A multi-centre, retrospective case series of oocyte cryopreservation in unmarried women diagnosed with haematological malignancies.

STUDY QUESTION: Is oocyte cryopreservation an applicable option for fertility preservation in unmarried patients with haematological malignancies? SUMMARY ANSWER: Oocyte cryopreservation via the vitrification method is accessible and may be considered an option for fertility preservation in unmarried patients with haematological malignancies. WHAT IS KNOWN ALREADY: Haematological malignancies are most commonly observed amongst adolescent and young adult women. Although the survival rate and life expectancy of those with haematological malignancies have improved, chemotherapy and radiotherapy may impair their reproductive potential. Oocyte cryopreservation is thus an ideal option to preserve their fertility. STUDY DESIGN SIZE DURATION: This study retrospectively evaluated 193 unmarried patients (age: 26.2 ± 0.4 years) with haematological malignancies, who consulted for oocyte cryopreservation across 20 different fertility centres in Japan between February 2007 and January 2015. The primary outcome measures were the oocyte retrievals and oocyte cryopreservation outcomes. The secondary outcome measures were the outcomes following oocyte warming for IVF. PARTICIPANTS/MATERIALS SETTING METHODS: The patients had commenced ovarian stimulation cycles via antagonist, agonist, natural and minimal methods for oocyte retrievals, defined according to the treatment strategy of each respective fertility centre. A vitrification method using the Cryotop safety kit was used for oocyte cryopreservation. ICSIs were used for insemination of warmed oocytes. The endometrial preparation method for embryo transfer was hormonal replacement therapy, except in the case of a patient who underwent a spontaneous ovulatory cycle. MAIN RESULTS AND THE ROLE OF CHANCE: Among 193 patients, acute myeloid leukaemia (n = 45, 23.3%) was most common, followed by acute lymphoid leukaemia (n = 38, 19.7%) and Hodgkin's lymphoma (n = 30, 15.5%). In total, 162 patients (83.9%) underwent oocyte retrieval, and oocytes were successfully cryopreserved for 155 patients (80.3%). The mean number of oocyte retrieval cycles and cryopreserved oocytes were 1.7 ± 0.2 and 6.3 ± 0.4, respectively. As of December 2019, 14 patients (9.2%) had requested oocyte warming for IVF. The survival rate of oocytes after vitrification-warming was 85.2% (75/88). The rates of fertilisation and embryo development were 80.0% (60/75) and 46.7% (28/60), respectively. Ten patients (71.4%) had successful embryo transfers, and seven live births (50.0%) were achieved. LIMITATIONS REASONS FOR CAUTION: This study was limited by its retrospective nature. Additionally, there remains an insufficient number of cases regarding the warming of vitrified oocytes to reliably conclude whether oocyte cryopreservation is effective for patients with haematological malignancies. Further long-term follow-up study is required. WIDER IMPLICATIONS OF THE FINDINGS: Oocyte retrieval and oocyte cryopreservation were accessible for patients with haematological malignancies; however, the number of oocyte retrievals may have been limited due to the initiation of cancer treatments. Acceptable embryonic and pregnancy outcomes could be achieved following oocyte warming; therefore, our results suggest that oocyte cryopreservation can be considered an option for fertility preservation in patients with haematological malignancies. STUDY FUNDING/COMPETING INTERESTS: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Post-occlusional hyperemia for fractional flow reserve assessment and pull-back curve analysis.

