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ID PMID Title PublicationDate abstract
35184115 Medication-Related Osteonecrosis of the Jaw Associated in a Patient Treated With Etanercep 2022 Feb 17 Medication-related osteonecrosis of the jaws (MRONJ) is defined as a pathologic condition affecting the maxillary and mandibular bones arising subsequently to pharmacological treatment with antiresorptive and antiangiogenic drugs.In this case report, the occurrence of MRONJ is described in a 66-year-old female patient affected by rheumatoid arthritis and treated with Etanercept, a Tumor Necrosis Factor (TNF)-α inhibitor. The patient developed a mandibular MRONJ following the extraction of teeth 3.4 and 3.5. The patient was then treated with conservative surgery of the necrotic bone. At 12-month follow-up complete resolution was observed. According to the data presented, the evaluation of the effects of new immunosuppressive biological therapies on the oral cavity appears of utmost importance in preventing the development of MRONJ. Although the risk related to TNF-α inhibitors has not been quantified yet, the clinician should be aware of the potential adverse effects on the oral cavity.
35641389 Radiocarpal Fusion: Indications, Technique, and Modifications. 2022 May 28 Degenerative disorders of the wrist may affect isolated joints and inhibit normal functions of the wrist secondary to pain and stiffness. These processes that affect only the radiocarpal joint may be secondary to posttraumatic osteoarthritis, primary osteoarthritis, or rheumatoid arthritis. Radiocarpal wrist arthrodesis may help preserve some of the native wrist kinematics while alleviating pain and improving the range of motion. However, the surgeon must ensure that the patient's pathologic process primarily affects the radiocarpal articulations while relatively sparing the midcarpal articulations. Depending on the location of the pathology, isolated radiolunate or radioscapholunate arthrodesis have been described to preserve some motion in the midcarpal joint. To maximize motion in the midcarpal joint after radiocarpal arthrodesis, techniques for distal scaphoid and triquetrum excision have been described. We report patient outcomes for various techniques and describe our preferred technique for radioscapholunate arthrodesis using distal scaphoid excision.
35551269 Variants of beta-glucan polysaccharides downregulate autoimmune inflammation. 2022 May 12 Common infections and polysaccharides, from bacteria and yeasts, could trigger psoriasis and psoriatic arthritis (PsA), and possibly rheumatoid arthritis (RA). The objective of this study was to investigate the effects of β-glucan polysaccharides in the effector phase of arthritis and as regulators of psoriasis and PsA-like symptoms in mice. Collagen antibody induced arthritis was studied as a model of RA and mannan-induced psoriasis (MIP) was used as model for psoriasis and PsA, using mice with a mutation of Ncf1 on the B10.Q genetic background, making them highly disease susceptible. The mice were exposed to three common variants: 1,6-β-glucan, 1,3-β-glucan and 1,3-1,6-β-glucan. These β-glucans down-regulated disease in mice if administered simultaneously, before or after mannan. Interestingly, the protection was macrophage mannose receptor (MMR/CD206) dependent with a more pronounced protection long-term than short-term. The number of resident peritoneal macrophages decreased after in vivo challenge with β-glucan and mannan compared to mannan alone, whereas the numbers of infiltrating cells correspondingly increased, further indicating macrophages as key for β-glucan mediated regulation. At the doses tested, β-glucans could not induce arthritis, psoriasis or PsA in wild-type mice. However, β-glucans could ameliorate the PsA-like symptoms representing a new unforeseen possibility to explore for future clinical treatment.
35036874 The calcitonin receptor protects against bone loss and excessive inflammation in collagen 2022 Jan 21 Pharmacological application of teleost calcitonin (CT) has been shown to exert chondroprotective and anti-resorptive effects in patients with rheumatoid arthritis (RA). However, the role of endogenous CT that signals through the calcitonin receptor (CTR) remains elusive. Collagen II antibody-induced arthritis (CAIA) was stimulated in wild type (WT) and CTR-deficient (Calcr(-/-)) mice. Animals were monitored over 10 or 48 days. Joint inflammation, cartilage degradation, and bone erosions were assessed by clinical arthritis score, histology, histomorphometry, gene expression analysis, and μ-computed tomography. CAIA was accompanied by elevated systemic CT levels and CTR expression in the articular cartilage. Inflammation, cartilage degradation, and systemic bone loss were more pronounced in Calcr(-/-) CAIA mice. Expression of various pro-inflammatory, bone resorption, and catabolic cartilage markers were exclusively increased in Calcr(-/-) CAIA mice. Endogenous CT signaling through the mammalian CTR has the potential to protect against joint inflammation, cartilage degradation, and excessive bone remodeling in experimental RA.
