Extension of the frontal sinus into the roof of the optic canal: a cadaveric case report

This case reports a bilateral asymmetrical posterior extension of the frontal sinuses into the orbital roof with an unusual expansion into the roof of the optic canal in a 55-year-old male cadaver. The posterior extensions of the sinus were lined by mucoperiosteum and were separated from the underlying orbital contents and optic nerve by a thin plate of bone. This knowledge of an unusual anatomic variation of the frontal sinus may help understand better the ocular and intracranial complications associated with frontal sinus pathologies.     

Challenges in the management of patients with systemic light chain (AL) amyloidosis during the COVID-19 pandemic

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated coronavirus disease 2019 (COVID-19) is primarily manifested as a respiratory tract infection, but may affect and cause complications in multiple organ systems (cardiovascular, gastrointestinal, kidneys, haematopoietic and immune systems), while no proven specific therapy exists. The challenges associated with COVID-19 are even greater for patients with light chain (AL) amyloidosis, a rare multisystemic disease affecting the heart, kidneys, liver, gastrointestinal and nervous system. Patients with AL amyloidosis may need to receive chemotherapy, which probably increases infection risk. Management of COVID-19 may be particularly challenging in patients with AL amyloidosis, who often present with cardiac dysfunction, nephrotic syndrome, neuropathy, low blood pressure and gastrointestinal symptoms. In addition, patients with AL amyloidosis may be more susceptible to toxicities of drugs used to manage COVID-19. Access to health care may be difficult or limited, diagnosis of AL amyloidosis may be delayed with detrimental consequences and treatment administration may need modification. Both patients and treating physicians need to adapt in a new reality.     

PET/CT in oncology--a major advance

The concept of hardware fusion between positron emission tomography (PET) and computed tomography (CT) has only been introduced commercially in the last 4 years. The advantages of this combined technique over PET alone have become obvious. There is increasing evidence to suggest that PET/CT adds complementary information in staging, re-staging and follow-up in oncology patients, leading to changes in management plans. The present paper is a review of the strengths, weaknesses, current evidence and future directions of this technique.     

Intermediate dose thalidomide (200 mg daily) has comparable efficacy and less toxicity than higher doses in relapsed multiple myeloma

Thalidomide at doses >200 mg has 100% grade 1-2 and 25% grade 3-4 toxicities requiring discontinuation. We report a retrospective study of relapsed myeloma patients treated with thalidomide 200 mg with no dose escalation. Thirty patients were identified; 43% of patients responded with paraprotein decline >75% -- 2 (6%), 50-75% -- 7 (23%), 25-50% -- 4 (14%) and 2 (6%) were stable. All five patients with 13q deletion responded. Only 54% reported grade 1-2 toxicities (none reporting > grade 2) with 5 (17%) discontinuing treatment due to toxicity. Thalidomide 200 mg daily with no dose escalation appears as effective and better tolerated than escalated doses for relapsed myeloma patients.     

Diagnosis,Pathogenesis, Treatment,and Prognosis of Hereditary Fibrinogen Aα-Chain Amyloidosis

