The association between early rehabilitation and ambulatory ability at discharge in patients with hip fractures at acute-phase rehabilitation wards: a survey of the Japan Association of Rehabilitation Database.

This study aimed to examine the effectiveness of early rehabilitation in patients with femoral neck fractures admitted to acute care settings in Japan using the data registered with the Japan Association of Rehabilitation Databases (JARD). We included data for 401 patients (out of 3088 patients) aged ≥ 65 years (85 males, 316 females) from nine hospitals who sustained a femoral neck fracture between July 2005 and September 2015. Using the number of days until surgery or the number of days until the start of rehabilitation or both as the explanatory variables, and the indoor mobility at discharge as the outcome variable, we calculated the adjusted rate ratio (ARR) and 95% confidence interval (CI) using Poisson regression analysis (age, sex, cognitive impairment, concurrent symptoms, and previous history of fracture adjusted as covariates). The ARR for independent walking at the discharge of the early-rehabilitation group (starting rehabilitation within two days after the injury) was significantly higher (ARR: 2.01, 95% CI: 1.34-3.02) than that of the non-early rehabilitation group. These results suggest that early acute-phase rehabilitation after a femoral neck fracture in older patients allows for better ambulatory ability at discharge, regardless of the time to surgery.

Immunostimulatory effects of a subcritical water extract of Ganoderma.

Ganoderma, a medicinal mushroom with various physiological activities, has been extensively investigated regarding its effectiveness. The aim of the present study was to examine the effects of a subcritical water extract of Ganoderma (SWEG) on the immune system. The use of subcritical water with a higher temperature and pressure than hot water allows efficient elution of components from natural products. As an evaluation of the effectiveness of SWEG, a cell proliferation and a cell differentiation test were carried out using A-6 cells, a model of hematopoietic stem cells. Furthermore, an oral administration test in mice was conducted to examine the effects of SWEG on the number and function of immune cells. As a result, SWEG was revealed to promote both self-renewal and differentiation into immune cells such as T cells and natural killer (NK) cells in experiments with A-6 cells. These results were not obtained in experiments using hot water extract of Ganoderma lucidum and Ganoderma sinense. The oral administration test in mice demonstrated that SWEG increased hematopoietic precursor cells, immature B cells, and NK cells in the bone marrow, and T cells in the thymus. In addition, SWEG enhanced the immune functions in the spleen by promoting granzyme B expression and NK cell activity. SWEG was demonstrated to be a food material that acts on HSCs and regulates immunity in vivo.

Staged coil embolization after thoracic endovascular stent grafting for aneurysmal chronic type B aortic dissection: A case report.

We herein describe a 38-year-old woman with Marfan syndrome and chronic type A aortic dissection. Computed tomography showed that the sinus of Valsalva and thoracoabdominal aorta had a diameter of 62 and 55 mm, respectively. After 7 months of a Bentall operation and total arch replacement with the elephant trunk technique, we performed thoracic endovascular aortic repair for an aneurysm of the descending aorta, but we preserved the retrograde flow into the false lumen because it supplied vessels perfusing the spinal cord. Computed tomography angiography 14 months after thoracic endovascular aortic repair showed that the thoracic aortic diameter had increased to 68 mm. We then performed partial (proximal only) coil embolization of the false lumen. After 6 months, the thoracic aortic diameter had decreased to 60 mm and the spinal cord remained perfused via the distal false lumen. Staged coil embolization after thoracic endovascular aortic repair for aneurysmal chronic type B aortic dissection is feasible and can be beneficial.

First surveillance and molecular identification of the Cryptosporidium skunk genotype and Cryptosporidium parvum in wild raccoons (Procyon lotor) in Osaka, Japan.

Recent research suggests that raccoons (Procyon lotor) can transmit several important pathogens affecting humans, including protozoans. In Japan, the number of wild raccoons has increased since they were first introduced more than 50 years ago. Here, we report the first survey of Cryptosporidium infection using fecal swabs of raccoons captured in Osaka, Japan. Of 116 raccoons examined by PCR targeting of the Cryptosporidium 18S rRNA gene, 7 (6.03%; 2 adults and 5 young animals) were positive, and the isolates were identified as Cryptosporidium skunk genotype (subtype XVIa) and C. parvum based on sequence and phylogenetic analyses. Both species and the genotype are zoonotic; thus, our results suggest that raccoons could transmit Cryptosporidium infections to humans in Japan.

