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INTRODUCTION: Long-term medication leads some people with HIV (PWH) to limited treatment options (LTO) due to multiple factors. The present study investigated the prevalence of PWH with LTO in Japan and their clinical characteristics, persistence, and adherence. METHODS: PWH who received antiretroviral therapy (ART) between 2017 and 2022 were identified in the Medical Data Vision (MDV) Japanese claims database. PWH with LTO were defined as: 1) receiving regimens indicative for LTO or 2) having a complex treatment history (≥4 different core agents, ≥11 ART agents). Prevalence by calendar year, clinical characteristics, persistence, and adherence measured by the proportion of days covered (PDC) of ART were investigated. RESULTS: A total of 5740 PWH were included, and 207 (3.6 %) were identified as LTO. Mean (SD) age was 50.3 (11.8) years, 148 (71.5 %) had evidence of AIDS-defining condition, and 25 (12.1 %) had hemophilia. The prevalence of PWH with LTO increased from 2.58 % in 2017 to 3.55 % in 2022. Persistence at 1 year was estimated as 70.3 % and mean PDC through 1 year was 96.7 %. CONCLUSION: Between the years 2017-2022, 3.6 % (approximately 200) Japanese PWH were identified as having LTO. The results of this analysis found clinical characteristics of PWH with LTO as older age and higher percentages with an AIDS-defining condition and hemophilia than the general HIV population. Low persistence indicates that treatment optimization is required in this population. These results will help health care providers to understand the clinical characteristics of PWH with LTO and may contribute to the establishment of appropriate treatment strategies.
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Suicide attempts in humans due to injections of the veterinary drug pentobarbital sodium have been rarely reported. Herein, we present a case of a suicide attempt by intramuscular injection of pentobarbital sodium into the rectus abdominis muscle, which was suggested by computed tomography (CT). A 73-year-old man was brought to the emergency department with GCS 3 (E1V1M1) and an incised wound on the right side of the neck. A bottle of Somnopentyl® (pentobarbital sodium, 64.8 mg/ml), a 20-ml empty syringe with an 18-mm needle, and no. 10 scalpel were present at the scene. At the emergency department, the patient was intubated and was admitted to the intensive care unit. A urine drug screen test by SIGNIFY® ER was positive for benzodiazepines and barbiturates, and continuous veno-venous hemofiltration (CHF) was initiated. The route of drug administration was initially unknown; however, a CT scan revealed swelling of the left rectus abdominis muscle with a wound suggestive of a needle puncture, and the CT analysis suggested 38.16 ml as the maximum dose of pentobarbital sodium. On day 3, the patient's consciousness improved, and he was weaned off CHF and mechanical ventilation. There have been several reports of postmortem CT yielding information on the site of administration of intoxicants, but there have been none for surviving intoxicated patients. This is the first report of the usefulness of CT to identify the site of administration of the causative agent of intoxication while the patient is still alive.
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Pentobarbital , Tentativa de Suicídio , Masculino , Humanos , Idoso , Injeções Intramusculares , Reto do Abdome/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
The treatment of advanced lower gingival carcinoma requires postoperative chemoradiotherapy; therefore, simultaneous hard-tissue reconstruction may not be indicated. In these cases, mandibular reconstruction is performed using a temporal reconstruction plate and various skin flaps. Herein, we reported 2 cases of advanced lower gingival carcinoma treated with a novel computer-assisted patient-specific, fully custom-made mandibular reconstruction plate system(Cosmofix®)in combination with a pedicle/free flap. In case 1, an 80-year-old female patient was diagnosed with right lower gingival carcinoma( cT4aN3bM0, Stage â £B). Under general anesthesia, she underwent tracheostomy, bilateral neck dissection, segmental mandibulectomy, and mandibular reconstruction using Cosmofix® in combination with an ulnar forearm free flap. In case 2, an 81-year-old male patient was diagnosed with right lower gingival carcinoma(cT4aN2bM0, Stage â £A). The patient underwent maintenance dialysis and required minimally invasive surgery using a pedicle flap. Under general anesthesia, the patient underwent tracheostomy, right modified radical neck dissection, segmental mandibulectomy, and mandibular reconstruction using Cosmofix® in combination with a pectoralis major myocutaneous flap. Postoperative facial morphology, occlusion, eating, swallowing, articulation, and other dysfunctions were minimal in both the cases. Adjuvant chemoradiotherapy was recommended. In conclusion, the utilization of the Cosmofix® system enabled both esthetic and functional reconstruction following segmental mandibulectomy for advanced lower gingival carcinoma.
