COVID-19 infection in first trimester of pregnancy marked by a liver cytolysis in a woman previously treated by hydroxychloroquine for repeated implantation failure: a case report.

BACKGROUND: In December 2019, a new disease (COVID-19) caused by a novel coronavirus called SARS-CoV-2 emerged in China and spread to many other countries. There is only limited data about the clinical features of COVID-19 during pregnancy, especially in first trimester. CASE PRESENTATION: We report a COVID-19 infection in a 35 years-old patient in first trimester of pregnancy and its consequent medical care. At 7 weeks of pregnancy, the patient, who did not have any pregestational comorbidities, complained of intense nausea and asthenia. An important liver cytolysis was discovered with biological perturbations of transaminases levels. No respiratory symptoms were recorded. Classical viral aetiologies and drug-related toxicity were discarded. Because of the aggravation of the symptoms and the occurrence of the breathlessness, the patient was tested for the COVID-19 in a nasopharyngeal swab. The RTq-PCR assay indicated the presence of SARS-CoV-2 RNA. In the absence of severe symptoms, the patient was monitored at home according to the French government guidelines. After a few days, the symptoms resolved without any complications. The pregnancy is still ongoing without any visible sequelae on the foetus so far. CONCLUSIONS: This first case illustrated the difficulty of COVID-19 diagnosis in patients with isolated digestive symptoms in first trimester of pregnancy that could be confused with gravida hyperemesis. Monitoring of pregnancy after an episode of COVID-19 should be strengthened with bimonthly foetal growth ultrasounds and doppler assessments because of the risks for intrauterine growth restriction. Comprehensive data on larger numbers of first trimester gravid women with COVID-19 are required to better understanding the overall impact of SARS-CoV-2 on maternal and birth outcomes.

Prediction of tumor grade and lymphovascular space invasion in endometrial adenocarcinoma with MR imaging-based radiomic analysis.

PURPOSE: To evaluate the capabilities of two-dimensional magnetic resonance imaging (MRI)-based texture analysis features, tumor volume, tumor short axis and apparent diffusion coefficient (ADC) in predicting histopathological high-grade and lymphovascular space invasion (LVSI) in endometrial adenocarcinoma. MATERIALS AND METHODS: Seventy-three women (mean age: 66±11.5 [SD] years; range: 45-88 years) with endometrial adenocarcinoma who underwent MRI of the pelvis at 1.5-T before hysterectomy were retrospectively included. Texture analysis was performed using TexRAD® software on T2-weighted images and ADC maps. Primary outcomes were high-grade and LVSI prediction using histopathological analysis as standard of reference. After data reduction using ascending hierarchical classification analysis, a predictive model was obtained by stepwise multivariate logistic regression and performances were assessed using cross-validated receiver operator curve (ROC). RESULTS: A total of 72 texture features per tumor were computed. Texture model yielded 52% sensitivity and 75% specificity for the diagnosis of high-grade tumor (areas under ROC curve [AUC]=0.64) and 71% sensitivity and 59% specificity for the diagnosis of LVSI (AUC=0.59). Volumes and tumor short axis were greater for high-grade tumors (P=0.0002 and P=0.004, respectively) and for patients with LVSI (P=0.004 and P=0.0279, respectively). No differences in ADC values were found between high-grade and low-grade tumors and for LVSI. A tumor short axis≥20mm yielded 95% sensitivity and 75% specificity for the diagnosis of high-grade tumor (AUC=0.86). CONCLUSION: MRI-based texture analysis is of limited value to predict high grade and LVSI of endometrial adenocarcinoma. A tumor short axis≥20mm is the best predictor of high grade and LVSI.

Diagnosis of acute overt gastrointestinal bleeding with CT-angiography: Comparison of the diagnostic performance of individual acquisition phases.

