Effectiveness of Clinical Management of COVID-19 Based on Structured Clinical Knowledge and Process Paths.

This study examined the effectiveness of a systematic approach to the clinical management of COVID-19, focusing on nursing turnover. METHODS: Between 2017 and 2019, a clinical process support system based on structured clinical knowledge (Team Compass with the Patient Condition Adaptive Path System; TC-PCAPS) was developed, and implemented in hospitals. In 2020, the COVID-19 clinical management system (COVID-19-CMS) was developed. In this study, the effectiveness of implementing both systems was analyzed. The analysis covered hospitals N, T, and B, where TC-PCAPS implementation started in 2019, 2020, and 2022, respectively. Data for the period from 2018 to 2022 were collected and compared. RESULTS: Hospitals N and T implemented TC-PCAPS in the first year and the COVID-19-CMS in the following year. The nurse turnover rates of these hospitals were lower than those of the prefectures in which they were located. There was a trend towards a gradual reduction in nurse turnover. In contrast, hospital B, which had only just started to introduce these systems, saw a gradual increase in nurse turnover. CONCLUSION: The data collected from these three hospitals suggested that this systematic approach has the potential to reduce nurse turnover, in addition to the previously reported ability of TC-PCAPS to reduce nurse overtime. In Japan, there is a need to respond to future pandemics and reform the work styles of physicians and nurses. The abovementioned systematic approach has great potential for contributing to both of these aims.

Case report: Saccadic ping-pong gaze in progressive supranuclear palsy with predominant postural instability.

We report a 63-year-old female patient with progressive supranuclear palsy (PSP). She presented predominant postural instability and "saccadic ping-pong gaze" (SPPG). She had unprovoked falls recurrently within a year from the onset of gait disturbance. She tended to fall backward with eye closure but had no freezing of gait on examination. She showed no signs of nuchal dystonia, limb tremor, rigidity, spasticity, or ataxia. The dopaminergic response was negative. On the initial examination, her vertical eye movements were normal, but frequent macro square wave jerks and SPPG were observed. SPPG consisted of short-cycle, horizontal conjugate irregular pendular oscillations of the eye position from the midpoint with superimposed small saccades. SPPG was observed usually in the dark, not in the daylight, and with eye closure by using electrooculogram and infrared charge-coupled device imaging. One and a half years after the first examination, she was diagnosed as probable PSP with vertical supranuclear gaze palsy. SPPG was first described in patients who are unconscious by Johkura in 1998 as a "saccadic" variant of "ping-pong gaze (PPG)." PPG, short-cycle periodic alternating gaze, has been described in comatose patients since 1967. On the other hand, abnormal eye movement, which looks the same as SPPG in coma, has been described in conscious patients with PSP or spinocerebellar degeneration (SCD) in Japanese literature since 1975. However, it has been called "transient alternating saccades (TAS)." Nowadays, we believe it is more appropriate to call this abnormal eye movement "SPPG" instead of TAS. Here, we propose that PSP, a neuro-degenerative disease, should be added as one of the etiologies of SPPG. We discuss the differences between PPG/SPPG in coma and SPPG in PSP and the possible pathophysiological mechanism of SPPG in relation to cerebellar oculomotor dysfunctions.

Analysis of Relationships between Spinal Deformity and Walking Ability in Parkinson's Disease Patients.

