Conservative or surgical treatment of pyogenic spinal infection: a retrospective multicenter binational retrospective cohort study [Abstract]

Spinal Tumors / Infections (Spine Parallel Session v.3), September 27, 2023, 8:30 AM - 10:00 AM Background: The optimal treatment of patients with spinal infections remains a controversial topic. While there is some consensus regarding the indication for surgical intervention in infections with neurologic deficit, significant deformity or progressive disease, other situations remain controversial. Within Europe, fundamentally different therapeutic concepts are found. Therefore, the aim of this study was to compare the outcome of patients who received surgical vs. antibiotic treatment alone for primary pyogenic spondylodiscitis in an international cohort analysis. Methods: The retrospectively compiled databases of tertiary high-volume spine centers served as the baseline for this study. All documented cases of primary spondylodiscitis treated surgically and conservatively in the period of 2017-2022 were included and grouped according to the therapeutic concept: conservative vs. surgical treatment. Independent investigators collected the relevant clinical and radiological data. The primary endpoint of this study was mortality rate; secondary endpoints were relapse rate and persisting neurological deficit. Results: A total of 392 patients were included in the analysis (155 females and 237 males with a mean age of 68 years). Of these, 95 cases were treated conservatively (CoT) and 297 cases were treated surgically (SuT). Most of conservatively treated patients were treated in the United Kingdom (CoT 81/ SuT 7), while most of the surgically treated cases were treated in Germany (CoT 14/ SuT 290). There was no significant difference (p<0.01) related to patient’s disease characteristics: Lumbar was the main location (n=240, CoT 58/ SuT 182, p=0.97) followed by thoracic (n=70, CoT 24/ SuT 46, p=0,03) and cervical (n=47, CoT 7/ SuT 40, p=0.11) region. A multilocular spinal infection was present in 32 patients (CoT 3/ SuT 29, p=0.04). 181 cases (CoT 36/ SuT 145, p=0.06) presented with an epidural abscess. Neurological deficits were recorded in 100 cases (CoT 26/ SuT 74, p=0.63), and septic conditions in 88 cases (CoT 26/ SuT 62, p=0.19). Pre-existing conditions like Diabetes (CoT 20/, SuT 71, p=0.57), renal failure (CoT 19/ SuT 60, p= 0.97), hepatopathy (CoT 4/ SuT 26, p= 0.15), malignoma (CoT 9/ SuT 38, p=0.39) or i.v. drug abuse (CoT 5/, SuT 15, p=0.93) did also not differ between the groups. The mortality rate of all conservatively treated was 24.2% (23 cases) and 6.7% (20 cases) in all surgically treated patients (p<0.001). A follow-up of ≥ 6 weeks was available in 289 cases (CoT 83, SuT 206 ). In this subset of patients relapse of infection occurred in six (7.2%) and 23 (11.2%) cases in the conservative and early surgical treatment group, respectively (p=0.69). Persisting neurological deficit was recorded in 21 (25.3%) of conservatively treated and 51 (24.8%) of surgically treated cases (p=0.92). Conclusions: Whereas relapse rates and persisting neurological deficit were not found to differ significantly, the results of this international data analyses, with their respective limitations, clearly support the growing evidence of a significantly reduced mortality rate after surgical therapy for primary pyogenic spondylodiscitis when compared to conservative treatment regimen

The role of innate and adaptive immune cells during liver regeneration under subseptic conditions after partial hepatectomy in mice

