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Prognostic factors and outcome for nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal cancer (NPC) is a distinct form of cancer of the upper respiratory or digestive tract in which the epidemiologic features, origin, histopathologic types, treatment, and prognosis are different from those associated with other malignant neoplasms of this anatomical area. Recent publications have demonstrated the advantage of aggressive multimodality treatment for advanced NPC. OBJECTIVES: To evaluate the results of standardized treatment of NPC during 11 years and to identify pertinent factors for clinical outcome. METHODS: Between January 1, 1989, and December 31, 2000, 173 patients with newly diagnosed NPC were treated at Instituto Nacional de Cancer. Clinical records and radiographic studies of the patients were retrospectively reviewed. Documented data of the initial presenting symptoms, head and neck examination, radiotherapy protocols, chemotherapy regimens, and surgical technique were analyzed. To determine important prognostic factors, we correlated survival rates with age, clinical stage, tumor extent, histopathological type, and therapeutic approach. The major end point used for assessment was relapse-free survival. Survival curves were estimated by the Kaplan-Meier product-limit method. Multivariate analysis was performed using the Wilcoxon signed rank and Cox proportional hazards regression tests. RESULTS: Most patients (88.5%) had locoregional advanced disease, mostly (53.4%) of the nonkeratinizing subtype. Forty-seven percent of patients had clinical cervical nodal metastases at first consultation. Gross extension of the primary tumor involving the facial bones and skull base was observed in 39.3% and 20.8%, respectively. Just under 75% of patients were treated with radiotherapy (median dose, 6600 cGy), and 25.4% underwent concomitant chemoradiotherapy with adjuvant chemotherapy (cisplatin plus 5-fluorouracil) (median dose, 6800 cGy). The 5-year disease-specific survival for the 173 patients was 32.3%. The disease-specific survival for the radiotherapy group was 22.5%, compared with 61.4% for the chemoradiotherapy plus adjuvant chemotherapy group (P =.004). Factors associated with adverse outcomes were age older than 40 years at treatment (P =.001), advanced TNM stage (P =.002), skull base invasion (P =.004), and facial bone invasion (P<.001). CONCLUSIONS: Compared with radiotherapy alone, concomitant chemoradiotherapy with adjuvant chemotherapy improved the treatment outcome of patients with NPC treated in our institution. Advanced age, local extension, and stage of the disease adversely affected the prognosis in our patients. Compared with reirradiation, salvage brachytherapy and radical neck dissection for local and regional residual or recurrent NPC were associated with increased rates of locoregional control and survival.

Adolescent↗

Voxel-based analysis of confounding effects of age and dementia severity on cerebral metabolism in Alzheimer's disease.

Alzheimer's disease is characterized by early hippocampal lesions, but neuropathological and functional imaging studies have also demonstrated involvement of associative cortices in patients suffering from this illness. New image-processing technologies have led to demonstration of predominant posteromedial cortical metabolic impairment in the disease. Confounding effects of both age and dementia severity on brain metabolism were assessed using categorical and correlational analyses performed with Statistical Parametric Mapping. Posterior cingulate and precuneus metabolism, assessed by positron emission tomography, was significantly correlated with age in a population of 46 patients with probable Alzheimer's disease. Metabolism in posterior cingulate and precuneus was higher in elderly than in younger patients with a diagnosis of Alzheimer's disease, even when dementia severity was taken as a confounding covariate. The data suggest that the sensitivity of positron emission tomography for the diagnosis of Alzheimer's disease is reduced in elderly cases, where less severe pathology is sufficient to induce clinical symptoms of dementia. Conversely, higher posteromedial metabolic impairment in early onset cases may reflect greater density of regional cerebral lesions or major decrease of functional afferences in a richly connected multimodal associative area. Posterior cingulate metabolism was also correlated to dementia severity, even when age was taken as a confounding covariate, whereas metabolism in the hippocampal formation was not shown to correlate with global cognitive deficit. Functional correlation was maintained between posterior cingulate and middle frontal cortex in demented patients as in elderly controls. The key role of posteromedial cortex in cognitive dysfunction assessed in Alzheimer's disease is probably related to its highly integrated position within attentional, visuospatial and memory neuronal networks.

Age Factors↗

Spinal pain syndromes: nociceptive, neuropathic, and psychologic mechanisms.