INTRODUCTION: This study aimed to determine impacts on walking ability of spinal deformity and imbalance as distinct from movement disorders in Parkinson's disease (PD). METHODS: Thirty-two patients (15 males, 17 females; mean age 72.5 years) were analyzed. Three, thirteen, eleven, and five were at Hoehn-Yahr stages I, II, III, and IV, respectively. In addition to various spinal imbalance and deformity classifications the following were assessed: Cobb angle (CA) for scoliosis, thoracic kyphosis (TK) at T2-12, thoracolumbar kyphosis(TLK) at T12-L2, lumbar lordosis(LL) at L1-S1, pelvic tilt(PT), pelvic incidence(PI), and sagittal vertical axis(SVA). The Timed Up and Go (TUG) test was used to measure walking ability. Patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) part III, and bone mineral density (BMD) scans. RESULTS: Nineteen patients (59%) had spinal deformity and imbalance within the following classifications: thoracic scoliosis, 1; thoracic kyphosis, 2; lumbar scoliosis, 15; Pisa syndrome, 3; camptocormia, 2. Mean values were 20.0° CA for scoliosis, 42.3° TK, 14.8° TLK, 26.7° LL, 20.8° PT, 48.8° PI, and 66.4 mm SVA. The mean TUG score was 13.9s. The UPDRS III mean was 36.6±24.5 points. Mean BMD was 0.856 g/cm2 at lumbar L2-4 and 0.585 g/cm2 at the femoral neck. UPDRS part III (P<0.001), LL (P<0.05), and femoral neck BMD (P<0.05) significantly correlated to TUG test results. CONCLUSIONS: Distinct from the movement disorders of PD (UPDRS III), loss of normal LL and loss of BMD at the femoral neck were shown to be correlated with diminished walking ability (TUG test) in PD patients. When UPDRS improved in response to L-dopa, walking ability improved. In addition to any PD-specific interventions that contribute to the maintenance of ambulation, interventions specific to the restoration of LL, as well as early treatment for osteoporosis may positively affect HRQOL in PD.

GCH1 mutations in dopa-responsive dystonia and Parkinson's disease.

Guanosine triphosphate cyclohydrolase I (GCH1) mutations are associated with increased risk for dopa-responsive dystonia (DRD) and Parkinson's disease (PD). Herein, we investigated the frequency of GCH1 mutations and clinical symptoms in patients with clinically diagnosed PD and DRD. We used the Sanger method to screen entire exons in 268 patients with PD and 26 patients with DRD, with the examinations of brain magnetic resonance imaging scans, striatal dopamine transporter scans, and [123I] metaiodobenzylguanidine (MIBG) myocardiac scintigraphy scans. We identified 15 patients with heterozygous GCH1 mutations from seven probands and five sporadic cases. The prevalence of GCH1 mutations in probands was different between PD [1.9% (5/268)] and DRD [26.9% (7/26)] (p value < 0.0001). The onset age tends to be different between PD and DRD patients: 35.4 ± 25.3 and 16.5 ± 13.6, respectively (average ± SD; p = 0.08). Most of the patients were women (14/15). Dystonia was common symptom, and dysautonomia and cognitive decline were uncommon in our PD and DRD. All patients presented mild parkinsonism or dystonia with excellent response to levodopa. Seven of seven DRD and three of five PD presented normal heart-to-mediastinum ratio on MIBG myocardial scintigraphy. Five of six DRD and three of four PD demonstrated normal densities of dopamine transporter. Our findings elucidated the clinical characteristics of PD and DRD patients due to GCH1 mutations. PD patients with GCH1 mutations also had different symptoms from those seen in typical PD. The patients with GCH1 mutations had heterogeneous clinical symptoms.

Deep cerebral venous thrombosis mimicking influenza-associated acute necrotizing encephalopathy: a case report.

BACKGROUND: Acute necrotizing encephalopathy is one of the most devastating neurological complications of influenza virus infection. Acute necrotizing encephalopathy preferentially affects the thalamus bilaterally, as does deep cerebral venous thrombosis, which can lead to misdiagnosis. CASE PRESENTATION: A 52-year-old Japanese woman infected with seasonal influenza B virus presented to the emergency care unit in our hospital with progressive alteration of her level of consciousness. Bilateral thalamic lesions were demonstrated by magnetic resonance imaging, leading to a tentative diagnosis of acute necrotizing encephalopathy. However, she had deep cerebral venous thrombosis, and the presence of diminished signal and enlargement of deep cerebral veins on T2*-weighted imaging contributed to a revised diagnosis of deep cerebral venous thrombosis. Anticoagulant therapy was initiated, leading to her gradual recovery, with recanalization of the deep venous system and straight sinus. CONCLUSIONS: To the best of our knowledge, these results represent the first report of deep cerebral venous thrombosis associated with influenza infection. It is clinically important to recognize that deep cerebral venous thrombosis, although rare, might be one of the neurological complications of influenza infection. In the presence of bilateral thalamic lesions in patients with influenza infection, deep cerebral venous thrombosis should be considered in addition to acute necrotizing encephalopathy. Delays in diagnosis and commencement of anticoagulant therapy can lead to unfavorable outcomes.

