Clinical characteristics and outcomes of pheochromocytoma crisis: a literature review of 200 cases.

PURPOSE: Pheochromocytoma crisis is a life-threatening endocrine emergency that requires prompt diagnosis and treatment. Because of its rarity, sudden onset, and lack of internationally uniform and validated diagnostic criteria, pheochromocytoma crisis remains to be fully clarified. Therefore, we aimed to describe the clinical characteristics and outcomes of pheochromocytoma crisis through a literature review. METHODS: We performed a systematic literature search of PubMed/MEDLINE database, Igaku-Chuo-Zasshi (Japanese database), and Google Scholar to identify case reports of pheochromocytoma crisis published until February 5, 2021. Information was extracted and analyzed from the literature that reported adequate individual patient data of pheochromocytoma crisis in English or Japanese. Cases were also termed as pheochromocytoma multisystem crisis (PMC) if patients had signs of hyperthermia, multiple organ failure, encephalopathy, and labile blood pressure. RESULTS: In the 200 cases of pheochromocytoma crisis identified from 187 articles, the mean patient age was 43.8 ± 15.5 years. The most common symptom was headache (39.5%). The heart was the most commonly damaged organ resulting from a complication of a pheochromocytoma crisis (99.0%), followed by the lungs (44.0%) and the kidney (21.5%). PMC accounted for 19.0% of all pheochromocytoma crisis cases. After excluding 12 cases with unknown survival statuses, the mortality rate was 13.8% (26/188 cases). Multivariable logistic regression analysis revealed that nausea and vomiting were significantly associated with a higher mortality rate. CONCLUSION: Pheochromocytoma can present with different symptomatology, affecting different organ systems. Clinicians should be aware that patients with nausea or vomiting are at a higher risk of death because of pheochromocytoma crisis.

Calculation of an Enhanced A_{1g} Symmetry Mode Induced by Higgs Oscillations in the Raman Spectrum of High-Temperature Cuprate Superconductors.

In superconductors the Anderson-Higgs mechanism allows for the existence of a collective amplitude (Higgs) mode which can couple to eV light mainly in a nonlinear Raman-like process. The experimental nonequilibrium results on isotropic superconductors have been explained going beyond the BCS theory including the Higgs mode. Furthermore, in anisotropic d-wave superconductors strong interaction effects with other modes are expected. Here we calculate the Raman contribution of the Higgs mode from a new perspective, including many-body Higgs oscillations effects and their consequences in conventional, spontaneous Raman spectroscopy. Our results suggest a significant contribution to the intensity of the A_{1g} symmetry Raman spectrum in d-wave superconductors. In order to test our theory, we predict the presence of measurable characteristic oscillations in THz quench-optical probe time-dependent reflectivity experiments.

Pyogenic spondylitis with acute course caused by Corynebacterium simulans.

Corynebacterium simulans was first reported in 2000. Although it is a member of the normal skin flora, some cases of C. simulans infection have been reported. Other Corynebacterium spp. rarely cause chronic pyogenic spondylitis, and pyogenic spondylitis caused by C. simulans has not been reported at all. Here we report a case of acute pyogenic spondylitis due to C. simulans. A 78-year-old man with diabetes mellitus visited our hospital with a 3-day history of lower back pain and fever. Blood culture revealed C. simulans and magnetic resonance images of lumbar vertebrae showed pyogenic spondylitis. He recovered after treatment by vancomycin for 9 weeks and was discharged home. No recurrence has been observed for half a year. This is likely the first reported case of pyogenic spondylitis by C. simulans. In general, Corynebacterium spp. cause chronic pyogenic spondylitis, but this case showed an acute course.

Nationwide survey on cerebral amyloid angiopathy in Japan.