PURPOSE: To compare the respective values of arterial phase, portal venous phase and combination of phases using 64-section multidetector computed tomography (MDCT) for diagnosing acute overt gastrointestinal bleeding (AOGIB). PATIENTS AND METHODS: Forty-nine patients with AOGIB were included. There were 30 men and 19 women, with a mean age of 65.4±15.6 (SD) years [range, 34-91years]. Two observers reviewed MDCT examinations in consensus for presence of active bleeding, location of bleeding site and nature of causative lesion. The different acquisition phases were reviewed independently. RESULTS: AOGIB was identified in 28/49 patients (57%) with the multiphasic set, in 26/49 patients (53%) with arterial phase and in 25/49 patients (51%) with portal venous phase. Multiphasic set helped locate the bleeding site in 40/49 patients (82%). The cause was elucidated in 23/49 patients (47%) with multiphasic set. The differences between set performances were not statistically significant. Sensitivity for depicting AOGIB with the multiphasic set was 92% and specificity was 76%. CONCLUSION: Multiphasic 64-section MDCT has high diagnostic performances in patients with AOGIB. Further studies with a larger population are needed to reach statistical significance and demonstrate better diagnostic performance of multiphasic MDCT in comparison with the arterial or portal phase alone.

[Impact of preoperative breast magnetic resonance imaging on surgical management: experience of two university hospitals]. / Impact de l'IRM mammaire préopératoire sur la prise en charge chirurgicale des cancers du sein: expérience de deux centres hospitaliers universitaires.

OBJECTIVES: Breast magnetic resonance imaging (MRI) has attained a solid position in the diagnosis of breast cancer but its benefit is still to be confirmed in the preoperative staging. The authors assessed the impact of preoperative breast MRI on surgical management of breast cancer in two university hospitals. PATIENTS AND METHODS: This retrospective review was realized in two university hospitals and concerned all patients with breast carcinoma who had a surgical first therapy. We selected 89 patients who underwent preoperative breast MRI in the period between January 2008 and December 2009. RESULTS: The sensitivity of breast MRI for detecting breast tumor was 95%. Fourteen percent of patients had a multifocal disease, 10% a multicentric disease and 2% a synchronous bilateral cancer. The correlation of radiological tumor size with histopathological size was r=0.68 in IRM compared to r=0.45 in conventional imaging (P<0.001). Nineteen additional biopsies were performed and 9.9% of false-positive findings were detected. Retrospectively, planned surgical management was altered in 9% of patients, resulted from use of breast MRI. Six patients had conversion of planned breast conservation to mastectomy and two patients underwent contralateral lumpectomy after discover synchronous bilateral cancer. DISCUSSION AND CONCLUSION: Breast MRI was very sensitive for the detection of breast carcinoma and improved local staging in almost 9% of patients. But, low specificity of this imaging requires a systematically validation of additional lesions by biopsy before surgical planning.

Evaluation and impact of residual disease in locally advanced cervical cancer after concurrent chemoradiation therapy: results of a multicenter study.

BACKGROUND: The aim of this study was to evaluate the diagnosis and impact of residual disease (RD) after concurrent chemoradiation therapy (CRT) in locally advanced cervical cancer (FIGO IB2-IVA). METHODS: This retrospective multicenter study included 159 patients who were treated with completion surgery after CRT between 2006 and 2012. Magnetic resonance imaging (MRI) was performed 4-6 weeks after CRT and compared to pathological evidence of residual disease. Kaplan-Meier survival curves were plotted and univariate/multivariate analyses were performed to assess the association between RD and the outcome. RESULTS: Residual disease was present in 45.3% of the patients and detected by MRI in 57.1%. The MRI had a 29.2% false positive rate and an 11.1% false negative rate. The overall survival (OS) rates at 3 and 5 years were 78.6% (CI 95% [71%-86.9%]) and 76.5% (CI 95% [68.2%-85.7%]), respectively. The disease free survival (DFS) rates at 3 and 5 years were 73.4% (CI 95% [65.6%-82%]) and 71.1% (CI 95% [62.7%-80.1%]), respectively. RD greater than 10 mm decreased DFS (HR = 4.84, p = 0.03), whereas RD between 1 and 10 mm (HR = 0.31, p = 0.58) and less than 1 mm (HR = 0.37, p = 0.54) had no impact on DFS. The OS was not changed by RD. DISCUSSION: The MRI accuracy value is not sufficient to select patients who might benefit from completion surgery. Residual disease over 10 mm decreased DFS but did not impact OS.

Efficacy and safety of transurethral alprostadil therapy in men with erectile dysfunction. MUSE Study Group.

