Retroperitoneal Hemorrhage in Patients with COVID-19 Undergoing Hemodialysis: Three Case Reports.

A 73-year-old man receiving hemodialysis and antiplatelets was admitted with a mild case of COVID-19. Heparin was added, and iliopsoas hemorrhage developed. He was successfully treated by interventional radiology. A 76-year-old man receiving hemodialysis and antiplatelets was admitted with mild COVID-19. Heparin was added, and iliacus hemorrhage developed. Despite heparin discontinuation, he died of worsening pneumonia. A 74-year-old man undergoing hemodialysis was admitted with severe COVID-19. Gastrointestinal bleeding developed during continuous hemodiafiltration with heparin. Upon switching to nafamostat and increasing the dose, iliopsoas hemorrhage developed. Despite interventional radiology, he died of infectious complications. Attention to hemorrhagic complications is therefore needed in patients with COVID-19.

Normothermic machine perfusion system satisfying oxygen demand of liver could maintain liver function more than subnormothermic machine perfusion.

Liver transplantation plays an important role in the medical field. To improve the quality of a donor liver, there is a need to establish a preservation system to prevent damage and maintain liver function. In response to this demand, machine perfusion (MP) has been proposed as a new liver preservation method instead of the conventional static cold storage. There is controversy about the optimal MP temperature of the donor liver. Since the oxygen consumption of the liver differs depending on the temperature, construction of a system that satisfies the oxygen demand of the liver is crucial for optimizing the preservation temperature. In this study, an MP system, which satisfies the oxygen demand of liver at each temperature, was constructed using an index of oxygen supply; the overall volumetric oxygen transfer coefficient, the amount of oxygen retention of perfusate and oxygen saturation. Both subnormothermic MP (SNMP, 20-25 °C) and normothermic MP (NMP, 37 °C) could maintain liver viability at a high level (94%). However, lactate metabolism of the liver during NMP was more active than that during SNMP. Furthermore, the ammonia metabolism of liver after NMP was superior to that after SNMP. Hence, NMP, which maintains the metabolic activity of the liver, is more suitable for preservation of the donor liver than SNMP, which suppresses the metabolic activity. In summary, normothermia is the optimal temperature for liver preservation, and we succeeded in constructing an NMP system that could suppress liver damage and maintain function.

Lidocaine-Propitocain Cream, a Eutectic Mixture of Local Anesthetics, Effectively Relieves Pain Associated With Vascular Access Intervention Therapy in Patients Undergoing Hemodialysis: A Placebo-Controlled, Double-Blind, Crossover Study.

Vascular access intervention therapy (VAIVT) is necessary to maintain vascular access in patients undergoing hemodialysis. VAIVT-associated vasodilatation is painful. However, few reports have focused on effective pain relief at the time of VAIVT. The present study was performed to determine whether lidocaine-propitocain cream, a eutectic mixture of local anesthetics (EMLA), effectively reduces VAIVT-associated pain in patients undergoing hemodialysis. This placebo-controlled, double-blind, crossover study was conducted in a single center. Among 210 patients who underwent a total of 437 VAIVT procedures from August 2017 to June 2018, 30 patients were randomly allocated to either the EMLA-placebo arm or placebo-EMLA arm at the time of VAIVT. EMLA application significantly reduced the visual analog scale score compared with placebo (47.0 ± 21.1 vs. 68.6 ± 20.7 mm, respectively; P < 0.05). EMLA is a safe and effective treatment for relief of VAIVT-associated pain in patients undergoing hemodialysis.

Severe Hypocalcemia and Resulting Seizure Caused by Vitamin D Deficiency in an Older Patient Receiving Phenytoin: Eldecalcitol and Maxacalcitol Ointment as Potential Therapeutic Options for Hypocalcemia.

An 82-year-old man treated with phenytoin for the prevention of symptomatic epilepsy was hospitalized to treat consciousness disturbance, seizure, and hypocalcemia (serum calcium: 4.6 mg/dL). Serum 25-hydroxyvitamin D level was very low (5.4 ng/mL), whereas serum calcitriol level was normal (27 pg/mL) and serum intact parathyroid hormone level was increased (369 pg/mL). He was finally diagnosed with vitamin D deficiency associated with low sunlight exposure and long-term phenytoin use for symptomatic epilepsy: phenytoin is shown to accelerate catabolism of 25-hydroxyvitamin D. Combination treatment with eldecalcitol and maxacalcitol ointments successfully normalized corrected serum calcium level: both eldecalcitol and maxacalcitol are vitamin D receptor activators used for osteoporosis and psoriasis, respectively. Our case illustrates the importance of periodic serum calcium level monitoring in patients receiving anti-epileptic drugs and the usefulness of eldecalcitol and maxacalcitol ointment as a therapeutic option for hypocalcemia, especially in countries where native vitamin D and 25-hydroxyvitamin D are not available.

