Medium-term Outcomes of Excision Using Surgical Microscope of Tenosynovial Giant Cell Tumors of the Hand.

BACKGROUND/AIM: The recurrence rate following the excision of tenosynovial giant cell tumors (TSGCT) of the hand is very high. Intraoperative application of a surgical microscope has been reported. However, to date, there are no reports of medium-term outcomes related to this technique. This study aimed to evaluate the medium-term outcomes of tumor excision using surgical microscope for TSGCT of the hand. PATIENTS AND METHODS: A total of 27 patients, who underwent an initial surgery for histologically-confirmed TSGCT of the hand, between 2008 and 2020, were included and evaluated. The mean follow-up time postoperatively was 6.8 years. Tumor recurrence and preoperative tumor characteristics were assessed. RESULTS: All tumors were adherent to tendons, tendon sheaths, neurovascular structures or periarticular ligaments and capsules. Bony lesions were observed in 11 tumors. The surgical microscope was used in 13 tumors. Recurrences were observed in three tumors (overall recurrence rate: 11%). Tumor characteristics were similar in both groups, but the recurrence rate in the group treated using the surgical microscope was 0%, whereas the recurrence rate in the group treated without the surgical microscope was 21%. Re-operations using the surgical microscope for recurrent tumors were performed, without recurrence postoperatively. CONCLUSION: Among patients with TSGCT of the hand treated with tumor excision using the surgical microscope, the postoperative recurrence rate was 0%. Based on the results of this study, the surgical microscope might be used for excision of TSGCTs of the hand.

Silent spinal epidural abscess due to facet joint arthritis.

Spinal epidural abscess (SEA) is an abscess that forms between the dura mater and vertebrae. SEA is characterized by back pain and neuropathy associated with fever, of which early diagnosis and treatment are necessary to avoid irreversible neurological sequelae. However, its diagnosis is often difficult because specific symptoms are rarely present in the early stages of the disease. A 25-month-old boy, healthy by nature and free of risk factors, was referred and admitted for fever symptoms only, without back pain or neurological symptoms. We focused on the residual activation of the coagulation-fibrinolytic system, which was contrary to the response to therapy, and were able to establish a diagnosis of SEA. After the initiation of antibiotics, the patient responded well to treatment and made a mild recovery without the need for surgical intervention. To date, there are no reported cases of SEA with only febrile symptoms without localized spinal cord tenderness. SEA is easily overlooked and should be considered in the differential diagnosis of pediatric fever of unknown origin. Although imaging studies have drawbacks, such as radiation exposure and sedation, they should be immediately performed if SEA is suspected.

Size control of induced pluripotent stem cells colonies in two-dimensional culture for differentiation into functional monocyte-like cells.

BACKGROUND AIMS: Monocytes, derived from hematopoietic stem cells (HSCs), play a pivotal role in the immune response to cancer. Although they are an attractive source of cell therapy for cancer, a method for ex vivo expansion has not yet been established. Monocytes differentiated from pluripotent stem cells (PSCs), including induced pluripotent stem cells (iPSCs), can be an alternative source of HSC-derived monocytes because of their self-renewal and pluripotency. To develop a standardized method for the generation of iPSC-derived monocytes for future clinical applications, we aim to control the size of the iPSC colony. METHODS: To this end, we developed a plate with multiple dots containing a chemical substrate for the iPSC scaffold. iPSCs placed in the plate expanded only on the dots and created colonies of the same size. The cells were then differentiated into monocytes by adding cytokines to the colonies. RESULTS: The dot plate substantially reduced variability in monocyte-like cell generation when compared with cultivating cells on a plate with the substrate covering the entire surface area. Furthermore, more monocyte-like cells were obtained by adjusting the dot size and the distance between the dots. The iPSC-derived monocyte-like cells phagocytosed cancer cells and secreted proinflammatory cytokines. The cells also expressed Fc receptors and exerted immunoglobulin G-mediated killing of cancer cells with the corresponding antibodies. CONCLUSIONS: The dot plate enabled the control of iPSC colony size in two-dimensional culture, which resulted in a reduction in the generation-variation of functional monocyte-like cells. This standardized method for generating iPSC-derived monocyte-like cells using the dot plate could also facilitate the development of an automated closed system on a large scale for clinical applications.