Mutations in the fibrinogen Aα-chain gene are the most common cause of hereditary renal amyloidosis in the United Kingdom. Previous reports of fibrinogen Aα-chain amyloidosis have been in isolated kindreds, usually in the context of a novel amyloidogenic mutation. Here, we describe 71 patients with fibrinogen amyloidosis, who were prospectively studied at the UK National Amyloidosis Centre. Median age at presentation was 58 yr, and renal involvement led to diagnosis in all cases. Even after a median follow-up of 4 yr, clinically significant extra-renal disease was rare. Renal histology was characteristic: striking glomerular enlargement with almost complete obliteration of the normal architecture by amyloid deposition and little or no vascular or interstitial amyloid. We discovered four amyloidogenic mutations in fibrinogen (P552H, E540V, T538K, and T525fs). A family history of renal disease was frequently absent. Median time from presentation to ESRD was 4.6 yr, and the estimated median patient survival from presentation was 15.2 yr. Among 44 patients who reached ESRD, median survival was 9.3 yr. Twelve renal transplants survived for a median of 6.0 (0–12.2) yr. Seven grafts had failed after median follow up from transplantation of 5.8 yr, including three from recurrent amyloid after 5.8, 6.0, and 7.4 yr; three grafts failed immediately for surgical reasons and one failed from transplant glomerulopathy after 5.8 yr with no histological evidence of amyloid. At censor, the longest surviving graft was 12.2 yr. In summary, fibrinogen amyloidosis is predominantly a renal disease characterized by variable penetrance, distinctive histological appearance, proteinuria, and progressive renal impairment. Survival is markedly better than observed with systemic AL amyloidosis, and outcomes with renal replacement therapy are comparable to those for age-matched individuals with nondiabetic renal disease.Hereditary non-neuropathic systemic amyloidosis, first described by Ostertag in 1932,¹ is a rare autosomal dominant condition in which progressive amyloid deposition in the viscera, especially the kidneys, frequently leads to organ failure. Mutations in the genes encoding apoAI,^2–12 apoAII,¹³ fibrinogen Aα-chain,^14–17 and lysozyme¹⁸ have been identified as the cause of the disease in different kindreds. The clinical amyloidosis syndromes that accompany the various mutations in these different genes are diverse with respect to age of onset, mode of presentation, pattern of organ distribution, rate of progression, and prognosis.Hereditary fibrinogen amyloidosis (AFib) was first characterized in 1993 in a Peruvian kindred.¹⁴ Patients with AFib present with renal disease and typically progress to ESRD. The natural history and clinical outcome of the disease has been little characterized, previous reports having been only of isolated kindreds, usually in the context of discovery of a novel amyloidogenic fibrinogen mutation.^15–17,19Here we report the clinical presentation, histologic features, molecular basis (including four novel causative fibrinogen Aα-chain gene mutations), and outcome among 71 patients with AFib who were diagnosed and prospectively studied at the U.K. National Amyloidosis Center (NAC) between 1992 and 2007.     

Osteoclast-Associated Receptor (OSCAR) Distribution in the Synovial Tissues of Patients with Active RA and TNF-α and RANKL Regulation of Expression by Osteoclasts <Emphasis Type="Italic">In Vitro</Emphasis>

Osteoclast-associated receptor (OSCAR) is a co-stimulatory receptor in osteoclastogenesis. Synovial tissues from active rheumatoid arthritis (RA) patients express higher levels of OSCAR compared with osteoarthritic and normal patients; however, the comparison of OSCAR levels in different regions of active RA synovium has not been reported. The regulation of OSCAR by TNF-α and receptor activator of NF kappa β ligand (RANKL) in pre-osteoclasts/osteoclasts in vitro is unclear. OSCAR and tartrate-resistant acid phosphatase (TRAP) expression levels did not differ between the cartilage pannus junction (CPJ) and non-CPJ regions in active RA. We demonstrate a similar pattern of OSCAR expression in the CPJ and non-CPJ synovial tissue from patients with active RA. OSCAR was associated with mononuclear cells in both the lining and sub-lining and endothelial cells (von Willebrand factor positive). Pre-osteoclasts (TRAP-positive cells) were present in the lining and sub-lining of both regions. OSCAR messenger RNA (mRNA) expression and release by pre-oscteoclasts/osteoclasts was modulated by RANKL with/without TNF-α in vitro. Osteoclast resorption on dentine slices was significantly greater with TNF-α pre-treatment and RANKL (10 ng/ml) than RANKL 10 or 50 ng/ml alone or RANKL 10 ng/ml with TNF-α given from day 3 post-RANKL. The lower levels of OSCAR mRNA expression corresponded with high osteoclast activity levels.