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Journal of Clinical Medicine Jun 2022Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory disease of the pilosebaceous unit leading to formation of painful, inflammatory nodules, abscesses... (Review)
Review
Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory disease of the pilosebaceous unit leading to formation of painful, inflammatory nodules, abscesses and tunnels in apocrine gland-bearing areas of the skin. Pain and drainage are the most important symptoms associated with reduction of quality of life in HS. On the other hand, an overlooked symptom in quality of life studies is itch, despite the fact that several studies have reported its importance. Various theories have tried to explain the pathogenesis of itch in HS, such as the presence of mast cells in the cell infiltrates and elevated Ig E levels in the lesional skin. Smoking and advanced stage of disease have been found to be associated with increased intensity of itch. A PUBMED search was conducted to perform a systematic literature review using the term "hidradenitis suppurativa" [all fields], the keywords "pruritus", "itching", "itch" [all fields] and with "AND" as operator. Mast cells and mTor signaling were found to be raised in both lesional and perilesional skin. Itch as a presenting symptom has been found in 35-82.6% of patients across multiple studies. It often co-presents with pain and may be misinterpreted as burning, stinging, tickling, tweaking, prickling, etc. The presence of itch is associated with reduced quality of life, depression and impairment of social life. Brodalumab, a monoclonal antibody against IL-17A receptor, produced significant improvements in itch, pain, QoL and depression in patients with moderate to severe HS. Statins have shown some reduction in itch intensity score. Further studies are required to gain a better understanding of the etiopathogenesis and optimal therapeutic modalities for itch in HS that will allow clinicians to better address issue and reduce its impact on quality of life.
PubMed: 35807098
DOI: 10.3390/jcm11133813 -
International Journal of Molecular... Aug 2022Space travelers are exposed to microgravity (µ), which induces enhanced bone loss compared to the age-related bone loss on Earth. Microgravity promotes an increased... (Review)
Review
Space travelers are exposed to microgravity (µ), which induces enhanced bone loss compared to the age-related bone loss on Earth. Microgravity promotes an increased bone turnover, and this obstructs space exploration. This bone loss can be slowed down by exercise on treadmills or resistive apparatus. The objective of this systematic review is to provide a current overview of the state of the art of the field of bone loss in space and possible treatment options thereof. A total of 482 unique studies were searched through PubMed and Scopus, and 37 studies met the eligibility criteria. The studies showed that, despite increased bone formation during µ, the increase in bone resorption was greater. Different types of exercise and pharmacological treatments with bisphosphonates, RANKL antibody (receptor activator of nuclear factor κβ ligand antibody), proteasome inhibitor, pan-caspase inhibitor, and interleukin-6 monoclonal antibody decrease bone resorption and promote bone formation. Additionally, recombinant irisin, cell-free fat extract, cyclic mechanical stretch-treated bone mesenchymal stem cell-derived exosomes, and strontium-containing hydroxyapatite nanoparticles also show some positive effects on bone loss.
Topics: Bone Density; Bone Diseases, Metabolic; Bone Resorption; Bone and Bones; Humans; Receptor Activator of Nuclear Factor-kappa B; Space Flight; Weightlessness
PubMed: 35955775
DOI: 10.3390/ijms23158650 -
Journal of Bone Oncology Oct 2019Hormonal therapies for receptor positive-breast and prostate cancer patients have shown clinical efficacy but also several side effects including osteoporosis, loss of... (Review)
Review
Hormonal therapies for receptor positive-breast and prostate cancer patients have shown clinical efficacy but also several side effects including osteoporosis, loss of bone mass and increased fracture risk. Denosumab represents an anti RANKL (receptor activator of nuclear factor-kB ligand) monoclonal anti-body acting as inhibitor of osteoclasts formation, function, and survival, then increasing bone mass. Herein, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the role of Denosumab in saving bone health in prostate and breast cancer patients receiving respectively androgen deprivation therapy and adjuvant endocrine therapy. Moreover, selected patients have to be treated with Denosumab at the dose of 60 mg every six month or placebo. Outcomes studied included the bone mass density (BMD) increase at 24 and 36 months, BMD loss, reduction of fractures risk (in particular vertebral) at 24 and 36 months and safety (overall, serious adverse events - SAEs and discontinuation rate). Our results showed a reduction of the BMD loss up to 36 months both at the lumbar and femoral level and a BMD increase both at 24 and 36 months. It was also found a reduction in the number of new vertebral and femoral fractures at 24 and 36 months. Finally, our pooled analysis showed that Denosumab did not affect both the SAEs and therapy discontinuation risk. In conclusion, Denosumab administration can be considered effective and safe in the prevention and management of the above mentioned adverse events related to hormonal therapies designed for breast and prostate tumors.
