Seasonal Patterns of Body Temperature Daily Rhythms in Group-Living Cape Ground Squirrels Xerus inauris

Organisms respond to cyclical environmental conditions by entraining their endogenous biological rhythms. Such physiological responses are expected to be substantial for species inhabiting arid environments which incur large variations in daily and seasonal ambient temperature (Ta). We measured core body temperature (Tb) daily rhythms of Cape ground squirrels Xerus inauris inhabiting an area of Kalahari grassland for six months from the Austral winter through to the summer. Squirrels inhabited two different areas: an exposed flood plain and a nearby wooded, shady area, and occurred in different social group sizes, defined by the number of individuals that shared a sleeping burrow. Of a suite of environmental variables measured, maximal daily Ta provided the greatest explanatory power for mean Tb whereas sunrise had greatest power for Tb acrophase. There were significant changes in mean Tb and Tb acrophase over time with mean Tb increasing and Tb acrophase becoming earlier as the season progressed. Squirrels also emerged from their burrows earlier and returned to them later over the measurement period. Greater increases in Tb, sometimes in excess of 5°C, were noted during the first hour post emergence, after which Tb remained relatively constant. This is consistent with observations that squirrels entered their burrows during the day to ‘offload’ heat. In addition, greater Tb amplitude values were noted in individuals inhabiting the flood plain compared with the woodland suggesting that squirrels dealt with increased environmental variability by attempting to reduce their Ta-Tb gradient. Finally, there were significant effects of age and group size on Tb with a lower and less variable Tb in younger individuals and those from larger group sizes. These data indicate that Cape ground squirrels have a labile Tb which is sensitive to a number of abiotic and biotic factors and which enables them to be active in a harsh and variable environment

Effects of experiment start time and duration on measurement of standard physicological variables

Duration and start time of respirometry experiments have significant effects on the measurement of basal values for several commonly measured physiological variables (metabolic rate, evaporative water loss and body temperature). A longer measurement duration reduced values for all variables for all start times, and this was an effect of reduced animal activity rather than random sampling. However, there was also an effect of circadian rhythm on the timing of minimal physiological values. Experiment start time had a significant effect on time taken to reach minimal values for all variables, ranging from 4:00 h ± 38 min (body temperature, start time 23:00 h) to 8:54 h ± 52 min (evaporative water loss, start time 17:00 h). It also influenced the time of day that minimal values were obtained, ranging from 22:24 h ± 40 min (carbon dioxide production, start time 15:00 h) to 06:00 h ± 57 min (oxygen consumption, start time 23:00 h), and the minimum values measured. Consequently both measurement duration and experiment start time should be considered in experimental design to account for both a handling and a circadian effect on the animal’s physiology. We suggest that experiments to measure standard physiological variables for small diurnal birds should commence between 17:00 h and 21:00 h, and measurement duration should be at least 9 h

The contribution of Positron Emission Tomography with F-18 fluorodeoxyglucose in the diagnostic work-up of patients with CUP syndrome

