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While the impacts of black (Rattus rattus) and brown (Rattus norvegicus) rats on human society are well documented-including the spread of disease, broad-scale environmental destruction, and billions spent annually on animal control-little is known about their ecology and behavior in urban areas due to the challenges of studying animals in city environments. We use isotopic and ZooMS analysis of archaeological (1550s-1900 CE) rat remains from eastern North America to provide a large-scale framework for species arrival, interspecific competition, and dietary ecology. Brown rats arrived earlier than expected and rapidly outcompeted black rats in coastal urban areas. This replacement happened despite evidence that the two species occupy different trophic positions. Findings include the earliest molecularly confirmed brown rat in the Americas and show a deep ecological structure to how rats exploit human-structured areas, with implications for understanding urban zoonosis, rat management, and ecosystem planning as well as broader themes of rat dispersal, phylogeny, evolutionary ecology, and climate impacts.
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Evolución Biológica , Ecosistema , Animales , Ratas , América del Norte , Filogenia , Estudios RetrospectivosRESUMEN
BACKGROUND & AIMS: In ACLF patients, an adequate risk stratification is essential, especially for liver transplant allocation, since ACLF is associated with high short-term mortality. The CLIF-C ACLF score is the best prognostic model to predict outcome in ACLF patients. While lung failure is generally regarded as signum malum in ICU care, this study aims to evaluate and quantify the role of pulmonary impairment on outcome in ACLF patients. METHODS: In this retrospective study, 498 patients with liver cirrhosis and admission to IMC/ICU were included. ACLF was defined according to EASL-CLIF criteria. Pulmonary impairment was classified into three groups: unimpaired ventilation, need for mechanical ventilation and defined pulmonary failure. These factors were analysed in different cohorts, including a propensity score-matched ACLF cohort. RESULTS: Mechanical ventilation and pulmonary failure were identified as independent risk factors for increased short-term mortality. In matched ACLF patients, the presence of pulmonary failure showed the highest 28-day mortality (83.7%), whereas mortality rates in ACLF with mechanical ventilation (67.3%) and ACLF without pulmonary impairment (38.8%) were considerably lower (p < .001). Especially in patients with pulmonary impairment, the CLIF-C ACLF score showed poor predictive accuracy. Adjusting the CLIF-C ACLF score for the grade of pulmonary impairment improved the prediction significantly. CONCLUSIONS: This study highlights that not only pulmonary failure but also mechanical ventilation is associated with worse prognosis in ACLF patients. The grade of pulmonary impairment should be considered in the risk assessment in ACLF patients. The new score may be useful in the selection of patients for liver transplantation.
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Insuficiencia Hepática Crónica Agudizada , Humanos , Estudios Retrospectivos , Enfermedad Crítica , Cirrosis Hepática/complicaciones , Pronóstico , PulmónRESUMEN
Fatal dog poisoning after uptake of neurotoxic cyanobacteria associated with aquatic macrophytes in Tegeler See (Berlin, Germany) raised concerns about critical exposure of humans, especially children, to cyanotoxins produced by macrophyte associated cyanobacteria during recreational activity. From 2017 to 2021 a total of 398 samples of macrophytes washed ashore at bathing sites located at 19 Berlin lakes were analysed for anatoxins, microcystins, and cylindrospermopsins, as were 463 water samples taken in direct proximity to macrophyte accumulations. Cyanotoxins were detected in 66 % of macrophyte samples and 50 % of water samples, with anatoxins being the most frequently detected toxin group in macrophyte samples (58 %) and cylindrospermopsins in water samples (41 %). Microcoleus sp. associated with the water moss Fontinalis antipyretica was identified as anatoxin producing cyanobacterium in isolated strains as well as in field samples from Tegeler See. Anatoxin contents in macrophyte samples rarely exceeded 1 µg/g macrophyte fresh weight and peaked at 9. 2 µg/g f.w. Based on established toxicological points of departure, a critical anatoxin content of macrophyte samples of 3 µg/g f.w. is proposed. Five samples, all taken in Tegeler See and all associated with the water moss Fontinalis antipyretica, exceeded this value. Contents and concentrations of microcystins and cylindrospermopsins did not reach critical levels. The potential exposure risks to anatoxins for children and dogs are assessed and recommendations are given.
