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Glucocorticoid-induced osteoporosis (GIOP) is a side effect of glucocorticoid (GC) treatment; however, despite established prevention guidelines in various countries, a gap persists between these guidelines and clinical practice. To address this gap, we implemented a collaborative intervention between hospitals and community pharmacists, aiming to assess its effectiveness. Pharmacists recommended to the prescribing doctor osteoporosis treatment for patients who did not undergo osteoporosis treatment with a fracture risk score of ≥3 via tracing reports (TRs), between 15 December 2021, and 21 January 2022. Data were extracted from electronic medical records, including prescriptions, concomitant medications, reasons for not pursuing osteoporosis treatment, and TR contents. Of 391 evaluated patients, 45 were eligible for TRs, with 34 (75.6%) being males. Prednisolone was the most common GCs administered, and urology was the predominant treatment department. Among the 45 patients who received TRs, prescription suggestions were accepted for 19 (42.2%). After undertaking the intervention, guideline adherence significantly increased from 87% to 92.5%. This improvement indicates that TRs effectively bridged the evidence–practice gap in GIOP prevention among GC patients, suggesting their potential utility. Expansion of this initiative is warranted to further prevent GIOP.

Although 5-Aminosalicylate (5-ASA) has been shown to act on the local mucosa, when 5-ASA is orally administered, most of it is absorbed in the upper gastrointestinal tract and does not reach the large intestine, where lesions are present. Therefore, different drug delivery systems have been developed for each oral 5-ASA formulation. Currently, the oral 5-ASA formulation approved in Japan is salazosulfapyridine (SALAZOPYRIN®; Pfizer Japan Inc.: Tokyo, Japan), in which 5-ASA and sulfapyridine are azo-bonded. In addition, there are several 5-ASA release formulations, including ASACOL®; ZERIA Pharmaceutical Co., Ltd.: Tokyo, Japan (delayed release formulation dependent on pH), PENTASA®; KYORIN Pharmaceutical Co., Ltd.: Tokyo, Japan (delayed release formulation dependent on time), and LIALDA®; MOCHIDA Pharmaceutical Co., Ltd.: Tokyo, Japan (delayed release formulation dependent on pH and time). Adverse events may occur because of differences in the drug delivery systems of these products. In this study, we focused on the adverse events of different 5-ASA formulations and investigated differences in the detection of safety signals for each 5-ASA formulation using disproportionality analysis. There were 15 adverse events detected only with SALAZOPYRIN®. On the other hand, ASACOL®, PENTASA®, and LIALDA® have different drug delivery systems. Although the detected signal intensities varied, the detected adverse events were not significantly different. These findings provide important insights, which should be considered by physicians during treatment selection and drug manufacturers during drug development.

Abstract Wearable sensors have seen remarkable recent technological developments, and their role in healthcare is expected to expand. Specifically, monitoring tissue circulation in patients who have undergone reconstructive surgery is critical because blood flow deficiencies must be rescued within hours or the transplant will fail due to thrombosis/haematoma within the artery or vein. We design a wearable, wireless, continuous, multipoint sensor to monitor tissue circulation. The system measures pulse waves, skin colour, and tissue temperature to reproduce physician assessment. Data are analysed in real time for patient risk using an algorithm. This multicentre clinical trial involved 73 patients who underwent transplant surgery and had their tissue circulation monitored until postoperative day 7. Herein, we show that the overall agreement rate between physician and sensor findings is 99.2%. In addition, the patient questionnaire results indicate that the device is easy to wear. The sensor demonstrates non-invasive, real-time, continuous, multi-point, wireless, and reliable monitoring for postoperative care. This wearable system can improve the success rate of reconstructive surgeries.

