Short-term mortality and risk factors associated with reoperation after emergency amputation of the lower limbs.

BACKGROUND: As Japan has an aging population, elderly patients with multiple complicating comorbidities have increased in number. The purpose of the present study was to examine the 90-day mortality and reoperation rate after emergency amputation of the lower limbs and to clarify patient characteristics and preoperative comorbidities that are risk factors for reoperations. METHODS: This retrospective case study was conducted between January 2005 and December 2017. Ninety-one patients with 108 limbs who had undergone emergency amputation of the lower limbs were included in this study. Baseline data, medical comorbidities, surgical procedures and laboratory data including C-reactive protein (CRP), white blood cells (WBC) and hemoglobin A1c (HbA1c) were evaluated. Outcome measurements were mortality, reoperation rate, and factors associated with reoperation in 90 days and any complication after amputation of the lower limbs. RESULTS: The patients (male/female ratio = 64/27) had a mean age of 64.9 years, a mean WBC count of 16,747/µL, a mean CRP value of 15.6 mg/dL, and a mean HbA1c value of 7.5%. The 90-day mortality rate in the study population was 12.1%. The 90-day reoperation rate was 35.2% (32/91) patients with 32.4% (35/108) limbs. The factor significantly associated with reoperation in 90 days was peripheral arterial disease (PAD) (p = 0.022, HR = 2.75), identified with Cox proportional hazards regression analysis. A total of 41.8% (38/91) patients with 40.7% (44/108) limbs experienced postoperative wound complications. The overall rate of medical complications was 18.7% (17/91) patients with 16.7% (18/108) limbs. CONCLUSIONS: This study indicates that the 90-day mortality and reoperation rates after emergency amputation of the lower limbs were high. Furthermore, PAD influences the rate of reoperation in 90 days. However, there was no association between laboratory results or diabetes mellitus and reoperation. These findings will have important implications for the treatment of lower leg amputation and prevention of reoperation.

Association between preexisting lung involvements and the risk of diffuse alveolar hemorrhage in patients with microscopic polyangiitis: A multi-center retrospective cohort study.

Objectives: To identify the factors associated with the risk of diffuse alveolar hemorrhage (DAH) in patients with microscopic polyangiitis (MPA), focusing on other preexisting lung involvements such as interstitial lung disease (ILD) and airway disease.Methods: In this retrospective cohort study, we analyzed consecutive patients with myeloperoxidase-antineutrophil cytoplasmic antibody-positive MPA who had undergone chest computed tomography (CT) before starting treatment between 2006 and 2016. Patients who already had DAH at initial CT imaging were excluded. CT images were evaluated for the presence of ILD and airway disease. The association between preexisting lung involvements and the development of DAH was assessed using logistic regression models adjusted for various clinical characteristics.Results: We identified 113 patients (median age 72 years; median follow-up duration 39 months), and 27 (24%) of them developed DAH during the follow-up. Airway disease was identified in 41 (36%) patients and was independently associated with the development of DAH (adjusted odds ratio 6.86, 95% confidence interval 1.85-25.4). However, ILD identified in 45 (40%) patients was not associated with DAH.Conclusion: Our findings suggest that DAH in MPA occurs frequently in patients with airway disease. Attention to preexisting airway disease may help predict the development of DAH.

Associated injury complicated by pediatric lower limb shaft fractures and clinical efficacy of flexible stainless-steel intramedullary nailing in children less than 15 years old.

Although pediatric lower limb shaft fractures are common, little is known about associated injuries. The purpose of this study was to examine associated injuries complicated by pediatric lower limb shaft fractures and the efficacy of surgical treatment using a flexible stainless-steel intramedullary Ender nail in children less than 15 years old. This is a retrospective review of 29 children younger than 15 years old who were diagnosed with femoral or tibial shaft fractures and treated using Ender nails from 2005 to 2016. Baseline data, etiology, associated injuries, fracture site and patterns, operative and post-operative assessment were evaluated. The average age of the patients was 9.0 years, and mean follow-up was 18.2 months. Eleven patients (79%) had associated injury. At the final follow up, six patients (43%) sustained complications associated with the insertion area of the nail. There was no evidence of deep infection or nonunion at either fracture site. The clinical results were excellent in 10 (67%) fractures, and good in 5 (33%) fractures, based on the modified Flynn criteria. Almost all patients with a femoral fracture had an associated injury including abdominal visceral injury, cerebral contusion or other fractures. This study indicated good clinical and functional outcomes. On the other hand, the minor complications rate was high. Nevertheless, elastic stable intramedullary nailing recently has become available in Japan, and a prospective and comparative study is needed.