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Toxinas Bacterianas , Cianobacterias , Niño , Humanos , Perros , Animales , Microcistinas/análisis , Toxinas de Cianobacterias , Berlin , Toxinas Bacterianas/análisis , Medición de Riesgo , Agua/análisisRESUMEN
Hellweger et al. (Reports, 27 May 2022, pp. 1001) predict that phosphorus limitation will increase concentrations of cyanobacterial toxins in lakes. However, several molecular, physiological, and ecological mechanisms assumed in their models are poorly supported or contradicted by other studies. We conclude that their take-home message that phosphorus load reduction will make Lake Erie more toxic is seriously flawed.
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Toxinas Bacterianas , Lagos , Microcystis , Fósforo , Monitoreo del Ambiente , Lagos/química , Lagos/microbiología , Fósforo/deficiencia , Microcystis/metabolismo , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/toxicidadRESUMEN
OBJECTIVES: Stenosis of the biliary anastomosis predisposes liver graft recipients to bacterial cholangitis. Antibiotic therapy (AT) is performed according to individual clinical judgment, but duration of AT remains unclear. METHODS: All liver graft recipients with acute cholangitis according to the Tokyo criteria grade 1 and 2 after endoscopic retrograde cholangiography (ERC) were included. Outcome of patients treated with short AT (<7 days) was compared to long AT (>6 days). Recurrent cholangitis (RC) within 28 days was the primary end point. RESULTS: In total, 30 patients were included with a median of 313 (range 34-9849) days after liver transplantation until first proven cholangitis. Among 62 cases in total, 51/62 (82%) were graded as Tokyo-1 and 11/62 (18%) as Tokyo-2. Overall median duration of AT was 6 days (1-14) with 36 cases (58%) receiving short AT and 26 (42%) receiving long AT. RC was observed in 10 (16%) cases, without significant difference in occurrence of RC in short versus long AT cases. CRP and bilirubin were significantly higher in patients with long AT, while low serum albumin and low platelets were associated with risk of RC. CONCLUSION: A shorter antibiotic course than 7 days shows good results in selected, ERC-treated patients for post-transplantation biliary strictures.
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Colangitis , Colestasis , Trasplante de Hígado , Antibacterianos/uso terapéutico , Colangitis/tratamiento farmacológico , Colestasis/etiología , Colestasis/cirugía , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Complicaciones Posoperatorias/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND: The transition from compensated to decompensated liver cirrhosis is a hallmark of disease progression, however, reliable predictors to assess the risk of decompensation in individual patients from routine diagnostics are lacking. Here, we characterize serum levels of cell death-associated markers and routine biochemistry from patients with chronic liver disease with and without decompensation. METHODS: A post-hoc analysis was based on prospectively collected clinical data from 160 patients with chronic liver disease, stably compensated or decompensated at baseline or during follow-up, over a median period of 721 days. Serum levels of damage-associated molecular patterns (DAMPs) and routine biochemistry are quantified at baseline (for all patients) and during follow-up (for patients with acute decompensation). The panel of DAMPs assessed in this study comprises high-mobility group-box protein 1 (HMGB1), cytochrome C (cyt C), soluble Fas-ligand (sFasL), interleukin 6 (IL-6), soluble cytokeratin-18 (CK18-M65) and its caspase-cleaved fragment CK18-M30. RESULTS: In this cohort study, 80 patients (50%) were diagnosed with alcoholic liver cirrhosis, 60 patients (37.5%) with hepatitis C virus- and 20 patients (13.5%) with hepatitis B virus-related liver cirrhosis. At baseline, 17 patients (10.6%) showed decompensated liver disease and another 28 patients (17.5%) developed acute decompensation during follow-up (within 24 months). One hundred fifteen patients showed stable liver disease (71.9%). We found DAMPs significantly elevated in patients with decompensated liver disease versus compensated liver disease. Patients with acute decompensation during follow-up showed higher baseline levels of IL-6, sFasL, CK18-M65 and-M30 (P<0.01) compared to patients with stably compensated liver disease. In multivariate analyses, we found an independent association of baseline serum levels of sFasL (P = 0.02; OR = 2.67) and gamma-glutamyl transferase (GGT) (P<0.001; OR = 2.1) with acute decompensation. Accuracy of the marker combination for predicting acute decompensation was high (AUC = 0.79). Elevated aminotransferase levels did not correlate with decompensated liver disease and acute decompensation. CONCLUSIONS: DAMPs are elevated in patients with decompensated liver disease and patients developing acute decompensation. The prognostic value of a marker combination with soluble Fas-ligand and GGT in patients with liver cirrhosis should be further evaluated.
