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Journal of Viral Hepatitis Dec 2022We investigated the clinical characteristics and therapeutic strategies for paediatric liver transplant (PLT) recipients who experienced de novo hepatitis B virus...
We investigated the clinical characteristics and therapeutic strategies for paediatric liver transplant (PLT) recipients who experienced de novo hepatitis B virus infection and the features of HBsAg seroconversion. A total of 821 PLT were performed in HBV-free recipients between January 2013 and January 2019 in Paediatric Organ Transplant Center, Tianjin First Central Hospital. Twenty-one recipients developed de novo HBV infection, the clinical data were analysed. The overall incidence of de novo HBV infection was 2.5%. Only one recipient received an HBcAb-negative graft, 20 recipients received HBcAb-positive grafts. The incidence of de novo HBV infection in HBcAb-negative and HBcAb-positive graft recipients were 0.2% and 6.3%, respectively. Fifteen de novo HBV-infected recipients showed HBsAg seroconversion, the incidence of HBsAg seroconversion was 71.4%. The median time from the diagnosis of de novo HBV infection to HBsAg seroconversion was 15 (1, 73) months. Recipients with hepatitis B surface antigen (HBsAg) titre <1000 IU/L and negative hepatitis B e antigen (HBeAg) at the time of de novo HBV infection diagnosis were more likely to achieve HBsAg seroconversion. Nucleotide analogues were effective in treating recipients with de novo HBV infection. De novo HBV infection does not impact liver graft function as well as recipient and graft survival rate. De novo HBV infection does not impact PLT recipient outcomes under close monitoring and appropriate treatment. High incidence of HBsAg seroconversion can be achieved after anti-viral therapy.
Topics: Child; Humans; Hepatitis B Surface Antigens; Hepatitis B virus; Liver Transplantation; Seroconversion; Hepatitis B Core Antigens; Hepatitis B; Hepatitis B Antibodies; Antiviral Agents
PubMed: 36094676
DOI: 10.1111/jvh.13749 -
International Journal of Gynaecology... Jun 2021To identify urodynamic predictors for de novo overactive bladder (OAB) after single-incision sling implantation.
OBJECTIVE
To identify urodynamic predictors for de novo overactive bladder (OAB) after single-incision sling implantation.
METHODS
This retrospective study analyzed women with pure, urodynamically proven stress urinary incontinence, without OAB, between 2008 and 2015, in a university hospital. De novo OAB was investigated during clinical interviews.
RESULTS
A total of 192 patients were analyzed; 21 patients with de novo OAB were considered as group A while 171 control patients formed group B. Univariate analysis demonstrated that patients with de novo OAB have the first desire to void at a lower bladder volume (124 mL versus 160 mL, P = 0.0052), smaller maximum cystometric capacity (357 mL versus 406 mL, P = 0.0061), lower maximum flow (17 mL/s versus 23 mL/s, P = 0.0006), and higher bladder outlet obstruction index (BOOI; -11 versus -23, P = 0.0022) compared with controls. According to multivariate analysis, maximum cystometric capacity (parameter estimate [PE] =0.008, P = 0.04) and BOOI (PE = -0.029, P = 0.01) were independent urodynamic predictors of de novo OAB. The final model showed good predictive accuracy (area under the curve =0.81).
CONCLUSION
The present study identified maximum cystometric capacity and BOOI as independent predictors of de novo overactive bladder after single-incision sling implantation. Therefore, preoperative urodynamics may be useful to improve preoperative counseling and to tailor surgical treatment.
Topics: Female; Humans; Middle Aged; Postoperative Complications; Retrospective Studies; Suburethral Slings; Urinary Bladder, Overactive; Urinary Incontinence, Stress; Urodynamics
PubMed: 33251577
DOI: 10.1002/ijgo.13503 -
Familial Cancer Jul 2020A 14-year-old male presented with abdominal pain. Imaging illustrated a left-sided adrenal mass; he underwent a left nephrectomy, confirming an extra-adrenal PGL....