BACKGROUND: Pain continues to be the main symptom reported by patients. Frequently, clinicians incorrectly diagnose patients and resulting treatments are ineffective, which may promote the development of chronic pain. This situation may arise as a result of a lack of clarity in the literature regarding pain syndromes. OBJECTIVE: To discuss the differences between nociceptive, neuropathic, and psychologic induction of pain and provide important clinical correlates to aid in diagnosis and treatment. DATA SOURCES: The data were accumulated over a period of years by reviewing contemporary articles and books and subsequently retrieving relevant papers. Articles also were selected from MEDLINE searches and from manual library searches. DATA SYNTHESIS: Nociceptive pain syndromes are responsible for the majority of pain complaints in clinical practice. Care must be taken to avoid the common mistake of the diagnosis of neuropathic pain, which can lead to inappropriate treatments. CONCLUSION: Although the treatment of neuropathic pain is difficult, sufficient evidence in the literature demonstrates that the treatment of nociceptive pain should be multimodal and involve spinal manipulation, muscle lengthening/stretching, trigger point therapy, rehabilitation exercises, electrical modalities, a variety of nutritional factors, and mental/emotional support.

Acute Disease↗

Incorporating functional imaging information into radiation treatment.

Three-dimensional treatment planning systems allow the clinician to define tumor and normal anatomy of computed tomograpy (CT) scans and project the result onto a digitally reconstructed radiograph (DRR) for comparison with a simulation or portal film. Unfortunately, the CT scan does not always show the tumor accurately. First, the tumor may have either been removed surgically, or cytoreduced with chemotherapy before the treatment planning scan was taken. Or, the planning CT may not be the ideal imaging modality for a particular tumor, magnetic resonance imaging (MRI) or positron-emission tomography (PET) being much better. In either case, the nonplanning images provide more reliable data as to the position and extent of tumor than do the CT. A 3D/3D registration between the diagnostic and planning image must then be performed to make the data from both images available for the planning process. Methods of performing accurate 3D/3D registration of dissimilar images have been studied extensively by experts in image processing, but the techniques have not yet been fully adopted by the medical community. In addition, there is no standard way of dealing with the multiple tumor volumes that will be generated by full multimodality treatment planning. This article ends with speculation as to the extent to which multimodality image-based treatment planning can improve cancer treatment rates. New imaging modalities such as magnetic resonance spectroscopy, PET, or functional imaging, tuned to the particular tumor type, might reveal more than just the gross tumor volume seen on CT or MRI. One could imagine radiation treatment to many sites in the body under image guidance that would result in cure of metastatic disease, should the cancer be confined to a reasonable number of discrete sites.

Aged↗

Single-cell profiling of trabecular meshwork identifies mitochondrial dysfunction in a glaucoma model that is protected by vitamin B3 treatment.

Since the trabecular meshwork (TM) is central to intraocular pressure (IOP) regulation and glaucoma, a deeper understanding of its genomic landscape is needed. We present a multimodal, single-cell resolution analysis of mouse limbal cells (includes TM). In total, we sequenced 9,394 wild-type TM cell transcriptomes. We discovered three TM cell subtypes with characteristic signature genes validated by immunofluorescence on tissue sections and whole-mounts. The subtypes are robust, being detected in datasets for two diverse mouse strains and in independent data from two institutions. Results show compartmentalized enrichment of critical pathways in specific TM cell subtypes. Distinctive signatures include increased expression of genes responsible for 1) extracellular matrix structure and metabolism (TM1 subtype), 2) secreted ligand signaling to support Schlemm's canal cells (TM2), and 3) contractile and mitochondrial/metabolic activity (TM3). ATAC-sequencing data identified active transcription factors in TM cells, including LMX1B. Mutations in LMX1B cause high IOP and glaucoma. LMX1B is emerging as a key transcription factor for normal mitochondrial function and its expression is much higher in TM3 cells than other limbal cells. To understand the role of LMX1B in TM function and glaucoma, we single-cell sequenced limbal cells from Lmx1b V265D/+ mutant mice (2,491 TM cells). In V265D/+ mice, TM3 cells were uniquely affected by pronounced mitochondrial pathway changes. Mitochondria in TM cells of V265D/+ mice are swollen with a reduced cristae area, further supporting a role for mitochondrial dysfunction in the initiation of IOP elevation in these mice. Importantly, treatment with vitamin B3 (nicotinamide), to enhance mitochondrial function and metabolic resilience, significantly protected Lmx1b mutant mice from IOP elevation.