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Alarminas/sangre , Biomarcadores/sangre , Cirrosis Hepática/patología , Índice de Severidad de la Enfermedad , Anciano , Estudios de Casos y Controles , Muerte Celular , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Queratina-18/sangre , Cirrosis Hepática/sangre , Masculino , Persona de Mediana Edad , Pronóstico , Estudios ProspectivosRESUMEN
Background: Carbapenem-resistant Gram-negative bacteria (CRGN) cause life-threatening infections due to limited antimicrobial treatment options. The occurrence of CRGN is often linked to hospitalization and antimicrobial treatment but remains incompletely understood. CRGN are common in patients with severe illness (e.g., liver transplantation patients). Using whole-genome sequencing (WGS), we aimed to elucidate the evolution of CRGN in this vulnerable cohort and to reconstruct potential transmission routes. Methods: From 351 patients evaluated for liver transplantation, 18 CRGN isolates (from 17 patients) were analyzed. Using WGS and bioinformatic analysis, genotypes and phylogenetic relationships were explored. Potential epidemiological links were assessed by analysis of patient charts. Results: Carbapenem-resistant (CR) Klebsiella pneumoniae (n=9) and CR Pseudomonas aeruginosa (n=7) were the predominating pathogens. In silico analysis revealed that 14/18 CRGN did not harbor carbapenemase-coding genes, whereas in 4/18 CRGN, carbapenemases (VIM-1, VIM-2, OXA-232, and OXA-72) were detected. Among all isolates, there was no evidence of plasmid transfer-mediated carbapenem resistance. A close phylogenetic relatedness was found for three K. pneumoniae isolates. Although no epidemiological context was comprehensible for the CRGN isolates, evidence was found that the isolates resulted of a transmission of a carbapenem-susceptible ancestor before individual radiation into CRGN. Conclusion: The integrative epidemiological study reveals a high diversity of CRGN in liver cirrhosis patients. Mutation of carbapenem-susceptible ancestors appears to be the dominant way of CR acquisition rather than in-hospital transmission of CRGN or carbapenemase-encoding genetic elements. This study underlines the need to avoid transmission of carbapenem-susceptible ancestors in vulnerable patient cohorts.
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Long-term effects on cirrhosis and portal hypertension of direct antiviral agent (DAA)-based eradication of hepatitis C virus (HCV) are still under debate. We analysed dynamics of liver and spleen elastography to assess potential regression of cirrhosis and portal hypertension 3 years post-treatment. Fifty-four patients with HCV-associated cirrhosis and DAA-induced SVR were included. Liver and spleen stiffness were measured at baseline (BL), end of treatment (EOT), 24 weeks after EOT (FU24) and 1, 2 and 3 (FU144) years post-treatment by transient liver elastography (L-TE) and point shear wave elastography (pSWE) using acoustic radiation force impulse (ARFI) of the liver (L-ARFI) and spleen (S-ARFI). Biochemical, virological and clinical data were also obtained. Liver stiffness assessed by L-TE decreased between BL [median (range), 32.5(9.1-75) kPa] and EOT [21.3(6.7-73.5) kPa; p < .0001] and EOT and FU144 [16(4.1-75) kPa; p = .006]. L-ARFI values improved between EOT [2.5(1.2-4.1) m/s] and FU144 [1.7(0.9-4.1) m/s; p = .001], while spleen stiffness remained unchanged. Overall, L-TE improved in 38 of 54 (70.4%) patients at EOT and 29 of 38 (76.3%) declined further until FU144, whereas L-ARFI values decreased in 30/54 (55.6%) patients at EOT and continued to decrease in 28/30 (93.3%) patients at FU144. Low bilirubin and high albumin levels at BL were associated with improved L-ARFI values (p = .048) at EOT or regression of cirrhosis (<12.5 kPa) by L-TE at FU144 (p = .005), respectively. Liver stiffness, but not spleen stiffness, continued to decline in a considerable proportion of patients with advanced liver disease after HCV eradication.