OBJECTIVE: To examine the safety and efficacy of transurethral pharmacotherapy for erectile dysfunction, involving the use of a novel therapeutic system to administer alprostadil (prostaglandin E1) to the urethral mucosa in a double-blind, randomized, parallel, placebo-controlled study conducted in five countries in Europe. PATIENTS AND METHODS: In an outpatient setting, patients with primarily organic erectile dysfunction of at least 3 months' duration were treated with transurethral alprostadil, in an open-label, dose-escalating study. Testing stopped when the dose provided an erection sufficient for intercourse, as assessed by the patient and the investigator. Patients who achieved a sufficient response were then randomized to either active medication at the selected dose or to placebo for use at home for 3 months. After each home administration, patients recorded in diaries whether or not sexual intercourse occurred and any adverse reactions to the drug. RESULTS: A total of 249 patients were treated in an outpatient setting; of these patients, 159 (64%) achieved an erection sufficient for intercourse and were randomized (1:1) to either active medication or placebo for home treatment. Of the patients randomized to alprostadil for home treatment, 69% reported intercourse at least once, compared with 11% of patients randomized to placebo (P < 0.001). The most common adverse reaction, urethral pain/burning, was reported by 7% of patients in the clinic. Most patients (83%) graded transurethral alprostadil as causing minimal or no discomfort in the clinic. No patient reported priapism or developed penile fibrosis. CONCLUSION: Alprostadil delivered transurethrally by this system was well tolerated and effective in treating erectile dysfunction.

Erectile response to transurethral alprostadil, prazosin and alprostadil-prazosin combinations.

PURPOSE: Transurethral alprostadil has been shown to be efficacious in many men with erectile dysfunction. We compared transurethral alprostadil and prazosin alone, and in combination to treat this disorder. MATERIALS AND METHODS: In this double-blind, placebo controlled study the erectile responses to transurethral alprostadil, prazosin and alprostadil-prazosin combinations were assessed in 234 men 26.8 to 81.5 years old with complete organic erectile dysfunction. Patients self-administered a random sequence of 7 doses in the clinic in 4 weeks. The erectile response was assessed using categorical and visual analog scales. RESULTS: Full penile enlargement or rigidity was achieved by 165 of the 234 men (70.5%) after at least 1 active dose of medication. The most effective alprostadil dose (500 microg.) resulted in full penile enlargement or rigidity in 51.8% of administrations, whereas the most effective prazosin dose (2,000 microg.) and placebo resulted in a similar response in 12.7 and 2.7%, respectively (p <0.001). The 500/2,000 microg. alprostadil/prazosin combination, which resulted in full enlargement or rigidity in 58.9% of doses, was only slightly better than the most effective dose of alprostadil alone (500 microg.). However, combinations of 125/500 and 250/500 microg. alprostadil/prazosin were more effective (p <0.01) than 125 and 250 microg. alprostadil given alone, respectively. The most common side effect of therapy was penile pain, which rarely led to study discontinuation. Hypotension most commonly developed at the higher alprostadil-prazosin combination. CONCLUSIONS: Transurethral alprostadil and alprostadil-prazosin combinations produced erections in men with complete organic erectile dysfunction. This combination therapy may be an option in patients who do not respond to transurethral alprostadil alone.

The effect of transurethral alprostadil on the quality of life of men with erectile dysfunction, and their partners. MUSE Study Group.

OBJECTIVE: To evaluate the impact of treatment for erectile dysfunction on the quality of life of men and their partners. PATIENTS AND METHODS: The study included 249 men with organic erectile dysfunction of more than 3 months' duration who self-administered transurethral alprostadil in an open-label, dose-escalating manner in an outpatient medical setting. Patients with a sufficient response (159) were randomly assigned in a double-blind protocol to either active medication or placebo for 3 months at home. Patients and partners each completed quality-of-life questionnaires before and after treatment. RESULTS: In the clinic 159 of the 249 men (64%) had an erection sufficient for intercourse when using transurethral alprostadil. At home, 46 of 67 men (69%) reported intercourse at least once on transurethral alprostadil, compared with eight of 73 (11%) on placebo (P < 0.001). Patients on alprostadil showed a 34% improvement in their 'relationship with partner', a 5% improvement in 'personal wellness', and a 71% improvement in 'quality of erection' domains, compared with a decline of 11%, 8% and 1%, respectively, in patients on placebo (P < 0.005 for each comparison). Partners of patients on alprostadil showed a 35% improvement in the 'relationship with partner' domain, compared with a 12% improvement in the placebo group (P = 0.028). There was a trend toward improvement in other partner domains. Urogenital pain was reported by 14% of patients during home treatment. CONCLUSION: The resumption of sexual intercourse with the use of transurethral alprostadil was accompanied by an improvement in several important quality-of-life domains in patients and their partners.