Journal Article↗

Verification of the optimal probabilistic basis of aural processing in pitch of complex tones.

Periodicity pitch for complex tones has been quantitatively accounted for by a two-stage process of Fourier-frequency analysis subject to random errors and significant nonlinearities, followed by an harmonic pattern recognizer that makes an optimum probabilistic estimate of the fundamental period of musical and speech sounds. The theory predicts that periodicity pitch is a multimodal probabilistic function of a given stimulus. A clear and empirically supported distinction is made between limitations on the pitch mechanism caused by the stochastic nature of aural frequency representation and by the deterministic resolution bandwidths of aural frequency analysis. This model was developed earlier [J. L. Goldstein, J. Acoust. Soc. Am 54, 1496-1516 (1973)] to account for probabilistic data on pitch errors [A. J. M. Houtsma and J. L. Goldstein, J. Acoust. Soc. Am. 51, 520 (1972)] measured with periodic stimuli comprising two successive harmonics. This paper presents new predictions by the theory that were calculated, with computer simulation where needed, for known probabilistic pitch data from stimuli comprising three to six successive harmonics. Predicted pitch errors increase with increasing errors in estimating the frequencies of stimulus harmonics and decrease as more harmonics are added to the stimulus. Optimum processor theory fully accounts for the multicomponent pitch data on the basis of similar errors in estimating component stimulus frequencies as reported earlier, thus providing further evidence for the optimum probabilistic basis of aural signal processing in pitch of complex tones.

Auditory Cortex↗

Gemcitabine (Gemzar) in non-small cell lung cancer.

Of the new chemotherapeutic substances of the last decade, gemcitabine (Gemzar, Eli Lilly) is probably the most valuable for the treatment of early and advanced stage non-small cell lung cancer (NSCLC). When used as a single agent in both chemotherapeutically pretreated and chemotherapy-naive patients, gemcitabine shows an objective tumor regression rate of approximately 20%. Gemcitabine's unique mechanism of action and its lack of overlapping toxicity with other cytotoxic agents also define it as an ideal candidate for combination therapy. Early clinical development has included single-agent first- and second-line treatment, doublet combination regimens and incorporation into multimodality treatment strategies for operable and inoperable locally advanced nonmetastatic NSCLC. Gemcitabine/platinum-based combination chemotherapy has become the most attractive treatment standard for NSCLC patients in good clinical condition. The role of gemcitabine in the concurrent or sequential application of chemo- and radiotherapy for inoperable locally advanced NSCLC has also been addressed in several Phase I and II studies. Based on data available, gemcitabine can be safely administered in combination with radiotherapy. This review summarizes results from representative Phase I, II and III studies in order to underline gemcitabine's clinical importance for patients suffering from early and advanced NSCLC.

Animals↗

[Doxorubicin-induced myocardial damage in elderly patients with hematologic malignancies].

Cardiac function was evaluated in 53 elderly patients with hematologic malignancies who were being treated with doxorubicin (DXR). The left ventricular ejection fraction was measured by radionuclide angiocardiography, the washout rate by 123I-MIBG myocardial SPECT, the extent and severity scores by 123I-BMIPP myocardial SPECT, and the frequency of premature ventricular contractions by Holter electrocardiography. 1) In some patients, both the washout rate and the extent and severity scores were abnormally high before treatment. 2) Because the washout rate correlated with the total dose of DXR, it may be an early indicator of cardiac sympathetic nervous dysfunction. 3) The left ventricular ejection fraction correlated with the extent and severity scores, but not with the washout rate or with the frequency of premature ventricular contractions. 4) The washout rate correlated with the frequency of premature ventricular contractions. These data show that elderly patients had abnormal cardiac function even before treatment with DXR; that cardiac sympathetic dysfunction and cardiac mitochondrial dysfunction developed at total DXR doses of 250 to 300 mg/m2 or higher; and that the left ventricular ejection fraction was less than or equal to 50% in many patients. Consequently, when DXR is used to treat elderly patients, multimodal evaluation of cardiac function is necessary to detect cardiotoxicity and to determine the optimal total dose and the optimal dosage.