BACKGROUND AND PURPOSE: A nationwide survey was conducted to understand the epidemiology of cerebral amyloid angiopathy-related intracerebral hemorrhage (CAA-related ICH) and cerebral amyloid angiopathy-related inflammation/vasculitis (CAA-ri) in Japan. METHODS: To estimate the total number and clinical features of patients with CAA-related ICH and CAA-ri between January 2012 and December 2014 and to analyze their clinical features, questionnaires were sent to randomly selected hospitals in Japan. RESULTS: In the first survey, 2348 of 4657 departments responded to the questionnaire (response rate 50.4%). The total numbers of reported patients with CAA-related ICH and CAA-ri were 1338 and 61, respectively, and their total numbers in Japan were estimated to be 5900 [95% confidence interval (CI) 4800-7100] and 170 (95% CI 110-220), respectively. The crude prevalence rates were 4.64 and 0.13 per 100 000 population, respectively. The clinical information of 474 patients with CAA-related ICH obtained in the second survey was as follows: (i) the average age of onset was 78.4 years; (ii) the prevalence increased with age; (iii) the disease was common in women; and (iv) hematoma most frequently occurred in the frontal lobe. Sixteen patients with CAA-ri for whom data were collected in the second survey had the following characteristics: (i) median age of onset was 75 years; (ii) cognitive impairment and headache were the most frequent initial manifestations; and (iii) focal neurological signs, such as motor paresis and visual disturbance, were frequently observed during the clinical course. CONCLUSIONS: The numbers of patients with CAA-related ICH and CAA-ri in Japan were estimated.

Risk of serious adverse events and fatal adverse events with sorafenib in patients with solid cancer: a meta-analysis of phase 3 randomized controlled trials†.

Background: Sorafenib is a multikinase-tyrosine kinase inhibitor commonly used in a variety of cancers. There are concerns about the increased risk of serious adverse events (SAEs) and fatal adverse events (FAEs) with sorafenib. We performed an up-to-date meta-analysis of all phase 3 randomized controlled trials (RCTs) of sorafenib to quantify the increased risk of SAEs and FAEs. Patients and methods: We carried out a systematic search of electronic databases for studies published from inception to February 2016 without any restrictions. Eligibility criteria included phase 3 RCTs of solid tumors comparing sorafenib, alone or in combination with nontargeted chemotherapy (Sorafenib arm) versus placebo or nontargeted chemotherapy (control arm). Data on SAEs and FAEs for both the arms were extracted from each study and pooled to determine the overall incidence, relative risks (RRs) and 95% Confidence Intervals (CIs). Results: Of 471 studies identified, a total of 12 phase 3 RCTs involving 6797 solid cancer patients comparing sorafenib with control met the eligibility criteria and were included. The overall incidence of SAEs and FAEs with sorafenib were 26.4% (95% CI, 18.0-36.9%) and 1.3% (95% CI: 0.8-2.2%), respectively. Compared with control, sorafenib use significantly increased the risk of both SAEs (RR: 1.49, 95% CI: 1.18-1.89, P = 0.001) and FAEs (RR: 1.82, 95% CI: 1.05-3.14, P = 0.033). This association varied significantly with cancer types (P < 0.001) and approval status (P = 0.012) for SAEs but no evidence of heterogeneity was found for FAEs. Conclusions: This meta-analysis of phase 3 RCTs demonstrates an increased risk of both SAEs and FAEs with sorafenib use in adult patients with solid cancers. This quantification of increased risks of SAEs and FAEs will be important in considering the trade-off of sorafenib treatment during shared decision-making.

Periodontal disease and percentage of calories from fat using national data.

BACKGROUND AND OBJECTIVE: The association between periodontal disease and nutrient intake was examined using linked data from the 2005 National Health and Nutrition Survey, the Comprehensive Survey of Living Conditions and the Survey of Dental Diseases from the same year 'using linked data from the National Health and Nutrition Survey, the Comprehensive Survey of Living Conditions and the Survey of Dental Diseases, all from 2005'. There has been increasing focus on the importance of nutritional factors in disease in recent years, but very few studies in Japan have looked at the association between periodontal disease and nutrients. Therefore, in the present study we investigated factors associated with periodontal disease, particularly in terms of nutrient intake. MATERIAL AND METHODS: Data from 3043 individuals, ≥ 20 years of age (the original study sample comprised 4873 individuals, but those younger than 20 years of age and pregnant women were excluded from the present study) were compiled from linked responses to these three surveys from the same year. Permission to use the data was obtained from the Lifestyle-Related Diseases Control General Affairs Division of the Ministry of Health, Labor, and Welfare, Japan. Information including basic attributes, family structure, economic status, physical condition, lifestyle habits, diet, dental habits, blood data, intake of foods (including the categories of food) and nutrient-related information were obtained from the linked data. The individual maximum Community Periodontal Index (CPI) was used as an index of periodontal disease. Subjects were divided, according to maximum CPI, into groups in which CPI = 0-2 or CPI = 3-4, and associations between CPI and basic attributes, family structure, economic status, physical condition, lifestyle habits, diet, blood data and food intake were analyzed. RESULTS: Multivariate analysis revealed that the percentage of calories from fat was a nutrient factor associated with periodontal disease, with the percentage of calories from fat being significantly lower in the group with advanced periodontal disease. CONCLUSION: The results suggest that a low-fat, high-carbohydrate diet is related to periodontal disease. A more detailed analysis of this topic will be conducted in the future using different indices of periodontal disease.

