Prednisolone plus low-dose aspirin improves the implantation rate in women with autoimmune conditions who are undergoing in vitro fertilization

Objective: To evaluate the effect of prednisolone plus low-dose aspirin (PSL/LDA) in women with autoimmune conditions who were enrolled in an IVF-ET program.

Design: A retrospective clinical study.

Setting: In vitro fertilization unit, Niigata University Hospital, Niigata, Japan.

Patient(s): Three hundred seven women who underwent IVF-ET between January 1996 and December 1997.

Intervention(s): Prednisolone (10 mg/d) and aspirin (81 mg/d) were administered to the women with autoantibodies who chose to participate.

Main Outcome Measure(s): Pregnancy and implantation rates with IVF-ET.

Result(s): Women undergoing IVF who had positive antinuclear antibodies, with or without antiphospholipid antibodies, had significantly lower pregnancy and implantation rates than did women without autoantibodies (14.8% versus 21.7% and 6.8% versus 10.4%, respectively). The administration of PSL/LDA to women with antinuclear antibodies significantly improved the outcome of IVF-ET (40.6% pregnancy rate and 20.3% implantation rate).

Conclusion(s): A high proportion of women who are undergoing IVF-ET have autoantibodies, which are associated with poor IVF outcomes. The administration of PSL/LDA to these women may improve their implantation rate.     

Double stapling method for closure of intraoperative alveolar air leakage adjacent to the staple line: a randomized experimental study on ex vivo porcine lungs

BackgroundAlveolar air leakage from a pleural defect around the staple line is one of the complications after wedge resection of the lung. An intraoperative closure of the pleural defect by suturing can cause additional pleural rupture due to tension of the pleura adjacent to staple lines. Therefore, we have introduced a novel closure method for pleural defect adjacent to the staple line, named the double stapling method. This study compared the efficacy of two closure methods; the double stapling method and conventional suturing method with pledgets using ex vivo porcine lungs.MethodsThe double stapling method involves closing the pleural defect by suturing the two parallel staple lines at both sides of the pleural defect. This method was developed to distribute the pleural tension around the needle holes of suturing. As a model of pleural defect adjacent to the staple line after wedge resection, wedge resection of the caudal lobe of left porcine lungs was performed, and a superficial square pleural defect (10 mm × 10 mm) adjacent to the staple line was made by scalpel. The defect was closed using the following two methods: (I) suturing with pledgets (n=10); and (II) double stapling method (n=10). The lobe was inflated in water at an airway pressure of 20, 25, and 30 cmH₂O; closure success or failure was judged by the absence or presence of air leakage.ResultsThe closure success was confirmed in 2 (20%) out of 10 cases in the suturing with pledgets group and 9 (90%) out of 10 in the double stapling method group (P=0.007). In 4 out of 10 cases in the suturing with pledgets group, new pleural clefts longer than 3 mm were created around the needle holes of suturing.ConclusionsEx vivo experiments have suggested the superiority of the double stapling method for the intraoperative closure of alveolar air leakage adjacent to the staple line after wedge resection, compared to conventional suturing with the pledget method.     

A tumor metastasis‐associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity

Although neoantigens are one of the most favorable targets in cancer immunotherapy, it is less versatile and costly to apply neoantigen‐derived cancer vaccines to patients due to individual variation. It is, therefore, important to find highly immunogenic antigens between tumor‐specific or associated antigens that are shared among patients. Considering the cancer immunoediting theory, immunogenic tumor cells cannot survive in the early phase of tumor progression including two processes: elimination and equilibrium. We hypothesized that highly immunogenic molecules are allowed to be expressed in tumor cells after an immune suppressive tumor microenvironment was established, if these molecules contribute to tumor survival. In the current study, we focused on TWIST1 as a candidate for highly immunogenic antigens because it is upregulated in tumor cells under hypoxia and promotes tumor metastasis, which is observed in the late phase of tumor progression. We demonstrated that TWIST1 had an immunogenic peptide sequence TWIST1_140–162, which effectively activated TWIST1‐specific CD4⁺ T‐cells. In a short‐term culture system, we detected more TWIST1‐specific responses in breast cancer patients compared with in healthy donors. Vaccination with the TWIST1 peptide also showed efficient expansion of TWIST1‐reactive HTLs in humanized mice. These findings indicate that TWIST1 is a highly immunogenic shared antigen and a favorable target for cancer immunotherapy.     

Segregation Behavior of Miscible PC/PMMA Blends during Injection Molding

Miscible blends composed of bisphenol-A polycarbonate (PC) and poly(methyl methacrylate) (PMMA), in which one of them has low molecular weight, were employed to study the surface segregation behavior during flow. The blend samples showed typical rheological behaviors, such as simple polymer melts without a long-time relaxation mechanism ascribed to phase separation, demonstrating that they were miscible. After injection molding, the amounts of a low molecular weight component on the blend surface were found to be larger than the actual blend ratio. Because the injection-molded products were transparent despite a huge difference in refractive indices between PC and PMMA, they showed no phase separation. This result demonstrated that surface segregation of a low molecular weight component occurred under flow field, which expands the material design such as tough plastics with good scratch resistance and optical fibers with tapered refractive index.     