PubMed: 31440444
DOI: 10.1016/j.jbo.2019.100252 -
Bone Reports Dec 2021Denosumab is a monoclonal antibody that has been approved to treat osteoporosis, skeletal metastasis, and giant cell tumor of bone in skeletally mature patients. Due to... (Review)
Review
Denosumab is a monoclonal antibody that has been approved to treat osteoporosis, skeletal metastasis, and giant cell tumor of bone in skeletally mature patients. Due to its potential adverse effects on normal bone growth, its use has not yet been approved in skeletally immature patients; however, the use of this agent in such patients with overt or dysregulated bone resorptive conditions has been explored in recent years. While most studies have proven the effectiveness of denosumab in controlling the progression of various disorders in skeletally immature patients, they have also revealed that refractory hypercalcemia often follows the discontinuation of denosumab treatment, raising a concern over the use of this agent in these patients. Thus, this study was designed to better understand the pathology of this condition through a systematic review of the published literature. Our analysis suggests that this condition has a potential male predisposition, that there is a correlation between the duration of denosumab treatment and patient age, and that this condition often occurs within 3 months after the last administration of denosumab in skeletally immature patients but is significantly less likely in adults. These results may further underscore that high bone formation and bone turnover rates are critically associated with hypercalcemia after the discontinuation of denosumab. In contrast, given that not all skeletally immature patients develop hypercalcemia, it is probable that other unidentified factors are involved in the pathology of this condition.
PubMed: 34825020
DOI: 10.1016/j.bonr.2021.101148 -
Vaccine Jun 2023Within-host models describe the dynamics of immune cells when encountering a pathogen, and how these dynamics can lead to an individual-specific immune response. This... (Review)
Review
BACKGROUND
Within-host models describe the dynamics of immune cells when encountering a pathogen, and how these dynamics can lead to an individual-specific immune response. This systematic review aims to summarize which within-host methodology has been used to study and quantify antibody kinetics after infection or vaccination. In particular, we focus on data-driven and theory-driven mechanistic models.
MATERIALS
PubMed and Web of Science databases were used to identify eligible papers published until May 2022. Eligible publications included those studying mathematical models that measure antibody kinetics as the primary outcome (ranging from phenomenological to mechanistic models).
RESULTS
We identified 78 eligible publications, of which 8 relied on an Ordinary Differential Equations (ODEs)-based modelling approach to describe antibody kinetics after vaccination, and 12 studies used such models in the context of humoral immunity induced by natural infection. Mechanistic modeling studies were summarized in terms of type of study, sample size, measurements collected, antibody half-life, compartments and parameters included, inferential or analytical method, and model selection.
CONCLUSIONS
Despite the importance of investigating antibody kinetics and underlying mechanisms of (waning of) the humoral immunity, few publications explicitly account for this in a mathematical model. In particular, most research focuses on phenomenological rather than mechanistic models. The limited information on the age groups or other risk factors that might impact antibody kinetics, as well as a lack of experimental or observational data remain important concerns regarding the interpretation of mathematical modeling results. We reviewed the similarities between the kinetics following vaccination and infection, emphasising that it may be worth translating some features from one setting to another. However, we also stress that some biological mechanisms need to be distinguished. We found that data-driven mechanistic models tend to be more simplistic, and theory-driven approaches lack representative data to validate model results.
