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Preferentially Expressed Antigen in Melanoma (PRAME) and Ten-Eleven Translocation (TET) dioxygenase-mediated 5-hydroxymethylcytosine (5hmC) are emerging melanoma biomarkers. We observed an inverse correlation between PRAME expression and 5hmC levels in benign nevi, melanoma in situ, primary invasive melanoma, and metastatic melanomas via immunohistochemistry and multiplex immunofluorescence: nevi exhibited high 5hmC and low PRAME, whereas melanomas showed the opposite pattern. Single-cell multiplex imaging of melanoma precursors revealed that diminished 5hmC coincides with PRAME upregulation in premalignant cells. Analysis of TCGA and GTEx databases confirmed a negative relationship between TET2 and PRAME mRNA expression in melanoma. Additionally, 5hmC levels were reduced at the PRAME 5' promoter in melanoma compared to nevi, suggesting a role for 5hmC in PRAME transcription. Restoring 5hmC levels via TET2 overexpression notably reduced PRAME expression in melanoma cell lines. These findings establish a function of TET2-mediated DNA hydroxymethylation in regulating PRAME expression and demonstrate epigenetic reprogramming as pivotal in melanoma tumorigenesis. Teaser: Melanoma biomarker PRAME expression is negatively regulated epigenetically by TET2-mediated DNA hydroxymethylation.
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This study aimed to create a robust prediction model for sepsis patient mortality and identify key biomarkers in those with myocardial injury. A retrospective analysis of 261 sepsis inpatients was conducted, with 44 deaths and 217 recoveries. Key factors were assessed via univariate and multivariate analyses, revealing myocardial injury, shock, and pulmonary infection as independent mortality risk factors. Using LASSO regression, a reliable prediction model was developed and internally validated. Additionally, procalcitonin (PCT) emerged as a sensitive biomarker for myocardial injury prediction in sepsis patients. In summary, this study highlights myocardial injury, shock, and pulmonary infection as independent risk factors for sepsis-related deaths. The LASSO-based prediction model effectively forecasts the prognosis of septic patients with myocardial injury, with PCT showing promise as a predictive biomarker.
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Complement-mediated diseases can be treated using systemic inhibitors. However, complement components are abundant in circulation, affecting systemic inhibitors' exposure and efficacy. Furthermore, because of complement's essential role in immunity, systemic treatments raise infection risk in patients. To address these challenges, we developed antibody fusion proteins combining the alternative-pathway complement inhibitor factor H (fH1-5) with an anti-C3d monoclonal antibody (C3d-mAb-2fH). Because C3d is deposited at sites of complement activity, this molecule localizes to tissue complement while minimizing circulating complement engagement. These fusion proteins bind to deposited complement in diseased human skin sections and localize to activated complement in a primate skin injury model. We further explored the pharmacology of C3d-mAb-2fH proteins in rodent models with robust tissue complement activation. Doses of C3d-mAb-2fH >1 mg/kg achieved >75% tissue complement inhibition in mouse and rat injury models while avoiding circulating complement blockade. Glomerular-specific complement inhibition reduced proteinuria and preserved podocyte foot-process architecture in rat membranous nephropathy, indicating disease-modifying efficacy. These data indicate that targeting local tissue complement results in durable and efficacious complement blockade in skin and kidney while avoiding systemic inhibition, suggesting broad applicability of this approach in treating a range of complement-mediated diseases.
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Fator H do Complemento , Nefropatias , Humanos , Camundongos , Ratos , Animais , Fator H do Complemento/genética , Complemento C3d/metabolismo , Nefropatias/etiologia , Anticorpos , Ativação do ComplementoRESUMO
Lanthipeptides make up a large group of natural products that belong to the ribosomally synthesized and post-translationally modified peptides (RiPPs). Lanthipeptides contain lanthionine and methyllanthionine bis-amino acids that have varying stereochemistry. The stereochemistry of new lanthipeptides is often not determined because current methods require equipment that is not standard in most laboratories. In this study, we developed a facile, efficient, and user-friendly method for detecting lanthipeptide stereochemistry, utilizing advanced Marfey's analysis with detection by liquid chromatography coupled with mass spectrometry (LC-MS). Under optimized conditions, 0.05 mg of peptide is sufficient to characterize the stereochemistry of five (methyl)lanthionines of different stereochemistry using a simple liquid chromatography setup, which is a much lower detection limit than current methods. In addition, we describe methods to readily access standards of the three different methyllanthionine stereoisomers and two different lanthionine stereoisomers that have been reported in known lanthipeptides. The developed workflow uses a commonly used nonchiral column system and offers a scalable platform to assist antimicrobial discovery. We illustrate its utility with an example of a lanthipeptide discovered by genome mining.
