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1.
J Clin Med ; 12(16)2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37629259

RESUMO

Antibiotic therapy following surgical perianal abscess drainage is debated, but may be necessary for high-risk patients. Frailty has been shown to increase the risk of unfavorable outcomes in elderly surgical patients. This study aims to identify high-risk patients by retrospectively analyzing a single-center cohort and using a pretherapeutic score to predict the need for postoperative antibiotics and extended nursing care following perianal abscess drainage surgery. The perianal sepsis risk score was developed through univariable and multivariable analysis. Internal validation was assessed using the area under receiver-operating characteristic curve. Elderly, especially frail patients exhibited more severe perianal disease, higher frequency of antibiotic therapy, longer hospitalization, poorer clinical outcomes. Multivariable analysis revealed that scores in the 5-item modified frailty index, severity of local infection, and preoperative laboratory markers of infection independently predicted the need for prolonged hospitalization and anti-infective therapy after abscess drainage surgery. These factors were combined into the perianal sepsis risk score, which demonstrated better predictive accuracy for prolonged hospitalization and antibiotic therapy compared with chronological age or frailty status alone. Geriatric assessments are becoming increasingly important in clinical practice. The perianal sepsis risk score identifies high-risk patients before surgery, enabling early initiation of antibiotic therapy and allocation of additional nursing resources.

2.
World J Emerg Surg ; 18(1): 6, 2023 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639810

RESUMO

BACKGROUND: In contrast to adults, the situation for pediatric trauma care from an international point of view and the global management of severely injured children remain rather unclear. The current study investigates structural management of pediatric trauma in centers of different trauma levels as well as experiences with pediatric trauma management around the world. METHODS: A web-survey had been distributed to the global mailing list of the World Society of Emergency Surgery from 10/2021-03/2022, investigating characteristics of respondents and affiliated hospitals, case-load of pediatric trauma patients, capacities and infrastructure for critical care in children, trauma team composition, clinical work-up and individual experiences with pediatric trauma management in response to patients´ age. The collaboration group was subdivided regarding sizes of affiliated hospitals to allow comparisons concerning hospital volumes. Comparable results were conducted to statistical analysis. RESULTS: A total of 133 participants from 34 countries, i.e. 5 continents responded to the survey. They were most commonly affiliated with larger hospitals (> 500 beds in 72.9%) and with level I or II trauma centers (82.0%), respectively. 74.4% of hospitals offer unrestricted pediatric medical care, but only 63.2% and 42.9% of the participants had sufficient experiences with trauma care in children ≤ 10 and ≤ 5 years of age (p = 0.0014). This situation is aggravated in participants from smaller hospitals (p < 0.01). With regard to hospital size (≤ 500 versus > 500 in-hospital beds), larger hospitals were more likely affiliated with advanced trauma centers, more elaborated pediatric intensive care infrastructure (p < 0.0001), treated children at all ages more frequently (p = 0.0938) and have higher case-loads of severely injured children < 12 years of age (p = 0.0009). Therefore, the majority of larger hospitals reserve either pediatric surgery departments or board-certified pediatric surgeons (p < 0.0001) and in-hospital trauma management is conducted more multi-disciplinarily. However, the majority of respondents does not feel prepared for treatment of severe pediatric trauma and call for special educational and practical training courses (overall: 80.2% and 64.3%, respectively). CONCLUSIONS: Multi-professional management of pediatric trauma and individual experiences with severely injured children depend on volumes, level of trauma centers and infrastructure of the hospital. However, respondents from hospitals at all levels of trauma care complain about an alarming lack of knowledge on pediatric trauma management.


Assuntos
Hospitais , Centros de Traumatologia , Adulto , Criança , Humanos , Estudos Transversais , Inquéritos e Questionários
3.
J Robot Surg ; 17(2): 577-585, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35994194

