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Remdesivir plays a key role in the treatment of coronavirus disease in 2019 (COVID-19). Haemodialysis is sometimes required for hospitalised patients with COVID-19, and patients undergoing haemodialysis are at an increased risk of severe COVID-19. In the present study, we report the serum concentrations of GS-441524, the active metabolite of remdesivir, in four patients undergoing continuous renal replacement therapy (CRRT). Patient 1, a male aged 70s, received a loading dose of 200 mg remdesivir on day 1, followed by 100 mg remdesivir from day 2, according to the package insert as in non-haemodialysis patients. The mean trough serum concentration of GS-441524 was 783.5 ng/mL, which was approximately 7-fold higher than the mean for patients with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min. Patients 2-4 received a loading dose of 200 mg remdesivir on day 1, followed by 100 mg once every 2 days from day 2. The mean trough serum concentrations of GS-441524 were 302.2 ng/mL, 585.8 ng/mL and 677.3 ng/mL, respectively. These were 3 to 6-fold higher than the mean for patients with eGFR ≥60 mL/min. The target doses for patients 1, 2, 3, and 4 receiving CRRT were 13.6 mL/kg/h, 6.0-12.5 mL/kg/h, 20.1 mL/kg/h, and 15.1 mL/kg/h, respectively, using a polysulphone membrane. The package insert dose of remdesivir is an overdose for CRRT patients with a target dose of 10-20 mL/kg/h. In low-intensity CRRT, as in Japan, it may be necessary to extend the interval between the doses of remdesivir.
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Monofosfato de Adenosina/análogos & derivados , Adenosina/análogos & derivados , Alanina/análogos & derivados , COVID-19 , Terapia de Substituição Renal Contínua , Humanos , Masculino , Monofosfato de Adenosina/uso terapêuticoRESUMO
BACKGROUND: Delirium is common in critically ill patients. Haloperidol has long been used for the treatment of delirium. Dexmedetomidine has recently been used to treat delirium among intubated critically ill patients. However, the efficacy of dexmedetomidine for delirium in non-intubated critically ill patients remains unknown. We hypothesize that dexmedetomidine is superior to haloperidol for sedation of patients with hyperactive delirium, and would reduce the prevalence of delirium among non-intubated patients after administration. We will conduct a randomized controlled trial to compare dexmedetomidine and haloperidol for the treatment of nocturnal hyperactive delirium in non-intubated patients in high dependency units (HDUs). METHODS: This is an open-label, parallel-group, randomized controlled trial to compare the efficacy and safety of dexmedetomidine and haloperidol for nocturnal hyperactive delirium in non-intubated patients at two HDUs of a tertiary hospital. We will recruit consecutive non-intubated patients who are admitted to the HDU from the emergency room, and allocate them in a 1:1 ratio to the dexmedetomidine or haloperidol group in advance. The allocated investigational drug will be administered only when participants develop hyperactive delirium (Richmond Agitation-Sedation Scale [RASS] score ≥1 and a positive score on the Confusion Assessment Method for the ICU between 19:00 and 6:00 the next day) during the night at an HDU. Dexmedetomidine is administered continuously, while haloperidol is administered intermittently. The primary outcome is the proportion of participants who achieve the targeted sedation level (RASS score of between -3 and 0) 2h after the administration of the investigational drug. Secondary outcomes include the sedation level and prevalence of delirium on the day following the administration of the investigational drugs, and safety. We plan to enroll 100 participants who develop nocturnal hyperactive delirium and receive one of the two investigational drugs. DISCUSSION: This is the first randomized controlled trial to compare the efficacy and safety of dexmedetomidine and haloperidol for sedation of non-intubated critically ill patients with hyperactive delirium in HDUs. The results of this study may confirm whether dexmedetomidine could be another option to sedate patients with hyperactive delirium. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCT1051220015, registered on 21 April 2022.
