RESUMO
Management of patients with glioblastoma (GBM) often includes radiation (RT) and temozolomide (TMZ). The association between severe treatment-related lymphopenia (TRL) after the standard chemoradiation and reduced survival has been reported in GBM patients with the median age of 57. Similar findings were described in patients with head and neck, non-small cell lung, and pancreatic cancers. This retrospective study is designed to evaluate whether elderly GBM patients (age ≥65) develop similar TRL after RT/TMZ and whether such TRL is associated with decreased survival. Serial total lymphocyte counts (TLC) were retrospectively reviewed in patients (age ≥65) with newly diagnosed GBM undergoing RT/TMZ and associated with treatment outcomes. Seventy-two patients were eligible: median KPS 70, median age 71 years (range 65-86) with 56 % of patients >70 years, 53% female, 31% received RT ≤45 Gy. Baseline median TLC was 1100 cells/mm(3) which fell by 41% to 650 cells/mm(3) 2 months after initiating RT/TMZ (p < 0.0001). Patients with TLC <500 cells/mm(3) at 2 months had a shorter survival than those with higher TLCs with a median overall survival of 4.6 versus 11.6 months, respectively. Multivariate analysis revealed a significant association between TRL and survival (HR 2.76, 95% CI 1.30-5.86, p = 0.008). Treatment-related lymphopenia is frequent, severe, and an independent predictor for survival in elderly patients with GBM. These findings add to the body of evidence that immunosuppression induced by chemoradiation is associated with inferior clinical outcomes. Prospective studies are needed to confirm these findings suggesting that immune preservation is important in this cancer.
Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/terapia , Quimiorradioterapia/efeitos adversos , Dacarbazina/análogos & derivados , Glioblastoma/terapia , Linfopenia/mortalidade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/diagnóstico , Dacarbazina/efeitos adversos , Feminino , Seguimentos , Glioblastoma/diagnóstico , Humanos , Linfopenia/etiologia , Linfopenia/patologia , Masculino , Gradação de Tumores , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida , TemozolomidaRESUMO
BACKGROUND CONTEXT: Cutibacterium acnes (C. acnes) is a gram-positive facultative anaerobe found in the deep sebaceous follicles of the skin on the shoulder and back. C. acnes has been increasingly recognized as a pathogen in spinal surgical site infection (SSI) especially in the presence of instrumentation. PURPOSE: This study assesses whether a silver carboxylate-doped titanium dioxide-polydimethylsiloxane (TiO2-PDMS) coating can decrease C. acnes adherence and biofilm formation on PEEK and four other commonly used spinal implant materials, stainless steel, cobalt chromium, titanium, and titanium alloy. STUDY DESIGN: We compared the adherence of C. acnes over 24 hours between uncoated, 95:5 TiO2 to PDMS ratio with 10× silver carboxylate coating and a 100% silver carboxylate coating on each implant material, which were uniformly saw cut and sterilized. Implants were then subjected to scanning electron microscopy (SEM) and confocal scanning laser microscopy (CSLM). METHODS: Samples were coated using 95:5 TiO2-PDMS 10× silver carboxylate, 100% silver carboxylate, or left uncoated. C. acnes was applied onto the samples and allowed to adhere for periods of 4, 8, 12, 16, or 20 hours. Nonadherent bacteria were then washed from the samples. These samples were then allowed to continue incubating for a total of 24 hours. SEM and confocal laser scanning microscope were used to visualize all samples for the presence of biofilm and quantification of C. acnes adherence at each time point. RESULTS: The 95:5 TiO2-PDMS 10× silver carboxylate coating was able to significantly decrease C. acnes adherence on PEEK after 8, 12, 16, and 20 hours of adherence. No statistical difference was found between the 95:5 TiO2-PDMS 10× silver carboxylate coating and the 100% silver carboxylate positive control. We previously observed extensive C. acnes biofilm formation on uncoated PEEK, but none on PEEK coated with either the 95:5 TiO2-PDMS 10× silver carboxylate or 100% Ag coating . Furthermore, no biofilm formation was observed on stainless steel, cobalt chromium, titanium, and titanium alloy coated with 95:5 TiO2-PDMS 10× silver carboxylate or 100% Ag coating. CONCLUSION: A 95:5 TiO2-PDMS 10× silver carboxylate coating decreases C. acnes adhesion and prevents biofilm formation on PEEK and other common orthopedic implant materials. CLINICAL SIGNIFICANCE: A 95:5 TiO2-PDMS 10× silver carboxylate coating may help decrease spinal SSI due to C. acnes, especially in procedures with instrumentation.
Assuntos
Prata , Titânio , Benzofenonas , Biofilmes , Materiais Revestidos Biocompatíveis , Dimetilpolisiloxanos , Éteres , Humanos , Cetonas , PolímerosRESUMO
BACKGROUND: Cutibacterium acnes (C. acnes) is associated with infection following shoulder and spine surgery due to follicular pore concentrations in these anatomic regions. It has been established that it can form biofilms on surgical implant materials, which may contribute to its role in perioperative infection, but its behavior of early colonization on those materials is not yet well understood. PURPOSE: The purpose of this study was to evaluate the time to adherence and subsequent biofilm formation of C. acnes in the first 24 hours on implant materials commonly used in spinal surgery. STUDY DESIGN: We compared the colonization and behavior of C. acnes over time when applied to five commonly used spine implant materials - polyether ether ketone (PEEK), cobalt chromium (CC), stainless steel (SS), titanium, and titanium alloy. METHODS: C. acnes was applied onto the samples of PEEK, CC, SS, titanium, and titanium alloy, and allowed to adhere for periods of 4, 8, 12, 16, and 20 hours. Nonadherent bacteria were then washed from the samples. These samples were then allowed to continue incubating for a total 24 hours. Scanning electron microscopy and confocal laser scanning microscopy were used to visualize all samples for the presence and quantification of C. acnes adherence at each time period. Subsequent transition to biofilm formation on these samples was assessed via scanning electron microscopy at each time period. RESULTS: The PEEK specimens exhibited the highest amount of surface biological burden in the first 24 hours compared with the other materials, which displayed little or no adherence. Rapid biofilm formation first observed at 8 hours of allowed adhesion on PEEK, whereas no significant biofilm formation was seen on the other materials during the observed time period. CONCLUSIONS: Although C. acnes is known to have a slow proliferation rate, the results of this investigation demonstrate that it can rapidly adhere to and form a biofilm on PEEK. These data suggest that the use of PEEK implants placed during spinal surgery may facilitate early intraoperative colonization, and subsequent infection, compared with metallic implants. CLINICAL SIGNIFICANCE: The findings of this study suggest that PEEK may prove to be problematic as a choice of implant material in cases were C. acnes infection is a possibility.