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Carcinoma , Neoplasias Gengivais , Reconstrução Mandibular , Procedimentos de Cirurgia Plástica , Masculino , Feminino , Humanos , Idoso de 80 Anos ou mais , Neoplasias Gengivais/cirurgia , Retalhos Cirúrgicos/cirurgia , Carcinoma/cirurgiaRESUMO
Hepatitis B virus (HBV) is a global major health problem, with over one million deaths annually caused by chronic liver damage. Understanding host factors that modulate HBV replication may aid the development of anti-HBV therapies. Our recent genome-wide small interfering RNA screen using recombinant HBV demonstrated that TIP60 inhibited HBV infection. Here, we show that TIP60 complex contributes to anti-HBV defense. The TIP60 complex bound to the HBV promoter and suppressed HBV transcription driven by the precore/core promoter. The silencing of EP400, TRRAP, BAF53a, RUVBL1, and RUVBL2, which form the TIP60 complex, also resulted in increased HBV transcription. These results contribute to our enhanced understanding of the molecular mechanism of HBV transcription associated with the chromatin structure of HBV covalently closed circular DNA (cccDNA). Exploiting these intrinsic cellular defenses might help develop new anti-HBV agents.IMPORTANCE Investigating the molecular mechanism of HBV replication is important to understand the persistent nature of HBV infection and to aid the development of new HBV agents, which are currently limited to HBV polymerase inhibitors. Previously, we developed a new reporter HBV. By screening host factors using this recombinant virus, we identified several gene products that regulate HBV infection, including TIP60. Here, we showed that TIP60, a catalytic subunit of the NuA4 complex, inhibited HBV replication. Depletion of TIP60 increased the level of HBV mRNA. Moreover, TIP60 localized in the HBV cccDNA chromatin complex catalyzed the acetylation of histone H4 to recruit Brd4. These results suggest that TIP60, in concert with other cellular factors, plays an important role in the regulation of the HBV chromatin structure by acting as a critical component of the intrinsic antiviral defense, which sheds new light on the regulation of HBV replication.
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Vírus da Hepatite B/fisiologia , Hepatite B/metabolismo , Lisina Acetiltransferase 5/metabolismo , Complexos Multiproteicos/metabolismo , Transcrição Gênica , Replicação Viral/fisiologia , Acetilação , Proteínas de Ciclo Celular , Cromatina/genética , Cromatina/metabolismo , Cromatina/patologia , Cromatina/virologia , Células Hep G2 , Hepatite B/genética , Hepatite B/patologia , Histonas/genética , Histonas/metabolismo , Humanos , Lisina Acetiltransferase 5/genética , Complexos Multiproteicos/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Pancreatic damage is commonly observed as a consequence of accidental hypothermia (core body temperature below 35⯰C). We aimed to investigate the risk factors for pancreatic damage and the causal relationship in patients with accidental hypothermia. METHODS: This retrospective, single-center, observational case-control study was conducted in the emergency department of a tertiary care medical center. We investigated patients who were admitted for accidental hypothermia over a course of ten years (January 2008 to December 2017). RESULTS: Of the 138 enrolled patients, 70 had elevated serum amylase levels (51%). We observed a correlation between initial core body temperature and serum amylase level (Spearman's rank correlation coefficient -0.302, pâ¯<â¯0.001). Patients who developed acute pancreatitis had a significantly lower initial core body temperature than those who did not develop it (odds ratioâ¯=â¯0.76; 95% confidence interval [CI]â¯=â¯0.61-0.94; pâ¯=â¯0.011). Receiver operating characteristic analysis showed that a body temperature lower than 28.5⯰C at the time of visit was predictive of acute pancreatitis (area under the curveâ¯=â¯0.71, 95% CIâ¯=â¯0.54-0.88, sensitivityâ¯=â¯0.67, specificityâ¯=â¯0.69, pâ¯=â¯0.017). CONCLUSIONS: We concluded that an initial core body temperature lower than 28.5⯰C was a risk factor for acute pancreatitis in accidental hypothermia cases. In such situations, careful follow-up is necessary.