RESUMO

The use of robotic systems in bariatric surgery has constantly increased over the last years. However, beside its technical advantages in morbidly obese patients the conclusive role of robotics in bariatric and metabolic surgery is still under controversial debate. This is an analysis of prospectively collected data of consecutive patients undergoing fully robotic Roux-en-Y gastric bypasses (TR-RYGB) during the first year after implementation of a robotic bariatric program at a tertiary university hospital. All patients were operated by a previously untrained robotic but experienced laparoscopic bariatric surgeon using the daVinci Xi system (Intuitive Surgical, Sarl). Data recording included patient characteristics, operative and functional outcomes, complications and learning curves for surgeon and assistants. In total, 80 patients underwent primary or revisional robotic bariatric surgery. Seventy-two patients (90%) received a TR-RYGB. There were no major complications, re-interventions or readmissions. The overall complication rate was 2.5% (Clavien-Dindo grade I and II). The overall operation time was 140.7 ± 24.6 min and decreased significantly from the first to the last decade of procedures (procedure 1-10: 171.2 ± 26.3 min versus procedure 63-72: 116.0 ± 10.9 min, p < 0.0001). A stabilization of the learning curve was observed after 30 procedures for the surgeon and after five procedures for the bedside assistant. With immediate effect, TR-RYGB is a safe procedure with low complication rates for an experienced laparoscopic bariatric surgeon without prior robotic skills. Learning curves are steep and operation times can be effectively decreased by increasing the experience of the surgeon.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Procedimentos Cirúrgicos Robóticos , Humanos , Derivação Gástrica/métodos , Curva de Aprendizado , Centros de Atenção Terciária , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Cirurgia Bariátrica/métodos , Laparoscopia/métodos , Resultado do Tratamento
4.
Am J Respir Crit Care Med ; 207(3): 283-299, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047984

RESUMO

Rationale: Although type II alveolar epithelial cells (AEC2s) are chronically injured in idiopathic pulmonary fibrosis (IPF), they contribute to epithelial regeneration in IPF. Objectives: We hypothesized that Notch signaling may contribute to AEC2 proliferation, dedifferentiation characterized by loss of surfactant processing machinery, and lung fibrosis in IPF. Methods: We applied microarray analysis, kinome profiling, flow cytometry, immunofluorescence analysis, western blotting, quantitative PCR, and proliferation and surface activity analysis to study epithelial differentiation, proliferation, and matrix deposition in vitro (AEC2 lines, primary murine/human AEC2s), ex vivo (human IPF-derived precision-cut lung slices), and in vivo (bleomycin and pepstatin application, Notch1 [Notch receptor 1] intracellular domain overexpression). Measurements and Main Results: We document here extensive SP-B and -C (surfactant protein-B and -C) processing defects in IPF AEC2s, due to loss of Napsin A, resulting in increased intra-alveolar surface tension and alveolar collapse and induction of endoplasmic reticulum stress in AEC2s. In vivo pharmacological inhibition of Napsin A results in the development of AEC2 injury and overt lung fibrosis. We also demonstrate that Notch1 signaling is already activated early in IPF and determines AEC2 fate by inhibiting differentiation (reduced lamellar body compartment, reduced capacity to process hydrophobic SP) and by causing increased epithelial proliferation and development of lung fibrosis, putatively via altered JAK (Janus kinase)/Stat (signal transducer and activator of transcription) signaling in AEC2s. Conversely, inhibition of Notch signaling in IPF-derived precision-cut lung slices improved the surfactant processing capacity of AEC2s and reversed fibrosis. Conclusions: Notch1 is a central regulator of AEC2 fate in IPF. It induces alveolar epithelial proliferation and loss of Napsin A and of surfactant proprotein processing, and it contributes to fibroproliferation.


Assuntos
Fibrose Pulmonar Idiopática , Surfactantes Pulmonares , Humanos , Camundongos , Animais , Tensoativos , Pulmão , Células Epiteliais Alveolares , Bleomicina , Receptor Notch1
5.
Sci Rep ; 12(1): 14866, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050427

