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Cureus Nov 2023Osteosarcoma (OS) is a debilitating cancer of the bone that commonly afflicts the young and old. This may be de novo or associated with tumorigenic syndromes. However,... (Review)
Review
Osteosarcoma (OS) is a debilitating cancer of the bone that commonly afflicts the young and old. This may be de novo or associated with tumorigenic syndromes. However, many molecular mechanisms are still being uncovered and may offer greater avenues for screening and therapy. Cadherins, including E-cadherin and N-cadherin/vimentin, are involved in epithelial-to-mesenchymal transmission (EMT), which is key for tumor invasion. A study reviewing the relationship between OS and cadherins might elucidate a potential target for therapy and screening. A robust literature review was conducted by searching PubMed with the keywords "osteosarcoma", "cadherin", "e-cadherin" and "n-cadherin". Of a preliminary 266 papers, 25 were included in the final review. Review articles and those without primary data were excluded. Loss of E-cadherin is noted in metastatic cell lines of osteosarcoma. Overexpression of E-cadherin or knockout of N-cadherin/vimentin results in loss of metastatic potential. There are several methods of gene knockout, including CRISPR-Cas9 gene editing, viral vector insertion with micro RNA complementary to long noncoding RNA within gene segments, or proteomic editing. Screening for EMT and genetic treatment of EMT is a possible avenue for the treatment of refractory osteosarcoma. Several studies were conducted ex vivo. Further testing involving in vitro therapy is necessary to validate these methods. Limitations of this study involve a lack of in vivo trials to validate methods.
PubMed: 38156135
DOI: 10.7759/cureus.49521 -
American Journal of Medical Genetics.... May 2024RASopathies are a group of malformation syndromes known to lead to nonimmune hydrops fetalis (NIHF) in severe presentations. Pathogenic variants can be de novo or... (Meta-Analysis)
Meta-Analysis Review
RASopathies are a group of malformation syndromes known to lead to nonimmune hydrops fetalis (NIHF) in severe presentations. Pathogenic variants can be de novo or parentally inherited. Despite being a known frequent presentation, the fraction of monogenic NIHF cases due to RASopathies is limited in the literature. Also, the specific parental contribution of RASopathies to NIHF is not well described. Our objective was to review pooled exome sequencing (ES) diagnostic yield of RASopathies for NIHF and to determine the parental contribution of RASopathy to NIHF. We performed a systematic review of prenatal ES studies from January 1, 2000 to August 1, 2022. Thirty-six studies met inclusion criteria. Cases with RASopathy gene variants were reviewed. NIHF cases were further classified as isolated or non-isolated. Thirty-six ES studies including 46 pregnancies with NIHF and a diagnosed RASopathy were reviewed. Forty-four diagnostic variants and 2 variants of uncertain significance in 12 RASopathy genes were identified. Expanding on what was previously published, a total of 506 NIHF cases were extracted with 191 cases yielding a positive diagnosis by ES. The overall rate of RASopathy diagnosis in clinically diagnosed NIHF cases was 9% (44/506). The rate of RASopathy diagnosis among NIHF cases with positive genetic diagnosis by ES was 23% (44/191). Of the 46 cases identified, 13 (28%) variants were parentally inherited; specifically, 5/13 (38%) maternal, 3/13 (23%) paternal, 2/13 (15%) biparental, and 3/13 (23%) unspecified. Majority of NIHF cases 29/46 (63%) were isolated. Among NIHF cases with positive ES diagnoses, RASopathy diagnostic yield by ES was 23%. NIHF secondary to RASopathies was parentally inherited in 28% of cases. Most cases of NIHF due to RASopathy were isolated, with no prenatal detection of associated anomalies.
Topics: Pregnancy; Male; Female; Humans; Hydrops Fetalis; Exome Sequencing; Fathers
PubMed: 38156365
DOI: 10.1002/ajmg.a.63494 -
Frontiers in Pharmacology 2023The work aimed to compare the pharmacokinetic (PK) profiles and other outcomes reported in observational studies in kidney transplant recipients (KTRs) receiving novel...