A study of brain metabolism in fibromyalgia by positron emission tomography.

PURPOSE: The aim of the present study was to determine the brain regions with altered metabolism in patients with treatment-naïve fibromyalgia (FM). METHODS: We used [18F] fluoro-d-glucose positron emission tomography to examine a total of 18 treatment-naïve FM patients and 18 age- and sex-matched healthy controls not suffering from pain. A voxel-by-voxel group analysis was performed using statistical parametric mapping. RESULTS: No significant voxel (peak)-level results were detected in this study; however, some regions were detected as significant-size clusters. There were no significant differences in brain metabolism between FM patients and controls. However, the right thalamus and left lentiform nucleus were hypermetabolic areas in FM patients with poor prognosis compared to the healthy controls. In contrast, the left insula and left lentiform nucleus were hypometabolic areas in FM patients with good prognosis compared to the healthy controls. Compared to FM patients with good prognosis, FM patients with poor prognosis showed significant hypermetabolism in the left thalamus, bilateral lentiform nucleus, and right parahippocampal gyrus. CONCLUSION: The present findings suggest an association between the metabolism in the thalamus, lentiform nucleus, and parahippocampal gyrus and prognosis in FM patients. Further study with a larger number of patients is required to confirm this association.

Cytomegalovirus-associated encephalomyelitis in an immunocompetent adult: a two-stage attack of direct viral and delayed immune-mediated invasions. case report.

BACKGROUND: It is clinically rare to find cytomegalovirus (CMV)-associated encephalomyelitis in immunocompetent adults. Here, we present the case of an adult patient who developed acute transverse myelitis that was followed by immune-mediated disseminated encephalomyelitis. CASE PRESENTATION: A 38-year-old man developed acute paraplegia with paresthesia below the level of the T7-8 dermatome. Both brain and spinal cord MRIs performed at admission appeared normal. Corticosteroid therapy was initiated, with the later addition of high-dose intravenous immunoglobulins. After polymerase chain reaction analysis indicated the presence of CMV DNA in his cerebrospinal fluid (CSF), anti-viral therapy was added. Forty days after symptom onset, despite an initial positive response to this therapy, he developed dysarthria and truncal ataxia. Repeated magnetic resonance imaging scans demonstrated progressively expanding lesions involving not only the spinal cord but also the cerebral white matter, suggestive of extensive immune-mediated demyelination involving the central nervous system (CNS), as is observed in acute disseminated encephalomyelitis (ADEM). CONCLUSION: This case report underscores the importance of careful patient observation following the initial diagnosis of a CMV-associated CNS infection, such as transverse myelitis, on the possibility that post-infectious ADEM may appear.

Cerebrospinal fluid dissemination of anaplastic intraventricular meningioma: report of a case presenting with progressive brainstem dysfunction and multiple cranial nerve palsies.