Ipsilateral hemiparesis in ischemic stroke patients.

OBJECTIVES: To investigate clinical characteristics of ipsilateral hemiparesis in ischemic stroke patients. MATERIALS AND METHODS: Patients with acute ischemic stroke were prospectively examined. Ipsilateral hemiparesis was defined as hemiparesis ipsilateral to recent stroke lesions. Patients with ipsilateral hemiparesis were examined with functional neuroimaging studies including transcranial magnetic stimulation (TMS) and functional MRI. RESULTS: Of 8360 patients, ipsilateral hemiparesis was detected in 14 patients (0.17%, mean age 71±6 years, eight men). Lesions responsible for the recent strokes were located in the frontal cortex in three patients, corona radiata in seven, internal capsule in one, and pons in three. These lesions were located along the typical route of the corticospinal tract in all but one patient. Thirteen patients also had a past history of stroke contralateral to the recent lesions; 12 of these had motor deficits contralateral to past stroke lesions. During TMS, ipsilateral magnetic evoked potentials were evoked in two of seven patients and contralateral potentials were evoked in all seven. Functional MRI activated cerebral hemispheres ipsilaterally in eight of nine patients and contralaterally in all nine. CONCLUSIONS: Most patients with ipsilateral hemiparesis had a past history of stroke contralateral to the recent one, resulting in motor deficits contralateral to the earlier lesions. Moreover, functional neuroimaging findings indicated an active crossed corticospinal tract in all of the examined patients. Both findings suggest the contribution of the uncrossed corticospinal tract contralateral to stroke lesions as a post-stroke compensatory motor system.

Gate-Tunable Spin-Charge Conversion and the Role of Spin-Orbit Interaction in Graphene.

The small spin-orbit interaction of carbon atoms in graphene promises a long spin diffusion length and the potential to create a spin field-effect transistor. However, for this reason, graphene was largely overlooked as a possible spin-charge conversion material. We report electric gate tuning of the spin-charge conversion voltage signal in single-layer graphene. Using spin pumping from an yttrium iron garnet ferrimagnetic insulator and ionic liquid top gate, we determined that the inverse spin Hall effect is the dominant spin-charge conversion mechanism in single-layer graphene. From the gate dependence of the electromotive force we showed the dominance of the intrinsic over Rashba spin-orbit interaction, a long-standing question in graphene research.

Measurement of small fibre pain threshold values for the early detection of diabetic polyneuropathy.

AIM: To investigate whether Aδ and C fibre pain threshold values, measured using intra-epidermal electrical stimulation (IES), in people with and without Type 2 diabetes are useful in evaluating diabetic polyneuropathy (DPN) severity. METHODS: Aδ and C fibre pain threshold values were measured in Japanese people with (n = 120) and without (n = 76) Type 2 diabetes by IES. Nerve conduction studies and other tests were performed to evaluate diabetic complications. RESULTS: Aδ and C fibre pain threshold values were high in people with diabetes compared with control subjects (Aδ fibre: 0.050 vs. 0.030 mA, P < 0.01; C fibre: 0.180 vs. 0.070 mA, P < 0.01). Participants with diabetes and neuropathy had significantly higher Aδ and C fibre pain threshold values than participants without neuropathy (Aδ fibres 0.063 vs. 0.039 mA, P < 0.01; C fibres 0.202 vs. 0.098 mA, P < 0.05). C fibre pain threshold values were significantly higher in participants with diabetes and diabetic microvascular complications than in participants without complications. Threshold values increased with complication progression. When DPN was diagnosed according to the Diabetic Neuropathy Study Group in Japan criteria, the cut-off for the C fibre pain threshold values was 0.125 mA (area under the curve 0.758, sensitivity 81.5%, specificity 61.5%). The IES test took less time (P < 0.01) and was less invasive (P < 0.01) than the nerve conduction studies. CONCLUSIONS: Intra-epidermal electrical stimulation is a non-invasive and easy measurement of small fibre pain threshold values. It may be clinically useful for C fibre measurement to diagnose early DPN as defined by the Diabetic Neuropathy Study Group in Japan criteria.