Balloon occlusion is a potential method for inducing hyperemia to measure post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR). The objective of this study was to determine the clinical usefulness of post-occlusional hyperemia. FFRs measured using post-occlusional hyperemia caused by 30 (FFRoccl30) and 60 s (FFRoccl60) of balloon occlusion after PCI were compared in 60 lesions from 60 patients. The duration of hyperemia was also measured. There was a strong correlation between FFRoccl30 and FFRoccl60 (r = 0.969, p < 0.01). The duration of hyperemia was significantly longer with FFRoccl60 than with FFRoccl30 (68 ± 23 vs. 37 ± 15 s, p < 0.01). The time required for pullback curve analysis was around 45 s. However, in 7 (12%) cases, the duration of hyperemia with FFRoccl60 was < 45 s, which was not enough for pull-back curve analysis. To predict the duration of hyperemia with FFRoccl60 ≥ 45 s, the receiver operating characteristic curve analysis revealed a cut-off value of 25 s of hyperemia with FFRoccl30. FFRoccl30 is sufficient for diagnostic purposes. FFRoccl60 is suitable for pull-back curve analysis in select cases based on predictions made using the duration of hyperemia with FFRoccl30.

Angiogram based fractional flow reserve in patients with dual/triple vessel coronary artery disease.

OBJECTIVE: To assess the performance of angiography derived Fractional Flow Reserve (FFRangio) in multivessel disease (MVD) patients undergoing angiography. BACKGROUND: FFR is the reference standard for physiologic assessment of coronary stenosis and guidance of revascularization, especially in patients with MVD, yet it remains grossly underutilized. The non-wire based FFRangio performs well in non-MVD patients, but its accuracy in MVD is unknown. METHODS: A prospective clinical study was conducted at Gifu Heart Centre, Japan. Patients underwent physiologic assessment of all relevant coronary lesions using wire-based FFR (wbFFR) and FFRangio. Primary outcome was diagnostic performance (sensitivity, specificity, accuracy) for FFRangio with wbFFR as reference. Other outcomes were the correlation between wbFFR/FFRangio, time required for wbFFR/FFRangio measurements, and the effect of wbFFR/FFRangio on the reclassification of coronary disease severity. RESULTS: Fifty patients (118 lesions in total) were included. Mean age was 72 ±â€¯9 years, 72% were male, 36% had triple vessel disease and the average SYNTAX score was 13. The mean measurement of wbFFR and FFRangio were 0.83 ±â€¯0.12 and 0.81 ±â€¯0.11, respectively. Accuracy, sensitivity and specificity for FFRangio were 92.3% (95% CI 79.1-98.4%), 92.4% (95% CI 84.3-97.2%) and 92.4% (95% CI 87.4-97.3%), respectively. Pearson's r between wbFFR and FFRangio was 0.83. FFRangio measurement was faster than wbFFR (9.6 ±â€¯3.4 vs. 15.0 ±â€¯8.9 min, p < 0.001). CONCLUSIONS: In patients with MVD, FFRangio shows good correlation and excellent diagnostic performance compared to wbFFR, and measuring FFRangio is faster than wbFFR. These results highlight the potential clinical benefits of utilizing FFRangio among patients with MVD.

A Precise Sampling Strip with Microstructures.

This paper presents a precise sampling microstructure formed as a paper strip. We have been developing dialysis system that can be implanted into a human body as an artificial kidney. For the safe use of our artificial kidney, the patients' urine needs to be constantly monitored to detect the abnormal value of ion concentration essential for human life. We are conceiving the monitoring system based on sampling by a paper strip. In this study, we fabricated the strip consisting of slanted and interlocked micropillars for the sampling, known as synthetic microfluidic paper. The paper-like substrate can be fabricated with a well-controlled geometry and subsequently enables precise sampling. Through the conducted experiments, it was shown that synthetic microfluidic paper had better mechanical properties, showed more precision in sampling than paper filter as well as corresponding liquid holding capability to the paper filter. Our proposed paper-based sampling system is expected to lead to the development of minimally invasive ion monitoring system with quantitative sampling strip.

Simple technique of repair for Barlow syndrome with posterior resection and chordal transfer via minimally invasive approach: primary experience in a consecutive series of 22 patients.

