18F-FDG brain PET hypometabolism in patients with long COVID.

PURPOSE: In the context of the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some patients report functional complaints after apparent recovery from COVID-19. This clinical presentation has been referred as "long COVID." We here present a retrospective analysis of 18F-FDG brain PET of long COVID patients from the same center with a biologically confirmed diagnosis of SARS-CoV-2 infection and persistent functional complaints at least 3 weeks after the initial infection. METHODS: PET scans of 35 patients with long COVID were compared using whole-brain voxel-based analysis to a local database of 44 healthy subjects controlled for age and sex to characterize cerebral hypometabolism. The individual relevance of this metabolic profile was evaluated to classify patients and healthy subjects. Finally, the PET abnormalities were exploratory compared with the patients' characteristics and functional complaints. RESULTS: In comparison to healthy subjects, patients with long COVID exhibited bilateral hypometabolism in the bilateral rectal/orbital gyrus, including the olfactory gyrus; the right temporal lobe, including the amygdala and the hippocampus, extending to the right thalamus; the bilateral pons/medulla brainstem; the bilateral cerebellum (p-voxel < 0.001 uncorrected, p-cluster < 0.05 FWE-corrected). These metabolic clusters were highly discriminant to distinguish patients and healthy subjects (100% correct classification). These clusters of hypometabolism were significantly associated with more numerous functional complaints (brainstem and cerebellar clusters), and all associated with the occurrence of certain symptoms (hyposmia/anosmia, memory/cognitive impairment, pain and insomnia) (p < 0.05). In a more preliminary analysis, the metabolism of the frontal cluster which included the olfactory gyrus was worse in the 7 patients treated by ACE drugs for high blood pressure (p = 0.032), and better in the 3 patients that had used nasal decongestant spray at the infectious stage (p < 0.001). CONCLUSION: This study demonstrates a profile of brain PET hypometabolism in long COVID patients with biologically confirmed SARS-CoV-2 and persistent functional complaints more than 3 weeks after the initial infection symptoms, involving the olfactory gyrus and connected limbic/paralimbic regions, extended to the brainstem and the cerebellum. These hypometabolisms are associated with patients' symptoms, with a biomarker value to identify and potentially follow these patients. The hypometabolism of the frontal cluster, which included the olfactory gyrus, seems to be linked to ACE drugs in patients with high blood pressure, with also a better metabolism of this olfactory region in patients using nasal decongestant spray, suggesting a possible role of ACE receptors as an olfactory gateway for this neurotropism.

18F-FDG brain PET hypometabolism in post-SARS-CoV-2 infection: substrate for persistent/delayed disorders?

PURPOSE: Several brain complications of SARS-CoV-2 infection have been reported. It has been moreover speculated that this neurotropism could potentially cause a delayed outbreak of neuropsychiatric and neurodegenerative diseases of neuroinflammatory origin. A propagation mechanism has been proposed across the cribriform plate of the ethmoid bone, from the nose to the olfactory epithelium, and possibly afterward to other limbic structures, and deeper parts of the brain including the brainstem. METHODS: Review of clinical examination, and whole-brain voxel-based analysis of 18F-FDG PET metabolism in comparison with healthy subjects (p voxel < 0.001, p-cluster < 0.05, uncorrected), of two patients with confirmed diagnosis of SARS-CoV-2 explored at the post-viral stage of the disease. RESULTS: Hypometabolism of the olfactory/rectus gyrus was found on the two patients, especially one with 4-week prolonged anosmia. Additional hypometabolisms were found within amygdala, hippocampus, parahippocampus, cingulate cortex, pre-/post-central gyrus, thalamus/hypothalamus, cerebellum, pons, and medulla in the other patient who complained of delayed onset of a painful syndrome. CONCLUSION: These preliminary findings reinforce the hypotheses of SARS-CoV-2 neurotropism through the olfactory bulb and the possible extension of this impairment to other brain structures. 18F-FDG PET hypometabolism could constitute a cerebral quantitative biomarker of this involvement. Post-viral cohort studies are required to specify the exact relationship between such hypometabolisms and the possible persistent disorders, especially involving cognitive or emotion disturbances, residual respiratory symptoms, or painful complaints.

Diagnostic performance of [(18)F]fluorodeoxyglucose positron emission tomography-computed tomography in cyst infection in patients with autosomal dominant polycystic kidney disease.