Objective: Although collateral lymphatic vessels are known to develop in patients with lymphedema, little is known about their significance. In this study, we investigated truncal collateral lymphatic drainage pathways in patients with lower limb lymphedema using indocyanine green (ICG) lymphography. Methods: The ICG fluorescence images and clinical characteristics of 80 consecutive patients (160 lower limbs) with secondary leg lymphedema who underwent ICG lymphography between September 2020 and September 2022 were retrospectively reviewed. Results: Seven patients were identified to have a truncal collateral lymphatic drainage pathway starting in the lateral abdomen and running in the direction of the ipsilateral axillary lymph nodes. These patients had particularly severe symptoms of lymphedema around the thigh or abdominal region or had genital lymphedema. Conclusions: A truncal collateral lymphatic drainage pathway may be associated with severe lower limb lymphedema, particularly if involving the genitals.

Single particle inductively coupled plasma mass spectrometry has been used for size measurements of individual nanoparticles (NPs). Here, uncertainties in size analysis based upon two calibration approaches were evaluated: (i) the use of particle size standard and (ii) the use of ion standard solution. For particle size standard approach, the source of uncertainty to determine the target NP diameter was related to the variation in the signal intensities of both target NPs and particle size standard, and the size distribution of the particle size standard. The relative uncertainties of the 50 nm silver NP as the target were 15.0%, 9.9%, and 10.8% when particle size standards of 30 nm, 60 nm, and 100 nm silver NPs were used, respectively. As for the ion standard solution approach, the sources of uncertainty were the concentration of working standard solution, sample flow rate, transport efficiency, slope of calibration curve, and variation in the signal intensity of the ion standard solution and of the target NPs. The relative uncertainties for the 50 nm silver NP were 18.5% for 1 ng/g, 7.6% for 10 ng/g, and 4.7% for 100 ng/g solutions. The lower uncertainty obtained with a high concentration working standard solution is recommended to improve precision on particle size determinations by spICP-MS.

Abstract Background Pembrolizumab is effective as first-line therapy against advanced non-small cell lung cancer (NSCLC) in patients with programmed death ligand-1 (PD-L1) expression levels ≥50% [1]. However, it is not effective in all patients, and the factors predicting responses among this population remain unknown. Methods We retrospectively analyzed patients with NSCLC and a PD-L1 tumor proportion score (TPS) > 50%, who received first-line monotherapy with pembrolizumab from February 1, 2017 to April 30, 2018. The study included 11 hospitals, which participated in the Hanshin Oncology clinical Problem Evaluation group (HOPE). We analyzed the differences between responders and non-responders in terms of age, sex, performance status score, degree of progression, histological type, smoking history, expression of PD-L1, use of steroids prior to treatment, metastasis site, and laboratory data. Results A total of 205 patients were included in this study. Of those, 108 patients exhibiting complete or partial response were defined as responders. Those exhibiting progressive disease (N = 52) were defined as non-responders. In the univariate analysis, Eastern Cooperative Oncology Group performance status score ≥ 2 (p = 0.0832), stage IV disease or recurrence (p = 0.0487), PD-L1 TPS 50–89% (p = 0.0657), use of steroids prior to the administration of pembrolizumab (p = 0.0243), malignant pleural effusion (p = 0.0032), and baseline C-reactive protein (CRP) levels > 1.0 mg/dL (p = 0.0390) were significantly associated with non-response to treatment. In the multivariate analysis, use of steroids prior to the administration of pembrolizumab (odds ratio [OR]: 5.86; 95% confidence interval [CI]: 1.32–31.8; p = 0.0200), malignant pleural effusion (OR: 2.68; 95% CI: 1.15–6.35; p = 0.0228), and baseline CRP > 1.0 mg/dL (OR: 2.17; 95% CI: 1.03–4.68; p = 0.0402) were significantly associated with non-response to treatment. Conclusion In real-world patients with NSCLC and a PD-L1 TPS ≥50%, use of steroids prior to treatment, malignant pleural effusion, and baseline CRP levels > 1.0 mg/dL reduced the response of first-line monotherapy with pembrolizumab.

When reconstructing a congenital floating thumb, we describe two children in whom preservation of all five digits is achieved through successful transfer of a thoracodorsal artery perforator (TAP) flap and vascularized scapula. Key words: Chimera flap, congenital anomaly, floating thumb, hand, thumb

Abstract Surgically invasive procedures involving the medial knee and inguinal regions can cause lymphedema. Lymphaticovenular anastomosis (LVA) could improve volume reduction and decrease the risk of cellulitis. However, it may be preferable to performed LVA as early as possible to achieve optimal results.

