Conservative treatment of fragility fracture of the pelvis: A retrospective study.

BACKGROUND: Although an increasing number of studies have reported the usefulness of early minimally invasive surgery (MIS) or fragility fracture of the pelvis (FFP), MIS is difficult to perform in every hospital, partly because of equipment problems. Moreover, different opinions exist on FFP treatment methods and the indication for surgery is usually determined by the fracture type. Since our hospital follows a conservative approach as the basic treatment, this study examined the outcomes of such an FFP approach. HYPOTHESIS: FFP outcomes are influenced by the fracture type and walking ability before the injury. PATIENTS AND METHODS: We investigated the bone fusion rate, bone fusion duration, unloading duration, walking ability trends, and outcomes in 76 patients with FFP treated conservatively at our hospital. RESULTS: The union rate, mean period until union, and follow-up period were 93.4%, 3.3 months, and 14.3 months, respectively. Walking ability significantly decreased from 5.1 points before the injury to 4.4 points during the last follow-up (p<0.01). The average unloading period was 12.8 days, and FFPs showed a high bone fusion rate, even with conservative treatment. DISCUSSION: Most patients eventually returned to their pre-injury status despite slightly decreased walking ability. Given the invasive nature of surgery, the indications for surgery should be carefully assessed after considering the risk-benefit ratio. LEVEL OF EVIDENCE: III; retrospective study.

Delayed surgery after hip fracture affects the incidence of venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is one of the most common complications of hip fracture surgeries, and it is unclear whether delayed surgery affects the incidence of VTE. This study aimed to examine the association between delayed surgery and VTE incidence by statistically adjusting for factors that may influence VTE incidence. METHODS: We included 862 patients ≥ 65 years with hip fractures who underwent surgery between October 2010 and December 2020. We examined the effect of surgical delay 48 h after injury on postoperative VTE. Patients with and without VTE were assigned to groups V and NV, respectively. Those with and without proximal deep venous thrombosis (DVT) were assigned to PD and NPD groups, respectively. Univariate analysis was performed to identify factors that might influence DVT development. Risk factors for developing VTE and proximal DVT were analyzed using logistic regression analysis to determine whether delayed surgery was a risk factor. RESULTS: VTE was observed in 436 patients (40%) and proximal DVT in 48 patients (5.6%). Univariate analysis showed significant differences in the time from trauma to surgery between the V and NV groups and between the PD and NPD groups. In multivariate analysis, surgery 48 h later was also a risk factor for developing VTE and proximal DVT. CONCLUSION: A delay in surgery beyond 48 h after a hip fracture injury is a risk factor for developing VTE and proximal DVT.

Pneumocephalus After Anterior Lumbar Spinal Surgery Due to Trauma: A Case Report.

Pneumocephalus as a complication of anterior lumbar spinal surgery is extremely rare. A 53-year-old male patient presented with L4 fracture. Posterior fixation from L3 to L5 was conducted one day after the trauma. As the patient's neurological deficit persisted, additional anterior surgery by L4 vertebral body replacement was performed on the 19th day. Both surgeries were completed without obvious intraoperative complications. Two weeks after the anterior lumbar surgery, the patient complained of severe headaches, and computed tomography scan revealed pneumocephalus and massive fluid retention in the abdomen. The symptoms improved with conservative treatment, including bed rest, spinal drainage, intravenous drip infusion, and prophylactic administration of antibiotics. Due to the lack of tamponade effect in the soft tissues, a large amount of cerebrospinal fluid leakage may induce and cause progression of pneumocephalus in anterior dural injury.

Minimally invasive surgery technique for unstable pelvic ring fractures with severe vertical shear displacement: A retrospective study.