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Delírio , Dexmedetomidina , Humanos , Dexmedetomidina/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Haloperidol/efeitos adversos , Drogas em Investigação/uso terapêutico , Estado Terminal , Delírio/tratamento farmacológico , Delírio/induzido quimicamente , Unidades de Terapia Intensiva , Agitação Psicomotora/tratamento farmacológico , Dor/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Tube thoracostomy is rarely associated with serious bleeding complications. Although intercostal artery injury is a well-known bleeding complication, other vascular injuries in the chest wall have only rarely been reported. CASE REPORT: A 58-year-old man with alcoholic liver cirrhosis presented to the emergency department with dyspnea. He was diagnosed by chest computed tomography with spontaneous hemopneumothorax, for which he underwent tube thoracostomy. However, bleeding in the chest wall continued, which required chest tube removal and blood transfusion. Contrast-enhanced computed tomography and angiography revealed contrast extravasation from the thoracodorsal artery, which confirmed a diagnosis of thoracodorsal artery injury. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Because the thoracodorsal artery gives branches to the serratus anterior muscles that are located in the "triangle of safety," chest tube placement in this area is not always safe; it can still cause major bleeding complications from vessels such as the thoracodorsal artery. Hence, close monitoring for bleeding is needed after tube thoracostomy.
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BACKGROUND: The hypothesis of this study is that latent class analysis could identify the subphenotypes of out-of-hospital cardiac arrest (OHCA) patients associated with the outcomes and allow us to explore heterogeneity in the effects of extracorporeal cardiopulmonary resuscitation (ECPR).MethodsâandâResults:This study was a retrospective analysis of a multicenter prospective observational study (CRITICAL study) of OHCA patients. It included adult OHCA patients with initial shockable rhythm. Patients from 2012 to 2016 (development dataset) were included in the latent class analysis, and those from 2017 (validation dataset) were included for evaluation. The association between subphenotypes and outcomes was investigated. Further, the heterogeneity of the association between ECPR implementation and outcomes was explored. In the study results, a total of 920 patients were included for latent class analysis. Three subphenotypes (Groups 1, 2, and 3) were identified, mainly characterized by the distribution of partial pressure of O2(PO2), partial pressure of CO2(PCO2) value of blood gas assessment, cardiac rhythm on hospital arrival, and estimated glomerular filtration rate. The 30-day survival outcomes were varied across the groups: 15.7% in Group 1; 30.7% in Group 2; and 85.9% in Group 3. Further, the association between ECPR and 30-day survival outcomes by subphenotype groups in the development dataset was as varied. These results were validated using the validation dataset. CONCLUSIONS: The latent class analysis identified 3 subphenotypes with different survival outcomes and potential heterogeneity in the effects of ECPR.
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Reanimação Cardiopulmonar , Oxigenação por Membrana Extracorpórea , Parada Cardíaca Extra-Hospitalar , Adulto , Reanimação Cardiopulmonar/métodos , Análise por Conglomerados , Oxigenação por Membrana Extracorpórea/métodos , Humanos , Aprendizado de Máquina , Parada Cardíaca Extra-Hospitalar/terapia , Estudos RetrospectivosRESUMO
PURPOSE: This study aimed to determine the association between sarcopenic findings of the psoas muscle and mortality in patients with sepsis; further, it aimed to assess its clinical utility, in addition to the sequential organ failure assessment (SOFA) score, in predicting mortality. METHOD: This retrospective single-center cohort study included adult patients with sepsis, who were admitted to the intensive care unit, between January 2012 and December 2018. The cross-sectional area of the psoas muscle at the L3 level was measured using computed tomography (CT) images, following which the subjects were categorized as "Above middle," "Middle," and "Sarcopenic." The association between sarcopenic findings and 90-day mortality was investigated by logistic regression analysis. A "modified SOFA score," by adding sarcopenic findings to the SOFA score, was developed and evaluated for its predictive performance. RESULTS: Here, 255 patients with sepsis, who were admitted to the intensive care unit (median age, 76 [64-84] years; SOFA score, 9 [5-14]), were included. The adjusted odds ratio for the "Middle" and "Sarcopenic" groups for 90-day mortality was 2.40 (95% confidence interval [CI]: 0.93-6.15) and 3.67 (95% CI: 1.39-9.68), respectively. The c-statistics of the SOFA and modified SOFA score was 0.731 [95% CI: 0.650-0.799] and 0.749 [95% CI: 0.673-0.813]. On decision curve analysis, a little additional net benefit was observed on using the modified SOFA score. CONCLUSION: The results suggested an association of the sarcopenic findings of the psoas muscle on CT imaging with 90-day mortality; however, the modified SOFA had few additional clinical values to that of SOFA in predicting 90-day mortality.