A 14-year-old male presented with abdominal pain. Imaging illustrated a left-sided adrenal mass; he underwent a left nephrectomy, confirming an extra-adrenal PGL. Germline genetic testing revealed a heterozygous, likely pathogenic mutation in the SDHB gene. The patient's family subsequently underwent genetic testing; his mother and sister were both positive for the familial SDHB mutation. Cascade testing for the proband's maternal aunt and maternal grandparents was negative for the familial mutation. SNP genotyping was used to confirm relationships. This is the second reported case of a de novo SDHB gene mutation and the first reported case of a confirmed de novo mutation in a patient who was not the initial proband. As SDHB-associated PGLs and PCCs are expected to be more aggressive and malignant, it is imperative to identify patients with SDHB mutations early. Given that many patients with germline mutations have no family history of PGL of PCC, the possibility of de novo mutations must be considered. Further studies are needed to determine the rate of de novo mutation in SDHB and other SDH-complex genes. Up to 41% of patients with paragangliomas (PGL) or pheochromocytomas (PCC) have an identifiable hereditary cancer predisposition syndrome. Mutations in 12 genes are known to increase the risk of PGL and/or PCC; however, the de novo rate is mostly unknown. Only one case report exists of a de novo SDHB mutation. We present the second case of a family with a de novo SDHB mutation.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Child; Family; Female; Genetic Testing; Germ-Line Mutation; Heterozygote; Humans; Male; Neoplastic Syndromes, Hereditary; Paraganglioma, Extra-Adrenal; Pheochromocytoma; Polymorphism, Single Nucleotide; Succinate Dehydrogenase
PubMed: 32200538
DOI: 10.1007/s10689-020-00174-5 -
The Journal of Craniofacial Surgery Sep 2022To confirm this hypothesis, this study aimed to explore the pathogenic factors, prognosis, and their relationship in de novo aneurysms and to reach a consensus on their...
OBJECTIVE
To confirm this hypothesis, this study aimed to explore the pathogenic factors, prognosis, and their relationship in de novo aneurysms and to reach a consensus on their management.
METHODS
First, the clinical data of 5 patients with de novo aneurysms from April 1998 to October 2021 were analyzed retrospectively. Then, the English literature on de novo aneurysms reported in Pubmed from 1985 to 2021 was systematically reviewed, and 18 case reports from 17 articles and 16 case series were identified. Univariate and multivariate analyses and modified Fisher test were used to analyze the relationship between pathogenic factors and prognosis.
RESULTS
Hypertension was noted in 60% of our clinical cases, 50% of the case series identified in the literature review, and 66.7% of the case reports in the literature review. In the case reports identified from our literature review, the proportion of original aneurysms in the anterior circulation was 96.3%. Moreover, in our 5 cases, all original aneurysms occurred in the anterior circulation. The rupture rate of original aneurysms in our 5 cases was 100%, and that of the cases reported in the literature review was 88.9%. Univariate logistic analysis showed that the time interval was related to the prognosis of de novo aneurysms with a P value of 0.048 and an odds ratio of 0.968 (95% confidence interval 0.938-1.000). Modified Fisher exact tests showed that patient age at the occurrence of de novo aneurysm P = 0.029) was related to the prognosis of de novo aneurysms.
CONCLUSIONS
Hypertension, an original aneurysms located in the anterior circulation and rupture represent the pathogenic factors associated with de novo aneurysms. The time interval to de novo aneurysm and patient age at the occurrence of de novo aneurysm are predictive of prognosis. Based on the above information, we can prevent and improve the prognosis of de novo aneurysms.
