Anterior knee pain after total knee arthroplasty: does it correlate with patellar blood flow?

Purpose: Total knee arthroplasty (TKA) disturbs patellar blood flow, an unintended accompaniment to TKA that may be a cause of postoperative anterior knee pain. We examine whether disrupted patellar blood flow correlates with anterior knee pain following TKA. Methods: In 50 patients (21 men, 29 women) undergoing TKA, we compared patellar blood flow at flexions 0° to 30°, 60°, 90°, and 110° before and after medial parapatellar arthrotomy to pre- and postoperative anterior knee pain scores by means of a laser Doppler flowmeter (LDF) probe. Anterior knee pain was assessed using the pain intensity numeric rating scale (NRS) of 0-10 (0-no, 10-worst pain). Based on the NRS pain values, patients were divided into two main groups: group A (n=34) with no pain or discomfort (NRS range 0-4) and group B (n=16) with anterior knee pain (NRS range 5-10). Results: Patients of group B demonstrated a significant decrease in blood flow before arthrotomy at flexions from 0° to 90°, and 110° and from 0° to 60°, 90°, and 110° after arthrotomy. For group A, a significant decrease in blood flow was detected at flexions from 0° to 90°, and 110° before and after arthrotomy. For both groups, medial arthrotomy did not have a statistically significant influence on patellar blood flow (margin of significance P<0.05). Prior to TKA, 16 of the 50 patients of group B (32%) complained of anterior knee pain (mean NRS 7.1±1.7). At 2-year follow-up, pain significantly decreased (NRS 3.1±2.1) and only 4 of the 16 patients (25%) complained of moderate anterior pain (average NRS 5.7±0.5), while 8 of 16 (50%) patients reported discomfort (mean NRS 3.5±1.8) around the patella. Patients in group A also demonstrated a significant decrease in pain intensity (from NRS 1.5±1.4 preoperatively to NRS 0.4±1.5 at 2-year follow-up). Statistical analysis demonstrated no statistically significant correlation between pre-arthrotomy/post-arthrotomy patellar blood flow and the presence of preoperative and postoperative anterior knee pain. Only the degree of flexion had an influence on patellar blood flow. Conclusion: Medial arthrotomy had no direct significant effect on patellar blood flow, and the diminished blood flow did not correlate with postoperative anterior knee pain. However, a significant correlation was revealed between patellar blood flow and the degree of flexion: in almost a quarter of patients, blood flow dropped to zero at flexions of 100° and above. Level of evidence: I

Arterial Stiffness in Patients with Sarcoidosis and Obstructive Sleep Apnea

Background: Obstructive sleep apnea (OSA) and sarcoidosis have both been implied to be risk factors for increased arterial stiffness. However, it is unclear whether an elevated apnea–hypopnea index (AHI) in sarcoidosis patients increases arterial stiffness and thus the cardiovascular risk. Methods: We performed non-invasive applanation tonometry in 57 adults with sarcoidosis. The participants underwent SphygmoCor to assess arterial stiffness using an aortic augmentation index with a heart rate of 75/min (AIx) and level-3 respiratory polygraphy. An AHI of ≥5/h, ≥15/h, and ≥30/h defined mild, moderate, and severe OSA, respectively. Multivariate regression analysis was used to investigate the association between AIx and AHI, adjusted for prespecified risk factors for AIx. Results: 23 (40%) sarcoidosis patients had at least mild OSA (AHI ≥ 5), while 7 (12%) patients showed AHI ≥ 15/h. AHI was significantly associated with AIx (coef. (95%CI) of 0.31 (0.09/0.52), p = 0.006) even after adjustment for known risk factors of arterial stiffness. While severe OSA was positively associated with increased AIx, mild and moderate OSA were not associated with increased AIx after adjusting for known risk factors. Conclusions: Increased AHI is independently associated with increased arterial stiffness in sarcoidosis patients. Further investigations are needed to underline the association between OSA severity and the magnitude of arterial stiffness

A randomized phase II study of radiation induced immune boost in operable non-small cell lung cancer (RadImmune trial)

