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Coronavirus disease 2019 (COVID-19) has affected more than 210 million people worldwide. An optimal therapeutic approach for COVID-19 remains uncertain, to date. Since the history of cancer was linked to higher mortality rates due to COVID-19, the establishment of a safe and effective vaccine coverage is crucial in these patients. However, patients with cancer were mostly excluded from vaccine candidates’ clinical trials. This systematic review aims to investigate the current available evidence about the immunogenicity of COVID-19 vaccines in patients with cancer (PsC).

All prospective studies that evaluated safety and efficacy of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included, with immunogenicity after the first and the second dose as the primary endpoint, when available.

Vaccination against COVID-19 for PsC seems overall safe and immunogenic after well-conducted vaccinations schedules. Yet, the seroconversion rate remains lower, lagged or both compared to the general population. Selleck FF-10101 Patients with hematologic malignancies, especially those receiving B cell depleting agents in the last 12 months are the most at risk of poor seroconversion.

A tailored approach to vaccination may be proposed to PsC, especially on the basis of the type of malignancy and of the specific oncologic treatments received.

A tailored approach to vaccination may be proposed to PsC, especially on the basis of the type of malignancy and of the specific oncologic treatments received.Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vascular remodeling, fibroblast activation and extra-cellular matrix production in excess and autoimmunity. Environmental factors including mainly silica and solvents have been assumed to contribute to the development of SSc, together with genetic factors including gene variants implicated in innate immunity such as IRF5 and STAT4, and epigenetic factors including histone post-translational modifications, DNA hypomethylation, and microRNAs or long- non coding RNAs system were reported to participate in immune activation and fibrosis processes in patients with SSc. A number of animal models of SSc have been set up over the years, including genetic and induced SSc models. These models, together with data obtained from human SSc patients, contributed to better understand the mechanisms contributing to vasculopathy and fibrosis. Alongside the pathophysiological process of SSc, several cellular and molecular actors are involved, such as dysregulations in the innate and adaptive immune cells, of the fibroblast, the implication of pro-inflammatory and pro-fibrosing signaling pathways such as the Wnt, TGF-β pathways or other cytokines, with a strong imprint of oxidative stress. The whole lead to the overactivity of the fibroblast with genetic dysregulation, apoptosis defect, hyperproduction of elements of extracellular matrix, and finally the phenomena of vasculopathy and fibrosis. These advances contribute to open new therapeutic areas through the design of biologics and small molecules.Cushing’s disease (CD) is the most prevalent cause of endogenous hypercortisolism. CD is responsible for multiple co-morbidities and increased mortality. Accurate and prompt diagnosis and optimal treatment are essential to improve the prognosis of CD. However, the diagnosis of CD is probably one of the most difficult in endocrinology and, therefore, diagnostic workup should be performed in an experienced center. Transsphenoidal surgery performed by an expert surgeon is the only therapeutic option that can offer definitive cure and remains the first-line treatment in most patients. Second-line treatments include pharmacotherapy, pituitary radiotherapy and bilateral adrenalectomy. The second-line therapeutic strategy is complex, must be individualized and performed in a multidisciplinary expert center. Symptomatic treatments of persisting co-morbidities after remission, which are responsible for increased mortality and impaired quality of life is an important part of medical management.Clinically non functioning pituitary adenomas (NFPAs) include all pituitary adenomas that are not hormonally active. They are not associated with clinical syndromes such as amenorrhea-galactorrhea (prolactinomas), acromegaly, Cushing’s disease or hyperthyroidism (TSH-secreting adenomas) and are therefore usually diagnosed by signs and symptoms related to a mass effect (headache, visual impairment, sometimes pituitary apoplexy), but also incidentally. Biochemical work up often documents several pituitary insufficiencies. In histopathology, the majority of NFPAs is gonadotroph. In the absence of an established medical therapy, surgery is the mainstay of treatment, unless contraindicated or in particular situations (e.g. small incidentalomas, distance from optic pathways). Resection, generally via a trans-sphenoidal approach (with the help of an endoscope), should be performed by a neurosurgeon with extensive experience in pituitary surgery, in order to maximize the chances of complete resection and to minimize complications. If a tumor remnant persists, watchful waiting is preferred to routine radiotherapy, as long as the tumor residue does not grow and is at distance to the optic pathways. NFPA can sometimes recur even after complete resection, but predicting the individual risk of tumor remnant progression is difficult. Postoperative irradiation is only considered in case of residual tumor growth or relapse, due to its potential side effects.Systemic sclerosis (SSc) is a rare connective tissue disease characterized by skin and visceral fibrosis, vascular hyperreactivity and obliterative vasculopathy. Some of its complications such as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH) and heart involvement can be life-threatening and are associated with a high mortality and a poor prognosis. Many clinical trials were carried out in order to improve the survival and prognosis of SSc patients. The management of SSc is based on the frequent and regular assessment of the potential organ damage, and if present, the establishment of graduated pharmacological therapeutic strategies, associated with non-pharmacological procedures. Several randomized clinical trials have showed significant positive outcomes regarding some specific involvements. link2 Many advances have been made, especially in the field of targeted therapies and personalized medicine, based on specific characteristics of the patient and the SSc.