Topics: Aneurysm, Ruptured; Humans; Intracranial Aneurysm; Prognosis; Retrospective Studies; Risk Factors; Virulence Factors
PubMed: 34974461
DOI: 10.1097/SCS.0000000000008451 -
Liver Transplantation : Official... Nov 2012Recipients of liver transplantation (LT) have a higher overall risk (2-3 times on average) of developing de novo malignancies than the general population, with... (Review)
Review
Recipients of liver transplantation (LT) have a higher overall risk (2-3 times on average) of developing de novo malignancies than the general population, with standardized incidence ratios ranging from 1.0 for breast and prostate cancers to 3-4 for colon cancer and up to 12 for esophageal and oropharyngeal cancers. Aside from immunosuppression, other identified risk factors for de novo malignancies include the patient's age, a history of alcoholic liver disease or primary sclerosing cholangitis, smoking, and viral infections with oncogenic potential. Despite outcome studies showing that de novo malignancies are major causes of mortality and morbidity after LT, there are no guidelines for cancer surveillance protocols or immunosuppression protocols to lower the incidence of de novo cancers. Patient education, particularly for smoking cessation and excess sun avoidance, and regular clinical follow-up remain the standard of care. Further research in epidemiology, risk factors, and the effectiveness of screening and management protocols is needed to develop evidence-based guidelines for the prevention and treatment of de novo malignancies.
Topics: Female; Graft Rejection; Humans; Immunosuppressive Agents; Liver Transplantation; Lymphoproliferative Disorders; Male; Medical Oncology; Neoplasms; Postoperative Complications; Risk Factors; Treatment Outcome
PubMed: 22887956
DOI: 10.1002/lt.23531 -
Cell Systems May 2021Metaproteomics has emerged as one of the most promising approaches for determining the composition and metabolic functions of complete microbial communities....
Metaproteomics has emerged as one of the most promising approaches for determining the composition and metabolic functions of complete microbial communities. Conventional metaproteomics approaches rely on the construction of protein sequence databases and efficient peptide-spectrum-matching algorithms, an approach that is intrinsically biased towards the content of the constructed sequence database. Here, we introduce a highly efficient, database-independent de novo metaproteomics approach and systematically evaluate its quantitative performance using synthetic and natural microbial communities comprising dozens of taxonomic families. Our work demonstrates that the de novo sequencing approach can vastly expand many metaproteomics applications by enabling rapid quantitative profiling and by capturing unsequenced community members that otherwise remain inaccessible for further interpretation. Kleikamp et al., describe a novel de novo metaproteomics pipeline (NovoBridge) that enables rapid community profiling without the need for constructing protein sequence databases.
Topics: Humans; Microbiota; Proteomics
PubMed: 34023022
DOI: 10.1016/j.cels.2021.04.003 -
Neurourology and Urodynamics Aug 2018To investigate storage symptoms following robot-assisted laparoscopic radical prostatectomy (RARP), focused on de novo overactive bladder (OAB), and to evaluate the...
AIMS
To investigate storage symptoms following robot-assisted laparoscopic radical prostatectomy (RARP), focused on de novo overactive bladder (OAB), and to evaluate the factors related to de novo OAB occurrence.
METHODS
We prospectively examined 245 patients without OAB who underwent RARP for localized prostate cancer. Subjective and objective symptoms in the lower urinary tract were evaluated before and after surgery. At 3 months after RARP, the patients were divided into two groups: patients with de novo OAB (de novo OAB group) and those without OAB (OAB-free group). We compared the operative and urodynamic parameters between both groups and evaluated the factors related to OAB.
RESULTS
De novo OAB was observed in 37.8% (87/230) of patients. Post-operative continence rate was significantly higher in the OAB-free group (79.7%) than in the de novo OAB group (8.0%). Although the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) in the de novo OAB group significantly deteriorated from 9.7 to 14.1 and from 2.4 to 8.3, respectively, no corresponding significant changes occurred in the OAB-free group. Additionally, there was a significant difference in pre-operative IPSS-QOL score, continence rate, pre-and post-operative maximum urethral closing pressure (MUCP), and post-operative functional profile length (FPL) between both groups. Multivariable logistic regression analysis showed pre-operative IPSS-QOL score and post-operative MUCP were significant predictive factors for de novo OAB.