RESUMO

Perianal abscesses are frequent diseases in general surgery. Principles of standard patient care are surgical drainage with exploration and concomitant treatment of fistula. Antiinfective therapy is frequently applied in cases of severe local disease and perianal sepsis. However, the role of microbiologic testing of purulence from perianal abscesses is disputed and the knowledge concerning bacteriology and bacterial resistances is very limited. A retrospective cohort study was performed of consecutive patients (≥ 12 years of age) from a tertiary care hospital, who underwent surgical treatment for perianal abscess from 01/2008 to 12/2019. Subdividing the cohort into three groups regarding microbiological testing results: no microbiological testing of purulence (No_Swab, n = 456), no detection of drug resistant bacteria [DR(-), n = 141] or detection of bacteria with acquired drug resistances from purulence [DR(+), n = 220]. Group comparisons were performed using Kruskall-Wallis test and, if applicable, followed by Dunn´s multiple comparisons test for continuous variables or Fishers exact or Pearson's X2 test for categorical data. Fistula persistence was estimated by Kaplan Meier and compared between the groups using Log rank test. Corralation analysis between perioperative outcome parameters and bacteriology was performed using Spearman´s rho rank correlation. Higher pretherapeutic C-reactive protein (p < 0.0001) and white blood cell count (p < 0.0001), higher rates of supralevatoric or pararectal abscesses (p = 0.0062) and of complicated fistula-in-ano requiring drainage procedure during index surgery (p < 0.0001) reflect more severe diseases in DR(+) patients. The necessity of antibiotic therapy (p < 0.0001), change of antibiotic regimen upon microbiologic testing results (p = 0.0001) and the rate of re-debridements during short-term follow-up (p = 0.0001) were the highest, the duration until definitive fistula repair was the longest in DR(+) patients (p = 0.0061). Escherichia coli, Bacteroides, Streptococcus and Staphylococcus species with acquired drug resistances were detected frequently. High rates of resistances against everyday antibiotics, including perioperative antibiotic prophylaxis were alarming. In conclusion, the knowledge about individual bacteriology is relevant in cases of complex and severe local disease, including locally advanced infection with extended soft tissue affection and perianal sepsis, signs of systemic inflammatory response as well as the need of re-do surgery for local debridements during short-term and fistula repair during long-term follow-up. Higher rates of acquired antibiotic resistances are to be expected in patients with more severe diseases.


Assuntos
Doenças do Ânus , Sepse , Dermatopatias , Abscesso/tratamento farmacológico , Abscesso/microbiologia , Antibacterianos/uso terapêutico , Doenças do Ânus/diagnóstico , Doenças do Ânus/tratamento farmacológico , Doenças do Ânus/cirurgia , Bactérias , Humanos , Estudos Retrospectivos , Sepse/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Resultado do Tratamento
6.
J Clin Med ; 11(14)2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-35887906

RESUMO

Chronic Lung Allograft Dysfunction (CLAD) is a life-threatening complication that limits the long-term survival of lung transplantation patients. Early diagnosis remains the basis of efficient management of CLAD, making the need for distinctive biomarkers critical. This explorative study aimed to investigate the predictive power of mitochondrial DNA (mtDNA) derived from bronchoalveolar lavages (BAL) to detect CLAD. The study included 106 lung transplant recipients and analyzed 286 BAL samples for cell count, cell differentiation, and inflammatory and mitochondrial biomarkers, including mtDNA. A receiver operating curve analysis of mtDNA levels was used to assess its ability to detect CLAD. The results revealed a discriminatory pro-inflammatory cytokine profile in the BAL fluid of CLAD patients. The concentration of mtDNA increased in step with each CLAD stage, reaching its highest concentration in stage 4, and correlated significantly with decreasing FEV1. The receiver operating curve analysis of mtDNA in BAL revealed a moderate prediction of CLAD when all stages were grouped together (AUROC 0.75, p-value < 0.0001). This study has found the concentration mtDNA in BAL to be a potential predictor for the early detection of CLAD and the differentiation of different CLAD stages, independent of the underlying pathology.

8.
J Nephrol ; 35(7): 1933-1941, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35763254

RESUMO

BACKGROUND: Association of cognitive impairment with chronic kidney disease has been reported over the last decade. Individuals show better cognitive performance after kidney transplantation than individuals on dialysis but are more likely to be affected by cognitive impairment than age-matched comparison groups. Better knowledge of the prevalence as well as course and profile of cognitive impairment is important for the design of future studies assessing the clinical impact of cognitive impairment and developing management strategies. The goal of our study is to examine the extent of cognitive impairment before and after transplantation and to derive a distinct profile of cognitive function using standard neurocognitive tests. Furthermore, we aim to assess whether transplantation per se leads to an improvement in cognitive performance. METHODS: We are conducting a prospective single-center cohort study involving 100 kidney transplant individuals. Individuals who are wait-listed to receive a kidney transplantation or have already received one will be included in this study. Individuals will undergo a battery of detailed neurocognitive tests at baseline (in part before surgery), and then 3 and 12 months afterwards. Furthermore, the enrolled patients will complete a validated German version of the Cognitive Failure Questionnaire for self-assessment (s-CFQ) as well as the Hospital Anxiety and Depression Scale -Deutsche (HADS-D), a self-report screening instrument with two scales that capture anxiety and depression. In addition, a hair sample will be taken at each measurement time point for the determination of hair cortisol levels as a parameter for the cumulative hypothalamic-pituitary-adrenocortical axis activity over the previous three months. The primary outcome measure will be (a) the effect of kidney transplantation on the cognitive performance up to 12 months after transplantation and (b) the course of cognitive performance following kidney transplantation over time. DISCUSSION: The results of our study have potentially important implications for the prevention and treatment of cognitive impairment in kidney transplant individuals. By increasing our knowledge of the neurocognitive profile and assigning the corresponding deficits, it might be possible to create an individualized training program to positively impact cognitive deficits in kidney transplant patients.