The work aimed to compare the pharmacokinetic (PK) profiles and other outcomes reported in observational studies in kidney transplant recipients (KTRs) receiving novel once-daily extended-release tablet tacrolimus (LCPT; LCP-tacrolimus; Envarsus XR) or receiving standard-of-care capsule tacrolimus (PR-Tac; prolonged-release tacrolimus; Advagraf/IR-Tac; immediate-release tacrolimus; Prograf). A systematic review was conducted for all randomized controlled trials (RCTs) and cohort studies investigating the outcomes in KTRs receiving LCPT or PR-Tac/IR-Tac. We systematically searched PubMed, Web of Science, and EMBASE, with no language restriction. The registered trials and references listed in relevant studies were also searched. Data were extracted for the PK profile, tacrolimus trough level (TTL), and changes in the estimated glomerular filtration rate (eGFR) and serum creatinine (Scr), biopsy-proven acute rejection (BPAR) rate, delayed graft function (DGF) rate, post-transplant diabetes mellitus (PTDM) rate, tremor rate (TR), death rate (DR), and rate of infection by cytomegalovirus (CMV). This study was registered with PROSPERO (registration number: CRD42023403787). A total of seven eligible articles including 1,428 patients with 712 in the LCPT group versus 716 in the PR-Tac/IR-Tac group were included in this study for evidence synthesis. The baseline characteristics of the LCPT, PR-Tac, and IR-Tac groups were similar. The pooled analysis showed a higher PK profile in the LCPT group, and this result was consistent with those of all the included studies. In addition, no significant difference was observed for other outcomes. Considering heterogeneity between studies and potential bias, care providers should select agents based on patient-specific factors and their clinical experience for the immunosuppressive treatment of KTRs.
PubMed: 38143499
DOI: 10.3389/fphar.2023.1310339 -
Medicine Dec 2023Immune system deregulation, including AAV, is a key event that may potentially evolve into ESRD. Abnormal activation of the cAP is also a cardinal feature of TMA,...
End stage renal disease in patient with microscopic polyangiitis and atypical hemolytic-uremic syndrome arose 3 weeks after the third dose of anti-SARS-CoV2 vaccine mRNA-1273: A case report with literature revision.
RATIONALE
Immune system deregulation, including AAV, is a key event that may potentially evolve into ESRD. Abnormal activation of the cAP is also a cardinal feature of TMA, particularly aHUS. The kidney is the most frequently involved organ, and renal-limited forms of TMA are often encountered in clinical practice. Isolated case reports described the occurrence of renal TMA in AAV patients. Some cases of both de novo and relapses of AAV and/or TMAs after anti-SARS-CoV2 vaccination have been reported. We reported, for the 1st time, a case of patients with new-onset MPA and aHUS occurring 3 weeks after the third dose of mRNA-1273 vaccine anti-SARS-CoV2.
PATIENT CONCERNS
We present a 67-year-old man, affected by arterial hypertension, reported, after mRNA-1273 vaccine anti-SARS-CoV2, anuria, fatigue, anorexia and nausea. Laboratory data revealed acute renal failure.
DIAGNOSIS
Positivity of MPO-ANCA was observed. 7 days after admission, we observed a worsening of anemia and thrombocytopenia with haptoglobin reduction, LDH increase and presence of schistocytes. Plasma levels of ADAMTS-13 were normal. A renal biopsy was performed, and findings were consistent with microscopic polyangiitis, with features of micro-thrombotic glomerulopathy. Genetic tests revealed absence of hybrid genes associated with the increased risk of aHUS.
INTERVENTIONS AND OUTCOMES
We started renal replacement treatment, including hemodialysis, and pulsed methylprednisolone, with no improvement of laboratory parameters. Then, plasma exchange was performed leading to partial haematological response. Only with Eculizumab, a human C5 inhibitor, we observed a normalization of haptoglobin levels and platelets' count. However, three months after discharge, the patient still required hemodialysis.