BACKGROUND: It is extremely rare to see cerebrospinal fluid dissemination of intraventricular meningioma, particularly with the development of acute, progressive brainstem/cerebellar dysfunction with an absence of mass formation in the corresponding anatomical sites. CASE PRESENTATION: An 81-year-old man was admitted because of double vision, right facial nerve palsy and truncal ataxia. Brain magnetic resonance imaging showed normal findings except for a tumor mass in the left lateral ventricle, which had been noted over 6 months previously. The patient developed hiccups, hyperventilation, and drowsiness, which worsened progressively, and did not respond to corticosteroid or intraventricular immunoglobulin therapy. Cerebrospinal fluid study revealed a mild elevation of protein, and cytology was negative. The patient died and an autopsy was performed. Postmortem investigation disclosed a malignant transformation of benign fibroid meningioma with cerebrospinal fluid dissemination of the malignant cells, diversely involving the surface of brainstem, cerebellum, and spinal cords, secondarily resulting in extensive ischemia in the brain parenchyma by vessel occlusion. CONCLUSION: If a patient with an intraventricular tumor develops acute, progressive neurological symptoms, the possibility that it is be caused by cerebrospinal fluid dissemination of tumor cells, after malignant transformation, should be considered.

A randomized double-blind multi-center trial of hydrogen water for Parkinson's disease: protocol and baseline characteristics.

BACKGROUND: Our previous randomized double-blind study showed that drinking hydrogen (H2) water for 48 weeks significantly improved the total Unified Parkinson's Disease Rating Scale (UPDRS) score of Parkinson's disease (PD) patients treated with levodopa. We aim to confirm this result using a randomized double-blind placebo-controlled multi-center trial. METHODS: Changes in the total UPDRS scores from baseline to the 8(th), 24(th), 48(th), and 72(nd) weeks, and after the 8(th) week, will be evaluated. The primary endpoint of the efficacy of this treatment in PD is the change in the total UPDRS score from baseline to the 72(nd) week. The changes in UPDRS part II, UPDRS part III, each UPDRS score, PD Questionnaire-39 (PDQ-39), and the modified Hoehn and Yahr stage at these same time-points, as well as the duration until the protocol is finished because additional levodopa is required or until the disease progresses, will also be analyzed. Adverse events and screening laboratory studies will also be examined. Participants in the hydrogen water group will drink 1000 mL/day of H2 water, and those in the placebo water group will drink normal water. One-hundred-and-seventy-eight participants with PD (88 women, 90 men; mean age: 64.2 [SD 9.2] years, total UPDRS: 23.7 [11.8], with levodopa medication: 154 participants, without levodopa medication: 24 participants; daily levodopa dose: 344.1 [202.8] mg, total levodopa equivalent dose: 592.0 [317.6] mg) were enrolled in 14 hospitals and were randomized. DISCUSSION: This study will confirm whether H2 water can improve PD symptoms. TRIAL REGISTRATION: UMIN000010014 (February, 13, 2013).

Acute psychosis as an initial manifestation of hypothyroidism: a case report.

INTRODUCTION: Hypothyroidism is one of the most important causes of treatable dementia, and psychosis occasionally associated with it is known as myxedema madness. We report a case of a 90-year-old patient who developed myxedema madness acutely without overt clinical symptoms and signs suggestive of hypothyroidism. CASE PRESENTATION: A 90-year-old Japanese man, a general practitioner, was admitted to our emergency room because of acute-onset lethargy, delusions, and hallucinations. He had been actively working until 3 days before the admission. Upon admission, his general physical examination was unremarkable. However, a blood investigation showed the presence of hypothyroidism, and computed tomography revealed pleural effusion and ascites. Electroencephalography revealed diffuse slow waves with a decrease of α-wave activity. A single-photon emission computed tomography scan revealed a decrease of cerebral blood flow in both frontal lobes. The patient was soon treated with thyroid hormone replacement therapy. Following normalization of his thyroid function, both pleural effusion and ascites diminished and his electroencephalographic activity improved simultaneously; however, he did not recover from his psychosis. CONCLUSIONS: Myxedema madness should be kept in mind in the differential diagnosis of acute psychosis in elderly patients, particularly the oldest patients as in our case, because manifestations of hypothyroidism often may be indistinguishable from the aging process.

Good's syndrome with opportunistic infection of the central nervous system: a case report.

