Carbon monoxide intoxication with a CO-Hb of 30% while smoking waterpipe: a case report.

Carbon monoxide (CO) poisoning is a significant public health issue and a considerable economic burden in developed countries. While the majority of non-fire-related CO poisonings are attributed to gas heating, there are several other less recognized sources that should be considered in the initial differential diagnosis.The patient in this case was a 21-year-old who experienced a brief episode of loss of consciousness and was subsequently admitted to the Emergency department. Upon evaluation, the patient was diagnosed with CO poisoning, which necessitated hyperbaric oxygen therapy to mitigate the effects of this toxic exposure.Despite exhibiting harmful symptoms initially, the patient stated in a phone interview two and a half years post-incident that they have not experienced any enduring effects such as cardiac arrhythmia or concentration deficits. While their understanding of the risks associated with waterpipe smoking has increased, it has not influenced any major changes in their waterpipe smoking habits.

Pain management with epidural catheter and epidural analgesia after spinal dorsal instrumentation of lumbar spine.

Spinal dorsal instrumentation (SDI) is an established treatment for degenerative spinal diseases. Adequate and immediate postoperative pain control is important for patient recovery and may be compromised by uncertainty about its efficacy and concern about early postoperative surgical complications or adverse events. The aim of the current study was to compare the use of epidural analgesia (EA) with systemic analgesia (SA) as regards pain reduction and early postoperative complications after SDI. Pain management with epidural or systemic analgesia in patients undergoing SDI by posterior approach between January 2019 and July 2020 was evaluated by clinical functional testing, measuring total opioid amounts used, and evaluating numerical rating scale values 24 and 96 hours postoperatively. The following were also monitored: demographic data, number of affected segments, length of hospital stay, inflammatory markers (leukocytes and serum C-reactive protein), early postoperative surgical complication rates, and adverse events. In total 79 patients were included (33 in the EA and 46 in the SA group). The SA group had significantly lower numerical rating scale values at days 1 to 4 after surgery (P ≤ .001) and lower cumulative opioid use than the EA group (P < .001). We found no difference in infection parameters, length of hospital stay or surgery-related complication rates. Our data demonstrate that epidural anesthesia was inferior to an opioid-based SA regime in reducing postoperative pain in patients undergoing spinal surgery. There is no benefit to the use of epidural catheters.

Postoperative prolonged mechanical ventilation correlates to poor survival in patients with surgically treated spinal metastasis.

Objective: Patients with spinal metastasis (SM) are at advanced stages of systemic cancer disease. Surgical therapy for SM is a common treatment modality enabling histopathological diagnosis and the prevention of severe neurological deficits. However, surgery for SM in this vulnerable patient cohort may require prolonged postoperative intensive care treatment, which could adversely affect the anticipated benefit of the surgery. We therefore assessed postoperative prolonged mechanical ventilation (PMV) as an indicator for intensive care treatment with regard to potential correlations with early postoperative mortality and overall survival (OS). Methods: Between 2015 and 2019, 198 patients were surgically treated for SM at the author´s neurosurgical department. PMV was defined as postoperative mechanical ventilation of more than 24 hours. A multivariate analysis was performed to identify pre- and perioperative collectable predictors for 30 days mortality. Results: Twenty out of 198 patients (10%) with SM suffered from postoperative PMV. Patients with PMV exhibited a median OS rate of 1 month compared to 12 months for patients without PMV (p < 0.0001). The 30 days mortality was 70% and after one year 100%. The multivariate analysis identified "PMV > 24 hrs" (p < 0.001, OR 0.3, 95% CI 0.02-0.4) as the only significant and independent predictor for 30 days mortality (Nagelkerke's R2 0.38). Conclusions: Our data indicate postoperative PMV to significantly correlate to high early postoperative mortality rates as well as to poor OS in patients with surgically treated SM. These findings might encourage the initiation of further multicenter studies to comprehensively investigate PMV as a so far underestimated negative prognostic factor in the course of surgical treatment for SM.

Patient Safety Comparison of Frameless and Frame-Based Stereotactic Navigation for Brain Biopsy-A Single Center Cohort Study.