Background: Lung cancer is the leading cause of cancer deaths worldwide. Surgery, radiotherapy at conventional and high dose and chemotherapy are the mainstay for lung cancer treatment. Insufficient migration and activation of tumour specific effector T cells seem to be important reasons for inadequate host anti-tumour immune response. Ionizing radiation can induce a variety of immune responses. The goal of this randomized trial is to assess if a preoperative single fraction low dose radiation is able to improve anti-tumour immune response in operable early stage lung cancer. Methods/Design: This trial has been designed as an investigator-initiated, prospective, randomized, 2-armed phase II trial. Patients who are candidates for elective resection of early stage non-small cell lung cancer will be randomized into 2 arms. A total of 36 patients will be enrolled. The patients receive either 2 Gy or no radiation prescribed to their primary tumour. Radiation will be delivered by external beam radiotherapy using 3D radiotherapy or intensity-modulated radiation technique (IMRT) 7 days prior to surgical resection. The primary objective is to compare CD8+ T cell counts detected by immunohistochemistry in resected tumours following preoperative radiotherapy versus no radiotherapy. Secondary objectives include the association between CD8+ T cell counts and progression free survival, the correlation of CD8+ T cell counts quantified by immunohistochemistry and flow cytometry, local tumour control and recurrence patterns, survival, radiogenic treatment toxicity and postoperative morbidity and mortality. Further, frequencies of tumour reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome. Discussion: This unique intervention combining preoperative low dose radiation and surgical removal of early stage non-small cell lung cancer is designed to address the problem of inadequate host anti-tumour immune response. If successful, this study may affect the role of radiotherapy in lung cancer treatment. Trial registration: NCT02319408; Registration: December 29, 2014

Augmentation Index in Patients with Thoracic Aortic Aneurysm: A Matched Case-Control Study

Thoracic aortic aneurysms (TAA) may be associated with complications such as rupture and dissection, which can lead to a fatal outcome. Increased central arterial stiffness has been proposed to be present in patients with TAA compared to unmatched controls. We aimed to assess whether wall properties in patients with TAA are also altered when compared to a matched control group. Applanation tonometry was performed in 74 adults with TAA and 74 sex, age, weight, height, and left ventricular ejection fraction matched controls. Subsequently analysis of the pulse wave was done using the SphygmoCor System. For comparing the two groups, AIx was adjusted to a heart rate of 75/min (AIx@75). 148 1-to-1 matched participants were included in the final model. There was no significant difference in the Alx@75 between the TAA group and the matched control group [mean (SD) of 24.7 (11.2) % and 22.8 (11.2) %, p = 0.240]. Adjusted for known cardiovascular risk factors, there was no association between TAA and AIx@75. Patients with TAA showed comparable arterial wall properties to cardiovascular risk factor matched controls. Since higher arterial stiffness is associated with TAA progression, it remains to be investigated if increased central arterial stiffness is a relevant factor of TAA emergence. Keywords: thoracic aortic aneurysm; augmentation index; arterial stiffnes

Tracking cell turnover in human brain using 15N-thymidine imaging mass spectrometry

Microcephaly is often caused by an impairment of the generation of neurons in the brain, a process referred to as neurogenesis. While most neurogenesis in mammals occurs during brain development, it thought to continue to take place through adulthood in selected regions of the mammalian brain, notably the hippocampus. However, the generality of neurogenesis in the adult brain has been controversial. While studies in mice and rats have provided compelling evidence for neurogenesis occurring in the adult rodent hippocampus, the lack of applicability in humans of key methods to demonstrate neurogenesis has led to an intense debate about the existence and, in particular, the magnitude of neurogenesis in the adult human brain. Here, we demonstrate the applicability of a powerful method to address this debate, that is, the in vivo labeling of adult human patients with 15N-thymidine, a non-hazardous form of thymidine, an approach without any clinical harm or ethical concerns. 15N-thymidine incorporation into newly synthesized DNA of specific cells was quantified at the single-cell level with subcellular resolution by Multiple-isotype imaging mass spectrometry (MIMS) of brain tissue resected for medical reasons. Two adult human patients, a glioblastoma patient and a patient with drug-refractory right temporal lobe epilepsy, were infused for 24 h with 15N-thymidine. Detection of 15N-positive leukocyte nuclei in blood samples from these patients confirmed previous findings by others and demonstrated the appropriateness of this approach to search for the generation of new cells in the adult human brain. 15N-positive neural cells were easily identified in the glioblastoma tissue sample, and the range of the 15N signal suggested that cells that underwent S-phase fully or partially during the 24 h in vivo labeling period, as well as cells generated therefrom, were detected. In contrast, within the hippocampus tissue resected from the epilepsy patient, none of the 2,000 dentate gyrus neurons analyzed was positive for 15N-thymidine uptake, consistent with the notion that the rate of neurogenesis in the adult human hippocampus is rather low. Of note, the likelihood of detecting neurogenesis was reduced because of (i) the low number of cells analyzed, (ii) the fact that hippocampal tissue was explored that may have had reduced neurogenesis due to epilepsy, and (iii) the labeling period of 24 h which may have been too short to capture quiescent neural stem cells. Yet, overall, our approach to enrich NeuN-labeled neuronal nuclei by FACS prior to MIMS analysis provides a promising strategy to quantify even low rates of neurogenesis in the adult human hippocampus after in vivo15N-thymidine infusion. From a general point of view and regarding future perspectives, the in vivo labeling of humans with 15N-thymidine followed by MIMS analysis of brain tissue constitutes a novel approach to study mitotically active cells and their progeny in the brain, and thus allows a broad spectrum of studies of brain physiology and pathology, including microcephaly