LESSONS
To our knowledge we observed the first case aHUS, without genetic predisposition, associated with MPA occurring after the third dose of anti-SARS-CoV2 vaccine. This case report highlights the potential link between anti-SARS-CoV2 vaccine as a trigger of MPA and aHUS. This systematic review offers additional perspectives. It is plausible to hypothesize that the vaccine was the trigger for the development of these 2 diseases.Solid evidence on the mechanisms of interaction between vaccine and immune system, the role of genetic predisposition, and other variables, will shed additional light on the controversial link between anti-SARS-CoV2 vaccine and autoimmunity.
Topics: Male; Humans; Aged; Atypical Hemolytic Uremic Syndrome; 2019-nCoV Vaccine mRNA-1273; Microscopic Polyangiitis; Haptoglobins; COVID-19; Kidney Failure, Chronic; Genetic Predisposition to Disease
PubMed: 38115241
DOI: 10.1097/MD.0000000000036560 -
Current Medical Research and Opinion Feb 2024Critique the available systematic review and de novo assessment of the role of psychedelics in the treatment of alcohol use disorder. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Critique the available systematic review and de novo assessment of the role of psychedelics in the treatment of alcohol use disorder.
METHODS
A systematic literature search of PubMed was completed from 1960 to 9/9/2023. We pooled randomized controlled trials comparing psychedelics to control therapy for the treatment of alcohol use disorder.
RESULTS
At the first recorded follow-up, LSD [ = 3, Odds Ratio (OR) 1.99 (95% Confidence interval (CI): 1.10 to 3.61)] and any psychedelic [ = 4, OR 2.16 (95%CI: 1.26 to 3.69)] enhanced the odds of patients achieving abstinence or a substantial reduction in drinking alcohol versus placebo in randomized, double-blind, placebo-controlled trials. When the inclusion criteria were relaxed to include controlled trials without double-blinding or placebo control, LSD [ = 5, OR 1.79 (95%CI: 1.36 to 2.34)] and any psychedelic therapy [ = 6, OR 1.89 (95%CI: 1.42 to 2.50)] still enhanced the odds of patients achieving abstinence or a substantial reduction in drinking alcohol. Four of 6 trials had high risk of bias and other methodological issues. One trial found an instance of suicidal ideation as well as transient increases in blood pressure that requires further exploration before the balance of benefits to harms can be determined.
CONCLUSIONS
The use of psychedelics to treat alcohol use disorder is promising, but the weaknesses in the literature base preclude making definitive statements about its value. Future trials with greater methodological rigor are needed.
Topics: Humans; Hallucinogens; Alcoholism; Alcohol Drinking; Ethanol; Randomized Controlled Trials as Topic
PubMed: 38111216
DOI: 10.1080/03007995.2023.2296968 -
Cancers Nov 2023Radiation-induced soft tissue sarcomas (RISs) are rare secondary malignancies with a dire prognosis. The literature on the management of these tumors remains scarce due... (Review)
Review
INTRODUCTION
Radiation-induced soft tissue sarcomas (RISs) are rare secondary malignancies with a dire prognosis. The literature on the management of these tumors remains scarce due to their low incidence. Our systematic review sought to assess the treatment alternatives and outcomes of patients with RIS.
METHODS
A systematic review was conducted following the PRISMA guidelines. Our study was registered in PROSPERO (ID: CRD42023438415). Quality assessment was performed using the STROBE checklist. Weighted means for both continuous and categorical values were calculated.
RESULTS
Twenty-one studies comprising 1371 patients with RIS were included. The mean latency period from radiation to RIS diagnosis was 14 years, and the mean radiation dose delivered to the primary malignancy was 29.2 Gy. The most common histological type was undifferentiated pleomorphic sarcoma (42.2%), and 64% of all tumors were high-grade. The trunk was the most common location (59%), followed by extremities (21%) and pelvis (11%). Surgery was performed in 68% of patients and, among those with an appendicular tumor, the majority (74%) underwent limb-salvage surgery. Negative margins were attained in 58% of patients. Chemotherapy and radiotherapy were administered in 29% and 15% of patients, respectively. The mean 5-year overall survival was 45%, and the local recurrence and metastasis rates were 39% and 27%, respectively.
CONCLUSIONS
In our study, the most common treatment was surgical resection, with RT and chemotherapy being administered in less than one third of patients. Patients with RIS exhibited poor oncologic outcomes. Future studies should compare RIS with de novo STS while controlling for confounders.