Leksell stereotactic system-based aspiration biopsy is a common procedure in the neurosurgical treatment of deep-seated or multiple brain lesions. This study aimed to evaluate the benefit of frameless biopsy using VarioGuide compared to frame-based biopsy using the Leksell stereotactic system (LSS). We analyzed all brain biopsies using VarioGuide or LSS at our neurooncological Department of Neurosurgery in the University Hospital of Bonn between January 2018 and August 2020. We analyzed demographic data, duration of surgery, size of lesion, localization, and early complications. Uni-variable analyses were carried out on data from both groups. In total, 109 biopsies were compared (40 VarioGuide vs. 69 LSS). Patients with VarioGuide were significant older (74 (62−80) years vs. 67 (57−76) years; p = 0.03) and had a shorter duration of general anesthesia (163 (138−194) min vs. 193 (167−215) min, p < 0.001). We found no significant differences in surgery duration (VarioGuide median 28 min (IQR 20−38); LSS: median 30 min (IQR 25−39); p = 0.1352) or in early complication rates (5% vs. 7%; p = 0.644). A slightly higher false negative biopsy rate was registered in the LSS group (3 vs. 1; p = 0.1347). The size of the lesions also did not differ significantly between the two groups (18.31 ± 26.35 cm3 vs. 12.63 ± 14.62; p = 0.15). Our data showed that biopsies performed using VarioGuide took significantly less time than LSS biopsies and did not differ in complication rates. Both systems offered a high degree of patient safety.

A Validation Study for SHE Score for Acute Subdural Hematoma in the Elderly.

OBJECTIVE: The aim of this study was the verification of the Subdural Hematoma in the Elderly (SHE) score proposed by Alford et al. as a mortality predictor in patients older than 65 years with nontraumatic/minor trauma acute subdural hematoma (aSDH). Additionally, we evaluated further predictors associated with poor outcome. METHODS: Patients were scored according to age (1 point is given if patients were older than 80 years), GCS by admission (1 point for GCS 5-12, 2 points for GCS 3-4), and SDH volume (1 point for volume 50 mL). The sum of points determines the SHE score. Multivariate logistic regression analysis was performed to identify additional independent risk factors associated with 30-day mortality. RESULTS: We evaluated 131 patients with aSDH who were treated at our institution between 2008 and 2020. We observed the same 30-day mortality rates published by Alford et al.: SHE 0: 4.3% vs. 3.2%, p = 1.0; SHE 1: 12.2% vs. 13.1%, p = 1.0; SHE 2: 36.6% vs. 32.7%, p = 0.8; SHE 3: 97.1% vs. 95.7%, p = 1.0 and SHE 4: 100% vs. 100%, p = 1.0. Additionally, 18 patients who developed status epilepticus (SE) had a mortality of 100 percent regardless of the SHE score. The distribution of SE among the groups was: 1 for SHE 1, 6 for SHE 2, 9 for SHE 3, and 2 for SHE 4. The logistic regression showed the surgical evacuation to be the only significant risk factor for developing the seizure. All patients who developed SE underwent surgery (p = 0.0065). Furthermore, SHE 3 and 4 showed no difference regarding the outcome between surgical and conservative treatment. CONCLUSIONS: SHE score is a reliable mortality predictor for minor trauma acute subdural hematoma in elderly patients. In addition, we identified status epilepticus as a strong life-expectancy-limiting factor in patients undergoing surgical evacuation.

Safety Evaluation of Cervical Dorsal Instrumentation in Geriatric Patients: Experience at a Level 1 Center for Spinal Surgery-A Single Center Cohort Study.