CONCLUSIONS
The incidence rate of de novo OAB after RARP was about 40%, and seemed unexpectedly high. Decreased urethral function was significantly related to de novo OAB after surgery.
Topics: Aged; Humans; Laparoscopy; Lower Urinary Tract Symptoms; Male; Middle Aged; Postoperative Complications; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Robotic Surgical Procedures; Urethra; Urinary Bladder, Overactive; Urinary Incontinence; Urodynamics
PubMed: 29635709
DOI: 10.1002/nau.23556 -
G3 (Bethesda, Md.) Aug 2023De novo genes are genes that emerge as new genes in some species, such as primate de novo genes that emerge in certain primate species. Over the past decade, a great...
De novo genes are genes that emerge as new genes in some species, such as primate de novo genes that emerge in certain primate species. Over the past decade, a great deal of research has been conducted regarding their emergence, origins, functions, and various attributes in different species, some of which have involved estimating the ages of de novo genes. However, limited by the number of species available for whole-genome sequencing, relatively few studies have focused specifically on the emergence time of primate de novo genes. Among those, even fewer investigate the association between primate gene emergence with environmental factors, such as paleoclimate (ancient climate) conditions. This study investigates the relationship between paleoclimate and human gene emergence at primate species divergence. Based on 32 available primate genome sequences, this study has revealed possible associations between temperature changes and the emergence of de novo primate genes. Overall, findings in this study are that de novo genes tended to emerge in the recent 13 MY when the temperature continues cooling, which is consistent with past findings. Furthermore, in the context of an overall trend of cooling temperature, new primate genes were more likely to emerge during local warming periods, where the warm temperature more closely resembled the environmental condition that preceded the cooling trend. Results also indicate that both primate de novo genes and human cancer-associated genes have later origins in comparison to random human genes. Future studies can be in-depth on understanding human de novo gene emergence from an environmental perspective as well as understanding species divergence from a gene emergence perspective.
Topics: Animals; Humans; Evolution, Molecular; Primates; Genome
PubMed: 37313728
DOI: 10.1093/g3journal/jkad135 -
World Journal of Gastroenterology Sep 2019Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to...
BACKGROUND
Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and malignancies in liver transplant patients.
AIM
To study the role of immunosuppression on the incidence of malignancies in liver transplant recipients.
METHODS
A systematic literature examination about malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy.
RESULTS
Emerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences.
CONCLUSION
The selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of malignancies and may also help in treating liver transplant patients suffering from cancer.
Topics: Adult; Allografts; Child; Graft Rejection; Humans; Immune Tolerance; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Liver; Liver Transplantation; Neoplasms; Patient Selection; Postoperative Complications; Withholding Treatment
PubMed: 31558879
DOI: 10.3748/wjg.v25.i35.5356 -
Medicinal Research Reviews Sep 2003De novo design programs such as LEGEND, LUDI, and LeapFrog can identify novel structures that are predicted to fit the active site of a target protein. However, in the... (Review)
Review
De novo design programs such as LEGEND, LUDI, and LeapFrog can identify novel structures that are predicted to fit the active site of a target protein. However, in the conventional de novo design strategy, the output structures obtained from the programs can be problematic with regard to synthetic accessibility and binding affinity prediction. Thus it has been practically difficult to obtain novel lead compounds that are appropriate for medicinal chemists through the de novo design strategy. Since the late 1990s, several new strategies for lead identification have been reported and the successful examples have been disclosed. One of the strategies is validation of small fragments, which can be substructures of de novo ligands, by using NMR, X-ray, or MS spectra. Another method is prioritization of output structures obtained from de novo design programs by chemical accessibility. This review describes these new strategies with practical applications and future perspectives of de novo design.
Topics: Binding Sites; Computer-Aided Design; Drug Design; Humans; Ligands; Magnetic Resonance Spectroscopy; Mass Spectrometry; Models, Chemical; Models, Molecular; Molecular Structure; Protein Binding; Software; Thermodynamics; X-Rays
PubMed: 12789688
DOI: 10.1002/med.10046