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Sarcopenia/diagnóstico , Sepse/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Valor Preditivo dos Testes , Músculos Psoas/diagnóstico por imagem , Músculos Psoas/patologia , Estudos Retrospectivos , Sarcopenia/mortalidade , Tomografia Computadorizada por Raios X/métodosRESUMO
Anterior choroidal artery (AchA) infarction remains a challenging diagnosis although it was first described almost 100 years prior. N-isopropyl-p-[123I]-iodoamphetamine single-photon emission computed tomography (123I-IMP SPECT) and 7 Tesla magnetic resonance angiography (7T-MRA) are not routinely performed in cases of AchA infarction. Therefore, the application of 123I-IMP SPECT and 7T-MRA for AchA infarction has not been reported previously. A 67-year-old man presented with disturbed consciousness, gaze preference to the left, aphasia, right homonymous hemianopia, and right hemiparesis. Brain magnetic resonance imaging revealed infarction of the left posterior limb of the internal capsule. Left middle cerebral artery was clearly seen on MRA. However, 123I-IMP SPECT on day 13 showed cortical hypoperfusion which indicated thalamus involvement with neural deactivation. Additionally, 7T-MRA on day 15 revealed an intact left AchA suggesting reperfusion. The neurological deficits improved gradually after treatment and rehabilitation. This case demonstrates AchA infarction with cortical hypoperfusion associated with thalamus involvement, which was clarified by performing 123I-IMP SPECT and 7T-MRA. Perfusion analysis and evaluation of detailed vascular anatomy in stroke can be expected to elucidate pathological conditions.
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Angiografia Cerebral/métodos , Infarto Cerebral/diagnóstico por imagem , Iofetamina/administração & dosagem , Angiografia por Ressonância Magnética , Imagem de Perfusão/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Infarto Cerebral/fisiopatologia , Infarto Cerebral/terapia , Circulação Cerebrovascular , Humanos , Masculino , Valor Preditivo dos Testes , Resultado do TratamentoRESUMO
Severe cholestatic hepatitis C (SCH) is a unique variant of recurrent hepatitis C that occurs after liver transplantation. Unfortunately, the prognosis of SCH is poor, and interferon (IFN) therapy has been reported to not improve the prognosis. We herein report a case of progressive SCH with acute cellular rejection (ACR) and bacterial infection, which was successfully treated using IFN-free therapy with daclatasvir and asunaprevir. A 43-year-old man was diagnosed with SCH and mild ACR at day 48 after liver transplantation, and IFN-free therapy with daclatasvir and asunaprevir was started. Although he experienced catheter-related bacteremia on the first day, the IFN-free therapy was safely continued, which immediately caused his liver function to improve. His bilirubin levels decreased from 11.1 to 2.1 mg/dL and serum hepatitis C virus RNA levels became undetectable after 4 weeks of the treatment. This case indicates that IFN-free therapy for progressive SCH with acute cellular rejection and bacterial infection is safe and effective, and may improve the outcomes of hepatitis C virus positive transplant recipients.