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Hipotermia/complicações , Pancreatite/etiologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Amilases/sangue , Temperatura Corporal , Estudos de Casos e Controles , Diagnóstico Precoce , Serviço Hospitalar de Emergência , Feminino , Humanos , Hipotermia/etiologia , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnóstico por imagem , Pancreatite/enzimologia , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
A 78-year-old man with anemia (Hb 9.6 g/dl) and elevated serum immunoglobulin M (IgM 3,577 mg/dl) levels was referred to our hospital. Bone marrow aspiration yielded a dry tap, and bone marrow biopsy revealed the infiltration of CD20 positive lymphoplasmacytic lymphoma cells and myelofibrosis. The patient was diagnosed with Waldenström's macroglobulinemia complicated with myelofibrosis. TGF-ß plasma concentration was elevated. Further, after chemotherapy with bendamustine and rituximab, remission of both Waldenström's macroglobulinemia and myelofibrosis was achieved, and TGF-ß levels normalized. MYD88 L265P mutation was detected using highly sensitive digital PCR, which compared with currently used direct PCR product sequencing, has a superior sensitivity. The use of digital PCR has additional advantages toward MYD88 L265P detection, particularly when the available amount of sample DNA is limited owing to myelofibrosis.
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Fator 88 de Diferenciação Mieloide/genética , Mielofibrose Primária , Macroglobulinemia de Waldenstrom , Idoso , Humanos , Imunoglobulina M , Masculino , Mutação , Reação em Cadeia da Polimerase , Mielofibrose Primária/complicações , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/genéticaRESUMO
Chronic infection with hepatitis B virus (HBV) increases the risk of developing fibrosis, cirrhosis or hepatocellular carcinoma. Current therapies are limited to type-I interferons and/or nucleos(t)ide analogues; however, these are only partially effective. The development of novel anti-HBV agents for new treatment strategies has been hampered by the lack of a suitable system that allows the in vitro replication of HBV. Studies of virus infection/replication at the molecular level using wild-type HBV are labor-intensive and time-consuming. To overcome these problems, we previously constructed a recombinant reporter HBV bearing the NanoLuc gene and showed its usefulness in identifying factors that affect HBV proliferation. Because this system mimics the early stage of the HBV life cycle faithfully, we conducted a quantitative analysis of HBV infectivity to several human hepatocyte cell lines as well as the effect of dimethyl sulfoxide and HBV protein X on the early stage of HBV proliferation using this system. Furthermore, we developed a system to produce a reporter HBV expressing a pol gene. These reporter HBV may provide an opportunity to enhance our understanding of the HBV life cycle and aid strategies for the development of new anti-HBV agents.
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Genes Reporter , Engenharia Genética/métodos , Vírus da Hepatite B/crescimento & desenvolvimento , Hepatite B/virologia , Linhagem Celular Tumoral , Dimetil Sulfóxido , Células Hep G2 , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Humanos , Estágios do Ciclo de Vida , Transativadores/metabolismo , Proteínas Virais Reguladoras e Acessórias , Replicação ViralRESUMO
A recombinant hepatitis B virus (HBV) expressing NanoLuc (NL) (HBV/NL) was produced by cotransfecting a plasmid containing a 1.2-fold HBV genome carrying the NL gene with a plasmid bearing a packaging-defective 1.2-fold HBV genome into a human hepatoma cell line, HepG2. We found that NL activity in HBV/NL-infected primary hepatocytes or sodium taurocholate cotransporting polypeptide-transduced human hepatocyte-derived cell lines increased linearly for several days after infection and was concordant with HBV RNA levels in the cells. Treatment of the virus-infected cells with HBV inhibitors reduced NL activity in a dose-dependent manner. Detection of HBV/NL infection, monitored by NL activity, was highly sensitive and less expensive than detection using the conventional method to evaluate HBV infection. In addition, because we also studied host factors, this system is applicable not only for studying the HBV life cycle, but also for exploring agent(s) that regulate HBV proliferation.