Topics: Antibody Formation; Vaccination; Immunity, Humoral; Models, Theoretical
PubMed: 37198016
DOI: 10.1016/j.vaccine.2023.04.030 -
Pharmacotherapy Jan 2021Tacrolimus therapy in solid organ transplant (SOT) recipients is challenging due to its narrow therapeutic window and pharmacokinetic variability both between patients...
BACKGROUND
Tacrolimus therapy in solid organ transplant (SOT) recipients is challenging due to its narrow therapeutic window and pharmacokinetic variability both between patients and within a single patient. Intrapatient variability (IPV) of tacrolimus trough concentrations has become a novel marker of interest for predicting transplant outcomes. The purpose of this review is to evaluate the association of tacrolimus IPV with graft and patient outcomes and identify interventions to improve IPV in SOT recipients.
METHODS
A systematic review of the literature was performed using PubMed and Embase from database inception to September 20, 2020. Studies were eligible only if they evaluated an association between tacrolimus IPV and transplant outcomes. Both pediatric and adult studies were included. Measures of variability were limited to standard deviation, coefficient of variation, and time in therapeutic range.
RESULTS
Forty-four studies met the inclusion criteria. Studies were published between 2008 and 2020 and were observational in nature. Majority of data were published in adult kidney transplant recipients and identified an association with rejection, de novo donor specific antibody (dnDSA) formation, graft loss, and patient survival. Evaluation of IPV-directed interventions was limited to small preliminary studies.
CONCLUSIONS
High tacrolimus IPV has been associated with poor outcomes including acute rejection, dnDSA formation, graft loss, and patient mortality in SOT recipients. Future research should prospectively explore IPV-directed interventions to improve transplant outcomes.
Topics: Graft Survival; Heart; Humans; Immunosuppressive Agents; Kidney; Liver; Lung; Organ Transplantation; Tacrolimus
PubMed: 33131078
DOI: 10.1002/phar.2480 -
PloS One 2020Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of...
BACKGROUND
Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020.
METHODS
Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised.
RESULTS
150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14-22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase.
CONCLUSIONS
Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.
Topics: Antibodies, Neutralizing; Antibodies, Viral; Antibody Formation; COVID-19; Cross Reactions; Female; Humans; Male; SARS-CoV-2
PubMed: 33382764
DOI: 10.1371/journal.pone.0244126 -
American Journal of Obstetrics and... Jan 2022Severe pertussis infection has been reported in infants before receiving routine immunization series. This problem could be solved by vaccinating mothers during... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Severe pertussis infection has been reported in infants before receiving routine immunization series. This problem could be solved by vaccinating mothers during pregnancy or children at birth. This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) and real-world evidence to evaluate the optimal strategy for pertussis vaccination.
DATA SOURCES
PubMed, Embase, and the Cochrane Library databases were searched until December 2020.
STUDY ELIGIBILITY CRITERIA
RCTs, cohort studies, case-control studies, and case series were included if they investigated the efficacy, immunogenicity, and safety of acellular pertussis vaccine during pregnancy and at birth.
METHODS
Number of pertussis cases, severe adverse events (SAEs), and pertussis antibody concentration in infants before and after they receive routine vaccination series were extracted and random-effect model was used to pool the analyses.
RESULTS
Overall, 29 studies were included. Our meta-analysis revealed that pertussis immunization during pregnancy significantly increased the concentrations of 3 pertussis antibodies and reduced the incidence rates of infected infants below 3 months of age (odds ratio, 0.22; 95% confidence interval, 0.14-0.33). Similarly, infants vaccinated at birth had higher levels of pertussis antibody than those who were not. No significant difference in rates of severe adverse events was seen in all vaccination groups (during pregnancy [risk ratio, 1.18; 95% confidence interval, 0.76-1.82] and at birth [risk ratio, 0.72; 95% confidence interval, 0.34-1.54]).
CONCLUSION
Pertussis vaccination during pregnancy could protect infants against pertussis disease before the routine vaccination. Pertussis immunization at birth would be an alternative for infants whose mothers did not receive pertussis vaccines during pregnancy.