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BACKGROUND Nephrogenic diabetic insipidus (NDI) poses a challenge in clinical management, particularly when associated with lithium ingestion. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the treatment of numerous diseases worldwide, including NDI. However, many studies have reported the diverse adverse effects of long-term use of non-selective NSAIDs. Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a better drug to relieve pain and inflammation in terms of long-term safety and efficacy than non-selective NSAIDs. Nevertheless, there are few reports describing the effectiveness of celecoxib in treating NDI. CASE REPORT We report a case of a 46-year-old woman with schizophrenia who presented with severe hypernatremia and refractory polyuria due to lithium-induced NDI. Cessation of lithium ingestion and traditional treatments, including trichlormethiazide and desmopressin, yielded minimal improvement in her hypernatremia and polyuria. Her sodium level needed to be strictly controlled with the infusion of dextrose 5% in water. Given the safety of celecoxib, we decided to initiate celecoxib as the treatment of lithium-induced NDI instead of indomethacin. Notably, the introduction of celecoxib led to a substantial and sustained amelioration of polyuria and hypernatremia without any celecoxib-associated adverse effects. Even after transfer to another hospital, stability in serum sodium levels persisted with celecoxib. CONCLUSIONS We presented a case of lithium-induced NDI successfully treated with celecoxib, a selective COX-2 inhibitor. To the best of our knowledge, this is the first reported case of successful treatment of lithium-induced NDI with celecoxib, and suggests celecoxib is a viable therapeutic option warranting further exploration. Physicians should consider its use when faced with the challenging management of lithium-induced NDI.
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Diabetes Insípido Nefrogênico , Diabetes Mellitus , Hipernatremia , Feminino , Humanos , Pessoa de Meia-Idade , Diabetes Insípido Nefrogênico/induzido quimicamente , Diabetes Insípido Nefrogênico/tratamento farmacológico , Lítio/uso terapêutico , Celecoxib/uso terapêutico , Poliúria/induzido quimicamente , Poliúria/tratamento farmacológico , Hipernatremia/induzido quimicamente , Hipernatremia/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , SódioRESUMO
Importance: Current trauma-care protocols advocate early administration of fresh frozen plasma (FFP) in a ratio close to 1:1 with red blood cells (RBCs) to manage trauma-induced coagulopathy in patients with severe blunt trauma. However, the benefits of a higher FFP to RBC ratio have not yet been established. Objective: To investigate the effectiveness of a high FFP to RBC transfusion ratio in the treatment of severe blunt trauma and explore the nonlinear relationship between the ratio of blood products used and patient outcomes. Design, Setting, and Participants: This was a multicenter cohort study retrospectively analyzing data from the Japan Trauma Data Bank, including adult patients with severe blunt trauma without severe head injury (Injury Severity Score ≥16 and head Abbreviated Injury Scale <3) between 2019 and 2022. Exposures: Patients were categorized into 2 groups based on the ratio of FFP to RBC: the high-FFP group (ratio >1) and the low-FFP group (ratio ≤1). Main Outcomes and Measures: All-cause in-hospital mortality was the primary outcome. Additionally, the occurrence of transfusion-related adverse events was evaluated. Results: Among the 1954 patients (median [IQR] age, 61 [41-77] years; 1243 male [63.6%]) analyzed, 976 (49.9%) had a high FFP to RBC ratio. Results from logistic regression, weighted by inverse probability treatment weighting, demonstrated an association between the group with a high-FFP ratio and lower in-hospital mortality (odds ratio, 0.73; 95% CI, 0.56-0.93) compared with a low-FFP ratio. Nonlinear trends were noted, suggesting a potential ceiling effect on transfusion benefits. Conclusions and Relevance: In this cohort study, a high FFP to RBC ratio was associated with favorable survival in patients with severe blunt trauma. These outcomes highlight the importance of revising the current transfusion protocols to incorporate a high FFP to RBC ratio, warranting further research on optimal patient treatment.