Objective: Dorsal instrumentation of the cervical spine is an established treatment in spine surgery. However, careful planning is required, particularly in elderly patients. This study evaluates early clinical outcomes in geriatric patients undergoing complex spine surgery. Methods: In this retrospective, single center cohort study, we included all geriatric patients (aged ≥65 years) who underwent dorsal instrumentation between January 2013 and December 2020. We analyzed postoperative complications and the 30-day in-hospital mortality rate. Furthermore, the Charlson comorbidity index (CCI) and Clavien-Dindo grading system (CDG) were used to assess the patients' comorbidity burden. Results: In total, 153 patients were identified and included. The mean age of patients was 78 years (SD ± 7). Traumatic injury (53.6%) was the most common reason for surgery. 60.8% of the patients underwent dorsal instrumentation with 3 or more levels. The most common comorbidities were arterial hypertension (64%), diabetes mellitus (22.2%), coronary heart disease and atrial fibrillation (19.6%). The most common adverse event (AE) was pneumonia (4%) and the most common surgery-related complication was wound infection (5.2%). Among patients categorized as high risk for AE (CCI > 5), 14.6% suffered a postoperative AE. In our univariate analysis, we found no risk factors for high rates of complications or mortality. Conclusion: Our data demonstrates that older patients were at no significant risk of postoperative complications. The CCI/CDG scores may identify patients at higher risk for adverse events after dorsal instrumentation, and these assessments should become an essential component of stratification in this older patient population.

The necessity for routine intensive care unit admission following elective craniotomy for epilepsy surgery: a retrospective single-center observational study.

OBJECTIVE: Traditionally, patients who underwent elective craniotomy for epilepsy surgery are monitored postoperatively in an intensive care unit (ICU) overnight in order to sufficiently respond to potential early postoperative complications. In the present study, the authors investigated the frequency of early postoperative events that entailed ICU monitoring in patients who had undergone elective craniotomy for epilepsy surgery. In a second step, they aimed at identifying pre- and intraoperative risk factors for the development of unfavorable events to distinguish those patients with the need for postoperative ICU monitoring at the earliest possible stage. METHODS: The authors performed a retrospective observational cohort study assessing patients with medically intractable epilepsy (n = 266) who had undergone elective craniotomy for epilepsy surgery between 2012 and 2019 at a tertiary care epilepsy center, excluding those patients who had undergone invasive diagnostic approaches and functional hemispherectomy. Postoperative complications were defined as any unfavorable postoperative surgical and/or anesthesiological event that required further ICU therapy within 48 hours following surgery. A multivariate analysis was performed to reveal preoperatively identifiable risk factors for postoperative adverse events requiring an ICU setting. RESULTS: Thirteen (4.9%) of 266 patients developed early postoperative adverse events that required further postoperative ICU care. The most prevalent event was a return to the operating room because of relevant postoperative intracranial hematoma (5 of 266 patients). Multivariate analysis revealed intraoperative blood loss ≥ 325 ml (OR 6.2, p = 0.012) and diabetes mellitus (OR 9.2, p = 0.029) as risk factors for unfavorable postoperative events requiring ICU therapy. CONCLUSIONS: The present study revealed routinely collectable risk factors that would allow the identification of patients with an elevated risk of postsurgical complications requiring a postoperative ICU stay following epilepsy surgery. These findings may offer guidance for a stepdown unit admission policy following epilepsy surgical interventions after an external validation of the results.

Perioperative red blood cell transfusion is associated with poor functional outcome and overall survival in patients with newly diagnosed glioblastoma.

The influence of perioperative red blood cell (RBC) transfusion on prognosis of glioblastoma patients continues to be inconclusive. The aim of the present study was to evaluate the association between perioperative blood transfusion (PBT) and overall survival (OS) in patients with newly diagnosed glioblastoma. Between 2013 and 2018, 240 patients with newly diagnosed glioblastoma underwent surgical resection of intracerebral mass lesion at the authors' institution. PBT was defined as the transfusion of RBC within 5 days from the day of surgery. The impact of PBT on overall survival was assessed using Kaplan-Meier analysis and multivariate regression analysis. Seventeen out of 240 patients (7%) with newly diagnosed glioblastoma received PBT. The overall median number of blood units transfused was 2 (95% CI 1-6). Patients who received PBT achieved a poorer median OS compared to patients without PBT (7 versus 18 months; p < 0.0001). Multivariate analysis identified "age > 65 years" (p < 0.0001, OR 6.4, 95% CI 3.3-12.3), "STR" (p = 0.001, OR 3.2, 95% CI 1.6-6.1), "unmethylated MGMT status" (p < 0.001, OR 3.3, 95% CI 1.7-6.4), and "perioperative RBC transfusion" (p = 0.01, OR 6.0, 95% CI 1.5-23.4) as significantly and independently associated with 1-year mortality. Perioperative RBC transfusion compromises survival in patients with glioblastoma indicating the need to minimize the use of transfusions at the time of surgery. Obeying evidence-based transfusion guidelines provides an opportunity to reduce transfusion rates in this population with a potentially positive effect on survival.