Cyst infection is a common complication of autosomal dominant polycystic kidney disease (ADPKD). Diagnosis is challenging with standard imaging techniques. We aimed to evaluate the diagnostic performance of [(18)F]fluorodeoxyglucose positron emission tomography-computed tomography (18-FDG PET-CT) for the diagnosis of cyst infections among ADPKD patients, in comparison with computed tomography (CT) and magnetic resonance imaging (MRI). All APKD patients who underwent 18-FDG PET-CT for suspected cyst infection between 2006 and 2013 in a French teaching hospital were included. Diagnosis of cyst infection was retained a posteriori on an index of clinical suspicion. 18-FDG PET-CT findings were was considered to be positive in cases of cyst wall hypermetabolism. CT or MRI findings were were considered to be positive in cases of cyst wall thickening (and enhancement if contrast medium was injected) and infiltration of the adjacent fat. A control group of ADPKD patients with 18-FDG PET-CT performed for other reasons was included. Thirty-two 18-FDG PET-CT scans were performed in 24 ADPKD patients with suspected cyst infection. A diagnosis of cyst infection was retained in 18 of 32 cases: 14 with positive 18-FDG PET-CT findings, and four false negatives. There were no false positives and no hypermetabolism of cyst walls in nine ADPKD control patients. 18-FDG PET-CT had a sensitivity of 77%, a specificity of 100%, and a negative predictive value of 77%. 18-FDG PET-CT allowed a differential diagnosis in three patients. In contrast, CT had a sensitivity of 7% and a negative predictive value of 35% (p <0.001 vs. 18-FDG PET-CT). Only eight MRI scans were performed. The diagnostic performance of 18-FDG PET-CT is superior to that of CT in cyst infections, for comparable radiation doses and with no injection of nephrotoxic contrast medium, in ADPKD patients.

[Lymphatic drainage of skin areas of head and neck: in vivo approach by the location of the sentinel node]. / Drainage lymphatique des territoires cutanés de la tête et du cou : approche in vivo par la localisation du ganglion sentinelle.

INTRODUCTION: The objective of the study was to determine the preferential territories of drainage of skin areas of the face and neck. This knowledge can guide the strategies of diagnostic (search for primary tumor skin to cervical lymphadenopathy) and treatment (determination of the extent of neck dissection to achieve in case of skin tumor). MATERIALS AND METHODS: This is a retrospective study of the surgical procedures of sentinel node research between January 2003 and April 2011. The lymphoscintigraphic and intraoperative localization of the initial tumor site and sentinel lymph node were collected. RESULTS AND DISCUSSION: One hundred and thirty-seven patients were included in the study. The parotid gland is a privileged territory of drainage of the head and neck skin. At cervical level, the submental region drains the lower and median part of the face (lips and chin). The posterior segments (IIb and V sector) were represented for the posterior locations of the head (ear, vertex), and cervical region.

Sentinel lymph node biopsy in head and neck melanoma: A single institution analysis.

INTRODUCTION: The aim of our study was to analyze a series of patients from our institution who underwent surgery for head and neck cutaneous melanoma and who received sentinel lymph node biopsy (SLNB). MATERIAL AND METHODS: A single-center observational cohort of 120 head and neck melanoma patients was investigated from 2002 to 2011. RESULTS: Among the 107 patients (89.2%) with lymph node identified during lymphoscintigraphy, at least one node was collected and analyzed in 96 patients (90.6%). A positive sentinel lymph node was found in 9.4% of patients. Our data showed higher failure rate of lymphoscintigraphic identification (11.7%), lower rate of SLN positivity (9.4%), and higher false-negative rate of SLNB (24.1%) than the usualfigures established for malignant melanomas in other locations. After a mean follow-up of 38.1 months, the disease-free survival (DFS) rate in the positive SLN group was 53% vs 75% for the negative SLN after 2 years of follow-up and 53% vs 48% after 5 years (p = 0.44). CONCLUSION: The complexity of lymphatic drainage and the anatomy of the cervical region probably accounts for a specificities which result in a lower predictive value of SLNB in head and neck melanoma than in MM in other locations.

[Prognostic value of sentinel lymph node in Merkel cell carcinoma of the head and neck]. / Intérêt pronostique du ganglion sentinelle dans les carcinomes a cellules de Merkel de la tête et du cou.

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin tumor. The aim of our study was to analyze the prognosis of patients operated on for CCM and having no lymph node involvement after analysis of sentinel lymph node (SLN). MATERIAL AND METHOD: This was a retrospective study of 10 cases of CCM stage I or II who received the SLN technique in our institution between 2003 and 2010. RESULTS Among the 10 patients, 7 had an identification of at least one SLN, among which the node could be surgically removed in 6 cases. In cases of failure of SLN technique, a neck dissection +/- parotidectomy was performed. No lymph node metastasis was found in our series. Mean follow-up was 38 months. The overall survival rate was 100% at 2 years and 50% at 5 years. The Disease-free survival was 85% at 2 and 5 years. CONCLUSION: Our results show that the technique of sentinel lymph node is a reliable tool for evaluating nodal status of patients with CCM and that pN0 patients have a good prognosis.