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Delayed post-hypoxic leukoencephalopathy (DPHL) is a poorly recognized syndrome characterized by neuropsychiatric symptoms following recovery from an acute hypoxic episode. Although most cases are related to carbon monoxide poisoning, some have been linked to excessive opioid use. Opioid intoxication has recently become known for manifesting the characteristic imaging findings involving cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER) syndrome. Herein, we present a patient with severe disturbances in consciousness who was initially diagnosed with CO poisoning but was later found to have taken excessive tramadol. Magnetic resonance imaging (MRI) in the acute phase revealed abnormal intensities in the bilateral globus pallidus and the cerebellum, indicative of CHANTER syndrome. After intensive care, his level of consciousness was restored. However, around the 3rd week after hospitalization, his consciousness gradually deteriorated and he developed severe neurological symptoms. Another MRI on day 25 revealed a new diffuse white matter abnormality; DPHL was suspected. Cerebrospinal fluid collected on day 28 revealed significantly elevated myelin basic protein levels. Although it was challenging to decide on a treatment plan, hyperbaric oxygen (HBO) therapy trials were initiated on day 58; the patient's condition improved after a series of HBO sessions. MRI revealed gradual shrinkage of the white matter abnormality. A total of 63 consecutive HBO sessions were performed, leading to the successful resolution of the serious neurological symptoms. While the effectiveness of HBO therapy for DPHL remains inconclusive, especially in opioid-related cases, this patient made a remarkable recovery, likely due to the therapeutic effect of improved cerebral blood flow and oxygenation.
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Background: The damage that may be caused to the operating table and patients under general anaesthesia when a large earthquake occurs is unclear. We aimed to evaluate the movement and damage to operating tables and patients under general anaesthesia during an earthquake. Methods: An operating table with a manikin resembling a patient on it was placed on a shaking table, and seismic waves were input into the shaking table. The effects of seismic waves were evaluated by altering surgical positions (supine and head-down positions), operating tables, flooring material, seismic waves, and output. We observed the movement of the operating table and measured the acceleration of the operating table and manikin head. Results: Under 90% output of long-period seismic waves, the operating table with the supine manikin was overturned. Under experimental conditions that did not cause rocking, shaking such as tilting of the operating table caused stronger acceleration in the manikin's head than in the operating table. There was no clear relationship between operating table rocking and maximum acceleration as a result of programmed seismic waves. In long-period earthquakes, rocking and overturning occurred >60 s after the onset of shaking, whereas in direct earthquakes, rocking occurred within 10 s. Conclusions: An earthquake could cause strong acceleration of the patient's head under general anaesthesia, and operating tables may overturn or shake violently. Regarding patient safety, further measures to prevent overturning should be considered.
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Acute coronary syndrome (ACS) includes myocardial infarction (MI) and unstable angina (UA). MI is defined by elevated necrosis markers, preferably high-sensitivity cardiac troponins (hs-cTn). However, it takes hours for cTn to become elevated after coronary occlusion; therefore, difficulties are associated with diagnosing early post-onset MI or UA. The aim of this prospective cohort study was to examine the diagnostic ability of serum nardilysin (NRDC) for the early detection of ACS. This study consisted of two sequential cohorts, the Phase I cohort, 435 patients presenting to the emergency room (ER) with chest pain, and the Phase II cohort, 486 patients with chest pain who underwent coronary angiography. The final diagnosis was ACS in 155 out of 435 patients (35.6%) in the phase I and 418 out of 486 (86.0%) in the phase II cohort. Among 680 patients who presented within 24 h of onset, 466 patients (68.5%) were diagnosed with ACS. Serum NRDC levels were significantly higher in patients with ACS than in those without ACS. The sensitivity of NRDC in patients who presented within 6 h after the onset was higher than that of hsTnI, and the AUC of NRDC within 1 h of the onset was higher than that of hsTnI (0.718 versus 0.633). Among hsTnI-negative patients (300 of 680 patients: 44.1%), 136 of whom (45.3%) were diagnosed with ACS, the sensitivity and the NPV of NRDC were 73.5 and 65.7%, respectively. When measured in combination with hsTnI, NRDC plays auxiliary roles in the early diagnosis of ACS.
