Is 18F-FDG PET/CT useful for imaging and management of patients with suspected occult recurrence of cancer?

Rising serum tumor markers may be associated with negative imaging in the presence of cancer. CT and (18)F-FDG PET may yield incongruent results in the assessment of tumor recurrence. The present study evaluates the incremental role of (18)F-FDG PET/CT for the diagnosis and management of cancer patients with increasing levels of tumor markers as the sole indicator of potential recurrence after initial successful treatment. METHODS: Thirty-six cancer patients with increasing levels of tumor markers during follow-up and negative CT underwent (18)F-FDG PET/CT, which showed 111 sites of increased tracer uptake. PET/CT was compared with PET results on a site-based analysis for characterization of (18)F-FDG foci and on a patient-based analysis for diagnosis of recurrence. The clinical impact of PET/CT on further patient management was evaluated. RESULTS: Thirty patients (83%) had recurrence in 85 malignant sites (77%). For the site-based analysis, PET had a sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 96%, 50%, 85%, 85%, and 82%, respectively, as compared with the performance indices of PET/CT of 100%, 89%, 97%, 97%, and 100%, respectively. There was a statistically significant difference between the specificity (P < 0.05) and accuracy (P < 0.001) of PET and PET/CT for precise characterization of suspected lesions. For the patient-based analysis, PET had a sensitivity, specificity, and accuracy of 93%, 50%, and 86%, respectively, as compared with PET/CT with values of 93%, 67%, and 89%, respectively (P = not significant). PET/CT was the single modality that directed further management and treatment planning in 12 patients (33%). CONCLUSION: The results of this study indicate that PET/CT may improve the accuracy of occult cancer detection and further lead to management changes in patients with increasing levels of tumor markers as the sole suspicion of recurrent malignancy.     

Analysis of products diffused into UHMWPE prosthetic components in vivo

Ten UHMWPE hip inserts, five ethylene oxide and five gamma-ray sterilised in air, were retrieved during surgical revision after aseptic failure. Time in situ varied from 6 to 23 years. First implant was carried out for degenerative arthritis in all cases. The retrieved inserts were cut into two parts perpendicular to the articulate surface and a series of 150 microm thick slices were obtained from the cross-section. These were studied by FTIR microscopy and the absorbed products were extracted with cyclohexane for identification by GC/MS and Py/GC/MS. All retrieved UHMWPE components, independent of the sterilisation method, showed species adsorbed on the surface, which were mainly synovial liquid protein components. In addition, species such as cholesterol, fatty esters of cholesterol and squalene, also originating from synovial liquid, were found in the bulk. The concentration of the different species varies depending on the individual patient.     

Genetic basis for individual variations in pain perception and the development of a chronic pain condition

Pain sensitivity varies substantially among humans. A significantpart of the human population develops chronic pain conditionsthat are characterized by heightened pain sensitivity. We identifiedthree genetic variants (haplotypes) of the gene encoding catecholamine-O-methyltransferase(COMT) that we designated as low pain sensitivity (LPS), averagepain sensitivity (APS) and high pain sensitivity (HPS). We showthat these haplotypes encompass 96% of the human population,and five combinations of these haplotypes are strongly associated(P=0.0004) with variation in the sensitivity to experimentalpain. The presence of even a single LPS haplotype diminishes,by as much as 2.3 times, the risk of developing myogenous temporomandibularjoint disorder (TMD), a common musculoskeletal pain condition.The LPS haplotype produces much higher levels of COMT enzymaticactivity when compared with the APS or HPS haplotypes. Inhibitionof COMT in the rat results in a profound increase in pain sensitivity.Thus, COMT activity substantially influences pain sensitivity,and the three major haplotypes determine COMT activity in humansthat inversely correlates with pain sensitivity and the riskof developing TMD.     