Eye closed learning time by Japanese during an English examination.

PURPOSE: To examine the difference of eye closed learning (iCLOL) time (time during which vision is not required), and the interblink interval (IBI), depending on the learning content, in order to consider the possibility of applying iCLOL to learning. METHODS: To examine iCLOL time during the listening, writing, and reading sections of an English examination, 19 Japanese subjects were asked to close their eyes whenever it did not interfere with their responses to the examination. Their eyes were video recorded with a video camera, and iCLOL time and the IBI were compared. RESULTS: The percentage of iCLOL time during the listening, writing, and reading sections of the examination was 50.7 ± 10.9%, 8.0 ± 6.5%, and 0.9 ± 1.0%, respectively with significant differences among the three. The iCLOL frequency during the listening, writing, and reading sections was 1.64 ± 0.54 times/min, 0.67 ± 0.50 times/min, and 0.26 ± 0.29 times/min, respectively, with significant differences among the three. The IBI during the listening, writing, and reading sections was 3.7 ± 1.7 s, 3.7 ± 1.6 s, and 5.0 ± 2.1 s, respectively; it was significantly shorter for listening and writing than for reading. CONCLUSION: iCLOL time was observed during the English examination, the percentage and frequency of which differed depending on the examination content. At times during the examination when the iCLOL time percentage and frequency were greater, the IBI was shorter. These results suggest that iCLOL may be applied as a method during learning.

Prognostic significance of spread through air spaces in pulmonary metastases from colorectal cancer.

OBJECTIVES: Surgical resection for pulmonary metastases from colorectal cancer could provide long-term survival in selected patients, and it is commonly performed in practice. However, surgical margin relapse sometimes occurs and is a problematic issue to resolve. Spread through air spaces (STAS) is one of the invasion forms in primary lung cancer and is associated with local recurrence and a poor prognosis. The aim of this study was to evaluate the prognostic significance of STAS for pulmonary metastases from colorectal cancer and to assess the predictability of STAS with preoperative clinical information. METHODS: A total of 96 pulmonary metastatic lesions from colorectal cancer in 37 patients who underwent metastasectomy at our institution from January 2008 to December 2013 were retrospectively analyzed. RESULTS: STAS was identified in 41.6 % of the 96 lesions. Surgical margin relapse was found in 8 lesions (8.3 %) from 7 patients (18.9 %). The distance of STAS was identified as an independent risk factor for surgical margin relapse on multivariable analysis (p =  0.033). The patients with STAS showed significantly worse overall survival than those without (5-year overall survival rate: 30.3 % vs. 76.9 %; p =  0.002). On multivariable analysis, patients with STAS had a significantly higher risk of death than those without (p =  0.019). An elevated pre-metastasectomy serum carcinoembryonic antigen level was independently correlated with STAS on multivariable analysis (p =  0.049). CONCLUSION: STAS was related to a poor prognosis and surgical margin relapse in pulmonary metastases from colorectal cancer.

Discovery of a new pyrimidine synthesis inhibitor eradicating glioblastoma-initiating cells.

BACKGROUND: Glioblastoma-initiating cells (GICs) comprise a tumorigenic subpopulation of cells that are resistant to radio- and chemotherapies and are responsible for cancer recurrence. The aim of this study was to identify novel compounds that specifically eradicate GICs using a high throughput drug screening approach. METHODS: We performed a cell proliferation/death-based drug screening using 10 560 independent compounds. We identified dihydroorotate dehydrogenase (DHODH) as a target protein of hit compound 10580 using ligand-fishing and mass spectrometry analysis. The medical efficacy of 10580 was investigated by in vitro cell proliferation/death and differentiation and in vivo tumorigenic assays. RESULTS: Among the effective compounds, we identified 10580, which induced cell cycle arrest, decreased the expression of stem cell factors in GICs, and prevented tumorigenesis upon oral administration without any visible side effects. Mechanistic studies revealed that 10580 decreased pyrimidine nucleotide levels and enhanced sex determining region Y-box 2 nuclear export by antagonizing the enzyme activity of DHODH, an essential enzyme for the de novo pyrimidine synthesis. CONCLUSION: In this study, we identified 10580 as a promising new drug against GICs. Given that normal tissue cells, in particular brain cells, tend to use the alternative salvage pathway for pyrimidine synthesis, our findings suggest that 10580 can be used for glioblastoma therapy without side effects.Key Points1. Chemical screening identified 10580 as a novel GIC-eliminating drug that targets DHODH, an essential enzyme for the de novo pyrimidine synthesis pathway. 2. Compound 10580 induced cell cycle arrest, apoptosis, and differentiation in GICs.