[Role of FDG-PET scanning in stage IIIAN2 non-small cell lung cancer]. / Intérêt de la TEP-FDG dans le cancer pulmonaire non à petites cellules de stade IIIAN2.

Patients with clinical stage IIIAN2 non-small cell lung cancer (NSCLC) are a heterogeneous subgroup in term of prognosis and therapeutic management. The optimal management of this patient group is a major focus for thoracic oncology research and the concept of multimodality treatment has recently been introduced. This approach combines induction chemotherapy or radiochemotherapy followed by surgery in the case of mediastinal lymph node down-staging. positron emission tomography computed tomography with [18F]-fluorodesoxyglucose (FDG-PET) is a molecular and metabolic imaging modality which combines the metabolic data of PET with morphological data from CT. FDG-PET has become a standard in lung cancer management since the different indications listed in the standards, options and recommendations (SOR) of the FNCLCC. However, the potential specific importance of FDG-PET in IIIAN2 patients needs to be addressed further. In this setting, the authors' objective is to review the potential role of metabolic imaging in stage IIIAN2 NSCLC, taking into account new multimodality treatments. In stage IIIAN2, FDG-PET has performed better than morphoradiological imaging for baseline and postinduction lymph node staging, the identification of distant metastasis, and determining prognosis, as well as assessing the response to treatment.

[Recurrent pericarditis revealing a systemic sarcoidosis]. / Péricardite récidivante révélant une sarcoïdose systémique.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disorder of unknown cause, mainly involving the lung and the mediastinum. Involvement of the pericardium and peritoneum is rare, but can be the first manifestation of the disease. CASE REPORT: A 55-year-old female patient was followed-up for a recurrent "idiopathic" pericarditis. Diagnostis was challenged when she secondarily presented with enlarged hilar and mediastinal lymph nodes associated with pulmonary "nodules". Imaging with (18)F-FDG positron emission tomography with computed tomography showed multiple hypermetabolic foci in the mediastinum and peritoneum, which suggested a malignant disorder. Finally, histopathological evaluation of the peritoneal nodules revealed a sarcoidosis. A corticosteroid therapy was initiated and disease course was favourable. CONCLUSION: This case report highlights the importance of a unique explanation for a patient presenting with recurrent pericarditis associated with a systemic disease. Although rare, sarcoidosis should be discussed and diagnostic procedures should be performed to obtain histological confirmation.

[Medico-surgical treatment of occlusion of the left pulmonary artery by extension of ductal tissue (pulmonary coarctation)]. / Traitement médico-chirurgical de l'occlusion de l'artère pulmonaire gauche par extension de tissu ductal (coarctation pulmonaire).

The authors report the results of surgical treatment completed by interventional catheterisation of occlusion of the left pulmonary artery by extension of ductal tissue. Since 2001, 7 patients operated for occlusive coarctation of the left pulmonary artery at an average age of 11 months (3 to 37 months) had a restenosis. The cardiac malformation was pulmonary atresia with ventricular septal defect (N=4), tetralofy of Fallot (N=2) and critical pulmonary valvular stenosis (N=1). Pulmonary artery surgery consisted of resection anastomosis in 4 cases and a plasty in 3 cases. A primary angioplasty was performed 5 to 170 months (median 12 months) later, at an average age and weight of 3.4 years (0.7 to 16.9 years) and 14 Kg (8 to 52 Kg) with implantation of 3 stents. The median diameter increased from 5 mm (1 to 9 mm) to 10 mm (6 to 16 mm). Tc-99m scintigraphy showed an increase in mean left pulmonary perfusion from 9% (6 to 28%) to 28% (18 to 42%). Secondarily, 3 repeat angioplasties were necessary with a total of 6 stents implanted in 7 patients. After an average of 2.9 years (0.8 to 6.3 years) follow-up, the patients were asymptomatic with normal right ventricular pressures and a mean left pulmonary perfusion of 33% (24 to 45%). The authors conclude that the treatment of left pulmonary occlusion by coarctation requires a medico-surgical approach in which angioplasty and stenting complete successfully the surgical revascularisation.

High negative predictive value of slow lymphatic drainage on metastatic node spread detection in malignant limb and trunk cutaneous melanoma.