Cholesterol Crystal Embolism Induced by Direct Factor Xa Inhibitor: A First Case Report.

An 80-year-old man presented at our hospital with renal failure. He had been treated with edoxaban, an oral direct factor Xa inhibitor, for deep vein thrombosis for 10 months prior to admission. Although the pulses in his bilateral pedal arteries were palpable, cyanosis was present in the bilateral toes. Laboratory data indicated azotemia and eosinophilia. A skin biopsy confirmed a diagnosis of cholesterol crystal embolism (CCE). Because no invasive vascular procedure was performed, we assumed that CCE was related to edoxaban. To the best of our knowledge, this is the first case report suggesting CCE induced by an Xa inhibitor.

Kisspeptin in the Hypothalamus of 2 Rat Models of Polycystic Ovary Syndrome.

Hyperandrogenism, disturbance of the hypothalamus-pituitary-ovary axis followed by elevated serum luteinizing hormone (LH) levels, and insulin resistance are involved in the complicated pathophysiology of polycystic ovary syndrome (PCOS). Kisspeptin is coexpressed with neurokinin B (NKB) in the arcuate nucleus (ARC), the center of the gonadotropin-releasing hormone pulse generator that is responsible for pulsatile LH secretion. We compared 2 androgenized rat models of PCOS to evaluate the estrous cycle, hormonal profiles, and expression of kisspeptin and NKB in the ARC. Rats in our postnatal dihydrotestosterone (DHT)-treatment model exhibited weight gain and persistent diestrus with normal LH levels. In contrast, irregular cycles, with elevated LH serum levels and normal body weight, were found in the prenatally DHT-treated rats. We also found increased signals of kisspeptin and NKB in the ARC of the prenatally DHT-treated rats, and not in the postnatally DHT-treated rats. Our results suggest that prenatal exposure to androgens may result in higher kisspeptin and NKB levels in the ARC, which could be associated with 1 phenotype of PCOS that is characterized by normal body weight and higher LH secretion, whereas in postnatally DHT-treated rats, characteristics such as weight gain and normal LH levels are seen in the obese PCOS phenotype.

Trunk deformity evaluation based on 3D measurements of front body surface landmarks in people with severe physical disabilities.

PURPOSE: To assess reliability and validity of a trunk deformity evaluation method expressed as rotational and lateral lean angles between the upper and the lower trunk and between the lower trunk and the pelvis using 3D positions of six front body surface landmarks. METHODS: Inter- and intra-rater reliabilities of the proposed method in adults with typical development (n = 22) were assessed, and its validity was also assessed through correlations between the Cobb angle and the analyzed trunk deformity parameters in adults with severe physical disabilities (n = 22). RESULTS: The mean differences between two raters and between the initial and second measures were within 2°. Moderate correlations were found between the Cobb angle and both the upper and the lower trunk lateral lean angle and the upper trunk rotation angle. CONCLUSIONS: The proposed trunk deformity evaluation appears to be a reliable and valid approach for bedridden people with physical disabilities.

Choosing the optimal therapeutic strategy for placental polyps using power Doppler color scoring: Transarterial embolization followed by hysteroscopic resection or expectant management?

OBJECTIVE: To evaluate a protocol for selection of placental polyp management, including expectant management and hysteroscopic resection with or without transarterial embolization (TAE), using power Doppler color score (PDCS) as the vascularity parameter. MATERIALS AND METHODS: This retrospective case-control study included 25 patients who were diagnosed with placental polyps. We evaluated the vascularity of placental polyps with PDCS measured by transvaginal ultrasonography as follows: PDCS 1, no blood flow; PDCS 2, minimal flow; PDCS 3, moderate flow; and PDCS 4, marked blood flow. We then selected expectant management or hysteroscopic resection with or without TAE. RESULTS: Three of 17 patients with PDCS 1 or 2 underwent surgical intervention, and expectant management was successful in 14. Seven of eight patients with PDCS 3 or 4 underwent surgical intervention, while expectant management was successful in only one patient. CONCLUSION: PDCS is a simple examination for evaluating the vascularity of placental polyps. PDCS might be useful for selecting the optimal treatment for placental polyps, such as expectant management or surgical intervention, according to their vascularity.

Increase of kisspeptin-positive cells in the hypothalamus of a rat model of polycystic ovary syndrome.