BACKGROUND: Unstable pelvic fractures, especially vertical shear fractures, require surgery for correct reduction, rigid fixation, and improved postoperative outcomes. Herein, we assess the effectiveness of our minimally invasive procedure for the management of unstable pelvic fractures. HYPOTHESIS: We hypothesized that this procedure would be useful for the management of unstable pelvic fractures. PATIENTS AND METHODS: This study included 28 patients with unstable pelvic fractures (vertical shear injuries; AO types C1-3) treated using minimally invasive surgery for spinopelvic fixation (MIS-SP) between 2014 and 2020 (mean follow-up time, 15 months). The MIS-SP requires four percutaneous pedicle screws and four iliac screw insertions. Subsequently, reduction and fixation are performed. RESULTS: The mean preoperative displacement of the posterior pelvic elements in craniocaudal correction was 17.6 (range, 9.0-32.2) mm. The mean length of the craniocaudal reduction was 16.5 (8.1-30.1) mm, with a mean reduction rate of 93.5% (78%-100%). The mean length of the mediolateral reduction was 11.3 (3.9-19.6) mm, with a mean reduction rate of 87.3% (76%-100%). DISCUSSION: Our novel reduction and fixation procedure is a powerful, minimally invasive option for the treatment of unstable pelvic ring fractures. LEVEL OF EVIDENCE: III.

Ultrastructural observation of filtration membrane in cell-free and concentrated ascites reinfusion therapy for malignant ascites.

INTRODUCTION: Cell-free and concentrated ascites reinfusion therapy (CART) is used for the treatment of diuretic-resistant ascites. An increase in circuit pressure and clogging of the filtration membrane often occur in CART for malignant ascites. METHODS: To clarify the precise mechanism of filter clogging, we performed an ultrastructural observation study of the filtration membrane after the filtration of malignant ascites. RESULTS: The deposition on the filtration membrane was composed of blood cells, fibrin, or both. Cellular deposition was associated with a greater number of blood cells in the original ascites fluid. In contrast, fibrin deposition was associated with higher levels of interleukin-6, α1-antitrypsin, haptoglobin, and fibrinogen/fibrin degradation products. CONCLUSION: Our results suggest that the specific pathophysiologies of malignancy (such as inflammation or coagulation/fibrinolysis) and characteristics of malignant ascites (highly concentrated and cell-rich) are associated with clogging of the filtration membrane during CART.

3DeeCellTracker, a deep learning-based pipeline for segmenting and tracking cells in 3D time lapse images.

Despite recent improvements in microscope technologies, segmenting and tracking cells in three-dimensional time-lapse images (3D + T images) to extract their dynamic positions and activities remains a considerable bottleneck in the field. We developed a deep learning-based software pipeline, 3DeeCellTracker, by integrating multiple existing and new techniques including deep learning for tracking. With only one volume of training data, one initial correction, and a few parameter changes, 3DeeCellTracker successfully segmented and tracked ~100 cells in both semi-immobilized and 'straightened' freely moving worm's brain, in a naturally beating zebrafish heart, and ~1000 cells in a 3D cultured tumor spheroid. While these datasets were imaged with highly divergent optical systems, our method tracked 90-100% of the cells in most cases, which is comparable or superior to previous results. These results suggest that 3DeeCellTracker could pave the way for revealing dynamic cell activities in image datasets that have been difficult to analyze.

Microscopes have been used to decrypt the tiny details of life since the 17th century. Now, the advent of 3D microscopy allows scientists to build up detailed pictures of living cells and tissues. In that effort, automation is becoming increasingly important so that scientists can analyze the resulting images and understand how bodies grow, heal and respond to changes such as drug therapies. In particular, algorithms can help to spot cells in the picture (called cell segmentation), and then to follow these cells over time across multiple images (known as cell tracking). However, performing these analyses on 3D images over a given period has been quite challenging. In addition, the algorithms that have already been created are often not user-friendly, and they can only be applied to a specific dataset gathered through a particular scientific method. As a response, Wen et al. developed a new program called 3DeeCellTracker, which runs on a desktop computer and uses a type of artificial intelligence known as deep learning to produce consistent results. Crucially, 3DeeCellTracker can be used to analyze various types of images taken using different types of cutting-edge microscope systems. And indeed, the algorithm was then harnessed to track the activity of nerve cells in moving microscopic worms, of beating heart cells in a young small fish, and of cancer cells grown in the lab. This versatile tool can now be used across biology, medical research and drug development to help monitor cell activities.

Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine.

INTRODUCTION: No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR) of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV). PATIENTS AND METHODS: AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. RESULTS: Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20) after comprehensive treatments including AFTV. The median overall survival time (60.0 months) and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988-2002) and in the nationwide population-based cohort study of Denmark (1999-2007). CONCLUSION: Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.

Positive affect and regional cerebral blood flow in Alzheimer's disease.

Quality of life (QOL) has been recently recognized as the central purpose of healthcare, and positive affect is one of the core dimension of QOL. However, positive affect among patients with dementia or Alzheimer's disease (AD) has not received much attention in the medical research field. One hundred sixteen consecutive patients with AD were recruited from the outpatient units of the Memory Clinic of Okayama University Hospital. The positive affect score was evaluated using the positive affect domain of the Quality of Life questionnaire for Dementia (QOL-D). Patients underwent brain SPECT with 99mTc-ethylcysteinate dimer. Positive affect scores were inversely related to apathy scores, subjective depressive scores, and delusion scores. After removing the effects of age, sex, duration of education, and cognitive function, positive affect scores showed a significant correlation with regional cerebral blood flow in the left premotor and superior frontal gyri. The left premotor and superior frontal area is significantly involved in the pathogenesis of the decrease of positive affect in AD. Apathy and depression are closely related to the prefrontal area in AD, and they may affect the relationship between positive affect and the left prefrontal area.

Suppression of postsurgical recurrence of hepatocellular carcinoma treated with autologous formalin-fixed tumor vaccine, with special reference to glypican-3.

Autologous formalin-fixed tumor vaccine (AFTV) suppressed re-recurrence for more than 32 months of multiple-recurrent hepatocellular carcinoma based on hepatitis C virus-induced liver cirrhosis in a case with previous recurrence interval, 51-, 28-, 12-, and 4-months. We detected glypican-3-specific cytotoxic T lymphocytes in the peripheral blood at 12 months after AFTV.

Prognostic relevance of apparent diffusion coefficient obtained by diffusion-weighted MRI in pancreatic cancer.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) is utilized as a method of oncologic imaging for predicting treatment outcomes. This study explored the role of DW-MRI in the treatment of patients with resected pancreatic cancer by comparing apparent diffusion coefficient (ADC) values with clinicopathological findings and survival rates. MATERIALS AND METHODS: Records of 54 patients in whom DW-MRI at 1.5T was performed (b values: 0 and 1000 mm(2) /s) before macroscopically curative resection were analyzed. ADC values were then calculated and compared with clinicopathological factors including age, gender, serum carcinoembryonic antigen levels, serum carbohydrate antigen 19-9 levels, lymph node metastasis, primary tumoral location, size, differentiation, resectability, and pT stage. A survival analysis of clinicopathological factors and ADC values was performed using the Kaplan-Meier method, and the results were evaluated with the log-rank test. Prognostic significance was assessed using the Cox proportional hazard model. RESULTS: Significant associations were found between tumor differentiation and ADC values (P = 0.001). In a univariate analysis of overall survival, tumor differentiation (P = 0.037) and ADC values (P = 0.002) were identified as significant prognostic factors. However, age, gender, carcinoembryonic antigen levels, carbohydrate antigen 19-9 levels, lymph node metastasis, primary tumoral location, size, resectability, and pT stage were not associated with overall survival. In a multivariate analysis of overall survival, only ADC values were identified as significant prognostic factors (hazard ratio 2.293, 95% confidence interval 1.147-4.585, P = 0.019). CONCLUSION: ADC values were found to be associated with prognosis in patients with resected pancreatic cancer.

Bone marrow stromal cells rescue ischemic brain by trophic effects and phenotypic change toward neural cells.

