The Intersection of COVID-19 and Autoimmunity: What is Our Current Understanding?

Viral infections have historically had a complex relationship with autoimmune diseases. For patients with preexisting autoimmune disorders, often complicated by immunosuppressive therapies, there are numerous potential effects of COVID-19, a disease of complex immunobiology, including the potential for an altered natural history of COVID-19 when infected. In addition, individuals without recognized autoimmune disease may be vulnerable to virally induced autoimmunity in the forms of autoantibody formation, as well as the development of clinical immune-mediated inflammatory diseases. Until quite recently in the pandemic, this relationship between COVID-19 and autoimmune diseases has been relatively underexplored; yet such investigation offers potential insights into immunopathogenesis as well as for the development of new immune-based therapeutics. Our review examines this relationship through exploration of a series of questions with relevance to both immunopathogenic mechanisms as well as some clinical implications.

African statue with goiter.

INTRODUCTION: Representations of thyroid swelling, intended as an enlarged anterior neck in the artworks of various periods are sporadically reported in the literature. MATERIALS AND METHODS: An African statue belonging to the African Yoruba culture has been analysed. RESULTS: Members of Ogboni Society in Yoruba culture used this statues to represent a real subject and to communicate between the living and dead. CONCLUSION: The statue reported seems to represent a case of real goiter.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors).

BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT: Patients receiving interleukin-1 (IL-1) -targeted (anakinra, canakinumab or rilonacept) or IL-5-targeted (mepolizumab) agents have a moderate risk of infection and no specific prevention strategies are recommended. The use of IL-6/IL-6 receptor-targeted agents (tocilizumab and siltuximab) is associated with a risk increase similar to that observed with anti-tumour necrosis factor-α agents. IL-12/23-targeted agents (ustekinumab) do not seem to pose a meaningful risk of infection, although screening for latent tuberculosis infection may be considered and antiviral prophylaxis should be given to hepatitis B surface antigen-positive patients. Therapy with IL-17-targeted agents (secukinumab, brodalumab and ixekizumab) may result in the development of mild-to-moderate mucocutaneous candidiasis. Pre-treatment screening for Strongyloides stercoralis and other geohelminths should be considered in patients who come from areas where these are endemic who are receiving IgE-targeted agents (omalizumab). C5-targeted agents (eculizumab) are associated with a markedly increased risk of infection due to encapsulated bacteria, particularly Neisseria spp. Meningococcal vaccination and chemoprophylaxis must be administered 2-4 weeks before initiating eculizumab. Patients with high-risk behaviours and their partners should also be screened for gonococcal infection. IMPLICATIONS: Preventive strategies are particularly encouraged to minimize the occurrence of neisserial infection associated with eculizumab.

Cytology and molecular mechanisms of drug-induced gingival hypertrophy: a rewiew.

INTRODUCTION: Gingival hypertrophy is a frequent condition associated to the increased number of patients taking some categories of drugs. The goal of this work is to emphasize the importance of diagnosis to set a proper therapy. MATERIAL AND METHODS: The plaque accumulation in patients having a poor oral hygiene damages the periodontium and requires the application of strict professional and home hygiene protocols. RESULTS AND CONCLUSION: The drug-induced gingival proliferation knowledge is essential in order to succeed in working with the internist and in planning a precise therapy, without interfering with the metabolism of drugs, often necessary and irreplaceable for patients' health.

Rheumatic immune-related adverse events of checkpoint therapy for cancer: case series of a new nosological entity.

Immunotherapy of cancer with checkpoint inhibitors has been associated with a spectrum of autoimmune and systemic inflammatory reactions known as immune-related adverse events (irAEs). Rheumatic irAEs are infrequently reported and extensively described. Here, we report our experience over an 18-month period with 15 patients evaluated in the rheumatology department for rheumatic irAEs. We identified 13 patients without pre-existing autoimmune disease (AID) who subsequently developed rheumatic irAEs, and two with established AID referred pre-emptively. irAEs encountered included: inflammatory arthritis, sicca syndrome, polymyalgia rheumatica-like symptoms and myositis. All cases required glucocorticoids, and three required a biological agent. Rheumatic irAEs led to temporary or permanent cessation of immunotherapy in all but five patients. One patient with pre-existing AID experienced a flare after starting immunotherapy. Our findings underscore that rheumatic irAEs are complex, at times require additional immunosuppressive therapy, and may influence ongoing immunotherapy regimens for the primary disease. Similar irAEs will be increasingly seen as checkpoint inhibitors adopted as standard of care in the community.