Distinct X chromosomal rearrangements in four haemophilia B patients with entire F9 deletion.

INTRODUCTION: Haemophilia B is an X-linked bleeding disorder caused by a coagulation factor IX gene (F9) abnormality. Numerous F9 defects have been identified to date; however, only a few with an entire F9 deletion have been reported in detail. AIM: To elucidate the cause of severe haemophilia B, we investigated the precise X chromosome abnormalities in four Japanese patients who did not show all amplifications in F9-specific PCR. METHODS: We analysed the patient's genomic DNA using Multiplex ligation-dependent probe amplification (MLPA). To assess the extent of any deletions, we further performed mapping PCRs, inverse PCRs or long-range PCRs and direct sequencing analyses of the X chromosome. RESULTS: We detected entire F9 deletions in four haemophilia B patients and identified the precise deleted regions of the X chromosome including F9. Patient 1 had a 149-kb deletion with breakpoints 90-kb upstream and 30-kb downstream from F9. Patients 2 and 3 showed 273-kb and 1.19-Mb deletions respectively. Patient 4 had two deleted regions: a 1663-bp deletion 1.34-Mb upstream from F9 and a 7.2-Mb deletion including F9. These distinct breakpoints found in four different patients suggest that the mechanism of X chromosome deletion may be different between individuals. Non-allelic homologous recombination (NAHR), microhomology-mediated break-induced replication (MMBIR) or fork stalling and template switching (FoSTeS) may occur in respective X chromosomes of the four haemophilia B patients analysed. CONCLUSIONS: We identified diverse X chromosomal rearrangements in four haemophilia B patients, which might be caused by distinct mechanisms of genomic rearrangement.

CMAP decrement as a potential diagnostic marker for ALS.

OBJECTIVE: We previously reported that decrement of compound muscle action potential (CMAP) by repetitive nerve stimulation (RNS) was greater in the median nerves than in the ulnar nerves of patients with amyotrophic lateral sclerosis (ALS). The aim of this study was to evaluate whether CMAP decrement by RNS is a feasible marker for the differentiation of ALS from other diseases. MATERIALS & METHODS: We performed RNS in the median and ulnar nerves of 51 patients with ALS and 40 patients with other diseases. RESULTS: The CMAP decrement was significantly greater in the median nerves of patients with ALS, compared to the disease control patients. In the median nerves of patients with ALS, CMAP decrement was significantly greater in the cervical region-onset group than in the other region-onset group. CONCLUSIONS: The finding of CMAP decrement in the median nerves can be useful for differentiating ALS patients with cervical region onset from other controls with active neuropathic diseases.

An internally and externally validated nomogram for predicting the risk of irinotecan-induced severe neutropenia in advanced colorectal cancer patients.