Pilot Trial on the Effect of 5-Aminolevulinic Acid on Glucose Tolerance in Patients with Maternally Inherited Diabetes and Deafness.

INTRODUCTION: The amino acid 5-aminolevulinic acid (5-ALA) is the first heme biosynthetic precursor. The combination of 5-ALA with sodium ferrous citrate (SFC) enhances heme production, leading to increased adenosine triphosphate (ATP) production in mitochondria. We investigated whether administering 5-ALA/SFC improves glucose tolerance with an increase in insulin secretion in patients with maternally inherited diabetes and deafness (MIDD), which is characterized by an insulin secretory disorder due to impaired mitochondrial ATP production. METHODS: This was a single-arm, open-label, interventional study. We prospectively administered the oral glucose tolerance test (OGTT) twice in five patients with MIDD who had received intensive insulin therapy: before and 24 weeks after an administration of 5-ALA/SFC (200/232 mg per day). We measured the concentrations of glucose, insulin, C-peptide, and proinsulin at fasting, and 30, 60, and 120 min after glucose load in each OGTT. The primary endpoint was the changes in the area under the curve (AUC) of serum insulin from 0 to 120 min during OGTT from baseline to 24 weeks. RESULTS: The serum insulin AUC (µU/mL) during the 120-min OGTT tended to increase from baseline to 24 weeks but not significantly (17.1 ± 13.7 versus 22.3 ± 13.4, p = 0.077). The plasma glucose AUC (mg/dL) during the 120-min OGTT at 24 weeks was not significantly decreased; the late phase of glucose excursion from 60 to 120 min was significantly decreased compared with baseline (357 ± 42 versus 391 ± 50, p = 0.041). The mean level of glycated hemoglobin (HbA1c) decreased from 8.3 ± 1.2% at baseline to 7.9 ± 0.3% at 24 weeks (p = 0.36) without increasing the daily dose of insulin injections. CONCLUSION: The 24-week administration of 5-ALA/SFC did not demonstrate a significant improvement in insulin secretion in patients with MIDD. Further investigations with a larger number of patients and a placebo control group are required to clarify the potential efficacy of 5-ALA/SFC for ameliorating mitochondrial dysfunctions in MIDD. TRIAL REGISTRATION: UMIN-CTR000040581 and jRCT071200025.

Adhesion Characteristics of Human Pancreatic Islets, Duct Epithelial Cells, and Acinar Cells to a Polymer Scaffold.

We reported in 2018 that among several extracellular matrices, fibronectin, type I collagen, type IV collagen, laminin I, fibrinogen, and bovine serum albumin, fibronectin is particularly useful for adhesion of porcine pancreatic tissue. Subsequently, we developed a technology that enables the chemical coating of the constituent motifs of fibronectin onto cell culture dishes. In this experiment, we used islets (purity ≥ 90%), duct epithelial cells (purity ≥ 60%), and acinar cells (purity ≥ 99%) isolated from human pancreas according to the Edmonton protocol published in 2000 and achieved adhesion to the constituent motifs of fibronectin. A solution including cGMP Prodo Islet Media was used as the assay solution. In islets, adhesion was enhanced with the constitutive motifs of fibronectin compared with uncoated islets. In the functional evaluation of islets, insulin mRNA expression and insulin secretion were enhanced by the constitutive motif of fibronectin compared with non-coated islets. The stimulation index was comparable between non-coated islets and fibronectin motifs. In duct epithelial cells, adhesion was mildly promoted by the fibronectin component compared with non-coated component, while in acinar cells, adhesion was inhibited by the fibronectin component compared with the non-coated component. These data suggest that the constitutive motifs of fibronectin are useful for the adhesion of islets and duct epithelial cells.

Correlation between blood ketones and exhaled acetone measured with a semiconducting gas sensor.