Treatment of men with erectile dysfunction with transurethral alprostadil. Medicated Urethral System for Erection (MUSE) Study Group.

BACKGROUND: Erectile dysfunction in men is common. We evaluated a system by which alprostadil (prostaglandin E1) is delivered transurethrally to treat this disorder. METHODS: Alprostadil was delivered transurethrally in a double-blind, placebo-controlled study of 1511 men, 27 to 88 years of age, who had chronic erectile dysfunction from various organic causes. The men were first tested in the clinic with up to four doses of the drug (125, 250, 500, and 1000 microg); those who had sufficient responses were randomly assigned to treatment with either the effective dose of alprostadil or placebo for three months at home. RESULTS: During in-clinic testing, 996 men (65.9 percent) had erections sufficient for intercourse. Of these men, 961 reported the results of at least one home treatment; 299 of the 461 treated with alprostadil (64.9 percent) had intercourse successfully at least once, as compared with 93 of the 500 who received placebo (18.6 percent, P<0.001). On average, 7 of 10 alprostadil administrations were followed by intercourse in men responsive to treatment. The efficacy of alprostadil was similar regardless of age or the cause of erectile dysfunction, including vascular disease, diabetes, surgery, and trauma (P<0.001 for all comparisons with placebo). The most common side effect was mild penile pain, which occurred after 10.8 percent of alprostadil treatments, but the pain rarely resulted in refusal to continue in the study. Hypotension occurred in the clinic in 3.3 percent of men receiving alprostadil. Hypotension-related symptoms were uncommon at home. No men had priapism or penile fibrosis. CONCLUSIONS: In men with erectile dysfunction, transurethral alprostadil therapy resulted in erections in the clinic and in intercourse at home.

A double-blind, placebo-controlled evaluation of the erectile response to transurethral alprostadil.

OBJECTIVES: Previous studies have indicated that the urethra may provide an effective route for administering vasoactive medication for the treatment of erectile dysfunction. We evaluated the safety and efficacy of alprostadil administered intraurethrally at home for the treatment of this disorder. METHODS: This prospective, multicenter, double-blind, placebo-controlled study evaluated the erectile response to randomly assigned doses of transurethral alprostadil at home in 68 men with long-standing (mean 41 months) erectile dysfunction of primarily organic etiology. Patients completing the study each administered a random sequence of four different doses (125, 250, 500, and 1000 micrograms) and placebo over a 2 to 4-week period. Assessments included the couples' ability to have intercourse, patient ratings of erectile response by both categorical and visual analogue scales, penile volume measurements, and overall assessments of comfort and ease of administration. RESULTS: Overall, 75.4% (49 of 65) of study patients achieved full enlargement of the penis and 49.2% (32 of 65) achieved an erection judged by the patient to be sufficient for intercourse. In addition, 63.6% (42 of 66) of patients reported intercourse. Efficacy was similar across etiologies. The most common side effect was penile pain, which occurred in association with 9.1% to 18.3% of alprostadil administrations, depending on dose. Mean comfort ratings ranged from 79 to 87, depending on dose, where 0 = severe discomfort and 100 = comfortable; ease of administration scores were above 90 for each dose, where 0 = difficult and 100 = easy. There were no episodes of priapism in this study. CONCLUSIONS: Short-term treatment with transurethral alprostadil produced erections resulting in sexual intercourse in most patients with chronic erectile dysfunction. This therapy may be a useful treatment option for patients with erectile dysfunction.

Effect of food on bioavailability of pseudoephedrine and brompheniramine administered from a gastrointestinal therapeutic system.