35003473 Successful removal of a thrombus in the setting of SVC syndrome using the INARI FlowTrieve 2022 Mar This case report describes a 56-year-old female who presented to the emergency department with diffuse facial and bilateral upper extremity swelling. The patient has a past medical history of Superior vena cava (SVC) syndrome secondary to a clot around her port-a-cath, adenocarcinoma of the lungs status post chemotherapy and radiation, hyperlipidemia, rheumatoid arthritis, diverticulitis status post colon resection, and hypothyroidism. Imaging confirmed the presence of a thrombus obstructing the SVC, likely due to her hypercoagulable state. This case report details the successful removal of a thrombus using the FlowTriever device by INARI in a patient with SVC syndrome. Although indicated for treatment of PE, FlowTriever has shown success in other conditions and nearly eliminates the risk of bleeding without the need for administering thrombolytics, as explained below in the setting of SVC syndrome.
35574060 Corrigendum to "Nanoenzyme engineered neutrophil-derived exosomes attenuate joint injury i [This corrects the article DOI: 10.1016/j.bioactmat.2022.02.017.].
35144348 [Chinese expert consensus on clinical diagnosis and treatment of immune-related peripheral 2022 Feb 11 Immune-related keratopathy is a type of corneal disease caused by systemic or ocular immune disorders, with abnormal immune response to normal or degenerated corneal tissue, leading to the damage to ocular structure and function and the visual impairment. It mainly includes Mooren's ulcer, blepharokeratoconjunctivitis, and peripheral corneal ulcer associated with rheumatoid arthritis or other systemic immune diseases. Due to the diverse clinical manifestations, repeated and prolonged disease course, and high misdiagnosis and missed diagnosis rates, immune-related peripheral keratopathy often has a poor prognosis. The Cornea Group of Ophthalmology Branch of Chinese Medical Association has convened experts to discuss and reach the current consensus, focusing on the principle of diagnosis, differential diagnosis, and treatment of immune-related peripheral keratopathy, which would play an important clinical guiding role in the early detection, timely intervention, and proper treatment of the disease.
29939661 Knee Osteoarthritis. 2022 Jan Knee osteoarthritis (OA), also known as degenerative joint disease, is typically the result of wear and tear and progressive loss of articular cartilage. It is most common in the elderly. Knee osteoarthritis can be divided into two types, primary and secondary. Primary osteoarthritis is articular degeneration without any apparent underlying reason. Secondary osteoarthritis is the consequence of either an abnormal concentration of force across the joint as with post-traumatic causes or abnormal articular cartilage, such as rheumatoid arthritis (RA). Osteoarthritis is typically a progressive disease that may eventually lead to disability. The intensity of the clinical symptoms may vary for each individual. However, they typically become more severe, more frequent, and more debilitating over time. The rate of progression also varies for each individual. Common clinical symptoms include knee pain that is gradual in onset and worse with activity, knee stiffness and swelling, pain after prolonged sitting or resting, and pain that worsens over time. Treatment for knee osteoarthritis begins with conservative methods and progresses to surgical treatment options when conservative treatment fails. While medications can help slow the progression of RA and other inflammatory conditions, no proven disease-modifying agents for the treatment of knee osteoarthritis currently exist.