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Diagnóstico por Imagen de Elasticidad , Hepatitis C Crónica , Hepatitis C , Hipertensión Portal , Antivirales/uso terapéutico , Estudios de Seguimiento , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/patología , Humanos , Hipertensión Portal/tratamiento farmacológico , Hipertensión Portal/patología , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/tratamiento farmacológico , Estudios Longitudinales , Estudios Prospectivos , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
SUMMARY: Wilson's disease (WD) is a rare disorder of copper metabolism usually presenting with variable liver damage and neuropsychiatric symptoms. Here we report a 39-year-old Taiwanese female with late manifestation of WD presenting with gonadotroph, thyreotroph and corticotroph hypopituitarism. Molecular genetic testing revealed compound heterozygosity for two mutations in exons 12 and 14 (c.2828G>A and c.3140A>T). Copper-chelating therapy with D-penicillamine and zinc was initiated along with supplementation of hydrocortisone and L-thyroxine. Hypopituitarism resolved when urinary copper excretion returned to normal levels under copper chelation. This case should raise awareness of pituitary function in WD patients. LEARNING POINTS: Hypopituitarism can complicate Wilson's disease (WD) and endocrinologists should be aware of it when caring for hypopituitary patients. Hepatologists should consider endocrinologic testing for hypopituitarism when WD patients present with symptoms of adrenal insufficiency, thyroid or gonadal dysfunction. Copper-chelating treatment is mandatory and may lead to the recovery of pituitary function in such patients.
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OBJECTIVES: Rising prevalence of multidrug-resistant organisms (MDRO) is a major health problem in patients with liver cirrhosis. The impact of MDRO colonization in liver transplantation (LT) candidates and recipients on mortality has not been determined in detail. METHODS: Patients consecutively evaluated and listed for LT in a tertiary German liver transplant center from 2008 to 2018 underwent screening for MDRO colonization including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant gram-negative bacteria (MDRGN), and vancomycin-resistant enterococci (VRE). MDRO colonization and infection status were obtained at LT evaluation, planned and unplanned hospitalization, three months upon graft allocation, or at last follow-up on the waiting list. RESULTS: In total, 351 patients were listed for LT, of whom 164 (47%) underwent LT after a median of 249 (range 0-1662) days. Incidence of MDRO colonization increased during waiting time for LT, and MRDO colonization was associated with increased mortality on the waiting list (HR = 2.57, p<0.0001. One patients was colonized with a carbapenem-resistant strain at listing, 9 patients acquired carbapenem-resistant gram-negative bacteria (CRGN) on the waiting list, and 4 more after LT. In total, 10 of these 14 patients died. CONCLUSIONS: Colonization with MDRO is associated with increased mortality on the waiting list, but not in short-term follow-up after LT. Moreover, colonization with CRGN seems associated with high mortality in liver transplant candidates and recipients.
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Carbapenémicos , Farmacorresistencia Bacteriana Múltiple , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas , Cirrosis Hepática , Trasplante de Hígado , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Enterococos Resistentes a la Vancomicina , Resistencia betalactámica , Adulto , Anciano , Femenino , Estudios de Seguimiento , Infecciones por Bacterias Gramnegativas/mortalidad , Humanos , Cirrosis Hepática/mortalidad , Cirrosis Hepática/cirugía , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Estudios Retrospectivos , Infecciones Estafilocócicas/etiología , Infecciones Estafilocócicas/mortalidad , Centros de Atención TerciariaRESUMEN
Improving long-term patient and graft survival after liver transplantation (LT) remains a major challenge. Compared to the early phase after LT, long-term morbidity and mortality of the recipients not only depends on complications immediately related to the graft function, infections, or rejection, but also on medical factors such as de novo malignancies, metabolic disorders (e.g., new-onset diabetes, osteoporosis), psychiatric conditions (e.g., anxiety, depression), renal failure, and cardiovascular diseases. While a comprehensive post-transplant care at the LT center and the connected regional networks may improve outcome, there is currently no generally accepted standard to the post-transplant management of LT recipients in Germany. We therefore described the structure and standards of post-LT care by conducting a survey at 12 German LT centers including transplant hepatologists and surgeons. Aftercare structures and form of cost reimbursement considerably varied between LT centers across Germany. Further discussions and studies are required to define optimal structure and content of post-LT care systems, aiming at improving the long-term outcomes of LT recipients.