Kisspeptin, a hypothalamic neuropeptide, is expressed in the arcuate nucleus (ARC) that is considered as the center of the gonadotropin-releasing hormone (GnRH)-pulse generator. We hypothesized that kisspeptin expressed in the ARC is implicated in the disturbance of the hypothalamus-pituitary-ovary axis observed in polycystic ovary syndrome (PCOS). To test this hypothesis, we evaluated the hormonal profiles, luteinizing hormone (LH) pulse, and ARC kisspeptin immunoreactivity in a PCOS rat model using the anti-progestin RU486. We found an alteration of the LH pulse, including a trend towards an increased mean LH concentration and area under the curve, and a significant upregulation of the mean LH pulse amplitude. Additionally, a higher number of kisspeptin-positive cells was observed in the ARC of RU486-treated rats than in the ARC of intact rats. These results suggest the possible involvement of hypothalamic kisspeptin in the hypothalamus-pituitary-ovary axis and therefore, in PCOS pathophysiology.

Anti-Müllerian hormone levels after laparoscopic cystectomy for endometriomas as a possible predictor for pregnancy in infertility treatments.

We assessed the associations between preoperative and postoperative serum anti-Müllerian hormone (AMH) levels and parameters of endometriosis and endometriomas surgery with the success of infertility treatments after cystectomy. Seventeen out of 54 patients got pregnant during the infertility treatments. In these patients, the median interval from surgery to conception was 16.3 months. The serum AMH levels 1-year postoperatively were significantly higher in the pregnant group compared to the non-pregnant group (3.44 ± 1.78 versus 2.17 ± 2.24 ng/ml, p = 0.049). The median interval from surgery to recurrence was 34.4 months, and no significant differences were found in the serum AMH levels at any time point between the recurrence and non-recurrence groups. Serum AMH levels 1 year after laparoscopic cystectomy for endometriomas may predict the success of postoperative infertility treatments, but not a recurrence of endometriomas.

CYP51A1 induced by growth differentiation factor 9 and follicle-stimulating hormone in granulosa cells is a possible predictor for unfertilization.

Growth differentiation factor 9 (GDF9), an oocyte-secreted factor, whose receptors exist in granulosa cells, is involved in follicle progression. Therefore, GDF9 is considered to potentially mediate signals necessary for follicular growth. However, the effect of GDF9 on human granulosa cells is not fully understood. Human immortalized nonluteinized granulosa cell line (HGrC1) which we have previously reported was stimulated with GDF9 and/or follicle-stimulating hormone (FSH). Granulosa cells obtained from in vitro fertilization (IVF) patients were also evaluated with quantitative reverse transcription polymerase chain reaction (RT-PCR). Real-time RT-PCR showed that GDF9 increased messenger RNA (mRNA) levels of enzymes required for cholesterol biosynthesis, such as 3-hydroxy-3-methylglutanyl-CoA synthase 1 (HMGCS1), farnesyl-diphosphate farnesyltransferase 1, squalene epoxidase, lanosterol synthase, and cytochrome P450, family 51, subfamily A, polypeptide 1 (CYP51A1). A greater increase in mRNA levels of HMGCS1 and CYP51A1 was observed by combined treatment with GDF9 and FSH. Clinical samples showed a significant increase in CYP51A1 mRNA in the group of granulosa cells connected with unfertilized oocytes. Our results suggest that GDF9, possibly with FSH, may play significant roles in the regulation of cholesterol biosynthesis and the expression of CYP51A1 which might be a predictor for unfertilization.

Anti-Müllerian hormone as a possible predictor of fecundability in subfertile women over 38 years: a retrospective cohort study.

Anti-Müllerian hormone (AMH) is a relatively novel method for examining the ovarian reserve that reflects female reproductive function. In the era in which the number of women delaying attempts to conceive has increased, a good predictor for long-term fecundability has been explored. We performed the retrospective cohort study to investigate whether initial serum AMH levels are useful for predicting long-term fertility during infertility treatments. We recruited 149 women in the retrospective cohort, and 52 women were gravid during the follow-up period. According to the multiple logistic analyses, only age was found to have a significant correlation with pregnancy success in all women. In women ≥38 years, significantly higher serum AMH levels were detected in the pregnant group (median = 2.83 ng/mL, range = 1.11-6.29 ng/mL) than the non-pregnant group (median = 1.22 ng/mL, range = 0-9.46 ng/mL; p = 0.015). None of the women with serum AMH levels <0.7 ng/mL were pregnant during treatment. AMH may be used to identify poor pregnancy prospects in women who are above 38 years.