Femoroacetabular impingement (FAI) after periacetabular osteotomy (PAO) may be affected by both anterior acetabular coverage and femoral head shape. This study aimed to radiographically evaluate the relationship of the combination of acetabular coverage and femoral head shape with the occurrence of FAI after curved PAO.

In this study, 76 hip joints from patients with symptomatic developmental dysplasia of the hip underwent curved PAO. The relationship between the combined postoperative anterior center-edge (CE) and alpha angles (i.e., the combination angle) and the occurrence of postoperative FAI was evaluated. Clinical factors and the pre- and postoperative three-dimensional CE angles, acetabular versions, femoral versions, radiographic alpha angles of the femoral head, and the combination angle were measured and compared to clinical outcomes.

The modified Harris Hip Scores (mHHS), University of California, Los Angeles (UCLA) activity scores, and acetabular coverage angles were significantly improved following curved PAO. ROC curve analysis demonstrated the combination angle over 108° may be a predictive factor for the occurrence of FAI after curved PAO. Multivariate analysis demonstrated that an age <40 years (OR, 6.6; 95% CI, 1.2-36.4, p=0.037) and a combination angle <108° (OR, 9.2; 95% CI, 1.7-50.0, p=0.010) were significantly associated with mHHS ≧90 points.

A combination angle >108° may be a predictive factor for the occurrence of FAI after curved PAO and impaired clinical outcomes. To avoid postoperative FAI, we propose that osteochondroplasty of the femoral head should be performed for patients with preoperative combination angles >90°.

90°.

As indications for elective total hip arthroplasty (THA) expand to younger patients, we sought to 1) compare revision risk following primary elective THA in patients <55 years at the time of their THA to patients aged ≥65 years and 2) identify specific risk factors for revision in patients <55 years.

A US integrated healthcare system’s total joint replacement registry was used to conduct a cohort study including primary elective THA patients aged ≥18 (2001-2018). link3 11,671 patients <55 and 53,106 patients ≥65 years were included. Multiple Cox regression was used to evaluate cause-specific revision risk, including septic revision, aseptic loosening, instability, and periprosthetic fracture (PPF). Stepwise Cox regression was used to identify patient and surgical factors associated with cause-specific revision in patients <55.

Patients <55 had a higher risk of septic revision (hazard ratio [HR]=1.30, 95% confidence interval [CI]=1.02-1.66), aseptic loosening (HR=2.60, 95% CI=1.99-3.40), and instability (HR=1.35, 95% CI=1.09-1.68), but a lower risk for revision for PPF (HR=0.36, 95% CI=0.22-0.59) compared to patients aged ≥65. In the <55 age group, risk factors for septic revision included higher body mass index, drug abuse, and liver disease. Hypertension, anterior approach, and ceramic-on-ceramic associated with aseptic loosening. White race, ASA ≥3, smoker, paralysis, posterior approach, ceramic-on-ceramic, and smaller head diameter associated with instability.

Identified risk factors varied depending on the cause for revision. While septic revisions were related to patient characteristics, more modifiable factors, such as implant or surgical approach, were associated with revision due to aseptic loosening and instability.

Identified risk factors varied depending on the cause for revision. While septic revisions were related to patient characteristics, more modifiable factors, such as implant or surgical approach, were associated with revision due to aseptic loosening and instability.Nonsense-mediated mRNA decay (NMD), a cellular RNA quality system, has been shown to be an ancestral form of cellular antiviral response that can restrict viral infection by targeting viral RNA for degradation or other various mechanisms. In support to this hypothesis, emerging evidences unraveled that viruses have evolved numerous mechanisms to circumvent or modulate the NMD pathway to ensure unhindered replication within the host cell. In this study, we investigated the potential interplay between the cellular NMD pathway and rotavirus (RV). Our data suggested that rotavirus infection resulted in global inhibition of NMD pathway by downregulating the expression of UPF1 in a strain independent manner. UPF1 expression was found to be regulated at the post-transcriptional level by ubiquitin-proteasome mediated degradation pathway. Subsequent studies revealed rotaviral non-structural protein 5 (NSP5) associates with UPF1 and promotes its cullin-dependent proteasome mediated degradation. Furthermore, ectopic expression of UPF1 during RV infection resulted in reduced expression of viral proteins and viral RNAs leading to diminished production of infective rotavirus particles, suggesting the anti-rotaviral role of UPF1.