COVID-19, liver transplant, and immunosuppression: Allies or foes?

Liver transplant (LT) recipients are considered at a particularly high risk for developing critical COVID-19 infection. To date, available data are heterogeneous and scarce and mortality in LT recipients seems to be higher compared to normal population, but whether this is caused by altered immunological status, immunosuppression (IS), or underlying comorbidities has not yet been fully clarified. Some evidences show that IS might play a role in the pathophysiology of this new disease. We searched all available data regarding LT recipients infected by COVID-19, focusing on the role of IS. To date, 244 LT recipients have been reported as COVID-19-positive. Trends among transplant physicians are to reduce overall IS, especially antimetabolite drugs, but the current available observations are still not enough to build strong evidences for recommendation and IS should be meticulously tailored case by case.

Pregnancy in women with physical and intellectual disability: psychiatric implications.

Women with disabilities feel the desire for motherhood as much as women without special clinical needs. Their fertility is often not impacted by disability and they can have children. However, several issues must be considered, depending on the physical, mental or developmental disability. Women with a physical disability often experience higher risks of caesarean section, preterm birth, growth restriction and low birth weight when compared to controls. Women with intellectual or developmental disabilities are often young, unmarried, unemployed and have limited access to care. They often struggle following instructions or recognizing the conditions that require medical help. They are more likely to experience preeclampsia, diabetes, venous thromboembolism, cesarean delivery, infant low birth weight, preterm birth, neonatal intensive care unit admission, and perinatal death. Moreover, an association between psychiatric morbidity and alcohol abuse was proved by several pieces of evidence and it can cause serious damage to fetus and newborn causing Fetal Alcohol Spectrum Disorders. Fetus and the newborn of disabled mothers are exposed to specific risks depending on the mother's conditions: the main risk fetuses are exposed to during pregnancy is exposure to drugs and therapies which cannot be suspended and whose effects over pregnancy are not known. Moreover, some conditions causing maternal disability could elevate the risk for the baby to be similarly affected. It is important that both women and men with disabilities could be provided with accurate, accessible, and understandable information about sexual health and options regarding contraception and reproduction. It's important for women with disabilities to have the chance to discuss sexual matters, pregnancy desires and concerns with healthcare providers so they can provide appropriate screenings, contraceptive services, preconception, and prenatal care. Among healthcare providers, midwives are the frontline healthcare professionals who have the role, the possibility and the education to perform influential counseling on women about lifestyles and reproductive health.

Metastases to extraocular muscles from breast cancer: case report and up-to-date review of the literature.

BACKGROUND: Unilateral or bilateral metastases to extraocular muscles are very rare in breast cancer. CASE PRESENTATION: We describe a case of inferior rectus extraocular muscle involved by ductal luminal B/Her-2 neu negative breast cancer, observed in a cohort of 580 patients. Our patient had received chemotherapy and hormonal therapy (tamoxifen for 3 years and letrozole in the following 3 years) for her primary cancer and developed an orbital metastasis while she was under aromatase inhibitor-based therapy. Diagnosis was confirmed by MRI and biopsy. Orbital radiotherapy, combined with fulvestrant, resulted in shrinking of the secondary mass. A third line hormonal therapy using palbociclib was then started. Twelve-months later, MRI showed no residual tumor mass. Currently, the patient is alive and in good general conditions after 20 months. CONCLUSIONS: Literature review yielded 57 patients with extraocular muscle metastases from breast cancer, mostly due to the invasive lobular subtype of carcinoma. In addition to the present case, only 4 other extraocular muscles metastases from invasive ductal carcinoma has been reported, pointing out to the rarity of ductal type spread to the orbit in the natural history of breast cancer. Surgery may be used as a single treatment, despite no improvement of symptoms. Radiotherapy alone or combined with chemotherapy, or with chemotherapy plus hormonal therapy are available options. Results are, however, missing or poor. The present case is the first one with complete and stable response after 20 months to radiotherapy, antiestrogen drug fulvestrant and selective inhibitor of CDK4 /CDK6 palbociclib. In this subset of patients, with unusual metastatic sites and frequent multi-organ metastatic impairment, a multidisciplinary approach is indicated in order to achieve the best therapeutic management and long-term surveillance.

To evaluate the feasibility of magnetic resonance imaging in predicting unusual site ectopic pregnancy: a retrospective cohort study.

OBJECTIVE: To evaluate the accuracy of pelvic MRI in the diagnosis of unusual ectopic pregnancy (EP), when ultrasound (US) examination is inconclusive. METHODS: We retrospectively reviewed the medical records of 150 patients with suspected EP. Clinical, US and MRI features of 15 unusual EPs were analysed. Two radiologists independently reviewed each case resolving by consensus any diagnostic discrepancy. Interobserver agreement was assessed using the Cohen κ test. RESULTS: MRI displayed a gestational sac-like structure surrounded by a thick wall in all cases. The thick wall displayed hyperintensity in 41 %, isointensity in 35 % and hypointensity in 24 % of cases on T1-weighted images. Diffusion- and fat saturation T1-weighted images were the most accurate sequences, as they enabled identification of 15/15 and 14/15 patients, respectively. Although US was false negative in detecting cervical and uterine infiltration underlying the caesarean scar, MRI was able to identify the invasion. Interobserver agreement was very good for all sequences (κ=0.892-1.0). CONCLUSIONS: MRI plays an important role in the early diagnosis of unusual EP. It should be considered after negative US findings, providing accurate evaluation of the site and the possible infiltration of these lesions, which help in the management of these patients. KEY POINTS: • MRI is being increasingly used as a problem-solving modality in ectopic pregnancy. • MRI plays an important role in early diagnosis of unusual ectopic pregnancy. • Knowledge of MRI features in EP is essential to determinate appropriate management.

Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Patients with Peritoneal Metastases from Endometrial Cancer.

BACKGROUND: More information is needed for selection of patients with peritoneal metastases from endometrial cancer (EC) to undergo cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: This study analyzed clinical, pathologic, and treatment data for patients with peritoneal metastases from EC who underwent CRS plus HIPEC at two tertiary centers. The outcome measures were morbidity, overall survival (OS), and progression-free survival (PFS) during a median 5 year follow-up period. Uni- and multivariate analyses were performed to identify significant factors related to outcome. RESULTS: A total of 33 patients met the inclusion criteria and completed the follow-up period. At laparotomy, the median peritoneal cancer index (PCI) was 15 (range 3-35). The CRS procedure required a mean 8.3 surgical procedures per patient, and for 22 patients (66.6%), a complete cytoreduction was achieved. The mean hospital stay was 18 days, and major morbidity developed in 21% of the patients. The operative mortality was 3%. When surgery ended, HIPEC was administered with cisplatin 75 mg/m2 for 60 min at 43 °C. During a median follow-up period of 73 months, Kaplan-Meier analysis indicated a 5 year OS of 30% (median 33.1 months) and a PFS of 15.5% (median 18 months). Multivariate analysis identified the completeness of cytoreduction (CC) score as the only significant factor independently influencing OS. Logistic regression for the clinicopathologic variables associated with complete cytoreduction (CC0) for patients with metachronous peritoneal spread from EC who underwent secondary CRS plus HIPEC identified the PCI as the only outcome predictor. CONCLUSIONS: For selected patients with peritoneal metastases from EC, when CRS leaves no residual disease, CRS plus HIPEC achieves outcomes approaching those for other indications such as colon and ovarian carcinoma.

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

BACKGROUND: Cancer 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. DISCUSSION: The 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. CONCLUSION: Pregnant 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.

Epirubicin: a new entry in the list of fetal cardiotoxic drugs? Intrauterine death of one fetus in a twin pregnancy. Case report and review of literature.

BACKGROUND: Current knowledge indicate that epirubicin administration in late pregnancy is almost devoid of any fetal cardiotoxicity. We report a twin pregnancy complicated by breast cancer in which epirubicin administration was causatively linked to the death of one twin who was small for gestational age (SGA) and in a condition of oligohydramnios and determined the onset of a transient cardiotoxicity of the surviving fetus/newborn. CASE PRESENTATION: A 38-year-old caucasic woman with a dichorionic twin pregnancy was referred to our center at 20 and 1/7 weeks for a suspected breast cancer, later confirmed by the histopathology report. At 31 and 3/7 weeks, after the second chemotherapy cycle, ultrasound examination evidenced the demise of one twin while cardiac examination revealed a monophasic diastolic ventricular filling, i.e. a diastolic dysfunction of the surviving fetus who was delivered the following day due to the occurrence of grade II placental abruption. The role of epirubicin cardiotoxicity in the death of the first twin was supported by post-mortem cardiac and placental examination and by the absence of structural or genomic abnormalities that may indicate an alternative etiology of fetal demise. The occurrence of epirubicin cardiotoxicity in the surviving newborn was confirmed by the report of high levels of troponin and transient left ventricular septal hypokinesia. CONCLUSION: Based on our findings we suggest that epirubicin administration in pregnancy should be preceded by the screening of some fetal conditions like SGA and oligohydramnios that may increase its cardiotoxicity and that, during treatment, the diastolic function of the fetal right ventricle should be specifically monitored by a pediatric cardiologist; also, epirubicin and desamethasone for lung maturation should not be closely administered since placental effects of glucocorticoids may increase epirubicin toxicity.

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.

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.

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

BACKGROUND: Metastases 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 PRESENTATION: Clinical 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. CONCLUSIONS: Immunohistochemistry 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.

Stone disease in pregnancy: imaging-guided therapy.

Renal 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.

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

PURPOSE: 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. METHODS: Fourteen interstitial ectopic pregnancies were treated with transabdominal ultrasound-guided injection of MTX (25 mg). All patients were hemodynamically stable. In all patients, the 10-cm distance between the GS and vaginal fornices was ≥10 cm, making transvaginal injection difficult. To evaluate feasibility and safety of the procedure, we assessed complications clinically and with imaging during a 1-year follow-up. RESULTS: In all 14 patients, MTX injected locally into the GS successfully terminated the interstitial pregnancy, thereby avoiding surgery. There was no complications during follow-up. CONCLUSIONS: The successful outcome in our patients suggests that the transabdominal route is feasible and safe as a nonsurgical option for terminating an ectopic interstitial pregnancy in patients in whom the transvaginal route is contraindicated or difficult, provided the patients are properly selected and operators have sufficient experience with the technique.

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 woman's 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.

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 Sjögren 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.

Myopathy complicating lupus pregnancy.

Systemic lupus erythematosus was diagnosed in a 34-year-old pregnant woman because of leukopenia, typical skin rash, clinical and biochemical signs of muscle involvement, and positive serology (antinuclear antibodies and anti-double-stranded DNA). Corticosteroids and hydroxychloroquine (HCQ) were started at 18 weeks of gestation with overall benefit except for muscle involvement, which proved resistant even to higher dose of corticosteroids and high-dose intravenous immunoglobulin. Muscle biopsy showed signs of HCQ toxicity, and the drug was stopped. After withdrawal, muscle involvement disappeared. Hydroxychloroquine could be safely reintroduced some months after delivery. It is hypothesized that pregnancy may have represented the second "hit" in this patient with systemic lupus erythematosus necessary for the rapid development of HCQ-related myopathy.