OBJECTIVE: Current techniques for mitral valve repair (MVR) in Barlow's disease require high level of surgical expertise due to a complex anatomy. A novel and simple standardized technique that particularly considers the pathological changes of the mitral valve in Barlow's disease has been developed. METHODS: Between 2009 and 2013, 22 patients underwent minimally invasive MVR for Barlow's disease and severe mitral regurgitation (MR). A simple, standardized technique was applied, including resection of P2 segment of posterior mitral leaflet (PML) with preservation of the shortest chordae, transfer of the preserved chordae to A2, and implantation of a semi-rigid open ring. In 2015, all patients were contacted for follow-up by transthoracic echocardiography (TTE) and interviewed for their clinical status. RESULTS: During follow-up (mean 2.8 ± 1.1 years; 100% complete), one patient died due to abdominal bleeding 4 months after the initial MVR and one patient with severe calcification of PML underwent valve replacement due to recurrence of MR. Among the remaining cohort (mean follow-up 3.0 ± 1.0 years), NYHA class I, II and III was present in 13, 6, and 1, respectively. TTE demonstrated MR grade 0, 1+, or 2+ in 40, 55, and 5%, respectively, with mean and maximum transvalvular gradients ranging at 1.9 ± 1.7 and 4.7 ± 3.3 mmHg, respectively. CONCLUSIONS: A simple and standardized technique facilitates the repair of MR in the presence of Barlow's, simultaneously addressing the height of PML and the position of the anterior leaflet. This technique has proven durable in the mid-term follow-up in our small series and warrants further validation in larger cohorts.

Geosmin-producing Species of Coelosphaerium (Synechococcales, Cyanobacteria) in Lake Shinji, Japan.

In Lake Shinji, Japan, periodic outbreaks of musty odour have occurred since mid-May 2007. Although the substance responsible for the odour was identified as geosmin, the odour-producing organism was unknown. We cultivated an axenic unialgal strain and determined that a species of Coelosphaerium (Synechococcales) was responsible for the production of geosmin in Lake Shinji. Our analysis was conducted using gas chromatography/mass spectrometry to determine the odorous compound. To determine the algae species, it was observed by optical microscopy to describe its morphological characteristics and the polymerase chain reaction was used to characterise the nucleotide sequence of the 16S rRNA gene and the 16S-23S rRNA internal transcribed spacer region. In addition, we explored the relationship between the number of cells of the Coelosphaerium sp. and the concentration of geosmin. In conclusion, geosmin, the cause of the musty odour in Lake Shinji in autumn 2009, was produced by Coelosphaerium sp., and to our knowledge, this is the first report of a geosmin-producing species in the family Coelosphaeriaceae.

Chromosomal anomalies and sperm retrieval outcomes of patients with non-obstructive azoospermia: a case series.

Some preoperative factors affecting the outcome of microdissection testicular sperm extraction (micro-TESE) have been previously evaluated. However, other than Klinefelter syndrome (KS), no other chromosomal anomalies have been discussed in the context of sperm retrieval outcomes. The objective of this study was to describe chromosomal anomalies and their relationship with sperm retrieval outcomes in patients with non-obstructive azoospermia (NOA). Of the 197 NOA patients whose clinical records were retrospectively reviewed, 144 (73.1%) had normal 46,XY karyotype, 40 (20.3%) had KS (47,XXY), and 13 (6.6%) had other chromosomal anomalies (autosomal in seven cases and sex-chromosomal anomalies in six). Of the seven patients with autosomal anomalies, two had the reportedly normal variant 46,XY,inv(9)(p12;q13). Testicular volume and serum hormone levels (luteinizing hormone, follicle-stimulating hormone, and total testosterone) of the patients with chromosomal anomalies other than KS were comparable to those of the patients with normal karyotype. The sperm retrieval rate of the patients with 46,XY karyotype, KS, or other chromosomal anomalies were 27.1%, 22.5%, and 15.4%, respectively, with no statistically significant difference. However, among the samples collected from the 13 patients with chromosomal anomalies other than KS, only those from the two patients with the normal variant 46,XY,inv(9)(p12;q13) contained spermatozoa. Among our series of NOA patients, the incidence of autosomal anomalies was higher than that generally noted among neonates, which suggests that not only sex-chromosomal anomalies but also autosomal anomalies may affect the development of NOA. Furthermore, our findings suggest that sperm retrieval outcome is more unfavorable in NOA patients with chromosomal anomalies than in NOA patients with 46,XY karyotype or KS, despite the use of micro-TESE.