In der vorliegenden Arbeit wurde der Einfluss des innaten sowie des adaptiven Immunsystems auf die Leberregeneration nach 2/3 partieller Hepatektomie (PH) unter sub-septischen Bedingungen im Mausmodell untersucht. Sub-septische Bedingungen wurden durch eine niedrig dosierte LPS-Gabe im Anschluss an die Operation erzeugt. Dabei konnte gezeigt werden, dass sub-septische Bedingungen die Leberregeneration nach PH negativ beeinflussen, sie jedoch nicht unterbinden. Darüber hinaus führen sub-septische Bedingungen nach PH zu einer größeren Leberschädigung. Eine Rekrutierung neutrophiler Granulozyten in das Lebergewebe nach PH und LPS-Gabe wurde festgestellt. Die Daten der vorliegenden Arbeit lassen allerdings vermuten, dass diese direkt auf LPS induzierte Mechanismen zurückzuführen ist und keinen maßgeblichen Einfluss auf die Regeneration der Leber besitzt. Für T-Lymphozyten wurde eine protektive Funktion postuliert, da eine verstärkte Schädigung der Leber und verzögerte Regeneration unter sub-septischen Bedingungen mit einer reduzierten Anzahl an T-Lymphozyten im Lebergewebe an den für die Regeneration relevanten Zeitpunkten einherging. Adhäsionsmoleküle sind in der Migration von Leukozyten essentiell. In Abwesenheit des Adhäsionsmoleküles LFA-1 wurde eine stärkere Leberschädigung sowie verzögerte Leberregeneration nach alleiniger PH sowie nach PH und LPS-Gabe festgestellt. Insbesondere unter sub-septischen Bedingungen ging dies mit einer deutlich reduzierten Anzahl an T-Lymphozyten im Lebergewebe einher. Es konnte gezeigt werden, dass v.a. der Anteil an intrahepatischen NKT-Zellen in Abwesenheit von LFA-1 deutlich abnahm, während der Anteil an NK-Zellen zunahm. Das Zytokinmilieu des Lebergewebes verhielt sich entsprechend. CCL5, das u.a. eine Rolle bei der Migration von NK-Zellen spielt, wurde vermehrt im Lebergewebe LFA-1-defizienter Tiere nach PH und LPS-Gabe detektiert. Darüber hinaus wurde eine verstärkte Expression von IL-10 in Abwesenheit von LFA-1 festgestellt. IL-10 wird während der akuten systemischen Entzündung sehr früh und sehr stark von NK-Zellen freigesetzt. Die Expression von IL-23, für welches NKT-Zellen eine Rezeptor konstitutiv exprimieren, war in Abwesenheit von LFA-1 vermindert. Zusammengefasst deuten die Ergebnisse der vorliegenden Arbeit auf einen positiven Einfluss der NKT-Zellen auf die Leberregeneration unter sub-septischen Bedingungen hin und weisen dabei LFA-1 eine essentielle Funktion bei der Rekrutierung von NKT-Zellen in das Lebergewebe zu. Aus den Ergebnissen der vorliegenden Arbeit ergeben sich folgende klinisch relevante Aussagen: Die Indikation für eine simultane Operation von Lebermetastasen und des dazugehörigen Primarius im Kolon muss streng geprüft werden, da eine durch LPS-Translokation induzierte sub-septische Situation die Leberregeneration verzögert. Ein zweizeitiges Vorgehen ist zu bevorzugen. Therapeutische Ansätze, bei denen die Funktion von NKT-Zellen gefördert wird, sind erfolgversprechend und könnten die Leberregeneration nach partieller Hepatektomie verbessern. Dies hätte positiven Einfluss auf ausgedehnte, onkologische Leberresektionen sowie auf Leberlebendspenden im Rahmen einer Transplantation.The activation of the immune system in terms of subseptic conditions during liver regeneration is of great clinical importance. However, its molecular mediators and mechanisms, which are responsible for hepatocyte proliferation, are not well understood. This work sought to determine the functional role of innate and adaptive immune cells in response to partial hepatectomy (PH), and to analyze whether integrin lymphocyte function-associated antigen (LFA-) 1 modulates liver regeneration in a subseptic setting. To analyze liver regeneration a 2/3 PH was performed on mice. Subseptic conditions were achieved via low dose LPS application after the operation. It was shown that low-dose LPS application after PH significantly delays liver regeneration, but does not prevent it. Moreover, greater liver damage after PH under subseptic conditions was noticed. A recruitment of neutrophils to the liver parenchyma after PH and LPS application was detected. The results of this work could show that this recruitment was due to LPS and not due to the PH suggesting that neutrophils do not influence liver regeneration after PH. For T-lymphocytes a protective role was postulated as a reduced number of T-cells in the liver was in line with greater liver damage and delayed liver regeneration in a subseptic setting. Integrins are essential for leucocyte migration. In LFA-1-/- mice an impaired regenerative capacity of the liver and greater liver damage was observed as well after PH as after PH and low-dose LPS application. Especially in a subseptic setting the number of T-lymphocytes in the liver parenchyma in absence of LFA-1 was reduced. Analysis of different leukocyte subpopulations showed less CD3+NK1.1+ NKT cells in the liver parenchyma of LFA-1-/- mice after PH and LPS application compared to WT controls, while CD3-NK1.1+ NK cells markedly increased. Concordantly with this observation, lower levels of the NKT cell related cytokine IL23 were expressed in LFA-1-/- mice, while the expression of CCL5 and IL-10 was increased compared to the WT mice. CCL5, among others, is important in the migration of NK cells. IL-10 is produced early and in a great amount by NK cells during acute systemic inflammation. In conclusion this work postulates a positive influence of NKT cells during liver regeneration in a subseptic setting and indicates a essential role of LFA-1 in the recruitment of NKT cells to the liver parenchyma. The results of this work will potentially play an important role in clinical decisions and in the development of novel therapy strategies: First, the indication for a simultaneously performed extensive operation on the liver and colon should be reevalutated critically because in case of an LPS-mediated, subseptic setting developing liver regeneration would be delated. Second, future therapeutic approaches that stimulate NKT cells might be successful in improving liver regeneration after partial hepatectomy, e.g., for oncological reasons or during living liver transplantation

