Recent Insights on the Maternal Microbiota: Impact on Pregnancy Outcomes

Abstract Hormonal changes during and after pregnancy are linked with modifications in the maternal microbiota. We describe the importance of the maternal microbiota in pregnancy and examine whether changes in maternal microbiotic composition at different body sites (gut, vagina, endometrium) are associated with pregnancy complications. We analyze the likely interactions between microbiota and the immune system. During pregnancy, the gastrointestinal (gut) microbiota undergoes profound changes that lead to an increase in lactic acid-producing bacteria and a reduction in butyrate-producing bacteria. The meaning of such changes needs clarification. Additionally, several studies have indicated a possible involvement of the maternal gut microbiota in autoimmune and lifelong diseases. The human vagina has its own microbiota, and changes in vaginal microbiota are related to several pregnancy-related complications. Recent studies show reduced lactobacilli, increased bacterial diversity, and low vaginal levels of beta-defensin 2 in women with preterm births. In contrast, early and healthy pregnancies are characterized by low diversity and low numbers of bacterial communities dominated by Lactobacillus. These observations suggest that early vaginal cultures that show an absence of Lactobacillus and polymicrobial vaginal colonization are risk factors for preterm birth. The endometrium is not a sterile site. Resident endometrial microbiota has only been defined recently. However, questions remain regarding the main components of the endometrial microbiota and their impact on the reproductive tract concerning both fertility and pregnancy outcomes. A classification based on endometrial bacterial patterns could help develop a microbiota-based diagnosis as well as personalized therapies for the prevention of obstetric complications and personalized treatments through nutritional, microbiotic, or pharmaceutical interventions. Keywords: endometrium; gut; immunity; inflammasome; microbiota; pregnancy; vagina

Effect of alpha‐lipoic acid and myoinositol on endometrial inflammasome from recurrent pregnancy loss women

Problem: A significant increased expression/activation of one of the most well‐characterized inflammasomes, the NAcht leucine‐rich‐repeat protein‐3 (NALP‐3), in the endometrium from idiopathic recurrent pregnancy loss women (RPL) has been previously found by our research group. We therefore, suggested this event as being one of the molecular mechanisms altering endometrial inflammatory status during early pregnancy. In the present research, we attempt to investigate whether molecules with anti‐inflammatory activity, alpha‐lipoic acid (ALA), and/or myoinositol affect the endometrial NALP‐3 expression and activation. Method of study: Women with a history of idiopathic RPL (n = 30) were included in the study and compared to a control group (n = 15). Endometrial tissues were collected by hysteroscopy during the mid‐luteal phase. RPL women underwent a three‐month prescription of tablets containing ALA plus myoinositol (Sinopol®). After treatment, hysteroscopic biopsies were repeated in RPL patients. Inflammasome expression was evaluated by immunohistochemical and Western blot analysis. NALP‐3 activation was studied by quantifying the secretion of both caspase‐1 and interleukin IL)‐1ß and IL‐18 through ELISA. In ex vivo experiments, the effects of each molecule on endometrial inflammasome were studied. Results: Sinopol® significantly reduced the RPL endometrial inflammasome expression and activation. ALA, but not myoinositol, significantly reduced the endometrial inflammasome expression and activity. Conclusion: Our data suggest a role for ALA on RPL inflammasome. Understanding the mechanisms involved in RPL and the observation that specific molecules are able to interfere with such complex at the endometrium might provide new rational design approaches to a personalized evaluation of endometrial status and, ultimately, a targeted medicine

Case series of four complex spinal deformities: new frontiers in pre-operative planning