Hintergrund und Fragestellung: Das CUP-Syndrom bezeichnet das Auftreten von Metastasen eines unbekannten Primärtumors (Cancer of Unknown Primary). In dieser Situation sind die Lokalisation des Primärtumors, die Ausdehnung der Metastasierung und potentielle tumorbedingte Komplikationen prognosebestimmende Faktoren. Ihre Kenntnis ist entscheidend für die Auswahl einer adäquaten kurativen oder palliativen Therapie. Die Positronen-Emissions-Tomographie mit F-18-Fluorodeoxyglucose (FDG-PET) wird mit diesen Fragestellungen in zunehmendem Maße als diagnostische Methode beim CUP-Syndrom eingesetzt. Ziel dieser Arbeit war es, den Beitrag zu evaluieren, den die FDG-PET im klinischen Alltag an einem nicht-universitären Krankenhaus der Maximalversorgung zur Detektion von Primärtumoren, zur Detektion bzw. zum Ausschluss weiterer, bislang nicht bekannter Metastasen und zur Detektion von potentiellen, therapierelevanten, komplikationsträchtigen Befunden beim CUP-Syndrom liefert. Weiterhin wurde der zusätzliche Nutzen der Computertomographie (CT) in der kombinierten FDG-PET/CT untersucht. Patienten und Methoden: Es erfolgte eine retrospektive Analyse der Untersuchungsergebnisse von 244 Patienten mit CUP-Syndrom, die mittels FDG-PET (Serie A, 169 Patienten) oder FDG-PET/CT (Serie B, 75 Patienten) untersucht wurden. Verlaufsuntersuchungen sowie zeitlich und räumlich separat durchgeführte weitere diagnostische Maßnahmen (wie z.B. CT, MRT, Histologie) wurden verwendet, um die PET- und PET/CT-Befunde zu verifizierten. Die Auswertung erfolgte im Hinblick auf die Detektion des Primärtumors, von Metastasen und von potentiellen tumorbedingten lokalen Komplikationen. Zur Evaluation des zusätzlichen Nutzens der kombinierten PET/CT im Vergleich zur alleinigen PET wurden zum einen die Ergebnisse der Serie A mit denen der Serie B verglichen, zum anderen erfolgte innerhalb der Serie B ein Vergleich der Ergebnisse der zusätzlich separat ausgewerteten PET alleine mit denen der kombinierten PET/CT. Ergebnisse: Insgesamt konnten in Serie A und B in 66/244 Fällen (27%) suspekte Primärtumorherde detektiert und als richtig-positiv verifiziert werden. In nur 5 Fällen (2% aller Untersuchungen) fanden sich falsch-positive Ergebnisse. Für die größte Untergruppe des Gesamtkollektivs, Patienten mit cervikalen Lymphknotenmetastasen, fand sich eine Primärtumor-Detektionsrate von 24% (27 von 112 Untersuchungen). Mit der FDG-PET(/CT) fanden sich bei 44% der Patienten (107 von 244) ossäre Metastasen und/oder multiple hepatische Metastasen und/oder multiple Lungenmetastasen und/oder Metastasen in verschiedenen Körperregionen, so dass diese Patienten einer prognostisch schlechteren Gruppe mit eingeschränkten Therapieoptionen zugeordnet werden mussten. Bei 9% der Patienten (21 von 244) war dies in dem gesamten Ausmaß anhand der Voruntersuchungen nicht erkennbar gewesen. Bei der Untergruppe der Patienten mit CUP-Syndrom mit cervikalen Lymphknotenmetastasen wurden bei 12% der Patienten (6 von 50) extracervikale Metastasen nachgewiesen, so dass für diese Patienten ausschließlich lokoregionäre Therapie¬maßnahmen onkologisch nicht indiziert waren. Der Vergleich der PET-Untersuchungen der Serie A mit den PET/CT-Untersuchungen der Serie B zeigte bezüglich der Detektionsrate von Primärtumoren eine geringe Verbesserung für die PET/CT-Untersuchung von 29% gegenüber 26%, für die Untergruppe der Patienten mit cervikalen Lymphknotenmetastasen erwies sich die Detektionsrate als nahezu identisch (24% gegenüber 25%). Der Vergleich innerhalb der Serie B ergab eine Detektionsrate für Primärtumore von 20% (15 von 75) mit der PET alleine gegenüber 29% (22 von 75) mit der PET/CT (statistisch nicht signifikant). In der Serie B (PET/CT) wurden anhand der CT-Komponente in 20% der Fälle (15 von 75) potentiell behandlungsbedürftige, lokale Komplikationen entdeckt. Schlussfolgerung: In der vorliegenden Studie erweis sich die FDG-PET als ein wichtiges diagnostisches Instrument bei Patienten mit CUP-Syndrom: Sie kann häufig (27%) den Primärtumor detektieren und als Ganzkörperuntersuchung die Ausdehnung der Tumorerkrankung in einem Untersuchungsgang zuverlässig darstellen. Diese Ergebnisse können in vielen Fällen die Basis für eine optimale Therapiewahl sein. Ein wesentlicher Fortschritt in der Anwendung von FDG-PET beim CUP-Syndrom ist die Einführung kombinierter PET/CT-Geräte. Die in dieser Studie gezeigte höhere Detektionsrate von Primärtumoren von 29% bei