PubMed: 38067287
DOI: 10.3390/cancers15235584 -
Head and Neck Pathology Dec 2023The intraosseous schwannoma (IS) is a benign peripheral nerve sheath tumor postulated to arise de novo or from nerve fibers in preexisting nutrient canals. ISs are... (Review)
Review
BACKGROUND
The intraosseous schwannoma (IS) is a benign peripheral nerve sheath tumor postulated to arise de novo or from nerve fibers in preexisting nutrient canals. ISs are uncommon and comprise less than 1% of neoplasms originating in bone. We herein present two cases of mandibular schwannomas-the first case was a 66-year-old female with a four-month history of pain and pressure associated with an anterior mandibular radiolucency, and the second case was an asymptomatic 12-year-old female with separate radiolucencies of her mandibular symphysis and right posterior mandible. Incisional biopsies of all three lesions showed a benign spindle cell neoplasm with histologic features of a schwannoma; the tumor cells were strongly reactive for S-100. The patients underwent complete enucleation of their lesions and are without evidence of disease at ten months and five years, respectively.
METHODS
A systematic review was undertaken to evaluate the diagnostic features, treatment, and patient outcomes of gnathic schwannomas.
RESULTS
A total of 93 cases were identified with the following demographic findings: predominance in females (57%); average age of occurrence of 37.3 years (8 to 77 years); mean size of 3.6 cm; and involvement of the mandibular body (37.6%), mandibular body and ramus (18.3%), and anterior mandible (18.3%). The predominant clinical sign was swelling (69.9%), and the most common radiographic presentation was a radiolucency (94.6%) with well-defined borders (72%).
CONCLUSION
All cases were treated surgically, with an average follow-up interval of 22.9 months and a recurrence rate of 5.4.
Topics: Female; Humans; Adult; Aged; Child; Neurilemmoma; Mandible; Biopsy; S100 Proteins; Diagnosis, Differential
PubMed: 38055108
DOI: 10.1007/s12105-023-01595-1 -
European Journal of Surgical Oncology :... Jan 2024The role of breast surgery in the treatment of patients with de novo metastatic breast cancer(dnMBC) remains controversial, with conflicting trial results. We did a... (Meta-Analysis)
Meta-Analysis Review
The role of breast surgery in the treatment of patients with de novo metastatic breast cancer(dnMBC) remains controversial, with conflicting trial results. We did a meta-analysis to comprehensively investigate and assess whether breast surgery is associated with survival and quality of life outcomes in patients with dnMBC.We systematically searched PubMed, Embase, Google Scholar, Scopus, and Web of Science, from database inception to March 30, 2022, for randomized controlled trials(RCTs) that compared breast surgery or locoregional therapy with non-surgical treatment based on systemic therapy for managing dnMBC.We also reviewed abstracts and presentations from major conference proceedings. We excluded non-randomised trials and considered only papers published in English. The primary outcomes were overall survival(OS),locoregional progression-free survival(LPFS), distant progression-free survival(DPFS), and quality of life(QoL). The quality of RCTs was appraised with the Cochrane Collaboration risk of bias tool. Random-effects model or fixed effects model were used to calculate the effect sizes of included RCTs.Quality of evidence was assessed with GRADE criteria. Data analysis was performed with STATA 17.0. A total of 1018 women from seven randomized clinical trials were included in the analysis. Pooled analyses revealed that compared with systemic therapy, breast surgery was not associated with beneficial outcomes in OS(hazard ratio [HR],0.87; 95%CI,0.68 to 1.11; I = 53.08 %; p = 0.265),DPFS(HR,1.20; 95%CI,0.94 to 1.54; I = 86.45 %; p = 0.136), or QoL-global health status (standardized mean difference[SMD],0.08; 95%CI,-0.15 to 0.32; I = 79.45 %; p = 0.478) and QoL-mental-physical functionality(SMD,-0.19; 95%CI,-0.50 to 0.13; I = 0.00 %; p = 0.255), but was associated with a benefit in LPFS(HR,0.27; 95%CI,0.19 to 0.38; I = 84.16 %; p < 0.001). These findings were consistent in subgroup analyses of the timing of surgery, site and number of metastases and tumor molecular subtype. The evidence grade was moderate because of the substantial heterogeneity among studies. Based on the RCTs evidence, we found that breast surgery may benefit locoregional control but does not prolong OS and improve QoL in patients with dnMBC. The Prospero registration number: CRD42020206460.