Aged↗

Importance of node dissection in relation to neoadjuvant and adjuvant therapy.

Since the advent of effective chemotherapeutic regimens for treating transitional cell carcinoma, multimodal therapy has become part of the contemporary management of patients with muscle-invasive bladder cancer. However, radical cystectomy with pelvic lymphadenectomy remains the cornerstone of treatment for patients with localized and regionally advanced muscle-invasive disease. The effectiveness of chemotherapy models in bladder cancer can depend greatly on the quality of surgery. Unfortunately, without sufficient level I data, the boundaries of lymphadenectomy and the diagnostic and therapeutic ramifications of variations in the pelvic lymph node dissection remain undetermined. This article examines the role of pelvic lymph node dissection during perioperative chemotherapy and discusses the current challenges in establishing standards for lymphadenectomy in patients undergoing treatment for muscle-invasive bladder cancer.

Antineoplastic Combined Chemotherapy Protocols↗

A multimodal assessment of behavioral and cognitive deficits in abused and neglected preschoolers.

42 preschool children who had a previous history of physical abuse, serious neglect, or no prior history of child maltreatment participated in a multimodal assessment of cognitive and behavioral functioning. In addition to standardized tests of cognitive ability and behavioral observations in the classrooms, both the parents and teachers rated the children on several measures. Results show that the abused and neglected children had lower scores on all the measures of cognitive functioning when compared to the matched comparison children. The behavioral observation data from the classrooms, however, were more complex. That is, differences among groups depended on the type of behavior observed. Neglected children engaged in the least number of interactions with other children, and the abused children demonstrated the most aggression. Both parents and teachers rated the maltreated children as more aggressive, less mature, and less ready to learn. In summary, differences between abused, neglected, and comparison children were present on a number of measures, indicating that maltreated children display significant cognitive and social deficits.

Aggression↗

Multimodality image display: desirable frame buffer characteristics.

The intent of this paper is to understand the characteristics of those frame buffers currently used to display images, versus more ideal frame buffers for medical image display purposes. This study is based on current needs and what characteristics might be desirable. Two case examples are presented: (1) a system developed for high quality computer graphics and (2) a system developed for nuclear medicine and radiation therapy treatment planning. Our study considers: (1) defining a pixel depth sufficient to hold data, (2) the desirability of multiple color look-up tables, (3) how cine loops are managed, and (4) display memory size.

Computer Graphics↗

Surgical aspects in the treatment of lung cancer.

PURPOSE OF REVIEW: The treatment of lung cancer has been most successful when surgery is involved. This review is a succinct overview of lung cancer treatment from the thoracic surgeon's perspective over the past 2 years. RECENT FINDINGS: Starting with the evidence-based guidelines developed by the American College of Chest Physicians, the main themes in the literature are a multimodality approach and the miniaturization of surgical approaches. Palliative procedures, staging, and extension of surgery to patients previously thought inoperable are other subjects covered. SUMMARY: We are standing on the verge of having a definitive answer to the 20-year-old question whether adjuvant or neoadjuvant chemotherapy benefits patients with early-stage non-small cell lung cancer. Sufficient data will be available shortly to determine whether minimally invasive surgical approaches yield similar long-term outcomes as traditional approaches.

Carcinoma, Non-Small-Cell Lung↗

Multimodality intraoperative monitoring during complex lumbosacral procedures: indications, techniques, and long-term follow-up review of 61 consecutive cases.