Breath acetone (BrAce) has been reported to be useful for monitoring the pathophysiology of patients with diabetes. However, devices that measure BrAce are expensive, complex and uncommon. The FM-001, originally designed to monitor a marker of weight loss in healthy people, is a device for measuring BrAce. The FM-001 is a loading semiconducting gas sensor that is a simple and reusable device. The aim of this study was to evaluate the correlation between blood total ketone bodies (TKB) and BrAce measured with the FM-001 in patients with diabetes. Furthermore, through evaluation of that correlation, we sought to detect patients at high risk of developing diabetic ketoacidosis (DKA). Thirty-five participants (age 52 [40-57], T2DM 32, T1DM 3) were enrolled. Scatter plots and linear regression lines relating BrAce to TKB and the correlation coefficients were calculated. Receiver-operating characteristic analysis was performed to determine the cut-off for predicting patients prone to DKA. The results showed that BrAce strongly correlates with TKB (R= 0.828), and the correlation was stronger in patients whose serum C-peptide was not low. The optimal BrAce cut-off for predicting risk of developing DKA was 3400 ppb (AUC 0.924, sensitivity 73.3%, specificity 100%), which corresponds to a TKB ⩾ 1000µmol l-1. BrAce also weakly correlated with free fatty acid. Thus, BrAce levels measured with the FM-001 strongly correlate with TKB, even in patients with diabetes. This suggests the FM-001 is a simple and potentially useful method for detecting diabetic ketosis. (UMIN-ID: UMIN000038086).

Clinical Comparable Corpus Describing the Same Subjects with Different Expressions.

Medical artificial intelligence (AI) systems need to learn to recognize synonyms or paraphrases describing the same anatomy, disease, treatment, etc. to better understand real-world clinical documents. Existing linguistic resources focus on variants at the word or sentence level. To handle linguistic variations on a broader scale, we proposed the Medical Text Radiology Report section Japanese version (MedTxt-RR-JA), the first clinical comparable corpus. MedTxt-RR-JA was built by recruiting nine radiologists to diagnose the same 15 lung cancer cases in Radiopaedia, an open-access radiological repository. The 135 radiology reports in MedTxt-RR-JA were shown to contain word-, sentence- and document-level variations maintaining similarity of contents. MedTxt-RR-JA is also the first publicly available Japanese radiology report corpus that would help to overcome poor data availability for Japanese medical AI systems. Moreover, our methodology can be applied widely to building clinical corpora without privacy concerns.

Natural Language Processing: from Bedside to Everywhere.

OBJECTIVES: Owing to the rapid progress of natural language processing (NLP), the role of NLP in the medical field has radically gained considerable attention from both NLP and medical informatics. Although numerous medical NLP papers are published annually, there is still a gap between basic NLP research and practical product development. This gap raises questions, such as what has medical NLP achieved in each medical field, and what is the burden for the practical use of NLP? This paper aims to clarify the above questions. METHODS: We explore the literature on potential NLP products/services applied to various medical/clinical/healthcare areas. RESULTS: This paper introduces clinical applications (bedside applications), in which we introduce the use of NLP for each clinical department, internal medicine, pre-surgery, post-surgery, oncology, radiology, pathology, psychiatry, rehabilitation, obstetrics, and gynecology. Also, we clarify technical problems to be addressed for encouraging bedside applications based on NLP. CONCLUSIONS: These results contribute to discussions regarding potentially feasible NLP applications and highlight research gaps for future studies.

In Carpal Tunnel Syndrome, Sensory Nerve Conduction Velocities Are Worst in the Middle Finger Than in the Index Finger.

Although the index finger is generally used for sensory nerve conduction study in cases of carpal tunnel syndrome, there are reports that the middle finger should be used. The purpose of this study was to compare the results of sensory nerve conduction studies of the index finger and middle finger in patients with carpal tunnel syndrome. Among the 120 hands of 93 patients who were diagnosed with carpal tunnel syndrome and underwent carpal tunnel release surgery at our hospital, 54 hands of 48 patients who showed waveforms in sensory nerve conduction studies both index and middle fingers were included. 6 hands of 6 patients who showed no waveform in the index or middle finger, and 60 hands of 39 patients who showed no waveform in both index and middle finger were excluded. The subjects were 14 males and 34 females, and their ages were 66.2 years. The preoperative sensory nerve action potential (µV) and sensory nerve conduction velocity (m/s) of the index and middle fingers were tested using Wilcoxon's signed rank test. Spearman's rank correlation coefficient was also calculated for the results of the index and middle fingers. Sensory nerve action potentials were 2.0 in the index finger and 1.8 in the middle finger, with significantly lower in the middle finger. Sensory nerve conduction velocity was 30.1 in the index finger and 27.2 in the middle finger, with significantly lower in the middle finger. The correlation coefficients of sensory nerve action potentials and conduction velocities between the index finger and middle finger were 0.82 and 0.96, respectively, both of which showed a significant correlation. The results of the sensory nerve conduction studies of the middle finger were significantly worse than those of the index finger in cases of carpal tunnel syndrome. In addition, there was a strong correlation between the results of the index finger and the middle finger. The results of this study suggest that the nerve bundle to the middle finger may be more strongly affected than the nerve bundle to the index finger in cases of carpal tunnel syndrome.