Topics: Humans; Female; Breast Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Mastectomy; Progression-Free Survival
PubMed: 38048724
DOI: 10.1016/j.ejso.2023.107308 -
Journal of Cardiothoracic Surgery Nov 2023The aim of this review was the creation of uniform protocols to carry out and disclose First-In-Human and preliminary clinical trials of biological mitral valve... (Review)
Review
BACKGROUND
The aim of this review was the creation of uniform protocols to carry out and disclose First-In-Human and preliminary clinical trials of biological mitral valve replacement. The need for consistent methodology in these early trials was highlighted by the observation of significant variability in the methods and protocols used across different research.
METHODS
An extensive search through six major databases was carried out to retrieve First-In-Human (FIH) clinical studies evaluating surgically implanted bio-prostheses in the mitral position.
RESULTS
Following the PRISMA guideline, a systematic search identified 2082 published articles until March 2023. After removing duplicates (189), 1862 citations were screened, resulting in 22 eligible studies with 3332 patients for analysis. The mitral valve prostheses in these studies ranged from 21 to 37 mm, with the 29 mm size being most prevalent. Patient numbers varied, with the FIH subgroup including 31 patients and the older subgroup including 163 patients. Average study durations differed: the older subgroup lasted 4.57 years, the FIH subgroup 2.85 years, and the early phase studies spanned 8.05 years on average.
CONCLUSION
FIH clinical report is essential to assess the significance of clinical data required for a "de novo" surgical implant. In addition, understanding the performance of the device, and recognizing the difficulties associated with the innovation constitute important lessons. These insights could be beneficial for the development of bioprosthetic heart valves and formulating a protocol for an FIH clinical trial.
Topics: Humans; Mitral Valve; Prosthesis Design; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Bioprosthesis; Prosthesis Failure
PubMed: 38037117
DOI: 10.1186/s13019-023-02464-2 -
Annals of Indian Academy of Neurology 2023COVID-19 infection is associated with neurological manifestations, including various types of movement disorders (MD). A thorough review of individual patients with...
BACKGROUND
COVID-19 infection is associated with neurological manifestations, including various types of movement disorders (MD). A thorough review of individual patients with COVID-19-induced MD would help in better understanding the clinical profile and outcome of these patients and in prognostication.
OBJECTIVE
We conducted an individual patient-systematic review to study the clinical and imaging profile and outcomes of patients with COVID-19-associated MD.
METHODS
A systematic literature search of PubMed, EMBASE, and Cochrane databases was conducted by two independent reviewers. Individual patient data COVID from case reports and case series on COVID-19-associated MD, published between December 2019 and December 2022, were extracted and analyzed.
RESULTS
Data of 133 patients with COVID-19-associated MD from 82 studies were analyzed. Mean age was 55 ± 18 years and 77% were males. A mixed movement disorder was most commonly seen (41%); myoclonus-ataxia was the most frequent (44.4%). Myoclonus significantly correlated with age (odds ratio (OR) 1.02 = 0.03, CI 1-1.04). Tremor had the longest latency to develop after SARS-CoV-2 infection [median (IQR) 21 (10-40) days, = 0.009, CI 1.01-1.05]. At short-term follow-up, myoclonus improved (OR 14.35, value = 0.01, CI 1.71-120.65), whereas parkinsonism (OR 0.09, value = 0.002, CI 0.19-0.41) and tremor (OR 0.16, value = 0.016, CI 0.04-0.71) persisted.
CONCLUSION
Myoclonus-ataxia was the most common movement disorder after COVID-19 infection. Myoclonus was seen in older individuals and usually improved. Tremor and parkinsonism developed after a long latency and did not improve in the short-term.
PubMed: 38022478
DOI: 10.4103/aian.aian_572_23