Background. Transplantation of bone marrow stromal cells (BMSCs) may contribute to functional recovery after stroke. This study was designed to clarify their mechanisms, trophic effects of neurotrophic factors, and neural differentiation. Methods. Mouse neurons exposed to glutamate were cocultured with mouse BMSCs. Either neutralizing antibodies against brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF) or Trk inhibitor K252a was added to explore the mechanism of their protective effects. Fluorescence in situ hybridization (FISH) was used to assess BDNF or NGF mRNA expression in BMSCs. The mice were subjected to permanent focal ischemia, and 7 days later, either BMSCs or the vehicle was stereotactically transplanted into the ipsilateral striatum. The mouse brains were processed for FISH and immunostaining 2 or 4 weeks after transplantation. Results. BMSCs significantly ameliorated glutamate-induced neuronal death. Treatment with anti-BDNF antibody significantly reduced their protective effects. FISH analysis showed that the majority of BMSCs expressed BDNF and NGF mRNA in vitro. BMSC transplantation significantly improved the survival of neurons in peri-infarct areas. FISH analysis revealed that approximately half of BMSCs expressed BDNF and NGF mRNA 2 weeks after transplantation; however, the percentage of BDNF and NGF mRNA-positive cells decreased thereafter. Instead, the percentage of microtubule-associated protein 2-positive BMSCs gradually increased during 4 weeks after transplantation. Conclusions. These findings strongly suggest that BDNF may be a key factor underlying the trophic effects of BMSCs. BMSCs might exhibit the trophic effect in the early stage of cell therapy and the phenotypic change toward neural cells thereafter.

Phase I/IIa trial of fractionated radiotherapy, temozolomide, and autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma.

OBJECT: Temozolomide (TMZ) may enhance antitumor immunity in patients with glioblastoma multiforme (GBM). In this paper the authors report on a prospective Phase I/IIa clinical trial of fractionated radiotherapy (FRT) concomitant with TMZ therapy, followed by treatment with autologous formalin-fixed tumor vaccine (AFTV) and TMZ maintenance in patients with newly diagnosed GBM. METHODS: Twenty-four patients (age 16-75 years, Karnofsky Performance Scale score ≥ 60% before initiation of FRT) with newly diagnosed GBM received a total dose of 60 Gy of FRT with daily concurrent TMZ. After a 4-week interval, the patients received 3 AFTV injections and the first course of TMZ maintenance chemotherapy for 5 days, followed by multiple courses of TMZ for 5 days in each 28-day cycle. RESULTS: This treatment regimen was well tolerated by all patients. The percentage of patients with progression-free survival (PFS) ≥ 24 months was 33%. The median PFS, median overall survival (OS), and the actuarial 2- and 3-year survival rates of the 24 patients were 8.2 months, 22.2 months, 47%, and 38%, respectively. The median PFS in patients with a delayed-type hypersensitivity (DTH) response after the third AFTV injection (DTH-2) of 10 mm or larger surpassed the median length of follow-up for progression-free patients (29.5 months), which was significantly greater than the median PFS in patients with a smaller DTH-2 response. CONCLUSIONS: The treatment regimen was well tolerated and resulted in favorable PFS and OS for newly diagnosed GBM patients. Clinical trial registration no.: UMIN000001426 (UMIN clinical trials registry, Japan).

Preoperative diagnosis and surgical management for solid pseudopapillary neoplasm of the pancreas.