Tumor-associated epilepsy in patients with brain metastases: necrosis-to-tumor ratio forecasts postoperative seizure freedom.

Surgical resection is highly effective in the treatment of tumor-related epilepsy (TRE) in patients with brain metastases (BM). Nevertheless, some patients suffer from postoperative persistent epilepsy which negatively impacts health-related quality of life. Therefore, early identification of patients with potentially unfavorable seizure outcome after BM resection is important. Patients with TRE that had undergone surgery for BM at the authors' institution between 2013 and 2018 were analyzed with regard to preoperatively identifiable risk factors for unfavorable seizure outcome. Tumor tissue and tumor necrosis ratios were assessed volumetrically. According to the classification of the International League Against Epilepsy (ILAE), seizure outcome was categorized as favorable (ILAE 1) and unfavorable (ILAE 2-6) after 3 months in order to avoid potential interference with adjuvant cancer treatment. Among all 38 patients undergoing neurosurgical treatment for BM with concomitant TRE, 34 patients achieved a favorable seizure outcome (90%). Unfavorable seizure outcome was significantly associated with larger tumor volumes (p = 0.012), a midline shift > 7 mm (p = 0.025), and a necrosis/tumor volume ratio > 0.2 (p = 0.047). The present study identifies preoperatively collectable risk factors for unfavorable seizure outcome in patients with BM and TRE. This might enable to preselect for highly vulnerable patients with postoperative persistent epilepsy who might benefit from accompanying neuro-oncological expertise during further systemical treatment regimes.

Characterization of Transverse Aortic Constriction in Mice Based on the Specific Recruitment of Leukocytes to the Hypertrophic Myocardium and the Aorta Ascendens.

Transverse aortic constriction (TAC) is a model that mimics pressure overload-induced left ventricular (LV) hypertrophy in mice. Alterations in immune cell functionality can promote cardiac and vascular remodeling. In the present study, we characterized the time course in innate immune cell dynamics in response to TAC in the different tissues of mice. It was determined whether TAC induces a characteristic leukocyte-driven immune response in the myocardium, aorta ascendens and descendens, spleen, blood, and draining lymph nodes supported by cytokine-driven chemotaxis in mice at 3, 6, and 21 days following surgery. We used complex flow cytometry staining combinations to characterize the various innate immune cell subsets and a multiplex array to determine cytokine concentrations in the serum. The results of the current study indicated that leukocytes accumulate in the myocardium and aorta ascendens in response to TAC. The leukocyte dynamics in the myocardium were dominated by the Ly6Clow macrophages with an early accumulation, whereas the response in the aorta ascendens was characterized by a long-lasting proinflammatory phenotype driven by Ly6Chigh macrophages, neutrophils, and activated DCs. In contrast to the high-pressure environment of the aorta ascendens, the tissue of the aorta descendens did not react to TAC with any leukocyte increase. The levels of proinflammatory cytokines in the blood were elevated in response to TAC, indicating a systemic reaction. Moreover, our findings strongly suggest that cardiac macrophages could origin from splenic pools and reach the site of the inflammation via the blood. Based on the current findings, it can be concluded that the high-pressure conditions in the aorta ascendens cause a characteristic immune response, dominated by the accumulation of leukocytes and the activation of DCs that varies in comparison to the immune cell dynamics in the myocardium and the aorta descendens.

Rapid Ventricular Pacing as a Safe Procedure for Clipping of Complex Ruptured and Unruptured Intracranial Aneurysms.