The purpose of this study was to determine how a high-fat meal affects the delivery and absorption of pseudoephedrine and brompheniramine maleate when delivered from a gastrointestinal therapeutic system (GITS). This study was a randomized, complete crossover trial with 12 healthy male volunteers who were given single doses of the 24-h GITS under fed and fasted conditions. Pharmacokinetic parameters for both drugs were comparable between fed and fasted treatments, except for a shorter time to maximum concentration of pseudoephedrine for fed subjects (p = 0.002). Bioavailability of pseudoephedrine was 91% for fed relative to fasted treatment; for brompheniramine it was 89%. These results indicate that codelivery of the two drugs from the GITS is reliable and prolonged, and that the resulting absorption of pseudoephedrine and brompheniramine is minimally affected by food.

Treatment of primary hypogonadism in men by the transdermal administration of testosterone.

We tested the efficacy of a thin flexible testosterone-impregnated membrane applied to the scrotum for the long term treatment of male hypogonadism. Ten men with primary hypogonadism were treated for 3 months (2 men) or 13 months (8 men). Serum testosterone concentrations increased in all 10 men, to within the normal range in 8. Serum dihydrotestosterone concentrations increased to supranormal values in all of the men, decreased to the normal range in 6, indicating the biological effectiveness of the testosterone in those subjects. Two men whose serum LH concentrations did not fall to normal had small or distorted scrotal surfaces. Seven of the 8 men whose serum testosterone concentrations became normal said that their hypogonadal symptoms were corrected by this treatment. We conclude that the transdermal administration of testosterone is an effective means of treating the majority of hypogonadal men who have a normal scrotum.

Substitution therapy of hypogonadal men with transdermal testosterone over one year.

Current testosterone substitution therapy either by injectable or oral testosterone esters suffers from markedly fluctuating serum testosterone levels often far above or below the physiological range. Recently, a transdermal therapeutic system (TTS) for the delivery of testosterone was developed which, when applied to the scrotum, provides smooth serum testosterone levels. Here we report results from seven hypogonadal men treated with the TTS for 14 months by applying a new patch every day. In all patients serum testosterone and dihydrotestosterone (DHT) determined 3-5 h after applying a new patch increased significantly and remained within the physiological range during the entire treatment period. The DHT/testosterone ratio remained constant. In 4 of these patients and 2 others under TTS treatment serum testosterone and DHT were also determined over a 24-h period at regular intervals. In these patients serum testosterone levels in the physiological range were seen during the entire observation period, whereas an increase in the DHT/testosterone ratio occurred towards the end of the one-day treatment phase. All patients in the 14-month treatment study were clinically well substituted and responded with good compliance. Clinical chemistry showed no abnormalities during treatment. Thus, the TTS appears to be an effective and safe new modality for the treatment of male hypogonadism.

Human buccal assay for evaluation of the mucosal irritation potential of drugs.

We applied drugs in aqueous gels to the buccal mucosae of normal volunteers to develop an assay of gastrointestinal irritation potential. We studied effects of pH, concentrations, and formulations. We evaluated irritation by subjects' reports of their sensations and observers' grading of visible reactions. On an irritation log ranking scaled 0 to 5, placebo gels produced virtually no irritation, except those formulated at pH 1, 2, and 14. Albuterol, furosemide, and methyldopa produced essentially no irritation. Minutes of exposure to sodium indomethacin, sodium naproxen, and propranolol (at, respectively, pH 8.2, 9.6, and 4.8 and concentrations of 12%, 40%, and 8%) caused ulceration that took up to weeks to heal. Acid forms of naproxen and indomethacin caused minimal or no irritation. Although irritation models based on one gastrointestinal area have limitations, our results indicate that the minimally invasive buccal assay allows ranking of contact irritation potential of drugs and formulations that could aid in selecting optimum formulations for clinical use.

Androgen therapy of hypogonadal men with transscrotal testosterone systems.

The need for improved controlled delivery of testosterone to hypogonadal men stimulated the development of a self-adherent transscrotal testosterone system to provide programmed testosterone delivery through the uniquely permeable scrotal skin. In this short- and long-term efficacy trial, the responses of testosterone and its metabolites to the application of transscrotal testosterone systems of varying testosterone content were compared with the response to 200 mg of testosterone enanthate. Daily transscrotal testosterone system administration resulted in a rapid increase of testosterone and bioavailable, non-sex hormone binding globulin-bound testosterone levels to normal, peaking at two hours, followed by a slow decline over 23 hours, resembling the diurnal variation of endogenous testosterone. One year of daily transscrotal testosterone system therapy demonstrated continued reliable absorption of testosterone and suppression to normal of the luteinizing hormone in two of three patients. There was a greatly disproportionate increase of serum dihydrotestosterone over testosterone, suggesting 5-alpha reduction at the scrotal site. The subjects reported marked subjective improvement. Thus, the transscrotal testosterone system is a novel, effective, and well-tolerated method of delivering testosterone to hypogonadal patients.