Impact of NKT Cells and LFA-1 on Liver Regeneration under Subseptic Conditions.

Activation of the immune system in terms of subseptic conditions during liver regeneration is of paramount clinical importance. However, little is known about molecular mechanisms and their mediators that control hepatocyte proliferation. We sought to determine the functional role of immune cells, especially NKT cells, in response to partial hepatectomy (PH), and to uncover the impact of the integrin lymphocyte function-associated antigen-1 (LFA-1) on liver regeneration in a subseptic setting.Wild-type (WT) and LFA-1-/- mice underwent a 2/3 PH and low-dose lipopolysaccharid (LPS) application. Hepatocyte proliferation, immune cell infiltration, and cytokine profile in the liver parenchyma were determined.Low-dose LPS application after PH results in a significant delay of liver regeneration between 48h and 72h, which is associated with a reduced number of CD3+ cells within the regenerating liver. In absence of LFA-1, an impaired regenerative capacity was observed under low-dose LPS application. Analysis of different leukocyte subpopulations showed less CD3+NK1.1+ NKT cells in the liver parenchyma of LFA-1-/- mice after PH and LPS application compared to WT controls, while CD3-NK1.1+ NK cells markedly increased. Concordantly with this observation, lower levels of NKT cell related cytokines IL-12 and IL-23 were expressed in the regenerating liver of LFA-1-/- mice, while the expression of NK cell-associated CCL5 and IL-10 was increased compared to WT mice.A subseptic situation negatively alters hepatocyte proliferation. Within this scenario, we suggest an important impact of NKT cells and postulate a critical function for LFA-1 during processes of liver regeneration

High-frequency spinal cord stimulation in failed back surgery syndrome patients with predominant low back pain: single-center experience

Treatment of patients with failed back surgery syndrome (FBSS) with predominant low back pain (LBP) remains challenging. High-frequency spinal cord stimulation (HF10 SCS) is believed to achieve significant pain reduction. We aimed to evaluate the real-life efficacy of HF-10 SCS in a tertiary spine center. A prospective observational study of all patients with FBSS and predominant LBP who underwent HF-10 SCS surgery was performed between 2016 and 2018. Patients &amp;gt; 18 years with Visual Analogue Scale (VAS) scores of ≥ 5 for LBP and pain duration &amp;gt; 6 months under stable medication were implanted percutaneous under general anesthesia and a trial phase of 7-14 days was accomplished. Primary end point was a successful trial defined as ≥ 50% VAS score reduction for LBP. Thirty-four of 39 (85%) subjects had a successful trial. Fifty-three percent were female and the mean age was 69 years. Median follow-up lasted for 10 months. Devices were removed after a median of 10 months in 5 cases. Remaining 29 patients stated significant VAS score reduction for LBP from 8.1 to 2.9 and VAS for leg pain from 4.9 to 2.2. Twenty-four percent of all patients were able to discontinue their opioids. Eight of 9 patients (89%) with signs of adjacent disc disease and 7 of 10 (70%) patients with hardware failure were successfully implanted with significant VAS reduction for LBP. HF-10 SCS achieves significant pain reduction in most patients with FBSS and predominant LBP. It might be an efficient alternative to revision surgery

Minimally invasive posterior pedicle screw fixation versus open instrumentation in patients with thoracolumbar spondylodiscitis

Due to the aging society, the incidence of pyogenic spondylodiscitis is still rising. Although surgical treatment for spondylodiscitis in general is increasingly accepted, an optimal surgical strategy for treatment of pyogenic spinal infection has not yet been established. The aim of this study was to investigate the suitability of percutaneous posterior pedicle screw fixation for surgical treatment in patients with spondylodiscitis of the thoracolumbar spine