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Peptídeos , Sulfetos , Peptídeos/química , Sulfetos/química , Alanina/química , Cromatografia LíquidaRESUMO
BACKGROUND: Gastric lavage (GL) is one of the most important early therapies to remove unabsorbed toxins from the gastrointestinal tract. However, the details of performing gastric lavage remain to be established. There is controversy in clinical practice regarding individual choice of the timing of GL and its efficiency. CASE SUMMARY: We report the case of a young woman who presented to the Emergency Department with drug intoxication for four hours. We used the latest toxicological screening techniques to compare drug concentrations in the patient's blood and gastric lavage fluid before and after gastric lavage. The results confirmed that gastric lavage was effective in reducing drug concentrations in the stomach; a small amount of drug remained in the stomach at the end of gastric lavage. CONCLUSION: Gastric lavage is effective in reducing drug concentrations in the stomach, with a small amount of drug remaining in the stomach at the end of gastric lavage.
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Bromadiolone, as a second-generation coumarin anticoagulant rodenticide, may accidently cause harm to humans and non-target animals when overused or misused due to its high toxicity and long-lasting effects. In some severe cases such as the presence of active bleeding, treatment should involve the administration of hemoperfusion therapy. Nafamostat mesylate is a synthesized protease inhibitor that inhibits most factors in the coagulation process, preventing clotting and ensuring smooth blood flow during the procedure. Nafamostat mesylate helps maintain the efficacy and safety of hemoperfusion treatment. Despite its wide application in Japan, the clinical practice and research of nafamostat mesylate are limited in China, especially for patients undergoing maintenance hemodialysis. This paper reports two cases of bromadiolone poisoning and describes the treatment procedure and therapeutic effect of anticoagulation in hemoperfusion therapy with nafamostat mesylate.
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Since its discovery in 2019, coronavirus disease 2019 (COVID-2019) spans a wide clinical spectrum from the asymptomatic stage, mild infection, to severe pneumonia. In patients with COVID-2019, factors such as advanced age, diabetes, or hypertension are associated with a significantly increased risk of severe diseases and death. Of note, the mechanisms underlying differences in the risk and symptoms of COVID-2019 among different populations are still poorly characterized. Accordingly, it is imperative to elucidate potential pathophysiological mechanisms and develop targeted therapeutic approaches for COVID-2019 infection. N6-methyladenosine (m6A) is one of the most common modifications in mammalian RNA transcripts and is widely found in messenger RNAs and some non-coding RNAs. It has been reported that m6A methylation modifications are present in viral RNA transcripts, which are of great significance for the regulation of the viral life cycle. Furthermore, m6A methylation has recently been found to be strongly associated with COVID-2019 infection. Therefore, this article reviews recent advances in studies related to the role of m6A methylation in COVID-2019 infection.
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BACKGROUND: Spontaneous pneumomediastinum (SPM) was defined by the appearance of free air in the mediastinum that was not preceded by trauma, surgery, or other medical procedures. Among the numerous manifestations of SPM, abdominal pain had seldom been described. CASE PRESENTATION: A 25-year-old man presented to the emergency department with nausea, vomiting, and abdominal pain for 7 days. The presenting clinical features and the radiological results were suggestive of psychogenic vomiting with spontaneous pneumomediastinum in a patient who suffered from abdominal pain. CONCLUSIONS: The special feature of this case was the elucidation of a rare cause of abdominal pain, which should be differentiated in patients with vomiting combined with abdominal pain. The importance of this case was that its recognition may prevent unnecessary procedures to rule out or treat other causes of abdominal pain.