Assuntos
Disfunção Cognitiva , Transplante de Rim , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Estudos de Coortes , Humanos , Transplante de Rim/efeitos adversos , Testes Neuropsicológicos , Estudos Prospectivos
9.
World J Emerg Surg ; 17(1): 34, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710386

RESUMO

BACKGROUND: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. METHODS: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. RESULTS: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. CONCLUSIONS: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years.


Assuntos
COVID-19 , Diverticulite , COVID-19/epidemiologia , Estudos Transversais , Humanos , Pandemias , SARS-CoV-2
10.
Clin Transplant ; 36(3): e14554, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34862985

RESUMO

BACKGROUND: The shortage of organs for transplantation remains a global problem. The retransplantation of a previously transplanted kidney might be a possibility to expand the pool of donors. We provide our experience with the successful reuse of transplanted kidneys in the Eurotransplant region. METHODS: A query in the Eurotransplant database was performed between January 1, 1995 and December 31, 2015, to find kidney donors who themselves had previously received a kidney graft. RESULTS: Nine out of a total of 68,554 allocated kidneys had previously been transplanted. Four of these kidneys were transplanted once again. The mean interval between the first transplant and retransplantation was 1689±1682 days (SD; range 55-5,333 days). At the time of the first transplantation the mean serum creatinine of the donors was 1.0 mg/dl (.6-1.3 mg/dl) and at the second transplantation 1.4 mg/dl (.8-1.5 mg/dl). The mean graft survival in the first recipient was 50 months (2-110 months) and in the second recipient 111 months (40-215 months). CONCLUSION: Transplantation of a previously transplanted kidney may successfully be performed with well-preserved graft function and long-term graft survival, even if the first transplantation was performed a long time ago. Such organs should be considered even for younger recipients in carefully selected cases.


Assuntos
Transplante de Rim , Obtenção de Tecidos e Órgãos , Sobrevivência de Enxerto , Humanos , Rim , Doadores de Tecidos
11.
World J Emerg Surg ; 15(1): 64, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33298131

RESUMO

BACKGROUND: The SARS-CoV-2 pandemic is a major challenge for health care services worldwide. It's impact on oncologic therapies and elective surgery has been described recently, and the literature provides guidelines regarding appropriate elective patient treatment during the pandemic. However, the impact of SARS-CoV-2 pandemic on emergency surgery services has been poorly investigated up to now. METHODS: A 17-item web survey had been distributed to emergency surgeons in June 2020 around the world, investigating the impact of SARS-CoV-2 pandemic on patients and septic diseases both requiring emergency surgery and the time-to-intervention in emergency surgery routine, as well as experiences with surgery in COVID-19 patients. RESULTS: Ninety-eight collaborators from 31 countries responded to the survey. The majority (65.3%) estimated the impact of the SARS-CoV-2 pandemic on emergency surgical patient care as being strong or very strong. Due to the pandemic, 87.8% reported a decrease in the total number of patients undergoing emergency surgery and approximately 25% estimated a delay of more than 2 h in the time-to-diagnosis and another 2 h in the time-to-intervention. Fifty percent make structural problems with in-hospital logistics (e.g. transport of patients, closed normal wards etc.) mainly responsible for delayed emergency surgery and the frequent need (56.1%) for a triage of emergency surgical patients. 56.1% of the collaborators observed more severe septic abdominal diseases during the pandemic, especially for perforated appendicitis and severe septic cholecystitis (41.8% and 40.2%, respectively). 62.2% had experiences with surgery in COVID-19-infected patients. CONCLUSIONS: The results of The WSES COVID-19 emergency surgery survey are alarming. The combination of an estimated decrease in numbers of emergency surgical patients and an observed increase in more severe septic diseases may be a result of the fear of patients from infection with COVID-19 and a consecutive delayed hospital admission and diagnosis. A critical delay in time-to-diagnosis and time-to-intervention may be a result of changes in in-hospital logistics and operating room as well as intensive care capacities. Both reflect the potentially harmful impact of SARS-CoV-2 pandemic on emergency surgery services.