BACKGROUND: Immunodeficiency with a thymoma (Good's syndrome) is a rare condition occurring in patients with adult-onset hypogammaglobulinemia that is progressive after the removal of thymoma. Recently, we encountered a patient with Good's syndrome who suddenly developed opportunistic encephalitis 4 years after the resection of thymoma without a history of infectious complications. CASE PRESENTATION: A 58-year-old man, who underwent surgery to remove a thymoma at the age of 54, was admitted because of speech difficulties. A brain MRI showed multiple lesions involving the frontal lobes, but the CSF finding was normal. Acyclovir was empirically administered, and fever as well as his neurological symptoms fully recovered within a few days. However, 1 week after admission, motor aphasia and mild right hemiparesis reappeared. MRI showed that the lesion involving the left cingulate gyrus expanded in size, and revealed an abnormal signal intensity lesion in the left corona radiata. Laboratory examination found increased CMV pp65 antigen-positive lymphocytes in serum. Antiviral therapy using ganciclovir and immunoglobulin replacement therapy was started. The patient has since been free from any neurological symptoms for 1 year, and lesions demonstrated by MRI are gradually improving. CONCLUSION: Early recognition of this rare condition and prompt initiation of therapy are crucially important. Awareness of immunodeficiency in a patient after removal of thymoma may help neurologists to consider the possibility that opportunistic infection may be the cause of cerebral lesions.

The predictive value of a change in natural killer cell activity for delirium.

PURPOSE: Few studies looking for an effective biomarker to predict delirium have been performed. This study was designed to investigate whether a change in inflammatory status, indicated by blood natural killer (NK) cell activity, predicts delirium. METHODS: This prospective study, performed in 4 university and 1 general hospital from September, 2011 to October, 2012, included 29 patients. Eligible patients were 65-89years old, newly and emergently admitted. Patients were assessed daily, up to 7days, for occurrence of DSM-IV-defined delirium. The main outcome measure was change in blood NK cell activity between the first and second mornings after admission. RESULTS: The mean change in blood NK cell activity on the second morning, compared to the first morning, in patients developing delirium (n=9) was significantly greater than that in patients without delirium (n=20) (6.0% [SD 8.4] vs. -1.4% [9.0], respectively, t=2.10, P=0.045). Significant difference between the groups was still found after adjusting for age, the history of previous delirium, and the Clinical Dementia Rating score (F=6.63, P=0.017). Of note is that 8 of 9 (89%) patients developing delirium had increased blood NK cell activity, as did only 8 of 20 (40%) patients without delirium, giving measurement of this parameter, for distinguishing the two groups, a sensitivity of 89%, specificity 60%, positive predictive value 50%, negative predictive value 92%, positive likelihood ratio 2.22, and negative likelihood ratio 0.19. When combining this predictor with another predictor, a Delirium Rating Scale-Revised-98 severity score of 5 or more at baseline, positive and negative likelihood ratios were 7.80 and 0.24, respectively. CONCLUSION: Increase in blood NK cell activity may be associated with developing delirium. Further studies including larger numbers of patients are needed to justify the preventive use of drugs for patients meeting criteria for both predictors.

Palliation of malignant tracheal stenosis with a second implantation of an expandable metallic stent under endotracheal intubation.

A 74-year-old man was admitted with respiratory failure and treated for tracheobronchial stenosis due to metastasis of renal cell carcinoma. It improved after implantation of an expandable metallic stent (EMS). One year later, the metastatic tumor at the near distal side of the EMS increased; eventually serious respiratory failure occurred again. However, the delivery catheter of EMS could not be inserted by the usual procedure because there was a strong tracheobronchial curve. Finally it passed along the inside of the endotracheal intubation tube. The respiratory failure was improved by the second implantation of EMS with the method of stent in stent. EMS is often effective in a case with a strong curve and twist of the trachea/bronchi. It was also considered one way of letting the delivery catheter pass inside the endotracheal intubation tube if the patient's respiratory condition was maintained.

Zonisamide reduces cell death in SH-SY5Y cells via an anti-apoptotic effect and by upregulating MnSOD.