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Síndrome Coronariana Aguda , Biomarcadores , Diagnóstico Precoce , Humanos , Estudos Prospectivos , Masculino , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/sangue , Feminino , Pessoa de Meia-Idade , Idoso , Biomarcadores/sangue , Metaloendopeptidases/sangue , Estudos de Coortes , Serviço Hospitalar de EmergênciaRESUMO
Hepatitis C virus (HCV) reinfects liver allografts in transplant recipients by replicating immediately after transplantation, causing a rapid increase in blood serum HCV RNA levels. We evaluated dynamic changes in the viral genetic complexity after HCV reinfection of the graft liver; we also identified the characteristics of replicating HCV clones using a massively parallel ultradeep sequencing technique to determine the full-genome HCV sequences in the liver and serum specimens of five transplant recipients with genotype 1b HCV infection before and after liver transplantation. The recipients showed extremely high genetic heterogeneity before transplantation, and the HCV population makeup was not significantly different between the liver and blood serum specimens of the individuals. Viral quasispecies complexity in serum was significantly lower after liver transplantation than before it, suggesting that certain HCV clones selectively proliferated after transplantation. Defective HCV clones lacking the structural region of the HCV genome did not increase in number, and full-genome HCV clones selectively increased in number immediately after liver transplantation. A re-increase in the same defective clone existing before transplantation was detected 22 months after transplantation in one patient. Ultradeep sequencing technology revealed that the genetic heterogeneity of HCV was reduced after liver transplantation. Dynamic changes in defective HCV clones after liver transplantation indicate that these clones have important roles in the HCV life cycle.
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Variação Genética , Hepacivirus/crescimento & desenvolvimento , Hepacivirus/genética , Hepatite C Crônica/virologia , Transplante de Fígado , Fígado/virologia , Transplante , Idoso , Sangue/virologia , Feminino , Genótipo , Hepacivirus/classificação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/genéticaRESUMO
BACKGROUND: Salmonella species are a leading cause of diarrheal diseases worldwide. Recent epidemiological studies have shown that Salmonella schwarzengrund (S. schwarzengrund) is highly prevalent in various regions. Herein, we report that S. schwarzengrund caused sacroiliac joint (SIJ) infection with septic shock in a young woman, although she was immunocompetent. CASE PRESENTATION: A 20-year-old woman presented with left hip pain, accompanied by vasopressor-requiring hypotension. Her imaging examinations showed fluid collection in her SIJ and a small abscess in the left iliac muscle. Later, the blood and aspiration fluid culture and genetic analysis revealed the presence of S. schwarzengrund. We diagnosed sacroiliac joint (SIJ) infection with septic shock caused by S. schwarzengrund. Her condition improved after performing several interventional radiology (IVR) procedures for SIJ abscesses and providing appropriate antibiotic treatment. Finally, she was discharged without any sequelae. Screening tests and genetic analysis about her immunodeficiency did not indicate a congenital disorder. CONCLUSION: These clinical courses indicate that S. schwarzengrund could cause the fatal SIJ infection irrespective of the host immunocompetence. Considering the recent increase in the diagnostic rate of S. schwarzengrund, this case emphasized the need to be more cautious about Salmonella species infection.
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ABSTRACT: Background : Nutritional management is crucial for severely ill patients. Measuring metabolism is believed to be necessary for the acute sepsis phase to accurately estimate nutrition. Indirect calorimetry (IDC) is assumed to be useful for acute intensive care; however, there are few studies on long-term IDC measurement in patients with systemic inflammation. Methods : Rats were categorized into the LPS received or control groups; LPS rats were categorized into underfeeding (UF), adjusted feeding (AF), and overfeeding (OF) groups. Indirect calorimetry measurement was performed until 72 or 144 h. Body composition was measured at -24 and 72 or 144 h, and tissue weight was measured at 72 or 144 h. Results : Low energy consumption and loss of diurnal variation of resting energy expenditure were observed in the LPS group compared with the control group until 72 h, after which the LPS group recovered. The resting energy expenditure in the OF group was higher than that in the UF and AF groups. In the first phase, low energy consumption was observed in all groups. In the second and third phases, higher energy consumption occurred in the OF group than in the UF and AF groups. In the third phase, diurnal variation recovered in all groups. Muscle atrophy caused body weight loss, but fat tissue loss did not occur. Conclusions : We observed metabolic changes with IDC during the acute systemic inflammation phase owing to differences in calorie intake. This is the first report of long-term IDC measurement using the LPS-induced systemic inflammation rat model.