OBJECT: The purpose of this study was to examine the neurological outcomes after complex lumbosacral surgery in patients undergoing multimodality neurophysiological monitoring. METHODS: Sixty-one patients were consecutively enrolled in this study. These patients underwent complex intra- and extradural lumbosacral procedures with concomitant intraoperative electromyography (EMG) monitoring of the lower-limb muscles, external anal and urethral sphincters (EAS and EUS), and lower-limb somatosensory evoked potentials (SSEPs). Long-term (minimum 2-year) clinical follow-up data were obtained in all cases. Most patients were treated for spinal/spinal cord tumors (61%) or adult tethered cord syndrome (25%). Recordable lower-extremity SSEPs were reported in 54 patients (89%). New postoperative neurological deficits occurred in only three patients (4.9%), and remained persistent in only one patient (1.6%) at long-term follow-up examination. In only one of these cases was a significant decrease in SSEP amplitude detected. Spontaneous EMG activity was observed in the lower-extremity muscles and/or EAS and EUS in 51 cases (84%). Intraoperatively, EMG demonstrated activity only in the EUS in 5% of patients and only in the EAS in 28%. In seven patients (11%) spontaneous intraoperative EMG activity was observed in both the EAS and the EUS; however, in only three of these cases was EMG activity recorded in both sphincters simultaneously. In addition to spontaneously recorded EMG activity, electrically evoked EMG activity was also used as an intraoperative adjunct. A bipolar stimulating electrode was used to identify functional neural tissue before undertaking microsurgical dissection in 58 individuals (95%). In the majority of these patients, evoked EMG activity occurred either in one (33%) or in two muscles (9%) simultaneously. The presence of electrically evoked EMG activity in structures encountered during microdissection altered the plan of treatment in 24 cases (42%). CONCLUSIONS: The authors conclude that the combined SSEP and EMG monitoring of lower-limb muscles, EAS, and EUS is a practical and reliable method for obtaining optimal electrophysiological feedback during complex neurosurgical procedures involving the conus medullaris and cauda equina. Analysis of the results indicates that these intraoperative adjunctive modalities positively influence decision making with regard to microsurgery and reduce the risk of perioperative neurological complications. Validation of the clinical value of these approaches, however, will require further assessment in a larger prospective cohort of patients.

Adolescent↗

[Laser therapy and cryomassage in rehabilitation of patients with facial nerve neuropathy].

Cryomassage and its combination with low-intensity infra-red laser radiation have been introduced as a novel treatment of facial nerve neuropathy (FNN) in 32 patients. Electrophysiological investigations (facial thermography, classical electrodiagnosis, electromyography of the mimic muscles) and clinical data including those of long-term follow-up show that neither cryomassage nor infra-red laser radiation studied promote transformation of facial tissues in FNN patients. Use of the above factors is effective in a preclinical stage of forming contracture of the mimic muscles. Special techniques of application of local hypothermia and laser radiation can be used in multimodality treatment of both the established contracture and sluggish paresis of the facial muscles.

Cryotherapy↗

Multimodal strategy for reduction of homologous transfusions in cranio-maxillofacial surgery.

The transfusion of homologous blood carries well-known risks that have prompted efforts to develop alternative techniques. Such measures are of particular interest to patients undergoing elective procedures. A total of 204 patients, out of 1470 patients who consecutively underwent major craniomaxillofacial procedures under general anesthesia over a two-year period, were enrolled in a prospective protocol to reduce homologous transfusion requirements when a blood loss in excess of 500 ml was anticipated. The data were compared with the results of a retrospective control group (n=2890) covering major procedures during the previous four years, when blood-saving measures were applied occasionally, but not based on a global strategy. Techniques for the reduction of homologous transfusions were acute normovolemic hemodilution, controlled moderate hypotension, cell saver and predeposit autologous blood. In addition, preoperative administration of human recombinant erythropoietin was introduced during the last year of the study. These techniques were applied individually or in combination, depending on contraindications specific for each technique, using invasive monitoring in order to maintain intraoperative hemodynamic stability. The goal of this study was to examine the extent to which homologous transfusions may be reduced with the systematic application of transfusion-sparing techniques. Of 204 patients qualifying for the transfusion-sparing protocol, 30 received homologous transfusions. In comparison to the control group, utilization of transfusion-sparing techniques had doubled. The overall reduction in the use of homologous transfusions was highly significant. When acute normovolemic hemodilution, controlled moderate hypotension and the cell saver were used in combination, a greater reduction in homologous transfusions was achieved than with the use of either a single modality or combination of any two. No transfusions were required in patients pretreated with erythropoietin.

Adolescent↗

Longitudinal effects of unimodal and multimodal stimulation on development and interaction of healthy infants.

The effects of unimodal and multimodal stimulation on mental, psychomotor, and behavioral development of healthy full-term infants were examined longitudinally. Subjects were randomly assigned to a control group or one of three experimental conditions: daily administration of a stroking procedure, placement on a multisensory hammock during sleep periods, or a combination of the two treatments. Interventions were conducted during the first 3 months of life. Data are presented on 49 infants who were available for 24-month follow up. The experimental conditions did not significantly affect scores on the Bayley Scales of Infant Development. Eyberg's Child Behavior Inventory, the Nursing Child Assessment Teaching Scales, or the HOME. These findings suggest that supplementary stimulation provided no benefits beyond those associated with natural caregiving and raise questions about the value of the interventions with nonrisk infants in middle-class families. Additional studies need to be conducted with larger samples of healthy infants to test sensory stimulation protocols before they are advocated for widespread consumer use.