35349410 Human epididymis protein 4 as a new diagnostic biomarker for rheumatoid arthritis-associat 2022 Mar 23 OBJECTIVES: This study aimed to evaluate the role of human epididymis protein 4 (HE4) in the diagnosis and determination of the severity of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. METHODS: HE4 levels in peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) samples were determined via electrochemiluminescence immunoassays in 102 RA patients (46 patients with ILD and 56 patients without ILD) and 51 healthy controls (HCs). RESULTS: Serum HE4 levels were significantly higher in RA-ILD patients (141.8±65.92 pmol/l) than those in the RA-no ILD patients (82.67±26.17 pmol/l) and healthy controls (35.72±7.6 pmol/l) (p<0.0001). Consistent with serum HE4 levels, BALF HE4 levels were significantly higher in RA-ILD patients (637.6±154.9 pmol/l) than those in the RA-no ILD patients (427.3±111.2 pmol/l) and healthy controls (206.9±30.46 pmol/l) (p<0.0001). In RA-ILD patients, HE4 levels were positively correlated with HRCT (high-resolution computed tomography) fibrosis scores, whereas a significant inverse relationship was found between HE4 levels and lung function parameters (such as, diffusion capacity of the lung for carbon monoxide (DLCO)). The logistic regression analysis showed that high levels of BALF HE4 (≥595 pmol/l) were associated with RA-ILD (odds ratio [OR] =8.09; 95% confidence interval [CI] =1.317-49.682; p=0.024). CONCLUSIONS: Serum and BALF HE4 levels were elevated in RA-ILD patients and strongly associated with the severity of ILD, thus supporting their potential clinical value as a new diagnostic aid for patients with RA-ILD.
34468080 Assessment of the Effect of Filgotinib on the Pharmacokinetics of Atorvastatin, Pravastati 2022 Feb Filgotinib, an oral Janus kinase-1 preferential inhibitor, is approved in Europe and Japan for adults with rheumatoid arthritis. Patients with rheumatoid arthritis are at higher risk of cardiovascular morbidity/mortality; thus, it is important to understand potential drug-drug interactions of filgotinib with lipid-lowering agents. This open-label, randomized, 2-way crossover study evaluated the pharmacokinetics of atorvastatin, pravastatin, and rosuvastatin with and without filgotinib coadministration. Healthy participants (N = 27) received single doses of atorvastatin (40 mg) and of a pravastatin (40 mg)/rosuvastatin (10 mg) cocktail-alone or with filgotinib (200 mg once daily for 11 days)-on 2 different occasions with washout in between. Serial pharmacokinetic blood samples were collected, and safety was assessed. Pharmacokinetic parameters were evaluated using 90% confidence intervals (CI) of the geometric least-squares mean (GLSM) ratio of the test treatment (statin coadministration with filgotinib) vs statin alone, with prespecified lack-of-interaction bounds of 0.70 to 1.43. Coadministration of filgotinib did not affect atorvastatin area under the plasma concentration-time curve extrapolated to infinity (AUC(inf) ; [GLSM ratios (90% CI): 0.91 (0.84-0.99)]), but maximum concentration [C(max) ] was slightly lower [0.82 (0.69-0.99)]. The exposure of 2-hydroxy-atorvastatin was unaffected (GLSM ratios [90% CI], 0.98 [0.81-1.19] for C(max) ; 1.11 [1.02-1.22] for AUC(inf) ). Pravastatin AUC(inf) was also unaffected (GLSM ratios, 1.22 [1.05-1.41], but C(max) was slightly higher 1.25 [1.01-1.54]). Rosuvastatin exposure was moderately higher with filgotinib coadministration-GLSM ratios (90% CI), 1.68 (1.43-1.97) for C(max) ; 1.42 (1.30-1.57) for AUC(inf) -but this was not considered clinically relevant. These results indicate that filgotinib has no clinically meaningful effect on exposure of atorvastatin, pravastatin, or rosuvastatin.