BACKGROUND: In Asians, the risk of irinotecan-induced severe toxicities is related in part to UGT1A1*6 (UGT, UDP glucuronosyltransferase) and UGT1A1*28, variant alleles that reduce the elimination of SN-38, the active metabolite of irinotecan. We prospectively studied the relation between the UGT1A1 genotype and the safety of irinotecan-based regimens in Japanese patients with advanced colorectal cancer, and then constructed a nomogram for predicting the risk of severe neutropenia in the first treatment cycle. METHODS: Safety data were obtained from 1312 patients monitored during the first 3 cycles of irinotecan-based regimen in a prospective observational study. In development of the nomogram, multivariable logistic regression analysis was used to test the associations of candidate factors to severe neutropenia in the first cycle. The final nomogram based on the results of multivariable analysis was constructed and validated internally using a bootstrapping technique and externally in an independent data set (n=350). RESULTS: The UGT1A1 genotype was confirmed to be associated with increased risks of irinotecan-induced grade 3 or 4 neutropenia and diarrhoea. The final nomogram included type of regimen, administered dose of irinotecan, gender, age, UGT1A1 genotype, Eastern Cooperative Oncology Group performance status, pre-treatment absolute neutrophil count, and total bilirubin level. The model was validated both internally (bootstrap-adjusted concordance index, 0.69) and externally (concordance index, 0.70). CONCLUSIONS: Our nomogram can be used before treatment to accurately predict the probability of irinotecan-induced severe neutropenia in the first cycle of therapy. Additional studies should evaluate the effect of nomogram-guided dosing on efficacy in patients receiving irinotecan.

Experimental Demonstration of Room-Temperature Spin Transport in n-Type Germanium Epilayers.

We report an experimental demonstration of room-temperature spin transport in n-type Ge epilayers grown on a Si(001) substrate. By utilizing spin pumping under ferromagnetic resonance, which inherently endows a spin battery function for semiconductors connected with a ferromagnet, a pure spin current is generated in the n-Ge at room temperature. The pure spin current is detected by using the inverse spin-Hall effect of either a Pt or Pd electrode on n-Ge. From a theoretical model that includes a geometrical contribution, the spin diffusion length in n-Ge at room temperature is estimated to be 660 nm. Moreover, the spin relaxation time decreases with increasing temperature, in agreement with a recently proposed theory of donor-driven spin relaxation in multivalley semiconductors.

Successful immunotherapy of autoimmune cholangitis by adoptive transfer of forkhead box protein 3(+) regulatory T cells.

Treatment of primary biliary cirrhosis (PBC) has lagged behind that of other autoimmune diseases. In this study we have addressed the potential utility of immunotherapy using regulatory T cells (Treg ) to treat murine autoimmune cholangitis. In particular, we have taken advantage of our ability to produce portal inflammation and bile duct cell loss by transfer of CD8(+) T cells from the dominant negative form of transforming growth factor beta receptor type II (dnTGF-ßRII) mice to recombination-activating gene (Rag)1(-/-) recipients. We then used this robust established adoptive transfer system and co-transferred CD8(+) T cells from dnTGF-ßRII mice with either C57BL/6 or dnTGF-ßRII forkhead box protein 3 (FoxP3(+) ) T cells. Recipient mice were monitored for histology, including portal inflammation and intralobular biliary cell damage, and also included a study of the phenotypical changes in recipient lymphoid populations and local and systemic cytokine production. Importantly, we report herein that adoptive transfer of Treg from C57BL/6 but not dnTGF-ßRII mice significantly reduced the pathology of autoimmune cholangitis, including decreased portal inflammation and bile duct damage as well as down-regulation of the secondary inflammatory response. Further, to define the mechanism of action that explains the differential ability of C57BL/6 Treg versus dnTGF-ßRII Treg on the ability to down-regulate autoimmune cholangitis, we noted significant differential expression of glycoprotein A repetitions predominant (GARP), CD73, CD101 and CD103 and a functionally significant increase in interleukin (IL)-10 in Treg from C57BL/6 compared to dnTGF-ßRII mice. Our data reflect the therapeutic potential of wild-type CD4(+) FoxP3(+) Treg in reducing the excessive T cell responses of autoimmune cholangitis, which has significance for the potential immunotherapy of PBC.

Abrupt transition from ferromagnetic to antiferromagnetic of interfacial exchange in perpendicularly magnetized L1(0)-MnGa/FeCo tuned by Fermi level position.

An abrupt transition of the interfacial exchange coupling from ferromagnetic to antiferromagnetic was observed in the interface of perpendicularly magnetized L10-MnGa/Fe1-xCox epitaxial bilayers when x was around 25%. By considering the special band structure of the MnGa alloy, we present a model explaining this transition by the spin-polarization reversal of Fe1-xCox alloys due to the rise of the Fermi level as the Co content increases. The effect of interfacial exchange coupling on the coercive force (Hc) and the spin-dependent tunneling effect in perpendicular magnetic tunnel junctions (pMTJs) based on the coupled composite were also studied. Changes from the normal spin valve to inverted magnetoresistance loops corresponding to the coupling transition were observed in pMTJs with MnGa/Fe1-xCox as an electrode.