Formation kinetics of particulate films in directional drying of a colloidal suspension.

We observed the kinetics of formation of colloidal films through directional drying with a pinned drying interface. The volume fraction of particles accumulated at the pinned drying interface increased in two stages: it rapidly increased in the initial stage of drying and then slowly increased. The final filling factor of the dried films decreased with increasing drying flux. We found a threshold drying flux for the formation of colloidal films below which uneven films are formed at the drying interface. This threshold flux is well explained by the competition between transport of particles by flow and transport by diffusion. We also found a minimum thickness for the formation of a packed layer of particles. The formation kinetics of a packed layer of particles due to drying was discussed.

[Mitral regurgitation in heart failure. Surgical therapy]. / Mitralinsuffizienz bei Herzinsuffizienz. Chirurgische Therapie.

The optimal treatment of mitral regurgitation concomitant to heart failure remains controversial. A lack of consensus between cardiologists and cardiac surgeons, because of limited studies and heterogeneous data, has led to vaguely defined guidelines and different handling in the clinical routine in the past. However, progress in the operative management with excellent results of individual experienced centers suggests that a variety of patients might benefit from surgical therapy. Each patient should be evaluated individually regarding the benefits of surgical therapy which requires an interdisciplinary approach ("heart team") due to the complex pathophysiology and demanding diagnostics.

A Shiga toxin-producing Escherichia coli O157 outbreak associated with consumption of rice cakes in 2011 in Japan.

In May 2011, an outbreak of Shiga toxin-producing Escherichia coli (STEC) O157 was reported from Yamagata Prefecture, Japan. Investigations, including a case-control study, revealed that the outbreak was linked to two varieties of rice cakes produced by a local manufacturer between 2 and 7 May. Active and passive surveillance identified 136 suspected cases, 142 confirmed cases, 26 asymptomatic cases, and 25 secondary cases. While no environmental samples taken from the manufacturing premises tested positive for STEC, other than a stool sample taken from one employee, on-site and epidemiological investigations indicated that STEC was introduced during the manufacturing process of rice cakes rather than through contamination of raw materials. This was the first reported outbreak of STEC associated with cakes and confectionery in Japan, which indicates that contamination and outbreaks of STEC can occur in any food unless proper precautions are taken.

A designed curved DNA sequence remarkably enhances transgene expression from plasmid DNA in mouse liver.

The intranuclear disposition of plasmid DNA is extremely important for transgene expression. The interactions between the plasmid DNA and the histone proteins are one of the keys for controlling the disposition. In this study, the effects of a left-handedly curved sequence (20-40 repeated A•T tracts) on transgene expression from a plasmid were examined in vivo. A naked luciferase plasmid with the curved sequence was delivered into mouse liver by a hydrodynamics-based injection, and the luciferase activities were quantitated at various time points. Interestingly, transgene expression was markedly increased by the addition of the curved sequence. An analysis of the nucleosome positions near the left-handedly curved sequence suggested that the sequence functions as an acceptor of the histone core and allows nucleosome sliding, resulting in transcriptional activation. These results suggested that the designed curved DNA sequences could control transgene expression from plasmid DNAs in vivo.

[Tissue engineering of heart valves]. / Tissue Engineering von Herzklappen.