Adult↗

Glioblastoma multiforme: morphology and biology.

Glioblastoma multiforme, representing about 50% of all gliomas, encompasses a group of intrinsic tumours of the brain in later years (age peak around 50 years), the morphological hallmarks of which are an ensemble of variations in tumour cell and tissue structure featuring its biological malignancy. Glioblastoma, while sometimes appearing as a distinct "primary" tumour type, is usually accepted as an extreme manifestation of anaplasia and dedifferentiation of glia, mostly astrocytic. The astrocytic nature of most glioblastomas has been confirmed by ultrastructural studies and progressive differentiation of tumours maintained in organotypic tissue culture. Reproducible experimental models are particularly induced by oncogenic RNA (oncorna) viruses. The cell kinetic parameters are similar to those of other solid malignant tumours except for a comparatively low growth fraction of glioblastoma. The frequent occurrence of giant cells as well as of regressive changes with necrosis and vascular responses are indirect (secondary) indicators of malignancy which coincide with histochemical (enzymatic anisochronia) and biochemical data (lower level of glia specific S100 protein than in differentiated gliomas). Vascular proliferation, a characteristic feature of glioblastoma, may occasionally progress to sarcomatous transformation with development of gliosarcomas (mixed glial-mesenchymal tumours). While dissemination of glioblastoma through the cerebrospinal pathways is not uncommon, extraneural distant metastatic spread is rare, and usually observed after craniotomy. The results of modern neuro-oncology support the pathogenetic view that glioblastoma results from neoplastic transformation of glial elements with continuing dedifferentiation. This transformation can be experimentally induced by various factors including oncogenic DNA (oncorna) viruses by using a reverse transcriptase, while there is indirect evidence for an oncorna-virus information in human glioblastoma. The significance of immunological factors in the pathogenesis of brain tumours and in the course of neoplastic transformation of glia is not yet understood, but both morphological and immunological data are in favour of a cell mediated immunological reaction against tumour-specific antibodies. Since immunological factors and changes in cytokinetics are apparently active after the transformed tumour cells proliferate, all available therapeutic methods, including radiation, chemotherapy, and immunotherapy of glioblastoma only influence the final stages of neoplastic development with clinical manifestation of the tumour. In spite of modern combination and multimodality therapy schemes the prognosis of glioblastoma is still poor.

Adult↗

Correlation of continuously monitored regional cerebral blood flow and brain tissue oxygen.

BACKGROUND: The purpose of this study was to investigate the relationship between continuously monitored regional cerebral blood flow (CBF) and brain tissue oxygen (PtiO2). METHODS: Continuous advanced multimodal neuromonitoring including monitoring of PtiO2 (Licox, GMS) and CBF (QFlow, Hemedex) was performed in eight patients after severe subarachnoid haemorrhage (n=5) and traumatic brain injury (n=3) for an average of 9.6 days. Parameters were measured using a flexible polarographic PtiO2-probe and a thermal diffusion CBF-microprobe. FINDINGS: Regarding the whole monitoring period in all patients, the data indicated a significant correlation between CBF and PtiO2 (r=0.36). In 72% of 400 analysed intervals of 30 minutes duration with PtiO2 changes larger than 5 mmHg, a strong correlation between CBF and PtiO2 existed (r>0.6). In 19% of intervals a still statistically significant correlation was observed (0.3<r<0.6). During the remaining 9% no correlation was found (r<0.3). Regarding the clinical stability of the monitoring devices, the CBF monitoring system allowed monitoring of CBF in 64% of the time when PtiO2 monitoring was possible only. Phases of non-monitoring were mostly due to fever of the patient, when the system does not allow monitoring to avoid overheating of the cerebral tissue. CONCLUSIONS: This study suggests a correlation between CBF and PtiO2. The level of PtiO2 seems to be predominately determined by regional CBF, since changes in PtiO2 were correlated in 90% of episodes to simultaneous changes of CBF.

Brain↗