Surgical treatment of intracranial aneurysm requires advanced technologies to achieve optimal results. Recently, rapid ventricular pacing (RVP) has been described to be an elegant technique that facilitates clip reconstruction of complex unruptured intracranial aneurysm (uIA). However, there is also a growing need for intraoperative tools to ensure safe clip reconstruction of complex ruptured intracranial aneurysm (rIA). We conducted a retrospective analysis of 17 patients who underwent RVP during surgical reconstruction of complex aneurysms. Nine patients had uIA while eight patients underwent surgery for rIA suffering from consecutive subarachnoid hemorrhage (SAH). Hemodynamic data, critical events, laboratory results, and anesthesia-related complications were evaluated. No complications were reported concerning anesthesia induction and induction times were similar between patients exhibiting uIA or rIA (p = 0.08). RVP induced a significant decline of median arterial pressure (MAP) in both groups (p < 0.0001). However, median MAP before and after RVP was not different in both groups (uIA group: p = 0.27; rIA group: p = 0.18). Furthermore, high-sensitive Troponin T (hsTnT) levels were not increased after RVP in any group. One patient in the rIA group exhibited ventricular fibrillation and required cardiopulmonary resuscitation, but has presented with cardiac arrest due to SAH. Otherwise, no arrhythmias or complications occurred. In summary, our data suggest RVP to be feasible in surgery for ruptured intracranial aneurysms.

Preoperative Metastatic Brain Tumor-Associated Intracerebral Hemorrhage Is Associated With Dismal Prognosis.

OBJECT: Intra-tumoral hemorrhage is considered an imaging characteristic of advanced cancer disease. However, data on the influence of intra-tumoral hemorrhage in patients with brain metastases (BM) remains scarce. We aimed at investigating patients with BM who underwent neurosurgical resection of the metastatic lesion for a potential impact of preoperative hemorrhagic transformation on overall survival (OS). METHODS: Between 2013 and 2018, 357 patients with BM were surgically treated at the authors' neuro-oncological center. Preoperative magnetic resonance imaging (MRI) examinations were assessed for the occurrence of malignant hemorrhagic transformation. RESULTS: 122 of 375 patients (34%) with BM revealed preoperative intra-tumoral hemorrhage. Patients with hemorrhagic transformed BM exhibited a median OS of 5 months compared to 12 months for patients without intra-tumoral hemorrhage. Multivariate analysis revealed preoperative hemorrhagic transformation as an independent and significant predictor for worsened OS. CONCLUSIONS: The present study identifies preoperative intra-tumoral hemorrhage as an indicator variable for poor prognosis in patients with BM undergoing neurosurgical treatment.

The Surgical Management of Brain Metastases in Non-Small Cell Lung Cancer (NSCLC): Identification of the Early Laboratory and Clinical Determinants of Survival.

BACKGROUND: Brain metastases (BM) indicate advanced states of cancer disease and cranial surgery represents a common treatment modality. In the present study, we aimed to identify the risk factors for a reduced survival in patients receiving a surgical treatment of BM derived from non-small cell lung cancer (NSCLC). METHODS: A total of 154 patients with NSCLC that had been surgically treated for BM at the authors' institution between 2013 and 2018 were included for a further analysis. A multivariate analysis was performed to identify the predictors of a poor overall survival (OS). RESULTS: The median overall survival (mOS) was 11 months (95% CI 8.2-13.8). An age > 65 years, the infratentorial location of BM, elevated preoperative C-reactive protein levels, a perioperative red blood cell transfusion, postoperative prolonged mechanical ventilation (>48 h) and the occurrence of postoperative adverse events were identified as independent factors of a poor OS. CONCLUSIONS: The present study identified several predictors for a worsened OS in patients that underwent surgery for BM of NSCLC. These findings might guide a better risk/benefit assessment in the course of metastatic NSCLC therapy and might help to more sufficiently cope with the challenges of cancer therapy in these advanced stages of disease.

Outcome of Elderly Patients With Surgically Treated Brain Metastases.