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Estado Terminal , Lipopolissacarídeos , Humanos , Lipopolissacarídeos/toxicidade , Calorimetria Indireta/métodos , Metabolismo Energético/fisiologia , Cuidados CríticosRESUMO
The introduction of direct oral anticoagulants (DOACs) has greatly changed the use of anticoagulant therapy in patients with non-valvular atrial fibrillation (Af). Therefore, this study aimed to examine changes in the proportions of oral anticoagulant prescriptions in patients with non-valvular Af aged ≥ 65 years, taking into consideration the risk of cerebral infarction and bleeding. Anticoagulant prescriptions in outpatients aged ≥ 65 years with Af were temporally analyzed using the nationwide claims database in Japan. Trends in anticoagulant prescriptions were examined according to cerebral infarction and bleeding risk. The proportion of anticoagulant prescriptions for 12,076 Af patients increased from 41% in 2011 to 56% in 2015. An increase in DOAC prescriptions was accompanied by an increase in the proportion of anticoagulant prescriptions in each group according to the CHA2DS2-VASc and HAS-BLED scores. The proportion of anticoagulant prescriptions for patients with a high risk of developing cerebral infarction and bleeding showed a marked increase. Trends in anticoagulant prescriptions in Af patient with a CHA2DS2-VASc score ≥ 2 and HAS-BLED scores ≥ 3 showed a marked increase in DOAC prescriptions. The widespread use of DOACs greatly changes the profile the prescription of anticoagulant therapy in patients with Af.
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Fibrilação Atrial , Acidente Vascular Cerebral , Idoso , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/induzido quimicamente , Acidente Vascular Cerebral/complicações , Fatores de Risco , Anticoagulantes/efeitos adversos , Hemorragia/tratamento farmacológico , Infarto Cerebral/tratamento farmacológico , Infarto Cerebral/etiologia , Administração OralRESUMO
The aldehyde degrading function of the ALDH2 enzyme is impaired by Glu504Lys polymorphisms (rs671, termed A allele), which causes alcohol flushing in east Asians, and elevates the risk of esophageal cancer among habitual drinkers. Recent studies suggested that the ALDH2 variant may lead to higher levels of DNA damage caused by endogenously generated aldehydes. This can be a threat to genome stability and/or cell viability in a synthetic manner in DNA repair-defective settings such as Fanconi anemia (FA). FA is an inherited bone marrow failure syndrome caused by defects in any one of so far identified 22 FANC genes including hereditary breast and ovarian cancer (HBOC) genes BRCA1 and BRCA2. We have previously reported that the progression of FA phenotypes is accelerated with the ALDH2 rs671 genotype. Individuals with HBOC are heterozygously mutated in either BRCA1 or BRCA2, and the cancer-initiating cells in these patients usually undergo loss of the wild-type BRCA1/2 allele, leading to homologous recombination defects. Therefore, we hypothesized that the ALDH2 genotypes may impact breast cancer development in BRCA1/2 mutant carriers. We genotyped ALDH2 in 103 HBOC patients recruited from multiple cancer centers in Japan. However, we were not able to detect any significant differences in clinical stages, histopathological classification, or age at clinical diagnosis across the ALDH2 genotypes. Unlike the effects in hematopoietic cells of FA, our current data suggest that there is no impact of the loss of ALDH2 function in cancer initiation and development in breast epithelium of HBOC patients.