"Lazarus Response" When Feto-Maternal Microchimerism Kicks in: Spontaneous Remission in Refractory Primary Mediastinal B Cell Lymphoma Following Twin Pregnancy.

Background: Spontaneous remission of cancer is a rare and poorly understood phenomenon characterized by complete or partial remission of a malignancy in the absence of or with inadequate treatment. The underlying mechanism for such occurrences is poorly understood, however, immune mechanisms seem to play an important role in such cases. In recent years increasingly more data have become available in favor of the clinical benefit of low levels of chimerism in hematologic malignancies. One such instance of naturally occurring low-level chimerism is feto-maternal microchimerism which has been shown to influence cancer progression and, in some instances, to be a protective factor against malignancy. Case report: We report a case of a young female patient with aggressive primary mediastinal large B cell lymphoma refractory to two lines of chemo-immunotherapy achieving sustained complete metabolic remission of tumor while pregnant with twins. Results: A focus on feto-maternal microchimerism during and after pregnancy revealed transient levels of feto-maternal microchimerism in the peripheral blood of the patient as measured by quantifying the Y-chromosome-linked SRY gene. Conclusions: Microchimerism presents significant potential for enhancing our comprehension of disease mechanisms, uncovering novel therapeutic targets, and refining diagnostic and treatment approaches, especially concerning cancer.

Exploring Patient Adherence to Post-Surgical Follow-Up in Pelvic Endometriosis.

Endometriosis is a significant cause of disability that affects 5-10% of reproductive-aged women. Laparoscopy with histological confirmation is the gold standard in establishing the diagnosis as therapeutic management surgery is addressed to a certain category of patients. The objective of this study was to assess patient adherence to follow-up after surgery for endometriosis as the primary endpoint, pain symptoms, quality of life, mental health, and fertility as the secondary endpoints. We have analyzed patients' adherence to follow-up after surgery for endometriosis after 1, 3, 5, and 7 years. Out of the 2538 total number of surgeries, 453 patients replied just to the first questionnaire (group A), 528 to the first and second (group B), and only 356 carried out the entire follow-up schedule. General health was significantly lower for group A (46.6 vs. 56.4) but with no statistical difference in the post-surgical improvement in both groups. Pain level score improvement was lower for group A (10.5 vs. 18.8), which is statistically significant. In this light, laparoscopy still remains the gold standard in diagnosis only. Furthermore, no malignancy was discovered. The mental component was improved by laparoscopy based on SF-36 in group B. Studies on patient preference for surgery versus alternative treatment are needed.

The added value of CA125, HE4, and CA72-4 as markers for ovarian endometriosis diagnosis.

OBJECTIVE: This study aimed to evaluate the prognostic value as diagnosis makers of cancer antigen (CA)125, human epididymis 4 (HE4), and CA72-4 serum levels in ovarian endometriosis (OvEndo). PATIENTS, MATERIALS AND METHODS: The serum levels of CA125, HE4, and CA72-4 were measured using enzyme-linked immunosorbent assay (ELISA) technique for a group of 29 cases of OvEndo and a control (CTR) group of 26 cases. RESULTS: Results were compared between groups and statistical correlation was analyzed between the three biomarkers. (i) For CA125, we found a statistically significant difference in-between the mean serum levels of the two groups: 9.02 U∕mL in the OvEndo group versus 7.1 U∕mL in the CTR group (p=0.0158). (ii) A similar situation was found for CA72-4 levels in OvEndo group, where the mean serum level was 6.1 U∕mL compared to 3.5 U∕mL in the CTR group, showing a significant difference (p=0.0185). (iii) The mean serum level of HE4 in the OvEndo group was 7.6 ng∕mL versus 7.8 ng∕mL in the CTR group, and we found it highly significant (p=0.0001). HE4 levels were highly correlated with CA72-4 levels (p<0.0001), while CA125 levels were not correlated with HE4 and CA72-4. CONCLUSIONS: Measurements of CA125 can be used in the diagnosis of OvEndo mainly in association with HE4 serum levels, which are lower in endometriosis patients. CA72-4 levels are highly correlated with HE4 levels in patients with OvEndo, while no correlation with the other two markers was found. This correlation needs further investigation to establish if it may be used as a possible diagnostic tool in clinical practice.

Hormonal, apoptotic, proliferative and inflammatory markers' expression in Desogestrel-treated women with ovarian endometriosis.