Surgical outcomes of nephron-sparing surgery for renal tumors

PURPOSE: We retrospectively assessed the surgical outcomes of nephron-sparing surgery (NSS) for patients with renal tumors. PATIENTS AND METHODS: From 1985 to March 2001, a total of 99 NSSs were performed on 94 patients with renal tumors. The patients were divided into three groups. Group I comprised of 22 patients who underwent imperative surgeries for renal cell carcinoma (RCC). The tumors were found in 18 patients bilaterally (including 8 patients with von Hippel-Lindau disease), in 3 with solitary kidney, and in 1 with chronic renal failure. The mean +/- standard deviation of patient age and tumor diameter was 46 +/- 23 years and 36 +/- 23 mm, respectively. Twenty-three in situ NSSs were performed on 18 patients in Group I, and the remaining 4 patients were treated with 3 simultaneous operations for bilateral renal tumors with or without 2 ex vivo surgeries. Group II consisted of 49 patients who had small RCCs with the normal contralateral kidney and underwent NSSs (elective indication). The mean age and tumor diameter was 54 +/- 10 years and 28 +/- 11 mm, respectively. Group III consisted of 23 patients with non-RCC tumor (10 angiomyolipomas, 8 cystic tumors, 2 adenomas, 2 metastatic tumors, and 1 degenerative lesion), all of whom were treated with NSS. The mean age and tumor diameter was 47 +/- 14 years and 41 +/- 29 mm, respectively. RESULTS: In Group I, 3 patients died of cancer including 2 patients who had had multiple lung metastases preoperatively. The five-year tumor specific survival rate was 87.3% with a postoperative follow-up of 49 +/- 36 months. In Group II, there were few peri-operative complications or no local recurrence at follow-up of 52 +/- 38 months. A patient developed lung metastasis, which was removed surgically with no evidence of recurrence at 159 months after NSS. Postoperative renal scintigraphy on 35 patients showed well-preserved renal function of the operated kidney. Improvement in surgical techniques resulted in less-invasive surgery in 22 operations during the last 4 years. The patients of Group III were also operated uneventfully, although 1 experienced postoperative bleeding. In 12 patients with solitary kidney (11 in Group I and 1 in Group III) serum creatinine level increased transiently, decreased to 1.3 times of preoperative values within 3 months, and almost recovered at 1-year follow-up. CONCLUSION: Excellent outcomes in cancer control and preservation of renal function support the validity of nephron-sparing surgery to treat renal tumors. The candidate patients may include those with bilateral kidney tumors, tumor occuring in the solitary kidney or small renal cell carcinomas with the normal contralateral kidney. Earlier detection of small lesions and less invasive surgical techniques will facilitate a wider indication of NSS.     

Callotasis lengthening in patients with brachymetacarpia

Callotasis lengthening is an established method, but few cases of metacarpal lengthening have been reported. The authors performed callotasis lengthening to treat brachymetacarpia in six digits in three patients. The patient age at the time of distraction ranged from 10 to 19 years. The period of application of an external fixator averaged 13.9 weeks (range 10-19 weeks). All the metacarpals achieved the target length, and all patients were satisfied with the esthetic improvement. The length of the metacarpal distraction averaged 15.2 mm (range 10-18 mm). Complete consolidation of the transport gap was achieved for five of six digits. One digit that had a history of previous lengthening required bone graft. The average healing index was 62.3 days/cm. There were no serious complications. In four digits, the range of flexion of the metacarpophalangeal joint was increased after lengthening, and this enabled the patient to use the digit easily in a palmar grasp. Brachymetacarpia is an appropriate indication for callotasis lengthening in congenital deformities of the upper extremities.     

Preparation and incubation conditions affect the DNA integrity of ejaculated human spermatozoa

Appropriate semen processing and assessment are critical for successful infertility treatment. We investigated whether laboratory procedures including semen preparation and incubation affect sperm DNA integrity. A total of 153 infertile men were involved. Conventional semen parameters and sperm chromatin structure assay （SCSA） parameters, that is, DNA fragmentation index （%DFI） and high DNA stainability （%HDS）, were assessed on the flesh ejaculated semen samples, which were treated and incubated under different conditions. Negative correlations were identified between the %DFI and sperm concentration, motility, progressive motility and morphology. A lower percentage of DFI was detected in spermatozoa when density gradient centrifugation （DGC） was followed by swimup treatment in comparison with DGC alone （P 〈 0.01）. Although the %DFI increased in a time-dependent manner with incubation both at room temperature （RT） and at 37℃ in air, the %DFI after 24 h at RT was significantly lower than that at 37℃ （P 〈 0.05）. Incubation with 5% CO2 was effective in maintaining sperm motility （P 〈 0.01）; however, it induced further elevation of %DFI （P 〈 0.001）. Thus, sperm DNA damage was associated with longer incubation periods. Interestingly, common culture conditions, such as maintaining pH and temperature, compromised the sperm DNA integrity.