34270700 Socio-demographic determinants in the evolution of pain in inflammatory rheumatic diseases 2022 Apr 11 OBJECTIVE: To determine whether socio-demographic factors are associated with heterogeneity in pain evolution in inflammatory rheumatic diseases (IRDs) after accounting for disease-specific characteristics in a system with universal health care. METHODS: This analysis included the data from two prospective observational cohorts of early IRDs (ESPOIR for early RA and DESIR for early SpA). Data on pain was measured, respectively, on 13 and 9 occasions spanning 10 and 6 years of follow-up using the Short-Form 36 bodily pain score for 810 participants of ESPOIR, and 679 participants of DESIR. Linear mixed models were used to characterize differences in pain evolution as a function of age (tertiles), sex, ethnicity, education, marital, and professional status, after accounting for disease-related, treatment, lifestyle, and health factors. RESULTS: While transitioning from early (disease duration ≤6 months for RA and ≤3 years for SpA) to long-standing disease, differences in pain evolution emerged as a function of age (P < 0.001), sex (P = 0.050), and ethnicity (P = 0.001) in RA, and as a function of age (P = 0.048) in SpA; younger age, males, and Caucasians exhibited lower pain in the latter phases of both diseases. Highly educated participants (RA, β = -3.8, P = 0.007; SpA, β = -6.0, P < 0.001) for both diseases, and Caucasians (β = -5.6, P = 0.021) for SpA presented with low pain early in the disease, with no changes throughout disease course. CONCLUSION: Being older, female, non-Caucasian and having lower education was found to be associated with worse pain in early and/or long-standing IRDs, despite universally accessible health-care. Early identification of at-risk populations and implementation of multidisciplinary strategies may reduce patient-reported health outcome disparities. TRIAL REGISTRATION REGISTRATIONS: ESPOIR: ClinicalTrials.gov, www.clinicaltrials.gov, NCT03666091. DESIR: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01648907.
34902784 Nanoparticle conjugated with aptamer anti-MUC1/Y for inflammatory arthritis. 2022 Mar Aptamers may form well-defined three-dimensional structures binding with high affinity and stability to a specific receptor. The aptamer anti-MUC1 isoform Y is one the most used due the affinity to MUC1, which is overexpressed in several types of cancer and inflammation process. In this study we have developed, characterized, in vitro as in vivo evaluated a nanoaptamer (anti-MUC1/Y) as a nanoagent for rheumatoid arthritis treatment. The results showed that a nanoaptamer with a size range of 241 nm was produced. The entrapment efficacy was 90% with a biodistribution showing a high hepatic uptake (>98%). The results in vivo showed a potent effect in arthritis experimental model, especially in low doses. The results corroborate the applicability of this nanosystem for RA treatment.
35303787 MAPK-Activated Protein Kinases: Servant or Partner? 2022 Feb 18 Mitogen-activated protein kinase (MAPK)-activated protein kinases (MAPKAPKs) are defined by their exclusive activation by MAPKs. They can be activated by classical and atypical MAPKs that have been stimulated by mitogens and various stresses. Genetic deletions of MAPKAPKs and availability of highly specific small-molecule inhibitors have continuously increased our functional understanding of these kinases. MAPKAPKs cooperate in the regulation of gene expression at the level of transcription; RNA processing, export, and stability; and protein synthesis. The diversity of stimuli for MAPK activation, the cross talk between the different MAPKs and MAPKAPKs, and the specific substrate pattern of MAPKAPKs orchestrate immediate-early and inflammatory responses in space and time and ensure proper control of cell growth, differentiation, and cell behavior. Hence, MAPKAPKs are promising targets for cancer therapy and treatments for conditions of acute and chronic inflammation, such as cytokine storms and rheumatoid arthritis. Expected final online publication date for the Annual Review of Biochemistry, Volume 91 is June 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
35394009 Controversies in rheumatology: Ultrasound for monitoring of RA - do we need it? 2022 Apr 8 Clinical joint examination is the cornerstone for evaluation of patients with rheumatoid arthritis (RA). However, since large discrepancies have been shown even between experienced rheumatologists in evaluation of joint inflammation, and tender joints may have limited value in reflecting inflammation, ultrasound has in the last decennials been introduced in the clinical assessments of RA patients. Ultrasound has high accordance with other imaging modalities and enables detection of clinically difficult pathologies and contributes to assessments of joints difficult to evaluate clinically. However, there is no general agreement on the optimal use of ultrasound in rheumatology and the prevalence of machines as well as the level of experience is highly different across the countries. In addition, standardized use of ultrasound in treat-to-target follow-up of RA patients was found not to have any added value. Thus, how to use ultrasound in monitoring of RA patients is open for debate. The present article will discuss the pros and cons for using ultrasound in the clinical setting.