Non-Gilbert-damping Mechanism in a Ferromagnetic Heusler Compound Probed by Nonlinear Spin Dynamics.

The nonlinear decay of propagating spin waves in the low-Gilbert-damping Heusler film Co_{2}Mn_{0.6}Fe_{0.4}Si is reported. Here, two initial magnons with frequency f_{0} scatter into two secondary magnons with frequencies f_{1} and f_{2}. The most remarkable observation is that f_{1} stays fixed if f_{0} is changed. This indicates, that the f_{1} magnon mode has the lowest instability threshold, which, however, cannot be understood if only Gilbert damping is present. We show that the observed behavior is caused by interaction of the magnon modes f_{1} and f_{2} with the thermal magnon bath. This evidences a significant contribution of the intrinsic magnon-magnon scattering mechanisms to the magnetic damping in high-quality Heusler compounds.

Human intrahepatic biliary epithelial cells engulf blebs from their apoptotic peers.

The phagocytic clearance of apoptotic cells is critical for tissue homeostasis; a number of non-professional phagocytic cells, including epithelial cells, can both take up and process apoptotic bodies, including the release of anti-inflammatory mediators. These observations are particularly important in the case of human intrahepatic biliary cells (HiBEC), because such cells are themselves a target of destruction in primary biliary cirrhosis, the human autoimmune disease. To address the apoptotic ability of HiBECs, we have focused on their ability to phagocytize apoptotic blebs from autologous HiBECs. In this study we report that HiBEC cells demonstrate phagocytic function from autologous HiBEC peers accompanied by up-regulation of the chemokines CCL2 [monocyte chemotactic protein-1 (MCP-1)] and CXCL8 [interleukin (IL)-8]. In particular, HiBEC cells express the phagocytosis-related receptor phosphatidylserine receptors (PSR), implying that HiBECs function through the 'eat-me' signal phosphatidylserine expressed by apoptotic cells. Indeed, although HiBEC cells acquire antigen-presenting cell (APC) function, they do not change the expression of classic APC function surface markers after engulfment of blebs, both with and without the presence of Toll-like receptor (TLR) stimulation. These results are important not only for understanding of the normal physiological function of HiBECs, but also explain the inflammatory potential and reduced clearance of HiBEC cells following the inflammatory cascade in primary biliary cirrhosis.

Optineurin is potentially associated with TDP-43 and involved in the pathogenesis of inclusion body myositis.

AIMS: Increasing evidences suggest a similarity in the pathophysiological mechanisms of neuronal cell death in amyotrophic lateral sclerosis (ALS) and myofibre degeneration in sporadic inclusion body myositis (sIBM). The aim of this study is to elucidate the involvement of ALS-causing proteins in the pathophysiological mechanisms in sIBM. METHODS: Skeletal muscle biopsy specimens of five patients with sIBM, two with oculopharyngeal muscular dystrophy (OPMD), three with polymyositis (PM), three with dermatomyositis (DM), three with neurogenic muscular atrophy, and three healthy control subjects were examined. We analysed the expression and localization of familial ALS-causing proteins, including transactive response DNA binding protein-43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), Cu/Zn superoxide dismutase (SOD1) and optineurin (OPTN) by immunohistochemistry. RESULTS: TDP-43, OPTN and, to a lesser extent, FUS/TLS were more frequently accumulated in the cytoplasm in patients with sIBM and OPMD than in patients with PM, DM, neurogenic muscular atrophy, or healthy control subjects. SOD1 was accumulated in a small percentage of myofibres in patients with sIBM and OPMD, and to a very small extent in patients with PM and DM. Confocal microscopy imaging showed that TDP-43 proteins more often colocalized with OPTN than with FUS/TLS, p62 and phosphorylated Tau. CONCLUSIONS: These findings suggest that OPTN in cooperation with TDP-43 might be involved in the pathophysiological mechanisms of skeletal muscular degeneration in myopathy with rimmed vacuoles. Further investigation into these mechanisms is therefore warranted.