Key Clinical Message Replantation combined with simultaneous ectopic implantation can be considered in patients with multiple finger amputation injury. This technique has the advantages of reducing the operating time and optimizing hemodynamic stability. However, it is only possible when multiple hand and microsurgery team can be organized at short notice.

Summary:. Syndactyly of the hand is commonly treated using local flaps with skin grafts; however, contractures and/or pigmentation pose a challenge, requiring repeated surgery. Here, we describe a case of a 1-year-old boy who underwent web transplantation for syndactyly. To the best of our knowledge, no “web for web” transplantations have been documented in pediatric literature. Because the patient had an “extra” web space, functional and aesthetic reconstruction was performed with careful preparation. The vascular pattern was assessed using high-resolution ultrasonography. The flap was harvested under a microscope, intravascular stenting was performed for secure anastomosis, and the adequacy of circulation in the flap was verified using the indocyanine green test. Each technique in the procedure used by us contributed to making the microsurgery safer. The present case suggests that “web for web” is a favorable treatment option for some cases, although these would be limited in number.

Summary:. Although the great toe plays important roles in walking, loading, and maintaining balance when compared with other toes, there are few reports on great toe reconstruction, including the reconstruction of distal phalanx. This report aims to describe the use of a superficial circumflex iliac artery perforator (SCIP)–osteocutaneous flap for reconstructing a complex tissue defect of the great toe. A 62-year-old man presented with a crush injury to the forefoot. Because the great toe was severely crushed, the defect distal to the proximal phalanx of the great toe was reconstructed using a SCIP-osteocutaneous flap. The immediate postoperative course was uneventful; however, surgical revision was necessary. Signs of osseous union could be observed on radiographic images taken 2 months after the initial surgery. Twenty-four months after surgery, the patient could freely walk without resorption of the transferred bone. We demonstrated that SCIP-osteocutaneous flaps may be promising free flaps in complex tissue defect reconstruction of the great toe.

Background:. Although patients with obesity-induced lymphedema can be treated by weight loss therapy, they find it difficult to lose the required amount of weight. The aims of this study were to clarify the characteristics of the lymphatic vessels in patients with obesity-induced lymphedema and to determine the feasibility and efficacy of lymphovenous anastomosis (LVA) in these patients. Methods:. Twenty-two patients (44 edematous lower limbs) with a body mass index (BMI) >35 kg/m2 (obese group) and 91 patients with lymphedema (141 edematous lower limbs) and BMI

Abstract Background Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer’s diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined. Methods We examined the association between the ALDH2*2 allele and lung function parameters in a population of healthy individuals. We also examined its association with the incidence of asthma and COPD in patient cohorts. We used the in vitro colony forming assay to detect the effect of the polymorphism on lung epithelial stem cells from both primary human surgical samples and Aldh2*2 transgenic (Tg) and Aldh2 −/− mice. Response to acute and chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 −/− mice. Results In humans, the ALDH2*2 allele was associated with lower FEV1/FVC in the general population, but not with the development of asthma or COPD. Both the bronchial and lung epithelium carrying the ALDH2*2 allele showed a tendency for lower colony forming efficiency (CFE) compared to ALDH2 allele. In mice, the tracheal epithelial thickness, nuclear density, and number of basal stem cells were significantly lower in Aldh2 −/− and Aldh2*2 Tg adult mice than in WT. Electron microscopy showed significantly increased number of morphologically abnormal mitochondria in the trachea of Aldh2 −/− mice. Aldh2 −/− tracheal and lung cells showed higher ROS levels and fewer functional mitochondria than those from WT mice. No significant differences were detected when tracheal and lung epithelial stem cells were examined for their in vitro CFE. When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to emphysema development, whereas influenza infection caused more epithelial damage in Aldh2 −/− mice than in WT mice. Conclusions ALDH2 polymorphism has several subtle effects on the lungs, some of which are similar to changes observed during normal aging, suggesting a “premature lung aging” effect.