Fungal brain infection—no longer a death sentence

The aim of this case series was to provide a modern cohort of patients with cerebral aspergillosis and show the effectiveness of modern treatment concepts. In a 10-year period from January 2009 to January 2019, we identified 10 patients (6 male, 4 female) who received surgery or frameless stereotactic drainage of a cerebral aspergilloma at our center. Patients' and disease characteristics were recorded. The median age was 65 (range 45 to 83). We conducted 133 cranial surgeries in 100 patients due to cerebral brain abscess (BA) during that time, which leads to a percentage of 10% of aspergilloma within BAs in our patient sample. We performed 3.1 surgeries per patient followed by antifungal treatment for 6 months (= median) according to the microbiological findings. Regarding comorbidities, the mean Charlson comorbidity index (CCI) at the time of admission was 5, representing an estimated 10-year survival of 21%. Six (60%) of 10 patients showed conditions of immunosuppression, one suffered endocarditis after replacement of aortic valves. Four patients showed associated frontobasal bone destruction, mycotic aneurysms, or thromboses. The mean duration of hospital stay was 37 days. Mortality was much lower than in literature. Sixty percent of the patients died during the follow-up period. The outcome of the two immunocompetent patients was more favorable. Cerebral aspergillosis is a rare, but still life-threatening, condition, which predominantly occurs in immunosuppressive conditions. Due to radical surgical and antifungal therapy for several months, mortality can be reduced dramatically

The implementation of an infection prevention bundle reduces surgical site infections following cranial surgery

The benefit of an infection prevention bundle made up of five basic procedures to avoid surgical site infections (SSIs) following cranial surgery was evaluated

Conservative or surgical treatment of pyogenic spinal infection. A retrospective multicenter binational retrospective cohort study

Introduction: The optimal treatment of patients with spinal infections remains a controversial topic. Within Europe, fundamentally different therapeutic concepts are found. Therefore, the aim of this study was to compare the outcome of patients who received surgical vs. antibiotic treatment alone for primary pyogenic spondylodiscitis in an international cohort analysis. Materials and Methods: The retrospectively compiled databases of tertiary high-volume spine centers served as the baseline for this study. All documented cases of primary spondylodiscitis treated surgically and conservatively in the period of 2017-2022 were included and grouped according to the therapeutic concept: conservative vs. surgical treatment. Independent investigators collected the relevant clinical and radiological data. The primary endpoint of this study was mortality rate; secondary endpoints were relapse rate and persisting neurological deficit. Results: A total of 392 patients were included in the analysis (155 females with a mean age of 68 years). Of these, 95 cases were treated conservatively (CoT) and 297 cases were treated surgically (SuT). There was no significant difference (p<0.01) related to patient’s disease characteristics: Lumbar was the main location (n=240, CoT 58/ SuT 182, p=0.97) followed by thoracic (n=70, CoT 24/ SuT 46, p=0,03) and cervical (n=47, CoT 7/ SuT 40, p=0.11) region. A multilocular spinal infection was present in 32 patients (CoT 3/ SuT 29, p=0.04). 181 cases (CoT 36/ SuT 145, p=0.06) presented with an epidural abscess. Neurological deficits were recorded in 100 cases (CoT 26/ SuT 74, p=0.63), and septic conditions in 88 cases (CoT 26/ SuT 62, p=0.19). Pre-existing conditions like Diabetes (p=0.57), renal failure (p= 0.97), hepatopathy (p= 0.15), malignoma (p=0.39) or i.v. drug abuse (p=0.93) did also not differ between the groups. The mortality rate of all conservatively treated was 24.2% (23 cases) and 6.7% (20 cases) in all surgically treated patients (p<0.001). A follow-up of ≥ 6 weeks was available in 289 cases (CoT 83, SuT 206 ). In this subset of patients relapse of infection occurred in six (7.2%) and 23 (11.2%) cases in the conservative and early surgical treatment group, respectively (p=0.69). Persisting neurological deficit was recorded in 21 (25.3%) of conservatively treated and 51 (24.8%) of surgically treated cases (p=0.92). Conclusion: Whereas relapse rates and persisting neurological deficit were not found to differ significantly, the results of this international data analyses, with their respective limitations, clearly support the growing evidence of a significantly reduced mortality rate after surgical therapy for primary pyogenic spondylodiscitis when compared to conservative treatment regimen