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BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a leading indication for liver transplantation (LT) worldwide. Early identification of patients at risk for HCC recurrence is of paramount importance since early treatment of recurrent HCC after LT may be associated with increased survival. We evaluated incidence of and predictors for HCC recurrence, with a focus on the course of AFP levels. METHODS: We performed a retrospective, single-center study of 99 HCC patients who underwent LT between January 28th, 1997 and May 11th, 2016. A multi-stage proportional hazards model with three stages was used to evaluate potential predictive markers, both by univariate and multivariable analysis, for influences on 1) recurrence after transplantation, 2) mortality without HCC recurrence, and 3) mortality after recurrence. RESULTS: 19/99 HCC patients showed recurrence after LT. Waiting time was not associated with overall HCC recurrence (HR = 1, p = 0.979). Similarly, waiting time did not affect mortality in LT recipients both with (HR = 0.97, p = 0.282) or without (HR = 0.99, p = 0.685) HCC recurrence. Log10-transformed AFP values at the time of LT (HR 1.75, p = 0.023) as well as after LT (HR 2.07, p = 0.037) were significantly associated with recurrence. Median survival in patients with a ratio (AFP at recurrence divided by AFP 3 months before recurrence) of 0.5 was greater than 70 months, as compared to a median of only 8 months in patients with a ratio of 5. CONCLUSION: A rise in AFP levels rather than an absolute threshold could help to identify patients at short-term risk for HCC recurrence post LT, which may allow intensification of the surveillance strategy on an individualized basis.
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Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , alfa-Fetoproteínas/análisis , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Human cytomegalovirus (CMV) remains a major cause of mortality and morbidity in human liver transplant recipients. Anti-CMV therapeutics can be used to prevent or treat CMV in liver transplant recipients, but their toxicity needs to be balanced against the benefits. The choice of prevention strategy (prophylaxis or preemptive treatment) depends on the donor/recipient sero-status but may vary between institutions. We conducted a series of consultations and roundtable discussions with German liver transplant center representatives. Based on 20 out of 22 centers, we herein summarize the current approaches to CMV prevention and treatment in the context of liver transplantation in Germany. In 90% of centers, transient prophylaxis with ganciclovir or valganciclovir was standard of care in high-risk (donor CMV positive, recipient CMV naive) settings, while preemptive therapy (based on CMV viremia detected during (bi) weekly PCR testing for circulating CMV-DNA) was preferred in moderate- and low-risk settings. Duration of prophylaxis or intense surveillance was 3-6 months. In the case of CMV infection, immunosuppression was adapted. In most centers, antiviral treatment was initiated based on PCR results (median threshold value of 1000 copies/mL) with or without symptoms. Therefore, German transplant centers report similar approaches to the prevention and management of CMV infection in liver transplantation.
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The effects of recipient cell growth temperature, vector choice, and DNA methylation on transformation efficiency were explored for Lactiplantibacillus plantarum strain B38 and Apilactobacillus kunkeei strains YH15 and 3L. All three parameters significantly affected transformation efficiency. L. plantarum B38 and A. kunkeei YH15 transformed at higher efficiencies with the pTW8 vector than with the pTRKH2 vector; conversely, A. kunkeei 3L transformed at higher efficiency with pTRKH2. Mean transformation efficiencies as high as 7.8â¯×â¯105 colony forming units (CFU) µg-1 were obtained with pTW8 for B38, as high as 1.2â¯×â¯105â¯CFU⯵g-1 with pTW8 for YH15, and as high as 3.4â¯×â¯106â¯CFU⯵g-1 with pTRKH2 for 3L. With respect to methylation, B38 and YH15 transformed at higher efficiencies with DNA that lacked dam methylation, while 3L transformed at higher efficiency with DNA that was dam methylated. Methylation at Escherichia coli dcm sites did not affect the ability of pTRKH2 or pTW8 to transform these strains. Recipient cell growth at 21⯰C rather than at 37⯰C significantly increased transformation efficiencies when using each strain's preferred vector and methylation state; pTW8 without dam methylation for B38 and YH15 and pTRKH2 with dam methylation for 3L.