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Vírus da Hepatite B/crescimento & desenvolvimento , Virologia/métodos , Técnicas de Inativação de Genes , Células Hep G2 , Humanos , Estágios do Ciclo de Vida , Luciferases/genética , Reação em Cadeia da Polimerase , RNA Interferente Pequeno , TransfecçãoRESUMO
BACKGROUND: One of the major functions of Nef is in the enhancement of the infectivity of the human and simian immunodeficiency viruses (HIV and SIV, respectively). However, the detailed mechanism of the enhancement of viral infectivity by Nef remains unclear. Additionally, studies of mechanisms by which Nef enhances the infectivity of SIV are not as intensive as those of HIV-1. METHODS: We generated short-lived Nef constructed by fusing Nef to a proteasome-mediated protein degradation sequence to characterize the Nef role in viral infectivity. RESULTS: The apparent expression level of the short-lived Nef was found to be extremely lower than that of the wild-type Nef. Moreover, the expression level of the short-lived Nef increased with the treatment with a proteasome inhibitor. The infectivity of HIV-1 with the short-lived Nef was significantly lower than that with the wild-type Nef. On the other hand, the short-lived Nef enhanced the infectivity of SIVmac239, an ability observed to be interestingly equivalent to that of the wild-type Nef. The short-lived Nef was not detected in SIVmac239, but the wild-type Nef was, suggesting that the incorporation of Nef into SIVmac239 is not important for the enhancement of SIVmac239 infectivity. CONCLUSIONS: Altogether, the findings suggest that the mechanisms of infectivity enhancement by Nef are different between HIV-1 and SIVmac239. Lastly, we propose the following hypothesis: even when the expression level of a protein is extremely low, the protein may still be sufficiently functional.
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HIV-1/fisiologia , Vírus da Imunodeficiência Símia/fisiologia , Proteínas Virais Reguladoras e Acessórias/metabolismo , Produtos do Gene nef do Vírus da Imunodeficiência Humana/metabolismo , HIV-1/crescimento & desenvolvimento , HIV-1/patogenicidade , Humanos , Vírus da Imunodeficiência Símia/crescimento & desenvolvimento , Vírus da Imunodeficiência Símia/patogenicidade , VirulênciaRESUMO
Objectives: Orthognathic surgery is a surgical procedure performed by intraoral approach with established and safe techniques; however, excessive blood loss has been reported in rare cases. In response, investigative efforts to identify methods to reduce the amount of blood loss have been made. Among such methods, the administration of tranexamic acid was reported to reduce the amount of intraoperative blood loss. However, few studies to date have reported the effect of tranexamic acid in orthognathic surgery under hypotensive anesthesia. The present study aimed to investigate the effect of the administration of tranexamic acid on intraoperative blood loss in patients undergoing bimaxillary (maxillary and mandibular) orthognathic surgery under hypotensive anesthesia. Patients andMethods: A total of 156 patients (mean age, 27.0±10.8 years) who underwent bimaxillary orthognathic surgery under hypotensive anesthesia performed by the same surgeon between June 2013 and February 2022 were included in this study. The following data were collected from the medical records of each patient: background factors (age, sex, and body mass index), use of tranexamic acid, surgical procedures, previous medical history, duration of surgery, American Society of Anesthesiology physical status findings before surgery, intraoperative blood loss as a primary outcome, in-out balance, and blood test results. Descriptive statistics were calculated for statistical analysis, and a t -test and the chi-squared test were used for between-group comparisons. Group comparisons were performed after 1:1 propensity score matching to adjust for confounding factors. Statistical significance was set at P<0.05. Results: Comparison between the groups based on the use of tranexamic acid revealed a significant difference in operation time. Propensity score matching analysis revealed that intraoperative blood loss was significantly lower in the tranexamic acid group. Conclusion: The administration of tranexamic acid was effective in reducing intraoperative blood loss in patients undergoing bimaxillary orthognathic surgery under hypotensive anesthesia.