Profunda femoris artery perforator flap for lateral knee joint reconstruction: A report of two cases.

The profunda femoris artery perforator flap (PAP) based on a proximal skin perforator is often used for breast reconstruction. We report two cases of lateral knee joint reconstruction using a PAP flap based on a distal skin perforator. Case 1 is a 16-year-old male adolescent who underwent inappropriate resection of a synovial sarcoma on the lateral aspect of the right knee joint, which necessitated additional wide resection that led to a soft tissue defect measuring 11 × 5 cm. We elevated a propeller PAP flap (23 × 7 cm) for defect reconstruction, and the flap survived completely. Case 2 is an 81-year-old woman who underwent wide resection of an undifferentiated pleomorphic sarcoma on the lateral aspect of the right knee joint showed a persistent soft tissue defect measuring 9 × 6 cm. We elevated a propeller PAP flap (25 × 7 cm) as described in Case 1, and the flap survived completely. Skin perforators of the profunda femoris artery are present both in the proximal and distal thigh; therefore, a PAP flap can also be elevated in the distal thigh. However, a few reports have discussed PAP flap elevation in the distal thigh for knee joint reconstruction. The PAP flap with a distal skin perforator can be elevated with a relatively large volume of skin paddle and may be a useful option for lateral knee joint reconstruction.

Bitiscetin-3, a Novel C-Type Lectin-like Protein Cloned from the Venom Gland of the Viper Bitis arietans, Induces Platelet Agglutination and Inhibits Binding of Von Willebrand Factor to Collagen.

Bitiscetin-1 (aka bitiscetin) and bitiscetin-2 are C-type lectin-like proteins purified from the venom of Bitis arietans (puff adder). They bind to von Willebrand factor (VWF) and-at least bitiscetin-1-induce platelet agglutination via enhancement of VWF binding to platelet glycoprotein Ib (GPIb). Bitiscetin-1 and -2 bind the VWF A1 and A3 domains, respectively. The A3 domain includes the major site of VWF for binding collagen, explaining why bitiscetin-2 blocks VWF-to-collagen binding. In the present study, sequences for a novel bitiscetin protein-bitiscetin-3-were identified in cDNA constructed from the B. arietans venom gland. The deduced amino acid sequences of bitiscetin-3 subunits α and ß share 79 and 80% identity with those of bitiscetin-1, respectively. Expression vectors for bitiscetin-3α and -3ß were co-transfected to 293T cells, producing the heterodimer protein recombinant bitiscetin-3 (rBit-3). Functionally, purified rBit-3 (1) induced platelet agglutination involving VWF and GPIb, (2) did not compete with bitiscetin-1 for binding to VWF, (3) blocked VWF-to-collagen binding, and (4) lost its platelet agglutination inducing ability in the presence of an anti-VWF monoclonal antibody that blocked VWF-to-collagen binding. These combined results suggest that bitiscetin-3 binds to the A3 domain, as does bitiscetin-2. Except for a small N-terminal fragment of a single subunit-which differs from that of both bitiscetin-3 subunits-the sequences of bitiscetin-2 have never been determined. Therefore, by identifying and analyzing bitiscetin-3, the present study is the first to present the full-length α- and ß-subunit sequences and recombinant expression of a bitiscetin-family toxin that blocks the binding of VWF to collagen.

Deep inferior epigastric artery as a collateral pathway to the lower extremities: A case report.

