicobacter pylori infection has been recently associated with Raynaud's phenomenon. The aim of this study was to assess the effects of H. pylori eradication on Raynaud's attacks. Forty-six patients affected by primary Raynaud's phenomenon were evaluated. H. pylori infection was assessed by [13C]urea breath test. Eradication therapy was given to infected patients for seven days. Discomfort and the duration and frequency of attacks of Raynaud's phenomenon per week were assessed. Thirty-six subjects were infected with H. pylori; the bacterium was eradicated in 83% of these after therapy. Attacks of Raynaud's phenomenon completely disappeared in 17% of the patients with H. pylori eradication. Discomfort and the duration and frequency of attacks of Raynaud's phenomenon were significantly reduced in 72% of the remaining patients. Conversely, attacks of Raynaud's disease did not change significantly during the 12-week follow-up period either in the H. pylori-negative patients or in the infected subjects in whom the bacterium was not eradicated by therapy. The study shows that H. pylori eradication causes a significant decrease in clinical attacks of Raynaud's disease. The reduction of vasoactive substances determined by the eradication of the bacterium may be the pathogenetic mechanism underlying the phenomenon.

Epidemiological aspects of inflammatory bowel disease in a north Italian population: a 4-year prospective study.

OBJECTIVE: To determine the incidence and clinical characteristics at presentation of inflammatory bowel disease (IBD) in a defined area of north Italy. DESIGN: A 4-year prospective population-based epidemiological study. SETTING: An area in Lombardia defined by the National Health Service scheme with about 294,000 inhabitants, two referral hospitals and 259 general practitioners (GPs). PATIENTS: Subjects presenting to a GP with symptoms compatible with IBD underwent a diagnostic work-up at one of the referral hospitals. Those with ulcerative colitis (UC), Crohn's disease (CD) or indeterminate colitis diagnosed according to a defined protocol were included, as were residents of the area with IBD diagnosed elsewhere. Rigid case ascertainment methods were used. Patients were followed for one year; 125 patients were identified. RESULTS: The patient ascertainment rate was constant over the 4 years; UC was diagnosed in 82 patients, CD in 40, and indeterminate colitis in three. The mean annual incidence of IBD for the whole period was 10.6/10(5) inhabitants (95% confidence limits, 7.2-15.1), 7.0/10(5) for UC (4.3-10.7) and 3.4/10(5) (1.6-6.3) for CD. The mean interval between onset of symptoms and diagnosis was under 6 months. The clinical characteristics of our patients were similar to those of north European and American series. CONCLUSION: The incidence of IBD was higher than previously observed in Italy but was still lower than in some north European countries and in the USA. Our data could be used as a basis for future longitudinal studies and in international comparative investigations.