OBJECT: In the light of an aging population and ongoing advances in cancer control, the optimal management in geriatric patients with brain metastases (BM) poses an increasing challenge, especially due to the scarce data available. We therefore analyzed our institutional data with regard to factors influencing overall survival (OS) in geriatric patients with BM. METHODS: Between 2013 and 2018, patients aged ≥ 65 years with surgically treated BM were included in this retrospective analysis. In search of preoperatively identifiable risk factors for poor OS, in addition to the underlying cancer, the preoperative frailty of patients was analyzed using the modified Frailty Index (mFI). RESULTS: A total of 180 geriatric patients with surgically treated BM were identified. Geriatric patients categorized as least-frail achieved a median OS of 18 months, whereas frailest patients achieved an OS of only 3 months (p<0.0001). Multivariable cox regression analysis detected "multiple intracranial metastases" (p=0.001), "infratentorial localization" (p=0.011), "preoperative CRP >5 mg/l" (p=0.01) and "frailest patients (mFI ≥ 0.27)" (p=0.002) as predictors for reduced OS in older patients undergoing surgical treatment for BM. CONCLUSIONS: In this retrospective series, pre-operative frailty was associated with poor survival in elderly patients with BM requiring surgery. Our analyses warrant thorough counselling and support of affected elderly patients and their families.

Combined Assessment of Preoperative Frailty and Sarcopenia Allows the Prediction of Overall Survival in Patients with Lung Cancer (NSCLC) and Surgically Treated Brain Metastasis.

Neurosurgical resection represents an important therapeutic pillar in patients with brain metastasis (BM). Such extended treatment modalities require preoperative assessment of patients' physical status to estimate individual treatment success. The aim of the present study was to analyze the predictive value of frailty and sarcopenia as assessment tools for physiological integrity in patients with non-small cell lung cancer (NSCLC) who had undergone surgery for BM. Between 2013 and 2018, 141 patients were surgically treated for BM from NSCLC at the authors' institution. The preoperative physical condition was assessed by the temporal muscle thickness (TMT) as a surrogate parameter for sarcopenia and the modified frailty index (mFI). For the ≥65 aged group, median overall survival (mOS) significantly differed between patients classified as 'frail' (mFI ≥ 0.27) and 'least and moderately frail' (mFI < 0.27) (15 months versus 11 months (p = 0.02)). Sarcopenia revealed significant differences in mOS for the <65 aged group (10 versus 18 months for patients with and without sarcopenia (p = 0.036)). The present study confirms a predictive value of preoperative frailty and sarcopenia with respect to OS in patients with NSCLC and surgically treated BM. A combined assessment of mFI and TMT allows the prediction of OS across all age groups.

Going to Extremes of Lung Physiology-Deep Breath-Hold Diving.

Breath-hold diving involves environmental challenges, such as water immersion, hydrostatic pressure, and asphyxia, that put the respiratory system under stress. While training and inherent individual factors may increase tolerance to these challenges, the limits of human respiratory physiology will be reached quickly during deep breath-hold dives. Nonetheless, world records in deep breath-hold diving of more than 214 m of seawater have considerably exceeded predictions from human physiology. Investigations of elite breath-hold divers and their achievements revised our understanding of possible physiological adaptations in humans and revealed techniques such as glossopharyngeal breathing as being essential to achieve extremes in breath-hold diving performance. These techniques allow elite athletes to increase total lung capacity and minimize residual volume, thereby reducing thoracic squeeze. However, the inability of human lungs to collapse early during descent enables respiratory gas exchange to continue at greater depths, forcing nitrogen (N2) out of the alveolar space to dissolve in body tissues. This will increase risk of N2 narcosis and decompression stress. Clinical cases of stroke-like syndromes after single deep breath-hold dives point to possible mechanisms of decompression stress, caused by N2 entering the vasculature upon ascent from these deep dives. Mechanisms of neurological injury and inert gas narcosis during deep breath-hold dives are still incompletely understood. This review addresses possible hypotheses and elucidates factors that may contribute to pathophysiology of deep freediving accidents. Awareness of the unique challenges to pulmonary physiology at depth is paramount to assess medical risks of deep breath-hold diving.

The Impact of Prolonged Mechanical Ventilation on Overall Survival in Patients With Surgically Treated Brain Metastases.