We describe a patient in whom the deep inferior epigastric artery served as a collateral pathway to the lower extremities, and free latissimus dorsi myocutaneous flap transfer was successfully used for reconstruction instead of the originally planned free rectus abdominis myocutaneous flap. A 74-year-old woman underwent subtotal tongue resection, followed by free flap tongue reconstruction for tongue cancer. Reconstruction using a free rectus abdominis myocutaneous flap was considered; however, preoperative contrast-enhanced computed tomography revealed complete occlusion of the bilateral external iliac arteries. Doppler ultrasonography revealed retrograde blood flow via the deep inferior epigastric artery, and the internal thoracic artery-deep inferior epigastric artery pathway served as a collateral pathway that supplied the lower extremities. The patient underwent reconstructive surgery using a free latissimus dorsi myocutaneous flap, and the flap completely survived. The internal thoracic artery-deep inferior epigastric artery pathway serves as a critical collateral pathway to the lower extremities in patients with aortoiliac occlusive disease. Blockage of the deep inferior epigastric artery in patients in whom this vessel shows retrograde blood flow may result in lower extremity ischemia. Therefore, preoperative Doppler ultrasonography is warranted to confirm the direction of the blood flow, in addition to evaluation of the deep inferior epigastric artery and its perforators before planning rectus abdominis myocutaneous flap or deep inferior epigastric artery perforator flap surgery.

A chemically-defined plastic scaffold for the xeno-free production of human pluripotent stem cells.

Clinical use of human pluripotent stem cells (hPSCs) is hampered by the technical limitations of their expansion. Here, we developed a chemically synthetic culture substrate for human pluripotent stem cell attachment and maintenance. The substrate comprises a hydrophobic polyvinyl butyral-based polymer (PVB) and a short peptide that enables easy and uniform coating of various types of cell culture ware. The coated ware exhibited thermotolerance, underwater stability and could be stored at room temperature. The substrate supported hPSC expansion in combination with most commercial culture media with an efficiency similar to that of commercial substrates. It supported not only the long-term expansion of examined iPS and ES cell lines with normal karyotypes during their undifferentiated state but also directed differentiation of three germ layers. This substrate resolves major concerns associated with currently used recombinant protein substrates and could be applied in large-scale automated manufacturing; it is suitable for affordable and stable production of clinical-grade hPSCs and hPSC-derived products.

Molecular profiling of extracellular vesicles via charge-based capture using oxide nanowire microfluidics.

Extracellular vesicles (EVs) have shown promising features as biomarkers for early cancer diagnoses. The outer layer of cancer cell-derived EVs consists of organotropic metastasis-induced membrane proteins and specifically enriched proteoglycans, and these molecular compositions determine EV surface charge. Although many efforts have been devoted to investigating the correlation between EV subsets obtained through density-, size-, and immunoaffinity-based captures and expressed membrane proteins, understanding the correlation between EV subsets obtained through surface charge-based capture and expressed membrane proteins is lacking. Here, we propose a methodology to profile membrane proteins of EV subsets obtained through surface charge-based capture. Nanowire-induced charge-based capture of EVs and in-situ profiling of EV membrane proteins are the two key methodology points. The oxide nanowires allowed EVs to be obtained through surface charge-based capture due to the diverse isoelectric points of the oxides and the large surface-to-volume ratios of the nanowire structures. And, with the ZnO nanowire device, whose use does not require any purification and concentration processes, we demonstrated the correlation between negatively-charged EV subsets and expressed membrane proteins derived from each cell. Furthermore, we determined that a colon cancer related membrane protein was overexpressed on negatively charged surface EVs derived from colon cancer cells.

Technical Note: Range verification of pulsed proton beams from fixed-field alternating gradient accelerator by means of time-of-flight measurement of ionoacoustic waves.