Pelvic tuberculous granuloma successfully treated with laparoscopy to preserve fertility: a case report and review of the published work.

Tuberculous granuloma must be considered in the differential diagnosis of pelvic masses in women of reproductive age because the major sequela of pelvic tuberculosis is infertility; however, currently there is very little information about its fertility-preserving treatment. We report the case of a woman with a history of tuberculous peritonitis who referred to our hospital for evaluation of an adnexal mass and primary infertility. The patient underwent excision of pelvic tuberculous granuloma with fertility-preserving laparoscopic surgery. We resected as much of the tuberculous granuloma as possible using the laparoscopic technique without causing damage to the uterus or ovaries. In particular, we report for the first time in the published work the laparoscopic removal of tuberculous granuloma without causing damage to the uterus or ovaries. Our experience from this case suggests that laparoscopic diagnosis and treatment of tuberculous granuloma is a feasible procedure in a patient who wants to conceive.

Time-lapse observations to analyze the effects of assisted hatching.

PURPOSE: Assisted hatching (AH) is an artificial disruption of the zona pellucida with the aim of facilitating embryo implantation. We used time-lapse observations of mouse embryos to examine the effect of AH in mouse blastocysts. METHODS: AH techniques were performed with acid Tyrode's solution. We compared the rates of blastocyst formation and blastocyst attachment to Ishikawa cells between the control (n = 28) and the AH group (n = 24). To analyze the effects of AH, 8-cell mice embryos were cultured under time-lapse observations (every 15 min). The time required for hatching, the hatching rates, the frequency of contraction, and the contraction rates in the blastocysts were analyzed. RESULTS: There were no significant differences between the two groups in hatching rate or attachment rate. The times required for hatching were 286 ± 22 min in the AH group and 990 ± 437 min in the control group (P = 0.018). The contraction frequencies in blastocysts were 3.5 ± 0.7 times in the AH group and 7.5 ± 2.5 times in the control group (P = 0.020). CONCLUSIONS: From the time-lapse observations we found that the time required for hatching and the frequency of contraction in blastocysts were both reduced by AH, although blastocyst formation and attachment were not affected.

Possible involvement of CD10 in the development of endometriosis due to its inhibitory effects on CD44-dependent cell adhesion.

A reduced response to progesterone in the eutopic endometrium with endometriosis and in endometriotic tissues is considered to be the underlying factor for endometriosis. CD10 is known to be expressed by endometrial and endometriotic stromal cells and may be induced by progestins, although the function of CD10 is not fully revealed in endometrial or endometriotic tissues. In the current study, the expression of CD10 was significantly increased by treatment of the cells with progesterone, 17ß-estradiol, and dibutyryl cyclic adenosine monophosphate (cAMP) in the endometrial stromal cells. On the other hand, the expression of CD10 following treatment with progesterone, 17ß-estradiol, and dibutyryl cAMP was not significantly increased in endometriotic stromal cells. The adhesion assay for endometrial and endometriotic stromal cells to hyaluronan using 5- or 6-(N-succinimidyloxycarbonyl)-fluorescein 3', 6'-diacetate-labeled cells demonstrated that the CD44-dependent adhesion of stromal cells was inhibited by CD10. As far as the induction of CD10 is concerned, the effect of progesterone was different between endometrial stromal cells and endometriotic stromal cells. CD10 might be involved in the development of endometriosis due to its influence on CD44-dependent cell adhesion.

A proteomic analysis of human follicular fluid: comparison between fertilized oocytes and non-fertilized oocytes in the same patient.

PURPOSE: Human follicular fluid constitutes the microenvironment of follicles and includes various biological active proteins that can affect follicle growth and oocyte fertilization. Conducting proteomic evaluations of human follicular fluid may be helpful for identifying potential biomarkers possibly possessing a predictive value for oocyte quality and the success of in vitro fertilization. METHOD: We performed proteomic profiling of human follicular fluids containing oocytes that were fertilized and resulted in pregnancy and follicular fluids containing oocytes that were not fertilized in the same patients undergoing intracytoplasmic sperm injection using the LTQ Orbitrap coupled with liquid chromatography-tandem mass spectrometry (LC/MS/MS) analyses. RESULTS: We identified a total of 503 proteins in human follicular fluids containing fertilized and non-fertilized oocytes obtained from 12 patients. We also found that 53 proteins exhibited significantly different spectral counts between the two groups, including heparan sulfate proteoglycan perlecan, which showed significant upregulation in the follicular fluids containing fertilized oocytes in comparison with that observed in the follicular fluids containing non-fertilized oocytes. CONCLUSION: Our results suggest a possibility that proteins identified by LC/MS/MS in follicular fluid might not only be involved in folliculogenesis, but also function as biomarkers possessing predictive potential for oocyte maturation and the success of IVF when their expression levels are significantly different between fertilized and non-fertilized oocytes, although no distinctive biomarkers were identified in the current study.