Background and aim: Osseous and medullar anomalies constitute a hard challenge for interpretation of complex vertebral deformities anatomy. To better frame these deformities three-Dimensional (3D) printing represents a new frontier in this field. The aim of this brief report is describing the use of 3D printed models for surgical planning in four complex vertebral deformity cases treatment. Methods: Four cases of severe scoliosis were treated between December 2017 and January 2019; patients' mean age was 12,25 years. Two patients underwent neurosurgical intervention for myelomeningocele at the time of birth. Standard and dynamics X-Ray, Computed Tomography (CT) and Magnetic Resonance (MR) of the column were performed pre-operatively. CT files were implemented to build the 3D model of each spine and selected ribs. The models were 3D printed in thermoplastic material, then used to study the deformities and for surgical planning. A survey proposal about 3D models' utility and accuracy has been made to 15 residents and 6 main surgeons. Results: Preparation of each 3D models required about 316.5 minutes and printing time was about 108 hours each. The average cost was 183.16 € to produce one 3D printed model, which resulted useful in surgical planning and educational. Conclusions: The manufacture of 3D models requires time, resources and multidisciplinary approach, it must be justified by complexity of the case. In this study 3D Printing allowed surgeons to carefully plan and simulate the surgery, ensuring for a better sizing of the implant

Surgical approach to single-level symptomatic thoracic disc herniations through costotransversectomy: A report of ten case series

Study Design: This was an observational study. Objectives: The treatment of symptomatic thoracic disc herniation (TDH) remains a matter of debate. We report our experience with ten patients affected by symptomatic TDH, surgically treated through costotransversectomy. Methods: A total of ten patients (four men and six women) with single-level symptomatic TDH were surgically treated by two senior spine surgeons at our institution between 2009 and 2021. The most common type was a soft hernia. TDHs were classified as lateral (5) or paracentral (5). Preoperative clinical symptoms were varied. The diagnosis was confirmed by computed tomography (CT) and magnetic resonance imaging of the thoracic spine. The mean follow-up period was 38 months (range: 12–67 months). The Oswestry Disability Index (ODI), the Frankel grading system, and the modified Japanese Orthopedic Association (mJOA) scoring system were used as outcome scores. Results: Postoperative CT study documented satisfactory decompression either on the nerve root or the spinal cord. All patients experienced a reduction of disability with an improved mean ODI score by 60%. Six patients reported total recovery of neurological function (Frankel Grade E) and four patients improved by 1 Grade (40%). The overall recovery rate estimated with the mJOA score was 43.5%. We reported the absence of significant difference in outcome compared to either calcified and noncalcified discs or paramedian and lateral location. Four patients had minor complications. No revision surgery was required. Conclusion: Costotransversectomy represents a valuable tool for spine surgeons. The major limit of this technique is the possibility to approach the anterior spinal cord

Pregnancy-Related Complications in Women with Recurrent Pregnancy Loss: A Prospective Cohort Study

The aim of this prospective cohort study was to determine whether women with recurrent pregnancy loss (RPL) have an increased risk of pregnancy complications compared to normal pregnant women. A total of 1092 singleton pregnancies were followed, 431 in women with RPL and 661 in normal healthy women. The prevalence of the following complications was observed: threatened miscarriage, miscarriage, cervical insuciency, chromosomal/genetic abnormalities, fetal anomalies, oligohydramnios, polyhydramnios, fetal growth restriction, intrauterine fetal death, gestational diabetes mellitus (GDM), preeclampsia, placenta previa, abruptio placentae, pregnancy-related liver disorders, and preterm premature rupture of the membranes. The odds ratio and 95% CI for each pregnancy complication considered were determined by comparing women with RPL and normal healthy women. Women with RPL had an overall rate of pregnancy complications higher than normal women (OR = 4.37; 95% CI: 3.353\u20135.714; p < 0.0001). Their risk was increased for nearly all the conditions considered. They also had an increased risk of multiple concomitant pregnancy complications (OR = 4.64; 95% CI: 3.10\u20136.94, p < 0.0001). Considering only women with RPL, women with 3 losses had a higher risk of pregnancy complications than women with two losses (OR = 1.269; 95% CI: 1.112\u20132.386, p < 0.02). No dierences were found in the overall risk of pregnancy complications according to the type, explained or unexplained, of RPL. Women with secondary RPL had an increased risk of GDM than women with primary RPL. Pregnancy in women with RPL should be considered at high risk

