Marialuisa Framarino-dei-Malatesta

Impact of mTOR-I on fertility and pregnancy: state of the art and review of the literature

Successful transplantation should lead to improvements in sexual function and sex hormone disturbances in both men and women, but immunosuppressive drugs may interfere with hormone metabolism. In this regard, several studies have showed a potential negative effect of mTOR inhibitors (mTORi) on male gonadal function, while their role in the female patients is not well documented in the literature. Successful pregnancy is possible after solid organ transplantation. The fetal effects of mTORi are still poorly defined but they seem not to represent an absolute contraindication for pregnancy. The aim of our study would be to review the impact of mTORi on fertility and pregnancy in order to have a clearer picture about their possible use after organ transplantation.

Outcome of pregnancy in Italian patients with primary sjogren syndrome

Objective. To investigate pregnancy and fetal outcomes in patients with primary Sjögren syndrome (pSS). Methods. An obstetric history of 36 women with established diagnosis of pSS at pregnancy was obtained from a multicenter cohort of 1075 patients. In a subgroup case-control analysis, 12 deliveries in patients with pSS were compared with 96 control deliveries. Results. Thirty-six women (31 with anti-SSA/Ro and/or anti-SSB/La antibodies) with an established diagnosis of pSS had 45 pregnancies with the delivery of 40 newborns. Two miscarriages, 2 fetal deaths, and 1 induced abortion were recorded. Mean age at the first pregnancy was 33.9 years; mean number of pregnancies was 1.25; 18/40 (45%) cesarean births were delivered; mean pregnancy length was 38.5 weeks (range 32–43), with 6 preterm deliveries. The mean Apgar score at 5 min was 8.9, mean birthweight was 2920 g (range 826–4060 g). Congenital heart block (CHB) occurred in 2/40 (5%) newborns. The reported rate of breastfeeding for at least 1 month was 60.5%. In 4/40 pregnancies (10%) a flare of disease activity was observed within a year from delivery. In the case-control subgroup analysis, 12 deliveries were compared with 96 controls and no significant differences were found. Conclusion. Patients with pSS can have successful pregnancies, which might be followed by a mild relapse. CHB was the only cause of death for offspring of mothers with pSS.

Quality of Sexual Life in Women with Primary Sjögren Syndrome

Objective. To assess the quality of sexual life of women with primary Sjögren syndrome (pSS) and to identify its correlations with disease activity and damage, quality of life, and mood disorders. Methods. The quality of sexual life of 24 women with pSS was assessed with the Female Sexual Function Index (FSFI). Twenty-four healthy women, matched by age and hormonal status, were enrolled as controls. Mood disorders and quality of life were investigated using the Hospital Anxiety and Depression Scale (HADS) and the Medical Outcomes Study Short Form-36. Patients underwent a gynecological visit with vaginal pH measurement, cervicovaginal swabs, and Pap smears. Disease activity and damage were assessed by the European League Against Rheumatism Sjögren syndrome disease activity and damage indexes. Results. Patients with pSS showed a pathological mean FSFI score (19.1 ± 7.33) significantly different from controls (p = 0.004), both in menstruating women (p = 0.006) and in menopausal women (p = 0.03). Major differences between the 2 groups were detected in dyspareunia (p < 0.005), lubrication (p = 0.006), desire (p = 0.004), and arousal (p = 0.018). The FSFI score was inversely correlated with age (p = 0.008) and anxiety HADS (p = 0.031). No early anatomical changes, swabs, and Pap smear alterations were revealed in patients with pSS; however, vaginal pH was higher than normal in premenopausal patients (6.0 ± 0.77). Conclusion. Both premenopausal and postmenopausal women with pSS have a worse sexual quality of life. We reported a greater prevalence of dyspareunia that is statistically significant when compared with controls. The FSFI could be a useful tool to assess this topic, but has been neglected in the care of patients with pSS heretofore.