[State of glycemic control in elderly diabetic patients].

AIM: The Japan Diabetes Society and The Japan Geriatric Society made a joint committee and published a new glycemic target in May 2016. Because reports on the state of glycemic control in elderly diabetic patients are insufficient, we investigated the state of glycemic control in this population before the new glycemic target was established. METHODS: We enrolled patients older than 65 years of age who had been prescribed antidiabetic drugs and hospitalized in the geriatric department of Nagoya University Hospital from April 1, 2015, to March 31, 2016. We investigated the participants' HbA1c, prescription of antidiabetic drugs carrying risks of severe hypoglycemia (risk drugs) at hospitalization, cognitive function, basic activities of daily living, and instrumental activities of daily living. RESULTS: A total of 63 patients were enrolled. Thirty-five patients were male, the mean age was 83.1±5.9 years old, and the average HbA1c was 7.6%±1.5%. The numbers of patients assigned to categories I, II, and III were 10, 12, and 41, respectively. For prescription of risk drugs, 6 participants were assigned to category I, 8 to category II, and 22 to category III. Prescription of risk drugs was associated with the HbA1c. Approximately one third of the patients using risk drugs had a lower HbA1c than the target value. CONCLUSIONS: Risk drugs was not significantly associated with the established categories or age. Many of the patients who were prescribed risk drugs had a lower HbA1c than the target values.

Retrograde Ascending Aortic Dissection after Stent Grafting for Stanford Type B Aortic Dissection with Severe Limb Ischemia.

We report a rare case of retrograde Stanford type A aortic dissection after endovascular repair for complicated Stanford type B aortic dissection. A 45-year-old man presented with a sudden onset of back pain and was transferred to our hospital. Computed tomography demonstrated acute Stanford type B aortic dissection with lower limb ischemia. Emergency endovascular surgery was planned for repair of the Stanford type B aortic dissection. The patient suddenly developed recurrent chest pain 10 days after the initial procedure. Computed tomography revealed retrograde Stanford type A aortic dissection involving the ascending aorta and aortic arch. The patient underwent a successful emergency total aortic arch replacement.

Compartmentalized microfluidic perfusion system to culture human induced pluripotent stem cell aggregates.

Microfluidic perfusion systems enable small-volume cell cultures under precisely controlled microenvironments, and are typically developed for cell-based high-throughput screening. However, most such systems are designed to manipulate dissociated single cells, not cell aggregates, and are thus unsuitable to induce differentiation in human induced pluripotent stem cells (hiPSCs), which is conventionally achieved by using cell aggregates to increase cell-cell interactions. We have now developed a compartmentalized microfluidic perfusion system with large flow channels to load, culture, and observe cell aggregates. Homogeneously sized cell aggregates to be loaded into the device were prepared by shredding flat hiPSC colonies into squares. These aggregates were then seeded into microchambers coated with fibronectin and bovine serum albumin (BSA) to establish adherent and floating cultures, respectively, both of which are frequently used to differentiate hiPSCs. However, the number of aggregates loaded in fibronectin-coated microchambers was much lower than in BSA-coated microchambers, suggesting that fibronectin traps cell aggregates before they reach the chambers. Accordingly, hiPSCs that reached the microchambers subsequently adhered. In contrast, BSA-coated microchambers did not allow cell aggregates to adhere, but were sufficiently deep to prevent cell aggregates from flowing out during perfusion of media. Immunostaining for markers of undifferentiated cells showed that cultures on both fibronectin- and BSA-coated microchambers were successfully established. Notably, we found that floating aggregates eventually adhered to surfaces coated with BSA upon differentiation, and that differentiation depends on the initial size of aggregates. Collectively, these results suggest that the microfluidic system is suitable for manipulating hiPSC aggregates in compartmentalized microchambers.

Human knee joint sound during the Lachman test: Comparison between healthy and anterior cruciate ligament-deficient knees.