AIM: Harvesting of the "sentinel lymph node" (SLN) as identified by lymphoscintigraphy (LSG) is becoming increasingly important in the staging of patients with malignant melanoma. The purpose of the current study was to determine whether the appearance time of the LSG had a prognostic value in predicting metastasis dissemination in thick cutaneous malignant melanoma. METHODS: Between July 1999 and July 2003, 88 consecutive patients with histologically proven melanoma with a Breslow's thickness > 1 mm, without clinical or radiological evidence of lymph node involvement or metastasis, prospectively underwent lymphoscintigraphy with 32 Mbq Tc 99m sulfur colloid prior to sentinel lymphadenectomy with sentinel lymph node (SLN) histological examination. RESULTS: LSG was performed in 88 patients with limb and trunk melanoma and identified a total of 149 sentinel nodes. Pathological examination revealed lymph node involvement in 21 patients (24%). All positive SLNs were imaged with a scintigraphic appearance time of less than 30 min. With a scintigraphic appearance time greater than 30 min, the negative predictive value (NPV) of spread in the SLN was 100% (27/27)(CI 87-100%). CONCLUSION: The strong NPV of LSG in identifying "slow" sentinel lymph nodes in patients with no clinical evidence of lymph node involvement suggests that patients could be spared sentinel lymph node biopsy when LSG detects "slow" sentinel lymph nodes. Another prospective study will be required to confirm that the scintigraphic appearance time of sentinel lymph nodes is an important predictive parameter of metastatic disease in sentinel lymph nodes and consequently might reduce the number of sentinel lymph node biopsies.

[Preliminary analysis of sentinel node detection during surgical treatment of head and neck melanoma]. / Etude préliminaire de la détection du ganglion sentinelle dans la prise en charge chirurgicale des mélanomes cervico-faciaux.

OBJECTIVE: The aim of this study was to define reliability of the sentinel lymph node technique in head and neck N0 melanoma. Identification of the sentinel node, which is the first evidence of melanoma metastasis, enables selective node dissection. MATERIALS AND METHODS: Twelve patients with untreated localized cutaneous or mucous N0 melanoma of the head and neck were included in this study. After resection of the sentinel lymph node, type III neck dissection was performed during the same operative time in all twelve patients. RESULTS: The sentinel node was successfully located by preoperative lymphoscintigraphy and confirmed at surgery in eleven patients. Five of these patients had evidence of metastatic node disease, always in the sentinel node. No other metastatic node were found in the neck dissection specimens. For the six other patients with a negative sentinel node, no other metastatic node was found in the neck dissection specimens. CONCLUSION: These preliminary results are promising. The sentinel node can be mapped and identified in most patients. No metastatic node was noted in patients with a negative sentinel node. If these results are confirmed, complete node dissection should only be performed in patients with a positive sentinel node in order to achieve more conservative surgical cure of head and neck melanoma.

Biodistribution of iodine-125 tyramine transforming growth factor alpha antisense oligonucleotide in athymic mice with a human mammary tumour xenograft following intratumoral injection.

The Watson-Crick base pairing rule provides the underlying principle for the antisense (AS) approach to inhibiting gene expression. Transforming growth factor alpha (TGFalpha) was the first growth factor to be associated with tumorigenesis, thus making the TGFalpha (mRNA) a potential target for AS therapy and offering the potential for monitoring of the progression of malignancy by non-invasive imaging with radiolabelled AS phosphodiester. Probe labelling and biodistribution were studied in the present report. A 23-mer oligonucleotide sequence was synthesized and grafted in 5' with a tyramine group which was further radioiodinated. The radiolabelled AS was injected intratumorally in mammary tumour-bearing BALB/c mice (3 weeks after inoculation of 7.10(6)NS2T2A mammary cells). Biodistribution was monitored by sequential scintigraphy and organ radioactivity after autopsy. The 5' tyramine group allowed specific and stable radiolabelling of the AS with 125I. The 125I AS oligonucleotide was rapidly cleared from the tumour by intestine and kidneys. Four hours after intratumoral injection, 6.5%+/-1.5% of the dose was retained in the tumour as non-degraded 125I AS. It is concluded that 5' tyraminylated AS provides information on the biodistribution of AS oligonucleotide following intratumoral injection. These data will contribute to the pharmacology of AS oligonucleotides which can be used for therapy.

Imaging and biodistribution of 125I tyramine oligonucleotide in nude mice bearing human breast tumor. Preliminary report.

Although the range of applications for antisense oligonucleotides is vast, current research concentrates mainly on virology and oncology. We have conducted in vivo and in vitro investigations of radiolabelling and biodistribution of a 22-mer phosphodiester oligonucleotide injected in athymic mice bearing xenograft of human mammary tumor (coculture: MCF7 and fibroblasts strain AF-11). Tumor/healthy tissue ratio of the 22-mer phosphodiester oligonucleotide fixation is high during the 24 hours after injection instead of fast elimination.

