Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis

The aim of this study was to systematically review and meta-analyze published data on the diagnostic performance of combined 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the detection of primary tumors in patients with cancer of unknown primary (CUP). A systematic search for relevant studies was performed of the PubMed/MEDLINE and Embase databases. Methodological quality of the included studies was assessed. Reported detection rates, sensitivities and specificities were meta-analyzed. Subgroup analyses were performed if results of individual studies were heterogeneous. The 11 included studies, comprising a total sample size of 433 patients with CUP, had moderate methodological quality. Overall primary tumor detection rate, pooled sensitivity and specificity of FDG-PET/CT were 37%, 84% (95% CI 78–88%) and 84% (95% CI 78–89%), respectively. Sensitivity was heterogeneous across studies (P = 0.0001), whereas specificity was homogeneous across studies (P = 0.2114). Completeness of diagnostic workup before FDG-PET/CT, location of metastases of unknown primary, administration of CT contrast agents, type of FDG-PET/CT images evaluated and way of FDG-PET/CT review did not significantly influence diagnostic performance. In conclusion, FDG-PET/CT can be a useful method for unknown primary tumor detection. Future studies are required to prove the assumed advantage of FDG-PET/CT over FDG-PET alone and to further explore causes of heterogeneity

Clinical and Epidemiological Characteristics of 1,420 European Patients with mild-to-moderate Coronavirus Disease 2019

Background: The clinical presentation of European patients with mild-to-moderate Covid-19 infection is still unknown. Objective: To study the clinical presentation of Covid-19 in Europe. Methods: Patients with positive diagnosis of Covid-19 were recruited from 18 European hospitals. Epidemiological and clinical data were obtained through a standardized questionnaire. Bayesian analysis was used for analyzing the relationship between outcomes. Results: 1,420 patients completed the study (962 females, 30.7% of health care workers). The mean age of patients was 39.17\ub112.09 years. The most common symptoms were headache (70.3%), loss of smell (70.2%), nasal obstruction (67.8%), cough (63.2%), asthenia (63.3%), myalgia (62.5%), rhinorrhea (60.1%), gustatory dysfunction (54.2%) and sore throat (52.9%). Fever was reported by on 45.4%. The mean duration of Covid-19 symptoms of mild-to-moderate cured patients was 11.5\ub15.7 days. The prevalence of symptoms significantly varied according to age and sex. Young patients more frequently had ear, nose, and throat complaints, whereas elderly individuals often presented fever, fatigue and loss of appetite. Loss of smell, headache, nasal obstruction and fatigue were more prevalent in female patients. The loss of smell was a key symptom of mild-to-moderate Covid19 patients and was not associated with nasal obstruction and rhinorrhea. Loss of smell persisted at least 7 days after the disease in 37.5% of cured patients. Conclusion: The clinical presentation of mild-to-moderate Covid-19 substantially varies according to the age and the sex characteristics of patients. Olfactory dysfunction seems to be an important underestimated symptom of mild-to-moderate Covid-19 that needs to be recognized as such by the WHO

Impact of HPV infection on the clinical outcome of p-CAIR trial in head and neck cancer

The purpose of the study was to analyse the influence of HPV infection on the outcome of a randomized clinical trial of conventional (CF) versus 7-days-a-week postoperative radiotherapy (p-CAIR) for squamous cell cancer of the head and neck (SCCHN). Between 2001 and 2004, 279 patients with high-risk SCC of the larynx or cancer of the oral cavity/oropharynx were randomized to receive 63 Gy in fractions of 1.8 Gy given 5 days a week or 7 days a week (Radiother Oncol 87:155–163, 2008). The presence of HPV DNA in 131 archival paraffin blocks was assessed with multiplex quantitative real-time PCR using five consensus primers for the conservative L1 region and molecular beacon probes targeting 14 high-risk HPV subtypes. Following the RT-PCR procedure, we could determine the presence and type of HPV16, HPV18 and the other 12 less frequent oncogenic subtypes. Out of 131 samples, 9 were positive for HPV infection (6.9%), all of them with HPV16 subtype. None of the 65 laryngeal tumours was HPV positive. The 5-year LRC in HPV-positive patients was 100%, compared to 58% in the HPV-negative group (p = 0.02, log-rank test). Amongst 122 patients with HPV-negative tumours, 5-year LRC was 50.3% in p-CF versus 65.2 in p-CAIR (p = 0.37). HPV infection was associated with low expression of EGFR and cyclin D. This study demonstrates a favourable outcome for HPV-positive patients with SCCHN treated with postoperative radiotherapy. While considering the small number of HPV+ tumours, the data set can be considered as hypothesis generating only, the outcome raises new questions on the necessity of aggressive postoperative treatment in HPV+ patients