35613504 Immune tolerance therapies for autoimmune diseases: Shifting the goalpost to cure. 2022 May 22 Autoimmune rheumatic diseases are characterised by an autoimmune inflammatory response to antigens of synovial tissue, muscles, and other organs. While the prognosis of these disorders has improved remarkably over recent years with the advent of biological therapeutics, prolonged drug-free remission is still rare. Advances in the understanding of the immunopathogenesis and response to immunotherapy of seropositive autoimmune rheumatic diseases, such as rheumatoid arthritis systemic lupus erythematosus, type 1 diabetes and the autoimmune-like celiac disease have revealed novel therapeutic opportunities. An improved understanding of preclinical disease states and how disease risk can be mitigated underpins further development of therapeutics to restore tolerance for disease prevention or early disease interception.
35126154 The Effects of Crocin on Bone and Cartilage Diseases. 2021 Crocin, the main biologically active carotenoid of saffron, generally is derived from the dried trifid stigma of Crocus sativus L. Many studies have demonstrated that crocin has several therapeutic effects on biological systems through its anti-oxidant and anti-inflammatory properties. The wide range of crocin activities is believed to be because of its ability to anchor to many proteins, triggering some cellular pathways responsible for cell proliferation and differentiation. It also has therapeutic potentials in arthritis, osteoarthritis, rheumatoid arthritis, and articular pain probably due to its anti-inflammatory properties. Anti-apoptotic effects, as well as osteoclast inhibition effects of crocin, have suggested it as a natural substance to treat osteoporosis and degenerative disease of bone and cartilage. Different mechanisms underlying crocin effects on bone and cartilage repair have been investigated, but remain to be fully elucidated. The present review aims to undertake current knowledge on the effects of crocin on bone and cartilage degenerative diseases with an emphasis on its proliferative and differentiative properties in mesenchymal stem cells.
35262276 Unmet Needs in Rheumatoid Arthritis: A Subgroup of Patients With High Levels of Pain, Fati 2022 Mar 9 OBJECTIVE: The study objective was to identify subgroups of patients with rheumatoid arthritis (RA) based on their health status 3 years after diagnosis and to assess potential associations to clinical presentation at diagnosis. METHODS: This observational study included patients with RA with 3-year follow-up data from the Swedish Epidemiological Investigation of RA study, collected from 2011 to 2018. Hierarchical agglomerative cluster analysis, based on symptoms of pain, fatigue, sleep quality, mood disturbances, and overall health-related quality of life (HRQoL), was used to identify subgroups 3 years after diagnosis. Modified Poisson regression was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for the associations between the subgroups and patient characteristics at diagnosis. RESULTS: A total of 1055 individuals constituted the study population, of whom 1011 had complete data on the clustering variables and were therefore eligible for analysis (73% women, median age 58 years). The following three clusters were identified: cluster 1 (466 patients with good health status), cluster 2 (398 patients in an intermediate group), and cluster 3 (147 patients with high levels of pain and fatigue together with markedly impaired HRQoL). Cluster 3 was associated to higher baseline pain (RR: 3.71 [95% CI: 2.14-6.41]), global health (RR: 6.60 [95% CI: 3.53-12.33]), and the Stanford Health Assessment Questionnaire (RR: 4.40 [95% CI: 2.46-7.87]), compared with cluster 1 (highest compared with lowest quartiles). An inverse association was seen for baseline swollen joint count (RR: 0.51 [95% CI: 0.34-0.85]). CONCLUSION: A subgroup of patients with RA experience high levels of pain, fatigue, and psychosocial distress 3 years after diagnosis. This subgroup already displayed pronounced pain and functional disabilities at diagnosis.
34970704 Comparison of AI-powered 3D automated ultrasound tomography with standard handheld ultraso 2022 Jul OBJECTIVE: To assess the ability of a newly developed AI-powered ultrasound 3D hand scanner to visualize joint structures in healthy hands and detect degenerative changes in cadaveric hands. MATERIALS AND METHODS: Twelve individuals (6 males, 6 females, age 43.5 ± 17.8 years) underwent four scans with the 3D ultrasound tomograph (right and left hand, dorsal and palmar, respectively) as well as four sets of handheld ultrasound of predefined anatomic regions. The 3D ultrasound tomographic images and the standard handheld ultrasound images were assessed by two radiologists with regard to visibility of bone contour, joint capsule and space, and tendons. In addition, three cadaveric hands were scanned with the 3D ultrasound tomograph and CT. RESULTS: Mean scan time for both hands was significantly faster with handheld ultrasound (10 min 30 s ± 95 s) compared to 3D ultrasound tomography (32 min 9 s ± 6 s; p < 0.001). Interreader and intermodality agreement was moderate (0.4 < κ ≤ 0.6) to substantial (0.6 < κ ≤ 0.8). Overall visibility of joint structures was comparable between the modalities at the level of the wrist (p = 0.408), and significantly better with handheld ultrasound at the level of the finger joints and the thumb (both p < 0.001). The 3D ultrasound tomograph was able to detect osteophytes in cadaveric hands which were confirmed by CT. CONCLUSION: The AI-powered 3D ultrasound tomograph was able to visualize joint structures in healthy hands and singular osteophytes in cadaveric hands. Further technical improvements are necessary to shorten scan times and improve automated scanning of the finger joints and the thumb.