Stone disease in pregnancy: imaging-guided therapy

AbstractRenal colic is the most frequent nonobstetric cause for abdominal pain and subsequent hospitalization during pregnancy. The physio-anatomical changes in the urinary tract and the presence of the fetus may complicate the clinical presentation and management of nephrolithiasis. Ultrasound (US) is the primary radiological investigation of choice. Magnetic resonance urography (MRU) and low-dose computed tomography (CT) have to be considered as a second- and third-line test, respectively. If a study that uses ionizing radiation has to be performed, the radiation dose to the fetus should be as low as possible. The initial management of symptomatic ureteric stones is conservative during pregnancy. Intervention will be necessary in patients who do not respond to conservative measures. Therefore, it is crucial to obtain a prompt and accurate diagnosis to optimize the management of these patients. Teaching Points • In pregnancy, renal colic is the most frequent nonobstetric cause for abdominal pain and hospitalization. • Magnetic resonance urography should be considered when ultrasound is nondiagnostic. • Low-dose CT should be considered as a last-line test during pregnancy.

Breast cancer during pregnancy: a retrospective study on obstetrical problems and survival.

OBJECTIVES Breast cancer is one of the most common cancers occurring in pregnancy. Data on survival of these patients and their obstetrical complications are still limited. STUDY DESIGN We conducted a case-control, retrospective study to evaluate the overall survival (OS) of 22 patients with breast cancer in pregnancy (BCP) and 45 non-pregnant women with breast cancer (BC) matched for age, stage and hormonal status. RESULTS Survival of BCP and BC patients using Kaplan-Meier analysis was similar (86.4% in cases and 80% in controls p=0.392) and BCP patients had survival consistent with the stage of the disease, providing that the treatment had been in agreement with the recommended protocols. The overall incidence of premature delivery was 54.6% and complications were observed in three newborns out of 23 (13%). CONCLUSIONS Preterm labor induction without any obstetrical indication following womans request to continue chemotherapy outside pregnancy can be reduced by explaining the risks of early delivery and the lack of effects of many chemotherapeutic regimens on the fetus.

Evaluating the Acute Abdomen in the Pregnant Patient

Acute abdominal pain in pregnancy presents diagnostic and therapeutic challenges. Ultrasound remains the primary imaging investigation of the pregnant abdomen because of its availability, portability, and lack of ionizing radiation. MR imaging has been shown to be useful in the diagnosis of gynecologic and obstetric problems and in the setting of acute abdomen during pregnancy. MR imaging is often used when ultrasound is inconclusive. Computed tomography is the investigation of choice when there is a life-threatening situation and in case of traumatic injuries, when a rapid diagnosis is required.

Breast cancer or metastasis? An unusual case of metastatic malignant pleural mesothelioma to the breast

BackgroundMetastases to the breast from extramammary malignancies are very rare, and ruling out the diagnosis of primary breast tumor is important in order to decide on clinical management and predict prognosis.Case presentationClinical examination revealed in a 49-year-old hairdresser a 3-cm hard lump adherent to the underlying layers in the right breast. Trucut biopsy was performed. Histology showed a solid proliferation of medium-sized neoplastic polygonal cells. Immunohistochemical analysis showed tumor cells diffusely positive for cytokeratin 8/18 and calretinin and focally positive for cytokeratin 5/6 and Wilms’ tumor 1, e-cadherin, and human bone marrow endothelial-1. Estrogen receptors and progesterone receptors were negative. The final diagnosis was metastatic epithelioid malignant pleural mesothelioma.ConclusionsImmunohistochemistry is an important tool for a conclusive diagnosis of malignant pleural mesothelioma. Owing to the degree of histological and immunohistochemical overlap, a high level of clinical suspicion is essential in order to avoid unnecessary mutilating surgery.

Transabdominal ultrasound‐guided injection of methotrexate in the treatment of ectopic interstitial pregnancies

In a retrospective observational study, we evaluated the feasibility and safety of medical therapy with transabdominal ultrasound‐guided injection of methotrexate (MTX) into the gestational sac (GS) in patients with interstitial ectopic pregnancies.