BACKGROUND: The Lachman test is clinically considered to be a reliable physical examination for anterior cruciate ligament (ACL) deficiency. However, the test involves subjective judgement of differences in tibial translation and endpoint quality. An auscultation system has been developed to allow assessment of the Lachman test. The knee joint sound during the Lachman test was analyzed using fast Fourier transformation. The purpose of the present study was to quantitatively evaluate knee joint sounds in healthy and ACL-deficient human knees. METHODS: Sixty healthy volunteers and 24 patients with ACL injury were examined. The Lachman test with joint auscultation was evaluated using a microphone. Knee joint sound during the Lachman test (Lachman sound) was analyzed by fast Fourier transformation. As quantitative indices of the Lachman sound, the peak sound (Lachman peak sound) as the maximum relative amplitude (acoustic pressure) and its frequency were used. RESULTS: In healthy volunteers, the mean Lachman peak sound of intact knees was 100.6 Hz in frequency and -45 dB in acoustic pressure. Moreover, a sex difference was found in the frequency of the Lachman peak sound. In patients with ACL injury, the frequency of the Lachman peak sound of the ACL-deficient knees was widely dispersed. In the ACL-deficient knees, the mean Lachman peak sound was 306.8 Hz in frequency and -63.1 dB in acoustic pressure. If the reference range was set at the frequency of the healthy volunteer Lachman peak sound, the sensitivity, specificity, positive predictive value, and negative predictive value were 83.3%, 95.6%, 95.2%, and 85.2%, respectively. CONCLUSION: Knee joint auscultation during the Lachman test was capable of judging ACL deficiency on the basis of objective data. In particular, the frequency of the Lachman peak sound was able to assess ACL condition.

Delayed intestinal stenosis of nonocclusive mesenteric ischemia after autologous blood collection: A case report.

INTRODUCTION: Nonocclusive mesenteric ischemia (NOMI) has been reported to be associated with high mortality. Early diagnosis of NOMI and prompt restoration of the intestinal blood flow is necessary in order to achieve a favorable outcome. PRESENTATION OF CASE: We present the case of a patient who developed NOMI after autologous blood collection and was treated by selective infusion of the superior mesenteric artery with papaverine, intestinal decompression using a long intestinal tube, the administration of antibiotics, and fluid replacement. Although this non-surgical management was successful, 8 weeks after the ischemic event, segmental bowel resection was necessary because of repeated intestinal obstruction caused by bowel stricture. DISCUSSION: Autologous blood collection might be a risk factor of NOMI. In addition, the possibility of delayed intestinal stenosis remains, even if bowel necrosis and surgical resection were avoided with non-surgical management including vasodilator therapy. CONCLUSION: Rapid diagnosis and intervention are essential to minimize intestinal ischemia.

Early and Late Outcomes of Surgical Repair for Stanford A Acute Aortic Dissection in Octogenarians.

BACKGROUND: Because increased age is a strong independent predictor of mortality and morbidity, surgery for octogenarians with Stanford type A aortic dissection (AAD) may be avoided.Methods and Results:From 2005 to 2015, 158 patients underwent surgical repair for AAD via a median sternotomy. We compared 24 (15.2%) octogenarians (83±3 years) with 134 (84.8%) patients aged ≤79 years (62±13 years), based on retrospectively collected clinical data. Octogenarians were predominantly female (79.2% vs. 44.8%, P=0.0033). Ascending aortic replacement was more frequently performed in the octogenarians (95.8% vs. 65.7%, P=0.0015) and total arch replacement in the younger patients (4.2% vs. 26.9%, P=0.0165). There were 14 hospital deaths among the younger patients, none among the octogenarians (0% vs. 10.4%, P=0.1303), and major morbidity rates were comparable. There were 3 late deaths among the octogenarians and 9 deaths among the younger patients. The respective 1-, 3-, and 5-year survival rates were 94.4%, 81.5%, and 81.5% in the octogenarians and 86.9%, 85.6%, and 83.9% in the younger patients, with no significant differences. CONCLUSIONS: Surgical repair for AAD in octogenarians showed favorable results when compared with a younger patient cohort, with low hospital mortality rate and excellent late outcomes. Therefore, this technique should not be disregarded just because the patient is an octogenarian. (Circ J 2016; 80: 2468-2472).