Transdermal delivery of testosterone.

We administered testosterone transdermally to six hypogonadal men by applying a thin flexible polymeric membrane containing testosterone to the scrotum. Each man wore a placebo membrane and three doses (5, 10, and 15 mg) of testosterone-containing membranes for 22 h/day. Each dose was worn for 1 week, and one dose was worn a second week. Blood was sampled frequently for one 22 h period on the seventh day of each treatment period. After the application of a membrane, the serum testosterone concentration rose rapidly, reached a peak in 2-3 h, and decreased slowly to 60-80% of the peak value by 22 h. The mean (+/- SE) 22-h average testosterone concentration during the wearing period was dependent on the testosterone content of the membrane (placebo, 135 +/- 38 ng/dl; 5 mg, 348 +/- 66 ng/dl; 10 mg, 455 +/- 77 ng/dl; and 15 mg, 624 +/- 65 ng/dl; P less than 0.001, by analysis of variance). When the same dose was worn twice, the mean coefficient of variation was 13.9%. We conclude that the transdermal application of testosterone to hypogonadal men reproducibly raises their serum testosterone concentrations to within the normal range, and that it, therefore, warrants evaluation as a treatment for male hypogonadism.

A double-blind comparative study of Estraderm and Premarin in the amelioration of postmenopausal symptoms.

Patients whose postmenopausal symptoms were being satisfactorily controlled with conjugated equine estrogens, either 0.625 mg/day (n = 57) or 1.25 mg/day (n = 67), participated in a study that compared the efficacy of these oral regimens with that of 17 beta-estradiol, 0.1 mg/day, administered through intact skin. The study was a multicenter, double-blind, randomized, parallel-group trial during which two thirds of the patients who received each dosage of conjugated equine estrogens were changed to an estradiol transdermal system while the remainder continued with conjugated equine estrogens. A total of 124 patients was included in the analysis of efficacy. The analysis revealed no significant differences between the estradiol transdermal system and conjugated equine estrogens in control of hot flushes or other postmenopausal symptoms and no statistically significant differences between treatment groups in regard to estrogen-related side effects. Minor topical reactions to the transdermal systems were reported during only about 20% of study weeks. Thus, transdermal estradiol, 0.1 mg/day, appears to be equally effective as conjugated equine estrogens, 0.625 or 1.25 mg/day, for controlling postmenopausal symptoms and is well tolerated.

Pharmacokinetics and pharmacodynamics of transdermal dosage forms of 17 beta-estradiol: comparison with conventional oral estrogens used for hormone replacement.

This open-label, multiple-crossover study compared the pharmacokinetics and pharmacodynamics of transdermal 17 beta-estradiol and two oral forms of estrogen replacement therapy in postmenopausal women. The transdermal systems delivered either 0.025, 0.05, or 0.1 mg/day; oral dosages were 2 mg of micronized 17 beta-estradiol or 1.25 mg of conjugated equine estrogens. Transdermal estradiol provided serum and urinary levels of estradiol conjugates typical of the early follicular phase of the premenopausal woman and an estradiol/estrone ratio that approximated 1. The increments of both serum and urinary estradiol showed dose proportionality. Serum levels of estradiol obtained 24 hours after oral administration of estrogens were in a range similar to the steady-state levels obtained with transdermal estradiol delivery. Oral estrogens, however, induced an excessive rise in estrone to levels far beyond those observed in premenopausal women. Continuous application of transdermal estradiol over 3 weeks did not result in any accumulation of estradiol or estradiol conjugates. After only three doses of oral estrogens, there were signs of retention of estrogens. Suppression of gonadotropins by oral and transdermal administration of estrogens was in a similar range. This observation supports the conclusions that levels of circulating estradiol are relevant to efficacy, and that excessively high levels of estrone after oral administration of estrogens merely represents a nonphysiologic precursor or metabolite pattern.