Does anthracycline-based chemotherapy in pregnant women with cancer offer safe cardiac and neurodevelopmental outcomes for the developing fetus?

BackgroundCancer treatment during pregnancy is a growing problem especially now that women delay childbearing. Systemic treatment of these malignancies during pregnancy centers mainly on the anticancer drugs anthracyclines, widely used in treating hematological and breast cancer during pregnancy and sometimes associated with early and late toxicity for the fetus. Owing to concern about their cardiac and neurodevelopmental toxicity more information is needed on which anthracycline to prefer and whether they can safely guarantee a cardiotoxicity-free outcome in the fetus.DiscussionThe major research findings underline anthracycline-induced dose-dependent effects, including cardiotoxicity, many avoidable. Partly because the placenta acts mainly as a barrier, research findings indicate low transplacental anthracycline transfer. Anthracycline-induced teratogenicity depends closely on when patients receive chemotherapy. Anthracycline cardiac toxicity may depend on the association with drugs that inhibit or induce placental P-glycoprotein (P-gp). P-gp-induced drug interactions may alter placental P-gp barrier function and subsequently change fetal exposure. Though many anthracyclines have acceptable safety profiles clinical studies suggest giving idarubicin with special caution. Patients and doctors who care for pregnant women should whenever possible avoid prematurity and hence reduce prematurity-induced medical complications at birth and in the long-term. Information is lacking on long-term anthracycline-induced effects.ConclusionPregnant women receiving anthracycline-based chemotherapy should undergo regular, state-of-the-art diagnostic imaging to detect fetal drug-induced cardiac damage early, and allow alternative therapeutic options. Recognizing drug-induced interactions and understanding the most vulnerable fetuses will help in choosing tailored therapy. Future research on placental transport, blood-brain barrier drug passage and pharmacokinetics will improve the way we manage these difficult-to-treat patients and their fetuses.

Placental, Lipid, and Glucidic Effects of Mammalian Target of Rapamycin Inhibitors: Impact on Fetal Growth and Metabolic Disorders During Pregnancy After Solid Organ Transplantation

BACKGROUND Mammalian target of rapamycin inhibitors (mTORi) are a promising new family of immunosuppressive drugs. No teratogenic effects have been reported to date. Their lipid and glucidic effects should not be underestimated, however, especially during pregnancy. Moreover, mTORi may affect fetal growth by mTOR placental activity. OBJECTIVE Our purpose was to highlight mTORi placental impact and metabolic implications to detect possible maternal or fetal effects and define management guidelines in pregnant women after solid organ transplantation. METHODS A literature search was performed for articles from the Medline and Pubmed databases with the use of the following keywords: mTOR inhibitors, pregnancy, placental transport, lipid metabolism, glucose metabolism. RESULTS mTOR works as a positive regulator of system A, system L, and taurine placental amino acid transporter activity, which are critical for the transport of amino acids to the fetus. Exposing trophoblast cells to rapamycin reduces system L activity; therefore, treatment with rapamycin in human pregnancies could alter fetal growth with intrauterine growth restriction (IUGR). Regarding the metabolic effects mTORi increase lipolysis, impair insulins antilipolytic effect and reduce lipid storage, which may potentially contribute to dyslipidemia. Chronic rapamycin treatment reduces adipose tissue size and β-cell mass/function, causes hyperlipidemia, severe insulin resistance, and glucose intolerance, and promotes hepatic gluconeogenesis. CONCLUSIONS The studies on mTORi treatment in transplanted pregnant women have not focused to date on the potential metabolic and placental effects. Selection of women at high risk for metabolic disorders could be needed and consideration of switching to another immunosuppressive drug required if diabetes and abnormal blood lipids have been diagnosed in prepregnancy counseling. It seems to be mandatory to encourage prompt reporting of any additional cases of pregnancy during mTORi exposure to provide a better understanding of the placental effects and safety profile of these immunosuppressive drugs.