Can joint sound assess soft and hard endpoints of the Lachman test?: A preliminary study.

The Lachman test is considered to be a reliable physical examination for anterior cruciate ligament (ACL) injury. Patients with a damaged ACL demonstrate a soft endpoint feeling. However, examiners judge the soft and hard endpoints subjectively. The purpose of our study was to confirm objective performance of the Lachman test using joint auscultation. Human and porcine knee joints were examined. Knee joint sound during the Lachman test (Lachman sound) was analyzed by fast Fourier transformation. As quantitative indices of Lachman sound, the peak sound as the maximum relative amplitude (acoustic pressure) and its frequency were used. The mean Lachman peak sound for healthy volunteer knees was 86.9 ± 12.9 Hz in frequency and -40 ± 2.5 dB in acoustic pressure. The mean Lachman peak sound for intact porcine knees was 84.1 ± 9.4 Hz and -40.5 ± 1.7 dB. Porcine knees with ACL deficiency had a soft endpoint feeling during the Lachman test. The Lachman peak sounds of porcine knees with ACL deficiency were dispersed into four distinct groups, with center frequencies of around 40, 160, 450, and 1600. The Lachman peak sound was capable of assessing soft and hard endpoints of the Lachman test objectively.

A Cranial-Sided Approach for Repeated Mitral Periprosthetic Leak After Right Pneumonectomy.

A 72-year-old man presented with worsening dyspnea on effort. He underwent right pneumonectomy 40 years ago, then mitral valve replacement through a right thoracotomy 8 years ago with repeat surgery to repair a periprosthetic valve leak; the mediastinum was displaced to the right, and the heart was rotated counterclockwise. Transthoracic echocardiography showed periprosthetic valve leak recurrence near the left atrial appendage. We repaired the periprosthetic valve leak through a median sternotomy. Transecting the main pulmonary artery allowed us to widely open the cranial-sided left atrium. We obtained good exposure of the mitral valve, and repaired the periprosthetic valve leak using pledgeted sutures and a pericardial patch.

Successful surgical treatment for total circumferential aortic and mitral annulus calcification: application of half-and-half technique.

Patients with total circumferential mitral annular calcification (MAC) extending into the intervalvular fibrous body and aortic annulus have a high risk of cardiac surgery, which remains a technical challenge for surgeons. Our technique for MAC is characterized as simple supra-mitral annular prosthesis insertion after minimum debridement of calcification ("half-and-half technique"). To date, our technique has been applied in only simple MAC cases and has good results. Herein, we report successful two cases of total circumferential MAC, extending into the intervalvular fibrous body and aortic annulus that were treated by a simple double valve replacement with application of our "half-and-half technique".

Mid-term outcomes of cardiovascular surgery for patients with Marfan syndrome.

OBJECTIVES: Cardiovascular manifestations determine the prognosis and survival of patients with Marfan syndrome (MFS). We assessed the early and mid-term outcomes of cardiovascular surgery for this patient population. PATIENTS AND METHODS: We conducted a retrospective evaluation of patients with MFS who underwent surgery in our department. The endpoint was the requirement for a second cardiovascular surgery, and death from any cause. RESULTS: From February 2002 to March 2013, we performed 24 surgeries on 13 patients with MFS. At the time of initial surgery, the patients' aged ranged from 19 to 64 years of age (mean 34.7 ± 11.3 years) and included 5 men (38.5 %). Five of 13 initial surgeries (38.5 %) were emergencies. Seven patients (53.8 %) presented with aortic dissection at initial surgery, and one of the remaining six patients suffered from new aortic dissection during follow-up. Eight patients (61.5 %) underwent a second surgery, and a second surgery was not required for 100, 75.0, and 53.6 % of patients at 1, 3, and 5 years, respectively. The mean time interval between the first and the second surgeries was 52.8 ± 28.2 months. No patient died while hospitalized, and three subsequently died from unknown causes. Survival rates were 100, 90.9 and 64.9 % at 3, 5, and 7 years, respectively. CONCLUSION: Although we obtained satisfactory early outcomes for patients with MFS, there were three late deaths from unknown causes. Therefore, we recommend that patients with MFS should remain under close surveillance.