The symptom of headache in Emergency Departments. The experience of a neurology emergency department

Although the symptom of headache is a frequent cause of Emergency Department examinations, it is often considered to be of little clinical relevance in comparison with other emergencies and is usually treated only symptomatically. But how frequently does a simple headache mask a severe cerebral pathology? To answer this question, we studied a consecutive series of patients examined at the Neurology Emergency Department of Turin's Ospedale Molinette over a period of three months; the patients were then followed-up for more than two years in order to confirm the diagnoses.Of 215 cases of acute headache, 121 (56%) were essential and 94 (44%) symptomatic; of the latter, 18 (8.3%) were the only clinical manifestation of a severe cerebral pathology (10 hemorrhages, 2 ischemias, 6 tumours). In diagnosing these 18 cases, 72 EEG, 57 CT and 4 rachicentesis examinations were carried out and their diagnostic efficacy is here analysed. Our data show the importance of a careful evaluation of the symptom of headache in Emergency Departments and the need to send any doubtful cases to a facility specialised in coping with such emergencies.

---

Sommario Il sintomo cefalea costituisce un frequente motivo di visita in Pronto Soccorso, spesso considerato di scarsa rilevanza clinica rispetto ad altre urgenze e per lo più trattato solo dal punto di vista sintomatico. Ma in quanti di questi casi una semplice cefalea nasconde una grave patologia cerebrale? A questo proposito abbiamo effettuato uno studio presso il Dipartimento di Emergenza di Neurologia dell'Ospedale Molinette di Torino su una serie consecutiva di pazienti che sono stati visitati per cefalea nell'arco di tre mesi, seguendoli quindi nel tempo con un follow-up di oltre due anni per la verifica diagnostica.Su 215 cefalee acute, le cefalee essenziali sono risultate 121 (56%), e quelle sintomatiche 94 (44%). Tra queste ultime, 18 (8,3%) erano l'unica manifestazione clinica di una grave patologia cerebrale (10 emorragie, 2 ischemie, 6 tumori). Per diagnosticare questi 18 casi sono stati eseguiti 72 EEG, 57 T.C e 4 rachicentesi; di questi esami viene quindi analizzata l'efficacia ai fini diagnostici. Da questi dati emerge quindi l'importanza di un'attenta valutazione del sintomo cefalea in Pronto Soccorso e la necessità di inviare, nei casi dubbi, il paziente in una struttura specializzata per queste emergenze.

     

Migration of murine intestinal dendritic cell subsets upon intrinsic and extrinsic TLR3 stimulation

Initiation of adaptive immunity to particulate antigens in lymph nodes largely depends on their presentation by migratory dendritic cells (DCs). DC subsets differ in their capacity to induce specific types of immunity, allowing subset-specific DC-targeting to influence vaccination and therapy outcomes. Faithful drug design, however, requires exact understanding of subset-specific versus global activation mechanisms. cDC1, the subset of DCs that excel in supporting immunity toward viruses, intracellular bacteria, and tumors, express uniquely high levels of the pattern recognition receptor TLR3. Using various murine genetic models, we show here that both, the cDC1 and cDC2 subsets of cDCs are activated and migrate equally well in response to TLR3 stimulation in a cell extrinsic and TNF-α dependent manner, but that cDC1 show a unique requirement for type I interferon signaling. Our findings reveal common and differing pathways regulating DC subset migration, offering important insights for the design of DC-based vaccination and therapy approaches.     

Long-term male-specific chronic pain via telomere- and p53‑mediated spinal cord cellular senescence

Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53‑mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53‑positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male‑specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male‑specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53‑specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male‑specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.     

Association of depression with agitation in elderly nursing home residents

Agitation is a serious problem for elderly individuals with dementia. It is often the major reason for admission to a restrictive environment such as a nursing home or hospital. The objectives of the current study were to (1) identify the components of agitation embedded in the Psychogeriatric Dependency Rating Scale (PGDRS) and (2) find race, gender, depression, and cognitive deficits associated with the factors extracted from the PGDRS in demographic variables and clinical variables. The study sample comprised 2285 subjects who were admitted to 59 nursing homes across Maryland. The factor analysis of the PGDRS confirmed that agitation is made up of a number of different elements ranging from physical and/or verbal aggression to wandering. Correlates of these elements varied, as did possible treatments. For example, physical and/or verbal aggression often accompanied severe depression, suggesting that treating the depression may alleviate this problem. However, wandering and psychotic behavior may be less amenable to existing treatments as these behaviors were associated with severe cognitive impairment.