Summary:. Orbital roof fracture is a relatively rare trauma. In most cases, surgical intervention is not needed since the fracture is slight. However, invasive surgical procedures are inevitable once pulsatile exophthalmos occurs if vision impairment is to be avoided. We report our rare experience of orbital roof fracture in a child with pulsatile exophthalmos. Good reconstruction of the anterior cranial base was achieved using a custom-made titanium mesh and a minimally invasive approach. A 3-year-old girl who had been diagnosed with subdural hematoma, brain contusion, and fracture of the right orbital roof caused by facial bruising underwent emergent external decompression by coronal skin incision and a transcranial approach on the same day as the trauma. Cranioplasty using autologous frozen bone in the same approach was performed 103 days posttrauma, but this was followed by pulsatile exophthalmos. After recovering from critical stage, the girl was brought to our department for reconstruction of the anterior base. Risk of vision impairment was also one reason for reconstruction, but the neurosurgeon hesitated to approach the region using a coronal approach considering the possibility of infection in the frozen autologous bone. Through cross-team discussion, reconstruction using a subeyebrow incision was performed with a custom-made titanium mesh plate. Pulsatile exophthalmos completely disappeared. Pulsatile exophthalmos is a very rare but serious complication that carries a risk of vision impairment. By applying a custom-made titanium mesh plate, precise reconstruction was enabled with minimal invasiveness and low risk.

Abstract Background Island pedicle flaps often have the problem of limited reach. In such cases, free flaps are useful for reconstruction but often have the issue of unavailability of suitable recipient vessels. Therefore, it would be helpful if the pedicle of an island flap could be extended as far as necessary. Methods Here, we describe the use of interpositional vein grafts to extend island pedicle flaps for the reconstruction of an ischemic above-knee amputation stump in one case and to seal an intractable fistula on the buttock after radiation therapy in another case. In the patient with the ischemic stump, a deep inferior epigastric perforator flap was extended by 6 cm using the great saphenous vein harvested from the contralateral side, allowing successful coverage of the stump. In the patient with an intractable fistula on the buttock, a thoracodorsal artery and vein graft that was extended by 25 cm using the cephalic vein harvested from the right forearm to upper arm allowed successful sealing of the fistula. Results Circulation was satisfactory in both cases and both flaps survived. The operative procedure was straightforward. Conclusion Interpositional vein grafts may be a feasible option for the extension of island pedicle flaps to include the features of an island pedicle flap and a free flap.

Background:. Although supermicrosurgical anastomosis is a widely known reconstructive microsurgical technique, it is difficult to perform. To expand the clinical use of supermicrosurgery, we used hemi-intravascular stenting (hemi-IVaS), which is performed by inserting an intravascular stent into one side of the vessel. We conducted lymphaticovenular anastomosis, free perforator flap transfer, and fingertip replantation with supermicrosurgical anastomosis using hemi-IVaS technique and examined its usefulness. Methods:. Between January 2013 and February 2015, 11 anastomoses in 11 cases of lymphaticovenular anastomosis for lymphedema patients, 14 anastomoses in 7 cases of free perforator flap transfer with supermicrosurgical perforator-to-perforator anastomosis, and 9 anastomoses in 5 cases of fingertip replantation were performed using hemi-IVaS. Time required for anastomosis and complications were examined. Flap survival rate was also examined in free perforator flap transfer cases and fingertip replantation cases. Results:. In all cases, anastomoses were performed without complications such as inadvertent catching of the back wall of the vessel during the procedure or the need for reanastomoses. The average time required to complete the anastomosis was 16.4 ± 3.20 minutes using the hemi IVaS technique. All flaps survived in the supermicrosurgical perforator-to-perforator anastomosis as well as fingertip replantation cases. Conclusions:. Hemi-IVaS could be a useful alternative to conventional intravascular stenting techniques and is also effective for supermicrosurgical perforator-to-perforator anastomosis. Further studies are needed to improve the success rate and to explore its other possible utilizations in supermicrosurgery.