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A lack of adherence to long-term antiretroviral therapy may impact viral suppression. The current study examined the relationship between medication adherence and clinical outcomes in people with human immunodeficiency virus infection (PWH) receiving bictegravir, emtricitabine, and tenofovir alafenamide fumarate (B/F/TAF). A retrospective cohort study using two Japanese claims databases was conducted. Adherence was measured by the proportion of days covered (PDC). Patients were grouped into 3 PDC category and persistence was estimated by Kaplan-Meier method. Cox regression analysis was performed to investigate whether the PDC was associated with treatment discontinuation. Among 952 patients, 820 (86.1%), 95 (10.0%), and 37 (3.9%) patients were grouped into the PDC ≥ 90%, 80- < 90%, and < 80% groups, respectively. Across all PDC groups, more than 90% of patients who received B/F/TAF were receiving treatment at 1 year. There was no significant difference in the risk of discontinuation between the lower PDC groups (80- < 90% and < 80%) and the PDC ≥ 90% group (0.400 [0.096, 1.661]; 2.244 [0.663, 7.594], hazard ratio [95% confidence interval], respectively). A drug resistance test was implemented for 15 patients, none of whom discontinued B/F/TAF after the test. The results suggest that events that could cause discontinuation, such as virologic failure, were not associated with PDC.
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Alanina , Fármacos Anti-HIV , Emtricitabina , Infecções por HIV , Adesão à Medicação , Piridonas , Tenofovir , Humanos , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Masculino , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Emtricitabina/uso terapêutico , Japão , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Fármacos Anti-HIV/uso terapêutico , Alanina/uso terapêutico , Alanina/análogos & derivados , Piridonas/uso terapêutico , Piperazinas/uso terapêutico , Resultado do Tratamento , Amidas/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Bases de Dados Factuais , Combinação de MedicamentosRESUMO
Chordoma is a rare tumor that arises from chordal tissue during fetal life. Recently, the concept of poorly differentiated chordoma, a subtype of chordoma characterized by loss of SMARCB1/INI1 with a poorer prognosis than conventional chordomas, was established. It predominantly occurs in children and is rare in adults. Here, we report a rare adult case of poorly differentiated chordoma of the skull base with a unique course that rapidly systemically metastasized and had the shortest survival time of any adult chordoma reported to date. The patient was a 32-year-old male with a chief complaint of diplopia. MRI showed a widespread neoplastic lesion with the clivus as the main locus. Endoscopic extended transsphenoidal tumor resection was performed. Pathological findings showed that the tumor was malignant, and immunohistochemistry revealed a Ki-67 labeling index of 80%, diffusely positive brachyury, and loss of INI1 expression. The final diagnosis was poorly differentiated chordoma. Postoperatively, the residual tumor in the right cavernous sinus showed rapid growth. The patient was promptly treated with gamma knife three fractions. The residual tumor regressed, but the tumor developed systemic metastasis in a short period, and the patient died seven months after diagnosis. This report of a rapidly progressing and fatal adult poorly differentiated chordoma shows the highest Ki-67 labeling index reported to date. Prompt multidisciplinary treatment should be considered when the Ki-67 labeling index is high.
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Second-generation acrylic (SGA) adhesives, possessing high strength and toughness, are applicable in automotive body structures. Few studies have considered the fracture toughness of the SGA adhesives. This study entailed a comparative analysis of the critical separation energy for all three SGA adhesives and an examination of the mechanical properties of the bond. Loading-unloading test was performed to evaluate crack propagation behaviors. In the loading-unloading test of the SGA adhesive with high ductility, plastic deformation was observed in the steel adherends; the arrest load dominated the propagation and non-propagation of crack for adhesive. The critical separation energy of this adhesive was assessed by the arrest load. In contrast, for the SGA adhesives with high tensile strength and modulus, the load suddenly decreased during loading, and the steel adherend was not plastically deformed. The critical separation energies of these adhesives were assessed using the inelastic load. The critical separation energies for all the adhesives were higher for thicker adhesive. Particularly, the critical separation energies of the highly ductile adhesives were more affected by the adhesive thickness than highly strength adhesives. The critical separation energy from the analysis using the cohesive zone model agreed with the experimental results.