[Applications of antisense oligonucleotides in oncology]. / Applications des oligonucléotides antisens en cancérologie.

The development of biotechnologies offers considerable potential for new therapeutical approaches, targetting nucleic acids as information bearing molecules responsible for various pathologies. Gene therapy has, up to now, mainly aimed at compensating deficiencies of gene expression, through complex molecular and cellular constructions. Recently, an increasing interest has focused on short nucleotidic sequences (thus relatively easy to synthetize), or oligonucleotides, which could be able to specifically block the expression of mutated or overexpressed genes. When the target of these oligonucleotides is the mRNA of such genes, the strategy is called "antisense". This strategy has already led to a number of successful results in experimental models in vitro. Much more rare are actual effects in animal models and clinical trials are just being sketched. A review on the current state of the art will enlighten the physiological potential of these new molecules but also underline the still numerous issues before controlling therapeutical applications.

Comparison of SPECT lung perfusion with transbronchial lung biopsy after lung transplantation.

The objective of this study was to evaluate the potential role for single photon-emission computed tomography (SPECT) using technetium 99m-macroaggregated albumin for diagnosing rejection in lung transplant patients. SPECT results were compared with those obtained from transbronchial biopsy (TBB) in patients undergoing bronchoscopy during routine surveillance and in cases of clinical, radiographic, or physiologic suspicion of lung rejection. This prospective, nonrandomized study was conducted by the Marseille Lung Transplant Group, Marseille University Hospitals South. It included 26 lung transplant recipients (19 double-lung, four single-lung, and three heart-lung). For each patient, SPECT lung perfusion was performed before TBB as part of routine surveillance protocol and when clinically indicated. Routine surveillance included TBB at 1, 3, 6, 9, and 12 months and every 6 months thereafter. SPECT was always performed within the 24 h preceding TBB. Whenever the SPECT was abnormal, biopsies were obtained from an area corresponding to a region of hypoperfusion. Results of the study were based on 79 paired SPECT and TBB obtained from 26 patients. Concordance between SPECT and biopsy occurred in 71 instances (89.9%). Among 25 cases of normal SPECT, TBB was normal in 24 and revealed subclinical lung rejection in one. Among 54 cases of abnormal SPECT, TBB was also abnormal in 47 (87.0%), with lung rejection being the abnormality in 23 (46%). For pairs performed as part of the routine surveillance protocol (61 pairs), clinically silent lung rejection was diagnosed in 16 (26.2%). SPECT was abnormal in 15 of 16 instances and normal in only one; this patient had minimal rejection that resolved without treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pulmonary perfusion tomoscintigraphy in pulmonary embolism. Preliminary study]. / Tomoscintigraphie pulmonaire de perfusion dans l'embolie pulmonaire. Etude préliminaire.

Tomoscintigraphy, a method developed over 10 years ago, is little used nowadays for the evaluation of suspected pulmonary embolism. The authors report the results of a preliminary study of 10 patients hospitalised for this condition. Tomoscintigraphy was normal in 2 cases and abnormal in 8 cases. Seven of these 8 patients underwent pulmonary angiography which confirmed the diagnosis of pulmonary embolism in 6 cases. The small number of patients, however, did not allow measurement of the sensitivity and specificity. Tomoscintigraphy, repeated at the 8th day and at the first month, provides an assessment of therapeutic efficacy. Some improvement is observed in all cases from the first control but the amount varies from one subject to another. At one month, 3 of the 6 patients undergoing control tomoscintigraphy had hypoperfusion sequellae. The simplicity of pulmonary tomoscintigraphy makes it a useful investigation for emergency diagnosis and follow-up pulmonary embolism.

Value of MRI and MIBG-I123 scintigraphy in the diagnosis of spinal bone marrow involvement in neuroblastoma in children.

The results of MRI and MIBG scintigraphy performed on the spine of 14 children with neuroblastoma are reported. In 6 cases of diffuse spinal bone marrow tumor infiltration, diagnosis is easier with MIBG scintigraphy than with MRI. In 5 cases, MRI detected hyposignal of the vertebral body without any spinal abnormality on MIBG scintigraphy. A discussion of the reasons for negative MIBG scintigraphy is presented and in these 5 cases, it is suggested that a lateral view of MIBG scintigraphy and HMDP-Tc99m scintigraphy may be performed, even vertebral body biopsy in order to assess bone marrow tumoral infiltration.