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Lactobacillus plantarum/genética , Lactobacillus/genética , Transformación Bacteriana , Metilación de ADN , ADN Bacteriano , Vectores Genéticos , Plásmidos , Replicón , TemperaturaRESUMEN
BACKGROUND: Acute liver failure (ALF) is a life-threatening event associated with high mortality. Currently, only estimates are available for its incidence. The aim of the study was to assess the incidence of ALF in Germany, using the accounting data of the largest statutory health insurance company, which represents 26.5 million people. METHODS: The analysis included patients insured from 1 January 2014 to 31 December 2018. Coding with the International Statistical Classification of Diseases and Related Health Problems and the German operation and procedure codes were used to identify the patients, whose age, sex, liver transplantations (LT), and fatal outcomes were then recorded and extrapolated to the total population. As a validity check, the extrapolated LT results were compared with the LT that were actually performed. RESULTS: The calculated incidence of ALF was 1.13/100 000 person-years, representing 4652 cases. Women were more often affected (52% versus 48%, p < 0.001). The overall rate of mortality within 3 months was 47%. A total of 203 LT were recorded in 176 patients. Men received 41% of the LT, women 59% (p < 0.137). The 1-year overall mortality rate after LT was 20%. The 203 calculated transplantations corresponded to 228 actually performed transplantations. CONCLUSION: The incidence of ALF was higher than previously estimated for Germany, with only a very low rate of LT despite high mortality. When extrapolating ny, it must be borne in mind that those insured by the company concerned do not represent a valid sample.
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Fallo Hepático Agudo/epidemiología , Femenino , Alemania/epidemiología , Humanos , Fallo Hepático Agudo/mortalidad , Fallo Hepático Agudo/terapia , Trasplante de Hígado/estadística & datos numéricos , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: The efficacy of antibiotic prophylaxis to prevent spontaneous bacterial peritonitis (SBP) in patients colonized with multidrug-resistant organisms (MDROs) is unknown. We evaluated the effectiveness of fluoroquinolone-based SBP prophylaxis in an era and area of frequent antibiotic resistance. METHODS: This is a prospective observational study in patients with liver cirrhosis and an indication for fluoroquinolone-based prophylaxis of SBP. Patients were recruited and followed in a large German tertiary reference center with comprehensive microbiological and clinical monitoring performed at baseline and after 30, 60, 90, and 180 days of prophylaxis. RESULTS: Overall, 77 patients received antibiotic prophylaxis for an average of 93 days. Baseline prevalence of colonization with MDROs was high (N = 39, 50.6%). At least one de novo MDRO was detected in 27 patients (35.1%) during antibiotic prophylaxis; 33 patients (42.9%) developed secondary infections, including 14 cases (17.9%) of infections with MDROs, and 13 cases (16.9%) of de novo/recurrent SBP. Thirty patients (39.0%) died during follow-up. Significantly higher risks of SBP development during antibiotic prophylaxis were observed for patients with versus without any apparent MDROs (P = .009), vancomycin-resistant enterococci (P = .008), multidrug-resistant gram-negative bacteria (P = .016), or quinolone-resistant gram-negative bacteria (QR-GNB) (P = .015). In competing risk analysis, QR-GNB were independently associated with prophylaxis failure (hazard ratio, 3.39; P = .045) and infections with QR-GNB were independently associated with death before SBP (subdistribution hazard risk, 6.47; P = .034). CONCLUSIONS: Antibiotic prophylaxis of SBP appears to be less efficient in patients with known MDROs. Regular MDRO screening seems to be useful to tailor treatment of secondary infections and re-evaluate antibiotic prophylaxis in case of selection of quinolone resistance.
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Infecciones Bacterianas , Peritonitis , Quinolonas , Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/prevención & control , Humanos , Cirrosis Hepática/tratamiento farmacológico , Peritonitis/tratamiento farmacológico , Peritonitis/prevención & controlRESUMEN
The two main pillars of clinical microbiological diagnostics are the identification of potentially pathogenic microorganisms from patient samples and the testing for antibiotic susceptibility (AST) to allow efficient treatment with active antimicrobial agents. While routine microbial species identification is increasingly performed with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), routine AST still largely relies on conventional and molecular techniques such as broth microdilution or disk and gradient diffusion tests, PCR and automated variants thereof. However, shortly after the introduction of MALDI-TOF MS based routine identification, first attempts to perform AST on the same instruments were reported. Today, a number of different approaches to perform AST with MALDI-TOF MS and other MS techniques have been proposed, some restricted to particular microbial taxa and resistance mechanisms while others being more generic. Further, while some of the methods are in a stage of proof of principles, others are already commercialized. In this review we discuss the different principal approaches of mass spectrometry based AST and evaluate the advantages and disadvantages compared to conventional and molecular techniques. At present, the possibility that MS will soon become a routine tool for AST seems unlikely - still, the same was true for routine microbial identification a mere 15 years ago.