Anwendung von PET/CT gegenüber 20% bei PET alleine muss allerdings anhand größerer Fallzahlen noch statistisch verlässlich abgesichert werden. Als zusätzlicher und relevanter Vorteil der kombinierten PET/CT-Untersuchung konnten durch die methodenbedingte Verfügbarkeit von Ganzkörper-CT-Daten bei einem wesentlichen Anteil der Patienten potentiell behandlungsbedürftige (auch tumorbedingte), lokale Komplikationen erkannt werden.Background: The term CUP syndrome stands for the occurrence of metastases of an unknown primary tumour (Cancer of Unknown Primary). In this situation, the location of the primary tumour, the extent of metastatic spread and potential local complications are determining factors for the patient’s prognosis. Their proper determination is essential for the selection of an appropriate curative or palliative treatment. Positron Emission Tomography with F-18 fluorodeoxyglucose (FDG-PET) is increasingly used to assess these factors in the diagnostic work-up of patients with CUP syndrome. The aim of this study was to evaluate the contribution of FDG-PET to the detection of the primary tumour, to the assessment of the extent of metastatic spread and to the detection of potentially tumour associated local complications in patients with CUP syndrome in clinical routine in a hospital of maximum care. Furthermore, the additional benefit of computed tomography (CT) in combined FDG-PET/CT was assessed. Patients and Methods: In a retrospective analysis, the examinations of 244 patients with CUP-syndrome undergoing FDG-PET (series A, 169 patients) or FDG-PET/CT (series B, 75 patients) were analysed. Follow-up examinations and additional diagnostic procedures like CT, MRI or biopsies served as a gold standard. The detection of the primary tumour, of metastases and of potential tumour associated local complications was evaluated. To determine the added benefit of PET/CT compared to PET, the results of series A were compared with the results of series B, and in series B, the results of combined PET/CT were compared to the results of an additional evaluation of the PET component alone. Results: In series A and B, a primary tumour was detected and verified as true-positive in a total of 66/244 cases (27%). In 5 cases (2%), false-positive results occurred. In the largest subgroup consisting of patients with cervical lymph node metastases, the primary tumour was detected in 27/112 cases (24%). FDG-PET(/CT) detected bone metastases and/or multiple hepatic metastases and/or multiple lung metastases and/or metastasis in different regions of the body in 107/244 patients (44%), indicating a poorer prognosis and limited therapeutic options. In 21/244 patients (9%), these results were not demonstrated in preceding examinations. In patients presenting with known cervical lymph node metastases only, extracervical metastases were found in 6/50 patients (12%). For these patients, a solely loco-regional therapy was not indicated. The comparison of PET (series A) and PET/CT (series B) demonstrated a higher detection rate of the primary tumour for PET/CT (29%) than for PET (26%), in patients with cervical lymph node metastases the detection rate was nearly identical (25% for PET/CT and 24% for PET). The comparison within series B showed an increase of the detection rate from 20% (15/75) for PET to 29% (22/75) for PET/CT (statistically not significant). In series B (PET/CT), imminent local complications needing treatment were detected by the CT component of the examination in 20% (15/75) of the patients. Conclusion: In this study, FDG-PET proved itself to be an important diagnostic tool for patients with CUP-syndrome. The primary tumour is frequently detected (27%) and the extent of metastatic spread can reliably be evaluated by this whole-body examination, delivering the foundation for the choice of the best treatment option in many cases. The introduction of combined PET/CT scanners is a significant progress for the use of FDG-PET in patients with CUP-syndrome. This study demonstrated a higher detection rate of primary tumours for PET/CT (29%) than for PET (20%), though these results need to be validated in studies with a larger patient collective in order to reach statistical significance. In addition, a clinically relevant advantage of the whole-body CT contained in the combined PET/CT examination is the frequent detection of potential tumour associated local complications needing specific treatment