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Enfisema Mediastínico , Masculino , Humanos , Adulto , Enfisema Mediastínico/diagnóstico , Enfisema Mediastínico/diagnóstico por imagem , Radiografia , Vômito/complicações , Dor Abdominal/etiologia , Serviço Hospitalar de EmergênciaRESUMO
BACKGROUND: Multidrug-resistant (MDR) bacteria-induced VAP often has high lethality. We present this systematic review and meta-analysis to assess the risk factors for MDR bacterial infection in patients with VAP. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were searched for studies regarding MDR bacterial infection in VAP patients, from Jan 1996 to Aug 2022. Study selection, data extraction, and quality assessment of included studies were conducted by two reviewers independently, and potential risk factors for MDR bacterial infection were identified. RESULTS: Meta-analysis showed that the score of the Acute Physiology and Chronic Health Evaluation II (APACHE-II) [OR = 1.009, 95% (CI 0.732, 1.287)], Simplified Acute Physiology Score II (SAPS-II) [OR = 2.805, 95%CI (0.854, 4.755)], length of hospital-stay before VAP onset (days) [OR = 2.639, 95%CI (0.387, 4.892)], in-ICU duration [OR = 3.958, 95%CI (0.894, 7.021)], Charlson index [OR = 1.000, 95%CI (0.889, 1.111)], overall hospital-stay [OR = 20.742, 95%CI (18.894, 22.591)], Medication of Quinolones [OR = 2.017, 95%CI (1.339, 3.038)], medication of carbapenems [OR = 3.527, 95%CI (2.476, 5.024)], combination of more than 2 prior antibiotics [OR = 3.181, 95%CI (2.102, 4.812)], and prior use of antibiotics [OR 2.971, 95%CI (2.001, 4.412)] were independent risk factors of MDR bacterial infection in VAP patients. Diabetes and mechanical ventilation duration before VAP onset showed no association with risk for MDR bacterial infection. CONCLUSIONS: This study has identified 10 risk factors associated with MDR bacterial infection in VAP patients. Identification of these factors would be able to facilitate the treatment and prevention of MDR bacterial infection in clinical practice.
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Infecções Bacterianas , Pneumonia Associada à Ventilação Mecânica , Humanos , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Respiração Artificial/efeitos adversos , Antibacterianos/uso terapêutico , Fatores de Risco , Unidades de Terapia Intensiva , Bactérias , Infecções Bacterianas/tratamento farmacológicoRESUMO
RATIONALE: Tuberculosis (TB) and post-transplant lymphoproliferative disorder are serious complications affecting the long-term survival of kidney transplant recipients (KTRs). Both of complications have overlapping clinical symptoms, signs, and high similar imaging presentation, which make early clinical diagnosis challenging. In this paper, we reported a rare case of post-transplant pulmonary TB combined with Burkitt lymphoma (BL) in KTR. PATIENT CONCERNS: A 20-year-old female KTR presented to our hospital with abdominal pain and multiple nodules throughout the body. DIAGNOSES: TB is diagnosed based on the lung histopathology showed fibrous connective tissue hyperplasia with number of chronic inflammatory changes, localized necrosis, granuloma formation and multinucleated giant cells were seen in the lung tissue. Moreover, lung histopathology specimen tested positive for TB gene. TB The culture for tuberculosis was positive. BL was diagnosed as metastatic after completion of liver and bone marrow biopsy. INTERVENTIONS: After an early diagnosis of TB, the patient received intensification of anti-tubercular therapy. Because the patient was diagnosed with BL, rituximab, cardioprotection, hepatoprotection and alkalinization of urine were added. OUTCOMES: After an early diagnosis of TB, the patient received anti-tubercular therapy and her clinical symptoms and imaging manifestations improved. After the diagnosis of BL was made, the patient's condition progressed rapidly, followed by multi-organ damage and died 3 months later. LESSONS: Therefore, in organ transplant patients, who present with multiple nodules and normal tumor markers, they should be alerted to the possibility of concurrent TB and post-transplant lymphoproliferative disorder, and perfect tests such as Epstein-Barr virus, ß2-microglobulin, lactate dehydrogenase, γ-interferon release test and Xpert Mycobacterium TB/rifampicin test and perform early lesion site biopsy to clarify the diagnosis with a view to improving the prognosis.