Assuntos
COVID-19 , Serviço Hospitalar de Emergência/estatística & dados numéricos , Utilização de Instalações e Serviços/estatística & dados numéricos , Saúde Global/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Cirurgia Geral/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Humanos , SARS-CoV-2
12.
J Clin Med ; 9(6)2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32560416

RESUMO

Patients undergoing esophageal cancer surgery are at high risk of developing severe pulmonary complications. Beneficial effects of minimally invasive esophagectomy had been discussed recently, but the incidence of perioperative respiratory impairment remains unclear. This is a retrospective single-center cohort study of patients, who underwent open (OE) or laparoscopically assisted, hybrid minimally invasive abdomino-thoracic esophagectomy (LAE) for cancer regarding respiratory impairment (PaO2/FiO2 ratio (P/FR) < 300 mmHg) and pneumonia. No differences were observed in the cumulative incidence of reduced P/FR between OE and LAE patients. Of note, until postoperative day (POD) 2, P/FR did not differ among both groups. Thereafter, the rate of patients with respiratory impairment was higher after OE on POD 3, 5, and 10 (p ≤ 0.05) and tended being higher on POD 7 and 9 (p ≤ 0.1). Although the duration of LAE procedure was slightly longer (total: p = 0.07, thoracic part: p = 0.004), the duration of surgery (Spearman's rank correlation coefficient (rsp) = -0.267, p = 0.006), especially of laparotomy (rsp = -0.242, p = 0.01) correlated inversely with respiratory impairment on POD 3 after OE. Pneumonia occurred on POD 5 (1-25) and 8.5 (3-14) after OE and LAE, respectively, with the highest incidence after OE (p = 0.01). In conclusion, respiratory impairment and pulmonary complications occur frequently after esophagectomy. Although early respiratory impairment is independent of the surgical approach, postoperative pneumonia rate is reduced after LAE.

13.
Am J Transplant ; 20(10): 2928-2932, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32400084

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has become a global health problem with pandemic character. Lung transplant recipients may be particularly at risk due to the high degree of immunosuppression and the lung being the organ primarily affected by COVID-19. We describe a 16-year-old male and a 64-year-old female recently lung transplanted patients with COVID-19 during inpatient rehabilitation. Both patients were receiving triple immunosuppressive therapy and had no signs of allograft dysfunction. Both patients had close contact with a person who developed COVID-19 and were tested positive for SARS-CoV-2. Subsequently, both patients underwent systematic screening and SARS-CoV-2 was ultimately detected. Although the 16-year-old boy was completely asymptomatic, the 64-year-old woman developed only mild COVID-19. Immunosuppressive therapy was unchanged and no experimental treatment was initiated. No signs of graft involvement or dysfunction were noticed. In conclusion, our report of patients with asymptomatic SARS-CoV-2 infection and mild COVID-19, respectively, may indicate that lung transplant recipients are not per se at risk for severe COVID-19. Further observations and controlled trials are urgently needed to study SARS-CoV-2 infection in lung transplant recipients.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Transplante de Pulmão , Pneumonia Viral/diagnóstico , Transplantados , Adolescente , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/transmissão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/transmissão , Período Pós-Operatório , RNA Viral/análise , SARS-CoV-2 , Tomografia Computadorizada por Raios X
14.
Transpl Infect Dis ; 21(5): e13138, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31278878

RESUMO

Human cytomegalovirus (HCMV) infections and reactivations are common after lung transplantation and are associated with the development of bronchiolitis obliterans syndrome. Against this background, temporary HCMV prophylaxis is an established standard regimen after lung transplantation in most centers. However, the optimal duration of prophylaxis is unclear. We conducted a retrospective two-center study to determine the efficacy of indefinite lifelong HCMV prophylaxis with oral valganciclovir in a cohort of 133 lung transplant recipients with a mean follow-up time of approximately 5 years. During the follow-up period, HCMV DNA was detected in 22 recipients (16.5%). In one case, HCMV pneumonitis developed after prophylaxis had been terminated. We observed a beneficial safety profile and tolerability in our cohort, as the majority of patients still received valganciclovir after a 1- and 3-year observation period, respectively. Compared to the literature, these data indicate a beneficial effect of extended valganciclovir prophylaxis with an acceptable safety profile.