PURPOSE: Ionoacoustics is one of the promising approaches to verify the beam range in proton therapy. However, the weakness of the wave signal remains a main hindrance to its application in clinics. Here we studied the potential use of a fixed-field alternating gradient accelerator (FFA), one of the accelerator candidates for future proton therapy. For such end, magnitude of the pressure wave and range accuracy achieved by the short-pulsed beam of FFA were assessed, using both simulation and experimental procedure. METHODS: A 100 MeV proton beam from the FFA was applied on a water phantom, through the acrylic wall. The beam range measured by the Bragg peak (BP)-ionization chamber (BPC) was 77.6 mm, while the maximum dose at BP was estimated to be 0.35 Gy/pulse. A hydrophone was placed 20 mm downstream of the BP, and signals were amplified and stored by a digital oscilloscope, averaged, and low-pass filtered. Time-of-flight (TOF) and two relative TOF values were analyzed in order to determine the beam range. Furthermore, an acoustic wave transport simulation was conducted to estimate the amplitude of the pressure waves. RESULTS: The range calculated when using two relative TOF was 78.16 ± 0.01 and 78.14 ± 0.01 mm, respectively, both values being coherent with the range measured by the BPC (the difference was 0.5-0.6 mm). In contrast, utilizing the direct TOF resulted in a range error of 1.8 mm. Fivefold and 50-fold averaging were required to suppress the range variation to below 1 mm for TOF and relative TOF measures, respectively. The simulation suggested the magnitude of pressure wave at the detector exceeded 7 Pascal. CONCLUSION: A submillimeter range accuracy was attained with a pulsed beam of about 21 ns from an FFA, at a clinical energy using relative TOF. To precisely quantify the range with a single TOF measurement, subsequent improvement in the measuring system is required.

A single-arm, open-label, intervention study to investigate the improvement of glucose tolerance after administration of the 5-aminolevulinic acid (5-ALA) in the patients with mitochondrial diabetes mellitus.

BACKGROUND: Mitochondrial diabetes mellitus (MDM) is characterized by maternal inheritance, progressive neurosensory deafness, insulin secretory disorder, and progressive microvascular complications. Mitochondria are critical organelles that provide energy in the form of adenosine triphosphate (ATP). An impairment of ATP production in pancreatic ß cells is regarded as the main cause of the insulin secretory disorder in patients with MDM, and these patients require insulin replacement therapy early after the diagnosis. The amino acid 5-aminolevulinic acid (5-ALA), a precursor of heme metabolites, is a non-proteinogenic δ amino acid synthesized in mitochondria. An addition of ferrous iron to 5-ALA enhances heme biosynthesis and increases ATP production through an upregulation of the respiratory complex. Several studies have reported that the administration of 5-ALA and ferrous iron to existing treatment improved the glycemic control in both patients with prediabetes and those with type 2 diabetes mellitus. The additional administration of 5-ALA and ferrous iron to MDM patients on insulin therapy may improve their insulin secretory capacity and glycemic control by improving their mitochondrial function. The findings of this study are expected to provide new treatment options for MDM and improve the patients' glycemic control and prognosis. METHODS/DESIGN: This study is a single-arm, open-label pilot intervention study using clinical endpoints to investigate the effects of treatment with 5-ALA plus sodium ferrous citrate (SFC) to patients with MDM on their glucose tolerance. A total of 5 patients with MDM will be administered 5-ALA/SFC (200 mg/d) for 24 weeks. We will perform a 75-g oral glucose tolerance test before and at 24 weeks after the start of this 5-ALA/SFC treatment to evaluate glucose-dependent insulin responses. DISCUSSION: To the best of our knowledge, this study will be the first assessment of the effects of 5-ALA/SFC in patients with MDM. This study will obtain an evidence regarding the effectiveness and safety of 5-ALA/SFC for patients with MDM. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network (UMIN000040581) on July 1, 2020 and with the Japan Registry of Clinical Trials (jRCTs071200025) on August 3, 2020.

Anaphylactic Reactions Caused by Nafamostat Mesylate during Hemodialysis before Surgery for Carpal Tunnel Syndrome.

Nafamostat mesylate (NM) has been used to treat pancreatitis and disseminated intravascular coagulation during hemodialysis (HD). However, there have been some reports of adverse effects related to anaphylactic reactions. We present a case in which anaphylactic reactions caused by NM during preoperative HD caused repeated postponement of surgery for carpal tunnel syndrome. Symptoms including fever, shivering, chills, low blood pressure, tachycardia, nausea, and vomiting appeared during preoperative HD, and surgery was postponed thrice. Initially, the patient was misdiagnosed with sepsis because of elevated C-reactive protein and procalcitonin levels. However, since the symptoms appeared only when NM was administered and disappeared quickly after the administration of NM was terminated, the condition was diagnosed as anaphylactic reactions caused by NM. Therefore, it is essential to consider anaphylactic reactions caused by NM as differential diagnoses, when symptoms, such as fever, are observed during perioperative HD.