Two-Week versus Six-Month Sampling Interval in a Short-Term Natural History Study of Oral HPV Infection in an HIV-Positive Cohort

BACKGROUND: Oral HPV infections detected six-months apart were compared to those detected bi-weekly, in an HIV-positive cohort, during the intervening months to elucidate systematic biases introduced into natural history studies by sampling interval. METHODS: Fourteen consecutive oral rinse samples were collected every two weeks for six months from an HIV-positive cohort (n = 112) and evaluated for the presence of 37 HPV types. The cumulative probability of type-specific HPV detection at visits 1 through 14 was determined as a function of infection categorized at visits 1 and 14 as persistent, newly detected, cleared or absent. Transition models were used to evaluate the effect of HPV viral load (measured by RT-PCR for HPV 16, 18, 31, 33, 35) on infection persistence. RESULTS: The average point prevalence of oral HPV infection was similar at two-week and six-month sampling intervals (45% vs. 47%, p = 0.52), but cumulative prevalence was higher with the former (82% vs. 53%, p<0.001) as was the cumulative prevalence of type-specific infections (9.3% vs 3.8%, p<0.0001). Type-specific infections persistent under a six-month sampling interval had a high probability (0.93, 95%CI 0.83-0.98) of detection at 50% or more of the intervening visits and infections that were absent had a high probability (0.94, 95% CI 0.93-0.95) of no interval detection. The odds of detection at any visit significantly increased for each unit increase in HPV viral load at the previous visit. CONCLUSIONS: Six-month sampling is appropriate to model factors associated with type-specific oral HPV infection persistence but may misclassify HPV-exposed individuals as unexposed

Paradox in the pursuit of a critical theorization of the development of self in family relationships

This article starts with my dissatisfaction with the post-structuralist treatment of the production of subjectivity within regulatory discourses and practices due to its neglect of psychological processes. Taking starting points from within the history set out in the previous article, it highlights the paradox for critical psychologists like myself involved in both applying a post-structuralist critique to 'psy' discourses and trying to theorize subjectivity in a way that goes beyond the dualism of individual and society, of psychology and sociology. The relational, or intersubjective, approach to self that originates in object relations psychoanalysis as it emerged in the mid-20th-century UK is central to both of these activities; object of the former and resource for the latter. I explore the paradox that this creates for critical psychology, both epistemological and ontological. In aiming to provide a psycho-social account of self in family relationships, I deploy the radical conceptualisation of intersubjectivity initiated in British object relations theory as a way of going beyond both the individualized self and the neglect of psychological processes in constructionist theorizing subjectivity

Activation of FGF Signaling Mediates Proliferative and Osteogenic Differences between Neural Crest Derived Frontal and Mesoderm Parietal Derived Bone

BACKGROUND: As a culmination of efforts over the last years, our knowledge of the embryonic origins of the mammalian frontal and parietal cranial bones is unambiguous. Progenitor cells that subsequently give rise to frontal bone are of neural crest origin, while parietal bone progenitors arise from paraxial mesoderm. Given the unique qualities of neural crest cells and the clear delineation of the embryonic origins of the calvarial bones, we sought to determine whether mouse neural crest derived frontal bone differs in biology from mesoderm derived parietal bone. METHODS: BrdU incorporation, immunoblotting and osteogenic differentiation assays were performed to investigate the proliferative rate and osteogenic potential of embryonic and postnatal osteoblasts derived from mouse frontal and parietal bones. Co-culture experiments and treatment with conditioned medium harvested from both types of osteoblasts were performed to investigate potential interactions between the two different tissue origin osteoblasts. Immunoblotting techniques were used to investigate the endogenous level of FGF-2 and the activation of three major FGF signaling pathways. Knockdown of FGF Receptor 1 (FgfR1) was employed to inactivate the FGF signaling. RESULTS: Our results demonstrated that striking differences in cell proliferation and osteogenic differentiation between the frontal and parietal bone can be detected already at embryonic stages. The greater proliferation rate, as well as osteogenic capacity of frontal bone derived osteoblasts, were paralleled by an elevated level of FGF-2 protein synthesis. Moreover, an enhanced activation of FGF-signaling pathways was observed in frontal bone derived osteoblasts. Finally, the greater osteogenic potential of frontal derived osteoblasts was dramatically impaired by knocking down FgfR1. CONCLUSIONS: Osteoblasts from mouse neural crest derived frontal bone displayed a greater proliferative and osteogenic potential and endogenous enhanced activation of FGF signaling compared to osteoblasts from mesoderm derived parietal bone. FGF signaling plays a key role in determining biological differences between the two types of osteoblasts