Ex Vivo Expanded Allogeneic Mesenchymal Stem Cells With Bone Marrow Transplantation Improved Osteogenesis in Infants With Severe Hypophosphatasia.

Patients with severe hypophosphatasia (HPP) develop osteogenic impairment with extremely low alkaline phosphatase (ALP) activity, resulting in a fatal course during infancy. Mesenchymal stem cells (MSCs) differentiate into various mesenchymal lineages, including bone and cartilage. The efficacy of allogeneic hematopoietic stem cell transplantation for congenital skeletal and storage disorders is limited, and therefore we focused on MSCs for the treatment of HPP. To determine the effect of MSCs on osteogenesis, we performed multiple infusions of ex vivo expanded allogeneic MSCs for two patients with severe HPP who had undergone bone marrow transplantation (BMT) from asymptomatic relatives harboring the heterozygous mutation. There were improvements in not only bone mineralization but also muscle mass, respiratory function, and mental development, resulting in the patients being alive at the age of 3. After the infusion of MSCs, chimerism analysis of the mesenchymal cell fraction isolated from bone marrow in the patients demonstrated that donor-derived DNA sequences existed. Adverse events of BMT were tolerated, whereas those of MSC infusion did not occur. However, restoration of ALP activity was limited, and normal bony architecture could not be achieved. Our data suggest that multiple MSC infusions, following BMT, were effective and brought about clinical benefits for patients with lethal HPP. Allogeneic MSC-based therapy would be useful for patients with other congenital bone diseases and tissue disorders if the curative strategy to restore clinically normal features, including bony architecture, can be established.

Unique and reliable rat model for the assessment of cell therapy: bone union in the rat mandibular symphysis using bone marrow stromal cells.

Many kinds of bone graft materials have been developed and reported to repair various bone defects. The defects are usually created by surgical resection of pre-existing bone tissue. However, spontaneous healing of bone defects without implantation of materials could be seen, because bone tissue possesses inherent repairing property. The central portion of the lower jaw bone in many animals consists of fibrous tissue and is called the mandibular symphysis. It persists even in old animals and thus can be interpreted as a physiological bone gap or a non-healing bone defect. We implanted calcium phosphate porous ceramics alone or composites of the ceramics and bone marrow stromal cells (BMSCs) into the bone defect (mandibular symphysis) to examine whether it could be filled with new bone tissue, resulting in bone union. Eight weeks after implantation, micro-computed tomography (micro-CT) and histological and biomechanical analyses demonstrated that bone union of the mandibles occurred in all rats with composites but in none of those with ceramics alone. These results showed that the rat mandibular symphysis is a unique bone defect site for the evaluation of bone graft materials. These analyses demonstrated that ceramics alone could not contribute to bone healing in the defect; however, supplementation with BMSCs drastically changed the properties of the ceramics (turning them into osteogenic ceramics), which completely healed the defect. As BMSCs can be culture-expanded using small amounts of bone marrow, the use of the composites might have clinical significance for the reconstruction of various bone tissues, including facial bone.

Evaluation of Aortic Valve Replacement via the Right Parasternal Approach without Rib Removal.

BACKGROUND: Although right parasternal approach (RPA) decreases the incidence of mediastinal infection, this approach is associated with lung hernia and flail chest. Our RPA employs thoracotomy with bending rib cartilages and wound closure performed by repositioning the ribs with underlying sheet reinforcement. METHODS: We evaluated 16 patients who underwent aortic valve replacement via the RPA from January 2010 to August 2013. We compared outcomes of 15 male patients had the RPA with 30 male patients had full median sternotomy. RESULTS: One patient with a history of radical breast cancer treatment underwent RPA with concomitant right coronary artery bypass grafting. No hospital deaths occurred. Four patients developed hospital-associated morbidity (re-exploration for bleeding, prolonged ventilation, cardiac tamponade, and perioperative myocardial infarction). There were no conversions to full median sternotomy, mediastinal infections, and lung hernias. Preoperative computed tomography showed that the distance from the right sternal border to the aortic root was significantly associated with operation times. With RPA, there was no significant difference in outcomes, despite significantly longer operation times compared with full median sternotomy. CONCLUSION: Our RPA provides satisfactory outcomes without lung hernia, especially in patients unsuitable for sternotomy. Preoperative computed tomography is useful for identifying appropriate candidates for the RPA.