18F-FDG PET/CT versus bone scintigraphy in the follow-up of gastric cancer / 18F-FDG PET/TC en comparación con la gammagrafía ósea en el seguimento del cancer gástrico

A 53-year-old patient underwent a positron emission tomography/computed tomography with 2-fluoro-2-deoxy-d-glucose (18F-FDG PET/CT) in the suspicious of gastric tumor recurrence (mediastinal and abdominal lymph nodes). PET/CT identified only an area of 18F-FDGuptake in the twelfth thoracic vertebrae. Unexpectedly, a bone scintigraphy revealed many "hot" spots changing the diagnosis (single metastasis versus plurimetastatic disease) and impacting on patient's management (AU)

Un paciente de 53 años fue sometido a una tomografía por emisión de positrones-tomografía computarizada con 18F-2-fluoro-2 deoxi-d-glucosa (18F-FDG PET/TC) ante la sospecha de recidiva de cáncer de estómago (nódulos linfáticos en mediastino y abdomen). El PET/TC identificó únicamente una zona de captación de 18F-FDG en la duodécima vértebra torácica. Sorpresivamente, la gammagrafía ósea reveló muchas imágenes hipercaptantes que modificaron el diagnóstico (metástasis única en lugar de metástasis múltiples) con el consiguiente impacto en el tratamiento del paciente (AU)

(18)F-FDG PET/CT versus bone scintigraphy in the follow-up of gastric cancer.

A 53-year-old patient underwent a positron emission tomography/computed tomography with 2-fluoro-2-deoxy-d-glucose ((18)F-FDG PET/CT) in the suspicious of gastric tumor recurrence (mediastinal and abdominal lymph nodes). PET/CT identified only an area of (18)F-FDGuptake in the twelfth thoracic vertebrae. Unexpectedly, a bone scintigraphy revealed many "hot" spots changing the diagnosis (single metastasis versus plurimetastatic disease) and impacting on patient's management.

Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance.

No consensus has previously been formed regarding the types and presentations of infectious pathogens to be considered as 'opportunistic infections' (OIs) within the setting of biologic therapy. We systematically reviewed published literature reporting OIs in the setting of biologic therapy for inflammatory diseases. The review sought to describe the OI definitions used within these studies and the types of OIs reported. These findings informed a consensus committee (infectious diseases and rheumatology specialists) in deliberations regarding the development of a candidate list of infections that should be considered as OIs in the setting of biologic therapy. We reviewed 368 clinical trials (randomised controlled/long-term extension), 195 observational studies and numerous case reports/series. Only 11 observational studies defined OIs within their methods; no consistent OI definition was identified across studies. Across all study formats, the most numerous OIs reported were granulomatous infections. The consensus group developed a working definition for OIs as 'indicator' infections, defined as specific pathogens or presentations of pathogens that 'indicate' the likelihood of an alteration in host immunity in the setting of biologic therapy. Using this framework, consensus was reached upon a list of OIs and case-definitions for their reporting during clinical trials and other studies. Prior studies of OIs in the setting of biologic therapy have used inconsistent definitions. The consensus committee reached agreement upon an OI definition, developed case definitions for reporting of each pathogen, and recommended these be used in future studies to facilitate comparison of infection risk between biologic therapies.

Update on the safety profile of certolizumab pegol in rheumatoid arthritis: an integrated analysis from clinical trials.

OBJECTIVE: To report the long-term safety data of certolizumab pegol (CZP) in rheumatoid arthritis (RA) accumulated as of 30 November 2011. DESIGN: Data from 10 completed randomised controlled trials (RCT) of CZP in RA and several open-label extensions (OLE) were pooled across all doses. Reported adverse events (AE) occurred between the first dose and 84 days after the last dose. All deaths, serious infectious events (SIE) and malignancies were reviewed by external experts, classified according to predefined rules, and validated by an external steering committee. Incidence rates (IR) and event rates (ER) per 100 patient-years (PY) are presented. RESULTS: 4049 RA patients who received CZP were included in the safety pooling; total exposure 9277 PY, mean exposure 2.1 years (range 0.04-7.6). SIE, most frequently pneumonia (IR 0.73/100 PY), were the most common serious AE, occurring more frequently in CZP compared to placebo-treated patients in RCT (IR 5.61/100 PY vs 1.35/100 PY, odds ratio (OR) 4.35, 95% CI 0.65 to 29.30). SIE rates were lower in the CZP-treated population including OLE (ER 4.33/100 PY). 44 patients developed tuberculosis (IR 0.47/100 PY), 39 from high endemic regions. 58 deaths occurred in CZP-exposed patients (IR 0.63/100 PY) and 70 developed malignancies excluding non-melanoma skin cancer (IR 0.76/100 PY), including five lymphomas (IR 0.05/100 PY). CONCLUSIONS: No new or unexpected safety signals associated with CZP emerged in this updated long-term safety analysis. While SIE rates were higher for CZP than for placebo in RCT, the rate decreased with continued exposure to CZP. These rates are consistent with data previously reported for CZP and other tumour necrosis factor inhibitors.

