Female obesity and infertility: outcomes and regulatory guidance

: Obesity has been associated with reduced fertility, although the dynamics and mechanisms which link excess weight to reduced fertility are not yet fully clarified. Obese women, especially those with central obesity, are less likely to conceive per cycle. Obese women suffer from perturbations of the hypothalamus-pituitary-ovary axis, disturbances of the menstrual cycle and are up to three times more likely to suffer from oligo/anovulation. A delicate hormonal balance regulates follicular development and the maturation of oocytes and it has been observed that obesity can alter the hormonal environment: adipocytes, in fact, are responsible for the production of a hormone called leptin (present in high quantities in obese women) which has been associated with reduced fecundity. In addition to compromising ovulation, obesity negatively affects the development and implantation of the endometrium. The expression of polycystic ovary syndrome (PCOS) is regulated, in part, by weight, so obese women with PCOS often have a more severe phenotype and higher subfertility rates. Furthermore, obesity impairs women's response to medically assisted procreation (MAP) treatments. The authors have set out to delineate a broad-ranging overview of obesity's impact on female fertility, by drawing upon sources spanning the 1994-2022 period. Assisted reproductive technology (ART) procedures are also discussed as they relate to obese patients. In addition the dynamics by which maternal obesity reportedly affects fetal, neonatal and child development have also been briefly enunciated

End-of-life in the operational functioning of public healthcare: ethical and legal issues

Background and aim: The article aims to outline the current scenario relative to the medical role in end-of-life issues. In order to do this, historical-legal references have been drawn upon relating to technical, legal and scientific thought and doctrine, as it has come down to us in the medical field through the evolution of ethical and philosophical frameworks. Methods: The authors have conducted a thorough analysis of end-of-life legislative initiatives, in Italy and across the EU, and court rulings to outline possible ways to harmonize and reconcile the current medical ethics frameworks with the needs and rights of all, especially the most vulnerable among us. To that end, the necessary operational choices and adjustments have not yet been made by our legal system, from a technical, as well as moral, standpoint. Results: An operational proposal has therefore been laid out to protect both healthcare providers and patients, in a relationship that goes beyond treatment in the strict sense, which prioritizes mutual needs as an integral part of a common, essential path. Conclusions: In order for doctors to consider themselves complete, they should in fact deal not only with life, but also with death

Death Due to Anaphylactic Reaction: The Role of the Forensic Pathologist in an Accurate Postmortem Diagnosis

Background and Objectives: The diagnosis of anaphylaxis comprehensively depends on both situational information and laboratory investigations. For this purpose, serum tryptase concentration is examined as an indicator of systemic mast cell mediator release, linked to an underlying anaphylactic process. Increased levels of tryptase may occur in some events different from anaphylaxis, but usually information from crime scene investigations is lacking and autoptic findings are not specific. For legal reasons, it is required to achieve a definite diagnosis of mast cell degranulation that can lead to a certain diagnosis of death from anaphylaxis. Immunohistochemistry seems to be a relatively simple, reliable, and easily repeatable method that can assist the forensic pathologist in the differential diagnosis of death from anaphylaxis. Materials and Methods: This work provides an overview of the current literature on immunohistochemical methods useful in the determination process of anaphylactic-related deaths. A systematic search, according to the PRISMA statement, was performed in databases to identify studies investigating immunohistochemical targets related to anaphylaxis death. Results: This work underscores the importance of anaphylaxis mediators such as tryptase, CD117, and chymase in the immunohistochemical analysis of anaphylactic deaths. Conclusions: According to the reviewed literature, the diagnosis of death due to anaphylaxis should depend not just on the suspicion of an anaphylactic reaction but also on confirming mast cell degranulation through the identification of IHC positivity for inflammatory mediators, particularly in the respiratory tract

Blood-brain barrier breakdown, central nervous system cell damage, and infiltrated T cells as major adverse effects in CAR-T-related deaths: a literature review