BackgroundWe established the Microvascular Research Center Training Program (MRCP) to help trainee surgeons acquire and develop microsurgical skills. Medical students were recruited to undergo the MRCP to assess the effectiveness of the MRCP for trainee surgeons.MethodsTwenty-two medical students with no prior microsurgical experience, who completed the course from 2005 to 2012, were included. The MRCP comprises 5 stages of training, each with specific passing requirements. Stages 1 and 2 involve anastomosing silicone tubes and blood vessels of chicken carcasses, respectively, within 20 minutes. Stage 3 involves anastomosing the femoral artery and vein of live rats with a 1-day patency rate of >80%. Stage 4 requires replantation of free superficial inferior epigastric artery flaps in rats with a 7-day success rate of >80%. Stage 5 involves successful completion of one case of rat replantation/transplantation. We calculated the passing rate for each stage and recorded the number of anastomoses required to pass stages 3 and 4.ResultsThe passing rates were 100% (22/22) for stages 1 and 2, 86.4% (19/22) for stage 3, 59.1% (13/22) for stage 4, and 55.0% (11/20) for stage 5. The number of anastomoses performed was 17.2±12.2 in stage 3 and 11.3±8.1 in stage 4.ConclusionsMajority of the medical students who undertook the MRCP acquired basic microsurgical skills. Thus, we conclude that the MRCP is an effective microsurgery training program for trainee surgeons.

Ciguatoxins are polyether marine toxins that act as sodium channel activators. These toxins cause ciguatera, one of the most widespread nonbacterial forms of food poisoning, which presents several symptoms in humans including long-term neurological alterations. Earlier work has shown that both acute and chronic exposure of primary cortical neurons to synthetic ciguatoxin CTX3C have profound impacts on neuronal function. Thus, the present work aimed to identify relevant neuronal genes and metabolic pathways that could be altered by ciguatoxin exposure. To study the effect of ciguatoxins in primary neurons in culture, we performed a transcriptomic analysis using whole mouse genome microarrays, for primary cortical neurons exposed during 6, 24, or 72 h in culture to CTX3C. Here, we have shown that the effects of the toxin on gene expression differ with the exposure time. The results presented here have identified several relevant genes and pathways related to the effect of ciguatoxins on neurons and may assist in future research or even treatment of ciguatera. Moreover, we demonstrated that the effects of the toxin on gene expression were exclusively consequential of its action as a voltage-gated sodium channel activator, since all the effects of CTX3C were avoided by preincubation of the neurons with the sodium channel blocker tetrodotoxin.

Lymph node dissection is often performed as a part of surgical treatment for breast cancer and malignant melanoma to prevent malignant cells from traveling via the lymphatic system. Currently little is known about postoperative lymphatic drainage pattern alterations. This knowledge may be useful for management of recurrent cancer and prevention of breast cancer related lymphedema. We mapped the complete superficial lymphatic system of a dog and used this canine model to perform preliminary studies of lymphatic architectural changes in postoperative condition.Lymphatic territories (lymphosomes) were mapped with 4 female mongrel carcasses using an indocyanine green (ICG) fluorescent lymphography and a radiographic microinjection technique. Two live dogs were then subjected to unilateral lymph node dissection of lymph basins of the forelimb, and ICG lymphography and lymphangiogram were performed 6 months after the surgery to investigate lymphatic changes. Lymphatic patterns in the carcass were then compared with postoperative lymphatic patterns in the live dogs.Ten lymphosomes were identified, corresponding with ten lymphatic basins. Postoperative fluorescent lymphographic images and lymphangiograms in the live dogs revealed small caliber lymphatic network fulfilling gaps in the surgical area and collateral lymphatic vessels arising from the network connecting to lymph nodes in the contralateral and ipsilateral neck in one dog and the ipsilateral subclavicular vein in another dog.Our canine lymphosome map allowed us to observe lymphatic collateral formations after lymph node dissection in live dogs. This canine model may help clarify our understanding of postoperative lymphatic changes in humans in future studies.