Endometriosis is a relatively frequent pathology in gynecological practice. We performed an analysis to demonstrate the molecular changes that occur in endometriosis synthetic progestin-treated patients, hoping to sketch a possible pathophysiological pathway that will help us to better understand and treat this debilitating disease. We conducted a prospective study that included a group of 40 women, evaluated in our hospital between 2020-2021. We evaluated immunohistochemical tissue expression of estrogen receptor (ER), progesterone receptor (PR), B-cell lymphoma 2 (Bcl-2) protein, Ki-67, and serum levels of osteopontin (OPN) and vascular endothelial growth factor (VEGF) in patients with ovarian endometrioma with and without progestin treatment. Our study revealed that Desogestrel treatment increases OPN serum levels, PR and Bcl-2 tissue expression and reduces VEGF serum levels and Ki-67 tissue expression. The results we have obtained are very interesting because the serum levels of OPN seem to be more influenced by progestin treatment, than by endometriosis itself. The study we have conducted gives a molecular complex view of what endometriosis represents and on how Desogestrel treatment works.

The added value of three-dimensional ultrasonography in uterine pathology.

The rapid development achieved over the last decades in volume rendering of ultrasound data, known as three-dimensional (3D) ultrasound technique, leads to new opportunities for refining the diagnosis in many gynaecologic conditions. The aim of the present study was to evaluate the advantages of 3D ultrasound over two-dimensional (2D) ultrasound in uterine pathology and to establish the optimal time point during the menstrual cycle to perform 3D ultrasound examination in order to achieve the maximum of useful information. A cross-sectional study on 200 patients who underwent gynaecologic 2D and 3D ultrasound examinations was performed. The addition of 3D examination to 2D ultrasound in uterine pathology provided the most useful information concerning: Congenital uterine anomalies, intrauterine devices (IUDs), adenomyosis, and submucous myomas. The findings showed that the 3D ultrasound scan is a useful tool in gynaecology, especially in cases with congenital uterine anomalies, myoma, and IUD. Although initially it was used for research purposes only, recent findings suggest its usefulness in routine ultrasound scan and the possibility of witnessing its introduction as a recommended examination procedure in the foreseeable future. Further research should be conducted in order to establish the sensitivity of 3D ultrasound in the detection of minor endometrial conditions, by correlating the imaging findings with the hysteroscopic results.

Ovarian Cancer: Biomarkers and Targeted Therapy.

Ovarian cancer is one of the most common causes of death in women as survival is highly dependent on the stage of the disease. Ovarian cancer is typically diagnosed in the late stage due to the fact that in the early phases is mostly asymptomatic. Genomic instability is one of the hallmarks of ovarian cancer. While ovarian cancer is stratified into different clinical subtypes, there still exists extensive genetic and progressive diversity within each subtype. Early detection of the disorder is one of the most important steps that facilitate a favorable prognosis and a good response to medical therapy for the patients. In targeted therapies, individual patients are treated by agents targeting the changes in tumor cells that help them grow, divide and spread. Currently, in gynecological malignancies, potential therapeutic targets include tumor-intrinsic signaling pathways, angiogenesis, homologous-recombination deficiency, hormone receptors, and immunologic factors. Ovarian cancer is usually diagnosed in the final stages, partially due to the absence of an effective screening strategy, although, over the times, numerous biomarkers have been studied and used to assess the status, progression, and efficacy of the drug therapy in this type of disorder.

Can Anorectal Atresia Be Diagnosed in the First Trimester of Pregnancy? A Systematic Literature Review.

Anorectal atresia (ARA) is a common congenital anomaly, but prenatal diagnosis is difficult, late, and unspecific. Utilizing a case of a 46 year old primipara with an egg donation In Vitro Fertilization (IVF) pregnancy, diagnosed at the first trimester scan with an anechoic isolated structure, which indicates anal atresia, we performed a systematic literature review in order to evaluate early prenatal ARA diagnosis. A total of 16 cases were reported as first trimester ARA suspicion, and only three had no associated anomalies. The most frequent ultrasound (US) sign was the presence of a cystic, anechoic pelvic structure of mainly tubular shape, or a plain abdominal cyst. In the majority of cases, structures were thin-walled and delimitated from the bladder. The presence of hyperechoic spots signifying enterolithiasis and peristaltic movements were helpful in order to establish the bowel origin of the lesion. Considering the high eventuality that the lesion is transitory, meaning later in pregnancy the fetus looks normal, early detection of such a sign should prompt further structural detailed evaluation, karyotyping, and appropriate pregnancy and postnatal counselling.

Logistic models and artificial intelligence in the sonographic assessment of adnexal masses - a systematic review of the literature.