OBJECTIVE: Surgical resection represents a common treatment modality in patients with brain metastasis (BM). Postoperative prolonged mechanical ventilation (PMV) might have an enormous impact on the overall survival (OS) of these patients suffering from advanced cancer disease. We therefore have analyzed our institutional database with regard to a potential impact of PMV on OS of patients who had undergone surgery for brain metastases. METHODS: 360 patients with surgically treated brain metastases were included. The definition of PMV consisted of postoperative mechanical ventilation lasting for more than 48 hours. Analysis of survival incorporating established prognostic factors such as age, location of BM, and preoperative physical status was performed. RESULTS: 14 of 360 patients with BM (4%) suffered from postoperative PMV after surgical treatment of BM. Patients with PMV presented in a significantly more impaired neurological condition preoperatively than patients without (p<0.0001). Multivariate analysis determined PMV to be a significant prognostic factor for OS after surgical treatment in patients with BM, independent of other predictive factors (p<0.0001). CONCLUSIONS: The present study demonstrates postoperative PMV as significantly related to poor OS in patients with surgically treated BM. Postoperative PMV is a so far underestimated prognostic predictor, but might be utilized for optimized patient management early in the postoperative phase. For this purpose, the results of the present study should encourage the initiation of further scientific efforts.

Prognostic Value of Preoperative Inflammatory Markers in Melanoma Patients with Brain Metastases.

BACKGROUND: Metastatic melanoma disease is accompanied by highly systemic inflammatory responses. The prognostic value of preoperative laboratory inflammation markers in brain metastatic melanoma patients has not been adequately investigated so far. METHODS: Preoperative inflammatory blood parameters were correlated to overall survival (OS) rates in melanoma patients that underwent surgery for brain metastasis (BM) between 2013 and 2019 at the authors' institution. Receiver operating characteristic (ROC) analyses were used for cutoff determination of routine laboratory parameters. RESULTS: Median OS in the present cohort of 30 melanoma patients with surgically treated BM was 7 months (95% confidence interval (CI) 5.7-8.3). Initial elevated C-reactive protein (CRP) levels (>10 mg/L), neutrophil-to-lymphocyte ratio (NLR) ≥ 4, platelet-to-lymphocyte ratio (PLR) ≥ 145, and lymphocyte-to-monocyte ratio (LMR) < 2 were associated with significantly reduced OS rates. CONCLUSIONS: The present study identifies several preoperative peripheral inflammatory markers as indicators for poor prognosis in melanoma patients with BM undergoing neurosurgical treatment. Elevated initial CRP values, higher NLR and PLR, and lower LMR were associated with reduced OS and, thus, might be incorporated into preoperative interdisciplinary treatment planning and counseling for affected patients.

CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in mice upon transverse aortic constriction.

The CX3CL1/CX3CR1 axis mediates recruitment and extravasation of CX3CR1-expressing subsets of leukocytes and plays a pivotal role in the inflammation-driven pathology of cardiovascular disease. The cardiac immune response differs depending on the underlying causes. This suggests that for the development of successful immunomodulatory therapy in heart failure due to chronic pressure overload induced left ventricular (LV) hypertrophy, the underlying immune patterns must be examined. Here, the authors demonstrate that Fraktalkine-receptor CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in a mouse model of transverse aortic constriction (TAC). The comparison of C57BL/6 mice with CX3CR1 deficient mice displayed reduced LV hypertrophy and preserved cardiac function in response to pressure overload in mice lacking CX3CR1. Moreover, the normal immune response following TAC induced pressure overload which is dominated by Ly6Clow macrophages changed to an early pro-inflammatory immune response driven by neutrophils, Ly6Chigh macrophages and altered cytokine expression pattern in CX3CR1 deficient mice. In this early inflammatory phase of LV hypertrophy Ly6Chigh monocytes infiltrated the heart in response to a C-C chemokine ligand 2 burst. CX3CR1 expression impacts the immune response in the development of LV hypertrophy and its absence has clear cardioprotective effects. Hence, suppression of CX3CR1 may be an important immunomodulatory therapeutic target to ameliorate pressure-overload induced heart failure.