Blind working time in visual display terminal users.

OBJECTIVES: Blind working (BW) time (time during which vision is not required), the interblink interval (IBI), and subjective symptoms were investigated in workers using visual display terminals (VDTs). SUBJECTS AND METHODS: To investigate BW time, 10 VDT users were instructed to close their eyes when this did not interfere with their work. They were video recorded for 60 minutes using a webcam attached to the display on which they were engaged in regular data input tasks, and BW time was measured. The values of the IBI during the final 20 minutes of the BW experiment and during the final 20 minutes of normal working without BW were compared. A questionnaire was administered to investigate subjective symptoms using a visual analogue scale. RESULTS: The total BW time during the final 20-minute period was 20.6-121.0 seconds (1.7%-10.1%). The mean IBI of 5.5 ± 4.5 seconds during the BW experiment was not significantly different from that of 6.2 ± 5.6 seconds during normal working, and the mean of three IBIs immediately after BW during the BW experiment was 2.7 ± 1.0 seconds, significantly shorter than the 6.2 ± 5.6 seconds during normal working. Dry eye, ocular fatigue, and blurred vision during normal working improved when subjects were engaged in BW. CONCLUSIONS: VDT users could engage in BW during VDT work, the IBI was shorter immediately after BW, and subjective symptoms improved. These results suggest that BW may provide a more effective measure for the management of VDT working time.

Stress fracture of the midshaft clavicle associated with sternocostoclavicular hyperostosis-Case report.

INTRODUCTION: Stress fracture is generally a result of cumulative and repetitive stress in athletes, which accelerates the normal remodeling process of bones, and the most frequently involved areas are the tibia and metatarsal bones. Therefore, stress fractures of the midshaft of the clavicle are very rare. PRESENTATION OF CASE: A 58-year-old female was admitted to our hospital because of pain in the middle of the right clavicle. Based on laboratory and radiographic inspection, it was concluded that the stress fracture of the midshaft of the clavicle in this case was caused by sternocostoclavicular hyperostosis (SCCH). Because the clavicular fracture had no displacement or callus formation, conservative treatment with a clavicle band was undertaken. Shoulder function at the final follow-up visit was satisfactory. DISCUSSION: SCCH is a rare chronic inflammatory disorder of the axial skeleton and ossifying diathesis associated with a predominantly osteogenic response. Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and ankylosing spondylitis (AS) should be considered in the differential diagnosis of SCCH. If a patient with this type of fracture has no history of traumatic injury or sports activity, the differential diagnosis might be very difficult. CONCLUSION: We report the case of a female who had a stress fracture of the midshaft of the clavicle associated with SCCH in SAPHO or AS. Although the patient was treated conservatively, and the shoulder function was satisfactory at the final follow-up visit, re-fracture may occur in the future.

Ice Ball Crack During CT-Guided Renal Cryoablation Using 1.5-mm-Diameter Cryoprobes.

Ice ball fracture and massive hemorrhage are serious complications associated with renal cryoablation. When cracks occur in an ice ball, it is usually associated with adjacent renal parenchymal fracture, leading to massive hemorrhage. However, few studies have examined ice ball fracture under image-guided percutaneous renal cryoablation. We herein describe an 80-year-old male patient who had undergone CT-guided cryoablation for a left renal tumor using four cryoprobes (1.5 mm diameter each). Ice ball cracks were observed on CT images during cryoablation. However, there was no massive hemorrhage and further treatments were not necessary. This is the first report of ice ball cracks with a smaller diameter cryoprobe, which has not been considered to be associated with ice ball fracture.

[Questionnaire survey by anesthesia information sheet and patient's opinions about a visiting anesthesiologist].

For a visiting anesthesiologist, the time allowed for explaining anesthesia for patients is limited. A questionnaire survey by anesthesia information sheet was performed and patient's opinions about the work of a visiting anesthesiologist were evaluated. The anesthesia information sheet explaining anesthesia risks and complications in addition to the anesthesia method was useful to make the patient understand anesthesia. A visiting anesthesiologist had better avoid explaining anesthesia on the day of operation. However, it is important for a visiting anesthesiologist himself to explain the methods and risks of anesthesia to the patient in order to build a mutual trust between the patient and the anesthesiologist. It is important to obtain an informed consent on anesthesia by the visiting anesthesiologist, but the format of the consent can be variable decided by the anesthesiologist.

Acute Traumatic Patellar Tendon Rupture at the Tibial Tuberosity Attachment without Avulsion Fracture.