Adnexal masses are common, yet challenging, in gynecological practice. Making the differential diagnosis between their benign and malignant condition is essential for optimal surgical management, but reliable pre-surgical differentiation is sometimes difficult using clinical features, ultrasound examination, or tumor markers alone. A possible way to improve the diagnosis is using artificial intelligence (AI) or logistic models developed based on compiling and processing clinical, ultrasound, and tumor marker data together. Ample research has already been conducted in this regard that medical practitioners could benefit from. In this systematic review, we present logistic models and methods using AI, chosen based on their demonstrated high performance in clinical practice. Although some external validation of these models has been performed, further prospective studies are needed in order to select the best model or to create a new, more efficient, one for the pre-surgical evaluation of ovarian masses.

Pregnancy Outcomes in Couples with Males Exposed to Longterm Anti-tumor Necrosis Factor-α Inhibitor Therapies: A Prospective Study.

OBJECTIVE: To examine the pregnancy achievement and outcomes in couples in which men with spondyloarthritis (SpA) were exposed to tumor necrosis factor inhibitors (TNFi). METHODS: Information about pregnancies involving fathers with SpA was prospectively collected by 6 Romanian rheumatology centers. RESULTS: Twenty-seven patients achieved 33 pregnancies and fathered 30 healthy children. Three elective abortions (personal reasons) and no spontaneous abortions, preeclampsia/eclampsia, stillbirths, congenital malformations, or pathologies in the children were recorded. Five patients showed normospermia before and after longterm TNFi treatment. CONCLUSION: Pregnancy and child outcomes in male patients with SpA exposed to longterm TNFi therapy were reassuring.

Patency of uterine wall in pregnancies following assisted and spontaneous conception with antecedent laparoscopic and abdominal myomectomies - a difficult case and systematic review.

A case of uterine rupture at 24 weeks in a pregnancy succeeding myomectomy and triple embryo transfer is described and literature is reviewed systematically to evaluate the importance of uterine rupture in pregnancies after myomectomy in general and some important sub-populations. Systematic search identified 179 papers and following a strategical selection process 45 studies were analyzed in detail, including 6 cohort and 19 observational studies, 3 case series and 17 case reports. Comparison of risk of uterine rupture after abdominal and laparoscopic myomectomy is made. In pregnancies after IVF number of embryos transferred are determined. Optimal contraceptive intervals and surgical techniques are discussed. The consequences of these observations are analyzed and conclusions are made which can assist individualizing treatment options and improve patient selection.

Fertility preservation in Hodgkin's lymphoma patients that undergo targeted molecular therapies: an important step forward from the chemotherapy era.

In total, 80%-90% of Hodgkin's lymphoma (HL) patients are curable with combination chemoradiotherapy. Due to improvements in therapeutic strategies, 50% of all relapsed/refractory patients may undergo complete clinical responses and have long-term survival. Treatment options for HL are effective, but may have a negative impact on post-chemotherapy fertility. Thus, cryopreservation of semen prior to treatment is recommended for male patients. For female patients, assisted reproductive techniques (ART) consult and fertility preservation should be offered as a therapeutical option. In the last years, new targeted molecules have been available for HL treatment. These new drugs showed a high rate of overall responses in the setting of heavily pretreated patients, most of them in relapse after autologous stem cell transplantation, a group previously considered very poor risk. Up to 50% of patients have a complete response and an improved overall survival. Future studies will address the usefulness of novel molecules as a frontline therapy. Considering the high response and survival rates with monoclonal antibody-based therapeutics, fertility has become a concerning issue for long-term HL survivors. As progress has been made regarding ART, with the rigorous steps planned for HL patients, more survivors will become parents.

Ultrasound and magnetic resonance imaging in the prenatal diagnosis of open spina bifida.

Open spina bifida, also known as spina bifida aperta is a neural tube defect involving the lack of closure of vertebral arches and associated meninges and/or spinal cord abnormalities.Ultrasound examination is the gold standard for the diagnosis of spina bifida aperta. It represents the main imaging tool used to ascertain this diagnosis early in gestation. Three-dimensional ultrasound is necessary to detect the level and the size of the defect. Magnetic resonance imaging (MRI) represents a more sensitive tool, giving specific information of the defect and associated anomalies, playing an important role in ruling out differential diagnosis. Due to the advent of MRI use, it is possible today to achieve in utero treatment of fetuses with this pathology. The aim of the current review is to provide an update of literature regarding the role of ultrasound and MRI in the prenatal diagnosis of spina bifida aperta.

Detection and scavenging of hydroxyl radical via D-phenylalanine hydroxylation in human fluids.