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Introduction: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has entered clinical diagnostics and is today a generally accepted and integral part of the workflow for microbial identification. MALDI-TOF MS identification systems received approval from national and international institutions, such as the USA-FDA, and are continuously improved and adopted to other fields like veterinary and industrial microbiology. The question is whether MALDI-TOF MS also has the potential to replace other conventional and molecular techniques operated in routine diagnostic laboratories. Areas covered: We give an overview of new advancements of mass spectral analysis in the context of microbial diagnostics. In particular, the expansion of databases to increase the range of readily identifiable bacteria and fungi, the refined discrimination of species complexes, subspecies, and types, the testing for antibiotic resistance or susceptibility, progress in sample preparation including automation, and applications of other mass spectrometry techniques are discussed. Expert opinion: Although many new approaches of MALDI-TOF MS are still in the stage of proof of principle, it is expectable that MALDI-TOF MS will expand its role in the clinical microbiology laboratory of the future. New databases, instruments and analytical software modules will continue to be developed to further improve diagnostic efficacy.
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Técnicas Microbiológicas/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Animales , Bases de Datos Factuales , HumanosRESUMEN
OBJECTIVES: In Lambert and Welker (2017) we explored the association between subsistence economy and postcranial fracture prevalence, finding that low-intensity agriculturalists exhibited significantly lower fracture rates than foragers or high-intensity agriculturalists. Here, we explore the impacts of sampling strategy on fracture rates in a sample of high-intensity agriculturalists from the Moche Valley, Peru, and further test the hypothesis that postcranial fracture risks are higher for intensive agriculture. MATERIALS AND METHODS: The long bones and clavicles of 102 individuals from an Early Intermediate Period cemetery (400 B.C.-A.D. 200) at Cerro Oreja were examined for healed fractures. Sample composition was manipulated in six ways to investigate the effects of age and element completeness on estimates of fracture prevalence. Fracture rates at Cerro Oreja were then compared to those for other high-intensity agriculturalists. RESULTS: Both skeletal element completeness and age composition were found to influence fracture rate estimates, reflecting the greater likelihood of identifying healed fractures on better-preserved bones and the accrual of injuries with age. The fracture rate of 3.4% at Cerro Oreja was the median value among seven high-intensity agriculturalist samples. The fracture distribution at Cerro Oreja was most similar to that observed at Kulubnarti, Sudan (Kilgore et al., 1997). DISCUSSION: Skeletal element completeness and age composition can impact fracture rates estimated for skeletal samples and should be considered when conducting comparative analyses. All rates calculated for Cerro Oreja are within the range of those obtained for other high-intensity agriculturalists and support previous findings that traumatic injury risk is higher for high-intensity agriculturalists. Similarities between Cerro Oreja and Kulubnarti suggest that rugged terrain may exacerbate fracture risk for agriculturalists, illustrating the costs of intensive agriculture in suboptimal environments.
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Agricultura/historia , Fracturas Óseas , Antropología Física , Arqueología , Fracturas Óseas/epidemiología , Fracturas Óseas/historia , Fracturas Óseas/patología , Historia Antigua , Humanos , Perú , RiesgoRESUMEN
AIMS: Chronic kidney disease (CKD) is a common complication after liver transplantation (LT). The etiology of CKD is broad and may only be assessed accurately by renal histology. The current study aimed to analyze the safety of renal biopsy in daily clinical practice as well as its usefulness regarding management of CKD after LT. METHODS: We performed a retrospective analysis of clinical data and renal biopsies obtained from patients with severe renal impairment (overt proteinuria, progressive deterioration of renal function) after LT with respect to safety, etiology of renal disease, and therapeutic consequences. RESULTS: Renal biopsies were obtained from 14 patients at median (minimum-maximum) 3 (0.2-12) years after LT. No major complications associated with renal biopsy were observed. Histomorphological alterations were varied (nephrosclerosis, n = 5; IgA-glomerulonephritis, n = 4; tenofovir-associated nephropathy, membranoproliferative glomerulonephritis type 1, membranous glomerulonephritis, amyloid A amyloidosis, and calcineurin inhibitor nephropathy, n = 1, respectively). The diagnosis of specific renal diseases other than calcineurin-inhibitor nephrotoxicity facilitated specific treaments and avoided unnecessary modification of immunosuppression in the majority of patients. CONCLUSIONS: Renal biopsy in patients with CKD after LT seems safe and may offer specific therapeutic options. Furthermore, unnecessary changes of immunosuppression can be avoided in a considerable number of patients.