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Linfoma de Burkitt , Infecções por Vírus Epstein-Barr , Transplante de Rim , Tuberculose , Humanos , Feminino , Adulto Jovem , Adulto , Linfoma de Burkitt/complicações , Linfoma de Burkitt/diagnóstico , Transplante de Rim/efeitos adversos , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Tuberculose/diagnósticoRESUMO
Squamous Cell Carcinoma (SCC) develops in stratified epithelial tissues and demonstrates frequent alterations in transcriptional regulators. We sought to discover SCC-specific transcriptional programs and identified the transcription factor Basonuclin 1 (BNC1) as highly expressed in SCC compared to other tumor types. RNA-seq and ChIP-seq analysis identified pro-proliferative genes activated by BNC1 in SCC cells and keratinocytes. Inhibition of BNC1 in SCC cells suppressed proliferation and increased migration via FRA1. In contrast, BNC1 reduction in keratinocytes caused differentiation, which was abrogated by IRF6 knockdown, leading to increased migration. Protein interactome analysis identified PRMT1 as a co-activator of BNC1-dependent proliferative genes. Inhibition of PRMT1 resulted in a dose-dependent reduction in SCC cell proliferation without increasing migration. Importantly, therapeutic inhibition of PRMT1 in SCC xenografts significantly reduced tumor size, resembling functional effects of BNC1 knockdown. Together, we identify BNC1-PRMT1 as an SCC-lineage specific transcriptional axis that promotes cancer growth, which can be therapeutically targeted to inhibit SCC tumorigenesis.
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Diquat (DQ) has been confirmed to be toxic to humans and responsible for severe health impairment. While to date, very little is known about the toxicological mechanisms of DQ. Thus, investigations to discover the toxic targets and potential biomarkers of DQ poisoning are urgently needed. In this study, a metabolic profiling analysis was conducted to reveal the changes of metabolites of plasma and find out the potential biomarkers of DQ intoxication by GC-MS. First, multivariate statistical analysis demonstrated that acute DQ poisoning can lead to metabolomic changes in human plasma. Then, metabolomics studies showed that 31 of the identified metabolites were significantly altered by DQ. Pathway analysis indicated that three primarily metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine metabolism, and phenylalanine metabolism were affected by DQ, resulting in the perturbations of phenylalanine, tyrosine, taurine, and cysteine. Finally, the results of receiver operating characteristic analysis showed the above four metabolites could be used as reliable tools for the diagnosis and severity assessments of DQ intoxication. These data provided the theoretical basis for basic research to understand the potential mechanisms of DQ poisoning, and also identified the desirable biomarkers with great potential for clinical applications.
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Diquat , Venenos , Humanos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metabolômica/métodos , Biomarcadores/metabolismo , Fenilalanina , Tirosina , TaurinaRESUMO
Vascularized composite allografts (VCAs) of faces and extremities are subject to chronic rejection that is incompletely understood. Here we report on immunoproteomic evaluation of a full facial VCA removed 88 months after transplantation due to chronic rejection. CD8-positive T cells of donor (graft) origin infiltrate deep intragraft arteries in apposition to degenerating endothelium of chimeric recipient origin in association with arteriosclerotic alterations. Digital spatial proteomic profiling highlighted proteins expressed by activated cytotoxic T cells and macrophages as well as pathway components involved in atherogenic responses, including Indoleamine 2,3-Dioxygenase 1 (IDO1) and Stimulator of Interferon Response CGAMP Interactor (STING). Chronic facial VCA rejection thus involves T cell/macrophage-mediated accelerated arteriosclerosis not normally represented in punch biopsies and potentially driven by persistent graft-resident effector T cells and recipient target endothelium that chimerically repopulates graft arteries.
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Aloenxertos Compostos , Transplante de Face , Alotransplante de Tecidos Compostos Vascularizados , Sobrevivência de Enxerto , Proteômica , Aloenxertos Compostos/transplante , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologiaRESUMO
Central airway obstruction caused by neck and chest tumors is a very dangerous oncological emergency with high mortality. Unfortunately, there is few literature to discuss an effective way for this life-threating condition. Providing effective airway managements, adequate ventilation and emergency surgical interventions are very important. However, traditional airway managements and respiratory support has only limited effect. In our center, using extracorporeal membrane oxygenation (ECMO) as a novel approach to manage patient with central airway obstruction caused by neck and chest tumors has been adopted. We aimed to show the feasibility: using early ECMO to manage difficult airway, provide oxygenation and support surgical procedure for patients with critical airway stenosis caused by neck and chest tumors. We designed a single-center, small sample size retrospective study based on real-world. We identified 3 patients with central airway obstruction caused by neck and chest tumors. ECMO was used to ensure adequate ventilation to emergency surgery. Control group cannot be established. Because traditional manner very likely led to death of such patients. Details of clinical characteristics, ECMO, surgery and survival outcomes were recorded. Acute dyspnea and cyanosis were the most frequent symptoms. All patients (3/3) showed descending arterial partial pressure of oxygen (PaO2). Computed tomography (CT) revealed severe central airway obstruction caused by neck and chest tumors in all cases (3/3). All patients (3/3) had definite difficult airway. All cases (3/3) received ECMO support and emergency surgical procedure. Venovenous ECMO was the common mode for all cases. 3 patients weaned off ECMO successfully without any ECMO-related complications. Mean duration of ECMO was 3 h (range: 1.5-4.5 h). Under ECMO support, difficult airway management and emergency surgical procedure were finished successfully for all cases (3/3). The mean ICU stay was 3.3 days (range: 1-7 days), and the mean general ward stay was 3.3 days (range: 2-4 days). Pathology demonstrated the tumor dignity for 3 patients including 2 malignant cases and 1 benign case. All patients (3/3) were discharged from hospital successfully. We showed that early ECMO initiation was a safe and feasible approach to manage difficult airway for patients with severe central airway obstruction caused by neck and chest tumors. Meanwhile, early ECMO initiation could ensure security for airway surgical procedure.