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Patients with coronavirus disease 2019 (COVID-19) primarily develop respiratory symptoms, which sometimes can be serious. Respiratory failure is the most common cause of death from COVID-19. This disease also causes gastrointestinal (GI) symptoms. However, there are limited reports that severe GI disorders caused by COVID-19 can be fatal. Herein, we report three cases of fatal GI disorders caused by COVID-19. All patients developed severe pneumonia requiring mechanical ventilation and venovenous extracorporeal membrane oxygenation (V-V ECMO) support. The respiratory status improved, and the patients could be weaned off support. However, severe watery diarrhea (over a few liters per day) developed after the onset of respiratory failure. The CT, endoscopic, and pathological findings were similar to those observed in GI graft-versus-host disease (GI-GVHD). Despite various efforts, the GI disorders did not improve, and all patients died of multiple organ failures associated with sepsis due to intestinal mucosal disruption. COVID-19 can cause fatal GI disorders and may have similar characteristics to GI-GVHD. Further investigation will contribute to a comprehensive understanding of fatal GI disorders due to COVID-19.
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A 66-year-old female suffered from high-energy trauma due to a traffic accident, resulting in injuries to the iliac artery and the superior mesenteric artery. She underwent endovascular embolization for vascular occlusion and an open surgical procedure to control bleeding from the superior mesenteric artery. A substantial retroperitoneal hematoma was observed on the right side, making primary closure challenging. A hematoma evacuation procedure was performed using a right retroperitoneal approach, successfully relieving the compression from the posterior aspect.
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BACKGROUND: While global efforts have been made to prevent transmission of HIV, the epidemic persists. Men who have sex with men (MSM) are at high risk of infection. Despite evidence of its cost-effectiveness in other jurisdictions, pre-exposure prophylaxis (PrEP) for MSM is neither approved nor reimbursed in Japan. METHOD: The cost-effectiveness analysis compared the use of once daily PrEP versus no PrEP among MSM over a 30-year time horizon from a national healthcare perspective. Epidemiological estimates for each of the 47 prefectures informed the model. Costs included HIV/AIDS treatment, HIV and testing for sexually transmitted infections, monitoring tests and consults, and hospitalization costs. Analyses included health and cost outcomes, as well as the incremental cost-effectiveness ratio (ICER) reported as the cost per quality-adjusted life year (QALY) for all of Japan and each prefecture. Sensitivity analyses were performed. FINDINGS: The estimated proportion of HIV infections prevented with the use of PrEP ranged from 48% to 69% across Japan, over the time horizon. Cost savings due to lower monitoring costs and general medical costs were observed. Assuming 100% coverage, for Japan overall, daily use of PrEP costs less and was more effective; daily use of PrEP was cost-effective at a willingness to pay threshold of ¥5,000,000 per QALY in 32 of the 47 prefectures. Sensitivity analyses found that the ICER was most sensitive to the cost of PrEP. INTERPRETATION: Compared to no PrEP use, once daily PrEP is a cost-effective strategy in Japanese MSM, reducing the clinical and economic burden associated with HIV.
HIV remains an epidemic, and men who have sex with men (MSM) are at higher risk of infection. Pre-exposure prophylaxis (PrEP) is a preventive treatment that can reduce someone's risk of getting infected with HIV and has been shown to provide good value for money. PrEP, however, is neither approved nor reimbursed in Japan. In order to determine the value for money in Japan, an economic model was developed to estimate the number of HIV infections and AIDS cases that could be avoided, along with whether daily use of PrEP among MSM in Japan is cost effective. Findings showed that with use of daily PrEP, the proportion of HIV infections and AIDS cases prevented was 63% and 59%, respectively, across Japan. Over a 30-year time horizon, daily use of PrEP would cost the health system less and be more effective than no use of PrEP. Daily PrEP should therefore be considered for reimbursement in MSM in Japan, given its value for money.
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Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Masculino , Humanos , Infecções por HIV/tratamento farmacológico , Homossexualidade Masculina , Fármacos Anti-HIV/uso terapêutico , Análise de Custo-Efetividade , Japão , Análise Custo-BenefícioRESUMO
Since its discovery in late 2019, severe acute respiratory syndrome coronavirus 2 has spread around the world, causing millions of deaths due to coronavirus disease 2019 (COVID-19). Numerous clinical and post-mortem investigations of COVID-19 cases have found myriad clinical and pathological manifestations of the disease. In this report, we present three autopsy cases in which, despite weaning from extracorporeal membrane oxygenation (ECMO), extensive intestinal epithelial shedding, probably due to ischemia, was followed by massive watery diarrhea and the spread of infection via the portal vein due to bacterial translocation, which resulted in cholangitis lenta. Thrombophilia was attributed to ECMO usage and COVID-19-related vascular endothelial damage. These cases provide instructive findings showing that the loss of the intestinal barrier may be the underlying cause of severe watery diarrhea and liver failure in COVID-19 patients, especially with ECMO usage.