Background CAR-T-related deaths observed worldwide are rare. The underlying pathogenetic mechanisms are the subject of study, as are the findings that enable diagnosis. A systematic literature search of the PubMed database and a critical review of the collected studies were conducted from the inception of this database until January 2023. The aim of the study is to determine when death is related to CAR-T cell therapy and to develop a shareable diagnostic algorithm.Methods The database was searched by combining and meshing the terms ("CAR-t" OR "CART") AND ("Pathology" OR "Histology" OR "Histological" OR "Autopsy") AND ("Heart" OR "Cardiac" OR "Nervous System" OR "Kidney" OR "Liver") with 34 results and also the terms: [(Lethal effect) OR (Death)] AND (CAR-T therapy) with 52 results in titles, abstracts, and keywords [all fields]. One hundred scientific articles were examined, 14 of which were additional records identified through other sources. Fifteen records were included in the review.Results Neuronal death, neuronal edema, perivascular edema, perivascular and intraparenchymal hemorrhagic extravasation, as well as perivascular plasmatodendrosis, have been observed in cases with fatal cerebral edema. A cross-reactivity of CAR-T cells in cases of fatal encephalopathy can be hypothesized when, in addition to the increased vascular permeability, there is also a perivascular lymphocyte infiltrate, which appears to be a common factor among most authors.Conclusion Most CAR-T-related deaths are associated with blood-brain barrier breakdown, central nervous system cell damage, and infiltrated T cells. Further autopsies and microscopic investigations would shed more light on the lethal toxicity related to CAR-T cells. A differential diagnosis of CAR-T-related death is crucial to identifying adverse events. In this article, we propose an algorithm that could facilitate the comparison of findings through a systematic approach. Despite toxicity cases, CAR-T therapy continues to stand out as the most innovative treatment within the field of oncology, and emerging strategies hold the promise of delivering safer therapies in future

Research on supernumerary embryos. The challenge of reconciling opposing interests and fast-evolving technologies

The paper addresses the issue of the legality and ethical admissibility of invasive experiments on embryos and the correlated one of the degree of legal protection and dignity to be recognized for human embryos, particularly in light of the growing importance that scientific research on embryonic stem cells has been gaining from the clinical and biomedical standpoints in the therapeutic treatments of diseases so far considered incurable, in the interest of public health. Furthermore, the issue of experimentation on cryopreserved supernumerary human embryos is still extremely polarizing, which makes it harder to arrive at shared solutions. The author hopes for a broad-ranging debate at the international level, for the ultimate purpose of achieving shared regulatory frameworks

Traumatic Aneurysm Involving the Posterior Communicating Artery

Traumatic intracranial aneurysms (TICAs) are rare, accounting for less than 1% of all intracranial aneurysms. However, they are associated with a mortality rate of over 50%. The case presented herein focuses on a posterior communicating artery TICA caused by violent aggression. A 41-year-old man with massive subarachnoid hemorrhage (SAH), on admission to hospital, had a CT angiography that showed a ruptured left posterior communicating artery aneurysm with continuous blood loss and underwent neurosurgical cooling. The CT scan also showed fractures of the mandible, mastoid and left styloid process, as well as brain contusions caused by blows and kicks. Despite medical treatment and surgery, after four days, he died. The assault dynamics were recorded by a camera in the bar. The damage was caused by kicks to the neck and head. The forensic neuropathological examination showed the primary injury (SAH, subdural hemorrhage, cerebral contusions, head-neck fractures), as well as secondary damage following the attack (cerebral infarcts, edema, supratentorial hernia, midbrain hemorrhage). The coil was intact and well positioned. In this case, circumstantial information, medical records, and the type of injury could shed light on the mechanism of the production of a TICA. In addition, the CT angiography and histological investigations helped to distinguish a recent and traumatic aneurysm from a pre-existing one. Following precise steps, the study of aneurysms can be helpful in clarifying their traumatic origin even when the victim was taking drugs. The aim of this study is also to share the diagnostic process that we used in the forensic field for the assessment of suspected traumatic aneurysms