Zonisamide, originally known as an antiepileptic drug, has been approved in Japan as adjunctive therapy with levodopa for the treatment of Parkinson's disease (PD). Although zonisamide reduces neurotoxicity, the precise mechanism of this action is not known. Here, we show that zonisamide increases cell viability in SH-SY5Y cells via an anti-apoptotic effect and by upregulating levels of manganese superoxide dismutase (MnSOD). These results would give us novel evidences of PD treatment.

Increase of atypical lymphocytes expressing CD4+/CD45RO+ in an infectious mononucleosis-like syndrome associated with hepatitis A virus infection.

Subpopulations of regular and atypical lymphocytes in the peripheral blood of a 24-year-old man with an infectious mononucleosis (IM)-like syndrome associated with hepatitis A virus (HAV) infection were analyzed. The ratio of CD4+ to CD8+ cells was in the normal range (1.19 and 1.23 in the regular and atypical lymphocytes, respectively), with no increase in CD8+ cells. The percentage of CD8+/CD11b- cells was not increased in the atypical lymphocytes. However, CD45RO+ was expressed on 86.3% of CD4+ atypical lymphocytes. The present data suggest that atypical lymphocytes expressing CD4+/CD45RO+ may play the role of helper T cells in the immune system in the development of IM-like syndrome associated with HAV infection.

Progress in the pathogenesis and genetics of Parkinson's disease.

Recent progresses in the pathogenesis of sporadic Parkinson's disease (PD) and genetics of familial PD are reviewed. There are common molecular events between sporadic and familial PD, particularly between sporadic PD and PARK1-linked PD due to alpha-synuclein (SNCA) mutations. In sporadic form, interaction of genetic predisposition and environmental factors is probably a primary event inducing mitochondrial dysfunction and oxidative damage resulting in oligomer and aggregate formations of alpha-synuclein. In PARK1-linked PD, mutant alpha-synuclein proteins initiate the disease process as they have increased tendency for self-aggregation. As highly phosphorylated aggregated proteins are deposited in nigral neurons in PD, dysfunctions of proteolytic systems, i.e. the ubiquitin-proteasome system and autophagy-lysosomal pathway, seem to be contributing to the final neurodegenerative process. Studies on the molecular mechanisms of nigral neuronal death in familial forms of PD will contribute further on the understanding of the pathogenesis of sporadic PD.

[Reactivation of Epstein-Barr virus is involved in the pathogenesis of lymphomatoid granulomatosis].

Recent studies point to a role of Epstein-Barr virus in the pathogenesis of lymphomatoid granulomatosis. Little is however known about the association of the pathogenesis of the disease with Epstein-Barr virus reactivation. A 46-year-old man presented with fever and general malaise. He had been admitted with fever of unknown origin 10 years previously. Chest radiographs and CT scans showed multiple nodular shadows in both lung fields. PET/CT showed strong accumulation in lung nodules, femoral muscle, lumbar subcutaneous nodule. He died of rapidly progressive neurological lesions. The definitive diagnosis of lymphomatoid granulomatosis was made from histological findings of the surgical biopsy specimen and at autopsy. Elevation of early antigen-IgG titer in serum was shown in this case. This result suggests that reactivation of Epstein-Barr virus is involved in the development of the disease.

[A case of mesalazine-induced pleuritis with hemophagocytic findings].

A 25-year-old woman who had been receiving mesalazine for 2 weeks for ulcerative colitis presented with a nonproductive cough, high fever, and exertional dyspnea. Her chest radiograph showed bilateral pleural effusion. At first, infectious pleuritis was suspected and antibiotics were administered, but the pleural effusion increased and high fever continued. Because clinical and radiographic abnormalities markedly improved with discontinuation of mesalazine and treatment with corticosteroid, mesalazine was thought to be the cause of pleural effusion in this case. This case was thought to be of interest when we consider the onset mechanism of pleurisy by mesalazine. Mesalazine-induced pleuritis must be considered in patients who develop unexplained respiratory symptoms while taking this agent.