Patellar tendon rupture in children is especially rare. The fact that the area of traumatic rupture has wide variations makes surgical treatment difficult. We present an 11-year-old boy with acute traumatic patellar tendon rupture at the tibial tuberosity attachment without avulsion fracture. Primary end-to-end repair and reinforcement using 1.5 mm stainless steel wires as a surgical strategy were undertaken. Early range of motion began with a functional knee brace and the reinforced stainless wire was removed 3 months after surgery. Knee function at the final follow-up was satisfactory. We suggest that this strategy may provide a useful option for surgical treatment.

Discovery of nonpeptidic small-molecule AP-1 inhibitors: lead hopping based on a three-dimensional pharmacophore model.

We designed and synthesized small-molecule activator protein-1 (AP-1) inhibitors based on a three-dimensional (3D) pharmacophore model that we had previously derived from a cyclic decapeptide exhibiting AP-1 inhibitory activity. New AP-1 inhibitors with a 1-thia-4-azaspiro[4.5]decane or a benzophenone scaffold, which inhibit the DNA-binding and transactivation activities of AP-1, were discovered using a "lead hopping" procedure. An additional investigation of the benzophenone analogues confirmed the reliability of the pharmacophore model, its utility to discover AP-1 inhibitors, and the potency of the benzophenone derivatives as a lead series.

[Leak of anesthetic gases inside the anesthesia machine].

We experienced the leak of anesthetic gases inside the anesthesia machine in spite of performing the leak test before its use. After induction of anesthesia, a laryngeal mask airway was inserted and the patient was ventilated manually. At the beginning we could not find any signs of machine troubles. High airway pressure occurred immediately after switching to the mechanical ventilation. Because we could not detect the details of the machine trouble, tidal volume was set lower and the surgery was continued. After surgery, we found a crack in a fresh gas circuit valve. We have to check the anesthesia machine regularly and know its duration of use.

Excision repair cross complementing 3 expression is involved in patient prognosis and tumor progression in esophageal cancer.

The prognosis of patients with esophageal cancer remains poor. TNM classification is not sufficient to predict the prognosis. Therefore, novel predictive markers of the prognosis of esophageal cancer patients are awaited. The abnormality of the nucleotide excision repair (NER) is often involved in human cancers. Excision repair cross complementing 3 (ERCC3) contributes to NER. In esophageal cancer, ERCC3 expression has not been studied. Expression of ERCC3 was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) using LightCycler in 43 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We examined the correlation between the ERCC3 expression and the clinicopathological factors and prognosis of ESCC patients. ERCC3 expression level was significantly correlated with the pathologic stage, tumor size and local invasiveness (t-factor) in esophageal cancer tissues. Reduced expression of ERCC3 was accompanied with tumor progression (p=0.0049) and higher pathologic stage (p=0.020). Moreover, ESCC patients with low ERCC3 mRNA expression had significantly shorter post-operative survival time than those with high expression (p=0.0003). In esophageal cancer, reduced expression of ERCC3 was correlated with local tumor progression and poor prognosis after operation.

Low-back pain following surgery for lumbar disc herniation. A prospective study.

BACKGROUND: Lumbar disc herniation often causes sciatica. Although surgery may provide relief of sciatic pain, it is uncertain how surgery affects the relief of low-back pain. The purpose of the present prospective study was to assess the efficacy of discectomy in the treatment of low-back pain associated with lumbar disc herniation. METHODS: Between 1998 and 2001, forty consecutive patients with single-level, unilateral lumbar disc herniation were treated surgically. The first twenty patients (Group 1) underwent standard discectomy, and the second twenty (Group 2) underwent microendoscopic discectomy. Curettage of the disc space was not performed. All forty patients were prospectively followed, and clinical outcomes were evaluated with use of a questionnaire. The mean duration of follow-up was forty months. RESULTS: All forty patients were satisfied with the outcome. Leg pain decreased rapidly (within one month) in all patients and continued to decrease at the time of the latest follow-up. There was no significant difference between the two groups in terms of leg pain, with the numbers available (p = 0.39). A significant decrease in the mean low-back pain score was noted at the time of the latest follow-up (p = 0.0007). CONCLUSIONS: Excision of a herniated disc for relief of sciatica provided rapid relief of sciatica and low-back pain. The findings of the present small study suggest that lumbar disc herniation might be a possible cause of low-back pain.

Variations in transpiration rate and leaf cell turgor maintenance in saplings of deciduous broad-leaved tree species common in cool temperate forests in Japan.