One-year follow-up of serum antimüllerian hormone levels in patients with cystectomy: are different sequential changes due to different mechanisms causing damage to the ovarian reserve?

OBJECTIVE: To investigate whether the serum antimüllerian hormone (AMH) levels recover within 1 year after cystectomy for endometriomas, and to analyze the pattern of sequential changes in the serum AMH levels. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Thirty-nine patients undergoing cystectomy for unilateral endometrioma (n = 22) and bilateral endometriomas (n = 17). INTERVENTION(S): Serum samples collected 2 weeks before, and 1 month and 1 year after surgery were assayed for AMH levels. MAIN OUTCOME MEASURE(S): Assessment of the ovarian reserve damage based on alterations in the serum AMH levels and the association with parameters of endometriosis and surgery for endometriomas. RESULT(S): The median AMH levels were 3.56, 1.90, and 2.10 ng/mL before, 1 month after, and 1 year after surgery, respectively. Twenty patients showed higher AMH levels 1 year after surgery than 1 month after surgery (increase group); 19 patients showed lower AMH levels (decrease group). We found a statistically significant difference in the number of follicles removed by surgery between the two groups. CONCLUSION(S): The decrease in the serum AMH levels caused by cystectomy can recover. Our results suggest that removal of ovarian cortex might be involved in the decrease of the ovarian reserve just after surgery, and that a continuous decrease of the ovarian reserve after cystectomy might be attributed to other mechanisms.

Anti-Müllerian hormone as a marker of ovarian reserve following chemotherapy in patients with gestational trophoblastic neoplasia.

OBJECTIVE: The loss of primordial follicles from gonadal damage caused by chemotherapy results in decreased ovarian reserve. To assess the impact of chemotherapy for patients with gestational trophoblastic neoplasia (GTN) on the ovarian reserve, we evaluated the post-chemotherapy serum anti-Müllerian hormone (AMH) levels. STUDY DESIGN: In 22 patients with GTN receiving chemotherapy, serum AMH levels were measured after the administration of chemotherapy and compared with serum AMH levels measured in patients with hydatidiform mole who did not receive chemotherapy, as a control. We also analyzed differences in the serum AMH levels following the administration of different anti-cancer agents. RESULTS: The serum AMH levels measured in the GTN group after chemotherapy was administered (median 1.18, range 0.32-3.94 ng/mL) significantly decreased in comparison to those measured in the control group (median 4.22, range 0.77-6.53 ng/mL, P=0.002). Serum AMH levels were significantly lower in the patients who had received a regimen including etoposide than in the patients who had not received treatment with etoposide (0.71 vs. 1.30 ng/mL, P=0.027). CONCLUSION: Our results suggest that chemotherapy administered to treat GTN does indeed affect the ovarian reserve, especially in patients who receive a medication regimen that includes etoposide. Measuring their serum AMH levels might therefore be helpful for counseling GTN patients regarding their ovarian reserve.

Sphingosine-1-phosphate inhibits H2O2-induced granulosa cell apoptosis via the PI3K/Akt signaling pathway.

OBJECTIVE: To investigate the protective effect of sphingosine-1-phosphate (S1P) against H(2)O(2)-induced apoptosis in human granulosa cell cultures with freshly harvested granulosa cells. DESIGN: Experimental study. SETTING: Academic medical center for reproductive medicine. PATIENT(S): Cultures of primary granulosa cells isolated from women undergoing in vitro fertilization (IVF). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cell apoptosis and Western blot analysis of signaling pathway proteins. RESULT(S): We found that S1P (1 and 10 mM) statistically significantly decreased granulosa cell apoptosis after H(2)O(2) treatment. The decreased cell apoptosis induced by S1P was abolished after treatment with VPC23019, an inhibitor of S1P1 and S1P3 receptors, W146, an inhibitor of S1P1 receptors, and CAY10444, an inhibitor of S1P3 receptors. A Western blot analysis revealed that the level of phospho-Akt increased and peaked at 10 minutes after 10 mM S1P exposure. CONCLUSION(S): Treatment with S1P can inhibit the apoptosis of granulosa cells in response to oxidative stress induced by H(2)O(2). The protective effect of S1P is mediated by activating the PI3K/Akt pathway, and the antiapoptotic effect of S1P is mainly mediated through the S1P1 and S1P3 receptor.