BACKGROUND: Preoperative diagnosis of solid pseudopapillary neoplasm of the pancreas (SPN) remains difficult and optimal surgical management for SPN has yet to be fully defined. METHODS: Retrospective analysis was undertaken of all 10 patients (six women, four men) who underwent surgery for SPN between 2001 and 2013. RESULTS: Mean age was 26 years (range, 16-33 years) for women, and 50 years (range, 35-76 years) for men. Although large SPN showed typical imaging findings, small SPN (≤ 3.0 cm) appears as almost entirely solid tumors. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed in six patients with atypical findings of SPN for differentiation from other pancreatic neoplasms. Definitive preoperative cytological diagnosis was achieved in all patients who underwent EUS-FNA. All 10 patients underwent surgical exploration. One patient with portal vein invasion and multiple lung metastases underwent pancreaticoduodenectomy combined with portal vein resection and reconstruction, followed by two pulmonary resections. This patient remains alive as of 34 months after the initial operation. CONCLUSIONS: Endoscopic ultrasound-guided fine-needle aspiration is useful for definitive preoperative diagnosis of SPN. As long-term survival after surgical resection can be achieved even in patients with locally advanced and metastatic SPN, aggressive surgical resection should be performed.

Discovery of novel differentiation markers in the early stage of chondrogenesis by glycoform-focused reverse proteomics and genomics.

BACKGROUND: Osteoarthritis (OA) is one of the most common chronic diseases among adults, especially the elderly, which is characterized by destruction of the articular cartilage. Despite affecting more than 100 million individuals all over the world, therapy is currently limited to treating pain, which is a principal symptom of OA. New approaches to the treatment of OA that induce regeneration and repair of cartilage are strongly needed. METHODS: To discover potent markers for chondrogenic differentiation, glycoform-focused reverse proteomics and genomics were performed on the basis of glycoblotting-based comprehensive approach. RESULTS: Expression levels of high-mannose type N-glycans were up-regulated significantly at the late stage of differentiation of the mouse chondroprogenitor cells. Among 246 glycoproteins carrying this glycotype identified by ConA affinity chromatography and LC/MS, it was demonstrated that 52% are classified as cell surface glycoproteins. Gene expression levels indicated that mRNAs for 15 glycoproteins increased distinctly in the earlier stages during differentiation compared with Type II collagen. The feasibility of mouse chondrocyte markers in human chondrogenesis model was demonstrated by testing gene expression levels of these 15 glycoproteins during differentiation in human mesenchymal stem cells. CONCLUSION: The results showed clearly an evidence of up-regulation of 5 genes, ectonucleotide pyrophosphatase/phosphodiesterase family member 1, collagen alpha-1(III) chain, collagen alpha-1(XI) chain, aquaporin-1, and netrin receptor UNC5B, in the early stages of differentiation. GENERAL SIGNIFICANCE: These cell surface 5 glycoproteins become highly sensitive differentiation markers of human chondrocytes that contribute to regenerative therapies, and development of novel therapeutic reagents.

Randomized controlled study of gemcitabine plus S-1 combination chemotherapy versus gemcitabine for unresectable pancreatic cancer.

PURPOSE: The aim of this study was to evaluate efficacy and safety of gemcitabine plus S-1 (GS) combination chemotherapy in patients with unresectable pancreatic cancer. METHODS: Patients were randomly assigned to receive GS (oral S-1 60 mg/m(2) daily on days 1-15 every 3 weeks and gemcitabine 1,000 mg/m(2) on days 8 and 15) or gemcitabine (1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks). The primary endpoint was progression-free survival (PFS). RESULTS: One hundred and one patients were randomly assigned. PFS was significantly longer in the GS arm with an estimated hazard ratio (HR) of 0.65 (95 % CI 0.43-0.98; P = 0.039; median 5.3 vs 3.8 months). Objective response rate (ORR) was also better in the GS arm (21.6 vs 6 %, P = 0.048). Median survival was 8.6 months for GS and 8.6 months for GEM (HR 0.93; 95 % CI 0.61-1.41; P = 0.714). Grade 3-4 neutropenia (44 vs 19.6 %, P = 0.011) and thrombocytopenia (26 vs 8.7 %, P = 0.051) were more frequent in the GS arm. CONCLUSIONS: GS therapy improved PFS and ORR with acceptable toxicity profile in patients with unresectable pancreatic cancer.

Factors affecting the accuracy of endoscopic transpapillary sampling methods for bile duct cancer.