Assuntos
Antivirais/administração & dosagem , Infecções por Citomegalovirus/prevenção & controle , Transplante de Pulmão , Valganciclovir/administração & dosagem , Adulto , Idoso , Citomegalovirus , Infecções por Citomegalovirus/complicações , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Transplantados , Adulto Jovem
15.
Front Immunol ; 9: 1604, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30105015

RESUMO

Blood levels of the acute phase reactant C-reactive protein (CRP) are frequently measured as a clinical marker for inflammation, but the biological functions of CRP are still controversial. CRP is a phosphocholine (PC)-binding pentraxin, mainly produced in the liver in response to elevated levels of interleukin-1ß (IL-1ß) and of the IL-1ß-dependent cytokine IL-6. While both cytokines play important roles in host defense, excessive systemic IL-1ß levels can cause life-threatening diseases such as trauma-associated systemic inflammation. We hypothesized that CRP acts as a negative feedback regulator of monocytic IL-1ß maturation and secretion. Here, we demonstrate that CRP, in association with PC, efficiently reduces ATP-induced inflammasome activation and IL-1ß release from human peripheral blood mononuclear leukocytes and monocytic U937 cells. Effective concentrations are in the range of marginally pathologic CRP levels (IC50 = 4.9 µg/ml). CRP elicits metabotropic functions at nicotinic acetylcholine (ACh) receptors (nAChRs) containing subunits α7, α9, and α10 and suppresses the function of ATP-sensitive P2X7 receptors in monocytic cells. Of note, CRP does not induce ion currents at conventional nAChRs, suggesting that CRP is a potent nicotinic agonist controlling innate immunity without entailing the risk of adverse effects in the nervous system. In a prospective study on multiple trauma patients, IL-1ß plasma concentrations negatively correlated with preceding CRP levels, whereas inflammasome-independent cytokines IL-6, IL-18, and TNF-α positively correlated. In conclusion, PC-laden CRP is an unconventional nicotinic agonist that potently inhibits ATP-induced inflammasome activation and might protect against trauma-associated sterile inflammation.


Assuntos
Proteína C-Reativa/imunologia , Inflamassomos/imunologia , Inflamação , Adulto , Idoso , Biomarcadores , Proteína C-Reativa/farmacologia , Células Cultivadas , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Inflamassomos/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores Nicotínicos/imunologia , Receptores Nicotínicos/metabolismo , Receptores Purinérgicos P2X7/imunologia , Receptores Purinérgicos P2X7/metabolismo
16.
Eur J Cardiothorac Surg ; 52(6): 1049-1054, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28977370

RESUMO

OBJECTIVES: To reduce the shortage of organs for transplantation by expanding organ selection criteria as a means to increase the pool of potential lung donors. In this study, we sought to investigate the impact of using lungs from very old donors aged >70 years on outcomes after lung transplantation. METHODS: Between January 2010 and November 2016, 96 patients with end-stage lung disease underwent lung transplantation in our centres. Lung donors were divided into 3 groups according to age (donor aged <60 years, 60-69 years and ≥70 years). We examined the effect of donor age on various short- and long-term outcome parameters. RESULTS: Lungs harvested from very old donors had a lower percentage of smoking history and shorter ventilation time. Survival rates of recipients did not show significant differences between older and younger donor groups. Most of the short- and long-term outcome parameters in recipients of lungs from very old donors did not differ significantly among the 3 age groups, except for post-transplant best forced expiratory volume in 1 s and treated acute rejections, which were lower and higher, respectively, in donors aged ≥70 years. CONCLUSIONS: This dual-centre analysis showed that lung transplantation from donors aged ≥70 years was not associated with worse outcomes compared with the younger donors. This study supports the idea that it might be possible to use an extraordinarily cautious selection of lungs from very old donors to increase the pool of suitable donors, given the shortage of suitable organ donors available for lung transplantation.


Assuntos
Seleção do Doador/métodos , Pneumopatias/cirurgia , Transplante de Pulmão , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Alemanha/epidemiologia , Humanos , Pneumopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
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