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Obstrução das Vias Respiratórias , Oxigenação por Membrana Extracorpórea , Humanos , Estudos Retrospectivos , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/cirurgia , Manuseio das Vias Aéreas , Espinhas DendríticasRESUMO
Nowadays, the diagnosis and treatment of COPD are often based on the results of lung function tests. Certain individuals, however, are not candidates for lung function testing due to pulmonary bullae, cardiac failure, low lung function, and other factors. Therefore, we evaluated whether serum tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein ß (14-3-3ß) could be a biomarker for the diagnosis of stable COPD patients. The expression of serum 14-3-3ß protein was evaluated by an enzyme-linked immunosorbent assay. The association between its concentrations and clinical parameters of stable COPD patients were analyzed by correlation analysis and ROC curve. The results before propensity score matching (PSM) showed that serum 14-3-3ß protein concentrations (ng/ml) in stable COPD patients were significantly higher than in healthy controls (P < 0.001). Furthermore, serum 14-3-3ß protein concentrations were higher in GOLD 3&4 COPD patients compared with healthy participants, GOLD 1 and GOLD 2 COPD patients (P < 0.05), which shows that the concentration of 14-3-3ß protein correlates with disease severity in stable COPD patients. After 1:1 PSM, there was also a statistically significant rise in 14-3-3 protein levels in stable COPD patients compared to healthy controls (P < 0.01). Serum 14-3-3ß protein levels were positively correlated with blood neutrophil levels (P < 0.05), and negatively related to lung function parameters in stable COPD patients (P < 0.01). When the cutoff value was set at 29.53 ng/ml, the ROC curve yielded a sensitivity of 84.9% and a specificity of 68.3% for diagnosing stable COPD. The 14-3-3ß protein may be a potential serum biomarker for the diagnosis of stable COPD patients, which is associated with disease severity, systemic inflammation, and small airway obstruction.
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Proteínas 14-3-3 , Doença Pulmonar Obstrutiva Crônica , Humanos , Proteínas 14-3-3/metabolismo , Relevância Clínica , Estudos de Casos e Controles , BiomarcadoresRESUMO
BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is one of the most common opportunistic infections in immunocompromised patients. However, the accurate prediction of the development of PJP in non-HIV immunocompromised patients is still unclear. METHODS: Non-HIV immunocompromised patients confirmed diagnosis of PJP by the clinical symptoms, chest computed tomography and etiological results of metagenomic next-generation sequencing (mNGS) were enrolled as observation group. Another group of matched non-HIV immunocompromised patients with non-PJP pneumonia were enrolled to control group. The risk factors for the development of PJP and the co-pathogens in the bronchoalveolar lavage fluid (BALF) detected by mNGS were analyzed. RESULTS: A total of 67 (33 PJP, 34 non-PJP) participants were enrolled from Fujian Provincial Hospital. The ages, males and underlying illnesses were not significantly different between the two groups. Compared to non-PJP patients, PJP patients were more tends to have the symptoms of fever and dyspnea. The LYM and ALB were significantly lower in PJP patients than in non-PJP patients. Conversely, LDH and serum BDG in PJP patients were significantly higher than in non-PJP controls. For immunological indicators, the levels of immunoglobulin A, G, M and complement C3, C4, the numbers of T, B, and NK cells, had no statistical difference between these two groups. Logistic multivariate analysis showed that concomitant use of corticosteroids and immunosuppressant (OR 14.146, P = 0.004) and the lymphocyte counts < 0.7 × 109/L (OR 6.882, P = 0.011) were risk factors for the development of PJP in non-HIV immunocompromised patients. 81.82% (27/33) and 64.71% (22/34) mixed infections were identified by mNGS in the PJP group and non-PJP group separately. CMV, EBV and Candida were the leading co-pathogens in PJP patients. The percentages of CMV and EBV identified by mNGS in PJP group were significantly higher than those in the control group(p < 0.005). CONCLUSIONS: Clinicians should pay close attention to the development of PJP in non-HIV immunocompromised patients who possess the risk factors of concomitant use of corticosteroids and immunosuppressant and the lymphocyte counts < 0.7 × 109/L. Prophylaxis for PJP cannot rely solely on CD4+ T counts in non-HIV immunocompromised patients. Whether CMV infection increases the risk of PJP remains to be further investigated.