34963199 Caspase-8 Variant G Regulates Rheumatoid Arthritis Fibroblast-Like Synoviocyte Aggressive 2022 Apr OBJECTIVE: Fibroblast-like synoviocytes (FLS) play a pivotal role in rheumatoid arthritis (RA) by contributing to synovial inflammation and progressive joint damage. An imprinted epigenetic state is associated with the FLS aggressive phenotype. We identified CASP8 (encoding for caspase-8) as a differentially marked gene and evaluated its pathogenic role in RA FLSs. METHODS: RA FLS lines were obtained from synovial tissues at arthroplasty and used at passage 5-8. Caspase-8 was silenced using small interfering RNA, and its effect was determined in cell adhesion, migration and invasion assays. Quantitative reverse transcription PCR and western blot were used to assess gene and protein expression, respectively. A caspase-8 selective inhibitor was used determine the role of enzymatic activity on FLS migration and invasion. Caspase-8 isoform transcripts and epigenetic marks in FLSs were analyzed in FLS public databases. Crystal structures of caspase-8B and G were determined. RESULTS: Caspase-8 deficiency in RA FLSs reduced cell adhesion, migration, and invasion independent of its catalytic activity. Epigenetic and transcriptomic analyses of RA FLSs revealed that a specific caspase-8 isoform, variant G, is the dominant isoform expressed (~80% of total caspase-8) and induced by PDGF. The crystal structures of caspase-8 variant G and B were identical except for a unique unstructured 59 amino acid N-terminal domain in variant G. Selective knockdown of caspase-8G was solely responsible for the effects of caspase-8 on calpain activity and cell invasion in FLS. CONCLUSION: Blocking caspase-8 variant G could decrease cell invasion in diseases like RA without the potential deleterious effects of nonspecific caspase-8 inhibition.
35020852 SARS-CoV-2 vaccine responses following CD20-depletion treatment in patients with haematolo 2022 Jan 28 B-cell-depleting agents are among the most commonly used drugs to treat haemato-oncological and autoimmune diseases. They rapidly induce a state of peripheral B-cell aplasia with the potential to interfere with nascent vaccine responses, particularly to novel antigens. We have examined the relationship between B-cell reconstitution and SARS-CoV-2 vaccine responses in two cohorts of patients previously exposed to B-cell-depleting agents: a cohort of patients treated for haematological B-cell malignancy and another treated for rheumatological disease. B-cell depletion severely impairs vaccine responsiveness in the first 6 months after administration: SARS-CoV-2 antibody seroprevalence was 42.2% and 33.3% in the haemato-oncological patients and rheumatology patients, respectively and 22.7% in patients vaccinated while actively receiving anti-lymphoma chemotherapy. After the first 6 months, vaccine responsiveness significantly improved during early B-cell reconstitution; however, the kinetics of reconstitution was significantly faster in haemato-oncology patients. The AstraZeneca ChAdOx1 nCoV-19 vaccine and the Pfizer BioNTech 162b vaccine induced equivalent vaccine responses; however, shorter intervals between vaccine doses (<1 m) improved the magnitude of the antibody response in haeamto-oncology patients. In a subgroup of haemato-oncology patients, with historic exposure to B-cell-depleting agents (>36 m previously), vaccine non-responsiveness was independent of peripheral B-cell reconstitution. The findings have important implications for primary vaccination and booster vaccination strategies in individuals clinically vulnerable to SARS-CoV-2.