Mitral valve repair with loop technique via median sternotomy in 180 patients.

OBJECTIVES: Artificial chordal reconstruction technique uses several expanded polytetrafluoroethylene loops to achieve mitral valve repair. METHODS: We studied retrospectively 180 patients who underwent mitral valve repair using the loop technique via median sternotomy: 86 for posterior leaflet prolapse, 48 for anterior leaflet prolapse and 26 for bileaflet prolapse. RESULTS: Of the 180 patients, 138 required 1 loop set; 40 patients required 2 and 2 patients with Barlow's disease required 3. Loop sets contained two to nine loops ranging in length from 14 to 26 mm. Additional techniques required to ensure complete repair using the loop technique included commissural edge-to-edge suture in 78 patients, loop-in-loop technique for extension of the artificial loop in 18 and use of needle-side sutures in 18. Systolic anterior leaflet motion was observed in only 2 patients (1.1%). One patient with immune deficiency died of sepsis. Predischarge echocardiograms showed no or trace mitral regurgitation (MR) in 160 patients (89%), mild MR in 17 patients (9.4)% and mild-to-moderate MR in 3 patients (1.7%). Only 1 patient required redo operation due to recurrent MR freedom from MR greater than moderate was seen in 98.0 ± 1.4% of patients at 1 year, 91.5 ± 2.8% of patients at 3 years, and 91.5 ± 2.8% at 5 years postoperatively. No significant difference was seen in the rate of recurrence of MR among the sites of prolapsing leaflets. CONCLUSIONS: The loop technique via median sternotomy to treat posterior, anterior and, especially, bileaflet prolapse provided satisfactory mid-term outcomes.

Extended posterior leaflet extension for mitral regurgitation in giant left atrium.

Giant left atrium is a rare condition, with a reported incidence of 0.3%, that is normally caused by rheumatic mitral valve disease but very rarely is caused by other etiologies. In such patients, annular dilatation with tenting and reduced height of the posterior leaflet result in significant mitral regurgitation. At surgery, the posterior leaflet was incised from the posterior mitral annulus, starting the incision at the mid portion of the mitral annulus and, if necessary, extending it to the anterolateral portion of the mitral annulus and the posteromedial portion of the mitral annulus. An autologous pericardial patch was harvested, depending on the incision. Herein is reported a surgical technique for posterior leaflet extension in patients with giant left atrium, without rheumatic disease.

Detachably assembled microfluidic device for perfusion culture and post-culture analysis of a spheroid array.

Microfluidic devices permit perfusion culture of three-dimensional (3D) tissue, mimicking the flow of blood in vascularized 3D tissue in our body. Here, we report a microfluidic device composed of a two-part microfluidic chamber chip and multi-microwell array chip able to be disassembled at the culture endpoint. Within the microfluidic chamber, an array of 3D tissue aggregates (spheroids) can be formed and cultured under perfusion. Subsequently, detailed post-culture analysis of the spheroids collected from the disassembled device can be performed. This device facilitates uniform spheroid formation, growth analysis in a high-throughput format, controlled proliferation via perfusion flow rate, and post-culture analysis of spheroids. We used the device to culture spheroids of human hepatocellular carcinoma (HepG2) cells under two controlled perfusion flow rates. HepG2 spheroids exhibited greater cell growth at higher perfusion flow rates than at lower perfusion flow rates, and exhibited different metabolic activity and mRNA and protein expression under the different flow rate conditions. These results show the potential of perfusion culture to precisely control the culture environment in microfluidic devices. The construction of spheroid array chambers allows multiple culture conditions to be tested simultaneously, with potential applications in toxicity and drug screening.