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Infecções por Citomegalovirus , Pneumocystis carinii , Pneumonia por Pneumocystis , Masculino , Humanos , Pneumonia por Pneumocystis/diagnóstico , Fatores de Risco , Corticosteroides/uso terapêutico , Imunossupressores/uso terapêutico , Hospedeiro Imunocomprometido , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
RATIONALE: Pneumocystis pneumonia (PCP) is an opportunistic infection of patients with congenital or acquired immunodeficiency. It is most frequently occurred in human immunodeficiency virus (HIV) infection, organ transplantation, leukemia, and immunosuppressive therapy. Here we describe the rare case of PCP in a non-HIV-infected diabetic patient and find possible reasons for the association through a literature review. PATIENT CONCERNS: A 65-years-old male was admitted to our hospital due to a 10-year history of abnormal blood glucose levels and edema of both lower extremities for half a month. However, the patient developed a high fever and progressive dyspnea during hospitalization. DIAGNOSES: The patient had elevated blood sugar levels, a low white blood cell count within normal limits, and severe lymphopenia. His blood G test and lactate dehydrogenase levels increased significantly. Multiple sputa and bronchoalveolar lavage fluid specimens for Pneumocystis jirovecii (PJ) nucleic acid detection were positive. Chest computed tomography scan demonstrated hazy patchy shadows in the lungs suspected to be pulmonary infections. No tumor, transplantation, or an autoimmune disease was found in the examinations. The patient was diagnosed with PCP finally. INTERVENTIONS: A combination of oral trimethoprim-sulfamethoxazole and intravenous caspofungin was administered immediately against PJ. The patient was also treated with noninvasive ventilator-assisted ventilation, subcutaneous insulin, and hemodialysis therapy. OUTCOMES: The patient was discharged home finally with a fair general condition and was followed up without respiratory symptoms. LESSONS: The compromised immunity in HIV-negative patients with diabetes may be related to lymphocyte decrease and dysfunction, which may cause diabetic patients prone to PJ. Although PCP is rare in diabetes, it should be paid attention to the high rate of misdiagnosis and missed diagnosis.
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Diabetes Mellitus , Infecções por HIV , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Masculino , Idoso , Pneumonia por Pneumocystis/complicações , Combinação Trimetoprima e Sulfametoxazol , Infecções por HIV/complicaçõesRESUMO
Background: Metagenomic Next Generation Sequencing (mNGS) has the potential to detect pathogens rapidly. We aimed to assess the diagnostic performance of mNGS in hospitalized patients with suspected sepsis and evaluate its role in guiding antimicrobial therapy. Methods: A multicenter, prospective cohort study was performed. We enrolled patients with suspected sepsis, collected clinical characteristics and blood samples, and recorded the 30-day survival. Diagnostic efficacy of mNGS test and blood culture was compared, and the clinical impact of mNGS on antibiotic regimen modification was analyzed. Results: A total of 277 patients were enrolled, and 162 were diagnosed with sepsis. The mortality was 44.8% (121/270). The mNGS test exhibited shorter turn-out time (27.0 (26.0, 29.0) vs. 96.0 (72.0, 140.3) hours, p < 0.001) and higher sensitivity (90.5% vs. 36.0%, p < 0.001) compared with blood culture, especially for fungal infections. The mNGS test showed better performance for patients with mild symptoms, prior antibiotic use, and early stage of infection than blood culture, and was capable of guiding antibiotic regimen modification and improving prognosis. Higher reads of pathogens detected by mNGS were related to 30-day mortality (p = 0.002). Conclusions: Blood mNGS testing might be helpful for early etiological diagnosis of patients with suspected sepsis, guiding the antibiotic regimen modification and improving prognosis.