With the introduction of heart valve prostheses cardiac valvular disease has become much more accessible to therapeutic options. However, currently available prostheses display significant limitations, such as limited long-term durability (biological prostheses) and a long-term necessity for anticoagulation therapy. Hence, alternative prosthesis types have been extensively explored in recent years particularly aiming at the development of vital and regenerative prostheses by means of tissue engineering. In the scientific field, different competing concepts have been introduced, including biological or synthetic scaffolds which can be further enhanced by cellular or extracellular components to promote further in vivo development of the prosthesis after implantation. Nowadays, decellularized donor heart valves are among the most advanced prosthesis types experiencing growing clinical attention and widespread use.

Palmitate induces apoptosis in Schwann cells via both ceramide-dependent and independent pathways.

Peripheral neuropathy has been reported to prevail in obese or pre-diabetic individuals, yet its etiology remains unknown. Palmitate, a saturated fatty acid increased in obesity and diabetes, is known to induce apoptosis in multiple types of cells and this effect may be mediated by ceramide, a member of the sphingolipid family. To clarify whether de novo ceramide synthesis from palmitate contributes to apoptosis of Schwann cells, we cultured immortalized mouse Schwann cells (IMS) and rat primary Schwann cells with palmitate, a ceramide analogue C2-ceramide as well as inhibitors of the de novo ceramide synthesis (myriocin and fumonisin B1). Apoptosis of IMS detected by nuclear staining and cell membrane inversion was significantly increased by incubation with palmitate for 48 h in a dose-dependent fashion. This enhanced apoptosis was partially but significantly suppressed by myriocin and fumonisin B1. Western blot analysis and immunostaining revealed that palmitate clearly activated caspase-3 in IMS. Unexpectedly, the ceramide synthesis inhibitors failed to suppress the palmitate-induced caspase-3 activation in spite of complete restoration in ceramide accumulation. The results seemed relevant to the observations that C2-ceramide did not activate caspase-3 while provoking apoptosis with a clear dose-dependency. In agreement, the pro-apoptotic action of C2-ceramide was not attenuated by caspase inhibitors that partially suppressed palmitate-induced apoptosis. These results in IMS were well reproducible in rat primary Schwann cells, indicating that the observed phenomena are not specific to the cell line. Collectively, we have reached a conclusion that palmitate induces apoptosis in Schwann cells via both a ceramide-mediated, caspase-3-independent pathway and ceramide-independent, caspase-3-dependent pathways. Given the fact that palmitate and ceramide are increased in obese or pre-diabetic subjects, these lipids may be implicated in the pathogenesis of peripheral neuropathy observed in these disorders.

Household transmission of pandemic 2009 influenza A (H1N1) virus in Osaka, Japan in May 2009.

OBJECTIVE: To assess household transmission of pandemic influenza A (H1N1) and effectiveness of postexposure prophylaxis (PEP) of antiviral drugs among household contacts of patients during the first pandemic influenza A (H1N1) outbreak in Osaka, Japan in May 2009. METHODS: Active surveillance of patients and their families was conducted. Public Health Center staff visited each home with an infected patient and advised every household member with regard to precautionary measures, and PEP was provided to household contacts to prevent secondary infection. We analyzed the effectiveness of PEP and characteristics of secondary infection. RESULTS: The secondary attack rate (SAR) among household contacts was 3.7%. The SAR among household contacts without PEP was 26.1%. However, the SAR among those with PEP was 0.6%. Only two of 331 household contacts with PEP became infected. One of the two was infected with an oseltamivir-resistant strain. Analysis of SAR by age group showed that those under 20 years of age were at higher risk than those over 20 (relative risk [RR] = 7.9; 95% confidence interval [CI] = 2.24-27.8). Significant differences with respect to sex, number of household contacts, and use of antiviral medications in the index cases were not observed. CONCLUSIONS: Our present results indicate that PEP is effective for preventing secondary H1N1 infection among household contacts.

Clinical features of cases of influenza A (H1N1)v in Osaka prefecture, Japan, May 2009.