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Nef is one of the accessory proteins of human immunodeficiency viruses. Here, we noted that the relative expression level of Nef(NL4-3) is much lower than that of NefJR-CSF in HEK293 cells. By evaluating the expression level using a Nef mutant, it was indicated that amino acids 129-206 of Nef(NL4-3), that is, the C-terminal region named NLAA129-206, could contain the region responsible for the induction of the low protein expression level. In addition, the expression levels of the enhanced green fluorescent protein and Renilla luciferase became extremely low with the fusion of NLAA129-206. Interestingly, the NLAA129-206-corresponding sequences of other Nef variants with relatively high expression levels also induced the extremely low protein expression level by fusion. These results suggest that the C-terminal region of Nef can generally induce an extremely low protein expression level. Here, we propose that the C-terminal region of Nef could become an excellent tool for the induction of an extremely low expression level of arbitrary proteins by attachment as fusion proteins.
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Regulação Viral da Expressão Gênica/genética , Produtos do Gene nef/genética , HIV-1/genética , Proteínas Recombinantes de Fusão/genética , Western Blotting , Citometria de Fluxo , Produtos do Gene nef/metabolismo , Vetores Genéticos/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Luciferases de Renilla/metabolismo , Mutação , Plasmídeos/genética , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Proteínas Recombinantes de Fusão/metabolismoRESUMO
BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is a postacute coronavirus disease 2019 (COVID-19) syndrome occurring weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although this hyperinflammatory syndrome causes significant morbidity, mortality is low. Reports of MIS-A following acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 infection have rarely been reported. We describe two cases of MIS-A that developed after recovery from critical acute COVID-19. CASE PRESENTATION: We present two cases of MIS-A. In both cases, approximately 4 weeks after the onset of COVID-19, the patients developed gastrointestinal disorders, complicated by other organ damage, and died. CONCLUSION: ARDS and MIS-A can occur in a patient with COVID-19 at different times of onset. Clinicians should consider MIS-A when unexplained multisystemic abnormalities are noted after the treatment of ARDS due to COVID-19.
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Background: In patients with severe coronavirus disease (COVID-19), the use of acrylonitrile hemofilters can reduce cytokine concentrations. However, acrylonitrile hemofilters can easily coagulate, and the effect of hemofilters on improvement in patient prognosis remains unclear. Therefore, we aimed to investigate the changes in serum cytokine concentrations, alleviation of organ damage, and improvement in patient prognosis with continuous renal replacement therapy (CRRT) using a cellulose triacetate (CTA) filter with excellent anticoagulation property in patients with severe COVID-19. Methods: This was a retrospective, single-center study conducted by the Advanced Critical Care Center in Sapporo Medical University Hospital, Japan. Seven patients with severe COVID-19 between March 01 and June 30, 2020, were included. The patients were under mechanical ventilation and received continuous blood purification therapy with a CTA filter. We summarized the CRRT status and patient prognosis and measured their serum cytokine (interleukin [IL]-1ß, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α, and interferon-γ) and serum marker levels, before and after CRRT. In addition, we evaluated the changes in their respiratory status, hemodynamics, and organ dysfunction scores. The average age of the patients was 61.5 years, and five patients were male. Extracorporeal membrane oxygenation was used in five patients. The treatment outcome included three deaths. Results: The median CRRT duration was 7 days. The hemofilter was replaced once a day. After CRRT, the IL-6 concentration decreased from 393 to 85 pg/mL (p = 0.016), the Krebs von den Lungen-6 concentration decreased from 554 to 350 U/mL, and the PaO2/FiO2 ratio increased significantly from 90 to 248, and therefore, oxygenation improved. In addition, the norepinephrine dose and lactate level decreased, and the circulation tended to improve; however, the renal function and Sequential Organ Failure Assessment score did not change. Conclusions: The serum IL-6 level decreased, and the respiratory status improved upon CRRT using a CTA filter in patients with severe COVID-19.