Hydroxyl radical (.OH) is highly reactive, and therefore very short-lived. Finding new means to accurately detect .OH, and testing the ability of known .OH scavengers to neutralize them in human biological fluids would leverage our ability to more effectively counter oxidative (.OH) stress-mediated damage in human diseases. To achieve this, we pursued the evaluation of secondary products resulting from .OH attack, using a detection system based on Fenton reaction-mediated D-phenylalanine (D-Phe) hydroxylation. This reaction in turn generates o-tyrosine (o-tyr), m-tyrosine (m-tyr) and p-tyrosine (p-tyr). Here, these isomers were separated by HPLC, equipped with fluorescence detectors due to the natural fluorescence of these hydrotyrosines. By extension, we found that, adding radical scavengers competed with D-Phe on .OH attack, thus allowing to determine the .OH quenching capacity of a given compound expressed as inhibition ratio percent (IR%). Using a kinetic approach, we then tested the .OH scavenging capacity (OHSC) of well-known antioxidant molecules. In a test tube, N,N'-dimethylthiourea (DMTU) was the most efficient scavenger as compared to Trolox and N-Acethyl-L-cysteine, with NAC being the less effective. OHSC assay was then applied to biological fluid samples as seminal plasma, human serum from normal subjects and patients undergoing hemodialysis (HD), colostrum and human breast milk from mothers that received daily doses of 30g of chocolate (70% cocoa) during pregnancy. We found that a daily administration of dark chocolate during pregnancy almost doubled OHSC levels in breast milk (1.88 ± 0.12 times, p < 0.01). Furthermore, HD treatment determined a significant reduction of serum OHSC concentration (54.63 ± 2.82%, p < 0.001). Our results provide evidence that Fenton reaction-mediated D-Phe hydroxylation is a suitable method for routine and non-invasive evaluation of .OH detection and its scavenging in human biological fluids.

Current strategies and future perspectives in fertility preservation for cancer patients.

Nowadays, cancer is being detected at younger ages. Health care providers should consider cancer patients' desire towards fertility preservation before the initiation of possibly sterilizing treatments. The aim of the current review was to register the current state of fertility preservation procedures available for male and female cancer patients.

Schwannoma of the median nerve mimicking carpal tunnel syndrome in a pregnant patient. Case report.

In patients with symptoms of a peripheral neuropathy especially during pregnancy, use of imaging techniques such as Ultrasound (US) and Magnetic Resonance Imaging (MRI) may be essential for the diagnostic accomplishment. A 30-weekspregnant diabetic female attending US evaluation due to intermittent hand pain, numbness, and weakness bilaterally. Although, the US evaluation revealed the median nerve (MN) normal size, echogenicity and echo-texture within the right carpal tunnel; the US assessment applied proximally to the carpal tunnel, revealed a hypoechoic tumor-like mass and increased MN cross section area. In transverse view, the MN was detected as an eccentric, hypoechoic structure compressed by the aforementioned mass. A presence of MN schwannoma or neurofibroma was suspected. US has been proved to be extremely useful to determine location, extent as well as the type of nerve lesion.

TNF-α inhibitors do not impair sperm quality in males with ankylosing spondylitis after short-term or long-term treatment.

OBJECTIVE: The aim of this study was to study the influence of active disease status and TNF-α antagonists on sperm quality in a group of AS patients. METHODS: Twenty-three active AS patients and 42 controls were recruited. Patients' sperm samples were analysed at baseline (previous to) and at 3-6 months after TNF-α therapy (adalimumab, infliximab, etanercept) administration. Baseline assessment was made for only 20 patients, 2 of them proving to have normal fertility, 2 having a pregnant stable partner and the third having a 9-month-old child. Six patients were retested after 12 months of biologic therapy. Each patient acted as his own comparator. Results were further compared with sperm samples from age-matched controls. Sperm analysis was performed according to the World Health Organization (WHO) 1999 guidelines. RESULTS: Patients' baseline assessment showed normozoospermia in 91% and oligozoospermia in 9% of patients. No significant differences in sperm quality were noticed at follow-up visits compared with baseline. Comparison to controls showed no statistically significant differences in semen quality, with some exceptions: the control group presented a higher percentage of non-progressive and immobile sperm cells and higher numbers of head and tail atypias. CONCLUSION: Sperm quality in patients with active AS and after receiving short- and long-term TNF-α blocker therapy is comparable to sperm quality in healthy controls. Our study confirms that the disease process of AS does not have a major impact on sperm quality and that treatment with anti-TNF has no negative impact on sperm quality even under long-term treatment.