This report describes the clinical characteristics of influenza A(H1N1)v virus infection in Osaka. By the end of May, 171 cases had been reported in Osaka. Most patients were from one school. No patient had a serious underlying medical condition.Clinical symptoms were mild and resembled those of seasonal influenza. The sensitivity of the rapid antigen test was 77%. Antivirals were given to the majority of the cases. Early antiviral treatment may have shortened the duration of fever.

Epidemiology of influenza A(H1N1)v virus infection in Japan, May-June 2009.

Between 9 May and 4 June 2009, a total of 401 laboratory-confirmed cases of influenza A(H1N1)v virus were reported in Japan, from 16 of the 47 Japanese prefectures. The two areas most affected were Osaka prefecture and Kobe city where outbreaks in high schools occurred leading to school closures. To date all cases have had symptoms consistent with seasonal influenza and no severe or fatal cases have been reported.

The minimized extracorporeal circulation system causes less inflammation and organ damage.

The minimized extracorporeal circulation system (MECC) is being used to reduce priming volume and blood/polymer contact during cardiac procedures. In this study, we evaluated the efficacy and potential advantages of the system in coronary artery bypass graft (CABG) patients. We included two groups of patients destined for CABG in a prospective, randomized study: Group A was operated on the usual pump (n = 30) while Group B was operated using the MECC (n = 50). Pre-operative demographics, intra-operative times and values as well as a series of post-operative outcome data (blood loss, transfusion requirements, ventilation time, ICU and hospital stay) were recorded. CK, CK-MB, troponin-T, IL-6 and IL-8 were measured. Pre-operative and post-operative lung function were assessed. In the MECC-operated group, patients developed less post-operative troponin-T (0.2 +/- 0.3 vs. 0.5 +/- 0.5 ng/mL, p=0.031) and less IL-8 (13.8 +/- 5 vs. 22.5 +/- 0.5 microg/L, p = 0.05). While blood loss was comparable in both groups, packed red blood cells and fresh frozen plasma were given less frequently in the MECC group (p = 0.015 resp. 0.022). The one-tailed Student's t-test revealed shorter bypass time in the MECC group (74 +/- 17 vs. 82 +/- 24 min). There was no difference in ventilation and ICU-time (patients were not treated in a fast-track fashion). The FEV1 was better in the MECC group (relative values: 70.1 +/- 18.2% vs. 61.1 +/- 12.3%, p = 0.02). Utilization of the MECC may cause less cytokine (IL-8) liberation, owing to less blood/tubing contact, as well as less red blood cell and fresh frozen plasma demand. It may also be the circuit in patients with chronic obstructive pulmonary disease (COPD).

Intraoperative bypass graft angiography: cooperation between cardiologist and surgeons in the operation room for optimal postoperative results -- is this the way for the future?

OBJECTIVE: To confirm the quality of total arterial CABG carried out using the left internal thoracic artery (LITA) and a radial artery (RA) T-graft and distal anastomoses immediately in the OR, we developed a new technique using intraoperative graft angiography. METHODS: A 5-Fr sheath is inserted in the proximal radial artery stump, through which a catheter for LITA angiography is later introduced. From July 2004 to March 2005, 23 patients underwent total arterial CABG with the T-graft and intraoperative graft angiography. RESULTS: On-pump CABG was performed in 22 patients and off-pump CABG in 1 patient. Mean procedure time for the angiography was 13.7 +/- 7.3 minutes, and mean fluoroscopy time was 6.2 +/- 4.6 minutes. In two patients, the RA-marginal artery side-to-side anastomosis was stenosed and had to be revised as demonstrated by graft angiography. In one patient, the RA was kinked and in another, there was a kinking of the LITA. In both cases, kinking was corrected. The remaining anastomoses were seen to have unobstructed flow with no evidence of stenosis. CONCLUSIONS: Intraoperative graft angiography can be performed in patients undergoing total arterial CABG. This concept of intraoperative cooperation between an interventional cardiologist and surgeons could significantly improve the operative outcome in CABG surgery.