Is There Any Additional Benefit of Contrast-Enhanced CT as Part of Routine PET/CT Protocols for the Differentiation of Suspicious Incidental Gastrointestinal. 2-Deoxy-F-18-FDG Uptake?

OBJECTIVE: Suspicious incidental gastrointestinal FDG uptake during positron-emission tomography/computed tomography (PET/CT) examinations can be caused by different diseases, including malignancies. However, differentiation with PET alone is difficult. The aim of this study was to investigate the potential of PET alone, contrast-enhanced CT (ceCT), and low-dose CT (ldCT) in routine PET/CT protocols for differentiation of incidental gastrointestinal lesions. MATERIALS AND METHODS: Sixty patients with incidental gastrointestinal lesions who underwent a routine PET/CT protocol with ldCT and ceCT were retrospectively analysed. The PET lesions were evaluated regarding their FDG uptake patterns and the standard uptake value. The anatomical correlates in both CT protocols were compared in regard to the correct lesion classification with the reference standard endoscopy. RESULTS: Sixty-two lesions were found in 60 patients (17 malignant, 10 premalignant, 5 benign, 13 inflammatory, 17 physiological). The differentiation of the FDG uptake patterns did not enable reliable lesion classification. The positive predictive value for pathology was 0.81 for ceCT in PET/CT and 0.70 for ldCT. Malignancies were detected in 100% of the patients by ceCT vs. 29.4% by ldCT. The false negative rate of ceCT for all pathologies was 31.1%, vs. 68.9% for ldCT. False positive results (17/62) could not be excluded sufficiently by either CT protocol. CONCLUSION: PET/ceCT protocols provide additional benefit especially in detecting gastrointestinal malignancies as a cause of suspicious incidental gastrointestinal FDG uptake. However, since follow-up endoscopy cannot be forgone due to the considerable false negative rate even with ceCT, the addition of ceCT to a routine PET/ldCT protocol cannot be recommended for this purpose

[18F]fluoro-ethylcholine-PET Plus 4D-CT (FEC-PET-CT): A Break-Through Tool to Localize the “Negative” Parathyroid Adenoma. One Year Follow Up Results Involving 170 Patients

Background: The diagnostic performance of [18F]fluoro-ethylcholine-PET-CT&4D-CT (FEC-PET&4D-CT) to identify parathyroid adenomas (PA) was analyzed when ultrasound (US) or MIBI-Scan (MS) failed to localize. Postsurgical one year follow-up data are presented. Methods: Patients in whom US and MS delivered either incongruent or entirely negative findings were subjected to FEC-PET&4D-CT and cases from July 2017 to June 2020 were analyzed, retrospectively. Cervical exploration with intraoperative PTH-monitoring (IO-PTH) was performed. Imaging results were correlated to intraoperative findings, and short term and one year postoperative follow-up data. Results: From July 2017 to June 2020 in 171 FEC-PET&4D-CTs 159 (92.9%) PAs were suggested. 147 patients already had surgery, FEC-PET&4D-CT accurately localized in 141; false neg. 4, false pos. 2, global sensitivity 0.97; accuracy 0.96, PPV 0.99. All of the 117 patients that already have completed their 12-month postoperative follow up had normal biochemical parameter, i.e., no signs of persisting disease. However, two cases may have a potential for recurrent disease, for a cure rate of at least 98.3%. Conclusion: FEC-PET&4D-CT shows unprecedented results regarding the accuracy localizing PAs. The one-year-follow-up data demonstrate a high cure rate. We, therefore, suggest FEC-PET-CT as the relevant diagnostic tool for the localization of PAs when US fails to localize PA, especially after previous surgery to the neck