Patients' survival after free flap reconstructive surgery of head and neck squamous cell carcinoma: a retrospective multicentre study.

Head and neck squamous cell carcinoma of the (HNSCC) represents approximately 5% of malignant tumours in Italy. HNSCC are commonly treated with surgery or radiotherapy, or a combination of such therapies. The objectives of treatment are maximum cure rate balanced with organ preservation, restoration of form and function, reduction of morbidities and improvement or maintenance of the patient's quality of life. Immediate reconstructive surgery: local, regional or free flaps are now widely advised in the treatment of these patients. Microsurgical transfer requires expertise, is time and resource consuming, and as a whole requires substantial costs. These considerations introduce some concerns about the wide or indiscriminate use of free flap reconstructive surgery. When considering cost-benefit outcomes of such treatment, the main objective is undoubtedly, survival. This data is underreported in the current literature, whereas functional outcomes of free flaps have been largely diffused and accepted. This study collects data from 1178 patients treated with free flap reconstructive surgery following ablation of HNSCC in a group of Italian tertiary hospitals, all members of the Head & Neck Group affiliated with the Italian Society of Microsurgery. According to many authors, free flap surgery for HNSCC seems to be a beneficial option for treatment even in terms of survival.

Repeated change-of-direction test for collegiate male soccer players.

AIM: The aim of the study was to investigate the applicability of a repeated change-of-direction (RCoD) test for NCAA Division-I male soccer players. METHODS: The RCoD test consisted of 5 diagonal direction changes per repetition with a soccer ball to be struck at the end. Each player performed 15 repetitions with approximately 10 seconds to jog back between repetitions. Data were collected in two sessions. In the first session, 13 players were examined for heart rate responses and blood lactate concentrations. In the second session, 22 players were examined for the test's ability to discriminate the primary from secondary players (78.0±16.1 and 10.4±13.3 minutes per match, respectively). RESULTS: Heart rate data were available only from 9 players due to artifacts. The peak heart rate (200.2±6.6 beats∙min-1: 99.9±3.0% maximum) and blood lactate concentration (14.8±2.4 mmol∙L-1 immediately after) resulted in approximately 3.5 and 6.4-fold increases from the resting values, respectively. These values appear comparable to those during intense periods of soccer matches. In addition, the average repetition time of the test was found to discriminate the primary (4.85±0.23 s) from the secondary players (5.10±0.24 s) (P=0.02). CONCLUSION: The RCoD test appears to induce physiological responses similar to intense periods of soccer matches with respect to heart rate and blood lactate concentration. Players with better average repetition times tend to be those who play major minutes.

High-resolution MRI vessel wall imaging: spatial and temporal patterns of reversible cerebral vasoconstriction syndrome and central nervous system vasculitis.

BACKGROUND AND PURPOSE: High-resolution MR imaging is an emerging tool for evaluating intracranial artery disease. It has an advantage of defining vessel wall characteristics of intracranial vascular diseases. We investigated high-resolution MR imaging arterial wall characteristics of CNS vasculitis and reversible cerebral vasoconstriction syndrome to determine wall pattern changes during a follow-up period. MATERIALS AND METHODS: We retrospectively reviewed 3T-high-resolution MR imaging vessel wall studies performed on 26 patients with a confirmed diagnosis of CNS vasculitis and reversible cerebral vasoconstriction syndrome during a follow-up period. Vessel wall imaging protocol included black-blood contrast-enhanced T1-weighted sequences with fat suppression and a saturation band, and time-of-flight MRA of the circle of Willis. Vessel wall characteristics including enhancement, wall thickening, and lumen narrowing were collected. RESULTS: Thirteen patients with CNS vasculitis and 13 patients with reversible cerebral vasoconstriction syndrome were included. In the CNS vasculitis group, 9 patients showed smooth, concentric wall enhancement and thickening; 3 patients had smooth, eccentric wall enhancement and thickening; and 1 patient was without wall enhancement and thickening. Six of 13 patients had follow-up imaging; 4 patients showed stable smooth, concentric enhancement and thickening; and 2 patients had resoluton of initial imaging findings. In the reversible cerebral vasoconstriction syndrome group, 10 patients showed diffuse, uniform wall thickening with negligible-to-mild enhancement. Nine patients had follow-up imaging, with 8 patients showing complete resolution of the initial findings. CONCLUSIONS: Postgadolinium 3T-high-resolution MR imaging appears to be a feasible tool in differentiating vessel wall patterns of CNS vasculitis and reversible cerebral vasoconstriction syndrome changes during a follow-up period.