Treatment of menstrual migraine. utility of control of related mood disturbances

Menstrual migraine (MM) has a prevalence in the general population of approximately 7%, although it seems to be much higher within the population of females with migraine. Episodes of MM have been reported to be longer, more intense, more disabling, less responsive to acute therapy and more prone to recurrence than those of other types of migraine. MM is demonstrated to have a bi-directional link to affective illnesses such as premenstrual dysphoric disorder and depression. There is clinical and pathophysiological evidence suggesting that the relationship between MM and affective disorders could be linked to ovarian hormones. The aim of this review is to analyze treatment strategies in patients with co-existent MM and affective disorders

The role of fillers in aesthetic medicine: medico-legal aspects

In recent years there has been an exponential increase of fillers use in aesthetic medicine. The popularity of this anti-wrinkle product is based on their capacity to offer significant improvement in the aesthetic field, particularly to skin rejuvenating processes with non-invasive and less expensive techniques, if compared to the surgical methods (i.e. surgical lifting). The great number of fillers on the market is composed of a large heterogenic number of biomaterials. The aim of this review was to provide an overview and a classification of the filling materials that are most commonly used. A synthesis of the literature concerning fillers and related side effects was also reported. The law decree no. 23 of 1998, converted in the law no. 94 of 1998 and the principal judgments of the Italian Court of Cassation have been examined with the medico-legal issues related to fillers use in medicine. With respect to their degradation, filler materials may be classified as temporary (degradable), semi-permanent and permanent (not degradable). The temporary fillers such as hyaluronic acid and collagen are completely degraded by the surrounding tissue in a few months. The permanent fillers, such as the ones derived from silicon oil and minerals are not biodegradable and may cause serious and irreversible side effects. Their use requires a physician with a high level of specialization to perform the treatment, a deep knowledge of face anatomy and a great degree of experience

Ovarian Stimulation Protocol in IVF: An Up-to-Date Review of the Literature

The Assisted Reproductive Technology (ART) was born in order to help couples with infertility issues in having a baby. The first treatments of IVF used the spontaneous cycle of the women, with the retrieval of only one oocyte. Further studies have shown that it is possible to induce ovulation by administrating gonadotropins during the menstrual cycle, in order to obtain a higher number of oocytes. Many stimulation protocols have been introduced for controlled ovarian hyperstimulation of patients undergoing in vitro fertilization treatment. This review describe the different stimulation protocols using follicle-stimulating hormone (FSH) in combination with Gonadotropin releasing hormone (GnRH) either agonist or antagonist, oral supplementations and ovarian triggering. Using GnRH antagonist protocols have been demonstrated to improve significantly the clinical pregnancy rates for expected poor and high-responders, and in those women at high risk of developing ovarian hyperstimulation syndrome (OHSS). Two meta-analyses showed a better outcome in terms of the live birth rate when highly purified human menopausal gonadotropin (HMG) was used for ovarian stimulation compared with recombinant follicle stimulating hormone (rFSH) in the GnRH agonist long protocol. One of the most efficient stimulation protocol is the use of a combined protocol of human derived urinary FSH (uFSH) and rFSH. Combined protocol has resulted in a significant increase in the proportion of mature metaphase II oocytes and grade 1 embryos when compared to either rFSH or uFSH alone. A significantly higher delivery rate was achieved in rFSH+uFSH compared to the other protocols in poor and normal responders. Studying the combination of melatonin with myo-inositol and folic acid has also showed a higher percentage of mature oocytes in the melatonin group and a higher percentage of G1 embryos as well. However, It remains a crucial step to confirm the efficacy of such protocols for clinical application and it is still needs to comparison studies on larger scale with more focused on the differences in patients' response criteria and additional confounding variables, in order to draw more defined conclusions