Topics: Antibody Formation; Child, Preschool; Diphtheria-Tetanus-acellular Pertussis Vaccines; Female; Humans; Infant; Infant, Newborn; Male; Mothers; Pertussis Vaccine; Pregnancy; Randomized Controlled Trials as Topic; Vaccination; Whooping Cough
PubMed: 34224687
DOI: 10.1016/j.ajog.2021.06.096 -
Pediatrics Jun 2021Children are at increased risk of influenza-related complications. Public health agencies recommend 2 doses of influenza vaccine for children 6 months through 8 years of...
CONTEXT
Children are at increased risk of influenza-related complications. Public health agencies recommend 2 doses of influenza vaccine for children 6 months through 8 years of age receiving the vaccine for the first time.
OBJECTIVE
To systematically review studies comparing vaccine effectiveness (VE) and immunogenicity after 1 or 2 doses of inactivated influenza vaccine (IIV) in children.
DATA SOURCES
Data sources included Medline, Embase, and Cochrane Library databases.
STUDY SELECTION
We included studies published in a peer reviewed journal up to April 2, 2019, with available abstracts, written in English, and with children aged 6 months through 8 years.
DATA EXTRACTION
VE among fully and partially vaccinated children was compared with that of unvaccinated children. We extracted geometric mean titers of serum hemagglutination inhibition (HAI) antibodies against influenza A(H1N1), A(H3N2), and B-lineage vaccine antigens after 1 and 2 IIV doses. Outcomes were evaluated by age, timing of doses, vaccine composition, and prevaccination titers.
RESULTS
A total of 10 VE and 16 immunogenicity studies were included. VE was higher for fully vaccinated groups than partially vaccinated groups, especially for children aged 6-23 months. Our findings show increased HAI titers after 2 doses, compared with 1. Older children and groups with prevaccination antibodies have robust HAI titers after 1 dose. Similar vaccine strains across doses, not the timing of doses, positively affects immune response.
LIMITATIONS
Few studies focused on older children. Researchers typically administered one-half the standard dose of IIV. HAI antibodies are an imperfect correlate of protection.
CONCLUSIONS
Findings support policies recommending 2 IIV doses in children to provide optimal protection against influenza.
Topics: Antibody Formation; Child; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza, Human; Vaccine Efficacy
PubMed: 34039716
DOI: 10.1542/peds.2020-019901 -
Clinical Nutrition ESPEN Dec 2021There are some studies indicating the effects of probiotic-containing foods or supplements on viral diseases. We aimed to conduct a rapid review of probiotics with... (Review)
Review
BACKGROUND & AIMS
There are some studies indicating the effects of probiotic-containing foods or supplements on viral diseases. We aimed to conduct a rapid review of probiotics with specific emphasis on their potential for early administration in patients at greater risk of SARS-CoV-2 infection.
METHODS
We searched on PubMed, EMBASE, Google Scholar, Science Direct, Scopus and Web of Science up to February 2021 to identify interventional and observational studies documenting the effects of probiotics strains on interleukins, virus titers, and antibody production with a focus on probiotic-containing foods (PROSPERO Registration ID. CRD42020181453) RESULTS: From a total of 163 records, 21 studies were classified into three domains based on the efficacy of probiotics on 1) the level of interleukins (n = 7), 2) virus titers (n = 2), and 3) interferon (IFN) and antibody production (n = 12). The suppuration of pro-inflammatory interleukins and type I INF production seemed to be the main anti-viral effect of probiotics. Nine studies also indicated the beneficial effects of probiotics and fermented foods on viral diseases.
CONCLUSION
Based on evidence, some probiotic strains may be useful in viral infections; randomized trials are needed to confirm these findings.
Topics: Antibody Formation; Humans; Probiotics; SARS-CoV-2; Viral Load; Virus Diseases; COVID-19 Drug Treatment
PubMed: 34857182
DOI: 10.1016/j.clnesp.2021.10.016