Diagnostic and Therapeutic Management of Primary Orbital Neuroendocrine Tumors (NETs): Systematic Literature Review and Clinical Case Presentation

Background: The ocular involvement of neuroendocrine neoplasms (NENs) is uncommon and mainly represented by metastases from gastrointestinal and lung neuroendocrine tumors. Primary orbital NENs are even less common and their diagnostic and therapeutic management is a challenge. Methods: A systematic review of the literature was conducted from 1966 to September 2023 on PubMed to identify articles on orbital NENs and to summarize their clinical–pathological features, diagnosis and therapeutic management. Furthermore, we presented a case of a locally advanced retro-orbital primary neuroendocrine tumor that was referred to the certified Center of Excellence of Sant’Andrea Hospital, La Sapienza University of Rome, Italy. Results: The final analysis included 63 records on orbital NENs and 11 records focused on primary orbital NENs. The localization was mostly unilateral and in the right orbit; proptosis or exophthalmos represented the initial symptoms. The diagnostic work-up and therapeutic management was discussed and a diagnostic algorithm for the suspicion of primary orbital NENs was proposed. Conclusions: A multidisciplinary approach is required for the management of primary orbital NENs, emphasizing the importance of early referral to dedicated centers for prompt differential diagnosis, tailored treatment, and an improved quality of life and survival

Arthrodesis versus dynamic neutralization: A short/mid- and long-term retrospective evaluation in degenerative disk disease treatment

Study Design: This was a retrospective comparative study. Objectives: The aim of this study was to perform a clinical and radiological retrospective evaluation of the most used techniques for the lumbar degenerative disk disease (DDD) treatment: arthrodesis versus dynamic neutralization (DN)-Dynesys dynamic stabilization system. Methods: The study included 58 consecutive patients affected by lumbar DDD, 28 treated with rigid stabilization and 30 with DN at our department between 2003 and 2013. The clinical evaluation was performed through the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI). The radiographic evaluation was performed through standard and dynamic X-ray projections and magnetic resonance imaging. Results: Both techniques determined a clinical improvement in the postoperative period compared to the preoperative one. There were no significant differences between the postoperative VAS of the two techniques. The DN group postoperative ODI percentage showed a significant improvement (P = 0.026) compared to the arthrodesis group. During the follow-up, no clinically significant differences were highlighted between the two techniques. At a long term follow up period, radiographic results showed, in both groups, a L3–L4 disk mean height reduction and an increase of segmental and lumbar lordosis without significant differences between the two techniques. During an average of 96-month follow-up period, 5 (18%) patients developed an adjacent segment disease in the arthrodesis group and 6 (20%) patients developed this syndrome in the DN group. Conclusions: We are confident in recommending arthrodesis and DN as effective techniques for lumbar DDD treatment. Both techniques are potentially burdened, with similar frequency, by the development of long-term adjacent segment disease

Celiac disease and reproductive failures: An update on pathogenic mechanisms

Celiac disease (CD) is an autoimmune disorder that occurs in genetically predisposed people in which the ingestion of gluten leads to damage in the small intestine that clinically presents with malabsorption-related symptoms. CD can also be the underlying cause of several non-gastrointestinal symptoms. This review summarizes evidence on the relationship between CD and gynecological/obstetric disorders like reproductive failures. Although much has been reported on such a linkage, the pathogenic mechanisms remain unclear, especially those underlying extra-gastrointestinal clinical manifestations. Studies conducted on celiac subjects presenting gynecological/ obstetric disorders have pointed to intestinal malabsorption, coagulation alterations, immune-mediated tissue damage, and endometrial inflammation as the main responsible pathogenic mechanisms. Currently, however, the knowledge of such mechanisms is insufficient, and further studies are needed to gain a more thorough understanding of the matter