Contemporary role of pectoralis major regional flaps in head and neck surgery.

Countless disadvantages of the "old" pectoralis major have been listed while the amazing versatility of the free flap armamentarium gives the opportunity to suit the defect deriving from virtually every ablative head and neck surgery with a tailored reconstruction. Nevertheless, pectoralis major is still the "workhorse" for head and neck reconstruction in developing countries thanks to its ease of harvest, and minimal requirements in term of instrumentation. Furthermore, even in facilities with a high volume of reconstructions by free flaps, a certain number of pectoralis major flaps is still raised every year. The history, present role and current indications of the most widely head and neck reconstructive procedure ever has been reviewed.

Bilateral and multifocal Warthin's tumor of parotid gland: two case reports and review of literature.

Warthin's tumor is the second most common benign neoplasm of the parotid. Most of cases are represented by a single localization, while only a small percentage of patients presents bilateral lesions or unilateral multifocal pattern. Warthin's tumor has an excellent prognosis due to the low rate of recurrence after surgical treatment. Malignant transformation occurs in less than 1% of cases. The aim of this article is to present two unusual cases of Warthin's tumor and an updated review of the latest scientific literature.

A complication following tooth extraction: chronic suppurative osteomyelitis.

UNLABELLED: A complication following tooth extraction: a case report of chronic suppurative osteomyelitis. OBJECTIVE: This article presents a case report about the surgery treatment of chronic suppurative osteomyelitis following a tooth extraction. METHODS: Cone beam computed tomography revealed a sequestrum bone formation that required the sequestrectomy and the debridement of the involved area. The prescription of oral penicillin and metronidazole were necessary after and before the surgery. Also 20 sessions of hyperbaric oxygen therapy were important for the healing of the marrow space. RESULTS: The histologic test confirmed the diagnosis of "Chronic suppurative osteomyelitis". Clinically the post-operative course showed no complications but a good healing of the bone tissue. Culture reports revealed two microorganisms, streptococcus viridans and staphylococcus, that are sensitive to penicillin. CONCLUSIONS: Clinical results confirmed the validity of the sequestrectomy and the debridement of the involved area for the treatment of chronic suppurative osteomyelitis. Such approach has always to be preferred because it guarantees the healing of bone tissue.

High-dose chemotherapy in relapsed or refractory Hodgkin lymphoma patients: a reappraisal of prognostic factors.

High-dose chemotherapy (HDCT) has a consolidated role in the treatment of patients with refractory or relapsed Hodgkin lymphoma (HL). We report clinical results of 97 HL patients who underwent HDCT for refractory (62 patients) or relapsed (35 patients) diseases in Istituto Europeo di Oncologia, from 1995 to 2009. Treatment included high-dose carmustine, etoposide, cytarabine and melphalan in 84 patients and high-dose idarubicin and melphalan in 13 patients with subsequent peripheral hemopoietic stem cells transplant. Outcomes were evaluated in terms of progression-free survival (PFS) and overall survival (OS). In order to identify prognostic factors for outcome, a multivariate analysis for age, sex, disease status (refractory/relapsed), disease stage, B symptoms, presence of extranodal involvement, bulky disease, elevated lactate dehydrogenase, number of previous chemotherapy lines, remission status before transplant, 18F-fluoro-deoxy-d-glucose positron emission tomography ((18) FDG-PET) status before and after transplant was done. A clinical response was achieved in 91% of patients, with complete remissions in 76/97 patients. With a median follow-up of 45 months (range 1-164 months), 5-year PFS and OS were 64% and 71%, respectively. Remission status after induction therapy, 18F-fluoro-deoxy-d-glucose positron emission tomography status before and after transplant were the most important prognostic factors for PFS and OS in univariate or multivariate analyses. HDCT is able to induce a high remission rate and a prolonged PFS in more than 50% of the patients with refractory and relapsed HL.