To clarify mechanisms underlying variation in transpiration rate among deciduous broad-leaved tree species, we measured diurnal changes in stomatal conductance (gs) and leaf water potential, and calculated the maximum transpiration rate (Emax), leaf-specific hydraulic conductance (K(s-l)) and difference between the soil water potential and the daily minimum leaf water potential (Psis - Psi(l,min)). Pressure-volume (P-V) measurements were made on leaves. Saplings of eight broad-leaved tree species that are common in Japanese cool temperate forests were studied. Maximum transpiration rate varied significantly among species. There was a statistically significant difference in Psis - Psi(l,min), but not in K(s-l). Species with large Emax also had large Psis - Psi(l,min) and gs. The results of the P-V analyses showed that species with a large Psis - Psi(l,min) maintained turgor even at low leaf water potentials. The similar daily minimum leaf pressure potentials (Psip) across all eight species indicate that Psip values below this minimum are critical. Based on these results, we suggest that the leaf cell capacity for turgor maintenance strongly affects Psis - Psi(l,min) and consequently Emax via stomatal regulation.

Ocular discomfort at the initial wearing of rigid gas permeable contact lenses.

PURPOSE: To evaluate the relationship between ocular discomfort in the initial wearing of rigid gas permeable contact lenses (RGPCL) and the time required to adapt to RGPCL as measured by using the visual analogue scale (VAS). METHODS: RGPCL were prescribed for 89 patients (178 eyes) with myopia or myopic astigmatism and no history of wearing contact lenses. The patients who stopped wearing RGPCL after 1 week because of ocular discomfort were defined as dropouts, and those who adapted to regular full-time RGPCL wear were defined as successful wearers. VAS scores were measured at several intervals for 1 month after the initial wearing of the lenses. The number of days required to adapt to wearing RGPCL was defined as the adaptation time. RESULTS: Four patients were dropouts due to ocular discomfort (eight eyes; 4.5%). VAS scores were significantly lower in successful wearers than in dropouts at 1 week, although their VAS scores were not different at 1 day. VAS scores of the successful wearers at 1 week were significantly lower than those at 1 day. The average time required to adapt to RGPCL was 23.0 +/- 22.1 days for the 85 successful wearers. Lower VAS scores at 1 day or 1 week were significantly correlated with a shorter adaptation time in the successful RGPCL wearers. CONCLUSIONS: Our results indicate that the VAS score might be useful for predicting successful RGPCL use and the adaptation time required by successful wearers.

[AO classification of fractures].

In the AO classification, the diagnosis of a fracture is expressed by its location (bone and segment) and morphological features, which is characterized by the hierarchical organization into triad. This classification is comprehensive and very useful in a daily clinical practice.

Short-segment fixation without fusion for thoracolumbar burst fractures with neurological deficit can preserve thoracolumbar motion without resulting in post-traumatic disc degeneration: a 10-year follow-up study.

STUDY DESIGN: Prospective consecutive series. OBJECTIVE: To evaluate the post-traumatic disc degeneration and range of motion 10 years after short-segment fixation without fusion for thoracolumbar burst fractures with neurological deficit. SUMMARY OF BACKGROUND DATA: Early clinical results of short-segment fixation without fusion for thoracolumbar burst fractures were satisfactory. However, the long-term results have not been reported, and post-traumatic disc degeneration and preservation of thoracolumbar motion have not been elucidated. METHODS: Twelve patients who had thoracolumbar burst fractures and associated incomplete neurological deficit, operatively treated within 4 days of admission and had their implants removed within 1 year, were prospectively followed for at least 10 years. Following indirect reduction and pedicle screw fixation, transpedicular intracorporeal hydroxyapatite grafting to the fractured vertebrae was performed. RESULTS: Sagittal alignment was improved from a mean preoperative kyphosis of 17° to -2° (lordosis) by operation, but was found to have slightly deteriorated to 2° at the final follow-up observation. With respect to back pain, 8 patients did not report back pain. Three reported occasional minimal pain, and 1 reported moderate pain. None reported severe pain or needed daily dosages of analgesics.Regarding disc degeneration, the shape of the disc adjacent to the fractured vertebra had not changed from the preoperative to the 10-year postoperative magnetic resonance image (MRI). Although signal intensity of the disc had decreased by 1 grade from the preoperative to the 2-year postoperative MRI, the intensity had not changed from the 2-year postoperative MRI to the 10-year postoperative MRI. At the 10-year follow-up, flexion-extension radiographs revealed that a mean range of motion at the disc adjacent to the fractured vertebra was 12º (range; 5-19). CONCLUSION: This unprecedented 10-year follow-up study demonstrated that posterior indirect reduction, transpedicular hydroxyapatite grafting, and pedicle screw fixation does not require fusion to a segment, thereby preserves thoracolumbar motion without resulting in post-traumatic disc degeneration. LEVEL OF EVIDENCE: 4.