BACKGROUND AND AIM: Various methods for endoscopic transpapillary sampling have been developed. However, the factors affecting the accuracy of these methods for bile duct cancer are unknown. The aim of the present study was to determine the factors affecting the accuracy of endoscopic transpapillary sampling methods. METHODS: We reviewed the results from 101 patients with bile duct cancer who underwent transpapillary sampling by aspiration bile cytology, brushing cytology, and fluoroscopic forceps biopsy. The final diagnosis of bile duct cancer was made on the basis of pathological evaluation of specimens obtained at surgery and the clinical course over at least 1 year in patients not operated on. We carried out subgroup analyses for the factors affecting the accuracy of each transpapillary sampling method. RESULTS: Aspiration bile cytology was carried out 238 times in 77 patients, brushing cytology was carried out 67 times in 60patients, and fluoroscopic forceps biopsy was carried out 64 times in 53 patients. Accuracies of aspiration bile cytology were significantly higher for longer (≥15 mm) biliary cancerous lesions than for shorter (<15 mm) lesions (30% vs 18%, respectively, P = 0.049). Accuracies of brushing cytology and fluoroscopic forceps biopsy were significantly higher for non-flat than for flat-type biliary cancerous lesions (brushing: 58% vs 38%, respectively, P = 0.032; forceps biopsy: 60% vs 33%, respectively, P = 0.043). CONCLUSION: Endoscopic transpapillary sampling methods are more accurate for longer or elevated (non-flat) biliary cancerous lesions than for shorter or flat lesions.

Hypertonic saline-epinephrine local injection therapy for post-endoscopic sphincterotomy bleeding: removal of blood clots using pure ethanol local injection.

PURPOSE: Bleeding following endoscopic sphincterotomy (EST) is a rare but unavoidable complication of the procedure. We routinely perform local injection of hypertonic saline-epinephrine (HSE) for the treatment of post-EST bleeding. Any blood clot is removed only by irrigation with water after local injection of pure ethanol into the blood clot to cause crusting. We evaluated the usefulness of this treatment method. METHODS: Subjects were 8 patients (1.2%) with post-EST bleeding requiring hemostatic intervention among 682 patients undergoing EST. After determination of the bleeding point, local injection of HSE was performed. When an adherent blood clot was present, pure ethanol was injected into the blood clot and then irrigation with water was performed to remove the blood clot. RESULTS: Endoscopic hemostasis was successfully achieved in all the 8 patients (100%). In 4 patients (50%), the adherent blood clots were successfully removed only with pure ethanol local injection into the blood clot followed by irrigation with water. No complications of the hemostatic procedure occurred in any patients. CONCLUSIONS: This study indicated that hemostasis with HSE local injection can be safe and useful for the treatment of post-EST bleeding, and also that blood clot removal with pure ethanol local injection can be useful.

Accelerated tau aggregation, apoptosis and neurological dysfunction caused by chronic oral administration of aluminum in a mouse model of tauopathies.

To clarify whether long-term oral ingestion of aluminum (Al) can increase tau aggregation in mammals, we examined the effects of oral Al administration on tau accumulation, apoptosis in the central nervous system (CNS) and motor function using tau transgenic (Tg) mice that show very slowly progressive tau accumulation. Al-treated tau Tg mice had almost twice as many tau-positive inclusions in the spinal cord as tau Tg mice without Al treatment at 12 months of age, a difference that reached statistical significance, and the development of pretangle-like tau aggregates in the brain was also significantly advanced from 9 months. Al exposure did not induce any tau pathology in wild-type (WT) mice. Apoptosis was observed in the hippocampus in Al-treated tau Tg mice, but was virtually absent in the other experimental groups. Motor function as assessed by the tail suspension test was most severely impaired in Al-treated tau Tg mice. Given our results, chronic oral ingestion of Al may more strongly promote tau aggregation, apoptosis and neurological dysfunction if individuals already had a pathological process causing tau aggregation. These findings may also implicate chronic Al neurotoxicity in humans, who frequently have had mild tau pathology from a young age.