Case Report: Prophylactic Plate Fixation for Incomplete Atypical Ulnar Fractures Resulting From the Use of Denosumab for Bone Metastases.

Patients with bone metastases are treated with long-term bone resorption inhibitors such as bisphosphonates and denosumab. However, resorption inhibitors have been known to cause fractures, such as atypical femoral fractures (AFFs). In recent years, there have been an increasing number of reports of atypical ulna fractures (AUFs) caused by bone resorption inhibitor usage. Treatment of AUFs is complicated, especially when they occur in patients with bone metastases, because it is difficult to discontinue bone resorption inhibitor treatment without the risk of aggravating metastatic lesions. Prophylactic surgery is recommended in AFFs when fractures are predicted, but there are few reports of prophylactic surgery for AUFs. Here, we report a case of incomplete AUF in a 74-year-old woman which was surgically treated with prophylactic plate fixation. The patient had been using denosumab for 6 years to treat bone metastases due to thyroid cancer. After surgery, no fractures were observed for 2 years without discontinuing denosumab, and her forearm function was adequate. AUFs are rare and difficult to treat, so oncologists who treat bone metastases need to pay special attention to diagnose this incomplete AUF before the fracture worsens. We believe that detection of a possible fracture and prophylactic surgery can improve prognosis.

A retrospective cohort study for the treatment of Asian diabetic ketoacidosis: optimizing initial doses of insulin.

AIM: An insulin dose of 0.1 U/kg/h recommended by Western guidelines occasionally induces a precipitous decreasing blood glucose in Asian diabetic ketoacidosis (DKA). It is known that clinical factors, such as insulin sensitivity, differ between Asians and Americans/Europeans. We investigated how treatment options affect the time to DKA resolution to determine the optimal treatment for Asian DKA patients. METHODS: This was a retrospective cohort study from a single institution in Japan. A total of 34 adult DKA patients were observed. Baseline characteristics and treatment-related parameters were compared between patients whose DKA was resolved within 18 h and those in which it was not. RESULTS: Significant differences were observed in the initial insulin dose (mean [standard deviation]: 0.053 [0.021] versus 0.031 [0.014] U/kg/h; P = 0.003) and the baseline ß-hydroxybutyrate (7.2 [3.2] versus 9.9 [2.6] mmol/L; P = 0.024) and HCO 3 - levels (11.2 [4.1] versus 7.7 [3.1] mmol/L; P = 0.014). Multivariable logistic regression analysis revealed that the initial insulin dose was significantly associated with early resolution of DKA and was independent of basal conditions. Receiver operating characteristic curve analysis indicated that the optimal cut-off point for the initial insulin dose was 0.051 U/kg/h. With an initial insulin dose of 0.051 U/kg/h or higher, early resolution of DKA was obtained in 92.9% of patients. CONCLUSION: An initial insulin dose of more than 0.05 U/kg/h provides an early resolution of DKA in Asian patients. Lower insulin doses significantly delay resolution. These results provide practical information for acute phase treatment of Asian DKA.

On-line range verification for proton beam therapy using spherical ionoacoustic waves with resonant frequency.

In contrast to conventional X-ray therapy, proton beam therapy (PBT) can confine radiation doses to tumours because of the presence of the Bragg peak. However, the precision of the treatment is currently limited by the uncertainty in the beam range. Recently, a unique range verification methodology has been proposed based on simulation studies that exploit spherical ionoacoustic waves with resonant frequency (SPIREs). SPIREs are emitted from spherical gold markers in tumours initially introduced for accurate patient positioning when the proton beam is injected. These waves have a remarkable property: their amplitude is linearly correlated with the residual beam range at the marker position. Here, we present proof-of-principle experiments using short-pulsed proton beams at the clinical dose to demonstrate the feasibility of using SPIREs for beam-range verification with submillimetre accuracy. These results should substantially contribute to reducing the range uncertainty in future PBT applications.